Intraventricular Milrinone for Vasospasm After Subarachnoid Hemorrhage

Introduction/Purpose Cerebral vasospasm is a major complication following subarachnoid hemorrhage (SAH) or traumatic brain injury (TBI), it contributes significantly to morbidity and mortality in such cases. Conventional therapies involve the use of oral and intra‐arterial vasodilators such as nimodipine along with the Triple‐H therapy of hypervolemia, hypertension and hemodilution. In spite of these interventions, a significant number of patients present with refractory vasospasm. Milrinone, a phosphodiesterase inhibitor, is emerging as a promising adjunct therapy for refractory vasospasm cases. In this case series three patients are treated with intrathecal milrinone for severe vasospasm and their subsequent clinical course has been shown. Methods This is a retrospective case series that includes three patients who had developed severe vasospasm following aSAH or TBI. The patients were given conventional therapies initially, failing which intraventricular or intrathecal milrinone was administered. Administration of milrinone 4 ml of cerebrospinal fluid was extracted via an extraventricular drain (EVD) and 2 ml (0.87mg) of milrinone was administered. EVD was then flushed with 2 mL of preservative‐free saline and clamped for 1 hour. Serial transcranial doppler (TCD) ,diagnostic angiography and clinical neurological status were used to assess response to milrinone and to determine further actions. Results Case 1 : A 70 year old male presented with grade IV aneurysmal SAH. On day 9 the patient developed severe vasospasm of the vertebral and basilar arteries. Milrinone was administered from day 9 to day 12. A ventriculoperitoneal shunt was also placed. Subsequent TCDs and angiograms showed improvement in vasospasm. Residual spasm was treated by intra‐arterial milrinone and verapamil. The patient was discharged to rehabilitation on day 30. Case 2 : A 30 year old male presented with traumatic SAH and intraventricular hemorrhage. Oral nimodipine, IV milrinone and intrathecal milrinone were administered. From day 11 the patient exhibited a waxing and waning course of severe vasospasm in multiple anterior and posterior circulation segments.The left M2 division was treated with balloon angioplasty. Vasospasm diminished significantly on repeat angiograms done 6 hrs after the last milrinone dose and the patient exhibited clinical improvement as well. Case 3 : A 38 year old male presented with severe TBI, intraventricular hemorrhage and obstructive hydrocephalus. TCD showed worsening vasospasm from day 6. The patient was placed on triple H therapy and nimodipine and repeated intra‐arterial verapamil till day 12. Due to worsening vasospasm the patient was placed on intraventricular and intravenous milrinone therapy between days 13 to 17. Initiation of milrinone correlated with improvement of vasospasm and TCD velocities. Even after vascular improvement the prognosis remains guarded because of the severity of the brain injury and development of multiple ischemic infarcts due to the persistent vasospasm. Conclusion Intraventricular milrinone has the potential to be an effective adjunctive modality for treatment of vasospasm refractory to conventional interventions. Additional studies are required to further define optimal dosing, side effects and outcome expectations for this novel therapeutic approach.