Combination of olanzapine with bispectral index guided anesthesia to prevent postoperative delirium in elderly patients undergoing major gastrointestinal elective surgery: a randomized, double-blind, placebo-controlled study protocol

Abstract

Introduction: Postoperative delirium (POD) is an important complication of major surgery in elderly patients. It increases morbidity and mortality, hospital stay, and total healthcare costs. Since no treatment has proven effective once POD is established, prevention is key. Evidence exists that bispectral index guided anesthesia (BIS-GA) and antipsychotics may independently reduce incidence of POD, but the efficacy of combining these preventive strategies is unknown. Objective: To compare the combination of olanzapine + BIS-GA with BIS-GA alone for prevention of POD in elderly patients undergoing major elective surgery.
Methods: We propose a Phase II, multi-center, randomized, double-blind, parallel, placebo-controlled trial. The study arms will be BIS-GA + two doses of olanzapine 5mg given pre and postoperatively compared with BIS-GA + placebo in patients ≥65 years hospitalized for major elective surgery. Exclusion criteria include cardiac- and neurosurgery, dementia history, concurrent antipsychotic, anticholinergic, or sedative-hypnotic use, olanzapine allergy, delirium at hospital admission, cognitive impairment and inability to be interviewed. The primary outcome is incidence of POD diagnosed by DSM-V criteria and assessed by the Confusion Assessment Method (CAM) scale. Secondary outcomes include delirium severity, rescue therapy use, length of hospital stay and incidence of adverse events.
Discussion: There is an increasing need for trials that advance knowledge in prophylactic methods to prevent delirium. By combining two preventive methods, we expect to decrease the incidence of POD, which will result in decreased morbidity, mortality, and total healthcare costs.