Multiple Organ Dysfunction in Children Mechanically Ventilated for Acute Respiratory Failure

Abstract

Objectives: The impact of extrapulmonary organ dysfunction, independent from sepsis and lung injury severity, on outcomes in pediatric acute respiratory failure is unclear. We sought to determine the frequency, timing, and risk factors for extrapulmonary organ dysfunction and the independent association of multiple organ dysfunction syndrome with outcomes in pediatric acute respiratory failure.

Design: Secondary observational analysis of the Randomized Evaluation of Sedation Titration for Respiratory Failure cluster-randomized prospective clinical trial conducted between 2009 and 2013.

Setting: Thirty-one academic PICUs in the United States.

Patients: Two thousand four hundred forty-nine children mechanically ventilated for acute respiratory failure enrolled in Randomized Evaluation of Sedation Titration for Respiratory Failure.

Measurements and main results: Organ dysfunction was defined using criteria published for pediatric sepsis. Multiple organ dysfunction syndrome was defined as respiratory dysfunction one or more extrapulmonary organ dysfunctions. We used multivariable logistic regression to identify risk factors for multiple organ dysfunction syndrome, and logistic or proportional hazards regression to compare clinical outcomes. All analyses accounted for PICU as a cluster variable. Overall, 73% exhibited extrapulmonary organ dysfunction, including 1,547 (63%) with concurrent multiple organ dysfunction syndrome defined by onset on day 0/1 and 244 (10%) with new multiple organ dysfunction syndrome with onset on day 2 or later. Most patients (93%) with indirect lung injury from sepsis presented with concurrent multiple organ dysfunction syndrome, whereas patients with direct lung injury had both concurrent (56%) and new (12%) multiple organ dysfunction syndrome. Risk factors for concurrent multiple organ dysfunction syndrome included older age, illness severity, sepsis, cancer, and moderate/severe lung injury. Risk factors for new multiple organ dysfunction syndrome were moderate/severe lung injury and neuromuscular blockade. Both concurrent and new multiple organ dysfunction syndrome were associated with 90-day in-hospital mortality (concurrent: adjusted odds ratio, 6.54; 95% CI, 3.00-14.25 and new: adjusted odds ratio, 3.21; 95% CI, 1.48-6.93) after adjusting for sepsis, moderate/severe lung injury, and other baseline characteristics.

Conclusions: Extrapulmonary organ dysfunction was common, generally occurred concurrent with respiratory dysfunction (especially in sepsis), and was a major risk factor for mortality in pediatric acute respiratory failure.

Figure 1. Time to first extrapulmonary organ dysfunction by etiology of respiratory failure

Time to onset of first extrapulmonary organ dysfunction differed according to etiology of acute respiratory failure (log-rank p<0.001). Patients were removed from the number at risk after the first day of meeting criteria for at least one extrapulmonary organ dysfunction. Patients who never developed extrapulmonary organ dysfunction were included through day 28, including those patients who left the hospital for whom it was presumed that no further organ dysfunction occurred beyond discharge. RAD reactive airways disease, PICU pediatric intensive care unit

Figure 2. Time course of organ dysfunction

Time course of respiratory and extrapulmonary organ dysfunction (A) and individual extrapulmonary organ system dysfunctions (B). Data for each day were calculated as the proportion of patients with the specified organ dysfunction amongst all patients remaining in the PICU on that day. All patients who remained in the PICU with organ dysfunction were included in the numerator irrespective of whether organ dysfunction developed on that day or a prior day but were removed from the numerator if organ dysfunction resolved. Patients were included in the denominator if they remained in the PICU on that day, irrespective of whether organ dysfunction continued or resolved. PICU pediatric intensive care unit