Delayed cerebral ischemia prevention

Local intraparenchymal neuromonitoring in the anterior cerebral artery/middle cerebral artery watershed area might detect the vast majority of delayed cerebral ischemias for all intracranial aneurysm locations, except for basilar artery aneurysms. In ACA and AcomA aneurysms, bilateral DCI of the ACA territory was common, and bilateral probe positioning might be considered for monitoring high-risk patients. Non-focal monitoring methods might be preferably used after BA aneurysm rupture 1).

The calcium channel blocker nimodipine remains the only therapeutic intervention proven to improve functional outcomes after SAH. The recent failure of the drug clazosentan to improve functional outcomes despite reducing vasoconstriction has moved the focus of research into DCI away from cerebral artery constriction towards a more multifactorial aetiology. 2).

Nimodipine and induced hypertension using vasopressors are an integral part of standard therapy. Consequences of the opposite effect of nimodipine and vasopressors on blood pressure on patient outcome remain unclear 3).

Aggressive therapy combining hemodynamic augmentation, transluminal balloon angioplasty, and intra-arterial infusion of vasodilator drugs is, to varying degrees, usually implemented. A panoply of drugs, with different mechanisms of action, has been studied in SAH related vasospasm. Currently, the most promising are magnesium sulfate, 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, nitric oxide donors and endothelin-1 antagonists 4).

Early goal directed fluid therapy (EGDT) is beneficial for reducing DCI and improving postoperative functional outcome in patients with poor clinical grade 5).

Current treatment guidelines to prevent delayed cerebral ischemia is limited to oral nimodipine, maintenance of euvolemia, induction of hypertension if ischemic signs occur and endovascular therapy for patients with continued ischemia after induced hypertension. Future investigations will involve agents targeting vasodilation, anticoagulation, inhibition of apoptosis pathways, free radical neutralization, suppression of cortical spreading depolarization and attenuation of inflammation 6).

Metaanalysis indicated that the use of statins decreases the occurrence of cerebral vasospasm, whereas did not support a beneficial effect of statins on the occurrence of delayed ischemic neurological deficit (DIND), death or poor neurological outcomes in patients with aneurysmal SAH 7).

Volume expansion and hypertension are widely used for the hemodynamic management of patients with subarachnoid hemorrhage to prevent delayed cerebral ischemia.

For small, unruptured, unprotected intracranial aneurysms in SAH patients, the frequency of aneurysm rupture during Vasopressor-induced hypertension (VIH) therapy is rare. Reynolds et al. do not recommend withholding VIH therapy from these patients 8).

A randomized pilot trial using a 2-way factorial design allocating patients within 72 hours of subarachnoid hemorrhage to either normovolemia (NV) or volume expansion (HV) and simultaneously to conventional (CBP) or augmented blood pressure (ABP) for 10 days. The study endpoints were protocol adherence and retention to follow-up. The quality of endpoints for a larger trial were 6-month modified Rankin Scale score, comprehensive neurobehavioral assessment, delayed cerebral ischemia, new stroke, and discharge disposition.

This pilot study showed adequate feasibility and excellent retention to follow-up. Given the suggestion of possible worse neurobehavioral outcome with ABP, a larger trial to determine the optimal blood pressure management in this patient population is warranted. ( NCT01414894.) 9).

Hurth H, Steiner J, Birkenhauer U, Roder C, Hauser TK, Ernemann U, Tatagiba M, Ebner FH. Relationship of the vascular territory affected by delayed cerebral ischemia and the location of the ruptured aneurysm in patients with aneurysmal subarachnoid hemorrhage. Neurosurg Rev. 2021 Mar 29. doi: 10.1007/s10143-021-01522-4. Epub ahead of print. PMID: 33782797.
Rowland MJ, Hadjipavlou G, Kelly M, Westbrook J, Pattinson KT. Delayed cerebral ischaemia after subarachnoid haemorrhage: looking beyond vasospasm. Br J Anaesth. 2012 Sep;109(3):315-29. doi: 10.1093/bja/aes264. PMID: 22879655.
Paľa A, Schick J, Klein M, Mayer B, Schmitz B, Wirtz CR, König R, Kapapa T. The influence of nimodipine and vasopressors on outcome in patients with delayed cerebral ischemia after spontaneous subarachnoid hemorrhage. J Neurosurg. 2019 Mar 8:1-9. doi: 10.3171/2018.11.JNS182891. [Epub ahead of print] PubMed PMID: 30849754.
Keyrouz SG, Diringer MN. Clinical review: Prevention and therapy of vasospasm in subarachnoid hemorrhage. Crit Care. 2007;11(4):220. Review. PubMed PMID: 17705883; PubMed Central PMCID: PMC2206512.
Mutoh T, Kazumata K, Terasaka S, Taki Y, Suzuki A, Ishikawa T. Early intensive versus minimally invasive approach to postoperative hemodynamic management after subarachnoid hemorrhage. Stroke. 2014 May;45(5):1280-4. doi: 10.1161/STROKEAHA.114.004739. Epub 2014 Apr 1. PubMed PMID: 24692480.
Serrone JC, Maekawa H, Tjahjadi M, Hernesniemi J. Aneurysmal subarachnoid hemorrhage: pathobiology, current treatment and future directions. Expert Rev Neurother. 2015 Feb 26:1-14. [Epub ahead of print] PubMed PMID: 25719927.
Zhu RL, Chen ZJ, Li S, Lu XC, Tang LJ, Huang BS, Yu W, Wang X, Qian TD, Li LX. Statin-treated patients with aneurysmal subarachnoid haemorrhage: a meta-analysis. Eur Rev Med Pharmacol Sci. 2016 May;20(10):2090-8. PubMed PMID: 27249609.
Reynolds MR, Buckley RT, Indrakanti SS, Turkmani AH, Oh G, Crobeddu E, Fargen KM, El Ahmadieh TY, Naidech AM, Amin-Hanjani S, Lanzino G, Hoh BL, Bendok BR, Zipfel GJ. The safety of vasopressor-induced hypertension in subarachnoid hemorrhage patients with coexisting unruptured, unprotected intracranial aneurysms. J Neurosurg. 2015 Oct;123(4):862-71. doi: 10.3171/2014.12.JNS141201. Epub 2015 Jul 24. PubMed PMID: 26207606.
Togashi K, Joffe AM, Sekhar L, Kim L, Lam A, Yanez D, Broeckel-Elrod JA, Moore A, Deem S, Khandelwal N, Souter MJ, Treggiari MM. Randomized Pilot Trial of Intensive Management of Blood Pressure or Volume Expansion in Subarachnoid Hemorrhage (IMPROVES). Neurosurgery. 2015 Feb;76(2):125-35. doi: 10.1227/NEU.0000000000000592. PubMed PMID: 25549192.
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