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Critical Care Medicine Apr 2024This systematic review and Bayesian network meta-analysis evaluated the efficacy and safety of hydrocortisone combined with fludrocortisone or hydrocortisone alone,... (Meta-Analysis)
Meta-Analysis
Do We Need to Administer Fludrocortisone in Addition to Hydrocortisone in Adult Patients With Septic Shock? An Updated Systematic Review With Bayesian Network Meta-Analysis of Randomized Controlled Trials and an Observational Study With Target Trial Emulation.
OBJECTIVES
This systematic review and Bayesian network meta-analysis evaluated the efficacy and safety of hydrocortisone combined with fludrocortisone or hydrocortisone alone, compared with placebo in adult patients with septic shock.
DATA SOURCES
By extending a prior Cochrane review, databases, including PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov , along with other relevant websites, were searched until August 31, 2023.
STUDY SELECTION
Randomized controlled trials (RCTs) and observational studies using target trial emulation were included.
DATA EXTRACTION
The primary outcome was short-term mortality with an emphasis on 28- or 30-day mortality as the main measure and in-hospital or ICU mortality as the nearest surrogate of this measure. Three of the most common adverse events, namely, gastroduodenal bleeding, superinfection, and hyperglycemia, were also considered.
DATA SYNTHESIS
A total of 19 studies involving 95,841 patients were included. Hydrocortisone plus fludrocortisone showed the lowest short-term mortality versus placebo (odds ratio [OR]: 0.79; 95% credible interval [CrI], 0.64-0.99; number needed to treat [NNT]: 21, range: 12-500; low certainty of evidence) in terms of informative priors. The surface under the cumulative ranking curve values for hydrocortisone plus fludrocortisone, hydrocortisone alone, and placebo were 0.9469, 0.4542, and 0.0989, respectively. Consistent results were observed in RCTs alone and those using a daily 200-mg dose of hydrocortisone. Although gastroduodenal bleeding or superinfection showed no clear increase, hyperglycemia risk increased. The ORs were 0.53 for placebo versus hydrocortisone plus fludrocortisone and 0.64 for placebo versus hydrocortisone alone, with very low certainty of evidence.
CONCLUSIONS
In adults with septic shock, hydrocortisone plus fludrocortisone improved short-term survival with minimal adverse events compared with hydrocortisone alone or placebo. However, these findings are not definitive due to the limited certainty of evidence and wide NNT range. Additional large-scale, placebo-controlled RCTs are needed to provide conclusive evidence.
Topics: Adult; Humans; Hydrocortisone; Fludrocortisone; Shock, Septic; Network Meta-Analysis; Superinfection; Randomized Controlled Trials as Topic; Hyperglycemia; Observational Studies as Topic
PubMed: 38156911
DOI: 10.1097/CCM.0000000000006161 -
Transactions of the Royal Society of... Oct 2023Strongyloidiasis is a parasitosis representing a significant public health problem in tropical countries. It is often asymptomatic in immunocompetent individuals but its... (Meta-Analysis)
Meta-Analysis
Strongyloidiasis is a parasitosis representing a significant public health problem in tropical countries. It is often asymptomatic in immunocompetent individuals but its mortality rate increases to approximately 87% in severe forms of the disease. We conducted a systematic review, including case reports and case series, of Strongyloides hyperinfection and dissemination from 1998 to 2020 searching PubMed, EBSCO and SciELO. Cases that met the inclusion criteria of the Preferred Reported Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist were analysed. Statistical analysis was performed using Fisher's exact test and Student's t-test and a Bonferroni correction for all the significant values. A total of 339 cases were included in this review. The mortality rate was 44.83%. The presence of infectious complications, septic shock and a lack of treatment were risk factors for a fatal outcome. Eosinophilia and ivermectin treatment were associated with an improved outcome.
Topics: Animals; Humans; Strongyloidiasis; Strongyloides stercoralis; Superinfection; Ivermectin
PubMed: 37300462
DOI: 10.1093/trstmh/trad032 -
Journal of Cardiovascular Pharmacology Jan 2024Sepsis and septic shock are life-threatening conditions that are associated with high mortality and considerable health care costs. The association between prior... (Meta-Analysis)
Meta-Analysis
Prior Use of Angiotensin-converting Enzyme Inhibitors or Angiotensin II Receptor Blockers and Clinical Outcomes of Sepsis and Septic Shock: A Systematic Review and Meta-analysis.
Sepsis and septic shock are life-threatening conditions that are associated with high mortality and considerable health care costs. The association between prior angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) use and outcomes after sepsis is elusive. The aim of this study was to evaluate the role of the prior use of ACEi or ARBs and outcomes after sepsis and septic shock. A relevant literature review was performed in 4 databases from inception until July 2022. Independent reviewers first screened the title, abstract, and full text, and then, data extraction and analysis were performed. One post hoc analysis of a trial and 6 retrospective cohort studies were included in this review. There were 22% lower odds of in-hospital/30-day mortality among patients who have used ACEi/ARBs in the past [23.83% vs. 37.20%; odds ratio (OR), 0.78, 95% confidence interval (CI), 0.64-0.96], and reduced 90-day mortality (OR, 0.80, 95% CI, 0.69-0.92). ACEi/ARBs users were found to have 31% lesser odds of developing acute kidney injury as compared with nonusers (OR, 0.69, 95% CI, 0.63-0.76). There was no significant difference in the length of hospital stay (MD 1.26, 95% CI, ‒7.89 to 10.42), need for renal replacement therapy (OR, 0.71, 95% CI, 0.13-3.92), mechanical ventilation (OR, 1.10, 95% CI, 0.88-1.37) or use of vasopressors (OR, 1.21, 95% CI, 0.91-1.61). Based on this analysis, prior use of ACEi/ARBs lowers the risk of mortality and adverse renal events in patients with sepsis and septic shock.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Shock, Septic; Retrospective Studies; Kidney
PubMed: 37815234
DOI: 10.1097/FJC.0000000000001491 -
Anaesthesia Mar 2024Dysregulation of the host immune response has a central role in the pathophysiology of sepsis. There has been much interest in immunomodulatory drugs as potential... (Review)
Review
Dysregulation of the host immune response has a central role in the pathophysiology of sepsis. There has been much interest in immunomodulatory drugs as potential therapeutic adjuncts in sepsis. We conducted a systematic review and meta-analysis of randomised controlled trials evaluating the safety and clinical effectiveness of immunomodulatory drugs as adjuncts to standard care in the treatment of adults with sepsis. Our primary outcomes were serious adverse events and all-cause mortality. Fifty-six unique, eligible randomised controlled trials were identified, assessing a range of interventions including cytokine inhibitors; anti-inflammatories; immune cell stimulators; platelet pathway inhibitors; and complement inhibitors. At 1-month follow-up, the use of cytokine inhibitors was associated with a decreased risk of serious adverse events, based on 11 studies involving 7138 patients (RR (95%CI) 0.95 (0.90-1.00), I = 0%). The only immunomodulatory drugs associated with an increased risk of serious adverse events were toll-like receptor 4 antagonists (RR (95%CI) 1.18 (1.04-1.34), I = 0% (two trials, 567 patients)). Based on 18 randomised controlled trials, involving 11,075 patients, cytokine inhibitors reduced 1-month mortality (RR (95%CI) 0.88 (0.78-0.98), I = 57%). Mortality reduction was also shown in the subgroup of 13 randomised controlled trials that evaluated anti-tumour necrosis factor α interventions (RR (95%CI) 0.93 (0.87-0.99), I = 0%). Anti-inflammatory drugs had the largest apparent effect on mortality at 2 months at any dose (two trials, 228 patients, RR (95%CI) 0.64 (0.51-0.80), I = 0%) and at 3 months at any dose (three trials involving 277 patients, RR (95%CI) 0.67 (0.55-0.81), I = 0%). These data indicate that, except for toll-like receptor 4 antagonists, there is no evidence of safety concerns for the use of immunomodulatory drugs in sepsis, and they may show some short-term mortality benefit for selected drugs.
PubMed: 38523060
DOI: 10.1111/anae.16263 -
Molecular Psychiatry May 2024There have been conflicting reports regarding the case-fatality outcomes associated with sepsis and septic shock in patients with severe mental illness (SMI).
BACKGROUND
There have been conflicting reports regarding the case-fatality outcomes associated with sepsis and septic shock in patients with severe mental illness (SMI).
METHODS
We searched Medline®, Web of Science® and the Cochrane Library® databases (from inception to 4-July-2023) for papers reporting outcomes associated with sepsis and septic shock in adult with (cases) vs. without SMI (controls). The main study outcome was the unadjusted case-fatality rate at hospital discharge, or 30 days if unavailable. Secondary outcomes included the rates of adjusted case-fatality at hospital discharge.
RESULTS
A total of six studies were included in the systematic review, of which four provided data for meta-analysis involving 2,124,072 patients. Compared to controls, patients with SMI were younger and more frequently women. Unadjusted analyses showed that SMI patients had a lower case-fatality rate associated with sepsis and septic shock than their non-SMI counterparts (OR 0.61, 95% CI [0.58-0.65], PI 95% CI [0.49-0.77], I = 91%). Meta-regression and subgroup analyses showed that the denominator of the study population (i.e. septic shock or sepsis) was associated with the outcome with an R of 59.7%.
CONCLUSION
In conclusion, our study reveals a survival advantage of SMI patients over their non-SMI counterparts. Further research is needed to fully elucidate the mechanisms involved and to develop targeted interventions that can improve the prognosis of both SMI and non-SMI patients facing sepsis.
PubMed: 38769373
DOI: 10.1038/s41380-024-02603-8 -
Advances in Clinical and Experimental... Mar 2024Over 48 million cases of sepsis and 11 million sepsis-related deaths were reported in 2017, making it one of the leading causes of mortality. This meta-analysis compared... (Meta-Analysis)
Meta-Analysis
Over 48 million cases of sepsis and 11 million sepsis-related deaths were reported in 2017, making it one of the leading causes of mortality. This meta-analysis compared mortality risk among patients with sepsis or septic shock and associated hypoglycemia or euglycemia on admission by searching for observational studies in PubMed, Embase and Scopus databases. The eligible studies included patients with sepsis and/or severe sepsis/septic shock and compared mortality rates between those with hypoglycemia on admission and those who were euglycemic. A stratified analysis based on sepsis or severe sepsis/septic shock and diabetes on admission included 14 studies. Patients with hypoglycemia had a significantly higher risk of in-hospital mortality and mortality during the 1st month after discharge. In addition, hypoglycemic patients with sepsis had a slightly increased risk of in-hospital mortality, but no increase in the mortality risk was observed within 1 month of follow-up. However, in patients with severe sepsis and/or septic shock, hypoglycemia was associated with a higher risk of both in-hospital mortality and mortality during 1 month of follow-up. In patients with diabetes, hypoglycemia was not associated with an increased risk of in-hospital mortality or mortality within 1 month of follow-up. Patients with sepsis or severe sepsis/septic shock and hypoglycemia had an increased mortality risk, and the association was stronger in cases of severe sepsis/septic shock. Hypoglycemia in diabetic patients did not correlate with increased mortality risk. Careful monitoring of blood glucose in sepsis and/or severe sepsis/septic shock patients is required.
Topics: Humans; Blood Glucose; Diabetes Mellitus; Hospital Mortality; Hypoglycemia; Observational Studies as Topic; Sepsis; Shock, Septic
PubMed: 37386859
DOI: 10.17219/acem/166656 -
Postgraduate Medical Journal Aug 2023Previous studies evaluating the impact of antibiotic timing on mortality in sepsis have shown conflicting results. We performed a meta-analysis to evaluate the... (Meta-Analysis)
Meta-Analysis
PURPOSE
Previous studies evaluating the impact of antibiotic timing on mortality in sepsis have shown conflicting results. We performed a meta-analysis to evaluate the association between door-to-antibiotic time (each hour of delay) and mortality in sepsis.
METHODS
We searched PubMed and Embase through 10 November 2022 to identity cohort studies that evaluated the adjusted association between door-to-antibiotic time (each hour of delay) and mortality in adult patients with sepsis. The primary outcome was mortality. Analysis was based on inverse-variance weighting using a fixed-effects model. The variances were derived from the logarithms of the reported confidence intervals (CIs) for associations. We estimated the odds ratio, 95% CI, and number needed to treat for the pooled data.
RESULTS
Fifteen cohort studies involving 106 845 patients were included in the meta-analysis. Door-to-antibiotic time (each hour of delay) was associated with increased risk of mortality (odds ratio: 1.07; 95% CI: 1.06-1.08; P < 0.0001; number needed to treat = 91), with high heterogeneity (I2 = 82.2%). The association was robust in sensitivity analyses and consistent in subgroup analyses. No publication bias was found.
CONCLUSION
In adult patients with sepsis, each hour of delay in antibiotic administration is associated with increased odds of mortality. Key messages What is already known on this topic Sepsis is a common and lethal syndrome that affects millions of people worldwide. The updated 2018 Surviving Sepsis Campaign guidelines recommended initiating empirical broad-spectrum antibiotic coverage within 1 hour of identification of sepsis and septic shock. Delay in antibiotic administration may increase the risk of mortality in patients with sepsis. What this study adds This meta-analysis evaluates and quantifies the association between door-to-antibiotic time (each hour of delay) and mortality in patients with sepsis. Each hour of delay in antibiotic administration is associated with increased odds of mortality in sepsis. The number needed to treat (NNT) with delayed antibiotic administration for one additional death was 91. How this study might affect research, practice, or policy: More efforts should be made to speed up the diagnosis of sepsis or sepsis shock.
Topics: Humans; Anti-Bacterial Agents; Sepsis; Shock, Septic
PubMed: 36917816
DOI: 10.1093/postmj/qgad024 -
European Journal of Trauma and... Dec 2023This systematic review aimed to summarize the literature regarding the prognostic accuracy of the emergency surgery score (ESS). (Review)
Review
PURPOSE
This systematic review aimed to summarize the literature regarding the prognostic accuracy of the emergency surgery score (ESS).
METHOD
PubMed, Embase, Web of Science, and Scopus were comprehensively searched by May 30, 2023. Two independent researchers performed the initial screening by reviewing the titles and abstracts of the non-duplicate records and selecting the full text of articles meeting our inclusion criteria. Finally, original studies that reported the prognostic accuracy of ESS in any emergency surgeries were included. Data from the included studies were extracted into a checklist designed based on the PRISMA guidelines. The area under the curve (AUC) was used to compare the prognostic accuracy of ESS in different settings.
RESULTS
Twenty-six studies met the inclusion criteria. ESS performed excellently in 30-day post-op mortality (AUC 0.84-0.89) and incidence of cardiac arrest (AUC 0.86-0.88) in emergency general surgeries. The AUC of ESS in overall 30-day morbidities varied from 0.72 to 0.82 in five cohort studies. In predicting the need for ICU admission, the study with the largest sample size reported the best sensitivity of ESS at 80% and the specificity at 85%. Moreover, an outstanding accuracy was observed for the prediction of 30-day sepsis/septic shock in emergency general surgeries (AUC 0.75-0.92).
CONCLUSION
Despite the acceptable prognostic accuracy of ESS in 30-day mortality, morbidities, and in-hospital ICU admission in different emergency surgeries, the high number of required variables and the high probability of missing data highlight the need for modifications to this scoring system.
PubMed: 38108839
DOI: 10.1007/s00068-023-02396-5 -
European Journal of Pediatrics Jun 2024This study aimed to evaluate the current evidence on various aspects of fluid therapy such as type, volume, and timing of fluid bolus administration in children with...
UNLABELLED
This study aimed to evaluate the current evidence on various aspects of fluid therapy such as type, volume, and timing of fluid bolus administration in children with septic shock. Systematic review and meta-analysis of clinical trials including children less than 18 years of age admitted to the pediatric emergency and intensive care unit with severe infection and shock requiring fluid resuscitation. The intervention included balanced crystalloids (BC) vs normal saline (NS), colloids vs NS, restricted vs liberal fluid bolus, and slow vs fast fluid bolus. The primary outcome was mortality rate. Of the 219 citations retrieved, 12 trials (3526 children with severe infection with or without malaria and shock) were included. The pooled results found no significant difference in the mortality rate between groups comparing balanced crystalloids (BC) vs normal saline (NS), colloids vs NS, restricted vs liberal fluid bolus, and slow vs fast fluid bolus. The risk of acute kidney injury (AKI) was significantly less in the BC group compared to the NS group. The certainty of evidence for mortality was of "moderate certainty" in the BC vs NS group, and was of "very low certainty" for the other two groups.
CONCLUSIONS
The current meta-analysis found no significant difference in the mortality rate between the types of resuscitation fluid, and their speed or volume of administration. However, a significantly decreased risk of AKI was found in the BC group. More evidence is needed regarding the speed and volume of administration of fluid boluses in critically ill children.Prospero registration: CRD42020209066.
WHAT IS KNOWN
• Balanced crystalloids (BC) may be better than normal saline (NS) for fluid resuscitation in critically ill children.
WHAT IS NEW
• BC are better than NS for fluid resuscitation in critically ill children as they decrease AKI and hyperchloremia.
PubMed: 38916738
DOI: 10.1007/s00431-024-05653-w -
Nutrients May 2024Medical nutrition therapy provides the opportunity to compensate for muscle wasting and immune response activation during stress and trauma. The objective of this... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Medical nutrition therapy provides the opportunity to compensate for muscle wasting and immune response activation during stress and trauma. The objective of this systematic review is to assess the safety and effectiveness of early enteral nutrition (EEN) in adults with sepsis or septic shock.
METHODS
The MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov, and ICTRP tools were searched from inception until July 2023. Conference proceedings, the reference lists of included studies, and expert content were queried to identify additional publications. Two review authors completed the study selection, data extraction, and risk of bias assessment; disagreements were resolved through discussion. Inclusion criteria were randomized controlled trials (RCTs) and non-randomized studies (NRSs) comparing the administration of EEN with no or delayed enteral nutrition (DEE) in adult populations with sepsis or septic shock.
RESULTS
Five RCTs ( = 442 participants) and ten NRSs ( = 3724 participants) were included. Low-certainty evidence from RCTs and NRSs suggests that patients receiving EEN could require fewer days of mechanical ventilation (MD -2.65; 95% CI, -4.44-0.86; and MD -2.94; 95% CI, -3.64--2.23, respectively) and may show lower SOFA scores during follow-up (MD -1.64 points; 95% CI, -2.60--0.68; and MD -1.08 points; 95% CI, -1.90--0.26, respectively), albeit with an increased frequency of diarrhea episodes (OR 2.23, 95% CI 1.115-4.34). Even though the patients with EEN show a lower in-hospital mortality rate both in RCTs (OR 0.69; 95% CI, 0.39-1.23) and NRSs (OR 0.89; 95% CI, 0.69-1.13), this difference does not achieve statistical significance. There were no apparent differences for other outcomes.
CONCLUSIONS
Low-quality evidence suggests that EEN may be a safe and effective intervention for the management of critically ill patients with sepsis or septic shock.
Topics: Humans; Enteral Nutrition; Randomized Controlled Trials as Topic; Respiration, Artificial; Sepsis; Shock, Septic; Time Factors; Treatment Outcome
PubMed: 38892494
DOI: 10.3390/nu16111560