Cerebrovascular autoregulation ensures adequate perfusion of the brain when mean arterial blood pressure (MAP) is changed. According to Ohm's law (flow = pressure/resistance), with a decreased pressure, resistance is decreased to maintain the same flow. In cases of cardiac arrest, cerebral autoregulation may be disrupted and cerebral blood flow is compromised. Then, according to the aforementioned law, a higher mean arterial pressure is then required to maintain adequate cerebral perfusion.
Multiple small trials have investigated whether a higher MAP will result into a better outcome in the treatment of comatose survivors after cardiac arrest. These trials used a surrogate end points such as neuron-specific enolase rather than a well-defined patient-centered outcome. The results of these trial were neutral and all lacked the power for to detect a clinical outcome or to ensure safety.
The Carbon dioxide, Oxygen and Mean arterial pressure After Cardiac Arrest and REsuscitation (COMACARE) trial investigated the low-normal MAP (65-75 mmHg) compared to the high-normal MAP (80-100 mmHg) in relation to the serum concentration of neuron-specific enolase (NSE) at 48 h after cardiac arrest. The study included 120 patients and revealed that NSE concentration at 48 h after cardiac arrest was not different between the two groups [1].
In a study that was published in the European Heart Journal, the authors investigated whether an early goal directed hemodynamic optimization strategy (EGDHO); that involved targeting a MAP of 85-100 mmHg and SvO2 of 65-75%; could improve cerebral oxygenation, reduce anoxic brain damage, and improve outcome when compared with a MAP 65 mmHg strategy. The study included 112 out-of-hospital cardiac arrest patients and revealed that EGDHO improved cerebral oxygenation but did not improve the extent of anoxic brain damage or neurological outcome [2].
Grand et al. randomized 50 comatose patients with out-of-hospital cardiac arrest in a single center study to a mean arterial pressure target of 65 mm Hg or 72 mm Hg and measured biomarkers of organ injury including markers of endothelial integrity (soluble trombomodulin), brain damage (neuron-specific enolase), and renal function (estimated glomerular filtration rate). There was no difference in the biomarkers level between the two groups, however, there was a trend towards preserved renal functions in the higher MAP group [3].
The the Blood Pressure and Oxygenation Targets in Post Resuscitation Care (BOX) trial was recently published in NEJM and compared two different blood pressure targets on the clinical outcome in patients with out-of-hospital cardiac arrest. A total of 789 comatose adults after cardiac arrest 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). The primary outcome (a composite of death, disability, or coma within 90 days) 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). The study does not support the use of a higher blood pressure target in comatose patients after out-of-hospital cardiac arrest. However, there is a generalizability limitation of the study as it was conducted at only two centers in Denmark and included patients with a high prevalence of acute coronary syndrome and a relatively good prognosis based on risk factors on arrival at the hospital. Nevertheless, the study provides adequate support not to initiate a higher target of blood pressure unless further evidence proved otherwise [4].
REFERENCES
1. Jakkula P, et al; COMACARE study group. Targeting low-normal or high-normal mean arterial pressure after cardiac arrest and resuscitation: a randomised pilot trial. Intensive Care Med. 2018 Dec;44(12):2091-2101. doi: 10.1007/s00134-018-5446-8. Epub 2018 Nov 15. PMID: 30443729; PMCID: PMC6280836.
2. Ameloot K, et al. Early goal-directed haemodynamic optimization of cerebral oxygenation in comatose survivors after cardiac arrest: the Neuroprotect post-cardiac arrest trial. Eur Heart J. 2019 Jun 7;40(22):1804-1814. doi: 10.1093/eurheartj/ehz120. PMID: 30895296.
3. Grand J, et al. A randomised double-blind pilot trial comparing a mean arterial pressure target of 65 mm Hg versus 72 mm Hg after out-of-hospital cardiac arrest. Eur Heart J Acute Cardiovasc Care. 2020 Nov;9(4_suppl):S100-S109. doi: 10.1177/2048872619900095. Epub 2020 Jan 31. PMID: 32004081.
4. Kjaergaard J, et al. Blood-Pressure Targets in Comatose Survivors of Cardiac Arrest. N Engl J Med. 2022 Aug 27. doi: 10.1056/NEJMoa2208687. Epub ahead of print. PMID: 36027564.