Neuromuscular blocking agents in acute respiratory distress syndrome: a systematic review and meta-analysis of randomized controlled trials

Introduction

Randomized trials investigating neuromuscular blocking agents in adult acute respiratory distress syndrome (ARDS) have been inconclusive about effects on mortality, which is very high in this population. Uncertainty also exists about the associated risk of ICU-acquired weakness.

Methods

We conducted a systematic review and meta-analysis. We searched the Cochrane (Central) database, MEDLINE, EMBASE, ACP Journal Club, and clinical trial registries for randomized trials investigating survival effects of neuromuscular blocking agents in adults with ARDS. Two independent reviewers abstracted data and assessed methodologic quality. Primary study investigators provided additional unpublished data.

Results

Three trials (431 patients; 20 centers; all from the same research group in France) met inclusion criteria for this review. All trials assessed 48-hour infusions of cisatracurium besylate. Short-term infusion of cisatracurium besylate was associated with lower hospital mortality (RR, 0.72; 95% CI, 0.58 to 0.91; P = 0.005; I² = 0). This finding was robust on sensitivity analyses. Neuromuscular blockade was also associated with lower risk of barotrauma (RR, 0.43; 95% CI, 0.20 to 0.90; P = 0.02; I² = 0), but had no effect on the duration of mechanical ventilation among survivors (MD, 0.25 days; 95% CI, 5.48 to 5.99; P = 0.93; I² = 49%), or the risk of ICU-acquired weakness (RR, 1.08; 95% CI, 0.83 to 1.41; P = 0.57; I² = 0). Primary studies lacked protracted measurements of weakness.

Conclusions

Short-term infusion of cisatracurium besylate reduces hospital mortality and barotrauma and does not appear to increase ICU-acquired weakness for critically ill adults with ARDS.     

Effect of omega-3 fatty acids supplementation on anthropometric indices in children and adolescents: A systematic review and meta-analysis of randomized controlled trials

• •Background Childhood obesity is a major public health problem with a global prevalence greater than 23 %. Omega-3 polyunsaturated fatty acids (omega-3 FAs) supplementation may improve anthropometric indices by increased energy expenditure, attenuated appetite, elevated adiponectin levels, though current evidence is still inconclusive.
• •Objective The aim of this systematic review was to conduct the first comprehensive meta-analysis of randomized controlled trials on the association between omega-3 FAs supplementation and anthropometric indices in children and adolescents.
• •Methods We performed an extensive online database search of the published literature using the SCOPUS, Web of Science, PubMed, EMBASE, and Cochrane library databases from the index date through April 2019. Six studies met inclusion criteria. Changes in anthropometric indices (weight, BMI and waist circumference) were extracted from each article. Statistical heterogeneity was assessed by calculating the I² statistic. We used the standardized mean difference (SMD) with 95 % confidence interval. The meta-analysis was performed based on a random effects model.
• •Results This meta-analysis demonstrated that omega-3 FAs supplementation had no effect on reducing body weight (SMD = -0.00, 95 % CI -0.26 to 0.25), BMI (SMD = -0.07, 95 % CI -0.32 to 0.17) and waist circumference (SMD = -0.16, 95 % CI -0.51 to 0.19).
• •Conclusions Omega-3 FAs supplementation did not change anthropometric indices in children and adolescents. Further large-scale studies with larger sample sizes in children and adolescents are needed to clarify the effects of omega-3 FAs.

     

Effect of different levels of PEEP on mortality in ICU patients without acute respiratory distress syndrome: systematic review and meta-analysis with trial sequential analysis

ObjectiveTo determine whether higher positive end- expiratory pressure (PEEP) could provide a survival advantage for patients without acute respiratory distress syndrome (ARDS) compared with lower PEEP.MethodsEligible studies were identified through searches of Embase, Cochrane Library, Web of Science, Medline, and Wanfang database from inception up to 1 June 2021. Trial sequential analysis (TSA) was used in this meta-analysis.Data synthesisTwenty-seven randomized controlled trials (RCTs) were identified for further evaluation. Higher and lower PEEP arms included 1330 patients and 1650 patients, respectively. A mean level of 9.6±3.4 cmH₂O was applied in the higher PEEP groups and 1.9±2.6 cmH₂O was used in the lower PEEP groups. Higher PEEP, compared with lower PEEP, was not associated with reduction of all-cause mortality (RR 1.03; 95% CI 0.91–1.18; P =0.627), and 28-day mortality (RR 1.07 ; 95% CI 0.92–1.24; P =0.365). In terms of risk of ARDS (RR 0.43; 95% CI 0.24–0.78; P =0.005), duration of intensive care unit (MD -1.04; 95%CI-1.36 to −0.73; P < 0.00001), and oxygenation (MD 40.30; 95%CI 0.94 to 79.65; P = 0.045), higher PEEP was superior to lower PEEP. Besides, the pooled analysis showed no significant differences between groups both in the duration of mechanical ventilation (MD 0.00; 95%CI-0.13 to 0.13; P = 0.996) and hospital stay (MD -0.66; 95%CI-1.94 to 0.61; P = 0.309). More importantly, lower PEEP did not increase the risk of pneumonia, atelectasis, barotrauma, hypoxemia, or hypotension among patients compared with higher PEEP. The TSA analysis showed that the results of all-cause mortality and 28-day mortality might be false-negative results.ConclusionsOur results suggest that a lower PEEP ventilation strategy was non-inferior to a higher PEEP ventilation strategy in ICU patients without ARDS, with no increased risk of all-cause mortality and 28-day mortality. Further high-quality RCTs should be performed to confirm these findings.     

The effect of prone positioning on mortality in patients with acute respiratory distress syndrome: a meta-analysis of randomized controlled trials

Introduction

Prone positioning (PP) has been reported to improve the survival of patients with severe acute respiratory distress syndrome (ARDS). However, it is uncertain whether the beneficial effects of PP are associated with positive end-expiratory pressure (PEEP) levels and long durations of PP. In this meta-analysis, we aimed to evaluate whether the effects of PP on mortality could be affected by PEEP level and PP duration and to identify which patients might benefit the most from PP.

Methods

Publications describing randomized controlled trials (RCTs) in which investigators have compared prone and supine ventilation were retrieved by searching the following electronic databases: PubMed/MEDLINE, the Cochrane Library, the Web of Science and Elsevier Science (inception to May 2013). Two investigators independently selected RCTs and assessed their quality. The data extracted from the RCTs were combined in a cumulative meta-analysis and analyzed using methods recommended by the Cochrane Collaboration.

Results

A total of nine RCTs with an aggregate of 2,242 patients were included. All of the studies received scores of up to three points using the methods recommended by Jadad et al. One trial did not conceal allocation. This meta-analysis revealed that, compared with supine positioning, PP decreased the 28- to 30-day mortality of ARDS patients with a ratio of partial pressure of arterial oxygen/fraction of inspired oxygen ≤100 mmHg (n = 508, risk ratio (RR) = 0.71, 95 confidence interval (CI) = 0.57 to 0.89; P = 0.003). PP was shown to reduce both 60-day mortality (n = 518, RR = 0.82, 95% CI = 0.68 to 0.99; P = 0.04) and 90-day mortality (n = 516, RR = 0.57, 95% CI = 0.43 to 0.75; P < 0.0001) in ARDS patients ventilated with PEEP ≥10 cmH₂O. Moreover, PP reduced 28- to 30-day mortality when the PP duration was >12 h/day (n = 1,067, RR = 0.73, 95% CI = 0.54 to 0.99; P = 0.04).

Conclusions

PP reduced mortality among patients with severe ARDS and patients receiving relatively high PEEP levels. Moreover, long-term PP improved the survival of ARDS patients.     

Albuterol in the treatment of acute respiratory distress syndrome: A meta-analysis of randomized controlled trials

BACKGROUND: This meta-analysis of randomized controlled trials aimed to systematically evaluate the value of albuterol in the treatment of patients with acute respiratory distress syndrome(ARDS).DATA SOURCES: Randomized controlled trials on albuterol treatment of ARDS from its inception to October 2014 were searched systematically. The databases searched included: Pub Med, Ovid EMBASE, Ovid Cochrane, CNKI, WANFANG and VIP. The trials were screened according to the pre-designed inclusion and exclusion criteria. We performed a systematic review and meta-analysis of the randomized controlled trials(RCTs) on albuterol treatment, attempting to improve outcomes, i.e. lowering the 28-day mortality and ventilator-free days.RESULTS: Three RCTs involving 646 patients met the inclusion criteria. There was no significant decrease in the 28-day mortality(risk difference=0.09; P=0.07, P for heterogeneity=0.22, I2=33%). The ventilator-free days and organ failure-free days were significantly lower in the patients who received albuterol(mean difference=–2.20; P0.001, P for heterogeneity=0.49, I2=0% and mean difference=–1.71, P0.001, P for heterogeneity=0.60, I2=0%).CONCLUSIONS: Current evidences indicate that treatment with albuterol in the early course of ARDS was not effective in increasing the survival, but significantly decreasing the ventilator-free days and organ failure-free days. Owing to the limited number of included trails, strong recommendations cannot be made.     

Factors associated with acute respiratory distress syndrome in brain-injured patients: A systematic review and meta-analysis

PurposeAcute respiratory distress syndrome (ARDS) is common in patients with acute brain injury admitted to the ICU. We aimed to identify factors associated with ARDS in this population.MethodsWe searched MEDLINE, Embase, Cochrane Central, Scopus, and Web of Science from inception to January 14, 2022. Three reviewers independently screened articles and selected English-language studies reporting risk factors for ARDS in brain-injured adult patients. Data were extracted on ARDS incidence, adjusted and unadjusted risk factors, and clinical outcomes. Risk of bias was reported using the Quality in Prognostic Studies tool. Certainty of evidence was assessed using GRADE.ResultsWe selected 23 studies involving 6,961,284 patients with acute brain injury. The pooled cumulative incidence of ARDS after brain injury was 17.0% (95%CI 10.7–25.8). In adjusted analysis, factors associated with ARDS included sepsis (odds ratio (OR) 4.38, 95%CI 2.37–8.10; high certainty), history of hypertension (OR 3.11, 95%CI 2.31–4.19; high certainty), pneumonia (OR 2.69, 95%CI 2.35–3.10; high certainty), acute kidney injury (OR 1.44, 95%CI 1.30–1.59; moderate certainty), admission hypoxemia (OR 1.67, 95%CI 1.29–2.17; moderate certainty), male sex (OR 1.30, 95%CI 1.06–1.58; moderate certainty), and chronic obstructive pulmonary disease (OR 1.27, 95%CI 1.13–1.44; moderate certainty). Development of ARDS was independently associated with increased odds of in-hospital mortality (OR 3.12, 95% CI 1.39–7.00).ConclusionsMultiple risk factors are associated with ARDS in brain-injured patients. These findings could be used to develop prognostic models for ARDS or as prognostic enrichment strategies for patient enrolment in future clinical trials.     

体外膜肺氧合对成人急性呼吸窘迫综合征患者预后影响的Meta分析和系统评价

目的 探讨体外膜肺氧合(ECMO)对急性呼吸窘迫综合征(ARDS)患者预后的影响.方法 计算机检索和手工检索收集1966-2010年ECMO治疗成人ARDS的英文和中文临床研究,按纳入与排除标准选择文献,提取资料,采用RevMan 5.0软件对数据进行Meta分析,对ECMO临床研究进行系统评价.结果 共纳入3篇随机对照研究,随机效应模型显示ECMO不降低成人重症ARDS患者病死率[RR=0.95(95%CI:0.76-1.18),P=0.64],但按发表时间的累积Meta分析显示ECMO呈现保护性效应;与以往临床研究相比,最近一项观察性临床研究显示ECMO明显降低甲型H1N1流感导致的重症ARDS患者病死率.结论 现有研究尚不能证实ECMO能改善成人ARDS患者预后,但对于病因可逆的重症ARDS患者早期应用ECMO可取得较好临床效益.

Abstract：

Objective To investigate the effects of extracorporeal membrane oxygenation (ECMO) on survival of adult from acute respiratory distress syndrome (ARDS). Method We searched Pubmed, Embase, Cochrane Library, Web of Science databases to find relevant literatues on ECMO in treatment of ARDS, which are reported from January 1966 to June 2010. Meta analyses was performed. Results Three papers about randomized controlled trial (RCT) of evaluating ECMO in patients with severe ARDS were enrolled for analyses. Meta-analysis of the three randomized controlled trials revealed ECMO did not decrease the mortality of ARDS patients. However, the cumulative meta-analysis of randomized trials showed ECMO had a protective effect on patients with ARDS. The most recent observational studies suggested that ECMO significantly decreased the mortality of ARDS caused by H1 N1 viral pneumonia. Conclusions There is no evidence to prove the benefit of ECMO in patients with ARDS. However, ECMO should be considered to use in early stage of ARDS as a last rescue resort for potentially reversible severe acute respiratory failure. Further investigation of large sample of high quality RCTs is needed.     

Albumin versus crystalloid solutions in patients with the acute respiratory distress syndrome: a systematic review and meta-analysis

Introduction

In patients with acute respiratory distress syndrome (ARDS) fluid therapy might be necessary. The aim of this systematic review and meta-analysis is to determine the effects of colloid therapy compared to crystalloids on mortality and oxygenation in adults with ARDS.

Methods

Randomized controlled trials (RCTs) were identified through a systematic literature search of MEDLINE, EMBASE, CENTRAL and LILACS. Articles published up to 15^th February 2013 were independently screened, abstracted, and assessed (Cochrane Risk of Bias Tool) to provide evidence-based therapy recommendations. RCTs were eligible if they compared colloid versus crystalloid therapy on lung function, inflammation, damage or mortality in adults with ARDS. Primary outcome parameters were respiratory mechanics, gas exchange lung inflammation and damage as well as hospital mortality. Kidney function, need for renal replacement therapy, hemodynamic stabilization and intensive care unit (ICU) length of stay served as secondary outcomes.

Results

A total of 3 RCTs out of 4130 potential trials found in the databases were selected for qualitative and quantitative analysis totaling 206 patients who received either albumin or saline. Overall risk of bias was unclear to high in the identified trials. Calculated pooled risk of death was not statistically significant (albumin 34 of 100 (34.0%) versus 40 of 104 (38.5%), relative risk (RR) = 0.89, 95% confidence interval (CI) 0.62 to 1.28, P = 0.539). Weighted mean difference (WMD) in PaO₂/FiO₂ (mmHg) improved in the first 48 hours (WMD = 62, 95% CI 47 to 77, P <0.001, I² = 0%) after therapy start and remained stable after 7 days (WMD = 20, 95% CI 4 to 36, P = 0.017, I² = 0%).

Conclusions

There is a high need for RCTs investigating the effects of colloids in ARDS patients. Based on the findings of this review, colloid therapy with albumin improved oxygenation but did not affect mortality.     

体外膜肺氧合对成人急性呼吸窘迫综合征患者预后影响的Meta分析和系统评价

目的 探讨体外膜肺氧合(ECMO)对急性呼吸窘迫综合征(ARDS)患者预后的影响.方法 计算机检索和手工检索收集1966-2010年ECMO治疗成人ARDS的英文和中文临床研究,按纳入与排除标准选择文献,提取资料,采用RevMan 5.0软件对数据进行Meta分析,对ECMO临床研究进行系统评价.结果 共纳入3篇随机对照研究,随机效应模型显示ECMO不降低成人重症ARDS患者病死率[RR=0.95(95%CI:0.76-1.18),P=0.64],但按发表时间的累积Meta分析显示ECMO呈现保护性效应;与以往临床研究相比,最近一项观察性临床研究显示ECMO明显降低甲型H1N1流感导致的重症ARDS患者病死率.结论 现有研究尚不能证实ECMO能改善成人ARDS患者预后,但对于病因可逆的重症ARDS患者早期应用ECMO可取得较好临床效益.     

Low-dose corticosteroids for adult patients with septic shock: a systematic review with meta-analysis and trial sequential analysis

Purpose

To assess the effect of low dose corticosteroids on outcomes in adults with septic shock.

Methods

We systematically reviewed randomised clinical trials (RCTs) comparing low-dose corticosteroids to placebo in adults with septic shock. Trial selection, data abstraction and risk of bias assessment were performed in duplicate. The primary outcome was short-term mortality. Secondary and tertiary outcomes included longer-term mortality, adverse events, quality of life, and duration of shock, mechanical ventilation and ICU stay.

Results

There were 22 RCTs, including 7297 participants, providing data on short-term mortality. In two low risk of bias trials, the relative risk (RR) of short-term mortality with corticosteroid versus placebo was 0.98 [95% confidence interval (CI) 0.89–1.08, p?=?0.71]. Sensitivity analysis including all trials was similar (RR 0.96; 95% CI 0.91–1.02, p?=?0.21) as was analysis of longer-term mortality (RR 0.96; 95% CI 0.90–1.02, p?=?0.18). In low risk of bias trials, the risk of experiencing any adverse event was higher with corticosteroids; however, there was substantial heterogeneity (RR 1.66; 95% CI 1.03–2.70, p?=?0.04, I²?=?78%). No trials reported quality of life outcomes. Duration of shock [mean difference (MD) ?1.52 days; 95% CI ?1.71 to ?1.32, p?<?0.0001], duration of mechanical ventilation (MD ?1.38 days; 95% CI ?1.96 to ?0.80, p?<?0.0001), and ICU stay (MD ?0.75 days; 95% CI ?1.34 to ?0.17, p?=?0.01) were shorter with corticosteroids versus placebo.

Conclusions

In adults with septic shock treated with low dose corticosteroids, short- and longer-term mortality are unaffected, adverse events increase, but duration of shock, mechanical ventilation and ICU stay are reduced.PROSPERO registration no. CRD42017084037.

     

Effect of omega-3 supplements on plasma apolipoprotein C-III concentrations: a systematic review and meta-analysis of randomized controlled trials

Abstract

Background: Apolipoprotein C-III (apo C-III) is a key regulator of triglycerides metabolism. The aim of this meta-analysis was to assess the effect of fish omega-3 polyunsaturated fatty acids (PUFAs) on apo C-III levels.

Methods: Randomized placebo-controlled trials investigating the impact of omega-3 on apo C-III levels were searched in PubMed-Medline, SCOPUS, Web of Science and Google Scholar. A random-effects model and generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. A weighted random-effects meta-regression was performed to evaluate the impact of potential confounders on glycemic parameters.

Results: This meta-analysis comprising 2062 subjects showed a significant reduction of apo C-III concentrations following treatment with omega-3 (WMD: ?22.18?mg/L, 95% confidence interval: ?31.61, ?12.75, p?<?.001; I²: 88.24%). Subgroup analysis showed a significant reduction of plasma apo C-III concentrations by eicosapentaenoic acid (EPA) ethyl esters but not omega-3 carboxylic acids or omega-3 ethyl esters. There was a greater apo C-III reduction with only EPA as compared with supplements containing EPA and docosahexaenoic acid (DHA) or only DHA. A positive association between the apo C-III-lowering effect of omega-3 with baseline apo C-III concentrations and treatment duration was found.

Conclusions: This meta-analysis has shown that omega-3 PUFAs might significantly decrease apo C-III.

• Key messages

• Omega-3 PUFA supplements significantly reduce apo C-III plasma levels, particularly in hypertriglyceridemic patients when applied in appropriate dose (more than 2?g/day)

• Triglyceride (TG)-lowering effect is achieved via peroxisome proliferator-activated receptors α

• Further studies should address the effect of omega-3 PUFAs alone or with other lipid-lowering drugs in order to provide a final answer whether apo C-III could be an important target for prevention of cardiovascular disease

• New apo C-III antisense oligonucleotide drug (Volanesorsen) showed to be promising in decreasing elevated TGs by reducing levels of apo C-III mRNA

     

Milrinone for cardiac dysfunction in critically ill adult patients: a systematic review of randomised clinical trials with meta-analysis and trial sequential analysis

Introduction

Milrinone is an inotrope widely used for treatment of cardiac failure. Because previous meta-analyses had methodological flaws, we decided to conduct a systematic review of the effect of milrinone in critically ill adult patients with cardiac dysfunction.

Methods

This systematic review was performed according to The Cochrane Handbook for Systematic Reviews of Interventions. Searches were conducted until November 2015. Patients with cardiac dysfunction were included. The primary outcome was serious adverse events (SAE) including mortality at maximum follow-up. The risk of bias was evaluated and trial sequential analyses were conducted. The quality of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation criteria.

Results

A total of 31 randomised clinical trials fulfilled the inclusion criteria, of which 16 provided data for our analyses. All trials were at high risk of bias, and none reported the primary composite outcome SAE. Fourteen trials with 1611 randomised patients reported mortality data at maximum follow-up (RR 0.96; 95% confidence interval 0.76–1.21). Milrinone did not significantly affect other patient-centred outcomes. All analyses displayed statistical and/or clinical heterogeneity of patients, interventions, comparators, outcomes, and/or settings and all featured missing data.

Discussion

The current evidence on the use of milrinone in critically ill adult patients with cardiac dysfunction suffers from considerable risks of both bias and random error and demonstrates no benefits. The use of milrinone for the treatment of critically ill patients with cardiac dysfunction can be neither recommended nor refuted. Future randomised clinical trials need to be sufficiently large and designed to have low risk of bias.

     

ω-3多不饱和脂肪酸对急性呼吸窘迫综合征患者血清炎症介质的影响

目的观察ω-3多不饱和脂肪酸对急性呼吸窘迫综合征（ARDS）患者血清炎症介质释放的影响。方法将42例ARDS患者按随机化数字表原则,分为对照组和研究组,每组各21例。两组患者均接受等氮、等热量的全胃肠外营养,热量25kcal·kg^-1·d^-1、氮摄入量0.2g/kg,其中研究组加用ω-3多不饱和脂肪酸（0.2g·kg^-1·d^-1）,共7d。分别检测治疗前和治疗后第1、3、7天血清白细胞介素1（IL-1）、IL-6、肿瘤坏死因子α（TNF-α）水平,并观察动脉血氧分压和氧合指数的变化。结果加用ω-3多不饱和脂肪酸治疗后,研究组在不同时间点IL-1、IL-6、TNF-α均明显低于对照组（P均〈0.05）;两组患者动脉血氧分压和氧合指数均有改善,且研究组氧合指数较高,差异均有统计学意义（P均〈0.05）。结论ω-3多不饱和脂肪酸可降低ARDS患者IL-1、IL-6、TNF-α水平,在一定程度上有利于ARDS患者呼吸功能的恢复。     

Enteral glutamine supplementation in critically ill patients: a systematic review and meta-analysis

IntroductionGlutamine (GLN) has been suggested to have a beneficial influence on outcomes of critically ill patients. However, recent large-scale trials have suggested harm associated with GLN supplementation. Recently, systematic reviews on the use of parenteral GLN have been published; however, less information is available on the role of enteral GLN. Therefore, the aim of this systematic review was to study the effects of enteral GLN supplementation in patients with critical illness.MethodsWe identified randomized controlled trials conducted from 1980 to 2014 with enterally administered GLN in adult critically ill patients. Studies of parenteral GLN only or combined enteral-parenteral GLN were excluded. The methodological quality of studies was scored, and trial data were statistically combined. We examined a priori the treatment effects in subgroups of trials of burn and trauma patients.ResultsA total of 11 studies involving 1079 adult critically ill patients and enteral GLN supplementation were identified. Enteral GLN supplementation was not associated with a reduction of hospital mortality (risk ratio [RR] 0.94, 95 % confidence interval [CI] 0.65–1.36; p =0.74), infectious complications (RR 0.93, 95 % CI 0.79–1.10; p =0.39) or stay in the intensive care unit (weighted mean difference [WMD] −1.36 days, 95 % CI −5.51 to 2.78; p =0.52). However, there was a significant reduction in hospital stay (WMD 4.73 days, 95 % CI −8.53 to −0.90; p =0.02). In the subset of studies of patients with burns, enteral GLN supplementation was associated with significant reductions in hospital mortality (RR 0.19, 95 % 0.06–0.67; p =0.010) and hospital stay (WMD −9.16, 95 % CI −15.06 to −3.26; p =0.002). There was no effect in trauma patients.ConclusionsEnteral GLN supplementation does not confer significant clinical benefit in critically ill patients, with the exception of reduced hospital stay. There may be a significant benefit in patients with burns, but data are sparse and larger randomized trials are warranted to confirm this effect.     

Prone positioning of patients with acute respiratory distress syndrome: a systematic review.

A computerized bibliographic search of published research and a citation review of English-language publications about prone positioning of patients with acute respiratory distress syndrome were done. Information on prone positioning related to technique, patients' responses, complications, and recommendations to prevent complications was extracted. In the 20 pertinent clinical studies found, 297 patients (mean age, 39 years) with acute respiratory failure were positioned prone. Timing from the onset of respiratory failure to when the patient was first positioned prone varied, as did the frequency of prone positioning. Patients spent from 30 minutes to 42 hours prone. In 47% of the studies in which abdominal position was noted, chest and pelvic cushions were used to allow the abdomen to protrude while the patient was prone. Improved oxygenation within 2 hours was reported in 69% of patients, and the improvements were cumulative and persistent. Aside from early intervention, factors predictive of patients' responses were inconsistent, and patients' initial responses were not predictive of subsequent responses. Iatrogenic critical events were rare. Dependent edema of the face was prevalent. Pressure ulcers were reported in studies with longer periods of prone positioning. The most serious complication, corneal abrasion requiring corneal transplantation, was reported in one patient. Clinical knowledge about prone positioning is limited. Phase 1 studies focusing on how to safely turn and care for critically ill patients positioned prone for prolonged periods are needed.     

The effects of thiamine supplementation on patients with heart failure: A systematic review and meta-analysis of randomized controlled trials

BackgroundMicronutrients can benefit patients with heart failure (HF). Thiamine is a critical vitamin, while the impact of thiamine supplementation on patients with HF remains unclear. Systematic review and meta-analysis were conducted to evaluate the effects of thiamine supplementation on clinical outcomes in patients with HF.MethodsDatabases including Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, Scopus, and CNKI were searched from inception to June 29th 2022. Randomized controlled trials (RCTs) comparing thiamine supplementation with placebo were included. Meta-analysis was conducted with the software Review Manager 5.4. The quality assessment was performed according to Cochrane Risk of Bias Tool 2.0.ResultsEight studies including 384 patients were included in this review. The results of overall systematic review showed no benefit of thiamine supplementation in HF patients. Compared with the control group, the experimental group had no statistically significant improvements in LVEF (Mean Difference, − 0.19; 95 % CI, − 2.78 to 0.96; I² = 49 %; P = 0.10) in patients with chronic heart failure (CHF). Other outcomes including NYHA class, BNP or NT-proBNP, thiamine status, symptom changes, and quality of life were not improved by thiamine supplementation in CHF patients. Similarly, no improvements in clinical outcomes were found in patients with acute heart failure (AHF) in the studies included.ConclusionsThis systematic review and meta-analysis found no evidence to support the effects of thiamine supplementation in patients with HF, though thiamine supplementation is promising in improving cardiac functions, thiamine status and relieving HF-related symptoms. More well-designed RCTs with large sample sizes are required.     

Efficacy of omega-3 fatty acid supplementation on improvement of bipolar symptoms: a systematic review

The purpose of this review was to examine the current level of evidence regarding the efficacy of omega-3 fatty acid supplementation in improving bipolar disorder symptoms. Of 99 articles meeting initial search criteria, 5 randomized control trials and 2 quasi-experimental studies were selected for review. Omega-3 fatty acid supplementation was effective in 4 of 7 studies. Those using an omega-3 combination of eicosapentaenoic acid and docosahexanoic acid demonstrated a statistically significant improvement in bipolar symptoms, whereas those using a single constituent did not. Dosage variations did not demonstrate statistically significant differences. Due to its benign side effect profile and some evidence supporting its usefulness in bipolar illness, omega-3 may be a helpful adjunct in treatment of selected patients. Future studies are needed to conclusively confirm the efficacy of omega-3s in bipolar disorder, uncovering a new well-tolerated treatment option.     

The effects of carnitine supplementation on clinical characteristics of patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials

ObjectiveThe beneficial effects of carnitine supplementation on nonalcoholic fatty liver disease are unclear. We conducted a systematic review and meta-analysis to evaluate the effects of carnitine supplementation on liver function, lipid profile, body mass index, body weight, and homeostasis model assessment of insulin resistance in patients with nonalcoholic fatty liver disease.MethodsA comprehensive search of PubMed, Web of Science, Scopus, Cochrane Library, and Google Scholar databases were performed. Only randomized placebo-controlled human studies that examined the effects of carnitine supplementation on liver function, lipid profile, body mass index, body weight, and homeostasis model assessment of insulin resistance up to September 2019 were included. Fixed effects or random-effects models were applied to compute the pooled effect size. Heterogeneity assessments were performed using Cochran’s Q test and I-squared statistics. The quality of the studies was assessed using the Jaded scale.ResultsA total of 5 articles were selected, including 334 individuals (167 in control and 167 in intervention groups). The results demonstrated that carnitine supplementation significantly reduced homeostasis model assessment of insulin resistance (HOMA-IR) (WMD: −0.91; 95 % CI: −1.11, −0.72; p < 0.001, I² = 0.0 %) and the levels of aspartate aminotransferase (AST) (WMD: −16.62; 95 % CI: −28.11, −5.14; IU/l; p = 0.005, I² = 93.5 %), alanine aminotransferase (ALT) (WMD: -33.39; 95 % CI: −45.13, −21.66; IU/l; p < 0.001, I² = 93.4 %), and triglycerides (TG) (WMD: −22.13; 95 % CI: −38.91, −5.34; mg/dl; p = 0.01; I² = 0.0 %). However, the results of the pooled effect size did not show any significant effect of carnitine supplementation on body mass index (BMI) (WMD: 0.07; 95 % CI: −0.15, 0.29; p = 0.55; I² = 0.0 %), body weight (WMD: −0.28; 95 % CI: −2.23, 1.68; p = 0.78; I² = 45.7 %), the levels of gamma-glutamyl transferase (γGT) (WMD: −11.31; 95 % CI: −24.35, 1.73; IU/l; p = 0.09, I² = 61.1 %), cholesterol (WMD: −13.58; 95 % CI: −46.77, 19.60; mg/dl; p = 0.42; I² = 94.9 %), high-density lipoprotein-cholesterol (HDL-C) (WMD: 1.36; 95 % CI: −0.96, 3.68; mg/dl; p = 0.25; I² = 64.7 %), and low density lipoprotein-cholesterol (LDL-C) (WMD: −14.85; 95 % CI: −45.43, 15.73; mg/dl; p = 0.34; I² = 96.4 %).ConclusionsThis analysis shows that carnitine supplementation for patients with nonalcoholic fatty liver disease demonstrates a reduction in AST, ALT, TG levels and HOMA-IR. However, no significant effect of carnitine supplementation was observed on BMI, body weight, the levels of γGT, TC, HDL-cholesterol and LDL-cholesterol.     

Prevention of sudden cardiac death with omega-3 fatty acids in patients with coronary heart disease: A meta-analysis of randomized controlled trials

Aim. To systematically review trials concerning the effects of omega-3 fatty acids on sudden cardiac death (SCD), cardiac death, and all-cause mortality in coronary heart disease (CHD) patients.

Methods. PubMed, Embase, and the Cochrane database (1966–2007) were searched. We identified randomized controlled trials that compared dietary or supplementary intake of omega-3 fatty acids with control diet or placebo in CHD patients. Eligible studies had at least 6 months of follow-up data, and cited SCD as an end-point. Two reviewers independently assessed methodological quality. Meta-analysis of relative risk was carried out using the random effect model.

Results. Eight trials were identified, comprising 20,997 patients. In patients with prior myocardial infarction (MI), omega-3 fatty acids reduced relative risk (RR) of SCD (RR = 0.43; 95% CI: 0.20–0.91). In patients with angina, omega-3 fatty acids increased RR of SCD (RR = 1.39; 95% CI: 1.01–1.92). Overall, RR for cardiac death and all-cause mortality were 0.71 (95% CI: 0.50–1.00) and 0.77 (95% CI: 0.58–1.01), respectively.

Conclusions. Dietary supplementation with omega-3 fatty acids reduces the incidence of sudden cardiac death in patients with MI, but may have adverse effects in angina patients.