Removal of piperacillin in critically ill patients undergoing continuous venovenous hemofiltration.
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.


METHODS
Prospective study of blood and ultrafiltrate concentrations of piperacillin to assess the pharmacokinetics of the antibiotic.


METHODS
The medical intensive care unit of a teaching hospital.


METHODS
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.


METHODS
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.


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.
Capellier
G
G
Centre Hospitalier Universitaire Jean Minjoz, Faculté de Pharmacie, Besançon, France.
Cornette
C
C
Boillot
A
A
Guinchard
C
C
Jacques
T
T
Blasco
G
G
Barale
F
F
D000368:Aged; D000369:Aged, 80 and over; D002851:Chromatography, High Pressure Liquid; D016638:Critical Illness / Q000628:therapy; D015314:Dialysis Solutions / Q000032:analysis; D006207:Half-Life; D006440:Hemofiltration; D006801:Humans; D007262:Infusions, Intravenous; D017093:Liver Failure / Q000209:etiology / Q000378:metabolism* / Q000628:therapy; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000209:etiology / Q000378:metabolism* / Q000628:therapy; D010406:Penicillins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010878:Piperacillin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000209:etiology / Q000378:metabolism* / Q000628:therapy; D012770:Shock, Cardiogenic / Q000150:complications; D012772:Shock, Septic / Q000150:complications
D015314:Dialysis Solutions; D010406:Penicillins; D010878:Piperacillin