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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 -
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 -
Journal of Cardiothoracic and Vascular... Sep 2023Hydroxocobalamin inhibits nitric oxide-mediated vasodilation, and has been used in settings of refractory shock. However, its effectiveness and role in treating... (Meta-Analysis)
Meta-Analysis Review
Hydroxocobalamin inhibits nitric oxide-mediated vasodilation, and has been used in settings of refractory shock. However, its effectiveness and role in treating hypotension remain unclear. The authors systematically searched Ovid Medline, Embase, EBM Reviews, Scopus, and Web of Science Core Collection for clinical studies reporting on adult persons who received hydroxocobalamin for vasodilatory shock. A meta-analysis was performed with random-effects models comparing the hemodynamic effects of hydroxocobalamin to methylene blue. The Risk of Bias in Nonrandomized Studies of Interventions tool was used to assess the risk of bias. A total of 24 studies were identified and comprised mainly of case reports (n = 12), case series (n = 9), and 3 cohort studies. Hydroxocobalamin was applied mainly for cardiac surgery vasoplegia, but also was reported in the settings of liver transplantation, septic shock, drug-induced hypotension, and noncardiac postoperative vasoplegia. In the pooled analysis, hydroxocobalamin was associated with a higher mean arterial pressure (MAP) at 1 hour than methylene blue (mean difference 7.80, 95% CI 2.63-12.98). There were no significant differences in change in MAP (mean difference -4.57, 95% CI -16.05 to 6.91) or vasopressor dosage (mean difference -0.03, 95% CI -0.12 to 0.06) at 1 hour compared to baseline between hydroxocobalamin and methylene blue. Mortality was also similar (odds ratio 0.92, 95% CI 0.42-2.03). The evidence supporting the use of hydroxocobalamin for shock is limited to anecdotal reports and a few cohort studies. Hydroxocobalamin appears to positively affect hemodynamics in shock, albeit similar to methylene blue.
Topics: Adult; Humans; Hydroxocobalamin; Methylene Blue; Vasodilation; Vasoplegia; Shock; Hypotension
PubMed: 37147207
DOI: 10.1053/j.jvca.2023.04.006 -
Shock (Augusta, Ga.) Dec 2023Background: Septic shock is a distributive shock with decreased systemic vascular resistance and MAP. Septic shock contributes to the most common causes of death in the... (Meta-Analysis)
Meta-Analysis
Background: Septic shock is a distributive shock with decreased systemic vascular resistance and MAP. Septic shock contributes to the most common causes of death in the intensive care unit (ICU). Current guidelines recommend the use of norepinephrine as the first-line vasopressor, whereas adrenergic agonists and vasopressin analogs are also commonly used by physicians. To date, very few studies have synthetically compared the effects of multiple types of vasoactive medications. The aim of this study was to systemically evaluate the efficacy of vasoactive agents both individually and in combination to treat septic shock. Methods: The PubMed, MEDLINE, Embase, Web of Science, and Cochrane Central Register for Controlled Trials (CENTRAL) were searched up to May 12, 2022, to identify relevant randomized controlled trials. A network meta-analysis was performed to evaluate the effect of different types of vasopressors. The primary outcome was 28-day all-cause mortality. The secondary outcome was the ICU length of stay. Adverse events are defined as any undesirable outcomes, including myocardial infarction, cardiac arrhythmia, peripheral ischemia, or stroke and cerebrovascular events. Findings: Thirty-three randomized controlled trials comprising 4,966 patients and assessing 8 types of vasoactive treatments were included in the network meta-analysis. The surface under the cumulative ranking curve provided a ranking of vasoactive medications in terms of 28-day all-cause mortality from most effective to least effective: norepinephrine plus dobutamine, epinephrine, vasopressin, terlipressin, norepinephrine, norepinephrine plus vasopressin, dopamine, and dobutamine. Dopamine was associated with a significantly shorter ICU stay than norepinephrine, terlipressin, and vasopressin, whereas other vasoactive medications showed no definite difference in ICU length of stay. Regarding adverse events, norepinephrine was associated with the highest incidences of myocardial infarction and peripheral ischemia. Dopamine was associated with the highest incidence of cardiac arrhythmia. Epinephrine and terlipressin were associated with the highest incidences of myocardial infarction and peripheral ischemia. Interpretation: The results of this network meta-analysis suggest that norepinephrine plus dobutamine is associated with a lower risk of 28-day mortality in septic shock patients than other vasoactive medications, and the use of dopamine is associated with a higher risk of 28-day mortality due to septic shock than norepinephrine, terlipressin, and vasopressin.
Topics: Humans; Shock, Septic; Dopamine; Terlipressin; Dobutamine; Network Meta-Analysis; Vasoconstrictor Agents; Epinephrine; Norepinephrine; Vasopressins; Arrhythmias, Cardiac; Ischemia; Myocardial Infarction
PubMed: 37548686
DOI: 10.1097/SHK.0000000000002193 -
JAMA Jun 2024There is uncertainty about whether prolonged infusions of β-lactam antibiotics improve clinically important outcomes in critically ill adults with sepsis or septic shock.
IMPORTANCE
There is uncertainty about whether prolonged infusions of β-lactam antibiotics improve clinically important outcomes in critically ill adults with sepsis or septic shock.
OBJECTIVE
To determine whether prolonged β-lactam antibiotic infusions are associated with a reduced risk of death in critically ill adults with sepsis or septic shock compared with intermittent infusions.
DATA SOURCES
The primary search was conducted with MEDLINE (via PubMed), CINAHL, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from inception to May 2, 2024.
STUDY SELECTION
Randomized clinical trials comparing prolonged (continuous or extended) and intermittent infusions of β-lactam antibiotics in critically ill adults with sepsis or septic shock.
DATA EXTRACTION AND SYNTHESIS
Data extraction and risk of bias were assessed independently by 2 reviewers. Certainty of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation approach. A bayesian framework was used as the primary analysis approach and a frequentist framework as the secondary approach.
MAIN OUTCOMES AND MEASURES
The primary outcome was all-cause 90-day mortality. Secondary outcomes included intensive care unit (ICU) mortality and clinical cure.
RESULTS
From 18 eligible randomized clinical trials that included 9108 critically ill adults with sepsis or septic shock (median age, 54 years; IQR, 48-57; 5961 men [65%]), 17 trials (9014 participants) contributed data to the primary outcome. The pooled estimated risk ratio for all-cause 90-day mortality for prolonged infusions of β-lactam antibiotics compared with intermittent infusions was 0.86 (95% credible interval, 0.72-0.98; I2 = 21.5%; high certainty), with a 99.1% posterior probability that prolonged infusions were associated with lower 90-day mortality. Prolonged infusion of β-lactam antibiotics was associated with a reduced risk of intensive care unit mortality (risk ratio, 0.84; 95% credible interval, 0.70-0.97; high certainty) and an increase in clinical cure (risk ratio, 1.16; 95% credible interval, 1.07-1.31; moderate certainty).
CONCLUSIONS AND RELEVANCE
Among adults in the intensive care unit who had sepsis or septic shock, the use of prolonged β-lactam antibiotic infusions was associated with a reduced risk of 90-day mortality compared with intermittent infusions. The current evidence presents a high degree of certainty for clinicians to consider prolonged infusions as a standard of care in the management of sepsis and septic shock.
TRIAL REGISTRATION
PROSPERO Identifier: CRD42023399434.
PubMed: 38864162
DOI: 10.1001/jama.2024.9803 -
Nutrients Jul 2023The optimal timing of enteral nutrition (EN) in sepsis patients is controversial among societal guidelines. We aimed to evaluate the evidence of early EN's impact on... (Review)
Review
The optimal timing of enteral nutrition (EN) in sepsis patients is controversial among societal guidelines. We aimed to evaluate the evidence of early EN's impact on critically ill sepsis patients' clinical outcomes. We searched the MEDLINE, Embase, CINAHL, Cochrane Library, ClinicalTrials.gov, and ICTRP databases on 10 March 2023. We included studies published after 2004 that compared early EN versus delayed EN in sepsis patients. We included randomized controlled trials (RCTs), non-RCTs, cohort studies, and case-control studies. Forest plots were used to summarize risk ratios (RRs), including mortality and mean difference (MD) of continuous variables such as intensive care unit (ICU) length of stay and ventilator-free days. We identified 11 eligible studies with sample sizes ranging from 31 to 2410. The RR of short-term mortality from three RCTs was insignificant, and the MD of ICU length of stay from two RCTs was -2.91 and -1.00 days (95% confidence interval [CI], -5.53 to -0.29 and -1.68 to -0.32). Although the RR of intestinal-related complications from one RCT was 3.82 (95% CI, 1.43 to 10.19), indicating a significantly higher risk for the early EN group than the control group, intestinal-related complications of EN reported in five studies were inconclusive. This systematic review did not find significant benefits of early EN on mortality in sepsis patients. Evidence, however, is weak due to inconsistent definitions, heterogeneity, risk of bias, and poor methodology in the existing studies.
Topics: Humans; Enteral Nutrition; Critical Illness; Intensive Care Units; Sepsis; Case-Control Studies; Length of Stay
PubMed: 37513620
DOI: 10.3390/nu15143201 -
Chest Oct 2023IV fluids are recommended for adults with sepsis. However, the optimal strategy for IV fluid management in sepsis is unknown, and clinical equipoise exists.
BACKGROUND
IV fluids are recommended for adults with sepsis. However, the optimal strategy for IV fluid management in sepsis is unknown, and clinical equipoise exists.
RESEARCH QUESTION
Do lower vs higher fluid volumes improve patient-important outcomes in adult patients with sepsis?
STUDY DESIGN AND METHODS
We updated a systematic review with meta-analysis and trial sequential analysis of randomized clinical trials assessing lower vs higher IV fluid volumes in adult patients with sepsis. The coprimary outcomes were all-cause mortality, serious adverse events, and health-related quality of life. We followed the recommendations from the Cochrane Handbook and used the Grading of Recommendations Assessment, Development and Evaluation approach. Primary conclusions were based on trials with low risk of bias if available.
RESULTS
We included 13 trials (N = 4,006) with four trials (n = 3,385) added to this update. The meta-analysis of all-cause mortality in eight trials with low risk of bias showed a relative risk of 0.99 (97% CI, 0.89-1.10; moderate certainty evidence). Six trials with predefined definitions of serious adverse events showed a relative risk of 0.95 (97% CI, 0.83-1.07; low certainty evidence). Health-related quality of life was not reported.
INTERPRETATION
Among adult patients with sepsis, lower IV fluid volumes probably result in little to no difference in all-cause mortality compared with higher IV fluid volumes, but the interpretation is limited by imprecision in the estimate, which does not exclude potential benefit or harm. Similarly, the evidence suggests lower IV fluid volumes result in little to no difference in serious adverse events. No trials reported on health-related quality of life.
TRIAL REGISTRATION
PROSPERO; No.: CRD42022312572; URL: https://www.crd.york.ac.uk/prospero/.
PubMed: 37142091
DOI: 10.1016/j.chest.2023.04.036 -
Journal of Intensive Care Medicine Sep 2023The prevalence and its impact on mortality of sepsis-induced cardiomyopathy (SICM) remain controversial. In this systematic review and meta-analysis, we investigated... (Meta-Analysis)
Meta-Analysis Review
The prevalence and its impact on mortality of sepsis-induced cardiomyopathy (SICM) remain controversial. In this systematic review and meta-analysis, we investigated the prevalence and prognosis of SICM. We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase. Titles and abstracts were evaluated based on the following criteria: (1) published in English, (2) randomized controlled trials, cohort studies, or cross-sectional studies, (3) ≥ 18 years with sepsis, (4) reporting the prevalence and/or comparison of short-term mortality between those with and without SICM, defined as the new-onset reduction in left ventricular ejection fraction (LVEF) within 72 h on admission or from the diagnosis of sepsis. The random-effect model was used for all analyses. This meta-analysis was registered at PROSPERO (CDR42022332896). Sixteen studies reported the prevalence of SICM and the pooled prevalence of SICM was 20% (95% confidence interval [CI], 16-25%; = 89.9%, P < 0.01). Eleven studies reported short-term mortality and SICM was associated with significantly higher short-term mortality (The pooled odds ratio: 2.30, 95% CI, 1.43-3.69; = 0%, P = 0.001). The prevalence of SICM was 20% in patients with sepsis, and the occurrence of SICM was associated with significantly higher short-term mortality.
Topics: Humans; Stroke Volume; Ventricular Function, Left; Prevalence; Cross-Sectional Studies; Sepsis; Cardiomyopathies; Prognosis; Shock, Septic
PubMed: 37272081
DOI: 10.1177/08850666231180526 -
Critical Care Medicine Dec 2023This study aimed to conduct a comprehensive and updated systematic review with network meta-analysis (NMA) to assess the outcome benefits of various blood purification... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This study aimed to conduct a comprehensive and updated systematic review with network meta-analysis (NMA) to assess the outcome benefits of various blood purification modalities for adult patients with severe infection or sepsis.
DATA SOURCES
We conducted a search of PubMed, MEDLINE, clinical trial registries, Cochrane Library, and Embase databases with no language restrictions.
STUDY SELECTION
Only randomized controlled trials (RCTs) were selected.
DATA EXTRACTION
The primary outcome was overall mortality. The secondary outcomes were the length of mechanical ventilation (MV) days and ICU stay, incidence of acute kidney injury (AKI), and kidney replacement therapy requirement.
DATA SYNTHESIS
We included a total of 60 RCTs with 4,595 participants, comparing 16 blood purification modalities with 17 interventions. Polymyxin-B hemoperfusion (relative risk [RR]: 0.70; 95% CI, 0.57-0.86) and plasma exchange (RR: 0.61; 95% CI, 0.42-0.91) were associated with low mortality (very low and low certainty of evidence, respectively). Because of the presence of high clinical heterogeneity and intransitivity, the potential benefit of polymyxin-B hemoperfusion remained inconclusive. The analysis of secondary outcomes was limited by the scarcity of available studies. HA330 with high-volume continuous venovenous hemofiltration (CVVH), HA330, and standard-volume CVVH were associated with shorter ICU stay. HA330 with high-volume CVVH, HA330, and standard-volume CVVH were beneficial in reducing MV days. None of the interventions showed a significant reduction in the incidence of AKI or the need for kidney replacement therapy.
CONCLUSIONS
Our NMA suggests that plasma exchange and polymyxin-B hemoperfusion may provide potential benefits for adult patients with severe infection or sepsis/septic shock when compared with standard care alone, but most comparisons were based on low or very low certainty evidence. The therapeutic effect of polymyxin-B hemoperfusion remains uncertain. Further RCTs are required to identify the specific patient population that may benefit from extracorporeal blood purification.
Topics: Adult; Humans; Shock, Septic; Network Meta-Analysis; Randomized Controlled Trials as Topic; Sepsis; Polymyxin B; Acute Kidney Injury
PubMed: 37470680
DOI: 10.1097/CCM.0000000000005991 -
Shock (Augusta, Ga.) Nov 2023Background: Vasopressor plays a crucial role in septic shock. However, the time for vasopressor initiation remains controversial. We conducted a systematic review and... (Meta-Analysis)
Meta-Analysis
Background: Vasopressor plays a crucial role in septic shock. However, the time for vasopressor initiation remains controversial. We conducted a systematic review and meta-analysis to explore its initiation timing for septic shock patients. Methods: PubMed, Cochrane Library, Embase, and Web of Sciences were searched from inception to July 12, 2023, for relevant studies. Primary outcome was short-term mortality. Meta-analysis was performed using Stata 15.0. Results: Twenty-three studies were assessed, including 2 randomized controlled trials and 21 cohort studies. The early group resulted in lower short-term mortality than the late group (OR [95% CI] = 0.775 [0.673 to 0.893], P = 0.000, I2 = 67.8%). The significance existed in the norepinephrine and vasopressin in subgroup analysis. No significant difference was considered in the association between each hour's vasopressor delay and mortality (OR [95% CI] = 1.02 [0.99 to 1.051], P = 0.195, I2 = 57.5%). The early group had an earlier achievement of target MAP ( P < 0.001), shorter vasopressor use duration ( P < 0.001), lower serum lactate level at 24 h ( P = 0.003), lower incidence of kidney injury ( P = 0.001), renal replacement therapy use ( P = 0.022), and longer ventilation-free days to 28 days ( P < 0.001). Conclusions: Early initiation of vasopressor (1-6 h within septic shock onset) would be more beneficial to septic shock patients. The conclusion needs to be further validated by more well-designed randomized controlled trials.
Topics: Humans; Shock, Septic; Vasoconstrictor Agents; Norepinephrine; Cohort Studies; Renal Replacement Therapy
PubMed: 37695641
DOI: 10.1097/SHK.0000000000002214