Journal of Artificial Organs

, Volume 21, Issue 2, pp 215–219 | Cite as

Acetaminophen clearance during ex vivo continuous renal replacement therapies

  • Bridget A. Scoville
  • Vera Vulaj
  • Bruce A. Mueller
  • Gail M. Annich
  • Deborah S. Wagner
Original Article Artificial Kidney / Dialysis


Intravenous acetaminophen is an adjuvant to opioid use in critically ill and surgical patients requiring continuous renal replacement therapy (CRRT). The objective of this study was to determine the ex vivo transmembrane clearance of intravenous acetaminophen during continuous hemofiltration and hemodialysis. Transmembrane clearance was assessed using a validated ex vivo bovine blood model for CRRT using an F8 or HF1400 hemodiafilter. Ultrafiltrate and dialysate flow rates were 1, 2, and 3 L/h. Urea and acetaminophen clearances were calculated and compared. Acetaminophen was readily cleared by continuous hemofiltration with both hemodiafilters. Acetaminophen clearance rates were 92–98% of ultrafiltrate production rates. Similarly, dialytic acetaminophen clearances approximated dialysate flow rates for both hemodiafilters. Acetaminophen is readily cleared by CRRT. Patients receiving CRRT and acetaminophen may require increased doses for adequate pain control.


Intravenous acetaminophen Critical care Continuous renal replacement therapy Dialysisex vivo clearance 


  1. 1.
    Abelha FJ, Botelho M, Fernandes V, Barros H. Determinants of postoperative acute kidney injury. Crit Care. doi: 10.1186/cc7894.
  2. 2.
    Uchino S, Kellum JA, Bellomo R, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005;294:813–8.CrossRefPubMedGoogle Scholar
  3. 3.
    Scoville BA, Mueller BA. Medication dosing in critically ill patients with acute kidney injury treated with renal replacement therapy. Am J Kidney Dis. 2013;61:490–500.CrossRefPubMedGoogle Scholar
  4. 4.
    Lewis SJ, Mueller BA. Antibiotic dosing in patients with acute kidney injury: “enough but not too much”. J Intens Care Med. doi: 10.1177/0885066614555490 .
  5. 5.
    Sinatra RS, Jahr JS, Reynolds LW, Viscusi ER, Groudine SB, Payen-Champenois C. Efficacy and safety of single and repeated administration of 1 gram intravenous acetaminophen injection (paracetamol) for pain management after major orthopedic surgery. Anesthesiology. 2005;102(4):822–31.CrossRefPubMedGoogle Scholar
  6. 6.
    American Society of Anesthesiologists Task Force on Acute Pain Management. Practice guidelines for acute pain management in the perioperative setting: an updated report by the American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2012; 116(2):248–73.CrossRefGoogle Scholar
  7. 7.
    Ali MA, Shamim F, Chughtai S. Comparison between intravenous paracetamol and fentanyl for intraoperative and posterative pain relive in dilatation and evacuation: prospective, randomized interventional trial. J Anaesthesiol Clin Pharmacol. 2015;31(1):54–8.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Ofirmev. [package insert]. San Diego, CA: Cadence Pharmaceuticals, Inc; 2010.Google Scholar
  9. 9.
    Churchwell MD, Pasko DA, Mueller BA. Daptomycin Clearance during modeled continuous renal replacement therapy. Blood Purif. 2006;24(5–6):548.CrossRefPubMedGoogle Scholar
  10. 10.
    Patel JH, Churchwell MD, Seroogy JD, Barriere SL, Grio M, Mueller B. Telavancin and hydroxy propyl-beta-cyclodextrin clearance during continuous renal replacement therapy: an in vitro study. Int J Artif Organs. 2009;32(10):745.CrossRefPubMedGoogle Scholar
  11. 11.
    Stevenson JM, Patel JH, Churchwell MD, Vilay AM, Depestel DD, Sörgel F, et al. Ertapenem clearance during modeled continuous renal replacement therapy. Int J Artif Organs. 2008;31(12):1027.CrossRefPubMedGoogle Scholar
  12. 12.
    Bourquin V, Ponte B, Pugin J, Martin P, Saudan P. Use of high-volume haemodiafiltration in patients with refractory septic shock and acute kidney injury. Clin Kidney J. 2013;6(1):40–4.CrossRefPubMedGoogle Scholar
  13. 13.
    Gillogly A, Kilbourn C, Waldvogel J, Martin J, Annich G, Wagner D. In vitro clearance of intravenous acetaminophen in extracorporeal membrane oxygenation. Perfusion. 2013;28(2):141–5.CrossRefPubMedGoogle Scholar
  14. 14.
    Vilay AM, Churchwell MD, Mueller BA. Clinical review: drug metabolism and nonrenal clearance in acute kidney injury. Crit Care. 2008;12(6):235.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Boucher BA, Wood GC, Swanson JM. Pharmacokinetic changes in critical illness. Crit Care Clin. 2006;22(2):255–71.CrossRefPubMedGoogle Scholar
  16. 16.
    Kidney Disease: Improving global outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012;2:1–138.CrossRefGoogle Scholar
  17. 17.
    Martin U, Temple RM, Winney RJ, Prescott LF. The disposition of paracetamol and its conjugates during multiple dosing in patients with end-stage renal failure maintained on haemodialysis. Eur J Clin Pharmacol. 1993;45(2):141–5.CrossRefPubMedGoogle Scholar
  18. 18.
    Agarwal R, Farber MO. Is continuous veno-venous hemofiltration for acetaminophen-induced acute liver and renal failure worthwhile? Clin Nephrol. 2002;57:167–70.CrossRefPubMedGoogle Scholar
  19. 19.
    Sivilotti ML, Juurlink DN, Garland JS, Lenga I, Poley R, Hanly LN, Thompson M. Antidote removal during haemodialysis for massive acetaminophen overdose. Clin Toxicol (Phila). 2013;51(9):855–63.CrossRefGoogle Scholar

Copyright information

© The Japanese Society for Artificial Organs 2017

Authors and Affiliations

  1. 1.Saint Alexius Medical CenterHoffman EstatesUSA
  2. 2.University of Michigan College of PharmacyAnn ArborUSA
  3. 3.Department of Pediatric Critical CareHospital for Sick ChildrenTorontoCanada
  4. 4.Department of Pediatric Anesthesiology, C.S. Mott Children’s Hospital and Von Voigtlander Women’s HospitalUniversity of MichiganAnn ArborUSA

Personalised recommendations