Vancomycin clearance during continuous venovenous haemofiltration in critically ill patients

Objective: To study the pharmacokinetics of vancoymcin in critically ill patients with acute renal failure treated with continuous venovenous haemofiltration (CVVHF).¶Design: Open-label study.¶Setting: Hospital pharmacy centre and medical intensive care unit of the University Medical Centre Utrecht.¶Materials and 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.¶Intervention: CVVHF with the following operational characteristics: blood flow 200 ml/min, ultrafiltrate flow 25 ml/min, postdilution, PAN 06 hollow fibre haemofilter.¶Measurements and 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, ¶t_{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.¶Conclusion: 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.     

Hemoperfusion is ineffectual in severe chloroquine poisoning

OBJECTIVES: To study the toxicokinetics in severe chloroquine poisoning, and to evaluate the efficacy of hemoperfusion. DESIGN: Case report on one observation. SETTING: Medical intensive care unit (ICU) of the University Medical Center Utrecht, The Netherlands. PATIENT HISTORY: A previously healthy, 52-yr-old woman ingested 100 tablets containing 100 mg chloroquine base 1 hr before admission. At admission, she was drowsy, agitated, hypotensive, and in respiratory distress. Shortly thereafter, she was resuscitated from cardiac arrest. After hemodynamic and respiratory stabilization, the patient was transferred to the medical ICU. TOXICOKINETICS EVALUATION: During the course of her stay at the ICU, blood samples were taken for the determination of chloroquine and the metabolite desethylchloroquine concentration. Hemoperfusion was started 3.5 hrs after ingestion of the chloroquine tablets. MEASUREMENTS AND MAIN RESULTS: The following toxicokinetics data during this severe chloroquine poisoning were calculated: apparent volume of the central compartment 181 L, apparent volume of distribution 1137 L, half-life in the distribution phase 6.4 hrs, half-life in the elimination phase 392.8 hrs, and total body clearance 2.01 L/hour. The average extraction ratio during hemoperfusion was 0.07, 0.28, and 0.25, in plasma, erythrocytes and whole blood, respectively. The total amount of chloroquine removed by hemoperfusion was only 480 mg (5.3% of the amount ingested). Simulation of a hemoperfusion session over 5 hrs by using a column with an optimal extraction ratio of 1.0 would have removed 1,816 mg chloroquine, only 18.2% of the amount ingested. This limited contribution of hemoperfusion to the total clearance makes it ineffective. CONCLUSION: Hemoperfusion is not effective in severe chloroquine poisoning, even when started (relatively) early in the course of the intoxication. Toxicokinetic evaluation of a chloroquine poisoning should be based on the evaluation of plasma and whole blood concentrations.     

Homozygous cystinuria and the oculo-cerebro-renal dystrophy of Lowe in same family

The mother and daughter in a family had homozygous cystinuria and were also heterozygous carriers of the oculo-cerebro-renal dystrophy of Lowe. The daughter was also epileptic. The son had Lowe's syndrome and the father an increased urinary excretion of cystine and lysine. This evidence together with other case reports suggests that the defect in cystinuria and that of Lowe's syndrome may be connected.     

Urinalysis and the plain abdominal radiograph in the diagnosis of ureteric colic

Objectives : 1. To investigate the diagnostic accuracy of urinalysis and the plain abdominal radiograph in predicting positive intravenous pyelography for patients with a history and examination suggestive of ureteric colic. 2. To examine the disposition of patients presenting to the emergency department with ureteric colic. Methods : A retrospective cohort study set in a tertiary referral hospital emergency department over a 12‐month period was conducted. Three hundred and eighteen patients who presented with a provisional diagnosis of ureteric colic and had intravenous pyelography were identified from radiology department logs and emergency department discharge International Classification of Disease‐9 codes. Results : Three hundred and eighteen patients were identified. Sixty‐nine per cent had positive intravenous pyelography. Sensitivity and specificity of: urinalysis were 93% and 41%; abdominal X‐ray, 57% and 83%; and urinalysis plus abdominal X‐ray, 99% and 36%, respectively. Seventy‐seven per cent were admitted to the emergency department observation ward. Twenty‐seven per cent were subsequently admitted under the hospital’s urology service. Conclusions : Sex, haematuria and the presence of a calculus on abdominal X‐ray were all significant predictors of positive intravenous pyelography. Haematuria was sensitive but not specific for positive intravenous pyelography. The addition of the abdominal X‐ray marginally improves the diagnostic accuracy.