Side Effects of Long-Term Continuous Intra-arterial Nimodipine Infusion in Patients with Severe Refractory Cerebral Vasospasm after Subarachnoid Hemorrhage.

BACKGROUND: Long-term continuous intra-arterial nimodipine infusion (CIAN) is a rescue therapy option in cases of severe refractory cerebral vasospasm (CV) following acute non-traumatic subarachnoid hemorrhage (SAH). However, CIAN therapy can be associated with relevant side effects. Available studies focus on intracerebral complications, whereas extracerebral side effects are rarely examined. Aim of the present study was to generate descriptive data on the clinical course during CIAN therapy and expectable extracerebral side effects.
METHODS: All patients treated with CIAN therapy for at least 5 days between May 2011 and December 2015 were included. We retrospectively extracted data from the patient data management system regarding the period between 2 days before the beginning and 5 days after the termination of CIAN therapy to analyze the course of ventilation parameters and pulmonary gas exchange, hemodynamic support, renal and liver function, integrity of the gastrointestinal tract, and the occurrence of infectious complications. In addition, we recorded the mean daily values of intracranial pressure (ICP) and intracerebral problems associated with CIAN therapy.
RESULTS: Data from 28 patients meeting inclusion criteria were analyzed. The mean duration of long-term CIAN therapy was 10.5 ± 4.5 days. Seventeen patients (60.7%) reached a good outcome level (Glasgow Outcome Scale [GOS] 4-5) 6 months after SAH. An impairment of the pulmonary gas exchange occurred only at the very beginning of CIAN therapy. The required vasopressor support with norepinephrine was significantly higher on all days during and the first day after CIAN therapy compared to the situation before starting CIAN therapy. Two patients required short-time resuscitation due to cardiac arrest during CIAN therapy. Acute kidney injury was observed in four patients, and one of them required renal replacement therapy with sustained low-efficiency daily dialysis. During CIAN therapy, 23 patients (82.1%) needed the escalation of a previous antiinfective therapy or the onset of antibiotics which was in line with a significant increase of C-reactive protein and white blood cell count. Obstipation was observed in 22 patients (78.6%). Ten patients (35.7%) even showed insufficient defecation on at least seven consecutive days. Compared to the situation before, ICP was significantly higher during the whole period of CIAN therapy.
CONCLUSIONS: Long-term CIAN therapy is associated with diverse side effects. The leading problems are an impairment of the hemodynamic situation and cardiac problems, an increase in infectious complications, a worsening of the motility of the gastrointestinal tract, and rising ICP values. Teams on neurointensive care units must be aware of these side effects to avoid that the beneficial effects of CIAN therapy on CV reported elsewhere are foiled by the problems this technique can be associated with.