Repetitive intraarterial Therapy with Milrinone and Nimodipine for severe refractory Vasospasm: own series and narrative literature review

Introduction: Cerebral vasospasm (VSP) following aneurysmal subarachnoid hemorrhage remains a major source of morbidity. The best rescue treatment option remains uncertain. Intraarterial (ia) Milrinone and Nimodipine were suggested as safe treatment options. Research question: We aimed to evaluate the effect of repetitive endovascular intraarterial (ia) combined Milrinone and Nimodipine administration as rescue therapy for severe refractory cerebral VSP. Material & methods: In this retrospective single center series, we included only patients with refractory VSP despite maximum standard conservative therapy. Inclusion criteria for endovascular rescue treatment were elevated transcranial Doppler (TCD) > 180 cm/s and/or significant clinical neurological deterioration. Patients received ia therapy with Nimodipine 2 mg followed by Milrinone 5 mg. Repetitive reinterventions were indicated in cases of refractory VSP. We evaluated pre- and direct posttreatment neurological status, mRS at final clinical follow-up, TCD values and measured the DSA pre-postinterventional vessel diameters. Results: 38 aSAH patients received ia therapy. Of those, 18 patients (47.4 %) received ≥3 interventions (average:3.4 ± 2.6; maximum:11). Immediate improvement of neurological deficits was seen in 31/38 patients (81.6 %). Overall mortality was low (3/38, 7.9 %). The clinical follow-up after 4 months showed persistent improvement in 24/38 patients (63.2 %) with good clinical outcomes (mRS ≤3). Immediate postinterventional angiographic improvement of vessel diameter was shown in 97,7 % (127/130) of all interventions. Neither severe cardiovascular nor reintervention-related adverse events were observed. Discussion and conclusion: In this series repetitive ia interventions combining Milrinone and Nimodipine showed promising clinical results and low mortality for refractory VSP. Larger prospective randomized clinical trials are warranted. Trial registration: ISRCTN, study ID ISRCTN36126862 registered 21.11.2018, retrospectively registered, http://www.isrctn.com/ISRCTN36126862.