治疗流程
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
轻度 COVID-19
考虑采取家庭隔离
疑似或确诊为轻症患者(即符合 COVID-19 病例定义,但无缺氧或肺炎证据的有症状患者)和无症状患者应进行隔离,以阻断病毒传播。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19
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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 [3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [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。[531]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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19
建议患者及其家庭成员采取适当的感染防控措施:
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:检测呈阳性后 10 天(无症状患者);症状发作后 10 天以及至少 3 天无发热和呼吸道症状(有症状患者)。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 美国疾病预防控制中心(Centers for Disease Control and Prevention, CDC)建议,如果采用基于症状的策略,自症状首次出现以来至少经过 10 天,且自上次发热以来至少 24 小时未使用解热药物,同时若症状有所改善,则可停止居家隔离。对于无症状者,CDC 建议,自检测呈阳性之日起至少经过 10 天,就可停止居家隔离。另外,其建议如果采用基于检测的策略,则在隔离结束之前,应至少获得两次间隔 24 小时呼吸道样本的逆转录聚合酶链反应(reverse-transcription polymerase chain reaction, RT-PCR)阴性结果。[551]Centers for Disease Control and Prevention. Discontinuation of isolation for persons with COVID-19 not in healthcare settings. 2020 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/disposition-in-home-patients.html 如果患者收住入院,CDC 停止隔离的指导与中度疾病的指导相同(见下文)。关于何时停止隔离的建议,取决于当地情况,各国之间可能有所不同。例如,在英国,进行社区管理的轻症病例隔离时间为 10 天。[552]Public Health England. Guidance for stepdown of infection control precautions and discharging COVID-19 patients. 2020 [internet publication]. https://www.gov.uk/government/publications/covid-19-guidance-for-stepdown-of-infection-control-precautions-within-hospitals-and-discharging-covid-19-patients-from-hospital-to-home-settings/guidance-for-stepdown-of-infection-control-precautions-and-discharging-covid-19-patients
监测
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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 [3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/
症状管理和支持性治疗
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。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。[540]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing symptoms (including at the end of life) in the community. 2020 [internet publication]. https://www.nice.org.uk/guidance/ng163 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)。[559]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. 2020 Aug 18 [Epub ahead of print]. https://ebm.bmj.com/content/early/2020/07/28/bmjebm-2020-111336 http://www.ncbi.nlm.nih.gov/pubmed/32817011?tool=bestpractice.com
嘱患者补充足够的营养和进行适当的补液。过多液体将使氧合恶化。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19
建议患者通过开窗或开门改善空气流通(风扇可使感染传播,不应使用)。[540]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing symptoms (including at the end of life) in the community. 2020 [internet publication]. https://www.nice.org.uk/guidance/ng163
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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19
如果嗅觉功能障碍持续超过 2 周,需考虑给予治疗(例如进行嗅觉训练)。暂无证据对 COVID-19 患者给予此类治疗提供支持。[560]Whitcroft KL, Hummel T. Olfactory dysfunction in COVID-19: diagnosis and management. JAMA. 2020 May 20 [Epub ahead of print]. https://jamanetwork.com/journals/jama/fullarticle/2766523 http://www.ncbi.nlm.nih.gov/pubmed/32432682?tool=bestpractice.com
解热/镇痛药物
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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 [540]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing symptoms (including at the end of life) in the community. 2020 [internet publication]. https://www.nice.org.uk/guidance/ng163 目前尚无证据表明 COVID-19 患者服用非甾体抗炎药(non-steroidal anti-inflammatory drug, NSAID)(例如布洛芬)将产生严重不良事件,或 NSAID 紧急用药将对 COVID-19 患者长期生存或生活质量产生不良影响。[553]European Medicines Agency. EMA gives advice on the use of non-steroidal anti-inflammatories for COVID-19. 2020 [internet publication]. https://www.ema.europa.eu/en/news/ema-gives-advice-use-non-steroidal-anti-inflammatories-covid-19 [554]US Food and Drug Administration. FDA advises patients on use of non-steroidal anti-inflammatory drugs (NSAIDs) for COVID-19. 2020 [internet publication]. https://www.fda.gov/drugs/drug-safety-and-availability/fda-advises-patients-use-non-steroidal-anti-inflammatory-drugs-nsaids-covid-19 [555]Little P. Non-steroidal anti-inflammatory drugs and covid-19. BMJ. 2020 Mar 27;368:m1185. https://www.bmj.com/content/368/bmj.m1185 http://www.ncbi.nlm.nih.gov/pubmed/32220865?tool=bestpractice.com [556]Medicines and Healthcare products Regulatory Agency; Commission on Human Medicines. Commission on Human Medicines advice on ibuprofen and coronavirus (COVID-19). 2020 [internet publication]. https://www.gov.uk/government/news/commission-on-human-medicines-advice-on-ibuprofen-and-coronavirus-covid-19 [557]World Health Organization. The use of non-steroidal anti-inflammatory drugs (NSAIDs) in patients with COVID-19: scientific brief. 2020 [internet publication]. https://www.who.int/news-room/commentaries/detail/the-use-of-non-steroidal-anti-inflammatory-drugs-(nsaids)-in-patients-with-covid-19 [558]National Institute for Health and Care Excellence. COVID-19 rapid evidence summary: acute use of non-steroidal anti-inflammatory drugs (NSAIDs) for people with or at risk of COVID-19. 2020 [internet publication]. https://www.nice.org.uk/advice/es23/chapter/Key-messages
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。
第一选择
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
布洛芬: 儿童:查询当地药物处方集,以获取剂量指导;成人:必要时,每 6-8 小时口服 300-600 mg,每日最多 2400 mg
中度 COVID-19
考虑居家隔离或收入院
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)患者应进行隔离,阻断病毒传播。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19
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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 [3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/
管理 COVID-19 患者时,应实施当地感染防控规程。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:
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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 [561]Centers for Disease Control and Prevention. Discontinuation of transmission-based precautions and disposition of patients with COVID-19 in healthcare settings (interim guidance). 2020 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/disposition-hospitalized-patients.html 美国疾病预防控制中心(Centers for Disease Control and Prevention, CDC)建议,如果采用基于症状的策略,自症状首次出现以来至少经过 10 天(不伴重度免疫功能低下)或 20 天(伴重度免疫功能低下),且自上次发热以来至少 24 小时未使用解热药物,同时若症状有所改善,则可停止隔离。对于无症状者,CDC 建议,自检测呈阳性之日起至少经过 10 天(不伴重度免疫功能低下)或 20 天(伴重度免疫功能低下),就可停止隔离。另外,其建议如果采用基于检测的策略,则在隔离结束之前,应至少获得两次间隔 24 小时呼吸道样本的逆转录聚合酶链反应(reverse-transcription polymerase chain reaction, RT-PCR)阴性结果。此类患者首选基于症状的策略。[561]Centers for Disease Control and Prevention. Discontinuation of transmission-based precautions and disposition of patients with COVID-19 in healthcare settings (interim guidance). 2020 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/disposition-hospitalized-patients.html 如果患者居家隔离,CDC 停止隔离的指导与轻度疾病的指导相同(见下文)。关于何时停止隔离的建议,取决于当地情况,各国之间可能有所不同。例如,在英国,从住院患者检测阳性起计,隔离时间为 14 天,进行社区管理的轻症病例则为 10 天。[552]Public Health England. Guidance for stepdown of infection control precautions and discharging COVID-19 patients. 2020 [internet publication]. https://www.gov.uk/government/publications/covid-19-guidance-for-stepdown-of-infection-control-precautions-within-hospitals-and-discharging-covid-19-patients-from-hospital-to-home-settings/guidance-for-stepdown-of-infection-control-precautions-and-discharging-covid-19-patients
监测
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。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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19
症状管理和支持性治疗
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。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。[540]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing symptoms (including at the end of life) in the community. 2020 [internet publication]. https://www.nice.org.uk/guidance/ng163 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)。[559]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. 2020 Aug 18 [Epub ahead of print]. https://ebm.bmj.com/content/early/2020/07/28/bmjebm-2020-111336 http://www.ncbi.nlm.nih.gov/pubmed/32817011?tool=bestpractice.com
嘱患者补充足够的营养和进行适当的补液。过多液体将使氧合恶化。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19
建议患者通过开窗或开门改善空气流通(风扇可使感染传播,不应使用)。[540]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing symptoms (including at the end of life) in the community. 2020 [internet publication]. https://www.nice.org.uk/guidance/ng163
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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19
如果嗅觉功能障碍持续超过 2 周,需考虑给予治疗(例如进行嗅觉训练)。暂无证据对 COVID-19 患者给予此类治疗提供支持。[560]Whitcroft KL, Hummel T. Olfactory dysfunction in COVID-19: diagnosis and management. JAMA. 2020 May 20 [Epub ahead of print]. https://jamanetwork.com/journals/jama/fullarticle/2766523 http://www.ncbi.nlm.nih.gov/pubmed/32432682?tool=bestpractice.com
抗生素
针对特定患者群中部分患者治疗的附加建议
如果临床怀疑细菌感染,可考虑使用经验性抗生素。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 [3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/ 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。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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19
解热/镇痛药物
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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 [540]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing symptoms (including at the end of life) in the community. 2020 [internet publication]. https://www.nice.org.uk/guidance/ng163 目前尚无证据表明 COVID-19 患者服用非甾体抗炎药(non-steroidal anti-inflammatory drug, NSAID)(例如布洛芬)将产生严重不良事件,或 NSAID 紧急用药将对 COVID-19 患者长期生存或生活质量产生不良影响。[553]European Medicines Agency. EMA gives advice on the use of non-steroidal anti-inflammatories for COVID-19. 2020 [internet publication]. https://www.ema.europa.eu/en/news/ema-gives-advice-use-non-steroidal-anti-inflammatories-covid-19 [554]US Food and Drug Administration. FDA advises patients on use of non-steroidal anti-inflammatory drugs (NSAIDs) for COVID-19. 2020 [internet publication]. https://www.fda.gov/drugs/drug-safety-and-availability/fda-advises-patients-use-non-steroidal-anti-inflammatory-drugs-nsaids-covid-19 [555]Little P. Non-steroidal anti-inflammatory drugs and covid-19. BMJ. 2020 Mar 27;368:m1185. https://www.bmj.com/content/368/bmj.m1185 http://www.ncbi.nlm.nih.gov/pubmed/32220865?tool=bestpractice.com [556]Medicines and Healthcare products Regulatory Agency; Commission on Human Medicines. Commission on Human Medicines advice on ibuprofen and coronavirus (COVID-19). 2020 [internet publication]. https://www.gov.uk/government/news/commission-on-human-medicines-advice-on-ibuprofen-and-coronavirus-covid-19 [557]World Health Organization. The use of non-steroidal anti-inflammatory drugs (NSAIDs) in patients with COVID-19: scientific brief. 2020 [internet publication]. https://www.who.int/news-room/commentaries/detail/the-use-of-non-steroidal-anti-inflammatory-drugs-(nsaids)-in-patients-with-covid-19 [558]National Institute for Health and Care Excellence. COVID-19 rapid evidence summary: acute use of non-steroidal anti-inflammatory drugs (NSAIDs) for people with or at risk of COVID-19. 2020 [internet publication]. https://www.nice.org.uk/advice/es23/chapter/Key-messages
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。
第一选择
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
布洛芬: 儿童:查询当地药物处方集,以获取剂量指导;成人:必要时,每 6-8 小时口服 300-600 mg,每日最多 2400 mg
法匹拉韦
针对特定患者群中部分患者治疗的附加建议
考虑将 remdesivir(一种广谱试验性抗病毒药物)用于中度疾病的住院患者。[544]Qaseem A, Yost J, Etxeandia-Ikobaltzeta I, et al. Should remdesivir be used for the treatment of patients with COVID-19? Rapid, living practice points from the American College of Physicians (version 1). Ann Intern Med. 2020 Oct 5 [Epub ahead of print]. https://www.acpjournals.org/doi/10.7326/M20-5831 http://www.ncbi.nlm.nih.gov/pubmed/33017175?tool=bestpractice.com 美国内科医师学会的这项建议基于低确定性证据,该证据表明与标准治疗相比,remdesivir 可略微降低死亡率和减少严重不良事件,缩短临床改善和恢复所需的时间,并减少中度疾病住院患者对有创机械通气或体外膜肺氧合的需要。[562]Wilt TJ, Kaka AS, MacDonald R, et al. Remdesivir for adults with COVID-19: a living systematic review for an American College of Physicians practice points. Ann Intern Med. 2020 Oct 5 [Epub ahead of print]. https://www.acpjournals.org/doi/10.7326/M20-5752 http://www.ncbi.nlm.nih.gov/pubmed/33017170?tool=bestpractice.com
在美国,由于数据不足,美国国立卫生研究院指南专家组既不建议亦不反对使用 remdesivir 治疗轻中度疾病。但是,专家组认识到,在某些情况下,临床医生会认为 remdesivir 是适合中度疾病住院患者(例如临床恶化风险极高患者)的适当治疗方法。[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/ 由于缺乏证据,美国传染病学会通常不建议对中度疾病患者使用 remdesivir。[543]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. 2020 [internet publication]. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/
美国食品药品监督管理局已批准 remdesivir 用于住院儿童(≥12 岁且 ≥40 kg)和成人患者 COVID-19 治疗。该项批准并未把先前在原始紧急用途授权下已授权的全部人群包括在内。目前对紧急使用授权进行了修订,授权对于体重在 3.5 kg 至 40 kg 之间的住院儿童和体重 3.5 kg 以下的 <12 岁儿童使用 remdesivir。[563]US Food and Drug Administration. FDA approves first treatment for COVID-19. 2020 [internet publication]. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-covid-19 在英国和欧洲,仅对于满足 ≥ 12岁青少年和需给予辅助供养的肺炎成人(通常被归类为重症)等条件,方批准使用 remdesivir。[564]European Medicines Agency. First COVID-19 treatment recommended for EU authorisation. 2020 [internet publication]. https://www.ema.europa.eu/en/news/first-covid-19-treatment-recommended-eu-authorisation
与标准治疗或安慰剂相比,remdesivir 对于住院患者可以降低死亡率和缩短症状消退所需时间;但无令人信服的证据表明 remdesivir 减少了对机械通气的需求。疾病早期给予 remdesivir 获益则更为显著。[542]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 [565]Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of Covid-19: final report. N Engl J Med. 2020 Nov 5 [Epub ahead of print]. https://www.nejm.org/doi/full/10.1056/NEJMoa2007764 http://www.ncbi.nlm.nih.gov/pubmed/32445440?tool=bestpractice.com 但是,WHO 团结试验中期结果发现,remdesivir 似乎对住院患者 28 天死亡率或住院疗程几乎不具影响。[566]Pan H, Peto R, Karim QA, et al; medRxiv. Repurposed antiviral drugs for COVID-19 – interim WHO SOLIDARITY trial results. 2020 [internet publication]. https://www.medrxiv.org/content/10.1101/2020.10.15.20209817v1
remdesivir 可能引起胃肠症状,转氨酶水平升高和凝血酶原时间延长。也有报道称给药过程中和给药后出现了超敏反应。对估算的肾小球滤过率 <30 mL/min 的患者不应使用 remdesivir,肝脏损伤患者应谨慎使用。尚未针对孕妇、母乳喂养的女性或儿童评价安全性和有效性。除非有其他适应证,否则不应将 remdesivir 用于孕妇。remdesivir 可能与羟氯喹/氯喹产发生相互作用,但通常认为其可安全的与皮质类固醇一起使用。[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/
欧洲药品管理局已经开始对一项安全性讯息进行审查,以评估某些患者发生急性肾损伤的报道。在此阶段,尚不确定 remdesivir 与急性肾损伤之间是否存在因果关系。[567]European Medicines Agency. Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 28 September - 1 October 2020. 2020 [internet publication]. https://www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-risk-assessment-committee-prac-28-september-1-october-2020
第一选择
法匹拉韦: 儿童:咨询专科医师以获取剂量指导;成人:第 1 天 200 mg,静脉使用,之后 100 mg,每天一次,持续 4-9 天
更多 法匹拉韦一些指南建议对 5 天后仍未显示出临床改善的患者进行疗程 10 天的治疗。[544]Qaseem A, Yost J, Etxeandia-Ikobaltzeta I, et al. Should remdesivir be used for the treatment of patients with COVID-19? Rapid, living practice points from the American College of Physicians (version 1). Ann Intern Med. 2020 Oct 5 [Epub ahead of print]. https://www.acpjournals.org/doi/10.7326/M20-5831 http://www.ncbi.nlm.nih.gov/pubmed/33017175?tool=bestpractice.com
重症 COVID-19
住院
疑似或确诊为重症的患者有快速临床恶化风险,应在专科团队指导下收入适当的医疗机构。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)。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19
抛开年龄和 COVID-19 状况,使用临床衰弱量表(Clinical Frailty Scale, CFS)对所有成人入院时机体衰弱程度进行评估。 Clinical frailty scale Opens in new window 危重症诊疗团队参与危重症诊疗施行方案讨论。[539]National Institute for Health and Care Excellence. COVID-19 rapid guideline: critical care in adults. 2020 [internet publication]. https://www.nice.org.uk/guidance/ng159 一项大型观察性研究发现,与年龄或合并症相比,体质虚弱可以更好的预测疾病结局。体弱(CFS 评分 5-8 分)与死亡更早和住院时间更长相关,并且通过对年龄和合并症进行调整后发现,体质越弱,则结局越发恶劣。[568]Hewitt J, Carter B, Vilches-Moraga A, et al. The effect of frailty on survival in patients with COVID-19 (COPE): a multicentre, European, observational cohort study. Lancet Public Health. 2020 Jun 30 [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326416/ http://www.ncbi.nlm.nih.gov/pubmed/32619408?tool=bestpractice.com
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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 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。[626]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
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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 美国疾病预防控制中心(Centers for Disease Control and Prevention, CDC)建议,如果采用基于症状的策略,自症状首次出现以来至少经过 20 天,且自上次发热以来至少 24 小时未使用解热药物,同时若症状有所改善,则可停止隔离。对于无症状者,CDC 建议,自检测呈阳性之日起至少经过 20 天,就可停止隔离。另外,其建议如果采用基于检测的策略,则在隔离结束之前,应至少获得两次间隔 24 小时呼吸道样本的逆转录聚合酶链反应(reverse-transcription polymerase chain reaction, RT-PCR)阴性结果。此类患者首选基于症状的策略。[561]Centers for Disease Control and Prevention. Discontinuation of transmission-based precautions and disposition of patients with COVID-19 in healthcare settings (interim guidance). 2020 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/disposition-hospitalized-patients.html 关于何时停止隔离的建议,取决于当地情况,各国之间可能有所不同。例如,在英国,从住院患者检测阳性起计,隔离时间为 14 天。[552]Public Health England. Guidance for stepdown of infection control precautions and discharging COVID-19 patients. 2020 [internet publication]. https://www.gov.uk/government/publications/covid-19-guidance-for-stepdown-of-infection-control-precautions-within-hospitals-and-discharging-covid-19-patients-from-hospital-to-home-settings/guidance-for-stepdown-of-infection-control-precautions-and-discharging-covid-19-patients
考虑给予氧疗
针对特定患者群中所有患者的治疗建议
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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 [3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 部分指南建议 SpO₂ 应维持于不超过 96%。[570]Alhazzani W, Møller MH, Arabi YM, et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Intensive Care Med. 2020 May;46(5):854-87. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101866/ http://www.ncbi.nlm.nih.gov/pubmed/32222812?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。举例而言,英格兰 NHS 建议将目标设定为 92% 至 95%(若临床适宜,则为 90% 至 94%)。[571]NHS England. Clinical guide for the optimal use of oxygen therapy during the coronavirus pandemic. 2020 [internet publication]. https://www.england.nhs.uk/coronavirus/wp-content/uploads/sites/52/2020/04/C0256-specialty-guide-oxygen-therapy-and-coronavirus-9-april-2020.pdf
考虑使用体位技术(例如高支撑坐姿、俯卧位),以及气道清除管理,协助成人分泌物清除。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 氧供可通过使用非再呼吸型面罩和采取俯卧位予以增加。[572]Dondorp AM, Hayat M, Aryal D, et al. Respiratory support in novel coronavirus disease (COVID-19) patients, with a focus on resource-limited settings. Am J Trop Med Hyg. 2020 Apr 21 [Epub ahead of print]. http://www.ajtmh.org/content/journals/10.4269/ajtmh.20-0283 http://www.ncbi.nlm.nih.gov/pubmed/32319424?tool=bestpractice.com 考虑进行清醒俯卧位试验,以对无气管插管指征,虽提升辅助供氧需求,仍呈持续性低氧血症患者的氧合进行改善,[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/ 早期自行俯卧的未插管清醒患者呈现出血氧饱和度改善,并可延迟或减少危重症诊疗需求。[573]Caputo ND, Strayer RJ, Levitan R. Early self-proning in awake, non-intubated patients in the emergency department: a single ED's experience during the COVID-19 pandemic. Acad Emerg Med. 2020 May;27(5):375-8. https://onlinelibrary.wiley.com/doi/abs/10.1111/acem.13994 http://www.ncbi.nlm.nih.gov/pubmed/32320506?tool=bestpractice.com [574]Ng Z, Tay WC, Ho CHB. Awake prone positioning for non-intubated oxygen dependent COVID-19 pneumonia patients. Eur Respir J. 2020 May 26 [Epub ahead of print]. https://erj.ersjournals.com/content/early/2020/05/22/13993003.01198-2020 http://www.ncbi.nlm.nih.gov/pubmed/32457195?tool=bestpractice.com [575]Golestani-Eraghi M, Mahmoodpoor A. Early application of prone position for management of Covid-19 patients. J Clin Anesth. 2020 May 26;66:109917. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247987/ http://www.ncbi.nlm.nih.gov/pubmed/32473503?tool=bestpractice.com [576]Thompson AE, Ranard BL, Wei Y, et al. Prone positioning in awake, nonintubated patients with COVID-19 hypoxemic respiratory failure. JAMA Intern Med. 2020 Jun 17 [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301298/ http://www.ncbi.nlm.nih.gov/pubmed/32584946?tool=bestpractice.com [577]Coppo A, Bellani G, Winterton D, et al. Feasibility and physiological effects of prone positioning in non-intubated patients with acute respiratory failure due to COVID-19 (PRON-COVID): a prospective cohort study. Lancet Respir Med. 2020 Jun 19 [Epub ahead of print]. https://www.thelancet.com/pdfs/journals/lanres/PIIS2213-2600(20)30268-X.pdf http://www.ncbi.nlm.nih.gov/pubmed/32569585?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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 [3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/
症状管理和支持性治疗
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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 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。[578]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
咳嗽:建议患者避免仰卧,因为这会使排痰不力。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。若无禁忌症,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)。[540]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing symptoms (including at the end of life) in the community. 2020 [internet publication]. https://www.nice.org.uk/guidance/ng163 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)。[559]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. 2020 Aug 18 [Epub ahead of print]. https://ebm.bmj.com/content/early/2020/07/28/bmjebm-2020-111336 http://www.ncbi.nlm.nih.gov/pubmed/32817011?tool=bestpractice.com
呼吸困难: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)。如有条件,可考虑试行给氧。对于中重度呼吸困难或感到严重焦虑的患者,可考虑给予阿片类药物和苯二氮卓类药物联合应用。[540]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing symptoms (including at the end of life) in the community. 2020 [internet publication]. https://www.nice.org.uk/guidance/ng163
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)。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 [540]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing symptoms (including at the end of life) in the community. 2020 [internet publication]. https://www.nice.org.uk/guidance/ng163 考虑给予苯二氮卓类药物治疗对其他措施无反应的焦虑或躁动。考虑给予氟哌啶醇或吩噻嗪治疗谵妄。[540]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing symptoms (including at the end of life) in the community. 2020 [internet publication]. https://www.nice.org.uk/guidance/ng163 低剂量氟哌啶醇(或另一种合适的抗精神病药物)也可以考虑用于躁动的治疗。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 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。[579]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/
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,以及正在接受疗后护理或临终护理的患者,口腔护理是患者整体护理重要组成部分。[580]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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19
静脉血栓栓塞预防
针对特定患者群中所有患者的治疗建议
若无禁忌,则按照其他无 COVID-19 住院患者标准治疗,为 COVID-19 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。COVID-19 诊断不应影响儿科医生关于住院儿童 VTE 预防的建议。孕妇应由专科医生管理。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 [3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/ [581]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 May 21 [Epub ahead of print]. https://link.springer.com/article/10.1007/s11239-020-02138-z http://www.ncbi.nlm.nih.gov/pubmed/32440883?tool=bestpractice.com [582]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 Jun 2 [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265858/ http://www.ncbi.nlm.nih.gov/pubmed/32502594?tool=bestpractice.com
为减少患者接触,低分子肝素或磺达肝癸钠优于普通肝素。普通肝素禁忌用于重度血小板减少症患者。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。不建议给予直接口服抗凝剂。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)。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 [582]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 Jun 2 [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265858/ http://www.ncbi.nlm.nih.gov/pubmed/32502594?tool=bestpractice.com [583]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
最佳剂量尚未明晰。标准预防剂量比中剂量或全剂量给药方案更受推荐。[582]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 Jun 2 [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265858/ http://www.ncbi.nlm.nih.gov/pubmed/32502594?tool=bestpractice.com 部分临床医生因为担心无法发现的栓子,而使用中治疗剂量或全治疗剂量方案,而非预防剂量;然而,这可能会导致严重出血事件。[584]Bikdeli B, Madhavan MV, Jimenez D, et al. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up. J Am Coll Cardiol. 2020 Apr 15 [Epub ahead of print]. https://www.sciencedirect.com/science/article/pii/S0735109720350087?via%3Dihub http://www.ncbi.nlm.nih.gov/pubmed/32311448?tool=bestpractice.com 无足够数据建议临床试验之外增加抗凝药物剂量以预防 COVID-19 患者 VTE。[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/ 然而,部分指南推荐,对危重症患者可考虑加大剂量。[581]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 May 21 [Epub ahead of print]. https://link.springer.com/article/10.1007/s11239-020-02138-z http://www.ncbi.nlm.nih.gov/pubmed/32440883?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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19
除某些高危患者外,一般不建议给予常规出院后 VTE 预防。[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/ [581]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 May 21 [Epub ahead of print]. https://link.springer.com/article/10.1007/s11239-020-02138-z http://www.ncbi.nlm.nih.gov/pubmed/32440883?tool=bestpractice.com [582]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 Jun 2 [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265858/ http://www.ncbi.nlm.nih.gov/pubmed/32502594?tool=bestpractice.com
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。[585]Flumignan RLG, de Sá Tinôco JD, Pascoal PIF, et al. Prophylactic anticoagulants for people hospitalised with COVID‐19. Cochrane Database Syst Rev. 2020 Oct 2:CD013739. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013739/full 对超过 4000 名患者进行的回顾性分析发现,抗凝治疗与 COVID-19 住院患者死亡率降低和气管插管减少具有相关性。与预防性抗凝相比,治疗性抗凝与死亡率降低呈现相关性,但差异无统计学意义。[586]Nadkarni GN, Lala A, Bagiella E, et al. Anticoagulation, mortality, bleeding and pathology among patients hospitalized with COVID-19: a single health system study. J Am Coll Cardiol. 2020 Aug 24 [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449655/ http://www.ncbi.nlm.nih.gov/pubmed/32860872?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。[581]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 May 21 [Epub ahead of print]. https://link.springer.com/article/10.1007/s11239-020-02138-z http://www.ncbi.nlm.nih.gov/pubmed/32440883?tool=bestpractice.com
第一选择
依诺肝素: 请向专科医生咨询使用剂量
或
达肝素: 请向专科医生咨询使用剂量
或
磺达肝癸钠: 请向专科医生咨询使用剂量
第二选择
肝素: 请向专科医生咨询使用剂量
监测
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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19
抗生素
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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 [3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/ [511]National Institute for Health and Care Excellence. COVID-19 rapid guideline: antibiotics for pneumonia in adults in hospital. 2020 [internet publication]. https://www.nice.org.uk/guidance/ng173
部分指南建议对于未确诊 COVID-19 的所有社区获得性肺炎患者,对细菌性病原体使用经验性抗生素。COVID-19 合并肺炎患者的细菌性病原体似乎与既往社区获得性肺炎相同,因此经验性抗生素用药推荐亦应相同。[512]Metlay JP, Waterer GW. Treatment of community-acquired pneumonia during the coronavirus disease 2019 (COVID-19) pandemic. Ann Intern Med. 2020 May 7 [Epub ahead of print]. https://www.acpjournals.org/doi/10.7326/M20-2189 http://www.ncbi.nlm.nih.gov/pubmed/32379883?tool=bestpractice.com 但是,英国国家卫生与临床优化研究所建议,如果确信符合典型 COVID-19,则不起始经验性抗菌药物治疗被认为合理。[511]National Institute for Health and Care Excellence. COVID-19 rapid guideline: antibiotics for pneumonia in adults in hospital. 2020 [internet publication]. https://www.nice.org.uk/guidance/ng173 在没有其他适应证的情况下,当前尚无足够证据推荐经验性使用广谱抗菌药物。[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/
根据临床情况(例如不论严重急性呼吸综合征冠状病毒 2 [severe acute respiratory syndrome coronavirus 2, SARS-CoV-2] 检测结果如何呈现,或 SARS-CoV-2 检测结果阳性但 COVID-19 临床特征不典型,存在细菌感染临床或微生物学检测证据),一旦 COVID-19 得到确认,部分患者即可能需给予持续性抗生素治疗。这些情况中,应根据微生物学检测结果考虑抗生素选择,并在适当时改用窄谱抗生素,在 48 小时内考虑静脉使用抗生素,并考虑改用口服治疗,除非有继续使用的明确适应症,否则共用药 5 天。[511]National Institute for Health and Care Excellence. COVID-19 rapid guideline: antibiotics for pneumonia in adults in hospital. 2020 [internet publication]. https://www.nice.org.uk/guidance/ng173
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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19
皮质类固醇
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(World Health Organization, WHO)强烈建议对于伴严重或危重疾病的成年人,给予全身皮质类固醇治疗(低剂量静脉用药,或口服地塞米松,或氢化可的松)7 至 10 天。该建议基于两项荟萃分析,其分析汇总了 8 项随机试验数据(超过 7000 例患者),包括英国 RECOVERY 试验。中等质量证据表明,全身皮质类固醇治疗可能降低重症和危重 COVID-19 患者 28 天死亡率。它们亦可能减少对于有创通气的需求。暂无地塞米松和氢化可的松直接比较证据。在此情境中,治疗危害被认为较小。尚不清楚此类建议是否适用于儿童或免疫功能低下者。[541]World Health Organization. Corticosteroids for COVID-19: living guidance. 2020 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-Corticosteroids-2020.1 [542]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 [587]WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group; Sterne JAC, Murthy S, Diaz JV, et al. Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis. JAMA. 2020 Sep 2 [Epub ahead of print]. https://jamanetwork.com/journals/jama/article-abstract/2770279 http://www.ncbi.nlm.nih.gov/pubmed/32876694?tool=bestpractice.com [588]Lamontagne F, Agoritsas T, Macdonald H, 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 http://www.ncbi.nlm.nih.gov/pubmed/32887691?tool=bestpractice.com
BMJ rapid recommendations: a living WHO guideline on drugs for COVID-19 Opens in new window
在英国,英国国家卫生与临床优化研究所建议对于重症 COVID-19 患者使用地塞米松或氢化可的松(符合 WHO 指南)。在英国,上市销售授权包括了此项指征。[539]National Institute for Health and Care Excellence. COVID-19 rapid guideline: critical care in adults. 2020 [internet publication]. https://www.nice.org.uk/guidance/ng159
NICE: COVID-19 prescribing brief – corticosteroids Opens in new window
在欧洲,欧洲药品管理局已认同将地塞米松用于需要氧疗或机械通气的重症患者。[589]European Medicines Agency. EMA endorses use of dexamethasone in COVID-19 patients on oxygen or mechanical ventilation. 2020 [internet publication]. https://www.ema.europa.eu/en/news/ema-endorses-use-dexamethasone-covid-19-patients-oxygen-mechanical-ventilation
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患者,给予地塞米松单药治疗,或给予地塞米松联合 remdesivir 治疗。专家组不建议对于无需辅助供氧的患者给予地塞米松治疗。无法给予地塞米松时,可使用其他皮质类固醇。[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [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。[543]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. 2020 [internet publication]. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/
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。[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/ 皮质类固醇治疗期间根据当地常规采取胃肠道保护措施。remdesivir 和皮质类固醇不易产生临床显著相互作用;然而,洛匹那韦/利托那韦可增加氢化可的松浓度。[539]National Institute for Health and Care Excellence. COVID-19 rapid guideline: critical care in adults. 2020 [internet publication]. https://www.nice.org.uk/guidance/ng159
若患者在 10 日疗程完成前予以出院,则应停止治疗。[539]National Institute for Health and Care Excellence. COVID-19 rapid guideline: critical care in adults. 2020 [internet publication]. https://www.nice.org.uk/guidance/ng159
第一选择
地塞米松: 成人:6 mg,口服/静脉使用,每天一次,持续 7-10 天
或
氢化可的松: 成人:50 mg,口服/静脉使用,每 8 小时一次,持续 7-10 天
第二选择
泼尼松龙: 成人:40 mg/d,口服,分 1-2 次给药,持续 7-10 天
或
甲泼尼龙: 成人:32 mg/d,口服/静脉使用,分 1-2 次给药,持续 7-10 天
法匹拉韦
针对特定患者群中部分患者治疗的附加建议
考虑对需要给予辅助供氧的某些肺炎患者使用 remdesivir。[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/ [543]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. 2020 [internet publication]. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/ remdesivir 在英国和欧洲获得针对这一适应证的有条件批准,可用于 ≥12 岁的青少年和成人。[564]European Medicines Agency. First COVID-19 treatment recommended for EU authorisation. 2020 [internet publication]. https://www.ema.europa.eu/en/news/first-covid-19-treatment-recommended-eu-authorisation 美国食品药品监督管理局已批准 remdesivir 用于住院儿童(≥12 岁且 ≥40 kg)和成人患者 COVID-19 治疗。该项批准并未把先前在原始紧急用途授权下已授权的全部人群包括在内。目前对紧急使用授权进行了修订,授权对于体重在 3.5 kg 至 40 kg 之间的住院儿童和体重 3.5 kg 以下的 <12 岁儿童使用 remdesivir。[563]US Food and Drug Administration. FDA approves first treatment for COVID-19. 2020 [internet publication]. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-covid-19
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患者,给予地塞米松单药治疗,或给予地塞米松联合 remdesivir 治疗。如果患者在接受 remdesivir 治疗的过程中进展为需要高流量吸氧、通气或体外膜肺氧合,专家组建议完成 remdesivir 疗程。[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/ 美国传染病学会亦建议对接受氧疗的住院重症患者给予 remdesivir。[543]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. 2020 [internet publication]. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/
与标准治疗或安慰剂相比,remdesivir 对于住院患者可以降低死亡率和缩短症状消退所需时间;但无令人信服的证据表明 remdesivir 减少了对机械通气的需求。疾病早期给予 remdesivir 获益则更为显著。[542]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 [565]Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of Covid-19: final report. N Engl J Med. 2020 Nov 5 [Epub ahead of print]. https://www.nejm.org/doi/full/10.1056/NEJMoa2007764 http://www.ncbi.nlm.nih.gov/pubmed/32445440?tool=bestpractice.com 但是,WHO 团结试验中期结果发现,remdesivir 似乎对住院患者 28 天死亡率或住院疗程几乎不具影响。[566]Pan H, Peto R, Karim QA, et al; medRxiv. Repurposed antiviral drugs for COVID-19 – interim WHO SOLIDARITY trial results. 2020 [internet publication]. https://www.medrxiv.org/content/10.1101/2020.10.15.20209817v1
专家指南组对于重症病例使用 remdesivir 的建议强度较弱,且由于证据质量低下,因此支持进行更多随机试验。[590]Rochwerg B, Agarwal A, Zeng L, et al. Remdesivir for severe covid-19: a clinical practice guideline. BMJ. 2020 Jul 30;370:m2924. https://www.bmj.com/content/370/bmj.m2924 http://www.ncbi.nlm.nih.gov/pubmed/32732352?tool=bestpractice.com
英国国家卫生与临床优化研究所一项综述表明,与安慰剂相比,对于减少支持性措施(包括机械通气),或减少接受氧疗的 COVID-19 患者康复时间,remdesivir 具有一定获益。但是,对于死亡率和严重不良事件未发现统计学显著差异。[591]National Institute for Health and Care Excellence. COVID 19 rapid evidence summary: remdesivir for treating hospitalised patients with suspected or confirmed COVID-19. 2020 [internet publication]. https://www.nice.org.uk/advice/es27/chapter/Key-messages
remdesivir 可能引起胃肠症状,转氨酶水平升高和凝血酶原时间延长。也有报道称给药过程中和给药后出现了超敏反应。对估算的肾小球滤过率 <30 mL/min 的患者不应使用 remdesivir,肝脏损伤患者应谨慎使用。尚未针对孕妇、母乳喂养的女性或儿童评价安全性和有效性。除非有其他适应证,否则不应将 remdesivir 用于孕妇。remdesivir 可能与羟氯喹/氯喹产发生相互作用,但通常认为其可安全的与皮质类固醇一起使用。[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/
欧洲药品管理局已经开始对一项安全性讯息进行审查,以评估某些患者发生急性肾损伤的报道。在此阶段,尚不确定 remdesivir 与急性肾损伤之间是否存在因果关系。[567]European Medicines Agency. Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 28 September - 1 October 2020. 2020 [internet publication]. https://www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-risk-assessment-committee-prac-28-september-1-october-2020
第一选择
法匹拉韦: 儿童:咨询专科医师以获取剂量指导;成人:第 1 天 200 mg,静脉使用,之后 100 mg,每天一次,持续 4-9 天
更多 法匹拉韦建议疗程为 5 天或直到出院为止,以时间较早者为准。部分专家建议对 5 天后仍未显示出临床改善的患者进行疗程 10 天的治疗。[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/
混合感染治疗
针对特定患者群中部分患者治疗的附加建议
根据当地规程,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)。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 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。[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/
解热/镇痛药物
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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 [570]Alhazzani W, Møller MH, Arabi YM, et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Intensive Care Med. 2020 May;46(5):854-87. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101866/ http://www.ncbi.nlm.nih.gov/pubmed/32222812?tool=bestpractice.com 目前尚无证据表明 COVID-19 患者服用非甾体抗炎药(non-steroidal anti-inflammatory drug, NSAID)(例如布洛芬)将产生严重不良事件,或 NSAID 紧急用药将对 COVID-19 患者长期生存或生活质量产生不良影响。[553]European Medicines Agency. EMA gives advice on the use of non-steroidal anti-inflammatories for COVID-19. 2020 [internet publication]. https://www.ema.europa.eu/en/news/ema-gives-advice-use-non-steroidal-anti-inflammatories-covid-19 [554]US Food and Drug Administration. FDA advises patients on use of non-steroidal anti-inflammatory drugs (NSAIDs) for COVID-19. 2020 [internet publication]. https://www.fda.gov/drugs/drug-safety-and-availability/fda-advises-patients-use-non-steroidal-anti-inflammatory-drugs-nsaids-covid-19 [555]Little P. Non-steroidal anti-inflammatory drugs and covid-19. BMJ. 2020 Mar 27;368:m1185. https://www.bmj.com/content/368/bmj.m1185 http://www.ncbi.nlm.nih.gov/pubmed/32220865?tool=bestpractice.com [556]Medicines and Healthcare products Regulatory Agency; Commission on Human Medicines. Commission on Human Medicines advice on ibuprofen and coronavirus (COVID-19). 2020 [internet publication]. https://www.gov.uk/government/news/commission-on-human-medicines-advice-on-ibuprofen-and-coronavirus-covid-19 [557]World Health Organization. The use of non-steroidal anti-inflammatory drugs (NSAIDs) in patients with COVID-19: scientific brief. 2020 [internet publication]. https://www.who.int/news-room/commentaries/detail/the-use-of-non-steroidal-anti-inflammatory-drugs-(nsaids)-in-patients-with-covid-19 [558]National Institute for Health and Care Excellence. COVID-19 rapid evidence summary: acute use of non-steroidal anti-inflammatory drugs (NSAIDs) for people with or at risk of COVID-19. 2020 [internet publication]. https://www.nice.org.uk/advice/es23/chapter/Key-messages
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。
第一选择
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
布洛芬: 儿童:查询当地药物处方集,以获取剂量指导;成人:必要时,每 6-8 小时口服 300-600 mg,每日最多 2400 mg
试验性治疗
针对特定患者群中部分患者治疗的附加建议
仅在临床试验中,或根据当地常规,方考虑采用实验性治疗(例如恢复期血浆、洛匹那韦/利托那韦)。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 更多信息,请参阅新兴治疗章节。
出院和康复计划
针对特定患者群中部分患者治疗的附加建议
定期评估老年患者活动能力、吞咽功能、认知障碍和心理健康问题,并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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19
缓和医疗
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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 遵循当地缓和医疗指南。
危重 COVID-19
收入重症/危重症监护病房
危重症(例如出现急性呼吸窘迫综合征、脓毒症或脓毒性休克)患者应收入院治疗,或在专科医生团队指导下转入重症监护病房。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19
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。[540]National Institute for Health and Care Excellence. COVID-19 rapid guideline: managing symptoms (including at the end of life) in the community. 2020 [internet publication]. https://www.nice.org.uk/guidance/ng163
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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 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。[626]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
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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 美国疾病预防控制中心(Centers for Disease Control and Prevention, CDC)建议,如果采用基于症状的策略,自症状首次出现以来至少经过 20 天,且自上次发热以来至少 24 小时未使用解热药物,同时若症状有所改善,则可停止隔离。对于无症状者,CDC 建议,自检测呈阳性之日起至少经过 20 天,就可停止隔离。另外,其建议如果采用基于检测的策略,则在隔离结束之前,应至少获得两次间隔 24 小时呼吸道样本的逆转录聚合酶链反应(reverse-transcription polymerase chain reaction, RT-PCR)阴性结果。此类患者首选基于症状的策略。[561]Centers for Disease Control and Prevention. Discontinuation of transmission-based precautions and disposition of patients with COVID-19 in healthcare settings (interim guidance). 2020 [internet publication]. https://www.cdc.gov/coronavirus/2019-ncov/hcp/disposition-hospitalized-patients.html 关于何时停止隔离的建议,取决于当地情况,各国之间可能有所不同。例如,在英国,从住院患者检测阳性起计,隔离时间为 14 天。[552]Public Health England. Guidance for stepdown of infection control precautions and discharging COVID-19 patients. 2020 [internet publication]. https://www.gov.uk/government/publications/covid-19-guidance-for-stepdown-of-infection-control-precautions-within-hospitals-and-discharging-covid-19-patients-from-hospital-to-home-settings/guidance-for-stepdown-of-infection-control-precautions-and-discharging-covid-19-patients
症状管理和支持性治疗
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。建议对危重患者行静脉血栓预防治疗。低分子肝素为推荐选择,普通肝素则被认为是合适的替代品,优于磺达肝癸钠。[582]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 Jun 2 [Epub ahead of print]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265858/ http://www.ncbi.nlm.nih.gov/pubmed/32502594?tool=bestpractice.com 请参阅上方重度 COVID 部分内容以获取更详细的信息。
对于疼痛、镇静和谵妄的管理,应遵循当地指南。[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19
考虑高流量鼻套管吸氧或无创通气
针对特定患者群中所有患者的治疗建议
对于轻度急性呼吸窘迫综合征特定患者,考虑试验性给予高流量鼻套管吸氧(high-flow nasal oxygen, HFNO)或无创通气(例如持续气道正压通气[Continuous Positive Airway Pressure, CPAP]或双水平气道正压通气[Bilevel Positive Airway Pressure, BiPAP])。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19
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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19
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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19
机械通气之前最佳呼吸支持模式的争论一直在持续。[596]McEnery T, Gough C, Costello RW. COVID-19: respiratory support outside the intensive care unit. Lancet Respir Med. 2020 Apr 9 [Epub ahead of print]. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30176-4/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32278367?tool=bestpractice.com 英格兰 NHS 建议将 CPAP 作为低氧血症(1 型)呼吸衰竭患者无创通气的首选形式。由于缺乏功效、消耗氧气(HFNO 可为氧供带来压力,导致出现地区补给不足风险)和传播感染,因此不主张使用 HFNO。[597]NHS England. Guidance for the role and use of non-invasive respiratory support in adult patients with COVID19 (confirmed or suspected). 2020 [internet publication]. https://www.england.nhs.uk/coronavirus/wp-content/uploads/sites/52/2020/03/specialty-guide-NIV-respiratory-support-and-coronavirus-v3.pdf 其他指南建议采用 HFNO,而非无创通气,除非无法给予 HFNO。[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/ [570]Alhazzani W, Møller MH, Arabi YM, et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Intensive Care Med. 2020 May;46(5):854-87. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101866/ http://www.ncbi.nlm.nih.gov/pubmed/32222812?tool=bestpractice.com 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。[598]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
早期 CPAP 可为有创机械通气架设桥梁。BiPAP 留予高碳酸血症性急慢性通气衰竭(2 型呼吸衰竭)患者使用。[597]NHS England. Guidance for the role and use of non-invasive respiratory support in adult patients with COVID19 (confirmed or suspected). 2020 [internet publication]. https://www.england.nhs.uk/coronavirus/wp-content/uploads/sites/52/2020/03/specialty-guide-NIV-respiratory-support-and-coronavirus-v3.pdf
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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 [570]Alhazzani W, Møller MH, Arabi YM, et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Intensive Care Med. 2020 May;46(5):854-87. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101866/ http://www.ncbi.nlm.nih.gov/pubmed/32222812?tool=bestpractice.com
考虑有创机械通气
针对特定患者群中所有患者的治疗建议
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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 [3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/
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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 建议尽可能通过可视喉镜实施插管。[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19
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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 [3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/ [570]Alhazzani W, Møller MH, Arabi YM, et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Intensive Care Med. 2020 May;46(5):854-87. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101866/ http://www.ncbi.nlm.nih.gov/pubmed/32222812?tool=bestpractice.com 英格兰 NHS 建议在无需进行肺复张时,对于具有正常顺应性的患者应采取低 PEEP 策略。[606]NHS England. Clinical guide for the management of critical care for adults with COVID-19 during the coronavirus pandemic. 2020 [internet publication]. https://www.england.nhs.uk/coronavirus/wp-content/uploads/sites/52/2020/03/C0216_Specialty-guide_AdultCritiCare-and-coronavirus_V2.pdf
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。[607]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 [608]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 [609]Gattinoni L, Chiumello D, Caironi P, et al. COVID-19 pneumonia: different respiratory treatments for different phenotypes? Intensive Care Med. 2020 Apr 14 [Epub ahead of print]. https://link.springer.com/article/10.1007%2Fs00134-020-06033-2 http://www.ncbi.nlm.nih.gov/pubmed/32291463?tool=bestpractice.com [610]Marini JJ, Gattinoni L. Management of COVID-19 respiratory distress. JAMA. 2020 Apr 24 [Epub ahead of print]. https://jamanetwork.com/journals/jama/fullarticle/2765302 http://www.ncbi.nlm.nih.gov/pubmed/32329799?tool=bestpractice.com [611]Rello J, Storti E, Belliato M, et al. Clinical phenotypes of SARS-CoV-2: implications for clinicians and researchers. Eur Respir J. 2020 Apr 27 [Epub ahead of print]. https://erj.ersjournals.com/content/early/2020/04/20/13993003.01028-2020 http://www.ncbi.nlm.nih.gov/pubmed/32341111?tool=bestpractice.com [612]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。[613]Bos LD, Paulus F, Vlaar APJ, et al. Subphenotyping ARDS in COVID-19 patients: consequences for ventilator management. Ann Am Thorac Soc. 2020 May 12 [Epub ahead of print]. https://www.atsjournals.org/doi/pdf/10.1513/AnnalsATS.202004-376RL http://www.ncbi.nlm.nih.gov/pubmed/32396457?tool=bestpractice.com [614]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 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。[615]Rice TW, Janz DR. In defense of evidence-based medicine for the treatment of COVID-19 ARDS. Ann Am Thorac Soc. 2020 Apr 22 [Epub ahead of print]. https://www.atsjournals.org/doi/pdf/10.1513/AnnalsATS.202004-325IP 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。[607]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。[572]Dondorp AM, Hayat M, Aryal D, et al. Respiratory support in novel coronavirus disease (COVID-19) patients, with a focus on resource-limited settings. Am J Trop Med Hyg. 2020 Apr 21 [Epub ahead of print]. http://www.ajtmh.org/content/journals/10.4269/ajtmh.20-0283 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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 [3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/ [570]Alhazzani W, Møller MH, Arabi YM, et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Intensive Care Med. 2020 May;46(5):854-87. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101866/ http://www.ncbi.nlm.nih.gov/pubmed/32222812?tool=bestpractice.com 某些患者中更长的持续时间可能可行。[616]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。[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/ [570]Alhazzani W, Møller MH, Arabi YM, et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Intensive Care Med. 2020 May;46(5):854-87. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101866/ http://www.ncbi.nlm.nih.gov/pubmed/32222812?tool=bestpractice.com
吸入性肺血管扩张药
针对特定患者群中部分患者治疗的附加建议
尽管通气得到优化,但对于存在急性呼吸窘迫综合征和低氧血症的成年人,考虑试验性给予吸入性肺血管扩张剂。如果氧合未能得到迅速改善,则应逐渐减少其剂量。[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/ [570]Alhazzani W, Møller MH, Arabi YM, et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Intensive Care Med. 2020 May;46(5):854-87. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101866/ http://www.ncbi.nlm.nih.gov/pubmed/32222812?tool=bestpractice.com
体外膜肺氧合
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)。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 [570]Alhazzani W, Møller MH, Arabi YM, et al. Surviving Sepsis Campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Intensive Care Med. 2020 May;46(5):854-87. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101866/ http://www.ncbi.nlm.nih.gov/pubmed/32222812?tool=bestpractice.com [620]American Thoracic Society. Diagnosis and management of COVID-19 disease. 2020 [internet publication]. https://www.thoracic.org/patients/patient-resources/resources/covid-19-diagnosis-and-mgmt.pdf [621]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 ECMO 并不适合所有患者,只有满足特定纳入标准的患者,方可考虑使用 ECMO。[622]NHS England. Clinical guide for extra corporeal membrane oxygenation (ECMO) for respiratory failure in adults during the coronavirus pandemic. 2020 [internet publication]. https://www.england.nhs.uk/coronavirus/wp-content/uploads/sites/52/2020/04/C0156-Extra-Corporeal-Membrane-Oxygenation-ECMO-Adult-Speciality-Guide-1.pdf
目前尚无充分证据支持或反对常规使用 ECMO 治疗。[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/
经 ECMO 救治的 COVID-19 患者 60 天生存率估计值(31%)与对重度 ARDS 患者给予 ECMO 治疗的既往研究结果相似。[623]Schmidt M, Hajage D, Lebreton G, et al. Extracorporeal membrane oxygenation for severe acute respiratory distress syndrome associated with COVID-19: a retrospective cohort study. Lancet Respir Med. 2020 Aug 13 [Epub ahead of print]. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30328-3/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32798468?tool=bestpractice.com
一项针对 1035 名患者的国际队列研究发现,ECMO 启动后 90 天估计死亡率,以及获得最终结局或出院的患者死亡率均 <40%,与先前报道的急性低氧血症性呼吸衰竭患者生存率一致。[624]Barbaro RP, MacLaren G, Boonstra PS, et al. Extracorporeal membrane oxygenation support in COVID-19: an international cohort study of the Extracorporeal Life Support Organization registry. Lancet. 2020 Sep 25 [Epub ahead of print]. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32008-0/fulltext http://www.ncbi.nlm.nih.gov/pubmed/32987008?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。[625]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 [Epub ahead of print]. https://jamanetwork.com/journals/jamasurgery/fullarticle/2769429 http://www.ncbi.nlm.nih.gov/pubmed/32780089?tool=bestpractice.com
脓毒症/脓毒性休克管理
针对特定患者群中部分患者治疗的附加建议
COVID-19 患者脓毒症和脓毒性休克的管理不在本专题讨论范围内。参见并发症章节。
皮质类固醇
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(World Health Organization, WHO)强烈建议对于伴严重或危重疾病的成年人,给予全身皮质类固醇治疗(低剂量静脉用药,或口服地塞米松,或氢化可的松)7 至 10 天。该建议基于两项荟萃分析,其分析汇总了 8 项随机试验数据(超过 7000 例患者),包括英国 RECOVERY 试验。中等质量证据表明,全身皮质类固醇治疗可能降低重症和危重 COVID-19 患者 28 天死亡率。它们亦可能减少对于有创通气的需求。暂无地塞米松和氢化可的松直接比较证据。在此情境中,治疗危害被认为较小。尚不清楚此类建议是否适用于儿童或免疫功能低下者。[541]World Health Organization. Corticosteroids for COVID-19: living guidance. 2020 [internet publication]. https://www.who.int/publications/i/item/WHO-2019-nCoV-Corticosteroids-2020.1 [542]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 [587]WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group; Sterne JAC, Murthy S, Diaz JV, et al. Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis. JAMA. 2020 Sep 2 [Epub ahead of print]. https://jamanetwork.com/journals/jama/article-abstract/2770279 http://www.ncbi.nlm.nih.gov/pubmed/32876694?tool=bestpractice.com [588]Lamontagne F, Agoritsas T, Macdonald H, 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 http://www.ncbi.nlm.nih.gov/pubmed/32887691?tool=bestpractice.com
BMJ rapid recommendations: a living WHO guideline on drugs for COVID-19 Opens in new window
在英国,英国国家卫生与临床优化研究所建议对于重症 COVID-19 患者使用地塞米松或氢化可的松(符合 WHO 指南)。在英国,上市销售授权包括了此项指征。[539]National Institute for Health and Care Excellence. COVID-19 rapid guideline: critical care in adults. 2020 [internet publication]. https://www.nice.org.uk/guidance/ng159
NICE: COVID-19 prescribing brief – corticosteroids Opens in new window
在欧洲,欧洲药品管理局已认同将地塞米松用于需要氧疗或机械通气的重症患者。[589]European Medicines Agency. EMA endorses use of dexamethasone in COVID-19 patients on oxygen or mechanical ventilation. 2020 [internet publication]. https://www.ema.europa.eu/en/news/ema-endorses-use-dexamethasone-covid-19-patients-oxygen-mechanical-ventilation
在美国,国立卫生研究院指南专家组建议对于需给予高流量氧、无创通气、机械通气或体外膜肺氧合的住院患者,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。[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [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。[543]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. 2020 [internet publication]. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/
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。[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/ 皮质类固醇治疗期间根据当地常规采取胃肠道保护措施。remdesivir 和皮质类固醇不易产生临床显著相互作用;然而,洛匹那韦/利托那韦可增加氢化可的松浓度。[539]National Institute for Health and Care Excellence. COVID-19 rapid guideline: critical care in adults. 2020 [internet publication]. https://www.nice.org.uk/guidance/ng159
若患者在 10 日疗程完成前予以出院,则应停止治疗。[539]National Institute for Health and Care Excellence. COVID-19 rapid guideline: critical care in adults. 2020 [internet publication]. https://www.nice.org.uk/guidance/ng159
第一选择
地塞米松: 成人:6 mg,口服/静脉使用,每天一次,持续 7-10 天
或
第二选择
泼尼松龙: 成人:40 mg/d,口服,分 1-2 次给药,持续 7-10 天
或
甲泼尼龙: 成人:32 mg/d,口服/静脉使用,分 1-2 次给药,持续 7-10 天
法匹拉韦
针对特定患者群中部分患者治疗的附加建议
考虑对需要给予辅助供氧的某些肺炎患者使用 remdesivir。[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/ [543]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. 2020 [internet publication]. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/ remdesivir 在英国和欧洲获得针对这一适应证的有条件批准,可用于 ≥12 岁的青少年和成人。[564]European Medicines Agency. First COVID-19 treatment recommended for EU authorisation. 2020 [internet publication]. https://www.ema.europa.eu/en/news/first-covid-19-treatment-recommended-eu-authorisation 美国食品药品监督管理局已批准 remdesivir 用于住院儿童(≥12 岁且 ≥40 kg)和成人患者 COVID-19 治疗。该项批准并未把先前在原始紧急用途授权下已授权的全部人群包括在内。目前对紧急使用授权进行了修订,授权对于体重在 3.5 kg 至 40 kg 之间的住院儿童和体重 3.5 kg 以下的 <12 岁儿童使用 remdesivir。[563]US Food and Drug Administration. FDA approves first treatment for COVID-19. 2020 [internet publication]. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-covid-19
在美国,国立卫生研究院建议对于需给予高流量氧、无创通气、机械通气或体外膜肺氧合(extracorporeal membrane oxygenation, ECMO)的住院患者,给予地塞米松单药治疗,或给予地塞米松联合 remdesivir 治疗。[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/ 美国传染病学会建议对接受吸氧、机械通气或 ECMO 治疗的住院重症患者使用 remdesivir;但也建议仅在供应有限的情况下,优先对接受氧疗的患者进行治疗。[543]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. 2020 [internet publication]. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/
与标准治疗或安慰剂相比,remdesivir 对于住院患者可以降低死亡率和缩短症状消退所需时间;但无令人信服的证据表明 remdesivir 减少了对机械通气的需求。疾病早期给予 remdesivir 获益则更为显著。[542]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 [565]Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the treatment of Covid-19: final report. N Engl J Med. 2020 Nov 5 [Epub ahead of print]. https://www.nejm.org/doi/full/10.1056/NEJMoa2007764 http://www.ncbi.nlm.nih.gov/pubmed/32445440?tool=bestpractice.com 但是,WHO 团结试验中期结果发现,remdesivir 似乎对住院患者 28 天死亡率或住院疗程几乎不具影响。[566]Pan H, Peto R, Karim QA, et al; medRxiv. Repurposed antiviral drugs for COVID-19 – interim WHO SOLIDARITY trial results. 2020 [internet publication]. https://www.medrxiv.org/content/10.1101/2020.10.15.20209817v1
专家指南组对于重症病例使用 remdesivir 的建议强度较弱,且由于证据质量低下,因此支持进行更多随机试验。[590]Rochwerg B, Agarwal A, Zeng L, et al. Remdesivir for severe covid-19: a clinical practice guideline. BMJ. 2020 Jul 30;370:m2924. https://www.bmj.com/content/370/bmj.m2924 http://www.ncbi.nlm.nih.gov/pubmed/32732352?tool=bestpractice.com
英国国家卫生与临床优化研究所一项综述表明,与安慰剂相比,对于减少支持性措施(包括机械通气),或减少接受氧疗的 COVID-19 患者康复时间,remdesivir 具有一定获益。但是,对于死亡率和严重不良事件未发现统计学显著差异。[591]National Institute for Health and Care Excellence. COVID 19 rapid evidence summary: remdesivir for treating hospitalised patients with suspected or confirmed COVID-19. 2020 [internet publication]. https://www.nice.org.uk/advice/es27/chapter/Key-messages
remdesivir 可能引起胃肠症状,转氨酶水平升高和凝血酶原时间延长。也有报道称给药过程中和给药后出现了超敏反应。对估算的肾小球滤过率 <30 mL/min 的患者不应使用 remdesivir,肝脏损伤患者应谨慎使用。尚未针对孕妇、母乳喂养的女性或儿童评价安全性和有效性。除非有其他适应证,否则不应将 remdesivir 用于孕妇。remdesivir 可能与羟氯喹/氯喹产发生相互作用,但通常认为其可安全的与皮质类固醇一起使用。[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/
欧洲药品管理局已经开始对一项安全性讯息进行审查,以评估某些患者发生急性肾损伤的报道。在此阶段,尚不确定 remdesivir 与急性肾损伤之间是否存在因果关系。[567]European Medicines Agency. Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 28 September - 1 October 2020. 2020 [internet publication]. https://www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-risk-assessment-committee-prac-28-september-1-october-2020
第一选择
法匹拉韦: 儿童:咨询专科医师以获取剂量指导;成人:第 1 天 200 mg,静脉使用,之后 100 mg,每天一次,持续 4-9 天
更多 法匹拉韦建议疗程为 5 天或直到出院为止,以时间较早者为准。部分专家建议对 5 天后仍未显示出临床改善的患者进行疗程 10 天的治疗。[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/ 对于接受机械通气或 ECMO 治疗的患者,也建议进行疗程 10 天的治疗。[543]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. 2020 [internet publication]. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/
混合感染治疗
针对特定患者群中部分患者治疗的附加建议
根据当地规程,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)。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 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。[3]National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. 2020 [internet publication]. https://covid19treatmentguidelines.nih.gov/
试验性治疗
针对特定患者群中部分患者治疗的附加建议
仅在临床试验中,或根据当地常规,方考虑采用实验性治疗(例如恢复期血浆、洛匹那韦/利托那韦)。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 更多信息,请参阅新兴治疗章节。
出院和康复计划
针对特定患者群中部分患者治疗的附加建议
定期评估重症患者活动能力、吞咽功能、认知障碍和心理健康问题,并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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19
缓和医疗
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。[2]World Health Organization. Clinical management of COVID-19: interim guidance. 2020 [internet publication]. https://www.who.int/publications-detail/clinical-management-of-covid-19 遵循当地缓和医疗指南。
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