Patient, Process, and System Predictors of Iatrogenic Withdrawal Syndrome in Critically Ill Children*

Abstract

To generate a multidimensional predictive model of risk factors for iatrogenic withdrawal syndrome in critically ill children. Secondary analysis of prospective data from the Randomized Evaluation of Sedation Titration for Respiratory Failure clinical trial. PICU. Children who received greater than or equal to 5 days of sedation during mechanical ventilation for acute respiratory failure. The Randomized Evaluation of Sedation Titration for Respiratory Failure study tested the effect of a nurse-led, goal-directed sedation protocol on clinical outcomes. There was no additional intervention in this secondary analysis. Data included 1,157 children from 31 PICUs. Iatrogenic withdrawal syndrome was defined as having at least two Withdrawal Assessment Tool-Version 1 scores greater than or equal to 3 after the start of opioid weaning. Logistic regression with generalized estimating equations to account for clustering by site was used to evaluate patient, process, and healthcare system risk factors for iatrogenic withdrawal syndrome. Subjects with iatrogenic withdrawal syndrome (544/1,157; 47%) were younger and more likely to have preexisting cognitive or functional impairment. They also received higher sedative doses and longer exposure periods. In multivariable analyses, significant predictors of iatrogenic withdrawal syndrome included younger age, preexisting cognitive impairment, higher preweaning mean daily opioid dose, longer duration of sedation, receipt of three or more preweaning sedative classes, higher nursing workload, and more one-to-one nurse staffing. Iatrogenic withdrawal syndrome is common in children recovering from critical illness, and several risk factors are predictive, including patient characteristics, sedative exposure, additional sedative agents, and system-level factors. High-risk patients could be identified before weaning to better prevent iatrogenic withdrawal syndrome among at-risk patients.