Authors: Roberts BW, Kilgannon JH, Hunter BR, et al. Association Between Elevated Mean Arterial Blood Pressure and Neurologic Outcome After Resuscitation From Cardiac Arrest: Results From a Multicenter Prospective Cohort Study. Critical Care Medicine. 47(1):93–100.
Reviewed by: Lara L. Zimmermann, MD, Co-Director, Neurocritical Care Service, Assistant Professor of Neurological Surgery and Neurology, UC Davis School of Medicine
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Targeted temperature management (TTM) to 32-36 degrees Celsius is recommended in comatose adults following return of spontaneous circulation (ROSC) after cardiac arrest to improve neurological outcomes. Post-cardiac arrest hypotension is associated with increased mortality and worse neurological function, and avoiding and immediately correcting hypotension during post-resuscitation care is generally standard practice. While we do know that cerebrovascular pressure autoregulation may be disrupted in the hours following ROSC, the optimal blood pressure to minimize ongoing brain injury is undetermined. In this study, authors examined the relationship between early elevated mean arterial blood pressure (MAP) and neurological outcome after resuscitation from cardiac arrest. Following IRB approval, authors performed a retrospective analysis of prospectively collected data across six hospitals in the United States. Adult patients who experienced in- and out-of-hospital cardiac with ROSC > 20 minutes who remained comatose and were candidates for TTM were dichotomized into two groups: MAP 70-90 mmHg and MAP > 90 mmHg. Patients with persistent hypotension (MAP < 70) during the initial six hours after ROSC were excluded due to known association with worse outcomes. Mean arterial blood pressure was measured non-invasively immediately after ROSC and then hourly for six hours. The primary outcome was good neurologic function at hospital discharge, defined as a modified Rankin Scale (mRS) <= 3, or individuals requiring some help but able to walk without assistance. Secondary outcomes were survival to hospital discharge and good early neurologic response, defined as Full Outline of UnResponsiveness (FOUR) score > six at 72 hours. Conflicts of interest were declared, and none evident.
The prospective cohort included 280 patients. Eleven patients were excluded due to MAP < 70 mmHg, leaving 269 subjects in the cohort analyzed. In the entire cohort, the mean MAP was 95 +/- 15 mmHg and 59 percent of subjects had a MAP > 90 mmHg during the initial six hours after ROSC. The primary outcome, good neurological function at hospital discharge, occurred in 30 percent of patients overall and was significantly higher in patients with a MAP > 90 mmHg (42 percent) as compared with a MAP 70-90mmHg (15 percent) (absolute difference, 27 percent; 95 percent CI 17-37 percent). Additionally, the mean MAP was significantly higher for subjects with a good neurological outcome at hospital discharge (101 +/- 14 mmHg vs. 93 +/- 14 mmHg, p<0.001). In a multivariable Poisson regression model adjusting for potential confounders, MAP > 90 mmHg was associated with good neurological function (adjusted RR 2.46; 95 percent CI 2.09 – 2.88). Also, over increasing ranges of MAP, there was a dose-response increase in likelihood of good neurological outcome. A MAP > 110 mmHg had the strongest association with good neurological outcome (adjusted RR 2.97; 95 percent CI 1.86 – 4.76) and for each additional hour with MAP > 90 mmHg there was a 15 percent increase in the probability of good neurological outcome (adjusted RR 1.15; 95 percent CI 1.11 – 1.18, P=0.001). The association between MAP > 90 mmHg and good neurologic outcome was significantly stronger in subjects with a history of hypertension compared to those without hypertension. Secondary outcomes analyzed revealed that a MAP > 90 mmHg was associated with good early neurological response (RR 1.36; 95 percent CI 1.17 -1.58) and increased survival to hospital discharge (RR 1.90; 1.64 – 2.20). A higher proportion of patients with MAP 70-90 mmHg had withdrawal of life support (58 percent versus 35 percent, P<0.001). Among patients who survived to hospital discharge, MAP > 90 mmHg, remained an independent predictor of good neurological outcome (RR, 1.36; 95 percent CI 1.08 – 1.72).
This study revealed that an elevated mean arterial blood pressure (MAP > 90 mmHg) during the early period (six hours) after resuscitation from cardiac arrest is independently associated with good neurological function at hospital discharge. This relationship was dose dependent with longer duration of exposure to higher MAPs being more strongly associated with good neurological outcome, which adds weight to a causative relationship between these associated factors. Subgroup analysis revealed this relationship held true for both in- and out-of-hospital cardiac arrest victims with both shockable and non-shockable rhythms and was independent of vasopressor administration. The relationship between MAP and neurological outcome was strongest for patients with a history of hypertension. These results suggest that brain injury is ongoing in the early hours after resuscitation from cardiac arrest and that the optimal blood pressure target to minimize secondary brain injury may be both patient specific and higher than the current 2015 American Heart Association recommendations (SBP > 90 mmHg, MAP > 65 mmHg). These data suggest that thinking beyond targeted temperature management and optimizing hemodynamics targets after cardiac arrest is necessary to minimize secondary brain injury and improve neurological outcomes. Limitations of this study include the design, which is a retrospective analysis of prospectively collected data and precludes drawing any conclusions about cause and effect of mean arterial pressure on neurological outcome. A prospective randomized controlled study is needed to determine if targeting an elevated blood pressure improves neurological outcomes after cardiac arrest.
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