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Clinical Infectious Diseases : An... Oct 2018We evaluated the effect of intravenous immunoglobulin (IVIG) on mortality in clindamycin-treated streptococcal toxic shock syndrome using a meta-analysis. In association... (Meta-Analysis)
Meta-Analysis
We evaluated the effect of intravenous immunoglobulin (IVIG) on mortality in clindamycin-treated streptococcal toxic shock syndrome using a meta-analysis. In association with IVIG, mortality fell from 33.7% to 15.7% with remarkable consistency across the single randomized and four nonrandomized studies.
Topics: Clindamycin; Humans; Immunoglobulins, Intravenous; Shock, Septic; Streptococcal Infections; Streptococcus pyogenes; Treatment Outcome
PubMed: 29788397
DOI: 10.1093/cid/ciy401 -
American Journal of Respiratory and... May 2024The use of hydrocortisone in adult patients with septic shock is controversial, and the effectiveness of adding fludrocortisone to hydrocortisone remains uncertain. To... (Meta-Analysis)
Meta-Analysis Comparative Study
Effectiveness of Fludrocortisone Plus Hydrocortisone versus Hydrocortisone Alone in Septic Shock: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.
The use of hydrocortisone in adult patients with septic shock is controversial, and the effectiveness of adding fludrocortisone to hydrocortisone remains uncertain. To assess the comparative effectiveness and safety of fludrocortisone plus hydrocortisone, hydrocortisone alone, and placebo or usual care in adults with septic shock. A systematic review and a Bayesian network meta-analysis of peer-reviewed randomized trials were conducted. The primary outcome was all-cause mortality at last follow-up. Treatment effects are presented as relative risks (RRs) with 95% credible intervals (CrIs). Placebo or usual care was the reference treatment. Among 7,553 references, we included 17 trials (7,688 patients). All-cause mortality at last follow-up was lowest with fludrocortisone plus hydrocortisone (RR, 0.85; 95% CrI, 0.72-0.99; 98.3% probability of superiority, moderate-certainty evidence), followed by hydrocortisone alone (RR, 0.97; 95% CrI, 0.87-1.07; 73.1% probability of superiority, low-certainty evidence). The comparison of fludrocortisone plus hydrocortisone versus hydrocortisone alone was based primarily on indirect evidence (only two trials with direct evidence). Fludrocortisone plus hydrocortisone was associated with a 12% lower risk of all-cause mortality compared with hydrocortisone alone (RR, 0.88; 95% CrI, 0.74-1.03; 94.2% probability of superiority, moderate-certainty evidence). In adult patients with septic shock, fludrocortisone plus hydrocortisone was associated with lower risk of all-cause mortality at last follow-up than placebo and hydrocortisone alone. The scarcity of head-to-head trials comparing fludrocortisone plus hydrocortisone versus hydrocortisone alone led our network meta-analysis to rely primarily on indirect evidence for this comparison. Although we undertook several sensitivity analyses and assessments, these findings should be considered while also acknowledging the heterogeneity of included trials.
Topics: Humans; Fludrocortisone; Hydrocortisone; Shock, Septic; Randomized Controlled Trials as Topic; Drug Therapy, Combination; Anti-Inflammatory Agents; Network Meta-Analysis; Treatment Outcome; Male; Bayes Theorem; Female; Adult; Middle Aged
PubMed: 38271488
DOI: 10.1164/rccm.202310-1785OC -
Circulation Oct 2020
Topics: Advanced Cardiac Life Support; American Heart Association; Cardiology; Cardiology Service, Hospital; Cardiopulmonary Resuscitation; Consensus; Emergencies; Emergency Service, Hospital; Evidence-Based Medicine; Heart Arrest; Humans; Risk Factors; Treatment Outcome; United States
PubMed: 33081530
DOI: 10.1161/CIR.0000000000000918 -
Annals of Internal Medicine Sep 2014Fluid resuscitation is the cornerstone of sepsis treatment. However, whether balanced or unbalanced crystalloids or natural or synthetic colloids confer a survival... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fluid resuscitation is the cornerstone of sepsis treatment. However, whether balanced or unbalanced crystalloids or natural or synthetic colloids confer a survival advantage is unclear.
PURPOSE
To examine the effect of different resuscitative fluids on mortality in patients with sepsis.
DATA SOURCES
MEDLINE, EMBASE, ACP Journal Club, CINAHL, HealthSTAR, the Allied and Complementary Medicine Database, and the Cochrane Central Register of Controlled Trials through March 2014.
STUDY SELECTION
Randomized trials that evaluated different resuscitative fluids in adult patients with sepsis or septic shock and death. No language restrictions were applied.
DATA EXTRACTION
Two reviewers extracted data on study characteristics, methods, and outcomes. Risk of bias for individual studies and quality of evidence were assessed.
DATA SYNTHESIS
14 studies (18916 patients) were included with 15 direct comparisons. Network meta-analysis at the 4-node level showed higher mortality with starches than with crystalloids (high confidence) and lower mortality with albumin than with crystalloids (moderate confidence) or starches (moderate confidence). Network meta-analysis at the 6-node level showed lower mortality with albumin than with saline (moderate confidence) and low-molecular-weight starch (low confidence) and with balanced crystalloids than with saline (low confidence) and low- and high-molecular-weight starches (moderate confidence).
LIMITATIONS
These trials were heterogeneous in case mix, fluids evaluated, duration of fluid exposure, and risk of bias. Imprecise estimates for several comparisons in this network meta-analysis contribute to low confidence in most estimates of effect.
CONCLUSION
Among patients with sepsis, resuscitation with balanced crystalloids or albumin compared with other fluids seems to be associated with reduced mortality.
PRIMARY FUNDING SOURCE
The Hamilton Chapter of the Canadian Intensive Care Foundation and the Critical Care Medicine Residency Program and Critical Care Division Alternate Funding Plan at McMaster University.
Topics: Albumins; Colloids; Crystalloid Solutions; Fluid Therapy; Gelatin; Humans; Hydroxyethyl Starch Derivatives; Isotonic Solutions; Molecular Weight; Rehydration Solutions; Saline Solution, Hypertonic; Sepsis; Shock, Septic
PubMed: 25047428
DOI: 10.7326/M14-0178 -
Critical Care Explorations Jan 2024To perform a systematic review and meta-analysis to assess the efficacy and safety of corticosteroids in patients with sepsis.
OBJECTIVES
To perform a systematic review and meta-analysis to assess the efficacy and safety of corticosteroids in patients with sepsis.
DATA SOURCES
We searched PubMed, Embase, and the Cochrane Library, up to January 10, 2023.
STUDY SELECTION
We included randomized controlled trials (RCTs) comparing corticosteroids with placebo or standard care with sepsis.
DATA EXTRACTION
The critical outcomes of interest included mortality, shock reversal, length of stay in the ICU, and adverse events.
DATA ANALYSIS
We performed both a pairwise and dose-response meta-analysis to evaluate the effect of different corticosteroid doses on outcomes. We used Grading of Recommendations Assessment, Development and Evaluation to assess certainty in pooled estimates.
DATA SYNTHESIS
We included 45 RCTs involving 9563 patients. Corticosteroids probably reduce short-term mortality (risk ratio [RR], 0.93; 95% CI, 0.88-0.99; moderate certainty) and increase shock reversal at 7 days (RR, 1.24; 95% CI, 1.11-1.38; high certainty). Corticosteroids may have no important effect on duration of ICU stay (mean difference, -0.6 fewer days; 95% CI, 1.48 fewer to 0.27 more; low certainty); however, probably increase the risk of hyperglycemia (RR, 1.13; 95% CI, 1.08-1.18; moderate certainty) and hypernatremia (RR, 1.64; 95% CI, 1.32-2.03; moderate certainty) and may increase the risk of neuromuscular weakness (RR, 1.21; 95% CI, 1.01-1.45; low certainty). The dose-response analysis showed a reduction in mortality with corticosteroids with optimal dosing of approximately 260 mg/d of hydrocortisone (RR, 0.90; 95% CI, 0.83-0.98) or equivalent.
CONCLUSIONS
We found that corticosteroids may reduce mortality and increase shock reversal but they may also increase the risk of hyperglycemia, hypernatremia, and neuromuscular weakness. The dose-response analysis indicates optimal dosing is around 260 mg/d of hydrocortisone or equivalent.
PubMed: 38250247
DOI: 10.1097/CCE.0000000000001000 -
Intensive Care Medicine Jul 2018To assess the effect of low dose corticosteroids on outcomes in adults with septic shock. (Comparative Study)
Comparative Study Meta-Analysis Review
PURPOSE
To assess the effect of low dose corticosteroids on outcomes in adults with septic shock.
METHODS
We systematically reviewed randomised clinical trials (RCTs) comparing low-dose corticosteroids to placebo in adults with septic shock. Trial selection, data abstraction and risk of bias assessment were performed in duplicate. The primary outcome was short-term mortality. Secondary and tertiary outcomes included longer-term mortality, adverse events, quality of life, and duration of shock, mechanical ventilation and ICU stay.
RESULTS
There were 22 RCTs, including 7297 participants, providing data on short-term mortality. In two low risk of bias trials, the relative risk (RR) of short-term mortality with corticosteroid versus placebo was 0.98 [95% confidence interval (CI) 0.89-1.08, p = 0.71]. Sensitivity analysis including all trials was similar (RR 0.96; 95% CI 0.91-1.02, p = 0.21) as was analysis of longer-term mortality (RR 0.96; 95% CI 0.90-1.02, p = 0.18). In low risk of bias trials, the risk of experiencing any adverse event was higher with corticosteroids; however, there was substantial heterogeneity (RR 1.66; 95% CI 1.03-2.70, p = 0.04, I = 78%). No trials reported quality of life outcomes. Duration of shock [mean difference (MD) -1.52 days; 95% CI -1.71 to -1.32, p < 0.0001], duration of mechanical ventilation (MD -1.38 days; 95% CI -1.96 to -0.80, p < 0.0001), and ICU stay (MD -0.75 days; 95% CI -1.34 to -0.17, p = 0.01) were shorter with corticosteroids versus placebo.
CONCLUSIONS
In adults with septic shock treated with low dose corticosteroids, short- and longer-term mortality are unaffected, adverse events increase, but duration of shock, mechanical ventilation and ICU stay are reduced. PROSPERO registration no. CRD42017084037.
Topics: Adult; Dose-Response Relationship, Drug; Glucocorticoids; Humans; Randomized Controlled Trials as Topic; Shock, Septic
PubMed: 29761216
DOI: 10.1007/s00134-018-5197-6 -
Intensive Care Medicine Dec 2017To update the 2008 consensus statements for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in adult and pediatric patients.
Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017.
OBJECTIVE
To update the 2008 consensus statements for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in adult and pediatric patients.
PARTICIPANTS
A multispecialty task force of 16 international experts in Critical Care Medicine, endocrinology, and guideline methods, all of them members of the Society of Critical Care Medicine and/or the European Society of Intensive Care Medicine.
DESIGN/METHODS
The recommendations were based on the summarized evidence from the 2008 document in addition to more recent findings from an updated systematic review of relevant studies from 2008 to 2017 and were formulated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The strength of each recommendation was classified as strong or conditional, and the quality of evidence was rated from high to very low based on factors including the individual study design, the risk of bias, the consistency of the results, and the directness and precision of the evidence. Recommendation approval required the agreement of at least 80% of the task force members.
RESULTS
The task force was unable to reach agreement on a single test that can reliably diagnose CIRCI, although delta cortisol (change in baseline cortisol at 60 min of <9 µg/dl) after cosyntropin (250 µg) administration and a random plasma cortisol of <10 µg/dl may be used by clinicians. We suggest against using plasma free cortisol or salivary cortisol level over plasma total cortisol (conditional, very low quality of evidence). For treatment of specific conditions, we suggest using intravenous (IV) hydrocortisone <400 mg/day for ≥3 days at full dose in patients with septic shock that is not responsive to fluid and moderate- to high-dose vasopressor therapy (conditional, low quality of evidence). We suggest not using corticosteroids in adult patients with sepsis without shock (conditional recommendation, moderate quality of evidence). We suggest the use of IV methylprednisolone 1 mg/kg/day in patients with early moderate to severe acute respiratory distress syndrome (PaO/FiO < 200 and within 14 days of onset) (conditional, moderate quality of evidence). Corticosteroids are not suggested for patients with major trauma (conditional, low quality of evidence).
CONCLUSIONS
Evidence-based recommendations for the use of corticosteroids in critically ill patients with sepsis and septic shock, acute respiratory distress syndrome, and major trauma have been developed by a multispecialty task force.
Topics: Adrenal Cortex Hormones; Adrenal Insufficiency; Adrenocorticotropic Hormone; Adult; Advisory Committees; Anti-Inflammatory Agents; Cosyntropin; Critical Care; Dose-Response Relationship, Drug; Drug Administration Schedule; Evidence-Based Medicine; Hormones; Humans; Hydrocortisone; Infusions, Intravenous; Methylprednisolone; Pituitary-Adrenal System; Respiratory Distress Syndrome; Shock, Septic; Systemic Inflammatory Response Syndrome
PubMed: 28940011
DOI: 10.1007/s00134-017-4919-5 -
Intensive Care Medicine May 2021Corticosteroids are now recommended for patients with severe COVID-19 including those with COVID-related ARDS. This has generated renewed interest regarding whether... (Meta-Analysis)
Meta-Analysis
PURPOSE
Corticosteroids are now recommended for patients with severe COVID-19 including those with COVID-related ARDS. This has generated renewed interest regarding whether corticosteroids should be used in non-COVID ARDS as well. The objective of this study was to summarize all RCTs examining the use of corticosteroids in ARDS.
METHODS
The protocol of this study was pre-registered on PROSPERO (CRD42020200659). We searched online databases including MEDLINE, EMBASE, CDC library of COVID research, CINAHL, and COCHRANE. We included RCTs that compared the effect of corticosteroids to placebo or usual care in adult patients with ARDS, including patients with COVID-19. Three reviewers abstracted data independently and in duplicate using a pre-specified standardized form. We assessed individual study risk of bias using the revised Cochrane ROB-2 tool and rated certainty in outcomes using GRADE methodology. We pooled data using a random effects model. The main outcome for this review was 28-day-mortality.
RESULTS
We included 18 RCTs enrolling 2826 patients. The use of corticosteroids probably reduced mortality in patients with ARDS of any etiology (2740 patients in 16 trials, RR 0.82, 95% CI 0.72-0.95, ARR 8.0%, 95% CI 2.2-12.5%, moderate certainty). Patients who received a longer course of corticosteroids (over 7 days) had higher rates of survival compared to a shorter course.
CONCLUSION
The use of corticosteroids probably reduces mortality in patients with ARDS. This effect was consistent between patients with COVID-19 and non-COVID-19 ARDS, corticosteroid types, and dosage.
Topics: Adrenal Cortex Hormones; Adult; COVID-19; Humans; Respiration, Artificial; Respiratory Distress Syndrome; SARS-CoV-2
PubMed: 33876268
DOI: 10.1007/s00134-021-06394-2 -
BMJ Open Dec 2022To quantify the prognostic effects of demographic and modifiable factors in streptococcal toxic shock syndrome (STSS). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To quantify the prognostic effects of demographic and modifiable factors in streptococcal toxic shock syndrome (STSS).
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
MEDLINE, EMBASE and CINAHL from inception to 19 September 2022, along with citations of included studies.
ELIGIBILITY CRITERIA
Pairs of reviewers independently screened potentially eligible studies of patients with Group A -induced STSS that quantified the association between at least one prognostic factor and outcome of interest.
DATA EXTRACTION AND SYNTHESIS
We performed random-effects meta-analysis after duplicate data extraction and risk of bias assessments. We rated the certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluation approach.
RESULTS
One randomised trial and 40 observational studies were eligible (n=1918 patients). We found a statistically significant association between clindamycin treatment and mortality (n=144; OR 0.14, 95% CI 0.06 to 0.37), but the certainty of evidence was low. Within clindamycin-treated STSS patients, we found a statistically significant association between intravenous Ig treatment and mortality (n=188; OR 0.34, 95% CI 0.15 to 0.75), but the certainty of evidence was also low. The odds of mortality may increase in patients ≥65 years when compared with patients 18-64 years (n=396; OR 2.37, 95% CI 1.47 to 3.84), but the certainty of evidence was low. We are uncertain whether non-steroidal anti-inflammatory drugs increase the odds of mortality (n=50; OR 4.14, 95% CI 1.13 to 15.14; very low certainty). Results failed to show a significant association between any other prognostic factor and outcome combination (very low to low certainty evidence) and no studies quantified the association between a prognostic factor and morbidity post-infection in STSS survivors.
CONCLUSIONS
Treatment with clindamycin and within clindamycin-treated patients, IVIG, was each significantly associated with mortality, but the certainty of evidence was low. Future research should focus on morbidity post-infection in STSS survivors.
PROSPERO REGISTRATION NUMBER
CRD42020166961.
Topics: Humans; Shock, Septic; Clindamycin; Prognosis; Streptococcal Infections; Streptococcus pyogenes; Immunoglobulins, Intravenous
PubMed: 36456018
DOI: 10.1136/bmjopen-2022-063023 -
Critical Care Medicine Sep 2015We sought to systematically review and meta-analyze the available data on the association between timing of antibiotic administration and mortality in severe sepsis and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
We sought to systematically review and meta-analyze the available data on the association between timing of antibiotic administration and mortality in severe sepsis and septic shock.
DATA SOURCES
A comprehensive search criteria was performed using a predefined protocol.
INCLUSION CRITERIA
adult patients with severe sepsis or septic shock, reported time to antibiotic administration in relation to emergency department triage and/or shock recognition, and mortality.
EXCLUSION CRITERIA
immunosuppressed populations, review article, editorial, or nonhuman studies.
DATA EXTRACTION
Two reviewers screened abstracts with a third reviewer arbitrating. The effect of time to antibiotic administration on mortality was based on current guideline recommendations: 1) administration within 3 hours of emergency department triage and 2) administration within 1 hour of severe sepsis/septic shock recognition. Odds ratios were calculated using a random effect model. The primary outcome was mortality.
DATA SYNTHESIS
A total of 1,123 publications were identified and 11 were included in the analysis. Among the 11 included studies, 16,178 patients were evaluable for antibiotic administration from emergency department triage. Patients who received antibiotics more than 3 hours after emergency department triage (< 3 hr reference) had a pooled odds ratio for mortality of 1.16 (0.92-1.46; p = 0.21). A total of 11,017 patients were evaluable for antibiotic administration from severe sepsis/septic shock recognition. Patients who received antibiotics more than 1 hour after severe sepsis/shock recognition (< 1 hr reference) had a pooled odds ratio for mortality of 1.46 (0.89-2.40; p = 0.13). There was no increased mortality in the pooled odds ratios for each hourly delay from less than 1 to more than 5 hours in antibiotic administration from severe sepsis/shock recognition.
CONCLUSION
Using the available pooled data, we found no significant mortality benefit of administering antibiotics within 3 hours of emergency department triage or within 1 hour of shock recognition in severe sepsis and septic shock. These results suggest that currently recommended timing metrics as measures of quality of care are not supported by the available evidence.
Topics: Anti-Bacterial Agents; Emergency Service, Hospital; Hospital Mortality; Humans; Length of Stay; Sepsis; Shock, Septic; Triage
PubMed: 26121073
DOI: 10.1097/CCM.0000000000001142