1 / 54

The use of steroids in septic shock patients Charles L. Sprung, M.D.

Department of Anesthesiology and Critical Care Medicine Hadassah Medical Center. The use of steroids in septic shock patients Charles L. Sprung, M.D. Treating the Septic Shock Patient- An interactive case.

abla
Download Presentation

The use of steroids in septic shock patients Charles L. Sprung, M.D.

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Department of Anesthesiology and Critical Care MedicineHadassah Medical Center The use of steroids in septic shock patients Charles L. Sprung, M.D.

  2. Treating the Septic Shock Patient- An interactive case • A 65 year old man is admitted with septic shock. After two fluid challenges of a liter of normal saline each and noradrenaline 0.02 mcg/kg/min, the BP was 95/45 mmHg after 30 minutes. • This patient SHOULD receive adjunct therapy with intravenous hydrocortisone 50 mg every 6 hours for 5-7 days. • 1. Strongly agree • 2. Agree • 3. No opinion or Unsure • 4. Disagree • 5. Strongly disagree

  3. Treating the Septic Shock Patient • The difference between the mortalities of patients and the steroid affect in the Annane (JAMA 2002) and the Corticus (NEJM 2008) studies were primarily due to: • 1. The entry window of 8 hours vs. 72 hours • 2. SBP < 90 mmHg greater than 1 hour or not • 3. Fludrocortisone treatment or not • 4. Treatment duration of 7 or 11 days • 5. Weaning or not

  4. Treating the Septic Shock Patient • The following statements concerning the use of steroids for patients with septic shock are true according to the latest Surviving Sepsis Campaign guidelines (Crit Care Med 2008;36:296-327). • 1. Treat patients who still require vasopressors despite fluid replacement with hydrocortisone. • 2. ACTH stimulation tests should be used to identify the subset of adults with septic shock who should receive hydrocortisone. • 3. Fludrocortisone must be added to hydrocortisone • 4. Wean the patient from steroid therapy once the septic shock has resolved • 5. Hydrocortisone should be administered for severe sepsiswithout shock

  5. Balancing Risks and Benefits of Steroids BENEFIT RISK

  6. Steroids For Treatment of Infections, Sepsis and Septic Shock - Ups and Downs YES „high-dose“ „low-dose“ Used in Clinical Practice NO Surviving Sepsis Campaign 2004 Bollaert 1998 Weizmann (review) 1974 Schumer 1976 Sprung 1984 VA-Coop Bone 1987 Corticus 2008 Briegel 1999 Cronin Lefering (meta_ analyses) 1995 Annane 2002

  7. Surviving Sepsis Campaign (SSC) Guidelines- Steroids • Treat patients who still require vasopressors despite fluid replacement with hydrocortisone 200-300 mg/day, for 7 days in three or four divided doses or by continuous infusion Grade C • Optional: - Adrenocorticotropic hormone (ACTH) stimulation test (250-µg) - Continue treatment only in nonresponders (delta cortisol  9 µg/dl) Grade E Dellinger P. Crit Care Med 2004;32:858-873

  8. STUDY DESIGN H0 ONSET OF SHOCK ELIGIBILITY AND ACTH TEST RANDOMIZATION H8 HC (IV 50 mg q 6h)+ FC (PO 50 µg/d) FOR 7 D PLACEBO FOR 7 DAYS DAY 28 Annane D. JAMA 2002:288:862-871

  9. STEROID THERAPY OF SEPTIC SHOCK • 18 YEARS OR OLDER • DOCUMENTED INFECTION OR SUSPICION • TEMPERATURE > 38.3OC OR < 35.6OC • HEART RATE > 90 BEATS/MIN • SBP < 90 mmHg > 1 HR DESPITE FLUID & VP • UO < 0.5 ml/kg/hr OR PaO2/FIO2 < 280 • NEED FOR MECHANICAL VENTILATION • ACTH STIMULATION TEST Annane D. JAMA 2002:288:862-871

  10. 28-Day Survival All PATIENTS Hazard Ratio: 0.71 (95% CI, 0.53-0.97) p = 0.03 Annane JAMA 2002;288:862-871

  11. 28-Day Survival NON RESPONDER Hazard Ratio: 0.67 (95% CI, 0.47-0.95) p = 0.02 Annane JAMA 2002;288:862-871

  12. 28-Day Survival RESPONDERS Log-Rank-Test, 2= 0.56 p = 0.81 Annane JAMA 2002;288:862-871

  13. Sprung CL. 2008;358:111-124

  14. CORTICUS STUDY • Investigator-initiated, European double-blind PRCT • Patients enrolled from March ‘02 - Nov ‘05 • 52 enrolling centers • Intended sample size: 800 (80% power to detect 10% absolute fall in mortality) • Final enrollment: 500 patients • 499 patients analyzable Sprung CL. NEJM 2008;358:111-124

  15. CORTICUS INCLUSION CRITERIA • Clinical evidence of infection within previous 72h Any of… • presence of neutrophils in normally sterile body fluid (excluding blood) • positive culture or Gram stain of blood, sputum, urine or normally sterile body fluid • identified focus of infection • other clinical evidence of infection - pneumonia, purpura fulminans, necrotising fascitis, etc.

  16. CORTICUS INCLUSION CRITERIA 2. Systemic response to infection … as defined by ≥2 of following signs within previous 72h: • fever (>38.30C) or hypothermia (<35.60C) • tachycardia (>90 bpm) • tachypnea (> 20 breaths/min, PaCO2<32mmHg) .or patient requires mechanical ventilation • WBC count >12,000 or < 4000 cells/mm3 or >10% immature neutrophils

  17. CORTICUS INCLUSION CRITERIA 3. Evidence of shock • Systolic BP < 90 mmHg or >50 mmHg fall despite adequate fluid or need for pressors >1h (dopamine 5g/kg/min or any dose of adr, noradr, vasopressin or phenylephrine)to maintain SBP > 90mmHg • Hypoperfusion or organ dysfunction attributable to sepsis within previous 72h including one of: • sustained oliguria (<0.5 ml/kg/h for >1 hr) • metabolic acidosis [pH <7.3, base deficit ≥ 5, lactate >2] • platelets ≤ 100,000/mm3 • GCS < 14 (or acute change from baseline) 4. Informed consent 5. ACTH stimulation test

  18. CORTICUS EXCLUSION CRITERIA • Chronic corticosteroid therapy in last 6 months or acute steroid therapy (any dose) within 4 months (including inhaled steroids) • Drug-induced immunosuppression, including chemotherapy or radiation therapy within 4 weeks • Presence of advanced directive to withhold or withdraw life sustaining treatment • Moribund patients likely to die within 24 hours • In ICU >2 months at time of onset of septic shock • HIV positivity

  19. CORTICUS STUDY MEDICATION IV bolus • 50mg hydrocortisone q 6h x 5 days (days 1-5) • 50mg hydrocortisone q 12h x 3 days (days 6-8) • 50mg hydrocortisone q 24h x 3 days (days 9-11) no repeat dose or “real” steroids no fludrocortisone Sprung CL. NEJM 2008;358:111-124

  20. RESULTS Demographics Sprung CL. NEJM 2008;358:111-124

  21. RESULTS Source of infection Sprung CL. NEJM 2008;358:111-124

  22. RESULTS: ACTH stimulation test Sprung CL. NEJM 2008;358:111-124

  23. % mortality 100 80 60 40 86 (34.3%) 78 (31.5%) 20 0 RESULTS: 28-day mortality - all patients Sprung CL. NEJM 2008;358:111-124 P = 0.51 steroids (n=251) placebo (n=248)

  24. % mortality % mortality Responders Non-responders 100 100 80 80 60 60 40 40 20 20 39 (28.7%) 34 (28.8%) 39 (36.1%) 49 (39.2%) 0 0 steroids (n=118) placebo (n=136) steroids (n=125) placebo (n=108) RESULTS: 28-day mortality - by response to ACTH stimulation Sprung CL. NEJM 2008;358:111-124 P = 1.000 P =0.69

  25. survival 1.00 0.75 steroid placebo 0.50 0.25 0 day 0 5 10 15 20 25 30 RESULTS: 28 day survival curves - all patients Sprung CL. NEJM 2008;358:111-124 P value for log rank test: 0.753

  26. survival 1.00 0.75 steroid placebo 0.50 0.25 0 day 0 5 10 15 20 25 30 RESULTS: 28 day survival curves - ACTH non-responders Sprung CL. NEJM 2008;358:111-124 P value for log rank test: 0.786

  27. survival 1.00 0.75 steroid placebo 0.50 0.25 0 day 0 5 10 15 20 25 30 RESULTS: 28 day survival curves - ACTH responders Sprung CL. NEJM 2008;358:111-124 P value for log rank test: 0.937

  28. RESULTS Reversal of shock Sprung CL. NEJM 2008;358:111-124

  29. RESULTS: Time to reversal of shock Median time in days (95% CI) Sprung CL. NEJM 2008;358:111-124

  30. Frequency of superinfections SI- Relative risk (95% CI) = 1.27 (0.96-1.68) SI+ new S + SS- Relative risk (95% CI) = 1.37 (1.05-1.79) Sprung CL. NEJM 2008;358:111-124

  31. Adverse events

  32. Corticus Harmonization Study Central Method: Roche Briegel J. Am J Resp CCM 2007, 175: A436

  33. Conclusions • Hydrocortisone Rx • did not decrease mortality in non-responders, responders or all patients • did not reverse shock in non-responders, responders or all patients • did decrease the time to shock reversal in non-responders,responders and all patients

  34. Conclusions • Hydrocortisone Rx • was not associated with an increased incidence of polyneuropathy • was associated with an increased incidence of superinfection and new sepsis and septic shock

  35. Conclusions • The short corticotropin test does not appear useful for guiding steroid therapy • The gain achieved by earlier shock reversal in patients receiving hydrocortisone was counterbalanced by later superinfections and new sepsis and septic shock

  36. Recommendations • Hydrocortisone therapy cannot be recommended as routine adjuvant therapy for septic shock nor can corticotropin testing • Hydrocortisone may have a role among patients who are treated early after the onset of septic shock who remain hypotensive despite the administration of high-dose vasopressors

  37. 28-day Mortality AnnaneCorticus Steroids 82/150 (55%) 86/251 (34.3%) Placebo 91/149 (61%) 78/248 (31.5%) Total 173/299 (58%) 164/499 (32.9%)

  38. STUDY DIFFERENCES AnnaneCorticus Entry window 8 hours 72 hours SBP < 90 mmHg > 1 hour < 1 hour Treatment Fludrocortisone None Treatment duration 7 days 11 days Weaning No Yes Practice/Guidelines NoneSteroids used SAPS II 59 + 21 49 + 17 Non-responders 229 (77%) 233 (47%)

  39. Meta-analysis of treatment with hydrocortisone on shock reversal at day 7 in patients with septic shock Marik P et al. Crit Care Med. 2008;36:1937-1949

  40. Meta-analysis of treatment with hydrocortisone on 28-day survival in patients with septic shock Marik P et al. Crit Care Med. 2008;36:1937-1949

  41. Steroids and ARDS prevention Peter, J. V. et al. BMJ 2008;336:1006-1009

  42. Steroids and ARDS mortality Peter, J. V. et al. BMJ 2008;336:1006-1009

  43. STEROID USE • Doctors see the reversal of shock very quickly and associate the improvement to steroid use • Doctors do not associate the late complications with steroids as they are not temporally related • These include superinfections, new sepsis, new septic shock, CMV and ARDS mortality

  44. Surviving Sepsis Campaign (SSC) Guidelines for Management of Severe Sepsis and Septic ShockUpdatedGuidelines Dellinger P et al. Crit Care Med. 2008;36:296-327

  45. Surviving Sepsis Campaign (SSC) Updated Guidelines- Steroids • We suggest intravenous hydrocortisone be given only to adult septic shock patients after blood pressure is identified to be poorly responsive to fluid resuscitation and vasopressor therapy Grade 2C Annane JAMA 2002;288:862-871 Sprung CL. NEJM 2008;358:111-124 Dellinger P. Crit Care Med. 2008;36:296-327

  46. Surviving Sepsis Campaign (SSC) Updated Guidelines- Steroids • We suggest the ACTH stimulation test not be used to identify the subset of adults with septic shock who should receive hydrocortisoneGrade 2B Sprung CL. NEJM 2008;358:111-124 Briegel AJRCCM (abst). 2007: 175:A436 • Oral fludrocortisone (50 µg) is considered optional if hydrocortisone is used Grade 2C Annane JAMA 2002;288:862-871 Sprung CL. NEJM 2008;358:111-124 Dellinger P. Crit Care Med. 2008;36:296-327

  47. Surviving Sepsis Campaign (SSC) Updated Guidelines- Steroids • Wean the patient from steroid therapy once the septic shock has resolvedGrade 2DKeh AJRCCM 2003; 167:512-520 • Do not use corticosteroids >300 mg/day of hydrocortisone to treat septic shock Grade 1ABone, et al. NEJM 1987; 317-658 VA Sepsis Study Group. NEJM 1987; 317:659-665 • In the absence of shock, corticosteroids should not be administered for the treatment of sepsis Grade 1D • There is no contraindication to continuing maintenance steroid therapy or to using stress does steroids if the patient’s endocrine or corticosteroid administration history warrants Grade 1D Dellinger P. Crit Care Med 2008;36:296-327

  48. Corticosteroids in Septic Shock Déjà vu

  49. Sprung CL. N Engl J Med 1984; 11:1137-43;358:111-124

  50. MORTALITY REVERSAL OF SHOCK SPRUNG CL. N ENGL J MED 1984; 311:1137-1143

More Related