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Pharmacokinetics of Transdermal Fentanyl

Thompson, Jonathan P. BSc, MD, FRCA; Rowbotham, David J. MD, MRCP, FRCA, FFARCSI

doi: 10.1213/00000539-200209000-00051
LETTERS TO THE EDITOR: Letters & Announcements

University Department of Anaesthesia

Critical Care and Pain Management

University Hospitals of Leicester NHS Trust

Leicester Royal Infirmary

Leicester, England

Dr. Frölich does not wish to respond.

To the Editor:

We read with interest the report of Frolich and colleagues (1) of opioid toxicity in a patient with a 3-day-old transdermal fentanyl patch in situ, undergoing surgery under lumbar epidural anesthesia and IV propofol. The opioid toxicity was related temporally to the use of a body-warming blanket to correct intraoperative hypothermia. In our study of the perioperative pharmacokinetics of transdermal fentanyl, we found that two elderly patients experienced marked respiratory depression that persisted after fentanyl patch removal. In one of these patients, plasma fentanyl concentrations were high (2.22 ng · mL 1), and in the other, plasma concentrations were low (0.645 ng · mL 1), but the patient had required relatively large amounts of morphine via a patient-controlled analgesia device (2). Neither of these patients was being rewarmed, but reported our concerns that transdermal absorption was variable in the perioperative period, owing to variations in cutaneous blood flow related to alterations in cardiac output, circulating volume, and temperature. Shoemaker and colleagues demonstrated that the local application of heat augmented the transdermal absorption of fentanyl in volunteers, resulting in significantly higher maximal plasma concentrations (3), which supports the mechanism for toxicity proposed by Frolich et al. (1). Together, these data support our conclusions that transdermal fentanyl patches are unsuitable for postoperative pain management, and that the possibility of variability in absorption should be considered in those with a transdermal fentanyl patch already in place. Furthermore, the unpredictable effects of sustained transdermal fentanyl absorption from the subcutaneous depot in surgical patients under conditions of changing cutaneous blood flow mean that toxicity may continue to occur despite removal of the patch. These may be particularly important in the elderly or those receiving concomitant opioids, respiratory depressant, or vasoactive drugs.

Jonathan P. Thompson, BSc, MD, FRCA

David J. Rowbotham, MD, MRCP, FRCA, FFARCSI

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1. Frolich M, Giannotti A, Modell JH. Opioid overdose in a patient using a fentanyl patch during treatment with a warming blanket. Anesth Analg 2001; 93: 747–8.
2. Thompson JP, Bower S, Liddle AM, Rowbotham DJ. Perioperative pharmacokinetics of transdermal fentanyl in elderly and young adult patients. Br J Anaesth 1998; 81: 152–4.
3. Shoemaker TS, Zhang J, Ashbum MA. Assessing the impact of heat on the systemic delivery of fentanyl through the transdermal fentanyl delivery system. Pain Med 2000; 1: 225–30.
© 2002 International Anesthesia Research Society