Effect of oxygen targets on pulmonary hemodynamics after out-of-hospital cardiac arrest – A sub-study of the BOX cardiac arrest trial

Aim: Hypoxia may induce harmful effects in critically ill patients, potentially including pulmonary vasoconstriction. We aimed to assess the impact of two different oxygen targets on pulmonary hemodynamics in comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA). Furthermore, we assessed the prevalence of pulmonary hypertension in patients with OHCA and its association with outcome. Methods: Predefined, two-centre, prospective, double-blinded sub-study of the “Blood pressure and oxygenation targets after out-of-hospital cardiac arrest (BOX)”-trial. Patients were randomized to a restrictive oxygen target of a partial pressure of arterial oxygen (PaO₂) of 9–10 kPa or a liberal oxygen target of a PaO₂ of 13–14 kPa. Invasive hemodynamic assessment was recorded from pulmonary artery catheterization and serial blood-gas analyses for an initial 48 h. The primary endpoint was the difference in pulmonary vascular resistance (PVR) within 48 h between oxygen groups using linear mixed models for repeated measures. Results: Among 789 randomized patients, 730 (93%), who had right heart catheterization, were included in this sub-study. At admission, the median PVR, mean pulmonary artery pressure (mPAP), and pulmonary artery pulsatility index (PAPi) were 2.4 wood unit (WU) (95% CI, 1.7–3.4), 25 mmHg (95% CI, 21–30) and 1.3 (95% CI, 0.8–1.8), respectively. The average PVR in the liberal oxygen group was comparable to that of the restrictive group (mean difference 0.05 WU, 95% CI, −0.09 to 0.18, p = 0.50). mPAP, PAPi, and right atrial pressure did not differ between groups (p > 0.05). The adjusted odds ratio for one-year mortality increased progressively and linearly over a wide mPAP range. Compared with mPAP < 20 mmHg, pulmonary hypertension (mPAP > 30 mmHg) was associated with an increased risk of mortality (OR = 4.2; 95% CI, 2.0–9.2, p < 0.001). Conclusion: Pulmonary hypertension is an independent risk factor for mortality in comatose resuscitated patients after OHCA. However, a restrictive oxygen strategy aiming at a PaO₂ of 9–10 kPa during post-resuscitation critical care was not associated with a higher PVR or deterioration of right ventricular function compared to a liberal oxygen strategy.