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A randomised controlled trial of induced hypermagnesaemia following aneurysmal subarachnoid haemorrhage

@celiabradford 2013. Crit Care Resusc.15(2):119-125

Clinical Question

  • In patients with aneurysmal subarachnoid haemorrhage does induced hypermagnesaemia reduce the incidence of cerebral artery vasospasm?

Design

  • Randomised controlled trial
  • Randomisation stratified by World Federation of Neurosurgical Society Grade of SAH
  • Variable block size
  • Allocation concealment maintained through use of sealed opaque envelopes
  • Clinical staff in intensive care non-blinded to treatment allocation
  • Outcome assessors and neurosurgical staff blinded to treatment allocation
  • Sample size calculation: 190 patients would provide 80% power to detect a reduction in the incidence of vasospasm from 60% to 40%

Setting

  • 2 tertiary centres in Australia
  • April 2005 – December 2009

Population

  • Inclusion:
    • Clinical history consistent with aneurysmal SAH occurring within the previous 72 hours
    • Aneurysmal SAH confirmed on CT
  • Exclusion:
    • Age <18; creatinine >200mmol/L; death thought imminent within 72 hours; myasthenia gravis; pregnancy; cerebral vasospasm present before inclusion
  • 162 patients randomised

Comparing intervention to control group:

  • Age (mean) 55.8 vs. 56.6
  • Aneurysm size <5mm: 27.1% vs. 34%
  • Aneurysm size >10mm: 22% vs. 8%
  • GCS on admissiona (mean): 12.3 vs. 12.4
  • WFNS grade:
    • 1: 48.1% vs. 42%
    • 2: 23.5% vs. 28.4%
    • 3: 2.5% vs. 3.7%
    • 4: 11.1% vs. 13.6%
    • 5: 44.9% vs. 58%
  • Hydrocephalous present: 44.9% vs. 58%
  • APACHE II (mean): 14.1 vs. 13.4

Intervention

  • High target range for serum magnesium (1.60-2.50 mmol/L)
    • Mean serum magnesium in intervention group during study period: 1.70

Control

  • Standard target range for serum magnesium (0.65-1.05 mmol/L)
    • Mean serum magnesium in control group during study period: 0.87

In both intervention and control groups

  • Patients received an IV infusion of magnesium sulphate at a constant rate of 20ml/hr; the concentration was adjusted to achieve the target concentration.
  • The trial intervention was discontinued 12 days post original haemorrhage or on discharge from ICU, or if death thought to be imminent.
  • Management of SAH based upon standard treament strategies
    • Wherever possible, ruptured aneurysms secured by surgical or endovascualr treatment within 48 hours
    • All patients received nimodipine
    • BP supported with noradrenaline aiming for systolic BP of 120-160mmHg once aneurysm secure.
    • Patients underwent cerebral angiography on day 5, or earlier if they developed clinical signs of suggestive of vasospasm.
    • Clinically relevant vasospasm treated with chemical or balloon angioplasty and angiography was repeated daily until vasospasm resolved

Outcome

  • Primary outcome: Incidence of cerebral arterial vasospasm diagnosed by digital subtraction angiography and adjusted for baseline characteristics – No significant difference
    • Odds Ratio 0.51 (95% C.I. 0.26-1.02, P=0.06)
  • Secondary outcomes: No significant difference
    • Glasgow outcome score at 90 days
    • Modified rankin score at 90 days
    • Proportion of patients requiring endovascular treatment for vasospasm
    • Duration of ICU stay
  • Tertiary outcomes
    • Median amount of noradrenaline administered was significantly higher in the intervention group
    • The mean serum calcium concentration was significantly lower in the intervention group

Authors’ Conclusions

  • Targeting high-range magensium levels in patients with SAH decreased vasospasm, but this was not statistically significant

Strengths

  • Randomised controlled trial
  • Allocation concealment maintained
  • Blinding of assessors of primary outcome
  • Good separation of magnesium level between intervention and control group
  • Intention to treat analysis

Weaknesses

  • Under powered
  • ICU clinicians non-blinded
  • Did not assess level of agreement (Kappa score) between assessors of primary outcome
  • Did not record BP of patients in study. Any differences may have influenced results.

The Bottom Line

  • This underpowered study found a non-significant reduction in vasospasm post SAH in patients treated with hypermagnesaemia. Larger trials will be required to determine if there is a significant difference and if this is results in improvements in patient-orientated outcomes.

Competing Interests

  • The lead author is an editor for The Bottom Line. However, this summary and critique has been written and peer-reviewed independently from the authors

External Links

Metadata

Summary author: @davidslessor
Summary date: 3rd Nov 2015
Peer-review editor: @DuncanChambler

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