Handgrip strength association with weaning outcome in mechanically ventilated ICU patients: a systematic review and meta-analysis

Critical Care volume 29, Article number: 478 (2025) Published: 07 November 2025

Abstract

Weaning from mechanical ventilation is a critical process in the intensive care unit (ICU), and extubation failure remains associated with poor outcomes. ICU-acquired weakness has been identified as a risk factor for delayed weaning. Maximal handgrip strength (HGS) is a simple bedside measure proposed as a surrogate marker of global muscle strength. This systematic review and meta-analysis aimed to assess the association between HGS and weaning outcomes in ICU patients. A systematic search of MEDLINE, EMBASE, CINAHL, and Cochrane Library was conducted up to December 2024. We included prospective cohort studies assessing maximal HGS prior to extubation in mechanically ventilated adults, and its association with extubation failure, spontaneous breathing trial (SBT) failure, or weaning classification (simple, difficult, or prolonged). Meta-analyses pooled mean differences in HGS between outcome groups, and diagnostic accuracy was evaluated using a hierarchical summary ROC model. Risk of bias was assessed using the QUIPS tool. Seven studies were included in the review (n = 707 patients), and six in the meta-analysis. No significant difference in HGS was found between extubation failure and success (mean difference: − 3.62 kg; 95% CI: − 7.92 to 0.62). However, significantly lower HGS was associated with SBT failure (–3.00 kg; 95% CI: − 4.64 to − 1.36) and non-simple weaning (–3.94 kg; 95% CI: − 5.31 to − 2.58). Pooled sensitivity and specificity of HGS were 72% and 60% respectively, in predicting either extubation failure or non-simple weaning. Negative predictive values ranged from 90% to 95%, for 10% and 20% pre-test probability. Maximal HGS does not appear to significantly differentiate extubation success from failure Given the limited number of studies and their heterogeneity, further high-quality research is needed to clarify its prognostic value across different patient subgroups and timeframes.

 

Melatonin and delirium in the intensive care units: a systematic review and meta-analysis of randomized controlled trials

 

Intensive Care Medicine Published: 06 October 2025

Background

Delirium is frequent in critically ill patients and is associated with increased mortality. Discrepancies were found in the results of recent randomized controlled trials (RCTs) regarding the effect of melatonin to prevent delirium onset in critically ill patients.

Methods

We searched MEDLINE, Embase, and Web of Science from inception to 5 July 2025 for RCTs evaluating melatonin in critically ill patients. The primary outcome was the incidence of delirium. The main secondary outcome was mortality. We generated pooled risk ratios (RR). To base our conclusions on the highest quality of evidence, our primary analysis was based only on the trials with low to moderate risk of bias for each outcome. A secondary analysis was conducted, including all the trials.

The study was registered with PROSPERO (CRD420251041661).

Findings

Our primary analysis was based on six RCTs with 2209 patients and did not show any difference in the incidence of delirium attributable to the treatment with melatonin (RR 0.89, [95% confidence interval (CI) 0.73—1.09]). This result was consistent with the secondary analysis including thirteen RCTs with 2830 patients (RR 0.86, [95% CI 0.70–1.04]). No association was found between mortality and melatonin in the primary (seven RCTs, 2165 patients, RR 0.87, [95% CI 0.73–1.02]) and secondary (8 RCTs, 2396 patients, RR 0.92, [95% CI 0.79–1.06]) analyses.

Interpretation

The results suggest that compared to placebo, melatonin does not reduce delirium incidence in critically ill patients. Similarly, no effect was observed on mortality.

 

Intraosseous versus intravenous vascular access in out-of-hospital cardiac arrest: a systematic review and meta-analysis of randomized controlled trials

 

Critical Care volume 29, Article number: 124 (2025) Published: 19 March 2025

 

Background

Rapid and reliable vascular access is crucial during cardiopulmonary resuscitation for out-of-hospital cardiac arrest (OHCA). While intraosseous (IO) and intravenous (IV) access are used, their comparative effectiveness for patient outcomes remains uncertain.

Methods

We searched PubMed, Embase, and ClinicalTrials.gov for RCTs comparing IO vs. IV access in adults with OHCA. The primary outcome was survival (30 days or until discharge), while secondary outcomes included sustained ROSC, favorable neurological outcome, successful first-attempt vascular access, and time from emergency medical service arrival to access. Pooled odds ratios (OR), mean differences (MD), and 95% confidence intervals (CI) were calculated.

Results

Four RCTs with 9475 patients were included. No significant differences were found between IO and IV groups in survival (6.6% vs. 6.9%, OR 0.99, 95% CI 0.84–1.18) or favorable neurological outcome (4.7% vs. 4.6%, OR 1.07, 95% CI 0.88–1.30). The sustained ROSC rate was numerically, but not significantly, lower in IO vs. IV access (24.6% vs. 27.0%, OR 0.92, 95% CI 0.80–1.06). IO access had a higher first-attempt success rate (92.3% vs. 62.3%; OR 6.18, 95% CI 3.50–10.91) and was 15 s faster than IV for vascular access (IO: 11.03 ± 5.57, IV: 11.35 ± 6.16 min, MD − 0.25, 95% CI − 0.48 to − 0.01).

Conclusions

IO access had a higher first-attempt success rate and faster establishment than IV access, but no significant differences were found in survival or favorable neurological outcomes in adults with OHCA. Sustained ROSC was numerically lower with IO access than IV access, although the difference was not statistically significant.

 

Extremely early initiation of vasopressors might not decrease short-term mortality for adults with septic shock: a systematic review and meta-analysis

Annals of Intensive Care volume 15, Article number: 18 (2025)

Published: 27 January 2025

Background

The optimal timing for initiating vasopressor therapy in patients with septic shock remains unclear. This study aimed to assess the impact of early versus late vasopressor initiation on clinical outcomes.

Methods

A systematic review and meta-analysis were conducted by searching PubMed, Embase, and Cochrane databases. Studies comparing early and late vasopressor administration in septic shock patients were included. The primary outcome was short-term mortality, and subgroup analyses were performed based on different initiation timings.

Results

Eleven studies with 6,661 patients were included. Different studies define the ‘early administration’ timeframe variously, ranging from one to seven hours. No significant difference in short-term mortality was observed between early and late administration in the combined analysis of 3,757 patients from two RCTs and three quasi-experimental studies (OR: 0.66, 95% CI: [0.36, 1.19], I²: 82%). However, lower mortality was found in subgroups with early but not extremely early initiation (one to three hours, OR: 0.70, 95% CI: [0.60, 0.82], I²: 0%), and those using septic shock diagnosis as time zero (OR: 0.64, 95% CI: [0.48, 0.85], I²: 39%).

Conclusion

Our findings found that earlier initiation of vasopressor therapy, particularly within one to three hours after the diagnosis of septic shock, may be associated with reduced short-term mortality in certain subgroups. However, due to the heterogeneity in study definitions and potential confounding factors, these results should be interpreted cautiously. Further standardized investigations are warranted to precisely determine the optimal timing for vasopressor initiation to maximize survival outcomes in patients with septic shock.

 

Assessing palliative care practices in intensive care units and interpreting them using the lens of appropriate care concepts. An umbrella review

Intensive Care Medicine, Published: 14 August 2024

Purpose

Intensive care units (ICUs) have significant palliative care needs but lack a reliable care framework. This umbrella review addresses them by synthesising palliative care practices provided at end-of-life to critically ill patients and their families before, during, and after ICU admission.

Methods

Seven databases were systematically searched for systematic reviews, and the umbrella review was conducted according to the guidelines laid out by the Joanna Briggs Institute (JBI).

Results

Out of 3122 initial records identified, 40 systematic reviews were included in the synthesis. Six key themes were generated that reflect the palliative and end-of-life care practices in the ICUs and their outcomes. Effective communication and accurate prognostications enabled families to make informed decisions, cope with uncertainty, ease distress, and shorten ICU stays. Inter-team discussions and agreement on a plan are essential before discussing care goals. Recording care preferences prevents unnecessary end-of-life treatments. Exceptional end-of-life care should include symptom management, family support, hydration and nutrition optimisation, avoidance of unhelpful treatments, and bereavement support. Evaluating end-of-life care quality is critical and can be accomplished by seeking family feedback or conducting a survey.

Conclusion

This umbrella review encapsulates current palliative care practices in ICUs, influencing patient and family outcomes and providing insights into developing an appropriate care framework for critically ill patients needing end-of-life care and their families.

 

Low Versus High Blood Pressure Targets in Critically Ill and Surgical Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

 by D’Amico, Filippo; Pruna, Alessandro; Putowski, Zbigniew; Dormio, Sara; Ajello, Silvia; Scandroglio, Anna Mara; Lee, Todd C.; Zangrillo, Alberto; Landoni, Giovanni 

 Critical Care Medicine, April 24, 2024.

 Objectives: 

Hypotension is associated with adverse outcomes in critically ill and perioperative patients. However, these assumptions are supported by observational studies. This meta-analysis of randomized controlled trials aims to compare the impact of lower versus higher blood pressure targets on mortality.

Data Sources: 

We searched PubMed, Cochrane, and Scholar from inception to February 10, 2024.

Study Selection: 

Randomized trials comparing lower versus higher blood pressure targets in the management of critically ill and perioperative settings.

Data Extraction: 

The primary outcome was all-cause mortality at the longest follow-up available. This review was registered in the Prospective International Register of Systematic Reviews, CRD42023452928.

Data Synthesis: 

Of 2940 studies identified by the search string, 28 (12 in critically ill and 16 in perioperative settings) were included totaling 15,672 patients. Patients in the low blood pressure target group had lower mortality (23 studies included: 1019/7679 [13.3%] vs. 1103/7649 [14.4%]; relative risk 0.93; 95% CI, 0.87–0.99; p = 0.03; I2 = 0%). This corresponded to a 97.4% probability of any increase in mortality with a Bayesian approach. These findings were mainly driven by studies performed in the ICU setting and with treatment lasting more than 24 hours; however, the magnitude and direction of the results were similar in the majority of sensitivity analyses including the analysis restricted to low risk of bias studies. We also observed a lower rate of atrial fibrillation and fewer patients requiring transfusion in low-pressure target groups. No differences were found in the other secondary outcomes.

Conclusions: 

Based on pooled randomized trial evidence, a lower compared with a higher blood pressure target results in a reduction of mortality, atrial fibrillation, and transfusion requirements. Lower blood pressure targets may be beneficial but there is ongoing uncertainty. However, the present meta-analysis does not confirm previous findings and recommendations. These results might inform future guidelines and promote the study of the concept of protective hemodynamics.

 

Ketamine versus etomidate as an induction agent for tracheal intubation in critically ill adults: a Bayesian meta-analysis

 

by Takatoshi Koroki, Yuki Kotani, Takahiko Yaguchi, Taisuke Shibata, Motoki Fujii, Stefano Fresilli, Mayuko Tonai, Toshiyuki Karumai, Todd C. Lee, Giovanni Landoni and Yoshiro Hayashi 

 

Critical Care volume 28, Article number: 48 (2024)  Published: 17 February 2024

 

Background

Tracheal intubation is a high-risk intervention commonly performed in critically ill patients. Due to its favorable cardiovascular profile, ketamine is considered less likely to compromise clinical outcomes. This meta-analysis aimed to assess whether ketamine, compared with other agents, reduces mortality in critically ill patients undergoing intubation.

Methods

We searched MEDLINE, Embase, and the Cochrane Library from inception until April 27, 2023, for randomized controlled trials and matched observational studies comparing ketamine with any control in critically ill patients as an induction agent. The primary outcome was mortality at the longest follow-up available, and the secondary outcomes included Sequential Organ Failure Assessment score, ventilator-free days at day 28, vasopressor-free days at day 28, post-induction mean arterial pressure, and successful intubation on the first attempt. For the primary outcome, we used a Bayesian random-effects meta-analysis on the risk ratio (RR) scale with a weakly informative neutral prior corresponding to a mean estimate of no difference with 95% probability; the estimated effect size will fall between a relative risk of 0.25 and 4. The RR and 95% credible interval (CrI) were used to estimate the probability of mortality reduction (RR < 1). The secondary outcomes were assessed with a frequentist random-effects model. We registered this study in Open Science Framework (https://osf.io/2vf79/).

Results

We included seven randomized trials and one propensity-matched study totaling 2978 patients. Etomidate was the comparator in all the identified studies. The probability that ketamine reduced mortality was 83.2% (376/1475 [25%] vs. 411/1503 [27%]; RR, 0.93; 95% CrI, 0.79–1.08), which was confirmed by a subgroup analysis excluding studies with a high risk of bias. No significant difference was observed in any secondary outcomes.

Conclusions

All of the included studies evaluated ketamine versus etomidate among critically ill adults requiring tracheal intubation. This meta-analysis showed a moderate probability that induction with ketamine is associated with a reduced risk of mortality.

Critical Care Bulletin: June 2023

 

Definitions of massive transfusion in adults with critical bleeding: a systematic review

 

by Victor S. Lin, Emily Sun, Serine Yau, Chathuri Abeyakoon, Georgia Seamer, Simran Bhopal, Harriet Tucker, Carolyn Doree, Susan J. Brunskill, Zoe K. McQuilten, Simon J. Stanworth, Erica M. Wood and Laura Green 

 

Critical Care volume 27, Article number: 265 Published: 05 July 2023

 

Background

Definitions for massive transfusion (MT) vary widely between studies, contributing to challenges in interpretation of research findings and practice evaluation. In this first systematic review, we aimed to identify all MT definitions used in randomised controlled trials (RCTs) to date to inform the development of consensus definitions for MT.

Methods

We systematically searched the following databases for RCTs from inception until 11 August 2022: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Cumulative Index to Nursing and Allied Health Literature, and Transfusion Evidence Library. Ongoing trials were sought from CENTRAL, ClinicalTrials.gov, and World Health Organisation International Clinical Trials Registry Platform. To be eligible for inclusion, studies had to fulfil all the following three criteria: (1) be an RCT; (2) include an adult patient population with major bleeding who had received, or were anticipated to receive, an MT in any clinical setting; and (3) specify a definition for MT as an inclusion criterion or outcome measure.

Results

Of the 8,458 distinct references identified, 30 trials were included for analysis (19 published, 11 ongoing). Trauma was the most common clinical setting in published trials, while for ongoing trials, it was obstetrics. A total of 15 different definitions of MT were identified across published and ongoing trials, varying greatly in cut-offs for volume transfused and time period. Almost all definitions specified the number of red blood cells (RBCs) within a set time period, with none including plasma, platelets or other haemostatic agents that are part of contemporary transfusion resuscitation. For completed trials, the most commonly used definition was transfusion of ≥ 10 RBC units in 24 h (9/19, all in trauma), while for ongoing trials it was 3–5 RBC units (n = 7), with the timing for transfusion being poorly defined, or in some trials not provided at all (n = 5).

Conclusions

Transfusion of ≥ 10 RBC units within 24 h was the most commonly used definition in published RCTs, while lower RBC volumes are being used in ongoing RCTs. Any consensus definitions should reflect the need to incorporate different blood components/products for MT and agree on whether a ‘one-size-fits-all’ approach should be used across different clinical settings.

 

Mechanical ventilation in patients with acute brain injury: a systematic review with meta-analysis

 

by Karim Asehnoune, Paul Rooze, Chiara Robba, Marwan Bouras, Luciana Mascia, Raphaël Cinotti, Paolo Pelosi and Antoine Roquilly 

 

Critical Care volume 27, Article number: 221 Published: 06 June 2023

 

Objective

To describe the potential effects of ventilatory strategies on the outcome of acute brain-injured patients undergoing invasive mechanical ventilation.

Design

Systematic review with an individual data meta-analysis.

Setting

Observational and interventional (before/after) studies published up to August 22nd, 2022, were considered for inclusion. We investigated the effects of low tidal volume Vt < 8 ml/Kg of IBW versus Vt >  = 8 ml/Kg of IBW, positive end-expiratory pressure (PEEP) < or >  = 5 cmH2O and protective ventilation (association of both) on relevant clinical outcomes.

Population

Patients with acute brain injury (trauma or haemorrhagic stroke) with invasive mechanical ventilation for ≥ 24 h.

Main outcome measures

The primary outcome was mortality at 28 days or in-hospital mortality. Secondary outcomes were the incidence of acute respiratory distress syndrome (ARDS), the duration of mechanical ventilation and the partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio.

Results

The meta-analysis included eight studies with a total of 5639 patients. There was no difference in mortality between low and high tidal volume [Odds Ratio, OR 0.88 (95%Confidence Interval, CI 0.74 to 1.05), p = 0.16, I2 = 20%], low and moderate to high PEEP [OR 0.8 (95% CI 0.59 to 1.07), p = 0.13, I2 = 80%] or protective and non-protective ventilation [OR 1.03 (95% CI 0.93 to 1.15), p = 0.6, I2 = 11]. Low tidal volume [OR 0.74 (95% CI 0.45 to 1.21, p = 0.23, I2 = 88%], moderate PEEP [OR 0.98 (95% CI 0.76 to 1.26), p = 0.9, I2 = 21%] or protective ventilation [OR 1.22 (95% CI 0.94 to 1.58), p = 0.13, I2 = 22%] did not affect the incidence of acute respiratory distress syndrome. Protective ventilation improved the PaO2/FiO2 ratio in the first five days of mechanical ventilation (p < 0.01).

Conclusions

Low tidal volume, moderate to high PEEP, or protective ventilation were not associated with mortality and lower incidence of ARDS in patients with acute brain injury undergoing invasive mechanical ventilation. However, protective ventilation improved oxygenation and could be safely considered in this setting. The exact role of ventilatory management on the outcome of patients with a severe brain injury needs to be more accurately delineated.

 

Comparison of clinical outcomes between aggressive and non-aggressive intravenous hydration for acute pancreatitis: a systematic review and meta-analysis

by Xiu-Wei Li, Chien-Ho Wang, Jhih-Wei Dai, Shu-Han Tsao, Po-Hsi Wang, Cheng-Chen Tai, Rong-Nan Chien, Shih-Chieh Shao and Edward Chia-Cheng Lai 

Critical Care volume 27, Article number: 122 (2023) Published: 22 March 2023

Background

Current practice guidelines for optimal infusion rates during early intravenous hydration in patients with acute pancreatitis (AP) remain inconsistent. This systematic review and meta-analysis aimed to compare treatment outcomes between aggressive and non-aggressive intravenous hydration in severe and non-severe AP.

Methods

This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We systematically searched PubMed, Embase and Cochrane Library for randomized controlled trials (RCTs) on November 23, 2022, and hand-searched the reference lists of included RCTs, relevant review articles and clinical guidelines. We included RCTs that compared clinical outcomes from aggressive and non-aggressive intravenous hydration in AP. Meta-analysis was performed using a random-effects model for participants with severe AP and non-severe AP. Our primary outcome was all-cause mortality, and several secondary outcomes included fluid-related complications, clinical improvement and APACHE II scores within 48 h.

Results

We included a total of 9 RCTs with 953 participants. The meta-analysis indicated that, compared to non-aggressive intravenous hydration, aggressive intravenous hydration significantly increased mortality risk in severe AP (pooled RR: 2.45, 95% CI: 1.37, 4.40), while the result in non-severe AP was inconclusive (pooled RR: 2.26, 95% CI: 0.54, 9.44). However, aggressive intravenous hydration significantly increased fluid-related complication risk in both severe (pooled RR: 2.22, 95% CI 1.36, 3.63) and non-severe AP (pooled RR: 3.25, 95% CI: 1.53, 6.93). The meta-analysis indicated worse APACHE II scores (pooled mean difference: 3.31, 95% CI: 1.79, 4.84) in severe AP, and no increased likelihood of clinical improvement (pooled RR:1.20, 95% CI: 0.63, 2.29) in non-severe AP. Sensitivity analyses including only RCTs with goal-directed fluid therapy after initial fluid resuscitation therapy yielded consistent results.

Conclusions

Aggressive intravenous hydration increased the mortality risk in severe AP, and fluid-related complication risk in both severe and non-severe AP. More conservative intravenous fluid resuscitation protocols for AP are suggested.

 

Does tidal volume challenge improve the feasibility of pulse pressure variation in patients mechanically ventilated at low tidal volumes? A systematic review and meta-analysis

 

by Xiaoying Wang, Shuai Liu, Ju Gao, Yang Zhang and Tianfeng Huang 

 

Critical Care volume 27, Article number: 45 (2023)

 

Background

Pulse pressure variation (PPV) has been widely used in hemodynamic assessment. Nevertheless, PPV is limited in low tidal volume ventilation. We conducted this systematic review and meta-analysis to evaluate whether the tidal volume challenge (TVC) could improve the feasibility of PPV in patients ventilated at low tidal volumes.

Methods

PubMed, Embase and Cochrane Library inception to October 2022 were screened for diagnostic researches relevant to the predictability of PPV change after TVC in low tidal volume ventilatory patients. Summary receiving operating characteristic curve (SROC), pooled sensitivity and specificity were calculated. Subgroup analyses were conducted for possible influential factors of TVC.

Results

Ten studies with a total of 429 patients and 457 measurements were included for analysis. The predictive performance of PPV was significantly lower than PPV change after TVC in low tidal volume, with mean area under the receiving operating characteristic curve (AUROC) of 0.69 ± 0.13 versus 0.89 ± 0.10. The SROC of PPV change yielded an area under the curve of 0.96 (95% CI 0.94, 0.97), with overall pooled sensitivity and specificity of 0.92 (95% CI 0.83, 0.96) and 0.88 (95% CI 0.76, 0.94). Mean and median cutoff value of the absolute change of PPV (△PPV) were 2.4% and 2%, and that of the percentage change of PPV (△PPV%) were 25% and 22.5%. SROC of PPV change in ICU group, supine or semi-recumbent position group, lung compliance less than 30 cm H2O group, moderate positive end-expiratory pressure (PEEP) group and measurements devices without transpulmonary thermodilution group yielded 0.95 (95%0.93, 0.97), 0.95 (95% CI 0.92, 0.96), 0.96 (95% CI 0.94, 0.97), 0.95 (95% CI 0.93, 0.97) and 0.94 (95% CI 0.92, 0.96) separately. The lowest AUROCs of PPV change were 0.59 (95% CI 0.31, 0.88) in prone position and 0.73 (95% CI 0.60, 0.84) in patients with spontaneous breathing activity.

Conclusions

TVC is capable to help PPV overcome limitations in low tidal volume ventilation, wherever in ICU or surgery. The accuracy of TVC is not influenced by reduced lung compliance, moderate PEEP and measurement tools, but TVC should be cautious applied in prone position and patients with spontaneous breathing activity.

 

Association Between Socioeconomic Status and Outcomes in Critical Care: A Systematic Review and Meta-Analysis

 

by McHenry, Ryan D.; Moultrie, Christopher E. J.; Quasim, Tara; Mackay, Daniel F.; Pell, Jill P.

 

Critical Care Medicine, December 26, 2022.

 

Objectives: 

Socioeconomic status is well established as a key determinant of inequalities in health outcomes. Existing literature examining the impact of socioeconomic status on outcomes in critical care has produced inconsistent findings. Our objective was to synthesize the available evidence on the association between socioeconomic status and outcomes in critical care.

Data Sources: 

A systematic search of CINAHL, Ovid MEDLINE, and EMBASE was undertaken on September 13, 2022.

Study Selection: 

Observational cohort studies of adults assessing the association between socioeconomic status and critical care outcomes including mortality, length of stay, and functional outcomes were included. Two independent reviewers assessed titles, abstracts, and full texts against eligibility and quality criteria.

Data Extraction: 

Details of study methodology, population, exposure measures, and outcomes were extracted.

Data Synthesis: 

Thirty-eight studies met eligibility criteria for systematic review. Twenty-three studies reporting mortality to less than or equal to 30 days following critical care admission, and eight reporting length of stay, were included in meta-analysis. Random-effects pooled analysis showed that lower socioeconomic status was associated with higher mortality at less than or equal to 30 days following critical care admission, with pooled odds ratio of 1.13 (95% CIs, 1.05–1.22). Meta-analysis of ICU length of stay demonstrated no significant difference between socioeconomic groups. Socioeconomic status may also be associated with functional status and discharge destination following ICU admission.

Conclusions: 

Lower socioeconomic status was associated with higher mortality following admission to critical care.

 

Association of sepsis-induced cardiomyopathy and mortality: a systematic review and meta-analysis

 

by Yu-Min Lin, Mei-Chuan Lee, Han Siong Toh, Wei-Ting Chang, Sih-Yao Chen, Fang-Hsiu Kuo, Hsin-Ju Tang, Yi-Ming Hua, Dongmei Wei, Jesus Melgarejo, Zhen-Yu Zhang and Chia-Te Liao 

 

Annals of Intensive Care volume 12, Article number: 112 (2022) 

 

Background

The implication of  (SIC) to prognosis is controversial, and its association with mortality at different stages remains unclear. We conducted a systematic review and meta-analysis to understand the association between SIC and mortality in septic patients.

Methods

We searched and appraised observational studies regarding the mortality related to SIC among septic patients in PubMed and Embase from inception until 8 July 2021. Outcomes comprised in-hospital and 1-month mortality. We adopted the random-effects model to examine the mortality risk ratio in patients with and without SIC. Meta-regression, subgroup, and sensitivity analyses were applied to examine the outcome’s heterogeneity.

Results

Our results, including 20 studies and 4,410 septic patients, demonstrated that SIC was non-statistically associated with increased in-hospital mortality, compared to non-SIC (RR 1.28, [0.96–1.71]; p = 0.09), but the association was statistically significant in patients with the hospital stay lengths longer than 10 days (RR 1.40, [1.02–1.93]; p = 0.04). Besides, SIC was significantly associated with a higher risk of 1-month mortality (RR 1.47, [1.17–1.86]; p < 0.01). Among SIC patients, right ventricular dysfunction was significantly associated with increased 1-month mortality (RR 1.72, [1.27–2.34]; p < 0.01), while left ventricular dysfunction was not (RR 1.33, [0.87–2.02]; p = 0.18).

Conclusions

With higher in-hospital mortality in those hospitalized longer than 10 days and 1-month mortality, our findings imply that SIC might continue influencing the host’s system even after recovery from cardiomyopathy. Besides, right ventricular dysfunction might play a crucial role in SIC-related mortality, and timely biventricular assessment is vital in managing septic patients.

 

High-flow nasal cannula versus non-invasive ventilation for acute hypercapnic respiratory failure in adults: a systematic review and meta-analysis of randomized trials

by N. Ovtcharenko, E. Ho, W. Alhazzani, A. Cortegiani, B. Ergan, R. Scala, G. Sotgiu, D. Chaudhuri, S. Oczkowski and K. Lewis 

Critical Care volume 26, Article number: 348 (2022)

Background

Non-invasive ventilation (NIV) with bi-level positive pressure ventilation is a first-line intervention for selected patients with acute hypercapnic respiratory failure. Compared to conventional oxygen therapy, NIV may reduce endotracheal intubation, death, and intensive care unit length of stay (LOS), but its use is often limited by patient tolerance and treatment failure. High-flow nasal cannula (HFNC) is a potential alternative treatment in this patient population and may be better tolerated.

Research question

For patients presenting with acute hypercapnic respiratory failure, is HFNC an effective alternative to NIV in reducing the need for intubation?

Methods

We searched EMBASE, MEDLINE, and the Cochrane library from database inception through to October 2021 for randomized clinical trials (RCT) of adults with acute hypercapnic respiratory failure assigned to receive HFNC or NIV. The Cochrane risk-of-bias tool for randomized trials was used to assess risk of bias. We calculated pooled relative risks (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with corresponding 95% confidence intervals (CI) using a random-effects model.

Results

We included eight RCTs (n = 528) in the final analysis. The use of HFNC compared to NIV did not reduce the risk of our primary outcome of mortality (RR 0.86, 95% CI 0.48–1.56, low certainty), or our secondary outcomes including endotracheal intubation (RR 0.80, 95% CI 0.46–1.39, low certainty), or hospital LOS (MD − 0.82 days, 95% CI − 1.83–0.20, high certainty). There was no difference in change in partial pressure of carbon dioxide between groups (MD − 1.87 mmHg, 95% CI − 5.34–1.60, moderate certainty).

Interpretation

The current body of evidence is limited in determining whether HFNC may be either superior, inferior, or equivalent to NIV for patients with acute hypercapnic respiratory failure given imprecision and study heterogeneity. Further studies are needed to better understand the effect of HFNC on this population.

 

 

 

 

Prophylactic Postoperative Noninvasive Ventilation in Adults Undergoing Upper Abdominal Surgery: A Systematic Review and Meta-Analysis

 

by Lockstone, Jane; Denehy, Linda; Truong, Dominic; Whish-Wilson, Georgina A.; Boden, Ianthe; Abo, Shaza; Parry, Selina M. 

 

Critical Care Medicine: October 2022 - Volume 50 - Issue 10 - p 1522-1532

 

OBJECTIVES: 

Postoperative pulmonary complications (PPCs) are a leading cause of morbidity and mortality following upper abdominal surgery. Applying either noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP) in the early postoperative period is suggested to prevent PPC. We aimed to assess whether postoperative NIV or CPAP or both prevent PPCs compared with standard care in adults undergoing upper abdominal surgery, including in those identified at higher PPC risk. Additionally, the different interventions used were evaluated to assess whether there is a superior approach.

DATA SOURCES: 

We searched PubMed, Embase‚ CINAHL, CENTRAL, and Scopus from inception to May 17, 2021.

STUDY SELECTION: 

We performed a systematic search of the literature for randomized controlled trials evaluating prophylactic NIV and/or CPAP in the postoperative period.

DATA EXTRACTION: 

Two authors independently performed study selection and data extraction. Individual study risk of bias was assessed using the PEDro scale, and certainty in outcomes was assessed using the Grading of Recommendations Assessment, Development, and Evaluation framework.

DATA SYNTHESIS: 

We included 17 studies enrolling 6,108 patients. No significant benefit was demonstrated for postoperative NIV/CPAP to reduce PPC (risk ratio [RR], 0.89; 95% CI, 0.78–1.01; very low certainty), including in adults identified at higher PPC risk (RR, 0.91; 95% CI, 0.77–1.07; very low certainty). No intervention approach was identified as superior, and no significant benefit was demonstrated when comparing: 1) CPAP (RR, 0.90; 95% CI, 0.79–1.04; very low certainty), 2) NIV (RR, 0.68; 95% CI, 0.41–1.13; very low certainty), 3) continuous NIV/CPAP (RR, 0.90; 95% CI, 0.77–1.05; very low certainty), or 4) intermittent NIV/CPAP (RR, 0.66; 95% CI, 0.39–1.10; very low certainty) to standard care.

CONCLUSIONS: 

These findings suggest routine provision of either prophylactic NIV or CPAP following upper abdominal surgery may not be effective to reduce PPCs‚ including in those identified at higher risk.

 

 

 

Administration of vitamin D and its metabolites in critically ill adult patients: an updated systematic review with meta-analysis of randomized controlled trials

 

by Johannes Menger, Zheng-Yii Lee, Quirin Notz, Julia Wallqvist, M. Shahnaz Hasan, Gunnar Elke, Martin Dworschak, Patrick Meybohm, Daren K. Heyland and Christian Stoppe 

 

Critical Care volume 26, Article number: 268 (2022)

 

Background

The clinical significance of vitamin D administration in critically ill patients remains inconclusive. The purpose of this systematic review with meta-analysis was to investigate the effect of vitamin D and its metabolites on major clinical outcomes in critically ill patients, including a subgroup analysis based on vitamin D status and route of vitamin D administration.

Methods

Major databases were searched through February 9, 2022. Randomized controlled trials of adult critically ill patients with an intervention group receiving vitamin D or its metabolites were included. Random-effect meta-analyses were performed to estimate the pooled risk ratio (dichotomized outcomes) or mean difference (continuous outcomes). Risk of bias assessment included the Cochrane tool for assessing risk of bias in randomized trials.

Results

Sixteen randomized clinical trials with 2449 patients were included. Vitamin D administration was associated with lower overall mortality (16 studies: risk ratio 0.78, 95% confidence interval 0.62–0.97, p = 0.03; I2 = 30%), reduced intensive care unit length of stay (12 studies: mean difference − 3.13 days, 95% CI − 5.36 to − 0.89, n = 1250, p = 0.006; I2 = 70%), and shorter duration of mechanical ventilation (9 studies: mean difference − 5.07 days, 95% CI − 7.42 to − 2.73, n = 572, p < 0.0001; I2 = 54%). Parenteral administration was associated with a greater effect on overall mortality than enteral administration (test of subgroup differences, p = 0.04), whereas studies of parenteral subgroups had lower quality. There were no subgroup differences based on baseline vitamin D levels.

Conclusions

Vitamin D supplementation in critically ill patients may reduce mortality. Parenteral administration might be associated with a greater impact on mortality. Heterogeneity and assessed certainty among the studies limits the generalizability of the results.

 

 

Use of dexmedetomidine in patients with sepsis: a systematic review and meta-analysis of randomized-controlled trials

 

by Ting Zhang, Qimin Mei, Shabai Dai, Yecheng Liu and Huadong Zhu 

 

Annals of Intensive Care volume 12, Article number: 81 (2022) 

 

Background

Dexmedetomidine is widely used in patients with sepsis. However, its effect on septic patients remains controversial. The objective of this study was to summarize all randomized controlled trials (RCTs) examining dexmedetomidine use in sepsis patients.

Methods

This systematic review and meta-analysis included RCTs comparing dexmedetomidine with other sedatives in adult sepsis patients. We generated pooled relative risks (RRs) and standardized mean differences and performed trial sequential analysis and a cumulative meta-analysis. The primary outcome was mortality, and the secondary outcomes were the length of the intensive care unit stay, duration of mechanical ventilation, number of ventilation-free days, incidence of total adverse event, incidence of delirium, and levels of interleukin 6, tumor necrosis factor alpha, and alanine aminotransferase.

Results

We included 19 RCTs that enrolled 1929 patients. Compared with other sedatives, dexmedetomidine decreased the all-cause mortality (RR 0.83; 95% confidence interval [CI] [0.69, 0.99]) and inflammatory response (interleukin 6 and tumor necrosis factor alpha levels at 24 h: standardized mean difference (SMD) − 2.15; 95% CI [− 3.25, − 1.05] and SMD − 1.07, 95% CI [− 1.92, − 0.22], respectively). Trial sequential analysis showed that it is not up to required information size. The overall risk adverse events was similar between dexmedetomidine and the other sedatives (RR 1.27, 95% CI [0.69, 2.36]), but dexmedetomidine increased the risk of arrhythmias (RR 1.43, 95% CI [0.59, 3.51]). Length of intensive care unit stay (SMD − 0.22; 95% CI [− 0.85, − 0.41]), duration of mechanical ventilation (SMD 0.12; 95% CI [− 1.10, 1.35]), incidence of delirium (RR 0.98; 95% CI [0.72, 1.33]), and levels of alanine aminotransferase and creatinine at 24 h were not significantly reduced.

Conclusions

Dexmedetomidine in sepsis patients could significantly reduce mortality compared with benzodiazepines but not with propofol. In addition, dexmedetomidine can significantly decrease inflammatory response in patients with sepsis compared with other sedatives. Dexmedetomidine might lead to an increased incidence of arrhythmias, but its safety profile did not show significant differences in the incidence of total adverse events. Future RCTs are needed to determine the sepsis patient population that would benefit most from dexmedetomidine and its optimal dosing regimen.

 

 

 

Effectiveness of Continuous Cuff Pressure Control in Preventing Ventilator-Associated Pneumonia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

 

Maertens, Bert; Lin, Frances; Chen, Yingyan; Rello, Jordi; Lathyris, Dimitrios; Blot, Stijn 

 

Critical Care Medicine: July 26, 2022 - Volume - Issue - 10.1097

 

Objectives: 

Microaspiration of subglottic secretions is the main pathogenic mechanism for ventilator-associated pneumonia (VAP). Adequate inflation of the endotracheal cuff is pivotal to providing an optimal seal of the extraluminal airway. However, cuff pressure substantially fluctuates due to patient or tube movements, which can induce microaspiration. Therefore, devices for continuous cuff pressure control (CCPC) have been developed in recent years. The purpose of this systematic review and meta-analysis is to assess the effectiveness of CCPC in VAP prevention.

Data Sources: 

A systematic search of Embase, the Cochrane Central Register of Controlled Trials, and the International Clinical Trials Registry Platform was conducted up to February 2022.

Study Selection: 

Eligible studies were randomized controlled trials (RCTs) and quasi-RCTs comparing the impact of CCPC versus intermittent cuff pressure control on the occurrence of VAP.

Data Extraction: 

Random-effects meta-analysis was used to calculate odds ratio (OR) and 95% CI for VAP incidence between groups. Secondary outcome measures included mortality and duration of mechanical ventilation (MV) and ICU stay. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach.

Data Synthesis: 

Eleven RCTs with 2,092 adult intubated patients were included. The use of CCPC was associated with a reduced risk of VAP (OR, 0.51). Meta-analyses of secondary endpoints showed no significant difference in mortality but significant differences in durations of MV (mean difference, –1.07 d) and ICU stay (mean difference, –3.41 d) in favor of CCPC. However, the risk of both reporting and individual study bias was considered important. The main issues were the lack of blinding, potential commercial conflicts of interest of study authors and high heterogeneity due to methodological differences between studies, differences in devices used for CCPC and in applied baseline preventive measures. Certainty of the evidence was considered “very low.”

Conclusions: 

The use of CCPC was associated with a reduction in VAP incidence; however, this was based on very low certainty of evidence due to concerns related to risk of bias and inconsistency.

 

 

 

Intravascular Versus Surface Cooling in Patients Resuscitated From Cardiac Arrest: A Systematic Review and Network Meta-Analysis With Focus on Temperature Feedback

 

by Ramadanov, Nikolai; Arrich, Jasmin; Klein, Roman; Herkner, Harald; Behringer, Wilhelm 

 

Critical Care Medicine: June 2022 - Volume 50 - Issue 6 - p 999-1009

 

OBJECTIVE: 

The aim of the study was to compare the effect of intravascular cooling (IC), surface cooling with temperature feedback (SCF), and surface cooling without temperature feedback (SCnoF) on neurologic outcome and survival in patients successfully resuscitated from cardiac arrest (CA) and treated with targeted temperature management (TTM) at 32–34°C.

DATA SOURCES: 

We performed a systematic review on Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, MEDLINE, SCOPUS, CINAHL, Web of Science, and Clinical Trials up to June 30, 2021.

STUDY SELECTION: 

We included randomized and nonrandomized studies on IC, SCF, and SCnoF in adult humans resuscitated from CA undergoing TTM, reporting neurologic outcome or survival.

DATA EXTRACTION: 

We performed a network meta-analysis to assess the comparative effects of IC, SCF, and SCnoF. The overall effect between two cooling methods included the effect of direct and indirect comparisons. Results are given as odds ratios (OR) and 95% CIs. Rankograms estimated the probability of TTM methods being ranked first, second, and third best interventions.

DATA SYNTHESIS: 

A total of 14 studies involving 4,062 patients met the inclusion criteria. Four studies were randomized controlled studies, and 10 studies were nonrandomized observational studies. IC compared with SCnoF was significantly associated with better neurologic outcome (OR, 0.6; 95% CI, 0.49–0.74) and survival (OR, 0.8; 95% CI, 0.66–0.96). IC compared with SCF, and SCF compared with SCnoF did not show significant differences in neurologic outcome and survival. The rankogram showed that IC had the highest probability to be the most beneficial cooling method, followed by SCF and SCnoF.

CONCLUSIONS: 

Our results suggest that in patients resuscitated from CA and treated with TTM at 32–34°C, IC has the highest probability of being the most beneficial cooling method for survival and neurologic outcome.

 

 

 

Pentraxin-3 as a predictive marker of mortality in sepsis: an updated systematic review and meta-analysis

by Guobin Wang, Chunyan Jiang, Junjun Fang, Zhitao Li and Hongliu Cai 

Critical Care volume 26, Article number: 167 (2022) Published: 08 June 2022

 

Background

The purpose of this study was to clarify the prognostic value of Pentraxin-3 (PTX3) on the mortality of patients with sepsis.

Methods

Publications published up to January 2021 were retrieved from PubMed, EMBASE, and the Cochrane library. Data from eligible cohort and case–control studies were extracted for the meta-analysis. Multivariate regression analysis was used to evaluate the correlation of the outcomes with sample size and male proportion.

Results

A total of 17 studies covering 3658 sepsis patients were included. PTX3 level was significantly higher in non-survivor compared to survivor patients (SMD (95% CI): −1.06 (−1.43, −0.69), P < 0.001). Increased PTX3 level was significantly associated with mortality (HR (95% CI): 2.09 (1.55, 2.81), P < 0.001). PTX3 showed good predictive capability for mortality (AUC:ES (95% CI): 0.73 (0.70, 0.77), P < 0.001). The outcome comparing PTX3 level in non-survivors vs. survivors and the outcome of the association between PTX3 and mortality were associated with sample size but not male proportion. AUC was associated with both sample size and male proportion.

Conclusions

PTX3 level was significantly higher in non-survivor compared to survivor patients with sepsis. Elevated PTX3 level was significantly associated with mortality. Furthermore, the level of PTX3 might predict patient mortality.