Abstract
INTRODUCTION: Delirium is a major public health issue for surgical patients and their families because it is associated with increased mortality, cognitive and functional decline, prolonged hospital admission and increased healthcare expenditures. Based on preliminary data, this trial tests the hypothesis that intravenous caffeine, given postoperatively, will reduce the incidence of delirium in older adults after major non-cardiac surgery. METHODS AND ANALYSIS: The CAffeine, Postoperative Delirium And CHange In Outcomes after Surgery-2 (CAPACHINOS-2) Trial is a single-centre, placebo-controlled, randomised clinical trial that will be conducted at Michigan Medicine. The trial will be quadruple-blinded, with clinicians, researchers, participants and analysts all masked to the intervention. The goal is to enrol 250 patients with a 1:1:1: allocation ratio: dextrose 5% in water placebo, caffeine 1.5 mg/kg and caffeine 3 mg/kg as a caffeine citrate infusion. The study drug will be administered intravenously during surgical closure and on the first two postoperative mornings. The primary outcome will be delirium, assessed via long-form Confusion Assessment Method. Secondary outcomes will include delirium severity, delirium duration, patient-reported outcomes and opioid consumption patterns. A substudy analysis will also be conducted with high-density electroencephalography (72-channel system) to identify neural abnormalities associated with delirium and Mild Cognitive Impairment at preoperative baseline. ETHICS AND DISSEMINATION: This study was approved by the University of Michigan Medical School Institutional Review Board (HUM00218290). An independent data and safety monitoring board has also been empanelled and has approved the clinical trial protocol and related documents. Trial methodology and results will be disseminated via clinical and scientific journals along with social and news media. TRIAL REGISTRATION NUMBER: NCT05574400.