Mass spectrometry-based method for quantification of nimodipine and glutamate in cerebrospinal fluid. Pilot study with patients after aneurysmal subarachnoid haemorrhage.

WHAT IS KNOWN AND OBJECTIVE: Delayed cerebral ischaemia is an important cause of morbidity and mortality after aneurysmal subarachnoid haemorrhage (aSAH). Nimodipine is the only drug approved by the FDA for improving outcome after aSAH. Clinically, however, there are no specific values of this drug in cerebrospinal fluid (CSF) during aSAH treatment that could be associated to outcome improvement. Furthermore, the neurotransmitter glutamate acts as a secondary marker for brain injury. The aim was to establish a method to measure nimodipine and glutamate concentrations simultaneously in CSF of patients after aSAH. METHODS: From June 2017 to June 2018, we prospectively collected clinical data of patients with aSAH admitted to our neurointensive care unit. All included patients received nimodipine orally (60 mg every 4 hours). Patients, who developed clinical vasospasm during their in-hospital stay, underwent intra-arterial application of nimodipine (IAN), followed by angiographic control. A method using high-performance liquid chromatography coupled with mass spectrometric analysis (LC-MS/MS) was established for quantification of both analytes in CSF. RESULTS AND DISCUSSION: In 15 (60%) of 25 patients, nimodipine and glutamate concentrations were measured. After IAN for treatment of vasospasms, CSF nimodipine concentrations were slightly higher than in patients who received nimodipine only orally (0.60 ± 0.27 ng/mL vs 0.48 ± 0.18 ng/mL). Patients developing vasospasm exhibited higher glutamate concentrations than patients without vasospasm (188.84 ng/mL vs136.07 ng/mL). WHAT IS NEW AND CONCLUSION: The developed method allowed the simultaneous quantification of nimodipine and glutamate in CSF. Furthermore, we demonstrated that IAN resulted in higher concentrations in CSF, when compared to oral application only.

Amiodarone Administration during Cardiopulmonary Resuscitation Is Not Associated with Changes in Short-Term Mortality or Neurological Outcomes in Cardiac Arrest Patients with Shockable Rhythms.

Background: The search for the best therapeutic approach in cardiopulmonary resuscitations (CPR) remains open to question. In this study, we evaluated if Amiodarone administration during CPR was associated with short-term mortality or neurological development. Methods: A total of 232 patients with sudden cardiac arrest (CA) with shockable rhythms were included in our analysis. Propensity score matching based on age, gender, type of CA, and CPR duration was used to stratify between patients with and without Amiodarone during CPR. Primary endpoints were short-term mortality (30-day) and neurological outcomes assessed by the cerebral performance category. Secondary endpoints were plasma lactate, phosphate levels at hospital admission, and the peak Neuron-specific enolase. Results: Propensity score matching was successful with a caliper size used for matching of 0.089 and a sample size of n = 82 per group. The 30-day mortality rates were similar between both groups (p = 0.24). There were no significant differences in lactate levels at hospital admission and during the following five days between the groups. Patients receiving Amiodarone showed slightly higher phosphate levels at hospital admission, while the levels decreased to a similar value during the following days. Among CA survivors to hospital discharge, no differences between the proportion of good neurological outcomes were detected between the two groups (p = 0.58), despite slightly higher peak neuron-specific enolase levels in CA patients receiving Amiodarone (p = 0.03). Conclusions: Amiodarone administration is not associated with short-term mortality or neurological outcomes in CA patients with shockable rhythms receiving CPR.