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. 2022 Mar 20:2022:7541378.
doi: 10.1155/2022/7541378. eCollection 2022.

Naloxegol to Prevent Constipation in ICU Adults Receiving Opioids: A Randomized Double-Blind Placebo-Controlled Pilot Trial

Matthew S Duprey  1 , Harmony Allison  2 , Erik Garpestad  3 , Andrew M Riselli  4 , Anthony Faugno  2 , Eric Anketell  5 , John W Devlin  6
Affiliations

Naloxegol to Prevent Constipation in ICU Adults Receiving Opioids: A Randomized Double-Blind Placebo-Controlled Pilot Trial

Matthew S Duprey et al. Crit Care Res Pract. .

Abstract

Background: Constipation is frequent in critically ill adults receiving opioids. Naloxegol (N), a peripherally acting mu-receptor antagonist (PAMORA), may reduce constipation. The objective of this trial was to evaluate the efficacy and safety of N to prevent constipation in ICU adults receiving opioids. Methods and Patients. In this single-center, double-blind, randomized trial, adults admitted to a medical ICU receiving IV opioids (≥100 mcg fentanyl/day), and not having any of 17 exclusion criteria, were randomized to N (25 mg) or placebo (P) daily randomized to receive N (25mg) or placebo (P) and docusate 100 mg twice daily until ICU discharge, 10 days, or diarrhea (≥3 spontaneous bowel movement (SBM)/24 hours) or a serious adverse event related to study medication. A 4-step laxative protocol was initiated when there was no SBM ≥3 days.

Results: Only 318 (20.6%) of the 1542 screened adults during the 1/17-10/19 enrolment period met all inclusion criteria. Of these, only 19/381 (4.9%) met all eligibility criteria. After 7 consent refusals, 12 patients were randomized. The study was stopped early due to enrolment futility. The N (n = 6) and P (n = 6) groups were similar. The time to first SBM (N 41.4 ± 31.7 vs. P 32.5 ± 25.4 hours, P = 0.56) was similar. The maximal daily abdominal pressure was significantly lower in the N group (N 10 ± 4 vs. P 13 ± 5, P = 0.002). The median (IQR) daily SOFA scores were higher in N (N 7 (4, 8) vs. P 4 (3, 5), P < 0.001). Laxative protocol use was similar (N 83.3% vs. P 66.6%; P = 0.51). Diarrhea prevalence was high but similar (N 66.6% vs. P 66.6%; P = 1.0). No patient experienced opioid withdrawal.

Conclusions: Important recruitment challenges exist for ICU trials evaluating the use of PAMORAs for constipation prevention. Despite being underpowered, our results suggest time to first SBM with naloxegol, if different than P, may be small. The effect of naloxegol on abdominal pressure, SOFA, and the interaction between the two requires further research.

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Conflict of interest statement

The authors declare that there are no conflicts of interest regarding the publication of this article.

Figures

Figure 1
Figure 1
Patient screening, recruitment, and randomization. The number of patients excluded for each criterion sum is more than the total because some patients met more than one exclusion criteria.
Figure 2
Figure 2
Time to first spontaneous bowel movement from the time of enrolment. The Kaplan–Meier curve for the time to the first spontaneous bowel movement occurrence between the naloxegol and placebo groups during the ICU stay from the time of enrolment (log rank P value = 0.56). The naloxegol and placebo lines at the bottom of the figure refer to the patients still receiving study drug.
See this image and copyright information in PMC

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