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Albumin dialysis: a new therapeutic strategy for intoxication from protein-bound drugs

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Abstract

Objective

Although water-soluble drugs can be removed by haemofiltration/haemodialysis, morbidity and mortality from intoxication with protein-bound drugs remains high. The present study investigates whether albumin dialysis in the form of the Molecular Adsorbents Recirculating System (MARS) is effective in removal of protein-bound drugs.

Design

Prospective animal study.

Setting

Surgical research laboratory in a university hospital.

Subjects

Seven female Norwegian Landrace pigs.

Intervention

We studied whether midazolam (97% albumin-bound) and fentanyl (85% alpha-1-acid glycoprotein-bound), administered as anaesthetics to pigs with induced acute liver failure, could be removed by MARS dialysis lasting for 4 h.

Measurements

After 4 h of dialysis, total and free anaesthetic concentrations were measured in the blood and dialysate from different segments of the MARS circuit.

Main results

Midazolam: total plasma concentrations fell by 47.1±2.1% (in 4 h) across the MARS filter (p<0.01). The charcoal component of the system reduced the total dialysate drug concentration by 16.4±2.2% (p<0.05). Free midazolam removal followed a similar pattern. Fentanyl: total plasma concentrations fell by 56.1±2.4% (in 4 h) across the MARS filter (p<0.01). Clearance of fentanyl from the dialysate by the charcoal was 70±0.7% at 4 h (p<0.001).

Conclusions

The results of the study show that MARS can remove both albumin and other protein-bound drugs efficiently from the plasma, and it may have a place for the treatment of patients suffering from intoxication with this class of compounds.

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Acknowledgements

This work was supported by the Liver Research Foundation, the Norwegian Research Council and the Sir Siegmund Warburg Voluntary Settlement. Teraklin AG provided the MARS kits free of cost.

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Authors and Affiliations

  1. Liver Failure Group, Institute of Hepatology, 69–75 Chenies Mews, London, WC1E 6HX, UK

    Sambit Sen, Nathan A. Davies, Roger Williams & Rajiv Jalan

  2. Department of Digestive Surgery, University Hospital Northern Norway, Tromsø, Norway

    Lars M. Ytrebø, Geir I. Nedredal & Arthur Revhaug

  3. Department of Cellular Neuroscience, Max-Delbrück Center for Molecular Medicine, Berlin, Germany

    Christopher Rose

  4. Department of Clinical Pharmacology, University Hospital Northern Norway, Tromsø, Norway

    Ole-Martin Fuskevaag

Authors
  1. Sambit Sen
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  2. Lars M. Ytrebø
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  3. Christopher Rose
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  4. Ole-Martin Fuskevaag
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  5. Nathan A. Davies
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  6. Geir I. Nedredal
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  7. Roger Williams
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  8. Arthur Revhaug
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  9. Rajiv Jalan
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Corresponding author

Correspondence to Rajiv Jalan.

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Sen, S., Ytrebø, L.M., Rose, C. et al. Albumin dialysis: a new therapeutic strategy for intoxication from protein-bound drugs. Intensive Care Med 30, 496–501 (2004). https://doi.org/10.1007/s00134-003-2141-0

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  • DOI: https://doi.org/10.1007/s00134-003-2141-0

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