title: Preventive effect of continuous cisternal irrigation with magnesium sulfate solution on angiographic cerebral vasospasms associated with aneurysmal subarachnoid hemorrhages: a randomized controlled trial.
abstract: OBJECT Although cerebral vasospasm (CV) is one of the most important predictors for the outcome in patients with subarachnoid hemorrhage (SAH), no treatment has yet been established for this condition. This study investigated the efficacy of continuous direct infusion of magnesium sulfate (MgSO4) solution into the intrathecal cistern in patients with an aneurysmal SAH. METHODS An SAH caused by a ruptured aneurysm was identified on CT scans within 72 hours after SAH onset. All patients were treated by surgical clipping and randomized into 2 groups: a control group of patients undergoing a standard treatment and a magnesium (Mg) group of patients additionally undergoing continuous infusion of 5 mmol/L MgSO4 solution for 14 days. The Mg(2+) concentrations in serum and CSF were recorded daily. Neurological examinations were performed by intensive care clinicians. Delayed cerebral ischemia was monitored by CT or MRI. To assess the effect of the Mg treatment on CV, the CVs were graded on the basis of the relative degree of constriction visible on cerebral angiograms taken on Day 10 after the SAH, and transcranial Doppler ultrasonography was performed daily to measure blood flow velocity in the middle cerebral artery (MCA). Neurological outcomes and mortality rates were evaluated with the Glasgow Outcome Scale and modified Rankin Scale at 3 months after SAH onset. RESULTS Seventy-three patients admitted during the period of April 2008 to March 2013 were eligible and enrolled in this study. Three patients were excluded because of violation of protocol requirements. The 2 groups did not significantly differ in age, sex, World Federation of Neurosurgical Societies grade, or Fisher grade. In the Mg group, the Mg(2+) concentration in CSF gradually increased from Day 4 after initiation of the continuous MgSO4 intrathecal administration. No such increase was observed in the control group. No significant changes in the serum Mg(2+) levels were observed for 14 days, and no cardiovascular complications such as bradycardia or hypotension were observed in any of the patients. However, bradypnea was noted among patients in the Mg group. The Mg group had a significantly better CV grade than the control group (p < 0.05). Compared with the patients in the Mg group, those in the control group had a significantly elevated blood flow velocity in the MCA. Both groups were similar in the incidences of cerebral infarction, and the 2 groups also did not significantly differ in clinical outcomes. CONCLUSIONS Continuous cisternal irrigation with MgSO4 solution starting on Day 4 and continuing to Day 14 significantly inhibited CV in patients with aneurysmal SAH without severe cardiovascular complications. However, this improvement in CV neither reduced the incidence of delayed cerebral ischemia nor improved the functional outcomes in patients with SAH.
authors.affiliation: Department of Neurosurgery, Juntendo University Shizuoka Hospital, Izunokuni, Shizuoka;
authors.forename: Takuji
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Neurosurgery, National Defense Medical College, Tokorozawa, Saitama; and.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Mori
authors.affiliation: Department of Rehabilitation, Gifu Central Hospital, Gifu, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Esaki
authors.affiliation: Department of Neurosurgery, Juntendo University Shizuoka Hospital, Izunokuni, Shizuoka;
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Nakao
authors.affiliation: Department of Neurosurgery, Juntendo University Shizuoka Hospital, Izunokuni, Shizuoka;
authors.forename: Joji
authors.initials: J
authors.lastname: Tokugawa
authors.affiliation: Department of Neurosurgery, Juntendo University Shizuoka Hospital, Izunokuni, Shizuoka;
authors.forename: Mitsuya
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000328:Adult; D000368:Aged; D002533:Cerebral Angiography; D002946:Cisterna Magna; D005260:Female; D006801:Humans; D007278:Injections, Spinal; D008278:Magnesium Sulfate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D019999:Pharmaceutical Solutions; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D007507:Therapeutic Irrigation / Q000379:methods*; D014057:Tomography, X-Ray Computed; D017585:Ultrasonography, Doppler, Transcranial; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000209:etiology*
chemical_list: D019999:Pharmaceutical Solutions; D008278:Magnesium Sulfate
keywords: CV = cerebral vasospasm; DCI = delayed cerebral ischemia; GCS = Glasgow Coma Scale; GOS = Glasgow Outcome Scale; IQR = interquartile range; MCA = middle cerebral artery; Mg = magnesium; Mg2+CSF = Mg2+ concentration in the CSF; Mg2+serum = Mg2+ concentration in the serum; MgSO4 = magnesium sulfate; PaCO2 = partial pressure of carbon dioxide; SAH = subarachnoid hemorrhage; TCD = transcranial Doppler; WFNS = World Federation of Neurosurgical Societies; cisternal irrigation; magnesium; subarachnoid hemorrhage; vascular disorders; vasospasm