P0473 - Naloxegol for Treatment of Opioid-Induced Constipation in the Pediatric Intensive Care Unit

Background:
Opioid-induced constipation may cause significant morbidity in critically ill children. While constipation in this population is often multi-factorial, ubiquitous opioid usage in the PICU provides the opportunity for targeted therapy, especially in cases refractory to standard therapies. Naloxegol is an oral FDA-approved peripherally acting mu-opioid receptor antagonist for chronic opioid-induced constipation use in adults, but data on its use in children is lacking.

Methods:
A single-center retrospective analysis of children who received naloxegol from January 2018 - December 2019 was performed. Study included patients that were <18 years of age admitted to the PICU or CVICU during the study period. Patients who had undergone abdominal surgery in the week prior to administration were excluded. Demographic information, stool frequency, adjuvant therapies, type of nutrition, and Withdrawal Assessment Tool (WAT-1) scores were recorded for 96 hours before and after naloxegol administration.


Results:
45 patients met criteria. The mean age was 4.59 years with a mean weight of 19.14 kg. Length of stay in the ICU range from 4-128 days with an average of 28.8 days. The primary diagnosis of the patients were categorized as respiratory (78%), neurologic (9%), cardiac (7%), or trauma (6%). All patients were receiving a bowel regimen when naloxegol was started (polyethylene glycol 97%, magnesium hydroxide 80%, suppositories 64%, docusate 18%, and lactulose 9%) with 80% on a multi-drug regimen. At the time naloxegol was initiated, 42 patients were receiving enteral feeds while 3 were receiving parenteral nutrition due to feeding intolerance and abdominal distention. Dosages of naloxegol ranged from 0.09-0.91 mg/kg with an average dose of 0.32 mg/kg. All patients received once daily dosing over an average of 14 days (range, 1-89). Mean stool frequency increased significantly from 0.63 ±0.12 stools per day to 1.17 ±0.13 stools per day after starting naloxegol [95% CI (0.75, 1.4), p <0.001]. There was no significant difference in the average WAT-1 score in the 24 hours before and after receiving the first dose [95% CI (-0.25, 0.40), p=0.63]. While the average WAT-1 scores did significantly increase over the 96 hours after the first dose, 0.53 ±0.13 to 0.92 ±0.14, [95% CI (0.11, 0.78), p<0.01], the increase is clinically insignificant. Treatment was stopped in one patient after a single episode of emesis associated with administration and was held for a single dose in three patients after watery stool output, but was then subsequently resumed. The medication was not discontinued in any patients for withdrawal concerns.

Discussion:
Naloxegol is effective in increasing stool output in critically ill children receiving opioids without an increase in opioid-withdrawal symptoms and may be an effective adjunctive therapy for this population. Further study is required.