title: Vancomycin clearance during continuous venovenous haemofiltration in critically ill patients.
abstract: OBJECTIVE
  To study the pharmacokinetics of vancoymcin in critically ill patients with acute renal failure treated with continuous venovenous haemofiltration (CVVHF).
  
  
  METHODS
  Open-label study.
  
  
  METHODS
  Hospital pharmacy centre and medical intensive care unit of the University Medical Centre Utrecht.
  
  
  METHODS
  In a laboratory setting, the sieving coefficient (s) of vancomycin by polyacrilonitrile (PAN) haemofilters of different surface areas was studied. In one patient, the pharmacokinetics of vancomycin were studied following a single dose of vancomycin. Another patient was treated with a vancomycin dosing regimen based on data from the literature, but high trough concentrations made dose reduction necessary after 24 h of withholding therapy. After two doses of 250 mg, serum and ultrafiltrate samples were collected for pharmacokinetic evaluation. INTERVENTIONS++: CVVHF with the following operational characteristics: blood flow 200 ml/min, ultrafiltrate flow 25 ml/min, postdilution, PAN 06 hollow fibre haemofilter.
  
  
  RESULTS
  The average sieving coefficient in vitro was 0.73 +/- 0.06, 0.86 +/- 0.11, and 0.80 +/- 0.06 for the PAN 03, 06, and 10 haemofilters, respectively. Changes in the sieving coefficient by increasing the ultrafiltration rate were not clinically significant. The first patient was given a single dose of vancomycin, 1000 mg by intravenous infusion. The following pharmacokinetic data were obtained: apparent volume of distribution (Vd) 55.8 l, terminal half-life time (t(1/2 term)) 15.4 h, total clearance (Cl(tot)) 2.5 l/h, CVVHF clearance (CL(CVVHF, form 1)) 1.4 l/h, and body clearance (Cl(body)) 1.1 l/h. The average sieving coefficient during the study period was 0.89 +/- 0.03. In the second patient, the pharmacokinetics of vancomycin were studied following dose reduction: Vd 41.7 l, (1/2 term) 20.3 h, Cl(tot) 1.4 l/h, Cl(CVVHF, form 1) 1.4 l/h, and Cl(body) < 0.1 l/h. The average sieving coefficient during the study period was 0.88 +/- 0. 03. The cumulative amount of vancomycin removed by means of CVVHF during the 12-h study period was 245 mg in patient 1 and 228 mg in patient 2. CONCLUSIONS++: CVVHF with a PAN 06 haemofilter effectively removed vancomycin in two critically ill patients. The amount of vancomycin removed with CVVHF was about 250 mg per 12 h. A clear difference in body clearance in the two patients was observed. Our dosage recommendation for vancomycin in critically ill patients receiving CVVHF is a loading dose of 15-20 mg/kg followed after 24 h by 250 to 500 mg twice daily with close monitoring of the serum and ultrafiltrate vancomycin concentration.
authors.affiliation: Division of Internal Medicine and Dermatology, Department of Intensive Care and Clinical Toxicology, University Medical Centre Utrecht, PO box 85500, 3508 GA Utrecht, The Netherlands. f.t.j.boereboom@digd.azu.nl
authors.forename: F T
authors.initials: FT
authors.lastname: Boereboom
authors.forename: F F
authors.initials: FF
authors.lastname: Ververs
authors.forename: P J
authors.initials: PJ
authors.lastname: Blankestijn
authors.forename: T J
authors.initials: TJ
authors.lastname: Savelkoul
authors.forename: A
authors.initials: A
authors.lastname: van Dijk
mesh_terms: D000180:Acrylic Resins; D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism* / Q000628:therapy*; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D016638:Critical Illness; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005260:Female; D006440:Hemofiltration / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000150:complications; D012772:Shock, Septic / Q000150:complications; D013997:Time Factors; D014640:Vancomycin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000180:Acrylic Resins; D000900:Anti-Bacterial Agents; C010504:polyacrylonitrile; D014640:Vancomycin