Large-pore haemodialysis membranes: an efficient tool for rapid removal of vancomycin after accidental overdose

Sir,

The usual dosage of vancomycin is 40–60 mg/kg per day divided into four 1 h infusions. Its elimination is mainly renal. An overdose can be responsible for severe ototoxicity and nephrotoxicity, especially if combined with other nephrotoxic drugs such as aminoglycoside antibiotics. As long as renal function remains normal, vancomycin plasma t1/2 is 4–6 h, suggesting forced diuresis alone to reduce drug serum levels rapidly [1].

Renal failure provoked by a vancomycin overdose is responsible for an increase in plasma t1/2 suggesting the necessity of efficient extracorporal drug removal. Standard haemodialysis with cuprophane and cellulose acetate membranes has a limited capacity to remove substances larger than 500 Da. As vancomycin has a molecular weight of ~1500 Da it is only marginally removed by standard HD or peritoneal dialysis [2], whereas continuous haemodiafiltration [3], charcoal haemoperfusion [4] and haemodialysis with high flux polysulfone membranes [5] have been shown to clear vancomycin successfully from the circulation.

The patient, a 9-year-old girl (17 kg, 90 cm), was suffering from cystic fibrosis (homozygous F508del mutation) with chronic airway obstruction and multiple infectious episodes. She accidentally received toxic doses of vancomycin (260 mg/kg/day in four daily doses) over 9 days and usual doses of gentamycin (3 mg/kg/day) in an outside hospital. No controls of vancomycin and gentamycin serum levels were performed until the ninth day. The girl developed progressive malaise and acute generalized exanthematous pustulosis (AGEP) associated with fever of 38°C. On day 10 the vancomycin serum level was 420 mg/l and antibiotic treatment was interrupted. She developed non-oliguric renal failure. Serum creatinine increased to 650 µmol/l and BUN to 42.6 mmol/l 8 days after discontinuation of vancomycin (Figure 1), whereas serum potassium, phosphorus and calcium levels remained in the normal range. She was then transferred to our hospital. On arrival she presented with weight loss of 2 kg, severe anorexia and irritability. The vancomycin serum level was 96 mg/l (calculated t1/2 = 216 h). She had normal blood pressure and a constant diuresis without volume overload.



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Fig. 1. Time course of serum creatinine (closed circles) and vancomycin levels (closed triangles) in relation to vancomycin overdose (260 mg/kg per day) over 9 days (grey arrows) and haemodialysis sessions (black arrows) using a high-flux large pore size haemodialysis membrane.

 
Vascular access was obtained via a femoral 9.0-Fr MedComp dual lumen catheter. A Gambro AK-100 haemodialysis machine was used with a high flux large pore-size polymethylmethacrylate dialysis membrane (BK-F 1.3; Toray, Tokyo, Japan) and paediatric lines giving an extracorporal volume of 150 ml. The filter was prepared using NaCl 0.9% containing heparin 1000 UI/l. Low molecular weight heparin (1 mg/kg) was administered at the onset of haemodialysis. Blood flow was 6 ml/kg per min (100 ml/min); duration of treatment was 4 h using standard dialysis baths. Ultrafiltration was 1000 ml/h compensated by a continuous infusion of NaCl 0.9% at 1000 ml/h. The post-run vancomycin level was 26 mg/l demonstrating a 73% intravascular vancomycin removal (calculated vancomycin t1/2 = 2.0 h), BUN was 13 mmol/l and serum creatinine 205 µmol/l. A second haemodialysis session was initiated 24 h later resulting in a vancomycin plasma level of 12 mg/l after 2 h (t1/2 = 1.8 h). The skin lesions disappeared progressively.

Renal function recovered rapidly 3 days after admission and the patient left the hospital in a good general condition 7 days after discontinuation of haemodialysis with a serum creatinine of 80 µmol/l. One month later serum creatinine was 40 µmol/l, proteinuria was negative and blood pressure was normal.

This case demonstrates efficient removal of vancomycin using a high-flux, large pore size haemodialysis membrane (cut off 70 000 Da). Despite the relatively high extracorporal volume (150 ml), no blood priming was necessary and haemodialysis was well tolerated.

Once renal function decreased, vancomycin plasma t1/2 increases and resulted in an asymptotic kinetic of drug plasma levels (Figure 1).

Earlier reports discuss the benefits of charcoal haemoperfusion or haemodialysis with high efficiency membranes in the treatment of vancomycin overdose. Both methods have been shown to remove vancomycin efficiently. However, charcoal haemoperfusion exposes to the potential risk of excessive calcium and phosphate removal, hypothermia or thrombocytopaenia. In order to avoid such electrolyte disturbances, a haemodialysis filter is placed in line after the charcoal circuit. In order to obtain an efficient toxine clearance, charcoal haemoperfusion requires high blood flow rates. This may cause difficulties concerning the prevention of the above-mentioned potential risks, which are aggravated by higher blood flow. Direct comparison of continuous haemofiltration, charcoal haemoperfusion and haemodialysis with either high efficiency or high flux membranes is not possible because the efficiency of each technique depends on multiple variables such as blood/dialysate flow rates, age of patients and the exact type of haemodialysis filter. The choice of technique should take into consideration the availability and experience in the medical centre as well as the patient's age. In conclusion, haemodialysis with high-flux, large pore size membranes should be considered rapidly in patients with toxic vancomycin serum levels and concomitant or pre-existing renal failure.

Tim Ulinski, Georges Deschênes and Albert Bensman

Department of Pediatric Nephrology Hôpital Trousseau 26, avenue du Docteur Arnold-Netter 75571 Paris Cedex 12 France Email: tim.ulinski{at}trs.aphp.fr

Acknowledgments

We are grateful to all members of our paediatric haemodialysis team, in particular Nathalie Bouvet, Marie-René Mellat, Chalma Badouraly and Linda Delbreil, for their great expertise in all technical aspects of paediatric haemodialysis.

Conflict of interest statement. None declared.

References

  1. Miner LJ, Faix RG. Large vancomycin overdose in two premature infants with minimal toxicity. Am J Perinatol 2004; 21: 433–438[CrossRef][ISI][Medline]
  2. Pai AB, Pai MP. Vancomycin dosing in high flux hemodialysis: a limited-sampling algorithm. Am J Health Syst Pharm 2004; 61: 1812–1816[ISI][Medline]
  3. Akil IO, Mir S. Hemodiafiltration for vancomycin overdose in a patient with end-stage renal failure. Pediatr Nephrol 2001; 16: 1019–1021[CrossRef][ISI][Medline]
  4. Panzarino VM, Feldstein TJ, Kashtan CE. Charcoal hemoperfusion in a child with vancomycin overdose and chronic renal failure. Pediatr Nephrol 1998; 12: 63–64[CrossRef][ISI][Medline]
  5. Bunchman TE, Valentini RP, Gardner J et al. Treatment of vancomycin overdose using high-efficiency dialysis membranes. Pediatr Nephrol 1999; 13: 773–774[CrossRef][ISI][Medline]




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