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.

BACKGROUND: Constipation 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. METHODS: Case-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 RESULTS: A 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 & INFERENCES: In 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.

Incidence, clinical characteristics and outcome of barotrauma in critically ill patients with COVID-19: a systematic review and meta-analysis.

INTRODUCTION: Barotrauma is rare in patients with acute respiratory distress syndrome undergoing mechanical ventilation. Its incidence seems increased among critically ill COVID-19 patients. We performed a systematic review and meta-analysis to investigate the incidence, risk factors and clinical outcomes of barotrauma among critically ill COVID-19 patients. EVIDENCE ACQUISITION: PubMed was searched from March 1st, 2020 to August 31st, 2021; case series and retrospective cohort studies concerning barotrauma in adult critically ill COVID-19 patients, either hospitalized in the Intensive Care Unit (ICU) or invasively ventilated were included. Primary outcome was the incidence of barotrauma in COVID-19 versus non-COVID-19 patients. Secondary outcomes were clinical characteristics, ventilator parameters, mortality and length of stay between patients with and without barotrauma. EVIDENCE SYNTHESIS: We identified 21 studies (six case series, 15 retrospective cohorts). The overall incidence of barotrauma was 11 [95% CI: 8-14]% in critically ill COVID-19 patients, vs. 2 [1-3]% in non-COVID-19, P<0.001; the incidence in mechanically ventilated patients was 14 [11-17]% vs. 4 [2-5]% non-COVID-19 patients, P<0.001. There were no differences in demographic, clinical, ventilatory parameters between patients who did and did not develop barotrauma, while, on average, protective ventilation criteria were always respected. Among COVID-19 patients, those with barotrauma had a higher mortality (60 [55-66] vs. 48 [42-54]%, P<0.001) and a longer ICU length of stay (20 [14-26] vs. 13 [10,5-16] days, P=0.03). CONCLUSIONS: Barotrauma is a frequent complication in critically ill COVID-19 patients and is associated with a poor prognosis. Since lung protective ventilation was delivered, the ventilatory management might not be the sole factor in the development of barotrauma.