Matt Harmon

138 Chapter seven TTM protocol The entire duration of the TTM-protocol was 36 hours, which started at randomization to either 33°C (TTM33) or 36°C (TTM36). The assigned target temperature was achieved as soon as possible after which patients were kept at their target temperature until 28 hours after randomization. After 28 hours, patients were gradually rewarmed to 37°C at a maximum speed of 0.5°C per hour. Sedation was mandatory for both groups during the entire TTM intervention. Patients were ventilated in either a pressure or a volume controlled mode. Post-hoc survey Participating centers of the TTM-trial were asked to complete an additional online case report form with data on mechanical ventilation at three time points: prior to the TTM intervention, after 24 hours of TTM (before rewarming) and after rewarming was completed (at the start of the normothermic phase). Collected data are tidal volume (V T ), positive end expiratory pressure (PEEP), plateau pressure of the respiratory system (Pplat), respiratory rate (RR) and end tidal CO 2 (etCO 2 ). Data on lactate, arterial PO 2 (PaO 2 ), arterial PCO 2 (PaCO 2 ) , base excess, pHa and mean arterial pressurewere derived from the original TTM-database. Blood gasses were measured alpha-stat. Respiratory minute volume (RMV) was calculated as the V T x RR. Static compliance of the respiratory system (Cstat) was calculated as V T /Pplat – PEEP. Driving pressure (ΔP) was calculated as V T /Cstat. Alveolar dead space ventilation was calculated as (PaCO 2 -etCO 2 )/PaCO 2 . 13 Supranormal arterial oxygen content was defined as a PaO 2 level >13.3 kPa. 14 Statistical Analysis All analyses were performed in R (version 3.1.1). Baseline differences and differences in mechanical ventilation parameters were assessed using either the students t-test or the Wilcoxon rank sum test depending on normality of the data. To study the relationship between mechanical ventilation on 28-day mortality, a logistic regression model was performed. A priori, age, SOFA score, asthma/ COPD, time from cardiac arrest to ROSC, first measured body temperature, lactate and cardiovascular diseases were put into the model. Mechanical ventilation variables with a P-value below 0.2 were also included. Collinearity diagnostics were performed using the variance inflation factor to check for variable independence. Missing data was imputed using the “MICE” package. 15 A restricted cubic spline function was used for non-linear variables. Variables were sequentially removed from the model based on likelihood ratio tests.