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A 29 year old man was referred to our department from a local hospital in November 2000, for treatment of acute subarachnoid haemorrhage. At examination, he presented with stupor and a Glasgow coma scale score of 7 and was intubated and artificially ventilated. Diagnostic angiography was performed the same day and demonstrated a ruptured arterior cerebral artery aneurysm. The complex configuration of the aneurysm precluded embolisation as a treatment option. Surgery was performed the next day and the aneurysm was successfully clipped. After surgery, the patient received the calcium channel blocker nimodipine intravenously at a dosage of 2 mg/hour and moderate hypervolaemic haemodilution using isotonic solutions to prevent vasospasm induced brain ischaemia. Transcranial Doppler flow velocities were less than 140 cm/s from day 1 to 5 postoperatively. At day 6, Transcranial Doppler flow values increased up to 200 cm/s indicating severe cerebral vasospasm. Cerebral angiography was performed demonstrating 80% vasospasm on the left internal carotid artery (C1 segment). Because the patient remained in a medically induced coma, a Clark-type intraparenchymal brain tissue oxygen sensor was implanted in the left middle cerebral artery territory to monitor brain tissue oxygenation. Initial values showed tissue hypoxia (tissue oxygen pressure <10 mm Hg), therefore, aggressive hypertensive hypervolaemic haemodilution therapy was initiated to improve cerebral circulation. After temporary improvement, the next day brain tissue oxygen pressure decreased below 5 mm Hg and emergency endovasular balloon dilatation of the C1 segment of the internal carotid artery was performed. Again, tissue oxygen improved temporarily but critical tissue hypoxia developed 4 hours after balloon dilatation. Brain CT was performed and showed no signs of established cerebral infarction. At a brain tissue oxygen value of 2 mm Hg, a total dose of 40 mg sodium nitroprusside was administered over a period of 30 minutes via the ventricular catheter. The dosage was chosen from an earlier clinical report.1 Seventy minutes after sodium nitroprusside administration, brain tissue oxygen increased continuously and persisted at normal values of >15 mm Hg for the next days (fig 1). The clinical course was further complicated by bilateral pneumonia and acute respiratory distress syndrome. Follow up CT showed no major infarction but an atypical left frontal 2×2×2 cm hypodense white matter lesion. The patient was discharged at Rankin grade 5 and slightly improved to Rankin grade 4 after 6 months.
Cerebral vasospasm is the most significant cause of morbidity and mortality in patients surviving subarachnoid haemorrhage long enough to reach medical care. Using the data from the vehicle group of the recent randomised, double blind, vehicle controlled trials on tirilazad mesylate,2 symptomatic vasospasm occurred in 33%−38% and cerebral infarctions from vasospasm were found in 10%−13% of all patients after subarachnoid haemorrhage. Prevention and treatment of cerebral vasospasm were achieved despite the use of nimodipine, hypertensive hypervolaemic hemodilutive therapy, angioplasty and intra-arterial papaverine administration. So far, there is no other established treatment modality that could be offered to those patients with severe vasospasm, decreasing blood flow, and impending cerebral infarction.
The reduction in the concentration of nitric oxide is one purported mechanism of delayed vasospasm after subarachnoid haemorrhage. Evidence in support of a causative role for nitric oxide includes the disappearance of nitric oxide synthase from the adventitia of vessels in spasm, the destruction of nitric oxide by haemoglobin released from the clot into the subarachnoid space, and reversal of vasospasm by intracarotid nitric oxide.
Recently, Thomas et al have suggested intraventricularly administered sodium nitroprusside as a treatment for severe medically refractory vasospasm after subarachnoid haemorrhage.1,3 After intraventricular administration, sodium nitroprusside is supposed to attenuate vasospasm by releasing nitric oxide on the abluminal side of the basal cerebral vessels.
Apart from the original description of the clinical and angiographic effects there is only one report that repeated intraventricular sodium nitroprusside administration indeed may improve crirically reduced cerebral oxygenation and blood flow.4 Our data demonstrate for the first time that despite the short half life of sodium nitroprusside a single intraventricular dose may lead to permanent improvement of reduced cerebral oxygenation in the territory of a severely vasospastic artery. Our finding supports the concept that nitric oxide is playing a critical part in the pathophysiology of cerebral vasospasm after subarachnoid haemorrhage and that intraventricular sodium nitroprusside may offer a a novel therapeutic option in patients with otherwise medically refractory vasospasm and impending cerebral infarction.
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