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

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

3.  Universal Distal Vasodysregulation  Episodic Proximal Arteritis Mark Angle, MNH, April 13th 2013 3 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 Mark Angle, MNH, April 13th 2013 4 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 Mark Angle, MNH, April 13th 2013 5 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 Mark Angle, MNH, April 13th 2013 6 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 Mark Angle, MNH, April 13th 2013 7 Milrinone and the treatment of clinical vasospasm

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

9. Results1999-2007 SAH562 Treated171 Submitted88 Adverse Events1 (arrhythmia) Induced Hypertension11 Angioplasty1 New Hypodensities30 Mark Angle, MNH, April 13th 2013 9 Milrinone and the treatment of clinical vasospasm

10. Patient Characteristics(N = 88) HH1-366 4-522 IVH44 EVD70 Fisher1-214 3-474 Mark Angle, MNH, April 13th 2013 10 Milrinone and the treatment of clinical vasospasm

11. Outcomes (mRS ≤ 2) Senbokuya et al. J. Neurosurgery 118:121 (2013) Lannes et al. NeuroCritical Care 16:354 (2012) 1 month34/5434/88 6 months48/5444/88 12 monthsN/A53/66 Death45 Mark Angle, MNH, April 13th 2013 11 Milrinone and the treatment of clinical vasospasm

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

13. Daily mean alpha power in patient trended against the modulation of the dose of milrinone. Mark Angle, MNH, April 13th 2013 13 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 Mark Angle, MNH, April 13th 2013 14 Milrinone and the treatment of clinical vasospasm

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

16. Mark Angle, MNH, April 13th 2013 16 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 Mark Angle, MNH, April 13th 2013 17 Milrinone and the treatment of clinical vasospasm