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

OBJECTIVES: 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 Pao2/Fio2 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.

Evaluation of Optimal Esophageal Catheter Balloon Inflation Volume in Mechanically Ventilated Children.

BACKGROUND: Accuracy of esophageal pressure measured by an air-filled esophageal balloon catheter is dependent on balloon filling volume. However, this has been understudied in mechanically ventilated children. We sought to study the optimal filling volume in children receiving ventilation by using previously reported calibration methods. Secondary objectives included to examine the difference in pressure measurements at individualized optimal filling volume versus a standardized inflation volume and to study if a static hold during calibration is required to identify the optimal filling volume. METHODS: An incremental inflation calibration procedure was performed in children receiving ventilation, <18 y, instrumented with commercially available catheters (6 or 8 French) who were not breathing spontaneously. The balloon was manually inflated by 0.2 to 1.6 mL (6 French) or 2.6 mL (8 French). Esophageal pressure (Pes) and airway pressure tracings were recorded during the procedure. Data were analyzed offline by using 2 methods: visual determination of filling range with the calculation of the highest difference between expiratory and inspiratory Pes and determination of a correctly filled balloon by calculating the esophageal elastance. RESULTS: We enrolled 40 subjects with median (interquartile range [IQR]) age 6.8 (2-25) months. The optimal filling volume ranged from 0.2 to 1.2 mL (median [IQR] 0.6 [0.2-1.0] mL) in the subjects with a 6 French catheter and 0.2-2.0 mL (median [IQR] 0.7 [0.5-1.2] mL) for 8 French catheters. Inflating the balloon with 0.6 mL (median computed from the whole cohort) gave an absolute difference in transpulmonary pressure that ranged from -4 to 7 cm H2O compared with the personalized volume. Pes calculated over 5 consecutives breaths differed with a maximum of 1 cm H2O compared to Pes calculated during a single inspiratory hold. The esophageal elastance was correlated with weight, age, and sex. CONCLUSIONS: The optimal balloon inflation volume was highly variable, which indicated the need for an individual calibration procedure. Pes was not overestimated when an inspiratory hold was not applied.

Paediatric Acute Respiratory Distress Syndrome Neuromuscular Blockade study (PAN-study): a phase IV randomised controlled trial of early neuromuscular blockade in moderate-to-severe paediatric acute respiratory distress syndrome.

BACKGROUND: Paediatric acute respiratory distress syndrome (PARDS) is a manifestation of severe, life-threatening lung injury necessitating mechanical ventilation with mortality rates ranging up to 40-50%. Neuromuscular blockade agents (NMBAs) may be considered to prevent patient self-inflicted lung injury in PARDS patients, but two trials in adults with severe ARDS yielded conflicting results. To date, randomised controlled trials (RCT) examining the effectiveness and efficacy of NMBAs for PARDS are lacking. We hypothesise that using NMBAs for 48 h in paediatric patients younger than 5 years of age with early moderate-to-severe PARDS will lead to at least a 20% reduction in cumulative respiratory morbidity score 12 months after discharge from the paediatric intensive care unit (PICU). METHODS: This is a phase IV, multicentre, randomised, double-blind, placebo-controlled trial performed in level-3 PICUs in the Netherlands. Eligible for inclusion are children younger than 5 years of age requiring invasive mechanical ventilation with positive end-expiratory pressure (PEEP) ≥ 5 cm H2O for moderate-to-severe PARDS occurring within the first 96 h of PICU admission. Patients are randomised to continuous infusion of rocuronium bromide or placebo for 48 h. The primary endpoint is the cumulative respiratory morbidity score 12 months after PICU discharge, adjusted for confounding by age, gestational age, family history of asthma and/or allergy, season in which questionnaire was filled out, day-care and parental smoking. Secondary outcomes include respiratory mechanics, oxygenation and ventilation metrics, pulmonary and systemic inflammation markers, prevalence of critical illness polyneuropathy and myopathy and metrics for patient outcome including ventilator free days at day 28, length of PICU and hospital stay, and mortality DISCUSSION: This is the first paediatric trial evaluating the effects of muscular paralysis in moderate-to-severe PARDS. The proposed study addresses a huge research gap identified by the Paediatric Acute Lung Injury Consensus Collaborative by evaluating practical needs regarding the treatment of PARDS. Paediatric critical care practitioners are inclined to use interventions such as NMBAs in the most critically ill. This liberal use must be weighed against potential side effects. The proposed study will provide much needed scientific support in the decision-making to start NMBAs in moderate-to-severe PARDS. TRIAL REGISTRATION: ClinicalTrials.gov NCT02902055 . Registered on September 15, 2016.