Statistical analysis
delirium, V.4.1.1
REGRESSION, SECONDARY
The main analysis was the comparison of the proportion of patients with delirium between the two arms in the intention-to-treat population (ITT; all registered and randomised patients) using univariate logistic regression. As sensitivity analyses, the proportion of patients with delirium was also compared between the two arms in the modified ITT (mITT, that is, ITT but excluding patients who were found to be ineligible after randomisation) and safety population (ie, all patients who underwent craniotomy). A multivariable logistic regression analysis with the stratification factors in the ITT population was also performed as sensitivity analysis, while multivariable analyses in the mITT and safety population should be considered as descriptive and therefore as hypothesis generating only. All secondary outcomes were analyses in the mITT population and should only be considered as descriptive only.A 2-hour recording of BIS (blinded from the anaesthesiologist between operation minutes 60 and 180) was split into samples of 15 min as time points. A 30-minute recording of HRV was split into samples of 5 min as time points. Subsequently, we ran a linear mixed model with unstructured covariance for BIS and HRV, as a within-subject variability was suspected, with time point and interaction group/time point as independent variables, as presented with fixed effects (beta/βA two-sided p value of 0.05 or less was considered statistically significant. All statistical analyses were conducted using R (V.4.1.1).