Peripherally‐active mu‐opioid receptor antagonists for constipation in critically ill patients receiving opioids: A case‐series and a systematic review and meta‐analysis of the literature

Abstract

AbstractBackgroundConstipation is frequent in critically ill patients, and potentially related to adverse outcomes. Peripherally‐active mu‐opioid receptor antagonists (PAMORAs) are approved for opioid‐induced constipation, but information on their efficacy and safety in critically ill patients is limited. We present a single‐center, retrospective, case‐series of the use of naldemedine for opioid‐associated constipation, and we systematically reviewed the use of PAMORAs in critically ill patients.MethodsCase‐series included consecutive mechanically‐ventilated patients; constipation was defined as absence of bowel movements for >3 days. Naldemedine was administered after failure of the local laxation protocol. Systematic review: PubMed was searched for studies of PAMORAs to treat opioid‐induced constipation in adult critically ill patients. Primary outcomes: time to laxation, and number of patients laxating at the shortest follow‐up. Secondary outcomes: gastric residual volumes and adverse events.Key ResultsA total of 13 patients were included in the case‐series; the most common diagnosis was COVID‐19 ARDS. Patients had their first bowel movement 1 [0;2] day after naldemedine. Daily gastric residual volume was 725 [405;1805] before vs. 250 [45;1090] mL after naldemedine, p = 0.0078. Systematic review identified nine studies (two RCTs, one prospective case‐series, three retrospective case‐series and three case‐reports). Outcomes were similar between groups, with a trend toward a lower gastric residual volume in PAMORAs group.Conclusions & InferencesIn a highly‐selected case‐series of patients with refractory, opioid‐associated constipation, naldemedine was safe and associated to reduced gastric residuals and promoting laxation. In the systematic review and meta‐analysis, the use of PAMORAs (mainly methylnaltrexone) was safe and associated with a reduced intolerance to enteral feeding but no difference in the time to laxation.