Milrinone and the treatment of clinical vasospasm : The MNH Protocol

Report
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
66
4-5
22
IVH
44
EVD
70
Fisher
1-2
14
3-4
74
Milrinone and the treatment of
clinical vasospasm
Mark Angle, MNH,
April 13th 2013
10
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
N/A
53/66
4
5
12 months
Death
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

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