Kevin O’Connor, MD
Anetsberger A, Gempt J, Blobner M, Ringel F, Bogdanski R, Heim M, Schneider G, Meyer B, Schmid S, Ryang YM, et al. Impact of Goal-Directed Therapy on Delayed Ischemia After Aneurysmal Subarachnoid Hemorrhage: Randomized Controlled Trial. Stroke. 2020;51:2287-2296.
Delayed cerebral ischemia (DCI) is one of the complications of aneurysmal subarachnoid hemorrhage (SAH) that can lead to increased morbidity and mortality. The risk of DCI is associated with the initial volume of hemorrhage and the extent of the neurologic injury. Anetsberger et al. conducted a randomized controlled trial to compare goal-directed hemodynamic therapy (GDHT) to standard clinical care in reducing the frequency of DCI in patients with aneurysmal SAH.
Treatment for both groups included enteral nimodipine, normothermia, euglycemia, electrolyte stability, and appropriate ventilation with similar systolic blood pressure (BP) and mean arterial pressure (MAP) goals before and after identified vasospasm. A transpulmonary thermodilution monitor was used in all patients to monitor hemodynamic variables such as cardiac output, ejection fraction, and extravascular lung water.
Regardless of the presence of vasospasm, the GDHT group received volume therapy according to a standardized algorithm (Supplemental Figure I). The study did not explicitly define standard clinical care, but it was noted that avoidance of hypovolemia and hyponatremia are recommended and that there is an absence of consensus guidance for achieving those goals.
The primary outcome was presence of DCI, defined as focal neurologic deficits and/or observed radiologic infarction with concomitant vasospasm. Functional outcome using the Glasgow Outcome Scale (GOS) was assessed 3-months after discharge.
The study (n = 108) used an intention-to-treat analysis to compare thermodilution data between the groups in three phases: early (before vasospasm), vasospasm onset, and late (after onset). Although there was no difference in the rates of vasospasm between the groups, DCI occurred in 13% of GDHT patients (7 of 54) and in 32% of controls (17 of 54; OR= 0.324 [95% CI, 0.11–0.86]; P=0.021). The benefit remained after adjustment for potentially confounding variables (age, sex, Hunt-Hess grade, surgical procedure, modified Fisher Scale, and World Federation of Neurosurgical Societies grade). No serious adverse events were reported because of GDHT. There was no difference between the two groups in ICU or hospital stay, pulmonary or cardiovascular events, or mortality. At three months, more patients had a low disability (GOS 5, minor or no deficits) in the GDHT group compared with the controls (66% versus 44%; P=0.025) with no difference in mortality.
A possible explanation for the beneficial effect of GDHT is the timing of fluid administration that helped achieve euvolemia and oxygen delivery prior to onset of vasospasm. The use of an algorithm, as in the GDHT group, helped direct volume therapy to achieve goals such as MAP. Additionally, vascular and neural changes such as microcirculatory dysfunction and impaired autoregulation may contribute to DCI independent of vasospasm. The approach will need to be tested in other settings.