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Seizures in the critically ill: the role of imipenem
B S Koppel1, W A Hauser, C Politis
1Department of Neurology, Metropolitan Hospital Center, New York, New York 10029, USA.
Purpose:
To determine the risk of seizures in critically ill patients receiving the antibiotic imipenem, a broad-spectrum antibiotic that has been associated with seizures. Reports generally have not considered other contributing factors such as dose, seizure history, and morbidity index of the underlying illness necessitating the antibiotic.
Methods:
Charts of all patients in a 450-bed municipal hospital who received imipenem in a 6-month period, as determined by pharmacy records, were reviewed for dosage and duration of imipenem use, occurrence of seizures. and mortality outcome. Attention was paid to demographic features; pattern of seizure occurrence during, before, and after imipenem use; renal function; and correction for dosage based on size.
Results:
Seventy-five charts were reviewed. Sixty-three patients had no seizures during the hospitalization, four had seizures while receiving imipenem, and eight had seizures during the hospitalization but before or after imipenem use. The incidence of seizures was 4/1,000 patient-days on, and 3.9/1,000 patient-days off imipenem (not significant). The risk of seizure in both groups was considerably higher in those patients with a history of seizures before hospitalization. The presence of other factors that could contribute to increased concentration of imipenem in the brain, such as renal failure or acute stroke, did not contribute to seizure incidence. Metabolic derangement, anoxia, and phenytoin discontinuation did contribute to seizure incidence.
Conclusions:
Seizure incidence is increased in all critically ill patients (16% of patients studied), but with no added risk during the period patients received imipenem. Determining the proper dose based on a patient's body mass, correction of dose in the presence of renal failure, and avoidance of excess of 2 g/day of imipenem removes any added risk for seizures from imipenem. Despite experimental data to suggest action of imipenem on the glutamate/N-methyl-d-aspartate receptor, or interference with binding to the gamma-aminobutyric acid receptor, and early clinical studies that warned against its use because of seizure risk, we found that careful use of this antibiotic is safe.
Insights
Critically ill patients receiving imipenem (a broad-spectrum antibiotic) do not face an increased seizure risk when dosed appropriately. Careful administration, considering renal function and dosage limits, ensures safety despite prior concerns.
Area of Science:
- Pharmacology
- Critical Care Medicine
- Infectious Diseases
Background:
- Imipenem is a broad-spectrum antibiotic associated with seizure risk.
- Previous reports often overlooked contributing factors like dosage and patient morbidity.
Purpose of the Study:
- To determine the risk of seizures in critically ill patients treated with imipenem.
- To evaluate the influence of dose, seizure history, and illness severity on imipenem-associated seizures.
Main Methods:
- Retrospective chart review of 75 critically ill patients who received imipenem over six months.
- Analysis included imipenem dosage, duration, seizure occurrence, renal function, and mortality.
- Consideration of demographic features and seizure patterns before, during, and after imipenem administration.
Main Results:
- No significant difference in seizure incidence was observed between patients on imipenem (4/1,000 patient-days) and those not (3.9/1,000 patient-days).
- Patients with a prior seizure history had a considerably higher risk.
- Renal failure or stroke did not increase seizure risk, but metabolic derangement, anoxia, and phenytoin discontinuation did.
Conclusions:
- Seizure incidence is elevated in critically ill patients generally, but imipenem use did not add to this risk.
- Proper dosing based on body mass, renal function, and not exceeding 2 g/day mitigates seizure risk.
- Careful use of imipenem is safe in critically ill patients, despite theoretical concerns regarding its mechanism of action.
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