Clinical Evidence for Intravenous Milrinone to Treat Secondary Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage-A Narrative Review

Abstract

Purpose: Intravenous and intra-arterial milrinone as a rescue measure for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) has been adopted by several groups, but so far, evidence for the clinical benefit is unclear and the effect on brain perfusion is contradictory. We recently published our experience with intravenous milrinone as a rescue strategy for DCI. The aim of the actual analysis was to contextualize our experience with the currently available evidence from clinical trials on the effect of intravenous milrinone in preventing or treating DCI following aneurysmal SAH.

Methods: PubMed was searched for clinical studies using intravenous milrinone for the prevention or treatment of DCI after aneurysmal subarachnoid hemorrhage.

Results: In our series, using intravenous milrinone as a rescue strategy together with using norepinephrine to elevate blood pressure, improvements in cerebral perfusion as measured by perfusion computed tomography (CT) and in clinical symptoms were seen after the induction of rescue therapy. At long-term follow-up, patients suffering DCI had only modestly worse outcomes than patients not suffering DCI. The PubMed search provided four comparative clinical studies. In a preventive setup, Soliman et al. compared intravenous milrinone with magnesium. The incidence of cerebral vasospasm was significantly lower and patients' neurological condition in terms of the Glasgow Coma Scale (GCS) better with magnesium compared to milrinone. Milrinone was associated with hypotension and the need for dopamine and norepinephrine. Rouanet et al. compared milrinone with norepinephrine as a rescue strategy. They found that transcranial Doppler (TCD) flow velocities decreased after milrinone therapy only, not after norepinephrine, whereas clinical improvement was achieved with both treatment strategies. Labeyrie et al. compared balloon angioplasty plus intravenous milrinone with induced hypertension alone. They did not find any significant differences regarding the outcomes. Finally, Lakhal and coauthors compared intravenous milrinone plus induced hypertension as a rescue strategy, where a historical control group received induced hypertension alone. Milrinone was associated with a lower rate of additional endovascular angioplasty and a positive impact on long-term neurological and radiological outcomes.

Conclusion: Our study showed that cerebral perfusion in the setting of secondary cerebral ischemia following SAH is measurably improved via intravenous milrinone and norepinephrine-based hyperdynamic therapy. In the context of the available literature, when used as a rescue strategy, milrinone appears to be beneficial if additional norepinephrine is given to maintain adequate arterial pressure.

Keywords: Delayed cerebral ischemia; Intra-arterial spasmolysis; Milrinone; Nimodipine; Subarachnoid hemorrhage; Vasospasm.