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Dear Friends,
In the PICU of the university hospital where I'm being trained there is
a child who is being treated with Continuous Veno-Venous Haemofiltration
(no fluid removal). This child is also receiving ceftazidime for
pseudomonas infection.
Can anyone please tell me how the dosage of ceftazidime needs to be
adjusted? I have found only little information about ceftazidime and
CVVH in the literature (Medline), and it is full of PK considerations,
but offers no conclusions or practical implications. What I really need
is a quick, simple, applicable answer. Also, if you have any good
refernces, please let me know.
Tanks a lot,
Lilach
Lilach Kleinberg, B.Pharm
clinical pharmacy graduate student
Israel
lilachkl.-at-.netvision.net.il
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Dear Lilach,
Ceftazidime is a betalactame antibiotic poorly bound to plasma proteins (fu
=3D 85%) and mainly eliminated by glomerular filtration and renal tubular
secretion (in adults: total CL =3D ~6.7 L/h, extrarenal elimination ~ 5% ->
non-renal CL =3D ~0.34 L/h). If your patient has severe renal failure, he
mainly relies unpon CVVH to eliminate the drug, but extrarenal CL now plays
a larger relative role. In first approximation, the drug clearance through
CVVH is the product of the drug sieving coefficient (fairly well estimated
as =3D fu) by the ultrafiltrate flow. For example, if the CVVH produces 0.5
L/h of ultrafiltrate, you would estimate the CVVH clearance to be 0.43 L/h.
Adding the nonrenal clearance, supposed to be unaltered (0.34 L/h in an
adult - adjust according to body weight in a child), you will obtain an
estimation of the total clearance in your patient (0.77 L/h in this
example). Now the amount of drug you have to give to your patient during a
given time period is a fraction of the amount you would administer in a
subject without renal impairment, and this fraction is given by the ratio
of the estimated patient CL over the normal CL (in the example 0.77/6.7 =3D
11%). It is traditional to alter the dosing interval rather than the unit
dose amount for ceftazidime adaptation in renal failure. However it seems
reasonable to both reduce the unit dose and increase the interval in
patients severely impaired, so that {dose/interval} reaches the target
fraction of {dose/interval} recommended in standard conditions. For
example, if an adult is to receive 1000 mg q 8 h in the absence of renal
problem, I would formally suggest 330 mg q 24 h in an anuric patient with
CVVH, (and practically 500 mg q 24 h, to account for uncertainity in the
estimation, and considering the convenient safety margin of ceftazidime).
This kind of approach is certainly approximative, but fits well with
published observations on PK of ceftazidime in CVVH.
See for example :
1. Golper TA. Sieberth HG, Mann H, Stummvoll HK, editors. Continuous
Hemofiltration. Basel: Karger; 1991; Pharmacokinetics. p. 110-45.
2. Vincent HJ, Vos MC, Ak=E7ahuseyin E, Goessens WHF, Van Duyl WA, Schalekam=
p
MADH. Drug clearance by continuous haemodiafiltration. Analysis of sieving
coefficients and mass transfer coefficients of diffusion. Blood Purif
1993;11:99-107.
3. Joos B, Schmidli M, Keusch G. Pharmacokinetics of antimicrobial agents
in anuric patients during continuous venovenous haemofiltration. Nephrol
Dial Transplant 1996;11:1582-5.
4. Banner W, Swenson D, Vernon D, Dean JM, Gooch WM. Ceftazidime dosing in
continuous arteriovenous hemofiltration. Clin Pharm 1989;8:91
I hope this will help
Thierry BUCLIN, Dr m=E9d
Division de Pharmacologie clinique
CHUV, Centre hospitalier universitaire vaudois
H=F4pital Beaumont 633
CH 1011 Lausanne - SWITZERLAND
Tel: +41 21 314 42 61 - Fax: +41 21 314 42 66
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Dear friends,
I just want to thank everyone who answered my question regarding
ceftazidime in CVVH for the good will and for the valuable information.
The child is a little better by now.
Many thanks,
Lilach
Lilach Kleinberg, B.Pharm
clinical pharmacy graduate student
Israel
lilachkl.aaa.netvision.net.il
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)