Continuous Dexmedetomidine Infusion Reduces Postoperative Cognitive Dysfunction and Postoperative Pain in Patients Undergoing Laparotomy Surgery: Single-Blinded, Randomized Controlled Trial
-
Hendrikus Gede Surya Adhi Putra
,
Made Wiryana
,
Tjokorda Gde Agung Senapathi
,
I Gusti Ngurah Mahaalit Aribawa
,
I Made Gede Widnyana
,
Dewa Ayu Mas Shintya Dewi
,
André A.J. van Zundert
,
Christopher Ryalino
Abstract
Background: Postoperative cognitive dysfunction (POCD) is a major concern in anesthesia, leading to increased morbidity and longer hospital stays. Our study aimed to evaluate the efficacy of target-controlled infusion (TCI) dexmedetomidine in reducing the incidence of POCD following laparotomy surgery.
Methods: A single-blinded, randomized controlled trial involving 107 patients aged >18 years old undergoing laparotomy surgery was conducted. Patients were randomly assigned to 54 patients in Group D (TCI dexmedetomidine with a target plasma of 1 ng/ml) and 53 patients in Group I (sevoflurane at 0.8% concentration).
Results: Our study showed subjects whose anesthesia was maintained by TCI dexmedetomidine had a lower chance of developing POCD (p=0.043) and experienced less pain at 12 hours (p=0.049) and 24 hours (p=0.049) in the postoperative period, compared to the control group. There were no significant differences between both groups in intraoperative MAP (p=0.290) and HR (p=0.453).
Conclusion: Maintaining anesthesia using Conox®-guided TCI dexmedetomidine reduces the incidence of POCD and postoperative pain in laparotomy patients who underwent general anesthesia.
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[2] Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, Canet J, et al. Long-term postoperative cognitive dysfunction in the elderly: ISPOCD1 study. Lancet. 1998;351(9106):857-861.
[3] Cascella M, Muzio MR, Bimonte S, Cuomo A, Jakobsson JG. Postoperative delirium and postoperative cognitive dysfunction: Updates in pathophysiology, potential translational approaches to clinical practice and further research perspectives. Minerva Anestesiol. 2018;84:246-260.
[4] Magni G, Bilotta F. Postoperative Cognitive Dysfunction. In: Complications in Neuroanesthesia. Elsevier; 2016. p. 411–27.
[5] Gold S, Forryan S. Postoperative cognitive decline: A current problem with a difficult future. Trends Anaesth Crit Care. 2019;24:49-58.
[6] Van Zundert A, Gatt S, Van Zundert T. Prevention and treatment of noncognitive complications. Saudi J Anaesth. 2023;17:557-565.
[7] Dunlop RN, Van Zundert A. A systematic review of predictive accuracy via c-statistic of preoperative frailty tests for extended length of stay, postoperative complications, and mortality. Saudi J Anaesth. 2023;17:575-580.
[8] Silbert BS, Evered LA, Scott DA. Incidence of postoperative cognitive dysfunction after general or spinal anaesthesia for extracorporeal shock wave lithotripsy. Br J Anaesth. 2014;113(5):784-791.
[9] Jensen EW, Valencia JF, López A, Anglada T, Agustí M, Ramos Y, et al. Monitoring hypnotic effect and nociception with two EEG-derived indices, qCON and qNOX, during general anaesthesia. Acta Anaesthesiol Scand. 2014;58(8):933-941.
[10] Colin PJ, Hannivoort LN, Eleveld DJ, Reyntjens KMEM, Absalom AR, Vereecke HEM, et al. Dexmedetomidine pharmacokinetic-pharmacodynamic modelling in healthy volunteers: 1. Influence of arousal on bispectral index and sedation. Br J Anaesth. 2017;119(2):200-210.
[11] Ketut Suyasa I, Ryalino C, Pradnyani NPN. Dexmedetomidine provides better hemodynamic stability compared to clonidine in spine surgery. Bali J Anesthsiol. 2018;2(3):90-94.
[12] Sundar S, Jahagirdar SM, Kumar VRH, Krishnaveni N. A comparative randomised clinical trial to assess the efficacy between dexmedetomidine and midazolam infusions for procedural sedation during septoplasty. Bali J Anesthesiol. 2021;5(1):21-25.
[13] Van Zundert T, Gatt S, Van Zundert A. Anesthesia and perioperative pain relief in the frail elderly patient. Saudi J Anaesth. 2023;17:566-574.
[14] Li WX, Luo RY, Chen C, Li X, Ao JS, Liu Y, et al. Effects of propofol, dexmedetomidine, and midazolam on postoperative cognitive dysfunction in elderly patients: A randomised controlled preliminary trial. Chin Med J (Engl). 2019;132(4):473-445.
[15] Xu H ying, Fu G hua, Wu G sheng. Effect of dexmedetomidine-induced anesthesia on the postoperative cognitive function of elder patients after laparoscopic ovarian cystectomy. Saudi J Biol Sci. 2017;24(8):1771-1775.
[16] Gong Z, Li J, Zhong Y, Guan X, Huang A, Ma L. Effects of dexmedetomidine on postoperative cognitive function in patients undergoing coronary artery bypass grafting. Exp Ther Med. 2018;4685-4689.
[17] Vanacore N, De Carolis A, Sepe-Monti M, Bomboi G, Stazi A, Bianchetti A, et al. Validity of the Italian telephone version of the mini-mental state examination in the elderly healthy population. Acta Neurol Belg. 2006;106(3):132-136.
[18] Schnider TW, Minto CF, Gambus PL, Andresen C, Goodale DB, Shafer SL, et al. The influence of method of administration and covariates on the pharmacokinetics of propofol in adult volunteers. Anesthesiology. 1998;88(5):1170-1182.
[19] Gropper MA, Miller RD. Miller's Anesthesia. 9th ed. Philadelphia: Elsevier; 2020. 2639 p.
[20] Ryalino C, Sahinovic MM, Drost G, Absalom AR. Intraoperative monitoring of the central and peripheral nervous systems: a narrative review. Br J Anaesth. 2024 Feb;132(2):285–99.
[21] De Jonghe B, Cook D, Appere-De-Vecchi C, Guyatt G, Meade M, Outin H. Using and understanding sedation scoring systems: A systematic review. Intensive Care Med. 2000;26:275-285.
[22] Harsha MS, Bhatia PK, Sharma A, Sethi P. Comparison of Quantium Consciousness Index and Richmond Agitation Sedation Scale in Mechanically Ventilated Critically Ill Patients: An Observational Study. Indian J Crit Care Med. 2022;26(4):491-495.
[23] Sachdeva A, Jaswal S, Walia HS, Batra YK. Correlating the Depth of Sedation Between the Ramsay Sedation Scale and Bispectral Index Using Either Intravenous Midazolam or Intravenous Propofol in Elderly Patients Under Spinal Anaesthesia. Cureus. 2023 Dec;15(12):e50763.
[24] Senapathi TGA, Wiryana M, Aribawa IGNM, Ryalino C. Bispectral index value correlates with Glasgow Coma Scale in traumatic brain injury patients. Open Access Emerg Med. 2017;9:43-46.
[25] Ling L, Yang TX, Lee SWK. Effect of Anaesthesia Depth on Postoperative Delirium and Postoperative Cognitive Dysfunction in High-Risk Patients: A Systematic Review and Meta-Analysis. Cureus. 2022;55–9.
[26] Quan C, Chen J, Luo Y, Zhou L, He X, Liao Y, et al. BIS-guided deep anesthesia decreases short-term postoperative cognitive dysfunction and peripheral inflammation in elderly patients undergoing abdominal surgery. Brain Behav. 2019;9(4):1238.
[27] Lu X, Jin X, Yang S, Xia Y. The correlation of the depth of anesthesia and postoperative cognitive impairment: A meta-analysis based on randomised controlled trials. J Clin Anesth. 2018;45.
[28] Chew WZ, Teoh WY, Sivanesan N, Loh PS, Shariffuddin II, Ti LK, et al. Bispectral Index (BIS) Monitoring and Postoperative Delirium in Elderly Patients Undergoing Surgery: A Systematic Review and Meta-Analysis With Trial Sequential Analysis. J Cardiothorac Vasc Anesth. 2022;36:4449–59.
[29] Parami P, Ryalino C. The incidence of postoperative cognitive dysfunction in elderly patients underwent elective surgery at Sanglah General Hospital. Bali J Anesth. 2020;4(6):61-63.
[30] Arefayne NR, Berhe YW, van Zundert AA. Incidence and Factors Related to Prolonged Postoperative Cognitive Decline (POCD) in Elderly Patients Following Surgery and Anaesthesia: A Systematic Review. J Multidiscip Healthc. 2023;16:3405–13.
[31] Li T, Han W, Yang X, Wang Y, Peng L, He L, et al. Effects of Different Injection Rates of Propofol on Postoperative Cognition in Elderly Patients Undergoing Laparoscopic Inguinal Hernia Repair. Drug Des Devel Ther. 2023;17:1741-1752.
[32] Ackenbom MF, Butters MA, Davis EM, Abebe KZ, Baranski L, Zyczynski HM. Incidence of postoperative cognitive dysfunction in older women undergoing pelvic organ prolapse surgery. Int Urogynecol J. 2021;32(2):433-442.
[33] Fu Y, Wei Q, Wang Z, Zhao Q, Shi W. Effects of dexmedetomidine on postoperative pain and early cognitive impairment in older male patients undergoing laparoscopic cholecystectomy. Exp Ther Med. 2024 May;27(5):189.
[34] Lei D, Sha Y, Wen S, Xie S, Liu L, Han C. Dexmedetomidine May Reduce IL-6 Level and the Risk of Postoperative Cognitive Dysfunction in Patients After Surgery: A Meta-Analysis. Dose-Response. 2020;18:1559325820902345.
[35] Belrose JC, Noppens RR. Anesthesiology and cognitive impairment: A narrative review of current clinical literature. BMC Anesthesiology. 2019;19:241.
[36] Safavynia SA, Goldstein PA. The role of neuroinflammation in postoperative cognitive dysfunction: Moving from hypothesis to treatment. Front Psychiatry. 2019;9:752.
[37] Ye Q, Wang F, Xu H, Wu L, Gao X. Effects of dexmedetomidine on intraoperative hemodynamics, recovery profile and postoperative pain in patients undergoing laparoscopic cholecystectomy: a randomised controlled trial. BMC Anesthesiol. 2021;21(1):63.
[38] Chilkoti GT, Karthik G, Rautela R. Evaluation of postoperative analgesic efficacy and perioperative hemodynamic changes with low dose intravenous dexmedetomidine infusion in patients undergoing laparoscopic cholecystectomy-A randomised, double-blinded, placebo-controlled trial. J Anaesthesiol Clin Pharmacol. 2020;36(1):72-77.
[39] Bakri MH, Ismail EA, Ibrahim A. Comparison of dexmedetomidine and dexamethasone for prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy. Korean J Anesthesiol. 2015;68(3):254-260.
[40] Drummond JC, Dao A V., Roth DM, Cheng CR, Atwater BI, Minokadeh A, et al. Effect of dexmedetomidine on cerebral blood flow velocity, cerebral metabolic rate, and carbon dioxide response in normal humans. Anesthesiology. 2008;108(2):225-232.
[41] Asano Y, Koehler RC, Kawaguchi T, McPherson RW. Pial arteriolar constriction to alpha 2-adrenergic agonist dexmedetomidine in the rat. Am J Physiol. 1997 Jun;272(6 Pt 2):2547-56.
[42] Bekker A, Sturaitis MK. Dexmedetomidine for neurological surgery. Neurosurgery. 2005;57:1-10.
[43] Cohen Z, Molinatti G, Hamel E. Astroglial and vascular interactions of noradrenaline terminals in the rat cerebral cortex. J Cerebral Blood Flow Metab. 1997;17(8):894-904.
[44] Zhao W, Hu Y, Chen H, Wang X, Wang L, Wang Y, et al. The Effect and Optimal Dosage of Dexmedetomidine Plus Sufentanil for Postoperative Analgesia in Elderly Patients With Postoperative Delirium and Early Postoperative Cognitive Dysfunction: A Single-Center, Prospective, Randomized, Double-Blind, Controlled Trial. Front Neurosci. 2020;14: 549516.
[2] Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, Canet J, et al. Long-term postoperative cognitive dysfunction in the elderly: ISPOCD1 study. Lancet. 1998;351(9106):857-861.
[3] Cascella M, Muzio MR, Bimonte S, Cuomo A, Jakobsson JG. Postoperative delirium and postoperative cognitive dysfunction: Updates in pathophysiology, potential translational approaches to clinical practice and further research perspectives. Minerva Anestesiol. 2018;84:246-260.
[4] Magni G, Bilotta F. Postoperative Cognitive Dysfunction. In: Complications in Neuroanesthesia. Elsevier; 2016. p. 411–27.
[5] Gold S, Forryan S. Postoperative cognitive decline: A current problem with a difficult future. Trends Anaesth Crit Care. 2019;24:49-58.
[6] Van Zundert A, Gatt S, Van Zundert T. Prevention and treatment of noncognitive complications. Saudi J Anaesth. 2023;17:557-565.
[7] Dunlop RN, Van Zundert A. A systematic review of predictive accuracy via c-statistic of preoperative frailty tests for extended length of stay, postoperative complications, and mortality. Saudi J Anaesth. 2023;17:575-580.
[8] Silbert BS, Evered LA, Scott DA. Incidence of postoperative cognitive dysfunction after general or spinal anaesthesia for extracorporeal shock wave lithotripsy. Br J Anaesth. 2014;113(5):784-791.
[9] Jensen EW, Valencia JF, López A, Anglada T, Agustí M, Ramos Y, et al. Monitoring hypnotic effect and nociception with two EEG-derived indices, qCON and qNOX, during general anaesthesia. Acta Anaesthesiol Scand. 2014;58(8):933-941.
[10] Colin PJ, Hannivoort LN, Eleveld DJ, Reyntjens KMEM, Absalom AR, Vereecke HEM, et al. Dexmedetomidine pharmacokinetic-pharmacodynamic modelling in healthy volunteers: 1. Influence of arousal on bispectral index and sedation. Br J Anaesth. 2017;119(2):200-210.
[11] Ketut Suyasa I, Ryalino C, Pradnyani NPN. Dexmedetomidine provides better hemodynamic stability compared to clonidine in spine surgery. Bali J Anesthsiol. 2018;2(3):90-94.
[12] Sundar S, Jahagirdar SM, Kumar VRH, Krishnaveni N. A comparative randomised clinical trial to assess the efficacy between dexmedetomidine and midazolam infusions for procedural sedation during septoplasty. Bali J Anesthesiol. 2021;5(1):21-25.
[13] Van Zundert T, Gatt S, Van Zundert A. Anesthesia and perioperative pain relief in the frail elderly patient. Saudi J Anaesth. 2023;17:566-574.
[14] Li WX, Luo RY, Chen C, Li X, Ao JS, Liu Y, et al. Effects of propofol, dexmedetomidine, and midazolam on postoperative cognitive dysfunction in elderly patients: A randomised controlled preliminary trial. Chin Med J (Engl). 2019;132(4):473-445.
[15] Xu H ying, Fu G hua, Wu G sheng. Effect of dexmedetomidine-induced anesthesia on the postoperative cognitive function of elder patients after laparoscopic ovarian cystectomy. Saudi J Biol Sci. 2017;24(8):1771-1775.
[16] Gong Z, Li J, Zhong Y, Guan X, Huang A, Ma L. Effects of dexmedetomidine on postoperative cognitive function in patients undergoing coronary artery bypass grafting. Exp Ther Med. 2018;4685-4689.
[17] Vanacore N, De Carolis A, Sepe-Monti M, Bomboi G, Stazi A, Bianchetti A, et al. Validity of the Italian telephone version of the mini-mental state examination in the elderly healthy population. Acta Neurol Belg. 2006;106(3):132-136.
[18] Schnider TW, Minto CF, Gambus PL, Andresen C, Goodale DB, Shafer SL, et al. The influence of method of administration and covariates on the pharmacokinetics of propofol in adult volunteers. Anesthesiology. 1998;88(5):1170-1182.
[19] Gropper MA, Miller RD. Miller's Anesthesia. 9th ed. Philadelphia: Elsevier; 2020. 2639 p.
[20] Ryalino C, Sahinovic MM, Drost G, Absalom AR. Intraoperative monitoring of the central and peripheral nervous systems: a narrative review. Br J Anaesth. 2024 Feb;132(2):285–99.
[21] De Jonghe B, Cook D, Appere-De-Vecchi C, Guyatt G, Meade M, Outin H. Using and understanding sedation scoring systems: A systematic review. Intensive Care Med. 2000;26:275-285.
[22] Harsha MS, Bhatia PK, Sharma A, Sethi P. Comparison of Quantium Consciousness Index and Richmond Agitation Sedation Scale in Mechanically Ventilated Critically Ill Patients: An Observational Study. Indian J Crit Care Med. 2022;26(4):491-495.
[23] Sachdeva A, Jaswal S, Walia HS, Batra YK. Correlating the Depth of Sedation Between the Ramsay Sedation Scale and Bispectral Index Using Either Intravenous Midazolam or Intravenous Propofol in Elderly Patients Under Spinal Anaesthesia. Cureus. 2023 Dec;15(12):e50763.
[24] Senapathi TGA, Wiryana M, Aribawa IGNM, Ryalino C. Bispectral index value correlates with Glasgow Coma Scale in traumatic brain injury patients. Open Access Emerg Med. 2017;9:43-46.
[25] Ling L, Yang TX, Lee SWK. Effect of Anaesthesia Depth on Postoperative Delirium and Postoperative Cognitive Dysfunction in High-Risk Patients: A Systematic Review and Meta-Analysis. Cureus. 2022;55–9.
[26] Quan C, Chen J, Luo Y, Zhou L, He X, Liao Y, et al. BIS-guided deep anesthesia decreases short-term postoperative cognitive dysfunction and peripheral inflammation in elderly patients undergoing abdominal surgery. Brain Behav. 2019;9(4):1238.
[27] Lu X, Jin X, Yang S, Xia Y. The correlation of the depth of anesthesia and postoperative cognitive impairment: A meta-analysis based on randomised controlled trials. J Clin Anesth. 2018;45.
[28] Chew WZ, Teoh WY, Sivanesan N, Loh PS, Shariffuddin II, Ti LK, et al. Bispectral Index (BIS) Monitoring and Postoperative Delirium in Elderly Patients Undergoing Surgery: A Systematic Review and Meta-Analysis With Trial Sequential Analysis. J Cardiothorac Vasc Anesth. 2022;36:4449–59.
[29] Parami P, Ryalino C. The incidence of postoperative cognitive dysfunction in elderly patients underwent elective surgery at Sanglah General Hospital. Bali J Anesth. 2020;4(6):61-63.
[30] Arefayne NR, Berhe YW, van Zundert AA. Incidence and Factors Related to Prolonged Postoperative Cognitive Decline (POCD) in Elderly Patients Following Surgery and Anaesthesia: A Systematic Review. J Multidiscip Healthc. 2023;16:3405–13.
[31] Li T, Han W, Yang X, Wang Y, Peng L, He L, et al. Effects of Different Injection Rates of Propofol on Postoperative Cognition in Elderly Patients Undergoing Laparoscopic Inguinal Hernia Repair. Drug Des Devel Ther. 2023;17:1741-1752.
[32] Ackenbom MF, Butters MA, Davis EM, Abebe KZ, Baranski L, Zyczynski HM. Incidence of postoperative cognitive dysfunction in older women undergoing pelvic organ prolapse surgery. Int Urogynecol J. 2021;32(2):433-442.
[33] Fu Y, Wei Q, Wang Z, Zhao Q, Shi W. Effects of dexmedetomidine on postoperative pain and early cognitive impairment in older male patients undergoing laparoscopic cholecystectomy. Exp Ther Med. 2024 May;27(5):189.
[34] Lei D, Sha Y, Wen S, Xie S, Liu L, Han C. Dexmedetomidine May Reduce IL-6 Level and the Risk of Postoperative Cognitive Dysfunction in Patients After Surgery: A Meta-Analysis. Dose-Response. 2020;18:1559325820902345.
[35] Belrose JC, Noppens RR. Anesthesiology and cognitive impairment: A narrative review of current clinical literature. BMC Anesthesiology. 2019;19:241.
[36] Safavynia SA, Goldstein PA. The role of neuroinflammation in postoperative cognitive dysfunction: Moving from hypothesis to treatment. Front Psychiatry. 2019;9:752.
[37] Ye Q, Wang F, Xu H, Wu L, Gao X. Effects of dexmedetomidine on intraoperative hemodynamics, recovery profile and postoperative pain in patients undergoing laparoscopic cholecystectomy: a randomised controlled trial. BMC Anesthesiol. 2021;21(1):63.
[38] Chilkoti GT, Karthik G, Rautela R. Evaluation of postoperative analgesic efficacy and perioperative hemodynamic changes with low dose intravenous dexmedetomidine infusion in patients undergoing laparoscopic cholecystectomy-A randomised, double-blinded, placebo-controlled trial. J Anaesthesiol Clin Pharmacol. 2020;36(1):72-77.
[39] Bakri MH, Ismail EA, Ibrahim A. Comparison of dexmedetomidine and dexamethasone for prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy. Korean J Anesthesiol. 2015;68(3):254-260.
[40] Drummond JC, Dao A V., Roth DM, Cheng CR, Atwater BI, Minokadeh A, et al. Effect of dexmedetomidine on cerebral blood flow velocity, cerebral metabolic rate, and carbon dioxide response in normal humans. Anesthesiology. 2008;108(2):225-232.
[41] Asano Y, Koehler RC, Kawaguchi T, McPherson RW. Pial arteriolar constriction to alpha 2-adrenergic agonist dexmedetomidine in the rat. Am J Physiol. 1997 Jun;272(6 Pt 2):2547-56.
[42] Bekker A, Sturaitis MK. Dexmedetomidine for neurological surgery. Neurosurgery. 2005;57:1-10.
[43] Cohen Z, Molinatti G, Hamel E. Astroglial and vascular interactions of noradrenaline terminals in the rat cerebral cortex. J Cerebral Blood Flow Metab. 1997;17(8):894-904.
[44] Zhao W, Hu Y, Chen H, Wang X, Wang L, Wang Y, et al. The Effect and Optimal Dosage of Dexmedetomidine Plus Sufentanil for Postoperative Analgesia in Elderly Patients With Postoperative Delirium and Early Postoperative Cognitive Dysfunction: A Single-Center, Prospective, Randomized, Double-Blind, Controlled Trial. Front Neurosci. 2020;14: 549516.
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How to Cite
1.
Adhi Putra HGS, Wiryana M, Senapathi TG, Mahaalit Aribawa IGN, Widnyana IMG, Shintya Dewi DAM, Zundert AA, Ryalino C. Continuous Dexmedetomidine Infusion Reduces Postoperative Cognitive Dysfunction and Postoperative Pain in Patients Undergoing Laparotomy Surgery: Single-Blinded, Randomized Controlled Trial. Arch Anesth & Crit Care. 2025;.
