The Association of Iatrogenic Withdrawal With Opioid and Benzodiazepine Weaning in Children With Bronchiolitis: A Single-Center, Retrospective Cohort Study, 2012-2022.

OBJECTIVES

This study aimed to determine the decrease in opioid and benzodiazepine doses associated with the development of withdrawal in children.

SETTING

Electronic health record data.

INTERVENTION: None.

PATIENTS: Four hundred and seven children who received invasive mechanical ventilation (IMV) between January 1, 2012 and January 1, 2022 with Withdrawal Assessment Tool-1 (WAT-1) scores during their IV opioid wean were included.

MEASUREMENTS AND MAIN

RESULTS

The primary outcome was development of withdrawal, defined as a WAT-1 score greater than or equal to 3, during the IV opioid weaning phase. Descriptive data included age, weight, insurance, race, ethnicity, language, comorbidities, length of stay, and IMV duration. WAT-1 scores were recorded, and the cumulative IV and enteral opioids, benzodiazepines, and A2As were calculated. Recent changes in IV opioid and benzodiazepine doses were assessed in the 16 hours before each WAT-1 score divided into 4-hour periods. Doses were compared across 4-hour periods, and a multivariable mixed-effects model was used to assess their association with withdrawal. The presence of greater than or equal to 2 pediatric complex chronic condition classification system version 2 (CCC-V2) diagnosis categories (odds ratio [OR] 3.35; 95% CI, 2.61-5.15) was associated with withdrawal. Heart disease, prematurity, and IV opioid class switching did not qualify for model inclusion. Cumulative IV opioid dose and a decrease in opioid exposure between 16-12 and 4-0 hours before the WAT-1 score were associated with withdrawal (OR 1.02; 95% CI, 1.01-1.03; OR 1.92; 95% CI, 1.38-3.16). Morphine was associated with increased odds of withdrawal compared with fentanyl and hydromorphone (OR 1.48; 95% CI, 1.37-1.81). The model did not establish an association between cumulative IV benzodiazepine exposure or IV benzodiazepine dose decrease and withdrawal.

CONCLUSIONS

Patients with a higher cumulative IV opioid dose, an IV opioid wean in the preceding 8-12 hours, and greater than or equal to 2 CCC-V2 categories had the highest odds of withdrawal in this single-center study. Morphine was associated with increased odds of withdrawal as well.