April 2013
Mark Angle, M.D.
Kuwait City
Milrinone and the treatment of clinical vasospasm
Mark Angle, MNH,
April 13th 2013 1


Syndromic

Hemolysate Induced

Systemic and Local Inflammatory Response
Milrinone and the treatment of clinical vasospasm
Mark Angle, MNH,
April 13th 2013 2


Universal Distal Vasodysregulation

Episodic Proximal Arteritis
Milrinone and the treatment of clinical vasospasm
Mark Angle, MNH,
April 13th 2013 3


Symptomatic in 30-40% of sub-arachnoid hemorrhage

20-50% stroke (delayed neurological deficits) despite current therapy :
I.
HHH
II.
Angioplasty
III.
Magic Bullets
Milrinone and the treatment of clinical vasospasm
Mark Angle, MNH,
April 13th 2013 4


Phosphodiesterase III inhibitor

Inotrope, peripheral vasodilator

Dosage (cardiac) :
◦ 50 µc/kg bolus
◦ 0.75 µc/kg/min infusion
Milrinone and the treatment of clinical vasospasm
Mark Angle, MNH,
April 13th 2013 5






Normovolemia (CVP ~ 6 mmHg)
Normonatremia ([Na] > 140 meq/L)
Normoglycemia
Normothermia
Permissive Hypertension

Milrinone :
◦ 150 µc/kg bolus
◦ 0.75 µc/kg/min infusion
Milrinone and the treatment of clinical vasospasm
Mark Angle, MNH,
April 13th 2013 6


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
Milrinone and the treatment of clinical vasospasm
Mark Angle, MNH,
April 13th 2013 7


For refractory symptoms
1.
Induced Hypertension
2.
Angiography/Angioplasty/Intra-arterial Infusion
Milrinone and the treatment of clinical vasospasm
Mark Angle, MNH,
April 13th 2013 8

Results 1999-2007
SAH 562
Treated 171
Submitted 88
Adverse Events 1 (arrhythmia)
Induced Hypertension 11
Angioplasty 1
New Hypodensities 30
Milrinone and the treatment of clinical vasospasm
Mark Angle, MNH,
April 13th 2013 9

Patient Characteristics (N = 88)
HH 1-3
4-5
IVH
EVD
Fisher 1-2
3-4
70
14
74
66
22
44
Milrinone and the treatment of clinical vasospasm
Mark Angle, MNH,
April 13th 2013 10

Outcomes (mRS ≤ 2)
1 month
6 months
12 months
Death
Senbokuya et al.
J. Neurosurgery
118:121 (2013)
34/54
48/54
N/A
4
Lannes et al.
NeuroCritical Care
16:354 (2012)
34/88
44/88
53/66
5
Milrinone and the treatment of clinical vasospasm
Mark Angle, MNH,
April 13th 2013 11

Daily mean alpha power in patient trended against the modulation of the dose of milrinone.
Milrinone and the treatment of clinical vasospasm
Mark Angle, MNH,
April 13th 2013 12

Daily mean alpha power in patient trended against the modulation of the dose of milrinone.
Milrinone and the treatment of clinical vasospasm
Mark Angle, MNH,
April 13th 2013 13


Possible Contributory Effects:
1.
Increased Cardiac Output
2.
Altered Blood Rheology
3.
Anti-inflammatory Effects
4.
Direct Cerebral Vascular Dilatation
Milrinone and the treatment of clinical vasospasm
Mark Angle, MNH,
April 13th 2013 14

Milrinone and the treatment of clinical vasospasm
Mark Angle, MNH,
April 13th 2013 15

Milrinone and the treatment of clinical vasospasm
Mark Angle, MNH,
April 13th 2013 16


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
Milrinone and the treatment of clinical vasospasm
Mark Angle, MNH,
April 13th 2013 17