Matt Harmon

158 Chapter eight Methods This study is based on the TTM-trial conducted between 2010 and 2013 and was approved by the TTM-trial steering group before the completion of the trial. 24 Ethical committees in each participating country approved the TTM-trial protocol and informed consent was waived or obtained according to national legislations, in line with the Helsinki declaration. The patients included were unconscious (GCS < 8) adults (≥ 18 years of age) with stable ROSC after OHCA of presumed cardiac cause. Main exclusion criteria were unwitnessed cardiac arrest with asystole as primary rhythm, known or suspected intracranial hemorrhage or stroke, and time from ROSC to screening > 240 minutes. 24 All patients were admitted to an intensive care unit (ICU), intubated, sedated and mechanically ventilated. After inclusion, the patients were randomized to the 33°C or the 36°C group and temperature controlled during the intervention period of 36 hours, which commenced at inclusion into the trial. Mandatory sedation was discontinued 36 hours after inclusion. The TTM study analyzed 939 eligible patients with no difference in survival or neurological outcome at 6 months between the two allocation groups. 24 For this sub-study we included patients surviving the intervention period in order to have a defined exposure period for carbon dioxide. Patient data and blood sampling Pre-hospital data were reported according to the Utstein criteria. 25 Baseline, intervention related and physiological variables, comorbidities, demographic, pre- hospital and admission data, as well as characteristics of the cardiac arrest and baseline laboratory analyses were collected. A complete arterial blood gas analysis was performed in all patients at admission to hospital, start of intervention (T0, which also was the time of randomization) and after 4, 12, 20, 28, 32 and 36 hours. All arterial blood gases were managed according to the alpha-stat method. The median time from ROSC to randomization was 133 (interquartile range 83 - 188) minutes. To include the admission blood gas (after ROSC, but before randomization) we timed this PaCO 2 value to one hour before T0; (T-1). PaCO 2 data were surveyed for physiological plausibility and in 4 of measurements we corrected a misplaced decimal point. Corrections were conducted by FE and NN in accordance with other data registered on the same patient. Outcome The primary outcome was overall neurological function at 6-month follow-up, using the Cerebral Performance Category (CPC)-Scale (CPC 1 good cerebral