april 2013 mark angle, m.d. kuwait city 1 mark angle, mnh, april 13th 2013 milrinone and the...
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Milrinone and the treatment of clinical vasospasm
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Milrinone and the treatment of clinical vasospasm :
The MNH Protocol
April 2013Mark Angle, M.D.
Kuwait City
Mark Angle, MNH, April 13th 2013
Milrinone and the treatment of clinical vasospasm
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Syndromic
Hemolysate Induced
Systemic and Local Inflammatory Response
Vasospasm
Mark Angle, MNH, April 13th 2013
Milrinone and the treatment of clinical vasospasm
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Universal Distal Vasodysregulation
Episodic Proximal Arteritis
Vasospasm
Mark Angle, MNH, April 13th 2013
Milrinone and the treatment of clinical vasospasm
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Symptomatic in 30-40% of sub-arachnoid
hemorrhage
20-50% stroke (delayed neurological
deficits) despite current therapy :
I. HHH
II. Angioplasty
III. Magic Bullets
Cerebral Vasospasm
Mark Angle, MNH, April 13th 2013
Milrinone and the treatment of clinical vasospasm
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Phosphodiesterase III inhibitor
Inotrope, peripheral vasodilator
Dosage (cardiac) :
◦ 50 µc/kg bolus
◦ 0.75 µc/kg/min infusion
Milrinone
Mark Angle, MNH, April 13th 2013
Milrinone and the treatment of clinical vasospasm
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Normovolemia (CVP ~ 6 mmHg)
Normonatremia ([Na] > 140 meq/L)
Normoglycemia
Normothermia
Permissive Hypertension
Milrinone :
◦ 150 µc/kg bolus
◦ 0.75 µc/kg/min infusion
MNH Protocol
Mark Angle, MNH, April 13th 2013
Milrinone and the treatment of clinical vasospasm
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Levophed to maintain mean blood pressure at pre-
milrinone level
Rebolus and increase by 0.25 µc/kg/min for persistent or
recurrent symptoms
Weaning protocol :
◦ 0.75 µc/kg/min X 72 hours
◦ 0.50 µc/kg/min X 48 hours
◦ 0.25 µc/kg/min X 48 hours
MNH Protocol
Mark Angle, MNH, April 13th 2013
Milrinone and the treatment of clinical vasospasm
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For refractory symptoms
1. Induced Hypertension
2. Angiography/Angioplasty/Intra-arterial Infusion
MNH Protocol
Mark Angle, MNH, April 13th 2013
Milrinone and the treatment of clinical vasospasm
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Results 1999-2007
SAH 562
Treated 171
Submitted 88
Adverse Events 1 (arrhythmia)
Induced Hypertension 11
Angioplasty 1
New Hypodensities 30
MNH Protocol
Mark Angle, MNH, April 13th 2013
Milrinone and the treatment of clinical vasospasm
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Patient Characteristics (N = 88)
HH 1-3 66
4-5 22
IVH 44
EVD 70
Fisher 1-2 14
3-4 74
MNH Protocol
Mark Angle, MNH, April 13th 2013
Milrinone and the treatment of clinical vasospasm
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MNH Protocol
Outcomes (mRS ≤ 2)
Senbokuya et al.J. Neurosurgery 118:121 (2013)
Lannes et al.NeuroCritical Care
16:354 (2012)
1 month 34/54 34/88
6 months 48/54 44/88
12 months N/A 53/66
Death 4 5
Mark Angle, MNH, April 13th 2013
Milrinone and the treatment of clinical vasospasm
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MNH Protocol
Daily mean alpha power in patient trended against the modulation of the dose of milrinone.
Mark Angle, MNH, April 13th 2013
Milrinone and the treatment of clinical vasospasm
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MNH Protocol
Daily mean alpha power in patient trended against the modulation of the dose of milrinone.
Mark Angle, MNH, April 13th 2013
Milrinone and the treatment of clinical vasospasm
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Possible Contributory Effects:
1. Increased Cardiac Output
2. Altered Blood Rheology
3. Anti-inflammatory Effects
4. Direct Cerebral Vascular Dilatation
Milrinone
Mark Angle, MNH, April 13th 2013
Milrinone and the treatment of clinical vasospasm
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Milrinone and the treatment of clinical vasospasm
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Milrinone and the treatment of clinical vasospasm
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Cerebral vasospasm remains an important determinant of outcome after SAH
Standard therapy is resource intensive, physiologically challenging and only partially effective
Milrinone therapy is simple, well-tolerated and highly effective in a “real-world” trial
Conclusions
Mark Angle, MNH, April 13th 2013