Milrinone vs norepinephrine administration in preventing delayed cerebral ischaemia in cerebral vasospasm: a systematic review

Abstract

Background: Subarachnoid haemorrhage is a form of stroke, classified as traumatic or aneurysmal in origin. Subarachnoid haemorrhage from aneurysmal rupture can cause significant side effects—most frequently, cerebral vasospasm, which increases the risk of developing delayed cerebral ischaemia. Medical and endovascular interventions differ between institutions and regions. However, the most common intervention is medication management with milrinone and norepinephrine. Aims: This systematic review determines the effectiveness of milrinone versus norepinephrine administration in preventing delayed cerebral ischaemia in aneurysmal subarachnoid haemorrhage patients with cerebral vasospasm. Methods: Critical appraisal of 13 studies, consisting of randomised controlled trials, prospective/retrospective case series and reports and cross setional studies, was conducted. Findings: There was considerable variation in dosing and co-interventions for both milrinone and norepinephrine administration. Some 11 studies agreed milrinone was more beneficial in increasing cerebral blood flow than norepinephrine. For milrinone, good functional outcomes were identified in 60–100% of assessed populations, compared to 44–64% with norephinephrine. For both medications poor outcomes related to an increased severity of haemorrhage. Adverse effects following milrinone administration were seen in three studies, but were deemed negligible compared to treatment benefit. Only one norepinephrine study reported severe adverse events. Conclusions: Milrinone appears to be more beneficial than norepinephrine in preventing delayed cerebral ischaemia, improving functional outcomes and causing less adverse effects. Owing to the low quality of evidence supporting milrinone use in subarachnoid haemorrhgae, further research is needed.