The Relationship of Postoperative Delirium With Psychoactive Medications

OBJECTIVE: To examine the role of medications with known psychoactive properties in the development of postoperative delirium. DESIGN: Nested case-control study within a prospective cohort study. SETTING: General surgery, orthopedic surgery, and gynecology services at Brigham and Women's Hospital, Boston, Mass. PATIENTS: Cases (n = 91) were patients enrolled in a prospective cohort study who developed delirium during postoperative days 2 through 5. One or two controls (n = 154) were matched to each case by the calculated preoperative risk for delirium using a predictive model developed and validated in the prospective cohort study. MAIN OUTCOME MEASURES: Medication exposures were ascertained from the medical record by a reviewer blinded to the study hypothesis. Exposures to narcotics, benzodiazepines, and anticholinergics were recorded for the 24-hour period before delirium developed in the 91 cases and for the same 24-hour postoperative period for the 154 matched controls. RESULTS: Delirium was significantly associated with postoperative exposure to meperidine (odds ratio OR, 2.7; 95% confidence interval CI, 1.3 to 5.5) and to benzodiazepines (OR, 3.0; 95% CI, 1.3 to 6.8). Meperidine had similar associations with delirium whether administered via epidural or patient-controlled routes, although only the epidural route reached significance (OR, 2.4; 95% CI, 1.3 to 4.4; OR, 2.1; 95% CI, 0.4 to 10.7, respectively). For benzodiazepines, long-acting agents had a trend toward stronger association with delirium than did short-acting agents (OR, 5.4; 95% CI, 1.0 to 29.2; vs 2.6; 1.1 to 6.5), and high-dose exposures had a trend toward slightly stronger association than low-dose exposures (OR, 3.3; 95% CI, 1.0 to 11.0; vs 2.6; 0.8 to 9.1). Neither narcotics (OR, 1.4; 95% CI, 0.5 to 4.3) nor anticholinergic drugs (OR, 1.5; 95% CI, 0.6 to 3.4) were significantly associated with delirium as a class, although statistical power was limited because of the high use of narcotics and the low use of anticholinergics in the study population. CONCLUSIONS: Clinicians caring for patients at risk for delirium should carefully evaluate the need for meperidine and benzodiazepines in the postoperative period and consider alternative therapies whenever possible.