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Practice Rapid Recommendations

Corticosteroid therapy for sepsis: a clinical practice guideline

BMJ 2018; 362 doi: https://doi.org/10.1136/bmj.k3284 (Published 10 August 2018) Cite this as: BMJ 2018;362:k3284

Population

Recommendation applies to: Recommendation does not apply to: Adults and children Patients with pre-existing adrenal insufficiency Non-infectious causes of shock Neonates Pregnant women Any infectious source Patients with and without shock Intra abdominal infections Pneumonia Anaphylactic Cardiogenic Hypovolaemic People with sepsis SOFA score of at least 2

Comparison

or Corticosteroid therapy No corticosteroid therapy Usual care only Intravenous corticosteroids plus usual care Corticosteroids No corticosteroids Usualcare Usualcare + CCS

More details We suggest corticosteroid therapy rather than no corticosteroid therapy. Either option is reasonable. Strong Benefits outweigh harms for almost everyone. All or nearly all informed patients would likely want this option. Weak Benefits outweigh harms for the majority, but not for everyone. The majority of patients would likely want this option. Weak Benefits outweigh harms for the majority, but not for everyone. The majority of patients would likely want this option. Strong Benefits outweigh harms for almost everyone. All or nearly all informed patients would likely want this option.

Comparison of benefits and harms

Favours corticosteroids Favours no corticosteroids Evidence quality Events per 1000 people No important difference The panel found that these differences were not important for most patients, because the intervention effects were negligible and/or very imprecise (such as statistically not significant)

18 fewer Mortality Low More 254 236

Risk of Bias No serious concerns Imprecision Serious Indirectness No serious concerns Inconsistency Serious Publication bias No serious concerns Short term (28-31 days) Corticosteroids may achieve a small or no reduction in short term mortality

Neuromuscular weakness Low More 303 53 fewer 250

Risk of Bias No serious concerns Imprecision Serious Indirectness Serious Inconsistency Borderline Publication bias No serious concerns Corticosteroids may increase the risk of neuromuscular weakness

Quality of Life None More Unknown

Not reported in any of the included studies

Stroke Very low More 5 10 No important difference

Risk of Bias No serious concerns Imprecision Very serious Indirectness Serious Inconsistency No serious concerns Publication bias No serious concerns Whether or not corticosteroids impact the risk of stroke is uncertain

Myocardial infarction Very Low More 30 27 No important difference

Risk of Bias No serious concerns Imprecision Very serious Indirectness Serious Inconsistency No serious concerns Publication bias No serious concerns Whether or not corticosteroids impact the risk of myocardial infarction is uncertain
Mean number of days

Length of ICU stay Moderate More 13.1 0.7 fewer 12.4

Risk of Bias No serious concerns Imprecision Serious Indirectness No serious concerns Inconsistency No serious concerns Publication bias No serious concerns Corticosteroids probably achieve a small reduction in the duration of initial stay in an intensive care unit (ICU)

Length of hospital stay Moderate More 32.0 0.7 fewer 31.3

Risk of Bias No serious concerns Imprecision Serious Indirectness No serious concerns Inconsistency No serious concerns Publication bias No serious concerns Corticosteroids probably achieve a small reduction in the duration of hospitalization
See patient decision aids
See all outcomes
Those who place more value on avoiding functional deterioration and maximising quality of life than on avoiding death may be more likely to choose not to use corticosteroids Preferences and values Patients at greatest risk of death (such as those with shock, high qSOFA/SOFA scores) will probably have the greatest reduction in risk of death with corticosteroids Risk of death There are no clear differences in efficacy or adverse effects between different corticosteroids or corticosteroid combinations. Most studies used hydrocortisone Choice of corticosteroid Key practical issues No key practical issues Infusion or intermittent bolus dosing Monitoring for serum sodium, potassium, and glucose Corticosteroids No corticosteroids

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Find recommendations, evidence summaries and consultation decision aids for use in your practice
  1. Francois Lamontagne, chair, critical care clinician1 2,
  2. Bram Rochwerg, critical care clinician3 4,
  3. Lyubov Lytvyn, patient partnership liaison4,
  4. Gordon H Guyatt, general internist4,
  5. Morten Hylander Møller, anesthesiologist and critical care clinician5,
  6. Djillali Annane, critical care clinician6,
  7. Michelle E Kho, physiotherapist7,
  8. Neill K J Adhikari, critical care clinician8 9,
  9. Flavia Machado, critical care clinician10 11,
  10. Per O Vandvik, general internist12 13,
  11. Peter Dodek, critical care clinician14,
  12. Rebecca Leboeuf, endocrinologist15,
  13. Matthias Briel, corticosteroid trialist4 16,
  14. Madiha Hashmi, critical care clinician17,
  15. Julie Camsooksai, critical care nurse18,
  16. Manu Shankar-Hari, critical care clinician19 20,
  17. Mahder Kinfe Baraki, anaesthesiologist and critical care clinician21,
  18. Karie Fugate, family caregiver of patient22,
  19. Shunjie Chua, family caregiver of patient23,
  20. Christophe Marti, critical care clinician24,
  21. Dian Cohen, patient25,
  22. Edouard Botton, patient26,
  23. Thomas Agoritsas, general internist4 27,
  24. Reed A C Siemieniuk, methods co-chair, general internist4
  1. 1Department of Medicine, Université de Sherbrooke, Sherbrooke, Canada
  2. 2Centre de recherche du CHU de Sherbrooke, Centre intégré universitaire de santé et de services sociaux - Estrie, Sherbrooke, Canada
  3. 3Department of Medicine, McMaster University, Hamilton, Canada
  4. 4Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
  5. 5Department of Intensive Care, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
  6. 6Service de Médecine Intensive et Réanimation, Hôpital Raymond Poincaré, Garches, France
  7. 7School of Rehabilitation Science, McMaster University, Hamilton, Canada
  8. 8Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto Canada
  9. 9Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada
  10. 10Federal University of Sao Paulo, Sao Paulo, Brazil
  11. 11Latin America Sepsis Institute, Sao Paulo, Brazil
  12. 12Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway
  13. 13Department of Medicine, Innlandet Hospital Trust-division, Gjøvik, Norway
  14. 14Center for Health Evaluation and Outcome Sciences and Division of Critical Care Medicine, St Paul's Hospital and University of British Columbia, Vancouver, Canada
  15. 15Department of Medicine, Centre Hospitalier de l’Université de Montréal, Montréal, Canada
  16. 16Basel Institute for Clinical Epidemiology and Biostatistics, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland
  17. 17Department of Anaesthesiology, Aga Khan University, Karachi, Pakistan
  18. 18Poole Hospital NHS Foundation Trust, Dorset, United Kingdom
  19. 19Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom
  20. 20NIHR Clinician Scientist, School of Immunology & Microbial Sciences, Kings College London, United Kingdom
  21. 21Department of Anesthesiology, Addis Ababa University, Addis Ababa, Ethiopia
  22. 22Renton, USA
  23. 23Carevise Mexico, Mexico City, Mexico
  24. 24Division of General Internal Medicine, Rehabilitation and Geriatrics, University Hospitals of Geneva, Geneva, Switzerland
  25. 25Centre de santé de la vallée Massawippi, Ayer’s Cliff, Canada
  26. 26Comité stratégique patient-partenaire, Centre de recherche du CHU de Sherbrooke, Centre intégré universitaire de santé et de services sociaux - Estrie, Sherbrooke, Canada
  27. 27Division General Internal Medicine & Division of Clinical Epidemiology, University Hospitals of Geneva, Geneva, Switzerland
  1. Correspondence to: R A C Siemieniuk reed.siemieniuk{at}medportal.ca

What you need to know

  • Sepsis is a syndrome of life threatening infection with organ dysfunction, and most guidelines do not advise use of corticosteroids to treat it in the absence of refractory shock

  • Two new trials of corticosteroid treatment for sepsis came to differing conclusions

  • Corticosteroids may reduce the risk of death by a small amount and increase neuromuscular weakness by a small amount, but the evidence is not definitive

  • This guideline makes a weak recommendation for corticosteroids in patients with sepsis; both steroids and no steroids are reasonable management options

  • Fully informed patients who value avoiding death over quality of life and function would likely choose corticosteroids

Do corticosteroids reduce death or improve recovery in people with sepsis or septic shock? Our panel make a weak recommendation to give corticosteroids to people with all types and severity of sepsis, based on new evidence. Because we are not certain that they are beneficial, it is also reasonable not to prescribe them. Patients’ values and preferences may guide this decision-making process.

This rapid recommendation was triggered by two trials, with differing conclusions whose results might change practice:

  • ADRENAL (3658 patients who had septic shock) found no statistically significant difference in 90 day mortality between the hydrocortisone and placebo groups.1

  • APROCCHSS (1241 patients who had septic shock) found that hydrocortisone plus fludrocortisone reduced 90 day mortality.2

The trials are incorporated into a linked systematic review comparing corticosteroids with placebo.3 This BMJ Rapid Recommendation promptly and transparently translates this evidence using GRADE methodology for trustworthy guidelines. Sepsis is a life threatening organ dysfunction from infection. Currently most guidelines advise against giving corticosteroids in sepsis in the absence of refractory shock, but these guidelines have not taken into account the new evidence. We do not anticipate that new clinical trials will substantively alter the evidence …

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