Artikel
Nimodipine concentration in serum, CSF and cerebral microdialysate during established and experimental treatment for cerebral vasospasm – A prospective, observational study
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Veröffentlicht: | 8. Juni 2016 |
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Gliederung
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Objective: Oral nimodipine is an established prophylactic agent for cerebral vasospasm after subarachnoid hemorrhage (SAH). In highly selected cases, intraarterial or intravenous application of nimodipine may be considered whereas the optimum dosage and modality of application remains a matter of debate. Analysis of nimodipine concentration in serum, CSF and cerebral microdialysate in context of currently effective dose and route of application (oral, IA, IV) is the purpose of this investigation.
Method: A total of 155 samples (serum: n=65; CSF: n=57; intracerebral microdialysis: n=33) of 35 patients treated for aneurysmal subarachnoid hemorrhage from 05/2014 to 07/2015 were included for this analysis. Treatment groups were stratified according to modality of application and respective doses: oral nimodipin (123 ± 44.6µg/kg/h vs. 200.4 ± 51µg/kg/h), continuous intraarterial or intravenous nimodipine (≤15µg/kg/h vs >15µg/kg/h). Serum, CSF and microdialysate samples were analysed via HPLC and tandem mass spectrometry. At time of sampling, current dose and modality of application effectively sustained cerebral perfusion as documented by clinical exam, CT perfusion and/or invasive neuromonitoring.
Results: In the majority of cases (95.7%), nimodipine remained below the limit of quantification (0.5ng/ml) within the target organ itself (microdialysis or CSF), even during “targeted, local” application (intraarterial nimodipin). Average serum concentration of nimodipine for all treatment groups was 19.7 ± 17.9ng/ml. Modality of application (oral, IA, IV) was not associated with significant differences in serum concentrations (p=0.37), even after stratification for low- and high-dose treatment (p=0.38), implying also a comparable systemic effect.
Conclusions: Nimodipine does not accumulate sufficiently within the target organ for treatment monitoring. Comparable systemic concentrations can be observed irrespective of application modality and dosing, each of which carries a specific side effect and complication profile. Further studies will have to determine the role of efficacy-driven (rather than empiric) treatment algorithms, where the lowest dose and least invasive mode of application still effective is identified.