Nefopam pharmacokinetics in patients with end-stage renal disease.

R?animation Chirurgicale Polyvalente, CHU de Poitiers, 86021 Poitiers Cedex, France. o.mimoz@chu-poitiers.f.

BACKGROUND: Treatment of intense postoperative pain in patients with end-stage renal disease (ESRD) is a recurrent problem for anesthesiologists because of the risk of accumulation of numerous molecules and their metabolites. Nefopam is a potent analgesic metabolized by the liver and weakly eliminated intact in urine that may offer advantages for use in patients with ESRD because it lacks respiratory-depressive effects. However, the effects of renal failure on nefopam disposition have never been investigated.

METHODS: We studied 12 ESRD patients (creatinine clearance <20 mL/min, mean age 57 ? 13 years) having surgery under general anesthesia to create or repair an arteriovenous fistula. Postoperatively, after complete recovery from anesthesia, each patient received a single 20-mg dose of nefopam IV over 30 minutes. Nefopam and desmethyl-nefopam concentrations in plasma samples obtained over 48 hours were determined by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameter values obtained were compared with those of 12 healthy 50- to 60-year-old volunteers who also received a single 20-mg nefopam infusion over 30 minutes using a population pharmacokinetic approach.

RESULTS: Healthy volunteers and ESRD patients had comparable demographic characteristics. In comparison with those volunteers, ESRD patients had a lower volume of central compartment (115 and 53 L vs. 264 L for patients not yet hemodialyzed and on chronic hemodialysis, respectively; P < 0.001) and lower mean nefopam clearance (37.0 and 27.3 L/h vs. 52.9 L/h, P < 0.001), resulting in higher mean nefopam peak concentration (121 and 223 ng/mL vs. 61 ng/mL, P < 0.001).

CONCLUSIONS: Nefopam distribution and elimination are altered in patients with ESRD, resulting in heightened exposure. To avoid too-high concentration peaks, it is suggested that the daily nefopam dose be reduced by 50%.

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Phosphate‐containing dialysis solution prevents hypophosphatemia during continuous renal replacement therapy

Phosphate?containing dialysis solution prevents hypophosphatemia during continuous renal replacement therapy - BROMAN - 2010 - Acta Anaesthesiologica Scandinavica - Wiley Online LibrarySkip to Main Content

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DOI: 10.1111/j.1399-6576.2010.02338.x

? 2010 The Authors. Journal compilation ? 2010 The Acta Anaesthesiologica Scandinavica Foundation

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How to CiteBROMAN, M., CARLSSON, O., FRIBERG, H., WIESLANDER, A. and GODALY, G. , Phosphate?containing dialysis solution prevents hypophosphatemia during continuous renal replacement therapy. Acta Anaesthesiologica Scandinavica, no. doi: 10.1111/j.1399-6576.2010.02338.x

Author Information1

Department of Anaesthesiology and Intensive Care, Lund University Hospital, Lund, Sweden

2

Gambro Lundia AB, Lund, Sweden

*Correspondence: Address:?Dr Marcus Broman?Department of Anaesthesiology and Intensive Care?Lund University Hospital?S?221 85 Lund?Sweden?e?mail: marcus.broman@skane.se

Publication HistoryArticle first published online: 29 OCT 2010Accepted for publication 21 September 2010 SEARCH Search Scope All contentPublication titlesIn this journalIn this issue Search String Advanced >Saved Searches > SEARCH BY CITATION Volume: Issue: Page: ARTICLE TOOLSGet PDF (252K)Save to My ProfileE-mail Link to this ArticleExport Citation for this ArticleRequest Permissions AbstractArticleReferencesCited By View Full Article (HTML) Get PDF (252K)

Background: Hypophosphatemia occurs in up to 80% of the patients during continuous renal replacement therapy (CRRT). Phosphate supplementation is time?consuming and the phosphate level might be dangerously low before normophosphatemia is re?established. This study evaluated the possibility to prevent hypophosphatemia during CRRT treatment by using a new commercially available phosphate?containing dialysis fluid.

Methods: Forty?two heterogeneous intensive care unit patients, admitted between January 2007 and July 2008, undergoing hemodiafiltration, were treated with a new Gambro dialysis solution with 1.2?mM phosphate (Phoxilium) or with standard medical treatment (Hemosol B0). The patients were divided into three groups: group 1 (n=14) receiving standard medical treatment and intravenous phosphate supplementation as required, group 2 (n=14) receiving the phosphate solution as dialysate solution and Hemosol B0 as replacement solution and group 3 (n=14) receiving the phosphate?containing solution as both dialysate and replacement solutions.

Results: Standard medical treatment resulted in hypophosphatemia in 11 of 14 of the patients (group 1) compared with five of 14 in the patients receiving phosphate solution as the dialysate solution and Hemosol B0 as the replacement solution (group 2). Patients treated with the phosphate?containing dialysis solution (group 3) experienced stable serum phosphate levels throughout the study. Potassium, ionized calcium, magnesium, pH, pCO2 and bicarbonate remained unchanged throughout the study.

Conclusion: The new phosphate?containing replacement and dialysis solution reduces the variability of serum phosphate levels during CRRT and eliminates the incidence of hypophosphatemia.

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