Ghafouri, Kimia

Background Postoperative respiratory depression (PRD) is potentially preventable yet remains difficult to preemptively detect. We evaluated whether three post anesthesia care unit (PACU) events—oversedation, caffeine administration for impaired arousal, and naloxone administration—can serve as early markers of delayed PRD requiring naloxone administration on wards. Methods We retrospectively identified patients who underwent general anesthesia between 2018 and 2023 at a quaternary care academic medical center. From electronic medical records, we retrieved PACU naloxone and caffeine treatments, scores of sedation assessments using the Richmond Agitation-Sedation Scale (RASS), and ward naloxone administrations within 24 hours after PACU discharge. Results Among 95 870 patients, 186 (0.19%, 95% CI 0.17-0.22) required naloxone for respiratory depression after PACU discharge. Ward naloxone administration was independently associated with naloxone (OR 9.11, 95% CI 4.69-17.71, P < 0.001) and caffeine (OR 2.00, 95% CI 1.21-3.32, P = 0.007) administrations, and with PACU RASS scores ≤ −3 (OR 2.16, 95% CI 1.56-2.99, P < 0.001). Conclusions Naloxone administration in PACU was the strongest predictor of delayed PRD, followed by oversedation and PACU caffeine administration, indicating that information routinely collected during PACU recovery may offer insight into delayed respiratory risk before transition to hospital wards. In light of the overall low incidence of ward naloxone use, these findings support selective, risk-based vigilance for patients exhibiting these PACU events rather than broad adjustments to existing monitoring practices.

This systematic review examined multicenter randomized controlled trials (RCTs) conducted during the Sepsis-3 era that evaluated pharmaceutical and mechanistic interventions in adult patients with sepsis or septic shock, with a focus on identifying interventions that demonstrated mortality benefit. A comprehensive search was performed across Ovid MEDLINE, Embase, Cochrane Central, ClinicalTrials.gov, WHO ICTRP, and Web of Science for trials published since 2016. Studies were included if they enrolled adult patients with sepsis or septic shock using Sepsis-3 criteria and reported mortality as either a primary or secondary outcome. Data were extracted by two independent reviewers and included trial design characteristics, funding source, randomization methods, and reported outcomes. Among the 31 eligible multicenter RCTs enrolling over 7,000 patients across 550 centers, only four trials showed a mortality benefit. These included three studies from China—two evaluating herbal anti-inflammatory compounds and one evaluating aminophylline—and one European study assessing corticosteroid therapy in vasopressor-dependent septic shock. The remaining 27 trials reported no mortality benefit, and substantial heterogeneity was observed in patient populations, sepsis definitions, and outcome reporting. Median mortality in control arms was 31.6% (IQR 24.1–45.5), and 35.4% (IQR 25.7–49.6) in intervention arms. These findings suggest that despite extensive efforts, most interventions have not reduced mortality in multicenter sepsis trials. Future research should focus on optimizing trial design, refining patient selection, and incorporating patient-centered outcomes beyond mortality.