Impact of oxygenations targets on inflammation after out-of-hospital cardiac arrest in males and females - a substudy of the BOX trial

Patients resuscitated after out-of-hospital cardiac arrest (OHCA) will often be in a coma at hospital admittance. Accordingly, the majority of these patients will be admitted to the ICU and mechanically ventilated. In the Blood Pressure and Oxygenation Targets in Post Resuscitation Care (BOX) trial, patients were randomized to a restrictive or liberal oxygen target during the initial period of mechanical ventilation. While the BOX trial found no differences in survival according to oxygenation targets, the higher or lower oxygen availability and related differences in ventilator settings, may affect both local inflammation in the lungs as well as systemically, and responses may vary between females and males.

To evaluate the impact of a liberal or restrictive oxygenation target after cardiac arrest, and whether the response is similar for females and males.

This investigation reports on the oxygen target intervention from the BOX trial (NCT03141099), in which comatose OHCA patients were randomized at hospital admission to three different interventions in parallel: a restrictive (9-10kPa) or liberal oxygenation (13-14kPa) target, as well as a lower or higher blood pressure target, and a shorter or longer duration of device based fever prevention. All patients were sedated and ventilated for a minimum of 24 hours after randomization. Systemic inflammation was assessed by CRP and measured at 0, 24, 48, and 72 hours. Survival status was assessed at 1 year.

The trial included 789 patients, with 19% being females and 81% males. Overall, the time to ROSC was a median of 18 minutes (IQR 12–26), and 64% of patients were alive at 1 year. There were no differences in CRP at 24 or 48 hours according to oxygenation target for the total cohort. When assessing females and males separately, a statistically significant difference at 24 hours were found for females but not males (See figures). Females randomized to a restrictive oxygenation target had lower CRP at 24 hours compared to a liberal oxygenation target (p=0.02).

A restrictive versus a liberal oxygenation target did not affect systemic inflammatory response, neither when assessing the total cohort or in males selectively. However, females randomized to a restrictive oxygenation target had a lesser systemic inflammatory response at 24 hours, compared to a liberal target. The mechanism behind this is unknown, and while this could be a chance finding, it is possible that physiologic responses in males and females differ when a higher or lower PaO2 is targeted, either related to oxygen availability, or due to the associated differences in ventilator settings including the fraction of inspired oxygen and positive end expiratory pressure.Fig. 1

, CRP shown for all patients