Pharmacokinetics of Meropenem in Critically Ill Patients with Acute Renal Failure Treated by Continuous Hemodiafiltration

W. A. Krueger; T. H. Schroeder; M. Hutchison; E. Hoffmann; H.-J. Dieterich; A. Heininger; C. Erley; A. Wehrle; K. Unertl

doi:10.1128/AAC.42.9.2421

DOI: 10.1128/AAC.42.9.2421

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Fig. 1.
Levels of meropenem in plasma (means and standard deviations) in eight anuric critically ill patients treated by continuous hemodiafiltration. A dose of 1,000 mg of meropenem was administered as an i.v. infusion over 30 min.

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Table 1.

Demographic and diagnostic information and pharmacokinetic parameters following administration of 1,000 mg of meropenem i.v. for nine anuric critically ill patients treated by continuous hemodiafiltration^a

Patient no.	Sex^b	Age (yr)	Weight (kg)	Diagnosis	Infection (APACHE-II scores)^c	Diafiltrate (liters/h)	t_1/2α^d (t_1/2β) (h)	AUC_0–12 (μg · h/ml)	CL_total (CL_CVVHDF) (ml/min)	V_ss^d (liters/kg of body wt)
1^e	F	39	65	Mitral valve endocarditis, respiratory failure, progressive liver failure, pelvic venous thrombosis	Endocarditis, brain abscess (34, 21)	1,850	0.15 (7.38)	287.5	57.98 (31.5)	0.32
2	M	65	66	Thoracoabdominal aortic aneurysm, aortic valve regurgitation, hemorrhage, compartment syndrome of left lower limb	Pneumonia (28, 20)	1,725	0.21 (3.92)	343.1	48.59 (30.0)	0.27
3^e	F	68	66	Low output syndrome after bivalvular replacement, pulmonary edema	Sepsis^f (15, 14)	1,875	0.16 (4.51)	295.4	56.43 (33.4)	0.28
4^e	M	75	76	Coronary bypass, hemorrhage, respiratory failure	Pneumonia^f (36, 24)	1,650	0.12 (4.75)	354.3	47.05 (29.2)	0.25
5^g	F	19	65	Polytrauma, subdural hematoma	Pneumonia, sepsis (37, 24)
6	M	66	91	Myocardial infarctions, mitral valve regurgitation, coronary bypass, postoperative ventricular fibrillation, thrombopenia	Pneumonia^f (28, 22)	1,725	0.02 (4.82)	539.2	30.92 (30.2)	0.08
7	F	30	56	Cardiomyopathy, respiratory failure, thyreotoxicosis	Pneumonia (14, 20)	1,625	0.21 (2.80)	480.9	34.66 (27.5)	0.17
8	M	65	70	Thoracic aortic aneurysm, hematothorax, respiratory failure	Sepsis^f (26, 34)	1,850	0.12 (4.54)	250.1	66.65 (32.5)	0.30
9	M	61	70	Cardiopulmonary resuscitation, aortic valve replacement, recurrent ventricular fibrillation	Pneumonia (39, 22)	1,625	0.17 (3.50)	201.6	82.69 (28.9)	0.38
Mean		54.2	69.4		(28.6, 22.3)	1,741	0.15 (4.53)	344.0	53.12 (30.4)	0.26
SD		19.7	9.7		(9.1, 5.3)	105	0.06 (1.35)	114.4	16.83 (2.0)	0.09

↵a t_1/2α, distribution half-life; t_1/2β, elimination half-life; AUC_0–12, area under the concentration-time curve of plasma meropenem concentrations; CL_total, total body clearance of meropenem; CL_CVVHDF, clearance of meropenem by continuous venovenous hemodiafiltration;V_ss, apparent volume of distribution at steady state.
↵b F, female; M, male.
↵c APACHE-II scores were determined within 24 h of admission to the intensive-care unit and on the day of the pharmacokinetic investigation.
↵d Values derived from fitted biexponential model.
↵e Patient died in intensive-care unit.
↵f Clinical diagnosis could not be proven by microbiological culture.
↵g Patient recovered from renal failure; no pharmacokinetic analysis was done.