Study Protocol: The Effect of Blood Pressure on Cerebral Blood Flow in Comatose Out-of-hospital Cardiac Arrest Patients

Background Patients suffering out-of-hospital cardiac arrest (OCHA) have poor prognosis, and of the patients admitted to a hospital after return of spontaneous circulation, the 1 year survival is approximately 50% or lower. Anoxia during cardiac arrest and the subsequent reperfusion after resuscitation, affects the brain and other organs, and for patients admitted to an intensive care unit, the most frequent cause of death is hypoxic-ischemic brain injury. In the minutes after resuscitation, cerebral blood flow (CBF) increases markedly whereafter CBF is often reduced in the following 12 to 24 hours with regional differences whereby blood flow to some brain regions may be markedly reduced.

Mean arterial pressure (MAP) and cardiac output are often reduced following cardiac arrest due to myocardial dysfunction caused by ischemia-reperfusion injury, possible myocardial infarction that may have triggered the cardiac arrest, preexisting cardiac disease, and further, many patients develop a sepsis-like inflammatory response. Comatose survivors after cardiac arrest are generally cooled, intubated, and sedated using propofol that both lowers MAP and approximately halves both CBF and cerebral metabolic rate. Traditionally, CBF has been considered to be unaffected by changes in MAP between 60 to 150 mmHg by so-called cerebral autoregulation. Yet, CBF may be influenced by changes within this range of MAP and cerebral autoregulation is reported to be impaired in patients resuscitated after cardiac arrest whereby CBF becomes dependent on MAP.

Only limited data is available on the effect of MAP on CBF in OHCA patients. Cerebral oxygenation, as determined by near-infrared spectroscopy (NIRS), is unaffected by an increase in MAP from 65 to 85 mmHg using noradrenaline. However, evaluation of cerebral oxygenation using NIRS is affected by noradrenaline due to cutaneous vasoconstriction. In a similar study in anesthetized patients undergoing surgery, NIRS determined cerebral oxygenation was unaffected by an increase in MAP from 62 to 82 mmHg using noradrenaline whereas CBF increased by 15%.

Patients resuscitated after cardiac arrest are often hypotensive (generally defined as MAP < 60-65 mmHg) and hypotension is associated to poor neurologic outcome which may relate to reduced CBF and a larger degree of hypoxic-ischemic brain injury. It remains unclear, however, whether an increase in MAP using vasopressors such as noradrenaline, improves clinical outcome. Two small studies did not demonstrate any clear effect of maintaining MAP at 80-100 mmHg as compared to 65-75 mmHg on radiographic measurements or on biomarkers of neuronal damage. In clinical practice, a MAP of ≥ 65 mmHg is often aimed for, but it is unclear whether CBF and its metabolism may be increased by maintaining MAP at a higher level.

The study will include twenty comatose patients resuscitated after OCHA, due to a suspected or confirmed cardiac cause, and will be conducted within 2 days after resuscitation. The study will evaluate whether CBF and cerebral metabolism is affected by a short term increase in MAP to a level higher than that aimed for in clinical practice. MAP will be adjusted to 65, 80, and 95 mmHg in random order. Noradrenaline will be used as a tool to evaluate the effect of MAP as it has no direct effect on CBF.