levetiracetam and Hypotension

The choice of drugs for patients with status epilepticus that is refractory to treatment with benzodiazepines has not been thoroughly studied.. In a randomized, blinded, adaptive trial, we compared the efficacy and safety of three intravenous anticonvulsive agents - levetiracetam, fosphenytoin, and valproate - in children and adults with convulsive status epilepticus that was unresponsive to treatment with benzodiazepines. The primary outcome was absence of clinically evident seizures and improvement in the level of consciousness by 60 minutes after the start of drug infusion, without additional anticonvulsant medication. The posterior probabilities that each drug was the most or least effective were calculated. Safety outcomes included life-threatening hypotension or cardiac arrhythmia, endotracheal intubation, seizure recurrence, and death.. A total of 384 patients were enrolled and randomly assigned to receive levetiracetam (145 patients), fosphenytoin (118), or valproate (121). Reenrollment of patients with a second episode of status epilepticus accounted for 16 additional instances of randomization. In accordance with a prespecified stopping rule for futility of finding one drug to be superior or inferior, a planned interim analysis led to the trial being stopped. Of the enrolled patients, 10% were determined to have had psychogenic seizures. The primary outcome of cessation of status epilepticus and improvement in the level of consciousness at 60 minutes occurred in 68 patients assigned to levetiracetam (47%; 95% credible interval, 39 to 55), 53 patients assigned to fosphenytoin (45%; 95% credible interval, 36 to 54), and 56 patients assigned to valproate (46%; 95% credible interval, 38 to 55). The posterior probability that each drug was the most effective was 0.41, 0.24, and 0.35, respectively. Numerically more episodes of hypotension and intubation occurred in the fosphenytoin group and more deaths occurred in the levetiracetam group than in the other groups, but these differences were not significant.. In the context of benzodiazepine-refractory convulsive status epilepticus, the anticonvulsant drugs levetiracetam, fosphenytoin, and valproate each led to seizure cessation and improved alertness by 60 minutes in approximately half the patients, and the three drugs were associated with similar incidences of adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ESETT ClinicalTrials.gov number, NCT01960075.).

Topics: Adolescent; Adult; Anticonvulsants; Benzodiazepines; Child; Child, Preschool; Double-Blind Method; Drug Resistance; Female; Humans; Hypotension; Infusions, Intravenous; Injections, Intramuscular; Levetiracetam; Male; Middle Aged; Phenytoin; Status Epilepticus; Valproic Acid; Young Adult

Medication administration via intravenous push presents multiple potential advantages; however, there may be an increased risk of adverse drug reactions. In 2020, Brigham and Women's Hospital changed levetiracetam intravenous administration to intravenous push (IVP).. The purpose of this analysis was to compare the safety profile of IVP to intravenous piggyback (IVPB) levetiracetam administration.. This institutional review board-approved, single-center, pre-post analysis was performed between 1 November, 2019 and 30 May, 2020. The electronic health record was used to identify all administrations of intravenous levetiracetam greater than 1000 mg in patients ≥ 18 years old. The major safety outcomes included hypotension, bradycardia, drug-induced sedation, and intravenous site reactions such as phlebitis and infiltration. The major efficiency outcome was the time from pharmacy order verification to first-dose administration.. A total of 498 administrations in 162 patients were included in the analysis: 252 administrations in 84 patients in the IVP group and 246 administrations in 78 patients in the IVPB group. The incidence of bradycardia was 7 vs 3 (3.2% vs 1.5%, p = 0.34); hypotension 10 vs 6 (5.2% vs 3.5%, p = 0.44); sedation 21 vs 36 (19.3% vs 27.9%, p = 0.12); and peripheral IV site reactions 0 vs 1 (0% vs 0.6%, p = 0.39) in the IVP vs IVPB groups, respectively. The median time between order verification and first-dose administration was significantly reduced in the IVP vs IVPB group (23.5 vs 55 min, p < 0.001).. Intravenous push levetiracetam administration of doses up to 4000 mg was associated with a similar incidence of cardiovascular, sedation, and infusion site-related adverse events compared to IVPB and resulted in a significant reduction in time to first-dose administration. Intravenous push levetiracetam in doses as high as 4000 mg may be considered safe with appropriate monitoring.

Topics: Academic Medical Centers; Administration, Intravenous; Adolescent; Bradycardia; Female; Humans; Hypotension; Infusions, Intravenous; Levetiracetam; Retrospective Studies

Perioperative seizure prophylaxis with antiepileptic drugs (AED) has been advocated in patients undergoing supratentorial craniotomy. The practice remains controversial. The reasoning presupposes that the possibility of an adverse drug reaction from the AED is lower than the probability of harm from a seizure. Even short periods of hypotension during the operation can lead to acute kidney and myocardial injury. We retrospectively evaluated cardiovascular effects and tolerability of levetiracetam (LEV) alone, LEV and lacosamid (LCM) as compared to phenytoin (PHT).. After IRB approval, the charts of individuals who underwent craniotomy from April 2007 to September 2011 were reviewed. Those receiving PHT were compared to those receiving LEV alone and LEV/LCM. The patient data included demographic, indication and procedure related data. The cumulative dose of norepinephrine (NET), atropine (ATR) and the change in systolic blood pressure during and after the administration of the AED were analyzed.. Five hundred thirty-eight patients were screened of which 122 were included for analysis. 40 patients with primary or secondary supratentorial brain tumors received LEV (19 female, 21 male; mean age 56 years), 41 patients received LEV/ LCM (16 female, 25 male; mean age 56 years) and 41 patients received PHT (15 female, 26 male; mean age 50 years). The commonest indications for craniotomy were glioblastoma (N.=14 vs. N.=12 vs. N.=15), meningiomas (N.=9 vs. N.=7 vs. N.=10), low-grade gliomas (N.=6 vs. N.=13 vs. N.=6) and brain metastases (N.=5 vs. N.=4 vs. N.=5). 1 LEV/LCM patient (2%) and 4 PHT patients (4.5%) had a seizure despite prophylaxis. Possible side effects were observed in 2 patients associated with PHT. During anesthesia there was a significant drop in systolic blood pressure in the PHT group after administration of the AED perioperatively when compared to LEV (P=0.001) and LEV/LCM (P≤0.0001) respectively. The mean cumulative doses of NET and ATR over the course of the operation did not differ significantly.. LEV alone and in combination with LCM for patients without and with symptomatic epilepsy as seizure prophylaxis provides a safe and feasible alternative to PHT. PHT was associated with an unfavorable drop in blood pressure during anesthesia and more adverse reactions.

Topics: Acetamides; Adult; Anticonvulsants; Blood Pressure; Craniotomy; Female; Humans; Hypotension; Lacosamide; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Pre-Exposure Prophylaxis; Retrospective Studies; Seizures; Supratentorial Neoplasms

Cardiac dysfunction occurring secondary to neurologic disease, termed neurogenic stunned myocardium, is an incompletely understood phenomenon that has been described after several distinct neurologic processes. We present a case of neurogenic stunned myocardium, discovered intraoperatively after anesthetic induction, in a patient who presented to our operating room with a recent intraparenchymal hemorrhage. We discuss the longitudinal cardiac functional course after neurogenic stunned myocardium. Finally, we discuss the pathophysiology of neurogenic stunned myocardium, as well as its implications for anesthesiologists caring for neurosurgical patients.

Topics: Adult; Anesthesia, General; Cerebral Hemorrhage; Emergency Service, Hospital; Heart; Hemangioma, Cavernous, Central Nervous System; Humans; Hypertension; Hypotension; Levetiracetam; Male; Methamphetamine; Myocardial Stunning; Nicardipine; Perioperative Period; Phenylephrine; Piracetam; Seizures; Substance-Related Disorders; Takotsubo Cardiomyopathy

To describe the cardiovascular toxicity and pharmacokinetics of levetiracetam in overdose.. A 43-year-old female presented 8 h post ingestion of 60-80 g of levetiracetam with mild central nervous system depression, bradycardia, hypotension and oliguria. Her cardiovascular toxicity transiently responded to atropine and intravenous fluids. A bedside echocardiogram demonstrated normal left and right ventricular contractility. Despite her cardiovascular toxicity and oliguria, she had normal serial venous lactates and renal function; and made a complete recovery over 48 h. Her levetiracetam concentration was 463 mcg/ml 8 h post ingestion (therapeutic range 10-40 mcg/ml) and her concentration-time data best fitted a one-compartment model with first-order input and an elimination half-life of 10.4 h.. Levetiracetam in large ingestions appears to cause bradycardia and hypotension that is potentially responsive to atropine and intravenous fluids. Based on a normal echocardiogram, the mechanism for this effect may be levetiracetam acting at muscarinic receptors at high concentration. The pharmacokinetics of levetiracetam in overdose appeared to be similar to therapeutic levetiracetam dosing.

Topics: Adult; Atropine; Bradycardia; Cardiovascular System; Drug Overdose; Female; Humans; Hypotension; Levetiracetam; Oliguria; Piracetam

To study the incidence and extent of the occasionally noted hypotension after intravenous (IV) infusions of fosphenytoin (FOS) and levetiracetam (LEV) in patients presenting with acute cerebral symptoms.. Retrospective data collection of consecutive patients with acute cerebral symptoms who received IV infusions of a single dose of 750 mg or more of either fosphenytoin or levetiracetam and had documented blood pressure values in the 2h prior and the 2h after their IV infusion.. More than 10 mmHg drop in the systolic, diastolic and MBP was observed in the FOS group following the IV infusion (-16.82 mmHg, -11.60 mmHg, and 13.34 mmHg, respectively). However, there was not a significant change in the MBP after LEV infusion (1.54 mmHg, 1.84 mmHg, and 1.74 mmHg for systolic, diastolic and MBP change, respectively). The difference in the systolic, diastolic and MBP changes between the two groups was statistical significant (all p values are <0.0001) after adjusting for age, clinical presentations of the patients and if they were on any antihypertensive medication in the hospital. Sixty two percent of patients who received FOS had >10 mmHg decrease in their MBP. In the LEV group, only 2 of the 50 patients (4%) had >10 mmHg decrease in their MBP. The difference in proportion of the patients with >10 mmHg drop in MBP between the two study groups is also statistically significant (p<0.001) for age, clinical presentations of the patients and if they were on any antihypertensive medication in the hospital.. IV infusion of FOS in subjects presenting with acute cerebral symptoms may cause significant decreases in their blood pressure. This was not seen in patients receiving IV LEV infusions. Since maintaining adequate cerebral perfusion pressure is a key point in the management of patients with acute cerebral symptoms, the results of this study may carry a clinical impact on the management of this subgroup of patients.

Topics: Adult; Aged; Aged, 80 and over; Blood Pressure; Chi-Square Distribution; Female; Humans; Hypotension; Levetiracetam; Male; Medical Records; Middle Aged; Patient Selection; Phenytoin; Piracetam; Regression Analysis; Retrospective Studies; Seizures; Treatment Outcome

Topics: Adrenergic alpha-Agonists; Anticonvulsants; Antidepressive Agents; Chronic Disease; Clonidine; Depression; Dyskinesia, Drug-Induced; Female; Humans; Hypotension; Levetiracetam; Lithium Carbonate; Middle Aged; Piracetam