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Background/Objectives: The use of levetiracetam (LEV) in the management of drug-induced seizures has not been systematically investigated. Repetitive and continuous seizures that do not respond to benzodiazepines require second line therapy. Levetiracetam has a unique receptor binding site, rapid absorption, no known cardiac effects at therapeutic doses, and is theoretically a good candidate for use in drug-induced seizures. We evaluate the safety of LEV and its association with seizure cessation in this retrospective chart review of patients who received LEV as a control agent in drug-induced seizures. Methods: We identified the medical records of patients presenting to an urban, level 1 trauma center between 1 January 2010 and 31 May 2015 by ICD-9 codes based on the following: (1) a poisoning diagnosis, (2) a seizure diagnosis, and (3) administration of LEV. We included patients with a drug-induced seizure based on history, electroencephalogram results, blood alcohol concentrations, urine drug screens, and adequate documentation. We excluded patients with alcohol withdrawal, anoxic brain injury, subtherapeutic concentrations of other antiepileptics, hypoglycemia, and pseudoseizures. Primary outcomes of interest included cessation of active seizures or the prevention of seizure recurrence. We assessed safety by the presence or absence of adverse drug effects (ADE) attributed to the administration of LEV. Results: Thirty-four patients met inclusion and exclusion criteria. Half of the study cohort (17) presented with generalized tonic-clonic seizures (TCS); half (17) presented in generalized convulsive status epilepticus (GCSE). Six patients in GCSE received LEV during their seizures; 2 also received fosphenytoin. One improved immediately following LEV administration, and the remaining 5 had seizure control. Eleven GCSE patients (65%) remained seizure free after LEV therapy. The patients with TCS (17) received LEV after seizure(s) control. Sixteen (94%) were seizure-free during their hospital course. We found no adverse drug effects. In total, 27 of 34 patients (79%) had a return to baseline neurological and physical health. Six had long-term sequelae; none of which are known LEV side-effects. We identified 46 toxic substances and 22 known seizurogenic agents (48%). The median length of stay was 3.7 days (0.4–96), and the median duration of in-hospital LEV therapy was 1.6 days (0–49). Conclusions: Levetiracetam used as a second-line agent was associated with control of drug-induced seizures and prevention of seizure recurrence without obvious adverse effects. A prospective study is needed to confirm these results. [ABSTRACT FROM AUTHOR]

Objective: Retrospective clinical data and case studies support a therapeutic effect of ketamine in suppression of spreading depolarization (SD) following brain injury. Preclinical data strongly support efficacy in terms of frequency of SD as well as recovery from electrocorticography (ECoG) depression. The authors present the results of the first prospective controlled clinical trial testing the role of ketamine used for clinical sedation on occurrence of SD., Methods: Ten patients with severe traumatic brain injury (TBI) or aneurysmal subarachnoid hemorrhage (SAH) were recruited for this pilot trial. A standard ECoG strip was placed at the time of craniotomy, and the patients were then placed on an alternating every-6-hour schedule of ketamine or other sedation agent. The order of treatment was randomized. The ketamine dose was adjusted to clinical effect or maintained at a subanesthetic basal dose (0.1 mg/kg/hr) if no sedation was required. SD was scored using standard criteria, blinded to ketamine dosing. Occurrence of SD was compared with the hourly dose of ketamine to determine the effect of ketamine on SD occurrence., Results: Successful ECoG recordings were obtained in all 10 patients: 8 with SAH and 2 with TBI. There were a total of 1642 hours of observations with adequate ECoG: 833 hours off ketamine and 809 hours on ketamine. Analysis revealed a strong dose-dependent effect such that hours off ketamine or on doses of less than 1.15 mg/kg/hr were associated with an increased risk of SD compared with hours on doses of 1.15 mg/kg/hr or more (OR 13.838, 95% CI 1.99-1000). This odds ratio decreased with lower doses of 1.0 mg/kg/hr (OR 4.924, 95% CI 1.337-43.516), 0.85 mg/kg/hr (OR 3.323, 95% CI 1.139-16.074), and 0.70 mg/kg/hr (OR 2.725, 95% CI 1.068-9.898) to a threshold of no effect at 0.55 mg/kg/hr (OR 1.043, 95% CI 0.565-2.135). When all ketamine data were pooled (i.e., on ketamine at any dose vs off ketamine), a nonsignificant overall trend toward less SD during hours on ketamine (χ2 = 3.86, p = 0.42) was observed., Conclusions: Ketamine effectively inhibits SD over a wide range of doses commonly used for sedation, even in nonintubated patients. These data also provide the first prospective evidence that the occurrence of SD can be influenced by clinical intervention and does not simply represent an unavoidable epiphenomenon after injury. These data provide the basis for future studies assessing clinical improvement with SD-directed therapy.Clinical trial registration no.: NCT02501941 (clinicaltrials.gov).