Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
Start treatment immediately if a senior clinical decision-maker makes a diagnosis of suspected sepsis, based on acute deterioration (e.g., National Early Warning Score 2 [NEWS2] score of 5 or more, or a similar trigger using another validated scoring system) in a patient with known or likely infection.[41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf [42]Royal College of Physicians. National early warning score (NEWS) 2: standardising the assessment of acute-illness severity in the NHS. December 2017 [internet publication]. https://www.rcplondon.ac.uk/projects/outputs/national-early-warning-score-news-2
In the UK, a senior clinical decision-maker is CT3/ST3 or higher, or a trained nurse with prescribing rights in acute care.[41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf
For any acutely ill and deteriorating patient with a suspected or known bacterial infection and suspected sepsis, above all else prioritise (if needed):[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [45]Levy MM, Evans LE, Rhodes A. The Surviving Sepsis Campaign bundle: 2018 update. Crit Care Med. 2018 Jun;46(6):997-1000. http://www.ncbi.nlm.nih.gov/pubmed/29767636?tool=bestpractice.com [46]Nutbeam T, Daniels R; The UK Sepsis Trust. Professional resources: clinical [internet publication]. https://sepsistrust.org/professional-resources/clinical/
Securing their airway
Correcting hypoxaemia
Establishing venous access for the early administration of antibiotics and fluids.
Where there is evidence of a bacterial infection and a strong suspicion of sepsis (based on acute deterioration [e.g., NEWS2 score of 5 or more, or a similar trigger using another validated scoring system]), give broad-spectrum intravenous antibiotics within 1 hour of the risk of sepsis being recognised.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf [43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [46]Nutbeam T, Daniels R; The UK Sepsis Trust. Professional resources: clinical [internet publication]. https://sepsistrust.org/professional-resources/clinical/ Do this before a pathogen is identified but after blood cultures have been taken.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf [43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [46]Nutbeam T, Daniels R; The UK Sepsis Trust. Professional resources: clinical [internet publication]. https://sepsistrust.org/professional-resources/clinical/
The Surviving Sepsis Campaign international guideline recommends empirical combination therapy (using at least two antibiotics of different antimicrobial classes) aimed at the most likely bacterial pathogen(s) for the initial management of septic shock.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Follow local policy and consider discussing with microbiology/infectious disease colleagues to determine the most appropriate choice.
Use a 'start smart then focus' approach.[41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf [136]Public Health England. Antimicrobial stewardship: start smart – then focus. March 2015 [internet publication]. https://www.gov.uk/government/publications/antimicrobial-stewardship-start-smart-then-focus
NHS England recommends following a 'start smart then focus’ approach for antibiotic use in people with sepsis.[41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf This is derived from Public Health England guidance, which outlines an evidence-based approach to improving antimicrobial prescribing and stewardship in hospital settings.[136]Public Health England. Antimicrobial stewardship: start smart – then focus. March 2015 [internet publication]. https://www.gov.uk/government/publications/antimicrobial-stewardship-start-smart-then-focus The prevalence of antimicrobial resistance (AMR) has risen alarmingly over the last 50 years and no new classes of antibiotics have been developed in decades. By 2050 it is estimated that AMR will kill 10 million people per year, more than cancer and diabetes combined.[143]Health and Social Care Committee. Antimicrobial resistance. October 2018 [internet publication]. https://publications.parliament.uk/pa/cm201719/cmselect/cmhealth/962/962.pdf The relationship between antibiotic exposure and antibiotic resistance is unambiguous not only at the population level but also in individual patients.[144]Goossens H, Ferech M, Vander Stichele R, et al. Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet. 2005 Feb 12-18;365(9459):579-87. http://www.ncbi.nlm.nih.gov/pubmed/15708101?tool=bestpractice.com [145]Costelloe C, Metcalfe C, Lovering A, et al. Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis. BMJ. 2010 May 18;340:c2096. https://www.bmj.com/content/340/bmj.c2096.long http://www.ncbi.nlm.nih.gov/pubmed/20483949?tool=bestpractice.com
Start smart – in the context of sepsis:[136]Public Health England. Antimicrobial stewardship: start smart – then focus. March 2015 [internet publication]. https://www.gov.uk/government/publications/antimicrobial-stewardship-start-smart-then-focus
Do not start antimicrobial therapy unless there is clear evidence of infection
Take a thorough drug allergy history
Initiate prompt effective antibiotic treatment within 1 hour of diagnosis (or as soon as possible) in patients with sepsis or life-threatening infections. Avoid inappropriate use of broad-spectrum antibiotics
Comply with local antimicrobial prescribing guidance
Document clinical indication (and disease severity if appropriate), drug name, dose, and route on drug chart and in clinical notes
Include review/stop date or duration
Obtain cultures prior to starting therapy where possible (but do not delay therapy).
Then focus – in the context of sepsis:[136]Public Health England. Antimicrobial stewardship: start smart – then focus. March 2015 [internet publication]. https://www.gov.uk/government/publications/antimicrobial-stewardship-start-smart-then-focus
Review the clinical diagnosis and the continuing need for antibiotics at 48 to 72 hours* and document in a clear plan of action – the ‘antimicrobial prescribing decision’
The ‘antimicrobial prescribing decision’ options are:
Stop antibiotics if there is no evidence of infection
Switch antibiotics from intravenous to oral
Change antibiotics – ideally to a narrower spectrum, or broader if required
Continue and document next review date or stop date
It is essential that the review and subsequent decision is clearly documented in the clinical notes and on the drug chart where possible (e.g., ‘stop antibiotic’).
*In clinical practice, daily prompting about de-escalation is encouraged.
Target the presumed site of infection.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
If there is no clinical evidence to suggest a specific site of infection but a senior clinical decision-maker strongly suspects the presence of a bacterial infection, still give empirical broad-spectrum intravenous antibiotics.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf Choose an empirical antibiotic based on:[146]Ferrer R, Martin-Loeches I, Phillips G, et al. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med. 2014 Aug;42(8):1749-55. http://www.ncbi.nlm.nih.gov/pubmed/24717459?tool=bestpractice.com [147]Kumar A, Ellis P, Arabi Y, et al. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest. 2009 Nov;136(5):1237-48. http://www.ncbi.nlm.nih.gov/pubmed/19696123?tool=bestpractice.com
Local antibiotic protocols and resistance patterns
Consult microbiology/infectious disease colleagues to determine the most appropriate choice
The likely causative organism
The patient’s immune function.
Practical tip
Check local policies regarding repeat cultures, which are particularly indicated if there are persistent or repeated fever spikes or if you identify a potential new site of infection. Observations from studies to date support taking as many as four blood culture sets over a 24-hour period for >99% test sensitivity.[148]Lee A, Mirrett S, Reller LB, et al. Detection of bloodstream infections in adults: how many blood cultures are needed? J Clin Microbiol. 2007 Sep 19;45(11):3546-8. www.doi.org/10.1128/JCM.01555-07 http://www.ncbi.nlm.nih.gov/pubmed/17881544?tool=bestpractice.com
Practical tip
If a patient has a mild allergy (e.g., rash) to an unknown antibiotic, you should still give empirical broad-spectrum antibiotics if indicated to prevent delay in the treatment of sepsis, which is likely to worsen outcome. If the antibiotic is known and is part of the empirical protocol for your hospital, discuss with potential alternatives with a microbiologist.
There is widespread agreement that appropriate and timely recognition of sepsis and subsequent resuscitation are key approaches to the management of the severely ill patient with sepsis. However, guideline-derived antibiotic delivery goals (as outlined by the UK National Institute for Health and Care Excellence [NICE], the Surviving Sepsis Campaign [SSC], and the UK Sepsis Trust) have been challenged owing to gaps in the evidence and concerns about over-treatment of the individual patient and the subsequent effect on antimicrobial resistance.[57]Spiegel R, Farkas JD, Rola P, et al. The 2018 Surviving Sepsis Campaign's treatment bundle: when guidelines outpace the evidence supporting their use. Ann Emerg Med. 2019 Apr;73(4):356-8. https://www.annemergmed.com/article/S0196-0644(18)30607-3/fulltext http://www.ncbi.nlm.nih.gov/pubmed/30193754?tool=bestpractice.com [58]Talan DA, Yealy DM. Challenging the one-hour bundle goal for sepsis antibiotics. Ann Emerg Med. 2019 Apr;73(4):359-62. http://www.ncbi.nlm.nih.gov/pubmed/30902163?tool=bestpractice.com
The 1-hour antibiotic targets outlined by NICE,[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 the SSC,[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com and the UK Sepsis Trust (Sepsis Six)[46]Nutbeam T, Daniels R; The UK Sepsis Trust. Professional resources: clinical [internet publication]. https://sepsistrust.org/professional-resources/clinical/ are derived from data that appear to draw a direct correlation between each hour of delayed treatment of the patient with sepsis and an increased risk of further deterioration or death.[93]Alam N, Oskam E, Stassen PM, et al. Prehospital antibiotics in the ambulance for sepsis: a multicentre, open label, randomised trial. Lancet Respir Med. 2018 Jan;6(1):40-50. http://www.ncbi.nlm.nih.gov/pubmed/29196046?tool=bestpractice.com [149]Kumar A, Roberts D, Wood KE, et al. Duration of hypotension prior to initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006 Jun;34(6):1589-96. http://www.ncbi.nlm.nih.gov/pubmed/16625125?tool=bestpractice.com [150]Whiles BB, Deis AS, Simpson SQ. Increased time to initial antimicrobial administration is associated with progression to septic shock in severe sepsis patients. Crit Care Med. 2017 Apr;45(4):623-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374449/ http://www.ncbi.nlm.nih.gov/pubmed/28169944?tool=bestpractice.com However, examining some of these data closely shows that 1-hour antibiotic targets may not be possible or necessarily advantageous for all patients with eventual sepsis diagnoses.[58]Talan DA, Yealy DM. Challenging the one-hour bundle goal for sepsis antibiotics. Ann Emerg Med. 2019 Apr;73(4):359-62. http://www.ncbi.nlm.nih.gov/pubmed/30902163?tool=bestpractice.com
A retrospective cohort study of hypotensive inpatients with sepsis, published in 2006, first described a potential link between timing of antibiotics and outcomes.[149]Kumar A, Roberts D, Wood KE, et al. Duration of hypotension prior to initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006 Jun;34(6):1589-96. http://www.ncbi.nlm.nih.gov/pubmed/16625125?tool=bestpractice.com
The authors noted 79.9% survival if septic patients received in vitro-active antibiotics within 1 hour of the onset of hypotension, with a subsequent 7.6% survival rate decrement with each additional hour to treatment.
Looking closely at the data, however, there was a lower survival rate (52%) among patients who received antibiotics before hypotension compared with those who received them within the first few hours of the onset of septic shock.
Commentators note that ascribing a biological effect to antibiotics for either the improvement or the decreased survival is endemic to observational or natural experiment designs, which are prone to confounding and bias in their interpretation of results.[58]Talan DA, Yealy DM. Challenging the one-hour bundle goal for sepsis antibiotics. Ann Emerg Med. 2019 Apr;73(4):359-62. http://www.ncbi.nlm.nih.gov/pubmed/30902163?tool=bestpractice.com
More recently, another retrospective cohort study of 3929 patients with severe sepsis described an 8% hourly incremental increased risk of progression to septic shock with longer time to antibiotics.[150]Whiles BB, Deis AS, Simpson SQ. Increased time to initial antimicrobial administration is associated with progression to septic shock in severe sepsis patients. Crit Care Med. 2017 Apr;45(4):623-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374449/ http://www.ncbi.nlm.nih.gov/pubmed/28169944?tool=bestpractice.com
There was little change in rate of worsening (progression to septic shock rate) until after 5 hours; by then, approximately 75% of patients had received antibiotics. The remaining 25% of the cohort (who were treated later than the first patient group) differed from those treated earlier. Notably, the later-treated group had more comorbidities.
As noted in commentary on the study, this is in line with what’s commonly seen in clinical practice: sepsis is harder to recognise in people with comorbidities, and patients with sepsis and comorbid illness have a worse prognosis in general.[58]Talan DA, Yealy DM. Challenging the one-hour bundle goal for sepsis antibiotics. Ann Emerg Med. 2019 Apr;73(4):359-62. http://www.ncbi.nlm.nih.gov/pubmed/30902163?tool=bestpractice.com
Another recent trial randomised 2672 patients with suspected sepsis (>95% without shock) to receive antibiotics in ambulances or ‘quickly’ in an emergency department. The median 96-minute-earlier administration was not linked to improved outcomes, regardless of illness severity.[93]Alam N, Oskam E, Stassen PM, et al. Prehospital antibiotics in the ambulance for sepsis: a multicentre, open label, randomised trial. Lancet Respir Med. 2018 Jan;6(1):40-50. http://www.ncbi.nlm.nih.gov/pubmed/29196046?tool=bestpractice.com
In intensive care settings only, consider prolonged infusion when giving beta-lactam antibiotics to patients with sepsis (apart from those with kidney-related complications).[151]Vardakas KZ, Voulgaris GL, Maliaros A, et al. Prolonged versus short-term intravenous infusion of antipseudomonal β-lactams for patients with sepsis: a systematic review and meta-analysis of randomised trials. Lancet Infect Dis. 2018 Jan;18(1):108-20. http://www.ncbi.nlm.nih.gov/pubmed/29102324?tool=bestpractice.com Note that prolonged infusion times are not licensed, as most manufacturers advise infusion of beta-lactam antibiotics over 15 to 60 minutes.
Intravenous antibiotics, administered over 3 hours, are linked to lower death rates in sepsis.[151]Vardakas KZ, Voulgaris GL, Maliaros A, et al. Prolonged versus short-term intravenous infusion of antipseudomonal β-lactams for patients with sepsis: a systematic review and meta-analysis of randomised trials. Lancet Infect Dis. 2018 Jan;18(1):108-20. http://www.ncbi.nlm.nih.gov/pubmed/29102324?tool=bestpractice.com Prolonged infusion should be easy to apply in the intensive care setting, without the need for additional training or equipment.
A systematic review and meta-analysis pooled the results of 22 randomised controlled trials involving 1876 adults with sepsis. The trials compared prolonged versus short-term administration of any antipseudomonal beta-lactam. Carbapenems were studied in nine trials, penicillins in nine trials, and cephalosporins in eight trials.[151]Vardakas KZ, Voulgaris GL, Maliaros A, et al. Prolonged versus short-term intravenous infusion of antipseudomonal β-lactams for patients with sepsis: a systematic review and meta-analysis of randomised trials. Lancet Infect Dis. 2018 Jan;18(1):108-20. http://www.ncbi.nlm.nih.gov/pubmed/29102324?tool=bestpractice.com
Prolonged infusion was associated with lower all-cause mortality than short-term infusion, with 13.6% deaths compared with 19.8% (risk ratio [RR] 0.70, 95% CI 0.56 to 0.87; 17 studies, 1597 participants).
There was no significant difference between prolonged and short-term infusion for clinical cure or improvement (RR 1.06, 95% CI 0.96 to 1.17; 11 studies, 1219 participants).
There was no difference in reported adverse events between the groups (RR 0.88, 95% CI 0.71 to 1.09; 7 studies, 980 participants).
Two trials had no incidence of antibiotic resistance, and two trials had no difference in resistance between the two methods of antibiotic administration (RR 0.60, 95% CI 0.15 to 2.38).
Narrow choice of antibiotic as soon as a pathogen has been identified and sensitivities are available.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [137]Paul M, Dickstein Y, Raz-Pasteur A. Antibiotic de-escalation for bloodstream infections and pneumonia: systematic review and meta-analysis. Clin Microbiol Infect. 2016 Dec;22(12):960-7. http://www.ncbi.nlm.nih.gov/pubmed/27283148?tool=bestpractice.com Assess the need to de-escalate antimicrobial therapy daily.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Studies have shown that daily prompting about antimicrobial de-escalation is effective and may be associated with improved outcomes.[193]Weiss CH, Persell SD, Wunderink RG, et al. Empiric antibiotic, mechanical ventilation, and central venous catheter duration as potential factors mediating the effect of a checklist prompting intervention on mortality: an exploratory analysis. BMC Health Serv Res. 2012 Jul 13;12:198. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409043/ http://www.ncbi.nlm.nih.gov/pubmed/22794349?tool=bestpractice.com [194]Weiss CH, Moazed F, McEvoy CA, et al. Prompting physicians to address a daily checklist and process of care and clinical outcomes: a single-site study. Am J Respir Crit Care Med. 2011 Sep 15;184(6):680-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3208596/ http://www.ncbi.nlm.nih.gov/pubmed/21616996?tool=bestpractice.com
Continue broad-spectrum coverage to include all common pathogens if the source is unknown or unclear.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Bear in mind that a definite source of infection cannot be found in 20% to 30% of people with sepsis.[9]Martin GS, Mannino DM, Moss M. The effect of age on the development and outcome of adult sepsis. Crit Care Med. 2006 Jan;34(1):15-21. http://www.ncbi.nlm.nih.gov/pubmed/16374151?tool=bestpractice.com
Use the shortest effective course of antibiotics.[195]National Institute for Health and Care Excellence. Antimicrobial stewardship: systems and processes for effective antimicrobial medicine use. August 2015 [internet publication]. https://www.nice.org.uk/guidance/NG15
Unnecessarily prolonged antibiotic treatment is associated with resistance. See More info: Antimicrobial resistance above.
Consult local microbiology guidance for other specific recommendations on de-escalation.
Most protocols will recommend switching from intravenous to oral antibiotics as soon as possible.
According to the Surviving Sepsis Campaign (SSC), most serious infections associated with sepsis and septic shock will need 7 to 10 days of antibiotic treatment.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com However, in practice, shorter courses of antibiotics are often appropriate.[196]De Santis V, Gresoiu M, Corona A, et al. Bacteraemia incidence, causative organisms and resistance patterns, antibiotic strategies and outcomes in a single university hospital ICU: continuing improvement between 2000 and 2013. J Antimicrob Chemother. 2015 Jan;70(1):273-8. https://academic.oup.com/jac/article/70/1/273/2911167 http://www.ncbi.nlm.nih.gov/pubmed/25190722?tool=bestpractice.com The optimal duration of antibiotic treatment in patients with sepsis remains contentious, with concerns regarding not only under-treatment but also the potential encouragement of antibiotic resistance. Consider seeking advice from microbiology/infectious disease colleagues.
The SSC guideline suggests considering shorter courses in some patients, particularly those with rapid clinical resolution following effective source control of intra-abdominal or urinary sepsis and those with anatomically uncomplicated pyelonephritis.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Longer courses of treatment may be appropriate in patients who have:[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
A slow clinical response
Undrainable foci of infection
Bacteraemia with Staphylococcus aureus
Some fungal and viral infections
Immunological deficiencies, including neutropenia.
Baseline serum procalcitonin is increasingly being used in critical care settings to guide decisions on how long to continue antibiotic therapy.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [105]Lam SW, Bauer SR, Fowler R, et al. Systematic review and meta-analysis of procalcitonin-guidance versus usual care for antimicrobial management in critically ill patients: focus on subgroups based on antibiotic initiation, cessation, or mixed strategies. Crit Care Med. 2018 May;46(5):684-90. http://www.ncbi.nlm.nih.gov/pubmed/29293146?tool=bestpractice.com [106]Akagi T, Nagata N, Wakamatsu K, et al. Procalcitonin-guided antibiotic discontinuation might shorten the duration of antibiotic treatment without increasing pneumonia recurrence. Am J Med Sci. 2019 Jul;358(1):33-44. http://www.ncbi.nlm.nih.gov/pubmed/31084909?tool=bestpractice.com [107]Christ-Crain M, Stolz D, Bingisser R, et al. Procalcitonin guidance significantly reduces antibiotic duration in community-acquired pneumonia: the 'ProCAP' study. Crit Care. 2005; 9 (Suppl 1):P166. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4098316/
Procalcitonin is a peptide precursor of calcitonin, which is responsible for calcium homeostasis.
It is currently excluded from key guidelines, but increasingly used in practice.
Treatment recommended for ALL patients in selected patient group
Ensure frequent and ongoing monitoring.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Standard monitoring of vital signs, pulse oximetry, level of consciousness, and urinary output is important for any patient with suspected sepsis.
The UK National Institute for Health and Care Excellence (NICE) recommends continuous or half-hourly monitoring (depending on setting) for any patient considered to be at high risk of deterioration (defined in the NICE guideline as meeting one or more of its high-risk criteria for severe illness or death from sepsis).[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
See the Risk stratification subsection of Diagnosis recommendations for more information.
Use a track-and-trigger scoring system such as the National Early Warning Score 2 (NEWS2) to identify any signs of deterioration.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 Your monitoring should include:
Vital signs: heart rate, blood pressure, oxygen saturations, respiratory rate, and temperature
Measure blood pressure via an arterial line if the patient does not respond to initial treatment or needs vasoactive drugs. It provides precise, continuous monitoring, and access for arterial blood sampling
Hourly urine output[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [46]Nutbeam T, Daniels R; The UK Sepsis Trust. Professional resources: clinical [internet publication]. https://sepsistrust.org/professional-resources/clinical/
Lactate
The lactate level should decrease if the patient is clinically improving
Frequency of repeat lactate measurement depends on the cause of sepsis and treatment given.
Measure serum lactate, on a blood gas, to monitor response to treatment.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [46]Nutbeam T, Daniels R; The UK Sepsis Trust. Professional resources: clinical [internet publication]. https://sepsistrust.org/professional-resources/clinical/
Lactate is a marker of stress and may be a marker of a worse prognosis (as a reflection of the degree of stress). Raised serum lactate highlights the possibility of tissue hypoperfusion and may be present in many conditions.[77]Garcia-Alvarez M, Marik P, Bellomo R. Sepsis-associated hyperlactatemia. Crit Care. 2014 Sep 9;18(5):503. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4421917/ http://www.ncbi.nlm.nih.gov/pubmed/25394679?tool=bestpractice.com [78]Kapoor D, Srivastava M, Singh P. Point of care blood gases with electrolytes and lactates in adult emergencies. Int J Crit Illn Inj Sci. 2014 Jul;4(3):216-22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200547/ http://www.ncbi.nlm.nih.gov/pubmed/25337483?tool=bestpractice.com
Lactate may normalise quickly after fluid resuscitation. Patients whose lactate levels fail to normalise after adequate fluids are the group that fare worst.
Lactate >4 mmol/L (>36 mg/dL) is associated with worse outcomes.
One study found in-hospital mortality rates as follows:[79]Trzeciak S, Dellinger RP, Chansky ME, et al. Serum lactate as a predictor of mortality in patients with infection. Intensive Care Med. 2007 Jun;33(6):970-7. http://www.ncbi.nlm.nih.gov/pubmed/17431582?tool=bestpractice.com
Lactate <2 mmol/L (<18 mg/dL): 15%
Lactate 2.1 to 3.9 mmol/L (19 to 35mg/dL): 25%
Lactate >4 mmol/L (>36 mg/dL): 38%.
Sepsis guidelines from NICE and NHS England recommend escalating treatment depending on lactate level.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf Alert critical care immediately if the patient is acutely unwell and has persistent lactate > 4 mmol/L (36 mg/dL)[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 despite fluid resuscitation.
Do not be falsely reassured by a normal lactate (<2 mmol/L [<18 mg/dL]).
This does not rule out the patient being acutely unwell or at risk of deterioration or death due to organ dysfunction. You must take into account the full clinical picture of the individual patient in front of you including their NEWS2 score.
Practical tip
Lactate is typically measured using a blood gas analyser, although laboratory analysis can also be performed.
Traditionally, arterial blood gas has been recommended as the ideal means of measuring lactate accurately. However, in the emergency department setting it is more practical and quicker to use venous blood gas, which is recommended by NICE.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 Evidence suggests good agreement at lactate levels <2 mmol/L (<18 mg/dL) with small disparities at higher lactate levels.[80]Middleton P, Kelly AM, Brown J, et al. Agreement between arterial and central venous values for pH, bicarbonate, base excess, and lactate. Emerg Med J. 2006 Aug;23(8):622-4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2564165/ http://www.ncbi.nlm.nih.gov/pubmed/16858095?tool=bestpractice.com [81]Theerawit P, Na Petvicharn C, Tangsujaritvijit V, et al. The correlation between arterial lactate and venous lactate in patients with sepsis and septic shock. J Intensive Care Med. 2018 Feb;33(2):116-20. http://www.ncbi.nlm.nih.gov/pubmed/27502951?tool=bestpractice.com [82]Bloom B, Pott J, Freund Y, et al. The agreement between abnormal venous lactate and arterial lactate in the ED: a retrospective chart review. Am J Emerg Med. 2014 Jun;32(6):596-600. http://www.ncbi.nlm.nih.gov/pubmed/24745873?tool=bestpractice.com
The best available evidence supports lactate clearance (the rate at which lactate is cleared over a period of 6 hours) as being as useful as more invasive tests, such as central venous oxygen saturation (ScvO2), in determining a patient’s response to treatment.[197]Nguyen HB, Rivers EP, Knoblich BP, et al. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med. 2004 Aug;32(8):1637-42. http://www.ncbi.nlm.nih.gov/pubmed/15286537?tool=bestpractice.com [198]Jones AE, Shapiro NI, Trzeciak S, et al. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010 Feb 24;303(8):739-46. http://jama.ama-assn.org/content/303/8/739.long http://www.ncbi.nlm.nih.gov/pubmed/20179283?tool=bestpractice.com [199]Arnold RC, Shapiro NI, Jones AE, et al. Multicenter study of early lactate clearance as a determinant of survival in patients with presumed sepsis. Shock. 2009 Jul;32(1):35-9. http://www.ncbi.nlm.nih.gov/pubmed/19533847?tool=bestpractice.com [200]Marty P, Roquilly A, Vallée F, et al. Lactate clearance for death prediction in severe sepsis or septic shock patients during the first 24 hours in intensive care unit: an observational study. Ann Intensive Care. 2013 Feb 12;3(1):3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614435/ http://www.ncbi.nlm.nih.gov/pubmed/23398782?tool=bestpractice.com [201]Puskarich MA, Trzeciak S, Shapiro NI, et al. Whole blood lactate kinetics in patients undergoing quantitative resuscitation for severe sepsis and septic shock. Chest. 2013 Jun;143(6):1548-53. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3673659/ http://www.ncbi.nlm.nih.gov/pubmed/23740148?tool=bestpractice.com [202]Walker CA, Griffith DM, Gray AJ, et al. Early lactate clearance in septic patients with elevated lactate levels admitted from the emergency department to intensive care: time to aim higher? J Crit Care. 2013 Oct;28(5):832-7. http://www.ncbi.nlm.nih.gov/pubmed/23602032?tool=bestpractice.com
In one study that looked at patients with septic shock who were treated to normalise central venous and mean arterial pressure, additional management to normalise lactate clearance compared with additional management to normalise ScvO2 did not result in significantly different in-hospital mortality.[198]Jones AE, Shapiro NI, Trzeciak S, et al. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010 Feb 24;303(8):739-46. http://jama.ama-assn.org/content/303/8/739.long http://www.ncbi.nlm.nih.gov/pubmed/20179283?tool=bestpractice.com
Of 300 patients enrolled, 150 were assigned to each group and patients were well matched by demographics, comorbidities, and physiological features. There were no differences in treatments administered during the initial 72 hours of hospitalisation.
Thirty-four patients (23%) in the ScvO2 group died while in hospital (95% CI 17% to 30%) compared with 25 (17%, 95% CI 11% to 24%) in the lactate clearance group. This observed difference between mortality rates did not reach the predefined -10% threshold (intent-to-treat analysis: 95% CI for the 6% difference, -3% to 15%). There were no differences in treatment-related adverse events between the groups.
Several trials have assessed the diagnostic accuracy of percentage lactate clearance over 0 to 6 hours. It is worth noting that these studies provide very low-quality evidence, owing mainly to a presumed lack of blinding of treating physicians to the patient’s lactate status.
The studies’ findings agree that lactate clearance early in the hospital course is associated with decreased mortality rate. Patients with higher lactate clearance after 6 hours of emergency department intervention had improved outcomes compared with those with lower lactate clearance.[197]Nguyen HB, Rivers EP, Knoblich BP, et al. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med. 2004 Aug;32(8):1637-42. http://www.ncbi.nlm.nih.gov/pubmed/15286537?tool=bestpractice.com [199]Arnold RC, Shapiro NI, Jones AE, et al. Multicenter study of early lactate clearance as a determinant of survival in patients with presumed sepsis. Shock. 2009 Jul;32(1):35-9. http://www.ncbi.nlm.nih.gov/pubmed/19533847?tool=bestpractice.com [200]Marty P, Roquilly A, Vallée F, et al. Lactate clearance for death prediction in severe sepsis or septic shock patients during the first 24 hours in intensive care unit: an observational study. Ann Intensive Care. 2013 Feb 12;3(1):3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614435/ http://www.ncbi.nlm.nih.gov/pubmed/23398782?tool=bestpractice.com [201]Puskarich MA, Trzeciak S, Shapiro NI, et al. Whole blood lactate kinetics in patients undergoing quantitative resuscitation for severe sepsis and septic shock. Chest. 2013 Jun;143(6):1548-53. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3673659/ http://www.ncbi.nlm.nih.gov/pubmed/23740148?tool=bestpractice.com [202]Walker CA, Griffith DM, Gray AJ, et al. Early lactate clearance in septic patients with elevated lactate levels admitted from the emergency department to intensive care: time to aim higher? J Crit Care. 2013 Oct;28(5):832-7. http://www.ncbi.nlm.nih.gov/pubmed/23602032?tool=bestpractice.com
In the UK, use physiological track-and-trigger systems to monitor all adult patients in acute hospital settings.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Consider using a validated scale such as the Glasgow Coma Scale or AVPU ('Alert, responds to Voice, responds to Pain, Unresponsive') scale to monitor the mental state of a patient with suspected sepsis.[ Glasgow Coma Scale ][3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Practical tip
AVPU should raise concerns if the assessment shows the patient is anything other than 'alert'.
Any patient with sepsis may be at significant risk of severe illness or death so it is vital to consider escalation of care to senior colleagues and/or healthcare facilities where increased and more advanced monitoring can be given (e.g., high-dependency unit/intensive care unit).[7]Rhee C, Jones TM, Hamad Y, et al. Prevalence, underlying causes, and preventability of sepsis-associated mortality in us acute care hospitals. JAMA Netw Open. 2019 Feb 1;2(2):e187571. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484603/ http://www.ncbi.nlm.nih.gov/pubmed/30768188?tool=bestpractice.com [170]NHS England. Improving outcomes for patients with sepsis: a cross-system action plan. December 2015 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2015/08/Sepsis-Action-Plan-23.12.15-v1.pdf [171]McPherson D, Griffiths C, Williams M, et al. Sepsis-associated mortality in England: an analysis of multiple cause of death data from 2001 to 2010. BMJ Open. 2013 Aug 2;3(8). http://bmjopen.bmj.com/content/3/8/e002586 http://www.ncbi.nlm.nih.gov/pubmed/23913771?tool=bestpractice.com
Bear in mind that some patients (e.g., those who are frail) may not be suitable for management in intensive care settings. Consider the patient’s baseline health including their resuscitation status when determining the limits of treatment. Use this to feed into a personalised care plan appropriate to the individual patient.
Consult local protocols for specific escalation routes but in general:
Ensure immediate review by a senior clinician (CT3/ST3 or higher in the UK) of any patient with a NEWS2 score of 5 or more, or who meets one or more of the NICE sepsis high-risk criteria. Also ensure the patient is discussed with a consultant[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf
Discuss with the admitting consultant[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 and consider alerting critical care immediately if the patient is acutely unwell and:
Has a NEWS2 score of 7 or more, persisting high lactate (more than 4 mmol/L [36 mg/dL]) despite fluid resuscitation, or a systolic blood pressure of less than 90 mmHg[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Discuss with the admitting consultant[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Has hypotension that doesn’t respond to initial fluid resuscitation
Is likely to require central venous access and the initiation of inotropes or vasopressors[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Has any feature of septic shock
See our topic Shock
Has neutropenia
See our topic Febrile neutropenia
Is immunodeficient
Urgently discuss with a consultant or call them to attend if the patient:[41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf
Is treated with intravenous antibiotics and/or a fluid bolus for sepsis
Does not respond to initial therapy (antibiotics/fluid resuscitation/oxygen) within the first hour.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf Failure to respond to treatment is defined as:[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Systolic blood pressure remains less than 90 mmHg
Persistent reduced level of consciousness
Respiratory rate more than 25 breaths per minute or the new need for mechanical ventilation
Lactate has not reduced by more than 20%
Refer to critical care any patient who is likely to require central venous access and initiation of inotropes or vasopressors[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
This includes any patient with evidence of circulatory dysfunction or shock, or those who do not respond to initial therapy (as outlined above)
ECG can be used to determine which vasoactive drug(s) to proceed with in critical care.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Practical tip
Ensure a clear escalation plan has been discussed and agreed with the clinical team; include specific points of contact for nursing staff if you are leaving a patient for later review.
Involve a senior colleague and/or consider transferring to critical care sooner rather than later if the patient is not improving, or deemed high-risk. Examples include if the patient:
Is not responding to fluids
Needs inotropic support
Has a low Glasgow Coma Scale score
Needs ventilatory support.
Treatment recommended for ALL patients in selected patient group
Make intensive efforts to identify the anatomical site of infection as soon as possible.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com Consider the need for urgent source control as soon as the patient is stable.
Start with a thorough and focused clinical history and examination, as well as initial investigations including imaging.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Consider all lines and catheters as potential sources. Take cultures from the line tip. Remove lines where appropriate.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Assume that any intravenous route is likely to either be the source of the infection, or will seed infections in the bloodstream, making eradication particularly difficult. Therefore, the priority for source control is often to remove any intravenous devices after vascular access has been obtained.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
If you suspect an abdominal or pelvic source, involve the relevant surgical team early, particularly if surgery is likely.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
In practice, this may mean early transfer of the patient to a surgical centre if there are no facilities at your hospital.
Common non-specific signs and symptoms include:[21]Gauer RL. Early recognition and management of sepsis in adults: the first six hours. Am Fam Physician. 2013 Jul 1;88(1):44-53. http://www.ncbi.nlm.nih.gov/pubmed/23939605?tool=bestpractice.com [43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Those associated with a specific source of infection. Signs and symptoms of possible infection sources external link opens in a new window The most common sources are:[60]National Confidential Enquiry into Patient Outcome and Death. Just say sepsis! A review of the process of care received by patients with sepsis. November 2015 [internet publication]. https://www.ncepod.org.uk/2015report2/downloads/JustSaySepsis_FullReport.pdf
Respiratory tract (cough/pleuritic chest pain)
Urinary tract (flank pain/dysuria)
Abdominal/upper gastrointestinaI tract (abdominal pain)
Skin/soft tissue (abscess/wound/catheter site)
Surgical site or line/drain site
Tachypnoea
High (>38°C [>100.4°F]) or low (<36°C [<96.8°F]) temperature, sometimes with rigors
Tachycardia
Acutely altered mental status
Low oxygen saturation
Hypotension
Decreased urine output
Ask the patient when they last passed urine
Poor capillary refill, mottling of the skin, or ashen appearance
Cyanosis
Malaise/lethargy
Nausea/vomiting/diarrhoea
Purpura fulminans (a very late sign but may be seen on presentation)
Ileus
Jaundice.
Practical tip
Jaundice is a rare sign of sepsis unless it is associated with a specific source of infection (biliary sepsis).
[Figure caption and citation for the preceding image starts]: Capillary refill time. Top image: normal skin tone; middle image: pressure applied for 5 seconds; bottom image: time to hyperaemia measuredFrom the collection of Ron Daniels, MB, ChB, FRCA; used with permission [Citation ends].
[Figure caption and citation for the preceding image starts]: Severe purpura fulminans; classically associated with meningococcal sepsis but can occur with pneumococcal sepsisFrom the collection of Ron Daniels, MB, ChB, FRCA; used with permission [Citation ends].
If your examination of the patient identifies a clear source of infection, consider the need for urgent source control, as soon as the patient is stable, particularly for:[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Gastrointestinal sources (such as visceral abscesses, cholangitis, or peritonitis secondary to perforation)
Severe skin infections (e.g., necrotising fasciitis)
Infection involving an indwelling device, where a procedure or surgery is likely to be required.
Give immediate, targeted antibiotics in people with sepsis thought to arise from a central nervous system source (e.g., suspected meningitis or meningococcal sepsis).[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Immediately give a third-generation cephalosporin such as ceftriaxone or cefotaxime.
In community settings, pre-hospital administration of benzylpenicillin is recommended.
Follow local policy and consider discussing with microbiology/infectious disease colleagues to determine the most appropriate choice; use a 'start smart then focus' approach.[41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf [136]Public Health England. Antimicrobial stewardship: start smart – then focus. March 2015 [internet publication]. https://www.gov.uk/government/publications/antimicrobial-stewardship-start-smart-then-focus
Practical tip
If intravenous access is not feasible or is likely to lead to a delay in starting antibiotics and fluids, use intra-osseous access as an interim measure.
Treatment recommended for SOME patients in selected patient group
Give 500 mL of crystalloid fluid, with a sodium content between 130 mmol/L and 154 mmol/L (130 to 154 mEq/L) (e.g., 0.9% sodium chloride or Hartmann’s solution), over less than 15 minutes to patients who need fluid resuscitation (if there is any sign of circulatory insufficiency).[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf [66]National Institute for Health and Care Excellence. Intravenous fluid therapy in adults in hospital. May 2017 [internet publication]. https://www.nice.org.uk/guidance/cg174
Reassess the patient’s haemodynamic status after the first bolus to consider whether a second is required.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 If there is no response to either the first or second bolus, seek senior support.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Intravenous fluid resuscitation may be lifesaving in patients with hypotension. This is because in sepsis there is vasodilation and capillary leakage, which means that patients can rapidly become intravascularly deplete.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
In patients with sepsis-induced hypoperfusion (as indicated by a systolic blood pressure <90 mmHg, a raised lactate level, or signs of organ dysfunction), the Surviving Sepsis Campaign international guideline recommends a total of at least 30 mL/kg of intravenous crystalloid over the first 3 hours.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
If the patient’s initial lactate level is raised, the guideline recommends serial lactate measurements to guide the need for further intravenous fluids (with the goal of normalising lactate levels).[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Practical tip
The delivery of appropriate rapid fluid challenges is intended to restore the imbalance between oxygen supply and demand to the tissues. Patients who do not respond to rapid delivery of adequate volumes of intravenous fluids are in septic shock and need immediate referral to critical care. The immediate priority in this group of patients is to restore the circulation and oxygen delivery.
Practical tip
Monitor patients closely for signs of fluid overload such as pulmonary or systemic oedema before and after each additional fluid bolus, as they may require large volumes of fluid to support their circulating volume.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [152]Schuller D, Mitchell JP, Calandrino FS, et al. Fluid balance during pulmonary edema: is fluid gain a marker or a cause of poor outcome? Chest. 1991 Oct;100(4):1068-75. http://www.ncbi.nlm.nih.gov/pubmed/1914560?tool=bestpractice.com [153]National Institute for Health and Care Excellence. Neutropenic sepsis: prevention and management in people with cancer. September 2012 [internet publication]. https://www.nice.org.uk/guidance/cg151
Latest evidence suggests a balanced crystalloid may have marginal benefits over saline, but either option is a reasonable choice.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [154]Semler MW, Self WH, Wanderer JP, et al. Balanced crystalloids versus saline in critically ill adults. N Engl J Med. 2018 Mar 1;378(9):829-39. http://www.ncbi.nlm.nih.gov/pubmed/29485925?tool=bestpractice.com
Although early fluid resuscitation is a cornerstone of sepsis treatment that is given high priority by both Sepsis Six and the UK National Institute for Health and Care Excellence, choice of fluid has been the source of much discussion. In particular, there has been extensive debate over the choice between a balanced crystalloid (such as Hartmann’s solution, Ringer’s lactate, or PlasmaLyte) and normal saline (an unbalanced crystalloid). There have been very few high-quality studies, but latest evidence from critically ill patients points to marginal benefits from using a balanced crystalloid in preference to saline.[154]Semler MW, Self WH, Wanderer JP, et al. Balanced crystalloids versus saline in critically ill adults. N Engl J Med. 2018 Mar 1;378(9):829-39. http://www.ncbi.nlm.nih.gov/pubmed/29485925?tool=bestpractice.com
A 2018 US multicentre cluster-randomised trial among 15,802 critically ill adults receiving care in the intensive care unit found small benefits from balanced crystalloid compared with saline. The 30-day outcomes showed 10.3% mortality in the balanced crystalloid group compared with 11.1% in the saline group (P = 0.06), and a major adverse kidney event rate of 14.3% compared with 15.4% in the two groups, respectively (marginal odds ratio 0.91, 95% CI 0.84 to 0.99).[154]Semler MW, Self WH, Wanderer JP, et al. Balanced crystalloids versus saline in critically ill adults. N Engl J Med. 2018 Mar 1;378(9):829-39. http://www.ncbi.nlm.nih.gov/pubmed/29485925?tool=bestpractice.com
Colloids (e.g., starches, dextrans, gelatins, albumin, or fresh frozen plasma) are no longer used in emergency medicine in the UK.
Studies have not shown benefits from early goal-directed therapy and your focus should instead be on adjusting treatment according to i) lactate level and ii) clinical assessment of the patient’s haemodynamic response to initial fluids.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [155]Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77. http://www.nejm.org/doi/full/10.1056/NEJMoa010307#t=article http://www.ncbi.nlm.nih.gov/pubmed/11794169?tool=bestpractice.com [156]ARISE Investigators; ANZICS Clinical Trials Group; Peake SL, Delaney A, Bailey M, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014 Oct 16;371(16):1496-506. http://www.nejm.org/doi/full/10.1056/NEJMoa1404380#t=article http://www.ncbi.nlm.nih.gov/pubmed/25272316?tool=bestpractice.com [157]ProCESS Investigators; Yealy DM, Kellum JA, Huang DT, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014 May 1;370(18):1683-93. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101700/ http://www.ncbi.nlm.nih.gov/pubmed/24635773?tool=bestpractice.com [158]Mouncey PR, Osborn TM, Power GS, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015 Apr 2;372(14):1301-11. http://www.nejm.org/doi/full/10.1056/NEJMoa1500896#t=article http://www.ncbi.nlm.nih.gov/pubmed/25776532?tool=bestpractice.com [159]Levy MM, Dellinger RP, Townsend SR, et al. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med. 2010 Feb;36(2):222-31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826633/ http://www.ncbi.nlm.nih.gov/pubmed/20069275?tool=bestpractice.com [160]Levy MM, Rhodes A, Phillips GS, et al. Surviving Sepsis Campaign: association between performance metrics and outcomes in a 7.5-year study. Crit Care Med. 2015 Jan;43(1):3-12. http://www.ncbi.nlm.nih.gov/pubmed/25275252?tool=bestpractice.com
Previous versions of the Surviving Sepsis Campaign (SSC) guidelines recommended a protocoled approach to resuscitation, otherwise known as early goal-directed therapy (EGDT).[161]Dellinger RP, Carlet JM, Masur H, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Intensive Care Med. 2004 Apr;30(4):536-55. http://www.ncbi.nlm.nih.gov/pubmed/14997291?tool=bestpractice.com [162]Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008 Jan;36(1):296-327. http://www.ncbi.nlm.nih.gov/pubmed/18158437?tool=bestpractice.com [163]Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013 Feb;41(2):580-637. http://www.ncbi.nlm.nih.gov/pubmed/23353941?tool=bestpractice.com EGDT involves the use of a series of 'goals' including central venous pressure and central venous oxygen saturation (ScvO2). This recommendation was largely based on data from one study that showed a significant survival benefit for patients receiving EGDT.[155]Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77. http://www.nejm.org/doi/full/10.1056/NEJMoa010307#t=article http://www.ncbi.nlm.nih.gov/pubmed/11794169?tool=bestpractice.com
This approach has since been challenged following the failure to show a mortality reduction in three subsequent large multicentre randomised controlled trials: PROCESS, ARISE, and PROMISE.[156]ARISE Investigators; ANZICS Clinical Trials Group; Peake SL, Delaney A, Bailey M, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014 Oct 16;371(16):1496-506. http://www.nejm.org/doi/full/10.1056/NEJMoa1404380#t=article http://www.ncbi.nlm.nih.gov/pubmed/25272316?tool=bestpractice.com [157]ProCESS Investigators; Yealy DM, Kellum JA, Huang DT, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014 May 1;370(18):1683-93. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101700/ http://www.ncbi.nlm.nih.gov/pubmed/24635773?tool=bestpractice.com [158]Mouncey PR, Osborn TM, Power GS, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015 Apr 2;372(14):1301-11. http://www.nejm.org/doi/full/10.1056/NEJMoa1500896#t=article http://www.ncbi.nlm.nih.gov/pubmed/25776532?tool=bestpractice.com
It is worth bearing in mind that these three trials included patients who were less severely ill (lower baseline lactate levels, ScvO2 at or above the target value on admission, and lower mortality in the control group) than the patients in the original study that outlined EDGT as a recommended approach.
Based on this latest evidence, the SSC no longer specifically recommends EDGT; it does, however, acknowledge the need for guidance on how to approach this group of patients who have significant mortality and morbidity.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com The SSC therefore recommends that you:[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
View these patients as having a medical emergency that necessitates urgent assessment and treatment
Begin initial fluid resuscitation with 30 mL/kg of crystalloid within the first 3 hours
This fixed volume of fluid enables initiation of resuscitation while giving an opportunity to ascertain more specific information about the patient and while awaiting more precise measurements of haemodynamic status
Although scant data are available to support this volume of fluid, interventional studies have described this as usual practice in the early stages of resuscitation, and observational evidence supports the practice[159]Levy MM, Dellinger RP, Townsend SR, et al. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med. 2010 Feb;36(2):222-31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826633/ http://www.ncbi.nlm.nih.gov/pubmed/20069275?tool=bestpractice.com [160]Levy MM, Rhodes A, Phillips GS, et al. Surviving Sepsis Campaign: association between performance metrics and outcomes in a 7.5-year study. Crit Care Med. 2015 Jan;43(1):3-12. http://www.ncbi.nlm.nih.gov/pubmed/25275252?tool=bestpractice.com
The average volume of fluid pre-randomisation given was approximately 30 mL/kg in the PROCESS and ARISE trials, and approximately 2 L in the PROMISE trial.[156]ARISE Investigators; ANZICS Clinical Trials Group; Peake SL, Delaney A, Bailey M, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014 Oct 16;371(16):1496-506. http://www.nejm.org/doi/full/10.1056/NEJMoa1404380#t=article http://www.ncbi.nlm.nih.gov/pubmed/25272316?tool=bestpractice.com [157]ProCESS Investigators; Yealy DM, Kellum JA, Huang DT, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014 May 1;370(18):1683-93. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101700/ http://www.ncbi.nlm.nih.gov/pubmed/24635773?tool=bestpractice.com [158]Mouncey PR, Osborn TM, Power GS, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015 Apr 2;372(14):1301-11. http://www.nejm.org/doi/full/10.1056/NEJMoa1500896#t=article http://www.ncbi.nlm.nih.gov/pubmed/25776532?tool=bestpractice.com The SSC acknowledges that many patients will need more fluid than this, and advocates giving further fluid to this group in line with functional haemodynamic measurements.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
The UK National Institute for Health and Care Excellence guideline on sepsis focuses on initial management and treatment, and therefore makes no recommendations regarding intensive monitoring such as that used in EGDT.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Practical tip
To guide the need for further intravenous fluids, it can sometimes be helpful to use bedside ultrasound to monitor changes in inferior vena cava (IVC) diameter during respiration.[164]Feissel M, Michard F, Faller JP, et al. The respiratory variation in inferior vena cava diameter as a guide to fluid therapy. Intensive Care Med. 2004 Sep;30(9):1834-7. http://www.ncbi.nlm.nih.gov/pubmed/15045170?tool=bestpractice.com [165]Barbier C, Loubières Y, Schmit C, et al. Respiratory changes in inferior vena cava diameter are helpful in predicting fluid responsiveness in ventilated septic patients. Intensive Care Med. 2004 Sep;30(9):1740-6. http://www.ncbi.nlm.nih.gov/pubmed/15034650?tool=bestpractice.com
In the spontaneously breathing patient: consider additional fluid resuscitation if there is a collapsed (or collapsing) IVC.
In the mechanically ventilated patient: an increase in IVC size >18% (or visible to the naked eye) with positive pressure ventilation suggests fluid-responsiveness.
Practical tip
Use the passive leg-raising test to predict fluid-responsiveness if adequate monitoring is available.[66]National Institute for Health and Care Excellence. Intravenous fluid therapy in adults in hospital. May 2017 [internet publication]. https://www.nice.org.uk/guidance/cg174 [166]Monnet X, Teboul JL. Passive leg raising: five rules, not a drop of fluid! Crit Care. 2015 Jan 14;19:18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4293822/ http://www.ncbi.nlm.nih.gov/pubmed/25658678?tool=bestpractice.com
This is a useful indicator of fluid-responsiveness, which should be assessed using devices that can continuously monitor cardiac output in real time (e.g., Pulse index Continuous Cardiac Output [PiCCO] monitor or oesophageal Doppler), usually in an intensive care unit rather than a general ward setting.
Sit the patient upright at 45° and tilt the entire bed through 45°.
Patients with a positive test have a >10% increase in cardiac output or stroke volume, indicating more fluids may be required.
The passive leg-raise response may be misleading in conscious patients who are uncomfortable or in pain when lying flat.
Treatment recommended for SOME patients in selected patient group
If indicated, give oxygen to maintain target oxygen saturations >94%.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [46]Nutbeam T, Daniels R; The UK Sepsis Trust. Professional resources: clinical [internet publication]. https://sepsistrust.org/professional-resources/clinical/ [47]O'Driscoll BR, Howard LS, Earis J, et al. 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 Latest evidence suggests that liberal use of supplemental oxygen (target SpO2 >96%) in acutely ill adults is associated with higher mortality than more conservative oxygen therapy.[138]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 Therefore, a reasonable approach in practice is to maintain a target oxygen saturation of 94% to 96% in acutely ill patients who are not at risk of hypercapnia.
Target saturation of 88% to 92% if the patient is at risk of hypercapnic respiratory failure (e.g., patients with COPD).[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [46]Nutbeam T, Daniels R; The UK Sepsis Trust. Professional resources: clinical [internet publication]. https://sepsistrust.org/professional-resources/clinical/ [47]O'Driscoll BR, Howard LS, Earis J, et al. 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
Too much supplemental oxygen increases mortality.
Latest evidence supports a 96% upper limit for target oxygen saturation in non-hypercapnic acutely ill adults.
Guidelines differ in their recommendations on target oxygen saturation in acutely unwell adults who are receiving supplemental oxygen. The 2017 British Thoracic Society guideline recommends a target SpO2 range of 94% to 98% for patients not at risk of hypercapnia,[47]O'Driscoll BR, Howard LS, Earis J, et al. 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 whereas the 2015 Thoracic Society of Australia and New Zealand guideline recommends 92% to 96%.[167]Beasley R, Chien J, Douglas J, et al. Thoracic Society of Australia and New Zealand oxygen guidelines for acute oxygen use in adults: 'swimming between the flags'. Respirology. 2015 Nov;20(8):1182-91. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4654337/ http://www.ncbi.nlm.nih.gov/pubmed/26486092?tool=bestpractice.com
A 2018 systematic review including a meta-analysis of data from 25 randomised controlled trials found that in adults with acute illness, liberal oxygen therapy (broadly equivalent to a target saturation >96%) is associated with higher mortality than conservative oxygen therapy (broadly equivalent to a target saturation ≤96%).[138]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 In-hospital mortality was 11 per 1000 higher for the liberal oxygen therapy group versus the conservative therapy group (95% CI 2-22 per 1000 more). Mortality at 30 days was also higher in the group who had received liberal oxygen (risk ratio 1.14, 95% CI 1.01 to 1.29). The trials included adults with sepsis, critical illness, stroke, trauma, myocardial infarction, and cardiac arrest, and patients who had emergency surgery. Studies that were limited to people with chronic respiratory illness or psychiatric illness, patients on extracorporeal life support, patients receiving hyperbaric oxygen therapy, or those having elective surgery were all excluded from the review.
An upper SpO2 limit of 96% is therefore reasonable when administering supplemental oxygen to medical patients with acute illness who are not at risk of hypercapnia. However, a higher target may be appropriate for some specific conditions (e.g., pneumothorax, carbon monoxide poisoning, cluster headache, and sickle cell crisis).[168]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
There is no specific evidence to show that giving oxygen improves clinical outcomes in sepsis. However, respiratory failure will lead to tissue hypoxia and anaerobic respiration. This is likely to lead to acidosis and consequently a poorer outcome.[169]Kellum JA. Metabolic acidosis in patients with sepsis: epiphenomenon or part of the pathophysiology? Crit Care Resusc. 2004 Sep;6(3):197-203. http://www.ncbi.nlm.nih.gov/pubmed/16556122?tool=bestpractice.com
Treatment recommended for SOME patients in selected patient group
Any patient with sepsis may be at significant risk of severe illness or death so it is vital to consider escalation of care to senior colleagues and/or healthcare facilities where increased and more advanced monitoring can be given (e.g., high-dependency unit/intensive care unit).[7]Rhee C, Jones TM, Hamad Y, et al. Prevalence, underlying causes, and preventability of sepsis-associated mortality in us acute care hospitals. JAMA Netw Open. 2019 Feb 1;2(2):e187571. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484603/ http://www.ncbi.nlm.nih.gov/pubmed/30768188?tool=bestpractice.com [170]NHS England. Improving outcomes for patients with sepsis: a cross-system action plan. December 2015 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2015/08/Sepsis-Action-Plan-23.12.15-v1.pdf [171]McPherson D, Griffiths C, Williams M, et al. Sepsis-associated mortality in England: an analysis of multiple cause of death data from 2001 to 2010. BMJ Open. 2013 Aug 2;3(8). http://bmjopen.bmj.com/content/3/8/e002586 http://www.ncbi.nlm.nih.gov/pubmed/23913771?tool=bestpractice.com
Bear in mind that some patients (e.g., those who are frail) may not be suitable for management in intensive care settings. Consider the patient’s baseline health including their resuscitation status when determining the limits of treatment. Use this to feed into a personalised care plan appropriate to the individual patient.
Consult local protocols for specific escalation routes but in general:
Ensure immediate review by a senior clinician (CT3/ST3 or higher in the UK) of any patient with a National Early Warning Score 2 (NEWS2) score of 5 or more, or who meets one or more of the UK National Institute for Health and Care Excellence sepsis high-risk criteria. Also ensure the patient is discussed with a consultant[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf
Discuss with the admitting consultant[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 and consider alerting critical care immediately if the patient is acutely unwell and:
Has a NEWS2 score of 7 or more, persisting high lactate (more than 4 mmol/L [36 mg/dL]) despite fluid resuscitation, or a systolic blood pressure of less than 90 mmHg[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Discuss with the admitting consultant[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Has hypotension that doesn’t respond to initial fluid resuscitation
Is likely to require central venous access and the initiation of inotropes or vasopressors
Has any feature of septic shock
See our topic Shock
Has neutropenia
See our topic Febrile neutropenia
Is immunodeficient
Urgently discuss with a consultant or call them to attend if the patient:[41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf
Is treated with intravenous antibiotics and/or a fluid bolus for sepsis
Does not respond to initial therapy (antibiotics/fluid resuscitation/oxygen) within the first hour.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf Failure to respond to treatment is defined as:[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Systolic blood pressure remains less than 90 mmHg
Persistent reduced level of consciousness
Respiratory rate more than 25 breaths per minute or the new need for mechanical ventilation
Lactate has not reduced by more than 20%
Refer to critical care any patient who is likely to require central venous access and initiation of inotropes or vasopressors[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
This includes any patient with evidence of circulatory dysfunction or shock, or those who do not respond to initial therapy (as outlined above)
ECG can be used to determine which vasoactive drugs(s) to proceed with in critical care.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Practical tip
Ensure a clear escalation plan has been discussed and agreed with the clinical team; include specific points of contact for nursing staff if you are leaving a patient for later review.
Involve a senior colleague and/or consider transferring to critical care sooner rather than later if the patient is not improving, or deemed high-risk. Examples include if the patient:
Is not responding to fluids
Needs inotropic support
Has a low Glasgow Coma Scale score
Needs ventilatory support.
For any patient with suspected sepsis, consider the need for referral to a high-dependency unit for management by the critical care team.[155]Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77. http://www.nejm.org/doi/full/10.1056/NEJMoa010307#t=article http://www.ncbi.nlm.nih.gov/pubmed/11794169?tool=bestpractice.com [174]Hollenberg SM, Ahrens TS, Annane D, et al. Practice parameters for hemodynamic support of sepsis in adult patients; 2004 update. Crit Care Med. 2004 Sep;32(9):1928-48. http://www.ncbi.nlm.nih.gov/pubmed/15343024?tool=bestpractice.com
The following interventions should only be initiated by experienced members of the critical care team:[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [175]Rivers PE, McIntyre L, Morro DC, et al. Early and innovative interventions for severe sepsis and septic shock: taking advantage of a window of opportunity. CMAJ. 2005 Oct 25;173(9):1054-65. http://www.cmaj.ca/cgi/content/full/173/9/1054 http://www.ncbi.nlm.nih.gov/pubmed/16247103?tool=bestpractice.com
Glycaemic control
Vasoactive drugs (vasopressors/inotropes)
Corticosteroids.
Additional intensive care measures that will be considered include:[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [176]Trzeciak S, Dellinger RP. Other supportive therapies in sepsis: an evidence-based review. Crit Care Med. 2004 Nov;32(suppl 11):S571-7. http://www.ncbi.nlm.nih.gov/pubmed/15542966?tool=bestpractice.com [177]Nguyen HB, Rivers EP, Abrahamian FM, et al. Severe sepsis and septic shock: review of the literature and emergency department management guidelines. Ann Emerg Med. 2006 Jul;48(1):28-54. http://www.ncbi.nlm.nih.gov/pubmed/16781920?tool=bestpractice.com
Stress ulcer prophylaxis (in people at risk of gastrointestinal bleeding)
With an H2 antagonist or proton-pump inhibitor
Deep venous thrombosis prophylaxis
With heparin and compression stockings
Enteral or parenteral nutrition
Administration of human albumin solution 4% to 5% in patients with sepsis and shock[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com who have not responded to substantial volumes of crystalloids
Transfusion of packed cells
Consult local protocols for recommended threshold
The Surviving Sepsis Campaign recommends using a threshold of 70 g/L (7 g/dL).[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Studies in the general critical care population have shown no improvement with blood transfusions given at a higher haemoglobin threshold compared with a lower haemoglobin threshold,[178]Holst LB, Haase N, Wetterslev J, et al; TRISS Trial Group; Scandinavian Critical Care Trials Group. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014 Oct 9;371(15):1381-91. http://www.nejm.org/doi/full/10.1056/NEJMoa1406617#t=article http://www.ncbi.nlm.nih.gov/pubmed/25270275?tool=bestpractice.com and have shown potential harm associated with liberal transfusion.[179]Hébert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med. 1999 Feb 11;340(6):409-17. http://www.nejm.org/doi/full/10.1056/NEJM199902113400601#t=articleTop http://www.ncbi.nlm.nih.gov/pubmed/9971864?tool=bestpractice.com
One multicentre parallel group randomised trial analysed data from 998 patients with septic shock, split into two intervention groups with similar baseline characteristics. In the intensive care unit, the group assigned to blood transfusion at a lower haemoglobin threshold received a median of 1 unit of blood (interquartile range, 0 to 3) and the group assigned to blood transfusion at a higher haemoglobin threshold received a median of 4 units (interquartile range, 2 to 7).[178]Holst LB, Haase N, Wetterslev J, et al; TRISS Trial Group; Scandinavian Critical Care Trials Group. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014 Oct 9;371(15):1381-91. http://www.nejm.org/doi/full/10.1056/NEJMoa1406617#t=article http://www.ncbi.nlm.nih.gov/pubmed/25270275?tool=bestpractice.com
At 90 days after randomisation, 216 of 502 patients (43.0%) assigned to the lower-threshold group, compared with 223 of 496 (45.0%) assigned to the higher-threshold group, had died (relative risk 0.94, 95% CI 0.78 to 1.09; P = 0.44).
The results were similar in analyses adjusted for risk factors at baseline and in analyses of the per-protocol populations.
The numbers of patients who had ischaemic events, who had severe adverse reactions, and who required life support were similar in the two intervention groups.
A second multicentre randomised controlled trial compared the rates of death from all causes at 30 days and the severity of organ dysfunction in 838 critically ill patients receiving a restrictive strategy of red-cell transfusion compared with those receiving a liberal strategy.[179]Hébert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med. 1999 Feb 11;340(6):409-17. http://www.nejm.org/doi/full/10.1056/NEJM199902113400601#t=articleTop http://www.ncbi.nlm.nih.gov/pubmed/9971864?tool=bestpractice.com
Overall, 30-day mortality was similar in the two groups (18.7% vs. 23.3%, P = 0.11).
However, the rates were significantly lower with the restrictive transfusion strategy among patients who were less acutely ill and in patients younger than 55 years of age (5.7% and 13.0%, respectively; P = 0.02), but not in those with clinically significant cardiac disease (20.5% and 22.%, respectively; P = 0.69).
The mortality rate during hospitalisation was significantly lower in the restrictive-strategy group (22.3% vs. 28.1%, P = 0.05).
There may be a case to consider giving transfusions at a higher haemoglobin level in people with myocardial ischaemia, severe hypoxaemia, acute haemorrhage, cyanotic heart disease, or lactic acidosis.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
In the initial resuscitative phase, transfusion to achieve a higher haematocrit of ≥30% may be appropriate.[155]Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77. http://www.nejm.org/doi/full/10.1056/NEJMoa010307#t=article http://www.ncbi.nlm.nih.gov/pubmed/11794169?tool=bestpractice.com
In patients requiring prolonged ventilatory support, give lung-protective ventilation using minimal peak inspiratory pressures (<30 cm H2O) and permissive hypercapnia to specifically limit pulmonary compromise.[180]The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8. http://www.nejm.org/doi/full/10.1056/NEJM200005043421801#t=article http://www.ncbi.nlm.nih.gov/pubmed/10793162?tool=bestpractice.com
Titrate fraction of inspired oxygen (FiO2) to lowest effective levels to prevent oxygen toxicity and maintain central venous oxygen tension.
Place patients in a semi-recumbent position with the head elevated to 30° to 45°.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Glycaemic control
Although patients with sepsis are often hyperglycaemic, the optimal glucose target is unknown.
The Surviving Sepsis Campaign guideline recommends targeting a blood glucose level <10.0 mmol/L (<180 mg/dL).[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com The guideline also recommends a ‘sliding scale’ variable-rate intravenous insulin infusion.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
The UK National Institute for Health and Care Excellence makes no recommendations on glycaemic control in sepsis.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Recent years have seen a shift in opinion and practice regarding glycaemic control in critically ill people. Since 2001, the use of tight glycaemic control has been advocated in people with sepsis. More recent evidence, however, suggests an increase in adverse events (e.g., severe hypoglycaemia) in patients managed with very tight glycaemic control (targeting a blood glucose below 6.1 mmol/L [110 mg/dL]).[181]Brunkhorst FM, Engel C, Bloos F, et al; German Competence Network Sepsis (SepNet). Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med. 2008 Jan 10;358(2):125-39. http://www.nejm.org/doi/full/10.1056/NEJMoa070716#t=article http://www.ncbi.nlm.nih.gov/pubmed/18184958?tool=bestpractice.com [182]Wiener RS, Wiener DC, Larson RJ. Benefits and risks of tight glucose control in critically ill adults: a meta-analysis. JAMA. 2008 Aug 27;300(8):933-44. http://jama.ama-assn.org/content/300/8/933.long http://www.ncbi.nlm.nih.gov/pubmed/18728267?tool=bestpractice.com The conflicting evidence has led to variations in recommendations in different countries and settings. Follow your local protocol.
An international randomised controlled trial (RCT) of 6104 critically ill medical and surgical patients found increased 90-day mortality (odds ratio 1.14, 95% CI 1.02 to 1.28) with tighter glucose control, possibly due to more frequent episodes of hypoglycaemia.[183]NICE-SUGAR Study Investigators; Finfer S, Chittock DR, Su SY, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009 Mar 26;360(13):1283-97. http://www.nejm.org/doi/full/10.1056/NEJMoa0810625#t=article http://www.ncbi.nlm.nih.gov/pubmed/19318384?tool=bestpractice.com
A 2010 systematic review of 6 RCTs and a meta-analysis investigating tight glucose control (4.4 to 6.1 mmol/L [80-110 mg/dL]) versus less strict glucose control in critically ill patients in the intensive care unit setting found no significant improvement in mortality with tight glucose control, but it was associated with significantly more hypoglycaemic episodes compared with less strict glucose control.[184]Marik PE, Preiser JC. Toward understanding tight glycemic control in the ICU: a systematic review and metaanalysis. Chest. 2010 Mar;137(3):544-51. http://www.ncbi.nlm.nih.gov/pubmed/20018803?tool=bestpractice.com
An RCT of critically ill patients in a primarily surgical intensive care setting found lower patient mortality with tight glucose control, 4.4 to 6.1 mmol/L (80-110 mg/dL), compared with ‘conventional’ more liberal glucose control.[185]van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001 Nov 8;345(19):1359-67. https://www.nejm.org/doi/10.1056/NEJMoa011300 http://www.ncbi.nlm.nih.gov/pubmed/11794168?tool=bestpractice.com
Consider – vasopressor (should only be initiated by experienced members of the critical care team)
Treatment recommended for SOME patients in selected patient group
Vasopressors are used in a critical care setting to maintain a mean arterial pressure (MAP) ≥65 mmHg if the patient is unresponsive to fluid resuscitation.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [175]Rivers PE, McIntyre L, Morro DC, et al. Early and innovative interventions for severe sepsis and septic shock: taking advantage of a window of opportunity. CMAJ. 2005 Oct 25;173(9):1054-65. http://www.cmaj.ca/cgi/content/full/173/9/1054 http://www.ncbi.nlm.nih.gov/pubmed/16247103?tool=bestpractice.com
Failure to respond to initial fluid resuscitation is a sign of septic shock.[1]Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. http://jama.jamanetwork.com/article.aspx?articleid=2492881 http://www.ncbi.nlm.nih.gov/pubmed/26903338?tool=bestpractice.com
Noradrenaline (norepinephrine) is the vasopressor of choice, mainly because it increases MAP.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Noradrenaline is the vasopressor recommended by the Surviving Sepsis Campaign guideline.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com The UK National Institute for Health and Care Excellence makes no recommendation on the choice of vasopressor.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
If further vasopressor therapy is required to maintain adequate blood pressure or the noradrenaline dose needs to be reduced, add vasopressin or adrenaline (epinephrine) to noradrenaline.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Dopamine is an option, but has been associated with higher mortality than noradrenaline.[186]De Backer D, Aldecoa C, Njimi H, et al. Dopamine versus norepinephrine in the treatment of septic shock: a meta-analysis. Crit Care Med. 2012 Mar;40(3):725-30. http://www.ncbi.nlm.nih.gov/pubmed/22036860?tool=bestpractice.com [187]Vasu TS, Cavallazzi R, Hirani A, et al. Norepinephrine or dopamine for septic shock: Systematic review of randomized clinical trials. J Intensive Care Med. 2012 May-Jun;27(3):172-8. http://www.ncbi.nlm.nih.gov/pubmed/21436167?tool=bestpractice.com [
] How does norepinephrine compare with other vasopressors in people with hypotensive shock?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.1296/fullShow me the answer Therefore, it is only recommended in patients with a low risk of tachyarrhythmias and bradycardia.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com It is rarely used in the UK. Do not use low-dose dopamine for renal protection.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Practical tip
All infusions of vasoactive drugs to correct shock should be given via a secure catheter in a central vein with high flow, such as a central venous catheter. These patients should also have an arterial catheter inserted as soon as possible to ensure more accurate monitoring of arterial blood pressure.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Although a systematic review of 23 randomised trials of patients with shock found no convincing evidence for the superiority of one vasopressor over another,[188]Gamper G, Havel C, Arrich J, et al. Vasopressors for hypotensive shock. Cochrane Database Syst Rev. 2016 Feb 15;(2):CD003709. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003709.pub4/full http://www.ncbi.nlm.nih.gov/pubmed/26878401?tool=bestpractice.com more recent meta-analyses reported a higher mortality associated with dopamine than with noradrenaline.[186]De Backer D, Aldecoa C, Njimi H, et al. Dopamine versus norepinephrine in the treatment of septic shock: a meta-analysis. Crit Care Med. 2012 Mar;40(3):725-30. http://www.ncbi.nlm.nih.gov/pubmed/22036860?tool=bestpractice.com
Primary options
noradrenaline (norepinephrine): 0.4 to 0.8 mg/hour intravenous infusion initially, adjust dose according to response
More noradrenaline (norepinephrine)Dose refers to noradrenaline base.
Secondary options
noradrenaline (norepinephrine): 0.4 to 0.8 mg/hour intravenous infusion initially, adjust dose according to response
More noradrenaline (norepinephrine)Dose refers to noradrenaline base.
-- AND --
vasopressin: 0.01 units/minute intravenous infusion initially, adjust dose according to response, maximum 0.03 units/minute
or
adrenaline (epinephrine): 2-10 micrograms/minute intravenous infusion initially, adjust dose according to response
OR
dopamine: 2-5 micrograms/kg/minute intravenous infusion initially, adjust dose according to response
These drug options and doses relate to a patient with no comorbidities.
Primary options
noradrenaline (norepinephrine): 0.4 to 0.8 mg/hour intravenous infusion initially, adjust dose according to response
More noradrenaline (norepinephrine)Dose refers to noradrenaline base.
Secondary options
noradrenaline (norepinephrine): 0.4 to 0.8 mg/hour intravenous infusion initially, adjust dose according to response
More noradrenaline (norepinephrine)Dose refers to noradrenaline base.
-- AND --
vasopressin: 0.01 units/minute intravenous infusion initially, adjust dose according to response, maximum 0.03 units/minute
or
adrenaline (epinephrine): 2-10 micrograms/minute intravenous infusion initially, adjust dose according to response
OR
dopamine: 2-5 micrograms/kg/minute intravenous infusion initially, adjust dose according to response
Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.
Primary options
noradrenaline (norepinephrine)
Secondary options
noradrenaline (norepinephrine)
-- AND --
vasopressin
or
adrenaline (epinephrine)
OR
dopamine
The Renal Handbook
Treatment recommended for SOME patients in selected patient group
Inotropes can be considered for patients with low cardiac output despite adequate fluid resuscitation and vasopressor therapy.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Dobutamine is recommended first line by the Surviving Sepsis Campaign guideline for people with measured or suspected low cardiac output in the presence of adequate left ventricular filling pressure (or clinical assessment of adequate fluid resuscitation) and adequate mean arterial pressure.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
The UK National Institute for Health and Care Excellence makes no specific recommendations on inotrope selection in patients with sepsis.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Practical tip
Suspect low cardiac output if the clinical examination reveals prolonged capillary refill times, low urine output, or poor peripheral perfusion. Confirm with cardiac output monitoring or by sampling central venous or pulmonary arterial blood to measure oxygen saturations.
When using inotropes, keep the patient’s heart rate at less than 100 beats per minute to minimise myocardial ischaemia.[175]Rivers PE, McIntyre L, Morro DC, et al. Early and innovative interventions for severe sepsis and septic shock: taking advantage of a window of opportunity. CMAJ. 2005 Oct 25;173(9):1054-65. http://www.cmaj.ca/cgi/content/full/173/9/1054 http://www.ncbi.nlm.nih.gov/pubmed/16247103?tool=bestpractice.com
Primary options
dobutamine: 2.5 to 10 micrograms/kg/minute intravenous infusion initially, adjust dose according to response, maximum 40 micrograms/kg/minute
These drug options and doses relate to a patient with no comorbidities.
Primary options
dobutamine: 2.5 to 10 micrograms/kg/minute intravenous infusion initially, adjust dose according to response, maximum 40 micrograms/kg/minute
Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.
Primary options
dobutamine
The Renal Handbook
Treatment recommended for SOME patients in selected patient group
The Surviving Sepsis Campaign guideline recommends intravenous hydrocortisone as an option to consider for patients who are unresponsive to both fluid resuscitation and vasopressor therapy.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
The UK National Institute for Health and Care Excellence does not give any recommendations on the use of corticosteroids for managing sepsis in adults.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Corticosteroids are a late critical-care intervention for patients in whom all other attempts to raise their blood pressure have failed.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 In this critically ill group, corticosteroids may result in a small reduction in mortality.[189]Lamontagne F, Rochwerg B, Lytvyn L, et al. Corticosteroid therapy for sepsis: a clinical practice guideline. BMJ. 2018 Aug 10;362:k3284. https://www.bmj.com/content/362/bmj.k3284.long http://www.ncbi.nlm.nih.gov/pubmed/30097460?tool=bestpractice.com Possible harms include an increased risk of neuromuscular weakness, hyperglycaemia, and hypernatraemia with corticosteroids compared with no corticosteroids.[189]Lamontagne F, Rochwerg B, Lytvyn L, et al. Corticosteroid therapy for sepsis: a clinical practice guideline. BMJ. 2018 Aug 10;362:k3284. https://www.bmj.com/content/362/bmj.k3284.long http://www.ncbi.nlm.nih.gov/pubmed/30097460?tool=bestpractice.com
An international panel reviewing the inconsistent conclusions of large randomised controlled trials (RCTs) on the topic suggested in 2018 that the evidence for the use of corticosteroids was weak, but that “fully informed patients who value avoiding death over quality of life and function would likely choose corticosteroids”, although a no-corticosteroid approach remained reasonable.[189]Lamontagne F, Rochwerg B, Lytvyn L, et al. Corticosteroid therapy for sepsis: a clinical practice guideline. BMJ. 2018 Aug 10;362:k3284. https://www.bmj.com/content/362/bmj.k3284.long http://www.ncbi.nlm.nih.gov/pubmed/30097460?tool=bestpractice.com This judgement was based on an assessment that corticosteroids may reduce mortality by around 2% (this effect was seen in sepsis with and without shock although the greatest benefit was among patients with septic shock), but can increase the risk of neuromuscular weakness and resulting functional deterioration. Most notably, the panel reviewed the following trials:
ADRENAL: 3658 patients who had septic shock[191]Venkatesh B, Finfer S, Cohen J, et al; ADRENAL Trial Investigators and the Australian-New Zealand Intensive Care Society Clinical Trials Group. Adjunctive glucocorticoid therapy in patients with septic shock. N Engl J Med. 2018 Mar 1;378(9):797-808. http://www.nejm.org/doi/full/10.1056/NEJMoa1705835 http://www.ncbi.nlm.nih.gov/pubmed/29347874?tool=bestpractice.com
No statistically significant difference in 90-day mortality between the hydrocortisone and placebo groups
APROCCHSS: 1241 patients who had septic shock[192]Annane D, Renault A, Brun-Buisson C, et al; CRICS-TRIGGERSEP Network. Hydrocortisone plus fludrocortisone for adults with septic shock. N Engl J Med. 2018 Mar 1;378(9):809-18. http://www.ncbi.nlm.nih.gov/pubmed/29490185?tool=bestpractice.com
Hydrocortisone plus fludrocortisone reduced 90-day mortality.
[Figure caption and citation for the preceding image starts]: BMJ Rapid Recommendations: intravenous corticosteroids plus usual care versus usual care onlyLamontagne F, et al. BMJ 2018;362:k3284 [Citation ends].
A more recent systematic review and meta-analysis (comprising 37 RCTs, incorporating both ADRENAL and APROCHSS) included 9564 people with sepsis.[190]Fang F, Zhang Y, Tang J, et al. Association of corticosteroid treatment with outcomes in adult patients with sepsis: a systematic review and meta-analysis. JAMA Intern Med. 2019 Feb 1;179(2):213-23. http://www.ncbi.nlm.nih.gov/pubmed/30575845?tool=bestpractice.com The review found corticosteroid use to be associated with significant improvement in healthcare outcomes as shown by:[190]Fang F, Zhang Y, Tang J, et al. Association of corticosteroid treatment with outcomes in adult patients with sepsis: a systematic review and meta-analysis. JAMA Intern Med. 2019 Feb 1;179(2):213-23. http://www.ncbi.nlm.nih.gov/pubmed/30575845?tool=bestpractice.com
Reduced 28-day mortality (risk ratio [RR] 0.90, 95% CI 0.82 to 0.88) compared with placebo or standard supportive care
Reduced intensive care unit mortality (RR 0.85, 95% CI 0.77 to 0.94; I2 = 0%) compared with placebo or standard supportive care
Reduced in-hospital mortality (RR 0.88, 95% CI 0.79 to 0.99; I2 = 38%) compared with placebo or standard supportive care.
However, corticosteroid use was also associated with increased risk of hyperglycaemia (RR 1.19, 95% CI 1.08 to 1.30) and hypernatraemia (RR 1.57, 95% CI 1.24 to 1.99) compared with placebo or standard supportive care.[190]Fang F, Zhang Y, Tang J, et al. Association of corticosteroid treatment with outcomes in adult patients with sepsis: a systematic review and meta-analysis. JAMA Intern Med. 2019 Feb 1;179(2):213-23. http://www.ncbi.nlm.nih.gov/pubmed/30575845?tool=bestpractice.com
Primary options
hydrocortisone sodium succinate: 200 mg/day intravenously
These drug options and doses relate to a patient with no comorbidities.
Primary options
hydrocortisone sodium succinate: 200 mg/day intravenously
Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.
Primary options
hydrocortisone sodium succinate
The Renal Handbook
Use your clinical judgement. Use National Early Warning Score 2 (NEWS2) scoring (encouraged by NHS England) to refer urgently to hospital any acutely unwell patient with suspected or confirmed infection according to the following triggers:[41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf NHS England: Sepsis external link opens in a new window
Score 7 or more
Make an emergency referral to hospital (via blue-light ambulance) for immediate critical care input.
Score 5-6 total, or 3 or more on any single parameter
Make an immediate referral to an acute care setting and ensure the patient is reviewed by an acute clinician within an hour.
Alternatively, refer for emergency medical care in hospital (usually by blue-light ambulance in the UK) any acutely unwell patient with suspected or confirmed infection who:[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Meets one or more of the UK National Institute for Health and Care Excellence (NICE) high-risk criteria (red flags)
Objective evidence of new altered mental state (e.g., new deterioration in Glasgow Coma Scale score/AVPU ['Alert, responds to Voice, responds to Pain, Unresponsive'] scale)
Respiratory rate: ≥25 breaths per minute OR new need for oxygen (40% or more fraction of inspired oxygen [FiO2]) to maintain saturation >92% (or >88% in known chronic obstructive pulmonary disease)
Heart rate: >130 beats per minute
Systolic blood pressure ≤90 mmHg or more than 40 mmHg below normal
Not passed urine in previous 18 hours, or for catheterised patients passed <0.5 mL/kg of urine per hour
Mottled or ashen appearance
Cyanosis of skin, lips, or tongue
Non-blanching rash of skin
Is at risk of neutropenic sepsis and presents with symptoms and signs of infection
See our topic Febrile neutropenia.
Carefully consider whether emergency medical care is required or whether the patient can be safely managed in the community with safety netting advice.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 See box below on safety netting advice.
Practical tip
If you need to refer a patient for emergency medical care in hospital, it is important to inform the hospital clinical team that the patient is on the way. This will enable the hospital to initiate appropriate treatment as soon as the patient arrives.
In a patient with signs and symptoms of an infection and evidence of physiological deterioration, presume sepsis until it can safely be excluded. Take a cautious approach when deciding whether it is safe to treat the patient’s infection in the community. Using your clinical judgement in making a decision is paramount. In particular, carefully consider the need for hospital admission if:[50]Royal College of General Practitioners. Sepsis: guidance for GPs. November 2018 [internet publication]. https://www.rcgp.org.uk/-/media/sepsis-guidance-for-GPs---FINAL.ashx?la=en [74]Royal College of General Practitioners. 10 top tips for GPs and primary healthcare clinicians: a sepsis aware consultation. 2016 [internet publication]. https://www.dudleyformulary.nhs.uk/download/510/top-ten-tips-for-a-sepsis-aware-consultation- [140]The UK Sepsis Trust. Toolkits for general practice. 2016 [internet publication]. https://sepsistrust.org/professional-resources/clinical/
The patient has one or more risk factors for sepsis (as listed above)
The patient appears seriously unwell to you, based on experience and clinical judgement
The patient lives alone with poor access to communication and/or transport
A carer or parent expresses serious concern about the patient (e.g., “they’re just not right”).
See our Diagnosis recommendations section for details of the NICE risk criteria.
Treat the patient’s infection in line with local protocols and accepted practice. Antimicrobial prescribing guidelines from Public Health England and NICE are available for general practitioners in the UK.[203]Public Health England. Summary of antimicrobial prescribing guidance: managing common infections. July 2019 [internet publication]. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/825957/Common_Infect_PHE_context_references_and_rationale_July_2019.pdf [204]National Institute for Health and Care Excellence. Antimicrobial prescribing guidelines. September 2019 [internet publication]. https://www.nice.org.uk/about/what-we-do/our-programmes/nice-guidance/antimicrobial-prescribing-guidelines
Practical tip
If you decide that the patient is safe to treat in the community, written and verbal safety netting is vital.[50]Royal College of General Practitioners. Sepsis: guidance for GPs. November 2018 [internet publication]. https://www.rcgp.org.uk/-/media/sepsis-guidance-for-GPs---FINAL.ashx?la=en Ensure the information is clear and specific rather than generalised advice; for example, do not say “come back if you get worse” – instead, specify key symptoms to watch out for (such as a non-blanching rash, change in behaviour or mental state, mottled skin, or ashen appearance) and explain where and how to access immediate medical care both in and out of hours.[50]Royal College of General Practitioners. Sepsis: guidance for GPs. November 2018 [internet publication]. https://www.rcgp.org.uk/-/media/sepsis-guidance-for-GPs---FINAL.ashx?la=en
If you give the patient any safety netting advice, ensure you document this clearly in their medical notes, along with the patient’s observations and whether you have offered them any antibiotics. The 2015 national confidential enquiry into sepsis deaths found recorded evidence that safety netting advice had been provided in fewer than one quarter of cases.[60]National Confidential Enquiry into Patient Outcome and Death. Just say sepsis! A review of the process of care received by patients with sepsis. November 2015 [internet publication]. https://www.ncepod.org.uk/2015report2/downloads/JustSaySepsis_FullReport.pdf
The UK Sepsis Trust advises the following acronym:[140]The UK Sepsis Trust. Toolkits for general practice. 2016 [internet publication]. https://sepsistrust.org/professional-resources/clinical/
Slurred speech or confusion
Extreme shivering or muscle pain
Passing no urine (in a day)
Severe breathlessness
‘I feel I might die’
Skin mottled, ashen, blue, or very pale.
Advise the patient to call the emergency services if any of these symptoms develop. If the patient has a change in condition or deterioration that is not covered by the acronym above, advise them to arrange another appointment to see their general practitioner or to call their out of hours service provider.
It is also good practice to consider arranging a next-day review appointment or telephone call; if you will be unable to review the patient yourself, provide a written handover for your colleagues.[139]The UK Sepsis Trust. Toolkit: general practice recognition & management of sepsis in adults and children and young people over 12 years - 2016. 2016 [internet publication]. https://sepsistrust.org/wp-content/uploads/2018/06/GP-toolkit-2016-FINAL-3.pdf
Treatment recommended for SOME patients in selected patient group
If you have decided to refer the patient for emergency medical care and have called for an emergency ambulance, the UK Sepsis Trust/UK National Institute for Health and Care Excellence general practitioner toolkit recommends that, if indicated, you should start oxygen therapy while awaiting the ambulance if resources are available to do so.[139]The UK Sepsis Trust. Toolkit: general practice recognition & management of sepsis in adults and children and young people over 12 years - 2016. 2016 [internet publication]. https://sepsistrust.org/wp-content/uploads/2018/06/GP-toolkit-2016-FINAL-3.pdf [140]The UK Sepsis Trust. Toolkits for general practice. 2016 [internet publication]. https://sepsistrust.org/professional-resources/clinical/
Give oxygen immediately to maintain target oxygen saturations >94%.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [46]Nutbeam T, Daniels R; The UK Sepsis Trust. Professional resources: clinical [internet publication]. https://sepsistrust.org/professional-resources/clinical/ [47]O'Driscoll BR, Howard LS, Earis J, et al. 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 Latest evidence suggests that liberal use of supplemental oxygen (target SpO2 >96%) in acutely ill adults is associated with higher mortality than more conservative oxygen therapy.[138]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 Therefore, a reasonable approach in practice is to maintain a target oxygen saturation of 94% to 96% in acutely ill patients who are not at risk of hypercapnia.
Target saturation of 88% to 92% in people at risk of hypercapnic respiratory failure (e.g., those with COPD.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [46]Nutbeam T, Daniels R; The UK Sepsis Trust. Professional resources: clinical [internet publication]. https://sepsistrust.org/professional-resources/clinical/ [47]O'Driscoll BR, Howard LS, Earis J, et al. 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
Too much supplemental oxygen increases mortality.
Latest evidence supports a 96% upper limit for target oxygen saturation in non-hypercapnic acutely ill adults.
Guidelines differ in their recommendations on target oxygen saturation in acutely unwell adults who are receiving supplemental oxygen. The 2017 British Thoracic Society guideline recommends a target SpO2 range of 94% to 98% for patients not at risk of hypercapnia,[47]O'Driscoll BR, Howard LS, Earis J, et al. 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 whereas the 2015 Thoracic Society of Australia and New Zealand guideline recommends 92% to 96%.[167]Beasley R, Chien J, Douglas J, et al. Thoracic Society of Australia and New Zealand oxygen guidelines for acute oxygen use in adults: 'swimming between the flags'. Respirology. 2015 Nov;20(8):1182-91. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4654337/ http://www.ncbi.nlm.nih.gov/pubmed/26486092?tool=bestpractice.com
A 2018 systematic review including a meta-analysis of data from 25 randomised controlled trials found that in adults with acute illness, liberal oxygen therapy (broadly equivalent to a target saturation >96%) is associated with higher mortality than conservative oxygen therapy (broadly equivalent to a target saturation ≤96%).[138]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 In-hospital mortality was 11 per 1000 higher for the liberal oxygen therapy group versus the conservative therapy group (95% CI 2-22 per 1000 more). Mortality at 30 days was also higher in the group who had received liberal oxygen (risk ratio 1.14, 95% CI 1.01 to 1.29). The trials included adults with sepsis, critical illness, stroke, trauma, myocardial infarction, and cardiac arrest, and patients who had emergency surgery. Studies that were limited to people with chronic respiratory illness or psychiatric illness, patients on extracorporeal life support, patients receiving hyperbaric oxygen therapy, or those having elective surgery were all excluded from the review.
An upper SpO2 limit of 96% is therefore reasonable when administering supplemental oxygen to medical patients with acute illness who are not at risk of hypercapnia. However, a higher target may be appropriate for some specific conditions (e.g., pneumothorax, carbon monoxide poisoning, cluster headache, and sickle cell crisis).[168]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
Treatment recommended for SOME patients in selected patient group
Ensure you have a mechanism in place to administer antibiotics to any high-risk patient (either at your practice or via the ambulance service) if the transfer time to hospital is likely to be more than 1 hour.
Give immediate, targeted antibiotics in people with sepsis thought to arise from a central nervous system source.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Give benzylpenicillin before referring to hospital.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Once a definitive source has been identified, if appropriate to continue treating the patient with antibiotics, choose a treatment regimen in line with local or national policy (which will take into account specialist knowledge of resistance patterns).[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [137]Paul M, Dickstein Y, Raz-Pasteur A. Antibiotic de-escalation for bloodstream infections and pneumonia: systematic review and meta-analysis. Clin Microbiol Infect. 2016 Dec;22(12):960-7. http://www.ncbi.nlm.nih.gov/pubmed/27283148?tool=bestpractice.com Also consider discussing with microbiology/infectious disease colleagues to determine the most appropriate choice.
Assess the need to de-escalate antimicrobial therapy daily.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Studies have shown that daily prompting about antimicrobial de-escalation is effective and may be associated with improved outcomes.[193]Weiss CH, Persell SD, Wunderink RG, et al. Empiric antibiotic, mechanical ventilation, and central venous catheter duration as potential factors mediating the effect of a checklist prompting intervention on mortality: an exploratory analysis. BMC Health Serv Res. 2012 Jul 13;12:198. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409043/ http://www.ncbi.nlm.nih.gov/pubmed/22794349?tool=bestpractice.com [194]Weiss CH, Moazed F, McEvoy CA, et al. Prompting physicians to address a daily checklist and process of care and clinical outcomes: a single-site study. Am J Respir Crit Care Med. 2011 Sep 15;184(6):680-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3208596/ http://www.ncbi.nlm.nih.gov/pubmed/21616996?tool=bestpractice.com
Use the shortest effective course of antibiotics.[195]National Institute for Health and Care Excellence. Antimicrobial stewardship: systems and processes for effective antimicrobial medicine use. August 2015 [internet publication]. https://www.nice.org.uk/guidance/NG15
Unnecessarily prolonged antibiotic treatment is associated with resistance.
NHS England recommends following a 'start smart then focus’ approach for antibiotic use in people with sepsis.[41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf This is derived from Public Health England guidance, which outlines an evidence-based approach to improving antimicrobial prescribing and stewardship in hospital settings.[136]Public Health England. Antimicrobial stewardship: start smart – then focus. March 2015 [internet publication]. https://www.gov.uk/government/publications/antimicrobial-stewardship-start-smart-then-focus The prevalence of antimicrobial resistance (AMR) has risen alarmingly over the last 50 years and no new classes of antibiotics have been developed in decades. By 2050 it is estimated that AMR will kill 10 million people per year, more than cancer and diabetes combined.[143]Health and Social Care Committee. Antimicrobial resistance. October 2018 [internet publication]. https://publications.parliament.uk/pa/cm201719/cmselect/cmhealth/962/962.pdf The relationship between antibiotic exposure and antibiotic resistance is unambiguous not only at the population level but also in individual patients.[144]Goossens H, Ferech M, Vander Stichele R, et al. Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet. 2005 Feb 12-18;365(9459):579-87. http://www.ncbi.nlm.nih.gov/pubmed/15708101?tool=bestpractice.com [145]Costelloe C, Metcalfe C, Lovering A, et al. Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis. BMJ. 2010 May 18;340:c2096. https://www.bmj.com/content/340/bmj.c2096.long http://www.ncbi.nlm.nih.gov/pubmed/20483949?tool=bestpractice.com
Start smart – in the context of sepsis:[136]Public Health England. Antimicrobial stewardship: start smart – then focus. March 2015 [internet publication]. https://www.gov.uk/government/publications/antimicrobial-stewardship-start-smart-then-focus
Do not start antimicrobial therapy unless there is clear evidence of infection
Take a thorough drug allergy history
Initiate prompt effective antibiotic treatment within 1 hour of diagnosis (or as soon as possible) in patients with sepsis or life-threatening infections. Avoid inappropriate use of broad-spectrum antibiotics
Comply with local antimicrobial prescribing guidance
Document clinical indication (and disease severity if appropriate), drug name, dose, and route on drug chart and in clinical notes
Include review/stop date or duration
Obtain cultures prior to starting therapy where possible (but do not delay therapy).
Then focus – in the context of sepsis:[136]Public Health England. Antimicrobial stewardship: start smart – then focus. March 2015 [internet publication]. https://www.gov.uk/government/publications/antimicrobial-stewardship-start-smart-then-focus
Review the clinical diagnosis and the continuing need for antibiotics at 48 to 72 hours* and document in a clear plan of action – the ‘antimicrobial prescribing decision’
The ‘antimicrobial prescribing decision’ options are:
Stop antibiotics if there is no evidence of infection
Switch antibiotics from intravenous to oral
Change antibiotics – ideally to a narrower spectrum, or broader if required
Continue and document next review date or stop date
It is essential that the review and subsequent decision is clearly documented in the clinical notes and on the drug chart where possible (e.g., ‘stop antibiotic’).
*In clinical practice, daily prompting about de-escalation is encouraged.
Consult local microbiology guidance for other specific recommendations on de-escalation.
Most protocols will recommend switching from intravenous to oral antibiotics as soon as possible.
According to the Surviving Sepsis Campaign (SSC), most serious infections associated with sepsis and septic shock will need 7 to 10 days of antibiotic treatment.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com However, in practice, shorter courses of antibiotics are often appropriate.[196]De Santis V, Gresoiu M, Corona A, et al. Bacteraemia incidence, causative organisms and resistance patterns, antibiotic strategies and outcomes in a single university hospital ICU: continuing improvement between 2000 and 2013. J Antimicrob Chemother. 2015 Jan;70(1):273-8. https://academic.oup.com/jac/article/70/1/273/2911167 http://www.ncbi.nlm.nih.gov/pubmed/25190722?tool=bestpractice.com The optimal duration of antibiotic treatment in patients with sepsis remains contentious, with concerns regarding not only under-treatment but also the potential encouragement of antibiotic resistance. Consider seeking advice from microbiology/infectious disease colleagues.
The SSC guideline suggests considering shorter courses in some patients, particularly those with rapid clinical resolution following effective source control of intra-abdominal or urinary sepsis and those with anatomically uncomplicated pyelonephritis.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Longer courses of treatment may be appropriate in patients who have:[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
A slow clinical response
Undrainable foci of infection
Bacteraemia with Staphylococcus aureus
Some fungal and viral infections
Immunological deficiencies, including neutropenia.
Baseline serum procalcitonin is increasingly being used in critical care settings to guide decisions on how long to continue antibiotic therapy.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [105]Lam SW, Bauer SR, Fowler R, et al. Systematic review and meta-analysis of procalcitonin-guidance versus usual care for antimicrobial management in critically ill patients: focus on subgroups based on antibiotic initiation, cessation, or mixed strategies. Crit Care Med. 2018 May;46(5):684-90. http://www.ncbi.nlm.nih.gov/pubmed/29293146?tool=bestpractice.com [106]Akagi T, Nagata N, Wakamatsu K, et al. Procalcitonin-guided antibiotic discontinuation might shorten the duration of antibiotic treatment without increasing pneumonia recurrence. Am J Med Sci. 2019 Jul;358(1):33-44. http://www.ncbi.nlm.nih.gov/pubmed/31084909?tool=bestpractice.com [107]Christ-Crain M, Stolz D, Bingisser R, et al. Procalcitonin guidance significantly reduces antibiotic duration in community-acquired pneumonia: the 'ProCAP' study. Crit Care. 2005; 9 (Suppl 1):P166. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4098316/
Procalcitonin is a peptide precursor of calcitonin, which is responsible for calcium homeostasis.
It is currently excluded from key guidelines, but increasingly used in practice.
Respiratory
Ensure treatment regimens cover common respiratory pathogens and atypical organisms such as Legionella pneumophila.
The respiratory tract is the most common site of infection in people with sepsis.[20]Vincent JL, Rello J, Marshall J, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009 Dec 2;302(21):2323-9. https://jamanetwork.com/journals/jama/fullarticle/184963 http://www.ncbi.nlm.nih.gov/pubmed/19952319?tool=bestpractice.com [60]National Confidential Enquiry into Patient Outcome and Death. Just say sepsis! A review of the process of care received by patients with sepsis. November 2015 [internet publication]. https://www.ncepod.org.uk/2015report2/downloads/JustSaySepsis_FullReport.pdf
See our topic Overview of pneumonia.
Abdominal
Ensure gram-positive and gram-negative organisms including anaerobes are covered.[172]Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Surg Infect (Larchmt). 2010 Feb;11(1):79-109. http://www.ncbi.nlm.nih.gov/pubmed/20163262?tool=bestpractice.com
Arrange urgent surgical drainage or percutaneous drainage (where appropriate) for peritonitis or intra-peritoneal abscesses.[173]Laganà D, Carrafiello G, Mangini M, et al. Image-guided percutaneous treatment of abdominal-pelvic abscesses: a 5-year experience [in Italian]. Radiol Med. 2008 Oct;113(7):999-1007. http://www.ncbi.nlm.nih.gov/pubmed/18795233?tool=bestpractice.com
Urinary tract
Ensure gram-negative coliforms and Pseudomonas are covered. Ensuring patency of the urinary tract is vital.
In people older than 65 years of age, genitourinary tract infections are the most common cause of sepsis.[21]Gauer RL. Early recognition and management of sepsis in adults: the first six hours. Am Fam Physician. 2013 Jul 1;88(1):44-53. http://www.ncbi.nlm.nih.gov/pubmed/23939605?tool=bestpractice.com [22]Mylotte JM, Tayara A, Goodnough S. Epidemiology of bloodstream infection in nursing home residents: evaluation in a large cohort from multiple homes. Clin Infect Dis. 2002 Dec 15;35(12):1484-90. https://academic.oup.com/cid/article/35/12/1484/354722 http://www.ncbi.nlm.nih.gov/pubmed/12471567?tool=bestpractice.com
Soft tissue and joint
Includes septic arthritis, wound infections, cellulitis, and acute super-infections arising from chronic ulceration. Most infections are polymicrobial. Ensure gram-positive and gram-negative organisms including anaerobes are covered.
Beware necrotising fasciitis, which requires immediate surgical intervention (as does septic arthritis).
Practical tip
Necrotising fasciitis is notoriously difficult to diagnose. The initial symptoms are non-specific and the clinical course is often slower than might be expected. Typically, the first sign is pain disproportionate to the clinical findings, followed or accompanied by fever.[76]Sultan HY, Boyle AA, Sheppard N. Necrotising fasciitis. BMJ. 2012 Jul 20;345:e4274. http://www.ncbi.nlm.nih.gov/pubmed/22822005?tool=bestpractice.com
See our topic Necrotising fasciitis.
Central nervous system
Relatively uncommon but potentially devastating source of sepsis. Beware meningococcal sepsis, which can be extremely rapidly fatal; if survived, can lead to greater morbidity than other forms of sepsis.
Give immediate, targeted antibiotics in people with sepsis thought to arise from a central nervous system source.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Immediately give a third-generation cephalosporin, such as ceftriaxone or cefotaxime, for suspected meningitis or meningococcal sepsis.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Treatment recommended for ALL patients in selected patient group
Ensure frequent and ongoing monitoring.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Standard monitoring of vital signs, pulse oximetry, level of consciousness, and urinary output is important for any patient with suspected sepsis.
The UK National Institute for Health and Care Excellence (NICE) recommends continuous or half-hourly monitoring (depending on setting) for any patient considered to be at high risk of deterioration (defined in the NICE guideline as meeting one or more of its high-risk criteria for severe illness or death from sepsis).[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
See the Risk stratification subsection of Diagnosis recommendations for more information.
Use a track-and-trigger scoring system such as National Early Warning Score 2 (NEWS2) to identify any signs of deterioration.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 Your monitoring should include:
Vital signs: heart rate, blood pressure, oxygen saturations, respiratory rate, and temperature
Measure blood pressure via an arterial line if the patient does not respond to initial treatment or needs vasoactive drugs. It provides precise, continuous monitoring, and access for arterial blood sampling
Hourly urine output[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [46]Nutbeam T, Daniels R; The UK Sepsis Trust. Professional resources: clinical [internet publication]. https://sepsistrust.org/professional-resources/clinical/
Lactate
The lactate level should decrease if the patient is clinically improving
Frequency of repeat lactate measurement depends on the cause of sepsis and treatment given.
Measure serum lactate, on a blood gas, to monitor response to treatment.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [46]Nutbeam T, Daniels R; The UK Sepsis Trust. Professional resources: clinical [internet publication]. https://sepsistrust.org/professional-resources/clinical/
Lactate is a marker of stress and may be a marker of a worse prognosis (as a reflection of the degree of stress). Raised serum lactate highlights the possibility of tissue hypoperfusion and may be present in many conditions.[77]Garcia-Alvarez M, Marik P, Bellomo R. Sepsis-associated hyperlactatemia. Crit Care. 2014 Sep 9;18(5):503. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4421917/ http://www.ncbi.nlm.nih.gov/pubmed/25394679?tool=bestpractice.com [78]Kapoor D, Srivastava M, Singh P. Point of care blood gases with electrolytes and lactates in adult emergencies. Int J Crit Illn Inj Sci. 2014 Jul;4(3):216-22. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200547/ http://www.ncbi.nlm.nih.gov/pubmed/25337483?tool=bestpractice.com
Lactate may normalise quickly after fluid resuscitation. Patients whose lactate levels fail to normalise after adequate fluids are the group that fare worst.
Lactate >4 mmol/L (>36 mg/dL) is associated with worse outcomes.
One study found in-hospital mortality rates as follows:[79]Trzeciak S, Dellinger RP, Chansky ME, et al. Serum lactate as a predictor of mortality in patients with infection. Intensive Care Med. 2007 Jun;33(6):970-7. http://www.ncbi.nlm.nih.gov/pubmed/17431582?tool=bestpractice.com
Lactate <2 mmol/L (<18 mg/dL): 15%
Lactate 2.1 to 3.9 mmol/L (19 to 35mg/dL): 25%
Lactate >4 mmol/L (>36 mg/dL): 38%.
Sepsis guidelines from NICE and NHS England recommend escalating treatment depending on lactate level.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf Alert critical care immediately if the patient is acutely unwell and has persistent lactate >4 mmol/L (>36 mg/dL)[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 despite fluid resuscitation.
Do not be falsely reassured by a normal lactate (<2 mmol/L [<18 mg/dL]).
This does not rule out the patient being acutely unwell or at risk of deterioration or death due to organ dysfunction. You must take into account the full clinical picture of the individual patient in front of you including their NEWS2 score.
Practical tip
Lactate is typically measured using a blood gas analyser, although laboratory analysis can also be performed.
Traditionally, arterial blood gas has been recommended as the ideal means of measuring lactate accurately. However, in the emergency department setting it is more practical and quicker to use venous blood gas, which is recommended by NICE.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 Evidence suggests good agreement at lactate levels <2 mmol/L (<18 mg/dL) with small disparities at higher lactate levels.[80]Middleton P, Kelly AM, Brown J, et al. Agreement between arterial and central venous values for pH, bicarbonate, base excess, and lactate. Emerg Med J. 2006 Aug;23(8):622-4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2564165/ http://www.ncbi.nlm.nih.gov/pubmed/16858095?tool=bestpractice.com [81]Theerawit P, Na Petvicharn C, Tangsujaritvijit V, et al. The correlation between arterial lactate and venous lactate in patients with sepsis and septic shock. J Intensive Care Med. 2018 Feb;33(2):116-20. http://www.ncbi.nlm.nih.gov/pubmed/27502951?tool=bestpractice.com [82]Bloom B, Pott J, Freund Y, et al. The agreement between abnormal venous lactate and arterial lactate in the ED: a retrospective chart review. Am J Emerg Med. 2014 Jun;32(6):596-600. http://www.ncbi.nlm.nih.gov/pubmed/24745873?tool=bestpractice.com
The best available evidence supports lactate clearance (the rate at which lactate is cleared over a period of 6 hours) as being as useful as more invasive tests, such as central venous oxygen saturation (ScvO2), in determining a patient’s response to treatment.[197]Nguyen HB, Rivers EP, Knoblich BP, et al. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med. 2004 Aug;32(8):1637-42. http://www.ncbi.nlm.nih.gov/pubmed/15286537?tool=bestpractice.com [198]Jones AE, Shapiro NI, Trzeciak S, et al. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010 Feb 24;303(8):739-46. http://jama.ama-assn.org/content/303/8/739.long http://www.ncbi.nlm.nih.gov/pubmed/20179283?tool=bestpractice.com [199]Arnold RC, Shapiro NI, Jones AE, et al. Multicenter study of early lactate clearance as a determinant of survival in patients with presumed sepsis. Shock. 2009 Jul;32(1):35-9. http://www.ncbi.nlm.nih.gov/pubmed/19533847?tool=bestpractice.com [200]Marty P, Roquilly A, Vallée F, et al. Lactate clearance for death prediction in severe sepsis or septic shock patients during the first 24 hours in intensive care unit: an observational study. Ann Intensive Care. 2013 Feb 12;3(1):3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614435/ http://www.ncbi.nlm.nih.gov/pubmed/23398782?tool=bestpractice.com [201]Puskarich MA, Trzeciak S, Shapiro NI, et al. Whole blood lactate kinetics in patients undergoing quantitative resuscitation for severe sepsis and septic shock. Chest. 2013 Jun;143(6):1548-53. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3673659/ http://www.ncbi.nlm.nih.gov/pubmed/23740148?tool=bestpractice.com [202]Walker CA, Griffith DM, Gray AJ, et al. Early lactate clearance in septic patients with elevated lactate levels admitted from the emergency department to intensive care: time to aim higher? J Crit Care. 2013 Oct;28(5):832-7. http://www.ncbi.nlm.nih.gov/pubmed/23602032?tool=bestpractice.com
In one study that looked at patients with septic shock who were treated to normalise central venous and mean arterial pressure, additional management to normalise lactate clearance compared with additional management to normalise ScvO2 did not result in significantly different in-hospital mortality.[198]Jones AE, Shapiro NI, Trzeciak S, et al. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010 Feb 24;303(8):739-46. http://jama.ama-assn.org/content/303/8/739.long http://www.ncbi.nlm.nih.gov/pubmed/20179283?tool=bestpractice.com
Of 300 patients enrolled, 150 were assigned to each group and patients were well matched by demographics, comorbidities, and physiological features. There were no differences in treatments administered during the initial 72 hours of hospitalisation.
Thirty-four patients (23%) in the ScvO2 group died while in the hospital (95% CI 17% to 30%) compared with 25 (17%, 95% CI 11% to 24%) in the lactate clearance group. This observed difference between mortality rates did not reach the predefined -10% threshold (intent-to-treat analysis: 95% CI for the 6% difference, -3% to 15%). There were no differences in treatment-related adverse events between the groups.
Several trials have assessed the diagnostic accuracy of percentage lactate clearance over 0 to 6 hours. It is worth noting that these studies provide very low-quality evidence, owing mainly to a presumed lack of blinding of treating physicians to the patient’s lactate status.
The studies’ findings agree that lactate clearance early in the hospital course is associated with decreased mortality rate. Patients with higher lactate clearance after 6 hours of emergency department intervention had improved outcomes compared with those with lower lactate clearance.[197]Nguyen HB, Rivers EP, Knoblich BP, et al. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med. 2004 Aug;32(8):1637-42. http://www.ncbi.nlm.nih.gov/pubmed/15286537?tool=bestpractice.com [199]Arnold RC, Shapiro NI, Jones AE, et al. Multicenter study of early lactate clearance as a determinant of survival in patients with presumed sepsis. Shock. 2009 Jul;32(1):35-9. http://www.ncbi.nlm.nih.gov/pubmed/19533847?tool=bestpractice.com [200]Marty P, Roquilly A, Vallée F, et al. Lactate clearance for death prediction in severe sepsis or septic shock patients during the first 24 hours in intensive care unit: an observational study. Ann Intensive Care. 2013 Feb 12;3(1):3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614435/ http://www.ncbi.nlm.nih.gov/pubmed/23398782?tool=bestpractice.com [201]Puskarich MA, Trzeciak S, Shapiro NI, et al. Whole blood lactate kinetics in patients undergoing quantitative resuscitation for severe sepsis and septic shock. Chest. 2013 Jun;143(6):1548-53. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3673659/ http://www.ncbi.nlm.nih.gov/pubmed/23740148?tool=bestpractice.com [202]Walker CA, Griffith DM, Gray AJ, et al. Early lactate clearance in septic patients with elevated lactate levels admitted from the emergency department to intensive care: time to aim higher? J Crit Care. 2013 Oct;28(5):832-7. http://www.ncbi.nlm.nih.gov/pubmed/23602032?tool=bestpractice.com
In the UK, use physiological track-and-trigger systems to monitor all adult patients in acute hospital settings.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Consider using a validated scale such as the Glasgow Coma Scale or AVPU ('Alert, responds to Voice, responds to Pain, Unresponsive') scale to monitor the mental state of a patient with suspected sepsis.[ Glasgow Coma Scale ][3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Practical tip
AVPU should raise concerns if the assessment shows the patient is anything other than 'alert'.
Any patient with sepsis may be at significant risk of severe illness or death so it is vital to consider escalation of care to senior colleagues and/or healthcare facilities where increased and more advanced monitoring can be given (e.g., high-dependency unit/intensive care unit).[7]Rhee C, Jones TM, Hamad Y, et al. Prevalence, underlying causes, and preventability of sepsis-associated mortality in us acute care hospitals. JAMA Netw Open. 2019 Feb 1;2(2):e187571. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484603/ http://www.ncbi.nlm.nih.gov/pubmed/30768188?tool=bestpractice.com [170]NHS England. Improving outcomes for patients with sepsis: a cross-system action plan. December 2015 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2015/08/Sepsis-Action-Plan-23.12.15-v1.pdf [171]McPherson D, Griffiths C, Williams M, et al. Sepsis-associated mortality in England: an analysis of multiple cause of death data from 2001 to 2010. BMJ Open. 2013 Aug 2;3(8). http://bmjopen.bmj.com/content/3/8/e002586 http://www.ncbi.nlm.nih.gov/pubmed/23913771?tool=bestpractice.com
Bear in mind that some patients (e.g., those who are frail) may not be suitable for management in intensive care settings. Consider the patient’s baseline health including their resuscitation status when determining the limits of treatment. Use this to feed into a personalised care plan appropriate to the individual patient.
Consult local protocols for specific escalation routes but in general:
Ensure immediate review by a senior clinician (CT3/ST3 or higher in the UK) of any patient with a NEWS2 score of 5 or more, or who meets one or more of the NICE sepsis high-risk criteria. Also ensure the patient is discussed with a consultant[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf
Discuss with the admitting consultant[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 and consider alerting critical care immediately if the patient is acutely unwell and:
Has a NEWS2 score of 7 or more, persisting high lactate (more than 4 mmol/L [36 mg/dL]) despite fluid resuscitation, or a systolic blood pressure of less than 90 mmHg[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Discuss with the admitting consultant[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Has hypotension that doesn’t respond to initial fluid resuscitation
Is likely to require central venous access and the initiation of inotropes or vasopressors[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Has any feature of septic shock
See our topic Shock
Has neutropenia
See our topic Febrile neutropenia
Is immunodeficient
Urgently discuss with a consultant or call them to attend if the patient:[41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf
Is treated with intravenous antibiotics and/or a fluid bolus for sepsis
Does not respond to initial therapy (antibiotics/fluid resuscitation/oxygen) within the first hour.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf Failure to respond to treatment is defined as:[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Systolic blood pressure remains less than 90 mmHg
Persistent reduced level of consciousness
Respiratory rate more than 25 breaths per minute or the new need for mechanical ventilation
Lactate has not reduced by more than 20%
Refer to critical care any patient who is likely to require central venous access and initiation of inotropes or vasopressors[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
This includes any patient with evidence of circulatory dysfunction or shock, or those who do not respond to initial therapy (as outlined above)
ECG can be used to determine which vasoactive drug(s) to proceed with in critical care.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Practical tip
Ensure a clear escalation plan has been discussed and agreed with the clinical team; include specific points of contact for nursing staff if you are leaving a patient for later review.
Involve a senior colleague and/or consider transferring to critical care sooner rather than later if the patient is not improving, or deemed high-risk. Examples include if the patient:
Is not responding to fluids
Needs inotropic support
Has a low Glasgow Coma Scale score
Needs ventilatory support.
Treatment recommended for ALL patients in selected patient group
Once a site of infection has been identified, early and adequate source control is critical. Consider the need for urgent source control, as soon as the patient is stable, particularly for:[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Gastrointestinal sources (such as visceral abscesses, cholangitis, or peritonitis secondary to perforation)
Severe skin infections (e.g., necrotising fasciitis)
Infection involving an indwelling device, where a procedure or surgery is likely to be required.
Give immediate, targeted antibiotics in people with sepsis thought to arise from a central nervous system source (e.g., suspected meningitis or meningococcal sepsis).[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Immediately give a third-generation cephalosporin such as ceftriaxone or cefotaxime.
In community settings, pre-hospital administration of benzylpenicillin is recommended.
Follow local policy and consider discussing with microbiology/infectious disease colleagues to determine the most appropriate choice; use a ‘start smart then focus’ approach.[41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf [136]Public Health England. Antimicrobial stewardship: start smart – then focus. March 2015 [internet publication]. https://www.gov.uk/government/publications/antimicrobial-stewardship-start-smart-then-focus
Practical tip
If intravenous access is not feasible or is likely to lead to a delay in starting antibiotics and fluids, use intra-osseous access as an interim measure.
Treatment recommended for SOME patients in selected patient group
Give 500 mL of crystalloid fluid, with a sodium content between 130 mmol/L and 154 mmol/L (130 to 154 mEq/L) (e.g., 0.9% sodium chloride or Hartmann’s solution), over less than 15 minutes to patients who need fluid resuscitation (if there is any sign of circulatory insufficiency).[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf [66]National Institute for Health and Care Excellence. Intravenous fluid therapy in adults in hospital. May 2017 [internet publication]. https://www.nice.org.uk/guidance/cg174
Reassess the patient’s haemodynamic status after the first bolus to consider whether a second is required.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 If there is no response to either the first or second bolus, seek senior support.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Intravenous fluid resuscitation may be lifesaving in patients with hypotension. This is because in sepsis there is vasodilation and capillary leakage, which means that patients can rapidly become intravascularly deplete.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
In patients with sepsis-induced hypoperfusion (as indicated by a systolic blood pressure <90 mmHg, a raised lactate level, or signs of organ dysfunction), the Surviving Sepsis Campaign international guideline recommends a total of at least 30 mL/kg of intravenous crystalloid over the first 3 hours.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
If the patient’s initial lactate level is raised, the guideline recommends serial lactate measurements to guide the need for further intravenous fluids (with the goal of normalising lactate levels).[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Practical tip
The delivery of appropriate rapid fluid challenges is intended to restore the imbalance between oxygen supply and demand to the tissues. Patients who do not respond to rapid delivery of adequate volumes of intravenous fluids are in septic shock and need immediate referral to critical care. The immediate priority in this group of patients is to restore the circulation and oxygen delivery.
Practical tip
Monitor patients closely for signs of fluid overload such as pulmonary or systemic oedema before and after each additional fluid bolus, as they may require large volumes of fluid to support their circulating volume.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [152]Schuller D, Mitchell JP, Calandrino FS, et al. Fluid balance during pulmonary edema: is fluid gain a marker or a cause of poor outcome? Chest. 1991 Oct;100(4):1068-75. http://www.ncbi.nlm.nih.gov/pubmed/1914560?tool=bestpractice.com [153]National Institute for Health and Care Excellence. Neutropenic sepsis: prevention and management in people with cancer. September 2012 [internet publication]. https://www.nice.org.uk/guidance/cg151
Latest evidence suggests a balanced crystalloid may have marginal benefits over saline, but either option is a reasonable choice.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [154]Semler MW, Self WH, Wanderer JP, et al. Balanced crystalloids versus saline in critically ill adults. N Engl J Med. 2018 Mar 1;378(9):829-39. http://www.ncbi.nlm.nih.gov/pubmed/29485925?tool=bestpractice.com
Although early fluid resuscitation is a cornerstone of sepsis treatment that is given high priority by both Sepsis Six and the UK National Institute for Health and Care Excellence, choice of fluid has been the source of much discussion. In particular, there has been extensive debate over the choice between a balanced crystalloid (such as Hartmann’s solution, Ringer’s lactate, or PlasmaLyte) and normal saline (an unbalanced crystalloid). There have been very few high-quality studies, but latest evidence from critically ill patients points to marginal benefits from using a balanced crystalloid in preference to saline.[154]Semler MW, Self WH, Wanderer JP, et al. Balanced crystalloids versus saline in critically ill adults. N Engl J Med. 2018 Mar 1;378(9):829-39. http://www.ncbi.nlm.nih.gov/pubmed/29485925?tool=bestpractice.com
A 2018 US multicentre cluster-randomised trial among 15,802 critically ill adults receiving care in the intensive care unit found small benefits from balanced crystalloid compared with saline. The 30-day outcomes showed 10.3% mortality in the balanced crystalloid group compared with 11.1% in the saline group (P = 0.06), and a major adverse kidney event rate of 14.3% compared with 15.4% in the two groups, respectively (marginal odds ratio 0.91, 95% CI 0.84 to 0.99).[154]Semler MW, Self WH, Wanderer JP, et al. Balanced crystalloids versus saline in critically ill adults. N Engl J Med. 2018 Mar 1;378(9):829-39. http://www.ncbi.nlm.nih.gov/pubmed/29485925?tool=bestpractice.com
Colloids (e.g., starches, dextrans, gelatins, albumin, or fresh frozen plasma) are no longer used in emergency medicine in the UK.
Studies have not shown benefits from early goal-directed therapy and your focus should instead be on adjusting treatment according to i) lactate level and ii) clinical assessment of the patient’s haemodynamic response to initial fluids.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [155]Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77. http://www.nejm.org/doi/full/10.1056/NEJMoa010307#t=article http://www.ncbi.nlm.nih.gov/pubmed/11794169?tool=bestpractice.com [156]ARISE Investigators; ANZICS Clinical Trials Group; Peake SL, Delaney A, Bailey M, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014 Oct 16;371(16):1496-506. http://www.nejm.org/doi/full/10.1056/NEJMoa1404380#t=article http://www.ncbi.nlm.nih.gov/pubmed/25272316?tool=bestpractice.com [157]ProCESS Investigators; Yealy DM, Kellum JA, Huang DT, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014 May 1;370(18):1683-93. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101700/ http://www.ncbi.nlm.nih.gov/pubmed/24635773?tool=bestpractice.com [158]Mouncey PR, Osborn TM, Power GS, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015 Apr 2;372(14):1301-11. http://www.nejm.org/doi/full/10.1056/NEJMoa1500896#t=article http://www.ncbi.nlm.nih.gov/pubmed/25776532?tool=bestpractice.com [159]Levy MM, Dellinger RP, Townsend SR, et al. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med. 2010 Feb;36(2):222-31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826633/ http://www.ncbi.nlm.nih.gov/pubmed/20069275?tool=bestpractice.com [160]Levy MM, Rhodes A, Phillips GS, et al. Surviving Sepsis Campaign: association between performance metrics and outcomes in a 7.5-year study. Crit Care Med. 2015 Jan;43(1):3-12. http://www.ncbi.nlm.nih.gov/pubmed/25275252?tool=bestpractice.com
Previous versions of the Surviving Sepsis Campaign (SSC) guidelines recommended a protocoled approach to resuscitation, otherwise known as early goal-directed therapy (EGDT).[161]Dellinger RP, Carlet JM, Masur H, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Intensive Care Med. 2004 Apr;30(4):536-55. http://www.ncbi.nlm.nih.gov/pubmed/14997291?tool=bestpractice.com [162]Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008 Jan;36(1):296-327. http://www.ncbi.nlm.nih.gov/pubmed/18158437?tool=bestpractice.com [163]Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013 Feb;41(2):580-637. http://www.ncbi.nlm.nih.gov/pubmed/23353941?tool=bestpractice.com EGDT involves the use of a series of ‘goals’ including central venous pressure and central venous oxygen saturation (ScvO2). This recommendation was largely based on data from one study that showed a significant survival benefit for patients receiving EGDT.[155]Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77. http://www.nejm.org/doi/full/10.1056/NEJMoa010307#t=article http://www.ncbi.nlm.nih.gov/pubmed/11794169?tool=bestpractice.com
This approach has since been challenged following the failure to show a mortality reduction in three subsequent large multicentre randomised controlled trials: PROCESS, ARISE, and PROMISE.[156]ARISE Investigators; ANZICS Clinical Trials Group; Peake SL, Delaney A, Bailey M, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014 Oct 16;371(16):1496-506. http://www.nejm.org/doi/full/10.1056/NEJMoa1404380#t=article http://www.ncbi.nlm.nih.gov/pubmed/25272316?tool=bestpractice.com [157]ProCESS Investigators; Yealy DM, Kellum JA, Huang DT, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014 May 1;370(18):1683-93. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101700/ http://www.ncbi.nlm.nih.gov/pubmed/24635773?tool=bestpractice.com [158]Mouncey PR, Osborn TM, Power GS, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015 Apr 2;372(14):1301-11. http://www.nejm.org/doi/full/10.1056/NEJMoa1500896#t=article http://www.ncbi.nlm.nih.gov/pubmed/25776532?tool=bestpractice.com
It is worth bearing in mind that these three trials included patients who were less severely ill (lower baseline lactate levels, ScvO2 at or above the target value on admission, and lower mortality in the control group) than the patients in the original study that outlined EDGT as a recommended approach.
Based on this latest evidence, the SSC no longer specifically recommends EDGT; it does, however, acknowledge the need for guidance on how to approach this group of patients who have significant mortality and morbidity.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com The SSC therefore recommends that you:[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
View these patients as having a medical emergency that necessitates urgent assessment and treatment
Begin initial fluid resuscitation with 30 mL/kg of crystalloid within the first 3 hours
This fixed volume of fluid enables initiation of resuscitation while giving an opportunity to ascertain more specific information about the patient and while awaiting more precise measurements of haemodynamic status
Although scant data are available to support this volume of fluid, interventional studies have described this as usual practice in the early stages of resuscitation, and observational evidence supports the practice[159]Levy MM, Dellinger RP, Townsend SR, et al. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med. 2010 Feb;36(2):222-31. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826633/ http://www.ncbi.nlm.nih.gov/pubmed/20069275?tool=bestpractice.com [160]Levy MM, Rhodes A, Phillips GS, et al. Surviving Sepsis Campaign: association between performance metrics and outcomes in a 7.5-year study. Crit Care Med. 2015 Jan;43(1):3-12. http://www.ncbi.nlm.nih.gov/pubmed/25275252?tool=bestpractice.com
The average volume of fluid pre-randomisation given was approximately 30 mL/kg in the PROCESS and ARISE trials, and approximately 2 L in the PROMISE trial.[156]ARISE Investigators; ANZICS Clinical Trials Group; Peake SL, Delaney A, Bailey M, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014 Oct 16;371(16):1496-506. http://www.nejm.org/doi/full/10.1056/NEJMoa1404380#t=article http://www.ncbi.nlm.nih.gov/pubmed/25272316?tool=bestpractice.com [157]ProCESS Investigators; Yealy DM, Kellum JA, Huang DT, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014 May 1;370(18):1683-93. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4101700/ http://www.ncbi.nlm.nih.gov/pubmed/24635773?tool=bestpractice.com [158]Mouncey PR, Osborn TM, Power GS, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015 Apr 2;372(14):1301-11. http://www.nejm.org/doi/full/10.1056/NEJMoa1500896#t=article http://www.ncbi.nlm.nih.gov/pubmed/25776532?tool=bestpractice.com The SSC acknowledges that many patients will need more fluid than this, and it advocates giving further fluid to this group in line with functional haemodynamic measurements.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
The UK National Institute for Health and Care Excellence guideline on sepsis focuses on initial management and treatment, and therefore makes no recommendations regarding intensive monitoring such as that used in EGDT.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Practical tip
To guide the need for further intravenous fluids, it can sometimes be helpful to use bedside ultrasound to monitor changes in inferior vena cava (IVC) diameter during respiration.[164]Feissel M, Michard F, Faller JP, et al. The respiratory variation in inferior vena cava diameter as a guide to fluid therapy. Intensive Care Med. 2004 Sep;30(9):1834-7. http://www.ncbi.nlm.nih.gov/pubmed/15045170?tool=bestpractice.com [165]Barbier C, Loubières Y, Schmit C, et al. Respiratory changes in inferior vena cava diameter are helpful in predicting fluid responsiveness in ventilated septic patients. Intensive Care Med. 2004 Sep;30(9):1740-6. http://www.ncbi.nlm.nih.gov/pubmed/15034650?tool=bestpractice.com
In the spontaneously breathing patient: consider additional fluid resuscitation if there is a collapsed (or collapsing) IVC.
In the mechanically ventilated patient: an increase in IVC size >18% (or visible to the naked eye) with positive pressure ventilation suggests fluid-responsiveness.
Practical tip
Use the passive leg-raising test to predict fluid-responsiveness if adequate monitoring is available.[66]National Institute for Health and Care Excellence. Intravenous fluid therapy in adults in hospital. May 2017 [internet publication]. https://www.nice.org.uk/guidance/cg174 [166]Monnet X, Teboul JL. Passive leg raising: five rules, not a drop of fluid! Crit Care. 2015 Jan 14;19:18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4293822/ http://www.ncbi.nlm.nih.gov/pubmed/25658678?tool=bestpractice.com
This is a useful indicator of fluid-responsiveness, which should be assessed using devices that can continuously monitor cardiac output in real time (e.g., Pulse index Continuous Cardiac Output (PiCCO) monitor or oesophageal Doppler), usually in an intensive care unit rather than general ward setting.
Sit the patient upright at 45° and tilt the entire bed through 45°.
Patients with a positive test have a >10% increase in cardiac output or stroke volume, indicating more fluids may be required.
The passive leg-raise response may be misleading in conscious patients who are uncomfortable or in pain when lying flat.
Treatment recommended for SOME patients in selected patient group
If indicated, give oxygen to maintain target oxygen saturations 94% to 96%.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [46]Nutbeam T, Daniels R; The UK Sepsis Trust. Professional resources: clinical [internet publication]. https://sepsistrust.org/professional-resources/clinical/ [47]O'Driscoll BR, Howard LS, Earis J, et al. 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 Latest evidence suggests that liberal use of supplemental oxygen (target SpO2 >96%) in acutely ill adults is associated with higher mortality than more conservative oxygen therapy.[138]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 Therefore, a reasonable approach in practice is to maintain a target oxygen saturation of 94% to 96% in acutely ill patients who are not at risk of hypercapnia.
Target saturation of 88% to 92% if the patient is at risk of hypercapnic respiratory failure (e.g., those with COPD).[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [46]Nutbeam T, Daniels R; The UK Sepsis Trust. Professional resources: clinical [internet publication]. https://sepsistrust.org/professional-resources/clinical/ [47]O'Driscoll BR, Howard LS, Earis J, et al. 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
Too much supplemental oxygen increases mortality.
Latest evidence supports a 96% upper limit for target oxygen saturation in non-hypercapnic acutely ill adults.
Guidelines differ in their recommendations on target oxygen saturation in acutely unwell adults who are receiving supplemental oxygen. The 2017 British Thoracic Society guideline recommends a target SpO2 range of 94% to 98% for patients not at risk of hypercapnia,[47]O'Driscoll BR, Howard LS, Earis J, et al. 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 whereas the 2015 Thoracic Society of Australia and New Zealand guideline recommends 92% to 96%.[167]Beasley R, Chien J, Douglas J, et al. Thoracic Society of Australia and New Zealand oxygen guidelines for acute oxygen use in adults: 'swimming between the flags'. Respirology. 2015 Nov;20(8):1182-91. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4654337/ http://www.ncbi.nlm.nih.gov/pubmed/26486092?tool=bestpractice.com
A 2018 systematic review including a meta-analysis of data from 25 randomised controlled trials found that in adults with acute illness, liberal oxygen therapy (broadly equivalent to a target saturation >96%) is associated with higher mortality than conservative oxygen therapy (broadly equivalent to a target saturation ≤96%).[138]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 In-hospital mortality was 11 per 1000 higher for the liberal oxygen therapy group versus the conservative therapy group (95% CI 2-22 per 1000 more). Mortality at 30 days was also higher in the group who had received liberal oxygen (risk ratio 1.14, 95% CI 1.01 to 1.29). The trials included adults with sepsis, critical illness, stroke, trauma, myocardial infarction, and cardiac arrest, and patients who had emergency surgery. Studies that were limited to people with chronic respiratory illness or psychiatric illness, patients on extracorporeal life support, patients receiving hyperbaric oxygen therapy, or those having elective surgery were all excluded from the review.
An upper SpO2 limit of 96% is therefore reasonable when administering supplemental oxygen to medical patients with acute illness who are not at risk of hypercapnia. However, a higher target may be appropriate for some specific conditions (e.g., pneumothorax, carbon monoxide poisoning, cluster headache, and sickle cell crisis).[168]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
There is no specific evidence to show that giving oxygen improves clinical outcomes in sepsis. However, respiratory failure will lead to tissue hypoxia and anaerobic respiration. This is likely to lead to acidosis and consequently a poorer outcome.[169]Kellum JA. Metabolic acidosis in patients with sepsis: epiphenomenon or part of the pathophysiology? Crit Care Resusc. 2004 Sep;6(3):197-203. http://www.ncbi.nlm.nih.gov/pubmed/16556122?tool=bestpractice.com
Treatment recommended for SOME patients in selected patient group
Any patient with sepsis may be at significant risk of severe illness or death so it is vital to consider escalation of care to senior colleagues and/or healthcare facilities where increased and more advanced monitoring can be given (e.g., high-dependency unit/intensive care unit).[7]Rhee C, Jones TM, Hamad Y, et al. Prevalence, underlying causes, and preventability of sepsis-associated mortality in us acute care hospitals. JAMA Netw Open. 2019 Feb 1;2(2):e187571. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484603/ http://www.ncbi.nlm.nih.gov/pubmed/30768188?tool=bestpractice.com [170]NHS England. Improving outcomes for patients with sepsis: a cross-system action plan. December 2015 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2015/08/Sepsis-Action-Plan-23.12.15-v1.pdf [171]McPherson D, Griffiths C, Williams M, et al. Sepsis-associated mortality in England: an analysis of multiple cause of death data from 2001 to 2010. BMJ Open. 2013 Aug 2;3(8). http://bmjopen.bmj.com/content/3/8/e002586 http://www.ncbi.nlm.nih.gov/pubmed/23913771?tool=bestpractice.com
Bear in mind that some patients (e.g., those who are frail) may not be suitable for management in intensive care settings. Consider the patient’s baseline health including their resuscitation status when determining the limits of treatment. Use this to feed into a personalised care plan appropriate to the individual patient.
Consult local protocols for specific escalation routes but in general:
Ensure immediate review by a senior clinician (CT3/ST3 or higher in the UK) of any patient with a National Early Warning Score 2 (NEWS2) score of 5 or more, or who meets one or more of the UK National Institute for Health and Care Excellence (NICE) sepsis high-risk criteria. Also ensure the patient is discussed with a consultant[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf
Discuss with the admitting consultant[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 and consider alerting critical care immediately if the patient is acutely unwell and:
Has a NEWS2 score of 7 or more, persisting high lactate (more than 4 mmol/L [36 mg/dL]) despite fluid resuscitation, or a systolic blood pressure of less than 90 mmHg[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Discuss with the admitting consultant[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Has hypotension that doesn’t respond to initial fluid resuscitation
Is likely to require central venous access and the initiation of inotropes or vasopressors[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Has any feature of septic shock
See our topic Shock
Has neutropenia
See our topic Febrile neutropenia
Is immunodeficient
Urgently discuss with a consultant or call them to attend if the patient:[41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf
Is treated with intravenous antibiotics and/or a fluid bolus for sepsis
Does not respond to initial therapy (antibiotics/fluid resuscitation/oxygen) within the first hour.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [41]NHS England. Sepsis guidance implementation advice for adults. September 2017 [internet publication]. https://www.england.nhs.uk/wp-content/uploads/2017/09/sepsis-guidance-implementation-advice-for-adults.pdf Failure to respond to treatment is defined as:[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Systolic blood pressure remains less than 90 mmHg
Persistent reduced level of consciousness
Respiratory rate more than 25 breaths per minute or the new need for mechanical ventilation
Lactate has not reduced by more than 20%
Refer to critical care any patient who is likely to require central venous access and initiation of inotropes or vasopressors[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
This includes any patient with evidence of circulatory dysfunction or shock, or those who do not respond to initial therapy (as outlined above)
ECG can be used to determine which vasoactive drug(s) to proceed with in critical care.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Practical tip
Ensure a clear escalation plan has been discussed and agreed with the clinical team; include specific points of contact for nursing staff if you are leaving a patient for later review.
Involve a senior colleague and/or consider transferring to critical care sooner rather than later if the patient is not improving, or deemed high-risk. Examples include if the patient:
Is not responding to fluids
Needs inotropic support
Has a low Glasgow Coma Scale score
Needs ventilatory support.
For any patient with suspected sepsis, consider the need for referral to a high-dependency unit for management by the critical care team.[155]Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77. http://www.nejm.org/doi/full/10.1056/NEJMoa010307#t=article http://www.ncbi.nlm.nih.gov/pubmed/11794169?tool=bestpractice.com [174]Hollenberg SM, Ahrens TS, Annane D, et al. Practice parameters for hemodynamic support of sepsis in adult patients; 2004 update. Crit Care Med. 2004 Sep;32(9):1928-48. http://www.ncbi.nlm.nih.gov/pubmed/15343024?tool=bestpractice.com
The following interventions should only be initiated by experienced members of the critical care team:[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [175]Rivers PE, McIntyre L, Morro DC, et al. Early and innovative interventions for severe sepsis and septic shock: taking advantage of a window of opportunity. CMAJ. 2005 Oct 25;173(9):1054-65. http://www.cmaj.ca/cgi/content/full/173/9/1054 http://www.ncbi.nlm.nih.gov/pubmed/16247103?tool=bestpractice.com
Glycaemic control
Vasoactive drugs (vasopressors/inotropes)
Corticosteroids.
Additional intensive care measures that will be considered include:[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [176]Trzeciak S, Dellinger RP. Other supportive therapies in sepsis: an evidence-based review. Crit Care Med. 2004 Nov;32(suppl 11):S571-7. http://www.ncbi.nlm.nih.gov/pubmed/15542966?tool=bestpractice.com [177]Nguyen HB, Rivers EP, Abrahamian FM, et al. Severe sepsis and septic shock: review of the literature and emergency department management guidelines. Ann Emerg Med. 2006 Jul;48(1):28-54. http://www.ncbi.nlm.nih.gov/pubmed/16781920?tool=bestpractice.com
Stress ulcer prophylaxis (in people at risk of gastrointestinal bleeding)
With an H2 antagonist or proton-pump inhibitor
Deep venous thrombosis prophylaxis
With heparin and compression stockings
Enteral or parenteral nutrition
Administration of human albumin solution 4% to 5% in patients with sepsis and shock[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com who have not responded to substantial volumes of crystalloids
Transfusion of packed cells
Consult local protocols for recommended threshold
The Surviving Sepsis Campaign recommends using a threshold of 70 g/L (7 g/dL).[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Studies in the general critical care population have shown no improvement with blood transfusions given at a higher haemoglobin threshold compared with a lower haemoglobin threshold,[178]Holst LB, Haase N, Wetterslev J, et al; TRISS Trial Group; Scandinavian Critical Care Trials Group. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014 Oct 9;371(15):1381-91. http://www.nejm.org/doi/full/10.1056/NEJMoa1406617#t=article http://www.ncbi.nlm.nih.gov/pubmed/25270275?tool=bestpractice.com and have shown potential harm associated with liberal transfusion.[179]Hébert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med. 1999 Feb 11;340(6):409-17. http://www.nejm.org/doi/full/10.1056/NEJM199902113400601#t=articleTop http://www.ncbi.nlm.nih.gov/pubmed/9971864?tool=bestpractice.com
One multicentre parallel group randomised trial analysed data from 998 patients with septic shock, split into two intervention groups with similar baseline characteristics. In the intensive care unit, the group assigned to blood transfusion at a lower haemoglobin threshold received a median of 1 unit of blood (interquartile range, 0 to 3) and the group assigned to blood transfusion at a higher haemoglobin threshold received a median of 4 units (interquartile range, 2 to 7).[178]Holst LB, Haase N, Wetterslev J, et al; TRISS Trial Group; Scandinavian Critical Care Trials Group. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014 Oct 9;371(15):1381-91. http://www.nejm.org/doi/full/10.1056/NEJMoa1406617#t=article http://www.ncbi.nlm.nih.gov/pubmed/25270275?tool=bestpractice.com
At 90 days after randomisation, 216 of 502 patients (43.0%) assigned to the lower-threshold group, compared with 223 of 496 (45.0%) assigned to the higher-threshold group, had died (relative risk 0.94, 95% CI 0.78 to 1.09; P = 0.44).
The results were similar in analyses adjusted for risk factors at baseline and in analyses of the per-protocol populations.
The numbers of patients who had ischaemic events, who had severe adverse reactions, and who required life support were similar in the two intervention groups.
A second multicentre randomised controlled trial compared the rates of death from all causes at 30 days and the severity of organ dysfunction in 838 critically ill patients receiving a restrictive strategy of red-cell transfusion compared with those receiving a liberal strategy.[179]Hébert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med. 1999 Feb 11;340(6):409-17. http://www.nejm.org/doi/full/10.1056/NEJM199902113400601#t=articleTop http://www.ncbi.nlm.nih.gov/pubmed/9971864?tool=bestpractice.com
Overall, 30-day mortality was similar in the two groups (18.7% vs. 23.3%, P = 0.11).
However, the rates were significantly lower with the restrictive transfusion strategy among patients who were less acutely ill and in patients younger than 55 years of age (5.7% and 13.0%, respectively; P = 0.02), but not in those with clinically significant cardiac disease (20.5% and 22.9%, respectively; P = 0.69).
The mortality rate during hospitalisation was significantly lower in the restrictive-strategy group (22.3% vs. 28.1%, P= 0.05).
There may be a case to consider giving transfusions at a higher haemoglobin level in people with myocardial ischaemia, severe hypoxaemia, acute haemorrhage, cyanotic heart disease, or lactic acidosis.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
In the initial resuscitative phase, transfusion to achieve a higher haematocrit of ≥30% may be appropriate.[155]Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77. http://www.nejm.org/doi/full/10.1056/NEJMoa010307#t=article http://www.ncbi.nlm.nih.gov/pubmed/11794169?tool=bestpractice.com
In patients requiring prolonged ventilatory support, give lung-protective ventilation using minimal peak inspiratory pressures (<30 cm H2O) and permissive hypercapnia to specifically limit pulmonary compromise.[180]The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8. http://www.nejm.org/doi/full/10.1056/NEJM200005043421801#t=article http://www.ncbi.nlm.nih.gov/pubmed/10793162?tool=bestpractice.com
Titrate fraction of inspired oxygen (FiO2) to lowest effective levels to prevent oxygen toxicity and maintain central venous oxygen tension.
Place patients in a semi-recumbent position with the head elevated to 30° to 45°.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Glycaemic control
Although patients with sepsis are often hyperglycaemic, the optimal glucose target is unknown.
The Surviving Sepsis Campaign guideline recommends targeting a blood glucose level <10.0 mmol/L (<180 mg/dL).[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com The guideline also recommends a ‘sliding scale’ variable-rate intravenous insulin infusion.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
NICE makes no recommendations on glycaemic control in sepsis.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Recent years have seen a shift in opinion and practice regarding glycaemic control in critically ill people. Since 2001, the use of tight glycaemic control has been advocated in people with sepsis. More recent evidence, however, suggests an increase in adverse events (e.g., severe hypoglycaemia) in patients managed with very tight glycaemic control (targeting a blood glucose below 6.1 mmol/L [110 mg/dL]).[181]Brunkhorst FM, Engel C, Bloos F, et al; German Competence Network Sepsis (SepNet). Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med. 2008 Jan 10;358(2):125-39. http://www.nejm.org/doi/full/10.1056/NEJMoa070716#t=article http://www.ncbi.nlm.nih.gov/pubmed/18184958?tool=bestpractice.com [182]Wiener RS, Wiener DC, Larson RJ. Benefits and risks of tight glucose control in critically ill adults: a meta-analysis. JAMA. 2008 Aug 27;300(8):933-44. http://jama.ama-assn.org/content/300/8/933.long http://www.ncbi.nlm.nih.gov/pubmed/18728267?tool=bestpractice.com The conflicting evidence has led to variations in recommendations in different countries and settings. Follow your local protocol.
An international randomised controlled trial (RCT) of 6104 critically ill medical and surgical patients found increased 90-day mortality (odds ratio 1.14, 95% CI 1.02 to 1.28) with tighter glucose control, possibly due to more frequent episodes of hypoglycaemia.[183]NICE-SUGAR Study Investigators; Finfer S, Chittock DR, Su SY, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009 Mar 26;360(13):1283-97. http://www.nejm.org/doi/full/10.1056/NEJMoa0810625#t=article http://www.ncbi.nlm.nih.gov/pubmed/19318384?tool=bestpractice.com
A 2010 systematic review of 6 RCTs and a meta-analysis investigating tight glucose control (4.4 to 6.1 mmol/L [80-110 mg/dL]) versus less strict glucose control in critically ill patients in the intensive care unit setting found no significant improvement in mortality with tight glucose control, but it was associated with significantly more hypoglycaemic episodes compared with less strict glucose control.[184]Marik PE, Preiser JC. Toward understanding tight glycemic control in the ICU: a systematic review and metaanalysis. Chest. 2010 Mar;137(3):544-51. http://www.ncbi.nlm.nih.gov/pubmed/20018803?tool=bestpractice.com
An RCT of critically ill patients in a primarily surgical intensive care setting found lower patient mortality with tight glucose control, 4.4 to 6.1 mmol/L (80-110 mg/dL), compared with ‘conventional’ more liberal glucose control.[185]van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med. 2001 Nov 8;345(19):1359-67. https://www.nejm.org/doi/10.1056/NEJMoa011300 http://www.ncbi.nlm.nih.gov/pubmed/11794168?tool=bestpractice.com
Consider – vasopressor (should only be initiated by experienced members of the critical care team)
Treatment recommended for SOME patients in selected patient group
Vasopressors are used in a critical care setting to maintain a mean arterial pressure (MAP) ≥65 mmHg if the patient is unresponsive to fluid resuscitation.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com [175]Rivers PE, McIntyre L, Morro DC, et al. Early and innovative interventions for severe sepsis and septic shock: taking advantage of a window of opportunity. CMAJ. 2005 Oct 25;173(9):1054-65. http://www.cmaj.ca/cgi/content/full/173/9/1054 http://www.ncbi.nlm.nih.gov/pubmed/16247103?tool=bestpractice.com
Failure to respond to initial fluid resuscitation is a sign of septic shock.[1]Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. http://jama.jamanetwork.com/article.aspx?articleid=2492881 http://www.ncbi.nlm.nih.gov/pubmed/26903338?tool=bestpractice.com
Noradrenaline (norepinephrine) is the vasopressor of choice, mainly because it increases MAP.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Noradrenaline is the vasopressor recommended by the Surviving Sepsis Campaign guideline.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com The UK National Institute for Health and Care Excellence makes no recommendation on the choice of vasopressor.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
If further vasopressor therapy is required to maintain adequate blood pressure or the noradrenaline dose needs to be reduced, add vasopressin or adrenaline (epinephrine) to noradrenaline.
Dopamine is an option, but has been associated with higher mortality than noradrenaline.[186]De Backer D, Aldecoa C, Njimi H, et al. Dopamine versus norepinephrine in the treatment of septic shock: a meta-analysis. Crit Care Med. 2012 Mar;40(3):725-30. http://www.ncbi.nlm.nih.gov/pubmed/22036860?tool=bestpractice.com [187]Vasu TS, Cavallazzi R, Hirani A, et al. Norepinephrine or dopamine for septic shock: Systematic review of randomized clinical trials. J Intensive Care Med. 2012 May-Jun;27(3):172-8. http://www.ncbi.nlm.nih.gov/pubmed/21436167?tool=bestpractice.com [
] How does norepinephrine compare with other vasopressors in people with hypotensive shock?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.1296/fullShow me the answer Therefore, it is only recommended in patients with a low risk of tachyarrhythmias and bradycardia.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com It is rarely used in the UK. Do not use low-dose dopamine for renal protection.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Practical tip
All infusions of vasoactive drugs to correct shock should be given via a secure catheter in a central vein with high flow, such as a central venous catheter. These patients should also have an arterial catheter inserted as soon as possible to ensure more accurate monitoring of arterial blood pressure.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Although a systematic review of 23 randomised trials of patients with shock found no convincing evidence for the superiority of one vasopressor over another,[188]Gamper G, Havel C, Arrich J, et al. Vasopressors for hypotensive shock. Cochrane Database Syst Rev. 2016 Feb 15;(2):CD003709. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003709.pub4/full http://www.ncbi.nlm.nih.gov/pubmed/26878401?tool=bestpractice.com more recent meta-analyses reported a higher mortality associated with dopamine than with noradrenaline.[186]De Backer D, Aldecoa C, Njimi H, et al. Dopamine versus norepinephrine in the treatment of septic shock: a meta-analysis. Crit Care Med. 2012 Mar;40(3):725-30. http://www.ncbi.nlm.nih.gov/pubmed/22036860?tool=bestpractice.com
Primary options
noradrenaline (norepinephrine): 0.4 to 0.8 mg/hour intravenous infusion initially, adjust dose according to response
More noradrenaline (norepinephrine)Dose refers to noradrenaline base.
Secondary options
noradrenaline (norepinephrine): 0.4 to 0.8 mg/hour intravenous infusion initially, adjust dose according to response
More noradrenaline (norepinephrine)Dose refers to noradrenaline base.
-- AND --
vasopressin: 0.01 units/minute intravenous infusion initially, adjust dose according to response, maximum 0.03 units/minute
or
adrenaline (epinephrine): 2-10 micrograms/minute intravenous infusion initially, adjust dose according to response
OR
dopamine: 2-5 micrograms/kg/minute intravenous infusion initially, adjust dose according to response
These drug options and doses relate to a patient with no comorbidities.
Primary options
noradrenaline (norepinephrine): 0.4 to 0.8 mg/hour intravenous infusion initially, adjust dose according to response
More noradrenaline (norepinephrine)Dose refers to noradrenaline base.
Secondary options
noradrenaline (norepinephrine): 0.4 to 0.8 mg/hour intravenous infusion initially, adjust dose according to response
More noradrenaline (norepinephrine)Dose refers to noradrenaline base.
-- AND --
vasopressin: 0.01 units/minute intravenous infusion initially, adjust dose according to response, maximum 0.03 units/minute
or
adrenaline (epinephrine): 2-10 micrograms/minute intravenous infusion initially, adjust dose according to response
OR
dopamine: 2-5 micrograms/kg/minute intravenous infusion initially, adjust dose according to response
Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.
Primary options
noradrenaline (norepinephrine)
Secondary options
noradrenaline (norepinephrine)
-- AND --
vasopressin
or
adrenaline (epinephrine)
OR
dopamine
The Renal Handbook
Treatment recommended for SOME patients in selected patient group
Inotropes can be considered for patients with low cardiac output despite adequate fluid resuscitation and vasopressor therapy.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 [43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
Dobutamine is recommended first line by the Surviving Sepsis Campaign guideline for people with measured or suspected low cardiac output in the presence of adequate left ventricular filling pressure (or clinical assessment of adequate fluid resuscitation) and adequate mean arterial pressure.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
The UK National Institute for Health and Care Excellence makes no specific recommendations on inotrope selection in patients with sepsis.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Practical tip
Suspect low cardiac output if the clinical examination reveals prolonged capillary refill times, low urine output, or poor peripheral perfusion. Confirm with cardiac output monitoring or by sampling central venous or pulmonary arterial blood to measure oxygen saturations.
When using inotropes, keep the patient’s heart rate at less than 100 beats per minute to minimise myocardial ischaemia.[175]Rivers PE, McIntyre L, Morro DC, et al. Early and innovative interventions for severe sepsis and septic shock: taking advantage of a window of opportunity. CMAJ. 2005 Oct 25;173(9):1054-65. http://www.cmaj.ca/cgi/content/full/173/9/1054 http://www.ncbi.nlm.nih.gov/pubmed/16247103?tool=bestpractice.com
Primary options
dobutamine: 2.5 to 10 micrograms/kg/minute intravenous infusion initially, adjust dose according to response, maximum 40 micrograms/kg/minute
These drug options and doses relate to a patient with no comorbidities.
Primary options
dobutamine: 2.5 to 10 micrograms/kg/minute intravenous infusion initially, adjust dose according to response, maximum 40 micrograms/kg/minute
Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.
Primary options
dobutamine
The Renal Handbook
Treatment recommended for SOME patients in selected patient group
The Surviving Sepsis Campaign guideline recommends intravenous hydrocortisone as an option to consider for patients who are unresponsive to both fluid resuscitation and vasopressor therapy.[43]Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-77. https://link.springer.com/article/10.1007%2Fs00134-017-4683-6 http://www.ncbi.nlm.nih.gov/pubmed/28101605?tool=bestpractice.com
The UK National Institute for Health and Care Excellence does not give any recommendations on the use of corticosteroids for managing sepsis in adults.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51
Corticosteroids are a late critical-care intervention for patients in whom all other attempts to raise their blood pressure have failed.[3]National Institute for Health and Care Excellence. Sepsis: recognition, diagnosis and early management. September 2017 [internet publication]. https://www.nice.org.uk/guidance/ng51 In this critically ill group, corticosteroids may result in a small reduction in mortality.[189]Lamontagne F, Rochwerg B, Lytvyn L, et al. Corticosteroid therapy for sepsis: a clinical practice guideline. BMJ. 2018 Aug 10;362:k3284. https://www.bmj.com/content/362/bmj.k3284.long http://www.ncbi.nlm.nih.gov/pubmed/30097460?tool=bestpractice.com [190]Fang F, Zhang Y, Tang J, et al. Association of corticosteroid treatment with outcomes in adult patients with sepsis: a systematic review and meta-analysis. JAMA Intern Med. 2019 Feb 1;179(2):213-23. http://www.ncbi.nlm.nih.gov/pubmed/30575845?tool=bestpractice.com Possible harms include an increased risk of neuromuscular weakness, hyperglycaemia, and hypernatraemia with corticosteroids compared with no corticosteroids.[189]Lamontagne F, Rochwerg B, Lytvyn L, et al. Corticosteroid therapy for sepsis: a clinical practice guideline. BMJ. 2018 Aug 10;362:k3284. https://www.bmj.com/content/362/bmj.k3284.long http://www.ncbi.nlm.nih.gov/pubmed/30097460?tool=bestpractice.com
An international panel reviewing the inconsistent conclusions of large randomised controlled trials (RCTs) on the topic suggested in 2018 that the evidence for the use of corticosteroids was weak, but that “fully informed patients who value avoiding death over quality of life and function would likely choose corticosteroids”, although a no-corticosteroid approach remained reasonable.[189]Lamontagne F, Rochwerg B, Lytvyn L, et al. Corticosteroid therapy for sepsis: a clinical practice guideline. BMJ. 2018 Aug 10;362:k3284. https://www.bmj.com/content/362/bmj.k3284.long http://www.ncbi.nlm.nih.gov/pubmed/30097460?tool=bestpractice.com This judgement was based on an assessment that corticosteroids may reduce mortality by around 2% (this effect was seen in sepsis with and without shock although the greatest benefit was among patients with septic shock), but can increase the risk of neuromuscular weakness and resulting functional deterioration. Most notably, the panel reviewed the following trials:
ADRENAL: 3658 patients who had septic shock[191]Venkatesh B, Finfer S, Cohen J, et al; ADRENAL Trial Investigators and the Australian-New Zealand Intensive Care Society Clinical Trials Group. Adjunctive glucocorticoid therapy in patients with septic shock. N Engl J Med. 2018 Mar 1;378(9):797-808. http://www.nejm.org/doi/full/10.1056/NEJMoa1705835 http://www.ncbi.nlm.nih.gov/pubmed/29347874?tool=bestpractice.com
No statistically significant difference in 90-day mortality between the hydrocortisone and placebo groups
APROCCHSS: 1241 patients who had septic shock[192]Annane D, Renault A, Brun-Buisson C, et al; CRICS-TRIGGERSEP Network. Hydrocortisone plus fludrocortisone for adults with septic shock. N Engl J Med. 2018 Mar 1;378(9):809-18. http://www.ncbi.nlm.nih.gov/pubmed/29490185?tool=bestpractice.com
Hydrocortisone plus fludrocortisone reduced 90-day mortality.
[Figure caption and citation for the preceding image starts]: BMJ Rapid Recommendations: intravenous corticosteroids plus usual care versus usual care onlyLamontagne F, et al. BMJ 2018;362:k3284 [Citation ends].
A more recent systematic review and meta-analysis (comprising 37 RCTs, incorporating both ADRENAL and APROCHSS) included 9564 people with sepsis.[190]Fang F, Zhang Y, Tang J, et al. Association of corticosteroid treatment with outcomes in adult patients with sepsis: a systematic review and meta-analysis. JAMA Intern Med. 2019 Feb 1;179(2):213-23. http://www.ncbi.nlm.nih.gov/pubmed/30575845?tool=bestpractice.com The review found corticosteroid use to be associated with significant improvement in healthcare outcomes as shown by:[190]Fang F, Zhang Y, Tang J, et al. Association of corticosteroid treatment with outcomes in adult patients with sepsis: a systematic review and meta-analysis. JAMA Intern Med. 2019 Feb 1;179(2):213-23. http://www.ncbi.nlm.nih.gov/pubmed/30575845?tool=bestpractice.com
Reduced 28-day mortality (risk ratio [RR] 0.90, 95% CI 0.82 to 0.88) compared with placebo or standard supportive care
Reduced intensive care unit mortality (RR 0.85, 95% CI 0.77 to 0.94; I2 = 0%) compared with placebo or standard supportive care
Reduced in-hospital mortality (RR 0.88, 95% CI 0.79 to 0.99; I2 = 38%) compared with placebo or standard supportive care.
However, corticosteroid use was also associated with increased risk of hyperglycaemia (RR 1.19, 95% CI 1.08 to 1.30) and hypernatraemia (RR 1.57, 95% CI 1.24 to 1.99) compared with placebo or standard supportive care.[190]Fang F, Zhang Y, Tang J, et al. Association of corticosteroid treatment with outcomes in adult patients with sepsis: a systematic review and meta-analysis. JAMA Intern Med. 2019 Feb 1;179(2):213-23. http://www.ncbi.nlm.nih.gov/pubmed/30575845?tool=bestpractice.com
Primary options
hydrocortisone sodium succinate: 200 mg/day intravenously
These drug options and doses relate to a patient with no comorbidities.
Primary options
hydrocortisone sodium succinate: 200 mg/day intravenously
Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.
Primary options
hydrocortisone sodium succinate
The Renal Handbook
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