Milrinone and the treatment of clinical vasospasm

1

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

2

Syndromic

Hemolysate Induced

Systemic and Local Inflammatory Response

Vasospasm

Mark Angle, MNH, April 13th 2013

Milrinone and the treatment of clinical vasospasm

3

Universal Distal Vasodysregulation

Episodic Proximal Arteritis

Vasospasm

Mark Angle, MNH, April 13th 2013

Milrinone and the treatment of clinical vasospasm

4

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

5

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

6

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

7

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

8

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

9

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

10

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

11

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

12

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

13

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

14

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

15Mark Angle, MNH, April 13th 2013

Milrinone and the treatment of clinical vasospasm

16Mark Angle, MNH, April 13th 2013

Milrinone and the treatment of clinical vasospasm

17

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