治療蛛網膜下腔出血後引起的血管痙攣——綜說

Treatment of Cerebral Vasospasm after Subarachnoid Hemorrhage-- A Review

血管痙攣所引起的延遲性大腦局部缺血，是造成蛛網膜下腔出血病人死亡和失能最主要因素。若不予以治療，將造成17～40％以上的病人死亡，或有永久性的神經缺陷。臨床上診斷大腦血管痙攣，主要是根據病人的臨床症狀，如意識改變（嗜睡和意識混亂）、或是出現新的局部神經缺陷。此外，可能伴隨有頭痛加劇、假性腦脊隨膜炎和發燒等症狀。雖然經過了30多年的努力，在確認病人是否處於危險狀態、血管痙攣的可能機轉及處置上有很大的進步。然而，仍未能提供一個確切的治療方法，主要是我們對於這個複雜疾病得病理機轉理解仍是有限的。目前臨床證實口服專一性的鈣離子阻斷劑-nimodipine，可以有效地預防血管痙攣和改善其神經症狀。而常用的支持性療法，如triple H療法，主要藉由大量的靜脈注射體積擴張液，使得血液容積增加，進而使血壓升高和心輸出量增加，以提供足量的血流通過腦血管狹窄的區域。然而，目前仍未有足夠的證據顯示，它有正面的意義。許多醫學中心已將氣球血管修復術和化學的血管修復術（合併非常專一性的動脈內注射血管擴張劑），作為內科療法無法處理和控制的血管痙攣的主要治療方式，甚至將其視為預防性處理血管痙攣及緊急狀況的第一線治療方式。此外目前較有展望的治療方法包括硫酸鎂、fasudil鹽酸化合物、tirilazad mesylate、紅血球生成素和誘導的低體溫等，然而仍需更進一步的臨床證實。近年來，內皮細胞衍化的媒介物、血管平滑肌衍化的媒介物、血腦障蔽崩解有關的發炎前媒介物、細胞激素和黏著的分子、壓力引起的基因活化和血小板衍化的生長因子等有媒介物，已被確認和蛛網膜下腔出血引起的腦部血管痙攣有關。在許多實驗中，已證實阻斷這些媒介物，可以有效的治療或減少血管痙攣。然而，仍需更進一步的臨床試驗，才能證實這些理論和運用於臨床治療。

Delayed cerebral ischemia as a result of cerebral vasospasm is the most common cause of death and disability after aneurysmal subarachnoid hemorrhage (SAH). It leads to death or permanent neurologic deficits in over 17-40% of SAH patients. The initial and main symptom of cerebral vasospasm is diffuse headache and may be accompanied with a slight increase in discomfort from neck stiffness and fever. The clinical diagnosis of cerebral vasospasm is made when the patient experiences an altered level of consciousness or a new focal neurologic deficit. There has been a great progress in identifying the patients at risk, putative mechanisms, and possible treatment options for cerebral vasospasm. However, the problem is by no means solved, mainly due to a limited understanding of the pathologic mechanisms of this complex disease. The iatrogenic factors that can increase the risk of cerebral vasospasm include prolongation of the subarachnoid clot by antifibrinolytic drugs, hypotension, inappropriate treatment of hyponatremia, hypovolemia, hyperthermia and increased intracranial pressure. Nimodipine has been shown to improve neurologic outcome and decrease the incidence of cerebral vasospasm. Triple H therapy is a treatment designed to augment cerebral blood flow for patient with cerebral vasospasm. Hypervolemic hypertension is induced with intravenous volume expansion with crystalloid or colloid to increase cardiac output and raise blood pressure. However, small randomized trials showed no clear benefit. Recently, balloon and chemical angioplasty with superselective intra-arterial injection of vasodilators has emerged as the primary intervention for treating medically refractory ischemia from cerebral vasospasm and in many centers is being used as a first-line treatment or even prophylactically. In addition, promising new treatments for cerebral vasospasm or its ischemic complications include magnesium sulfate, fasudil hydrochloride, tirilazad mesylate, erythropoietin, and induced hypothermia; however, all still need further clinical trials. Newly recognized mediators of cerebral vasospasm after SAH include endothelium-derived mediators, vascular smooth-muscle-derived mediators, proinflammatory mediators involved in blood-brain barrier disruption, cytokines and adhesion molecules, stress-induced gene activation, and platelet-derived growth factors. Moreover, observations in the laboratory have, in many circumstances, matched those of reported small series. Larger, prospective, randomized trials are needed to verify several hypotheses of molecular pathophysiology and clinical treatment regimens.