Matt Harmon

167 Chapter eight Table 4. Results of the peak s-Tau nested cohort analysis for the employed multivariable models. Multivariable model Estimate CI P-value Hypocapnia vs non-hypocapnia* 1.07 0.73 – 1.57 0.71 Hypocapnia vs normocapnia* 1.37 0.45 – 4.15 0.57 Hypercapnia vs non-hypercapnia* 0.68 0.42 – 1.10 0.12 Hypercapnia vs normocapnia* 1.00 0.38 – 2.64 1.00 Amplitude** 1.04 0.91 – 1.20 0.53 AUC, all values** 1.08 0.83 – 1.42 0.56 AUC, first four values** 0.94 0.76 – 1.17 0.59 TTMH Mild hypercapnia vs normocapnia* 0.75 0.43 – 1.28 0.29 CI = 95% Confidence Interval. S-Tau = Serum Tau. AUC = Area under curve. TTMH = Therapeutic Targeted Mild Hypercapnia. For analyses of categorical data* the estimate indicates how many times higher the s-Tau is compared to reference group. For analyses of continuous data** the estimate indicates how much higher s-Tau is per 1kPa PaCO 2 increase. analysis were non-significant (Pinteraction = 0.11–0.83). Complete results are displayed in Table 4. Both sensitivity analyses revealed similar results as the analyses on the imputed dataset, for the complete sample cohort with 485 patients (P = 0.32-0.96) and the all-patient cohort with 939 patients (P = 0.15- 0.98). For details concerning the sensitivity analyses, see Supplementary Table 3 and 4, Additional File 1. Discussion In this exploratory sub-study of the TTM-trial, dyscarbia after ROSC was frequent. We were not able to detect a statistically significant association between hypercapnia, hypocapnia, PaCO 2 -AUC or ∆PaCO 2 and neurological outcome. There was no significant interaction between temperature group and carbon dioxide level in relation to outcome. PaCO 2 was not associated with peak s-Tau levels after 48 or 72 hours after randomization. Our results differ from a prospective single-center study by Roberts et al including 193 post cardiac arrest patients, suggesting an independent association between hypocapnia and hypercapnia and poor neurological function at hospital discharge. 17 In contrast to our study Roberts et al included mainly patients after in-hospital cardiac arrest and used TTM in 6 patients only. 17 Dyscarbia was less common compared to the present study (69% versus 96%). Our results also differ from database study by Schneider et al, analyzing PaCO 2 values of 16542 patients admitted after cardiac arrest showing a higher likelihood of discharge home for the group of patients exposed to hypercapnia after ROSC compared to normocapnia