Matt Harmon

160 Chapter eight 2.4 Therapeutic targeted mild hypercapnia (TTMH) From the AUC analysis, we extracted two PaCO 2 groups approximating PaCO 2 ranges employed by Eastwood et al, 4.5 - 6.0 kPa and 6.0 - 7.30 kPa and subdivided them according to target temperature (33°C and 36°C) in order to detect possible interactions between PaCO 2 and temperature in relation to outcome. 21 3. Analyses using a biomarker as outcome Association of PaCO 2 and s-Tau A nested cohort analysis was performed in 689 patients in a previous sub-study of the TTM-trial, evaluating s-Tau levels at 24, 48 and 72 hours after ROSC, showing the highest accuracy of predicting poor outcome after 6 months for peak s-Tau at 48 and 72 hours. 23 Therefore, we analyzed the association of PaCO 2 and peak s-Tau at these time points, employing the multivariable models used for our primary analyses. 4. Sensitivity analyses For sensitivity analysis we used the complete case cohort consisting of 485 patients (56%) with blood gas samples registered from all measuring points and the total case (n=939) cohort, including 100% of the patients, also those not surviving the full exposure period. Statistical considerations Proportions are expressed as percentages and continuous data as mean with standard deviations (SD). The association between PaCO 2 and neurological outcome was analyzed using logistic regression. Except for the maximum PaCO 2 and lowest pH analyses, all analyses were corrected for pre-specified, and relevant co-variates: age (years), sex (male/female), chronic heart failure (yes/no), asthma/ chronic obstructive pulmonary disease (yes/no), cardiac arrest witnessed (yes/ no), bystander CPR (yes/no), first rhythm shockable (yes/no), time to ROSC (minutes), GCS-Motor Score (1 versus 2 - 5), shock on admission (yes/no), pH at admission (units). Whether pooling of the two temperature groups was feasible was established by a term of interaction model between the PaCO 2 analysis groups and the two temperature groups. A significant term of interaction entailed subgroup analyses for the 33°C and the 36°C groups. A non-significant term of interaction entailed a combined group analysis.