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Neuromuscular blockers in the acute respiratory distress syndrome: A meta-analysis.

ABSTRACT: BACKGROUND:The effects of neuromuscular blocking agents (NMBAs) on adult patients with acute respiratory distress syndrome (ARDS) remain unclear. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate its effect on mortality. METHODS:We searched the Cochrane (Central) database, Medline, Embase, the Chinese Biomedical Literature Database (SinoMed), WanFang data and ClinicalTrials from inception to June 2019, with language restriction to English and Chinese. We included published RCTs and eligible clinical trials from ClinicalTrials.gov that compared NMBAs with placebo or usual treatment in adults with ARDS. We pooled data using random-effects models. The primary outcome was mortality. The secondary outcomes were the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FIO2), total positive end expiratory pressure (PEEP), plateau pressure (Pplat), days free of ventilator at day 28, barotrauma and ICU-acquired weakness. RESULTS:We included 6 RCTs (n = 1557). Compared with placebo or usual treatment, NMBAs were associated with lower 21 to 28-day mortality (RR 0.72, 95% CI 0.53-0.97, I2 = 59%). NMBAs significantly improved oxygenation (Pao2:Fio2 ratios) at 48 hours (MD 27.26 mm Hg, 95% CI 1.67, 52.84, I2 = 92%) and reduced the incidence of barotrauma (RR 0.55, 95% CI 0.35, 0.85, I2 = 0). However, NMBAs had no effect on oxygenation (Pao2:Fio2 ratios) (MD 18.41 mm Hg, 95% CI -0.33, 37.14, I2 = 72%) at 24 hours. We also found NMBAs did not affect total PEEP, plateau pressure, days free of ventilation at day 28 and ICU-acquired weakness. CONCLUSIONS:In patients with moderate-to-severe ARDS, the administration of NMBAs could reduce 21 to 28-day mortality and barotrauma, and improve oxygenation at 48 hours, but have no significant effects on 90-day/ICU mortality, days free of ventilation at day 28 and the risk of ICU-acquired weakness. Further large-scale, high-quality RCTs are needed to confirm our findings. Registration: PROSPERO (ID: CRD 42019139656).

SUBMITTER: Hua Y

PROVIDER: S-EPMC6974254 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Neuromuscular blockers in the acute respiratory distress syndrome: A meta-analysis.

Hua Yusi Y Ou Xiaofeng X Li Qian Q Zhu Tao T

PloS one 20200121 1

<h4>Background</h4>The effects of neuromuscular blocking agents (NMBAs) on adult patients with acute respiratory distress syndrome (ARDS) remain unclear. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate its effect on mortality.<h4>Methods</h4>We searched the Cochrane (Central) database, Medline, Embase, the Chinese Biomedical Literature Database (SinoMed), WanFang data and ClinicalTrials from inception to June 2019, with language restriction to English and Chinese. ...[more]

PMID: 31961896

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Project description:BACKGROUND:The benefits of early continuous neuromuscular blockade in patients with acute respiratory distress syndrome (ARDS) who are receiving mechanical ventilation remain unclear. METHODS:We randomly assigned patients with moderate-to-severe ARDS (defined by a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of <150 mm Hg with a positive end-expiratory pressure [PEEP] of ?8 cm of water) to a 48-hour continuous infusion of cisatracurium with concomitant deep sedation (intervention group) or to a usual-care approach without routine neuromuscular blockade and with lighter sedation targets (control group). The same mechanical-ventilation strategies were used in both groups, including a strategy involving a high PEEP. The primary end point was in-hospital death from any cause at 90 days. RESULTS:The trial was stopped at the second interim analysis for futility. We enrolled 1006 patients early after the onset of moderate-to-severe ARDS (median, 7.6 hours after onset). During the first 48 hours after randomization, 488 of the 501 patients (97.4%) in the intervention group started a continuous infusion of cisatracurium (median duration of infusion, 47.8 hours; median dose, 1807 mg), and 86 of the 505 patients (17.0%) in the control group received a neuromuscular blocking agent (median dose, 38 mg). At 90 days, 213 patients (42.5%) in the intervention group and 216 (42.8%) in the control group had died before hospital discharge (between-group difference, -0.3 percentage points; 95% confidence interval, -6.4 to 5.9; P?=?0.93). While in the hospital, patients in the intervention group were less physically active and had more adverse cardiovascular events than patients in the control group. There were no consistent between-group differences in end points assessed at 3, 6, and 12 months. CONCLUSIONS:Among patients with moderate-to-severe ARDS who were treated with a strategy involving a high PEEP, there was no significant difference in mortality at 90 days between patients who received an early and continuous cisatracurium infusion and those who were treated with a usual-care approach with lighter sedation targets. (Funded by the National Heart, Lung, and Blood Institute; ROSE ClinicalTrials.gov number, NCT02509078.).

Project description:Background:Neuromuscular blocking agent (NMBA) has been proposed by medical guidelines for early severe acute respiratory distress syndrome (ARDS) because of its survival benefits. However, new studies have provided evidence contradicting these results. Method:A search was performed of the Pubmed, Scopus, Clinicaltrials.gov, and Virtual Health Library databases for randomized controlled trials (RCT) evaluating 28-day mortality in ARDS patients treated with NMBA within 48?h. An English language restriction was applied. Relevant data were extracted and pooled into risk ratios (RR), mean differences (MD), and corresponding 95% confidence intervals (CI) using random-effect model. Sensitivity and meta-regression analysis were performed. Results:From 2675 studies, we included five RCTs in the analysis, for a total of 1461 patients with a mean PaO2/FIO2 of 104?±?35?mmHg. The cisatracurium group had the same risk of death at 28?days (RR, 0.90; 95% CI, 0.78-1.03; I 2 =?50%, p =?0.12) and 90?days (RR, 0.81; 95% CI, 0.62-1.06; I 2 =?56%, p =?0.06) as the control group (no cisatracurium). The secondary outcomes of mechanical ventilation duration and ventilator-free days were not different between the two groups. Cisatracurium had a significantly lower risk of barotrauma than the control group with no difference in intensive care unit (ICU)-induced weakness. The PaO2/FIO2 ratio was higher in the cisatracurium group but not until 48?h. Meta-regression analysis of the baseline PaO2/FIO2 ratio, positive end-expiratory pressure (PEEP) revealed no heterogeneity. Subgroup analysis excluding the trial using high PEEP and light sedation strategy yielded an improvement in all mortality outcomes. Conclusion:NMBA improves oxygenation only after 48?h in moderate, severe ARDS patients and has a lower barotrauma risk without affecting ICU weakness. However, NMBA does not reduce ventilator-free days, duration of mechanical ventilation or, most importantly, the mortality risk regardless of the severity of ARDS.

Project description:PurposeExisting clinical practice guidelines support the use of neuromuscular blocking agents (NMBA) in acute respiratory distress syndrome (ARDS); however, a recent large randomized clinical trial (RCT) has questioned this practice. Therefore, we updated a previous systematic review to determine the efficacy and safety of NMBAs in ARDS.MethodsWe searched MEDLINE, EMBASE (October 2012 to July 2019), the Cochrane (Central) database, and clinical trial registries ( ClinicalTrials.gov , ISRCTN Register, and WHO ICTRP) for RCTs comparing the effects of NMBA as a continuous infusion versus placebo or no NMBA infusion (but allowing intermittent NMBA boluses) on patient-important outcomes for adults with ARDS. Two independent reviewers assessed the methodologic quality of the primary studies and abstracted data.ResultsSeven RCTs, including four new RCTs, met eligibility criteria for this review. These trials enrolled 1598 patients with moderate to severe ARDS at centers in the USA, France, and China. All trials assessed short-term continuous infusions of cisatracurium or vecuronium. The pooled estimate for mortality outcomes showed significant statistical heterogeneity, which was only explained by a subgroup analysis by depth of sedation in the control arm. A continuous NMBA infusion did not improve mortality when compared to a light sedation strategy with no NMBA infusion (relative risk [RR] 0.99; 95% CI 0.86-1.15; moderate certainty; P = 0.93). On the other hand, continuous NMBA infusion reduced mortality when compared to deep sedation with as needed NMBA boluses (RR 0.71; 95% CI 0.57-0.89; low certainty; P = 0.003). Continuous NMBA infusion reduced the rate of barotrauma (RR 0.55; 95% CI 0.35-0.85, moderate certainty; P = 0.008) across eligible trials, but the effect on ventilator-free days, duration of mechanical ventilation, and ICU-acquired weakness was uncertain.ConclusionsInconsistency in study methods and findings precluded the pooling of all trials for mortality. In a pre-planned sensitivity analysis, the impact of NMBA infusion on mortality depends on the strategy used in the control arm, showing reduced mortality when compared to deep sedation, but no effect on mortality when compared to lighter sedation. In both situations, a continuous NMBA infusion may reduce the risk of barotrauma, but the effects on other patient-important outcomes remain unclear. Future research, including an individual patient data meta-analysis, could help clarify some of the observed findings in this updated systematic review.

Project description:ObjectiveTo determine whether neuromuscular blocking agents (NMBAs) can decrease the mortality of patients with acute respiratory distress syndrome (ARDS) and improve their clinical outcomes.DesignSystematic review, meta-analysis and meta-regression.Data sourcesPubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov.MethodsRandomised controlled trials (RCTs) comparing the treatment effect of NMBAs with that of placebo (or traditional treatment) in patients with ARDS were carefully selected. The primary outcome was 90-day mortality. The secondary outcomes were 21-28 days mortality, NMBA-related complications (barotrauma, pneumothorax and intensive care unit (ICU)-acquired muscle weakness), days free of ventilation and days not in the ICU by day 28, Medical Research Council score, Acute Physiology and Chronic Health Evaluation II score and arterial oxygen tension (PaO2)/fractional inspired oxygen (FiO2) (at 48 hours and 72 hours). Random-effects meta-regression was used to explore models involving potential moderators. Trial sequential analysis was performed to estimate the cumulative effect on mortality across RCTs.ResultsNMBAs were not associated with reduced 90-day mortality (risk ratio (RR) 0.85; 95% CI 0.66 to 1.09; p=0.20). However, they decreased the 21-28 days mortality (RR 0.71; 95% CI 0.53 to 0.96; p=0.02) and the rates of pneumothorax (RR 0.46; 95% CI 0.28 to 0.77; p=0.003) and barotrauma (RR 0.56; 95% CI 0.37 to 0.86; p=0.008). In addition, NMBAs increased PaO2/FiO2 at 48 hours (mean difference (MD) 18.91; 95% CI 4.29 to 33.53; p=0.01) and 72 hours (MD 12.27; 95% CI 4.65 to 19.89; p=0.002). Meta-regression revealed an association between sample size (p=0.042) and short-term mortality. Publication year (p=0.050), sedation strategy (p=0.047) and sample size (p=0.046) were independently associated with PaO2/FiO2 at 48 hours.ConclusionsIn summary, the results suggested that use of NMBAs might reduce 21-28 days mortality, NMBA-related complications and oxygenation. However, NMBAs did not reduce the 90-day mortality of patients with ARDS, which contradicts a previous meta-analysis.Prospero registration numberCRD42019139440.

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Neuromuscular blockers in the acute respiratory distress syndrome: A meta-analysis.

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Neuromuscular blockers in the acute respiratory distress syndrome: A meta-analysis.

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