Carl Muroi , Andrej Terzic , et. Al University Hospital Zurich,

1. Carl Muroi, Andrej Terzic, et. Al University Hospital Zurich, Surgical Neurology 69 (2008) 33 - 39 Magnesium sulfate in the management of patients with aneursmal sub arachnoid haemorrhage: a randomized, placebo-controlled, dose-adapted trial

2. To substantiate the efficacy of MgSo4 in preventing the occurence of delayed ischaemic neurologic deficit and secondary infarction. To evaluate the impact on clinical outcome. To assess the safety and side effects of MgSo4 infusion at a given dosage and concomitant with other medication. objective

3. December 2001 – November 2004 58 patients – 27 in placebo group, 31 in Mg group. Inclusion criteria: >17yrs, within 3 days of SAH, informed consent available Exclusion criteria: pregnancy, h/o allergy, renal and neuromuscular diseases, heart disease, hypotension or bradycardia (HR <55/min). All patients monitored in CCU until day 12 post-ictus. Mg2+ measured BD, ABG with Ca2+ done every 4hrs. Patient population

5. Day of admission – MgSO4 bolus of 16 mmol in a 150ml solution of Ringer’s lactate over 15 minutes followed by a continuous infusion of 64mmol/day • Serum Mg2+ maintained at twice the baseline level until day 12 after SAH. • Stopped if: systolic BP <110mmHg, increased need for catecholamines, AV conduction disturbances, asystole >2s, respiratory failure, oliguria, severe fluid/electrolyte disturbances. Administration of magnesium

6. Standard treatment protocol for SAH – early surgery/coiling for aneurysms, with prophylactic anti-epileptics and continuous infusion of nimodipine. • Daily TCDs between Day 4 and 12 by blinded radiologist. • If vasospasm – HHH initiated, if not responsive – angiogram + plasty/papaverine. • CT Head atleast twice before d/c from CCU. Treatment protocol

7. Incidence of TCD detected vasospasm, DIND, occurrence of infarction attributed to spasm, and outcome after 3 months and 1 year analysed. • GOS scores after 3 months and 1 year assessed by a blinded neurologist. DIND – new focal neurological deficits after exclusion of seizures, hydrocephalus, electrolyte disturbance or infection. Study end points

8. Continuous data analysed by independent t test, nominal variables by Fisher exact test. Differences between groups in severity of haemorrhage acc. to WFNS and Fisher scale and the GOS outcomes, were analysed by Mann-Whitney U test. analysis

9. Intention-to-treat analysis showed a trend towards fewer ultrasonographic evidence of severe vasospasm and significantly better outcome after 3 months, though occurrence of hypotension and hypocalcaemia was significantly higher. • On-treatment analysis – trend towards fewer CT-detected ischaemia, a statistically significant better outcome after 3 months and a trend towards better outcome after 1 year. Results

11. High-dose MgSO4 therapy might be effective as a prophylactic adjacent therapy in patients with SAH to reduce poor outcome. High-dose MgSO4 in combination with phenytoin and nimodipine, may be associated with relevant cardiovascular side-effects. Close monitoring of patients receiving Mg treatment in an ITU setting needed. conclusions

12. Pros: Simple, clear outcome measures Cons: Single centre, single blinded study. Large number of treatment group (16 of 31!) had infusion stopped due to side effects. discussion