Objectives:The clinical efficacy of short-acting beta-blockers in the management of sepsis remains uncertain. In particular, the comparative effects of two commonly used agents-esmolol and landiolol-have not been clearly established. This network meta-analysis aims to systematically evaluate and compare the effects of esmolol, landiolol, and standard of care (SOC) on mortality in patients with sepsis.Data Sources:A systematic search of PubMed, Web of Science, Embase, MEDLINE, CENTRAL, ClinicalTrials.gov, preprints, and citation searching was conducted before April 15, 2025.Study Selection:Randomized controlled trials that enrolled adult patients (>= 18 yr) diagnosed with sepsis or septic shock and treated with beta-blockers and conducted in ICUs.Data Extraction:Data were extracted on study characteristics, enrolled patients' characteristics, administration strategies of drugs, and key clinical outcomes (including 28-d mortality, ICU length of stay, and other relevant endpoints).Data Synthesis:A total of 1165 records were identified through searches of five databases, registries, and relevant references up to April 15, 2025. Ten studies involving 1035 patients were included, after screening and eligibility assessment. Compared with esmolol, landiolol was associated with increased 28-day mortality (relative risk [RR], 1.57; 95% CI, 1.08-2.30; low certainty) and higher norepinephrine requirements (mean difference [MD], 0.17 mu g/kg/min; 95% CI, 0.02-0.32; low certainty). Esmolol significantly reduced 28-day mortality (RR, 0.69; 95% CI, 0.56-0.85; moderate certainty) and 24-hour heart rate (MD, -16.92 beats/min; 95% CI, -23.49 to -10.36; moderate certainty) compared with SOC. In contrast, landiolol increased norepinephrine use compared with SOC (MD, 0.09 mu g/kg/min; 95% CI, 0.01-0.18; moderate certainty).Conclusions:Among patients with sepsis treated with beta-blockers, esmolol probably improves clinical outcomes compared with SOC. However, the effect of landiolol remains uncertain due to the low certainty of evidence. Esmolol may confer a relative clinical advantage over landiolol, but further studies are needed to confirm this finding and elucidate the underlying mechanisms.

Background: Vitamin D deficiency is a common condition in critically ill patients. A high dose of vitamin D3 can rapidly restore vitamin D levels. The aim of this meta-analysis was to synthesize the results from up-to-date randomized control trials (RCT) and validate the effect of vitamin D3 in critically ill patients.Study Methods: Several databases, including PubMed, Web of Science, EMBASE, and the Cochrane Central database, were searched up to December 4th, 2020. All RCTs that investigated the use of a high dose of vitamin D3 in critically ill patients and reported mortality data were included in themeta-analysis. The primary outcome was the mortality truncated to day 28 and day 90.Results: A total of 10 RCTs enrolling 2058 patients were finally included. The use of a high dose of vitamin D3 in critically ill patients could not decrease the mortality truncated to day 28 (RR 0.93, 95% CI 0.78-1.11, P = 0.43) or day 90 (RR 0.91, 95% CI 0.79-1.05, P = 0.21). A high dose of vitamin D3 could significantly reduce the ventilator days (MD -9.38, 95%CI -13.44 to -5.31, P < 0.001), but there were no statistic difference in length of ICU stay (MD -2.76, 95% CI -6.27 to 0.74, P = 0.12) and hospital stay (MD -2.42, 95% CI -6.21 to 1.36, P = 0.21). No significant difference was observed in adverse events between the vitamin D3 group and the placebo group.Conclusion: The use of high dose vitamin D3 was not associated with decreased mortality in critically ill patients, but could significantly reduce the ventilator days.

Background: Vitamin D deficiency is a common condition in critically ill patients. A high dose of vitamin D3 can rapidly restore vitamin D levels. The aim of this meta-analysis was to synthesize the results from up-to-date randomized control trials (RCT) and validate the effect of vitamin D3 in critically ill patients.Study Methods: Several databases, including PubMed, Web of Science, EMBASE, and the Cochrane Central database, were searched up to December 4th, 2020. All RCTs that investigated the use of a high dose of vitamin D3 in critically ill patients and reported mortality data were included in themeta-analysis. The primary outcome was the mortality truncated to day 28 and day 90.Results: A total of 10 RCTs enrolling 2058 patients were finally included. The use of a high dose of vitamin D3 in critically ill patients could not decrease the mortality truncated to day 28 (RR 0.93, 95% CI 0.78-1.11, P = 0.43) or day 90 (RR 0.91, 95% CI 0.79-1.05, P = 0.21). A high dose of vitamin D3 could significantly reduce the ventilator days (MD -9.38, 95%CI -13.44 to -5.31, P < 0.001), but there were no statistic difference in length of ICU stay (MD -2.76, 95% CI -6.27 to 0.74, P = 0.12) and hospital stay (MD -2.42, 95% CI -6.21 to 1.36, P = 0.21). No significant difference was observed in adverse events between the vitamin D3 group and the placebo group.Conclusion: The use of high dose vitamin D3 was not associated with decreased mortality in critically ill patients, but could significantly reduce the ventilator days.

Background: The efficacy of synbiotics, probiotics, prebiotics, enteral nutrition or adjuvant peripheral parenteral nutrition (EPN) and total parenteral nutrition (TPN) in preventing nosocomial infection (NI) in critically ill adults has been questioned. We conducted a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) to evaluate and rank the effectiveness of these therapies on NI amongst critically ill adults.Methods: Four electronic databases were systematically searched up to June 30, 2019 for RCTs comparing the administration of probiotics, prebiotics, synbiotics, EPN and TPN in critically ill adults. The primary outcome was NI. The relative efficacy of all outcomes was determined by a Bayesian framework with random effects NMA. We estimated the odds ratio (OR) and mean difference (MD) and ranked the comparative effects of all regimens with the surface under the cumulative ranking probabilities. The study has been registered on PROSPERO (CRD42019147032).Results: Fifty-five RCTs (7,119 patients) were identified. Primary outcome showed that synbiotics had the best effect in preventing NI than EPN (OR 0.37; 95% CrI 0.22-0.61), probiotics followed (OR 0.52; 95% CrI 0.34-0.77), whereas TPN significantly increased NI (OR 2.29; 95% CrI 1.48-3.67). Subgroup analysis showed that TPN significantly increased NI in intensive care unit (ICU) patients (OR 1.57; 95% CrI 1.01-2.56) and severe acute pancreatitis (SAP) patients (OR 3.93; 95% CrI 1.74-9.15). Secondary outcomes showed that synbiotics were more effective in preventing hospital-acquired pneumonia (HAP) (OR 0.34; 95% CrI 0.11-0.85), catheter-related bloodstream infection (OR 0.08; 95% CrI 0.01-0.80), urinary tract infection (OR 0.27; 95% CrI 0.08-0.71) and sepsis (OR 0.34; 95% CrI 0.16-0.70) than EPN. Amongst the treatments, probiotics were most effective for shortening the mechanical ventilation duration (MD -3.93; 95% CrI -7.98 to -0.02), prebiotics were most effective for preventing diarrhea (OR 0.24; 95% CrI 0.05-0.94) and TPN was the least effective in shortening hospital length of stay (MD 4.23; 95% CrI 0.97-7.33).Conclusions: Amongst the five therapies, synbiotics not only prevented NI in critically ill adults but also demonstrated the best treatment results. By contrast, TPN did not prevent NI and ranked last, especially in ICU and SAP patients.Take-Home Message: Nosocomial infection is a leading cause of mortality in critically ill patients in the ICU. However, the efficacy of synbiotics, probiotics, prebiotics, enteral nutrition or adjuvant peripheral parenteral nutrition and total parenteral nutrition in preventing nosocomial infection in critically ill adults has been questioned. The network meta-analysis provides evidence that amongst the five therapies, synbiotics not only prevented NI in critically ill adults but also demonstrated the best treatment results. By contrast, TPN did not prevent NI and ranked last, especially in ICU and SAP patients. The results of this study will provide a new scientific basis and a new idea for the debate on the efficacy of synbiotics and other treatments in the improvement of prognosis in critically ill adult patients.Tweet: Synbiotic prevents nosocomial infection in critically ill adults, while total parenteral nutrition has the adverse curative.