Corticosteroids in the ICU

Slides:



Advertisements
Similar presentations
A Comparison of Early Versus Late Initiation of Renal Replacement Therapy in Critically III Patients with Acute Kidney Injury: A Systematic Review and.
Advertisements

Adjunctive Pharmacotherapy In Sepsis นายแพทย์ เฉลิมไทย เอก ศิลป์ สถาบันสุขภาพเด็กแห่งชาติ มหาราชินี
Cardiovascular outcome in patients with dysglycemia with daily supplementation of n-3 fatty acids 1 ORIGIN trial (Outcome Reduction with an Initial Glargine.
Thiopurines still have a role in the management of pediatric IBD Athos Bousvaros MD, MPH Associate Director, IBD program Boston Children’s Hospital.
Journal Club General Medicine C- 4/3/14
1 Heparin-associated 30 Day Mortality Zarychanski et al, CCM 2008;36:
BY MELISSA JAKUBOWSKI PULMONARY DISEASE TREATMENT CONCERNING COPD.
C-Reactive Protein: a Prognosis Factor for Septic Patients Systematic Review and Meta-analysis Introduction to Medicine – 1 st Semester Class 4, First.
Sarah Struthers, MD March 19, 2015
Danny McAuley Queen’s University of Belfast Scottish Combined Critical Care Conference September 2010 Statins in ARDS.
Intensive versus Conventional Glucose Control in Critical Ill Patients N Engl J Med 2009; 360: 雙和醫院 劉慧萍藥師.
Department of Anesthesiology and Critical Care Medicine Hadassah Medical Center Steroids: Benefits vs. Risks Risk/Benefit: Where are we now? Charles L.
Study design P.Olliaro Nov04. Study designs: observational vs. experimental studies What happened?  Case-control study What’s happening?  Cross-sectional.
CHEST. 2007;131(4): Methylprednisolone Infusion in Early Severe ARDS - Results of a Randomized Controlled Trial.
Laura Mucci, Pharm.D. Candidate Mercer University 2012 Preceptor: Dr. Rahimi February 2012.
Meduri et all Chest 2007;131; Background  Inflammation in the first week of MV determines resolving vs un-resolving  Un-resolving ARDS LIS by.
A Comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit The SAFE Study Investigators N Engl J Med 2004: 350:
Binu George , Heather Bury Critical care Journal Club May 2014
ISIS-4: Fourth International Study of Infarct Survival Purpose To assess the separate and combined effects on all-cause mortality of adding early captopril,
Improved Survival in Patients with First Relapsed or Refractory Acute Myeloid Leukemia (AML) Treated with Vosaroxin plus Cytarabine versus Placebo plus.
1 EFFICACY OF SHORT COURSE AMOXICILLIN FOR NON-SEVERE PNEUMONIA IN CHILDREN (Hazir T*, Latif E*, Qazi S** AND MASCOT Study Group) *Children’s Hospital,
Haemofiltration for sepsis: burial or resurrection?
Copenhagen University Hospital Rigshospitalet, Denmark
R3 정수웅. Introduction Community-acquired pneumonia − Leading infectious cause of death in developed countries − The mortality in patients with treatment.
Steroid Therapy.
Diamantis P. Kofteridis, Christina Alexopoulou, Antonios Valachis, Sofia Maraki, Dimitra Dimopoulou Clinical Infectious Diseases 2010; 51(11):1238–1244.
HAART Initiation Within 2 Weeks of Seroconversion Associated With Virologic and Immunologic Benefits Slideset on: Hecht FM, Wang L, Collier A, et al. A.
Towards Global Eminence K Y U N G H E E U N I V E R S I T Y j 내과 R2 이지영.
LSU Journal Club Corticosteroid Therapy for Patients Hospitalized With Community-Acquired Pneumonia A Systematic Review and Meta-analysis Scott Hebert,
Alcohol dependence is independently associated with sepsis, septic shock, and hospital mortality among adult ICU patients Crit Care Med 2007 ; 35 :
Antibiotics in Addition to Systemic Corticosteroids for Acute Exacerbations of Chronic Obstructive Pulmonary Disease Johannes M.A. Daniels; Dominic snijders;
R1. 이정미 / prof. 이상열. INTRODUCTION Type 2 diabetes is a major risk factor for cardiovascular disease The presence of both type 2 diabetes and.
Traitements non Antibiotiques du Choc Septique Djillali ANNANE, Hôpital Raymond Poincaré Garches,
Cardiovascular Disease and Antihypertensives The RENAAL Trial Reference Brunner BM, and the RENAAL study group. Effects of losartan on renal and cardiovascular.
Fekri Abroug, Lamia Ouanes-Besbes, Mohamed Fkih-Hassen, Islem Ouanes, Samia Ayed, Laurent Brochard and Souheil ElAtrous Prednisone in COPD exacerbation.
Nephrology Journal Club The SPRINT Trial Parker Gregg
Eucrisa™ - Crisaborole
Effects of Uric acid- lowering therapy on renal outcomes: a systematic review and meta-analysis Nephrol Dial Transplant (2014) 29: Vaughan Washco.
Research where it is most needed National Respiratory Strategy
CLINICAL PROTOCOL DEVELOPMENT
Copenhagen University Hospital Rigshospitalet, Denmark
Saptharishi L G, Jayashree M, Singhi S, Bansal A
Alcohol, Other Drugs, and Health: Current Evidence
Advanced Ventilation Research
HOPE: Heart Outcomes Prevention Evaluation study
Neal B, et al. Diabetes Care 2015;38:403–411
The Anglo Scandinavian Cardiac Outcomes Trial
Goede V et al. Proc ASH 2014;Abstract 3327.
Assessed for eligibility (n = 38)
CANTOS: The Canakinumab Anti-Inflammatory Thrombosis Outcomes Study
Study Design AMI <12 hours, any age, cardiogenic shock excluded
Steroids in Sepsis.
Assessed for eligibility (N = )
Avoiding Cardiovascular events through COMbination therapy in Patients LIving with Systolic Hypertension (ACCOMPLISH): Design Randomized, double-blind.
CRASH 2 Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2):
Barrios C et al. SABCS 2009;Abstract 46.
SIGNIFY Trial design: Participants with stable coronary artery disease without clinical heart failure and resting heart rate >70 bpm were randomized to.
Vitolo U et al. Proc ASH 2011;Abstract 777.
Faderl S et al. Proc ASCO 2011;Abstract 6503.
CIBIS II: Cardiac Insufficiency Bisoprolol Study II
Risk of perioperative renal dysfunction with N-acetylcysteine or placebo in patients undergoing CABG surgery End point N-acetylcysteine Placebo Relative.
Domenica 03 giugno Highlight a cura di Filippo de Marinis
Screening, Lipid Stabilization, and Placebo Run-in
Table of Contents Why Do We Treat Hypertension? Recommendation 5
J Foland, J Fortenberry, B Warshaw,
pulmonary embolism protocol -- EMB review
Should I still screen for possible sepsis with SIRS criteria?
PPI prophylaxis for GI bleeding in ICU
The efficacy and safety of omalizumab in pediatric allergic asthma
Björn Bornkamp, Georgina Bermann
Presentation transcript:

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 Cytokines may suppress cortisol production or access to tissues, inducing corticosteroids insufficiency in almost half of septic shock

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

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.

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

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

Results 28-day Mortality (Long course of low dose)

Results Hospital Mortality (Long course of low dose)

Results Shock Reversal Favors Control Favors CS

Results Adverse Events (long course of low dose) Favors CS Favors Control

Corticosteroids in ARDS

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 drugs both at high doses and moderate doses

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

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

High Dose CS for Early ARDS (MP30mg/kg) Placebo P Weigelt 1985 46% of 39 31% of 42 0.18 Bone 1987 52% of 152 21% of 152 0.004 Luce 1988 58% of 38 54% of 37 ns

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

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

NO DATA

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

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

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

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

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

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

Serious Infections 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

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

Low Dose CS for Late ARDS Meduri (Jama 98) ARDS net (ATS05) n 24 180 Rx MP 2mg/kg 32 d MP 2mg/kg 21 d P/F Improved Static compliance Systemic & lung Inflammation Reduced Time on MV OSF free days Increased Mortality Decreased Unchanged Superinfection Muscle weakness ?

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

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

Day-28 mortality ICU mortality Hospital mortality NON RESPONDERS   p 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 ICU mortality 53 (79%) 36 (58%) 0.73 (0.57-0.94) 0.010 Hospital mortality 37 (60%) 0.75 (0.59-0.96) 0.016 Placebo (n = 67) Corticosteroids (n = 62) Adjusted odds ratio 0.35 (0.15-0.82) 0.38 (0.16-0.88) 0.025

Low Dose CS for Early ARDS 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) † Protocol violation (N = 5) ‡ Discontinued intervention (N = 1) || Day 7 analysis (N = 55) Exit study after day 7 (N = 4) ¶ Final analysis (N = 51) (N = 0) (N = 3) || Day 7 analysis (N = 24) Placebo (N = 28) Received allocated intervention > 24 h (N = 27) Received allocated intervention < 24 h (N = 1) † Exit study after day 7 (N = 3) ¶ Final analysis (N = 21) Meduri et al submitted

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

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

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?