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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 -
Cureus May 2024Sepsis is a life-threatening condition that occurs when the body's immune response to infection becomes unregulated, causing organ dysfunction and a heightened risk of... (Review)
Review
Sepsis is a life-threatening condition that occurs when the body's immune response to infection becomes unregulated, causing organ dysfunction and a heightened risk of mortality. Despite increased awareness campaigns, its prevalence escalates, annually afflicting over 1.7 million adults in the United States. This research explores the potential of therapeutic plasma exchange (TPE) in septic shock management, aiming to highlight its capacity to improve patient outcomes and reduce mortality. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, our comprehensive search across 51,534 studies, using keywords such as plasmapheresis, plasma exchange therapy, therapeutic plasma exchange, septic shock, and reduction in mortality integrated with medical subject headings terms, led to the meticulous selection of six pivotal studies. Through rigorous evaluation with tools such as the revised Cochrane Risk-of-Bias tool, Newcastle-Ottawa Scale, and Assessment of Methodological Quality of Systematic Reviews, we extracted strong evidence supporting TPE's significant impact on decreasing mortality in septic shock patients compared to standard care, as demonstrated in three randomized controlled trials and one cohort study, with an odds ratio (OR) of 0.43 (95% confidence interval (CI) = 0.26-0.72). Additionally, two meta-analyses further validate TPE's effectiveness, showing a mortality reduction with an OR of 0.30 (95% CI = 0.20-0.46). This advantage also extends to critically ill COVID-19 patients, underscoring TPE's crucial role in modulating the coagulation cascade, decreasing sepsis-related complications, and reducing the risk of bleeding and organ failure. Nevertheless, the benefits of TPE must be carefully balanced against potential risks such as hypocalcemia, hypotension, and citrate toxicity, especially in patients with underlying renal or liver issues, emphasizing the importance of shared decision-making. While TPE emerges as a promising therapy, its formal integration into standard care protocols awaits further confirmation, highlighting the critical need for more in-depth research to conclusively determine its efficacy and safety in septic shock management.
PubMed: 38910774
DOI: 10.7759/cureus.60947 -
Critical Care Explorations Jul 2024Although clinicians may use methylene blue (MB) in refractory septic shock, the effect of MB on patient-important outcomes remains uncertain. We conducted a systematic... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Although clinicians may use methylene blue (MB) in refractory septic shock, the effect of MB on patient-important outcomes remains uncertain. We conducted a systematic review and meta-analysis to investigate the benefits and harms of MB administration in patients with septic shock.
DATA SOURCES
We searched six databases (including PubMed, Embase, and Medline) from inception to January 10, 2024.
STUDY SELECTION
We included randomized clinical trials (RCTs) of critically ill adults comparing MB with placebo or usual care without MB administration.
DATA EXTRACTION
Two reviewers performed screening, full-text review, and data extraction. We pooled data using a random-effects model, assessed the risk of bias using the modified Cochrane tool, and used Grading of Recommendations Assessment, Development, and Evaluation to rate certainty of effect estimates.
DATA SYNTHESIS
We included six RCTs (302 patients). Compared with placebo or no MB administration, MB may reduce short-term mortality (RR [risk ratio] 0.66 [95% CI, 0.47-0.94], low certainty) and hospital length of stay (mean difference [MD] -2.1 d [95% CI, -1.4 to -2.8], low certainty). MB may also reduce duration of vasopressors (MD -31.1 hr [95% CI, -16.5 to -45.6], low certainty), and increase mean arterial pressure at 6 hours (MD 10.2 mm Hg [95% CI, 6.1-14.2], low certainty) compared with no MB administration. The effect of MB on serum methemoglobin concentration was uncertain (MD 0.9% [95% CI, -0.2% to 2.0%], very low certainty). We did not find any differences in adverse events.
CONCLUSIONS
Among critically ill adults with septic shock, based on low-certainty evidence, MB may reduce short-term mortality, duration of vasopressors, and hospital length of stay, with no evidence of increased adverse events. Rigorous randomized trials evaluating the efficacy of MB in septic shock are needed.
REGISTRATION
Center for Open Science (https://osf.io/hpy4j).
Topics: Methylene Blue; Humans; Shock, Septic; Randomized Controlled Trials as Topic; Length of Stay; Critical Illness
PubMed: 38904978
DOI: 10.1097/CCE.0000000000001110 -
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 -
International Archives of Allergy and... Jun 2024This systematic review aimed to assess the efficacy and safety of hydrocortisone, ascorbic acid, and thiamine (HAT) combination therapy in patients with sepsis and...
Efficacy and Safety of Hydrocortisone, Ascorbic Acid, and Thiamine Combination Therapy for the Management of Sepsis and Septic Shock: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.
INTRODUCTION
This systematic review aimed to assess the efficacy and safety of hydrocortisone, ascorbic acid, and thiamine (HAT) combination therapy in patients with sepsis and septic shock.
METHODS
We conducted a database search in MEDLINE, Embase, CENTRAL, Web of Science, and CNKI for randomised controlled trials (RCTs) comparing HAT against placebo/standard of care or against hydrocortisone in sepsis/septic shock patients. Outcomes included mortality, ICU/hospital length of stay (LOS), vasopressor durations, mechanical ventilation durations, change in SOFA at 72 h, and adverse events. RCT results were pooled in random-effects meta-analyses. Quality of evidence was assessed using GRADE.
RESULTS
Fifteen RCTs (N = 2,594) were included. At 72 h, HAT reduced SOFA scores from baseline (mean difference [MD] -1.16, 95% confidence interval [CI]: -1.58 to -0.74, I2 = 0%) compared to placebo/SoC, based on moderate quality of evidence. HAT also reduced the duration of vasopressor use (MD -18.80 h, 95% CI: -23.67 to -13.93, I2 = 64%) compared to placebo/SoC, based on moderate quality of evidence. HAT increased hospital LOS (MD 2.05 days, 95% CI: 0.15-3.95, I2 = 57%) compared to placebo/SoC, based on very low quality of evidence. HAT did not increase incidence of adverse events compared to placebo/SoC.
CONCLUSIONS
HAT appears beneficial in reducing vasopressor use and improving organ function in sepsis/septic shock patients. However, its advantages over hydrocortisone alone remain unclear. Future research should use hydrocortisone comparators and distinguish between sepsis-specific and comorbidity- or care-withdrawal-related mortality.
PubMed: 38870923
DOI: 10.1159/000538959 -
Experimental and Therapeutic Medicine Jul 2024It is unclear if premorbid use of beta-blockers affects sepsis outcomes. The present systematic review aimed to assess the impact of premorbid beta-blocker use on...
It is unclear if premorbid use of beta-blockers affects sepsis outcomes. The present systematic review aimed to assess the impact of premorbid beta-blocker use on mortality and the need for mechanical ventilation in patients with sepsis. Embase, Scopus, PubMed and Web of Science were searched for studies comparing outcomes of patients with sepsis based on the premorbid use of beta-blockers. The primary outcome was mortality, and the secondary outcome was the need for mechanical ventilation. The results were reported as odds ratios (ORs) with 95% confidence intervals (CIs). A total of 17 studies including 64,586 patients with sepsis were included. Of them, 8,665 patients received premorbid beta-blockers and 55,921 patients were not treated with premorbid beta-blockers and served as a control group. Pooled analysis of mortality rates revealed that premorbid use of beta-blockers did not affect in-hospital mortality (OR: 0.96; 95% CI: 0.78, 1.18; and I=63%) but significantly reduced one-month mortality rates (OR: 0.83; 95% CI: 0.72, 0.96; and I=63%). Combined analysis of adjusted data showed that premorbid beta-blockers were associated with a significant survival advantage in patients with sepsis (OR: 0.81; 95% CI: 0.72, 0.92; and I=70%). However, there was no effect of premorbid use of beta-blockers on the need for mechanical ventilation (OR: 0.93; 95% CI: 0.66, 1.30); and I=72%). The results of the present study indicated that premorbid use of beta-blockers is associated with improved survival in patients with sepsis. However, it does not impact the need for mechanical ventilation. The results should be interpreted with caution as the data is observational and unadjusted.
PubMed: 38868611
DOI: 10.3892/etm.2024.12589 -
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 -
New Microbes and New Infections 2024While mortality caused by sepsis remains an unsolved problem, studies showed conflicting results about effectiveness of monoclonal and polyclonal antibodies in patients... (Review)
Review
While mortality caused by sepsis remains an unsolved problem, studies showed conflicting results about effectiveness of monoclonal and polyclonal antibodies in patients suffering sepsis. For this reason, this current study provides an update of review clinical randomized trial studies until March 2024. The main object of this study is to determine effects of monoclonal and polyclonal antibodies on mortality rate and hospitalization of patients suffering sepsis. Search of Scopus, Web of science, EMBASE, PubMed and Cochrane were performed and randomized controlled trials which conducted in patients with septic shock or bacterial sepsis were included. Two reviewers assessed all searched trials for eligibility according to already defined criteria and did data collection and analyses afterwards. Present study showed monoclonal and polyclonal antibodies are a safe strategy with mild-to-moderate adverse effects. However, most studies indicate no significant change among inter-and intra-group comparison (p > 0.05) and further studies are needed, results showed an increase in survival rate, ventilator-and ICU-free days, resolve organ dysfunction, mediating inflammation related cytokines.
PubMed: 38860003
DOI: 10.1016/j.nmni.2024.101435 -
Annals of Saudi Medicine 2024Acute respiratory distress syndrome (ARDS), which results in lung injury as a consequence of sepsis and septic shock, is associated with severe systemic inflammation and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute respiratory distress syndrome (ARDS), which results in lung injury as a consequence of sepsis and septic shock, is associated with severe systemic inflammation and is responsible for a high worldwide mortality rate.
OBJECTIVE
Investigate whether corticosteroids could benefit clinical outcomes in adult with ARDS.
METHODS
A comprehensive search of electronic databases Ovid MEDLINE, Ovid EMbase, and Cochrane Library from their inception to 7 May 2023 was conducted to identify studies that met the eligibility criteria, including only randomized controlled trials. The study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the methods of trial sequential analysis.
MAIN OUTCOME MEASURES
Mortality rates, including including the 14-, 28-, 45-, and 60-day mortality, hospital mortality, and intensive care unit (ICU) mortality.
SAMPLE SIZE
17 studies with 2508 patients.
RESULTS
Data relating to mortality at 14, 28, 45, and 60 days were not significantly different when treatments with corticosteroids and placebo were compared. In terms of hospital and ICU mortality, the mortality of those who had received corticosteroids was significantly lower than that of those who had not. ARDS patients who received assisted ventilation benefited from corticosteroid therapy, as revealed by the significant difference in outcome days between those who received assisted ventilation and those who did not. Corticosteroid had significantly more days free from mechanical ventilation, ICU-free days, and MODS-free days during the first 28 days, but not more organ support-free days up to day 28.
CONCLUSION
Although corticosteroid therapy did not reduce mortality rates at different observation periods, it significantly reduced hospital and ICU mortality. Administering corticosteroids to ARDS patients significantly decreased the days of assisted ventilation and time cost consumption. This study confirmed that long-term use of low-dose glucocorticoids may have a positive effect on early ARDS.
LIMITATION
Risk of bias due to the differences in patient characteristics.
Topics: Adult; Humans; Adrenal Cortex Hormones; Hospital Mortality; Intensive Care Units; Randomized Controlled Trials as Topic; Respiration, Artificial; Respiratory Distress Syndrome; Treatment Outcome
PubMed: 38853475
DOI: 10.5144/0256-4947.2024.167 -
Medicina Clinica Jun 2024The present systematic review analyses the role of soluble fms-like tyrosine kinase-1 (sFLT-1) as an indirect biomarker of endothelial dysfunction in sepsis or septic...
INTRODUCTION
The present systematic review analyses the role of soluble fms-like tyrosine kinase-1 (sFLT-1) as an indirect biomarker of endothelial dysfunction in sepsis or septic shock from articles published in PubMed between 2010 and March 2022.
MATERIALS AND METHODS
A systematic review of studies studying sFLT-1 monitoring in intensive care units in adults with sepsis or septic shock vs. controls for sepsis diagnosis and prognosis has been carried out (PROSPERO CRD42023412929 Registry).
RESULTS
The endothelial dysfunction of sepsis is one of the keys to the development of the disease. VEGF binds to sFLT-1 acting as a competitive inhibitor of VEGF signalling in endothelial cells and thus neutralizes its pro-inflammatory effects. Endothelial dysfunction is reflected in increased sFLT-1 levels. High values of sFLT-1 were used for the differential diagnosis of sepsis versus other inflammatory pathologies, septic shock versus other types of shock, were elevated over time, estimation of disease prognosis, correlation with sepsis severity, organ dysfunction, and mortality prediction.
CONCLUSIONS
It is evident that sepsis is based on endothelial dysfunction. sFLT-1 is one of the main biomarkers of microvascular alteration and is a predictive diagnostic and prognostic biomarker.
PubMed: 38851948
DOI: 10.1016/j.medcli.2024.03.027