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Removal of piperacillin in critically ill patients undergoing continuous venovenous hemofiltration
G Capellier1, C Cornette, A Boillot
1Centre Hospitalier Universitaire Jean Minjoz, Faculté de Pharmacie, Besançon, France.
Objective:
Continuous hemofiltration is now widely used in the intensive care unit. Our study aimed to assess the removal of piperacillin under continuous hemofiltration and to define a suitable dosage regimen of administration.
Design:
Prospective study of blood and ultrafiltrate concentrations of piperacillin to assess the pharmacokinetics of the antibiotic.
Setting:
The medical intensive care unit of a teaching hospital.
Patients:
Ten patients were included in the study. Six patients were receiving their first dose of piperacillin (group 1) and four had already been treated for 2 to 6 days (group 2). The mean Simplified Acute Physiology II score was 74 +/- 6 (SEM), and the number of organ failures was 3.6 +/- 0.3 (range 3 to 5). Renal failure was related to septic shock in seven patients and to cardiogenic shock in three patients. Seven patients were anuric. Hepatic dysfunction was present in four of the ten patients.
Interventions:
Patients were treated with continuous venovenous hemofiltration using a hollow polysulfone capillary fiber. Piperacillin (4 g) was injected intravenously over 20 mins. Arterial blood and ultrafiltrate were sampled immediately before the injection and then every hour until 8 hrs after injection time. Piperacillin concentrations were assayed using high performance liquid chromatography.
Measurements And Main Results:
In group 1, the mean serum peak concentration of piperacillin was in the normal range (125 +/- 21 mg/L), but trough values were higher (48 +/- 8 mg/L) than in normal subjects. In group 2, trough values before the injection were increased in all patients (188 +/- 71 mg/L). At T1, blood peak concentration reached 470 +/- 127 mg/L. A small amount of piperacillin was retrieved from the ultrafiltrate. The elimination half-life was 5.1 +/- 1.4 and 4.8 +/- 1.4 hrs in groups 1 and 2, respectively.
Conclusions:
Piperacillin was not removed to a significant extent during continuous hemofiltration. Further, in the intensive care unit, patients in shock with multiple organ failure such as liver failure might behave differently from patients with stable end-stage renal disease. A 4-g dose of piperacillin twice a day is recommended in such patients.
Insights
Piperacillin is not significantly removed by continuous hemofiltration. Intensive care unit patients with shock and organ failure may require adjusted piperacillin dosing, with 4g twice daily recommended.
Area of Science:
- Pharmacology
- Critical Care Medicine
- Nephrology
Background:
- Continuous hemofiltration (CHF) is a common intensive care unit (ICU) therapy.
- Antibiotic dosing requires adjustment in critically ill patients with altered physiology.
- Piperacillin is a widely used antibiotic, but its pharmacokinetics during CHF are not well-defined.
Purpose of the Study:
- To evaluate piperacillin removal during continuous venovenous hemofiltration (CVVH).
- To determine appropriate piperacillin dosage regimens for ICU patients undergoing CVVH.
- To compare piperacillin pharmacokinetics in different patient groups within the ICU.
Main Methods:
- Prospective pharmacokinetic study involving ten ICU patients receiving piperacillin.
- Measurement of piperacillin concentrations in blood and ultrafiltrate during CVVH.
- High-performance liquid chromatography (HPLC) used for piperacillin assay.
Main Results:
- Piperacillin removal via ultrafiltration was minimal.
- Elimination half-life was prolonged in both patient groups (5.1 and 4.8 hours).
- Trough concentrations were higher than in normal subjects, especially in patients pre-treated with piperacillin.
Conclusions:
- Continuous hemofiltration does not significantly clear piperacillin.
- ICU patients with shock and multi-organ failure exhibit different drug handling compared to stable renal disease patients.
- A dosage of 4g piperacillin twice daily is suggested for these critically ill patients.