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Importance: Opioids are commonly used for pain control during and after invasive procedures. However, opioid-related adverse drug events (ORADEs) are common and have been associated with worse patient outcomes., Objectives: To examine the incidence of ORADEs in patients undergoing hospital-based surgical and endoscopic procedures and to evaluate the association of ORADEs with clinical and cost outcomes., Design, Setting, and Participants: In this retrospective study of clinical and administrative data, ORADEs were identified using International Classification of Diseases, Ninth Revision diagnosis codes for known adverse effects of opioids or by opioid antagonist use. Multivariable regression analysis was used to measure the association of ORADEs with outcomes after adjusting for potential confounding factors. The setting was 21 acute care hospitals in a large integrated health care delivery system. Participants were 135 379 patients (aged ≥18 years, admitted from January 1, 2013, to September 30, 2015) who underwent surgical and endoscopic procedures and were given opioids., Exposure: Opioid use, reported as morphine milligram equivalent doses., Main Outcomes and Measures: Opioid-related adverse drug events and their association with inpatient mortality, discharge to another care facility, length of stay, cost of hospitalization, and 30-day readmission., Results: Among 135 379 adult patients in this study (67.5% female), 14 386 (10.6%) experienced at least one ORADE. Patients with ORADEs were more likely to be older, of white race/ethnicity, and male and have more comorbidities. Patients with ORADEs received a higher total dose of opioids (median morphine milligram equivalent dose, 46.8 vs 30.0 mg; P < .001) and for a longer duration (median, 3.0 vs 2.0 days; P < .001). In adjusted analyses, ORADEs were associated with increased inpatient mortality (odds ratio [OR], 28.8; 95% CI, 24.0-34.5), greater likelihood of discharge to another care facility (OR, 2.9; 95% CI, 2.7-3.0), prolonged length of stay (OR, 3.1; 95% CI, 2.8-3.4), high cost of hospitalization (OR, 2.7; 95% CI, 2.4-3.0), and higher rate of 30-day readmission (OR, 1.3; 95% CI, 1.2-1.4). ORADEs were associated with a 2.9% increase in absolute mortality, an $8225 increase in cost for the index hospitalization, and a 1.6-day increase in length of stay for the index hospitalization., Conclusions and Relevance: Opioid-related adverse drug events were common among patients undergoing hospital-based invasive procedures and were associated with significantly worse clinical and cost outcomes. Hospital-acquired harm from ORADEs in the surgical patient population is an important opportunity for health systems to improve patient safety and reduce cost.

Background: It is unclear how best to measure sedative/analgesic drug exposure in the clinical care of critically ill patients. Large doses and prolonged use of sedatives and analgesics in the intensive care unit (ICU) may lead to oversedation and adverse effects, including delirium and long-term cognitive impairment. These issues are of particular concern in elderly patients (aged > or =65 years), who account for at least half of all ICU admissions and nearly two thirds of ICU days., Objective: This pilot study explored the relationships between clinical sedation scores, sedative/analgesic drug doses, and plasma drug concentrations in critically ill patients, the majority of whom were elderly., Methods: This was a prospective, observational study conducted in a 500-bed, tertiary care community hospital. Study patients included a cohort of mechanically ventilated, medical ICU patients who were admitted to the hospital between April and June 2004 who required use of fentanyl, lorazepam, or propofol. Sedative/analgesic medications were administered according to clinical guidelines. Patients' sedation levels were measured twice daily using the Richmond Agitation-Sedation Scale (RASS). Dosing of fentanyl, lorazepam, and propofol was recorded. Blood was sampled twice daily for up to 5 days to analyze plasma drug concentrations. To specifically evaluate the effects of acute, extended (rather than chronic) sedative and analgesic exposure, the study focused on an ICU population receiving these agents for at least 48 hours but <2 weeks., Results: Eighteen medical ICU patients (11 females, 7 males; mean [SD] age, 66.1 [18.1] years) on mechanical ventilation comprised the study cohort. Fifteen patients were aged >62 years, and 11 of those were aged > or =71 years. Plasma drug concentrations (median and interquartile range) were as follows: fentanyl--2.1 ng/mL, 0.9-3.4 ng/mL; lorazepam--266 ng/mL, 112-412 ng/mL; and propofol--845 ng/mL, 334-1342 ng/mL. Maximum concentrations were 3- to 12-fold higher than medians (fentanyl, 7.3 ng/mL; lorazepam, 3108 ng/mL; propofol, 10,000 ng/mL). Medication doses were only moderately correlated with RASS scores (Spearman rho): fentanyl--rho = -0.39, P = 0.002; lorazepam--rho = -0.28, P = 0.001; and propofol--rho = -0.46, P < 0.001. Plasma drug concentrations of fentanyl and lorazepam demonstrated moderate correlations with sedation scores (fentanyl--rho = -0.46, P = 0.002; lorazepam: rho = -0.49, P < 0.001), while propofol concentrations correlated poorly with sedation scores (rho = -0.18, P = 0.07). Associations between interval drug doses and plasma concentrations were as follows: fentanyl, rho = 0.84; lorazepam, rho = 0.76; and propofol, rho = 0.61 (all, P < 0.001). Instructive examples of discrepant dose versus plasma concentration profiles and drug interactions are provided, including 3 cases with patients aged > or =64 years., Conclusions: Elderly patients are commonly encountered in the ICU setting. Only moderate correlations existed between clinical sedation levels and dose or plasma concentration of sedative/analgesic medications in this study population. Further work is needed to understand appropriate and feasible measures of exposure to sedatives/analgesics relating to clinical outcomes.