The BOX Trial: Do Higher Blood Pressure Targets After Cardiac Arrest Improve Outcomes?

After cardiac arrest, therapeutic protocols typically target mean arterial blood pressure (MAP) >65 mm Hg to ensure adequate end-organ perfusion,1 with some suggesting that an even higher target of 75 mm Hg is needed to maintain cerebral blood flow.2 However, previous studies have been limited by their observational nature or small sample sizes, and there has been insufficient evidence to support specific hemodynamic goals during post–cardiac arrest care.

The BOX (Blood Pressure and OXygenation Targets After OHCA) trial enrolled 789 patients who were in comas following resuscitation after out-of-hospital cardiac arrest.3 Those with suspected intracranial bleed or stroke were excluded. Patients were randomized to either a high-MAP group of 77 mm Hg or a low-MAP group of 63 mm Hg. Target MAPs were achieved using a three-stage protocol that prioritized volume resuscitation, followed by norepinephrine infusion, and lastly dopamine infusion. Both participants and investigators were blinded, and the primary outcome was measured as death or hospital discharge with severe disability or a persistent vegetative state. There was no significant difference between groups at 90 days, with 34% versus 32% of patients in the high- and low-MAP groups, respectively, meeting the primary outcome (hazard ratio, 1.08; 95% confidence interval, 0.84-1.37). Furthermore, there was no significant difference in outcomes among major subgroups, including those with known hypertension.

In this large, double-blinded, randomized controlled trial, targeting higher MAPs in patients who are in comas after cardiac arrest did not improve clinical outcomes. Furthermore, there was no significant difference seen in a subset of patients with pre-existing hypertension. Adverse event rates were similar for both groups. These findings may help guide post-resuscitation care and provide evidence that a higher MAP goal does not provide any clinical benefit compared with a standard target of 63 mm Hg.


  1. Nolan JP, Sandroni C, Böttiger BW, et al. European Resuscitation Council and European Society of Intensive Care Medicine guidelines 2021: post-resuscitation care. Resuscitation 2021;161:220-69.
  2. Ameloot K, Meex I, Genbrugge C, et al. Hemodynamic targets during therapeutic hypothermia after cardiac arrest: a prospective observational study. Resuscitation 2015;91:56-62.
  3. Kjaergaard J, Møller JE, Schmidt H, et al. Blood-pressure targets in comatose survivors of cardiac arrest. N Engl J Med 2022;387:1456-66.

Clinical Topics: Arrhythmias and Clinical EP, SCD/Ventricular Arrhythmias, Prevention

Keywords: ESC Congress, ESC22, Norepinephrine, Sample Size, Patient Discharge, Dopamine, Confidence Intervals, Out-of-Hospital Cardiac Arrest, Blood Pressure, Perfusion, Randomized Controlled Trials as Topic, Observational Studies as Topic

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