Early Neuromuscular Blockade in Children with Pediatric Acute Respiratory Distress Syndrome

Chandra, Surabhi; Goel, Sahil; Dawra, Ritika

doi:10.1055/s-0040-1708557

Cited by 6 publications

(7 citation statements)

References 27 publications

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“…In particular, NMBA+ patients had a 60% increased risk of in-hospital mortality. Our findings are different from some smaller studies that did not demonstrate an increased mortality in patients who received NMBAs (4, 9, 20). However, previous studies were limited to narrow populations, such as PARDS patients, who may benefit significantly more from an NMBA infusion, as suggested by previous reports (20, 21).…”

Section: Discussioncontrasting

confidence: 99%

“…Our findings are different from some smaller studies that did not demonstrate an increased mortality in patients who received NMBAs (4, 9, 20). However, previous studies were limited to narrow populations, such as PARDS patients, who may benefit significantly more from an NMBA infusion, as suggested by previous reports (20, 21). Our study included children with a wide variety of diseases, including patients undergoing congenital heart surgery or bone marrow transplants, at the more severe end of the illness spectrum admitted to PICU.…”

Section: Discussioncontrasting

confidence: 99%

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Neuromuscular Blocker Use in Critically Ill Children: Assessing Mortality Risk by Propensity Score–Weighted Analysis

Daverio¹,

Sperotto

Stefani

et al. 2021

Critical Care Medicine

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We aim to describe the use of continuous infusion of neuromuscular blocking agents in mechanically ventilated critically ill children and to test its association with in-hospital mortality.DESIGN: Multicenter, registry-based, observational, two-cohort-comparison retrospective study using prospectively collected data from a web-based national registry. SETTING:Seventeen PICUs in Italy. PATIENTS:We included children less than 18 years who received mechanical ventilation and a neuromuscular blocking agent infusion from January 2010 to October 2017. A propensity score-weighted Cox regression analysis was used to assess the relationship between the use of neuromuscular blocking agents and in-hospital mortality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:Of the 23,227 patients admitted to the PICUs during the study period, 3,823 patients were included. Patients who received a continuous infusion of neuromuscular blocking agent were more likely to be younger (p < 0.001), ex-premature (p < 0.001), and presenting with less chronic respiratory insufficiency requiring home mechanical ventilation (p < 0.001). Reasons for mechanical ventilation significantly differed between patients who received a continuous infusion of neuromuscular blocking agent and patients who did not receive a continuous infusion of neuromuscular blocking agent, with a higher frequency of respiratory and cardiac diagnosis among patients who received neuromuscular blocking agents compared with other diagnoses (all p < 0.001). The covariates were well balanced in the propensity-weighted cohort. The mortality rate significantly differed among the two cohorts (patients who received a continuous infusion of neuromuscular blocking agent 21% vs patients who did not receive a continuous infusion of neuromuscular blocking agent 11%; p < 0.001 by weighted logistic regression). Patients who received a continuous infusion of neuromuscular blocking agent experienced longer mechanical ventilation and PICU stay (both p < 0.001 by weighted logistic regression). A weighted Cox regression analysis found the use of neuromuscular blocking agents to be a significant predictor of in-hospital mortality both in the unadjusted analysis (hazard ratio, 1.7; 95% CI, 1.3-2.2) and in the adjusted one (hazard ratio, 1.6; 95% CI, 1.2-2.1). CONCLUSIONS:Thirteen percent of mechanically ventilated children in PICUs received neuromuscular blocking agents. When adjusting for selection bias with a propensity score approach, the use of neuromuscular blocking agent was found to be a significant predictor of in-hospital mortality.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussioncontrasting

confidence: 99%

Neuromuscular Blocker Use in Critically Ill Children: Assessing Mortality Risk by Propensity Score–Weighted Analysis

Daverio¹,

Sperotto

Stefani

et al. 2021

Critical Care Medicine

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“…Literature characterizing outcomes of survivors of PARDS has grown substantially since PALICC 2015 (4). We now have information about recovery after PICU admission for PARDS in single-center, multicenter, and population-based studies (14, 17–20, 23–36, 39). Unfortunately, it is increasingly clear that morbidity after hospital discharge from PARDS is common and affects all domains of function, HRQL, and patients’ families.…”

Section: Discussionmentioning

confidence: 99%

“…In a separate study, patients evaluated 3-4 years following PARDS requiring extracorporeal membrane oxygenation (ECMO) had ongoing impairments as demonstrated by mean POPC score of 2.3 and mean PCPC score of 1.9 (27). In a study specifically evaluating neuromuscular outcomes following neuromuscular blockade for treatment of PARDS, neither myopathy nor neuropathy was identified at 3-month follow-up (39).…”

Section: Justificationmentioning

confidence: 99%

Outcomes of Children Surviving Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference

Killien

Maddux

Tse

et al. 2023

Pediatric Critical Care Medicine

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We conducted a scoping review to identify studies evaluating outcomes following PARDS. We included studies of survivors of PARDS, acute respiratory failure with a high proportion of PARDS patients, or other critical illnesses if PARDS-specific outcomes could be extracted.DATA EXTRACTION: Title/abstract review, full-text review, and data extraction using a standardized data collection form. DATA SYNTHESIS:The Grading of Recommendations Assessment, Development and Evaluation approach was used to identify and summarize evidence and develop recommendations. Of 8,037 abstracts screened, we identified 20 articles for inclusion. Morbidity following PARDS was common and affected multiple domains of pulmonary and nonpulmonary function. There was insufficient evidence to generate any evidence-based recommendations. We generated eight good practice statements and five research statements. A panel of 52 experts discussed each proposed good practice statement and research statement, and the agreement rate was measured with an online voting process. Good practice statements describe the approach to clinical outcome assessment, assessment of pulmonary outcomes of children surviving PARDS, and assessment of nonpulmonary outcomes of children surviving PARDS including health-related quality of life and physical, neurocognitive, emotional, family, and social functioning. The five research statements relate to assessment of patient preillness status, use of postdischarge endpoints for clinical trials, the association between short-term and longer term outcomes, the trajectory of recovery following PARDS, and practices to optimize follow-up. CONCLUSIONS:There is increasing evidence that children are at risk for impairments across a range of pulmonary and nonpulmonary health domains following hospitalization for PARDS. The results of this extensive scoping review and consensus conference involving experts in PARDS research, clinical care, and outcomes assessment provide guidance to clinicians and researchers on postdischarge follow-up to optimize the long-term health of patients surviving PARDS.

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“…Our group found that continuous administration of NMBAs significantly improved oxygenation in patients with moderate-tosevere PARDS [12]. The Paediatric Acute Lung Injury Consensus Conference (PALICC) and the Paediatric European Mechanical Ventilation Consensus Conference (PEMVECC) recommended that clinical trials investigating the short-and long-term outcomes of NMBA use are much needed, especially as-despite the lack of evidence-NMBAs are often used in the most critically ill paediatric patients [13][14][15][16][17][18]. Furthermore, the possible beneficial effects of NMBAs must be outweighed against side-effects such as critical illness polyneuropathy and myopathy (CIPNM), a phenomenon that has been observed especially in adults who are on concurrent corticosteroids or have renal failure [19].…”

Section: Background and Rationale {6a}mentioning

confidence: 99%

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

Rudolph

Slager

Burgerhof

et al. 2022

Trials

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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.govNCT02902055. Registered on September 15, 2016.

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Early Neuromuscular Blockade in Children with Pediatric Acute Respiratory Distress Syndrome

Cited by 6 publications

References 27 publications

Neuromuscular Blocker Use in Critically Ill Children: Assessing Mortality Risk by Propensity Score–Weighted Analysis

Neuromuscular Blocker Use in Critically Ill Children: Assessing Mortality Risk by Propensity Score–Weighted Analysis

Outcomes of Children Surviving Pediatric Acute Respiratory Distress Syndrome: From the Second Pediatric Acute Lung Injury Consensus Conference

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

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