Safety and efficacy of lacosamide versus phenytoin for refractory seizures in neurosurgical patients.

BACKGROUND: Postoperative neurosurgical patients have increased risk of seizures. Traditional anti-epileptics, such as phenytoin, are not always effective and cause adverse effects. Levetiracetam is the first-line therapy due to its similar efficacy and more favourable side effect profile. However, many patients continue to seize despite adequate dosing. Lacosamide has been used for refractory seizures and may offer similar seizure control without the negative aspects of traditional agents. The purpose of this study is to evaluate if lacosamide is as safe and effective as phenytoin in terminating seizures in neurosurgical patients already on levetiracetam. METHODS: This retrospective, single-centre cohort study identified neurosurgical intensive care unit (ICU) patients ≥18 years old who had received levetiracetam plus either phenytoin or lacosamide at Northwestern Memorial Hospital between 1 January 2016 and 31 August 2017. The primary endpoint was treatment failure and the secondary endpoint was safety assessed by liver function tests, blood pressure, heart rate and ECG. RESULTS: 70 patients were included in this study, 52 in the phenytoin group and 18 in the lacosamide group. Both phenytoin and lacosamide groups had similar treatment failure rates (25% vs 22% respectively, p=1). Phenytoin use resulted in a mean decrease in systolic blood pressure of 20.9 mm Hg compared with 9.8 mm Hg in the lacosamide group (p=0.019). There were no statistically significant differences in the rates of other adverse effects. CONCLUSIONS: The use of lacosamide for refractory seizures in neurosurgical ICU patients was associated with similar failure rates, but fewer adverse effects when compared with phenytoin.

Pentobarbital Removal During Continuous Venovenous Hemofiltration: Case Report and Review of the Literature.

BACKGROUND:: Renal replacement therapy may enhance the elimination of barbiturates. Pentobarbital clearance during continuous venovenous hemofiltration (CVVH) has not been described previously. We report a patient case involving the measurement of serial pentobarbital levels during CVVH and review relevant literature characterizing extracorporeal pentobarbital elimination. METHODS:: The following is a retrospective report of a previously healthy 26-year-old woman who sustained a severe traumatic brain injury (TBI) and required administration of pentobarbital on hospital day 0 for intracranial pressure (ICP) control. Given concern for interference with the patient's ongoing neurologic assessments, pentobarbital was discontinued on hospital day 4. The patient's hospital course was complicated by acute kidney injury (AKI), requiring initiation of CVVH on hospital day 5. Daily serum pentobarbital levels were obtained during CVVH. RESULTS:: While on CVVH, the patient's estimated pentobarbital clearance ranged from 6 to 44 mL/min and the elimination half-life ranged from 17.7 to 65.9 hours. Based on reductions in pentobarbital clearance during CVVH interruption, the elimination of drug was dependent upon extracorporeal removal in this patient. CVVH facilitated pentobarbital elimination in a manner approaching endogenous clearance in healthy individuals. CONCLUSION:: We report clinically significant pentobarbital removal by CVVH in a patient with severe TBI. Application of CVVH may expedite reliable neurologic assessments and facilitate the application of clinical brain death examination following pentobarbital exposure.

CENTRAL DIABETES INSIPIDUS AND CHEMOTHERAPY: USE OF A CONTINUOUS ARGININE VASOPRESSIN INFUSION FOR FLUID AND SODIUM BALANCE.

OBJECTIVE: Central diabetes insipidus can occur in the setting of primary or metastatic tumors that disrupt the hypothalamic-pituitary axis. Usual treatment consists of water intake to replace ongoing fluid losses and desmopressin administration aimed at decreasing the urine output to enable maintenance of eunatremia without polyuria. Marked derangement in plasma sodium concentration can occur when high-volume intravenous fluid administration is required during chemotherapy to prevent nephrotoxicity, particularly if obligate fluid intake exceeds the total daily fluid intake necessary to maintain eunatremia. METHODS: We developed a protocol for a rapidly titratable low-dose continuous intravenous arginine vasopressin infusion to maintain eunatremia in patients with central diabetes insipidus during periods of obligate fluid intake. RESULTS: We successfully maintained eunatremia in 2 patients with central nervous system lymphoma who underwent several cycles of obligate intravenous fluid administration with 5% dextrose in 0.45% sodium chloride for chemotherapy. CONCLUSION: Obligate fluid administration can result in dangerous and severe fluctuations in plasma sodium concentration in patients with central diabetes insipidus receiving conventional desmopressin therapy. The use of a rapidly titratable low-dose continuous vasopressin infusion successfully maintained eunatremia in this setting. This protocol can be replicated to prevent the wide and potentially dangerous fluctuations in plasma sodium concentration that can occur in patients with central diabetes insipidus who require high-volume intravenous fluid administration. This protocol has not been assessed among patients with impaired renal function and, thus, may not be generalizable to this population. (AACE Clinical Case Rep. 2018;4:e487-e492).