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.

Evaluation of Time to Administration, Benzodiazepine Use, and Safety of Intravenous Push Levetiracetam in a Neuro-Spine Intensive Care Unit.

PURPOSE: The purpose of this study was to evaluate the time to medication administration, clinical effect, and safety of a recent Pharmacy and Therapeutics Committee-approved change in the administration of levetiracetam from intravenous piggyback (IVPB) over 15 min to undiluted intravenous push (IVP) over 2-5 min at a large academic medical center. METHODS: The primary outcome was the time from order verification to the administration of IVP levetiracetam versus IVPB levetiracetam. The secondary outcome was any benzodiazepine administered in the time between levetiracetam order verification and administration in both groups. Adult patients admitted to the neuro-spine intensive care unit in the 6 months prior to and after the policy change, and who received at least one dose of 1000 mg or higher of IVP or IVPB levetiracetam for active seizures, were included in this retrospective, observational, institutional review board-approved study. Data were analyzed using descriptive statistics, χ2, and the Mann-Whitney U-test as appropriate. RESULTS: Of the 2055 hospital-wide levetiracetam doses ordered within the study period, 316 doses were screened for enrollment and 160 were enrolled with 60 and 100 patients assigned to the IVP and IVPB groups, respectively. There were no differences between the groups at baseline. The majority of the population was male, 57 years old, had no significant renal dysfunction (defined as a creatinine clearance of less than 60 ml/min), and had a seizure etiology of malignancy or traumatic brain injury. A significant reduction in the time to administration of levetiracetam was found with IVP compared with IVPB administration (28 vs. 80 min, p < 0.0001). A subsequent reduction in patients who received benzodiazepines in the interim of levetiracetam order verification and administration was also associated with IVP compared with IVPB (2% vs. 13%, p = 0.042). There were no differences found in the rates of adverse effects between groups. CONCLUSIONS: Administration of levetiracetam doses up to 2000 mg via IVP is a safe method of administration that results in a reduction of time to medication administration and a reduction of benzodiazepine use.

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.

Major publications in the critical care pharmacotherapy literature: January-December 2016.

PURPOSE: To summarize select critical care pharmacotherapy guidelines and studies published in 2016. SUMMARY: The Critical Care Pharmacotherapy Literature Update (CCPLU) Group screened 31 journals monthly for relevant pharmacotherapy articles and selected 107 articles for review over the course of 2016. Of those included in the monthly CCPLU, three guidelines and seven primary literature studies are reviewed here. The guideline updates included are as follows: hospital-acquired pneumonia and ventilator-associated pneumonia management, sustained neuromuscular blocking agent use, and reversal of antithrombotics in intracranial hemorrhage (ICH). The primary literature summaries evaluate the following: dexmedetomidine for delirium prevention in post-cardiac surgery, dexmedetomidine for delirium management in mechanically ventilated patients, high-dose epoetin alfa after out-of-hospital cardiac arrest, ideal blood pressure targets in ICH, hydrocortisone in severe sepsis, procalcitonin-guided antibiotic de-escalation, and empiric micafungin therapy. CONCLUSION: The review provides a synopsis of select pharmacotherapy publications in 2016 applicable to clinical practice.

Dual intraventricular plus systemic antibiotic therapy for the treatment of Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae ventriculitis.

OBJECTIVE: To report a case of Klebsiella pneumoniae carbapenemase (KPC)-producing K pneumoniae ventriculitis successfully treated with dual intraventricular plus systemic antibiotic therapy. CASE SUMMARY: A 43-year-old woman with a ventriculoperitoneal shunt was transferred from a nursing home with fever, altered mental status, and leukocytosis. She was found to have KPC-producing K pneumoniae ventriculitis. Combination intraventricular antibiotic therapy with colistin and gentamicin plus systemic colistin and amikacin led to the resolution of infection. DISCUSSION: Utilization of intraventricular or intrathecal antibiotics has been described in the literature for multidrug resistant (MDR) Gram-negative central nervous system (CNS) infections; however, none of the cases were caused by a KPC-producing organism. Given the pathogenicity and limited treatment options for this resistant organism, we utilized intraventricular colistin 10 mg and intraventricular gentamicin 10 mg in combination with systemic colistin and amikacin. An extensive literature search revealed several case reports and case series of documented MDR Acinetobacter baumanii CNS infections successfully treated with intraventricular colistin or aminoglycoside therapy with good tolerability. Additionally, recent pharmacokinetic analyses suggest improved cerebrospinal fluid (CSF) concentrations with direct CNS antimicrobial administration in combination with systemic therapy. Although our patient's cerebral spinal fluid cultures were cleared with dual intraventricular plus systemic therapy, she continued to deteriorate clinically because of her comorbid conditions and required hospice admission. CONCLUSIONS: This describes the first reported case of KPC-producing K pneumoniae ventriculitis microbiologically cured based on negative blood and CSF cultures with a combination of intraventricular and systemic therapy.