Magnesium sulfate in the management of patients with aneursmal sub arachnoid haemorrhage: a randomized, placebo-controlled, dose-adapted trial

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Magnesium sulfate in the management of patients
with aneursmal sub arachnoid haemorrhage a
randomized, placebo-controlled, dose-adapted
trial

• Carl Muroi, Andrej Terzic, et. Al
• University Hospital Zurich,
• Surgical Neurology 69 (2008) 33 - 39

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objective

• 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.

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Patient population

• December 2001 November 2004
• 58 patients 27 in placebo group, 31 in Mg
  group.
• Inclusion criteria gt17yrs, within 3 days of SAH,
  informed consent available
• Exclusion criteria pregnancy, h/o allergy, renal
  and neuromuscular diseases, heart disease,
  hypotension or bradycardia (HR lt55/min).
• All patients monitored in CCU until day 12
  post-ictus. Mg2 measured BD, ABG with Ca2 done
  every 4hrs.

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Administration of magnesium

• Day of admission MgSO4 bolus of 16 mmol in a
  150ml solution of Ringers 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 lt110mmHg, increased need
  for catecholamines, AV conduction disturbances,
  asystole gt2s, respiratory failure, oliguria,
  severe fluid/electrolyte disturbances.

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Treatment protocol

• 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.

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Study end points

• 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.

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analysis

• 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.

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Results

• 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.

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conclusions

• 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.

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discussion

• 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.