Adverse Events and Complications in Continuous Intra-arterial Nimodipine Infusion Therapy After Aneurysmal Subarachnoid Hemorrhage.

Ralph König,Julia Schick,Christian Rainer Wirtz,Benjamin Mayer,Thomas Kapapa,Michael Braun,Andrej Pala,Bernd Schmitz,Silwia Müller

doi:10.3389/fneur.2021.812898

Abstract

ObjectiveTo determine the frequency and severity of complications associated with the continuous intra-arterial infusion of nimodipine (CIANI) as a new treatment of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH).MethodsPatients from two centers (n = 718) treated for SAH between 2008 and 2016 were included. Demographic and SAH-related parameters were evaluated, and also the frequency of adverse events (AEs) and complications including their severity (mild, moderate, and severe). Clinical outcome was analyzed using Glasgow Outcome Scale (GOS). The unfavorable outcome was defined as GOS 1 to 3, and favorable outcome as GOS 4 to 5. The Short-Form 36 (SF-36) health-related quality-of-life (QoL) questionnaire served as a QoL measurement.ResultsOf 718 patients, 65 (9%) were treated by CIANI and had a higher clinical or imaging grade of bleeding severity. Clinical deterioration while on treatment happened more often in patients who were treated with CIANI than in others. In patients with CIANI, 67% had AEs and/or complications during the treatment. Nimodipine-associated hypotension was seen in 8% (mild). Catheter-associated thrombus occurred in 9% (moderate). New intracerebral hemorrhage was found in 14% (moderate). A total of 6% treated by CIANI died during the treatment period (severe). More than one-third (39%) of patients of CIANI reached at least moderate disability, and 23% showed good recovery. Patients who received CIANI showed reduced QoL, but differences in mental and general health, and also pain were minimal.ConclusionPatients who received CIANI had higher rates of AEs and complications. However, this does not exclude the possibility that the use of CIANI might be helpful in patients with severe and therapy-refractory CV and DCI. Controlled and randomized studies would be helpful to clarify this question but they are methodologically and ethically challenging.

Highlights

In the treatment of aneurysmal subarachnoid hemorrhage (SAH) a new neurological deficit and impaired consciousness, lasting more than 1 h, without direct connection to hydrocephalus, rebleeding or infectious situations, or the appearance of new ischemia or infarcts displayed in adequate imaging studies is defined as delayed cerebral ischemia (DCI) [1]
Continuous intra-arterial infusion of nimodipine is related to a high rate of adverse events (AEs) and complications
When patients experience cerebral vasospasm (CV) and DCI that is refractory to standard nimodipine regimens, Continuous intra-arterial nimodipine infusion (CIANI) may be a salvage therapy

Summary

Introduction

In the treatment of aneurysmal subarachnoid hemorrhage (SAH) a new neurological deficit and impaired consciousness, lasting more than 1 h, without direct connection to hydrocephalus, rebleeding or infectious situations, or the appearance of new ischemia or infarcts displayed in adequate imaging studies is defined as delayed cerebral ischemia (DCI) [1]. Effective protective measures and adequate treatment for DCI are still the subject of research [4, 5]. Nimodipine represents the only proven standard treatment regimen to prevent and treat cerebral vasospasm (CV) and DCI [6, 7]. New salvage therapeutic strategies such as intravenous, intra-arterial, or continuous intra-arterial infusion of calcium channel blockers have been introduced recently in the case of therapy refractory CV and DCI [8,9,10,11]. Continuous intra-arterial nimodipine infusion (CIANI) might be beneficial for cerebral perfusion pressure and prolong the vasodilatory effect of calcium channel blockers [12]. CIANI has been proposed to improve outcomes in patients with severe therapy refractory CV and DCI [8]

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