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. HHHII. AngioplastyIII. 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 1999-2007SAH 562

Treated 171Submitted 88

Adverse Events 1 (arrhythmia)Induced Hypertension 11

Angioplasty 1New 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 22IVH 44

EVD 70Fisher 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 44/8812 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