BOX Trial (MAP)

NEJM

August 27, 2022

Blood-Pressure Targets in Comatose Survivors of Cardiac Arrest

Summarized by: 

Mazen Kherallah

What was the research question?

  • Is a higher mean arterial pressure (MAP) (77 mm Hg) superior in preventing death or severe anoxic brain injury in comatose survivors of out-of-hospital cardiac arrest compared to a lower MAP or lower (63 mm Hg)?

How did they do it?

  • Double-blind, dual-center, randomized trial with a 2-by-2 factorial design in Denmark.

  • A total of 789 comatose adults who had been resuscitated after an out-of-hospital cardiac arrest of presumed cardiac cause were randomized to receive a mean arterial blood-pressure target of 77 mm Hg (high-target group: 393 patients) or 63 mm Hg (low-target group: 396 patients).

  • Patients were also assigned to one of two oxygen targets and results were reported separately.

  • The primary outcome was a composite of death from any cause or hospital discharge with a Cerebral Performance Category (CPC) of 3 or 4 within 90 days.

  • Secondary outcomes included neuron-specific enolase levels at 48 hours, death from any cause, scores on the Montreal Cognitive Assessment, modified Rankin scale at 3 months, and the CPC at 3 months.

What did they find?

  • The primary-outcome was not significantly different in the high-target group compared to the lower-target group (34% vs 32%, hazard ratio, 1.08; 95% confidence interval [CI], 0.84 to 1.37; P=0.56).

  • At 90 days, mortality was not different between the two groups (31% vs 29%, hazard ratio, 1.13; 95% CI, 0.88 to 1.46).

  • In both groups, the median CPC was 1; the corresponding median modified Rankin scale scores were 1, and the corresponding median Montreal Cognitive Assessment scores were 27 in the high-target group compared to 26 in the low-target group. The median neuron-specific enolase level at 48 hours was similar in the two groups.

  • Adverse events were not significantly different between the groups.

Are there any limitations?

  • The mean difference in blood pressure between the groups is 10.7 mm Hg which is lower than the expected value of 14 mm Hg (77 vs 63). However, this difference is clinically significant and was associated with a significantly higher use of vasopressors in the high-target group.

  • Follow up was a challenge due to COVID restriction.

  • Generalizability may be affected as the trial was conducted at two centers only and included a population of patients with a high prevalence of acute coronary syndrome and a relatively good prognosis based on risk factors on arrival at the hospital.

What does it mean?

  • In resuscitated patients after cardiac arrest, targeting a higher MAP did not result in a better percentage of death, severe disability, or coma.

  • No need to target MAP higher than 65 mm Hg in post cardiac arrest patients.

BOX Trial (MAP)