Er. Marcantonio et al., THE RELATIONSHIP OF POSTOPERATIVE DELIRIUM WITH PSYCHOACTIVE MEDICATIONS, JAMA, the journal of the American Medical Association, 272(19), 1994, pp. 1518-1522
Objective.-To examine the role of medications with known psychoactive
properties in the development of postoperative delirium. Design.-Neste
d case-control study within a prospective cohort study. Setting.-Gener
al 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 p
ostoperative days 2 through 5. One or two controls (n=154) were matche
d to each case by the calculated preoperative risk for delirium using
a predictive model developed and validated in the prospective cohort s
tudy. Main Outcome Measures.-Medication exposures were ascertained fro
m the medical record by a reviewer blinded to the study hypothesis. Ex
posures to narcotics, benzodiazepines, and anticholinergics were recor
ded for the 24-hour period before delirium developed in the 91 cases a
nd for the same 24-hour postoperative period for the 154 matched contr
ols. Results.-Delirium was significantly associated with postoperative
exposure to meperidine (odds ratio [OR], 2.7; 95% confidence interval
[Cl], 1.3 to 5.5) and to benzodiazepines (OR, 3.0; 95% Cl, 1.3 to 6.8
). Meperidine had similar associations with delirium whether administe
red via epidural or patient-controlled routes, although only the epidu
ral route reached significance (OR, 2.4; 95% Cl, 1.3 to 4.4; OR, 2.1;
95% Cl, 0.4 to 10.7, respectively). For benzodiazepines, long-acting a
gents had a trend toward stronger association with delirium than did s
hort-acting agents (OR, 5.4; 95% Cl, 1.0 to 29.2; vs 2.6; 1.1 to 6.5),
and high-dose exposures had a trend toward slightly stronger associat
ion than low-dose exposures (OR, 3.3; 95% Cl, 1.0 to 11.0; vs 2.6; 0.8
to 9.1). Neither narcotics (OR, 1.4; 95% Cl, 0.5 to 4.3) nor antichol
inergic drugs (OR, 1.5; 95% Cl, 0.6 to 3.4) were significantly associa
ted with delirium as a class, although statistical power was limited b
ecause of the high use of narcotics and the low use of anticholinergic
s in the study population. Conclusions.-Clinicians caring for patients
at risk for delirium should carefully evaluate the need for meperidin
e and benzodiazepines in the postoperative period and consider alterna
tive therapies whenever possible.