Higher dose intra-arterial milrinone and intra-arterial combined milrinone-nimodipine infusion as a rescue therapy for refractory cerebral vasospasm

Abstract

<jats:sec><jats:title>Background</jats:title><jats:p> Cerebral vasospasm (CV) is a major cause of delayed morbidity and mortality in patients with subarachnoid hemorrhage (SAH). Various cerebral protectants have been tested in patients with aneurysmal SAH. We aimed to research the success rate of treatment of CV via intra-arterial milrinone injection and aggressive pharmacological therapy for refractory CV. </jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p> A total of 25 consecutive patients who received intra-arterial milrinone and nimodipine treatment for CV following SAH between 2014 and 2017 were included in the study. Patients who underwent surgical clipping were excluded. Refractory vasospasm was defined as patients with CV refractory to therapies requiring ≥3 endovascular interventions. Overall, six patients had refractory CV. Long-term neurological outcome was assessed 6–18 months after SAH using a modified Rankin score and Barthel index. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> The median modified Rankin scores were 1 (min: 0, max: 3) and Barthel index scores were 85 (min: 70, max: 100) From each vasospastic territory maximal 10–16 mg milrinone was given to patients; a maximum of 24 mg milrinone was given to each patient in a session and a maximum of 42 mg milrinone was given to a patient in a day. Both milrinone and nimodipine were given to three patients. There was a large vessel diameter increase after milrinone and nimodipine injections. No patient died due to CV; only one patient had motor dysfunction on the right lower extremity. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> Higher doses of milrinone can be used effectively to control refractory CV. For exceptional patients with refractory CV, high dose intra-arterial nimodipine and milrinone infusion can be used as a rescue therapy. </jats:p></jats:sec>

Clinical and experimental aspects of aneurysmal subarachnoid hemorrhage

“…Chemical angioplasty consisting of intraarterial administration of vasodilators is also an option that is generally used for diffuse vasospasm involving smaller arterial branches. Intraarterial nicardipine, papaverine, milrinone, nimodipine, and verapamil have been utilized in treatment of symptomatic vasospasm …”

“…Intraarterial nicardipine, papaverine, milrinone, nimodipine, and verapamil have been utilized in treatment of symptomatic vasospasm. [152][153][154][155][156] Intraarterial papaverine causes vasodilatation, likely related to alteration in cAMP. It can result in transient reversal of cerebral hypoperfusion with improvement in blood flow velocities and CBF.…”

Efficacy and safety of milrinone in the treatment of cerebral vasospasm after subarachnoid hemorrhage: a systematic review

“…In most studies, the Fisher scale and Hunt & Hess scale were used to evaluate patients. Subarachnoid hemorrhage grade by the Fisher scale was described in 19 studies, ( 1 , 5 , 14 , 16 , 22 - 29 , 31 , 33 , 34 , 36 - 39 ) and 18 of those studies ( 1 , 5 , 14 , 16 , 23 - 29 , 31 , 33 , 34 , 36 - 39 ) included patients presenting moderate to severe subarachnoid hemorrhage (Fisher 3 - 4).…”

“…( 22 , 25 - 28 , 30 , 36 , 38 , 39 ) In six other studies, milrinone was administered by both routes. ( 5 , 16 , 23 , 24 , 33 , 37 ) Two studies used the intrathecal route, ( 31 , 35 ) one used the cisternal route ( 34 ) and the last study did not mention the administration route. ( 29 ) One study ( 37 ) compared the combination of intra-arterial milrinone infusion followed by intravenous administration versus a continuous intravenous milrinone infusion.…”

Symptomatic Cerebral Vasospasm after Spontaneous Subarachnoid Hemorrhage: Comparison of Single and Multiple Intra-arterial Treatment with Respect to the Functional Outcome

“…Moreover, we did not apply different agents such as milrinone or alternative administration strategies (e.g., continuous intraarterial nimodipine administration) that were propagated in other studies. 28,29 In particular, continuous IAT might be superior in the subgroup of recurrent sCVS.…”