The Effect of Different Doses of Ondansetron in Reducing Injection Pain of Etomidate: A Double-Blind Randomized Clinical Trial
-
Zahra Rahimi
,
Mehrdad Masoudifar
,
Behzad Nazemroaya
,
Mojtaba Rahimi Varposhti
,
Roozbeh Akhavanfar
Abstract
Background: Etomidate is an anesthetic induction medicine that is the first choice, particularly in elderly and cardiovascular patients, due to its favorable hemodynamic stability. There are some complications with etomidate administration nevertheless. Created pain during the injection, for instance, may be bothering.
Methods: 60 patients who were candidates for general anesthesia with Etomidate were divided into 3 groups randomly. After infusing 300 ml of normal saline for each patient, 2 minutes before induction, Ondansetron 8mg, Ondansetron 4mg, and normal saline were administered to groups first, second, and third, respectively. Then Etomidate was given to all patients in the form of 10 ml ampoules containing 20 mg of Etomidate equally. The pain score was rated using the FPRS criterion, which is from 0 to 10. Collected data were analyzed and interpreted.
Results: The factor of sex wasn’t an effective element in the level of pain, but height (p = 0.034) and age affected this level; patients who were in their seventh decade of life had no complaints (59.4%). There was no significant difference in the mean arterial blood pressure, the mean heart rate, and the mean arterial oxygen saturation between the three groups. The level of pain was considerably different in the study groups (p = 0.000), and the 8 mg ondansetron group had the lowest pain.
Conclusion: Ondansetron can reduce the injection pain of Etomidate, and the greatest effect is related to the 8 mg dose of Ondansetron.
[1] Azimaraghi O, Aghajani Y, Molaghadimi M, Khosravi M, Eslami K, Ghadimi F, et al. Ondansetron reducing pain on injection of etomidate: a controlled randomized study. Brazilian journal of anesthesiology (Elsevier). 2014;64(3):169-72.
[2] Aydin A, Kacmaz M, Boyaci A. Comparison of ondansetron, tropisetron, and palonosetron for the prevention of postoperative nausea and vomiting after middle ear surgery. Curr Ther Res Clin Exp. 2019; 91:17-21.
[3] Liu W, Liu A, Liu G, Wang D, Chen K, Wang H. Biophysical study on the interaction of etomidate and the carrier protein in vitro. Pharm Dev Technol. 2016;21(5):528-34.
[4] Adinehmehr L, Shetabi H, Moradi Farsani D, Salehi A, Noorbakhsh M. Comparison of the Sedation Quality of Etomidate, Propofol, and Midazolam in Combination with Fentanyl During Phacoemulsification Cataract Surgery: A Double-Blind, Randomized, Controlled, Clinical Trial. Anesth Pain Med. 2019; 9(2): e87415.
[5] Ye L, Xiao X, Zhu L. The Comparison of Etomidate and Propofol Anesthesia in Patients Undergoing Gastrointestinal Endoscopy: A Systematic Review and Meta-Analysis. Surg Laparosc Endosc Percutan Tech. 2017; 27(1):1-7.
[6] Henschke N, Kamper SJ, Maher CG. The epidemiology and economic consequences of pain. Mayo Clin Proc. 2015; 90(1):139-47.
[7] Liu J, Chen L, Tu Y, Chen X, Hu K, Tu Y, et al. Different exercise modalities relieve pain syndrome in patients with knee osteoarthritis and modulate the dorsolateral prefrontal cortex: a multiple mode MRI study. Brain Behav Immun. 2019; 82:253-263.
[8] Ye JH, Mui WC, Ren J, Hunt TE, Wu WH, Zbuzek VK. Ondansetron exhibits the properties of a local anesthetic. Anesth Analg. 1997;85(5):1116-21.
[9] Estan-Cerezo G, Jimenez-Pulido I, Rodriguez Lucena FJ, Matoses Chirivella C, Soriano-Irigaray L, Navarro-Ruiz A. Chemical stability of ondansetron hydrochloride with other drugs in admixtures via parenteral; a review. Farm Hosp. 2017;41(5):625-9.
[10] Browning KN. Role of central vagal 5-HT3 receptors in gastrointestinal physiology and pathophysiology. Front Neurosci. 2015; 9:413.
[11] Kerns RD, Sellinger J, Goodin BR. Psychological Treatment of Chronic Pain. Annual Review of Clinical Psychology. 2011;7(1):411-34.
[12] Jensen MP, Turner JA, Romano JM. Changes after multidisciplinary pain treatment in patient pain beliefs and coping are associated with concurrent changes in patient functioning. Pain. 2007; 131(1):38- 47.
[13] Williams ACdC, Craig KD. Updating the definition of pain. Pain. 2016; 157(11):2420-3.
[14] Keim SM, Erstad BL, Sakles JC, Davis V. Etomidate for procedural sedation in the emergency department. Pharmacotherapy. 2002; 22(5): 586-92.
[15] Jacoby J, Heller M, Nicholas J, Patel N, Cesta M, Smith G, et al. Etomidate versus midazolam for out-of-hospital intubation: a prospective, randomized trial. Ann Emerg Med. 2006; 47(6): 525-30.
[16] Gabor G, Judit T, Zsolt I. Comparison of propofol and etomidate regarding impact on seizure threshold during electroconvulsive therapy in patients with schizophrenia. Neuropsychopharmacol Hung. 2007; 9(3): 125-30.
[17] Passot S, Servin F, Pascal J, Charret F, Auboyer C, Molliex S. A comparison of target- and manually controlled infusion propofol and etomidate/desflurane anesthesia in elderly patients undergoing hip fracture surgery. Anesth Analg 2005; 100(5): 1338-42.
[18] Jabre P, Combes X, Lapostolle F, Dhaouadi M, Ricard-Hibon A, Vivien B, et al. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial. Lancet. 2009; 374(9686): 293-300.
[19] Lee-Jayaram JJ, Green A, Siembieda J, Gracely EJ, Mull CC, Quintana E, et al. Ketamine/midazolam versus etomidate/fentanyl: procedural sedation for pediatric orthopedic reductions. Pediatr Emerg Care 2010; 26(6): 408-12.
[20] Bordo D, Chan SB, Shin P. Patient satisfaction and return to daily activities using etomidate procedural sedation for orthopedic injuries. West J Emerg Med 2008; 9(2): 86-90.
[21] Liljeroth E, Grauers A, Akeson J. Pain on injection of propofol with or without infusion of carrier fluid. Acta Anaesthesiol Scand. 2001; 45(7):839-41.
[22] McCririck A, Hunter S. Pain on injection of propofol: The effect of injectate temperature. Anaesthesia. 1990; 45: 443-444.
[23] Rau J, Roizen MF, Doenicke AW, O'Connor MF, Strohschneider U. Propofol in an emulsion of long- and medium-chain triglycerides: the effect on pain. Anesth Analg. 2001; 93:382-4.
[24] Roth BL. The serotonin receptors: From molecular pharmacology to human therapeutics: Philadelphia: Humana Press; 2008.
[25] Meeter M, Talamini L, Schmitt JA, Riedel WJ. Effects of 5-HT on memory and the hippocampus: model and data. Neuropsychopharmacology 2006;31(4):712-20.
[26] Rudissaar R, Pruus K, Skrebuhhova T, Allikmets L, Matto V. Modulatory role of 5-HT 3 receptors in mediation of apomorphine-induced aggressive behaviour in male rats. Behav Brain Res 1999;106(1-2):91-6.
[27] Senthilvelan M, Ravindran R, Samson J, Devi RS. Serotonin turnover in different duration of sleep recovery in discrete regions of young rat brain after 24h REM sleep deprivation. Brain Dev 2006;28(8):526-8.
[28] Egashira N, Yano A, Ishigami N, Mishima K, Iwasaki K, Fujioka M, et al. Investigation of mechanisms mediating 8- OH-DPAT-induced impairment of spatial: Involvement of 5-HT 1A receptors in the dorsal hippocampus in rats. Brain Res. 2006;1069(1):54-62.
[29] Gonzalez R, Chávez-Pascacio K, Meneses A. Role of 5-HT 5A receptors in the consolidation of memory. Behav Brain Res. 2013; 252:246-51.
[30] Chegini H-R, Nasehi M, Zarrindast M-R. Differential role of the basolateral amygdala 5-HT3 and 5-HT4 serotonin receptors upon ACPA-induced anxiolytic-like behaviors and emotional memory deficit in mice. Behav Brain Res. 2014; 261:114-26.
[31] Naumenko VS, Kondaurova EM, Popova NK. Central 5-HT 3 receptor-induced hypothermia in mice: Interstrain differences and comparison with hypothermia mediated via 5-HT 1A receptor. Neurosci Lett. 2009;465(1):50-4.
[32] Charnay Y, Léger L. Brain serotonergic circuitries. Dialogues Clin Neurosci. 2010; 12(4):471-87.
[33] van Hooft JA, Yakel JL. 5-HT 3 receptors in the CNS: 3B or not 3B? Trends Pharmacol Sci. 2003; 24(4):160-57.
[34] Hannon J, Hoyer D. Molecular biology of 5-HT receptors. Behav Brain Res. 2008;195(1):198-213. PubMed
[35] Castro L, De Castro-e-Silva E, Lima A, Souza F, Maldonado I, Macedo D, et al. Central 5-HT 4 receptors and drinking behavior. Pharmacol Biochem Behav. 2000;66(2):443-8.
[36] Hao L, Hu X, Zhu B, Li W, Huang X, Kang F. Clinical observation of the combined use of propofol and etomidate in painless gastroscopy. Medicine (Baltimore). 2020; 99(45):1-7.
[37] Diagnostic and statistical manual of mental disorders. American Psychiatric Association. 2019.
[38] Aghdaii N, Sadat Navabi N, Azarfarin R. The effect of using "Pain Assessment Tool" by nurses on analgesics requirement and patients’ satisfaction after coronary bypass graft surgery. Cardiovascular Nursing J. 2016; 4(2): 14-22.
[39] Azimaraghi O, Aghajani Y, Molaghadimi M, et al. Ondansetron reducing pain on injection of etomidate: a controlled randomized study. Braz J Anesthesiol. 2014; 64(3):169-172.
[40] Malekian zadeh B, Hajian P, Manoochehrian N, Khazaei S. Determining the effect of intravenous ondansetron in pereventing hypotension in patients under elective cesarean section. Arak Medical University Journal. 2014;17(89): 71-79.
[41] Atikahmed GM, Raushan KJ, Madhuri AB, Comparative study of etomidate and fentanyl citrate with propofol (1%) and fentanyl citrate for total intravenous anaesthesia in short surgical procedures. IJCA. 2020;7(2): 348-354.
[42] Zahedi H, Maleki A, Rostami G. Ondansetron pretreatment reduces pain on injection of propofol. Acta Med Iran. 2012; 50(4):239-43.
[43] Banavasi A, Thippeswamy H, Bhat SP. Comparison of pre treatment with Ondansetron and Lignocaine over Pain on Etomidate Injection. A double blind prospective non randomised study. IOSR Journal of Dental and Medical Science. 2016;15(9):89-92.
[44] Khorasanizadeh S, Behnaz F, Mohseni G, Ebrahimi DM, Ommi D, Teymourian H. Ondansetron combined with aprepitant versus dexamethasone combined with metoclopramide; which is more efficient to reduce nausea and vomiting after etomidate induction in major vascular surgeries. Journal of Iranian Society of Aneasthesiology and Intensive Care unit.2020;42(3);2-10.
[45] Napolitano CA, Berg RJ, Terlea TC, Castro MI. Prophylactic administration of ondansetron and dolasetron have minimal effects on ventricular repolarization prior to and during the induction of general anesthesia in healthy females. Anesthesiology. 2004;101:A-1274.
[46] Kaushal RP, Vatal A, Pathak R. Effect of etomidate and propofol induction on hemodynamic and endocrine response in patients undergoing coronary artery bypass grafting/mitral valve and aortic valve replacement surgery on cardiopulmonary bypass. Annals of cardiac anaesthesia. 2015; 18(2):172.
[47] Rathore VS, GUPTA S. Comparative study of propofol, etomidate and 50% admixture of etomidate and propofol for induction in general anaesthesia. J Dent Med Sci. 2018.
[2] Aydin A, Kacmaz M, Boyaci A. Comparison of ondansetron, tropisetron, and palonosetron for the prevention of postoperative nausea and vomiting after middle ear surgery. Curr Ther Res Clin Exp. 2019; 91:17-21.
[3] Liu W, Liu A, Liu G, Wang D, Chen K, Wang H. Biophysical study on the interaction of etomidate and the carrier protein in vitro. Pharm Dev Technol. 2016;21(5):528-34.
[4] Adinehmehr L, Shetabi H, Moradi Farsani D, Salehi A, Noorbakhsh M. Comparison of the Sedation Quality of Etomidate, Propofol, and Midazolam in Combination with Fentanyl During Phacoemulsification Cataract Surgery: A Double-Blind, Randomized, Controlled, Clinical Trial. Anesth Pain Med. 2019; 9(2): e87415.
[5] Ye L, Xiao X, Zhu L. The Comparison of Etomidate and Propofol Anesthesia in Patients Undergoing Gastrointestinal Endoscopy: A Systematic Review and Meta-Analysis. Surg Laparosc Endosc Percutan Tech. 2017; 27(1):1-7.
[6] Henschke N, Kamper SJ, Maher CG. The epidemiology and economic consequences of pain. Mayo Clin Proc. 2015; 90(1):139-47.
[7] Liu J, Chen L, Tu Y, Chen X, Hu K, Tu Y, et al. Different exercise modalities relieve pain syndrome in patients with knee osteoarthritis and modulate the dorsolateral prefrontal cortex: a multiple mode MRI study. Brain Behav Immun. 2019; 82:253-263.
[8] Ye JH, Mui WC, Ren J, Hunt TE, Wu WH, Zbuzek VK. Ondansetron exhibits the properties of a local anesthetic. Anesth Analg. 1997;85(5):1116-21.
[9] Estan-Cerezo G, Jimenez-Pulido I, Rodriguez Lucena FJ, Matoses Chirivella C, Soriano-Irigaray L, Navarro-Ruiz A. Chemical stability of ondansetron hydrochloride with other drugs in admixtures via parenteral; a review. Farm Hosp. 2017;41(5):625-9.
[10] Browning KN. Role of central vagal 5-HT3 receptors in gastrointestinal physiology and pathophysiology. Front Neurosci. 2015; 9:413.
[11] Kerns RD, Sellinger J, Goodin BR. Psychological Treatment of Chronic Pain. Annual Review of Clinical Psychology. 2011;7(1):411-34.
[12] Jensen MP, Turner JA, Romano JM. Changes after multidisciplinary pain treatment in patient pain beliefs and coping are associated with concurrent changes in patient functioning. Pain. 2007; 131(1):38- 47.
[13] Williams ACdC, Craig KD. Updating the definition of pain. Pain. 2016; 157(11):2420-3.
[14] Keim SM, Erstad BL, Sakles JC, Davis V. Etomidate for procedural sedation in the emergency department. Pharmacotherapy. 2002; 22(5): 586-92.
[15] Jacoby J, Heller M, Nicholas J, Patel N, Cesta M, Smith G, et al. Etomidate versus midazolam for out-of-hospital intubation: a prospective, randomized trial. Ann Emerg Med. 2006; 47(6): 525-30.
[16] Gabor G, Judit T, Zsolt I. Comparison of propofol and etomidate regarding impact on seizure threshold during electroconvulsive therapy in patients with schizophrenia. Neuropsychopharmacol Hung. 2007; 9(3): 125-30.
[17] Passot S, Servin F, Pascal J, Charret F, Auboyer C, Molliex S. A comparison of target- and manually controlled infusion propofol and etomidate/desflurane anesthesia in elderly patients undergoing hip fracture surgery. Anesth Analg 2005; 100(5): 1338-42.
[18] Jabre P, Combes X, Lapostolle F, Dhaouadi M, Ricard-Hibon A, Vivien B, et al. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial. Lancet. 2009; 374(9686): 293-300.
[19] Lee-Jayaram JJ, Green A, Siembieda J, Gracely EJ, Mull CC, Quintana E, et al. Ketamine/midazolam versus etomidate/fentanyl: procedural sedation for pediatric orthopedic reductions. Pediatr Emerg Care 2010; 26(6): 408-12.
[20] Bordo D, Chan SB, Shin P. Patient satisfaction and return to daily activities using etomidate procedural sedation for orthopedic injuries. West J Emerg Med 2008; 9(2): 86-90.
[21] Liljeroth E, Grauers A, Akeson J. Pain on injection of propofol with or without infusion of carrier fluid. Acta Anaesthesiol Scand. 2001; 45(7):839-41.
[22] McCririck A, Hunter S. Pain on injection of propofol: The effect of injectate temperature. Anaesthesia. 1990; 45: 443-444.
[23] Rau J, Roizen MF, Doenicke AW, O'Connor MF, Strohschneider U. Propofol in an emulsion of long- and medium-chain triglycerides: the effect on pain. Anesth Analg. 2001; 93:382-4.
[24] Roth BL. The serotonin receptors: From molecular pharmacology to human therapeutics: Philadelphia: Humana Press; 2008.
[25] Meeter M, Talamini L, Schmitt JA, Riedel WJ. Effects of 5-HT on memory and the hippocampus: model and data. Neuropsychopharmacology 2006;31(4):712-20.
[26] Rudissaar R, Pruus K, Skrebuhhova T, Allikmets L, Matto V. Modulatory role of 5-HT 3 receptors in mediation of apomorphine-induced aggressive behaviour in male rats. Behav Brain Res 1999;106(1-2):91-6.
[27] Senthilvelan M, Ravindran R, Samson J, Devi RS. Serotonin turnover in different duration of sleep recovery in discrete regions of young rat brain after 24h REM sleep deprivation. Brain Dev 2006;28(8):526-8.
[28] Egashira N, Yano A, Ishigami N, Mishima K, Iwasaki K, Fujioka M, et al. Investigation of mechanisms mediating 8- OH-DPAT-induced impairment of spatial: Involvement of 5-HT 1A receptors in the dorsal hippocampus in rats. Brain Res. 2006;1069(1):54-62.
[29] Gonzalez R, Chávez-Pascacio K, Meneses A. Role of 5-HT 5A receptors in the consolidation of memory. Behav Brain Res. 2013; 252:246-51.
[30] Chegini H-R, Nasehi M, Zarrindast M-R. Differential role of the basolateral amygdala 5-HT3 and 5-HT4 serotonin receptors upon ACPA-induced anxiolytic-like behaviors and emotional memory deficit in mice. Behav Brain Res. 2014; 261:114-26.
[31] Naumenko VS, Kondaurova EM, Popova NK. Central 5-HT 3 receptor-induced hypothermia in mice: Interstrain differences and comparison with hypothermia mediated via 5-HT 1A receptor. Neurosci Lett. 2009;465(1):50-4.
[32] Charnay Y, Léger L. Brain serotonergic circuitries. Dialogues Clin Neurosci. 2010; 12(4):471-87.
[33] van Hooft JA, Yakel JL. 5-HT 3 receptors in the CNS: 3B or not 3B? Trends Pharmacol Sci. 2003; 24(4):160-57.
[34] Hannon J, Hoyer D. Molecular biology of 5-HT receptors. Behav Brain Res. 2008;195(1):198-213. PubMed
[35] Castro L, De Castro-e-Silva E, Lima A, Souza F, Maldonado I, Macedo D, et al. Central 5-HT 4 receptors and drinking behavior. Pharmacol Biochem Behav. 2000;66(2):443-8.
[36] Hao L, Hu X, Zhu B, Li W, Huang X, Kang F. Clinical observation of the combined use of propofol and etomidate in painless gastroscopy. Medicine (Baltimore). 2020; 99(45):1-7.
[37] Diagnostic and statistical manual of mental disorders. American Psychiatric Association. 2019.
[38] Aghdaii N, Sadat Navabi N, Azarfarin R. The effect of using "Pain Assessment Tool" by nurses on analgesics requirement and patients’ satisfaction after coronary bypass graft surgery. Cardiovascular Nursing J. 2016; 4(2): 14-22.
[39] Azimaraghi O, Aghajani Y, Molaghadimi M, et al. Ondansetron reducing pain on injection of etomidate: a controlled randomized study. Braz J Anesthesiol. 2014; 64(3):169-172.
[40] Malekian zadeh B, Hajian P, Manoochehrian N, Khazaei S. Determining the effect of intravenous ondansetron in pereventing hypotension in patients under elective cesarean section. Arak Medical University Journal. 2014;17(89): 71-79.
[41] Atikahmed GM, Raushan KJ, Madhuri AB, Comparative study of etomidate and fentanyl citrate with propofol (1%) and fentanyl citrate for total intravenous anaesthesia in short surgical procedures. IJCA. 2020;7(2): 348-354.
[42] Zahedi H, Maleki A, Rostami G. Ondansetron pretreatment reduces pain on injection of propofol. Acta Med Iran. 2012; 50(4):239-43.
[43] Banavasi A, Thippeswamy H, Bhat SP. Comparison of pre treatment with Ondansetron and Lignocaine over Pain on Etomidate Injection. A double blind prospective non randomised study. IOSR Journal of Dental and Medical Science. 2016;15(9):89-92.
[44] Khorasanizadeh S, Behnaz F, Mohseni G, Ebrahimi DM, Ommi D, Teymourian H. Ondansetron combined with aprepitant versus dexamethasone combined with metoclopramide; which is more efficient to reduce nausea and vomiting after etomidate induction in major vascular surgeries. Journal of Iranian Society of Aneasthesiology and Intensive Care unit.2020;42(3);2-10.
[45] Napolitano CA, Berg RJ, Terlea TC, Castro MI. Prophylactic administration of ondansetron and dolasetron have minimal effects on ventricular repolarization prior to and during the induction of general anesthesia in healthy females. Anesthesiology. 2004;101:A-1274.
[46] Kaushal RP, Vatal A, Pathak R. Effect of etomidate and propofol induction on hemodynamic and endocrine response in patients undergoing coronary artery bypass grafting/mitral valve and aortic valve replacement surgery on cardiopulmonary bypass. Annals of cardiac anaesthesia. 2015; 18(2):172.
[47] Rathore VS, GUPTA S. Comparative study of propofol, etomidate and 50% admixture of etomidate and propofol for induction in general anaesthesia. J Dent Med Sci. 2018.
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How to Cite
1.
Rahimi Z, Masoudifar M, Nazemroaya B, Rahimi Varposhti M, Akhavanfar R. The Effect of Different Doses of Ondansetron in Reducing Injection Pain of Etomidate: A Double-Blind Randomized Clinical Trial. Arch Anesth & Crit Care. 2025;.
