Early Neuromuscular Blockade in Moderate-to-Severe Pediatric Acute Respiratory Distress Syndrome

Abstract

The use of neuromuscular blocking agents (NMBAs) in pediatric acute respiratory distress syndrome (PARDS) is common but unsupported by efficacy data. We sought to compare the outcomes between patients with moderate-to-severe PARDS receiving continuous NMBA during the first 48 hours of endotracheal intubation (early NMBA) and those without.DESIGN: Secondary analysis of data from the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) clinical trial, a pediatric multicenter cluster randomized trial of sedation.SETTING: Thirty-one PICUs in the United States. PATIENTS:Children 2 weeks to 17 years receiving invasive mechanical ventilation (MV) for moderate-to-severe PARDS (i.e., oxygenation index ≥ 8 and bilateral infiltrates on chest radiograph on days 0-1 of endotracheal intubation). INTERVENTIONS:NMBA for the entire duration of days 1 and 2 after intubation. MEASUREMENTS AND MAIN RESULTS:Among 1,182 RESTORE patients with moderate-to-severe PARDS, 196 (17%) received early NMBA for a median of 50.0% ventilator days (interquartile range, 33.3-60.7%). The propensity score model predicting the probability of receiving early NMBA included high-frequency oscillatory ventilation on days 0-2 (odds ratio [OR], 7.61; 95% CI, 4.75-12.21) and severe PARDS on days 0-1 (OR, 2.16; 95% CI, 1.50-3.12). After adjusting for risk category, early use of NMBA was associated with a longer duration of MV (hazard ratio, 0.57; 95% CI, 0.48-0.68; p < 0.0001), but not with mortality (OR, 1.62; 95% CI, 0.92-2.85; p = 0.096) compared with no early use of NMBA. Other outcomes including cognitive, functional, and physical impairment at 6 months post-PICU discharge were similar. Outcomes did not differ when comparing high versus low NMBA usage sites or when patients were stratified by baseline Pao 2 /Fio 2 less than 150. CONCLUSIONS:Early NMBA use was associated with a longer duration of MV. This propensity score analysis underscores the need for a randomized controlled trial in pediatrics.

Nonpulmonary Treatments for Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference

“…Since PALICC 2015 (1), one small study ( n = 22) found that NMB decreased mean airway pressure, reduced transpulmonary pressure, and did not worsen atelectasis (31). Two small, single-center nonrandomized studies showed a decrease in mean oxygenation index (OI) after continuous NMB in the first 48 hours after initiation of invasive MV (32, 33). The small case-control study performed in a low-resource setting (LRS) showed lower mean OI and lower mortality (13.7% vs 46.7%) compared with case-matched patients not receiving continuous NMB (32).…”

“…The small case-control study performed in a low-resource setting (LRS) showed lower mean OI and lower mortality (13.7% vs 46.7%) compared with case-matched patients not receiving continuous NMB (32). However, a propensity score analysis of the Randomized Evaluation of Sedation Titration for Respiratory Failure trial (12) in patients with moderate-to-severe PARDS who received NMB for the entire duration of days 1 and 2 after initiation of invasive MV did not show significant differences in 90-day mortality, cognitive or functional impairment at hospital discharge or at 6 months post-PICU discharge (33). The authors did, however, observe a longer duration of MV with early NMB, even after stratifying and adjusting for patient characteristics associated with the use of early NMB.…”

“…It is unclear if there is potential benefit versus harm for daily NMB holidays. Selective use of NMB when sedation alone is inadequate to help achieve lung protective targets likely balances risks and benefits most appropriately, given there are no clear data supporting the routine use of early NMB in moderate-to-severe PARDS (33).…”

Continuous Neuromuscular Blockade for Bronchopulmonary Dysplasia

“…22,23 However, a secondary analysis of the prospective Randomized Evaluation of Sedation Titration for Respiratory Failure study demonstrated no increased mortality. 24 Although these CNMB studies provide some insights regarding mortality risk, they cannot be generalized to infants with severe BPD.…”

New and Progressive Medical Conditions After Pediatric Sepsis Hospitalization Requiring Critical Care

“…If pathophysiologic derangements of sepsis are mechanistic drivers of the development and progression of comorbid conditions, then efforts to better prevent and treat sepsis may serve to not only decrease the burden of hospitalization and mortality due to sepsis but also decrease the downstream development of comorbid conditions. We must also consider the acute sequelae of sepsis and critical illness and its associated treatments, such as ICU-acquired weakness, mechanical ventilation, and neuromuscular blockade, because these are likely to affect patient outcomes.…”