Appropriate Blood Pressure Target Unclear Among Comatose Patients

There is no significant difference in rates of mortality or poor neurological outcomes at discharge between patients who are comatose with low blood pressure target vs those with a high blood pressure target.

Among patients who had been resuscitated after experiencing an out-of-hospital cardiac arrest, targeting a mean arterial blood pressure of 77 mm Hg, compared with a mean arterial blood pressure of 63 mm Hg, was not associated with significantly different percentages of patients dying, or having severe disability or coma, according to study findings published in The New England Journal of Medicine.

The Blood Pressure and Oxygenation Targets in Post Resuscitation Care trial (BOX; ClinicalTrials.gov Identifier: NCT03141099) was an open-label, investigator-initiated, randomized trial with a 2-by-2 factorial design in which patients who are comatose who had experienced out-of-hospital cardiac arrest were assigned to 1 of 2 target blood pressures, as well as to either a restrictive or a liberal oxygen target. The portion of BOX regarding blood pressure targets is reported herein.

Currently, evidence supporting the selection of blood-pressure targets for the treatment of patients who are comatose after out-of-hospital cardiac arrest who are receiving intensive care is limited. This prompted the researchers to conduct the BOX trial, in which they explored whether a higher target mean arterial blood pressure (ie, 77 mm Hg) or lower target mean arterial blood pressure (ie, 63 mm Hg) would be superior in the prevention of death or severe anoxic brain injury among these patients who are comatose.

The trial used a 2×2 factorial design in patients who had experienced an out-of-hospital cardiac arrest of presumed cardiac cause. The primary study 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 (range, 0 to 5, with higher categories indicative of more severe disease). A CPC score of 3 or 4 is indicative of severe disability or coma.

… [N]o significant difference in the percentage of patients who died or were discharged from the hospital with a poor neurologic outcome (CPC of 3 or 4) within 90 days [was demonstrated].

Secondary outcomes included neuron-specific levels of the enzyme enolase at 48 hours, death from any cause, score on the Montreal Cognitive Assessment scale (range, 0 to 30, with higher scores indicative of better cognitive ability) at 3 months, score on the modified Rankin scale (range, 0 to 6, with higher scores indicative of greater disability) at 3 months, and CPC at 3 months.

A total of 789 patients aged 18 years and older were enrolled in the study — 393 in the high-target group and 396 in the low-target group. Study randomization was conducted from March 2017 through December 2021 at 2 tertiary cardiac arrest centers in Denmark. Participants who had been resuscitated after an out-of-hospital cardiac arrest with a presumed cardiac cause were eligible for study inclusion if they had experienced a sustained return of spontaneous circulation (ie, no chest compressions for more than 20 minutes) and remained comatose (ie, unable to obey verbal commands) on arrival at the hospital.

The researchers found that a primary-outcome event occurred in 34% (133 of 393) of participants in the high-target group and in 32% (127 of 396) of those in the low-target group (hazard ratio [HR], 1.08; 95% CI, 0.84-1.37; P =.56). At 90 days, 31% (122 of 393) of participants in the high-target group and 29% (114 of 396) of those in the low-target group had died (HR, 1.13; 95% CI, 0.88-1.46).

The median CPC was 1 (range, 1 to 5) in both the high-target arm and the low-target arm. Further, the median modified Rankin scale scores were 1 (range, 0 to 6) vs 1 (range, 0 to 6) in the high-target group and low-target group, respectively. Median Montreal Cognitive Assessment scores were 27 (range, 24 to 29) and 26 (range, 24 to 29) in the high-target arm and low-target am, respectively. Additionally, the median neuron-specific enolase level at 48 hours was similar in both groups. No significant difference in the percentage of patients with adverse events was observed between the groups.

Limitations of the study warrant mention. The mean difference in blood pressure between the 2 groups was 10.7 mm Hg, which was lower than the expected value of 14 mm Hg. The findings from the trial cannot be extrapolated to blood-pressure targets that are higher or lower than those used herein. Further, because of COVID-19 restrictions, the number of patients available for follow-up visits and evaluation of cognitive testing was lower than anticipated. The number of blood samples in the biobank was lower than expected as well.

According to the researchers, “…no significant difference in the percentage of patients who died or were discharged from the hospital with a poor neurologic outcome (CPC of 3 or 4) within 90 days [was demonstrated]. The results were consistent in the prespecified subgroups.”

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

References:

Kjaergaard J, Møller JE, Schmidt H, et al. Blood-pressure targets in comatose survivors of cardiac arrest. N Engl J Med. 2022;387(16):1456-1466. doi:10.1056/NEJMoa2208687