Matt Harmon

168 Chapter eight or hypocapnia 16. As in our study, dyscarbia after ROSC was common. However, important confounders on background information on the nature of cardiac arrest (initial rhythm, time to ROSC etc.) were not available and, apart from a nested cohort analysis, only single PaCO 2 values were analyzed. With exception of the CCC-trial21, randomizing to different targets of PaCO 2 , we are only aware of one study analyzing multiple PaCO 2 values over time during the post cardiac arrest phase. 20 This prospective observational study, including 409 OHCA patients, analyzed serial blood gases during the first 24 hours after ROSC and found that exposure to a moderately increased PaCO 2 level was an independent predictor for good outcome at 12 months. We chose a comparable approach in our analysis of PaCO 2 -AUC, but could not confirm this finding. In their study, blood gases were analyzed by either alpha- or pH-stat20, while the blood gas management method employed in our study was exclusively alpha-stat. The solubility of carbon dioxide in blood is temperature dependent and might influence the ventilation strategy. Ventilation has, via the coupling of CO 2 and cerebral vascular tone, influence on CBF in OHCA patients treated with TTM.31 Voicu et al showed a significant difference in PaCO 2 , arterial pH and CBF when alpha-stat was compared to pH- stat .31 These findings might identify a source of error in studies using mixed blood gas management32, and when comparing studies using different methods, which might explain the deviance of our results from other studies. pH was in our study independently associated with neurological outcome whereas maximum PaCO 2 was not. This confirms previous findings that pH is an independent outcome predictor after ROSC. 33,34 Our study does not indicate benefit of TTMH as investigated by Eastwood et al21, but also no harm. It is imperative to appreciate that we, in contrast to the pilot CCC-trial21, compared time weighted mean PaCO 2 values (observed, non-targeted PaCO 2 ), while the CCC-trial randomized patients to specific PaCO 2 ranges (prescribed, targeted PaCO 2 ). Additionally, we widened the mild hypercapnia group for our analysis to 6.0 – 7.30 kPa for increased robustness of our results. Whether TTMH is indeed beneficial remains to be proven in a definitive clinical trial. 21 Importantly, there was no significant interaction between temperature level and PaCO 2 in terms of outcome, supporting the possibility to co-enroll in trials investigating carbon dioxide and temperature targets. 22 The effects of PaCO 2 on biomarkers have to date only been evaluated in the above mentioned CCC-trial where mild hypercapnia reduced NSE and S100B (S100 calcium-binding protein B) levels. 21 In our cohort, PaCO 2 showed no association with peak s-Tau levels, which is in line with the lack of association between PaCO 2 and neurological outcome in our study. We have previously reported that s-Tau is superior to NSE in predicting outcome and that S-100 does not add to a prediction model including NSE and clinical information. 23,35