Milrinone for Treatment of Delayed Cerebral Ischaemia

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Catalina Sokoloff presents Milrinone for treatment of post-aneurysmal subarachnoid haemorrhage vasospasm (delayed cerebral ischaemia.)

Catalina firsts explains the pathophysiology of delayed cerebral ischaemia. She makes the point that there is still much we do not know. Probable mechanisms at the microcirculation level include release of free radicals, lipid peroxidation, cortical depression spreading and microthrombi formation.

The ideal treatment once delayed cerebral ischaemia is present is therefore unknown. Mechanical angioplasty seems to be favourable in some instances however has its shortcomings. As such it is often reserved as a rescue option. ‘Triple H’ therapy is intended to improve blood flow beyond constricted vessels; however, each component is flawed as Catalina explains. Intraarterial drugs have been tried however similarly, the evidence is lacking.

This brings Catalina to Milrinone. This drug is a phosphodiesterase 3 inhibitor that has vasodilating and inotropic properties. Relevantly, the cerebrovascular smooth muscle contains large amounts of phosphodiesterase 3, making Milrinone promising. The combination of increased cardiac output, alongside decreased afterload theoretically should increase cerebral blood flow and subsequently brain perfusion.

Milrinone has also been shown to be a potent anti-platelet aggregator as well as possessing anti-inflammatory properties. Both processes are likely involved in the pathophysiology of delayed cerebral ischaemia.

Catalina continues to discuss the trials (both animal and human studies) that look at the effect of this drug. Whilst there are still no randomised control trials (at the time of the talk) looking at Milrinone, the early retrospective trial data is promising.

There are of course still obstacles surrounding the drugs Namely, no standard dose, no guidelines regarding titration and concerns surrounding the vasodilating properties.

Catalina concludes by proposing the pros of this treatment as she sees it. She argues that the apparent improvement in mortality, the non-invasive nature, and the lack of haemodynamic compromise are all indicators of the potential future of the treatment.

Please note this episode was recorded in November 2018 as part of Brain, a CICM Neuro Special Interest Group meeting click here for more info.

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