Haloperidol prophylaxis decreases delirium incidence in elderly patients after noncardiac surgery: a randomized controlled trial*.

OBJECTIVES: To evaluate the efficacy and safety of short-term low-dose intravenous haloperidol for delirium prevention in critically ill elderly patients after noncardiac surgery. DESIGN: Prospective, randomized, double-blind, and placebo-controlled trial in two centers. SETTING: Intensive care units of two large tertiary teaching hospitals. PATIENTS: Four hundred fifty-seven patients 65 yrs or older who were admitted to the intensive care unit after noncardiac surgery. INTERVENTION: Haloperidol (0.5 mg intravenous bolus injection followed by continuous infusion at a rate of 0.1 mg/h for 12 hrs; n = 229) or placebo (n = 228) was randomly administered from intensive care unit admission. MEASURES: The primary end point was the incidence of delirium within the first 7 days after surgery. Secondary end points included time to onset of delirium, number of delirium-free days, length of intensive care unit stay, all-cause 28-day mortality, and adverse events. Delirium was assessed using the confusion assessment method for the intensive care unit. RESULTS: The incidence of delirium during the first 7 days after surgery was 15.3% (35/229) in the haloperidol group and 23.2% (53/228) in the control group (p = .031). The mean time to onset of delirium and the mean number of delirium-free days were significantly longer (6.2 days [95% confidence interval 5.9-6.4] vs. 5.7 days [95% confidence interval 5.4-6.0]; p = .021; and 6.8 ± 0.5 days vs. 6.7 ± 0.8 days; p = .027, respectively), whereas the median length of intensive care unit stay was significantly shorter (21.3 hrs [95% confidence interval 20.3-22.2] vs. 23.0 hrs [95% confidence interval 20.9-25.1]; p = .024) in the haloperidol group than in the control group. There was no significant difference with regard to all-cause 28-day mortality between the two groups (0.9% [2/229] vs. 2.6% [6/228]; p = .175). No drug-related side effects were documented. CONCLUSIONS: For elderly patients admitted to intensive care unit after noncardiac surgery, short-term prophylactic administration of low-dose intravenous haloperidol significantly decreased the incidence of postoperative delirium. The therapy was well-tolerated.

Incidence and risk factors of delirium in critically ill patients after non-cardiac surgery.

BACKGROUND: Delirium is a common and deleterious complication in critically ill patients after surgery. The purpose of this study was to determine the incidence and risk factors of delirium in critically ill patients after non-cardiac surgery, and to investigate the relationship between the serum cortisol level and the occurrence of postoperative delirium. METHODS: In a prospective cohort study, 164 consecutive patients who were admitted to the surgical intensive care unit after non-cardiac surgery were enrolled. Baseline characteristics and perioperative variables were collected. Blood samples were obtained on the first postoperative day and serum cortisol concentrations were measured. Delirium was assessed using the Nursing Delirium Screening Scale until the seventh postoperative day or the disappearance of delirious symptoms. RESULTS: Postoperative delirium occurred in 44.5% of patients (73 of 164). The median time to first onset of delirium is 0 (range 0 to 5 days) and the median duration of delirium is 3 (1 to 13) days. Independent risk factors of postoperative delirium included increasing age (odds ratio (OR) 2.646, 95% confidence interval (CI) 1.431 to 4.890, P = 0.002), a history of previous stroke (OR 4.499, 95%CI 1.228 to 16.481, P = 0.023), high Acute Physiology and Chronic Health Evaluation II score on surgical intensive care unite admission (OR 1.391, 95%CI 1.201 to 1.612, P < 0.001), and high serum cortisol level on the 1st postoperative day (OR 3.381, 95%CI 1.690 to 6.765, P = 0.001). The development of delirium was linked to higher incidence of postoperative complications (28.8% vs. 7.7%, P < 0.001), and longer duration of hospitalization (18 (7 to 74) days vs. 13 (3 to 48) days, P < 0.001). CONCLUSIONS: Delirium was a frequent complication in critically ill patients after non-cardiac surgery. High serum cortisol level was associated with increased incidence of postoperative delirium.