Research progress on the correlation between benzodiazepines and postoperative delirium_West China Medical Journal

Authors：

WU Yali ,  YANG Jing

Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

YANG Jing, Email: hxyangjing@qq.com

Keywords：

Postoperative delirium; benzodiazepines; research progress

DOI：

10.7507/1002-0179.202110087

Video：

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Postoperative delirium is one of the most common postoperative complications in elderly patients, affecting the outcome of approximately half of surgical patients. The pathogenesis of postoperative delirium is still unclear, but multivariate models of the etiology of postoperative delirium are well-validated and widely accepted, and 40% of postoperative delirium can be effectively prevented by targeting predisposing factors. Benzodiazepines have long been considered as predisposing factors for postoperative delirium. Although benzodiazepines are widely used in clinical practice, most relevant guidelines recommend avoiding the use of benzodiazepines in the perioperative period to reduce the incidence of postoperative delirium. Controversy exists regarding the association of benzodiazepine use with postoperative delirium. This article discusses the results of studies on perioperative benzodiazepines and postoperative delirium.

Citation： WU Yali, YANG Jing. Research progress on the correlation between benzodiazepines and postoperative delirium. West China Medical Journal, 2022, 37(9): 1405-1409. doi: 10.7507/1002-0179.202110087 Copy

1.	Aldecoa C, Bettelli G, Bilotta F, et al. European Society of Anaesthesiology evidence-based and consensus-based guideline on postoperative delirium. Eur J Anaesthesiol, 2017, 34(4): 192-214.
2.	Evered L, Silbert B, Knopman DS, et al. Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery-2018. Br J Anaesth, 2018, 121(5): 1005-1012.
3.	Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet, 2014, 383(9920): 911-922.
4.	Gleason LJ, Schmitt EM, Kosar CM, et al. Effect of delirium and other major complications on outcomes after elective surgery in older adults. JAMA Surg, 2015, 150(12): 1134-1140.
5.	Witlox J, Eurelings LS, de Jonghe JF, et al. Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis. JAMA, 2010, 304(4): 443-451.
6.	Kok L, Slooter AJ, Hillegers MH, et al. Benzodiazepine use and neuropsychiatric outcomes in the ICU: a systematic review. Crit Care Med, 2018, 46(10): 1673-1680.
7.	Wang ML, Min J, Sands LP, et al. Midazolam premedication immediately before surgery is not associated with early postoperative delirium. Anesth Analg, 2021, 133(3): 765-771.
8.	Hughes CG, Boncyk CS, Culley DJ, et al. American Society For Enhanced Recovery and Perioperative Quality Initiative Joint consensus statement on postoperative delirium prevention. Anesth Analg, 2020, 130(6): 1572-1590.
9.	万小健, 王东信, 方向明, 等. 成人术后谵妄防治的专家共识. (2014-07-15)[2021-10-12]. https://csahq.cma.org.cn/guide/detail_214.html.
10.	万小健, 王东信, 方向明, 等. 成人术后谵妄防治的专家共识. (2021-07-05)[2021-10-12]. https://csahq.cma.org.cn/guide/detail_1651.html.
11.	Jin Z, Hu J, Ma D. Postoperative delirium: perioperative assessment, risk reduction, and management. Br J Anaesth, 2020, 125(4): 492-504.
12.	Wildes TS, Mickle AM, Ben Abdallah A, et al. Effect of electroencephalography-guided anesthetic administration on postoperative delirium among older adults undergoing major surgery: the ENGAGES randomized clinical trial. JAMA, 2019, 321(5): 473-483.
13.	Liu X, Yu Y, Zhu S. Inflammatory markers in postoperative delirium (POD) and cognitive dysfunction (POCD): a meta-analysis of observational studies. PLoS One, 2018, 13(4): e0195659.
14.	Kassie GM, Nguyen TA, Kalisch Ellett LM, et al. Preoperative medication use and postoperative delirium: a systematic review. BMC Geriatr, 2017, 17(1): 298.
15.	2019 American Geriatrics Society Beers Criteria^® Update Expert Panel. American Geriatrics Society 2019 updated AGS beers criteria^® for potentially inappropriate medication use in older adults. J Am Geriatr Soc, 2019, 67(4): 674-694.
16.	Hui D, Frisbee-Hume S, Wilson A, et al. Effect of lorazepam with haloperidol vs haloperidol alone on agitated delirium in patients with advanced cancer receiving palliative care: a randomized clinical trial. JAMA, 2017, 318(11): 1047-1056.
17.	Wu YC, Tseng PT, Tu YK, et al. Association of delirium response and safety of pharmacological interventions for the management and prevention of delirium: a network meta-analysis. JAMA Psychiatry, 2019, 76(5): 526-535.
18.	Gaertner J, Eychmueller S, Leyhe T, et al. Benzodiazepines and/or neuroleptics for the treatment of delirium in palliative care?-a critical appraisal of recent randomized controlled trials. Ann Palliat Med, 2019, 8(4): 504-515.
19.	Schieveld JNM, Strik JJMH, Bruining H. On benzodiazepines, paradoxical agitation, hyperactive delirium, and chloride homeostasis. Crit Care Med, 2018, 46(9): 1558-1559.
20.	Lee D, Petersen F, Wu M, et al. A prospective observational cohort pilot study of the association between midazolam use and delirium in elderly endoscopy patients. BMC Anesthesiol, 2021, 21(1): 53.
21.	Gerecke M. Chemical structure and properties of midazolam compared with other benzodiazepines. Br J Clin Pharmacol, 1983, 16(Suppl 1): 11S-16S.
22.	Cui Y, Li G, Cao R, et al. The effect of perioperative anesthetics for prevention of postoperative delirium on general anesthesia: a network meta-analysis. J Clin Anesth, 2020, 59: 89-98.
23.	Weinstein SM, Poultsides L, Baaklini LR, et al. Postoperative delirium in total knee and hip arthroplasty patients: a study of perioperative modifiable risk factors. Br J Anaesth, 2018, 120(5): 999-1008.
24.	Memtsoudis S, Cozowicz C, Zubizarreta N, et al. Risk factors for postoperative delirium in patients undergoing lower extremity joint arthroplasty: a retrospective population-based cohort study. Reg Anesth Pain Med, 2019, 12: rapm-2019-100700.
25.	Poeran J, Cozowicz C, Zubizarreta N, et al. Modifiable factors associated with postoperative delirium after hip fracture repair: an age-stratified retrospective cohort study. Eur J Anaesthesiol, 2020, 37(8): 649-658.
26.	Spence J, Belley-Côté E, Jacobsohn E, et al. Restricted versus liberal intraoperative benzodiazepine use in cardiac anaesthesia for reducing delirium (B-Free Pilot): a pilot, multicentre, randomised, cluster crossover trial. Br J Anaesth, 2020, 125(1): 38-46.
27.	Marcantonio ER, Juarez G, Goldman L, et al. The relationship of postoperative delirium with psychoactive medications. JAMA, 1994, 272(19): 1518-1522.
28.	Kudoh A, Takase H, Takahira Y, et al. Postoperative confusion increases in elderly long-term benzodiazepine users. Anesth Analg, 2004, 99(6): 1674-1678.
29.	Herman J, Urman RD, Urits I, et al. Which interventions can reduce post-operative delirium in the elderly? Synthesis of multidisciplinary and pharmacological intervention data. J Clin Anesth, 2022, 79: 110117.
30.	Wang YY, Yue JR, Xie DM, et al. Effect of the tailored, family-involved hospital elder life program on postoperative delirium and function in older adults: a randomized clinical trial. JAMA Intern Med, 2020, 180(1): 17-25.
31.	Morandi A, Piva S, Ely EW, et al. Worldwide survey of the “assessing pain, both spontaneous awakening and breathing trials, choice of drugs, delirium monitoring/management, early exercise/mobility, and family empowerment” (ABCDEF) bundle. Crit Care Med, 2017, 45(11): e1111-e1122.
32.	Sieber FE, Neufeld KJ, Gottschalk A, et al. Effect of depth of sedation in older patients undergoing hip fracture repair on postoperative delirium: the STRIDE randomized clinical trial. JAMA Surg, 2018, 153(11): 987-995.
33.	Liu X, Nakano M, Yamaguchi A, et al. The association of bispectral index values and metrics of cerebral perfusion during cardiopulmonary bypass. J Clin Anesth, 2021, 74: 110395.
34.	Li YW, Li HJ, Li HJ, et al. Delirium in older patients after combined epidural-general anesthesia or general anesthesia for major surgery: a randomized trial. Anesthesiology, 2021, 135(2): 218-232.
35.	Xu X, Hu X, Wu Y, et al. Effects of different BP management strategies on postoperative delirium in elderly patients undergoing hip replacement: a single center randomized controlled trial. J Clin Anesth, 2020, 62: 109730.
36.	Devlin JW, Skrobik Y, Gélinas C, et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med, 2018, 46(9): e825-e873.
37.	American Geriatrics Society Expert Panel on Postoperative Delirium in Older Adults. Postoperative delirium in older adults: best practice statement from the American Geriatrics Society. J Am Coll Surg, 2015, 220(2): 136-148.e1.

1. Aldecoa C, Bettelli G, Bilotta F, et al. European Society of Anaesthesiology evidence-based and consensus-based guideline on postoperative delirium. Eur J Anaesthesiol, 2017, 34(4): 192-214.
2. Evered L, Silbert B, Knopman DS, et al. Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery-2018. Br J Anaesth, 2018, 121(5): 1005-1012.
3. Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet, 2014, 383(9920): 911-922.
4. Gleason LJ, Schmitt EM, Kosar CM, et al. Effect of delirium and other major complications on outcomes after elective surgery in older adults. JAMA Surg, 2015, 150(12): 1134-1140.
5. Witlox J, Eurelings LS, de Jonghe JF, et al. Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis. JAMA, 2010, 304(4): 443-451.
6. Kok L, Slooter AJ, Hillegers MH, et al. Benzodiazepine use and neuropsychiatric outcomes in the ICU: a systematic review. Crit Care Med, 2018, 46(10): 1673-1680.
7. Wang ML, Min J, Sands LP, et al. Midazolam premedication immediately before surgery is not associated with early postoperative delirium. Anesth Analg, 2021, 133(3): 765-771.
8. Hughes CG, Boncyk CS, Culley DJ, et al. American Society For Enhanced Recovery and Perioperative Quality Initiative Joint consensus statement on postoperative delirium prevention. Anesth Analg, 2020, 130(6): 1572-1590.
9. 万小健, 王东信, 方向明, 等. 成人术后谵妄防治的专家共识. (2014-07-15)[2021-10-12]. https://csahq.cma.org.cn/guide/detail_214.html.
10. 万小健, 王东信, 方向明, 等. 成人术后谵妄防治的专家共识. (2021-07-05)[2021-10-12]. https://csahq.cma.org.cn/guide/detail_1651.html.
11. Jin Z, Hu J, Ma D. Postoperative delirium: perioperative assessment, risk reduction, and management. Br J Anaesth, 2020, 125(4): 492-504.
12. Wildes TS, Mickle AM, Ben Abdallah A, et al. Effect of electroencephalography-guided anesthetic administration on postoperative delirium among older adults undergoing major surgery: the ENGAGES randomized clinical trial. JAMA, 2019, 321(5): 473-483.
13. Liu X, Yu Y, Zhu S. Inflammatory markers in postoperative delirium (POD) and cognitive dysfunction (POCD): a meta-analysis of observational studies. PLoS One, 2018, 13(4): e0195659.
14. Kassie GM, Nguyen TA, Kalisch Ellett LM, et al. Preoperative medication use and postoperative delirium: a systematic review. BMC Geriatr, 2017, 17(1): 298.
15. 2019 American Geriatrics Society Beers Criteria^® Update Expert Panel. American Geriatrics Society 2019 updated AGS beers criteria^® for potentially inappropriate medication use in older adults. J Am Geriatr Soc, 2019, 67(4): 674-694.
16. Hui D, Frisbee-Hume S, Wilson A, et al. Effect of lorazepam with haloperidol vs haloperidol alone on agitated delirium in patients with advanced cancer receiving palliative care: a randomized clinical trial. JAMA, 2017, 318(11): 1047-1056.
17. Wu YC, Tseng PT, Tu YK, et al. Association of delirium response and safety of pharmacological interventions for the management and prevention of delirium: a network meta-analysis. JAMA Psychiatry, 2019, 76(5): 526-535.
18. Gaertner J, Eychmueller S, Leyhe T, et al. Benzodiazepines and/or neuroleptics for the treatment of delirium in palliative care?-a critical appraisal of recent randomized controlled trials. Ann Palliat Med, 2019, 8(4): 504-515.
19. Schieveld JNM, Strik JJMH, Bruining H. On benzodiazepines, paradoxical agitation, hyperactive delirium, and chloride homeostasis. Crit Care Med, 2018, 46(9): 1558-1559.
20. Lee D, Petersen F, Wu M, et al. A prospective observational cohort pilot study of the association between midazolam use and delirium in elderly endoscopy patients. BMC Anesthesiol, 2021, 21(1): 53.
21. Gerecke M. Chemical structure and properties of midazolam compared with other benzodiazepines. Br J Clin Pharmacol, 1983, 16(Suppl 1): 11S-16S.
22. Cui Y, Li G, Cao R, et al. The effect of perioperative anesthetics for prevention of postoperative delirium on general anesthesia: a network meta-analysis. J Clin Anesth, 2020, 59: 89-98.
23. Weinstein SM, Poultsides L, Baaklini LR, et al. Postoperative delirium in total knee and hip arthroplasty patients: a study of perioperative modifiable risk factors. Br J Anaesth, 2018, 120(5): 999-1008.
24. Memtsoudis S, Cozowicz C, Zubizarreta N, et al. Risk factors for postoperative delirium in patients undergoing lower extremity joint arthroplasty: a retrospective population-based cohort study. Reg Anesth Pain Med, 2019, 12: rapm-2019-100700.
25. Poeran J, Cozowicz C, Zubizarreta N, et al. Modifiable factors associated with postoperative delirium after hip fracture repair: an age-stratified retrospective cohort study. Eur J Anaesthesiol, 2020, 37(8): 649-658.
26. Spence J, Belley-Côté E, Jacobsohn E, et al. Restricted versus liberal intraoperative benzodiazepine use in cardiac anaesthesia for reducing delirium (B-Free Pilot): a pilot, multicentre, randomised, cluster crossover trial. Br J Anaesth, 2020, 125(1): 38-46.
27. Marcantonio ER, Juarez G, Goldman L, et al. The relationship of postoperative delirium with psychoactive medications. JAMA, 1994, 272(19): 1518-1522.
28. Kudoh A, Takase H, Takahira Y, et al. Postoperative confusion increases in elderly long-term benzodiazepine users. Anesth Analg, 2004, 99(6): 1674-1678.
29. Herman J, Urman RD, Urits I, et al. Which interventions can reduce post-operative delirium in the elderly? Synthesis of multidisciplinary and pharmacological intervention data. J Clin Anesth, 2022, 79: 110117.
30. Wang YY, Yue JR, Xie DM, et al. Effect of the tailored, family-involved hospital elder life program on postoperative delirium and function in older adults: a randomized clinical trial. JAMA Intern Med, 2020, 180(1): 17-25.
31. Morandi A, Piva S, Ely EW, et al. Worldwide survey of the “assessing pain, both spontaneous awakening and breathing trials, choice of drugs, delirium monitoring/management, early exercise/mobility, and family empowerment” (ABCDEF) bundle. Crit Care Med, 2017, 45(11): e1111-e1122.
32. Sieber FE, Neufeld KJ, Gottschalk A, et al. Effect of depth of sedation in older patients undergoing hip fracture repair on postoperative delirium: the STRIDE randomized clinical trial. JAMA Surg, 2018, 153(11): 987-995.
33. Liu X, Nakano M, Yamaguchi A, et al. The association of bispectral index values and metrics of cerebral perfusion during cardiopulmonary bypass. J Clin Anesth, 2021, 74: 110395.
34. Li YW, Li HJ, Li HJ, et al. Delirium in older patients after combined epidural-general anesthesia or general anesthesia for major surgery: a randomized trial. Anesthesiology, 2021, 135(2): 218-232.
35. Xu X, Hu X, Wu Y, et al. Effects of different BP management strategies on postoperative delirium in elderly patients undergoing hip replacement: a single center randomized controlled trial. J Clin Anesth, 2020, 62: 109730.
36. Devlin JW, Skrobik Y, Gélinas C, et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med, 2018, 46(9): e825-e873.
37. American Geriatrics Society Expert Panel on Postoperative Delirium in Older Adults. Postoperative delirium in older adults: best practice statement from the American Geriatrics Society. J Am Coll Surg, 2015, 220(2): 136-148.e1.

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Research progress on the correlation between benzodiazepines and postoperative delirium

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