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Keywords:

  • delirium;
  • donepezil hydrochloride;
  • randomized controlled trial

Abstract

Objectives

This was a pilot, phase 2a study to assess methodological feasibility and the safety and efficacy of donepezil in preventing postoperative delirium after elective total hip replacement surgery in older people without pre-existing dementia. The hypothesis was that donepezil would reduce the incidence of postoperative delirium.

Methods

A double blind, placebo controlled, parallel group randomized trial was undertaken. Patients were block randomized pre-operatively to receive placebo or donepezil 5 mg immediately following surgery and every 24 h thereafter for a further three days. The main outcome was the incidence of delirium (using the Delirium Symptom Interview). The secondary outcome was length of hospital stay.

Results

Thirty-three patients (mean age 67 years; 17 males, 16 females) completed the study (19 donepezil, 14 placebo). Donepezil was well tolerated with no serious adverse events. Postoperative delirium occurred in 21.2% of subjects. Donepezil did not significantly reduce the incidence of delirium. The unadjusted risk ratio (donepezil vs placebo) for delirium was 0.29 (95% CI = 0.06,1.30) (χ2[1] = 3.06; p = 0.08). Mean length of hospital stay was 9.9 days for the donepezil group vs 12.1 days in the placebo group; difference in means = −2.2 days (95% CI = −0.39,4.78) (t[31] = 1.73: p = 0.09).

Conclusions

The experimental paradigm was feasible and acceptable. Donepezil did not significantly reduce the incidence of delirium or length of hospital stay, however for both outcomes there was a consistent trend suggesting possible benefit. The sample size required for a definitive trial (99% power, alpha 0.05) would be 95 subjects per arm. Copyright © 2006 John Wiley & Sons, Ltd.