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Corticosteroids in the ICU

Corticosteroids in the ICU. Fekri Abroug CHU F.Bourguiba Monastir Tunisia. Corticosteroids in Sepsis. Background. Systemic inflammation is the hallmark of sepsis Corticosteroids modulate immune response to sepsis through genomic and non-genomic effects

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Corticosteroids in the ICU

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  1. Corticosteroids in the ICU Fekri Abroug CHU F.Bourguiba Monastir Tunisia

  2. Corticosteroids in Sepsis

  3. Background • Systemic inflammation is the hallmarkof sepsis • Corticosteroids modulate immune response to sepsis through genomic and non-genomic effects • Cytokines may suppress cortisol production or access to tissues, inducing corticosteroids insufficiency in almost half of septic shock

  4. Clinical Question • In patients with sepsis, septic shock, does treatment with corticosteroids replacement-dose improve short-term survival?

  5. Inclusion Criteria • Types of studies: RCT or quasi-RCT with or without blinding. • Types of participants: Children & adults with sepsis, septic shock (ACCP/SCCM 1992). • Types of interventions - Intervention: - i.v. of any type of corticosteroid preparation - replacement therapy: ≤300mg HC (equivalent) for ≥5 days - Control: Standard therapy or placebo. • Types of outcome measures - Primary: 28-day all-cause mortality. - Secondary: Hospital mortality, shock reversal (day 7), Adverse events.

  6. Mixed population, n=3 Incomplete information, n=3 7 RCTs excluded Very short term effects, n=1 26 RCTs 1 Cross over, n=40 19 RCTs included 18 Parallel groups, n=2,137 CS-Replacement 9 RCTs N=570 Results

  7. Favors CS Favors Control Results 28-day Mortality (all trials) RR=0.88 (0.78 to 0.99) P=0.03

  8. Results28-day Mortality(Long course of low dose)

  9. ResultsHospital Mortality (Long course of low dose)

  10. Favors Control Favors CS ResultsShock Reversal

  11. Favors CS Favors Control ResultsAdverse Events (long course of low dose)

  12. Corticosteroids in ARDS

  13. Position of the Problem • Systemic Inflammation is the hallmark of ARDS both at the early phase and later in the course of the disease • Corticosteroids are the main anti-inflammatory drugsboth at high doses and moderate doses

  14. Position of the Problem Theoretically there are 4 therapeutic options • 1- High dose CS for early ARDS • 2- High dose of CS for late ARDS • 3- Low dose CS for early ARDS • 4- Low dose CS or late ARDS

  15. 1- High dose CS for early ARDS • 2- High dose of CS for late ARDS • 3- Low dose CS for early ARDS • 4- Low dose CS or late ARDS

  16. High Dose CS for Early ARDS

  17. No effect of early high doses and short courses (30mg/kg MP 1-2D)

  18. 1- High dose CS for early ARDS • 2- High dose of CS for late ARDS • 3- Low dose CS for early ARDS • 4- Low dose CS or late ARDS

  19. NO DATA

  20. 1- High dose CS for early ARDS • 2- High dose of CS for late ARDS • 3- Low dose CS for early ARDS • 4- Low dose CS for late ARDS

  21. PaO2/FIO2 * P < 0.05 Ratio * * * Day ARDS net study, ATS05

  22. Plateau Pressure and Static Compliance Plateau Pressure * * * Static Compliance * * * Day * P < 0.05 ARDS net study, ATS05

  23. Ventilator-Free Days • VFD @ 28 d (mean) • VFD @ 60 d (mean) • VFD @ 180 d (mean) Placebo MP P-Value 6.8 25.5 150 11.1 31.0 159 0.0007 0.02 0.04 ARDS net study, ATS05

  24. Median OrganFailure-Free Days to Day 28 Variable Placebo Methylprednisolone P-Value • Cardiovascular • Coagulation • Hepatic • Renal 17 23 24 23 21 23 24.5 25 0.03 0.84 0.70 0.36 ARDS net study, ATS05

  25. LaSRS: Adverse Events P Value Placebo MP • Total 26 32 NS • CNS 0 5 0.028 • MS 0 5 0.028 All 9 cases of neuromyopathy reported were in the methylprednisolone group ARDS net study, ATS05

  26. Serious Infections P=0.135 • Placebo 43 in 30 pts • Methylprednisolone 25 in 20 pts • More suspected/probable pneumonia in the placebo group (14.3 vs. 5.6%, P=0.049) • More septic shock episodes in the placebo group (17 vs. 15 pts vs 6 in 5 pts; P=0.031) ARDS net study, ATS05

  27. Effects of Corticosteroids Corticosteroids compared to placebo had: • Greater decrease in plasma IL-6 • Greater decrease in BAL neutrophils ARDS net study, ATS05

  28. Low Dose CS for Late ARDS

  29. 1- High dose CS for early ARDS • 2- High dose of CS for late ARDS • 3- Low dose CS for early ARDS • 4- Low dose CS or late ARDS

  30. GER-INF-05 300 SEPTIC SHOCK 177 WITH ARDS 123 WITHOUT ARDS 67 PLACEBO 62 STEROIDS

  31. p Placebo (n = 67) Corticosteroids (n = 62) Day-28 mortality 50 (75%) 33 (53%) Unadjusted hazard ratio 0.60 (0.38-0.93) 0.021 Adjusted hazard ratio 0.57 (0.36-0.89) 0.013 Relative risk 0.71 (0.54-0.94) 0.011 Adjusted odds ratio 0.35 (0.15-0.82) 0.016 ICU mortality 53 (79%) 36 (58%) Relative risk 0.73 (0.57-0.94) 0.010 Adjusted odds ratio 0.35 (0.15-0.82) 0.016 Hospital mortality 53 (79%) 37 (60%) Relative risk 0.75 (0.59-0.96) 0.016 Adjusted odds ratio 0.38 (0.16-0.88) 0.025 NON RESPONDERS

  32. Assessed for eligibility (N= 517) Excluded (N = 212) * Did not meet inclusion criteria (N =181) Refused to participate (N = 16) Randomized (n = 91) Methylprednisolone infusion (N= 63) Received allocated intervention > 24 h (N = 61) Received allocated intervention < 24 h (N = 2) † Placebo (N = 28) Received allocated intervention > 24 h (N = 27) Received allocated intervention < 24 h (N = 1) † Protocol violation (N = 5) ‡ Discontinued intervention (N = 1) || Protocol violation (N = 0) Discontinued intervention (N = 3) || Day 7 analysis (N = 55) Day 7 analysis (N = 24) Exit study after day 7 (N = 4) ¶ Exit study after day 7 (N = 3) ¶ Final analysis (N = 51) Final analysis (N = 21) Low Dose CS for Early ARDS Meduri et al submitted

  33. Low Dose CS for Early ARDS P=0.001 P<0.001 Meduri et al submitted

  34. Low Dose CS for Early ARDS P=0.13 P=0.28 Meduri et al submitted

  35. Summary • Low dose of CS consistently showed benefit on both early and late ARDS morbidity • Low Dose of CS may improve survival from ARDS both during the early and late phase. However data remained controversial • Efforts should be made to reduce CS induced muscle weakness – Glucose control?

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