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Levetiracetam is a first-line therapy for seizures in critically ill patients because of its clinical efficacy, minimal drug interactions, and wide therapeutic window. The primary mechanism of levetiracetam clearance is renal, and the drug has a low molecular weight. It is hydrophilic and exhibits minimal protein binding. Thus it is expected that levetiracetam will be removed by continuous venovenous hemofiltration (CVVH), with limited clearance by venoarterial extracorporeal membrane oxygenation (ECMO). We describe the case of a 67-year-old man who was admitted to the cardiovascular surgery intensive care unit after cardiac arrest and initiation of venoarterial ECMO. His course was complicated by multiorgan dysfunction including acute renal failure requiring CVVH. On hospital day 6, intravenous levetiracetam, at a loading dose of 2000 mg followed by a maintenance dose of 1000 mg every 12 hours, was initiated for new-onset seizures. The volume of distribution was 0.65 L/kg, and clearance was measured with peak (ranging from 26.5-39.8 μg/ml) and trough (ranging from 13.9-18.2 μg/ml) concentrations. Elimination half-life ranged from 8.7-10.1 hours. Renal dysfunction reduces levetiracetam clearance, and dosage reductions are recommended to prevent accumulation. Current CVVH dosing recommendations are based on predicted removal without clinical data. The volume of distribution and clearance in this case were similar to those of a normal healthy patient. Based on these results, we recommend considering an initial levetiracetam dose of 1000 mg every 12 hours for patients receiving CVVH, with dosage adjustments based on therapeutic drug monitoring.

Levetiracetam pharmacokinetics observed in this case approximated those seen in a normal healthy patient and a regimen of 1000 mg twice daily achieved serum trough concentrations at the lower limit of the target range. This case indicates that in a patient with acute liver dysfunction on CVVH, 1000 mg twice daily may be considered as an empiric levetiracetam regimen.

Cardiac vasoplegia remains a significant contributor of morbidity and mortality in cardiac surgery patients after cardiopulmonary bypass. Effective therapeutic options for vasopressor-refractory vasoplegia are limited. We report 3 patients in whom we administered high-dose intravenous ascorbic acid (vitamin C), a cofactor for endogenous catecholamine synthesis, to treat vasoplegia refractory to epinephrine, vasopressin, and norepinephrine after surgery requiring cardiopulmonary bypass. Reductions in vasopressor requirements were observed in all 3 patients, and, in 2 patients, norepinephrine was completely discontinued within 24 hours. Ascorbic acid is a novel potential therapeutic option for cardiac vasoplegia that warrants rigorous prospective studies.

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