(413) Starting a Movement in the ICU: Naloxegol Versus Methylnaltrexone for Opioid-Induced Constipation

Introduction: Constipation impacts critically ill patients and increases delirium risk, ventilator time, and intensive care unit (ICU) length of stay (LOS). Naloxegol (NGL) and methylnaltrexone (MNTX), are used to treat opioid-induced constipation (OIC). The purpose of this study was to evaluate the efficacy of NGL versus MNTX for OIC in ICU patients.

Methods: This was a retrospective, multi-center, cohort study of ICU patients admitted between January 1, 2014 and September 1, 2022. Patients were included if received opioid infusions for ≥4 hours prior to MNTX or NGL use and had no bowel movement (BM) within 48-hours before start of study drug. Patients were excluded if receiving nothing by mouth, had an ileus or small bowel obstruction, had gastric residuals >500mL, history of OIC, received another OIC drug, or received both study drugs. Primary outcome was time to first BM from MNTX or NGL initiation. Secondary outcomes were number of BMs at 72 hours, ICU length of stay (LOS), and cost-effectiveness. Safety outcomes included aspiration with NGL, injection reactions with MNTX, and development of delirium by positive CAM-ICU score after drug start. Primary outcome was assessed via weighted Cox proportional hazards model followed by use of a non-inferiority test with a preset margin of 10%.

Results: Final cohort included 161 patients: 110 in the NGL and 51 in the MNTX group. Baseline characteristics were similar among groups. Higher opioid dosages were administered prior to NGL initiation (p=0.0058). Median time to first BM was 18.3 and 23.7 hours for MNTX versus NGL, respectively. NGL was non-inferior to MNTX (Wald Statistic = 1.67; p=0.047). Median number of BMs 72 hours after drug initiation was 4 for MNTX and 3 for NGL (p=0.70). Median ICU LOS was 12 days with MNTX and 14 days with NGL (p=0.57). At least 1 positive CAM-ICU score occurred in 58.8% of MNTX and 54.5% of NGL patients (p=0.61). No aspiration or injection reactions were noted. Average cost to produce a BM was $159.71 for MNTX and $20.50 for NGL.

Conclusions: This study found NGL to be non-inferior to MNTX in time to produce a BM in ICU patients. No differences were seen in secondary outcomes, and no major safety events were observed. For this trial, NGL was found to be more cost-effective than MNTX.