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Hot Line - Balancing the risks and benefits of oxygenation and blood pressure levels in comatose patients with OHCA: Results from the BOX trial

Neurological injury and mortality remain high in comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA). Hypoxia and hypotension during post-resuscitation care have been associated with poor outcome, but the optimal levels of oxygenation and blood pressure (BP) are unknown.

Two Hot Line presentations yesterday discussed these pressing issues through the results of the BOX trial, which compared different targets for oxygenation and BP in the management of comatose OHCA survivors.

The 2x2 factorial investigator-initiated trial – carried out at two Danish high-volume cardiac arrest centres – enrolled 789 unconscious adult patients (Glasgow Coma Scale <8) who had return of spontaneous circulation for >20 minutes.1 All patients received standard-of-care management, including targeted temperature management (36 °C for 24 hours), sedation and multimodal neuro-prognostication. During intensive care unit stay, patients were randomised 1:1, in an open-label fashion, to restrictive (9–10 kPa) or liberal (13–14 kPa) arterial oxygen concentration (PaO2) during mechanical ventilation. Patients were also randomised 1:1, this time in a double-blind fashion, to one of two mean arterial BP targets (63 mmHg or 77 mmHg), which were maintained for the duration of invasive BP monitoring. The use of additional vasopressor or fluid therapy was at the discretion of the treating physician. The primary endpoint was a composite of death from any cause within 90 days or discharge from hospital in a poor neurological state (Cerebral Performance Category [CPC] 3 or 4), whichever occurred first.

Professor Jacob Moller (Odense University Hospital - Odense, Denmark) presented results from the comparison of restrictive and liberal oxygenation. The primary composite endpoint occurred in 32.0% of patients in the restrictive oxygen target group and 33.9% of patients in the liberal oxygen target group (hazard ratio [HR] 0.91; 95% CI 0.71 to 1.16; p=0.59). There were no differences between groups in the modified Rankin Scale, CPC or Montreal Cognitive Assessment (MoCA) score at 3 months.

Commenting on the results, Prof. Moller says: “BOX shows that targeting restrictive oxygenation in comatose patients resuscitated after OHCA does not alter survival or neurological outcome compared with targeting liberal oxygenation. The results suggest that oxygenation targets aiming at PaO2 between 9 and 14 kPa balance the risks of low and high oxygenation well.”

The results of BP targeting were presented by Doctor Jesper Kjaergaard (Copenhagen University Hospital Rigshospitalet - Copenhagen, Denmark). The primary composite endpoint occurred in 34% patients in the 77 mmHg group and in 32% in the 63 mmHg group (HR 1.08; 95% CI 0.84 to 1.37; p=0.56). Neuron-specific enolase levels at 48 hours were similar in the two groups. At 3 months, there were no differences in survival, modified Rankin Scale, CPC or MoCA scores.

Dr. Kjaergaard observes: “BP targets for comatose cardiac arrest survivors balance low afterload favouring cardiac recovery and sufficient perfusion pressure for the recovering brain. The BOX trial found no clinical benefit of a higher BP target versus a lower one. The results support guidelines on post-resuscitation care, which suggest maintaining a mean arterial BP of at least 65 mmHg.”2


1. Kjaergaard J, et al. Trials. 2022;23:177.

2. Nolan JP, et al. Intensive Care Med. 2021;47:369–421.

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.