Continuous Intravenous Nimodipine Infusion With Ethanol as Carrier in Aneurysmal Subarachnoid Hemorrhage Does Not Result in Measurable Cerebral Ethanol Levels

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An unimpaired neurological evaluation is essential for detecting delayed cerebral ischemia (DCI) in aneurysmal subarachnoid hemorrhage (aSAH) patients. Nimodipine is currently the only drug approved for DCI prevention. Intravenous nimodipine infusion contains 23.7 vol% ethanol as an excipient, resulting in up to 45 g of ethanol being infused daily, which may interfere with neurological assessment. Therefore, we aimed to measure ethanol concentrations in plasma, cerebrospinal fluid (CSF), and brain parenchyma during the infusion of 0.5-2 mg of nimodipine per hour in aSAH patients to quantify the ethanol neuronal exposure. Ethanol concentrations were determined by headspace gas chromatography-flame ionization detection in plasma and CSF and we set out brain parenchyma measurement using cerebral microdialysis, in 10 aSAH patients. In each compartment four samples were taken over a 6-hour interval during steady-state intravenous nimodipine infusion at four different doses (0.5, 1, 1.5 and 2 mg/hour). A total of 307 samples from plasma and CSF was measured. Ethanol levels were mostly below the quantification limit of 0.002 g/100 mL. In 36 samples ethanol concentration was ≥ 0.002 g/100 mL, ranging from 0.002 to 0.009 g/100 mL. These low values were not reproducible in a second measurement, suggesting these values likely reflected analytical variability rather than true ethanol concentrations. Nimodipine analysis in brain parenchyma was omitted due to insufficient microdialysate volume and low concentrations in blood and CSF. Continuous nimodipine infusion of up to 2 mg/hour is unlikely to impair neurological assessment in aSAH patients, as no significant CSF ethanol concentration (< 0.002 g/100 mL) was detected.

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