Lena Tran, PharmD, BCCCP
Senior Pharmacist
Brigham & Women's Hospital, Massachusetts, United States
Disclosure information not submitted.
Melanie Goodberlet, BCCCP, BCPS, PharmD
Clinical Pharmacy Specialist
Brigham and Women's Hospital, United States
Disclosure information not submitted.
Kenneth Lupi, PharmD, BCCCP, BCPS
Pharmacist
Brigham and Women's Hospital, United States
Disclosure information not submitted.
Kevin Dube, BCCCP, BCPS, PharmD
Clinical Pharmacy Specialist
Brigham & Women's Hospital
Boston, Massachusetts
Disclosure information not submitted.
Title: Naloxone Versus Methylnaltrexone for Opioid-Induced Constipation in Critically Ill Patients
Introduction: Opioid-induced constipation (OIC) may occur in up to 83% of critically ill patients and can result in abdominal distention, increased hospital length of stay, and bowel perforation. Opioid antagonists, as enteral naloxone (NLX) and subcutaneous (SC) methylnaltrexone (MNTX), bind to µ-opioid receptors in the gastrointestinal tract and may be used for managing OIC. The goal of this study was to assess the efficacy of NLX vs. MNTX for the treatment of OIC in critically ill patients.
Methods: This single-center, retrospective study was conducted at a tertiary academic medical center. Adult patients were included if they received at least one dose of NLX or MNTX from May 2015 to August 2020 and a continuous opioid infusion for at least 48 hours. Patients were excluded if they had a history of bowel dysfunction, did not receive the study medication in an intensive care unit (ICU), or had abdominal surgery during admission. The primary endpoint was time to resolution of constipation, defined as hours to first bowel movement (BM) after the first dose of opioid antagonist. Reversal of analgesia was assessed by comparing total number of morphine milligram equivalents (MME) 24 hours pre - and post - opioid antagonist administration. Univariate and multivariate analyses were conducted to assess treatment response within 48 hours.
Results: Of the 300 patients screened, 160 patients were included, 89 received NLX and 71 MTX. Baseline demographics were similar between the two groups; however, there were more medical ICU patients in the NLX group (79, 89%) compared to the MNTX group (50, 70%) (p < 0.05). The time to first BM with NLX was 18 hours compared to 41 hours with MNTX (p < 0.05). There was no difference in MME requirements 24 hours pre - and post - antagonist administration. Patients who had a BM within 48 hours were more likely to receive NLX and be located in the medical ICU. Naloxone administration was identified as a statistically significant predictor of bowel movement at 48 hours (OR 2.68 [1.33 to 5.38]).
Conclusion: This analysis demonstrates that both agents appear to be effective for the management of OIC without reversing analgesia. The time to first BM was shorter with enteral NLX, which may be considered an effective alternative to SC MNTX. However, future prospective trials are warranted.