Effective dose of intravenous oxycodone depending on sex and age for attenuation of intubation-related hemodynamic responses

Background/aim: Preoperative intravenous oxycodone may help to prevent or attenuate intubation-related hemodynamic responses (IRHRs), but its pharmacokinetics differs according to age and sex. Therefore, we investigated the 95% effective dose (ED95) of intravenous oxycodone for attenuating all IRHRs, depending on the age and sex of the study population. Materials and methods: All patients were allocated to one of 6 groups: 1) 20–40 year old males, 2) 41–65yearold males, 3) 66–80 year old males, 4) 20–40 year old females, 5) 41–65yearold females, and 6) 66–80 year old females (groups YM, OM, EM, YF, OF, and EF, respectively). Using Dixon’s up-and-down method, the first patient in each group was slowly injected with intravenous oxycodone (0.1 mg kg–1) 20 min before intubation. The subsequent patient received the next oxycodone dose, which was decreased or increased by 0.01 mg kg–1, depending on the “success” or “failure” of attenuation of all IRHRs to within 20% of the baseline values at 1 min after intubation in the previous patient. After obtaining 8 crossover points, predictive ED95 was estimated with probit regression analysis. Results: ED95 varied greatly according to age and sex. ED95was 0.133 mg kg–1, 0.181 mg kg–1, 0.332 mg kg–1, 0.183 mg kg–1, 0.108 mg kg–1, and 0.147 mg kg–1in groups YM, OM, EM, YF, OF, and EF, respectively. Conclusion: ED95 is higher in males with increasing age but is ambiguous for females. ED95 is higher in males than in females over 40 years of age but is higher in females than in males under 41 years of age. However, after considering the age and sex of the study population, these results can be used as reference doses for further studies to verify the clinical effects of oxycodone for attenuating all IRHRs.Key words: Hemodynamics, humans, intravenous administration, intubation, laryngoscopy, oxycodone

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1. Khan FA, Ullah H. Pharmacological agents for preventing morbidity associated with the haemodynamic response to tracheal intubation. Cochrane Database of Systematic Reviews 2013; (7): CD004087. doi: 10.1002/14651858.CD004087.pub2
2. Hilliard PE, Waljee J, Moser S, Metz L, Mathis M et al. Prevalence of preoperative opioid use and characteristics associated with opioid use among patients presenting for surgery. JAMA Surgery 2018; 153 (10): 929-937. doi: 10.1001/jamasurg.2018.2102
3. Fanelli G, Ghisi D, Berti M, Troglio R, Ortu A et al. Preoperative administration of controlled-release oxycodone as a transition opioid for total intravenous anaesthesia in pain control after laparoscopic cholecystectomy. Surgical Endoscopy 2008; 22 (10): 2220-2228. doi: 10.1007/s00464-008-0026-6
4. Wang J, Fu Y, Ma H, Wang N. Effect of preoperative intravenous oxycodone after transurethral resection of prostate under general anesthesia. International Surgery 2018; 102 (7-8): 377- 381. doi: 10.9738/intsurg-d-15-00087.1
5. Wang N, Wang Y, Pang L, Wang J. Effect of preemptive analgesia with intravenous oxycodone in the patients undergoing laparoscopic resection of ovarian tumor. Pakistan Journal of Medical Sciences 2015; 31 (2): 300-303. doi: 10.12669/ pjms.312.6686
6. Park YH, Lee SH, Lee OH, Kang H, Shin HY et al. Optimal dose of intravenous oxycodone for attenuating hemodynamic changes after endotracheal intubation in healthy patients: a randomized controlled trial. Medicine (Baltimore) 2017; 96 (11): e6234. doi: 10.1097/md.0000000000006234
7. Park KB, Ann J, Lee H. Effects of different dosages of oxycodone and fentanyl on the hemodynamic changes during intubation. Saudi Medical Journal 2016; 37 (8): 847-852. doi: 10.15537/ smj.2016.8.14822
8. Lee YS, Baek CW, Kim DR, Kang H, Choi GJ et al. Comparison of hemodynamic response to tracheal intubation and postoperative pain in patients undergoing closed reduction of nasal bone fracture under general anesthesia: a randomized controlled trial comparing fentanyl and oxycodone. BMC Anesthesiology 2016; 16 (1): 115. doi: 10.1186/s12871-016-0279-x
9. Kang XH, Bao FP, Zhang HG, Yu DJ, Ha K et al. Gender affects the median effective dose and 95% effective dose of oxycodone for blunting the hemodynamic response to tracheal intubation in narcotic-naive adult patients. Chinese Medical Journal 2018; 131 (16): 1958-1963. doi: 10.4103/0366-6999.238138
10. Liukas A, Kuusniemi K, Aantaa R, Virolainen P, Neuvonen M et al. Elimination of intravenous oxycodone in the elderly: a pharmacokinetic study in postoperative orthopaedic patients of different age groups. Drugs & Aging 2011; 28 (1): 41-50. doi: 10.2165/11586140-000000000-00000
11. Andreassen TN, Klepstad P, Davies A, Bjordal K, Lundstrom S et al. Influences on the pharmacokinetics of oxycodone: a multicentre cross-sectional study in 439 adult cancer patients. European Journal of Clinical Pharmacology 2011; 67 (5): 493- 506. doi: 10.1007/s00228-010-0948-5
12. Koh GH, Jung KT, So KY, Seo JS, Kim SH. Effect of different doses of intravenous oxycodone and fentanyl on intubation-related hemodynamic responses: a prospective double-blind randomized controlled trial (CONSORT). Medicine (Baltimore) 2019; 98 (18): e15509. doi: 10.1097/ md.0000000000015509
13. Dixon WJ. Efficient analysis of experimental observations. Annual Review of Pharmacology and Toxicology 1980; 20: 441-462. doi: 10.1146/annurev.pa.20.040180.002301
14. Sawano Y, Miyazaki M, Shimada H, Kadoi Y. Optimal fentanyl dosage for attenuating systemic hemodynamic changes, hormone release and cardiac output changes during the induction of anesthesia in patients with and without hypertension: a prospective, randomized, double-blinded study. Journal of Anesthesia 2013; 27 (4): 505-511. doi: 10.1007/s00540-012-1552-x
15. Liukas A, Kuusniemi K, Aantaa R, Virolainen P, Neuvonen M et al. Plasma concentrations of oral oxycodone are greatly increased in the elderly. Clinical Pharmacology & Therapeutics 2008; 84 (4): 462-467. doi: 10.1038/clpt.2008.64
16. Kumar A, Tyagi A. Dixon and Massey’s method: the starting dose. Anesthesia & Analgesia 2009; 108 (1): 378. doi: 10.1213/ ane.0b013e31818d4aa9
17. Low JM, Harvey JT, Prys-Roberts C, Dagnino J. Studies of anaesthesia in relation to hypertension: VII: adrenergic responses to laryngoscopy. British Journal of Anaesthesia 1986; 58 (5): 471-477. doi: 10.1093/bja/58.5.471
18. Sener EB, Ustun E, Ustun B, Sarihasan B. Hemodynamic responses and upper airway morbidity following tracheal intubation in patients with hypertension: conventional laryngoscopy versus an intubating laryngeal mask airway. Clinics 2012; 67 (1): 49-54. doi: 10.6061/clinics/2012(01)08
19. Nishikawa K, Omote K, Kawana S, Namiki A. A comparison of hemodynamic changes after endotracheal intubation by using the lightwand device and the laryngoscope in normotensive and hypertensive patients. Anesthesia & Analgesia 2000; 90 (5): 1203-1207. doi: 10.1097/00000539-200005000-00038