孕妇和儿童合并症
BMJ Best Practice 临床实践合并症诊疗工具中的信息涉及非妊娠成人。
这些信息不适用于孕妇患者或儿童。在这类情况下,请向产科/妇科专科医生或儿科专科医生寻求建议,了解患者的合并症可能会如何影响您对 COVID-19 的管理。
请注意药品名称和品牌、药品处方或地区之间的配方/用药途径和剂量可能有所不同。治疗建议针对患者特定群体提出: 查看免责声明
如果患者为孕妇或儿童,请勿使用该工具进行合并症选择。采用标准治疗流程,并就合并症寻求专科医生建议。
增加了以下合并症:
注意该图标: 指代由于受患者合并症影响而改变或添加的治疗选择。
隔离疑似或确诊的轻症患者(即符合 COVID-19 病例定义而无缺氧或肺炎证据的有症状患者)和无症状的患者以遏制病毒传播(遵循当地公共卫生当局的建议)。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
在医疗机构、社区机构或在家中管理患者。对于大多数患者,可考虑采用居家隔离,并酌情进行远程医疗或远程访视。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 [465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
该决策需进行仔细的临床判断,并应通过对患者家庭环境的评估进行告知,从而确保:可以满足感染防控措施要求以及其他要求(例如基本卫生、充分通风);照护者能够提供照护,并识别患者何时可能出现恶化;照护者得到足够支持(例如食物、补给、心理支持);训练有素的卫生工作者可在社区中提供支持。[738]World Health Organization. Home care for patients with suspected or confirmed COVID-19 and management of their contacts: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/home-care-for-patients-with-suspected-novel-coronavirus-(ncov)-infection-presenting-with-mild-symptoms-and-management-of-contacts
诊疗地点将取决于当地卫生部门的指导和可用资源。
除非担心快速恶化或无法迅速返回医院,否则疑似或确诊为轻症的孕妇可无需在医院接受急诊处理。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
BMJ Best Practice 临床实践合并症诊疗工具中的信息涉及非妊娠成人。
这些信息不适用于孕妇患者或儿童。在这类情况下,请向产科/妇科专科医生或儿科专科医生寻求建议,了解患者的合并症可能会如何影响您对 COVID-19 的管理。
对具有危险因素的患者进行密切监测,并对此类危险因素加以考虑,考虑最适合的照护环境。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
世界卫生组织将以下合并症列为重症和死亡危险因素:[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
心脏疾病
糖尿病
慢性肺疾病
慢性肾病
脑血管疾病
痴呆
精神障碍
肿瘤
免疫抑制
肥胖
高血压。
高龄患者以及脆弱程度较高的 COVID-19 患者,据报道具有更高的死亡风险。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1 [835]Chinnadurai R, Ogedengbe O, Agarwal P, et al. Older age and frailty are the chief predictors of mortality in COVID-19 patients admitted to an acute medical unit in a secondary care setting: a cohort study. BMC Geriatr. 2020 Oct 16;20(1):409 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563906 http://www.ncbi.nlm.nih.gov/pubmed/33066750?tool=bestpractice.com
虑与管理患者长期疾病的专科团队讨论患者情况,和/或转诊至多学科团队中的其他医疗卫生专业人士。
建议为 COVID-19 老年患者提供 多学科协作医疗,以帮助确保充分解决医护各方面问题(包括合并症)。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
建议患者及其家庭成员采取适当的感染防控措施:
何时停止隔离的指南各地有较大差异。
隔离时限可能取决于多种因素,包括疫苗接种状态、流行的 SARS-CoV-2 变体和患者因素(例如免疫功能正常/免疫功能低下、无症状/有症状、疾病严重程度)。
世界卫生组织建议停用基于防范传播的预防措施(包括隔离),且检测呈阳性后 10 天(无症状患者),或症状发作后 10 天加上至少 3 天无发热和呼吸道症状(有症状的患者)的患者,可移出诊疗路径。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
但是,部分国家目前建议隔离期可短至 5 天到 7 天。[836]Mahase E. Covid-19: is it safe to reduce the self-isolation period? BMJ. 2021 Dec 30;375:n3164. https://www.bmj.com/content/375/bmj.n3164 http://www.ncbi.nlm.nih.gov/pubmed/34969702?tool=bestpractice.com
参阅当地公共卫生指南,获取更多信息。
针对特定患者群中所有患者的治疗建议
密切监测伴有重症危险因素的患者,并就疾病恶化症状和征象,以及需要立刻开展紧急处理(例如呼吸困难、胸痛)的并发症,向患者交待清楚。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 [465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
对于有症状,且存在进展为重症风险,但未住院的患者,建议在家中进行脉搏血氧测定。需进行患者教育和给予适当的随访。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
如果伴慢性肾病(chronic kidney disease, CKD)或具有 CKD 危险因素的患者因急症而呈现不适,应对肾功能进行密切监测。[837]National Institute for Health and Care Excellence. Acute kidney injury: prevention, detection and management. 2019 [internet publication] https://www.nice.org.uk/guidance/ng148
CKD 为急性肾损伤(acute kidney injury, AKI)重要危险因素。[838]Hsu CY, Ordoñez JD, Chertow GM, et al. The risk of acute renal failure in patients with chronic kidney disease. Kidney Int. 2008 Apr 2;74(1):101-7 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673528 http://www.ncbi.nlm.nih.gov/pubmed/18385668?tool=bestpractice.com
伴 CKD 和 COVID-19 患者出现 AKI 风险将升高, 其可能与发热、脱水,以及非甾体抗炎药使用具有相关性。
COVID -19 患者伴 AKI 可能较为常见(但确切患病率尚不确定)。AKI 与死亡率增加具有相关性。[839]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication] https://www.nice.org.uk/guidance/ng191
向您的 CKD 患者解释,其患病后出现 AKI 的风险增加。确定机制,以便可以密切监测居家治疗患者疾病进展迹象。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
对于入院的所有 COVID-19 患者,包括 CKD 患者,院时需检查肾功能,并确保定期监测。
对于 CKD 患者:
与最近一次可获取结果的肾功能进行比较
每日监测肾功能,同时进行仔细的容量状态监测 ( 基于专家意见)。
对少尿进行监测并予以处理。[837]National Institute for Health and Care Excellence. Acute kidney injury: prevention, detection and management. 2019 [internet publication] https://www.nice.org.uk/guidance/ng148
针对特定患者群中所有患者的治疗建议
建议患者避免仰卧,因为这会使排痰不力。首先采用简单措施(例如对给予 1 岁及以上患者一茶匙蜂蜜)止咳。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
一项荟萃分析发现,蜂蜜对于改善上呼吸道感染症状,尤其是咳嗽频率和严重程度,优于常规治疗(例如镇咳药)。[741]Abuelgasim H, Albury C, Lee J. Effectiveness of honey for symptomatic relief in upper respiratory tract infections: a systematic review and meta-analysis. BMJ Evid Based Med. 2021 Apr;26(2):57-64. https://ebm.bmj.com/content/early/2020/07/28/bmjebm-2020-111336 http://www.ncbi.nlm.nih.gov/pubmed/32817011?tool=bestpractice.com
在决定是否建议将蜂蜜作为缓解咳嗽症状的一种选择时,要考虑到患者的整体情况,包括其糖尿病控制情况。
如果患者的糖尿病控制或临床状态通常不稳定,请考虑采用其他的对症疗法。
如果患者正在服用蜂蜜治疗咳嗽,并且发现它很有用,建议密切监测毛细血管血糖,以发检测有无高血糖。
嘱患者补充足够的营养和进行适当的补液。
建议患者规律饮水,以避免脱水。由于发热,需要的液体摄入量可能比平时更高。然而,过多液体将妨碍氧合。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 [530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
其他支持性治疗措施包括:
建议患者通过开窗或开门改善空气流通[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
为所有患者提供基本的心理健康和社会心理支持,并酌情处理失眠、抑郁或焦虑等症状。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
如果嗅觉功能障碍持续超过 2 周,考虑对其进行治疗,例如嗅觉训练、鼻内用皮质类固醇。[742]Whitcroft KL, Hummel T. Olfactory dysfunction in COVID-19: diagnosis and management. JAMA. 2020 Jun 23;323(24):2512-4. https://jamanetwork.com/journals/jama/fullarticle/2766523 http://www.ncbi.nlm.nih.gov/pubmed/32432682?tool=bestpractice.com [743]Nag AK, Saltagi AK, Saltagi MZ, et al. Management of post-infectious anosmia and hyposmia: a systematic review. Ann Otol Rhinol Laryngol. 2022 Aug 12:34894221118186. http://www.ncbi.nlm.nih.gov/pubmed/35959948?tool=bestpractice.com
一项 Cochrane 评价发现,不同干预措施对于预防感染后持续性嗅觉功能障碍的有效性证据非常有限。唯一可获取的证据是鼻内皮质类固醇应用,但其确定性极低,因此无法得出结论。[744]Webster KE, O'Byrne L, MacKeith S, et al. Interventions for the prevention of persistent post-COVID-19 olfactory dysfunction. Cochrane Database Syst Rev. 2021 Jul 22;(7):CD013877. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013877.pub2/full http://www.ncbi.nlm.nih.gov/pubmed/34291812?tool=bestpractice.com
一项系统评价和荟萃分析发现,使用鼻内/口服皮质类固醇与嗅觉训练的联合治疗相较于单独嗅觉训练的嗅觉评分改善差异无统计学意义。嗅觉功能在经嗅觉训练后显著改善。[745]Asvapoositkul V, Samuthpongtorn J, Aeumjaturapat S, et al. Therapeutic options of post-COVID-19 related olfactory dysfunction: a systematic review and meta-analysis. Rhinology. 2022 Sep 29 [Epub ahead of print]. https://www.rhinologyjournal.com/Rhinology_issues/manuscript_3028.pdf http://www.ncbi.nlm.nih.gov/pubmed/36173148?tool=bestpractice.com
大多数轻症患儿可仅采取支持性治疗,除非被认为存在进展为重症的高风险。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
对于因固有精神卫生疾患进行居家处理的患者,例如抑郁,给予支持治疗。他们可能正在经历更多的情绪困扰。
美国创伤性应激研究中心建议精神病医生与患者讨论策略,减轻苦恼和隔离影响,从而对高风险患者进行识别和提供额外支持。[840]Center for the Study of Traumatic Stress. Taking care of patients during the coronavirus outbreak: a guide for psychiatrists. 2020 [internet publication] https://www.cstsonline.org/assets/media/documents/CSTS_FS_Taking_Care_of_Patients_During_Coronavirus_Outbreak_A_Guide_for_Psychiatrists_03_03_2020.pdf
考虑使用远超医疗,使远超会诊顺利进行。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1 [841]Shore JH, Schneck CD, Mishkind MC. Telepsychiatry and the coronavirus disease 2019 pandemic-current and future outcomes of the rapid virtualization of psychiatric care. JAMA Psychiatry. 2020 Dec 1;77(12):1211-2 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2765954 http://www.ncbi.nlm.nih.gov/pubmed/32391861?tool=bestpractice.com [842]Hubley S, Lynch SB, Schneck C, et al. Review of key telepsychiatry outcomes. World J Psychiatry. 2016 Jun 22;6(2):269-82 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4919267 http://www.ncbi.nlm.nih.gov/pubmed/27354970?tool=bestpractice.com Royal College of Psychiatrists: digital - COVID-19 guidance for clinicians 在新窗口中打开
告知患者可以在哪里找到本地相关信息和支持性资源,例如:
针对特定患者群中所有患者的治疗建议
像对所有患者一样,应尽早与痴呆患者及其照护者商定治疗升级预案 (基于专家意见)。
内容应包括:[843]Fritz Z, Slowther AM, Perkins GD. Resuscitation policy should focus on the patient, not the decision. BMJ. 2017 Feb 28;356:j813 https://www.doi.org/10.1136/bmj.j813 http://www.ncbi.nlm.nih.gov/pubmed/28246084?tool=bestpractice.com
复苏状态(即“不尝试心肺复苏”[Do Not Attempt Cardiopulmonary Resuscitation, DNACPR] 的决定)
治疗上限(例如是否适合气管插管或重症监护病房收治)。
升级方案应将预立医疗照护计划纳入考量,包括合法绑定预立医嘱。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1 [843]Fritz Z, Slowther AM, Perkins GD. Resuscitation policy should focus on the patient, not the decision. BMJ. 2017 Feb 28;356:j813 https://www.doi.org/10.1136/bmj.j813 http://www.ncbi.nlm.nih.gov/pubmed/28246084?tool=bestpractice.com
在某些情况下,对于治疗升级计划,痴呆患者将缺乏做出决策的心智能力。
评估并记录心智能力(在需要作出决定的特定时间作出决定的能力)。[844]National Institute for Health and Care Excellence. Decision making and mental capacity. 2018 [internet publication] https://www.nice.org.uk/guidance/ng108 请遵守您所在地区的相应法律。
在英格兰和威尔士,医疗卫生专业人士必须遵守 2005 年心智能力法案。[845]Department of Health. Mental Capacity Act 2005 [internet publication] http://www.legislation.gov.uk/ukpga/2005/9/contents 进行评估时,应遵循该法案中的原则。[845]Department of Health. Mental Capacity Act 2005 [internet publication] http://www.legislation.gov.uk/ukpga/2005/9/contents
如果评估确定患者缺乏心智能力,请确保作出符合患者最大利益的决定。[844]National Institute for Health and Care Excellence. Decision making and mental capacity. 2018 [internet publication] https://www.nice.org.uk/guidance/ng108 [845]Department of Health. Mental Capacity Act 2005 [internet publication] http://www.legislation.gov.uk/ukpga/2005/9/contents
如果患者被评估为缺乏心智能力, 需与近亲属协商,并作出最大获益”决策。[845]Department of Health. Mental Capacity Act 2005 [internet publication] http://www.legislation.gov.uk/ukpga/2005/9/contents
根据英格兰和威尔士 2005 年心智能力法案,如果患者无家庭成员或其他照护者,且无需立即作出决定,应寻求独立心智能力代理人担纲任务。[846]Social Care Institute for Excellence. Independent mental capacity advocate (IMCA). January 2010 [internet publication] https://www.scie.org.uk/mca/imca/do
查看您所在地区的相应法律。
针对特定患者群中部分患者治疗的附加建议
建议给予对乙酰氨基酚或布洛芬。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 [530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
布洛芬只能在控制症状所需最短时间内以最低有效剂量服用。不建议在孕妇(尤其是孕晚期)或 <3 月龄儿童(年龄界值因国家而异)中使用。
慢性肾病和/或心力衰竭
避免将非甾体抗炎药(non-steroidal anti-inflammatory drug, NSAID)用于慢性肾病和/或心力衰竭的患者(基于专家意见)。
哮喘
NSAID 可能会使某些哮喘患者症状恶化,因此需询问患者对其是否存在已知的过度敏感不良反应。[847]Global Initiative for Asthma. Global strategy for asthma management and prevention. 2021 [internet publication] https://ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf
对乙酰氨基酚: 儿童:查询当地药物处方集,以获取剂量指导;成人:必要时,每 4-6 小时口服 500-1000 mg,每日最多 4000 mg
对乙酰氨基酚 : 儿童:查询当地药物处方集,以获取剂量指导;成人:必要时,每 4-6 小时口服 500-1000 mg,每日最多 4000 mg
对乙酰氨基酚: 儿童:查询当地药物处方集,以获取剂量指导;成人:必要时,每 4-6 小时口服 500-1000 mg,每日最多 4000 mg
或
对乙酰氨基酚
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
或
布洛芬
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
针对特定患者群中部分患者治疗的附加建议
考虑将单克隆抗体用于有临床进展高风险的患者。指南建议有所不同。
在英国,国家卫生与临床优化研究所建议对于 ≥12 岁,被认为具有重症进展高风险的未住院患者,可给予中和性单克隆抗体。查阅当地指南,了解目前在英国可以使用的单克隆抗体。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
在美国,国立卫生研究院指南专家组建议,将bebtelovimab用于治疗 ≥18 岁、有进展为重症高风险的轻至中度非住院患者。然而,仅建议用于首选治疗(即口服抗病毒药物)不可用、不可行或临床不适合时,因为尚未在安慰剂对照试验中对用于有进展高风险的患者进行评估。尚无充分证据可支持或反对将 bebtelovimab 用于轻至中度疾病的儿童和青少年。可考虑用于因 COVID-19 以外原因住院的轻至中度疾病患者,前提是患者的其他方面符合门诊治疗标准。专家组目前反对使用 casirivimab/imdevimab、bamlanivimab/etesevimab 和 sotrovimab,因为奥密克戎已成为美国的主导变异株,并且预计奥密克戎变异株及其亚型变异株对这些单克隆抗体制剂的敏感性将显著降低。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov 这些单克隆抗体目前未在美国获批使用。[848]US Food and Drug Administration. Coronavirus (COVID-19) update: FDA limits use of certain monoclonal antibodies to treat COVID-19 due to the omicron variant. 2022 [internet publication]. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-limits-use-certain-monoclonal-antibodies-treat-covid-19-due-omicron [849]US Food and Drug Administration. FDA updates sotrovimab emergency use authorization. 2022 [internet publication]. https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-sotrovimab-emergency-use-authorization
美国传染病学会支持,将有活性的单克隆抗体用于有进展至重症高风险的轻至中度门诊患者症状发作后 7 日内。[466]Bhimraj A, Morgan RL, Hirsch Shumaker A, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19 infection. 2022 [internet publication]. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management
世界卫生组织强烈反对将 sotrovimab 和casirivimab/imdevimab 用于非重症患者,因为体外研究数据表明这些药物不能中和当前流行的 SARS-CoV-2 变异株及其亚型变异株。世界卫生组织未针对其他单克隆抗体提出相关建议。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3 [736]Rochwerg B, Siemieniuk RA, Agoritsas T, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020 Sep 4;370:m3379. https://www.bmj.com/content/370/bmj.m3379.long http://www.ncbi.nlm.nih.gov/pubmed/32887691?tool=bestpractice.com [737]Rochwerg B, Siemieniuk RA, Lamontagne R, et al. Update to living WHO guideline on drugs for covid-19. BMJ. 2021 Jul 6;374:n1703. http://www.ncbi.nlm.nih.gov/pubmed/34230027?tool=bestpractice.com
单克隆抗体选择取决于可及性,以及临床和背景因素,包括对不同 SARS-CoV-2 变异株和亚型变异株疗效的信息。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov [530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191 [735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
选择包括 bebtelovimab、tixagevimab/cilgavimab、casirivimab/imdevimab、sotrovimab, bamlanivimab/etesevimab 和 regdanvimab,具体取决于所在地。
临床前证据表明,casirivimab/imdevimab 和 bamlanivimab/etesevimab 在体外对奥密克戎变异株及其亚型变异株缺乏中和活性。sotrovimab 和 bebtelovimab 似乎对奥密克戎变异株保持活性;然而,sotrovimab 对奥密克戎亚型变异株不具有活性。bebtelovimab 似乎对奥密克戎 BA.2、BA.2.75、BA.4 和 BA.5 亚型变异株保持活性。[850]Takashita E, Yamayoshi S, Simon V, et al. Efficacy of antibodies and antiviral drugs against Omicron BA.2.12.1, BA.4, and BA.5 subvariants. N Engl J Med. 2022 Aug 4;387(5):468-70. https://www.nejm.org/doi/full/10.1056/NEJMc2207519 http://www.ncbi.nlm.nih.gov/pubmed/35857646?tool=bestpractice.com [851]Hentzien M, Autran B, Piroth L, et al. A monoclonal antibody stands out against omicron subvariants: a call to action for a wider access to bebtelovimab. Lancet Infect Dis. 2022 Sep;22(9):1278. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00495-9/fulltext http://www.ncbi.nlm.nih.gov/pubmed/35863364?tool=bestpractice.com [852]Sheward DJ, Kim C, Fischbach J, et al. Evasion of neutralising antibodies by omicron sublineage BA.2.75. Lancet Infect Dis. 2022 Oct;22(10):1421-2. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00524-2/fulltext http://www.ncbi.nlm.nih.gov/pubmed/36058228?tool=bestpractice.com 查阅当地指南,获取特定变体和耐药性详细信息。
设施环境或药物供应限制使患者分流变得十分必要。治疗应优先给予具有重症进展高风险患者。
单克隆抗体在非住院患者中使用的证据尚不明确。
一项 Cochrane 评价发现,证据不足以对任何特定的单克隆抗体,以及应该加以使用的疾病阶段,得出有意义的结论。非住院患者的结局信息(例如死亡率、生活质量和严重不良事件)要么没有定论,要么完全缺乏,但 casirivimab/imdevimab、sotrovimab、bamlanivimab(单独使用或与 etesevimab 联合使用)和 regdanvimab 可降低收住院比率或死亡比率(低等确定性证据)。[761]Kreuzberger N, Hirsch C, Chai KL, et al. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;(9):CD013825. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013825.pub2/full http://www.ncbi.nlm.nih.gov/pubmed/34473343?tool=bestpractice.com
一项有关 27 项随机对照试验的系统评价和荟萃分析发现,单克隆抗体对非住院患者的大多数结局影响有限,关于大多数结局的证据确定性为极低至中等。单克隆抗体减少了住院治疗,但对死亡率无影响。[762]Hernandez AV, Piscoya A, Pasupuleti V, et al. Beneficial and harmful effects of monoclonal antibodies for the treatment and prophylaxis of COVID-19: systematic review and meta-analysis. Am J Med. 2022 Jul 23 [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307485 http://www.ncbi.nlm.nih.gov/pubmed/35878688?tool=bestpractice.com
新兴证据支持使用 tixagevimab/cilgavimab 治疗 COVID-19。[853]Wang Y, Zheng J, Zhu K, et al. The effect of tixagevimab-cilgavimab on clinical outcomes in patients with COVID-19: a systematic review with meta-analysis. J Infect. 2022 Aug 27 [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9420004 http://www.ncbi.nlm.nih.gov/pubmed/36031156?tool=bestpractice.com
单克隆抗体一般通过静脉注射给予。
需要在专科诊所进行门诊管理,因此该类治疗的可行性可能受到限制。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
检测呈现阳性后,以及症状出现后 7 天内,应尽快给药。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
各指南推荐剂量有所不同;参阅当地常规。
超敏反应(包括液体输注相关性反应和全身过敏反应)已见诸报道。
需在严重超敏反应可得到控制的环境中给药。输注过程中对患者进行监测,并在输注后观察至少 1 小时。
bebtelovimab: 12岁及以上儿童和成人:遵医嘱选择剂量
bebtelovimab : 12岁及以上儿童和成人:遵医嘱选择剂量
bebtelovimab: 12岁及以上儿童和成人:遵医嘱选择剂量
或
casirivimab 和 imdevimab: 12岁及以上儿童和成人:遵医嘱选择剂量
casirivimab 和 imdevimab : 12岁及以上儿童和成人:遵医嘱选择剂量
casirivimab 和 imdevimab: 12岁及以上儿童和成人:遵医嘱选择剂量
或
bamlanivimab: 儿童和成人:咨询专科医生,获得剂量指导(与 etesevimab 一同给药)
bamlanivimab : 儿童和成人:咨询专科医生,获得剂量指导(与 etesevimab 一同给药)
bamlanivimab: 儿童和成人:咨询专科医生,获得剂量指导(与 etesevimab 一同给药)
bebtelovimab: 12岁及以上儿童和成人:遵医嘱选择剂量
bebtelovimab : 12岁及以上儿童和成人:遵医嘱选择剂量
bebtelovimab: 12岁及以上儿童和成人:遵医嘱选择剂量
或
casirivimab 和 imdevimab: 12岁及以上儿童和成人:遵医嘱选择剂量
casirivimab 和 imdevimab : 12岁及以上儿童和成人:遵医嘱选择剂量
casirivimab 和 imdevimab: 12岁及以上儿童和成人:遵医嘱选择剂量
或
bamlanivimab: 儿童和成人:咨询专科医生,获得剂量指导(与 etesevimab 一同给药)
bamlanivimab : 儿童和成人:咨询专科医生,获得剂量指导(与 etesevimab 一同给药)
bamlanivimab: 儿童和成人:咨询专科医生,获得剂量指导(与 etesevimab 一同给药)
bebtelovimab
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
sotrovimab
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
或
casirivimab 和 imdevimab
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
或
bamlanivimab
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
针对特定患者群中部分患者治疗的附加建议
考虑使用抗病毒药物,选择包括奈玛特韦/利托那韦、莫努匹韦和 remdesivir。指南建议有所不同。
对于有极高住院风险的非重症患者,世界卫生组织强烈建议使用奈玛特韦/利托那韦,而有条件建议使用 remdesivir 或莫努匹韦。对于重症患者,奈玛特韦/利托那韦是优于其他治疗的选择,因其较其他治疗可更有效地减少住院治疗,较莫努匹韦具有更少的危害担忧,并且比静脉用 remdesivir 更易给药。然而,它确实存在显著且复杂的药物相互作用。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3 [736]Rochwerg B, Siemieniuk RA, Agoritsas T, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020 Sep 4;370:m3379. https://www.bmj.com/content/370/bmj.m3379.long http://www.ncbi.nlm.nih.gov/pubmed/32887691?tool=bestpractice.com [737]Rochwerg B, Siemieniuk RA, Lamontagne R, et al. Update to living WHO guideline on drugs for covid-19. BMJ. 2021 Jul 6;374:n1703. http://www.ncbi.nlm.nih.gov/pubmed/34230027?tool=bestpractice.com
在英国,国家卫生与临床优化研究所建议,对于无需辅助供氧而被认为具有进展为重症的高风险患者,可给予奈玛特韦/利托那韦、莫努匹韦或 remdesivir。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
在美国,国立卫生研究院指南专家组建议,对于具有临床进展高风险的轻至中度非住院患者,可将奈玛特韦/利托那韦和 remdesivir 作为首选治疗,将莫努匹韦作为替代治疗(即当首选治疗不可用、不可行或临床不适合时)。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
美国传染病学会支持对此类患者使用抗病毒药物。[466]Bhimraj A, Morgan RL, Hirsch Shumaker A, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19 infection. 2022 [internet publication]. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management
应在诊断后尽快开始治疗,理想情况下,应在症状发作后 5 日内开始使用奈玛特韦/利托那韦或莫努匹韦,症状发作后 7 日内开始使用 remdesivir。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov [530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191 [735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
如果患者起始治疗后需要收住院,完整疗程的完成可由医务人员自行把握。
设施环境或药物供应限制使患者抗病毒治疗分流变得十分必要。治疗应优先给予具有重症进展高风险患者。
由于 remdesivir 需要通过静脉输注给予,设施环境的制约可能使其在部分门诊环境中无法给药。
将抗病毒药物用于非重症患者的证据有限。
2/3 期 EPIC-HR 试验发现,与安慰剂相比,奈玛特韦/利托那韦可将非住院高危成人的住院或死亡风险降低 89%(症状发作后 3 日内)和 88%(症状发作后 5 日内)。[751]Hammond J, Leister-Tebbe H, Gardner A, et al. Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19. N Engl J Med. 2022 Feb 16 [Epub ahead of print]. https://www.nejm.org/doi/full/10.1056/NEJMoa2118542 http://www.ncbi.nlm.nih.gov/pubmed/35172054?tool=bestpractice.com
MOVe-OUT 试验发现,与安慰剂相比,莫努匹韦在使用后 29 日内使非住院高危成人的住院或死亡风险降低31%(将绝对风险从 9.7% 降至 6.8%)。[752]Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al. Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients. N Engl J Med. 2021 Dec 16 [Epub ahead of print]. https://www.nejm.org/doi/full/10.1056/NEJMoa2116044 http://www.ncbi.nlm.nih.gov/pubmed/34914868?tool=bestpractice.com
一项随机、双盲、安慰剂对照试验发现,与安慰剂相比,remdesivir 使非住院高危成人的住院或死亡风险降低 87%。[753]Gottlieb RL, Vaca CE, Paredes R, et al. Early remdesivir to prevent progression to severe Covid-19 in outpatients. N Engl J Med. 2021 Dec 22 [Epub ahead of print]. https://www.nejm.org/doi/full/10.1056/NEJMoa2116846 http://www.ncbi.nlm.nih.gov/pubmed/34937145?tool=bestpractice.com
关于奈玛特韦/利托那韦和莫努匹韦的临床疗效证据最初是基于对单一安慰剂对照试验(奥密克戎变异株出现前在未接种疫苗的成人中展开的试验)数据的中期分析。此后,在奥密克戎变异株(和亚型变异株)占主导地位期间进行的观察性研究表明,奈玛特韦/利托那韦或莫努匹韦治疗降低了进展至重症、住院或死亡的风险。[754]Najjar-Debbiny R, Gronich N, Weber G, et al. Effectiveness of Paxlovid in reducing severe COVID-19 and mortality in high risk patients. Clin Infect Dis. 2022 Jun 2 [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9214014 http://www.ncbi.nlm.nih.gov/pubmed/35653428?tool=bestpractice.com [755]Arbel R, Wolff Sagy Y, Hoshen M, et al. Nirmatrelvir use and severe Covid-19 outcomes during the Omicron surge. N Engl J Med. 2022 Sep 1;387(9):790-8. https://www.nejm.org/doi/full/10.1056/NEJMoa2204919 http://www.ncbi.nlm.nih.gov/pubmed/36001529?tool=bestpractice.com [756]Wong CKH, Au ICH, Lau KTK, et al. Real-world effectiveness of early molnupiravir or nirmatrelvir-ritonavir in hospitalised patients with COVID-19 without supplemental oxygen requirement on admission during Hong Kong's omicron BA.2 wave: a retrospective cohort study. Lancet Infect Dis. 2022 Aug 24 [Epub ahead of print]. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00507-2/fulltext http://www.ncbi.nlm.nih.gov/pubmed/36029795?tool=bestpractice.com
所有 3 种抗病毒药物似乎均对奥密克戎变异株及其亚型变异株具有体外活性。[854]Vangeel L, Chiu W, De Jonghe S, et al. Remdesivir, molnupiravir and nirmatrelvir remain active against SARS-CoV-2 Omicron and other variants of concern. Antiviral Res. 2022 Feb;198:105252. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8785409 http://www.ncbi.nlm.nih.gov/pubmed/35085683?tool=bestpractice.com [850]Takashita E, Yamayoshi S, Simon V, et al. Efficacy of antibodies and antiviral drugs against Omicron BA.2.12.1, BA.4, and BA.5 subvariants. N Engl J Med. 2022 Aug 4;387(5):468-70. https://www.nejm.org/doi/full/10.1056/NEJMc2207519 http://www.ncbi.nlm.nih.gov/pubmed/35857646?tool=bestpractice.com
如果有适应证,可将 remdesivir 用于孕妇。然而,不建议将奈玛特韦/利托那韦和莫努匹韦用于孕妇或母乳喂养的女性。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov [735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
在开始使用莫努匹韦前应进行妊娠试验,应为动物研究显示其具有生殖毒性,并且可能影响骨骼和软骨生长。
建议育龄女性在莫努匹韦治疗期间和末次服药后 4 日内采取避孕措施,同时建议与育龄女性发生性行为的有生育力男性在末次服药后至少 3 个月内采取避孕措施。
remdesivir 与肾毒性、肝毒性和超敏反应有关。
不建议将 remdesivir 用于估算肾小球滤过率(estimated glomerular filtration rate, eGFR)<30 mL/min 的患者。开始治疗前和治疗期间应根据临床情况进行肾功能监测。静脉用制剂含有溶解度增强剂磺丁基醚 β-环糊精钠(sulfobutyl ether beta-cyclodextrin sodium, SBECD),可通过肾脏清除。肾脏损伤患者体内 SBECD 的累积可能导致肝脏和肾脏毒性。如果可能,应考虑对肾脏损伤患者优先使用冻干粉针制剂,因其含有更少的 SBECD。与安慰剂相比,remdesivir 对急性肾损伤的影响极小或并无影响;然而,相关证据确定性级别为低。[855]Izcovich A, Siemieniuk RA, Bartoszko JJ, et al. Adverse effects of remdesivir, hydroxychloroquine and lopinavir/ritonavir when used for COVID-19: systematic review and meta-analysis of randomised trials. BMJ Open. 2022 Mar 2;12(3):e048502. https://bmjopen.bmj.com/content/12/3/e048502 http://www.ncbi.nlm.nih.gov/pubmed/35236729?tool=bestpractice.com
转氨酶升高已见诸报道。开始治疗前和治疗期间应根据临床情况,对肝功能进行监测。如果丙氨酸氨基转移酶(alanine aminotransferase, ALT)水平升高至正常上限 ≥ 10 倍,应考虑停止治疗。如果 ALT 升高伴有肝脏炎症征象或症状,应停止治疗。
开始治疗前和治疗期间应根据临床情况,对凝血酶原时间进行监测,因为凝血酶原时间延长已见诸报道。
需在严重超敏反应可得到控制的环境中给药。输注过程中对患者进行监测,并在输注后观察至少 1 小时。
一般认为奈玛特韦/利托那韦和莫努匹韦的不良反应为轻度。然而,关于这些新药的安全性数据有限,必须向当地的药物警戒计划报告所有的疑似不良反应。
奈玛特韦/利托那韦的常见不良反应包括腹泻、味觉障碍、高血压和肌痛。应慎用于已有肝脏疾病的患者(利托那韦与肝酶升高、肝炎和黄疸)。
莫努匹韦的常见不良反应包括腹泻、恶性、头痛和头晕。
据报道,有患者(包括已接种疫苗的患者)在完成 5 日奈玛特韦/利托那韦疗程康复后 2-8 日出现病毒反弹(即聚合酶链反应检测结果复阳)和症状复发。[746]Centers for Disease Control and Prevention. COVID-19 rebound after Paxlovid treatment. 2022 [internet publication]. https://emergency.cdc.gov/han/2022/han00467.asp [747]Malden DE, Hong V, Lewin BJ, et al. Hospitalization and emergency department encounters for COVID-19 after Paxlovid treatment: California, December 2021-May 2022. MMWR Morb Mortal Wkly Rep. 2022 Jun 24;71(25):830-3. https://www.cdc.gov/mmwr/volumes/71/wr/mm7125e2.htm http://www.ncbi.nlm.nih.gov/pubmed/35737591?tool=bestpractice.com [748]Charness ME, Gupta K, Stack G, et al. Rebound of SARS-CoV-2 infection after nirmatrelvir-ritonavir treatment. N Engl J Med. 2022 Sep 15;387(11):1045-7. https://www.nejm.org/doi/full/10.1056/NEJMc2206449 http://www.ncbi.nlm.nih.gov/pubmed/36069968?tool=bestpractice.com [749]Anderson AS, Caubel P, Rusnak JM, et al. Nirmatrelvir-ritonavir and viral load rebound in Covid-19. N Engl J Med. 2022 Sep 15;387(11):1047-9. https://www.nejm.org/doi/full/10.1056/NEJMc2205944 http://www.ncbi.nlm.nih.gov/pubmed/36069818?tool=bestpractice.com
奈玛特韦/利托那韦具有显著且复杂的药物相互作用,主要由该组合中的利托那韦成分所致。
开始治疗前,应仔细回顾患者用药史。
已在使用含利托那韦方案治疗 HIV 或丙型肝炎病毒感染的患者不需要调整其当前抗病毒治疗方案的剂量,并且用于这些患者的奈玛特韦/利托那韦剂量不变(除非根据患者的肾脏功能情况需要调整剂量)。
IDSA: management of drug interactions with nirmatrelvir/ritonavir 在新窗口中打开
请注意奈玛特韦/利托那韦具有显著且复杂的药物相互作用。
在开始治疗前仔细审查患者的用药史,以了解药物相互作用的风险。 IDSA: management of drug interactions with nirmatrelvir/ritonavir 在新窗口中打开
在治疗期间对患者进行密切监测。
CKD 患者抗病毒治疗前应接受肾功能检查,如同其他患者。[856]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication] https://www.covid19treatmentguidelines.nih.gov
如果患者的 eGFR <30 mL/min,则禁用 remdesivir。[856]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication] https://www.covid19treatmentguidelines.nih.gov
如果可能,应考虑对肾脏损伤患者优先使用冻干粉针,因其磺丁基醚 β-环糊精钠(sulfobutyl ether beta-cyclodextrin sodium, SBECD)含量更少,而 SBECD 通过肾脏进行清除。[856]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication] https://www.covid19treatmentguidelines.nih.gov
如果患者的 eGFR <30 mL/min,则不建议使用奈玛特韦/利托那韦。如果患者的 eGFR 为 30-59 mL/min,请遵循指南并开具减量处方。
参阅当地常规,寻求肾脏病学团队建议。
指南对抗病毒治疗的建议有所不同。
奈玛特韦和利托那韦: eGFR ≥60 mL/min 的成人:300 mg(奈玛特韦)/100 mg(利托那韦),口服,每日两次,连用 5 日;eGFR 为 30-59 mL/min 的成人:150 mg(奈玛特韦)/100 mg(利托那韦),口服,每日两次,连用 5 日
奈玛特韦和利托那韦 : eGFR ≥60 mL/min 的成人:300 mg(奈玛特韦)/100 mg(利托那韦),口服,每日两次,连用 5 日;eGFR 为 30-59 mL/min 的成人:150 mg(奈玛特韦)/100 mg(利托那韦),口服,每日两次,连用 5 日
奈玛特韦和利托那韦: eGFR ≥60 mL/min 的成人:300 mg(奈玛特韦)/100 mg(利托那韦),口服,每日两次,连用 5 日;eGFR 为 30-59 mL/min 的成人:150 mg(奈玛特韦)/100 mg(利托那韦),口服,每日两次,连用 5 日
更多 奈玛特韦和利托那韦奈玛特韦/利托那韦可能在部分国家/地区获批用于体重 ≥40 kg 的 12 岁及以上儿童。尚未获批用于 eGFR <30 mL/min 的患者或有严重肝脏损伤的患者。
或
或
remdesivir: 年龄 ≥12 岁和体重 ≥40 kg 的儿童和成人:第 1 天静脉输注 200 mg 作为负荷剂量,而后每 24 小时给予 100 mg,持续 2 天
remdesivir : 年龄 ≥12 岁和体重 ≥40 kg 的儿童和成人:第 1 天静脉输注 200 mg 作为负荷剂量,而后每 24 小时给予 100 mg,持续 2 天
remdesivir: 年龄 ≥12 岁和体重 ≥40 kg 的儿童和成人:第 1 天静脉输注 200 mg 作为负荷剂量,而后每 24 小时给予 100 mg,持续 2 天
更多 remdesivirremdesivir 可能在部分国家/地区获批用于 12 岁以下儿童。然而,尚无充分证据支持常规推荐将其用于 12 岁以下儿童(可根据和危险因素考虑治疗)。
奈玛特韦和利托那韦: eGFR ≥60 mL/min 的成人:300 mg(奈玛特韦)/100 mg(利托那韦),口服,每日两次,连用 5 日;eGFR 为 30-59 mL/min 的成人:150 mg(奈玛特韦)/100 mg(利托那韦),口服,每日两次,连用 5 日
奈玛特韦和利托那韦 : eGFR ≥60 mL/min 的成人:300 mg(奈玛特韦)/100 mg(利托那韦),口服,每日两次,连用 5 日;eGFR 为 30-59 mL/min 的成人:150 mg(奈玛特韦)/100 mg(利托那韦),口服,每日两次,连用 5 日
奈玛特韦和利托那韦: eGFR ≥60 mL/min 的成人:300 mg(奈玛特韦)/100 mg(利托那韦),口服,每日两次,连用 5 日;eGFR 为 30-59 mL/min 的成人:150 mg(奈玛特韦)/100 mg(利托那韦),口服,每日两次,连用 5 日
更多 奈玛特韦和利托那韦奈玛特韦/利托那韦可能在部分国家/地区获批用于体重 ≥40 kg 的 12 岁及以上儿童。尚未获批用于 eGFR <30 mL/min 的患者或有严重肝脏损伤的患者。
或
或
remdesivir: 年龄 ≥12 岁和体重 ≥40 kg 的儿童和成人:第 1 天静脉输注 200 mg 作为负荷剂量,而后每 24 小时给予 100 mg,持续 2 天
remdesivir : 年龄 ≥12 岁和体重 ≥40 kg 的儿童和成人:第 1 天静脉输注 200 mg 作为负荷剂量,而后每 24 小时给予 100 mg,持续 2 天
remdesivir: 年龄 ≥12 岁和体重 ≥40 kg 的儿童和成人:第 1 天静脉输注 200 mg 作为负荷剂量,而后每 24 小时给予 100 mg,持续 2 天
更多 remdesivirremdesivir 可能在部分国家/地区获批用于 12 岁以下儿童。然而,尚无充分证据支持常规推荐将其用于 12 岁以下儿童(可根据和危险因素考虑治疗)。
奈玛特韦和利托那韦
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
或
莫努匹韦
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
或
remdesivir
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
针对特定患者群中所有患者的治疗建议
多个专业呼吸科组织的指南均同意,应建议患有哮喘或 COPD 的患者继续按处方使用吸入剂(包括吸入皮质类固醇)(包括吸入皮质类固醇),无论其是否罹患 COVID-19。[857]Global Initiative for Asthma. Global strategy for asthma management and prevention. 2022 [internet publication] https://ginasthma.org/gina-reports [858]British Thoracic Society. Advice for healthcare professionals treating people with asthma (adults) in relation to COVID-19. 2020 [internet publication] https://www.brit-thoracic.org.uk/about-us/covid-19-information-for-the-respiratory-community [859]Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. 2021 [internet publication] https://goldcopd.org/2021-gold-reports [860]National Institute for Health and Care Excellence. COVID-19 rapid guideline: community-based care of patients with chronic obstructive pulmonary disease (COPD). 2020 [internet publication] https://www.nice.org.uk/guidance/ng168 [861]Hasan SS, Capstick T, Zaidi STR, et al. Use of corticosteroids in asthma and COPD patients with or without COVID-19. Respir Med. 2020 Aug-Sep;170:106045 https://www.resmedjournal.com/article/S0954-6111(20)30185-2/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32843175?tool=bestpractice.com
继续吸入皮质类固醇治疗的总体目标是降低哮喘或 COPD 加重的风险。[861]Hasan SS, Capstick T, Zaidi STR, et al. Use of corticosteroids in asthma and COPD patients with or without COVID-19. Respir Med. 2020 Aug-Sep;170:106045 https://www.resmedjournal.com/article/S0954-6111(20)30185-2/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32843175?tool=bestpractice.com
尚无证据表明吸入皮质类固醇与哮喘患者的 COVID-19 感染有关。[862]Centre for Evidence-Based Medicine; Hartmann-Boyce J, Hobbs R. Inhaled steroids in asthma during the COVID-19 outbreak. 2020 [internet publication] https://www.cebm.net/covid-19/inhaled-steroids-in-asthma-during-the-covid-19-outbreak 也无证据表明它们会增加 COPD 患者的 COVID-19 相关风险。[860]National Institute for Health and Care Excellence. COVID-19 rapid guideline: community-based care of patients with chronic obstructive pulmonary disease (COPD). 2020 [internet publication] https://www.nice.org.uk/guidance/ng168
居家或在医院接受诊疗的急症患者可能会对其被给予的 COPD 或哮喘吸入器遗忘向您告知。酌情谨记对吸入器进行检查以及给予药物。
许多吸入器含有多种药物,因此应确保勿重复给药。
对于出现急性肾损伤的 COPD 或哮喘患者,如果估算 GFR <50 mL/(min·1.73m²),可能需要暂时停用其常用的吸入性长效毒蕈碱受体拮抗剂,具体取决于使用哪种特定药物。查阅当地处方集或寻求药师建议。
其他处方药物
患有严重哮喘或 COPD 并使用口服皮质类固醇作为常规维持治疗处方的患者,也应以尽可能低的剂量继续使用这些药物,因为停用这些药物可能会导致其病情恶化。[857]Global Initiative for Asthma. Global strategy for asthma management and prevention. 2022 [internet publication] https://ginasthma.org/gina-reports [860]National Institute for Health and Care Excellence. COVID-19 rapid guideline: community-based care of patients with chronic obstructive pulmonary disease (COPD). 2020 [internet publication] https://www.nice.org.uk/guidance/ng168 [863]National Institute for Health and Care Excellence. COVID-19 rapid guideline: severe asthma. 2020 [internet publication] https://www.nice.org.uk/guidance/ng166
英国国家卫生与临床优化研究所关于严重哮喘的快速指南建议,在 COVID-19 大流行期间,常规使用生物治疗哮喘的患者应继续使用该药物,但是,若其罹患 COVID-19,则应联系负责其诊疗的专科医生团队。[863]National Institute for Health and Care Excellence. COVID-19 rapid guideline: severe asthma. 2020 [internet publication] https://www.nice.org.uk/guidance/ng166
针对特定患者群中所有患者的治疗建议
如果 COVID-19 患者在家中接受治疗,认为自身哮喘加重,寻求医疗建议,应建议其遵循个体化行动计划。[858]British Thoracic Society. Advice for healthcare professionals treating people with asthma (adults) in relation to COVID-19. 2020 [internet publication] https://www.brit-thoracic.org.uk/about-us/covid-19-information-for-the-respiratory-community
出现哮喘恶化时,遵循既定指南,并考虑收住入院。对于哮喘加重,可根据指征起始皮质类固醇治疗。[861]Hasan SS, Capstick T, Zaidi STR, et al. Use of corticosteroids in asthma and COPD patients with or without COVID-19. Respir Med. 2020 Aug-Sep;170:106045 https://www.resmedjournal.com/article/S0954-6111(20)30185-2/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32843175?tool=bestpractice.com [864]Primary Care Respiratory Society. PCRS pragmatic guidance: diagnosing and managing asthma attacks and people with COPD presenting in crisis during the UK Covid 19 epidemic. 2020 [internet publication] https://www.pcrs-uk.org/resource/pragmatic-guidance-crisis-management-asthma-and-copd-during-uk-covid-19-epidemic [865]British Thoracic Society; Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma: a national clinical guideline. 2019 [internet publication] https://www.brit-thoracic.org.uk/quality-improvement/guidelines/asthma
确保安全网络措施到位,以防患者病情未得到改善或情况发生变化。[864]Primary Care Respiratory Society. PCRS pragmatic guidance: diagnosing and managing asthma attacks and people with COPD presenting in crisis during the UK Covid 19 epidemic. 2020 [internet publication] https://www.pcrs-uk.org/resource/pragmatic-guidance-crisis-management-asthma-and-copd-during-uk-covid-19-epidemic
哮喘加重与 COVID-19 在临床上可能很难区分,并且可能同时出现。两者的共同特征是咳嗽和呼吸短促;但是,发热、乏力以及味觉或嗅觉改变等其他症状,更可能提示 COVID-19。[858]British Thoracic Society. Advice for healthcare professionals treating people with asthma (adults) in relation to COVID-19. 2020 [internet publication] https://www.brit-thoracic.org.uk/about-us/covid-19-information-for-the-respiratory-community 已知患有 COVID-19 的患者如果症状恶化,建议其寻求医疗建议。
针对特定患者群中所有患者的治疗建议
如果罹患 COVID-19 的固有 COPD 患者疑似 COPD 加重,需遵循患者个体化行动预案。如果患者居家,确保其知晓寻求医疗建议。[860]National Institute for Health and Care Excellence. COVID-19 rapid guideline: community-based care of patients with chronic obstructive pulmonary disease (COPD). 2020 [internet publication] https://www.nice.org.uk/guidance/ng168
对于 COPD 加重的管理,遵循既定指南,包括具备临床指征时,给予短期口服皮质类固醇。[859]Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. 2021 [internet publication] https://goldcopd.org/2021-gold-reports [861]Hasan SS, Capstick T, Zaidi STR, et al. Use of corticosteroids in asthma and COPD patients with or without COVID-19. Respir Med. 2020 Aug-Sep;170:106045 https://www.resmedjournal.com/article/S0954-6111(20)30185-2/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32843175?tool=bestpractice.com 寻求专科医生意见,并考虑收治入院。
对于 COPD 加重,口服皮质类固醇标准推荐用药疗程仅为 5 天。[866]British Thoracic Society. COPD and COVID-19 for healthcare professionals. 2020 [internet publication] https://www.brit-thoracic.org.uk/covid-19/covid-19-information-for-the-respiratory-community [867]Walters JA, Tan DJ, White CJ, et al. Different durations of corticosteroid therapy for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2018 Mar 19;(3):CD006897 https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006897.pub4/full http://www.ncbi.nlm.nih.gov/pubmed/29553157?tool=bestpractice.com
建议患者勿因 COVID-19 症状起始皮质类固醇和/或抗生素治疗,例如发热、肌痛和干咳。[860]National Institute for Health and Care Excellence. COVID-19 rapid guideline: community-based care of patients with chronic obstructive pulmonary disease (COPD). 2020 [internet publication] https://www.nice.org.uk/guidance/ng168
与其他疾病进行鉴别,例如急性冠脉综合征、急性心力衰竭和肺炎,以及 COVID-19 并发症。
请参阅 COPD 急性加重专题。
针对特定患者群中所有患者的治疗建议
世界卫生组织建议,于 COVID-19 患者,不应例行停用降压药,而应根据患者临床情况(尤其是血压和肾功能)进行调整。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
尽管担心使用 ACE 抑制剂或血管紧张素 Ⅱ 受体拮抗剂的患者出现感染风险或患更严重疾病的风险增加,但一项正在进行的系统评价发现,高确定性证据表明此类药物的使用与重症不具相关性。[868]Mackey K, King VJ, Gurley S, et al. Risks and impact of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers on SARS-CoV-2 infection in adults: a living systematic review. Ann Intern Med. 2020 Aug 4;173(3):195-203 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249560 http://www.ncbi.nlm.nih.gov/pubmed/32422062?tool=bestpractice.com [869]Mackey K, Kansagara D, Vela K. Update alert 7: risks and impact of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers on SARS-CoV-2 infection in adults. Ann Intern Med. 2021 Feb;174(2):W25-9 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791405 http://www.ncbi.nlm.nih.gov/pubmed/33395346?tool=bestpractice.com
一些专业学会建议,已经使用这些药物(例如用于治疗高血压、心力衰竭、冠状动脉疾病、CKD 或糖尿病并发症的药物)的患者可以在大流行期间继续使用(前提是其未罹患 COVID-19)。如果患者罹患 COVID-19,建议他们在决定停用此类药物之前接受医生全面临床评估。[870]American Heart Association; Heart Failure Society of America; American College of Cardiology. Patients taking ACE-i and ARBs who contract COVID-19 should continue treatment, unless otherwise advised by their physician. 2020 [internet publication] https://newsroom.heart.org/news/patients-taking-ace-i-and-arbs-who-contract-covid-19-should-continue-treatment-unless-otherwise-advised-by-their-physician [871]European Society of Cardiology Council on Hypertension. Position statement of the ESC Council on Hypertension on ACE-inhibitors and angiotensin receptor blockers. 2020 [internet publication] https://www.escardio.org/Councils/Council-on-Hypertension-(CHT)/News/position-statement-of-the-esc-council-on-hypertension-on-ace-inhibitors-and-ang [872]British Cardiovascular Society; British Society for Heart Failure. BSH & BCS joint statement on ACEi or ARB in relation to COVID-19. 2020 [internet publication] https://www.britishcardiovascularsociety.org/news/ACEi-or-ARB-and-COVID-19 [873]The Renal Association. The Renal Association, UK position statement on COVID-19 and ACE inhibitor/angiotensin receptor blocker use. 2020 [internet publication] https://renal.org/health-professionals/covid-19/ra-resources/renal-association-uk-position-statement-covid-19-and-ace
英国肾脏协会(Renal Association)和英国心血管学会(British Cardiovascular Society)建议,在权衡这些药物对疑似 COVID-19 患者的益处和风险时,遵循当前针对患任何并发急性疾病的患者的标准指导。[872]British Cardiovascular Society; British Society for Heart Failure. BSH & BCS joint statement on ACEi or ARB in relation to COVID-19. 2020 [internet publication] https://www.britishcardiovascularsociety.org/news/ACEi-or-ARB-and-COVID-19 [873]The Renal Association. The Renal Association, UK position statement on COVID-19 and ACE inhibitor/angiotensin receptor blocker use. 2020 [internet publication] https://renal.org/health-professionals/covid-19/ra-resources/renal-association-uk-position-statement-covid-19-and-ace [874]Clark AL, Kalra PR, Petrie MC, et al. Change in renal function associated with drug treatment in heart failure: national guidance. Heart. 2019 Jun;105(12):904-10 http://www.ncbi.nlm.nih.gov/pubmed/31118203?tool=bestpractice.com 其中包括:
进行个体临床评估
对所有肾素-血管紧张素-醛固酮系统(renin-angiotensin-aldosterone system, RAAS)拮抗剂 初始适应症加以考虑(ACE 抑制剂、血管紧张素-Ⅱ 受体拮抗剂、盐皮质激素受体/醛固酮拮抗剂),并对预后获益程度加以考虑
如果暂时停止药物治疗,需考虑健康状况得到改善后何时再次给药。
考虑计算脆弱评分,因为脆弱评分较高的患者,突发不适时更可能受到药物相关性伤害(基于专家意见)。
考虑停用其他在并发疾病期间与急性肾损伤风险增加相关药物的获益与风险,例如其他抗高血压药和利尿药。
如果慢性肾病患者一直在使用非甾体抗炎药,建议他们在并发疾病时停用此类药物。
在社区自我管理心力衰竭的患者可能希望在出现可能导致脱水的并发疾病期间减少利尿药剂量 (基于专家意见)。
如果患者病情复杂(例如正在进行肾脏替代治疗或免疫抑制治疗),可向患者心脏病学团队或肾病学团队寻求建议 。
针对特定患者群中所有患者的治疗建议
如果糖尿病患者罹患轻度 COVID-19,您认为他们满足居家观察条件:
建议他们遵循其个人医疗提供者或相关国家或地区专业糖尿病组织提供的病期规则。[875]European Society of Endocrinology. COVID-19 and endocrine diseases: a statement from the European Society of Endocrinology. 2020 [internet publication] https://www.ese-hormones.org/news/rss-feed-world-news/ese-covid-19-and-endocrine-diseases-statement [876]American Diabetes Association. COVID-19: if you do get sick, know what to do. 2020 [internet publication] https://www.diabetes.org/blog/coronavirus-covid-19-know-what-to-do [877]Trend Diabetes. Trend releases updated sick-day rules leaflets. 2020 [internet publication] https://trend-uk.org/trend-uk-releases-updated-sick-day-rules-leaflets [878]Primary Care Diabetes Society. How to advise on sick day rules. 2020 [internet publication] https://www.diabetesonthenet.com/journals/issue/607/article-details/how-to-advise-on-sick-day-rules [879]NHS England. Diabetes COVID-19 key information: sick day rules. 2020 [internet publication] https://www.england.nhs.uk/london/london-clinical-networks/our-networks/diabetes/diabetes-covid-19-key-information [880]International Diabetes Federation Europe. How to manage diabetes during an illness. 2020 [internet publication] https://www.idf.org/aboutdiabetes/what-is-diabetes/covid-19-and-diabetes/1-covid-19-and-diabetes.html [881]Diabetes Australia; Royal Australian College of General Practitioners. Diabetes management during the coronavirus pandemic: be proactive and prepared. 2020 [internet publication] https://static.diabetesaustralia.com.au/s/fileassets/diabetes-australia/6aab1606-d77f-45bc-8f4f-df58f0471d0e.pdf
尽管关于这种情况的证据有限,但 COVID-19 疾病期间糖尿病自我管理通常仍遵循标准的病期规则。[882]Centre for Evidence-Based Medicine; Hartmann-Boyce J, Morris E, Goyder C, et al. Managing diabetes during the COVID-19 pandemic. 2020 [internet publication] https://www.cebm.net/covid-19/managing-diabetes-during-the-covid-19-pandemic
如果患者无法摄入任何液体并且无法控制血糖,建议其立即就医。
确保患者具有足够的糖尿病药物和血糖监测设备供给。如果患者患有 1 型糖尿病,则确保他们还有血酮检测仪和血酮检测试纸。
加强血糖监测。
饮无糖液体以防止脱水,因为脱水可能会导致病情快速进展,出现:
高血糖
糖尿病酮症酸中毒(DKA)
保持碳水化合物摄入(如果无法进食或呕吐,可使用含糖液体)。
休息并避免剧烈运动。
了解应在什么阶段寻求进一步医疗帮助,例如:
患者血糖水平持续高于平时
患者感到不适,且无法得到改善
患者不确定如何进行疾病自我管理。
请注意,即使不进食,患病期间血糖亦可能升高。COVID-19 患者出现高血糖合并酮症的风险似乎会增加,包括伴 2 型糖尿病患者(尤其是若患者正在服用钠-葡萄糖协同转运蛋白-2(sodium-glucose cotransporter-2, SGLT-2)抑制剂)。[883]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19: front door guidance. 2020 [internet publication] https://abcd.care/resource/concise-advice-inpatient-diabetes-during-covid-19-front-door-guidance
除上述一般要点外,请确保 1 型糖尿病患者意识到以下需要:[878]Primary Care Diabetes Society. How to advise on sick day rules. 2020 [internet publication] https://www.diabetesonthenet.com/journals/issue/607/article-details/how-to-advise-on-sick-day-rules
至少每 4 至 6 小时监测一次血糖
检测其血液中的酮体,了解其水平的含义,以及需要采取的措施
切勿停止使用胰岛素,并在必要时调整剂量。
如果血糖水平 >11 mmol/L(>198 mg/dL),即使不进食或呕吐,也需要增加胰岛素的剂量。
有关管理胰岛素给药以及血糖和血酮监测频率的详细分步指导,请参考当地规程。
如果您的 1 型糖尿病患者通常使用 SGLT-2 抑制剂(例如达格列净、卡格列净、恩格列净),大多数与 COVID 相关的共识声明建议在急性患病期间应停用这些药物。[884]Hartmann-Boyce J, Morris E, Goyder C, et al. Diabetes and COVID-19: risks, management, and learnings from other national disasters. Diabetes Care. 2020 Aug;43(8):1695-703 https://care.diabetesjournals.org/content/43/8/1695 http://www.ncbi.nlm.nih.gov/pubmed/32546593?tool=bestpractice.com
建议您的患者即使血糖未升高,也应检测其血清酮体。[883]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19: front door guidance. 2020 [internet publication] https://abcd.care/resource/concise-advice-inpatient-diabetes-during-covid-19-front-door-guidance
使用 SGLT-2 抑制剂的患者有罹患正常血糖性酮症酸中毒的风险。[885]Peters AL, Buschur EO, Buse JB, et al. Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Diabetes Care. 2015 Jun 15;38(9):1687-93 http://www.ncbi.nlm.nih.gov/pubmed/26078479?tool=bestpractice.com [886]Medicines and Healthcare products Regulatory Agency. SGLT2 inhibitors: updated advice on the risk of diabetic ketoacidosis. 2016 [internet publication] https://www.gov.uk/drug-safety-update/sglt2-inhibitors-updated-advice-on-the-risk-of-diabetic-ketoacidosis 即使已停用 SGLT-2 抑制剂,也应检测其血清酮体。
COVID-19 感染会增加胰岛素抵抗,并减少胰岛 β 细胞胰岛素分泌。这会在 2 型糖尿病患者中甚至无糖尿病病史的人群中诱发 DKA。
除上述一般要点外,确保 2 型糖尿病患者了解以下须知:
联系其家庭医生以获取是否调整糖尿病药物的相关建议。
使用胰岛素治疗的 2 型糖尿病患者应至少每天监测四次血糖,通常需继续使用胰岛素,但剂量可能需要调整 (基于专家意见)。
大多数 COVID-19 共识声明建议,通常使用 SGLT-2 抑制剂(例如达格列净、卡格列净、恩格列净)的患者应在急性患病期间停用该药物。[884]Hartmann-Boyce J, Morris E, Goyder C, et al. Diabetes and COVID-19: risks, management, and learnings from other national disasters. Diabetes Care. 2020 Aug;43(8):1695-703 https://care.diabetesjournals.org/content/43/8/1695 http://www.ncbi.nlm.nih.gov/pubmed/32546593?tool=bestpractice.com 使用 SGLT-2 抑制剂会使他们有罹患正常血糖性酮症酸中毒的风险,即使他们停止药物治疗,也应检查血清酮体。[885]Peters AL, Buschur EO, Buse JB, et al. Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Diabetes Care. 2015 Jun 15;38(9):1687-93 http://www.ncbi.nlm.nih.gov/pubmed/26078479?tool=bestpractice.com [886]Medicines and Healthcare products Regulatory Agency. SGLT2 inhibitors: updated advice on the risk of diabetic ketoacidosis. 2016 [internet publication] https://www.gov.uk/drug-safety-update/sglt2-inhibitors-updated-advice-on-the-risk-of-diabetic-ketoacidosis [887]Trend Diabetes. Type 2 diabetes: what to do when you’re ill. 2020 [internet publication] https://trend-uk.org/wp-content/uploads/2020/03/A5_T2Illness_TREND_FINAL.pdf 患者可能不熟悉血酮检查,因此需安排紧急检查。[887]Trend Diabetes. Type 2 diabetes: what to do when you’re ill. 2020 [internet publication] https://trend-uk.org/wp-content/uploads/2020/03/A5_T2Illness_TREND_FINAL.pdf
大多数与 COVID 相关的共识声明还建议通常服用二甲双胍的患者在急性患病期间停用该药物。[884]Hartmann-Boyce J, Morris E, Goyder C, et al. Diabetes and COVID-19: risks, management, and learnings from other national disasters. Diabetes Care. 2020 Aug;43(8):1695-703 https://care.diabetesjournals.org/content/43/8/1695 http://www.ncbi.nlm.nih.gov/pubmed/32546593?tool=bestpractice.com 在这种情况下,二甲双胍会增加出现乳酸酸中毒的风险。
请注意,停用糖尿病药物(例如 SGLT-2 抑制剂或二甲双胍)可能会导致高血糖,因此,患者应就是否需要采取进一步行动寻求糖尿病专科医生建议(基于专家意见)。
通常使用格列齐特的患者在不进食进水的情况下,可能需要减少剂量或用药频率,以免在夜间出现低血糖 (基于专家意见)。另一方面,在患病期间,某些患者可能会出现高血糖,因此可能需要暂时增加剂量。[887]Trend Diabetes. Type 2 diabetes: what to do when you’re ill. 2020 [internet publication] https://trend-uk.org/wp-content/uploads/2020/03/A5_T2Illness_TREND_FINAL.pdf 血糖监测对于指导此类决策至关重要。
一些糖尿病组织的病期规则还建议患者停用胰高血糖素样肽-1(glucagon-like peptide-1, GLP-1)激动剂(例如度拉糖肽、艾塞那肽、利拉鲁肽、利司那肽)。[888]NHS London Clinical Networks. Sick day rules: how to manage type 2 diabetes if you become unwell with coronavirus and what to do with your medication. 2020 [internet publication] https://www.england.nhs.uk/london/wp-content/uploads/sites/8/2020/04/3.-Covid-19-Type-2-Sick-Day-Rules-Crib-Sheet-06042020.pdf 其他指导信息建议,由于 GLP-1 激动剂可导致伴发脱水的严重不良反应,应密切监测使用该药的患者。[889]Bornstein SR, Rubino F, Khunti K, et al. Practical recommendations for the management of diabetes in patients with COVID-19. Lancet Diabetes Endocrinol. 2020 Jun;8(6):546-50 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180013 http://www.ncbi.nlm.nih.gov/pubmed/32334646?tool=bestpractice.com
检查血酮,因为尿酮测量可能不可靠。
隔离疑似或确诊中度疾病(即出现肺炎临床征象,但无重症肺炎征象)患者以遏制病毒传播(遵循当地公共卫生当局的建议)。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
在医疗机构、社区机构或在家中管理患者。低危患者可考虑采用居家隔离,并酌情进行远程医疗或远程访视。在医疗机构中对恶化高风险患者和孕妇进行管理。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 [465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
BMJ Best Practice 临床实践合并症诊疗工具中的信息涉及非妊娠成人。
这些信息不适用于孕妇患者或儿童。在这类情况下,请向产科/妇科专科医生或儿科专科医生寻求建议,了解患者的合并症可能会如何影响您对 COVID-19 的管理。
对具有危险因素的患者进行密切监测,并对此类危险因素加以考虑,考虑最适合的照护环境。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
世界卫生组织将以下合并症列为重症和死亡危险因素:[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
心脏疾病
糖尿病
慢性肺疾病
慢性肾病
脑血管疾病
痴呆
精神障碍
肿瘤
免疫抑制
肥胖
高血压。
高龄患者以及脆弱程度较高的 COVID-19 患者,据报道具有更高的死亡风险。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1 [835]Chinnadurai R, Ogedengbe O, Agarwal P, et al. Older age and frailty are the chief predictors of mortality in COVID-19 patients admitted to an acute medical unit in a secondary care setting: a cohort study. BMC Geriatr. 2020 Oct 16;20(1):409 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563906 http://www.ncbi.nlm.nih.gov/pubmed/33066750?tool=bestpractice.com
虑与管理患者长期疾病的专科团队讨论患者情况,和/或转诊至多学科团队中的其他医疗卫生专业人士。
建议为 COVID-19 老年患者提供 多学科协作医疗,以帮助确保充分解决医护各方面问题(包括合并症)。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
衰弱是与一种衰老过程相关的独特健康状态,多个身体系统逐渐丧失其生理功能。
询问患者其在急性发作前 2 周的能力情况(以及可能的相关照护者的意见)。
如果患者的年龄 ≥65 岁,则使用临床衰弱量表。
这是确定虚弱的实用辅助工具,但不应仅仅依赖它。
通常情况下,急诊入院的老年患者中,较高的衰弱评分与发生不良结局的风险增加相关。 尤其对于 COVID-19 患者,据部分但非所有研究报告,衰弱程度越高的患者具有更高的死亡风险。 [890]Subramaniam A, Shekar K, Afroz A, et al. Frailty and mortality associations in patients with COVID-19: a systematic review and meta-analysis. Intern Med J. 2022 May;52(5):724-39 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314619 http://www.ncbi.nlm.nih.gov/pubmed/35066970?tool=bestpractice.com
如果患者的评分为 5 分或以上,应对恰当的本地转诊进行全面评估寻求上级医生的建议,全面评估应包括讨论患者的治疗预期和照护目标。
辅助实施多学科诊疗,并根据患者的价值观来调整管理方案。
管理 COVID-19 患者时,应实施当地感染防控方案。对于居家隔离患者,建议患者及其家庭成员采取适当的感染防控措施。
何时停止隔离的指南各地有较大差异。
隔离时限可能取决于多种因素,包括疫苗接种状态、流行的 SARS-CoV-2 变体和患者因素(例如免疫功能正常/免疫功能低下、无症状/有症状、疾病严重程度)。
世界卫生组织建议停用基于防范传播的预防措施(包括隔离),且检测呈阳性后 10 天(无症状患者),或症状发作后 10 天加上至少 3 天无发热和呼吸道症状(有症状的患者)的患者,可移出诊疗路径。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
但是,部分国家目前建议隔离期可短至 5 天到 7 天。[836]Mahase E. Covid-19: is it safe to reduce the self-isolation period? BMJ. 2021 Dec 30;375:n3164. https://www.bmj.com/content/375/bmj.n3164 http://www.ncbi.nlm.nih.gov/pubmed/34969702?tool=bestpractice.com
参阅当地公共卫生指南,获取更多信息。
针对特定患者群中所有患者的治疗建议
对患者疾病进展征象和症状进行密切监测。若患者居家管理,应就疾病恶化症状和征象,以及需要立刻开展紧急处理(例如呼吸困难、胸痛)的并发症,向患者交待清楚。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 [465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
对于有症状,且存在进展为重症风险,但未住院的患者,建议在家中进行脉搏血氧测定。需进行患者教育和给予适当的随访。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
如果患者正在医院接受治疗,需使用早期预警医学评分(例如国家早期预警评分 2 [National Early Warning Score 2, NEWS2])对患者临床恶化征象进行密切监测,并立即采取适当的支持性治疗干预。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
如果伴慢性肾病(chronic kidney disease, CKD)或具有 CKD 危险因素的患者因急症而呈现不适,应对肾功能进行密切监测。[837]National Institute for Health and Care Excellence. Acute kidney injury: prevention, detection and management. 2019 [internet publication] https://www.nice.org.uk/guidance/ng148
CKD 为急性肾损伤(acute kidney injury, AKI)重要危险因素。[838]Hsu CY, Ordoñez JD, Chertow GM, et al. The risk of acute renal failure in patients with chronic kidney disease. Kidney Int. 2008 Apr 2;74(1):101-7 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673528 http://www.ncbi.nlm.nih.gov/pubmed/18385668?tool=bestpractice.com
伴 CKD 和 COVID-19 患者出现 AKI 风险将升高, 其可能与发热、脱水,以及非甾体抗炎药使用具有相关性。
COVID -19 患者伴 AKI 可能较为常见(但确切患病率尚不确定)。AKI 与死亡率增加具有相关性。[839]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication] https://www.nice.org.uk/guidance/ng191
向您的 CKD 患者解释,其患病后出现 AKI 的风险增加。确定机制,以便可以密切监测居家治疗患者疾病进展迹象。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
对于入院的所有 COVID-19 患者,包括 CKD 患者,院时需检查肾功能,并确保定期监测。
对于 CKD 患者:
与最近一次可获取结果的肾功能进行比较
每日监测肾功能,同时进行仔细的容量状态监测 ( 基于专家意见)。
对少尿进行监测并予以处理。[837]National Institute for Health and Care Excellence. Acute kidney injury: prevention, detection and management. 2019 [internet publication] https://www.nice.org.uk/guidance/ng148
针对特定患者群中所有患者的治疗建议
建议患者避免仰卧,因为这会使排痰不力。首先采用简单措施(例如对给予 1 岁及以上患者一茶匙蜂蜜)止咳。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
一项荟萃分析发现,蜂蜜对于改善上呼吸道感染症状,尤其是咳嗽频率和严重程度,优于常规治疗(例如镇咳药)。[741]Abuelgasim H, Albury C, Lee J. Effectiveness of honey for symptomatic relief in upper respiratory tract infections: a systematic review and meta-analysis. BMJ Evid Based Med. 2021 Apr;26(2):57-64. https://ebm.bmj.com/content/early/2020/07/28/bmjebm-2020-111336 http://www.ncbi.nlm.nih.gov/pubmed/32817011?tool=bestpractice.com
在决定是否建议将蜂蜜作为缓解咳嗽症状的一种选择时,要考虑到患者的整体情况,包括其糖尿病控制情况。
如果患者的糖尿病控制或临床状态通常不稳定,请考虑采用其他的对症疗法。
如果患者正在服用蜂蜜治疗咳嗽,并且发现它很有用,建议密切监测毛细血管血糖,以发检测有无高血糖。
嘱患者补充足够的营养和进行适当的补液。
建议患者规律饮水,以避免脱水。由于发热,需要的液体摄入量可能比平时更高。然而,过多液体将妨碍氧合。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 [530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
维持最佳体液状态至关重要,但这很难在所有 COVID-19 患者中实现。[839]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication] https://www.nice.org.uk/guidance/ng191 寻求上级医生建议,尤其是对于病情复杂患者,例如患有心力衰竭和/或慢性肾病(chronic kidney disease, CKD)的患者。
心力衰竭和/或 CKD 患者具有液体复苏肺水肿高风险,因此应密切监测(最初每小时一次)。
监测项目应包括:
定期进行容量状态临床评估(脉搏、BP、颈静脉压 [jugular venous pressure, JVP],并检查有无肺水肿和外周水肿)
体液平衡(出入量表)和每日体重
肾功能检查,至少每日一次。
如果尿量难以测定,考虑进行膀胱导尿术,但要注意感染和创伤风险可能增加。
对于病情复杂患者,可能需监测中心静脉压,或置入肺动脉导管进行监测。[891]Verbrugge FH, Grieten L, Mullens W. Management of the cardiorenal syndrome in decompensated heart failure. Cardiorenal Med. 2014 Dec;4(3-4):176-88 https://www.doi.org/10.1159/000366168 http://www.ncbi.nlm.nih.gov/pubmed/25737682?tool=bestpractice.com
重要的是要知道何时降级液体治疗。考虑尽早向上级医生寻求意见支持该决定。
如果患者液体容量过负荷(体征包括脉率升高、肺水肿导致呼吸频率升高以及外周水肿相关的 JVP 升高),停止液体复苏,寻求上级医生帮助,并考虑静脉给予利尿药 (基于专家意见)。
除非存在合理情况,否则一般不会联用利尿药和静脉输液(基于专家意见)。
可能需要心脏病学医生和/或肾病学医生专科意见。
其他支持性治疗措施包括:
建议患者通过开窗或开门改善空气流通[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
为所有患者提供基本的心理健康和社会心理支持,并酌情处理失眠、抑郁或焦虑等症状。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
如果嗅觉功能障碍持续超过 2 周,考虑对其进行治疗,例如嗅觉训练、鼻内用皮质类固醇。[742]Whitcroft KL, Hummel T. Olfactory dysfunction in COVID-19: diagnosis and management. JAMA. 2020 Jun 23;323(24):2512-4. https://jamanetwork.com/journals/jama/fullarticle/2766523 http://www.ncbi.nlm.nih.gov/pubmed/32432682?tool=bestpractice.com [743]Nag AK, Saltagi AK, Saltagi MZ, et al. Management of post-infectious anosmia and hyposmia: a systematic review. Ann Otol Rhinol Laryngol. 2022 Aug 12:34894221118186. http://www.ncbi.nlm.nih.gov/pubmed/35959948?tool=bestpractice.com
一项 Cochrane 评价发现,不同干预措施对于预防感染后持续性嗅觉功能障碍的有效性证据非常有限。唯一可获取的证据是鼻内皮质类固醇应用,但其确定性极低,因此无法得出结论。[744]Webster KE, O'Byrne L, MacKeith S, et al. Interventions for the prevention of persistent post-COVID-19 olfactory dysfunction. Cochrane Database Syst Rev. 2021 Jul 22;(7):CD013877. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013877.pub2/full http://www.ncbi.nlm.nih.gov/pubmed/34291812?tool=bestpractice.com
一项系统评价和荟萃分析发现,使用鼻内/口服皮质类固醇与嗅觉训练的联合治疗相较于单独嗅觉训练的嗅觉评分改善差异无统计学意义。嗅觉功能在经嗅觉训练后显著改善。[745]Asvapoositkul V, Samuthpongtorn J, Aeumjaturapat S, et al. Therapeutic options of post-COVID-19 related olfactory dysfunction: a systematic review and meta-analysis. Rhinology. 2022 Sep 29 [Epub ahead of print]. https://www.rhinologyjournal.com/Rhinology_issues/manuscript_3028.pdf http://www.ncbi.nlm.nih.gov/pubmed/36173148?tool=bestpractice.com
大多数中度疾病患儿可仅采取支持性治疗,除非被认为存在进展为重症的高风险。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
对于因固有精神卫生疾患进行居家处理的患者,例如抑郁,给予支持治疗。他们可能正在经历更多的情绪困扰。
美国创伤性应激研究中心建议精神病医生与患者讨论策略,减轻苦恼和隔离影响,从而对高风险患者进行识别和提供额外支持。[840]Center for the Study of Traumatic Stress. Taking care of patients during the coronavirus outbreak: a guide for psychiatrists. 2020 [internet publication] https://www.cstsonline.org/assets/media/documents/CSTS_FS_Taking_Care_of_Patients_During_Coronavirus_Outbreak_A_Guide_for_Psychiatrists_03_03_2020.pdf
考虑使用远超医疗,使远超会诊顺利进行。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1 [841]Shore JH, Schneck CD, Mishkind MC. Telepsychiatry and the coronavirus disease 2019 pandemic-current and future outcomes of the rapid virtualization of psychiatric care. JAMA Psychiatry. 2020 Dec 1;77(12):1211-2 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2765954 http://www.ncbi.nlm.nih.gov/pubmed/32391861?tool=bestpractice.com [842]Hubley S, Lynch SB, Schneck C, et al. Review of key telepsychiatry outcomes. World J Psychiatry. 2016 Jun 22;6(2):269-82 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4919267 http://www.ncbi.nlm.nih.gov/pubmed/27354970?tool=bestpractice.com Royal College of Psychiatrists: digital - COVID-19 guidance for clinicians 在新窗口中打开
告知患者可以在哪里找到本地相关信息和支持性资源,例如:
针对特定患者群中部分患者治疗的附加建议
如果临床怀疑继发性细菌感染,可考虑使用经验性抗生素。
尽快起始治疗,参考当地指南,选择治疗方案。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 [465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov [530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191 给药方案应基于临床诊断、当地流行病学和药敏数据,以及当地治疗指南。
抗生素可考虑用于老年人(尤其是长期照护机构中)和 <5 岁的儿童,从而对于可能的肺炎提供经验性抗生素治疗。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
勿为预防 COVID-19 患者出现继发性肺炎给予抗生素。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
如果患者症状未得到改善,或迅速恶化,建议其立即就医。
再次评估时,应重新考虑患者是否存在更严重疾病征象和症状,以及是否应将其转诊至医院、接受其他急症社区支持服务或接受缓和医疗(亦称为安宁疗护)服务。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
针对特定患者群中部分患者治疗的附加建议
建议给予对乙酰氨基酚或布洛芬。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 [530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
布洛芬只能在控制症状所需最短时间内以最低有效剂量服用。不建议在孕妇(尤其是孕晚期)或 <3 月龄儿童(年龄界值因国家而异)中使用。
慢性肾病和/或心力衰竭
避免将非甾体抗炎药(non-steroidal anti-inflammatory drug, NSAID)用于慢性肾病和/或心力衰竭的患者(基于专家意见)。
哮喘
NSAID 可能会使某些哮喘患者症状恶化,因此需询问患者对其是否存在已知的过度敏感不良反应。[847]Global Initiative for Asthma. Global strategy for asthma management and prevention. 2021 [internet publication] https://ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf
对乙酰氨基酚: 儿童:查询当地药物处方集,以获取剂量指导;成人:必要时,每 4-6 小时口服 500-1000 mg,每日最多 4000 mg
对乙酰氨基酚 : 儿童:查询当地药物处方集,以获取剂量指导;成人:必要时,每 4-6 小时口服 500-1000 mg,每日最多 4000 mg
对乙酰氨基酚: 儿童:查询当地药物处方集,以获取剂量指导;成人:必要时,每 4-6 小时口服 500-1000 mg,每日最多 4000 mg
或
对乙酰氨基酚
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
或
布洛芬
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
针对特定患者群中所有患者的治疗建议
像对所有患者一样,应尽早与痴呆患者及其照护者商定治疗升级预案 (基于专家意见)。
内容应包括:[843]Fritz Z, Slowther AM, Perkins GD. Resuscitation policy should focus on the patient, not the decision. BMJ. 2017 Feb 28;356:j813 https://www.doi.org/10.1136/bmj.j813 http://www.ncbi.nlm.nih.gov/pubmed/28246084?tool=bestpractice.com
复苏状态(即“不尝试心肺复苏”[Do Not Attempt Cardiopulmonary Resuscitation, DNACPR] 的决定)
治疗上限(例如是否适合气管插管或重症监护病房收治)。
升级方案应将预立医疗照护计划纳入考量,包括合法绑定预立医嘱。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1 [843]Fritz Z, Slowther AM, Perkins GD. Resuscitation policy should focus on the patient, not the decision. BMJ. 2017 Feb 28;356:j813 https://www.doi.org/10.1136/bmj.j813 http://www.ncbi.nlm.nih.gov/pubmed/28246084?tool=bestpractice.com
在某些情况下,对于治疗升级计划,痴呆患者将缺乏做出决策的心智能力。
评估并记录心智能力(在需要作出决定的特定时间作出决定的能力)。[844]National Institute for Health and Care Excellence. Decision making and mental capacity. 2018 [internet publication] https://www.nice.org.uk/guidance/ng108 请遵守您所在地区的相应法律。
在英格兰和威尔士,医疗卫生专业人士必须遵守 2005 年心智能力法案。[845]Department of Health. Mental Capacity Act 2005 [internet publication] http://www.legislation.gov.uk/ukpga/2005/9/contents 进行评估时,应遵循该法案中的原则。[845]Department of Health. Mental Capacity Act 2005 [internet publication] http://www.legislation.gov.uk/ukpga/2005/9/contents
如果评估确定患者缺乏心智能力,请确保作出符合患者最大利益的决定。[844]National Institute for Health and Care Excellence. Decision making and mental capacity. 2018 [internet publication] https://www.nice.org.uk/guidance/ng108 [845]Department of Health. Mental Capacity Act 2005 [internet publication] http://www.legislation.gov.uk/ukpga/2005/9/contents
如果患者被评估为缺乏心智能力, 需与近亲属协商,并作出最大获益”决策。[845]Department of Health. Mental Capacity Act 2005 [internet publication] http://www.legislation.gov.uk/ukpga/2005/9/contents
根据英格兰和威尔士 2005 年心智能力法案,如果患者无家庭成员或其他照护者,且无需立即作出决定,应寻求独立心智能力代理人担纲任务。[846]Social Care Institute for Excellence. Independent mental capacity advocate (IMCA). January 2010 [internet publication] https://www.scie.org.uk/mca/imca/do
查看您所在地区的相应法律。
针对特定患者群中所有患者的治疗建议
如果患有糖尿病和中度 COVID-19 的患者在社区中进行自我管理,确保其熟悉病期规则并知道何时寻求医疗帮助(请参阅轻度 COVID-19 患者组中的“建议患者自我管理糖尿病”以了解更多详细信息)。
如果合并有糖尿病和中度 COVID-19 的患者入院,请勿停止任何 1 型糖尿病患者的胰岛素治疗,并查看重度 COVID-19 患者群体合并糖尿病的相关信息,以了解更多。
针对特定患者群中部分患者治疗的附加建议
考虑将单克隆抗体用于有临床进展高风险的患者。指南建议有所不同。
在英国,国家卫生与临床优化研究所建议对于 ≥12 岁,被认为具有重症进展高风险的未住院患者,可给予中和性单克隆抗体。查阅当地指南,了解目前在英国可以使用的单克隆抗体。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
在美国,国立卫生研究院指南专家组建议,将bebtelovimab用于治疗 ≥18 岁、有进展为重症高风险的轻至中度非住院患者。然而,仅建议用于首选治疗(即口服抗病毒药物)不可用、不可行或临床不适合时,因为尚未在安慰剂对照试验中对用于有进展高风险的患者进行评估。尚无充分证据可支持或反对将 bebtelovimab 用于轻至中度疾病的儿童和青少年。可考虑用于因 COVID-19 以外原因住院的轻至中度疾病患者,前提是患者的其他方面符合门诊治疗标准。专家组目前反对使用 casirivimab/imdevimab、bamlanivimab/etesevimab 和 sotrovimab,因为奥密克戎已成为美国的主导变异株,并且预计奥密克戎变异株及其亚型变异株对这些单克隆抗体制剂的敏感性将显著降低。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov 这些单克隆抗体目前未在美国获批使用。[848]US Food and Drug Administration. Coronavirus (COVID-19) update: FDA limits use of certain monoclonal antibodies to treat COVID-19 due to the omicron variant. 2022 [internet publication]. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-limits-use-certain-monoclonal-antibodies-treat-covid-19-due-omicron [849]US Food and Drug Administration. FDA updates sotrovimab emergency use authorization. 2022 [internet publication]. https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-sotrovimab-emergency-use-authorization
美国传染病学会支持,将有活性的单克隆抗体用于有进展至重症高风险的轻至中度门诊患者症状发作后 7 日内。[466]Bhimraj A, Morgan RL, Hirsch Shumaker A, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19 infection. 2022 [internet publication]. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management
世界卫生组织强烈反对将 sotrovimab 和casirivimab/imdevimab 用于非重症患者,因为体外研究数据表明这些药物不能中和当前流行的 SARS-CoV-2 变异株及其亚型变异株。世界卫生组织未针对其他单克隆抗体提出相关建议。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3 [736]Rochwerg B, Siemieniuk RA, Agoritsas T, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020 Sep 4;370:m3379. https://www.bmj.com/content/370/bmj.m3379.long http://www.ncbi.nlm.nih.gov/pubmed/32887691?tool=bestpractice.com [737]Rochwerg B, Siemieniuk RA, Lamontagne R, et al. Update to living WHO guideline on drugs for covid-19. BMJ. 2021 Jul 6;374:n1703. http://www.ncbi.nlm.nih.gov/pubmed/34230027?tool=bestpractice.com
单克隆抗体选择取决于可及性,以及临床和背景因素,包括对不同 SARS-CoV-2 变异株和亚型变异株疗效的信息。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov [530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191 [735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
选择包括 bebtelovimab、tixagevimab/cilgavimab、casirivimab/imdevimab、sotrovimab, bamlanivimab/etesevimab 和 regdanvimab,具体取决于所在地。
临床前证据表明,casirivimab/imdevimab 和 bamlanivimab/etesevimab 在体外对奥密克戎变异株及其亚型变异株缺乏中和活性。sotrovimab 和 bebtelovimab 似乎对奥密克戎变异株保持活性;然而,sotrovimab 对奥密克戎亚型变异株不具有活性。bebtelovimab 似乎对奥密克戎 BA.2、BA.2.75、BA.4 和 BA.5 亚型变异株保持活性。[850]Takashita E, Yamayoshi S, Simon V, et al. Efficacy of antibodies and antiviral drugs against Omicron BA.2.12.1, BA.4, and BA.5 subvariants. N Engl J Med. 2022 Aug 4;387(5):468-70. https://www.nejm.org/doi/full/10.1056/NEJMc2207519 http://www.ncbi.nlm.nih.gov/pubmed/35857646?tool=bestpractice.com [851]Hentzien M, Autran B, Piroth L, et al. A monoclonal antibody stands out against omicron subvariants: a call to action for a wider access to bebtelovimab. Lancet Infect Dis. 2022 Sep;22(9):1278. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00495-9/fulltext http://www.ncbi.nlm.nih.gov/pubmed/35863364?tool=bestpractice.com [852]Sheward DJ, Kim C, Fischbach J, et al. Evasion of neutralising antibodies by omicron sublineage BA.2.75. Lancet Infect Dis. 2022 Oct;22(10):1421-2. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00524-2/fulltext http://www.ncbi.nlm.nih.gov/pubmed/36058228?tool=bestpractice.com 查阅当地指南,获取特定变体和耐药性详细信息。
设施环境或药物供应限制使患者分流变得十分必要。治疗应优先给予具有重症进展高风险患者。
单克隆抗体在非住院患者中使用的证据尚不明确。
一项 Cochrane 评价发现,证据不足以对任何特定的单克隆抗体,以及应该加以使用的疾病阶段,得出有意义的结论。非住院患者的结局信息(例如死亡率、生活质量和严重不良事件)要么没有定论,要么完全缺乏,但 casirivimab/imdevimab、sotrovimab、bamlanivimab(单独使用或与 etesevimab 联合使用)和 regdanvimab 可降低收住院比率或死亡比率(低等确定性证据)。[761]Kreuzberger N, Hirsch C, Chai KL, et al. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;(9):CD013825. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013825.pub2/full http://www.ncbi.nlm.nih.gov/pubmed/34473343?tool=bestpractice.com
一项有关 27 项随机对照试验的系统评价和荟萃分析发现,单克隆抗体对非住院患者的大多数结局影响有限,关于大多数结局的证据确定性为极低至中等。单克隆抗体减少了住院治疗,但对死亡率无影响。[762]Hernandez AV, Piscoya A, Pasupuleti V, et al. Beneficial and harmful effects of monoclonal antibodies for the treatment and prophylaxis of COVID-19: systematic review and meta-analysis. Am J Med. 2022 Jul 23 [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307485 http://www.ncbi.nlm.nih.gov/pubmed/35878688?tool=bestpractice.com
新兴证据支持使用 tixagevimab/cilgavimab 治疗 COVID-19。[853]Wang Y, Zheng J, Zhu K, et al. The effect of tixagevimab-cilgavimab on clinical outcomes in patients with COVID-19: a systematic review with meta-analysis. J Infect. 2022 Aug 27 [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9420004 http://www.ncbi.nlm.nih.gov/pubmed/36031156?tool=bestpractice.com
单克隆抗体一般通过静脉注射给予。
需要在专科诊所进行门诊管理,因此该类治疗的可行性可能受到限制。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
检测呈现阳性后,以及症状出现后 7 天内,应尽快给药。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
各指南推荐剂量有所不同;参阅当地常规。
超敏反应(包括液体输注相关性反应和全身过敏反应)已见诸报道。
需在严重超敏反应可得到控制的环境中给药。输注过程中对患者进行监测,并在输注后观察至少 1 小时。
bebtelovimab: 12岁及以上儿童和成人:遵医嘱选择剂量
bebtelovimab : 12岁及以上儿童和成人:遵医嘱选择剂量
bebtelovimab: 12岁及以上儿童和成人:遵医嘱选择剂量
或
casirivimab 和 imdevimab: 12岁及以上儿童和成人:遵医嘱选择剂量
casirivimab 和 imdevimab : 12岁及以上儿童和成人:遵医嘱选择剂量
casirivimab 和 imdevimab: 12岁及以上儿童和成人:遵医嘱选择剂量
或
bamlanivimab: 儿童和成人:咨询专科医生,获得剂量指导(与 etesevimab 一同给药)
bamlanivimab : 儿童和成人:咨询专科医生,获得剂量指导(与 etesevimab 一同给药)
bamlanivimab: 儿童和成人:咨询专科医生,获得剂量指导(与 etesevimab 一同给药)
bebtelovimab: 12岁及以上儿童和成人:遵医嘱选择剂量
bebtelovimab : 12岁及以上儿童和成人:遵医嘱选择剂量
bebtelovimab: 12岁及以上儿童和成人:遵医嘱选择剂量
或
casirivimab 和 imdevimab: 12岁及以上儿童和成人:遵医嘱选择剂量
casirivimab 和 imdevimab : 12岁及以上儿童和成人:遵医嘱选择剂量
casirivimab 和 imdevimab: 12岁及以上儿童和成人:遵医嘱选择剂量
或
bamlanivimab: 儿童和成人:咨询专科医生,获得剂量指导(与 etesevimab 一同给药)
bamlanivimab : 儿童和成人:咨询专科医生,获得剂量指导(与 etesevimab 一同给药)
bamlanivimab: 儿童和成人:咨询专科医生,获得剂量指导(与 etesevimab 一同给药)
bebtelovimab
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
sotrovimab
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
或
casirivimab 和 imdevimab
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
或
bamlanivimab
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
针对特定患者群中部分患者治疗的附加建议
考虑使用抗病毒药物,选择包括奈玛特韦/利托那韦、莫努匹韦和 remdesivir。指南建议有所不同。
对于有极高住院风险的非重症患者,世界卫生组织强烈建议使用奈玛特韦/利托那韦,而有条件建议使用 remdesivir 或莫努匹韦。对于重症患者,奈玛特韦/利托那韦是优于其他治疗的选择,因其较其他治疗可更有效地减少住院治疗,较莫努匹韦具有更少的危害担忧,并且比静脉用 remdesivir 更易给药。然而,它确实存在显著且复杂的药物相互作用。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3 [736]Rochwerg B, Siemieniuk RA, Agoritsas T, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020 Sep 4;370:m3379. https://www.bmj.com/content/370/bmj.m3379.long http://www.ncbi.nlm.nih.gov/pubmed/32887691?tool=bestpractice.com [737]Rochwerg B, Siemieniuk RA, Lamontagne R, et al. Update to living WHO guideline on drugs for covid-19. BMJ. 2021 Jul 6;374:n1703. http://www.ncbi.nlm.nih.gov/pubmed/34230027?tool=bestpractice.com
在英国,国家卫生与临床优化研究所建议,对于无需辅助供氧而被认为具有进展为重症的高风险患者,可给予奈玛特韦/利托那韦、莫努匹韦或 remdesivir。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
在美国,国立卫生研究院指南专家组建议,对于具有临床进展高风险的轻至中度非住院患者,可将奈玛特韦/利托那韦和 remdesivir 作为首选治疗,将莫努匹韦作为替代治疗(即当首选治疗不可用、不可行或临床不适合时)。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
美国传染病学会支持对此类患者使用抗病毒药物。[466]Bhimraj A, Morgan RL, Hirsch Shumaker A, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19 infection. 2022 [internet publication]. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management
应在诊断后尽快开始治疗,理想情况下,应在症状发作后 5 日内开始使用奈玛特韦/利托那韦或莫努匹韦,症状发作后 7 日内开始使用 remdesivir。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov [530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191 [735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
如果患者起始治疗后需要收住院,完整疗程的完成可由医务人员自行把握。
设施环境或药物供应限制使患者抗病毒治疗分流变得十分必要。治疗应优先给予具有重症进展高风险患者。
由于 remdesivir 需要通过静脉输注给予,设施环境的制约可能使其在部分门诊环境中无法给药。
将抗病毒药物用于非重症患者的证据有限。
2/3 期 EPIC-HR 试验发现,与安慰剂相比,奈玛特韦/利托那韦可将非住院高危成人的住院或死亡风险降低 89%(症状发作后 3 日内)和 88%(症状发作后 5 日内)。[751]Hammond J, Leister-Tebbe H, Gardner A, et al. Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19. N Engl J Med. 2022 Feb 16 [Epub ahead of print]. https://www.nejm.org/doi/full/10.1056/NEJMoa2118542 http://www.ncbi.nlm.nih.gov/pubmed/35172054?tool=bestpractice.com
MOVe-OUT 试验发现,与安慰剂相比,莫努匹韦在使用后 29 日内使非住院高危成人的住院或死亡风险降低31%(将绝对风险从 9.7% 降至 6.8%)。[752]Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al. Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients. N Engl J Med. 2021 Dec 16 [Epub ahead of print]. https://www.nejm.org/doi/full/10.1056/NEJMoa2116044 http://www.ncbi.nlm.nih.gov/pubmed/34914868?tool=bestpractice.com
一项随机、双盲、安慰剂对照试验发现,与安慰剂相比,remdesivir 使非住院高危成人的住院或死亡风险降低 87%。[753]Gottlieb RL, Vaca CE, Paredes R, et al. Early remdesivir to prevent progression to severe Covid-19 in outpatients. N Engl J Med. 2021 Dec 22 [Epub ahead of print]. https://www.nejm.org/doi/full/10.1056/NEJMoa2116846 http://www.ncbi.nlm.nih.gov/pubmed/34937145?tool=bestpractice.com
关于奈玛特韦/利托那韦和莫努匹韦的临床疗效证据最初是基于对单一安慰剂对照试验(奥密克戎变异株出现前在未接种疫苗的成人中展开的试验)数据的中期分析。此后,在奥密克戎变异株(和亚型变异株)占主导地位期间进行的观察性研究表明,奈玛特韦/利托那韦或莫努匹韦治疗降低了进展至重症、住院或死亡的风险。[754]Najjar-Debbiny R, Gronich N, Weber G, et al. Effectiveness of Paxlovid in reducing severe COVID-19 and mortality in high risk patients. Clin Infect Dis. 2022 Jun 2 [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9214014 http://www.ncbi.nlm.nih.gov/pubmed/35653428?tool=bestpractice.com [755]Arbel R, Wolff Sagy Y, Hoshen M, et al. Nirmatrelvir use and severe Covid-19 outcomes during the Omicron surge. N Engl J Med. 2022 Sep 1;387(9):790-8. https://www.nejm.org/doi/full/10.1056/NEJMoa2204919 http://www.ncbi.nlm.nih.gov/pubmed/36001529?tool=bestpractice.com [756]Wong CKH, Au ICH, Lau KTK, et al. Real-world effectiveness of early molnupiravir or nirmatrelvir-ritonavir in hospitalised patients with COVID-19 without supplemental oxygen requirement on admission during Hong Kong's omicron BA.2 wave: a retrospective cohort study. Lancet Infect Dis. 2022 Aug 24 [Epub ahead of print]. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(22)00507-2/fulltext http://www.ncbi.nlm.nih.gov/pubmed/36029795?tool=bestpractice.com
所有 3 种抗病毒药物似乎均对奥密克戎变异株及其亚型变异株具有体外活性。[854]Vangeel L, Chiu W, De Jonghe S, et al. Remdesivir, molnupiravir and nirmatrelvir remain active against SARS-CoV-2 Omicron and other variants of concern. Antiviral Res. 2022 Feb;198:105252. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8785409 http://www.ncbi.nlm.nih.gov/pubmed/35085683?tool=bestpractice.com [850]Takashita E, Yamayoshi S, Simon V, et al. Efficacy of antibodies and antiviral drugs against Omicron BA.2.12.1, BA.4, and BA.5 subvariants. N Engl J Med. 2022 Aug 4;387(5):468-70. https://www.nejm.org/doi/full/10.1056/NEJMc2207519 http://www.ncbi.nlm.nih.gov/pubmed/35857646?tool=bestpractice.com
如果有适应证,可将 remdesivir 用于孕妇。然而,不建议将奈玛特韦/利托那韦和莫努匹韦用于孕妇或母乳喂养的女性。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov [735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
在开始使用莫努匹韦前应进行妊娠试验,应为动物研究显示其具有生殖毒性,并且可能影响骨骼和软骨生长。
建议育龄女性在莫努匹韦治疗期间和末次服药后 4 日内采取避孕措施,同时建议与育龄女性发生性行为的有生育力男性在末次服药后至少 3 个月内采取避孕措施。
remdesivir 与肾毒性、肝毒性和超敏反应有关。
不建议将 remdesivir 用于估算肾小球滤过率(estimated glomerular filtration rate, eGFR)<30 mL/min 的患者。开始治疗前和治疗期间应根据临床情况进行肾功能监测。静脉用制剂含有溶解度增强剂磺丁基醚 β-环糊精钠(sulfobutyl ether beta-cyclodextrin sodium, SBECD),可通过肾脏清除。肾脏损伤患者体内 SBECD 的累积可能导致肝脏和肾脏毒性。如果可能,应考虑对肾脏损伤患者优先使用冻干粉针制剂,因其含有更少的 SBECD。与安慰剂相比,remdesivir 对急性肾损伤的影响极小或并无影响;然而,相关证据确定性级别为低。[855]Izcovich A, Siemieniuk RA, Bartoszko JJ, et al. Adverse effects of remdesivir, hydroxychloroquine and lopinavir/ritonavir when used for COVID-19: systematic review and meta-analysis of randomised trials. BMJ Open. 2022 Mar 2;12(3):e048502. https://bmjopen.bmj.com/content/12/3/e048502 http://www.ncbi.nlm.nih.gov/pubmed/35236729?tool=bestpractice.com
转氨酶升高已见诸报道。开始治疗前和治疗期间应根据临床情况,对肝功能进行监测。如果丙氨酸氨基转移酶(alanine aminotransferase, ALT)水平升高至正常上限 ≥ 10 倍,应考虑停止治疗。如果 ALT 升高伴有肝脏炎症征象或症状,应停止治疗。
开始治疗前和治疗期间应根据临床情况,对凝血酶原时间进行监测,因为凝血酶原时间延长已见诸报道。
需在严重超敏反应可得到控制的环境中给药。输注过程中对患者进行监测,并在输注后观察至少 1 小时。
一般认为奈玛特韦/利托那韦和莫努匹韦的不良反应为轻度。然而,关于这些新药的安全性数据有限,必须向当地的药物警戒计划报告所有的疑似不良反应。
奈玛特韦/利托那韦的常见不良反应包括腹泻、味觉障碍、高血压和肌痛。应慎用于已有肝脏疾病的患者(利托那韦与肝酶升高、肝炎和黄疸)。
莫努匹韦的常见不良反应包括腹泻、恶性、头痛和头晕。
据报道,有患者(包括已接种疫苗的患者)在完成 5 日奈玛特韦/利托那韦疗程康复后 2-8 日出现病毒反弹(即聚合酶链反应检测结果复阳)和症状复发。[746]Centers for Disease Control and Prevention. COVID-19 rebound after Paxlovid treatment. 2022 [internet publication]. https://emergency.cdc.gov/han/2022/han00467.asp [747]Malden DE, Hong V, Lewin BJ, et al. Hospitalization and emergency department encounters for COVID-19 after Paxlovid treatment: California, December 2021-May 2022. MMWR Morb Mortal Wkly Rep. 2022 Jun 24;71(25):830-3. https://www.cdc.gov/mmwr/volumes/71/wr/mm7125e2.htm http://www.ncbi.nlm.nih.gov/pubmed/35737591?tool=bestpractice.com [748]Charness ME, Gupta K, Stack G, et al. Rebound of SARS-CoV-2 infection after nirmatrelvir-ritonavir treatment. N Engl J Med. 2022 Sep 15;387(11):1045-7. https://www.nejm.org/doi/full/10.1056/NEJMc2206449 http://www.ncbi.nlm.nih.gov/pubmed/36069968?tool=bestpractice.com [749]Anderson AS, Caubel P, Rusnak JM, et al. Nirmatrelvir-ritonavir and viral load rebound in Covid-19. N Engl J Med. 2022 Sep 15;387(11):1047-9. https://www.nejm.org/doi/full/10.1056/NEJMc2205944 http://www.ncbi.nlm.nih.gov/pubmed/36069818?tool=bestpractice.com
奈玛特韦/利托那韦具有显著且复杂的药物相互作用,主要由该组合中的利托那韦成分所致。
开始治疗前,应仔细回顾患者用药史。
已在使用含利托那韦方案治疗 HIV 或丙型肝炎病毒感染的患者不需要调整其当前抗病毒治疗方案的剂量,并且用于这些患者的奈玛特韦/利托那韦剂量不变(除非根据患者的肾脏功能情况需要调整剂量)。
IDSA: management of drug interactions with nirmatrelvir/ritonavir 在新窗口中打开
请注意奈玛特韦/利托那韦具有显著且复杂的药物相互作用。
在开始治疗前仔细审查患者的用药史,以了解药物相互作用的风险。 IDSA: management of drug interactions with nirmatrelvir/ritonavir 在新窗口中打开
在治疗期间对患者进行密切监测。
CKD 患者抗病毒治疗前应接受肾功能检查,如同其他患者。[856]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication] https://www.covid19treatmentguidelines.nih.gov
如果患者的 eGFR <30 mL/min,则禁用 remdesivir。[856]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication] https://www.covid19treatmentguidelines.nih.gov
如果可能,应考虑对肾脏损伤患者优先使用冻干粉针,因其磺丁基醚 β-环糊精钠(sulfobutyl ether beta-cyclodextrin sodium, SBECD)含量更少,而 SBECD 通过肾脏进行清除。[856]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication] https://www.covid19treatmentguidelines.nih.gov
如果患者的 eGFR <30 mL/min,则不建议使用奈玛特韦/利托那韦。如果患者的 eGFR 为 30-59 mL/min,请遵循指南并开具减量处方。
参阅当地常规,寻求肾脏病学团队建议。
指南对抗病毒治疗的建议有所不同。
奈玛特韦和利托那韦: eGFR ≥60 mL/min 的成人:300 mg(奈玛特韦)/100 mg(利托那韦),口服,每日两次,连用 5 日;eGFR 为 30-59 mL/min 的成人:150 mg(奈玛特韦)/100 mg(利托那韦),口服,每日两次,连用 5 日
奈玛特韦和利托那韦 : eGFR ≥60 mL/min 的成人:300 mg(奈玛特韦)/100 mg(利托那韦),口服,每日两次,连用 5 日;eGFR 为 30-59 mL/min 的成人:150 mg(奈玛特韦)/100 mg(利托那韦),口服,每日两次,连用 5 日
奈玛特韦和利托那韦: eGFR ≥60 mL/min 的成人:300 mg(奈玛特韦)/100 mg(利托那韦),口服,每日两次,连用 5 日;eGFR 为 30-59 mL/min 的成人:150 mg(奈玛特韦)/100 mg(利托那韦),口服,每日两次,连用 5 日
更多 奈玛特韦和利托那韦奈玛特韦/利托那韦可能在部分国家/地区获批用于体重 ≥40 kg 的 12 岁及以上儿童。尚未获批用于 eGFR <30 mL/min 的患者或有严重肝脏损伤的患者。
或
或
remdesivir: 年龄 ≥12 岁和体重 ≥40 kg 的儿童和成人:第 1 天静脉输注 200 mg 作为负荷剂量,而后每 24 小时给予 100 mg,持续 2 天
remdesivir : 年龄 ≥12 岁和体重 ≥40 kg 的儿童和成人:第 1 天静脉输注 200 mg 作为负荷剂量,而后每 24 小时给予 100 mg,持续 2 天
remdesivir: 年龄 ≥12 岁和体重 ≥40 kg 的儿童和成人:第 1 天静脉输注 200 mg 作为负荷剂量,而后每 24 小时给予 100 mg,持续 2 天
更多 remdesivirremdesivir 可能在部分国家/地区获批用于 12 岁以下儿童。然而,尚无充分证据支持常规推荐将其用于 12 岁以下儿童(可根据和危险因素考虑治疗)。
奈玛特韦和利托那韦: eGFR ≥60 mL/min 的成人:300 mg(奈玛特韦)/100 mg(利托那韦),口服,每日两次,连用 5 日;eGFR 为 30-59 mL/min 的成人:150 mg(奈玛特韦)/100 mg(利托那韦),口服,每日两次,连用 5 日
奈玛特韦和利托那韦 : eGFR ≥60 mL/min 的成人:300 mg(奈玛特韦)/100 mg(利托那韦),口服,每日两次,连用 5 日;eGFR 为 30-59 mL/min 的成人:150 mg(奈玛特韦)/100 mg(利托那韦),口服,每日两次,连用 5 日
奈玛特韦和利托那韦: eGFR ≥60 mL/min 的成人:300 mg(奈玛特韦)/100 mg(利托那韦),口服,每日两次,连用 5 日;eGFR 为 30-59 mL/min 的成人:150 mg(奈玛特韦)/100 mg(利托那韦),口服,每日两次,连用 5 日
更多 奈玛特韦和利托那韦奈玛特韦/利托那韦可能在部分国家/地区获批用于体重 ≥40 kg 的 12 岁及以上儿童。尚未获批用于 eGFR <30 mL/min 的患者或有严重肝脏损伤的患者。
或
或
remdesivir: 年龄 ≥12 岁和体重 ≥40 kg 的儿童和成人:第 1 天静脉输注 200 mg 作为负荷剂量,而后每 24 小时给予 100 mg,持续 2 天
remdesivir : 年龄 ≥12 岁和体重 ≥40 kg 的儿童和成人:第 1 天静脉输注 200 mg 作为负荷剂量,而后每 24 小时给予 100 mg,持续 2 天
remdesivir: 年龄 ≥12 岁和体重 ≥40 kg 的儿童和成人:第 1 天静脉输注 200 mg 作为负荷剂量,而后每 24 小时给予 100 mg,持续 2 天
更多 remdesivirremdesivir 可能在部分国家/地区获批用于 12 岁以下儿童。然而,尚无充分证据支持常规推荐将其用于 12 岁以下儿童(可根据和危险因素考虑治疗)。
奈玛特韦和利托那韦
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
或
莫努匹韦
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
或
remdesivir
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
针对特定患者群中所有患者的治疗建议
多个专业呼吸科组织的指南均同意,应建议患有哮喘或 COPD 的患者继续按处方使用吸入剂(包括吸入皮质类固醇)(包括吸入皮质类固醇),无论其是否罹患 COVID-19。[857]Global Initiative for Asthma. Global strategy for asthma management and prevention. 2022 [internet publication] https://ginasthma.org/gina-reports [858]British Thoracic Society. Advice for healthcare professionals treating people with asthma (adults) in relation to COVID-19. 2020 [internet publication] https://www.brit-thoracic.org.uk/about-us/covid-19-information-for-the-respiratory-community [859]Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. 2021 [internet publication] https://goldcopd.org/2021-gold-reports [860]National Institute for Health and Care Excellence. COVID-19 rapid guideline: community-based care of patients with chronic obstructive pulmonary disease (COPD). 2020 [internet publication] https://www.nice.org.uk/guidance/ng168 [861]Hasan SS, Capstick T, Zaidi STR, et al. Use of corticosteroids in asthma and COPD patients with or without COVID-19. Respir Med. 2020 Aug-Sep;170:106045 https://www.resmedjournal.com/article/S0954-6111(20)30185-2/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32843175?tool=bestpractice.com
继续吸入皮质类固醇治疗的总体目标是降低哮喘或 COPD 加重的风险。[861]Hasan SS, Capstick T, Zaidi STR, et al. Use of corticosteroids in asthma and COPD patients with or without COVID-19. Respir Med. 2020 Aug-Sep;170:106045 https://www.resmedjournal.com/article/S0954-6111(20)30185-2/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32843175?tool=bestpractice.com
尚无证据表明吸入皮质类固醇与哮喘患者的 COVID-19 感染有关。[862]Centre for Evidence-Based Medicine; Hartmann-Boyce J, Hobbs R. Inhaled steroids in asthma during the COVID-19 outbreak. 2020 [internet publication] https://www.cebm.net/covid-19/inhaled-steroids-in-asthma-during-the-covid-19-outbreak 也无证据表明它们会增加 COPD 患者的 COVID-19 相关风险。[860]National Institute for Health and Care Excellence. COVID-19 rapid guideline: community-based care of patients with chronic obstructive pulmonary disease (COPD). 2020 [internet publication] https://www.nice.org.uk/guidance/ng168
居家或在医院接受诊疗的急症患者可能会对其被给予的 COPD 或哮喘吸入器遗忘向您告知。酌情谨记对吸入器进行检查以及给予药物。
许多吸入器含有多种药物,因此应确保勿重复给药。
对于出现急性肾损伤的 COPD 或哮喘患者,如果估算 GFR <50 mL/(min·1.73m²),可能需要暂时停用其常用的吸入性长效毒蕈碱受体拮抗剂,具体取决于使用哪种特定药物。查阅当地处方集或寻求药师建议。
其他处方药物
患有严重哮喘或 COPD 并使用口服皮质类固醇作为常规维持治疗处方的患者,也应以尽可能低的剂量继续使用这些药物,因为停用这些药物可能会导致其病情恶化。[857]Global Initiative for Asthma. Global strategy for asthma management and prevention. 2022 [internet publication] https://ginasthma.org/gina-reports [860]National Institute for Health and Care Excellence. COVID-19 rapid guideline: community-based care of patients with chronic obstructive pulmonary disease (COPD). 2020 [internet publication] https://www.nice.org.uk/guidance/ng168 [863]National Institute for Health and Care Excellence. COVID-19 rapid guideline: severe asthma. 2020 [internet publication] https://www.nice.org.uk/guidance/ng166
英国国家卫生与临床优化研究所关于严重哮喘的快速指南建议,在 COVID-19 大流行期间,常规使用生物治疗哮喘的患者应继续使用该药物,但是,若其罹患 COVID-19,则应联系负责其诊疗的专科医生团队。[863]National Institute for Health and Care Excellence. COVID-19 rapid guideline: severe asthma. 2020 [internet publication] https://www.nice.org.uk/guidance/ng166
针对特定患者群中所有患者的治疗建议
世界卫生组织建议,于 COVID-19 患者,不应例行停用降压药,而应根据患者临床情况(尤其是血压和肾功能)进行调整。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
尽管担心使用 ACE 抑制剂或血管紧张素 Ⅱ 受体拮抗剂的患者出现感染风险或患更严重疾病的风险增加,但一项正在进行的系统评价发现,高确定性证据表明此类药物的使用与重症不具相关性。[868]Mackey K, King VJ, Gurley S, et al. Risks and impact of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers on SARS-CoV-2 infection in adults: a living systematic review. Ann Intern Med. 2020 Aug 4;173(3):195-203 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249560 http://www.ncbi.nlm.nih.gov/pubmed/32422062?tool=bestpractice.com [869]Mackey K, Kansagara D, Vela K. Update alert 7: risks and impact of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers on SARS-CoV-2 infection in adults. Ann Intern Med. 2021 Feb;174(2):W25-9 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791405 http://www.ncbi.nlm.nih.gov/pubmed/33395346?tool=bestpractice.com
一些专业学会建议,已经使用这些药物(例如用于治疗高血压、心力衰竭、冠状动脉疾病、CKD 或糖尿病并发症的药物)的患者可以在大流行期间继续使用(前提是其未罹患 COVID-19)。如果患者罹患 COVID-19,建议他们在决定停用此类药物之前接受医生全面临床评估。[870]American Heart Association; Heart Failure Society of America; American College of Cardiology. Patients taking ACE-i and ARBs who contract COVID-19 should continue treatment, unless otherwise advised by their physician. 2020 [internet publication] https://newsroom.heart.org/news/patients-taking-ace-i-and-arbs-who-contract-covid-19-should-continue-treatment-unless-otherwise-advised-by-their-physician [871]European Society of Cardiology Council on Hypertension. Position statement of the ESC Council on Hypertension on ACE-inhibitors and angiotensin receptor blockers. 2020 [internet publication] https://www.escardio.org/Councils/Council-on-Hypertension-(CHT)/News/position-statement-of-the-esc-council-on-hypertension-on-ace-inhibitors-and-ang [872]British Cardiovascular Society; British Society for Heart Failure. BSH & BCS joint statement on ACEi or ARB in relation to COVID-19. 2020 [internet publication] https://www.britishcardiovascularsociety.org/news/ACEi-or-ARB-and-COVID-19 [873]The Renal Association. The Renal Association, UK position statement on COVID-19 and ACE inhibitor/angiotensin receptor blocker use. 2020 [internet publication] https://renal.org/health-professionals/covid-19/ra-resources/renal-association-uk-position-statement-covid-19-and-ace
英国肾脏协会(Renal Association)和英国心血管学会(British Cardiovascular Society)建议,在权衡这些药物对疑似 COVID-19 患者的益处和风险时,遵循当前针对患任何并发急性疾病的患者的标准指导。[872]British Cardiovascular Society; British Society for Heart Failure. BSH & BCS joint statement on ACEi or ARB in relation to COVID-19. 2020 [internet publication] https://www.britishcardiovascularsociety.org/news/ACEi-or-ARB-and-COVID-19 [873]The Renal Association. The Renal Association, UK position statement on COVID-19 and ACE inhibitor/angiotensin receptor blocker use. 2020 [internet publication] https://renal.org/health-professionals/covid-19/ra-resources/renal-association-uk-position-statement-covid-19-and-ace [874]Clark AL, Kalra PR, Petrie MC, et al. Change in renal function associated with drug treatment in heart failure: national guidance. Heart. 2019 Jun;105(12):904-10 http://www.ncbi.nlm.nih.gov/pubmed/31118203?tool=bestpractice.com 其中包括:
进行个体临床评估
对所有肾素-血管紧张素-醛固酮系统(renin-angiotensin-aldosterone system, RAAS)拮抗剂 初始适应症加以考虑(ACE 抑制剂、血管紧张素-Ⅱ 受体拮抗剂、盐皮质激素受体/醛固酮拮抗剂),并对预后获益程度加以考虑
如果暂时停止药物治疗,需考虑健康状况得到改善后何时再次给药。
考虑计算脆弱评分,因为脆弱评分较高的患者,突发不适时更可能受到药物相关性伤害(基于专家意见)。
考虑停用其他在并发疾病期间与急性肾损伤风险增加相关药物的获益与风险,例如其他抗高血压药和利尿药。
如果慢性肾病患者一直在使用非甾体抗炎药,建议他们在并发疾病时停用此类药物。
在社区自我管理心力衰竭的患者可能希望在出现可能导致脱水的并发疾病期间减少利尿药剂量 (基于专家意见)。
如果患者病情复杂(例如正在进行肾脏替代治疗或免疫抑制治疗),可向患者心脏病学团队或肾病学团队寻求建议 。
针对特定患者群中所有患者的治疗建议
对于有卒中病史,且因急性疾病(包括 COVID-19)入院的患者,应在适当时机尽早进行基线神经系统评估。
通常,患有急性疾病(例如感染和疾病相关性低血压)的患者卒中(缺血性和出血性)风险增加。[892]Grau AJ, Urbanek C, Palm F. Common infections and the risk of stroke. Nat Rev Neurol. 2010 Nov 9;6(12):681-94 http://www.ncbi.nlm.nih.gov/pubmed/21060340?tool=bestpractice.com [893]Eigenbrodt ML, Rose KM, Couper DJ, et al. Orthostatic hypotension as a risk factor for stroke: the atherosclerosis risk in communities (ARIC) study, 1987-1996. Stroke. 2000 Oct;31(10):2307-13 https://www.doi.org/10.1161/01.str.31.10.2307 http://www.ncbi.nlm.nih.gov/pubmed/11022055?tool=bestpractice.com 有卒中病史的患者风险更高。
将基线评估结果与患者已知的 COVID-19 前神经系统状态进行比较。可通过询问患者、家属和照护者关于患者患病前的功能能力了解这一情况(基于专家意见)。
这样可以降低将入院时的神经系统体征错误归因于既往诊断卒中的风险。
如果住院期间神经系统状况发生变化,重复进行神经系统评估,以防再次发生卒中。
评估之后,确保对患者进行适当的监护(例如夜间意识模糊的风险和与体弱相关的跌倒风险)。
有卒中病史的患者跌倒和受伤的风险增加。[894]Winstein CJ, Stein J, Arena R, et al. Guidelines for adult stroke rehabilitation and recovery: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2016 May 4;47(6):e98-e169 https://www.doi.org/10.1161/STR.0000000000000098 http://www.ncbi.nlm.nih.gov/pubmed/27145936?tool=bestpractice.com
世界卫生组织建议密切监测 COVID-19 住院患者的临床恶化迹象,包括卒中征象或症状。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
见诸报道的 COVID-19 相关性神经系统表现包括急性缺血性和出血性卒中。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
针对特定患者群中所有患者的治疗建议
对于因急性病症入院,并有痴呆病史的任何患者,尽早进行基线认知评估。从家人、朋友或照护者处获取他人陈述病史。[895]Pendlebury ST, Klaus SP, Mather M, et al. Routine cognitive screening in older patients admitted to acute medicine: abbreviated mental test score (AMTS) and subjective memory complaint versus Montreal Cognitive Assessment and IQCODE. Age Ageing. 2015 Nov;44(6):1000-5 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621235 http://www.ncbi.nlm.nih.gov/pubmed/26464420?tool=bestpractice.com
使用在急症情况下可行的、经过验证的评分系统,例如:[895]Pendlebury ST, Klaus SP, Mather M, et al. Routine cognitive screening in older patients admitted to acute medicine: abbreviated mental test score (AMTS) and subjective memory complaint versus Montreal Cognitive Assessment and IQCODE. Age Ageing. 2015 Nov;44(6):1000-5 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621235 http://www.ncbi.nlm.nih.gov/pubmed/26464420?tool=bestpractice.com
简易智能测验评分/10(AMTS/10)。[896]Hodkinson HM. Evaluation of a mental test score for assessment of mental impairment in the elderly. Age Ageing. 1972 Nov;1(4):233-8 http://www.ncbi.nlm.nih.gov/pubmed/4669880?tool=bestpractice.com British Geriatrics Society: Abbreviated Mental Test Score. 2018 在新窗口中打开
旁证病史可确定患者的认知是否稳定,或者认知和功能是逐渐下降还是急性下降。
标准化认知评估评分将有助于监测所有临床改善, 以及确定出院需求。判读该分数时,最好结合功能评估(通常由经过培训的职业治疗师进行)。
每当痴呆患者出现急性疾病时都要进行谵妄评估。[897]National Institute for Health and Care Excellence. Delirium: prevention, diagnosis and management. 2019 [internet publication] https://www.nice.org.uk/guidance/CG103 世界卫生组织建议对 COVID-19 患者通过标准方案进行谵妄评估。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
伴痴呆者入院时和整个住院期间发生谵妄的风险增加。[898]National Institute for Health and Clinical Excellence. Dementia: assessment, management and support for people living with dementia and their carers. 2018 [internet publication] https://www.nice.org.uk/guidance/ng97 [899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium
谵妄与痴呆不同。[900]Nova Scotia Health Authority. This is not my Mom. 2012 [internet publication] https://www.thisisnotmymom.ca [901]Inouye SK, Schlesinger MJ, Lydon TJ. Delirium: a symptom of how hospital care is failing older persons and a window to improve quality of hospital care. Am J Med. 1999 May;106(5):565-73 http://www.ncbi.nlm.nih.gov/pubmed/10335730?tool=bestpractice.com 谵妄是指精神功能出现潜在致死性的急性波动性改变,伴有注意力缺乏、思维混乱和意识水平的改变。[901]Inouye SK, Schlesinger MJ, Lydon TJ. Delirium: a symptom of how hospital care is failing older persons and a window to improve quality of hospital care. Am J Med. 1999 May;106(5):565-73 http://www.ncbi.nlm.nih.gov/pubmed/10335730?tool=bestpractice.com
使用筛查工具检测可能出现的谵妄,例如:
The 4-AT 在新窗口中打开。[899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium [902]Bellelli G, Morandi A, Davis DH, et al. Validation of the 4AT, a new instrument for rapid delirium screening: a study in 234 hospitalised older people. Age Ageing. 2014 Jul;43(4):496-502 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066613 http://www.ncbi.nlm.nih.gov/pubmed/24590568?tool=bestpractice.com [903]MacLullich AM, Shenkin SD, Goodacre S, et al. The 4 'A's test for detecting delirium in acute medical patients: a diagnostic accuracy study. Health Technol Assess. 2019 Aug;23(40):1-194 https://www.journalslibrary.nihr.ac.uk/hta/hta23400#/abstract http://www.ncbi.nlm.nih.gov/pubmed/31397263?tool=bestpractice.com
伴痴呆者可出现沟通困难,因此更难报告 COVID-19 相关性症状。他们最初的表现可能为谵妄征象。[904]Public Health England. Coronavirus (COVID-19): admission and care of people in care homes. 2020 [internet publication] https://www.gov.uk/government/publications/coronavirus-covid-19-admission-and-care-of-people-in-care-homes
对于患有任何急性疾病的痴呆患者,考虑采取以下措施,作为入院期间降低谵妄风险的多元化诊疗一部分:[899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium [905]British Geriatrics Society. Coronavirus: managing delirium in confirmed and suspected cases. 2020 [internet publication] https://www.bgs.org.uk/resources/coronavirus-managing-delirium-in-confirmed-and-suspected-cases
帮助患者定向;确保患者有自己的眼镜和/或助听器
使患者尽早开始活动
充分控制疼痛
及时发现并治疗重叠感染
保证水的摄入量,并帮助患者充分进食
监测并维持正常的肠道和膀胱功能
根据指南的建议给予氧疗。
安排与经验丰富的医疗卫生专业人士一起进行用药评估。[899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium
与 COVID-19 尤其相关的挑战包括:[905]British Geriatrics Society. Coronavirus: managing delirium in confirmed and suspected cases. 2020 [internet publication] https://www.bgs.org.uk/resources/coronavirus-managing-delirium-in-confirmed-and-suspected-cases
隔离需要,这可能会加重部分患者的谵妄
对患者谵妄进行定期监测的能力,可能受人员配置和可用时间资源影响。
针对谵妄患者的初始检查
如果患者出现谵妄,请检查并治疗危及生命的病因:[899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium
缺氧
低血糖
低血压
药物中毒或戒断,包括酒精戒断。
其他检查包括(基于专家意见):
全血细胞计数、电解质、肾功能、甲状腺功能检测、肝功能检测、钙、血糖、CRP、叶酸和维生素 B12
血培养(如果怀疑菌血症)
尿培养
胸部 X 线。
根据具体临床发现,可能需要进行更高级的非常规检查,例如头颅 CT。请与上级医生讨论。[899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium
检查并治疗谵妄的所有可逆病因。[897]National Institute for Health and Care Excellence. Delirium: prevention, diagnosis and management. 2019 [internet publication] https://www.nice.org.uk/guidance/CG103 其中包括:
感染
疼痛
脱水
便秘
制动
睡眠差
感觉受损(如耵聍或眼镜丢失)
药物治疗
询问最近开的处方药,特别是阿片类镇痛药、抗焦虑药、镇静剂、抗精神病药物或抗胆碱能作用强的药物
考虑计算抗胆碱能药物总负担得分。
如果可能,首先按照推荐用于非 COVID-19 情境下谵妄管理的非药物治疗管理谵妄患者。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1 [897]National Institute for Health and Care Excellence. Delirium: prevention, diagnosis and management. 2019 [internet publication] https://www.nice.org.uk/guidance/CG103
通过提供一个光线充足的房间,且将时钟和日历放置在显眼位置(例如挂在墙上),可减轻定向障碍。
基于当前社区 COVID-19 传播水平,在当地探视政策允许的情况下,鼓励并促进家人、朋友和照护者探视患者。
使用语言和非语言技巧减轻冲突和苦恼。
如果非药物治疗无效,并且患者感到痛苦或可能对自己或他人构成危险,可以考虑短期(通常仅需要 1-2 天)使用抗精神病药物或镇静剂,但只能作为最后的治疗手段。必须定期评估为此目的新开的任何抗精神病药物,并在实际情况允许时停药(基于专家意见)。
英国老年医学会(British Geriatrics Society)指出,在管理 COVID-19 患者时,药物治疗可能需要早于在其他情况下通常考虑的时间,因为感染传播对他人造成伤害的风险可能大于对个人造成潜在伤害的风险。[905]British Geriatrics Society. Coronavirus: managing delirium in confirmed and suspected cases. 2020 [internet publication] https://www.bgs.org.uk/resources/coronavirus-managing-delirium-in-confirmed-and-suspected-cases
英国国家卫生与临床优化研究所关于谵妄的指南(在未患 COVID-19 的情况下)建议短期使用氟哌啶醇(通常少于 1 周),但这并不适合所有患者,并且绝不能用于帕金森病或路易体痴呆患者。[897]National Institute for Health and Care Excellence. Delirium: prevention, diagnosis and management. 2019 [internet publication] https://www.nice.org.uk/guidance/CG103
NICE COVID-19 管理快速指南亦建议将氟哌啶醇作为可完成吞咽动作的 COVID-19 患者谵妄药物治疗的一种选择。[839]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication] https://www.nice.org.uk/guidance/ng191
抗精神病药物治疗谵妄的有效性证据尚无定论,并且医院方案可能各有不同。[899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium 遵循当地医院的方案选择药物。
始终从最低剂量开始服用抗精神病药,并依据症状谨慎地逐渐调整剂量。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1 [897]National Institute for Health and Care Excellence. Delirium: prevention, diagnosis and management. 2019 [internet publication] https://www.nice.org.uk/guidance/CG103 只能通过口服或肌内注射药物(绝对不可静脉注射)对此进行治疗。(基于专家意见)。
向家庭/照护者提供信息,以便他们了解当前的情况以及如何与临床团队协作以帮助患者恢复正常生活。[899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium 提供本地可用信息资源。[905]British Geriatrics Society. Coronavirus: managing delirium in confirmed and suspected cases. 2020 [internet publication] https://www.bgs.org.uk/resources/coronavirus-managing-delirium-in-confirmed-and-suspected-cases
抗精神病药物与痴呆患者死亡率增加相关。
痴呆患者有时可能需要短期抗精神病药物以实现安全疗护。然而,抗精神病药物对老年人有多种不良作用,并与痴呆患者死亡风险增加相关。
一项 meta 分析发现,与服用安慰剂的人相比,服用非典型抗精神病药的痴呆患者死亡风险增加。[906]Ma H, Huang Y, Cong Z, et al. The efficacy and safety of atypical antipsychotics for the treatment of dementia: a meta-analysis of randomized placebo-controlled trials. J Alzheimers Dis. 2014;42(3):915-37 http://www.ncbi.nlm.nih.gov/pubmed/25024323?tool=bestpractice.com
一项针对老年人的大型队列研究发现,更高剂量的抗精神病药通常与更高的风险相关。在所有研究的抗精神病药中,使用氟哌啶醇的风险最高。[907]Huybrechts KF, Gerhard T, Crystal S, et al. Differential risk of death in older residents in nursing homes prescribed specific antipsychotic drugs: population based cohort study. BMJ. 2012 Feb 23;344:e977 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285717 http://www.ncbi.nlm.nih.gov/pubmed/22362541?tool=bestpractice.com
与普遍的看法相反,大多数痴呆患者的行为稳定后,就可以安全地停止长期抗精神病药处方。[908]Van Leeuwen E, Petrovic M, van Driel ML, et al. Withdrawal versus continuation of long-term antipsychotic drug use for behavioural and psychological symptoms in older people with dementia. Cochrane Database Syst Rev. 2018 Mar 30;(3):CD007726 https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007726.pub3/full http://www.ncbi.nlm.nih.gov/pubmed/29605970?tool=bestpractice.com
如果谵妄在 48 小时内未对初始治疗产生反应,转诊至在谵妄诊断方面经过培训且具备技能的医疗卫生专业人士,以确认诊断和治疗计划(基于专家意见)。
清楚记录谵妄的诊断。[897]National Institute for Health and Care Excellence. Delirium: prevention, diagnosis and management. 2019 [internet publication] https://www.nice.org.uk/guidance/CG103 [899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium
针对特定患者群中所有患者的治疗建议
哮喘加重与 COVID-19 临床可能难以区分,其可能同时出现。两者的共同特征是咳嗽和呼吸短促;但是,发热、疲劳以及味觉或嗅觉改变等其他症状更可能提示 COVID-19。[858]British Thoracic Society. Advice for healthcare professionals treating people with asthma (adults) in relation to COVID-19. 2020 [internet publication] https://www.brit-thoracic.org.uk/about-us/covid-19-information-for-the-respiratory-community
监测呼吸道症状急性恶化症状,并意识到这可能提示患者合并哮喘,正在出现哮喘急性发作。
寻求上级医生建议。
即使怀疑 COVID-19 为诱因,亦应对成人哮喘急性发作严重程度评估和管理遵循标准指南建议。[865]British Thoracic Society; Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma: a national clinical guideline. 2019 [internet publication] https://www.brit-thoracic.org.uk/quality-improvement/guidelines/asthma [909]Centers for Disease Control and Prevention. Clinical questions about COVID-19: questions and answers – patients with asthma. 2020 [internet publication] https://www.cdc.gov/coronavirus/2019-ncov/hcp/faq.html#Patients-with-Asthma
参阅成人哮喘急性发作主题。
考虑临床情况是否适宜使用定量吸入器(通过储雾罐装置输送)作为替代给药机制。[847]Global Initiative for Asthma. Global strategy for asthma management and prevention. 2021 [internet publication] https://ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf 遵循当地常规。
根据临床指征起始口服皮质类固醇治疗哮喘加重。[858]British Thoracic Society. Advice for healthcare professionals treating people with asthma (adults) in relation to COVID-19. 2020 [internet publication] https://www.brit-thoracic.org.uk/about-us/covid-19-information-for-the-respiratory-community [861]Hasan SS, Capstick T, Zaidi STR, et al. Use of corticosteroids in asthma and COPD patients with or without COVID-19. Respir Med. 2020 Aug-Sep;170:106045 https://www.resmedjournal.com/article/S0954-6111(20)30185-2/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32843175?tool=bestpractice.com
如果给予患者雾化吸入短效毒蕈碱受体拮抗剂(例如异丙托溴铵),则应暂时停用患者可能正在使用的任何用于维持治疗的长效毒蕈碱受体拮抗剂(long-acting muscarinic receptor antagonist, LAMA)(例如噻托溴铵、aclidinium、格隆溴铵、乌美溴铵 (基于专家意见)。
因为担心可能会出现抗胆碱能成瘾的不良反应。
一旦停止给予雾化治疗,需再给予 LAMA 药物治疗。
目前,对于使用雾化剂是否会产生气溶胶,以及是否因此需使用特定个人防护装备,不同国家组织之间存在不同看法。[847]Global Initiative for Asthma. Global strategy for asthma management and prevention. 2021 [internet publication] https://ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf [863]National Institute for Health and Care Excellence. COVID-19 rapid guideline: severe asthma. 2020 [internet publication] https://www.nice.org.uk/guidance/ng166 请遵循当地指南和常规。
针对特定患者群中所有患者的治疗建议
如果 COVID-19 和固有 COPD 患者可疑 COPD 加重,遵循患者个体化行动预案。[910]National Institute for Health and Care Excellence. COVID-19 rapid guideline: community-based care of patients with chronic obstructive pulmonary disease (COPD). 2020 [internet publication] https://www.nice.org.uk/guidance/ng168
与其他疾患进行鉴别,如急性冠脉综合征、急性心力衰竭和肺炎,以及 COVID-19 并发症。
对于 COPD 加重的管理,遵循既定指南,包括具备临床指征时,给予短期口服皮质类固醇。[859]Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. 2021 [internet publication] https://goldcopd.org/2021-gold-reports [861]Hasan SS, Capstick T, Zaidi STR, et al. Use of corticosteroids in asthma and COPD patients with or without COVID-19. Respir Med. 2020 Aug-Sep;170:106045 https://www.resmedjournal.com/article/S0954-6111(20)30185-2/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32843175?tool=bestpractice.com 请参阅 COPD 急性加重专题。
寻求上级医生或专科医生建议。
目前,对于使用雾化剂是否会产生气溶胶,以及是否因此需使用特定个人防护装备,不同国家组织之间存在不同看法。[859]Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. 2021 [internet publication] https://goldcopd.org/2021-gold-reports [863]National Institute for Health and Care Excellence. COVID-19 rapid guideline: severe asthma. 2020 [internet publication] https://www.nice.org.uk/guidance/ng166 对于未接受通气支持的非危重患者,考虑使用加压定量吸入器、干粉吸入器,或软雾吸入器进行药物输送。[859]Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. 2021 [internet publication] https://goldcopd.org/2021-gold-reports 请遵循当地指南和常规。
如果使用雾化器,支气管舒张剂雾化吸入疗法应仅持续 24 至 48 小时,然后患者应换回他们常用的吸入器。
如果为患者开处雾化吸入短效毒蕈碱受体拮抗剂(例如异丙托铵),则应暂时停止患者可能正在使用的任何用于维持治疗的长效毒蕈碱受体拮抗剂(long-acting muscarinic receptor antagonist, LAMA,例如噻托溴铵、aclidinium、格隆溴铵、乌美溴铵)(基于专家意见)。这是因为担心可能会出现叠加性抗胆碱能不良反应。
一旦停止雾化剂治疗,请确保重新给予 LAMA。
针对特定患者群中所有患者的治疗建议
对于任何急症糖尿病患者,每天至少监测血糖水平四次(餐前以及睡前 [如果进食])。[911]American Diabetes Association. Diabetes care in the hospital: standards of medical care in diabetes - 2021. Diabetes Care. 2021 Jan;44(Suppl 1):S211-20 https://care.diabetesjournals.org/content/44/Supplement_1/S211.long http://www.ncbi.nlm.nih.gov/pubmed/33298426?tool=bestpractice.com
对于患有糖尿病的 COVID-19 住院患者,遵循当地血糖监测常规。
对于患急性疾病的糖尿病住院患者目标血糖水平,目前尚未达成共识。
英国糖尿病学会联合会住院患者诊疗小组(Joint British Diabetes Societies for Inpatient Care, JBDS-IP)建议内科住院患者理想范围为 6 至 10 mmol/L(108-180 mg/dL),可接受上限为 12 mmol/L(216 mg/dL)。[912]Joint British Diabetes Societies for inpatient care. The use of variable rate intravenous insulin infusion (VRIII) in medical inpatients. 2014 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/JBDS_Guidelines_Current/JBDS_09_IP_VRIII.pdf 如果患者具有较高的跌倒风险、机体衰弱或患有痴呆,则认为适宜采用更宽松的血糖目标。[912]Joint British Diabetes Societies for inpatient care. The use of variable rate intravenous insulin infusion (VRIII) in medical inpatients. 2014 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/JBDS_Guidelines_Current/JBDS_09_IP_VRIII.pdf [913]Joint British Diabetes Societies for inpatient care. Inpatient care of the frail older adult with diabetes. 2019 [internet publication] https://www.diabetes.org.uk/resources-s3/2019-10/frailty-jbds-ipfinal-28-10-19.pdf
英国国家糖尿病住院患者 COVID-19 应对小组(National Inpatient Diabetes COVID-19 Response Group)对 COVID-19 住院患者提出了相同的建议。[914]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): guidance for managing inpatient hyperglycaemia. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/resources/COvID_Hyper_v4.2.pdf
一个国际专家组的共识指南建议将 COVID-19 患者的目标水平设为 4-10 mmol/L(72-180 mg/dL),但将衰弱患者的目标水平下限调整为 5 mmol/L(90 mg/dL)。[889]Bornstein SR, Rubino F, Khunti K, et al. Practical recommendations for the management of diabetes in patients with COVID-19. Lancet Diabetes Endocrinol. 2020 Jun;8(6):546-50 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180013 http://www.ncbi.nlm.nih.gov/pubmed/32334646?tool=bestpractice.com
美国糖尿病学会建议,对于大多数危重患者和非危重患者,目标范围为 7.8 至 10 mmol/L(140-180 mg/dL)(一旦因持续性高血糖起始胰岛素治疗;并非特别针对 COVID-19)。[911]American Diabetes Association. Diabetes care in the hospital: standards of medical care in diabetes - 2021. Diabetes Care. 2021 Jan;44(Suppl 1):S211-20 https://care.diabetesjournals.org/content/44/Supplement_1/S211.long http://www.ncbi.nlm.nih.gov/pubmed/33298426?tool=bestpractice.com
对高血糖进行治疗,避免糖尿病酮症酸中毒(diabetic ketoacidosis, DKA)和高渗性高血糖状态(hyperosmolar hyperglycaemic state, HHS),两者均为内科急症。
若患者毛细血管血糖 ≥12 mmol/L(≥216 mg/dL),应遵循当地医院常规。
COVID-19 指南通常强调高血糖管理的重要性。[884]Hartmann-Boyce J, Morris E, Goyder C, et al. Diabetes and COVID-19: risks, management, and learnings from other national disasters. Diabetes Care. 2020 Aug;43(8):1695-703 https://care.diabetesjournals.org/content/43/8/1695 http://www.ncbi.nlm.nih.gov/pubmed/32546593?tool=bestpractice.com
排除 DKA 或 HHS, 两者均需给予特定紧急处理。
考虑高血糖相关性其他病症,例如脓毒症。[883]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19: front door guidance. 2020 [internet publication] https://abcd.care/resource/concise-advice-inpatient-diabetes-during-covid-19-front-door-guidance
需注意,以下药物可能与高血糖具有相关性,可能需要进行评估:[915]Rehman A, Setter SM, Vue MH. Drug-induced glucose alterations part 2: drug-induced hyperglycemia. Diabetes Spect. 2011 Nov;24(4):234-8 https://spectrum.diabetesjournals.org/content/24/4/234
皮质类固醇(例如地塞米松)
部分 β 受体阻滞剂(如普萘洛尔、阿替洛尔)
噻嗪类利尿剂(例如氢氯噻嗪)
部分第二代抗精神病药物(如奥氮平、氯氮平)
某些氟喹诺酮类抗生素(如环丙沙星)
钙调磷酸酶抑制剂(如环孢素、他克莫司)
蛋白酶抑制剂(例如,作为抗逆转录病毒治疗的一部分,洛匹那韦/利托那韦可用于治疗某些 COVID-19 患者)。
部分用于 COVID-19 的试验性药物可能与高血糖具有相关性或因果关系。为糖尿病患者开具此类治疗处方之前,查看当地药物处方集,以获取更多信息。
如果患者血糖持续升高,他们可能需给予胰岛素治疗(静脉或皮下给药常规)。对于 COVID-19 患者高血糖管理,遵循当地常规。
重症监护病房(intensive care unit, ICU)外可能不提供输液泵装置,具体取决于其他地方对这些设备的需求。在这种情况下,部分方案建议,对于高血糖和轻度 DKA 管理,可给予替代性皮下给药。[914]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): guidance for managing inpatient hyperglycaemia. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/resources/COvID_Hyper_v4.2.pdf [916]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): guideline for managing DKA using subcutaneous insulin. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/resources/COvID_DKA_SC_v3.3.pdf
请注意,ICU 内的 2 型糖尿病患者可能存在显著胰岛素抵抗。[914]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): guidance for managing inpatient hyperglycaemia. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/resources/COvID_Hyper_v4.2.pdf
向住院患者糖尿病团队询问专家意见。
监测血糖并根据病情和住院就餐时间 调整用药,从而降低低血糖发作风险。
大约 1/5 英格兰和威尔士糖尿病住院患者在住院期间发生过低血糖。[917]NHS Digital. National diabetes inpatient audit (NaDIA) - 2019. 2020 [internet publication] https://digital.nhs.uk/data-and-information/publications/statistical/national-diabetes-inpatient-audit/2019
低血糖原因包括:[918]Joint British Diabetes Societies for inpatient care. The hospital management of hypoglycaemia in adults with diabetes mellitus. 5th ed. 2021 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/JBDS_01_Hypo_Guideline_FINAL_23042021_0.pdf
在急症中恢复
COVID-19 恢复患者可能出现胰岛素需求快速改变,因此谨慎监测和调整胰岛素用药方案[914]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): guidance for managing inpatient hyperglycaemia. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/resources/COvID_Hyper_v4.2.pdf
患者进食意外中断,COVID-19 患者以俯卧位接受护理时尤易出现[914]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): guidance for managing inpatient hyperglycaemia. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/resources/COvID_Hyper_v4.2.pdf
COVID-19 患者减少皮质类固醇剂量(特别是地塞米松)[914]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): guidance for managing inpatient hyperglycaemia. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/resources/COvID_Hyper_v4.2.pdf
胰岛素或口服降糖药用药错误
与进食有关的胰岛素给药时间错误
患者摄食较少,但却服用等量糖尿病药物
不享用睡前加餐
食欲减退或呕吐。
部分用于 COVID-19 的试验性药物可能与低血糖具有相关性(或具有因果关系)。为糖尿病患者开具此类治疗处方之前,查看当地药物处方集,以获取更多信息。
请注意,如果患者错过进餐或用药剂量过大,低血糖更易作为磺脲类药物不良反应出现(例如格列本脲、格列齐特、格列美脲、格列吡嗪)。
在急症医院环境中,餐时有可能被打乱,或无法每天同一时间进餐。
应在进食前或进食时给予磺脲类药物。查看当地药物处方集获取更为具体的指导信息,了解特定磺脲类药物给药时间与进食时间的关系。
切勿在睡前服用磺脲类药物,如果患者要在晚餐时服用一次,应考虑减少晚间剂量,以降低夜间低血糖发生风险(基于专家意见)。
睡前加餐可降低清晨低血糖风险。[917]NHS Digital. National diabetes inpatient audit (NaDIA) - 2019. 2020 [internet publication] https://digital.nhs.uk/data-and-information/publications/statistical/national-diabetes-inpatient-audit/2019
如果血糖低于 4 mmol/L(72 mg/dL),应积极治疗低血糖。 [918]Joint British Diabetes Societies for inpatient care. The hospital management of hypoglycaemia in adults with diabetes mellitus. 5th ed. 2021 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/JBDS_01_Hypo_Guideline_FINAL_23042021_0.pdf 请遵循医院方案。JBDS-IP 指南建议:[918]Joint British Diabetes Societies for inpatient care. The hospital management of hypoglycaemia in adults with diabetes mellitus. 5th ed. 2021 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/JBDS_01_Hypo_Guideline_FINAL_23042021_0.pdf
10 至 15 分钟后重新检测血糖,确定治疗反应
如果低血糖已经纠正,切勿停止胰岛素的下一次给药计划。否则会导致 1 型糖尿病患者出现反弹性高血糖和 DKA。
住院患者应遵循当地常规和血糖自我监测指南。
相关内容可能已针对 COVID-19 患者进行了修改。例如,美国部分医院一直在使用“虚拟”模式,包括扩充自我管理方案,以减少对个人防护装备的需求(在安全的情况下)。[884]Hartmann-Boyce J, Morris E, Goyder C, et al. Diabetes and COVID-19: risks, management, and learnings from other national disasters. Diabetes Care. 2020 Aug;43(8):1695-703 https://care.diabetesjournals.org/content/43/8/1695 http://www.ncbi.nlm.nih.gov/pubmed/32546593?tool=bestpractice.com
针对特定患者群中所有患者的治疗建议
成人糖尿病患者在入院时,或似乎更加不适时,均应对其足部进行检查。[919]National Institute for Health and Care Excellence. Diabetic foot problems: prevention and management. 2019 [internet publication] https://www.nice.org.uk/guidance/ng19 这也是针对因 COVID-19 入院的糖尿病成人患者的建议。[883]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19: front door guidance. 2020 [internet publication] https://abcd.care/resource/concise-advice-inpatient-diabetes-during-covid-19-front-door-guidance
需行足部检查,发现新发溃疡或感染,其可能被患者忽视。
检查足部病损,并检查保护性感觉是否丧失。
遵循当地指南,但有一个快速简单的试验:Ipswich Touch Test©️(伊普斯威奇触摸试验),即用食指指尖轻轻触摸/将其放置在第一、第三和第五趾趾尖上 1 到 2 秒。[920]Rayman G, Vas PR, Baker N, et al. The Ipswich Touch Test: a simple and novel method to identify inpatients with diabetes at risk of foot ulceration. Diabetes Care. 2011 Jul;34(7):1517-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3120164 http://www.ncbi.nlm.nih.gov/pubmed/21593300?tool=bestpractice.com
如果患者在这六个部位中的两个或以上没有感觉,则代表其保护性感觉减退。
如果患者感觉减退,则具有压疮高风险。告知护理人员,并提供减压装置。
护理人员或医疗人员应每日进行踝部检查,注意压力性创伤征象。
对于糖尿病患者是否应该使用弹力袜存在争议 – 如有血管疾病,勿予以使用。
针对特定患者群中所有患者的治疗建议
在临床情况允许以及患者有反应的情况下进行精神状态检查 (基于专家意见)。
精神状态检查是精神病学临床实践中常规使用的主要临床工具之一,有助于诊断和指导进一步的管理。情绪是其中一项评估内容。
考虑使用 PHQ-9 问卷,进行抑郁评估。[921]Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606-13 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1495268 http://www.ncbi.nlm.nih.gov/pubmed/11556941?tool=bestpractice.com
这是一份自填式问卷,只需不到 3 分钟即可完成。
结果可提示抑郁症状的严重程度。
评分 5 分或以上应启动转诊,转至联络精神病学服务机构 (基于专家意见)。
抑郁据报道为 COVID-19 住院患者常见发现。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
考虑可能影响患者精神状态的其他因素(例如违禁药物使用或饮酒的影响)。[922]Boden JM, Fergusson DM. Alcohol and depression. Addiction. 2011 May;106(5):906-14 http://www.ncbi.nlm.nih.gov/pubmed/21382111?tool=bestpractice.com
针对特定患者群中所有患者的治疗建议
询问患者他们正在服用哪些药物治疗抑郁。或查看其初级卫生保健记录,获取相关信息(若可获取)。
药物相互作用及其与 COVID-19 患者尤为相关的不良反应包括镇静、心脏毒性(QT 间期延长),以及呼吸抑制。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
为患者开具其常用的抗抑郁药,除非有充分的理由不得这样做(基于专家意见)。
如果突然停用抗抑郁药,患者可能出现停药症状。[923]Cleare A, Pariante CM, Young AH, et al. Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines. J Psychopharmacol. 2015 May;29(5):459-525 https://www.bap.org.uk/docdetails.php?docID=5 http://www.ncbi.nlm.nih.gov/pubmed/25969470?tool=bestpractice.com
药物停用的症状严重程度 可能各有所异,但可能令人不快,以及可能使急症管理复杂化。[924]National Institute for Health and Care Excellence. Depression in adults with a chronic physical health problem: recognition and management. 2009 [internet publication] https://www.nice.org.uk/guidance/cg91
审评当前药物时,需注意以下情况:
所察觉的当前和既往不良反应
近期用药剂量改变
最近更换了一种不同类别的药物
特定抑郁症亚型的药物细微差别(例如,精神病性抑郁症患者很可能会同时服用抗精神病处方药)
难治性抑郁症治疗中可能需要使用的增强策略(如选择性 5-羟色胺再摄取抑制剂 [selective serotonin-reuptake inhibitor, SSRI])的基础上加用锂剂或喹硫平。
对药物相互作用加以考虑。
抗抑郁药可能会与用于其他疾病的药物发生药代动力学(通过抑制 CYP450 通路)和药效动力学相互作用。[923]Cleare A, Pariante CM, Young AH, et al. Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines. J Psychopharmacol. 2015 May;29(5):459-525 https://www.bap.org.uk/docdetails.php?docID=5 http://www.ncbi.nlm.nih.gov/pubmed/25969470?tool=bestpractice.com [925]Taylor DM, Barnes TRE, Young AH. The Maudsley prescribing guidelines in psychiatry. 14th edition. Chichester: Wiley-Blackwell; 2021 对于为 COVID-19 患者开处的所有药物以及任何实验性治疗(请参阅新兴疗法章节),需考虑此问题。
请注意,戒烟或从吸烟转为任何其他替代方案(包括尼古丁替代疗法)可能导致患者服用的任何精神类药物(例如,用于治疗抑郁的药物)血药浓度发生变化。这是因为尼古丁替代疗法不会像吸烟那样影响肝酶活性。[926]Flowers L. Nicotine replacement therapy. Am J Psychiatry Resid J. 2016 Jun;11(6):4-7 https://psychiatryonline.org/doi/10.1176/appi.ajp-rj.2016.110602 [927]Desai HD, Seabolt J, Jann MW. Smoking in patients receiving psychotropic medications: a pharmacokinetic perspective. CNS Drugs. 2001;15(6):469-94 http://www.ncbi.nlm.nih.gov/pubmed/11524025?tool=bestpractice.com [928]Oliveira P, Ribeiro J, Donato H, et al. Smoking and antidepressants pharmacokinetics: a systematic review. Ann Gen Psychiatry. 2017 Mar 6;16:17 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340025 http://www.ncbi.nlm.nih.gov/pubmed/28286537?tool=bestpractice.com [929]National Centre for Smoking Cessation and Training. Smoking cessation and mental health: a briefing for front-line staff. 2014 [internet publication] https://www.ncsct.co.uk/shopdisp_mental_health_briefing.php 寻求相关建议,确认精神类药物剂量调整是否适当。
开具非精神类药物时,应考虑精神并发症。
给予皮质类固醇、抗惊厥药物和抗帕金森病药物时,应格外小心。
考虑不良反应,具体可能包括以下不良反应。[925]Taylor DM, Barnes TRE, Young AH. The Maudsley prescribing guidelines in psychiatry. 14th edition. Chichester: Wiley-Blackwell; 2021
与三环类抗抑郁药相关的 QT 间期延长、心律失常、心率加快或体位性低血压。进行 ECG 检查,特别是有心律失常风险的人群。
低钠血症,由抗抑郁药(尤其是 SSRI)引起,并因其他同时开具的药物(例如利尿药)加重。检查患者的血清电解质。
5-羟色胺综合征(精神状态改变、激越、震颤、反射亢进、阵挛、肌强直、大量出汗、心动过速、肠鸣音增加、体温 >38℃),尤其是在多重用药和/或 5-羟色胺能药物过量时。[930]Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005 Mar 17;352(11):1112-20 https://www.doi.org/10.1056/NEJMra041867 http://www.ncbi.nlm.nih.gov/pubmed/15784664?tool=bestpractice.com [931]Buckley NA, Dawson AH, Isbister GK. Serotonin syndrome. BMJ. 2014 Feb 19;348:g1626 http://www.ncbi.nlm.nih.gov/pubmed/24554467?tool=bestpractice.com
特别要注意的是,服用 SSRI 的终末期肾病患者出现 5-羟色胺综合征的风险增加。治疗肾脏损伤患者的抑郁需要采取多学科方法,并需要格外谨慎。
肝毒性。必要时调整肝功能受损患者的抗抑郁药物剂量,避免使用已知具有肝毒性的药物。
该不良反应和药物相互作用表单并不详尽 – 参阅当地处方集,获取更多信息。咨询联络精神病学同事和/或药剂师,获取建议。
尽可能向患者询问其采用哪些非药物治疗方法处理抑郁,并检查其在社区获得的支持情况。
其可包括参与其照护的其他医疗卫生专业人士、慈善力量、家庭和社交网络,以及心理治疗。
针对特定患者群中所有患者的治疗建议
考虑将所有因急症 收住入院,且确诊或疑似抑郁的患者转诊至联络精神病学团队/服务机构。[932]National Institute for Health and Care Excellence. Liaison psychiatry. In: Emergency acute medical care in over 16s: service delivery and organisation. 2018 [internet publication] https://www.nice.org.uk/guidance/ng94/evidence/23.liaison-psychiatry-pdf-172397464636 [933]National Confidential Enquiry into Patient Outcome and Death. Treat as one: bridging the gap between mental and physical healthcare in general hospitals. 2017 [internet publication] https://www.ncepod.org.uk/2017report1/downloads/TreatAsOne_Summary.pdf
COVID-19 大流行期间遵循医院的当地常规/转诊路径。
COVID-19 与精神和神经系统表现(包括抑郁)相关。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
合并抑郁症与对推荐的躯体健康治疗(从药物治疗到康复治疗)的依从性差有关。[934]DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med. 2000 Jul 24;160(14):2101-7 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/485411 http://www.ncbi.nlm.nih.gov/pubmed/10904452?tool=bestpractice.com
这可能会导致临床结局恶化,包括住院时间延长。[924]National Institute for Health and Care Excellence. Depression in adults with a chronic physical health problem: recognition and management. 2009 [internet publication] https://www.nice.org.uk/guidance/cg91 [935]Prina AM, Cosco TD, Dening T, et al. The association between depressive symptoms in the community, non-psychiatric hospital admission and hospital outcomes: a systematic review. J Psychosom Res. 2015 Jan;78(1):25-33 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4292984 http://www.ncbi.nlm.nih.gov/pubmed/25466985?tool=bestpractice.com [936]Clarke DM, Currie KC. Depression, anxiety and their relationship with chronic diseases: a review of the epidemiology, risk and treatment evidence. Med J Aust. 2009 Apr 6;190(s7):S54-60 http://www.ncbi.nlm.nih.gov/pubmed/19351294?tool=bestpractice.com
最重要的是,抑郁与死亡率升高有关。[937]World Health Organization. Excess mortality in persons with severe mental disorders. 2016 [internet publication] https://www.who.int/mental_health/evidence/excess_mortality_report/en
针对特定患者群中所有患者的治疗建议
考虑对因急性疾病入院的当前吸烟者给予尼古丁替代治疗。无论他们是否打算戒烟,均需纳入考虑范围。[938]National Institute for Health and Care Excellence. Tobacco: preventing uptake, promoting quitting and treating dependence. August 2022 [internet publication] https://www.nice.org.uk/guidance/ng209
尼古丁替代治疗可防止入院期间快速戒断,快速戒断可能会导致痛苦和不安。
对于因急性卒中、心肌梗死和/或未控制高血压入院的血流动力学不稳定患者,以及患有严重肾脏损伤的患者,应谨慎使用此疗法。
在开始对糖尿病患者使用尼古丁替代治疗后,密切监测血糖。
药品制剂包括皮肤贴剂以及针对皮肤过敏患者的吸入剂、含片、咀嚼胶或喷雾剂。剂量取决于每日吸烟量和所选择的制剂。
有关更全面的详细信息,参考当地药物处方集和医院指南。
请注意,从吸烟转为任何其他替代方案(包括尼古丁替代疗法)可能导致患者服用的任何精神类药物(例如用于治疗抑郁的药物)血药浓度发生变化。这是因为尼古丁替代治疗不会像吸烟那样影响肝酶活性。[926]Flowers L. Nicotine replacement therapy. Am J Psychiatry Resid J. 2016 Jun;11(6):4-7 https://psychiatryonline.org/doi/10.1176/appi.ajp-rj.2016.110602 寻求相关建议,确认精神类药物剂量调整是否适当。
有证据提示,吸烟与重症 COVID-19 风险升高具有相关性。
有鉴于此,由于存在公认的危害,因此世界卫生组织建议使用循证方法进行戒烟。[939]World Health Organization. Smoking and COVID-19: scientific brief. 2020 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-Sci_Brief-Smoking-2020.2
在专科医生团队指导下,疑似或确诊重症患者应收入适当的医疗机构,因为此类患者具有出现迅速临床恶化的风险。
成人重症被定义为具有肺炎临床征象,并伴有以下至少一项情况:呼吸频率 >30 次/分、重度呼吸窘迫,或在室内空气环境下 SpO₂ <90%。儿童重症被定义为具有肺炎临床征象,并伴有以下至少一项情况:中心性发绀或 SpO₂ <90%、重度呼吸窘迫、一般性危险征象(无法母乳喂养或饮水、昏睡或无意识,或出现惊厥)或呼吸加快(<2 月龄:呼吸 ≥60 次/分;2-11 月龄:呼吸 ≥50 次/分;1-5 岁:呼吸 ≥40 次/分)。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
孕妇应由多学科团队进行管理,包括产科、围产、新生儿和重症医学专科医生,以及助产、精神卫生和社会心理支持。建议采用以患者为中心、充满尊重、专业的诊疗方法。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 母体低氧血症出现后应尽快组建多学科团队,评估胎儿成熟度、疾病进展以及最佳分娩方式。[940]Chen L, Jiang H, Zhao Y. Pregnancy with Covid-19: management considerations for care of severe and critically ill cases. Am J Reprod Immunol. 2020 Jul 4:e13299. https://onlinelibrary.wiley.com/doi/10.1111/aji.13299 http://www.ncbi.nlm.nih.gov/pubmed/32623810?tool=bestpractice.com
管理 COVID-19 患者时,实施当地感染防控规程。
BMJ Best Practice 临床实践合并症诊疗工具中的信息涉及非妊娠成人。
这些信息不适用于孕妇患者或儿童。在这类情况下,请向产科/妇科专科医生或儿科专科医生寻求建议,了解患者的合并症可能会如何影响您对 COVID-19 的管理。
使用临床脆弱量表(Clinical Frailty Scale, CFS)评估基线健康状况,并适时在个体脆弱性评估范围内为治疗预期的讨论提供信息。 Clinical Frailty Scale 在新窗口中打开 勿将 CFS 用于年轻患者,以及存在长期稳定残疾(例如脑性瘫痪)、学习障碍或孤独症的患者。使用临床评估和替代评分方法,对此类人群脆弱状态进行个体化评估。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
无论使用何种脆弱评分/评估工具,与非脆弱住院患者相比,住院脆弱患者全因死亡风险均呈现升高。[941]Zou Y, Han M, Wang J, et al. Predictive value of frailty in the mortality of hospitalized patients with COVID-19: a systematic review and meta-analysis. Ann Transl Med. 2022 Feb;10(4):166. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8908186 http://www.ncbi.nlm.nih.gov/pubmed/35280387?tool=bestpractice.com
一项荟萃分析发现,CFS 上升与死亡率增加有关(CFS每增加 1 点即与死亡率增加 12% 呈现相关性)。[767]Pranata R, Henrina J, Lim MA, et al. Clinical frailty scale and mortality in COVID-19: a systematic review and dose-response meta-analysis. Arch Gerontol Geriatr. 2021 Mar-Apr;93:104324. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832565 http://www.ncbi.nlm.nih.gov/pubmed/33352430?tool=bestpractice.com 与评分为 1-3 分患者相比,评分在 4-9 分之间的患者死亡率显著升高。[766]Rottler M, Ocskay K, Sipos Z, et al. Clinical Frailty Scale (CFS) indicated frailty is associated with increased in-hospital and 30-day mortality in COVID-19 patients: a systematic review and meta-analysis. Ann Intensive Care. 2022 Feb 20;12(1):17. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8858439 http://www.ncbi.nlm.nih.gov/pubmed/35184215?tool=bestpractice.com 然而,一项系统评价和荟萃分析发现,脆弱和非脆弱患者的短期死亡率未见差异。[768]Subramaniam A, Shekar K, Afroz A, et al. Frailty and mortality associations in patients with COVID-19: a systematic review and meta-analysis. Intern Med J. 2022 Jan 23 [Epub ahead of print]. https://onlinelibrary.wiley.com/doi/10.1111/imj.15698 http://www.ncbi.nlm.nih.gov/pubmed/35066970?tool=bestpractice.com 部分研究表明,需对脆弱性和结局进行更细微的认识,讨论老年人预后时,应予以谨慎,切勿过度强调脆弱性影响。[769]Cosco TD, Best J, Davis D, et al. What is the relationship between validated frailty scores and mortality for adults with COVID-19 in acute hospital care? A systematic review. Age Ageing. 2021 May 5;50(3):608-16. https://academic.oup.com/ageing/article/50/3/608/6097011 http://www.ncbi.nlm.nih.gov/pubmed/33951151?tool=bestpractice.com
衰弱是与一种衰老过程相关的独特健康状态,多个身体系统逐渐丧失其生理功能。
询问患者其在急性发作前 2 周的能力情况(以及可能的相关照护者的意见)。
如果患者的年龄 ≥65 岁,则使用临床衰弱量表。
这是确定虚弱的实用辅助工具,但不应仅仅依赖它。
通常情况下,急诊入院的老年患者中,较高的衰弱评分与发生不良结局的风险增加相关。 尤其对于 COVID-19 患者,据部分但非所有研究报告,衰弱程度越高的患者具有更高的死亡风险。 [890]Subramaniam A, Shekar K, Afroz A, et al. Frailty and mortality associations in patients with COVID-19: a systematic review and meta-analysis. Intern Med J. 2022 May;52(5):724-39 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314619 http://www.ncbi.nlm.nih.gov/pubmed/35066970?tool=bestpractice.com
如果患者的评分为 5 分或以上,应对恰当的本地转诊进行全面评估寻求上级医生的建议,全面评估应包括讨论患者的治疗预期和照护目标。
辅助实施多学科诊疗,并根据患者的价值观来调整管理方案。
对于有卒中病史,且因急性疾病(包括 COVID-19)入院的患者,应在适当时机尽早进行基线神经系统评估。
通常,患有急性疾病(例如感染和疾病相关性低血压)的患者卒中(缺血性和出血性)风险增加。[892]Grau AJ, Urbanek C, Palm F. Common infections and the risk of stroke. Nat Rev Neurol. 2010 Nov 9;6(12):681-94 http://www.ncbi.nlm.nih.gov/pubmed/21060340?tool=bestpractice.com [893]Eigenbrodt ML, Rose KM, Couper DJ, et al. Orthostatic hypotension as a risk factor for stroke: the atherosclerosis risk in communities (ARIC) study, 1987-1996. Stroke. 2000 Oct;31(10):2307-13 https://www.doi.org/10.1161/01.str.31.10.2307 http://www.ncbi.nlm.nih.gov/pubmed/11022055?tool=bestpractice.com 有卒中病史的患者风险更高。
将基线评估结果与患者已知的 COVID-19 前神经系统状态进行比较。可通过询问患者、家属和照护者关于患者患病前的功能能力了解这一情况(基于专家意见)。
这样可以降低将入院时的神经系统体征错误归因于既往诊断卒中的风险。
如果住院期间神经系统状况发生变化,重复进行神经系统评估,以防再次发生卒中。
评估之后,确保对患者进行适当的监护(例如夜间意识模糊的风险和与体弱相关的跌倒风险)。
有卒中病史的患者跌倒和受伤的风险增加。[894]Winstein CJ, Stein J, Arena R, et al. Guidelines for adult stroke rehabilitation and recovery: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2016 May 4;47(6):e98-e169 https://www.doi.org/10.1161/STR.0000000000000098 http://www.ncbi.nlm.nih.gov/pubmed/27145936?tool=bestpractice.com
世界卫生组织建议密切监测 COVID-19 住院患者的临床恶化迹象,包括卒中征象或症状。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
见诸报道的 COVID-19 相关性神经系统表现包括急性缺血性和出血性卒中。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
何时停止隔离的指南各地有较大差异。
隔离时限可能取决于多种因素,包括疫苗接种状态、流行的 SARS-CoV-2 变体和患者因素(例如免疫功能正常/免疫功能低下、无症状/有症状、疾病严重程度)。
世界卫生组织建议,在症状发作后 10 天以及至少 3 天无发热和呼吸道症状的情况下,可停用基于防止传播的预防措施(包括隔离),并将患者从诊疗路径中移出。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 然而,指南各有不同,应参阅当地公共卫生指南,获取更多信息。
针对特定患者群中所有患者的治疗建议
像对所有患者一样,应尽早与痴呆患者及其照护者商定治疗升级预案 (基于专家意见)。
内容应包括:[843]Fritz Z, Slowther AM, Perkins GD. Resuscitation policy should focus on the patient, not the decision. BMJ. 2017 Feb 28;356:j813 https://www.doi.org/10.1136/bmj.j813 http://www.ncbi.nlm.nih.gov/pubmed/28246084?tool=bestpractice.com
复苏状态(即“不尝试心肺复苏”[Do Not Attempt Cardiopulmonary Resuscitation, DNACPR] 的决定)
治疗上限(例如是否适合气管插管或重症监护病房收治)。
升级方案应将预立医疗照护计划纳入考量,包括合法绑定预立医嘱。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1 [843]Fritz Z, Slowther AM, Perkins GD. Resuscitation policy should focus on the patient, not the decision. BMJ. 2017 Feb 28;356:j813 https://www.doi.org/10.1136/bmj.j813 http://www.ncbi.nlm.nih.gov/pubmed/28246084?tool=bestpractice.com
在某些情况下,对于治疗升级计划,痴呆患者将缺乏做出决策的心智能力。
评估并记录心智能力(在需要作出决定的特定时间作出决定的能力)。[844]National Institute for Health and Care Excellence. Decision making and mental capacity. 2018 [internet publication] https://www.nice.org.uk/guidance/ng108 请遵守您所在地区的相应法律。
在英格兰和威尔士,医疗卫生专业人士必须遵守 2005 年心智能力法案。[845]Department of Health. Mental Capacity Act 2005 [internet publication] http://www.legislation.gov.uk/ukpga/2005/9/contents 进行评估时,应遵循该法案中的原则。[845]Department of Health. Mental Capacity Act 2005 [internet publication] http://www.legislation.gov.uk/ukpga/2005/9/contents
如果评估确定患者缺乏心智能力,请确保作出符合患者最大利益的决定。[844]National Institute for Health and Care Excellence. Decision making and mental capacity. 2018 [internet publication] https://www.nice.org.uk/guidance/ng108 [845]Department of Health. Mental Capacity Act 2005 [internet publication] http://www.legislation.gov.uk/ukpga/2005/9/contents
如果患者被评估为缺乏心智能力, 需与近亲属协商,并作出最大获益”决策。[845]Department of Health. Mental Capacity Act 2005 [internet publication] http://www.legislation.gov.uk/ukpga/2005/9/contents
根据英格兰和威尔士 2005 年心智能力法案,如果患者无家庭成员或其他照护者,且无需立即作出决定,应寻求独立心智能力代理人担纲任务。[846]Social Care Institute for Excellence. Independent mental capacity advocate (IMCA). January 2010 [internet publication] https://www.scie.org.uk/mca/imca/do
查看您所在地区的相应法律。
针对特定患者群中部分患者治疗的附加建议
若患者有任何紧急征象(例如呼吸阻塞或缺乏呼吸、重度呼吸窘迫、中央型紫绀、休克、昏迷和/或惊厥),或患者无紧急征象但 SpO₂ <90%,应立即起始辅助供氧治疗。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 [465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
对于需给予紧急气道管理和氧疗,具有紧急征象的成人和儿童,复苏中的目标 SpO₂ 应 ≥94%。一旦病情稳定,建议儿童和非孕成人目标 SpO₂ >90%,孕妇则 ≥92% 至 95%。幼儿最好使用鼻翼管或鼻导管。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
部分指南建议 SpO₂ 应维持于不超过 96%。[771]Alhazzani W, Evans L, Alshamsi F, et al. Surviving Sepsis Campaign guidelines on the management of adults with coronavirus disease 2019 (COVID-19) in the ICU: first update. Crit Care Med. 2021 Mar 1;49(3):e219-34. https://journals.lww.com/ccmjournal/Abstract/9000/Surviving_Sepsis_Campaign_Guidelines_on_the.95371.aspx http://www.ncbi.nlm.nih.gov/pubmed/33555780?tool=bestpractice.com
部分中心则可能会建议设定不同的 SpO₂ 目标,从而为医院中病情最重的患者优先分配氧气流量给予支持。
考虑使用体位技术(例如高支撑坐姿),以及气道清除管理,优化氧合,协助成人分泌物清除。
对于需要辅助供氧的重病患者,考虑采取清醒俯卧位(每天 8-12 小时,将其在一天内分成多次较短时间进行)。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 [465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
非气管插管患者采取清醒态俯卧位与氧气变量(PaO₂/FiO₂、PaO₂和 SpO₂)改善、呼吸频率改善、气管插管率改善和死亡率改善具有相关性。但是证据有限。[772]Ponnapa Reddy M, Subramaniam A, Afroz A, et al. Prone positioning of nonintubated patients with coronavirus disease 2019: a systematic review and meta-analysis. Crit Care Med. 2021 Apr 30 [Epub ahead of print]. https://journals.lww.com/ccmjournal/Abstract/9000/Prone_Positioning_of_Nonintubated_Patients_With.95232.aspx http://www.ncbi.nlm.nih.gov/pubmed/33927120?tool=bestpractice.com [773]Chua EX, Zahir SMISM, Ng KT, et al. Effect of prone versus supine position in COVID-19 patients: a systematic review and meta-analysis. J Clin Anesth. 2021 Jun 22;74:110406. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216875 http://www.ncbi.nlm.nih.gov/pubmed/34182261?tool=bestpractice.com [774]Beran A, Mhanna M, Srour O, et al. Effect of prone positioning on clinical outcomes of non-intubated subjects with COVID-19: a comparative systematic review and meta-analysis. Respir Care. 2021 Nov 9 [Epub ahead of print]. http://rc.rcjournal.com/content/early/2021/11/09/respcare.09362.short http://www.ncbi.nlm.nih.gov/pubmed/34753813?tool=bestpractice.com [775]Li J, Luo J, Pavlov I, et al. Awake prone positioning for non-intubated patients with COVID-19-related acute hypoxaemic respiratory failure: a systematic review and meta-analysis. Lancet Respir Med. 2022 Mar 16 [Epub ahead of print]. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(22)00043-1/fulltext http://www.ncbi.nlm.nih.gov/pubmed/35305308?tool=bestpractice.com 然而,一项小型非随机对照试验发现,俯卧位对未进行机械通气的低氧血症患者无临床获益,因证据表明第 5 天临床结局出现恶化。[942]Qian ET, Gatto CL, Amusina O, et al. Assessment of awake prone positioning in hospitalized adults with COVID-19: a nonrandomized controlled trial. JAMA Intern Med. 2022 Apr 18 [Epub ahead of print]. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2791385 http://www.ncbi.nlm.nih.gov/pubmed/35435937?tool=bestpractice.com
对患者进行性急性低氧血症性呼吸衰竭征象进行密切监测。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 [465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
世界卫生组织建议,对于合并急性低氧血症性呼吸衰竭而无需紧急气管插管的重症住院患者,可使用高流量鼻导管氧疗(high-flow nasal oxygen, HFNO)、持续气道正压(continuous positive airway pressure, CPAP)通气或无创通气(头罩或面罩接口),非采取标准氧疗。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
选择取决于多种因素,如设备的可用性和氧气的供应,个人的舒适度和体验,以及患者特异性考虑因素(例如,使用 CPAP 或无创通气面罩的幽闭恐怖症,使用HFNO 的鼻腔不适)。
如果患者哮喘状态稳定,应遵循相关急症(即 COVID-19)发作时 氧饱和度目标值 的指南建议。[943]O'Driscoll BR, Howard LS, Earis J, et al; British Thoracic Society Emergency Oxygen Guideline Group; BTS Emergency Oxygen Guideline Development Group. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017 Jun;72(suppl 1):ii1-90 http://www.ncbi.nlm.nih.gov/pubmed/28507176?tool=bestpractice.com
对所有伴急性疾病的哮喘患者检查静息血氧饱和度。[943]O'Driscoll BR, Howard LS, Earis J, et al; British Thoracic Society Emergency Oxygen Guideline Group; BTS Emergency Oxygen Guideline Development Group. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017 Jun;72(suppl 1):ii1-90 http://www.ncbi.nlm.nih.gov/pubmed/28507176?tool=bestpractice.com 这是对 COVID-19 患者采取的常规做法。
如果 COVID-19 触发了患者哮喘病情急性加重,当前意见为遵循标准指南建议控制成人哮喘急性发作。[865]British Thoracic Society; Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma: a national clinical guideline. 2019 [internet publication] https://www.brit-thoracic.org.uk/quality-improvement/guidelines/asthma [909]Centers for Disease Control and Prevention. Clinical questions about COVID-19: questions and answers – patients with asthma. 2020 [internet publication] https://www.cdc.gov/coronavirus/2019-ncov/hcp/faq.html#Patients-with-Asthma
在 COVID-19 大流行期间,对于急性患病者,遵循当地医院常规所推荐的目标血氧饱和度 。
喘伴高碳酸血症是濒死迹象,表明患者衰竭,需要通气支持。[865]British Thoracic Society; Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma: a national clinical guideline. 2019 [internet publication] https://www.brit-thoracic.org.uk/quality-improvement/guidelines/asthma 需要立即提供重症监护支持。[865]British Thoracic Society; Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma: a national clinical guideline. 2019 [internet publication] https://www.brit-thoracic.org.uk/quality-improvement/guidelines/asthma
如果患者并 COPD,适合全面升级诊疗,存在以下情况时,可进行转诊,考虑给予通气支持:
尽管给予氧疗,但仍存在重度低氧血症(PaO2 <7.3kPa [54.8 mmHg])(基于专家意见)
高碳酸血症(PaCO₂ >6 kPa [45 mmHg]),伴呼吸性酸中毒(pH <7.35)[943]O'Driscoll BR, Howard LS, Earis J, et al; British Thoracic Society Emergency Oxygen Guideline Group; BTS Emergency Oxygen Guideline Development Group. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017 Jun;72(suppl 1):ii1-90 http://www.ncbi.nlm.nih.gov/pubmed/28507176?tool=bestpractice.com
和/或
表现出精神状态的变化(意识模糊、昏迷)。
如果患者合并 COPD,出现 2 型呼吸衰竭,并且一致认为其不适合给予涉及重症监护病房收治的全面升级诊疗:
遵循以下有关给氧的指导
与上级医生或呼吸专科医生讨论是否适合在病房中给予无创通气。
对于有 2 型呼吸衰竭风险的 COVID-19 患者,给予辅助供氧时应同对其他急性疾病患者一样进行照护。针对这类患者的氧疗基本上应始终受到控制。因此,高流量鼻套管吸氧(high-flow nasal oxygen, HFNO)不适合这些患者。可考虑将 HFNO 用于无 2 型呼吸衰竭风险但存在重度低氧血症的患者。[859]Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. 2021 [internet publication] https://goldcopd.org/2021-gold-reports 请注意,该治疗处方应由资深决策者开具,并且只能在仔细观察和重复测定 ABG 的情况下使用(基于专家意见)。
对于低氧 COPD 患者,应检测静息氧饱和度,并在给予氧疗时,注意其他需要考虑的因素。
英国胸科学会急救用氧指南(并非专门针对 COVID-19)建议,对任何需要辅助供氧的 COPD 患者,均需测定动脉血气(arterial blood gas, ABG)。[943]O'Driscoll BR, Howard LS, Earis J, et al; British Thoracic Society Emergency Oxygen Guideline Group; BTS Emergency Oxygen Guideline Development Group. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017 Jun;72(suppl 1):ii1-90 http://www.ncbi.nlm.nih.gov/pubmed/28507176?tool=bestpractice.com
对于所有患者,在 30 至 60 分钟后再次检查 ABG。[943]O'Driscoll BR, Howard LS, Earis J, et al; British Thoracic Society Emergency Oxygen Guideline Group; BTS Emergency Oxygen Guideline Development Group. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017 Jun;72(suppl 1):ii1-90 http://www.ncbi.nlm.nih.gov/pubmed/28507176?tool=bestpractice.com
英国胸科学会建议,对于罹患 COPD 的入院 COVID-19 患者,且有慢性 2 型呼吸衰竭急性发作证据的患者,应遵循标准方案,详见以下章节。[944]British Thoracic Society. BTS guidance: respiratory support of patients on medical wards. 2020 [internet publication] https://www.brit-thoracic.org.uk/about-us/covid-19-information-for-the-respiratory-community
如果 COPD 患者合并危重症(如休克、脓毒症、严重颅脑外伤、癫痫持续状态、全身过敏反应、严重创伤)并需给予高浓度吸氧:
英国胸科协会(British Thoracic Society, BTS)建议最初的目标血氧饱和度为 94%-98%,但最近的证据表明,在大多数情况下,上限目标值取 96% 可能更好。[943]O'Driscoll BR, Howard LS, Earis J, et al; British Thoracic Society Emergency Oxygen Guideline Group; BTS Emergency Oxygen Guideline Development Group. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017 Jun;72(suppl 1):ii1-90 http://www.ncbi.nlm.nih.gov/pubmed/28507176?tool=bestpractice.com [945]Chu DK, Kim LH, Young PJ, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet. 2018 Apr 28;391(10131):1693-705 http://www.ncbi.nlm.nih.gov/pubmed/29726345?tool=bestpractice.com [946]Siemieniuk RAC, Chu DK, Kim LH, et al. Oxygen therapy for acutely ill medical patients: a clinical practice guideline. BMJ. 2018 Oct 24;363:k4169 http://www.ncbi.nlm.nih.gov/pubmed/30355567?tool=bestpractice.com 在 COVID-19 大流行期间,按照您医院推荐的关于目标血氧饱和度的当地医院方案对急性患病者进行处理。
随后,您可能需要根据 ABG 结果调整为控制性氧疗,目标血氧饱和度为 88%-92%。[943]O'Driscoll BR, Howard LS, Earis J, et al; British Thoracic Society Emergency Oxygen Guideline Group; BTS Emergency Oxygen Guideline Development Group. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017 Jun;72(suppl 1):ii1-90 http://www.ncbi.nlm.nih.gov/pubmed/28507176?tool=bestpractice.com
如果合并 COPD 患者为急性患病但非危重患者,并有高碳酸血症性衰竭风险(包括所有中重度 COPD 患者,特别是长期接受氧疗,被配置疾病警告卡,或有高碳酸血症性呼吸衰竭既往史的患者):[943]O'Driscoll BR, Howard LS, Earis J, et al; British Thoracic Society Emergency Oxygen Guideline Group; BTS Emergency Oxygen Guideline Development Group. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017 Jun;72(suppl 1):ii1-90 http://www.ncbi.nlm.nih.gov/pubmed/28507176?tool=bestpractice.com
采用的初始目标血氧饱和度为 88%-92%
检查 ABG,然后在 30 至 60 分钟后再次检查。
如果合并 COPD 患者为急性患病但非危重患者 ,且无高碳酸血症性呼吸衰竭风险(例如稳定、轻度 COPD,症状轻微):
使用针对出现的急性病症的指南所建议的初始目标血氧饱和度。
BTS 建议,对于大多数急性患病者,在等待 ABG 结果时,目标氧饱和度采用 94%-98%,但最近的证据表明上限目标值取 96% 可能更好。[943]O'Driscoll BR, Howard LS, Earis J, et al; British Thoracic Society Emergency Oxygen Guideline Group; BTS Emergency Oxygen Guideline Development Group. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017 Jun;72(suppl 1):ii1-90 http://www.ncbi.nlm.nih.gov/pubmed/28507176?tool=bestpractice.com [945]Chu DK, Kim LH, Young PJ, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet. 2018 Apr 28;391(10131):1693-705 http://www.ncbi.nlm.nih.gov/pubmed/29726345?tool=bestpractice.com [946]Siemieniuk RAC, Chu DK, Kim LH, et al. Oxygen therapy for acutely ill medical patients: a clinical practice guideline. BMJ. 2018 Oct 24;363:k4169 http://www.ncbi.nlm.nih.gov/pubmed/30355567?tool=bestpractice.com 根据当地医院供氧情况,此目标血氧饱和度水平可能会更低(遵循当地规程)
尽快测定 ABG[943]O'Driscoll BR, Howard LS, Earis J, et al; British Thoracic Society Emergency Oxygen Guideline Group; BTS Emergency Oxygen Guideline Development Group. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017 Jun;72(suppl 1):ii1-90 http://www.ncbi.nlm.nih.gov/pubmed/28507176?tool=bestpractice.com
随后,您可能需要根据 ABG 结果调整为控制性氧疗,目标血氧饱和度为 88%-92%。[943]O'Driscoll BR, Howard LS, Earis J, et al; British Thoracic Society Emergency Oxygen Guideline Group; BTS Emergency Oxygen Guideline Development Group. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017 Jun;72(suppl 1):ii1-90 http://www.ncbi.nlm.nih.gov/pubmed/28507176?tool=bestpractice.com
针对特定患者群中所有患者的治疗建议
液体和电解质
对于无组织低灌注的成人和儿童,应对液体管理和液体反应性保持谨慎,因为积极液体复苏可能会使得氧合恶化。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
根据当地规程,对电解质或代谢异常进行纠正,例如高血糖或代谢性酸中毒。[776]Mojoli F, Mongodi S, Orlando A, et al. Our recommendations for acute management of COVID-19. Crit Care. 2020 May 8;24(1):207. https://ccforum.biomedcentral.com/articles/10.1186/s13054-020-02930-6 http://www.ncbi.nlm.nih.gov/pubmed/32384909?tool=bestpractice.com
需意识到,低血容量在心力衰竭和/或慢性肾病(chronic kidney disease, CKD)中较难进行评估。[947]National Institute for Health and Care Excellence. Intravenous fluid therapy in adults in hospital. 2017 [internet publication] https://www.nice.org.uk/guidance/cg174
评估:[947]National Institute for Health and Care Excellence. Intravenous fluid therapy in adults in hospital. 2017 [internet publication] https://www.nice.org.uk/guidance/cg174
脉搏
血压
外周灌注
毛细血管再充盈
颈静脉压
体位性低血压
肺水肿和外周水肿。
确立患者基线血压,因为相对于基线的下降幅度比绝对收缩压(systolic blood pressure, SBP)更为重要。
SBP <90 mmHg 可能表明存在低血压,但是接受慢性心力衰竭药物治疗患者的基线 SBP 可能 <90 mmHg (基于专家意见)。
CKD 患者在出现低血压,尤其是休克时,需要立即对其进行液体复苏 (基于专家意见)。
初次容量负荷试验后对患者进行重新评估,如果患者病情未迅速稳定,应向上级医生寻求意见。
考虑转至更高阶梯水平的诊疗。
心力衰竭患者可能需要接受液体复苏,但需寻求上级医生意见,评估容量状态和容量过负荷风险。
开始进行液体复苏之前,考虑将患者转诊,接受更高阶梯水平诊疗。
呼吸困难和咳嗽
保持房间凉爽,鼓励患者放松,采用一定的呼吸技巧和改变躯体姿态。识别并治疗呼吸困难的所有可逆病因(例如肺水肿、肺栓塞、COPD、哮喘)。如有条件,可考虑试行给氧。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
若无禁忌证,可对特定患者考虑短期使用镇咳药(例如如果咳嗽使患者感到不适)。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
焦虑、谵妄和躁动
识别并治疗任何潜在或可逆的原因(例如宽慰患者、治疗缺氧、纠正代谢或内分泌异常、治疗混合感染、尽量减少使用可能引起或加重谵妄的药物、治疗物质戒断、保持正常的睡眠周期、治疗疼痛或呼吸困难)。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 [530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
低剂量氟哌啶醇(或另一种合适的抗精神病药物)可考虑用于激越治疗。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
非药物干预应尽可能成为谵妄管理主要手段,而预防则为关键所在。[777]Centre for Evidence-Based Medicine; Jones L, Candy B, Roberts N, et al. How can healthcare workers adapt non-pharmacological treatment – whilst maintaining safety – when treating people with COVID-19 and delirium? 2020 [internet publication]. https://www.cebm.net/covid-19/how-can-healthcare-workers-adapt-non-pharmacological-treatment-whilst-maintaining-safety-when-treating-people-with-covid-19-and-delirium
对于因急性病症入院并有痴呆病史的任何患者,尽早进行基线认知评估。从家人、朋友或照护者处获取旁证病史。[895]Pendlebury ST, Klaus SP, Mather M, et al. Routine cognitive screening in older patients admitted to acute medicine: abbreviated mental test score (AMTS) and subjective memory complaint versus Montreal Cognitive Assessment and IQCODE. Age Ageing. 2015 Nov;44(6):1000-5 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621235 http://www.ncbi.nlm.nih.gov/pubmed/26464420?tool=bestpractice.com
使用在急症情况下可行的、经过验证的评分系统,例如:[895]Pendlebury ST, Klaus SP, Mather M, et al. Routine cognitive screening in older patients admitted to acute medicine: abbreviated mental test score (AMTS) and subjective memory complaint versus Montreal Cognitive Assessment and IQCODE. Age Ageing. 2015 Nov;44(6):1000-5 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621235 http://www.ncbi.nlm.nih.gov/pubmed/26464420?tool=bestpractice.com
简易智能测验评分/10(AMTS/10)。[948]Hodkinson HM. Evaluation of a mental test score for assessment of mental impairment in the elderly. Age Ageing. 1972 Nov;1(4):233-8 http://www.ncbi.nlm.nih.gov/pubmed/4669880?tool=bestpractice.com British Geriatrics Society: Abbreviated Mental Test Score. 2018 在新窗口中打开
旁证病史可确定患者的认知是否稳定,或者认知和功能是逐渐下降还是急性下降。
标准化认知评估评分将有助于监测所有临床改善, 以及确定出院需求。判读该分数时,最好结合功能评估(通常由经过培训的职业治疗师进行)。
每当痴呆患者出现急性疾病时都要进行谵妄评估。[897]National Institute for Health and Care Excellence. Delirium: prevention, diagnosis and management. 2019 [internet publication] https://www.nice.org.uk/guidance/CG103 世界卫生组织建议对 COVID-19 患者通过标准方案进行谵妄评估。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
伴痴呆者入院时和整个住院期间发生谵妄的风险增加。[898]National Institute for Health and Clinical Excellence. Dementia: assessment, management and support for people living with dementia and their carers. 2018 [internet publication] https://www.nice.org.uk/guidance/ng97 [899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium
谵妄与痴呆不同。[900]Nova Scotia Health Authority. This is not my Mom. 2012 [internet publication] https://www.thisisnotmymom.ca 谵妄是指精神功能出现潜在致死性的急性波动性改变,伴有注意力缺乏、思维混乱和意识水平的改变。[901]Inouye SK, Schlesinger MJ, Lydon TJ. Delirium: a symptom of how hospital care is failing older persons and a window to improve quality of hospital care. Am J Med. 1999 May;106(5):565-73 http://www.ncbi.nlm.nih.gov/pubmed/10335730?tool=bestpractice.com
使用筛查工具检测可能出现的谵妄,例如:
The 4-AT 在新窗口中打开。[899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium [902]Bellelli G, Morandi A, Davis DH, et al. Validation of the 4AT, a new instrument for rapid delirium screening: a study in 234 hospitalised older people. Age Ageing. 2014 Jul;43(4):496-502 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066613 http://www.ncbi.nlm.nih.gov/pubmed/24590568?tool=bestpractice.com [903]MacLullich AM, Shenkin SD, Goodacre S, et al. The 4 'A's test for detecting delirium in acute medical patients: a diagnostic accuracy study. Health Technol Assess. 2019 Aug;23(40):1-194 https://www.journalslibrary.nihr.ac.uk/hta/hta23400#/abstract http://www.ncbi.nlm.nih.gov/pubmed/31397263?tool=bestpractice.com
伴痴呆者可出现沟通困难,因此更难报告 COVID-19 相关性症状。他们最初的表现可能为谵妄征象。[904]Public Health England. Coronavirus (COVID-19): admission and care of people in care homes. 2020 [internet publication] https://www.gov.uk/government/publications/coronavirus-covid-19-admission-and-care-of-people-in-care-homes
对于患有任何急性疾病的痴呆患者,考虑采取以下措施,作为入院期间降低谵妄风险的多元化诊疗一部分:[899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium [905]British Geriatrics Society. Coronavirus: managing delirium in confirmed and suspected cases. 2020 [internet publication] https://www.bgs.org.uk/resources/coronavirus-managing-delirium-in-confirmed-and-suspected-cases
帮助患者定向;确保患者有自己的眼镜和/或助听器
使患者尽早开始活动
充分控制疼痛
及时发现并治疗重叠感染
保证水的摄入量,并帮助患者充分进食
监测并维持正常的肠道和膀胱功能
根据指南的建议给予氧疗。
安排与经验丰富的医疗卫生专业人士一起进行用药评估。[899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium
与 COVID-19 尤其相关的挑战包括:[905]British Geriatrics Society. Coronavirus: managing delirium in confirmed and suspected cases. 2020 [internet publication] https://www.bgs.org.uk/resources/coronavirus-managing-delirium-in-confirmed-and-suspected-cases
隔离需要,这可能会加重部分患者的谵妄
对患者谵妄进行定期监测的能力,可能受人员配置和可用时间资源影响。
针对谵妄患者的初始检查
如果患者出现谵妄,请检查并治疗危及生命的病因:[899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium
缺氧
低血糖
低血压
药物中毒或戒断,包括酒精戒断。
其他检查包括(基于专家意见):
全血细胞计数、电解质、肾功能、甲状腺功能检测、肝功能检测、钙、血糖、CRP、叶酸和维生素 B12
血培养(如果怀疑菌血症)
尿培养
胸部 X 线。
根据具体临床发现,可能需要进行更高级的非常规检查,例如头颅 CT。请与上级医生讨论。[899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium
检查并治疗谵妄的所有可逆病因。[897]National Institute for Health and Care Excellence. Delirium: prevention, diagnosis and management. 2019 [internet publication] https://www.nice.org.uk/guidance/CG103 其中包括:
感染
疼痛
脱水
便秘
制动
睡眠差
感觉受损(如耵聍或眼镜丢失)
药物治疗
询问最近开的处方药,特别是阿片类镇痛药、抗焦虑药、镇静剂、抗精神病药物或抗胆碱能作用强的药物
考虑计算抗胆碱能药物总负担得分。
最初应管理谵妄患者,如果可能,应按照推荐用于非 COVID-19 情况下谵妄管理的非药物疗法进行治疗。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1 [897]National Institute for Health and Care Excellence. Delirium: prevention, diagnosis and management. 2019 [internet publication] https://www.nice.org.uk/guidance/CG103
通过提供一个光线充足的房间,且将时钟和日历放置在显眼位置(例如挂在墙上),可减轻定向障碍。
基于当前社区 COVID-19 传播水平,在当地探视政策允许的情况下,鼓励并促进家人、朋友和照护者探视患者。
使用语言和非语言技巧减轻冲突和苦恼。
如果非药物治疗无效,并且患者感到痛苦或可能对自己或他人构成危险,可以考虑短期(通常仅需要 1-2 天)使用抗精神病药物或镇静剂,但只能作为最后的治疗手段。必须定期评估为此目的新开的任何抗精神病药物,并在实际情况允许时停药(基于专家意见)。
英国老年医学会(British Geriatrics Society)指出,在管理 COVID-19 患者时,药物治疗可能需要早于在其他情况下通常考虑的时间,因为感染传播对他人造成伤害的风险可能大于对个人造成潜在伤害的风险。[905]British Geriatrics Society. Coronavirus: managing delirium in confirmed and suspected cases. 2020 [internet publication] https://www.bgs.org.uk/resources/coronavirus-managing-delirium-in-confirmed-and-suspected-cases
英国国家卫生与临床优化研究所关于谵妄的指南(在未患 COVID-19 的情况下)建议短期使用氟哌啶醇(通常少于 1 周),但这并不适合所有患者,并且绝不能用于帕金森病或路易体痴呆患者。[897]National Institute for Health and Care Excellence. Delirium: prevention, diagnosis and management. 2019 [internet publication] https://www.nice.org.uk/guidance/CG103
NICE COVID-19 管理快速指南亦建议将氟哌啶醇作为可完成吞咽动作的 COVID-19 患者谵妄药物治疗的一种选择。[839]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication] https://www.nice.org.uk/guidance/ng191
抗精神病药物治疗谵妄的有效性证据尚无定论,并且医院方案可能各有不同。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1 [899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium 遵循当地医院的方案选择药物。
始终从最低剂量开始服用抗精神病药,并依据症状谨慎地逐渐调整剂量。[897]National Institute for Health and Care Excellence. Delirium: prevention, diagnosis and management. 2019 [internet publication] https://www.nice.org.uk/guidance/CG103 只能通过口服或肌内注射药物(绝对不可静脉注射)对此进行治疗。(基于专家意见)。
向家庭/照护者提供信息,以便他们了解当前的情况以及如何与临床团队协作以帮助患者恢复正常生活。[899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium 提供本地可用信息资源。[905]British Geriatrics Society. Coronavirus: managing delirium in confirmed and suspected cases. 2020 [internet publication] https://www.bgs.org.uk/resources/coronavirus-managing-delirium-in-confirmed-and-suspected-cases
抗精神病药物与痴呆患者死亡率增加相关。
痴呆患者有时可能需要短期抗精神病药物以实现安全疗护。然而,抗精神病药物对老年人有多种不良作用,并与痴呆患者死亡风险增加相关。
一项 meta 分析发现,与服用安慰剂的人相比,服用非典型抗精神病药的痴呆患者死亡风险增加。[906]Ma H, Huang Y, Cong Z, et al. The efficacy and safety of atypical antipsychotics for the treatment of dementia: a meta-analysis of randomized placebo-controlled trials. J Alzheimers Dis. 2014;42(3):915-37 http://www.ncbi.nlm.nih.gov/pubmed/25024323?tool=bestpractice.com
一项针对老年人的大型队列研究发现,更高剂量的抗精神病药通常与更高的风险相关。在所有研究的抗精神病药中,使用氟哌啶醇的风险最高。[907]Huybrechts KF, Gerhard T, Crystal S, et al. Differential risk of death in older residents in nursing homes prescribed specific antipsychotic drugs: population based cohort study. BMJ. 2012 Feb 23;344:e977 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285717 http://www.ncbi.nlm.nih.gov/pubmed/22362541?tool=bestpractice.com
与普遍的看法相反,大多数痴呆患者的行为稳定后,就可以安全地停止长期抗精神病药处方。[908]Van Leeuwen E, Petrovic M, van Driel ML, et al. Withdrawal versus continuation of long-term antipsychotic drug use for behavioural and psychological symptoms in older people with dementia. Cochrane Database Syst Rev. 2018 Mar 30;(3):CD007726 https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007726.pub3/full http://www.ncbi.nlm.nih.gov/pubmed/29605970?tool=bestpractice.com
如果谵妄在 48 小时内未对初始治疗产生反应,转诊至在谵妄诊断方面经过培训且具备技能的医疗卫生专业人士,以确认诊断和治疗计划(基于专家意见)。
清楚记录谵妄的诊断。[897]National Institute for Health and Care Excellence. Delirium: prevention, diagnosis and management. 2019 [internet publication] https://www.nice.org.uk/guidance/CG103 [899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium
口腔护理
对于接受人工通气或未接受人工通气的住院患者,以及正在接受中级护理或临终关怀的患者,口腔护理是患者整体护理的重要组成部分。[778]Public Health England. Mouth care for hospitalised patients with confirmed or suspected COVID-19. 2020 [internet publication]. https://www.gov.uk/government/publications/covid-19-mouth-care-for-patients-with-a-confirmed-or-suspected-case/mouth-care-for-hospitalised-patients-with-confirmed-or-suspected-covid-19
心理健康症状
为所有患者提供基本的心理健康和社会心理支持,并对失眠或抑郁等症状进行酌情处理。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
在临床情况允许以及患者有反应的情况下进行精神状态检查 (基于专家意见)。
精神状态检查是精神病学临床实践中常规使用的主要临床工具之一,有助于诊断和指导进一步的管理。情绪是其中一项评估内容。
考虑使用 PHQ-9 问卷,进行抑郁评估。[921]Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606-13 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1495268 http://www.ncbi.nlm.nih.gov/pubmed/11556941?tool=bestpractice.com
这是一份自填式问卷,只需不到 3 分钟即可完成。
结果可提示抑郁症状的严重程度。
评分 5 分或以上应启动转诊,转至联络精神病学服务机构 (基于专家意见)。
抑郁据报道为 COVID-19 住院患者常见发现。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
考虑可能影响患者精神状态的其他因素(例如违禁药物使用或饮酒的影响)。[922]Boden JM, Fergusson DM. Alcohol and depression. Addiction. 2011 May;106(5):906-14 http://www.ncbi.nlm.nih.gov/pubmed/21382111?tool=bestpractice.com
针对特定患者群中所有患者的治疗建议
与您的医院糖尿病专科团队进行联络,获取 COVID-19 和糖尿病患者管理支持。
对于伴有急症(包括 COVID-19)的 1 型糖尿病患者,不应停用基础胰岛素(长效/背景胰岛素 [例如地特胰岛素、甘精胰岛素或德谷胰岛素])。 [889]Bornstein SR, Rubino F, Khunti K, et al. Practical recommendations for the management of diabetes in patients with COVID-19. Lancet Diabetes Endocrinol. 2020 Jun;8(6):546-50 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180013 http://www.ncbi.nlm.nih.gov/pubmed/32334646?tool=bestpractice.com [949]Chowdhury TA, Cheston H, Claydon A. Managing adults with diabetes in hospital during an acute illness. BMJ. 2017 Jun 22;357:j2551 http://www.ncbi.nlm.nih.gov/pubmed/28642274?tool=bestpractice.com
胰岛素缺乏(例如由于用药延迟或漏用)会迅速引起酮症酸中毒。[949]Chowdhury TA, Cheston H, Claydon A. Managing adults with diabetes in hospital during an acute illness. BMJ. 2017 Jun 22;357:j2551 http://www.ncbi.nlm.nih.gov/pubmed/28642274?tool=bestpractice.com
通常,所有接受基础胰岛素治疗的 2 型糖尿病患者均应继续接受治疗,但情况并非总是如此,因此应咨询上级医生和/或糖尿病专科医生团队 (基于专家意见)。
需注意,COVID-19 似乎会增加潜在致死性急症的发生风险,包括:[883]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19: front door guidance. 2020 [internet publication] https://abcd.care/resource/concise-advice-inpatient-diabetes-during-covid-19-front-door-guidance [889]Bornstein SR, Rubino F, Khunti K, et al. Practical recommendations for the management of diabetes in patients with COVID-19. Lancet Diabetes Endocrinol. 2020 Jun;8(6):546-50 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180013 http://www.ncbi.nlm.nih.gov/pubmed/32334646?tool=bestpractice.com
高血糖伴酮症
糖尿病酮症酸中毒 (DKA)
高渗性高血糖状态 (HHS)
对于 COVID-19 患者,无论是否已知患有糖尿病,均有此风险。
入院时应进行以下检查:[883]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19: front door guidance. 2020 [internet publication] https://abcd.care/resource/concise-advice-inpatient-diabetes-during-covid-19-front-door-guidance
所有患者的血糖
所有糖尿病患者(1 型和 2 型)以及入院时血糖 >12 mmol/L(>216 mg/dL)者的血酮。
如符合以下标准,则可在已知患有糖尿病的患者中诊断 DKA:[883]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19: front door guidance. 2020 [internet publication] https://abcd.care/resource/concise-advice-inpatient-diabetes-during-covid-19-front-door-guidance
血酮水平 ≥3 mmol/L,并且
血 pH 值<7.3 或碳酸氢根 <15 mmol/L。
请注意,美国糖尿病协会和美国临床内分泌医师协会/美国内分泌学会都建议使用与上述标准不同的标准来诊断 DKA。[950]Karslioglu French E, Donihi AC, Korytkowski MT. Diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome: review of acute decompensated diabetes in adult patients. BMJ. 2019 May 29;365:l1114. https://www.bmj.com/content/365/bmj.l1114.long http://www.ncbi.nlm.nih.gov/pubmed/31142480?tool=bestpractice.com
在正常血糖性酮症酸中毒中,血糖水平可能不会显著升高。
如果存在以下情况,HHS 诊断可能性极高:[883]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19: front door guidance. 2020 [internet publication] https://abcd.care/resource/concise-advice-inpatient-diabetes-during-covid-19-front-door-guidance
血糖 ≥30 mmol/L(≥541 mg/dL),且
血清渗透压([(2 x Na) + 葡萄糖 + 尿素])>320 mOsm/kg 且
pH >7.3。
请注意,美国糖尿病协会建议使用与上述标准不同的标准诊断 HHS。[950]Karslioglu French E, Donihi AC, Korytkowski MT. Diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome: review of acute decompensated diabetes in adult patients. BMJ. 2019 May 29;365:l1114. https://www.bmj.com/content/365/bmj.l1114.long http://www.ncbi.nlm.nih.gov/pubmed/31142480?tool=bestpractice.com
对于伴 COVID-19 者,或怀疑混合性 DKA/HHS 者,在 DKA 或 HHS 的管理中,需同糖尿病专科医生团队保持联系,并遵循 当地指南。
如果血糖 <4 mmol/L(<72 mg/dL),即可诊断为低血糖。
遵循当地的低血糖管理常规。
停止以下药物治疗:[883]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19: front door guidance. 2020 [internet publication] https://abcd.care/resource/concise-advice-inpatient-diabetes-during-covid-19-front-door-guidance
钠-葡萄糖协同转运蛋白 2(sodium-glucose cotransporter-2, SGLT-2)抑制剂(例如达格列净、卡格列净、恩格列净)
SGLT-2 抑制剂可降低肾脏中的血糖重吸收(与胰岛素代谢葡萄糖无关)。[951]Peters AL, Buschur EO, Buse JB, et al. Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Diabetes Care. 2015 Sep;38(9):1687-93 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4542270 http://www.ncbi.nlm.nih.gov/pubmed/26078479?tool=bestpractice.com
它们可以掩盖潜在的酮症酸中毒,因为患者的血糖水平可能正常或接近正常(血糖正常的酮症酸中毒)。[951]Peters AL, Buschur EO, Buse JB, et al. Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Diabetes Care. 2015 Sep;38(9):1687-93 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4542270 http://www.ncbi.nlm.nih.gov/pubmed/26078479?tool=bestpractice.com
二甲双胍
严重肾脏损伤(估算 GFR <30 mL/(min·1.73m²),或代谢性酸中毒(包括乳酸酸中毒和 DKA)患者禁用二甲双胍。
如果患者有乳酸酸中毒的风险,例如有急性肾损伤或组织缺氧(包括脱水),或在将长期禁食的情况下,也应禁用此药物。
根据患者的血乳酸水平、肾功能和动脉血气结果,可考虑重新开始使用二甲双胍,因有证据表明二甲双胍可预防 COVID-19 向重症恶化。[883]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19: front door guidance. 2020 [internet publication] https://abcd.care/resource/concise-advice-inpatient-diabetes-during-covid-19-front-door-guidance
如果患者停用其通常使用的 SGLT-2 抑制剂或二甲双胍,则可能需要调整药物或开始使用胰岛素作为一种临时措施。寻求糖尿病专科团队建议。
针对特定患者群中所有患者的治疗建议
使用适当的风险评估工具,入院后或首次看诊时应尽快评估出血风险。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
若无禁忌,为急症入院成人和青少年起始静脉血栓栓塞(venous thromboembolism, VTE)预防治疗。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 [465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov [763]Barnes GD, Burnett A, Allen A, et al. Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the Anticoagulation Forum. J Thromb Thrombolysis. 2020 Jul;50(1):72-81. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241581 http://www.ncbi.nlm.nih.gov/pubmed/32440883?tool=bestpractice.com [952]Moores LK, Tritschler T, Brosnahan S, et al. Prevention, diagnosis, and treatment of VTE in patients with coronavirus disease 2019: CHEST guideline and expert panel report. Chest. 2020 Sep;158(3):1143-63. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265858 http://www.ncbi.nlm.nih.gov/pubmed/32502594?tool=bestpractice.com
在英国,国家卫生与临床优化研究所(National Institute for Health and Care Excellence, NICE)建议,需给予低流量氧,且出血风险未升高的青年和成人应尽快(入院 14 小时内)开始进行该治疗,并持续至少 7 天,包括出院后。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
在美国,国立卫生研究院指南专家组建议,对所有 ≥12 岁儿童进行预防性抗凝治疗,除非存在禁忌证。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
低分子肝素、普通肝素或磺达肝癸钠为标准血栓预防的推荐选择。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
在英国,NICE 建议低分子肝素作为一线药物,对于不能使用低分子肝素的患者,则可使用磺达肝癸钠或普通肝素。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
在美国,国立卫生研究院指南专家组的建议指出,使用胃肠外抗凝剂优于使用口服抗凝剂,如果使用肝素,则低分子肝素优于普通肝素。专家组不建议使用治疗剂量口服抗凝药物,除非是在临床试验背景下。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
普通肝素禁忌用于重度血小板减少症和具有肝素诱导的血小板减少症病史患者。磺达肝癸钠建议用于具有肝素诱导的血小板减少症史患者。如果抗凝药物存在给药禁忌或无法使用,则建议给予机械性血栓预防(例如间歇充气加压装备)。[952]Moores LK, Tritschler T, Brosnahan S, et al. Prevention, diagnosis, and treatment of VTE in patients with coronavirus disease 2019: CHEST guideline and expert panel report. Chest. 2020 Sep;158(3):1143-63. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265858 http://www.ncbi.nlm.nih.gov/pubmed/32502594?tool=bestpractice.com [782]American Society Of Hematology. COVID-19 and VTE/anticoagulation: frequently asked questions. 2020 [internet publication]. https://www.hematology.org/covid-19/covid-19-and-vte-anticoagulation
最佳剂量尚有待确定。
在多数指南中,对于无高剂量抗凝明确指征的患者,标准预防剂量一般比中剂量或全剂量给药方案更受推荐。[953]Kyriakoulis KG, Kollias A, Kyriakoulis IG, et al. Thromboprophylaxis in patients with COVID-19: systematic review of national and international clinical guidance reports. Curr Vasc Pharmacol. 2021 Aug 24 [Epub ahead of print]. http://www.ncbi.nlm.nih.gov/pubmed/34431465?tool=bestpractice.com 但是,对于该建议所持态度各异,您应参阅当地指南。
世界卫生组织建议,对于无明确高剂量抗凝治疗指征患者,给予抗凝治疗标准血栓预防剂量,而非治疗剂量或中间剂量。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
在英国,NICE 建议对需要低流量氧气且出血风险未增加的青年和成人给予预防剂量低分子肝素至少 7 天(包括出院后)。对于需要低流量氧气且出血风险未增加的青年和成人,可考虑给予治疗剂量的低分子肝素 14 天或直至出院(以更早时间为准);但是,这只是条件性建议。应仔细考虑该决定,并根据出血风险、临床判断和当地方案选择最合适的给药方案。对于无需补充供氧者,遵循标准 VTE 预防指南。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
在美国,国立卫生研究院指南专家组建议,对于 D-二聚体水平高于正常上限、需低流量给氧,且出血风险未见升高的患者,可给予治疗剂量肝素,除非存在用药禁忌。治疗应持续 14 天或直至出院,以更早出现者为准。对于未使用治疗剂量肝素的患者,专家组建议使用预防剂量肝素,除非存在禁忌证。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
对于极端体重或肾功能受损患者,可能需要调整剂量。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
对于已因其他基础疾患接受抗凝治疗的患者,除非临床情境出现变化,否则应继续给予患者当前药物治疗,并维持当前治疗剂量。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov [530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191 若患者临床状况恶化,当前未使用低分子肝素,则可考虑将低分子肝素作为静脉血栓栓塞预防首选用药。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
证据支持低剂量抗凝药物方案的使用。一项 Cochrane 评价发现,在住院患者中,较高剂量的药物治疗方案与较低剂量的药物治疗方案相比,全因死亡率几乎无差别;然而,较高剂量的药物治疗方案与 30 天内轻微出血风险升高具有相关性(高度确定性证据)。与低剂量药物治疗方案相比,高剂量抗凝药物可能减少肺栓塞,并使得 30 天内大出血轻度增多(中度确定性证据)。高剂量抗凝药物 30 天内导致深静脉血栓、卒中、主要不良肢体事件、心肌梗死、心房颤动或血小板减少的可能性与低剂量药物治疗方案相比几乎无差别(低等确定性证据)。与不使用抗凝药物相比,抗凝药物可降低全因死亡率,但证据十分不确定。[780]Flumignan RL, Civile VT, Tinôco JDS, et al. Anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2022 Mar 4;(3):CD013739. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013739.pub2/full http://www.ncbi.nlm.nih.gov/pubmed/35244208?tool=bestpractice.com
对患者血栓栓塞征象和症状进行监测,若临床疑似,采取适当的诊断和管理路径。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
若患者临床状况改变,需评估 VTE 风险,重新评估出血风险,并完善 VTE 预防措施。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
持续给予,直至出院。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
通常不建议在出院后进行常规 VTE 预防,除非对于某些高风险患者,在临床试验背景下,或存在 VTE 预防的其他指征时。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov [763]Barnes GD, Burnett A, Allen A, et al. Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the Anticoagulation Forum. J Thromb Thrombolysis. 2020 Jul;50(1):72-81. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241581 http://www.ncbi.nlm.nih.gov/pubmed/32440883?tool=bestpractice.com [952]Moores LK, Tritschler T, Brosnahan S, et al. Prevention, diagnosis, and treatment of VTE in patients with coronavirus disease 2019: CHEST guideline and expert panel report. Chest. 2020 Sep;158(3):1143-63. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265858 http://www.ncbi.nlm.nih.gov/pubmed/32502594?tool=bestpractice.com
出院后需要进行 VTE 预防的患者,应确保其能够正确进行预防,或安排专人对其施以帮助。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
目前尚无足够证据确定住院 COVID-19 患者进行预防性抗凝的风险和获益。[954]Flumignan RL, Tinôco JDS, Pascoal PI, et al. Prophylactic anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2020 Oct 2;(10):CD013739. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013739/full http://www.ncbi.nlm.nih.gov/pubmed/33502773?tool=bestpractice.com
一项系统评价和荟萃分析发现,抗凝和非抗凝住院患者的总体死亡率相似,但标准预防剂量组的死亡率较低。与未进行抗凝治疗相比,预防剂量抗凝治疗显著降低了院内死亡几率达 17%。中等剂量至治疗剂量组大出血风险增加,从而死亡率上升。[781]Moonla C, Sosothikul D, Chiasakul T, et al. Anticoagulation and in-hospital mortality from coronavirus disease 2019: a systematic review and meta-analysis. Clin Appl Thromb Hemost. 2021 Jan-Dec;27:10760296211008999. https://journals.sagepub.com/doi/10.1177/10760296211008999 http://www.ncbi.nlm.nih.gov/pubmed/33874753?tool=bestpractice.com
临床医生应凭借 COVID-19 前的循证抗凝治疗原则,结合合理的方法,应对临床挑战。[763]Barnes GD, Burnett A, Allen A, et al. Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the Anticoagulation Forum. J Thromb Thrombolysis. 2020 Jul;50(1):72-81. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241581 http://www.ncbi.nlm.nih.gov/pubmed/32440883?tool=bestpractice.com
查看当地药物处方集/肾病手册,了解对肾功能减退(慢性肾病、急性肾损伤)患者给予抗凝药物,进行静脉血栓栓塞预防的详细信息。
肾功能受损患者使用某些抗凝药物,可能使出血风险上升,需给予细致的患者监测。[955]Law JP, Pickup L, Townend JN, et al. Anticoagulant strategies for the patient with chronic kidney disease. Clin Med (Lond). 2020 Mar;20(2):151-5 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081809 http://www.ncbi.nlm.nih.gov/pubmed/32188649?tool=bestpractice.com
根据患者肾功能损害程度,您可能需要:
调整剂量
避免使用某些抗凝药物。
遵循当地药物处方集指南,建议监测抗 Xa 因子活性。
如果患者正在接受肾脏替代治疗,则寻求肾病专科医生建议。
或
或
依诺肝素
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
或
达肝素
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
磺达肝癸钠
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
或
针对特定患者群中所有患者的治疗建议
对患者的临床恶化给予密切监测,并立即采取适当的支持性治疗干预措施。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
如果伴慢性肾病(chronic kidney disease, CKD)或具有 CKD 危险因素的患者因急症而呈现不适,应对肾功能进行密切监测。[837]National Institute for Health and Care Excellence. Acute kidney injury: prevention, detection and management. 2019 [internet publication] https://www.nice.org.uk/guidance/ng148
CKD 为急性肾损伤(acute kidney injury, AKI)重要危险因素。[838]Hsu CY, Ordoñez JD, Chertow GM, et al. The risk of acute renal failure in patients with chronic kidney disease. Kidney Int. 2008 Apr 2;74(1):101-7 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673528 http://www.ncbi.nlm.nih.gov/pubmed/18385668?tool=bestpractice.com
伴 CKD 和 COVID-19 患者出现 AKI 风险将升高, 其可能与发热、脱水,以及非甾体抗炎药使用具有相关性。
COVID -19 患者伴 AKI 可能较为常见(但确切患病率尚不确定)。AKI 与死亡率增加具有相关性。[839]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication] https://www.nice.org.uk/guidance/ng191
向您的 CKD 患者解释,其患病后出现 AKI 的风险增加。确定机制,以便可以密切监测居家治疗患者疾病进展迹象。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
对于入院的所有 COVID-19 患者,包括 CKD 患者,院时需检查肾功能,并确保定期监测。
对于 CKD 患者:
与最近一次可获取结果的肾功能进行比较
每日监测肾功能,同时进行仔细的容量状态监测 ( 基于专家意见)。
对少尿进行监测并予以处理。[837]National Institute for Health and Care Excellence. Acute kidney injury: prevention, detection and management. 2019 [internet publication] https://www.nice.org.uk/guidance/ng148
维持最佳体液状态至关重要,但这很难在所有 COVID-19 患者中实现。[839]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication] https://www.nice.org.uk/guidance/ng191 寻求上级医生建议,尤其是对于病情复杂患者,例如患有心力衰竭和/或慢性肾病(chronic kidney disease, CKD)的患者。
心力衰竭和/或 CKD 患者具有液体复苏肺水肿高风险,因此应密切监测(最初每小时一次)。
监测项目应包括:
定期进行容量状态临床评估(脉搏、BP、颈静脉压 [jugular venous pressure, JVP],并检查有无肺水肿和外周水肿)
体液平衡(出入量表)和每日体重
肾功能检查,至少每日一次。
如果尿量难以测定,考虑进行膀胱导尿术,但要注意感染和创伤风险可能增加。
对于病情复杂患者,可能需监测中心静脉压,或置入肺动脉导管进行监测。[891]Verbrugge FH, Grieten L, Mullens W. Management of the cardiorenal syndrome in decompensated heart failure. Cardiorenal Med. 2014 Dec;4(3-4):176-88 https://www.doi.org/10.1159/000366168 http://www.ncbi.nlm.nih.gov/pubmed/25737682?tool=bestpractice.com
重要的是要知道何时降级液体治疗。考虑尽早向上级医生寻求意见支持该决定。
如果患者液体容量过负荷(体征包括脉率升高、肺水肿导致呼吸频率升高以及外周水肿相关的 JVP 升高),停止液体复苏,寻求上级医生帮助,并考虑静脉给予利尿药 (基于专家意见)。
除非存在合理情况,否则一般不会联用利尿药和静脉输液(基于专家意见)。
可能需要心脏病学医生和/或肾病学医生专科意见。
针对特定患者群中部分患者治疗的附加建议
如果临床怀疑继发性细菌感染,可考虑使用经验性抗生素。
对于怀疑患有脓毒症的患者,或符合高危标准的患者,应在初次评估后 1 小时内给药(或在确定为继发性细菌性肺炎的 4 小时内给药);勿等待微生物学检查结果。用药方案基于临床诊断(例如社区获得性肺炎、医院获得性肺炎、脓毒症)、地区流行病学及药敏数据,和当地治疗指南。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 [465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov [530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
若 SARS-CoV-2、另一病毒或真菌感染为肺炎可能病因,则勿给予抗生素进行预防或治疗。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
指南建议,在无经证实或疑似细菌感染的情况下,不要给予广谱抗生素进行经验性治疗。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
请咨询专科医师建议。
考虑为以下患者寻求专科医生意见:免疫功能低下;有耐药性病原体感染史;有肺部疾病反复感染性恶化病史;妊娠;或正在接受高级呼吸支持或器官支持。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
如果怀疑患者感染多药耐药细菌,可能需使用其他抗生素,或者存在临床或微生物学证据表明感染,48 至 72 小时抗生素治疗后病情未得到预期改善,寻求专科医生建议。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
每日对抗生素使用进行再评估。
根据微生物检测结果和临床判断给予降阶梯经验性治疗。定期审视静脉用药改为口服治疗的可能性。治疗时间应尽可能短(例如 5 至 7 天)。应制定抗生素管理计划。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
针对特定患者群中部分患者治疗的附加建议
考虑全身皮质类固醇治疗。指南建议各不相同。
世界卫生组织强烈建议,将全身皮质类固醇治疗(低剂量静脉用或口服地塞米松,或氢化可的松)用于重症成人患者,连用 7-10 日。该项建议是基于表明全身皮质类固醇治疗可能降低重症患者 28 日死亡率的中等质量证据。暂无直接比较地塞米松和氢化可的松的证据。在这种情况下,认为治疗的危害极小。尚不清楚此类建议是否适用于儿童或免疫功能低下者。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3 [736]Rochwerg B, Siemieniuk RA, Agoritsas T, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020 Sep 4;370:m3379. https://www.bmj.com/content/370/bmj.m3379.long http://www.ncbi.nlm.nih.gov/pubmed/32887691?tool=bestpractice.com [737]Rochwerg B, Siemieniuk RA, Lamontagne R, et al. Update to living WHO guideline on drugs for covid-19. BMJ. 2021 Jul 6;374:n1703. http://www.ncbi.nlm.nih.gov/pubmed/34230027?tool=bestpractice.com
在英国,英国国家卫生与临床优化研究所建议向需进行辅助供氧,以达到预期氧饱和度水平者,或达到缺氧水平,需进行辅助供氧,但却无法提供或无法耐受者,给予地塞米松进行治疗(或在地塞米松无法使用,或药物不可及时,给予诸如氢化可的松或泼尼松龙等替代药物)。治疗将持续达 10 天,除非有明确指征早期停止治疗。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
在美国,国立卫生研究院指南专家组建议对于需给予辅助供氧的住院成人,给予地塞米松单药治疗,或给予地塞米松联合 remdesivir 治疗。无法给予地塞米松时,可使用其他皮质类固醇。对于仅需给予低水平辅助供氧支持(即仅通过鼻氧管)的儿科患者,不作常规推荐。对于严重免疫功能低下儿童使用地塞米松治疗重症尚未得到评估,其可能有害,因此应根据具体病例加以考虑。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
美国传染病学会支持对重症住院患者给予地塞米松治疗。[466]Bhimraj A, Morgan RL, Hirsch Shumaker A, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19 infection. 2022 [internet publication]. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management
BMJ rapid recommendations: a living WHO guideline on drugs for COVID-19 在新窗口中打开
证据支持将皮质类固醇用于住院患者。
一项 Cochrane 评价发现,全身皮质类固醇治疗可能略微降低有症状的住院患者的全因死亡率(中等确定性证据)。研究中的多数参与者都接受了无创通气或有创机械通气治疗。低确定性证据表明,呼吸机撤机天数亦可能减少;然而,由于方法学限制,目前证据仍然不确定。对于无任何额外供氧需求的有症状住院患者,其死亡风险增加的证据因缺乏统计学意义而受限。目前尚不清楚哪一种全身皮质类固醇治疗最为有效。[787]Wagner C, Griesel M, Mikolajewska A, et al. Systemic corticosteroids for the treatment of COVID-19. Cochrane Database Syst Rev. 2021 Aug 16;(8):CD014963. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD014963/full http://www.ncbi.nlm.nih.gov/pubmed/34396514?tool=bestpractice.com
一项实时系统评价和网络荟萃分析发现,与标准治疗相比,皮质类固醇治疗可能降低死亡率。[788]Siemieniuk RA, Bartoszko JJ, Ge L, et al. Drug treatments for covid-19: living systematic review and network meta-analysis. BMJ. 2020 Jul 30;370:m2980. https://www.bmj.com/content/370/bmj.m2980 http://www.ncbi.nlm.nih.gov/pubmed/32732190?tool=bestpractice.com [789]Siemieniuk RA, Bartoszko JJ, Ge L, et al. Update to living systematic review on drug treatments for covid-19. BMJ. 2021 Mar 31;372:n858. https://www.bmj.com/content/372/bmj.n858.long http://www.ncbi.nlm.nih.gov/pubmed/33789885?tool=bestpractice.com
监测患者不良反应(例如高血糖、潜伏性感染、精神效应、潜伏感染再活化),并评估药物相互作用。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
对糖尿病患者给予皮质类固醇将使其血糖控制恶化,因此应每日至少四次进行血糖检测。[956]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): dexamethasone/glucocorticosteroid therapy in COVID-19 patients – implications and guidance for the management of blood glucose in people with and without diabetes. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/COncise%20adVice%20on%20Inpatient%20Diabetes%20-%20dexamethasone%20therapy%20in%20covid-19%20patients%20implications%20and%20guidance%20for%20the%20management%20of%20blood%20glucose%20in%20people%20with%20and%20without%20diabetes%20Version%202.3%20November%202020.pdf
对于糖尿病患者,使用与非糖尿病患者相同剂量皮质类固醇,但应调整糖尿病用药,原因在于其将使糖尿病控制变得更劣。
合成皮质类固醇可通过影响碳水化合物代谢和诱导胰岛素抵抗而导致高血糖。[957]Joint British Diabetes Societies for inpatient care. Management of hyperglycaemia and steroid (glucocorticosteroid) therapy. 2021 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/JBDS_08_Steroids_DM_Guideline_FINAL_28052021.pdf
COVID-19 亦与胰岛素抵抗增加和来自胰岛 β 细胞的胰岛素分泌减少具有相关性。[956]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): dexamethasone/glucocorticosteroid therapy in COVID-19 patients – implications and guidance for the management of blood glucose in people with and without diabetes. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/COncise%20adVice%20on%20Inpatient%20Diabetes%20-%20dexamethasone%20therapy%20in%20covid-19%20patients%20implications%20and%20guidance%20for%20the%20management%20of%20blood%20glucose%20in%20people%20with%20and%20without%20diabetes%20Version%202.3%20November%202020.pdf
如果出现高血糖,需排除糖尿病酮症酸中毒或高渗性高血糖状态,遵循所在医院常规,管理正在使用皮质类固醇的糖尿病合并 COVID-19 患者血糖。[956]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): dexamethasone/glucocorticosteroid therapy in COVID-19 patients – implications and guidance for the management of blood glucose in people with and without diabetes. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/COncise%20adVice%20on%20Inpatient%20Diabetes%20-%20dexamethasone%20therapy%20in%20covid-19%20patients%20implications%20and%20guidance%20for%20the%20management%20of%20blood%20glucose%20in%20people%20with%20and%20without%20diabetes%20Version%202.3%20November%202020.pdf
英国国家糖尿病住院患者 COVID-19 应对组(National Inpatient Diabetes COVID-19 Response Group)推荐的病房用药方案采用皮下注射胰岛素。[956]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): dexamethasone/glucocorticosteroid therapy in COVID-19 patients – implications and guidance for the management of blood glucose in people with and without diabetes. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/COncise%20adVice%20on%20Inpatient%20Diabetes%20-%20dexamethasone%20therapy%20in%20covid-19%20patients%20implications%20and%20guidance%20for%20the%20management%20of%20blood%20glucose%20in%20people%20with%20and%20without%20diabetes%20Version%202.3%20November%202020.pdf [958]Rayman G, Lumb AN, Kennon B, et al. Dexamethasone therapy in COVID-19 patients: implications and guidance for the management of blood glucose in people with and without diabetes. Diabet Med. 2021 Jan;38(1):e14378 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436853 http://www.ncbi.nlm.nih.gov/pubmed/32740972?tool=bestpractice.com
该团体强调,由于潜在的 β 细胞功能损害和可能的严重胰岛素抵抗,磺脲类药物 不建议加以使用。[956]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): dexamethasone/glucocorticosteroid therapy in COVID-19 patients – implications and guidance for the management of blood glucose in people with and without diabetes. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/COncise%20adVice%20on%20Inpatient%20Diabetes%20-%20dexamethasone%20therapy%20in%20covid-19%20patients%20implications%20and%20guidance%20for%20the%20management%20of%20blood%20glucose%20in%20people%20with%20and%20without%20diabetes%20Version%202.3%20November%202020.pdf
当停止皮质类固醇给药时,血糖控制将有可能得到改善,但可能需要数天时间。
遵循当地常规,逐渐调整抗糖尿病药物。
了解既往对皮质类固醇的反应。
既往皮质类固醇治疗期间出现过精神并发症,可增加后续治疗当中复发的风险。[959]Judd LL, Schettler PJ, Brown ES, et al. Adverse consequences of glucocorticoid medication: psychological, cognitive, and behavioral effects. Am J Psychiatry. 2014 Oct;171(10):1045-51 https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2014.13091264 http://www.ncbi.nlm.nih.gov/pubmed/25272344?tool=bestpractice.com
监测精神不良反应。[960]Kenna HA, Poon AW, de los Angeles CP, et al. Psychiatric complications of treatment with corticosteroids: review with case report. Psychiatry Clin Neurosci. 2011 Oct;65(6):549-60 https://onlinelibrary.wiley.com/doi/full/10.1111/j.1440-1819.2011.02260.x http://www.ncbi.nlm.nih.gov/pubmed/22003987?tool=bestpractice.com
这些不良反应的严重程度可能各有不同,并且包括:
细微的性情改变
剧烈的情绪改变,包括躁狂状态
认知障碍。
起始皮质类固醇治疗, 最常与躁狂发作和谵妄状态呈现关联。长期皮质类固醇治疗后,最常见的伴发表现为抑郁。[961]Warrington TP, Bostwick JM. Psychiatric adverse effects of corticosteroids. Mayo Clin Proc. 2006 Oct;81(10):1361-7 https://www.mayoclinicproceedings.org/article/S0025-6196(11)61160-9/fulltext http://www.ncbi.nlm.nih.gov/pubmed/17036562?tool=bestpractice.com
不良反应似乎与剂量有关,并且在使用长期方案或长效制剂时,以及在老年患者中更为常见。[959]Judd LL, Schettler PJ, Brown ES, et al. Adverse consequences of glucocorticoid medication: psychological, cognitive, and behavioral effects. Am J Psychiatry. 2014 Oct;171(10):1045-51 https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2014.13091264 http://www.ncbi.nlm.nih.gov/pubmed/25272344?tool=bestpractice.com 对于因停止长期皮质类固醇治疗而出现神经精神性不良反应的患者,也是如此。[962]Fardet L, Nazareth I, Whitaker HJ, et al. Severe neuropsychiatric outcomes following discontinuation of long-term glucocorticoid therapy: a cohort study. J Clin Psychiatry. 2013 Apr;74(4):e281-6 http://www.ncbi.nlm.nih.gov/pubmed/23656853?tool=bestpractice.com
与精神病学团队联络,获取患者情绪相关性并发症的适当管理建议(基于专家意见)。
这可能涉及:
如有临床指征,可调整剂量或停用皮质类固醇治疗。
如果停用皮质类固醇,需注意可能出现的停药反应。[962]Fardet L, Nazareth I, Whitaker HJ, et al. Severe neuropsychiatric outcomes following discontinuation of long-term glucocorticoid therapy: a cohort study. J Clin Psychiatry. 2013 Apr;74(4):e281-6 http://www.ncbi.nlm.nih.gov/pubmed/23656853?tool=bestpractice.com 这可能表现为虚弱、乏力、胃肠道症状、谵妄,以及包括抑郁在内的精神并发症
当有心境障碍病史的患者开始接受皮质类固醇治疗时,考虑进行预防性用药,降低精神不良反应风险。寻求精神科专家建议。
地塞米松: 儿童:咨询专科医生,获得剂量指导;成人:6 mg,口服/静脉注射,一天一次,持续 7-10 天
地塞米松 : 儿童:咨询专科医生,获得剂量指导;成人:6 mg,口服/静脉注射,一天一次,持续 7-10 天
地塞米松: 儿童:咨询专科医生,获得剂量指导;成人:6 mg,口服/静脉注射,一天一次,持续 7-10 天
或
氢化可的松琥珀酸钠: 儿童:咨询专科医生获取用药指导;成人:50 mg,静脉使用,每 8 小时一次,连用 7-10 日
氢化可的松琥珀酸钠 : 儿童:咨询专科医生获取用药指导;成人:50 mg,静脉使用,每 8 小时一次,连用 7-10 日
氢化可的松琥珀酸钠: 儿童:咨询专科医生获取用药指导;成人:50 mg,静脉使用,每 8 小时一次,连用 7-10 日
泼尼松龙: 儿童:咨询专科医生,获得剂量指导;成人:40 mg/天,口服,分 1-2 次给药,连续 7-10 天
泼尼松龙 : 儿童:咨询专科医生,获得剂量指导;成人:40 mg/天,口服,分 1-2 次给药,连续 7-10 天
泼尼松龙: 儿童:咨询专科医生,获得剂量指导;成人:40 mg/天,口服,分 1-2 次给药,连续 7-10 天
或
地塞米松: 儿童:咨询专科医生,获得剂量指导;成人:6 mg,口服/静脉注射,一天一次,持续 7-10 天
地塞米松 : 儿童:咨询专科医生,获得剂量指导;成人:6 mg,口服/静脉注射,一天一次,持续 7-10 天
地塞米松: 儿童:咨询专科医生,获得剂量指导;成人:6 mg,口服/静脉注射,一天一次,持续 7-10 天
或
氢化可的松琥珀酸钠: 儿童:咨询专科医生获取用药指导;成人:50 mg,静脉使用,每 8 小时一次,连用 7-10 日
氢化可的松琥珀酸钠 : 儿童:咨询专科医生获取用药指导;成人:50 mg,静脉使用,每 8 小时一次,连用 7-10 日
氢化可的松琥珀酸钠: 儿童:咨询专科医生获取用药指导;成人:50 mg,静脉使用,每 8 小时一次,连用 7-10 日
泼尼松龙: 儿童:咨询专科医生,获得剂量指导;成人:40 mg/天,口服,分 1-2 次给药,连续 7-10 天
泼尼松龙 : 儿童:咨询专科医生,获得剂量指导;成人:40 mg/天,口服,分 1-2 次给药,连续 7-10 天
泼尼松龙: 儿童:咨询专科医生,获得剂量指导;成人:40 mg/天,口服,分 1-2 次给药,连续 7-10 天
或
地塞米松
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
或
氢化可的松琥珀酸钠
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
泼尼松龙
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
或
甲泼尼龙
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
针对特定患者群中部分患者治疗的附加建议
对抗病毒药物 remdesivir 加以考虑。指南建议各不相同。
世界卫生组织有条件建议将静脉用抗病毒药物remdesivir用于重症成人患者。尚无充分证据支持儿童用药相关建议,并且已有试验并未纳入孕妇或母乳喂养的女性。该建议是基于表明 remdesivir 可能降低死亡率的低确定性证据,以及表明 remdesivir 可能减少机械通气需求的中等确定性证据。中等确定性证据表明,remdesivir 可能对症状改善时间的影响极小或没有影响。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3 [736]Rochwerg B, Siemieniuk RA, Agoritsas T, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020 Sep 4;370:m3379. https://www.bmj.com/content/370/bmj.m3379.long http://www.ncbi.nlm.nih.gov/pubmed/32887691?tool=bestpractice.com [737]Rochwerg B, Siemieniuk RA, Lamontagne R, et al. Update to living WHO guideline on drugs for covid-19. BMJ. 2021 Jul 6;374:n1703. http://www.ncbi.nlm.nih.gov/pubmed/34230027?tool=bestpractice.com
在英国,国家卫生与临床优化研究所建议,对于需低流量辅助供氧的住院成人和 ≥12 岁(体重 ≥40 kg)以上儿童,可考虑给予 remdesivir。该项建议是基于中等确定性证据,其表明 remdesivir 可能降低需低流量辅助供氧的住院患者的死亡风险。这可能是因为在病程早期给药。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
在美国,国立卫生研究院指南专家组建议将 remdesivir 用于需辅助供氧的住院儿童或成人患者。可单独给药(例如,对于有极低辅助供氧需求的患者),或与地塞米松联合使用(例如,对于辅助供氧量需求增加的患者)。专家组还建议将 remdesivir 单用于有重症风险因素但无辅助供氧需求的 12-17 岁住院患儿。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
美国传染病学会支持对需要氧疗的住院重症患者使用 remdesivir。[466]Bhimraj A, Morgan RL, Hirsch Shumaker A, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19 infection. 2022 [internet publication]. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management
BMJ rapid recommendations: a living WHO guideline on drugs for COVID-19 在新窗口中打开
应在症状发作后尽快给予 remdesivir。对该适应证的建议疗程为 5 日或持续使用直至出院,以先期达到者为准。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov [735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
证据未表明与 5 天疗程相比,remdesivir 10 天疗程可带来更多获益,但证据提示有害风险升高。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191 然而,部分专家则可能建议对第 5 天仍未显示出明显临床改善的患者进行疗程 10 天的治疗。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
如果患者病情出现进展,完成整个 remdesivir 疗程可能并无获益。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191 然而,如果患者进展至需给予高流量氧、无创通气、机械通气或体外膜肺氧合,美国指南则建议完成整个疗程。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
尽管指南建议将 remdesivir 用于重症患者,但其应用相关证据相互冲突。
一项 Cochrane 评价发现,与安慰剂或常规治疗相比,remdesivir 对住院患者 28 天全因死亡率的影响可能很小或几乎没有影响(中等确定性)。对临床有所改善或有所加重的影响尚不确定。暂无足够的有效数据,验证 remdesivir 对基线呼吸支持所定义亚组死亡率的影响。[791]Ansems K, Grundeis F, Dahms K, et al. Remdesivir for the treatment of COVID-19. Cochrane Database Syst Rev. 2021 Aug 5;(8):CD014962. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD014962/full http://www.ncbi.nlm.nih.gov/pubmed/34350582?tool=bestpractice.com
不良反应包括肾毒性和肝毒性。
remdesivir 不推荐用于估算的肾小球滤过率(estimated glomerular filtration rate, eGFR)<30 mL/min 的患者。开始治疗前和治疗期间应根据临床情况,对肾功能进行监测。静脉制剂含有溶解度增强剂磺丁基醚 β-环糊精钠(sulfobutyl ether beta-cyclodextrin sodium, SBECD),可通过肾脏清除。肾脏损伤患者体内 SBECD 的累积,可能导致肝肾毒性。如果可能,应考虑对肾脏损伤患者优先使用冻干粉针,因其 SBECD 含量更少。
与安慰剂相比,remdesivir 对急性肾损伤可能仅有极轻微的作用或者没有作用。[855]Izcovich A, Siemieniuk RA, Bartoszko JJ, et al. Adverse effects of remdesivir, hydroxychloroquine and lopinavir/ritonavir when used for COVID-19: systematic review and meta-analysis of randomised trials. BMJ Open. 2022 Mar 2;12(3):e048502. https://bmjopen.bmj.com/content/12/3/e048502 http://www.ncbi.nlm.nih.gov/pubmed/35236729?tool=bestpractice.com
转氨酶升高已见诸报道。开始治疗前和治疗期间应根据临床情况,对肝功能进行监测。如果丙氨酸氨基转移酶(alanine aminotransferase, ALT)水平升高至正常上限 ≥ 10 倍,应考虑停止治疗。如果 ALT 升高伴有肝脏炎症征象或症状,应停止治疗。
开始治疗前和治疗期间应根据临床情况,对凝血酶原时间进行监测,因为凝血酶原时间延长已见诸报道。
超敏反应(包括液体输注相关性反应和全身过敏反应)已见诸报道。
需在严重超敏反应可得到控制的环境中给药。输注过程中对患者进行监测,并在输注后观察至少 1 小时。
考虑所有接受 COVID-19 治疗患者的潜在不良反应和药物相互作用。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
世界卫生组织在其有关 COVID-19 临床管理的临时指南中强调了 remdesivir 的以下重要不良反应:[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
肾脏损伤(对估算 GFR <30 mL/min 的患者不应使用 remdesivir)
肝酶升高
低血压
胃肠道并发症
皮疹。
此清单并未详尽列出全部不良反应 – 参阅当地处方集,以获取更多信息。请咨询相关专业同事和/或药师以获取建议。
remdesivir: 年龄 ≥12 岁和体重 ≥40 kg 的儿童和成人:第 1 天静脉输注 200 mg 作为负荷剂量,而后每 24 小时给予 100 mg,持续 5-10 天
remdesivir : 年龄 ≥12 岁和体重 ≥40 kg 的儿童和成人:第 1 天静脉输注 200 mg 作为负荷剂量,而后每 24 小时给予 100 mg,持续 5-10 天
remdesivir: 年龄 ≥12 岁和体重 ≥40 kg 的儿童和成人:第 1 天静脉输注 200 mg 作为负荷剂量,而后每 24 小时给予 100 mg,持续 5-10 天
更多 remdesivirremdesivir 可能在部分国家/地区获批用于 12 岁以下儿童。然而,尚无充分证据支持常规推荐将其用于 12 岁以下儿童(可根据和危险因素考虑治疗)。
remdesivir: 年龄 ≥12 岁和体重 ≥40 kg 的儿童和成人:第 1 天静脉输注 200 mg 作为负荷剂量,而后每 24 小时给予 100 mg,持续 5-10 天
remdesivir : 年龄 ≥12 岁和体重 ≥40 kg 的儿童和成人:第 1 天静脉输注 200 mg 作为负荷剂量,而后每 24 小时给予 100 mg,持续 5-10 天
remdesivir: 年龄 ≥12 岁和体重 ≥40 kg 的儿童和成人:第 1 天静脉输注 200 mg 作为负荷剂量,而后每 24 小时给予 100 mg,持续 5-10 天
更多 remdesivirremdesivir 可能在部分国家/地区获批用于 12 岁以下儿童。然而,尚无充分证据支持常规推荐将其用于 12 岁以下儿童(可根据和危险因素考虑治疗)。
remdesivir
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
针对特定患者群中部分患者治疗的附加建议
考虑使用 IL-6 抑制剂。指南建议各不相同。
世界卫生组织强烈建议将 IL-6 抑制剂(托珠单抗或 sarilumab)用于重症患者。IL-6 抑制剂可与皮质类固醇和 Janus 激酶抑制剂联合使用,并且应与全身皮质类固醇同时开始使用。该建议基于表明 IL-6 抑制剂可降低死亡率和机械通气需求的高确定性证据,以及表明 IL-6 抑制剂还可缩短机械通气持续时间和住院时间的低确定性证据。关于严重不良事件的风险相关证据尚不确定。该建议对儿童的适用性目前尚不确定。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3 [736]Rochwerg B, Siemieniuk RA, Agoritsas T, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020 Sep 4;370:m3379. https://www.bmj.com/content/370/bmj.m3379.long http://www.ncbi.nlm.nih.gov/pubmed/32887691?tool=bestpractice.com [737]Rochwerg B, Siemieniuk RA, Lamontagne R, et al. Update to living WHO guideline on drugs for covid-19. BMJ. 2021 Jul 6;374:n1703. http://www.ncbi.nlm.nih.gov/pubmed/34230027?tool=bestpractice.com
在英国,英国国家卫生与临床优化研究所建议,若住院成人满足以下条件,可给予单剂托珠单抗:正在接收皮质类固醇激素(例如地塞米松)治疗,或已完成一个疗程(除非患者无法进行皮质类固醇激素治疗);本次入院期间未接受其他 IL-6 抑制剂治疗;无证据表明患者伴有可能因接受托珠单抗治疗而加重的细菌性或病毒性感染(除 SARS-CoV-2 外);以及患者要么需接受辅助供氧且 C 反应蛋白水平 ≥75 mg/L,要么处于高流量鼻套管吸氧、持续气道正压(通气)、无创通气或有创机械通气起始 48 小时以内。仅当患者年龄达到 1 岁及以上,且仅在临床试验中,可考虑将托珠单抗用于罹患重症或小儿炎性多系统综合征的儿童和年轻人。仅当托珠单抗无法使用或药物不可及时,方考虑将 sarilumab 作为成人替代选择(使用与托珠单抗相同的应用标准)。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
在美国,国立卫生研究院指南专家组建议对氧气需求迅速增加以及伴有全身炎症,使用皮质类固醇治疗的患者,给予托珠单抗(如果托珠单抗无法获取或无法应用,则可给予 sarilumab)。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov 除标准治疗(即皮质类固醇)之外,美国传染病学会建议对于呈现进行性加重且全身炎症标志物升高的住院成人患者,考虑给予托珠单抗,而非仅仅给予标准治疗。如果托珠单抗无法使用,则可使用 sarilumab。[466]Bhimraj A, Morgan RL, Hirsch Shumaker A, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19 infection. 2022 [internet publication]. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management
BMJ rapid recommendations: a living WHO guideline on drugs for COVID-19 在新窗口中打开
证据支持 IL-6 抑制剂的应用。
一项 Cochrane 评价发现,与单纯的标准治疗或安慰剂相比,托珠单抗降低了 28 日全因死亡率(高确定性证据),并且可能略微减少严重不良事件(中等确定性证据)。有证据表明,对第 60 日后死亡率的影响尚不确定。然而,托珠单抗对第 28 日的临床改善(即出院或临床试验员规定量表所测量的改善情况)影响可能很小或并无影响。托珠单抗对其他结局的影响尚不确定。有关 sarilumab 效力的证据尚不确定。[793]Ghosn L, Chaimani A, Evrenoglou T, et al. Interleukin-6 blocking agents for treating COVID-19: a living systematic review. Cochrane Database Syst Rev. 2021 Mar 18;(3):CD013881. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013881/full http://www.ncbi.nlm.nih.gov/pubmed/33734435?tool=bestpractice.com
一项实时系统评价和网络荟萃分析发现,与标准治疗相比,IL-6 抑制剂(与皮质类固醇联用)可能降低死亡率(中等确定性证据),可能减少机械通气需求(中等确定性证据),以及可能缩短住院时间(中等确定性证据)。[788]Siemieniuk RA, Bartoszko JJ, Ge L, et al. Drug treatments for covid-19: living systematic review and network meta-analysis. BMJ. 2020 Jul 30;370:m2980. https://www.bmj.com/content/370/bmj.m2980 http://www.ncbi.nlm.nih.gov/pubmed/32732190?tool=bestpractice.com [789]Siemieniuk RA, Bartoszko JJ, Ge L, et al. Update to living systematic review on drug treatments for covid-19. BMJ. 2021 Mar 31;372:n858. https://www.bmj.com/content/372/bmj.n858.long http://www.ncbi.nlm.nih.gov/pubmed/33789885?tool=bestpractice.com
一项针对来自 45 项随机试验的约 20,000 名患者的荟萃分析指出,托珠单抗(与皮质类固醇联用)可能降低严重或危重疾病患者的死亡率,sarilumab(与皮质类固醇联用)可能降低死亡率。现有证据显示,托珠单抗与 sarilumab 可能具有类似的有效性。当未与皮质类固醇联用时,这些药物可能没有益处。[963]Zeraatkar D, Cusano E, Martínez JPD, et al. Use of tocilizumab and sarilumab alone or in combination with corticosteroids for covid-19: systematic review and network meta-analysis. BMJ Medicine 2022 Mar 2;1:e000036. https://bmjmedicine.bmj.com/content/1/1/e000036
使用 IL-6 抑制剂的患者感染风险升高,包括活动性结核病、侵袭性真菌感染和机会性感染病原体。
起始治疗之前,应进行常规血液检查,包括白细胞计数、血小板计数、转氨酶和总胆红素。由于全身性皮质类固醇治疗患者免疫抑制风险升高,因此应对所有此类患者监测感染征象和症状。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
免疫功能低下患者应避免使用此类药物。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
托珠单抗: 儿童:咨询专科医生,获得剂量指导;成人:8 mg/kg,静脉使用,单次给药,最多 800 mg/剂
托珠单抗 : 儿童:咨询专科医生,获得剂量指导;成人:8 mg/kg,静脉使用,单次给药,最多 800 mg/剂
托珠单抗: 儿童:咨询专科医生,获得剂量指导;成人:8 mg/kg,静脉使用,单次给药,最多 800 mg/剂
更多 托珠单抗通常作为单剂静脉注射给药;但是,如果临床反应不足,可以在第一次给药后 12 至 48 小时给予第二次给药。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
或
Sarilumab: 儿童:咨询专科医生,获得剂量指导;成人:400 mg,静脉使用,单次给药
Sarilumab : 儿童:咨询专科医生,获得剂量指导;成人:400 mg,静脉使用,单次给药
Sarilumab: 儿童:咨询专科医生,获得剂量指导;成人:400 mg,静脉使用,单次给药
更多 Sarilumab通常作为单剂静脉注射给药;但是,如果临床反应不足,可以在第一次给药后 12 至 48 小时给予第二次给药。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
托珠单抗: 儿童:咨询专科医生,获得剂量指导;成人:8 mg/kg,静脉使用,单次给药,最多 800 mg/剂
托珠单抗 : 儿童:咨询专科医生,获得剂量指导;成人:8 mg/kg,静脉使用,单次给药,最多 800 mg/剂
托珠单抗: 儿童:咨询专科医生,获得剂量指导;成人:8 mg/kg,静脉使用,单次给药,最多 800 mg/剂
更多 托珠单抗通常作为单剂静脉注射给药;但是,如果临床反应不足,可以在第一次给药后 12 至 48 小时给予第二次给药。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
或
Sarilumab: 儿童:咨询专科医生,获得剂量指导;成人:400 mg,静脉使用,单次给药
Sarilumab : 儿童:咨询专科医生,获得剂量指导;成人:400 mg,静脉使用,单次给药
Sarilumab: 儿童:咨询专科医生,获得剂量指导;成人:400 mg,静脉使用,单次给药
更多 Sarilumab通常作为单剂静脉注射给药;但是,如果临床反应不足,可以在第一次给药后 12 至 48 小时给予第二次给药。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
托珠单抗
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
或
Sarilumab
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
针对特定患者群中部分患者治疗的附加建议
考虑给予 JAK 抑制剂。指南建议各不相同。
世界卫生组织强烈建议将 JAK 抑制剂(巴瑞替尼)用于重症患者。巴瑞替尼可与皮质类固醇和 IL-6 抑制剂联合使用,并且应与全身皮质类固醇同时开始使用。该项建议是基于巴瑞替尼可降低死亡率的高确定性证据,以及巴瑞替尼可能缩短机械通气持续时间和住院时间的中等确定性证据。该建议对儿童的适用性目前尚不确定。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3 [736]Rochwerg B, Siemieniuk RA, Agoritsas T, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020 Sep 4;370:m3379. https://www.bmj.com/content/370/bmj.m3379.long http://www.ncbi.nlm.nih.gov/pubmed/32887691?tool=bestpractice.com [737]Rochwerg B, Siemieniuk RA, Lamontagne R, et al. Update to living WHO guideline on drugs for covid-19. BMJ. 2021 Jul 6;374:n1703. http://www.ncbi.nlm.nih.gov/pubmed/34230027?tool=bestpractice.com
在英国, 国家卫生与临床优化研究所推荐巴瑞替尼用于以下住院成人:需给予辅助供氧,并且正在接受或已完成一个疗程皮质类固醇治疗(除非具有禁忌证),并且不存在可能因巴瑞替尼用药而恶化的感染证据(除 SARS-CoV-2 以外的其他感染)。巴瑞替尼亦可考虑用于 ≥2 岁儿童,只要其符合相同标准。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
在美国,国立卫生研究院指南专家组建议对氧气需求迅速增加以及伴有全身炎症,使用皮质类固醇治疗的患者,可给予巴瑞替尼。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
美国传染病学会建议对炎症标志物升高的重症住院成人,可给予巴瑞替尼(联合皮质类固醇)。对于因禁忌证而无法接受皮质类固醇治疗的患者,其建议巴瑞克替尼与 remdesivir 联合给药,而非 remdesivir 单独给药。[466]Bhimraj A, Morgan RL, Hirsch Shumaker A, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19 infection. 2022 [internet publication]. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management
BMJ rapid recommendations: a living WHO guideline on drugs for COVID-19 在新窗口中打开
该类别中的其他药物包括托法替布和芦可替尼。
世界卫生组织 不建议使用此类药物,除非巴瑞替尼或 IL-6 抑制剂无法获取。托法替布或芦可替尼对死亡率、机械通气需求和住院时间的影响仍不明确,需要更多试验证据。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3 [736]Rochwerg B, Siemieniuk RA, Agoritsas T, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020 Sep 4;370:m3379. https://www.bmj.com/content/370/bmj.m3379.long http://www.ncbi.nlm.nih.gov/pubmed/32887691?tool=bestpractice.com [737]Rochwerg B, Siemieniuk RA, Lamontagne R, et al. Update to living WHO guideline on drugs for covid-19. BMJ. 2021 Jul 6;374:n1703. http://www.ncbi.nlm.nih.gov/pubmed/34230027?tool=bestpractice.com
在美国,国立卫生研究院指南专家组建议,仅在巴瑞克替尼无法获取或无法应用时,方使用托法替布。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov 美国传染病学会建议对于未接受无创通气或有创机械通气的重症住院成人,给予托法替布。[466]Bhimraj A, Morgan RL, Hirsch Shumaker A, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19 infection. 2022 [internet publication]. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management
证据支持 JAK 抑制剂的应用。
一项 Cochrane 评价发现,JAK 抑制剂可能降低至第 28 日(中等确定性证据)和至第 60 日(高确定性证据)的全因死亡率。它们可能对临床状态或不良事件发生率的改善影响极小或并未影响(中等确定性证据)。巴瑞替尼是最常接受评估的 JAK 抑制剂。[794]Kramer A, Prinz C, Fichtner F, et al. Janus kinase inhibitors for the treatment of COVID-19. Cochrane Database Syst Rev. 2022 Jun 13;6(6):CD015209. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015209/full http://www.ncbi.nlm.nih.gov/pubmed/35695334?tool=bestpractice.com
一项实时系统评价和网络荟萃分析发现,与标准治疗相比,JAK 制剂可能降低死亡率(高确定性证据),缩短机械通气持续时间(高确定性证据),以及缩短住院时间(高确定性证据)。[788]Siemieniuk RA, Bartoszko JJ, Ge L, et al. Drug treatments for covid-19: living systematic review and network meta-analysis. BMJ. 2020 Jul 30;370:m2980. https://www.bmj.com/content/370/bmj.m2980 http://www.ncbi.nlm.nih.gov/pubmed/32732190?tool=bestpractice.com [789]Siemieniuk RA, Bartoszko JJ, Ge L, et al. Update to living systematic review on drug treatments for covid-19. BMJ. 2021 Mar 31;372:n858. https://www.bmj.com/content/372/bmj.n858.long http://www.ncbi.nlm.nih.gov/pubmed/33789885?tool=bestpractice.com
患者感染风险升高(包括活动性结核病、侵袭性真菌感染和机会性感染病原体)。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
避免在罹患已知活动性结核病的患者中使用。
由于全身性皮质类固醇治疗患者免疫抑制风险升高,因此应对所有此类患者监测感染征象和症状。
治疗前和治疗期间应执行不同的全血细胞监测策略。
巴瑞替尼不建议用于重度肾损害或肝损害患者。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
不建议将巴瑞替尼用于估算的肾小球滤过率 ≤15 mL/min 的成人(<9 岁儿童 ≤30 mL/min),或接受透析或肾脏替代治疗的患者。对于估算的肾小球滤过率 ≤60 mL/min 的患者,建议减少剂量。
巴瑞替尼尚未在重度肝功能不全患者中进行研究,尚不清楚此类患者是否需要调整剂量。应仅当潜在获益超过潜在风险时,方予以使用。
中重度肾功能不全患者(包括透析患者)应慎用托法替布和芦可替尼;可能需要调整剂量。
治疗前和治疗期间应监测肾功能和肝功能。
不良反应包括白细胞减少、淋巴细胞减少、血小板增多、贫血、凝血异常、肝功能损害和继发感染。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
其他严重不良反应包括静脉血栓形成和重度感染。
美国食品药品监督管理局已发出警告,称 JAK 抑制剂将使得严重心脏相关事件、肿瘤、血栓和死亡风险升高。[964]US Food and Drug Administration. FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions. 2021 [internet publication]. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death
CKD 患者起始 JAK 抑制剂用药之前应检查肾功能,如同其他患者一样。
由于可能需要调整剂量,因此应参阅当地处方集。
如果患者正在进行透析、患有终末期肾功能衰竭或患有急性肾损伤,则不推荐使用巴瑞替尼。[965]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.1
芦可替尼和托法替布在中重度肾功能损害患者中应谨慎应用,其剂量可能需要调整。参阅当地处方集,寻求肾脏病学团队建议。
CKD 患者接受 JAK 抑制剂治疗期间,需对肾功能予以特别密切的监测。
巴瑞克替尼 (Baricitinib): 儿童:咨询专科医生,获得剂量指导;成人:4 mg,口服,每日一次,持续 14 日
巴瑞克替尼 (Baricitinib) : 儿童:咨询专科医生,获得剂量指导;成人:4 mg,口服,每日一次,持续 14 日
巴瑞克替尼 (Baricitinib): 儿童:咨询专科医生,获得剂量指导;成人:4 mg,口服,每日一次,持续 14 日
或
巴瑞克替尼 (Baricitinib): 儿童:咨询专科医生,获得剂量指导;成人:4 mg,口服,每日一次,持续 14 日
巴瑞克替尼 (Baricitinib) : 儿童:咨询专科医生,获得剂量指导;成人:4 mg,口服,每日一次,持续 14 日
巴瑞克替尼 (Baricitinib): 儿童:咨询专科医生,获得剂量指导;成人:4 mg,口服,每日一次,持续 14 日
或
巴瑞克替尼 (Baricitinib)
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
托法替布
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
或
卢可替尼
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
针对特定患者群中部分患者治疗的附加建议
根据当地常规,酌情处理实验室确认的混合感染(例如疟疾、结核病、流行性感冒)。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
不论是否存在 SARS-CoV-2 混合感染,所有流感患者治疗均相同。对于疑似存在单纯流感感染,或存在两者混合感染的住院患者,须尽快给予奥司他韦,进行经验性治疗,无需等待流感检测结果。一旦排除流感,即可停止抗病毒治疗。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
针对特定患者群中部分患者治疗的附加建议
建议给予对乙酰氨基酚或布洛芬。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 [530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
布洛芬只能在控制症状所需最短时间内以最低有效剂量服用。不建议在孕妇(尤其是孕晚期)或 <3 月龄儿童(年龄界值因国家而异)中使用。
慢性肾病和/或心力衰竭
避免将非甾体抗炎药(non-steroidal anti-inflammatory drug, NSAID)用于慢性肾病和/或心力衰竭的患者(基于专家意见)。
哮喘
NSAID 可能会使某些哮喘患者症状恶化,因此需询问患者对其是否存在已知的过度敏感不良反应。[847]Global Initiative for Asthma. Global strategy for asthma management and prevention. 2021 [internet publication] https://ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf
对乙酰氨基酚: 儿童:查询当地药物处方集,以获取剂量指导;成人:必要时,每 4-6 小时口服 500-1000 mg,每日最多 4000 mg
对乙酰氨基酚 : 儿童:查询当地药物处方集,以获取剂量指导;成人:必要时,每 4-6 小时口服 500-1000 mg,每日最多 4000 mg
对乙酰氨基酚: 儿童:查询当地药物处方集,以获取剂量指导;成人:必要时,每 4-6 小时口服 500-1000 mg,每日最多 4000 mg
或
对乙酰氨基酚
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
或
布洛芬
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
针对特定患者群中所有患者的治疗建议
多个专业呼吸科组织的指南均同意,应建议患有哮喘或 COPD 的患者继续按处方使用吸入剂(包括吸入皮质类固醇)(包括吸入皮质类固醇),无论其是否罹患 COVID-19。[857]Global Initiative for Asthma. Global strategy for asthma management and prevention. 2022 [internet publication] https://ginasthma.org/gina-reports [858]British Thoracic Society. Advice for healthcare professionals treating people with asthma (adults) in relation to COVID-19. 2020 [internet publication] https://www.brit-thoracic.org.uk/about-us/covid-19-information-for-the-respiratory-community [859]Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. 2021 [internet publication] https://goldcopd.org/2021-gold-reports [860]National Institute for Health and Care Excellence. COVID-19 rapid guideline: community-based care of patients with chronic obstructive pulmonary disease (COPD). 2020 [internet publication] https://www.nice.org.uk/guidance/ng168 [861]Hasan SS, Capstick T, Zaidi STR, et al. Use of corticosteroids in asthma and COPD patients with or without COVID-19. Respir Med. 2020 Aug-Sep;170:106045 https://www.resmedjournal.com/article/S0954-6111(20)30185-2/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32843175?tool=bestpractice.com
继续吸入皮质类固醇治疗的总体目标是降低哮喘或 COPD 加重的风险。[861]Hasan SS, Capstick T, Zaidi STR, et al. Use of corticosteroids in asthma and COPD patients with or without COVID-19. Respir Med. 2020 Aug-Sep;170:106045 https://www.resmedjournal.com/article/S0954-6111(20)30185-2/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32843175?tool=bestpractice.com
尚无证据表明吸入皮质类固醇与哮喘患者的 COVID-19 感染有关。[862]Centre for Evidence-Based Medicine; Hartmann-Boyce J, Hobbs R. Inhaled steroids in asthma during the COVID-19 outbreak. 2020 [internet publication] https://www.cebm.net/covid-19/inhaled-steroids-in-asthma-during-the-covid-19-outbreak 也无证据表明它们会增加 COPD 患者的 COVID-19 相关风险。[860]National Institute for Health and Care Excellence. COVID-19 rapid guideline: community-based care of patients with chronic obstructive pulmonary disease (COPD). 2020 [internet publication] https://www.nice.org.uk/guidance/ng168
居家或在医院接受诊疗的急症患者可能会对其被给予的 COPD 或哮喘吸入器遗忘向您告知。酌情谨记对吸入器进行检查以及给予药物。
许多吸入器含有多种药物,因此应确保勿重复给药。
对于出现急性肾损伤的 COPD 或哮喘患者,如果估算 GFR <50 mL/(min·1.73m²),可能需要暂时停用其常用的吸入性长效毒蕈碱受体拮抗剂,具体取决于使用哪种特定药物。查阅当地处方集或寻求药师建议。
其他处方药物
患有严重哮喘或 COPD 并使用口服皮质类固醇作为常规维持治疗处方的患者,也应以尽可能低的剂量继续使用这些药物,因为停用这些药物可能会导致其病情恶化。[857]Global Initiative for Asthma. Global strategy for asthma management and prevention. 2022 [internet publication] https://ginasthma.org/gina-reports [860]National Institute for Health and Care Excellence. COVID-19 rapid guideline: community-based care of patients with chronic obstructive pulmonary disease (COPD). 2020 [internet publication] https://www.nice.org.uk/guidance/ng168 [863]National Institute for Health and Care Excellence. COVID-19 rapid guideline: severe asthma. 2020 [internet publication] https://www.nice.org.uk/guidance/ng166
英国国家卫生与临床优化研究所关于严重哮喘的快速指南建议,在 COVID-19 大流行期间,常规使用生物治疗哮喘的患者应继续使用该药物,但是,若其罹患 COVID-19,则应联系负责其诊疗的专科医生团队。[863]National Institute for Health and Care Excellence. COVID-19 rapid guideline: severe asthma. 2020 [internet publication] https://www.nice.org.uk/guidance/ng166
针对特定患者群中所有患者的治疗建议
世界卫生组织建议,于 COVID-19 患者,不应例行停用降压药,而应根据患者临床情况(尤其是血压和肾功能)进行调整。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
尽管担心使用 ACE 抑制剂或血管紧张素 Ⅱ 受体拮抗剂的患者出现感染风险或患更严重疾病的风险增加,但一项正在进行的系统评价发现,高确定性证据表明此类药物的使用与重症不具相关性。[868]Mackey K, King VJ, Gurley S, et al. Risks and impact of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers on SARS-CoV-2 infection in adults: a living systematic review. Ann Intern Med. 2020 Aug 4;173(3):195-203 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249560 http://www.ncbi.nlm.nih.gov/pubmed/32422062?tool=bestpractice.com [869]Mackey K, Kansagara D, Vela K. Update alert 7: risks and impact of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers on SARS-CoV-2 infection in adults. Ann Intern Med. 2021 Feb;174(2):W25-9 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791405 http://www.ncbi.nlm.nih.gov/pubmed/33395346?tool=bestpractice.com
一些专业学会建议,已经使用这些药物(例如用于治疗高血压、心力衰竭、冠状动脉疾病、CKD 或糖尿病并发症的药物)的患者可以在大流行期间继续使用(前提是其未罹患 COVID-19)。如果患者罹患 COVID-19,建议他们在决定停用此类药物之前接受医生全面临床评估。[870]American Heart Association; Heart Failure Society of America; American College of Cardiology. Patients taking ACE-i and ARBs who contract COVID-19 should continue treatment, unless otherwise advised by their physician. 2020 [internet publication] https://newsroom.heart.org/news/patients-taking-ace-i-and-arbs-who-contract-covid-19-should-continue-treatment-unless-otherwise-advised-by-their-physician [871]European Society of Cardiology Council on Hypertension. Position statement of the ESC Council on Hypertension on ACE-inhibitors and angiotensin receptor blockers. 2020 [internet publication] https://www.escardio.org/Councils/Council-on-Hypertension-(CHT)/News/position-statement-of-the-esc-council-on-hypertension-on-ace-inhibitors-and-ang [872]British Cardiovascular Society; British Society for Heart Failure. BSH & BCS joint statement on ACEi or ARB in relation to COVID-19. 2020 [internet publication] https://www.britishcardiovascularsociety.org/news/ACEi-or-ARB-and-COVID-19 [873]The Renal Association. The Renal Association, UK position statement on COVID-19 and ACE inhibitor/angiotensin receptor blocker use. 2020 [internet publication] https://renal.org/health-professionals/covid-19/ra-resources/renal-association-uk-position-statement-covid-19-and-ace
英国肾脏协会(Renal Association)和英国心血管学会(British Cardiovascular Society)建议,在权衡这些药物对疑似 COVID-19 患者的益处和风险时,遵循当前针对患任何并发急性疾病的患者的标准指导。[872]British Cardiovascular Society; British Society for Heart Failure. BSH & BCS joint statement on ACEi or ARB in relation to COVID-19. 2020 [internet publication] https://www.britishcardiovascularsociety.org/news/ACEi-or-ARB-and-COVID-19 [873]The Renal Association. The Renal Association, UK position statement on COVID-19 and ACE inhibitor/angiotensin receptor blocker use. 2020 [internet publication] https://renal.org/health-professionals/covid-19/ra-resources/renal-association-uk-position-statement-covid-19-and-ace [874]Clark AL, Kalra PR, Petrie MC, et al. Change in renal function associated with drug treatment in heart failure: national guidance. Heart. 2019 Jun;105(12):904-10 http://www.ncbi.nlm.nih.gov/pubmed/31118203?tool=bestpractice.com 其中包括:
进行个体临床评估
对所有肾素-血管紧张素-醛固酮系统(renin-angiotensin-aldosterone system, RAAS)拮抗剂 初始适应症加以考虑(ACE 抑制剂、血管紧张素-Ⅱ 受体拮抗剂、盐皮质激素受体/醛固酮拮抗剂),并对预后获益程度加以考虑
如果暂时停止药物治疗,需考虑健康状况得到改善后何时再次给药。
考虑计算脆弱评分,因为脆弱评分较高的患者,突发不适时更可能受到药物相关性伤害(基于专家意见)。
考虑停用其他在并发疾病期间与急性肾损伤风险增加相关药物的获益与风险,例如其他抗高血压药和利尿药。
如果慢性肾病患者一直在使用非甾体抗炎药,建议他们在并发疾病时停用此类药物。
在社区自我管理心力衰竭的患者可能希望在出现可能导致脱水的并发疾病期间减少利尿药剂量 (基于专家意见)。
如果患者病情复杂(例如正在进行肾脏替代治疗或免疫抑制治疗),可向患者心脏病学团队或肾病学团队寻求建议 。
针对特定患者群中部分患者治疗的附加建议
对一切适当的试验性或新兴治疗加以考虑。
抗病毒治疗将在疾病早期发挥更大的作用,而免疫抑制/抗炎治疗则可能在疾病晚期发挥更大的作用。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
更多信息请参阅 “新兴治疗”。
对 COVID-19 患者,应考虑潜在不良反应和药物相互作用。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
一个示例是对 QT 间期的影响。患者可能正在服用延长 QT 间期的药物。而后,患者可能会接受另一种延长 QT 间期的 COVID-19 药物治疗。
给予患者任何新药之前,需对其合并症和当前治疗加以考虑。
起始任何新治疗之前,遵循当地药物应用方案指南,并咨询上级医生。
针对特定患者群中部分患者治疗的附加建议
常规对老年患者进行活动能力、功能性吞咽、认知损害和心理健康等方面的评估。
根据评估结果确定患者是否适宜出院,以及患者是否需给予康复和随访处理。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
确保患者对于所有合并症的随访计划到位,以及明确 COVID-19 相关性出院和随访标准。
COVID-19 可能具有其他合并症相关性长期影响。患者和医疗卫生专业人士可在以下资源中获取实用信息:
遵循当地常规,寻求相关专科团队意见。
考虑使用远超医疗,协调特定患者进行远程会诊。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
针对特定患者群中部分患者治疗的附加建议
缓 和治疗应在每一个为 COVID-19 患者提供照护的机构中均可给予。
确定患者是否有预先护理计划,并在制定护理计划时尊重患者的取向和偏好。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
遵循当地缓和医疗(亦称为安宁疗护)指南。
缺乏 COVID-19 患者缓和医疗(亦称为安宁疗护)数据。
对用于此类患者缓和医疗的药理学策略快速系统评价(这是同类中的第一次国际评价)发现,与缓和医疗群体常见情况相比,需给予连续皮下输注给药的患者具有更高的比例。需给予适度剂量常用临终药物进行症状控制。然而,由于缺乏可用数据,应谨慎解释这些结论。[795]Heath L, Carey M, Lowney AC, et al. Pharmacological strategies used to manage symptoms of patients dying of COVID-19: a rapid systematic review. Palliat Med. 2021 Jun;35(6):1099-107. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189007 http://www.ncbi.nlm.nih.gov/pubmed/33983081?tool=bestpractice.com
针对特定患者群中所有患者的治疗建议
哮喘加重与 COVID-19 临床可能难以区分,其可能同时出现。两者的共同特征是咳嗽和呼吸短促;但是,发热、疲劳以及味觉或嗅觉改变等其他症状更可能提示 COVID-19。[858]British Thoracic Society. Advice for healthcare professionals treating people with asthma (adults) in relation to COVID-19. 2020 [internet publication] https://www.brit-thoracic.org.uk/about-us/covid-19-information-for-the-respiratory-community
监测呼吸道症状急性恶化症状,并意识到这可能提示患者合并哮喘,正在出现哮喘急性发作。
寻求上级医生建议。
即使怀疑 COVID-19 为诱因,亦应对成人哮喘急性发作严重程度评估和管理遵循标准指南建议。[865]British Thoracic Society; Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma: a national clinical guideline. 2019 [internet publication] https://www.brit-thoracic.org.uk/quality-improvement/guidelines/asthma [909]Centers for Disease Control and Prevention. Clinical questions about COVID-19: questions and answers – patients with asthma. 2020 [internet publication] https://www.cdc.gov/coronavirus/2019-ncov/hcp/faq.html#Patients-with-Asthma
参阅成人哮喘急性发作主题。
考虑临床情况是否适宜使用定量吸入器(通过储雾罐装置输送)作为替代给药机制。[847]Global Initiative for Asthma. Global strategy for asthma management and prevention. 2021 [internet publication] https://ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf 遵循当地常规。
根据临床指征起始口服皮质类固醇治疗哮喘加重。[858]British Thoracic Society. Advice for healthcare professionals treating people with asthma (adults) in relation to COVID-19. 2020 [internet publication] https://www.brit-thoracic.org.uk/about-us/covid-19-information-for-the-respiratory-community [861]Hasan SS, Capstick T, Zaidi STR, et al. Use of corticosteroids in asthma and COPD patients with or without COVID-19. Respir Med. 2020 Aug-Sep;170:106045 https://www.resmedjournal.com/article/S0954-6111(20)30185-2/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32843175?tool=bestpractice.com
如果给予患者雾化吸入短效毒蕈碱受体拮抗剂(例如异丙托溴铵),则应暂时停用患者可能正在使用的任何用于维持治疗的长效毒蕈碱受体拮抗剂(long-acting muscarinic receptor antagonist, LAMA)(例如噻托溴铵、aclidinium、格隆溴铵、乌美溴铵 (基于专家意见)。
因为担心可能会出现抗胆碱能成瘾的不良反应。
一旦停止给予雾化治疗,需再给予 LAMA 药物治疗。
目前,对于使用雾化剂是否会产生气溶胶,以及是否因此需使用特定个人防护装备,不同国家组织之间存在不同看法。[847]Global Initiative for Asthma. Global strategy for asthma management and prevention. 2021 [internet publication] https://ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf [863]National Institute for Health and Care Excellence. COVID-19 rapid guideline: severe asthma. 2020 [internet publication] https://www.nice.org.uk/guidance/ng166 请遵循当地指南和常规。
针对特定患者群中所有患者的治疗建议
如果 COVID-19 和固有 COPD 患者可疑 COPD 加重,遵循患者个体化行动预案。[910]National Institute for Health and Care Excellence. COVID-19 rapid guideline: community-based care of patients with chronic obstructive pulmonary disease (COPD). 2020 [internet publication] https://www.nice.org.uk/guidance/ng168
与其他疾患进行鉴别,如急性冠脉综合征、急性心力衰竭和肺炎,以及 COVID-19 并发症。
对于 COPD 加重的管理,遵循既定指南,包括具备临床指征时,给予短期口服皮质类固醇。[859]Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. 2021 [internet publication] https://goldcopd.org/2021-gold-reports [861]Hasan SS, Capstick T, Zaidi STR, et al. Use of corticosteroids in asthma and COPD patients with or without COVID-19. Respir Med. 2020 Aug-Sep;170:106045 https://www.resmedjournal.com/article/S0954-6111(20)30185-2/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32843175?tool=bestpractice.com 请参阅 COPD 急性加重专题。
寻求上级医生或专科医生建议。
目前,对于使用雾化剂是否会产生气溶胶,以及是否因此需使用特定个人防护装备,不同国家组织之间存在不同看法。[859]Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. 2021 [internet publication] https://goldcopd.org/2021-gold-reports [863]National Institute for Health and Care Excellence. COVID-19 rapid guideline: severe asthma. 2020 [internet publication] https://www.nice.org.uk/guidance/ng166 对于未接受通气支持的非危重患者,考虑使用加压定量吸入器、干粉吸入器,或软雾吸入器进行药物输送。[859]Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. 2021 [internet publication] https://goldcopd.org/2021-gold-reports 请遵循当地指南和常规。
如果使用雾化器,支气管舒张剂雾化吸入疗法应仅持续 24 至 48 小时,然后患者应换回他们常用的吸入器。
如果为患者开处雾化吸入短效毒蕈碱受体拮抗剂(例如异丙托铵),则应暂时停止患者可能正在使用的任何用于维持治疗的长效毒蕈碱受体拮抗剂(long-acting muscarinic receptor antagonist, LAMA,例如噻托溴铵、aclidinium、格隆溴铵、乌美溴铵)(基于专家意见)。这是因为担心可能会出现叠加性抗胆碱能不良反应。
一旦停止雾化剂治疗,请确保重新给予 LAMA。
针对特定患者群中所有患者的治疗建议
对于任何急症糖尿病患者,每天至少监测血糖水平四次(餐前以及睡前 [如果进食])。[911]American Diabetes Association. Diabetes care in the hospital: standards of medical care in diabetes - 2021. Diabetes Care. 2021 Jan;44(Suppl 1):S211-20 https://care.diabetesjournals.org/content/44/Supplement_1/S211.long http://www.ncbi.nlm.nih.gov/pubmed/33298426?tool=bestpractice.com
对于患有糖尿病的 COVID-19 住院患者,遵循当地血糖监测常规。
对于患急性疾病的糖尿病住院患者目标血糖水平,目前尚未达成共识。
英国糖尿病学会联合会住院患者诊疗小组(Joint British Diabetes Societies for Inpatient Care, JBDS-IP)建议内科住院患者理想范围为 6 至 10 mmol/L(108-180 mg/dL),可接受上限为 12 mmol/L(216 mg/dL)。[912]Joint British Diabetes Societies for inpatient care. The use of variable rate intravenous insulin infusion (VRIII) in medical inpatients. 2014 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/JBDS_Guidelines_Current/JBDS_09_IP_VRIII.pdf 如果患者具有较高的跌倒风险、机体衰弱或患有痴呆,则认为适宜采用更宽松的血糖目标。[912]Joint British Diabetes Societies for inpatient care. The use of variable rate intravenous insulin infusion (VRIII) in medical inpatients. 2014 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/JBDS_Guidelines_Current/JBDS_09_IP_VRIII.pdf [913]Joint British Diabetes Societies for inpatient care. Inpatient care of the frail older adult with diabetes. 2019 [internet publication] https://www.diabetes.org.uk/resources-s3/2019-10/frailty-jbds-ipfinal-28-10-19.pdf
英国国家糖尿病住院患者 COVID-19 应对小组(National Inpatient Diabetes COVID-19 Response Group)对 COVID-19 住院患者提出了相同的建议。[914]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): guidance for managing inpatient hyperglycaemia. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/resources/COvID_Hyper_v4.2.pdf
一个国际专家组的共识指南建议将 COVID-19 患者的目标水平设为 4-10 mmol/L(72-180 mg/dL),但将衰弱患者的目标水平下限调整为 5 mmol/L(90 mg/dL)。[889]Bornstein SR, Rubino F, Khunti K, et al. Practical recommendations for the management of diabetes in patients with COVID-19. Lancet Diabetes Endocrinol. 2020 Jun;8(6):546-50 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180013 http://www.ncbi.nlm.nih.gov/pubmed/32334646?tool=bestpractice.com
美国糖尿病学会建议,对于大多数危重患者和非危重患者,目标范围为 7.8 至 10 mmol/L(140-180 mg/dL)(一旦因持续性高血糖起始胰岛素治疗;并非特别针对 COVID-19)。[911]American Diabetes Association. Diabetes care in the hospital: standards of medical care in diabetes - 2021. Diabetes Care. 2021 Jan;44(Suppl 1):S211-20 https://care.diabetesjournals.org/content/44/Supplement_1/S211.long http://www.ncbi.nlm.nih.gov/pubmed/33298426?tool=bestpractice.com
对高血糖进行治疗,避免糖尿病酮症酸中毒(diabetic ketoacidosis, DKA)和高渗性高血糖状态(hyperosmolar hyperglycaemic state, HHS),两者均为内科急症。
若患者毛细血管血糖 ≥12 mmol/L(≥216 mg/dL),应遵循当地医院常规。
COVID-19 指南通常强调高血糖管理的重要性。[884]Hartmann-Boyce J, Morris E, Goyder C, et al. Diabetes and COVID-19: risks, management, and learnings from other national disasters. Diabetes Care. 2020 Aug;43(8):1695-703 https://care.diabetesjournals.org/content/43/8/1695 http://www.ncbi.nlm.nih.gov/pubmed/32546593?tool=bestpractice.com
排除 DKA 或 HHS, 两者均需给予特定紧急处理。
考虑高血糖相关性其他病症,例如脓毒症。[883]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19: front door guidance. 2020 [internet publication] https://abcd.care/resource/concise-advice-inpatient-diabetes-during-covid-19-front-door-guidance
需注意,以下药物可能与高血糖具有相关性,可能需要进行评估:[915]Rehman A, Setter SM, Vue MH. Drug-induced glucose alterations part 2: drug-induced hyperglycemia. Diabetes Spect. 2011 Nov;24(4):234-8 https://spectrum.diabetesjournals.org/content/24/4/234
皮质类固醇(例如地塞米松)
部分 β 受体阻滞剂(如普萘洛尔、阿替洛尔)
噻嗪类利尿剂(例如氢氯噻嗪)
部分第二代抗精神病药物(如奥氮平、氯氮平)
某些氟喹诺酮类抗生素(如环丙沙星)
钙调磷酸酶抑制剂(如环孢素、他克莫司)
蛋白酶抑制剂(例如,作为抗逆转录病毒治疗的一部分,洛匹那韦/利托那韦可用于治疗某些 COVID-19 患者)。
部分用于 COVID-19 的试验性药物可能与高血糖具有相关性或因果关系。为糖尿病患者开具此类治疗处方之前,查看当地药物处方集,以获取更多信息。
如果患者血糖持续升高,他们可能需给予胰岛素治疗(静脉或皮下给药常规)。对于 COVID-19 患者高血糖管理,遵循当地常规。
重症监护病房(intensive care unit, ICU)外可能不提供输液泵装置,具体取决于其他地方对这些设备的需求。在这种情况下,部分方案建议,对于高血糖和轻度 DKA 管理,可给予替代性皮下给药。[914]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): guidance for managing inpatient hyperglycaemia. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/resources/COvID_Hyper_v4.2.pdf [916]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): guideline for managing DKA using subcutaneous insulin. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/resources/COvID_DKA_SC_v3.3.pdf
请注意,ICU 内的 2 型糖尿病患者可能存在显著胰岛素抵抗。[914]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): guidance for managing inpatient hyperglycaemia. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/resources/COvID_Hyper_v4.2.pdf
向住院患者糖尿病团队询问专家意见。
监测血糖并根据病情和住院就餐时间 调整用药,从而降低低血糖发作风险。
大约 1/5 英格兰和威尔士糖尿病住院患者在住院期间发生过低血糖。[917]NHS Digital. National diabetes inpatient audit (NaDIA) - 2019. 2020 [internet publication] https://digital.nhs.uk/data-and-information/publications/statistical/national-diabetes-inpatient-audit/2019
低血糖原因包括:[918]Joint British Diabetes Societies for inpatient care. The hospital management of hypoglycaemia in adults with diabetes mellitus. 5th ed. 2021 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/JBDS_01_Hypo_Guideline_FINAL_23042021_0.pdf
在急症中恢复
COVID-19 恢复患者可能出现胰岛素需求快速改变,因此谨慎监测和调整胰岛素用药方案[914]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): guidance for managing inpatient hyperglycaemia. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/resources/COvID_Hyper_v4.2.pdf
患者进食意外中断,COVID-19 患者以俯卧位接受护理时尤易出现[914]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): guidance for managing inpatient hyperglycaemia. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/resources/COvID_Hyper_v4.2.pdf
COVID-19 患者减少皮质类固醇剂量(特别是地塞米松)[914]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): guidance for managing inpatient hyperglycaemia. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/resources/COvID_Hyper_v4.2.pdf
胰岛素或口服降糖药用药错误
与进食有关的胰岛素给药时间错误
患者摄食较少,但却服用等量糖尿病药物
不享用睡前加餐
食欲减退或呕吐。
部分用于 COVID-19 的试验性药物可能与低血糖具有相关性(或具有因果关系)。为糖尿病患者开具此类治疗处方之前,查看当地药物处方集,以获取更多信息。
请注意,如果患者错过进餐或用药剂量过大,低血糖更易作为磺脲类药物不良反应出现(例如格列本脲、格列齐特、格列美脲、格列吡嗪)。
在急症医院环境中,餐时有可能被打乱,或无法每天同一时间进餐。
应在进食前或进食时给予磺脲类药物。查看当地药物处方集获取更为具体的指导信息,了解特定磺脲类药物给药时间与进食时间的关系。
切勿在睡前服用磺脲类药物,如果患者要在晚餐时服用一次,应考虑减少晚间剂量,以降低夜间低血糖发生风险(基于专家意见)。
睡前加餐可降低清晨低血糖风险。[917]NHS Digital. National diabetes inpatient audit (NaDIA) - 2019. 2020 [internet publication] https://digital.nhs.uk/data-and-information/publications/statistical/national-diabetes-inpatient-audit/2019
如果血糖低于 4 mmol/L(72 mg/dL),应积极治疗低血糖。 [918]Joint British Diabetes Societies for inpatient care. The hospital management of hypoglycaemia in adults with diabetes mellitus. 5th ed. 2021 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/JBDS_01_Hypo_Guideline_FINAL_23042021_0.pdf 请遵循医院方案。JBDS-IP 指南建议:[918]Joint British Diabetes Societies for inpatient care. The hospital management of hypoglycaemia in adults with diabetes mellitus. 5th ed. 2021 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/JBDS_01_Hypo_Guideline_FINAL_23042021_0.pdf
10 至 15 分钟后重新检测血糖,确定治疗反应
如果低血糖已经纠正,切勿停止胰岛素的下一次给药计划。否则会导致 1 型糖尿病患者出现反弹性高血糖和 DKA。
住院患者应遵循当地常规和血糖自我监测指南。
相关内容可能已针对 COVID-19 患者进行了修改。例如,美国部分医院一直在使用“虚拟”模式,包括扩充自我管理方案,以减少对个人防护装备的需求(在安全的情况下)。[884]Hartmann-Boyce J, Morris E, Goyder C, et al. Diabetes and COVID-19: risks, management, and learnings from other national disasters. Diabetes Care. 2020 Aug;43(8):1695-703 https://care.diabetesjournals.org/content/43/8/1695 http://www.ncbi.nlm.nih.gov/pubmed/32546593?tool=bestpractice.com
针对特定患者群中所有患者的治疗建议
成人糖尿病患者在入院时,或似乎更加不适时,均应对其足部进行检查。[919]National Institute for Health and Care Excellence. Diabetic foot problems: prevention and management. 2019 [internet publication] https://www.nice.org.uk/guidance/ng19 这也是针对因 COVID-19 入院的糖尿病成人患者的建议。[883]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19: front door guidance. 2020 [internet publication] https://abcd.care/resource/concise-advice-inpatient-diabetes-during-covid-19-front-door-guidance
需行足部检查,发现新发溃疡或感染,其可能被患者忽视。
检查足部病损,并检查保护性感觉是否丧失。
遵循当地指南,但有一个快速简单的试验:Ipswich Touch Test©️(伊普斯威奇触摸试验),即用食指指尖轻轻触摸/将其放置在第一、第三和第五趾趾尖上 1 到 2 秒。[920]Rayman G, Vas PR, Baker N, et al. The Ipswich Touch Test: a simple and novel method to identify inpatients with diabetes at risk of foot ulceration. Diabetes Care. 2011 Jul;34(7):1517-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3120164 http://www.ncbi.nlm.nih.gov/pubmed/21593300?tool=bestpractice.com
如果患者在这六个部位中的两个或以上没有感觉,则代表其保护性感觉减退。
如果患者感觉减退,则具有压疮高风险。告知护理人员,并提供减压装置。
护理人员或医疗人员应每日进行踝部检查,注意压力性创伤征象。
对于糖尿病患者是否应该使用弹力袜存在争议 – 如有血管疾病,勿予以使用。
针对特定患者群中所有患者的治疗建议
询问患者他们正在服用哪些药物治疗抑郁。或查看其初级卫生保健记录,获取相关信息(若可获取)。
药物相互作用及其与 COVID-19 患者尤为相关的不良反应包括镇静、心脏毒性(QT 间期延长),以及呼吸抑制。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
为患者开具其常用的抗抑郁药,除非有充分的理由不得这样做(基于专家意见)。
如果突然停用抗抑郁药,患者可能出现停药症状。[923]Cleare A, Pariante CM, Young AH, et al. Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines. J Psychopharmacol. 2015 May;29(5):459-525 https://www.bap.org.uk/docdetails.php?docID=5 http://www.ncbi.nlm.nih.gov/pubmed/25969470?tool=bestpractice.com
药物停用的症状严重程度 可能各有所异,但可能令人不快,以及可能使急症管理复杂化。[924]National Institute for Health and Care Excellence. Depression in adults with a chronic physical health problem: recognition and management. 2009 [internet publication] https://www.nice.org.uk/guidance/cg91
审评当前药物时,需注意以下情况:
所察觉的当前和既往不良反应
近期用药剂量改变
最近更换了一种不同类别的药物
特定抑郁症亚型的药物细微差别(例如,精神病性抑郁症患者很可能会同时服用抗精神病处方药)
难治性抑郁症治疗中可能需要使用的增强策略(如选择性 5-羟色胺再摄取抑制剂 [selective serotonin-reuptake inhibitor, SSRI])的基础上加用锂剂或喹硫平。
对药物相互作用加以考虑。
抗抑郁药可能会与用于其他疾病的药物发生药代动力学(通过抑制 CYP450 通路)和药效动力学相互作用。[923]Cleare A, Pariante CM, Young AH, et al. Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines. J Psychopharmacol. 2015 May;29(5):459-525 https://www.bap.org.uk/docdetails.php?docID=5 http://www.ncbi.nlm.nih.gov/pubmed/25969470?tool=bestpractice.com [925]Taylor DM, Barnes TRE, Young AH. The Maudsley prescribing guidelines in psychiatry. 14th edition. Chichester: Wiley-Blackwell; 2021 对于为 COVID-19 患者开处的所有药物以及任何实验性治疗(请参阅新兴疗法章节),需考虑此问题。
请注意,戒烟或从吸烟转为任何其他替代方案(包括尼古丁替代疗法)可能导致患者服用的任何精神类药物(例如,用于治疗抑郁的药物)血药浓度发生变化。这是因为尼古丁替代疗法不会像吸烟那样影响肝酶活性。[926]Flowers L. Nicotine replacement therapy. Am J Psychiatry Resid J. 2016 Jun;11(6):4-7 https://psychiatryonline.org/doi/10.1176/appi.ajp-rj.2016.110602 [927]Desai HD, Seabolt J, Jann MW. Smoking in patients receiving psychotropic medications: a pharmacokinetic perspective. CNS Drugs. 2001;15(6):469-94 http://www.ncbi.nlm.nih.gov/pubmed/11524025?tool=bestpractice.com [928]Oliveira P, Ribeiro J, Donato H, et al. Smoking and antidepressants pharmacokinetics: a systematic review. Ann Gen Psychiatry. 2017 Mar 6;16:17 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340025 http://www.ncbi.nlm.nih.gov/pubmed/28286537?tool=bestpractice.com [929]National Centre for Smoking Cessation and Training. Smoking cessation and mental health: a briefing for front-line staff. 2014 [internet publication] https://www.ncsct.co.uk/shopdisp_mental_health_briefing.php 寻求相关建议,确认精神类药物剂量调整是否适当。
开具非精神类药物时,应考虑精神并发症。
给予皮质类固醇、抗惊厥药物和抗帕金森病药物时,应格外小心。
考虑不良反应,具体可能包括以下不良反应。[925]Taylor DM, Barnes TRE, Young AH. The Maudsley prescribing guidelines in psychiatry. 14th edition. Chichester: Wiley-Blackwell; 2021
与三环类抗抑郁药相关的 QT 间期延长、心律失常、心率加快或体位性低血压。进行 ECG 检查,特别是有心律失常风险的人群。
低钠血症,由抗抑郁药(尤其是 SSRI)引起,并因其他同时开具的药物(例如利尿药)加重。检查患者的血清电解质。
5-羟色胺综合征(精神状态改变、激越、震颤、反射亢进、阵挛、肌强直、大量出汗、心动过速、肠鸣音增加、体温 >38℃),尤其是在多重用药和/或 5-羟色胺能药物过量时。[930]Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005 Mar 17;352(11):1112-20 https://www.doi.org/10.1056/NEJMra041867 http://www.ncbi.nlm.nih.gov/pubmed/15784664?tool=bestpractice.com [931]Buckley NA, Dawson AH, Isbister GK. Serotonin syndrome. BMJ. 2014 Feb 19;348:g1626 http://www.ncbi.nlm.nih.gov/pubmed/24554467?tool=bestpractice.com
特别要注意的是,服用 SSRI 的终末期肾病患者出现 5-羟色胺综合征的风险增加。治疗肾脏损伤患者的抑郁需要采取多学科方法,并需要格外谨慎。
肝毒性。必要时调整肝功能受损患者的抗抑郁药物剂量,避免使用已知具有肝毒性的药物。
该不良反应和药物相互作用表单并不详尽 – 参阅当地处方集,获取更多信息。咨询联络精神病学同事和/或药剂师,获取建议。
尽可能向患者询问其采用哪些非药物治疗方法处理抑郁,并检查其在社区获得的支持情况。
其可包括参与其照护的其他医疗卫生专业人士、慈善力量、家庭和社交网络,以及心理治疗。
针对特定患者群中所有患者的治疗建议
考虑将所有因急症 收住入院,且确诊或疑似抑郁的患者转诊至联络精神病学团队/服务机构。[932]National Institute for Health and Care Excellence. Liaison psychiatry. In: Emergency acute medical care in over 16s: service delivery and organisation. 2018 [internet publication] https://www.nice.org.uk/guidance/ng94/evidence/23.liaison-psychiatry-pdf-172397464636 [933]National Confidential Enquiry into Patient Outcome and Death. Treat as one: bridging the gap between mental and physical healthcare in general hospitals. 2017 [internet publication] https://www.ncepod.org.uk/2017report1/downloads/TreatAsOne_Summary.pdf
COVID-19 大流行期间遵循医院的当地常规/转诊路径。
COVID-19 与精神和神经系统表现(包括抑郁)相关。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
合并抑郁症与对推荐的躯体健康治疗(从药物治疗到康复治疗)的依从性差有关。[934]DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med. 2000 Jul 24;160(14):2101-7 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/485411 http://www.ncbi.nlm.nih.gov/pubmed/10904452?tool=bestpractice.com
这可能会导致临床结局恶化,包括住院时间延长。[924]National Institute for Health and Care Excellence. Depression in adults with a chronic physical health problem: recognition and management. 2009 [internet publication] https://www.nice.org.uk/guidance/cg91 [935]Prina AM, Cosco TD, Dening T, et al. The association between depressive symptoms in the community, non-psychiatric hospital admission and hospital outcomes: a systematic review. J Psychosom Res. 2015 Jan;78(1):25-33 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4292984 http://www.ncbi.nlm.nih.gov/pubmed/25466985?tool=bestpractice.com [936]Clarke DM, Currie KC. Depression, anxiety and their relationship with chronic diseases: a review of the epidemiology, risk and treatment evidence. Med J Aust. 2009 Apr 6;190(s7):S54-60 http://www.ncbi.nlm.nih.gov/pubmed/19351294?tool=bestpractice.com
最重要的是,抑郁与死亡率升高有关。[937]World Health Organization. Excess mortality in persons with severe mental disorders. 2016 [internet publication] https://www.who.int/mental_health/evidence/excess_mortality_report/en
针对特定患者群中所有患者的治疗建议
考虑对因急性疾病入院的当前吸烟者给予尼古丁替代治疗。无论他们是否打算戒烟,均需纳入考虑范围。[938]National Institute for Health and Care Excellence. Tobacco: preventing uptake, promoting quitting and treating dependence. August 2022 [internet publication] https://www.nice.org.uk/guidance/ng209
尼古丁替代治疗可防止入院期间快速戒断,快速戒断可能会导致痛苦和不安。
对于因急性卒中、心肌梗死和/或未控制高血压入院的血流动力学不稳定患者,以及患有严重肾脏损伤的患者,应谨慎使用此疗法。
在开始对糖尿病患者使用尼古丁替代治疗后,密切监测血糖。
药品制剂包括皮肤贴剂以及针对皮肤过敏患者的吸入剂、含片、咀嚼胶或喷雾剂。剂量取决于每日吸烟量和所选择的制剂。
有关更全面的详细信息,参考当地药物处方集和医院指南。
请注意,从吸烟转为任何其他替代方案(包括尼古丁替代疗法)可能导致患者服用的任何精神类药物(例如用于治疗抑郁的药物)血药浓度发生变化。这是因为尼古丁替代治疗不会像吸烟那样影响肝酶活性。[926]Flowers L. Nicotine replacement therapy. Am J Psychiatry Resid J. 2016 Jun;11(6):4-7 https://psychiatryonline.org/doi/10.1176/appi.ajp-rj.2016.110602 寻求相关建议,确认精神类药物剂量调整是否适当。
有证据提示,吸烟与重症 COVID-19 风险升高具有相关性。
有鉴于此,由于存在公认的危害,因此世界卫生组织建议使用循证方法进行戒烟。[939]World Health Organization. Smoking and COVID-19: scientific brief. 2020 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-Sci_Brief-Smoking-2020.2
在专科医生团队指导下,将危重疾病(即出现急性呼吸窘迫综合征、脓毒症或脓毒性休克)患者收入或转入重症监护病房。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
与患者及其家属讨论治疗方案的风险、获益和可能结局,允许他们就其治疗表达倾向性意见。衡量治疗上限时,需考虑他们的意愿和期望。尽可能使用决策支持工具。制定治疗升级计划,并与晚期合并症患者就已有的预诊疗计划或拒绝治疗的提前决策进行讨论。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
管理 COVID-19 患者时,实施当地感染防控规程。
孕妇应由多学科团队进行管理,包括产科、围产、新生儿和重症医学专科医生,以及助产、精神卫生和社会心理支持。建议采用以患者为中心、充满尊重、专业的诊疗方法。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 母体低氧血症出现后应尽快组建多学科团队,评估胎儿成熟度、疾病进展以及最佳分娩方式。[940]Chen L, Jiang H, Zhao Y. Pregnancy with Covid-19: management considerations for care of severe and critically ill cases. Am J Reprod Immunol. 2020 Jul 4:e13299. https://onlinelibrary.wiley.com/doi/10.1111/aji.13299 http://www.ncbi.nlm.nih.gov/pubmed/32623810?tool=bestpractice.com
BMJ Best Practice 临床实践合并症诊疗工具中的信息涉及非妊娠成人。
这些信息不适用于孕妇患者或儿童。在这类情况下,请向产科/妇科专科医生或儿科专科医生寻求建议,了解患者的合并症可能会如何影响您对 COVID-19 的管理。
衰弱是与一种衰老过程相关的独特健康状态,多个身体系统逐渐丧失其生理功能。
询问患者其在急性发作前 2 周的能力情况(以及可能的相关照护者的意见)。
如果患者的年龄 ≥65 岁,则使用临床衰弱量表。
这是确定虚弱的实用辅助工具,但不应仅仅依赖它。
通常情况下,急诊入院的老年患者中,较高的衰弱评分与发生不良结局的风险增加相关。 尤其对于 COVID-19 患者,据部分但非所有研究报告,衰弱程度越高的患者具有更高的死亡风险。 [890]Subramaniam A, Shekar K, Afroz A, et al. Frailty and mortality associations in patients with COVID-19: a systematic review and meta-analysis. Intern Med J. 2022 May;52(5):724-39 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314619 http://www.ncbi.nlm.nih.gov/pubmed/35066970?tool=bestpractice.com
如果患者的评分为 5 分或以上,应对恰当的本地转诊进行全面评估寻求上级医生的建议,全面评估应包括讨论患者的治疗预期和照护目标。
辅助实施多学科诊疗,并根据患者的价值观来调整管理方案。
与痴呆患者及其照护者进行讨论后,同其他患者一样,尽早议定升级方案 (基于专家意见)。
内容应包括:[843]Fritz Z, Slowther AM, Perkins GD. Resuscitation policy should focus on the patient, not the decision. BMJ. 2017 Feb 28;356:j813 https://www.doi.org/10.1136/bmj.j813 http://www.ncbi.nlm.nih.gov/pubmed/28246084?tool=bestpractice.com
复苏状态(即“不尝试心肺复苏”[Do Not Attempt Cardiopulmonary Resuscitation, DNACPR] 的决定)
治疗上限(例如是否适合气管插管或重症监护病房收治)。
升级方案应将预立医疗照护计划纳入考量,包括合法绑定预立医嘱。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1 [843]Fritz Z, Slowther AM, Perkins GD. Resuscitation policy should focus on the patient, not the decision. BMJ. 2017 Feb 28;356:j813 https://www.doi.org/10.1136/bmj.j813 http://www.ncbi.nlm.nih.gov/pubmed/28246084?tool=bestpractice.com
在某些情况下,对于治疗升级计划,痴呆患者将缺乏做出决策的心智能力。
评估并记录心智能力(在需要作出决定的特定时间作出决定的能力)。[844]National Institute for Health and Care Excellence. Decision making and mental capacity. 2018 [internet publication] https://www.nice.org.uk/guidance/ng108 请遵守您所在地区的相应法律。
在英格兰和威尔士,医疗卫生专业人士必须遵守 2005 年心智能力法案。[845]Department of Health. Mental Capacity Act 2005 [internet publication] http://www.legislation.gov.uk/ukpga/2005/9/contents 进行评估时,应遵循该法案中的原则。[845]Department of Health. Mental Capacity Act 2005 [internet publication] http://www.legislation.gov.uk/ukpga/2005/9/contents
如果评估确定患者缺乏心智能力,请确保作出符合患者最大利益的决定。[844]National Institute for Health and Care Excellence. Decision making and mental capacity. 2018 [internet publication] https://www.nice.org.uk/guidance/ng108 [845]Department of Health. Mental Capacity Act 2005 [internet publication] http://www.legislation.gov.uk/ukpga/2005/9/contents
如果患者被评估为缺乏心智能力, 需与近亲属协商,并作出最大获益”决策。[845]Department of Health. Mental Capacity Act 2005 [internet publication] http://www.legislation.gov.uk/ukpga/2005/9/contents
根据英格兰和威尔士 2005 年心智能力法案,如果患者无家庭成员或其他照护者,且无需立即作出决定,应寻求独立心智能力代理人担纲任务。[846]Social Care Institute for Excellence. Independent mental capacity advocate (IMCA). January 2010 [internet publication] https://www.scie.org.uk/mca/imca/do
查看您所在地区的相应法律。
对于有高血压、冠心病、心力衰竭、卒中或 CKD 病史的患者,如果出现以下情况,请考虑停用降压药和/或利尿药:
患者出现休克或低血压[966]Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2016 May 20;37(27):2129-200 https://www.doi.org/10.1093/eurheartj/ehw128 http://www.ncbi.nlm.nih.gov/pubmed/27206819?tool=bestpractice.com
患者血压较基线降低 ≥40 mmHg,出现直立性低血压,或具有体位症状(基于专家意见)
直立性低血压的共识定义为:站立 3 分钟以内,收缩压下降 ≥20 mmHg 和/或舒张压下降 ≥10 mmHg。[967]Freeman R, Wieling W, Axelrod FB, et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res. 2011 Apr;21(2):69-72 http://www.ncbi.nlm.nih.gov/pubmed/21431947?tool=bestpractice.com
确立患者基线血压并评估容量状态。
已接受心力衰竭治疗的患者可能出现慢性低血压(例如收缩压 ≤90 mmHg)。如果患者收缩压下降 >10-15 mm/Hg,则可停用可能降低血压的药物。
您可能需要专家评估意见。
如果心力衰竭和/或 CKD 患者停用利尿药,则需要密切监测,因为液体会迅速积聚。
如果在急性疾病期间已停用抗高血压药或利尿药,请视临床情况考虑在出院前重新开始用药 (基于专家意见)。
以较低剂量重新开始用药(一次一种药物) ,并让患者全科医生逐渐调整 到正常剂量。
大多数患者无法耐受一下子以初始剂量重新开始使用所有药物。
如果患者的临床情况不适宜在出院前重新开始使用这些药物,请确保患者/照护者了解:需要患者的全科医生安排临床检查,以决定何时可以重新开始相关药物治疗。
确保您已与患者全科医生进行了清晰明确的沟通。
何时停止隔离的指南各地有较大差异。
隔离时限可能取决于多种因素,包括疫苗接种状态、流行的 SARS-CoV-2 变体和患者因素(例如免疫功能正常/免疫功能低下、无症状/有症状、疾病严重程度)。
世界卫生组织建议,在症状发作后 10 天以及至少 3 天无发热和呼吸道症状的情况下,可停用基于防止传播的预防措施(包括隔离),并将患者从诊疗路径中移出。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 然而,指南各有不同,应参阅当地公共卫生指南,获取更多信息。
针对特定患者群中所有患者的治疗建议
酌情考虑液体和电解质管理、抗菌药物治疗和对症治疗。
参阅以上 重症 COVID-19,获取更详细信息。
对于疼痛、镇静和谵妄的管理,应遵循当地指南。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
实施标准干预措施,预防与危重症相关的并发症。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
如果伴慢性肾病(chronic kidney disease, CKD)或具有 CKD 危险因素的患者因急症而呈现不适,应对肾功能进行密切监测。[837]National Institute for Health and Care Excellence. Acute kidney injury: prevention, detection and management. 2019 [internet publication] https://www.nice.org.uk/guidance/ng148
CKD 为急性肾损伤(acute kidney injury, AKI)重要危险因素。[838]Hsu CY, Ordoñez JD, Chertow GM, et al. The risk of acute renal failure in patients with chronic kidney disease. Kidney Int. 2008 Apr 2;74(1):101-7 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673528 http://www.ncbi.nlm.nih.gov/pubmed/18385668?tool=bestpractice.com
伴 CKD 和 COVID-19 患者出现 AKI 风险将升高, 其可能与发热、脱水,以及非甾体抗炎药使用具有相关性。
COVID -19 患者伴 AKI 可能较为常见(但确切患病率尚不确定)。AKI 与死亡率增加具有相关性。[839]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication] https://www.nice.org.uk/guidance/ng191
向您的 CKD 患者解释,其患病后出现 AKI 的风险增加。确定机制,以便可以密切监测居家治疗患者疾病进展迹象。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
对于入院的所有 COVID-19 患者,包括 CKD 患者,院时需检查肾功能,并确保定期监测。
对于 CKD 患者:
与最近一次可获取结果的肾功能进行比较
每日监测肾功能,同时进行仔细的容量状态监测 ( 基于专家意见)。
对少尿进行监测并予以处理。[837]National Institute for Health and Care Excellence. Acute kidney injury: prevention, detection and management. 2019 [internet publication] https://www.nice.org.uk/guidance/ng148
需意识到,低血容量在心力衰竭和/或慢性肾病(chronic kidney disease, CKD)中较难进行评估。[947]National Institute for Health and Care Excellence. Intravenous fluid therapy in adults in hospital. 2017 [internet publication] https://www.nice.org.uk/guidance/cg174
评估:[947]National Institute for Health and Care Excellence. Intravenous fluid therapy in adults in hospital. 2017 [internet publication] https://www.nice.org.uk/guidance/cg174
脉搏
血压
外周灌注
毛细血管再充盈
颈静脉压
体位性低血压
肺水肿和外周水肿。
确立患者基线血压,因为相对于基线的下降幅度比绝对收缩压(systolic blood pressure, SBP)更为重要。
SBP <90 mmHg 可能表明存在低血压,但是接受慢性心力衰竭药物治疗患者的基线 SBP 可能 <90 mmHg (基于专家意见)。
CKD 患者在出现低血压,尤其是休克时,需要立即对其进行液体复苏 (基于专家意见)。
初次容量负荷试验后对患者进行重新评估,如果患者病情未迅速稳定,应向上级医生寻求意见。
考虑转至更高阶梯水平的诊疗。
心力衰竭患者可能需要接受液体复苏,但需寻求上级医生意见,评估容量状态和容量过负荷风险。
开始进行液体复苏之前,考虑将患者转诊,接受更高阶梯水平诊疗。
维持最佳体液状态至关重要,但这很难在所有 COVID-19 患者中实现。[839]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication] https://www.nice.org.uk/guidance/ng191 寻求上级医生建议,尤其是对于病情复杂患者,例如患有心力衰竭和/或慢性肾病(chronic kidney disease, CKD)的患者。
心力衰竭和/或 CKD 患者具有液体复苏肺水肿高风险,因此应密切监测(最初每小时一次)。
监测项目应包括:
定期进行容量状态临床评估(脉搏、BP、颈静脉压 [jugular venous pressure, JVP],并检查有无肺水肿和外周水肿)
体液平衡(出入量表)和每日体重
肾功能检查,至少每日一次。
如果尿量难以测定,考虑进行膀胱导尿术,但要注意感染和创伤风险可能增加。
对于病情复杂患者,可能需监测中心静脉压,或置入肺动脉导管进行监测。[891]Verbrugge FH, Grieten L, Mullens W. Management of the cardiorenal syndrome in decompensated heart failure. Cardiorenal Med. 2014 Dec;4(3-4):176-88 https://www.doi.org/10.1159/000366168 http://www.ncbi.nlm.nih.gov/pubmed/25737682?tool=bestpractice.com
重要的是要知道何时降级液体治疗。考虑尽早向上级医生寻求意见支持该决定。
如果患者液体容量过负荷(体征包括脉率升高、肺水肿导致呼吸频率升高以及外周水肿相关的 JVP 升高),停止液体复苏,寻求上级医生帮助,并考虑静脉给予利尿药 (基于专家意见)。
除非存在合理情况,否则一般不会联用利尿药和静脉输液(基于专家意见)。
可能需要心脏病学医生和/或肾病学医生专科意见。
慢性肾病和/或心力衰竭
避免将非甾体抗炎药(non-steroidal anti-inflammatory drug, NSAID)用于慢性肾病和/或心力衰竭的患者(基于专家意见)。
哮喘
NSAID 可能会使某些哮喘患者症状恶化,因此需询问患者对其是否存在已知的过度敏感不良反应。[847]Global Initiative for Asthma. Global strategy for asthma management and prevention. 2021 [internet publication] https://ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf
对于因急性病症入院并有痴呆病史的任何患者,尽早进行基线认知评估。从家人、朋友或照护者处获取旁证病史。[895]Pendlebury ST, Klaus SP, Mather M, et al. Routine cognitive screening in older patients admitted to acute medicine: abbreviated mental test score (AMTS) and subjective memory complaint versus Montreal Cognitive Assessment and IQCODE. Age Ageing. 2015 Nov;44(6):1000-5 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621235 http://www.ncbi.nlm.nih.gov/pubmed/26464420?tool=bestpractice.com
使用在急症情况下可行的、经过验证的评分系统,例如:[895]Pendlebury ST, Klaus SP, Mather M, et al. Routine cognitive screening in older patients admitted to acute medicine: abbreviated mental test score (AMTS) and subjective memory complaint versus Montreal Cognitive Assessment and IQCODE. Age Ageing. 2015 Nov;44(6):1000-5 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621235 http://www.ncbi.nlm.nih.gov/pubmed/26464420?tool=bestpractice.com
简易智能测验评分/10(AMTS/10)。[948]Hodkinson HM. Evaluation of a mental test score for assessment of mental impairment in the elderly. Age Ageing. 1972 Nov;1(4):233-8 http://www.ncbi.nlm.nih.gov/pubmed/4669880?tool=bestpractice.com British Geriatrics Society: Abbreviated Mental Test Score. 2018 在新窗口中打开
旁证病史可确定患者的认知是否稳定,或者认知和功能是逐渐下降还是急性下降。
标准化认知评估评分将有助于监测所有临床改善, 以及确定出院需求。判读该分数时,最好结合功能评估(通常由经过培训的职业治疗师进行)。
每当痴呆患者出现急性疾病时都要进行谵妄评估。[897]National Institute for Health and Care Excellence. Delirium: prevention, diagnosis and management. 2019 [internet publication] https://www.nice.org.uk/guidance/CG103 世界卫生组织建议对 COVID-19 患者通过标准方案进行谵妄评估。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
伴痴呆者入院时和整个住院期间发生谵妄的风险增加。[898]National Institute for Health and Clinical Excellence. Dementia: assessment, management and support for people living with dementia and their carers. 2018 [internet publication] https://www.nice.org.uk/guidance/ng97 [899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium
谵妄与痴呆不同。[900]Nova Scotia Health Authority. This is not my Mom. 2012 [internet publication] https://www.thisisnotmymom.ca 谵妄是指精神功能出现潜在致死性的急性波动性改变,伴有注意力缺乏、思维混乱和意识水平的改变。[901]Inouye SK, Schlesinger MJ, Lydon TJ. Delirium: a symptom of how hospital care is failing older persons and a window to improve quality of hospital care. Am J Med. 1999 May;106(5):565-73 http://www.ncbi.nlm.nih.gov/pubmed/10335730?tool=bestpractice.com
使用筛查工具检测可能出现的谵妄,例如:
The 4-AT 在新窗口中打开。[899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium [902]Bellelli G, Morandi A, Davis DH, et al. Validation of the 4AT, a new instrument for rapid delirium screening: a study in 234 hospitalised older people. Age Ageing. 2014 Jul;43(4):496-502 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066613 http://www.ncbi.nlm.nih.gov/pubmed/24590568?tool=bestpractice.com [903]MacLullich AM, Shenkin SD, Goodacre S, et al. The 4 'A's test for detecting delirium in acute medical patients: a diagnostic accuracy study. Health Technol Assess. 2019 Aug;23(40):1-194 https://www.journalslibrary.nihr.ac.uk/hta/hta23400#/abstract http://www.ncbi.nlm.nih.gov/pubmed/31397263?tool=bestpractice.com
伴痴呆者可出现沟通困难,因此更难报告 COVID-19 相关性症状。他们最初的表现可能为谵妄征象。[904]Public Health England. Coronavirus (COVID-19): admission and care of people in care homes. 2020 [internet publication] https://www.gov.uk/government/publications/coronavirus-covid-19-admission-and-care-of-people-in-care-homes
对于患有任何急性疾病的痴呆患者,考虑采取以下措施,作为入院期间降低谵妄风险的多元化诊疗一部分:[899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium [905]British Geriatrics Society. Coronavirus: managing delirium in confirmed and suspected cases. 2020 [internet publication] https://www.bgs.org.uk/resources/coronavirus-managing-delirium-in-confirmed-and-suspected-cases
帮助患者定向;确保患者有自己的眼镜和/或助听器
使患者尽早开始活动
充分控制疼痛
及时发现并治疗重叠感染
保证水的摄入量,并帮助患者充分进食
监测并维持正常的肠道和膀胱功能
根据指南的建议给予氧疗。
安排与经验丰富的医疗卫生专业人士一起进行用药评估。[899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium
与 COVID-19 尤其相关的挑战包括:[905]British Geriatrics Society. Coronavirus: managing delirium in confirmed and suspected cases. 2020 [internet publication] https://www.bgs.org.uk/resources/coronavirus-managing-delirium-in-confirmed-and-suspected-cases
隔离需要,这可能会加重部分患者的谵妄
对患者谵妄进行定期监测的能力,可能受人员配置和可用时间资源影响。
针对谵妄患者的初始检查
如果患者出现谵妄,请检查并治疗危及生命的病因:[899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium
缺氧
低血糖
低血压
药物中毒或戒断,包括酒精戒断。
其他检查包括(基于专家意见):
全血细胞计数、电解质、肾功能、甲状腺功能检测、肝功能检测、钙、血糖、CRP、叶酸和维生素 B12
血培养(如果怀疑菌血症)
尿培养
胸部 X 线。
根据具体临床发现,可能需要进行更高级的非常规检查,例如头颅 CT。请与上级医生讨论。[899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium
检查并治疗谵妄的所有可逆病因。[897]National Institute for Health and Care Excellence. Delirium: prevention, diagnosis and management. 2019 [internet publication] https://www.nice.org.uk/guidance/CG103 其中包括:
感染
疼痛
脱水
便秘
制动
睡眠差
感觉受损(如耵聍或眼镜丢失)
药物治疗
询问最近开的处方药,特别是阿片类镇痛药、抗焦虑药、镇静剂、抗精神病药物或抗胆碱能作用强的药物
考虑计算抗胆碱能药物总负担得分。
最初应管理谵妄患者,如果可能,应按照推荐用于非 COVID-19 情况下谵妄管理的非药物疗法进行治疗。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1 [897]National Institute for Health and Care Excellence. Delirium: prevention, diagnosis and management. 2019 [internet publication] https://www.nice.org.uk/guidance/CG103
通过提供一个光线充足的房间,且将时钟和日历放置在显眼位置(例如挂在墙上),可减轻定向障碍。
基于当前社区 COVID-19 传播水平,在当地探视政策允许的情况下,鼓励并促进家人、朋友和照护者探视患者。
使用语言和非语言技巧减轻冲突和苦恼。
如果非药物治疗无效,并且患者感到痛苦或可能对自己或他人构成危险,可以考虑短期(通常仅需要 1-2 天)使用抗精神病药物或镇静剂,但只能作为最后的治疗手段。必须定期评估为此目的新开的任何抗精神病药物,并在实际情况允许时停药(基于专家意见)。
英国老年医学会(British Geriatrics Society)指出,在管理 COVID-19 患者时,药物治疗可能需要早于在其他情况下通常考虑的时间,因为感染传播对他人造成伤害的风险可能大于对个人造成潜在伤害的风险。[905]British Geriatrics Society. Coronavirus: managing delirium in confirmed and suspected cases. 2020 [internet publication] https://www.bgs.org.uk/resources/coronavirus-managing-delirium-in-confirmed-and-suspected-cases
英国国家卫生与临床优化研究所关于谵妄的指南(在未患 COVID-19 的情况下)建议短期使用氟哌啶醇(通常少于 1 周),但这并不适合所有患者,并且绝不能用于帕金森病或路易体痴呆患者。[897]National Institute for Health and Care Excellence. Delirium: prevention, diagnosis and management. 2019 [internet publication] https://www.nice.org.uk/guidance/CG103
NICE COVID-19 管理快速指南亦建议将氟哌啶醇作为可完成吞咽动作的 COVID-19 患者谵妄药物治疗的一种选择。[839]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication] https://www.nice.org.uk/guidance/ng191
抗精神病药物治疗谵妄的有效性证据尚无定论,并且医院方案可能各有不同。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1 [899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium 遵循当地医院的方案选择药物。
始终从最低剂量开始服用抗精神病药,并依据症状谨慎地逐渐调整剂量。[897]National Institute for Health and Care Excellence. Delirium: prevention, diagnosis and management. 2019 [internet publication] https://www.nice.org.uk/guidance/CG103 只能通过口服或肌内注射药物(绝对不可静脉注射)对此进行治疗。(基于专家意见)。
向家庭/照护者提供信息,以便他们了解当前的情况以及如何与临床团队协作以帮助患者恢复正常生活。[899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium 提供本地可用信息资源。[905]British Geriatrics Society. Coronavirus: managing delirium in confirmed and suspected cases. 2020 [internet publication] https://www.bgs.org.uk/resources/coronavirus-managing-delirium-in-confirmed-and-suspected-cases
抗精神病药物与痴呆患者死亡率增加相关。
痴呆患者有时可能需要短期抗精神病药物以实现安全疗护。然而,抗精神病药物对老年人有多种不良作用,并与痴呆患者死亡风险增加相关。
一项 meta 分析发现,与服用安慰剂的人相比,服用非典型抗精神病药的痴呆患者死亡风险增加。[906]Ma H, Huang Y, Cong Z, et al. The efficacy and safety of atypical antipsychotics for the treatment of dementia: a meta-analysis of randomized placebo-controlled trials. J Alzheimers Dis. 2014;42(3):915-37 http://www.ncbi.nlm.nih.gov/pubmed/25024323?tool=bestpractice.com
一项针对老年人的大型队列研究发现,更高剂量的抗精神病药通常与更高的风险相关。在所有研究的抗精神病药中,使用氟哌啶醇的风险最高。[907]Huybrechts KF, Gerhard T, Crystal S, et al. Differential risk of death in older residents in nursing homes prescribed specific antipsychotic drugs: population based cohort study. BMJ. 2012 Feb 23;344:e977 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285717 http://www.ncbi.nlm.nih.gov/pubmed/22362541?tool=bestpractice.com
与普遍的看法相反,大多数痴呆患者的行为稳定后,就可以安全地停止长期抗精神病药处方。[908]Van Leeuwen E, Petrovic M, van Driel ML, et al. Withdrawal versus continuation of long-term antipsychotic drug use for behavioural and psychological symptoms in older people with dementia. Cochrane Database Syst Rev. 2018 Mar 30;(3):CD007726 https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007726.pub3/full http://www.ncbi.nlm.nih.gov/pubmed/29605970?tool=bestpractice.com
如果谵妄在 48 小时内未对初始治疗产生反应,转诊至在谵妄诊断方面经过培训且具备技能的医疗卫生专业人士,以确认诊断和治疗计划(基于专家意见)。
清楚记录谵妄的诊断。[897]National Institute for Health and Care Excellence. Delirium: prevention, diagnosis and management. 2019 [internet publication] https://www.nice.org.uk/guidance/CG103 [899]Scottish Intercollegiate Guidelines Network. Risk reduction and management of delirium: a national clinical guideline. 2019 [internet publication] https://www.sign.ac.uk/our-guidelines/risk-reduction-and-management-of-delirium
对于有卒中病史,且因急性疾病(包括 COVID-19)入院的患者,应在适当时机尽早进行基线神经系统评估。
通常,患有急性疾病(例如感染和疾病相关性低血压)的患者卒中(缺血性和出血性)风险增加。[892]Grau AJ, Urbanek C, Palm F. Common infections and the risk of stroke. Nat Rev Neurol. 2010 Nov 9;6(12):681-94 http://www.ncbi.nlm.nih.gov/pubmed/21060340?tool=bestpractice.com [893]Eigenbrodt ML, Rose KM, Couper DJ, et al. Orthostatic hypotension as a risk factor for stroke: the atherosclerosis risk in communities (ARIC) study, 1987-1996. Stroke. 2000 Oct;31(10):2307-13 https://www.doi.org/10.1161/01.str.31.10.2307 http://www.ncbi.nlm.nih.gov/pubmed/11022055?tool=bestpractice.com 有卒中病史的患者风险更高。
将基线评估结果与患者已知的 COVID-19 前神经系统状态进行比较。可通过询问患者、家属和照护者关于患者患病前的功能能力了解这一情况(基于专家意见)。
这样可以降低将入院时的神经系统体征错误归因于既往诊断卒中的风险。
如果住院期间神经系统状况发生变化,重复进行神经系统评估,以防再次发生卒中。
评估之后,确保对患者进行适当的监护(例如夜间意识模糊的风险和与体弱相关的跌倒风险)。
有卒中病史的患者跌倒和受伤的风险增加。[894]Winstein CJ, Stein J, Arena R, et al. Guidelines for adult stroke rehabilitation and recovery: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2016 May 4;47(6):e98-e169 https://www.doi.org/10.1161/STR.0000000000000098 http://www.ncbi.nlm.nih.gov/pubmed/27145936?tool=bestpractice.com
世界卫生组织建议密切监测 COVID-19 住院患者的临床恶化迹象,包括卒中征象或症状。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
见诸报道的 COVID-19 相关性神经系统表现包括急性缺血性和出血性卒中。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
针对特定患者群中所有患者的治疗建议
与您的医院糖尿病专科团队进行联络,获取 COVID-19 和糖尿病患者管理支持。
对于伴有急症(包括 COVID-19)的 1 型糖尿病患者,不应停用基础胰岛素(长效/背景胰岛素 [例如地特胰岛素、甘精胰岛素或德谷胰岛素])。 [889]Bornstein SR, Rubino F, Khunti K, et al. Practical recommendations for the management of diabetes in patients with COVID-19. Lancet Diabetes Endocrinol. 2020 Jun;8(6):546-50 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180013 http://www.ncbi.nlm.nih.gov/pubmed/32334646?tool=bestpractice.com [949]Chowdhury TA, Cheston H, Claydon A. Managing adults with diabetes in hospital during an acute illness. BMJ. 2017 Jun 22;357:j2551 http://www.ncbi.nlm.nih.gov/pubmed/28642274?tool=bestpractice.com
胰岛素缺乏(例如由于用药延迟或漏用)会迅速引起酮症酸中毒。[949]Chowdhury TA, Cheston H, Claydon A. Managing adults with diabetes in hospital during an acute illness. BMJ. 2017 Jun 22;357:j2551 http://www.ncbi.nlm.nih.gov/pubmed/28642274?tool=bestpractice.com
通常,所有接受基础胰岛素治疗的 2 型糖尿病患者均应继续接受治疗,但情况并非总是如此,因此应咨询上级医生和/或糖尿病专科医生团队 (基于专家意见)。
需注意,COVID-19 似乎会增加潜在致死性急症的发生风险,包括:[883]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19: front door guidance. 2020 [internet publication] https://abcd.care/resource/concise-advice-inpatient-diabetes-during-covid-19-front-door-guidance [889]Bornstein SR, Rubino F, Khunti K, et al. Practical recommendations for the management of diabetes in patients with COVID-19. Lancet Diabetes Endocrinol. 2020 Jun;8(6):546-50 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180013 http://www.ncbi.nlm.nih.gov/pubmed/32334646?tool=bestpractice.com
高血糖伴酮症
糖尿病酮症酸中毒 (DKA)
高渗性高血糖状态 (HHS)
对于 COVID-19 患者,无论是否已知患有糖尿病,均有此风险。
入院时应进行以下检查:[883]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19: front door guidance. 2020 [internet publication] https://abcd.care/resource/concise-advice-inpatient-diabetes-during-covid-19-front-door-guidance
所有患者的血糖
所有糖尿病患者(1 型和 2 型)以及入院时血糖 >12 mmol/L(>216 mg/dL)者的血酮。
如符合以下标准,则可在已知患有糖尿病的患者中诊断 DKA:[883]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19: front door guidance. 2020 [internet publication] https://abcd.care/resource/concise-advice-inpatient-diabetes-during-covid-19-front-door-guidance
血酮水平 ≥3 mmol/L,并且
血 pH 值<7.3 或碳酸氢根 <15 mmol/L。
请注意,美国糖尿病协会和美国临床内分泌医师协会/美国内分泌学会都建议使用与上述标准不同的标准来诊断 DKA。[950]Karslioglu French E, Donihi AC, Korytkowski MT. Diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome: review of acute decompensated diabetes in adult patients. BMJ. 2019 May 29;365:l1114. https://www.bmj.com/content/365/bmj.l1114.long http://www.ncbi.nlm.nih.gov/pubmed/31142480?tool=bestpractice.com
在正常血糖性酮症酸中毒中,血糖水平可能不会显著升高。
如果存在以下情况,HHS 诊断可能性极高:[883]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19: front door guidance. 2020 [internet publication] https://abcd.care/resource/concise-advice-inpatient-diabetes-during-covid-19-front-door-guidance
血糖 ≥30 mmol/L(≥541 mg/dL),且
血清渗透压([(2 x Na) + 葡萄糖 + 尿素])>320 mOsm/kg 且
pH >7.3。
请注意,美国糖尿病协会建议使用与上述标准不同的标准诊断 HHS。[950]Karslioglu French E, Donihi AC, Korytkowski MT. Diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome: review of acute decompensated diabetes in adult patients. BMJ. 2019 May 29;365:l1114. https://www.bmj.com/content/365/bmj.l1114.long http://www.ncbi.nlm.nih.gov/pubmed/31142480?tool=bestpractice.com
对于伴 COVID-19 者,或怀疑混合性 DKA/HHS 者,在 DKA 或 HHS 的管理中,需同糖尿病专科医生团队保持联系,并遵循 当地指南。
如果血糖 <4 mmol/L(<72 mg/dL),即可诊断为低血糖。
遵循当地的低血糖管理常规。
停止以下药物治疗:[883]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19: front door guidance. 2020 [internet publication] https://abcd.care/resource/concise-advice-inpatient-diabetes-during-covid-19-front-door-guidance
钠-葡萄糖协同转运蛋白 2(sodium-glucose cotransporter-2, SGLT-2)抑制剂(例如达格列净、卡格列净、恩格列净)
SGLT-2 抑制剂可降低肾脏中的血糖重吸收(与胰岛素代谢葡萄糖无关)。[951]Peters AL, Buschur EO, Buse JB, et al. Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Diabetes Care. 2015 Sep;38(9):1687-93 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4542270 http://www.ncbi.nlm.nih.gov/pubmed/26078479?tool=bestpractice.com
它们可以掩盖潜在的酮症酸中毒,因为患者的血糖水平可能正常或接近正常(血糖正常的酮症酸中毒)。[951]Peters AL, Buschur EO, Buse JB, et al. Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Diabetes Care. 2015 Sep;38(9):1687-93 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4542270 http://www.ncbi.nlm.nih.gov/pubmed/26078479?tool=bestpractice.com
二甲双胍
严重肾脏损伤(估算 GFR <30 mL/(min·1.73m²),或代谢性酸中毒(包括乳酸酸中毒和 DKA)患者禁用二甲双胍。
如果患者有乳酸酸中毒的风险,例如有急性肾损伤或组织缺氧(包括脱水),或在将长期禁食的情况下,也应禁用此药物。
根据患者的血乳酸水平、肾功能和动脉血气结果,可考虑重新开始使用二甲双胍,因有证据表明二甲双胍可预防 COVID-19 向重症恶化。[883]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19: front door guidance. 2020 [internet publication] https://abcd.care/resource/concise-advice-inpatient-diabetes-during-covid-19-front-door-guidance
如果患者停用其通常使用的 SGLT-2 抑制剂或二甲双胍,则可能需要调整药物或开始使用胰岛素作为一种临时措施。寻求糖尿病专科团队建议。
针对特定患者群中所有患者的治疗建议
若无禁忌,为急症入院成人和青少年起始静脉血栓栓塞(venous thromboembolism, VTE)预防治疗。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 [465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov [763]Barnes GD, Burnett A, Allen A, et al. Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the Anticoagulation Forum. J Thromb Thrombolysis. 2020 Jul;50(1):72-81. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241581 http://www.ncbi.nlm.nih.gov/pubmed/32440883?tool=bestpractice.com [952]Moores LK, Tritschler T, Brosnahan S, et al. Prevention, diagnosis, and treatment of VTE in patients with coronavirus disease 2019: CHEST guideline and expert panel report. Chest. 2020 Sep;158(3):1143-63. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265858 http://www.ncbi.nlm.nih.gov/pubmed/32502594?tool=bestpractice.com
针对危重患者的建议可能与针对重症患者的建议不同(参阅上文)。参阅当地指南。
在英国,国家卫生与临床优化研究所建议,对于需要高流量鼻套管吸氧、持续气道正压通气、无创通气或有创机械通气,且出血风险未呈升高状态的青年和成人,应给予预防剂量低分子肝素。作为临床试验的一部分,仅建议对此类患者使用中等剂量或治疗剂量的低分子肝素。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
在美国,国立卫生研究院指南专家组建议,对于接受重症监护病房级别治疗(包括接受高流量氧的患者)的患者,可给予预防剂量肝素(低分子肝素优于普通肝素),除非存在禁忌证。专家组不建议对此类患者给予中等剂量或治疗剂量抗凝药物,除非在临床试验背景下。在非重症监护病房开始使用治疗剂量肝素,而后收入重症监护病房的患者,应从治疗剂量肝素转为预防剂量肝素,除非确认其存在静脉血栓栓塞。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
部分指南推荐,对危重症患者可考虑加大剂量。[763]Barnes GD, Burnett A, Allen A, et al. Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the Anticoagulation Forum. J Thromb Thrombolysis. 2020 Jul;50(1):72-81. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241581 http://www.ncbi.nlm.nih.gov/pubmed/32440883?tool=bestpractice.com [968]Thachil J, Tang N, Gando S, et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost. 2020 May;18(5):1023-6. https://onlinelibrary.wiley.com/doi/full/10.1111/jth.14810 http://www.ncbi.nlm.nih.gov/pubmed/32338827?tool=bestpractice.com
对于极端体重或肾功能受损患者,可能需要调整剂量。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
危重患者的证据有限。
一项对近 28,000 名住院患者进行的系统评价和荟萃分析发现,与预防剂量抗凝治疗相比,中等剂量和治疗剂量抗凝治疗降低了重症监护病房危重症患者的血栓事件风险,但这些治疗方案与出血风险升高和住院死亡率无改变具有相关性。[831]Zhang S, Li Y, Liu G, et al. Intermediate-to-therapeutic versus prophylactic anticoagulation for coagulopathy in hospitalized COVID-19 patients: a systemic review and meta-analysis. Thromb J. 2021 Nov 24;19(1):91. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611638 http://www.ncbi.nlm.nih.gov/pubmed/34819094?tool=bestpractice.com
参阅以上 重症 COVID-19,获取 VTE 预防更详细信息。
查看当地药物处方集/肾病手册,了解对肾功能减退(慢性肾病、急性肾损伤)患者给予抗凝药物,进行静脉血栓栓塞预防的详细信息。
肾功能受损患者使用某些抗凝药物,可能使出血风险上升,需给予细致的患者监测。[955]Law JP, Pickup L, Townend JN, et al. Anticoagulant strategies for the patient with chronic kidney disease. Clin Med (Lond). 2020 Mar;20(2):151-5 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081809 http://www.ncbi.nlm.nih.gov/pubmed/32188649?tool=bestpractice.com
根据患者肾功能损害程度,您可能需要:
调整剂量
避免使用某些抗凝药物。
遵循当地药物处方集指南,建议监测抗 Xa 因子活性。
如果患者正在接受肾脏替代治疗,则寻求肾病专科医生建议。
或
或
依诺肝素
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
或
达肝素
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
或
磺达肝癸钠
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
针对特定患者群中部分患者治疗的附加建议
世界卫生组织建议,对于合并急性低氧血症性呼吸衰竭而无需紧急气管插管的重症住院患者,可使用高流量鼻导管氧疗(high-flow nasal oxygen, HFNO)、持续气道正压(continuous positive airway pressure, CPAP)通气或无创通气(头罩或面罩接口),非采取标准氧疗。选择取决于多种因素,如设备的可用性和氧气的供应,个人的舒适度和体验,以及患者特异性考虑因素(例如,使用 CPAP 或无创通气面罩的幽闭恐怖症,使用HFNO 的鼻腔不适)。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
在英国,英国国家卫生与临床优化研究所建议对补充供氧无反应、吸入氧气分数 ≥0.4(40%)的低氧血症患者使用 CPAP,升级为有创机械通气是一种选择,前提是并非立即需要,或者对于呼吸支持不应升级至超出 CPAP 不持异议。确保可联系危重症诊疗工作者获得建议、定期复查和在需要时及时升级治疗,以及在予以有创呼吸支持的同时定期评估和管理症状。可对于以下人群考虑给予 HFNO:患者无法耐受 CPAP,但需要高流量速率的湿化氧气;最大常规给氧无法维持其目标氧饱和度,但患者无需立即进行有创机械通气,或不宜升级为有创机械通气,且不宜给予 CPAP;或者患者需要短暂中断 CPAP(例如进餐时间、缓解皮肤压力、进行口腔护理),需给予湿化氧气或给予雾化吸入(或两者均需给予),或需 CPAP 撤机。对于适合升级为有创机械通气的呼吸衰竭患者,勿常规给予 HFNO 作为呼吸支持的主要形式。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
在美国,国立卫生研究院指南小组建议,对于尽管接受常规氧疗仍发生急性低氧血症性呼吸衰竭的成人,HFNO 优于无创通气。如果 HFNO 不可用,专家组建议对成人尝试无创通气,并予以密切监测。对于常规氧疗后仍有持续呼吸衰竭而无气管插管指标的婴儿和儿童,建议尝试短时间的无创通气或 HFNO。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
尽管新兴数据表明,HFNO 可能对于轻中度和非恶化型高碳酸血症患者安全,但高碳酸血症、血流动力学不稳定、多器官功能衰竭或精神状态异常患者通常不应接受该处理。伴低氧血症性呼吸衰竭、血流动力学不稳定、多器官功能衰竭或精神状态异常患者,不应代替其他选择(例如有创通气)接受此类治疗。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
由于不确定气溶胶产生可能,建议对此类干预措施(包括气泡式 CPAP)采取空气预防措施。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 尽管医务人员倾向于避免采用 HFNO,但发现其气溶胶生成风险与标准氧气面罩相似。[969]Li J, Fink JB, Ehrmann S. High-flow nasal cannula for COVID-19 patients: low risk of bio-aerosol dispersion. Eur Respir J. 2020 May 14;55(5):2000892. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163690 http://www.ncbi.nlm.nih.gov/pubmed/32299867?tool=bestpractice.com
对于需给予 HFNO 或无创通气的重病患者,考虑采取清醒俯卧位(每天 8-12 小时,将其在一天内分成多次较短时间进行)。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
在英国,国家卫生与临床优化研究所建议,对于未行气管插管,且氧需求较高的住院患者,可尝试采取清醒态俯卧位。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
在美国,国立卫生研究院指南专家组建议,对于需给予 HFNO 且暂无其他气管插管指征的持续性低氧血症患者,可尝试采取清醒俯卧位通气。尚无充分证据来支持或反对在儿童中尝试采取清醒俯卧位通气。专家组建议,对于符合气管插管和有创机械通气指征的患者,勿将清醒俯卧位通气作为难治性低氧血症的挽救治疗以避免气管插管。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
非气管插管患者采取清醒态俯卧位与氧气变量(PaO₂/FiO₂、PaO₂和 SpO₂)改善、呼吸频率改善、气管插管率改善(尤其是在需给予高级呼吸支持者和重症监护病房患者中)和死亡率改善具有相关性。但是证据有限。[772]Ponnapa Reddy M, Subramaniam A, Afroz A, et al. Prone positioning of nonintubated patients with coronavirus disease 2019: a systematic review and meta-analysis. Crit Care Med. 2021 Apr 30 [Epub ahead of print]. https://journals.lww.com/ccmjournal/Abstract/9000/Prone_Positioning_of_Nonintubated_Patients_With.95232.aspx http://www.ncbi.nlm.nih.gov/pubmed/33927120?tool=bestpractice.com [773]Chua EX, Zahir SMISM, Ng KT, et al. Effect of prone versus supine position in COVID-19 patients: a systematic review and meta-analysis. J Clin Anesth. 2021 Jun 22;74:110406. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216875 http://www.ncbi.nlm.nih.gov/pubmed/34182261?tool=bestpractice.com [774]Beran A, Mhanna M, Srour O, et al. Effect of prone positioning on clinical outcomes of non-intubated subjects with COVID-19: a comparative systematic review and meta-analysis. Respir Care. 2021 Nov 9 [Epub ahead of print]. http://rc.rcjournal.com/content/early/2021/11/09/respcare.09362.short http://www.ncbi.nlm.nih.gov/pubmed/34753813?tool=bestpractice.com [775]Li J, Luo J, Pavlov I, et al. Awake prone positioning for non-intubated patients with COVID-19-related acute hypoxaemic respiratory failure: a systematic review and meta-analysis. Lancet Respir Med. 2022 Mar 16 [Epub ahead of print]. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(22)00043-1/fulltext http://www.ncbi.nlm.nih.gov/pubmed/35305308?tool=bestpractice.com
对患者急性恶化进行密切监测。
如果短暂尝试此类干预措施后患者仍无改善,则需行紧急气管插管。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 [771]Alhazzani W, Evans L, Alshamsi F, et al. Surviving Sepsis Campaign guidelines on the management of adults with coronavirus disease 2019 (COVID-19) in the ICU: first update. Crit Care Med. 2021 Mar 1;49(3):e219-34. https://journals.lww.com/ccmjournal/Abstract/9000/Surviving_Sepsis_Campaign_Guidelines_on_the.95371.aspx http://www.ncbi.nlm.nih.gov/pubmed/33555780?tool=bestpractice.com
有限证据表明,无创通气减少了气管插管需求,提高了资源利用率,可能与更佳的结局具有相关性,并且较为安全。[799]Weerakkody S, Arina P, Glenister J, et al. Non-invasive respiratory support in the management of acute COVID-19 pneumonia: considerations for clinical practice and priorities for research. Lancet Respir Med. 2021 Nov 9 [Epub ahead of print]. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00414-8/fulltext http://www.ncbi.nlm.nih.gov/pubmed/34767767?tool=bestpractice.com
无明确证据表明无创呼吸支持可增加或降低 COVID-19 急性呼吸衰竭患者的死亡率。[798]Schmid B, Griesel M, Fischer AL, et al. Awake prone positioning, high-flow nasal oxygen and non-invasive ventilation as non-invasive respiratory strategies in COVID-19 acute respiratory failure: a systematic review and meta-analysis. J Clin Med. 2022 Jan 13;11(2):391. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8782004 http://www.ncbi.nlm.nih.gov/pubmed/35054084?tool=bestpractice.com
间接和低确定性证据表明,与有创机械通气类似,无创通气可能会降低 COVID-19 患者的死亡率,但可能增加病毒传播风险。与不给予 HFNO 相比,给予 HFNO 可降低死亡率。[800]Schünemann HJ, Khabsa J, Solo K, et al. Ventilation techniques and risk for transmission of coronavirus disease, including COVID-19. Ann Intern Med. 2020 Aug 4;173(3):204-16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281716 http://www.ncbi.nlm.nih.gov/pubmed/32442035?tool=bestpractice.com [801]Ute Muti-Schüenemann GE, Szczeklik W, Solo K, et al. Update alert 3: ventilation techniques and risk for transmission of coronavirus disease, including COVID-19. Ann Intern Med. 2021 Dec 14 [Epub ahead of print]. https://www.acpjournals.org/doi/full/10.7326/L21-0424 http://www.ncbi.nlm.nih.gov/pubmed/34904866?tool=bestpractice.com
对于急性呼吸衰竭降低死亡率,HFNO 优于无创通气。然而,两组气管插管率和住院时间无显著差异。[802]Glenardi G, Chriestya F, Oetoro BJ, et al. Comparison of high-flow nasal oxygen therapy and noninvasive ventilation in COVID-19 patients: a systematic review and meta-analysis. Acute Crit Care. 2022 Feb;37(1):71-83. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8918719 http://www.ncbi.nlm.nih.gov/pubmed/35279978?tool=bestpractice.com [803]Beran A, Srour O, Malhas SE, et al. High-flow nasal cannula oxygen versus non-invasive ventilation in subjects with COVID-19: a systematic review and meta-analysis of comparative studies. Respir Care. 2022 Mar 22 [Epub ahead of print]. http://rc.rcjournal.com/content/respcare/early/2022/03/22/respcare.09987.full.pdf http://www.ncbi.nlm.nih.gov/pubmed/35318240?tool=bestpractice.com
RECOVERY-RS 试验(一项开放标签、多中心、适应性随机对照试验)发现,CPAP 减少了因急性呼吸衰竭入院的成人对有创机械通气的需求。与传统氧疗相比,CPAP 和 HFNO 均未降低死亡率。[804]Perkins GD, Ji C, Connolly BA, et al. Effect of noninvasive respiratory strategies on intubation or mortality among patients with acute hypoxemic respiratory failure and COVID-19: the RECOVERY-RS randomized clinical trial. JAMA. 2022 Jan 24 [Epub ahead of print]. https://jamanetwork.com/journals/jama/fullarticle/2788505 http://www.ncbi.nlm.nih.gov/pubmed/35072713?tool=bestpractice.com
HELMET-COVID 试验(一项多中心随机临床试验)发现,与一般的呼吸支持(根据临床疗效交替使用面罩无创通气、HFNO 或标准氧疗)相比,头罩无创通气并未显著降低急性低氧血症性呼吸衰竭的 28 日死亡率。然而,该研究存在几项重要的局限性,并且这些研究发现的解读因效果强弱估计的不准确性而受限。[805]Arabi YM, Aldekhyl S, Al Qahtani S, et al. Effect of helmet noninvasive ventilation vs usual respiratory support on mortality among patients with acute hypoxemic respiratory failure due to COVID-19: the HELMET-COVID randomized clinical trial. JAMA. 2022 Sep 20;328(11):1063-72. https://jamanetwork.com/journals/jama/fullarticle/2796380 http://www.ncbi.nlm.nih.gov/pubmed/36125473?tool=bestpractice.com
SOHO-COVID 试验(一项随机临床试验)发现,与标准氧疗相比,HFNO 并未显著降低呼吸衰竭患者的 28 日死亡率。[806]Frat JP, Quenot JP, Badie J, et al. Effect of high-flow nasal cannula oxygen vs standard oxygen therapy on mortality in patients with respiratory failure due to COVID-19: the SOHO-COVID randomized clinical trial. JAMA. 2022 Sep 27;328(12):1212-22. https://jamanetwork.com/journals/jama/article-abstract/2796693 http://www.ncbi.nlm.nih.gov/pubmed/36166027?tool=bestpractice.com 然而,另一项随机对照试验发现,与重症患者常规低流量氧疗相比,HFNO 治疗降低了有创机械通气的可能性,并缩短了临床恢复时间。[807]Ospina-Tascón GA, Calderón-Tapia LE, García AF, et al. Effect of high-flow oxygen therapy vs conventional oxygen therapy on invasive mechanical ventilation and clinical recovery in patients with severe COVID-19: a randomized clinical trial. JAMA. 2021 Dec 7;326(21):2161-71. http://www.ncbi.nlm.nih.gov/pubmed/34874419?tool=bestpractice.com
如果患者哮喘状态稳定,应遵循相关急症(即 COVID-19)发作时 氧饱和度目标值 的指南建议。[943]O'Driscoll BR, Howard LS, Earis J, et al; British Thoracic Society Emergency Oxygen Guideline Group; BTS Emergency Oxygen Guideline Development Group. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017 Jun;72(suppl 1):ii1-90 http://www.ncbi.nlm.nih.gov/pubmed/28507176?tool=bestpractice.com
对所有伴急性疾病的哮喘患者检查静息血氧饱和度。[943]O'Driscoll BR, Howard LS, Earis J, et al; British Thoracic Society Emergency Oxygen Guideline Group; BTS Emergency Oxygen Guideline Development Group. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017 Jun;72(suppl 1):ii1-90 http://www.ncbi.nlm.nih.gov/pubmed/28507176?tool=bestpractice.com 这是对 COVID-19 患者采取的常规做法。
如果 COVID-19 触发了患者哮喘病情急性加重,当前意见为遵循标准指南建议控制成人哮喘急性发作。[865]British Thoracic Society; Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma: a national clinical guideline. 2019 [internet publication] https://www.brit-thoracic.org.uk/quality-improvement/guidelines/asthma [909]Centers for Disease Control and Prevention. Clinical questions about COVID-19: questions and answers – patients with asthma. 2020 [internet publication] https://www.cdc.gov/coronavirus/2019-ncov/hcp/faq.html#Patients-with-Asthma
在 COVID-19 大流行期间,对于急性患病者,遵循当地医院常规所推荐的目标血氧饱和度 。
喘伴高碳酸血症是濒死迹象,表明患者衰竭,需要通气支持。[865]British Thoracic Society; Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma: a national clinical guideline. 2019 [internet publication] https://www.brit-thoracic.org.uk/quality-improvement/guidelines/asthma 需要立即提供重症监护支持。[865]British Thoracic Society; Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma: a national clinical guideline. 2019 [internet publication] https://www.brit-thoracic.org.uk/quality-improvement/guidelines/asthma
如果患者并 COPD,适合全面升级诊疗,存在以下情况时,可进行转诊,考虑给予通气支持:
尽管给予氧疗,但仍存在重度低氧血症(PaO2 <7.3kPa [54.8 mmHg])(基于专家意见)
高碳酸血症(PaCO₂ >6 kPa [45 mmHg]),伴呼吸性酸中毒(pH <7.35)[943]O'Driscoll BR, Howard LS, Earis J, et al; British Thoracic Society Emergency Oxygen Guideline Group; BTS Emergency Oxygen Guideline Development Group. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017 Jun;72(suppl 1):ii1-90 http://www.ncbi.nlm.nih.gov/pubmed/28507176?tool=bestpractice.com
和/或
表现出精神状态的变化(意识模糊、昏迷)。
如果患者合并 COPD,出现 2 型呼吸衰竭,并且一致认为其不适合给予涉及重症监护病房收治的全面升级诊疗:
遵循以下有关给氧的指导
与上级医生或呼吸专科医生讨论是否适合在病房中给予无创通气。
对于有 2 型呼吸衰竭风险的 COVID-19 患者,给予辅助供氧时应同对其他急性疾病患者一样进行照护。针对这类患者的氧疗基本上应始终受到控制。因此,高流量鼻套管吸氧(high-flow nasal oxygen, HFNO)不适合这些患者。可考虑将 HFNO 用于无 2 型呼吸衰竭风险但存在重度低氧血症的患者。[859]Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. 2021 [internet publication] https://goldcopd.org/2021-gold-reports 请注意,该治疗处方应由资深决策者开具,并且只能在仔细观察和重复测定 ABG 的情况下使用(基于专家意见)。
对于低氧 COPD 患者,应检测静息氧饱和度,并在给予氧疗时,注意其他需要考虑的因素。
英国胸科学会急救用氧指南(并非专门针对 COVID-19)建议,对任何需要辅助供氧的 COPD 患者,均需测定动脉血气(arterial blood gas, ABG)。[943]O'Driscoll BR, Howard LS, Earis J, et al; British Thoracic Society Emergency Oxygen Guideline Group; BTS Emergency Oxygen Guideline Development Group. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017 Jun;72(suppl 1):ii1-90 http://www.ncbi.nlm.nih.gov/pubmed/28507176?tool=bestpractice.com
对于所有患者,在 30 至 60 分钟后再次检查 ABG。[943]O'Driscoll BR, Howard LS, Earis J, et al; British Thoracic Society Emergency Oxygen Guideline Group; BTS Emergency Oxygen Guideline Development Group. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017 Jun;72(suppl 1):ii1-90 http://www.ncbi.nlm.nih.gov/pubmed/28507176?tool=bestpractice.com
英国胸科学会建议,对于罹患 COPD 的入院 COVID-19 患者,且有慢性 2 型呼吸衰竭急性发作证据的患者,应遵循标准方案,详见以下章节。[944]British Thoracic Society. BTS guidance: respiratory support of patients on medical wards. 2020 [internet publication] https://www.brit-thoracic.org.uk/about-us/covid-19-information-for-the-respiratory-community
如果 COPD 患者合并危重症(如休克、脓毒症、严重颅脑外伤、癫痫持续状态、全身过敏反应、严重创伤)并需给予高浓度吸氧:
英国胸科协会(British Thoracic Society, BTS)建议最初的目标血氧饱和度为 94%-98%,但最近的证据表明,在大多数情况下,上限目标值取 96% 可能更好。[943]O'Driscoll BR, Howard LS, Earis J, et al; British Thoracic Society Emergency Oxygen Guideline Group; BTS Emergency Oxygen Guideline Development Group. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017 Jun;72(suppl 1):ii1-90 http://www.ncbi.nlm.nih.gov/pubmed/28507176?tool=bestpractice.com [945]Chu DK, Kim LH, Young PJ, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet. 2018 Apr 28;391(10131):1693-705 http://www.ncbi.nlm.nih.gov/pubmed/29726345?tool=bestpractice.com [946]Siemieniuk RAC, Chu DK, Kim LH, et al. Oxygen therapy for acutely ill medical patients: a clinical practice guideline. BMJ. 2018 Oct 24;363:k4169 http://www.ncbi.nlm.nih.gov/pubmed/30355567?tool=bestpractice.com 在 COVID-19 大流行期间,按照您医院推荐的关于目标血氧饱和度的当地医院方案对急性患病者进行处理。
随后,您可能需要根据 ABG 结果调整为控制性氧疗,目标血氧饱和度为 88%-92%。[943]O'Driscoll BR, Howard LS, Earis J, et al; British Thoracic Society Emergency Oxygen Guideline Group; BTS Emergency Oxygen Guideline Development Group. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017 Jun;72(suppl 1):ii1-90 http://www.ncbi.nlm.nih.gov/pubmed/28507176?tool=bestpractice.com
如果合并 COPD 患者为急性患病但非危重患者,并有高碳酸血症性衰竭风险(包括所有中重度 COPD 患者,特别是长期接受氧疗,被配置疾病警告卡,或有高碳酸血症性呼吸衰竭既往史的患者):[943]O'Driscoll BR, Howard LS, Earis J, et al; British Thoracic Society Emergency Oxygen Guideline Group; BTS Emergency Oxygen Guideline Development Group. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017 Jun;72(suppl 1):ii1-90 http://www.ncbi.nlm.nih.gov/pubmed/28507176?tool=bestpractice.com
采用的初始目标血氧饱和度为 88%-92%
检查 ABG,然后在 30 至 60 分钟后再次检查。
如果合并 COPD 患者为急性患病但非危重患者 ,且无高碳酸血症性呼吸衰竭风险(例如稳定、轻度 COPD,症状轻微):
使用针对出现的急性病症的指南所建议的初始目标血氧饱和度。
BTS 建议,对于大多数急性患病者,在等待 ABG 结果时,目标氧饱和度采用 94%-98%,但最近的证据表明上限目标值取 96% 可能更好。[943]O'Driscoll BR, Howard LS, Earis J, et al; British Thoracic Society Emergency Oxygen Guideline Group; BTS Emergency Oxygen Guideline Development Group. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017 Jun;72(suppl 1):ii1-90 http://www.ncbi.nlm.nih.gov/pubmed/28507176?tool=bestpractice.com [945]Chu DK, Kim LH, Young PJ, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet. 2018 Apr 28;391(10131):1693-705 http://www.ncbi.nlm.nih.gov/pubmed/29726345?tool=bestpractice.com [946]Siemieniuk RAC, Chu DK, Kim LH, et al. Oxygen therapy for acutely ill medical patients: a clinical practice guideline. BMJ. 2018 Oct 24;363:k4169 http://www.ncbi.nlm.nih.gov/pubmed/30355567?tool=bestpractice.com 根据当地医院供氧情况,此目标血氧饱和度水平可能会更低(遵循当地规程)
尽快测定 ABG[943]O'Driscoll BR, Howard LS, Earis J, et al; British Thoracic Society Emergency Oxygen Guideline Group; BTS Emergency Oxygen Guideline Development Group. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017 Jun;72(suppl 1):ii1-90 http://www.ncbi.nlm.nih.gov/pubmed/28507176?tool=bestpractice.com
随后,您可能需要根据 ABG 结果调整为控制性氧疗,目标血氧饱和度为 88%-92%。[943]O'Driscoll BR, Howard LS, Earis J, et al; British Thoracic Society Emergency Oxygen Guideline Group; BTS Emergency Oxygen Guideline Development Group. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017 Jun;72(suppl 1):ii1-90 http://www.ncbi.nlm.nih.gov/pubmed/28507176?tool=bestpractice.com
针对特定患者群中部分患者治疗的附加建议
对于给予高级氧合/无创通气支持手段,仍出现急性恶化的患者,考虑气管插管和机械通气。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 [465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
COVID-19 患者使用机械通气具有较高的死亡风险。不同研究的死亡率差异较大,介于 21% 和 100% 之间。根据随机效应总体估计,总体住院死亡率风险比被报道为 0.70。然而,值得注意的是,随着大流行进展,结局似乎有所改善。[809]Elsayed HH, Hassaballa AS, Ahmed TA, et al. Variation in outcome of invasive mechanical ventilation between different countries for patients with severe COVID-19: a systematic review and meta-analysis. PLoS One. 2021;16(6):e0252760. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177443 http://www.ncbi.nlm.nih.gov/pubmed/34086779?tool=bestpractice.com
与后期接受气管插管的患者相比,早期气管插管可能与较低的全因死亡率相关。[811]Xixi NA, Kremmydas P, Xourgia E, et al. Association between timing of intubation and clinical outcomes of critically ill patients: a meta-analysis. J Crit Care. 2022 May 16;71:154062. http://www.ncbi.nlm.nih.gov/pubmed/35588639?tool=bestpractice.com
气管插管应由经验丰富的医务人员施行空气传播预防措施后进行。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
建议尽可能通过可视喉镜实施插管。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
幼儿,亦或是肥胖或妊娠成人,可能会在气管插管过程中迅速脱饱和,因此需要给予 100% 浓度吸入氧气(FiO 2)预给氧 5 分钟。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 相对于无套囊气管内插管,优选有套囊气管内插管用于儿童。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
合并急性呼吸窘迫综合征(acute respiratory distress syndrome, ARDS)的机械通气患者,应采用肺保护性、低潮气量/低吸气压通气策略(对于儿童推荐降低治疗目标)。
对于中重度 ARDS 患者,较高的呼气末正压(Positive End-expiratory Pressure, PEEP)策略优于较低的 PEEP 策略。然而,建议对 PEEP 进行个体化,在PEEP 滴定过程中对患者获益或有害作用,以及驱动压进行监测,同时对于 PEEP 滴定风险和获益加以考虑。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 [465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov [771]Alhazzani W, Evans L, Alshamsi F, et al. Surviving Sepsis Campaign guidelines on the management of adults with coronavirus disease 2019 (COVID-19) in the ICU: first update. Crit Care Med. 2021 Mar 1;49(3):e219-34. https://journals.lww.com/ccmjournal/Abstract/9000/Surviving_Sepsis_Campaign_Guidelines_on_the.95371.aspx http://www.ncbi.nlm.nih.gov/pubmed/33555780?tool=bestpractice.com
尽管部分 COVID-19 肺炎患者达到 ARDS 标准,但仍有部分关于 COVID-19 肺炎是否为具有非典型表型的自身特异性疾病讨论。个案证据提示,患者非典型表现的主要特征为完好保留的呼吸力学与低氧血症严重程度之间无关联。[813]Gattinoni L, Coppola S, Cressoni M, et al. Covid-19 does not lead to a "typical" acute respiratory distress syndrome. Am J Respir Crit Care Med. 2020 May 15;201(10):1299-300. https://www.atsjournals.org/doi/pdf/10.1164/rccm.202003-0817LE http://www.ncbi.nlm.nih.gov/pubmed/32228035?tool=bestpractice.com [814]Gattinoni L, Chiumello D, Rossi S. COVID-19 pneumonia: ARDS or not? Crit Care. 2020 Apr 16;24(1):154. https://ccforum.biomedcentral.com/articles/10.1186/s13054-020-02880-z http://www.ncbi.nlm.nih.gov/pubmed/32299472?tool=bestpractice.com [815]Gattinoni L, Chiumello D, Caironi P, et al. COVID-19 pneumonia: different respiratory treatments for different phenotypes? Intensive Care Med. 2020 Jun;46(6):1099-102. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154064 http://www.ncbi.nlm.nih.gov/pubmed/32291463?tool=bestpractice.com [816]Marini JJ, Gattinoni L. Management of COVID-19 respiratory distress. JAMA. 2020 Jun 9;323(22):2329-30. https://jamanetwork.com/journals/jama/fullarticle/2765302 http://www.ncbi.nlm.nih.gov/pubmed/32329799?tool=bestpractice.com [817]Rello J, Storti E, Belliato M, et al. Clinical phenotypes of SARS-CoV-2: implications for clinicians and researchers. Eur Respir J. 2020 May 21;55(5):2001028. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236837 http://www.ncbi.nlm.nih.gov/pubmed/32341111?tool=bestpractice.com [818]Tsolaki V, Siempos I, Magira E, et al. PEEP levels in COVID-19 pneumonia. Crit Care. 2020 Jun 6;24(1):303. https://ccforum.biomedcentral.com/articles/10.1186/s13054-020-03049-4 http://www.ncbi.nlm.nih.gov/pubmed/32505186?tool=bestpractice.com 但是,该方法已受到批评。[819]Bos LD, Paulus F, Vlaar APJ, et al. Subphenotyping acute respiratory distress syndrome in patients with COVID-19: consequences for ventilator management. Ann Am Thorac Soc. 2020 Sep;17(9):1161-3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462326 http://www.ncbi.nlm.nih.gov/pubmed/32396457?tool=bestpractice.com [820]Jain A, Doyle DJ. Stages or phenotypes? A critical look at COVID-19 pathophysiology. Intensive Care Med. 2020 May 18;:1-2. https://link.springer.com/article/10.1007%2Fs00134-020-06083-6 http://www.ncbi.nlm.nih.gov/pubmed/32425310?tool=bestpractice.com 三项大型观察性队列研究得出的急性呼吸衰竭危重患者数据结果发现,COVID-19 相关性 ARDS 在基线(有创通气开始时)时未表现出一致的呼吸亚型。然而,时间依赖性分析表明,机械通气开始后最初 4 天内,出现了两种亚型。通气率上升的患者出现静脉血栓事件的风险升高,出现急性肾损伤的比率更高,需要更长时间的有创机械通气,并且死亡率更高。[970]Bos LDJ, Sjoding M, Sinha P, et al. Longitudinal respiratory subphenotypes in patients with COVID-19-related acute respiratory distress syndrome: results from three observational cohorts. Lancet Respir Med. 2021 Oct 12 [Epub ahead of print]. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00365-9/fulltext http://www.ncbi.nlm.nih.gov/pubmed/34653374?tool=bestpractice.com 从非 COVID-19 相关性 ARDS 中提取数据的循证方法被认为 COVID-19 患者危重症诊疗最合理方法。[822]Rice TW, Janz DR. In defense of evidence-based medicine for the treatment of COVID-19 ARDS. Ann Am Thorac Soc. 2020 Jul;17(7):787-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328187 http://www.ncbi.nlm.nih.gov/pubmed/32320268?tool=bestpractice.com 因此,部分临床医生警告称,使用方案预设型呼吸机可能会对部分患者造成肺损伤,呼吸机设置应基于生理结果,而非使用标准方案。高 PEEP 可能会对依从性正常患者产生不利影响。[813]Gattinoni L, Coppola S, Cressoni M, et al. Covid-19 does not lead to a "typical" acute respiratory distress syndrome. Am J Respir Crit Care Med. 2020 May 15;201(10):1299-300. https://www.atsjournals.org/doi/pdf/10.1164/rccm.202003-0817LE http://www.ncbi.nlm.nih.gov/pubmed/32228035?tool=bestpractice.com PEEP 应始终小心进行调整。[823]Dondorp AM, Hayat M, Aryal D, et al. Respiratory support in COVID-19 patients, with a focus on resource-limited settings. Am J Trop Med Hyg. 2020 Jun;102(6):1191-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253105 http://www.ncbi.nlm.nih.gov/pubmed/32319424?tool=bestpractice.com
重症 ARDS 者,应考虑给予俯卧位通气 12 至 16 h/d。
孕晚期孕妇可能获益于侧卧体位。儿童需谨慎。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 [465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov [771]Alhazzani W, Evans L, Alshamsi F, et al. Surviving Sepsis Campaign guidelines on the management of adults with coronavirus disease 2019 (COVID-19) in the ICU: first update. Crit Care Med. 2021 Mar 1;49(3):e219-34. https://journals.lww.com/ccmjournal/Abstract/9000/Surviving_Sepsis_Campaign_Guidelines_on_the.95371.aspx http://www.ncbi.nlm.nih.gov/pubmed/33555780?tool=bestpractice.com
某些患者中更长的持续时间可能可行。[824]Carsetti A, Damia Paciarini A, Marini B, et al. Prolonged prone position ventilation for SARS-CoV-2 patients is feasible and effective. Crit Care. 2020 May 15;24(1):225. https://ccforum.biomedcentral.com/articles/10.1186/s13054-020-02956-w http://www.ncbi.nlm.nih.gov/pubmed/32414420?tool=bestpractice.com
建议给予手法肺复张,但不建议给予阶梯式手法肺复张。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov [771]Alhazzani W, Evans L, Alshamsi F, et al. Surviving Sepsis Campaign guidelines on the management of adults with coronavirus disease 2019 (COVID-19) in the ICU: first update. Crit Care Med. 2021 Mar 1;49(3):e219-34. https://journals.lww.com/ccmjournal/Abstract/9000/Surviving_Sepsis_Campaign_Guidelines_on_the.95371.aspx http://www.ncbi.nlm.nih.gov/pubmed/33555780?tool=bestpractice.com
针对特定患者群中部分患者治疗的附加建议
对于即使优化通气后仍存在重度急性呼吸窘迫综合征和难治性低氧血症的成人和儿童,可考虑尝试给予吸入性肺血管扩张剂。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov [771]Alhazzani W, Evans L, Alshamsi F, et al. Surviving Sepsis Campaign guidelines on the management of adults with coronavirus disease 2019 (COVID-19) in the ICU: first update. Crit Care Med. 2021 Mar 1;49(3):e219-34. https://journals.lww.com/ccmjournal/Abstract/9000/Surviving_Sepsis_Campaign_Guidelines_on_the.95371.aspx http://www.ncbi.nlm.nih.gov/pubmed/33555780?tool=bestpractice.com
如果氧合未能得到迅速改善,则应逐渐减少其剂量。
证据正在不断涌现。
一项系统评价和荟萃分析发现,与标准治疗相比,吸入性肺血管扩张剂可改善氧合作用,但并未显示出死亡率方面的获益。[825]Khokher W, Malhas SE, Beran A, et al. Inhaled pulmonary vasodilators in COVID-19 infection: a systematic review and meta-analysis. J Intensive Care Med. 2022 Oct;37(10):1370-82. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9346441 http://www.ncbi.nlm.nih.gov/pubmed/35915994?tool=bestpractice.com
针对特定患者群中部分患者治疗的附加建议
若上述方法失败,根据设备可及性和人员技能水平,考虑给予体外膜肺氧合(Extracorporeal Membrane Oxygenation, ECMO)。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2 [771]Alhazzani W, Evans L, Alshamsi F, et al. Surviving Sepsis Campaign guidelines on the management of adults with coronavirus disease 2019 (COVID-19) in the ICU: first update. Crit Care Med. 2021 Mar 1;49(3):e219-34. https://journals.lww.com/ccmjournal/Abstract/9000/Surviving_Sepsis_Campaign_Guidelines_on_the.95371.aspx http://www.ncbi.nlm.nih.gov/pubmed/33555780?tool=bestpractice.com [971]Ramanathan K, Antognini D, Combes A, et al. Planning and provision of ECMO services for severe ARDS during the COVID-19 pandemic and other outbreaks of emerging infectious diseases. Lancet Respir Med. 2020 May;8(5):518-26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102637 http://www.ncbi.nlm.nih.gov/pubmed/32203711?tool=bestpractice.com
目前尚无充分证据支持或反对常规使用 ECMO 治疗。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
一项系统回顾和荟萃分析发现,接受 ECMO 的成人住院死亡率为 39%,与接受 ECMO 的流感患者相比,死亡率更高(44% 对 38%)。[827]Bertini P, Guarracino F, Falcone M, et al. ECMO in COVID-19 patients: a systematic review and meta-analysis. J Cardiothorac Vasc Anesth. 2021 Nov 12 [Epub ahead of print]. https://www.jcvaonline.com/article/S1053-0770(21)00971-X/fulltext http://www.ncbi.nlm.nih.gov/pubmed/34906383?tool=bestpractice.com
另一项系统评价和荟萃分析发现,汇总死亡率为 48.8%,并且该数据随着大流行发展而增长。[828]Ling RR, Ramanathan K, Sim JJL, et al. Evolving outcomes of extracorporeal membrane oxygenation during the first 2 years of the COVID-19 pandemic: a systematic review and meta-analysis. Crit Care. 2022 May 23;26(1):147. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9125014 http://www.ncbi.nlm.nih.gov/pubmed/35606884?tool=bestpractice.com
一项基于登记数据的队列研究发现,对于伴 COVID-19 相关性呼吸衰竭的特定成人患者(即 PaO2/FiO2 <80 mmHg),与未使用 ECMO 的传统机械通气相比,ECMO 与死亡率降低 7.1% 具有相关性。其对于年龄 <65 岁的患者,以及 PaO2/FiO2 <80 mmHg,或在机械通气前 10 天内驱动压力 >15 cm H2O 的患者最为有效。[826]Urner M, Barnett AG, Bassi GL, et al. Venovenous extracorporeal membrane oxygenation in patients with acute covid-19 associated respiratory failure: comparative effectiveness study. BMJ. 2022 May 4;377:e068723. https://www.bmj.com/content/377/bmj-2021-068723 http://www.ncbi.nlm.nih.gov/pubmed/35508314?tool=bestpractice.com
单通道双阶梯静脉 ECMO 联合早期拔管对于 COVID-19 呼吸衰竭患者,似乎安全有效。[972]Mustafa AK, Alexander PJ, Joshi DJ, et al. Extracorporeal membrane oxygenation for patients with COVID-19 in severe respiratory failure. JAMA Surg. 2020 Aug 11;155(10):990-2. https://jamanetwork.com/journals/jamasurgery/fullarticle/2769429 http://www.ncbi.nlm.nih.gov/pubmed/32780089?tool=bestpractice.com
ECMO 患者存在神经系统并发症风险(例如颅内出血、缺血性卒中和缺氧缺血性脑损伤)。[830]Kannapadi NV, Jami M, Premraj L, et al. Neurological complications in COVID-19 patients with ECMO support: a systematic review and meta-analysis. Heart Lung Circ. 2021 Oct 28 [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553269 http://www.ncbi.nlm.nih.gov/pubmed/34756659?tool=bestpractice.com
针对特定患者群中部分患者治疗的附加建议
考虑全身皮质类固醇治疗。指南建议各不相同。
世界卫生组织强烈建议,将全身皮质类固醇治疗(低剂量静脉用或口服地塞米松,或氢化可的松)用于危重症成人患者,连用 7-10 日。该项建议是基于表明全身皮质类固醇治疗可能降低危重症患者 28 日死亡率的中等质量证据。它们也可能减少对有创通气的需求。暂无直接比较地塞米松和氢化可的松的证据。在这种情况下,认为治疗的危害极小。尚不清楚此类建议是否适用于儿童或免疫功能低下者。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3 [736]Rochwerg B, Siemieniuk RA, Agoritsas T, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020 Sep 4;370:m3379. https://www.bmj.com/content/370/bmj.m3379.long http://www.ncbi.nlm.nih.gov/pubmed/32887691?tool=bestpractice.com [737]Rochwerg B, Siemieniuk RA, Lamontagne R, et al. Update to living WHO guideline on drugs for covid-19. BMJ. 2021 Jul 6;374:n1703. http://www.ncbi.nlm.nih.gov/pubmed/34230027?tool=bestpractice.com
在英国,英国国家卫生与临床优化研究所建议向需进行辅助供氧,以达到预期氧饱和度水平者,或达到缺氧水平,需进行辅助供氧,但却无法提供或无法耐受者,给予地塞米松进行治疗(或在地塞米松无法使用,或药物不可及时,给予诸如氢化可的松或泼尼松龙等替代药物)。治疗将持续达 10 天,除非有明确指征早期停止治疗。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
在美国,国立卫生研究院指南专家组建议,将地塞米松联合巴瑞替尼或托珠单抗(或在不能获得另一种免疫调节剂时可单独使用地塞米松)用于需要高流量氧疗或无创通气的住院患者。在某些情况下可添加 remdesivir。对于在接受机械通气或体外膜肺氧合治疗的成人患者,专家组建议将地塞米松联合巴瑞替尼或托珠单抗(或在不能获得另一种免疫调节剂时可单独使用地塞米松)用于收入重症监护病房 24 小时内的患者。无法给予地塞米松时,可使用其他皮质类固醇。专家组建议,将地塞米松(联合或不联合 remdesivir)用于需要高流量氧疗或无创通气的住院患儿,或将地塞米松单独用于需要有创机械通气或体外膜肺氧合治疗的住院患儿。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
BMJ rapid recommendations: a living WHO guideline on drugs for COVID-19 在新窗口中打开
证据支持将皮质类固醇用于住院患者。
一项 Cochrane 评价发现,全身皮质类固醇治疗可能使得有症状疾病住院患者的全因死亡率呈现轻度降低。研究中的多数参与者都接受了无创通气或有创机械通气治疗。低确定性证据表明,呼吸机撤机天数亦可能减少;然而,由于方法学限制,目前证据仍然不甚确定。不伴任何其余氧需求的有症状住院患者死亡率升高的证据,由于缺乏统计学意义,因而较为有限。目前尚不清楚何种全身皮质类固醇治疗最为有效。[787]Wagner C, Griesel M, Mikolajewska A, et al. Systemic corticosteroids for the treatment of COVID-19. Cochrane Database Syst Rev. 2021 Aug 16;(8):CD014963. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD014963/full http://www.ncbi.nlm.nih.gov/pubmed/34396514?tool=bestpractice.com
一项荟萃分析发现,对于危重症患者,皮质类固醇激素使用可增加静脉血栓栓塞风险。然而,由于皮质类固醇给药方案不同,以及研究异质性,因此暂未得出明确结论。[973]Sarfraz A, Sarfraz Z, Razzack AA, et al. Venous thromboembolism, corticosteroids and COVID-19: a systematic review and meta-analysis. Clin Appl Thromb Hemost. 2021 Jan-Dec;27:1076029621993573. https://journals.sagepub.com/doi/10.1177/1076029621993573 http://www.ncbi.nlm.nih.gov/pubmed/33571009?tool=bestpractice.com
监测患者不良反应(例如高血糖、潜伏性感染、精神效应、潜伏感染再活化),并评估药物相互作用。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
对糖尿病患者给予皮质类固醇将使其血糖控制恶化,因此应每日至少四次进行血糖检测。[956]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): dexamethasone/glucocorticosteroid therapy in COVID-19 patients – implications and guidance for the management of blood glucose in people with and without diabetes. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/COncise%20adVice%20on%20Inpatient%20Diabetes%20-%20dexamethasone%20therapy%20in%20covid-19%20patients%20implications%20and%20guidance%20for%20the%20management%20of%20blood%20glucose%20in%20people%20with%20and%20without%20diabetes%20Version%202.3%20November%202020.pdf
对于糖尿病患者,使用与非糖尿病患者相同剂量皮质类固醇,但应调整糖尿病用药,原因在于其将使糖尿病控制变得更劣。
合成皮质类固醇可通过影响碳水化合物代谢和诱导胰岛素抵抗而导致高血糖。[957]Joint British Diabetes Societies for inpatient care. Management of hyperglycaemia and steroid (glucocorticosteroid) therapy. 2021 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/JBDS_08_Steroids_DM_Guideline_FINAL_28052021.pdf
COVID-19 亦与胰岛素抵抗增加和来自胰岛 β 细胞的胰岛素分泌减少具有相关性。[956]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): dexamethasone/glucocorticosteroid therapy in COVID-19 patients – implications and guidance for the management of blood glucose in people with and without diabetes. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/COncise%20adVice%20on%20Inpatient%20Diabetes%20-%20dexamethasone%20therapy%20in%20covid-19%20patients%20implications%20and%20guidance%20for%20the%20management%20of%20blood%20glucose%20in%20people%20with%20and%20without%20diabetes%20Version%202.3%20November%202020.pdf
如果出现高血糖,需排除糖尿病酮症酸中毒或高渗性高血糖状态,遵循所在医院常规,管理正在使用皮质类固醇的糖尿病合并 COVID-19 患者血糖。[956]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): dexamethasone/glucocorticosteroid therapy in COVID-19 patients – implications and guidance for the management of blood glucose in people with and without diabetes. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/COncise%20adVice%20on%20Inpatient%20Diabetes%20-%20dexamethasone%20therapy%20in%20covid-19%20patients%20implications%20and%20guidance%20for%20the%20management%20of%20blood%20glucose%20in%20people%20with%20and%20without%20diabetes%20Version%202.3%20November%202020.pdf
英国国家糖尿病住院患者 COVID-19 应对组(National Inpatient Diabetes COVID-19 Response Group)推荐的病房用药方案采用皮下注射胰岛素。[956]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): dexamethasone/glucocorticosteroid therapy in COVID-19 patients – implications and guidance for the management of blood glucose in people with and without diabetes. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/COncise%20adVice%20on%20Inpatient%20Diabetes%20-%20dexamethasone%20therapy%20in%20covid-19%20patients%20implications%20and%20guidance%20for%20the%20management%20of%20blood%20glucose%20in%20people%20with%20and%20without%20diabetes%20Version%202.3%20November%202020.pdf [958]Rayman G, Lumb AN, Kennon B, et al. Dexamethasone therapy in COVID-19 patients: implications and guidance for the management of blood glucose in people with and without diabetes. Diabet Med. 2021 Jan;38(1):e14378 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436853 http://www.ncbi.nlm.nih.gov/pubmed/32740972?tool=bestpractice.com
该团体强调,由于潜在的 β 细胞功能损害和可能的严重胰岛素抵抗,磺脲类药物 不建议加以使用。[956]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): dexamethasone/glucocorticosteroid therapy in COVID-19 patients – implications and guidance for the management of blood glucose in people with and without diabetes. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/COncise%20adVice%20on%20Inpatient%20Diabetes%20-%20dexamethasone%20therapy%20in%20covid-19%20patients%20implications%20and%20guidance%20for%20the%20management%20of%20blood%20glucose%20in%20people%20with%20and%20without%20diabetes%20Version%202.3%20November%202020.pdf
当停止皮质类固醇给药时,血糖控制将有可能得到改善,但可能需要数天时间。
遵循当地常规,逐渐调整抗糖尿病药物。
了解既往对皮质类固醇的反应。
既往皮质类固醇治疗期间出现过精神并发症,可增加后续治疗当中复发的风险。[959]Judd LL, Schettler PJ, Brown ES, et al. Adverse consequences of glucocorticoid medication: psychological, cognitive, and behavioral effects. Am J Psychiatry. 2014 Oct;171(10):1045-51 https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2014.13091264 http://www.ncbi.nlm.nih.gov/pubmed/25272344?tool=bestpractice.com
监测精神不良反应。[960]Kenna HA, Poon AW, de los Angeles CP, et al. Psychiatric complications of treatment with corticosteroids: review with case report. Psychiatry Clin Neurosci. 2011 Oct;65(6):549-60 https://onlinelibrary.wiley.com/doi/full/10.1111/j.1440-1819.2011.02260.x http://www.ncbi.nlm.nih.gov/pubmed/22003987?tool=bestpractice.com
这些不良反应的严重程度可能各有不同,并且包括:
细微的性情改变
剧烈的情绪改变,包括躁狂状态
认知障碍。
起始皮质类固醇治疗, 最常与躁狂发作和谵妄状态呈现关联。长期皮质类固醇治疗后,最常见的伴发表现为抑郁。[961]Warrington TP, Bostwick JM. Psychiatric adverse effects of corticosteroids. Mayo Clin Proc. 2006 Oct;81(10):1361-7 https://www.mayoclinicproceedings.org/article/S0025-6196(11)61160-9/fulltext http://www.ncbi.nlm.nih.gov/pubmed/17036562?tool=bestpractice.com
不良反应似乎与剂量有关,并且在使用长期方案或长效制剂时,以及在老年患者中更为常见。[959]Judd LL, Schettler PJ, Brown ES, et al. Adverse consequences of glucocorticoid medication: psychological, cognitive, and behavioral effects. Am J Psychiatry. 2014 Oct;171(10):1045-51 https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2014.13091264 http://www.ncbi.nlm.nih.gov/pubmed/25272344?tool=bestpractice.com 对于因停止长期皮质类固醇治疗而出现神经精神性不良反应的患者,也是如此。[962]Fardet L, Nazareth I, Whitaker HJ, et al. Severe neuropsychiatric outcomes following discontinuation of long-term glucocorticoid therapy: a cohort study. J Clin Psychiatry. 2013 Apr;74(4):e281-6 http://www.ncbi.nlm.nih.gov/pubmed/23656853?tool=bestpractice.com
与精神病学团队联络,获取患者情绪相关性并发症的适当管理建议(基于专家意见)。
这可能涉及:
如有临床指征,可调整剂量或停用皮质类固醇治疗。
如果停用皮质类固醇,需注意可能出现的停药反应。[962]Fardet L, Nazareth I, Whitaker HJ, et al. Severe neuropsychiatric outcomes following discontinuation of long-term glucocorticoid therapy: a cohort study. J Clin Psychiatry. 2013 Apr;74(4):e281-6 http://www.ncbi.nlm.nih.gov/pubmed/23656853?tool=bestpractice.com 这可能表现为虚弱、乏力、胃肠道症状、谵妄,以及包括抑郁在内的精神并发症
当有心境障碍病史的患者开始接受皮质类固醇治疗时,考虑进行预防性用药,降低精神不良反应风险。寻求精神科专家建议。
地塞米松: 儿童:咨询专科医生,获得剂量指导;成人:6 mg,口服/静脉注射,一天一次,持续 7-10 天
地塞米松 : 儿童:咨询专科医生,获得剂量指导;成人:6 mg,口服/静脉注射,一天一次,持续 7-10 天
地塞米松: 儿童:咨询专科医生,获得剂量指导;成人:6 mg,口服/静脉注射,一天一次,持续 7-10 天
或
氢化可的松琥珀酸钠: 儿童:咨询专科医生获取用药指导;成人:50 mg,静脉使用,每 8 小时一次,连用 7-10 日
氢化可的松琥珀酸钠 : 儿童:咨询专科医生获取用药指导;成人:50 mg,静脉使用,每 8 小时一次,连用 7-10 日
氢化可的松琥珀酸钠: 儿童:咨询专科医生获取用药指导;成人:50 mg,静脉使用,每 8 小时一次,连用 7-10 日
泼尼松龙: 儿童:咨询专科医生,获得剂量指导;成人:40 mg/天,口服,分 1-2 次给药,连续 7-10 天
泼尼松龙 : 儿童:咨询专科医生,获得剂量指导;成人:40 mg/天,口服,分 1-2 次给药,连续 7-10 天
泼尼松龙: 儿童:咨询专科医生,获得剂量指导;成人:40 mg/天,口服,分 1-2 次给药,连续 7-10 天
或
地塞米松: 儿童:咨询专科医生,获得剂量指导;成人:6 mg,口服/静脉注射,一天一次,持续 7-10 天
地塞米松 : 儿童:咨询专科医生,获得剂量指导;成人:6 mg,口服/静脉注射,一天一次,持续 7-10 天
地塞米松: 儿童:咨询专科医生,获得剂量指导;成人:6 mg,口服/静脉注射,一天一次,持续 7-10 天
或
氢化可的松琥珀酸钠: 儿童:咨询专科医生获取用药指导;成人:50 mg,静脉使用,每 8 小时一次,连用 7-10 日
氢化可的松琥珀酸钠 : 儿童:咨询专科医生获取用药指导;成人:50 mg,静脉使用,每 8 小时一次,连用 7-10 日
氢化可的松琥珀酸钠: 儿童:咨询专科医生获取用药指导;成人:50 mg,静脉使用,每 8 小时一次,连用 7-10 日
泼尼松龙: 儿童:咨询专科医生,获得剂量指导;成人:40 mg/天,口服,分 1-2 次给药,连续 7-10 天
泼尼松龙 : 儿童:咨询专科医生,获得剂量指导;成人:40 mg/天,口服,分 1-2 次给药,连续 7-10 天
泼尼松龙: 儿童:咨询专科医生,获得剂量指导;成人:40 mg/天,口服,分 1-2 次给药,连续 7-10 天
或
地塞米松
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
或
氢化可的松琥珀酸钠
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
泼尼松龙
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
或
甲泼尼龙
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
针对特定患者群中部分患者治疗的附加建议
考虑使用抗病毒药 remdesivir。各指南建议有所不同,并且国际指南之间对于危重症患者中的 remdesivir 应用建议存在冲突。remdesivir 可能增加危重患者的死亡风险,目前仅美国指南建议将其用于特定患者。
在美国,国立卫生研究院指南专家组建议,将remdesivir 联合地塞米松用于需高流量氧疗或无创通气的住院儿童和成人患者。专家组不建议将 remdesivir 用于需接受有创机械通气或体外膜肺氧合治疗的患者。然而,专家组建议,如果患者在接受低流量辅助氧疗时开始使用 remdesivir(参阅上文重症 COVID-19),而后进展至需高流量供氧、无创通气、机械通气或体外膜肺氧合治疗,则完成整个 remdesivir 疗程。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
在英国,国家卫生与临床优化研究所 反对将 remdesivir 用于接受高流量鼻套管氧疗、持续气道正压通气、无创机械通气或有创机械通气的住院患者,除非作为临床试验的一部分。该项建议是基于中等确定性证据,其表明 remdesivir 可能增加正在接受这些干预措施者的死亡风险。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
世界卫生组织有条件反对将 remdesivir 用于危重症患者,因为它可能对死亡率或机械通气需求的影响极小或没有影响,以及对症状改善时间有着不确定的影响。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3 [736]Rochwerg B, Siemieniuk RA, Agoritsas T, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020 Sep 4;370:m3379. https://www.bmj.com/content/370/bmj.m3379.long http://www.ncbi.nlm.nih.gov/pubmed/32887691?tool=bestpractice.com [737]Rochwerg B, Siemieniuk RA, Lamontagne R, et al. Update to living WHO guideline on drugs for covid-19. BMJ. 2021 Jul 6;374:n1703. http://www.ncbi.nlm.nih.gov/pubmed/34230027?tool=bestpractice.com
如果使用,对该适应证的建议疗程为 5 天或直到出院为止,以先期达到者为准。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
证据未表明与 5 天疗程相比,remdesivir 10 天疗程可带来更多获益,但证据提示有害风险升高。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191 然而,部分专家则可能建议对第 5 天仍未显示出明显临床改善的患者进行疗程 10 天的治疗。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
不良反应包括肾毒性和肝毒性。
remdesivir 不推荐用于估算的肾小球滤过率(estimated glomerular filtration rate, eGFR)<30 mL/min 的患者。开始治疗前和治疗期间应根据临床情况,对肾功能进行监测。静脉制剂含有溶解度增强剂磺丁基醚 β-环糊精钠(sulfobutyl ether beta-cyclodextrin sodium, SBECD),可通过肾脏清除。肾脏损伤患者体内 SBECD 的累积,可能导致肝肾毒性。如果可能,应考虑对肾脏损伤患者优先使用冻干粉针,因其 SBECD 含量更少。
与安慰剂相比,remdesivir 对急性肾损伤可能仅有极轻微的作用或者没有作用。[855]Izcovich A, Siemieniuk RA, Bartoszko JJ, et al. Adverse effects of remdesivir, hydroxychloroquine and lopinavir/ritonavir when used for COVID-19: systematic review and meta-analysis of randomised trials. BMJ Open. 2022 Mar 2;12(3):e048502. https://bmjopen.bmj.com/content/12/3/e048502 http://www.ncbi.nlm.nih.gov/pubmed/35236729?tool=bestpractice.com
转氨酶升高已见诸报道。开始治疗前和治疗期间应根据临床情况,对肝功能进行监测。如果丙氨酸氨基转移酶(alanine aminotransferase, ALT)水平升高至正常上限 ≥ 10 倍,应考虑停止治疗。如果 ALT 升高伴有肝脏炎症征象或症状,应停止治疗。
开始治疗前和治疗期间应根据临床情况,对凝血酶原时间进行监测,因为凝血酶原时间延长已见诸报道。
超敏反应(包括液体输注相关性反应和全身过敏反应)已见诸报道。
需在严重超敏反应可得到控制的环境中给药。输注过程中对患者进行监测,并在输注后观察至少 1 小时。
考虑所有接受 COVID-19 治疗患者的潜在不良反应和药物相互作用。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
世界卫生组织在其有关 COVID-19 临床管理的临时指南中强调了 remdesivir 的以下重要不良反应:[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
肾脏损伤(对估算 GFR <30 mL/min 的患者不应使用 remdesivir)
肝酶升高
低血压
胃肠道并发症
皮疹。
此清单并未详尽列出全部不良反应 – 参阅当地处方集,以获取更多信息。请咨询相关专业同事和/或药师以获取建议。
remdesivir: 年龄 ≥12 岁和体重 ≥40 kg 的儿童和成人:第 1 天静脉输注 200 mg 作为负荷剂量,而后每 24 小时给予 100 mg,持续 5-10 天
remdesivir : 年龄 ≥12 岁和体重 ≥40 kg 的儿童和成人:第 1 天静脉输注 200 mg 作为负荷剂量,而后每 24 小时给予 100 mg,持续 5-10 天
remdesivir: 年龄 ≥12 岁和体重 ≥40 kg 的儿童和成人:第 1 天静脉输注 200 mg 作为负荷剂量,而后每 24 小时给予 100 mg,持续 5-10 天
更多 remdesivirremdesivir 可能在部分国家/地区获批用于 12 岁以下儿童。然而,尚无充分证据支持常规推荐将其用于 12 岁以下儿童(可根据和危险因素考虑治疗)。
remdesivir: 年龄 ≥12 岁和体重 ≥40 kg 的儿童和成人:第 1 天静脉输注 200 mg 作为负荷剂量,而后每 24 小时给予 100 mg,持续 5-10 天
remdesivir : 年龄 ≥12 岁和体重 ≥40 kg 的儿童和成人:第 1 天静脉输注 200 mg 作为负荷剂量,而后每 24 小时给予 100 mg,持续 5-10 天
remdesivir: 年龄 ≥12 岁和体重 ≥40 kg 的儿童和成人:第 1 天静脉输注 200 mg 作为负荷剂量,而后每 24 小时给予 100 mg,持续 5-10 天
更多 remdesivirremdesivir 可能在部分国家/地区获批用于 12 岁以下儿童。然而,尚无充分证据支持常规推荐将其用于 12 岁以下儿童(可根据和危险因素考虑治疗)。
remdesivir
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
针对特定患者群中部分患者治疗的附加建议
考虑使用 IL-6 抑制剂。指南建议各不相同。
世界卫生组织强烈建议将 IL-6 抑制剂(托珠单抗或 sarilumab)用于危重症患者。IL-6 抑制剂可与皮质类固醇和 Janus 激酶抑制剂联合使用,并且应与全身皮质类固醇同时开始使用。该建议基于表明 IL-6 抑制剂可降低死亡率和机械通气需求的高确定性证据,以及表明 IL-6 抑制剂还可缩短机械通气持续时间和住院时间的低确定性证据。关于严重不良事件的风险相关证据尚不确定。该建议对儿童的适用性目前尚不确定。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3 [736]Rochwerg B, Siemieniuk RA, Agoritsas T, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020 Sep 4;370:m3379. https://www.bmj.com/content/370/bmj.m3379.long http://www.ncbi.nlm.nih.gov/pubmed/32887691?tool=bestpractice.com [737]Rochwerg B, Siemieniuk RA, Lamontagne R, et al. Update to living WHO guideline on drugs for covid-19. BMJ. 2021 Jul 6;374:n1703. http://www.ncbi.nlm.nih.gov/pubmed/34230027?tool=bestpractice.com
在美国,美国国立卫生研究院指南专家组建议,对于需接受无创机械通气或高流量鼻套管氧疗,给氧需求迅速增加及伴全身炎症的近期入院(例如,3 日内)患者,可在地塞米松(或合适的其他皮质类固醇)的基础上加用托珠单抗,或可将地塞米松与 remdesivir 联合使用。对于接受机械通气或体外膜肺氧合治疗的患者,专家组建议收入重症监护病房 24 小时内,在地塞米松基础上加用托珠单抗。如果托珠单抗不可用或不可行,则可给予 sarilumab 作为替代用药。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov 除标准治疗(即皮质类固醇)之外,美国传染病学会建议对于呈现危重症,且全身炎症标志物升高的住院成人患者,考虑给予托珠单抗,而非仅仅给予标准治疗。如果托珠单抗无法使用,则可使用 sarilumab。[466]Bhimraj A, Morgan RL, Hirsch Shumaker A, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19 infection. 2022 [internet publication]. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management
BMJ rapid recommendations: a living WHO guideline on drugs for COVID-19 在新窗口中打开
证据支持 IL-6 抑制剂的应用。
一项 Cochrane 评价发现,与单纯的标准治疗或安慰剂相比,托珠单抗降低了 28 日全因死亡率(高确定性证据),并且可能略微减少严重不良事件(中等确定性证据)。有证据表明,对第 60 日后死亡率的影响尚不确定。然而,托珠单抗对第 28 日的临床改善(即出院或临床试验员规定量表所测量的改善情况)影响可能很小或并无影响。托珠单抗对其他结局的影响尚不确定。有关 sarilumab 效力的证据尚不确定。[793]Ghosn L, Chaimani A, Evrenoglou T, et al. Interleukin-6 blocking agents for treating COVID-19: a living systematic review. Cochrane Database Syst Rev. 2021 Mar 18;(3):CD013881. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013881/full http://www.ncbi.nlm.nih.gov/pubmed/33734435?tool=bestpractice.com
一项实时系统评价和网络荟萃分析发现,与标准治疗相比,IL-6 抑制剂(与皮质类固醇联用)可能降低死亡率(中等确定性证据),可能减少机械通气需求(中等确定性证据),以及可能缩短住院时间(中等确定性证据)。[788]Siemieniuk RA, Bartoszko JJ, Ge L, et al. Drug treatments for covid-19: living systematic review and network meta-analysis. BMJ. 2020 Jul 30;370:m2980. https://www.bmj.com/content/370/bmj.m2980 http://www.ncbi.nlm.nih.gov/pubmed/32732190?tool=bestpractice.com [789]Siemieniuk RA, Bartoszko JJ, Ge L, et al. Update to living systematic review on drug treatments for covid-19. BMJ. 2021 Mar 31;372:n858. https://www.bmj.com/content/372/bmj.n858.long http://www.ncbi.nlm.nih.gov/pubmed/33789885?tool=bestpractice.com
一项针对来自 45 项随机试验的约 20,000 名患者的荟萃分析指出,托珠单抗(与皮质类固醇联用)可能降低严重或危重疾病患者的死亡率,sarilumab(与皮质类固醇联用)可能降低死亡率。现有证据显示,托珠单抗与 sarilumab 可能具有类似的有效性。当未与皮质类固醇联用时,这些药物可能没有益处。[963]Zeraatkar D, Cusano E, Martínez JPD, et al. Use of tocilizumab and sarilumab alone or in combination with corticosteroids for covid-19: systematic review and network meta-analysis. BMJ Medicine 2022 Mar 2;1:e000036. https://bmjmedicine.bmj.com/content/1/1/e000036
使用 IL-6 抑制剂的患者感染风险升高,包括活动性结核病、侵袭性真菌感染和机会性感染病原体。
起始治疗之前,应进行常规血液检查,包括白细胞计数、血小板计数、转氨酶和总胆红素。由于全身性皮质类固醇治疗患者免疫抑制风险升高,因此应对所有此类患者监测感染征象和症状。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
免疫功能低下患者应避免使用此类药物。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
托珠单抗: 儿童:咨询专科医生,获得剂量指导;成人:8 mg/kg,静脉使用,单次给药,最多 800 mg/剂
托珠单抗 : 儿童:咨询专科医生,获得剂量指导;成人:8 mg/kg,静脉使用,单次给药,最多 800 mg/剂
托珠单抗: 儿童:咨询专科医生,获得剂量指导;成人:8 mg/kg,静脉使用,单次给药,最多 800 mg/剂
更多 托珠单抗通常作为单剂静脉注射给药;但是,如果临床反应不足,可以在第一次给药后 12 至 48 小时给予第二次给药。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
或
Sarilumab: 儿童:咨询专科医生,获得剂量指导;成人:400 mg,静脉使用,单次给药
Sarilumab : 儿童:咨询专科医生,获得剂量指导;成人:400 mg,静脉使用,单次给药
Sarilumab: 儿童:咨询专科医生,获得剂量指导;成人:400 mg,静脉使用,单次给药
更多 Sarilumab通常作为单剂静脉注射给药;但是,如果临床反应不足,可以在第一次给药后 12 至 48 小时给予第二次给药。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
托珠单抗: 儿童:咨询专科医生,获得剂量指导;成人:8 mg/kg,静脉使用,单次给药,最多 800 mg/剂
托珠单抗 : 儿童:咨询专科医生,获得剂量指导;成人:8 mg/kg,静脉使用,单次给药,最多 800 mg/剂
托珠单抗: 儿童:咨询专科医生,获得剂量指导;成人:8 mg/kg,静脉使用,单次给药,最多 800 mg/剂
更多 托珠单抗通常作为单剂静脉注射给药;但是,如果临床反应不足,可以在第一次给药后 12 至 48 小时给予第二次给药。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
或
Sarilumab: 儿童:咨询专科医生,获得剂量指导;成人:400 mg,静脉使用,单次给药
Sarilumab : 儿童:咨询专科医生,获得剂量指导;成人:400 mg,静脉使用,单次给药
Sarilumab: 儿童:咨询专科医生,获得剂量指导;成人:400 mg,静脉使用,单次给药
更多 Sarilumab通常作为单剂静脉注射给药;但是,如果临床反应不足,可以在第一次给药后 12 至 48 小时给予第二次给药。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
托珠单抗
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
或
Sarilumab
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
针对特定患者群中部分患者治疗的附加建议
考虑给予 JAK 抑制剂。指南建议各不相同。
世界卫生组织强烈建议将 JAK 抑制剂(巴瑞替尼)用于危重症患者。巴瑞替尼可与皮质类固醇和 IL-6 抑制剂联合使用,并且应与全身皮质类固醇同时开始使用。该项建议是基于巴瑞替尼可降低死亡率的高确定性证据,以及巴瑞替尼可能缩短机械通气持续时间和住院时间的中等确定性证据。该建议对儿童的适用性目前尚不确定。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3 [736]Rochwerg B, Siemieniuk RA, Agoritsas T, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020 Sep 4;370:m3379. https://www.bmj.com/content/370/bmj.m3379.long http://www.ncbi.nlm.nih.gov/pubmed/32887691?tool=bestpractice.com [737]Rochwerg B, Siemieniuk RA, Lamontagne R, et al. Update to living WHO guideline on drugs for covid-19. BMJ. 2021 Jul 6;374:n1703. http://www.ncbi.nlm.nih.gov/pubmed/34230027?tool=bestpractice.com
在英国, 国家卫生与临床优化研究所推荐巴瑞替尼用于以下住院成人:需给予辅助供氧(或其他类型呼吸支持,包括高流量鼻导管吸氧、持续气道正压通气、无创通气或机械通气),并且正在接受或已完成一个疗程皮质类固醇治疗(除非具有禁忌证),并且不存在可能因巴瑞替尼用药而恶化的感染证据(除 SARS-CoV-2 以外的其他感染)。巴瑞替尼亦可考虑用于 ≥2 岁儿童,只要其符合相同标准。[530]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing COVID-19. 2022 [internet publication]. https://www.nice.org.uk/guidance/ng191
在美国,美国国立卫生研究院指南专家组建议,对于需接受无创机械通气或高流量鼻套管氧疗,且给氧需求迅速增加及伴全身炎症的近期入院患者,可在地塞米松(或合适的其他皮质类固醇)的基础上加用巴瑞替尼,或可将地塞米松与 remdesivir 联合使用。对于接受机械通气或体外膜肺氧合治疗的患者,专家组建议收入重症监护病房 24 小时内,在地塞米松基础上加用巴瑞替尼。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
美国传染病学会建议对炎症标志物升高的重症住院成人,可给予巴瑞替尼(联合皮质类固醇)。对于因禁忌证而无法接受皮质类固醇治疗的患者,其建议巴瑞克替尼与 remdesivir 联合给药,而非 remdesivir 单独给药。[466]Bhimraj A, Morgan RL, Hirsch Shumaker A, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19 infection. 2022 [internet publication]. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management
BMJ rapid recommendations: a living WHO guideline on drugs for COVID-19 在新窗口中打开
该类别中的其他药物包括托法替布和芦可替尼。
世界卫生组织不建议使用此类药物,除非巴瑞替尼或 IL-6 抑制剂无法获取。托法替布或芦可替尼对死亡率、机械通气需求和住院时间的影响仍不明确,需要更多试验证据。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3 [736]Rochwerg B, Siemieniuk RA, Agoritsas T, et al. A living WHO guideline on drugs for covid-19. BMJ. 2020 Sep 4;370:m3379. https://www.bmj.com/content/370/bmj.m3379.long http://www.ncbi.nlm.nih.gov/pubmed/32887691?tool=bestpractice.com [737]Rochwerg B, Siemieniuk RA, Lamontagne R, et al. Update to living WHO guideline on drugs for covid-19. BMJ. 2021 Jul 6;374:n1703. http://www.ncbi.nlm.nih.gov/pubmed/34230027?tool=bestpractice.com
在美国,国立卫生研究院指南专家组建议,仅在巴瑞克替尼无法获取或无法应用时,方使用托法替布。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov 美国传染病学会建议对于未接受无创通气或有创机械通气的重症住院成人,给予托法替布。[466]Bhimraj A, Morgan RL, Hirsch Shumaker A, et al. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19 infection. 2022 [internet publication]. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management
证据支持 JAK 抑制剂的应用。
一项 Cochrane 评价发现,JAK 抑制剂可能降低至第 28 日(中等确定性证据)和至第 60 日(高确定性证据)的全因死亡率。它们可能对临床状态或不良事件发生率的改善影响极小或并未影响(中等确定性证据)。巴瑞替尼是最常接受评估的 JAK 抑制剂。[794]Kramer A, Prinz C, Fichtner F, et al. Janus kinase inhibitors for the treatment of COVID-19. Cochrane Database Syst Rev. 2022 Jun 13;6(6):CD015209. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD015209/full http://www.ncbi.nlm.nih.gov/pubmed/35695334?tool=bestpractice.com
一项实时系统评价和网络荟萃分析发现,与标准治疗相比,JAK 制剂可能降低死亡率(高确定性证据),缩短机械通气持续时间(高确定性证据),以及缩短住院时间(高确定性证据)。[788]Siemieniuk RA, Bartoszko JJ, Ge L, et al. Drug treatments for covid-19: living systematic review and network meta-analysis. BMJ. 2020 Jul 30;370:m2980. https://www.bmj.com/content/370/bmj.m2980 http://www.ncbi.nlm.nih.gov/pubmed/32732190?tool=bestpractice.com [789]Siemieniuk RA, Bartoszko JJ, Ge L, et al. Update to living systematic review on drug treatments for covid-19. BMJ. 2021 Mar 31;372:n858. https://www.bmj.com/content/372/bmj.n858.long http://www.ncbi.nlm.nih.gov/pubmed/33789885?tool=bestpractice.com
患者感染风险升高(包括活动性结核病、侵袭性真菌感染和机会性感染病原体)。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
避免在罹患已知活动性结核病的患者中使用。
由于全身性皮质类固醇治疗患者免疫抑制风险升高,因此应对所有此类患者监测感染征象和症状。
治疗前和治疗期间应执行不同的全血细胞监测策略。
巴瑞替尼不建议用于重度肾损害或肝损害患者。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
不建议将巴瑞替尼用于估算的肾小球滤过率 ≤15 mL/min 的成人(<9 岁儿童 ≤30 mL/min),或接受透析或肾脏替代治疗的患者。对于估算的肾小球滤过率 ≤60 mL/min 的患者,建议减少剂量。
巴瑞替尼尚未在重度肝功能不全患者中进行研究,尚不清楚此类患者是否需要调整剂量。应仅当潜在获益超过潜在风险时,方予以使用。
中重度肾功能不全患者(包括透析患者)应慎用托法替布和芦可替尼;可能需要调整剂量。
治疗前和治疗期间应监测肾功能和肝功能。
不良反应包括白细胞减少、淋巴细胞减少、血小板增多、贫血、凝血异常、肝功能损害和继发感染。[735]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.3
其他严重不良反应包括静脉血栓形成和重度感染。
美国食品药品监督管理局已发出警告,称 JAK 抑制剂将使得严重心脏相关事件、肿瘤、血栓和死亡风险升高。[964]US Food and Drug Administration. FDA requires warnings about increased risk of serious heart-related events, cancer, blood clots, and death for JAK inhibitors that treat certain chronic inflammatory conditions. 2021 [internet publication]. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requires-warnings-about-increased-risk-serious-heart-related-events-cancer-blood-clots-and-death
CKD 患者起始 JAK 抑制剂用药之前应检查肾功能,如同其他患者一样。
由于可能需要调整剂量,因此应参阅当地处方集。
如果患者正在进行透析、患有终末期肾功能衰竭或患有急性肾损伤,则不推荐使用巴瑞替尼。[965]World Health Organization. Therapeutics and COVID-19: living guideline. 2022 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.1
芦可替尼和托法替布在中重度肾功能损害患者中应谨慎应用,其剂量可能需要调整。参阅当地处方集,寻求肾脏病学团队建议。
CKD 患者接受 JAK 抑制剂治疗期间,需对肾功能予以特别密切的监测。
巴瑞克替尼 (Baricitinib): 儿童:咨询专科医生,获得剂量指导;成人:4 mg,口服,每日一次,持续 14 日
巴瑞克替尼 (Baricitinib) : 儿童:咨询专科医生,获得剂量指导;成人:4 mg,口服,每日一次,持续 14 日
巴瑞克替尼 (Baricitinib): 儿童:咨询专科医生,获得剂量指导;成人:4 mg,口服,每日一次,持续 14 日
或
巴瑞克替尼 (Baricitinib): 儿童:咨询专科医生,获得剂量指导;成人:4 mg,口服,每日一次,持续 14 日
巴瑞克替尼 (Baricitinib) : 儿童:咨询专科医生,获得剂量指导;成人:4 mg,口服,每日一次,持续 14 日
巴瑞克替尼 (Baricitinib): 儿童:咨询专科医生,获得剂量指导;成人:4 mg,口服,每日一次,持续 14 日
或
巴瑞克替尼 (Baricitinib)
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
托法替布
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
或
卢可替尼
对于 CKD 患者:, 请查阅当地药物处方集
对于 CKD 患者: 请参照肾病药物手册中的剂量指导对于 CKD 患者: 请参照肾病药物手册中的剂量指导
针对特定患者群中部分患者治疗的附加建议
根据当地常规,酌情处理实验室确认的混合感染(例如疟疾、结核病、流行性感冒)。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
不论是否存在 SARS-CoV-2 混合感染,所有流感患者治疗均相同。对于疑似存在单纯流感感染,或存在两者混合感染的住院患者,须尽快给予奥司他韦,进行经验性治疗,无需等待流感检测结果。一旦排除流感,即可停止抗病毒治疗。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
针对特定患者群中所有患者的治疗建议
多个专业呼吸科组织的指南均同意,应建议患有哮喘或 COPD 的患者继续按处方使用吸入剂(包括吸入皮质类固醇)(包括吸入皮质类固醇),无论其是否罹患 COVID-19。[857]Global Initiative for Asthma. Global strategy for asthma management and prevention. 2022 [internet publication] https://ginasthma.org/gina-reports [858]British Thoracic Society. Advice for healthcare professionals treating people with asthma (adults) in relation to COVID-19. 2020 [internet publication] https://www.brit-thoracic.org.uk/about-us/covid-19-information-for-the-respiratory-community [859]Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. 2021 [internet publication] https://goldcopd.org/2021-gold-reports [860]National Institute for Health and Care Excellence. COVID-19 rapid guideline: community-based care of patients with chronic obstructive pulmonary disease (COPD). 2020 [internet publication] https://www.nice.org.uk/guidance/ng168 [861]Hasan SS, Capstick T, Zaidi STR, et al. Use of corticosteroids in asthma and COPD patients with or without COVID-19. Respir Med. 2020 Aug-Sep;170:106045 https://www.resmedjournal.com/article/S0954-6111(20)30185-2/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32843175?tool=bestpractice.com
继续吸入皮质类固醇治疗的总体目标是降低哮喘或 COPD 加重的风险。[861]Hasan SS, Capstick T, Zaidi STR, et al. Use of corticosteroids in asthma and COPD patients with or without COVID-19. Respir Med. 2020 Aug-Sep;170:106045 https://www.resmedjournal.com/article/S0954-6111(20)30185-2/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32843175?tool=bestpractice.com
尚无证据表明吸入皮质类固醇与哮喘患者的 COVID-19 感染有关。[862]Centre for Evidence-Based Medicine; Hartmann-Boyce J, Hobbs R. Inhaled steroids in asthma during the COVID-19 outbreak. 2020 [internet publication] https://www.cebm.net/covid-19/inhaled-steroids-in-asthma-during-the-covid-19-outbreak 也无证据表明它们会增加 COPD 患者的 COVID-19 相关风险。[860]National Institute for Health and Care Excellence. COVID-19 rapid guideline: community-based care of patients with chronic obstructive pulmonary disease (COPD). 2020 [internet publication] https://www.nice.org.uk/guidance/ng168
居家或在医院接受诊疗的急症患者可能会对其被给予的 COPD 或哮喘吸入器遗忘向您告知。酌情谨记对吸入器进行检查以及给予药物。
许多吸入器含有多种药物,因此应确保勿重复给药。
对于出现急性肾损伤的 COPD 或哮喘患者,如果估算 GFR <50 mL/(min·1.73m²),可能需要暂时停用其常用的吸入性长效毒蕈碱受体拮抗剂,具体取决于使用哪种特定药物。查阅当地处方集或寻求药师建议。
其他处方药物
患有严重哮喘或 COPD 并使用口服皮质类固醇作为常规维持治疗处方的患者,也应以尽可能低的剂量继续使用这些药物,因为停用这些药物可能会导致其病情恶化。[857]Global Initiative for Asthma. Global strategy for asthma management and prevention. 2022 [internet publication] https://ginasthma.org/gina-reports [860]National Institute for Health and Care Excellence. COVID-19 rapid guideline: community-based care of patients with chronic obstructive pulmonary disease (COPD). 2020 [internet publication] https://www.nice.org.uk/guidance/ng168 [863]National Institute for Health and Care Excellence. COVID-19 rapid guideline: severe asthma. 2020 [internet publication] https://www.nice.org.uk/guidance/ng166
英国国家卫生与临床优化研究所关于严重哮喘的快速指南建议,在 COVID-19 大流行期间,常规使用生物治疗哮喘的患者应继续使用该药物,但是,若其罹患 COVID-19,则应联系负责其诊疗的专科医生团队。[863]National Institute for Health and Care Excellence. COVID-19 rapid guideline: severe asthma. 2020 [internet publication] https://www.nice.org.uk/guidance/ng166
针对特定患者群中所有患者的治疗建议
世界卫生组织建议,于 COVID-19 患者,不应例行停用降压药,而应根据患者临床情况(尤其是血压和肾功能)进行调整。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
尽管担心使用 ACE 抑制剂或血管紧张素 Ⅱ 受体拮抗剂的患者出现感染风险或患更严重疾病的风险增加,但一项正在进行的系统评价发现,高确定性证据表明此类药物的使用与重症不具相关性。[868]Mackey K, King VJ, Gurley S, et al. Risks and impact of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers on SARS-CoV-2 infection in adults: a living systematic review. Ann Intern Med. 2020 Aug 4;173(3):195-203 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249560 http://www.ncbi.nlm.nih.gov/pubmed/32422062?tool=bestpractice.com [869]Mackey K, Kansagara D, Vela K. Update alert 7: risks and impact of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers on SARS-CoV-2 infection in adults. Ann Intern Med. 2021 Feb;174(2):W25-9 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791405 http://www.ncbi.nlm.nih.gov/pubmed/33395346?tool=bestpractice.com
一些专业学会建议,已经使用这些药物(例如用于治疗高血压、心力衰竭、冠状动脉疾病、CKD 或糖尿病并发症的药物)的患者可以在大流行期间继续使用(前提是其未罹患 COVID-19)。如果患者罹患 COVID-19,建议他们在决定停用此类药物之前接受医生全面临床评估。[870]American Heart Association; Heart Failure Society of America; American College of Cardiology. Patients taking ACE-i and ARBs who contract COVID-19 should continue treatment, unless otherwise advised by their physician. 2020 [internet publication] https://newsroom.heart.org/news/patients-taking-ace-i-and-arbs-who-contract-covid-19-should-continue-treatment-unless-otherwise-advised-by-their-physician [871]European Society of Cardiology Council on Hypertension. Position statement of the ESC Council on Hypertension on ACE-inhibitors and angiotensin receptor blockers. 2020 [internet publication] https://www.escardio.org/Councils/Council-on-Hypertension-(CHT)/News/position-statement-of-the-esc-council-on-hypertension-on-ace-inhibitors-and-ang [872]British Cardiovascular Society; British Society for Heart Failure. BSH & BCS joint statement on ACEi or ARB in relation to COVID-19. 2020 [internet publication] https://www.britishcardiovascularsociety.org/news/ACEi-or-ARB-and-COVID-19 [873]The Renal Association. The Renal Association, UK position statement on COVID-19 and ACE inhibitor/angiotensin receptor blocker use. 2020 [internet publication] https://renal.org/health-professionals/covid-19/ra-resources/renal-association-uk-position-statement-covid-19-and-ace
英国肾脏协会(Renal Association)和英国心血管学会(British Cardiovascular Society)建议,在权衡这些药物对疑似 COVID-19 患者的益处和风险时,遵循当前针对患任何并发急性疾病的患者的标准指导。[872]British Cardiovascular Society; British Society for Heart Failure. BSH & BCS joint statement on ACEi or ARB in relation to COVID-19. 2020 [internet publication] https://www.britishcardiovascularsociety.org/news/ACEi-or-ARB-and-COVID-19 [873]The Renal Association. The Renal Association, UK position statement on COVID-19 and ACE inhibitor/angiotensin receptor blocker use. 2020 [internet publication] https://renal.org/health-professionals/covid-19/ra-resources/renal-association-uk-position-statement-covid-19-and-ace [874]Clark AL, Kalra PR, Petrie MC, et al. Change in renal function associated with drug treatment in heart failure: national guidance. Heart. 2019 Jun;105(12):904-10 http://www.ncbi.nlm.nih.gov/pubmed/31118203?tool=bestpractice.com 其中包括:
进行个体临床评估
对所有肾素-血管紧张素-醛固酮系统(renin-angiotensin-aldosterone system, RAAS)拮抗剂 初始适应症加以考虑(ACE 抑制剂、血管紧张素-Ⅱ 受体拮抗剂、盐皮质激素受体/醛固酮拮抗剂),并对预后获益程度加以考虑
如果暂时停止药物治疗,需考虑健康状况得到改善后何时再次给药。
考虑计算脆弱评分,因为脆弱评分较高的患者,突发不适时更可能受到药物相关性伤害(基于专家意见)。
考虑停用其他在并发疾病期间与急性肾损伤风险增加相关药物的获益与风险,例如其他抗高血压药和利尿药。
如果慢性肾病患者一直在使用非甾体抗炎药,建议他们在并发疾病时停用此类药物。
在社区自我管理心力衰竭的患者可能希望在出现可能导致脱水的并发疾病期间减少利尿药剂量 (基于专家意见)。
如果患者病情复杂(例如正在进行肾脏替代治疗或免疫抑制治疗),可向患者心脏病学团队或肾病学团队寻求建议 。
针对特定患者群中所有患者的治疗建议
询问患者他们正在服用哪些药物治疗抑郁。或查看其初级卫生保健记录,获取相关信息(若可获取)。
药物相互作用及其与 COVID-19 患者尤为相关的不良反应包括镇静、心脏毒性(QT 间期延长),以及呼吸抑制。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
为患者开具其常用的抗抑郁药,除非有充分的理由不得这样做(基于专家意见)。
如果突然停用抗抑郁药,患者可能出现停药症状。[923]Cleare A, Pariante CM, Young AH, et al. Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines. J Psychopharmacol. 2015 May;29(5):459-525 https://www.bap.org.uk/docdetails.php?docID=5 http://www.ncbi.nlm.nih.gov/pubmed/25969470?tool=bestpractice.com
药物停用的症状严重程度 可能各有所异,但可能令人不快,以及可能使急症管理复杂化。[924]National Institute for Health and Care Excellence. Depression in adults with a chronic physical health problem: recognition and management. 2009 [internet publication] https://www.nice.org.uk/guidance/cg91
审评当前药物时,需注意以下情况:
所察觉的当前和既往不良反应
近期用药剂量改变
最近更换了一种不同类别的药物
特定抑郁症亚型的药物细微差别(例如,精神病性抑郁症患者很可能会同时服用抗精神病处方药)
难治性抑郁症治疗中可能需要使用的增强策略(如选择性 5-羟色胺再摄取抑制剂 [selective serotonin-reuptake inhibitor, SSRI])的基础上加用锂剂或喹硫平。
对药物相互作用加以考虑。
抗抑郁药可能会与用于其他疾病的药物发生药代动力学(通过抑制 CYP450 通路)和药效动力学相互作用。[923]Cleare A, Pariante CM, Young AH, et al. Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines. J Psychopharmacol. 2015 May;29(5):459-525 https://www.bap.org.uk/docdetails.php?docID=5 http://www.ncbi.nlm.nih.gov/pubmed/25969470?tool=bestpractice.com [925]Taylor DM, Barnes TRE, Young AH. The Maudsley prescribing guidelines in psychiatry. 14th edition. Chichester: Wiley-Blackwell; 2021 对于为 COVID-19 患者开处的所有药物以及任何实验性治疗(请参阅新兴疗法章节),需考虑此问题。
请注意,戒烟或从吸烟转为任何其他替代方案(包括尼古丁替代疗法)可能导致患者服用的任何精神类药物(例如,用于治疗抑郁的药物)血药浓度发生变化。这是因为尼古丁替代疗法不会像吸烟那样影响肝酶活性。[926]Flowers L. Nicotine replacement therapy. Am J Psychiatry Resid J. 2016 Jun;11(6):4-7 https://psychiatryonline.org/doi/10.1176/appi.ajp-rj.2016.110602 [927]Desai HD, Seabolt J, Jann MW. Smoking in patients receiving psychotropic medications: a pharmacokinetic perspective. CNS Drugs. 2001;15(6):469-94 http://www.ncbi.nlm.nih.gov/pubmed/11524025?tool=bestpractice.com [928]Oliveira P, Ribeiro J, Donato H, et al. Smoking and antidepressants pharmacokinetics: a systematic review. Ann Gen Psychiatry. 2017 Mar 6;16:17 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5340025 http://www.ncbi.nlm.nih.gov/pubmed/28286537?tool=bestpractice.com [929]National Centre for Smoking Cessation and Training. Smoking cessation and mental health: a briefing for front-line staff. 2014 [internet publication] https://www.ncsct.co.uk/shopdisp_mental_health_briefing.php 寻求相关建议,确认精神类药物剂量调整是否适当。
开具非精神类药物时,应考虑精神并发症。
给予皮质类固醇、抗惊厥药物和抗帕金森病药物时,应格外小心。
考虑不良反应,具体可能包括以下不良反应。[925]Taylor DM, Barnes TRE, Young AH. The Maudsley prescribing guidelines in psychiatry. 14th edition. Chichester: Wiley-Blackwell; 2021
与三环类抗抑郁药相关的 QT 间期延长、心律失常、心率加快或体位性低血压。进行 ECG 检查,特别是有心律失常风险的人群。
低钠血症,由抗抑郁药(尤其是 SSRI)引起,并因其他同时开具的药物(例如利尿药)加重。检查患者的血清电解质。
5-羟色胺综合征(精神状态改变、激越、震颤、反射亢进、阵挛、肌强直、大量出汗、心动过速、肠鸣音增加、体温 >38℃),尤其是在多重用药和/或 5-羟色胺能药物过量时。[930]Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005 Mar 17;352(11):1112-20 https://www.doi.org/10.1056/NEJMra041867 http://www.ncbi.nlm.nih.gov/pubmed/15784664?tool=bestpractice.com [931]Buckley NA, Dawson AH, Isbister GK. Serotonin syndrome. BMJ. 2014 Feb 19;348:g1626 http://www.ncbi.nlm.nih.gov/pubmed/24554467?tool=bestpractice.com
特别要注意的是,服用 SSRI 的终末期肾病患者出现 5-羟色胺综合征的风险增加。治疗肾脏损伤患者的抑郁需要采取多学科方法,并需要格外谨慎。
肝毒性。必要时调整肝功能受损患者的抗抑郁药物剂量,避免使用已知具有肝毒性的药物。
该不良反应和药物相互作用表单并不详尽 – 参阅当地处方集,获取更多信息。咨询联络精神病学同事和/或药剂师,获取建议。
尽可能向患者询问其采用哪些非药物治疗方法处理抑郁,并检查其在社区获得的支持情况。
其可包括参与其照护的其他医疗卫生专业人士、慈善力量、家庭和社交网络,以及心理治疗。
针对特定患者群中部分患者治疗的附加建议
对一切适当的试验性或新兴治疗加以考虑。
抗病毒治疗将在疾病早期发挥更大的作用,而免疫抑制/抗炎治疗则可能在疾病晚期发挥更大的作用。[465]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2022 [internet publication]. https://covid19treatmentguidelines.nih.gov
更多信息请参阅 “新兴治疗”。
对 COVID-19 患者,应考虑潜在不良反应和药物相互作用。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
一个示例是对 QT 间期的影响。患者可能正在服用延长 QT 间期的药物。而后,患者可能会接受另一种延长 QT 间期的 COVID-19 药物治疗。
给予患者任何新药之前,需对其合并症和当前治疗加以考虑。
起始任何新治疗之前,遵循当地药物应用方案指南,并咨询上级医生。
针对特定患者群中部分患者治疗的附加建议
常规对重症患者进行活动能力、功能性吞咽、认知损害和心理健康等方面的评估。
根据评估结果确定患者是否适宜出院,以及患者是否需给予康复和随访处理。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
确保患者对于所有合并症的随访计划到位,以及明确 COVID-19 相关性出院和随访标准。
COVID-19 可能具有其他合并症相关性长期影响。患者和医疗卫生专业人士可在以下资源中获取实用信息:
遵循当地常规,寻求相关专科团队意见。
考虑使用远超医疗,协调特定患者进行远程会诊。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
针对特定患者群中部分患者治疗的附加建议
每一个为 COVID-19 患者提供照护的机构均应可给予缓和治疗。
确定患者是否有预先护理计划,并在制定护理计划时尊重患者的取向和偏好。[88]World Health Organization. Living guidance for clinical management of COVID-19. 2021 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-2
遵循当地缓和医疗(亦称为安宁疗护)指南。
缺乏 COVID-19 患者缓和医疗(亦称为安宁疗护)数据。
对用于此类患者缓和医疗的药理学策略快速系统评价(这是同类中的第一次国际评价)发现,与缓和医疗群体常见情况相比,需给予连续皮下输注给药的患者具有更高的比例。需给予适度剂量常用临终药物进行症状控制。然而,由于缺乏可用数据,应谨慎解释这些结论。[795]Heath L, Carey M, Lowney AC, et al. Pharmacological strategies used to manage symptoms of patients dying of COVID-19: a rapid systematic review. Palliat Med. 2021 Jun;35(6):1099-107. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189007 http://www.ncbi.nlm.nih.gov/pubmed/33983081?tool=bestpractice.com
针对特定患者群中所有患者的治疗建议
哮喘加重与 COVID-19 临床可能难以区分,其可能同时出现。两者的共同特征是咳嗽和呼吸短促;但是,发热、疲劳以及味觉或嗅觉改变等其他症状更可能提示 COVID-19。[858]British Thoracic Society. Advice for healthcare professionals treating people with asthma (adults) in relation to COVID-19. 2020 [internet publication] https://www.brit-thoracic.org.uk/about-us/covid-19-information-for-the-respiratory-community
监测呼吸道症状急性恶化症状,并意识到这可能提示患者合并哮喘,正在出现哮喘急性发作。
寻求上级医生建议。
即使怀疑 COVID-19 为诱因,亦应对成人哮喘急性发作严重程度评估和管理遵循标准指南建议。[865]British Thoracic Society; Scottish Intercollegiate Guidelines Network. British guideline on the management of asthma: a national clinical guideline. 2019 [internet publication] https://www.brit-thoracic.org.uk/quality-improvement/guidelines/asthma [909]Centers for Disease Control and Prevention. Clinical questions about COVID-19: questions and answers – patients with asthma. 2020 [internet publication] https://www.cdc.gov/coronavirus/2019-ncov/hcp/faq.html#Patients-with-Asthma
参阅成人哮喘急性发作主题。
考虑临床情况是否适宜使用定量吸入器(通过储雾罐装置输送)作为替代给药机制。[847]Global Initiative for Asthma. Global strategy for asthma management and prevention. 2021 [internet publication] https://ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf 遵循当地常规。
根据临床指征起始口服皮质类固醇治疗哮喘加重。[858]British Thoracic Society. Advice for healthcare professionals treating people with asthma (adults) in relation to COVID-19. 2020 [internet publication] https://www.brit-thoracic.org.uk/about-us/covid-19-information-for-the-respiratory-community [861]Hasan SS, Capstick T, Zaidi STR, et al. Use of corticosteroids in asthma and COPD patients with or without COVID-19. Respir Med. 2020 Aug-Sep;170:106045 https://www.resmedjournal.com/article/S0954-6111(20)30185-2/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32843175?tool=bestpractice.com
如果给予患者雾化吸入短效毒蕈碱受体拮抗剂(例如异丙托溴铵),则应暂时停用患者可能正在使用的任何用于维持治疗的长效毒蕈碱受体拮抗剂(long-acting muscarinic receptor antagonist, LAMA)(例如噻托溴铵、aclidinium、格隆溴铵、乌美溴铵 (基于专家意见)。
因为担心可能会出现抗胆碱能成瘾的不良反应。
一旦停止给予雾化治疗,需再给予 LAMA 药物治疗。
目前,对于使用雾化剂是否会产生气溶胶,以及是否因此需使用特定个人防护装备,不同国家组织之间存在不同看法。[847]Global Initiative for Asthma. Global strategy for asthma management and prevention. 2021 [internet publication] https://ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf [863]National Institute for Health and Care Excellence. COVID-19 rapid guideline: severe asthma. 2020 [internet publication] https://www.nice.org.uk/guidance/ng166 请遵循当地指南和常规。
针对特定患者群中所有患者的治疗建议
如果 COVID-19 和固有 COPD 患者可疑 COPD 加重,遵循患者个体化行动预案。[910]National Institute for Health and Care Excellence. COVID-19 rapid guideline: community-based care of patients with chronic obstructive pulmonary disease (COPD). 2020 [internet publication] https://www.nice.org.uk/guidance/ng168
与其他疾患进行鉴别,如急性冠脉综合征、急性心力衰竭和肺炎,以及 COVID-19 并发症。
对于 COPD 加重的管理,遵循既定指南,包括具备临床指征时,给予短期口服皮质类固醇。[859]Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. 2021 [internet publication] https://goldcopd.org/2021-gold-reports [861]Hasan SS, Capstick T, Zaidi STR, et al. Use of corticosteroids in asthma and COPD patients with or without COVID-19. Respir Med. 2020 Aug-Sep;170:106045 https://www.resmedjournal.com/article/S0954-6111(20)30185-2/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32843175?tool=bestpractice.com 请参阅 COPD 急性加重专题。
寻求上级医生或专科医生建议。
目前,对于使用雾化剂是否会产生气溶胶,以及是否因此需使用特定个人防护装备,不同国家组织之间存在不同看法。[859]Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. 2021 [internet publication] https://goldcopd.org/2021-gold-reports [863]National Institute for Health and Care Excellence. COVID-19 rapid guideline: severe asthma. 2020 [internet publication] https://www.nice.org.uk/guidance/ng166 对于未接受通气支持的非危重患者,考虑使用加压定量吸入器、干粉吸入器,或软雾吸入器进行药物输送。[859]Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease. 2021 [internet publication] https://goldcopd.org/2021-gold-reports 请遵循当地指南和常规。
如果使用雾化器,支气管舒张剂雾化吸入疗法应仅持续 24 至 48 小时,然后患者应换回他们常用的吸入器。
如果为患者开处雾化吸入短效毒蕈碱受体拮抗剂(例如异丙托铵),则应暂时停止患者可能正在使用的任何用于维持治疗的长效毒蕈碱受体拮抗剂(long-acting muscarinic receptor antagonist, LAMA,例如噻托溴铵、aclidinium、格隆溴铵、乌美溴铵)(基于专家意见)。这是因为担心可能会出现叠加性抗胆碱能不良反应。
一旦停止雾化剂治疗,请确保重新给予 LAMA。
针对特定患者群中所有患者的治疗建议
对于任何急症糖尿病患者,每天至少监测血糖水平四次(餐前以及睡前 [如果进食])。[911]American Diabetes Association. Diabetes care in the hospital: standards of medical care in diabetes - 2021. Diabetes Care. 2021 Jan;44(Suppl 1):S211-20 https://care.diabetesjournals.org/content/44/Supplement_1/S211.long http://www.ncbi.nlm.nih.gov/pubmed/33298426?tool=bestpractice.com
对于患有糖尿病的 COVID-19 住院患者,遵循当地血糖监测常规。
对于患急性疾病的糖尿病住院患者目标血糖水平,目前尚未达成共识。
英国糖尿病学会联合会住院患者诊疗小组(Joint British Diabetes Societies for Inpatient Care, JBDS-IP)建议内科住院患者理想范围为 6 至 10 mmol/L(108-180 mg/dL),可接受上限为 12 mmol/L(216 mg/dL)。[912]Joint British Diabetes Societies for inpatient care. The use of variable rate intravenous insulin infusion (VRIII) in medical inpatients. 2014 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/JBDS_Guidelines_Current/JBDS_09_IP_VRIII.pdf 如果患者具有较高的跌倒风险、机体衰弱或患有痴呆,则认为适宜采用更宽松的血糖目标。[912]Joint British Diabetes Societies for inpatient care. The use of variable rate intravenous insulin infusion (VRIII) in medical inpatients. 2014 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/JBDS_Guidelines_Current/JBDS_09_IP_VRIII.pdf [913]Joint British Diabetes Societies for inpatient care. Inpatient care of the frail older adult with diabetes. 2019 [internet publication] https://www.diabetes.org.uk/resources-s3/2019-10/frailty-jbds-ipfinal-28-10-19.pdf
英国国家糖尿病住院患者 COVID-19 应对小组(National Inpatient Diabetes COVID-19 Response Group)对 COVID-19 住院患者提出了相同的建议。[914]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): guidance for managing inpatient hyperglycaemia. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/resources/COvID_Hyper_v4.2.pdf
一个国际专家组的共识指南建议将 COVID-19 患者的目标水平设为 4-10 mmol/L(72-180 mg/dL),但将衰弱患者的目标水平下限调整为 5 mmol/L(90 mg/dL)。[889]Bornstein SR, Rubino F, Khunti K, et al. Practical recommendations for the management of diabetes in patients with COVID-19. Lancet Diabetes Endocrinol. 2020 Jun;8(6):546-50 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180013 http://www.ncbi.nlm.nih.gov/pubmed/32334646?tool=bestpractice.com
美国糖尿病学会建议,对于大多数危重患者和非危重患者,目标范围为 7.8 至 10 mmol/L(140-180 mg/dL)(一旦因持续性高血糖起始胰岛素治疗;并非特别针对 COVID-19)。[911]American Diabetes Association. Diabetes care in the hospital: standards of medical care in diabetes - 2021. Diabetes Care. 2021 Jan;44(Suppl 1):S211-20 https://care.diabetesjournals.org/content/44/Supplement_1/S211.long http://www.ncbi.nlm.nih.gov/pubmed/33298426?tool=bestpractice.com
对高血糖进行治疗,避免糖尿病酮症酸中毒(diabetic ketoacidosis, DKA)和高渗性高血糖状态(hyperosmolar hyperglycaemic state, HHS),两者均为内科急症。
若患者毛细血管血糖 ≥12 mmol/L(≥216 mg/dL),应遵循当地医院常规。
COVID-19 指南通常强调高血糖管理的重要性。[884]Hartmann-Boyce J, Morris E, Goyder C, et al. Diabetes and COVID-19: risks, management, and learnings from other national disasters. Diabetes Care. 2020 Aug;43(8):1695-703 https://care.diabetesjournals.org/content/43/8/1695 http://www.ncbi.nlm.nih.gov/pubmed/32546593?tool=bestpractice.com
排除 DKA 或 HHS, 两者均需给予特定紧急处理。
考虑高血糖相关性其他病症,例如脓毒症。[883]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19: front door guidance. 2020 [internet publication] https://abcd.care/resource/concise-advice-inpatient-diabetes-during-covid-19-front-door-guidance
需注意,以下药物可能与高血糖具有相关性,可能需要进行评估:[915]Rehman A, Setter SM, Vue MH. Drug-induced glucose alterations part 2: drug-induced hyperglycemia. Diabetes Spect. 2011 Nov;24(4):234-8 https://spectrum.diabetesjournals.org/content/24/4/234
皮质类固醇(例如地塞米松)
部分 β 受体阻滞剂(如普萘洛尔、阿替洛尔)
噻嗪类利尿剂(例如氢氯噻嗪)
部分第二代抗精神病药物(如奥氮平、氯氮平)
某些氟喹诺酮类抗生素(如环丙沙星)
钙调磷酸酶抑制剂(如环孢素、他克莫司)
蛋白酶抑制剂(例如,作为抗逆转录病毒治疗的一部分,洛匹那韦/利托那韦可用于治疗某些 COVID-19 患者)。
部分用于 COVID-19 的试验性药物可能与高血糖具有相关性或因果关系。为糖尿病患者开具此类治疗处方之前,查看当地药物处方集,以获取更多信息。
如果患者血糖持续升高,他们可能需给予胰岛素治疗(静脉或皮下给药常规)。对于 COVID-19 患者高血糖管理,遵循当地常规。
重症监护病房(intensive care unit, ICU)外可能不提供输液泵装置,具体取决于其他地方对这些设备的需求。在这种情况下,部分方案建议,对于高血糖和轻度 DKA 管理,可给予替代性皮下给药。[914]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): guidance for managing inpatient hyperglycaemia. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/resources/COvID_Hyper_v4.2.pdf [916]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): guideline for managing DKA using subcutaneous insulin. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/resources/COvID_DKA_SC_v3.3.pdf
请注意,ICU 内的 2 型糖尿病患者可能存在显著胰岛素抵抗。[914]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): guidance for managing inpatient hyperglycaemia. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/resources/COvID_Hyper_v4.2.pdf
向住院患者糖尿病团队询问专家意见。
监测血糖并根据病情和住院就餐时间 调整用药,从而降低低血糖发作风险。
大约 1/5 英格兰和威尔士糖尿病住院患者在住院期间发生过低血糖。[917]NHS Digital. National diabetes inpatient audit (NaDIA) - 2019. 2020 [internet publication] https://digital.nhs.uk/data-and-information/publications/statistical/national-diabetes-inpatient-audit/2019
低血糖原因包括:[918]Joint British Diabetes Societies for inpatient care. The hospital management of hypoglycaemia in adults with diabetes mellitus. 5th ed. 2021 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/JBDS_01_Hypo_Guideline_FINAL_23042021_0.pdf
在急症中恢复
COVID-19 恢复患者可能出现胰岛素需求快速改变,因此谨慎监测和调整胰岛素用药方案[914]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): guidance for managing inpatient hyperglycaemia. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/resources/COvID_Hyper_v4.2.pdf
患者进食意外中断,COVID-19 患者以俯卧位接受护理时尤易出现[914]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): guidance for managing inpatient hyperglycaemia. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/resources/COvID_Hyper_v4.2.pdf
COVID-19 患者减少皮质类固醇剂量(特别是地塞米松)[914]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19 (COVID:Diabetes): guidance for managing inpatient hyperglycaemia. 2020 [internet publication] https://abcd.care/sites/abcd.care/files/resources/COvID_Hyper_v4.2.pdf
胰岛素或口服降糖药用药错误
与进食有关的胰岛素给药时间错误
患者摄食较少,但却服用等量糖尿病药物
不享用睡前加餐
食欲减退或呕吐。
部分用于 COVID-19 的试验性药物可能与低血糖具有相关性(或具有因果关系)。为糖尿病患者开具此类治疗处方之前,查看当地药物处方集,以获取更多信息。
请注意,如果患者错过进餐或用药剂量过大,低血糖更易作为磺脲类药物不良反应出现(例如格列本脲、格列齐特、格列美脲、格列吡嗪)。
在急症医院环境中,餐时有可能被打乱,或无法每天同一时间进餐。
应在进食前或进食时给予磺脲类药物。查看当地药物处方集获取更为具体的指导信息,了解特定磺脲类药物给药时间与进食时间的关系。
切勿在睡前服用磺脲类药物,如果患者要在晚餐时服用一次,应考虑减少晚间剂量,以降低夜间低血糖发生风险(基于专家意见)。
睡前加餐可降低清晨低血糖风险。[917]NHS Digital. National diabetes inpatient audit (NaDIA) - 2019. 2020 [internet publication] https://digital.nhs.uk/data-and-information/publications/statistical/national-diabetes-inpatient-audit/2019
如果血糖低于 4 mmol/L(72 mg/dL),应积极治疗低血糖。 [918]Joint British Diabetes Societies for inpatient care. The hospital management of hypoglycaemia in adults with diabetes mellitus. 5th ed. 2021 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/JBDS_01_Hypo_Guideline_FINAL_23042021_0.pdf 请遵循医院方案。JBDS-IP 指南建议:[918]Joint British Diabetes Societies for inpatient care. The hospital management of hypoglycaemia in adults with diabetes mellitus. 5th ed. 2021 [internet publication] https://abcd.care/sites/abcd.care/files/site_uploads/JBDS_01_Hypo_Guideline_FINAL_23042021_0.pdf
10 至 15 分钟后重新检测血糖,确定治疗反应
如果低血糖已经纠正,切勿停止胰岛素的下一次给药计划。否则会导致 1 型糖尿病患者出现反弹性高血糖和 DKA。
住院患者应遵循当地常规和血糖自我监测指南。
相关内容可能已针对 COVID-19 患者进行了修改。例如,美国部分医院一直在使用“虚拟”模式,包括扩充自我管理方案,以减少对个人防护装备的需求(在安全的情况下)。[884]Hartmann-Boyce J, Morris E, Goyder C, et al. Diabetes and COVID-19: risks, management, and learnings from other national disasters. Diabetes Care. 2020 Aug;43(8):1695-703 https://care.diabetesjournals.org/content/43/8/1695 http://www.ncbi.nlm.nih.gov/pubmed/32546593?tool=bestpractice.com
针对特定患者群中所有患者的治疗建议
成人糖尿病患者在入院时,或似乎更加不适时,均应对其足部进行检查。[919]National Institute for Health and Care Excellence. Diabetic foot problems: prevention and management. 2019 [internet publication] https://www.nice.org.uk/guidance/ng19 这也是针对因 COVID-19 入院的糖尿病成人患者的建议。[883]National Inpatient Diabetes COVID-19 Response Group. Concise advice on inpatient diabetes during COVID-19: front door guidance. 2020 [internet publication] https://abcd.care/resource/concise-advice-inpatient-diabetes-during-covid-19-front-door-guidance
需行足部检查,发现新发溃疡或感染,其可能被患者忽视。
检查足部病损,并检查保护性感觉是否丧失。
遵循当地指南,但有一个快速简单的试验:Ipswich Touch Test©️(伊普斯威奇触摸试验),即用食指指尖轻轻触摸/将其放置在第一、第三和第五趾趾尖上 1 到 2 秒。[920]Rayman G, Vas PR, Baker N, et al. The Ipswich Touch Test: a simple and novel method to identify inpatients with diabetes at risk of foot ulceration. Diabetes Care. 2011 Jul;34(7):1517-8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3120164 http://www.ncbi.nlm.nih.gov/pubmed/21593300?tool=bestpractice.com
如果患者在这六个部位中的两个或以上没有感觉,则代表其保护性感觉减退。
如果患者感觉减退,则具有压疮高风险。告知护理人员,并提供减压装置。
护理人员或医疗人员应每日进行踝部检查,注意压力性创伤征象。
对于糖尿病患者是否应该使用弹力袜存在争议 – 如有血管疾病,勿予以使用。
针对特定患者群中所有患者的治疗建议
在临床情况允许以及患者有反应的情况下进行精神状态检查 (基于专家意见)。
精神状态检查是精神病学临床实践中常规使用的主要临床工具之一,有助于诊断和指导进一步的管理。情绪是其中一项评估内容。
考虑使用 PHQ-9 问卷,进行抑郁评估。[921]Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001 Sep;16(9):606-13 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1495268 http://www.ncbi.nlm.nih.gov/pubmed/11556941?tool=bestpractice.com
这是一份自填式问卷,只需不到 3 分钟即可完成。
结果可提示抑郁症状的严重程度。
评分 5 分或以上应启动转诊,转至联络精神病学服务机构 (基于专家意见)。
抑郁据报道为 COVID-19 住院患者常见发现。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
考虑可能影响患者精神状态的其他因素(例如违禁药物使用或饮酒的影响)。[922]Boden JM, Fergusson DM. Alcohol and depression. Addiction. 2011 May;106(5):906-14 http://www.ncbi.nlm.nih.gov/pubmed/21382111?tool=bestpractice.com
针对特定患者群中所有患者的治疗建议
考虑将所有因急症 收住入院,且确诊或疑似抑郁的患者转诊至联络精神病学团队/服务机构。[932]National Institute for Health and Care Excellence. Liaison psychiatry. In: Emergency acute medical care in over 16s: service delivery and organisation. 2018 [internet publication] https://www.nice.org.uk/guidance/ng94/evidence/23.liaison-psychiatry-pdf-172397464636 [933]National Confidential Enquiry into Patient Outcome and Death. Treat as one: bridging the gap between mental and physical healthcare in general hospitals. 2017 [internet publication] https://www.ncepod.org.uk/2017report1/downloads/TreatAsOne_Summary.pdf
COVID-19 大流行期间遵循医院的当地常规/转诊路径。
COVID-19 与精神和神经系统表现(包括抑郁)相关。[834]World Health Organization. COVID-19 clinical management: living guidance. 2021 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1
合并抑郁症与对推荐的躯体健康治疗(从药物治疗到康复治疗)的依从性差有关。[934]DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med. 2000 Jul 24;160(14):2101-7 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/485411 http://www.ncbi.nlm.nih.gov/pubmed/10904452?tool=bestpractice.com
这可能会导致临床结局恶化,包括住院时间延长。[924]National Institute for Health and Care Excellence. Depression in adults with a chronic physical health problem: recognition and management. 2009 [internet publication] https://www.nice.org.uk/guidance/cg91 [935]Prina AM, Cosco TD, Dening T, et al. The association between depressive symptoms in the community, non-psychiatric hospital admission and hospital outcomes: a systematic review. J Psychosom Res. 2015 Jan;78(1):25-33 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4292984 http://www.ncbi.nlm.nih.gov/pubmed/25466985?tool=bestpractice.com [936]Clarke DM, Currie KC. Depression, anxiety and their relationship with chronic diseases: a review of the epidemiology, risk and treatment evidence. Med J Aust. 2009 Apr 6;190(s7):S54-60 http://www.ncbi.nlm.nih.gov/pubmed/19351294?tool=bestpractice.com
最重要的是,抑郁与死亡率升高有关。[937]World Health Organization. Excess mortality in persons with severe mental disorders. 2016 [internet publication] https://www.who.int/mental_health/evidence/excess_mortality_report/en
针对特定患者群中所有患者的治疗建议
考虑对因急性疾病入院的当前吸烟者给予尼古丁替代治疗。无论他们是否打算戒烟,均需纳入考虑范围。[938]National Institute for Health and Care Excellence. Tobacco: preventing uptake, promoting quitting and treating dependence. August 2022 [internet publication] https://www.nice.org.uk/guidance/ng209
尼古丁替代治疗可防止入院期间快速戒断,快速戒断可能会导致痛苦和不安。
对于因急性卒中、心肌梗死和/或未控制高血压入院的血流动力学不稳定患者,以及患有严重肾脏损伤的患者,应谨慎使用此疗法。
在开始对糖尿病患者使用尼古丁替代治疗后,密切监测血糖。
药品制剂包括皮肤贴剂以及针对皮肤过敏患者的吸入剂、含片、咀嚼胶或喷雾剂。剂量取决于每日吸烟量和所选择的制剂。
有关更全面的详细信息,参考当地药物处方集和医院指南。
请注意,从吸烟转为任何其他替代方案(包括尼古丁替代疗法)可能导致患者服用的任何精神类药物(例如用于治疗抑郁的药物)血药浓度发生变化。这是因为尼古丁替代治疗不会像吸烟那样影响肝酶活性。[926]Flowers L. Nicotine replacement therapy. Am J Psychiatry Resid J. 2016 Jun;11(6):4-7 https://psychiatryonline.org/doi/10.1176/appi.ajp-rj.2016.110602 寻求相关建议,确认精神类药物剂量调整是否适当。
有证据提示,吸烟与重症 COVID-19 风险升高具有相关性。
有鉴于此,由于存在公认的危害,因此世界卫生组织建议使用循证方法进行戒烟。[939]World Health Organization. Smoking and COVID-19: scientific brief. 2020 [internet publication] https://www.who.int/publications/i/item/WHO-2019-nCoV-Sci_Brief-Smoking-2020.2
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请注意药品名称和品牌、药物处方集或地区之间的配方/用药途径和剂量可能有所不同。治疗建议针对患者群体提出。查看免责声明
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