levetiracetam and Respiratory-Insufficiency

The coronavirus disease of 2019 (COVID-19) emerged as a global pandemic. Historically, the group of human coronaviruses can also affect the central nervous system leading to neurological symptoms; however, the causative mechanisms of the neurological manifestations of COVID-19 disease are not well known. Seizures have not been directly reported as a part of COVID-19 outside of patients with previously known brain injury or epilepsy. We report two cases of acute symptomatic seizures, in non-epileptic patients, associated with severe COVID-19 disease.. Two advanced-age, non-epileptic, male patients presented to our northeast Ohio-based health system with concern for infection in Mid-March 2020. Both had a history of lung disease and during their hospitalization tested positive for SARS-CoV-2. They developed acute encephalopathy days into their hospitalization with clinical and electrographic seizures. Resolution of seizures was achieved with levetiracetam.. Patients with COVID-19 disease are at an elevated risk for seizures, and the mechanism of these seizures is likely multifactorial. Clinical (motor) seizures may not be readily detected in this population due to the expansive utilization of sedatives and paralytics for respiratory optimization strategies. Many of these patients are also not electrographically monitored for seizures due to limited resources, multifactorial risk for acute encephalopathy, and the risk of cross-contamination. Previously, several neurological symptoms were seen in patients with more advanced COVID-19 disease, and these were thought to be secondary to multi-system organ failure and/or disseminated intravascular coagulopathy-related brain injury. However, these patients may also have an advanced breakdown of the blood-brain barrier precipitated by pro-inflammatory cytokine reactions. The neurotropic effect and neuroinvasiveness of SARS-Coronavirus-2 have not been directly established.. Acute symptomatic seizures are possible in patients with COVID-19 disease. These seizures are likely multifactorial in origin, including cortical irritation due to blood-brain barrier breakdown, precipitated by the cytokine reaction as a part of the viral infection. Patients with clinical signs of seizures or otherwise unexplained encephalopathy may benefit from electroencephalography monitoring and/or empiric anti-epileptic therapy. Further studies are needed to elucidate the risk of seizures and benefit of monitoring in this population.

Topics: Aged; Aged, 80 and over; Anticonvulsants; COVID-19; Critical Illness; Electroencephalography; Epidural Abscess; Humans; Laminectomy; Levetiracetam; Lumbar Vertebrae; Male; Radiculopathy; Respiration, Artificial; Respiratory Insufficiency; Sacrum; SARS-CoV-2; Seizures; Surgical Wound Infection

The effect of therapeutic plasma exchange (TPE) on antifactor Xa activity in a patient treated with enoxaparin and levetiracetam is reported.. A 52-year-old woman was treated with levetiracetam and prophylactic enoxaparin while receiving TPE to manage respiratory failure due to anti-MDA5 antibody-associated interstitial lung disease (ILD) with dermatomyositis. Due to a scant amount of evidence regarding the management of these medications in TPE, therapeutic monitoring principles were used to assess the effect TPE had on these medications. A pre-TPE antifactor Xa activity level and levetiracetam serum assay, a post-TPE antifactor Xa activity level and levetiracetam serum assay, levetiracetam serum assays at 1 and 6 hours after the patient received her next dose, and a levetiracetam assay of the waste plasma from the TPE were collected for therapeutic drug monitoring and pharmacokinetic calculations. Utilizing standard population pharmacokinetic data, the expected antifactor Xa activity without TPE was 0.14 IU/mL. This concentration was significantly higher than the undetectable concentration (<0.1 IU/mL) that was drawn immediately after TPE, suggesting significant removal of antifactor Xa activity. The measured levetiracetam level did not significantly differ from the expected post-TPE levetiracetam level that was calculated using patient-specific pharmacokinetic data.. In a patient receiving TPE to manage anti-MDA5 antibody ILD associated with dermatomyositis and a prior seizure, TPE significantly altered enoxaparin antifactor Xa activity as evidenced by the undetectable antifactor Xa activity level drawn after TPE. Alternatively, TPE had a minimal effect on the clearance of levetiracetam as evidenced by the post-TPE level and fraction elimination of only 5% of total body stores.

Topics: Enoxaparin; Factor Xa Inhibitors; Female; Humans; Levetiracetam; Lung Diseases, Interstitial; Middle Aged; Plasma Exchange; Respiratory Insufficiency

Levetiracetam (Keppra) is a new anticonvulsant used to treat partial complex seizures that is also being investigated for its mood-stabilizing properties. Although its precise mechanism of action is unknown, levetiracetam does not appear to directly interact with the GABA system. We report the first intentional overdose with levetiracetam including clinical effects and serial serum concentrations.. A 38-year-old woman reportedly ingested 60 (500 mg) tablets of levetiracetam that she used as a mood-stabilizing medication for bipolar disorder. She had no other prescription medications available and no other medical history. She vomited 4 hours after ingestion and presented to the ED 2 hours later. In the ED, the patient was obtunded and was intubated secondary to respiratory depression. Her only other significant clinical finding was diminished deep tendon reflexes. Serum ethanol, lithium, carbamazepine, phenytoin, and valproic acid levels were all negative as was a subsequent urine screen for drugs of abuse. Her levetiracetam serum concentration was 400 microg/mL at 6 hours, 72 microg/mL at 18 hours, and 60 microg/mL at 20.5 hours (therapeutic serum concentration is 10-37 microg/mL). The elimination half-life was calculated to be 5.14 hours. She was extubated the next hospital day and recovered without sequelae.. In overdose, levetiracetam is sedating and causes respiratory depression, however, recovery is rapid with supportive care. This is the first reported case of levetiracetam overdose; serial serum concentrations suggest first-order elimination even at concentrations 10-40 fold higher than therapeutic.

Topics: Adult; Anticonvulsants; Bipolar Disorder; Drug Overdose; Female; Half-Life; Humans; Levetiracetam; Neurologic Examination; Piracetam; Poisoning; Respiration, Artificial; Respiratory Insufficiency; Suicide, Attempted