The relationship of postoperative delirium with psychoactive medications

JAMA. 1994 Nov 16;272(19):1518-22.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Analgesia, Epidural
  • Analgesia, Patient-Controlled
  • Benzodiazepines / administration & dosage
  • Benzodiazepines / adverse effects*
  • Case-Control Studies
  • Cholinergic Antagonists / administration & dosage
  • Cholinergic Antagonists / adverse effects*
  • Delirium / diagnosis
  • Delirium / etiology*
  • Humans
  • Logistic Models
  • Matched-Pair Analysis
  • Mental Status Schedule
  • Middle Aged
  • Narcotics / administration & dosage
  • Narcotics / adverse effects*
  • Postoperative Period*
  • Prospective Studies
  • Psychiatric Status Rating Scales
  • Risk Factors


  • Cholinergic Antagonists
  • Narcotics
  • Benzodiazepines