Conditioning Effect of Inhalational Anesthetics on Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

Abstract

BACKGROUND Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) has been identified as an independent predictor of poor outcome in numerous studies. OBJECTIVE To investigate the potential protective role of inhalational anesthetics against angiographic vasospasm, DCI, and neurologic outcome in SAH patients. METHODS After Institutional Review Board approval, data were collected retrospectively for SAH patients who received general anesthesia for aneurysm repair between January 1st, 2010 and May 31st, 2018. Primary outcomes were angiographic vasospasm, DCI, and neurologic outcome as measured by modified Rankin scale at hospital discharge. Univariate and logistic regression analysis were performed to identify independent predictors of these outcomes. RESULTS The cohort included 390 SAH patients with an average age of 56 ± 15 (mean ± SD). Multivariate logistic regression analysis identified inhalational anesthetic only technique, Hunt-Hess grade, age, anterior circulation aneurysm and average intraoperative mean blood pressure as independent predictors of angiographic vasospasm. Inhalational anesthetic only technique and modified Fishers grade were identified as independent predictors of DCI. No impact on neurological outcome at time of discharge was noted. CONCLUSION Our data provide additional evidence that inhalational anesthetic conditioning in SAH patients affords protection against angiographic vasospasm and new evidence that it exerts a protective effect against DCI. When coupled with similar results from preclinical studies, our data suggest further investigation into the impact of inhalational anesthetic conditioning on SAH patients, including elucidating the most effective dosing regimen, defining the therapeutic window, determining whether a similar protective effect against early brain injury, and on long-term neurological outcome exists.

Sevoflurane and Desflurane Exposures Following Aneurysmal Subarachnoid Hemorrhage Confer Multifaceted Protection against Delayed Cerebral Ischemia

“…The key findings in our study are as follows: (1) both sevoflurane and desflurane conditioning provided strong protection against large artery vasospasm and microvessel thrombosis after SAH; and (2) sevoflurane and desflurane conditioning improved short-term neurological outcomes after SAH. These findings are important for three key reasons: (1) they provide additional evidence to the growing body of experimental literature indicating inhalational anesthetics as a conditioning agent class provide robust neurovascular protection in SAH; [12][13][14][15][16] (2) they show that the much more commonly used inhalational anesthetics, sevoflurane and desflurane, provide potent and multifaceted protection against DCI in SAH, very similar to that previously reported with isoflurane conditioning; [12][13][14][15][16] and (3) they provide preclinical support for the recently reported protective effect of sevoflurane and desflurane against angiographic vasospasm and DCI in SAH patients [30][31][32]. Given the pharmacologic advantages of sevoflurane and desflurane over isoflurane (e.g., the blood-gas and the oil-gas partition coefficient of isoflurane is significantly larger than that of sevoflurane and desflurane [25,26]-both of which lead to prolonged clinical emergence [19][20][21] from general anesthesia that can confound postprocedure neurological assessment), the very high usage rate of sevoflurane and desflurane in neurosurgical patients, and the proven safety track record of desflurane and sevoflurane in a wide variety of patients, the results from our study have relevant and meaningful implications for the care of SAH patients that deserve further investigation.…”

“…Several clinical studies, including our own, have suggested that desflurane exposure during aneurysm repair in SAH patients is associated with reduced incidence of angiographic vasospasm and DCI [30,31,36]. However, to date, no published preclinical studies have prospectively investigated this relationship.…”

Role of SIRT1 in Isoflurane Conditioning-Induced Neurovascular Protection against Delayed Cerebral Ischemia Secondary to Subarachnoid Hemorrhage

“…With respect to SAH-induced brain injury, SIRT1 has been linked to two of the most important forms of post-ictal secondary brain injury: EBI [34][35][36] and DCI [22]. In the case of anesthetic conditioning, there is a growing body of preclinical and clinical evidence indicating a strong protective effect of inhalational anesthetics against SAH-induced DCI [15,[37][38][39][40]. Milner et al [14] previously noted that isoflurane conditioning provides robust protection against multiple elements of DCI including improved neurologic outcomes in a mouse model of SAH.…”

Year in Review: Synopsis of Selected Articles in Neuroanesthesia and Neurocritical Care from 2021

“…Previous preclinical and clinical studies have shown that inhalational anesthetics were associated with reduced incidence of angiographic vasospasm and DCI. 13 Molecular mechanisms by which inhalational anesthetics provide this DCI protection include upregulation of hypoxia-inducible factor1-α7 and increased expression of endothelial nitric oxide synthase. 14 Similar protective effect with intravenous anesthetics is not known.…”