Targeting two different levels of both arterial carbon dioxide and arterial oxygen after cardiac arrest and resuscitation: a randomised pilot trial.

Jakkula, Pekka; Reinikainen, Matti; Hästbacka, Johanna; Loisa, Pekka; Tiainen, Marjaana; Pettilä, Ville; Toppila, Jussi; Lähde, Marika; Bäcklund, Minna; Okkonen, Marjatta; Bendel, Stepani; Birkelund, Thomas; Pulkkinen, Anni; Heinonen, Jonna; Tikka, Tuukka; Skrifvars, Markus B

PURPOSE We assessed the effects of targeting low-normal or high-normal arterial carbon dioxide tension (PaCO2) and normoxia or moderate hyperoxia after out-of-hospital cardiac arrest (OHCA) on markers of cerebral and cardiac injury. METHODS Using a 23 factorial design, we randomly assigned 123 patients resuscitated from OHCA to low-normal (4.5-4.7 kPa) or high-normal (5.8-6.0 kPa) PaCO2 and to normoxia (arterial oxygen tension [PaO2] 10-15 kPa) or moderate hyperoxia (PaO2 20-25 kPa) and to low-normal or high-normal mean arterial pressure during the first 36 h in the intensive care unit. Here we report the results of the low-normal vs. high-normal PaCO2 and normoxia vs. moderate hyperoxia comparisons. The primary endpoint was the serum concentration of neuron-specific enolase (NSE) 48 h after cardiac arrest. Secondary endpoints included S100B protein and cardiac troponin concentrations, continuous electroencephalography (EEG) and near-infrared spectroscopy (NIRS) results and neurologic outcome at 6 months. RESULTS In total 120 patients were included in the analyses. There was a clear separation in PaCO2 (p < 0.001) and PaO2 (p < 0.001) between the groups. The median (interquartile range) NSE concentration at 48 h was 18.8 µg/l (13.9-28.3 µg/l) in the low-normal PaCO2 group and 22.5 µg/l (14.2-34.9 µg/l) in the high-normal PaCO2 group, p = 0.400; and 22.3 µg/l (14.8-27.8 µg/l) in the normoxia group and 20.6 µg/l (14.2-34.9 µg/l) in the moderate hyperoxia group, p = 0.594). High-normal PaCO2 and moderate hyperoxia increased NIRS values. There were no differences in other secondary outcomes. CONCLUSIONS Both high-normal PaCO2 and moderate hyperoxia increased NIRS values, but the NSE concentration was unaffected. REGISTRATION ClinicalTrials.gov, NCT02698917. Registered on January 26, 2016.