R341Intravenous milrinone with induced hypertension for cerebral vasospasm in subarachnoid hemorrhage: a prospective single-center case-control pilot study. "Milrispasm study"

Réanimation / Urgences
J. Cadiet 1, A. Hivert 2, B. Rozec 1, V. Robert Edan 1, M. Fresco 1, P.A. Rodie Talbère 1, X. Ambrosi 1, P.L. Alexandre 3, R. Bourcier 3, K. Lakhal 1.
1Chu, Hôpital Nord Laennec, Anesthésie Réanimation - Saint-Herblain (France), 2Chd, Hôpital La Roche Sur Yon, Anesthésie - La Roche-sur-Yon (France), 3Chu, Hôpital Nord Laennec, Neuro-Radiologie - Saint-Herblain (France)

Conflits d'intérêt

All authors have no conflict of interest in connection with the work submitted

Position du problème et objectif(s) de l’étude

Among the complex mechanisms yielding poor outcomes following aneurysmal subarachnoid hemorrhage (aSAH), cerebral vasospasm is an important contributor. Vasospasm is the arterial narrowing occurring few days after aneurysm rupture and exposing to brain ischemia through decreased cerebral blood flow. Intravenous (IV) milrinone, a phosphodiesterase-3 inhibitor with cerebral vasodilatory properties, in combination with induced hypertension (maintenance of a mean arterial blood pressure (BP) of 100-120 mmHg), has been proposed to treat cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH). However, data on its safety and efficacy are scarce.

Matériel et méthodes

Prospective observational study conducted in an academic hospital. We compared consecutive patients receiving both IV milrinone (0.5 µg.kg.min-1) and induced hypertension (June 2018 to January 2020) with a historical control group receiving hypertension alone (from April 2012 to December 2014) . Comparisons in the whole population were verified after 1:1 matching of patients with respect to aSAH initial severity (SAPS2, WFNS and Fisher grades). We assessed 1) 6-month functional disability (defined as a score of 2 to 6 on the modified Rankin scale, mRS) and vasospasm-related brain infarction, 2) the incidence of first-line or rescue endovascular angioplasty, and 3) treatment immediate tolerance.

Résultats & Discussion

Ninety four patients were included (41 and 53 in the IV milrinone and the control group, respectively). IV milrinone infusion was independently associated with a lower likelihood of 6-month functional disability (OR 0.5 [95%CI 0.09-0.68], n=47 [50%]) (figure 1) and vasospasm-related brain infarction (OR 0.25 [95%CI 0.07-0.97], n=22 [23%]). IV milrinone (median duration of infusion: 5 [2;8] days) was prematurely discontinued because of poor tolerance in 12 patients, mostly (n=11) within 24 h and mostly (n=10) for “non-/hardly attained induced hypertension” (mean BP<100 mmHg despite 1.5 µg.kg.min-1 of norepinephrine). However, this event was similarly observed in IV milrinone and control patients (n=10 (24%) vs. 11 (21%), p=0.68) (figure 2). IV milrinone was associated with a higher incidence of polyuria (IV milrinone patients had creatinine clearance of 191 [153;238] mL.min-1) and hyponatremia or hypokalemia whereas arrhythmia, myocardial ischemia, thrombocytopenia were infrequent. Endovascular angioplasty was less frequent in the IV milrinone group (6 [15%] vs. 28 [53%] patients, p=0.0001). Similar results were found in the 60 matched patients. 


Despite premature discontinuation of IV milrinone because of poor tolerance in 29% patients, IV milrinone was associated with a lower rate of endovascular angioplasty and a positive impact on long-term neurological and radiological outcomes.





Factors associated with neurological prognosis

Blood pressure tolerance