Pethidine’s Half-life Alterations following Orthopedic Surgery: Is Available Literature Always Compatible with the Data Obtained at the Bedside?
Background: It is suggested that surgery results in changes in kinetic profile of some medication. The aim of this study was to investigate possible alterations in pethidine’s half-life in postoperative pain management following orthopedic surgery of the inferior limb.
Methods: Twelve patients who were classified as class I patients according to the American society of anesthesiologists physical status classification were enrolled. Following the surgery of the lower limb, 25 mg of pethidine was injected intravenously. After that, 5, 30, 60 and 180 minutes following the injection, blood samples were taken and concentration of pethidine in blood samples were measured by High Performance Liquid Chromatography method. Moreover, patients’ pain levels were assessed on visual analogue scales.
Results: The average half-life of pethidine was measured to be 29.68 minutes. Thirty minutes after the injection, significant relationship between plasma levels of pethidine and pain scale was reported (p= 0.041, r= 0.595). Moreover, men were found to perceive more pain than women. Pain scale was considerably different between smokers and non-smokers (p= 0.006), although blood concentration of pethidine was not significantly different between these two groups (p=0.09).
onclusions: Orthopedic surgery most probably results in alterations in pharmacokinetic profile of pethidine. Moreover, gender and smoking status of the patients influence pain perception. Thus, pharmacokinetic alterations due to inferior limb orthopedic surgery, gender-related factors and smoking status of the patients should be considered in pain management in clinical settings.
2. Voscopoulos C, Lema M. When does acute pain become chronic? Br J Anaesth 2010; 105: i69-i85.
3. Benhamou D, Berti M, Brodner G, et al. Postoperative Analgesic THerapy Observational Survey (PATHOS): a practice pattern study in 7 central/southern European countries. Pain 2008; 136(1-2): 134-41.
4. World health Organization. Access to controlled medication program. Geneva, Switzerland: World Health Organization. 2007. Available from: http://www.who.int/medicines/areas/quality_safety/Framework_ACMP_withcover.pdf
5. Kehlet H, Holte K. Effect of postoperative analgesia on surgical outcome. Br J Anaesth 2001; 87(1): 62-72.
6. Benyamin R, Trescot AM, Datta S, et al. Opioid complications and side effects. Pain Physician 2008; 11 (2 Suppl): S105-20.
7. Hjermstad MJ, Gibbins J, Haugen DF, Caraceni A, Loge JH, Kaasa S, EPCRC, European Palliative Care Research Collaborative. Pain assessment tools in palliative care: an urgent need for consensus. Palliat Med 2008; 22(8): 895-903.
8. Smith LA, Carroll D, Edwards JE, Moore RA, McQuay HJ. Single-dose ketorolac and pethidine in acute postoperative pain: systematic review with meta-analysis. Br J Anesth 2000; 84(1): 48-58.
9. Hartvig P, Tamsen A, Fagerlund C, Dahlström B. Pharmacokinetics of Pethidine During Anaesthesia and Patient-Controlled Analgesic Therapy. Acta Anaesthesiol Scand 1982; 74: 52–54.
10. Gallagher EJ, Bijur PE, Latimer C, Silver W. Reliability and validity of a visual analog scale for acute abdominal pain in the ED. Am J Emerg Med 2002; 20(4): 287-90.
11. Shang AB, Gan TJ. Optimising postoperative pain management in the ambulatory patient. Drugs 2003; 63(9): 855-67.
12. Glynn CJ, Mather LE. Clinical pharmacokinetics applied to patients with intractable pain: Studies with pethidine. Pain 1982; 13(3): 237-46.
13. Pokela ML, Olkkola KT, Koivisto M, Ryhänen P. Pharmacokinetics and pharmacodynamics of intravenous meperidine in neonates and infants. Clin Pharmacol Ther 1992; 52(4): 342-9.
14. Röper A, Lauven PM. Pharmacokinetics in newborns and infants. Anasthesiol Intensivmed Notfallmed Schmerzther 1999; 34(10): 616-25.
15. Buhari S, Kalthum H, Goh YM, Gan SH. Influence of surgery on the pharmacokinetics of Tramadol following intravenous administration in dogs. Asian J Anim Vet Adv 2013; 8(3): 483-492.
16. Kennedy JM, Van Riji AM. Effects of surgery on the pharmacokinetic parameters of drugs. Clin Pharmacokinetics 1998; 35(4): 293-312.
17. Gourlay GK, Kowalski SR, Plummer JL, Cousins MJ. Armstrong PJ. Fentanyl Blood Concentration-Analgesic Response Relationship in the Treatment of Postoperative Pain. Anesth Analg 1988; 67(4): 329-37.
18. Waterman AE, Kalthum W. Pharmacokinetics of intramuscularly administered pethidine in dogs and the influence of anesthesia and surgery. Vet Rec 1989; 124(12): 293-6.
19. Waterman AE, Amin A. The influence of surgery and anaesthesia on the pharmacokinetics of pethidine in the horse. Equine Vet J 1992; 11: 56-8.
20. Ruau D, Liu LY, Clark JD, Angst MS, Butte AJ. Sex differences in reported pain across 11,000 patients captured in electronic medical records. Journal of Pain 2012; 13(3): 228–234.
21. Unruh AM. Gender variations in clinical pain experience. Pain 1996; 65(2-3): 123–67.
22. Fillingim RB, Gear RW. Sex differences in opioid analgesia: clinical and experimental findings. Eur J Pain 2004; 8(5): 413-25
23. Aubrun F, Salvi N, Coriat P, Riou B. Sex- and age-related differences in morphine requirements for postoperative pain relief. Anesthesiology 2005; 103(1): 156-60.
24. Pereira MP, Pogatzki-Zahn E. Gender aspects in postoperative pain. Curr Opin Anaesthesiol 2015; 28(5): 546-558.
25. Girdler SS, Maixner W, Naftel HA, Stewart PW, Moretz RL, Light KC. Cigarette smoking, stress-induced analgesia and pain perception in men and women. Pain 2005; 114(3): 372- 85.
26. Shi Y, Weingarten TN, Mantilla CB, Hooten WM, Warner DO. Smoking and pain: pathophysiology and clinical implications. Anesthesiology 2010; 113(4): 977–992.
27. Kanarek RB, Carrington C. Sucrose consumption enhances the analgesic effects of cigarette smoking in male and female smokers. Psychopharmacology 2004; 173(1-2): 57–63.
28. Mishriky BM, Habib, AS. Nicotine for Postoperative Analgesia: A Systematic Review and Meta-Analysis. Anesth Analg 2014; 119(2): 268–275.
29. Boréus LO, Sköldefors E, Ehrnebo M. Appearance of pethidine and norpethidine in cerebrospinal fluid of man following intramuscular injection of pethidine. Acta Anaesthesiol Scand 1983; 27(3): 222-5.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.