Intranasal administration of insulin on the incidence of postoperative delirium in middle-aged patients undergoing elective on-pump cardiac surgery (INIPOD-MOPS): a prospective double-blinded randomized control study protocol.
Humans
Double-Blind Method
Administration, Intranasal
Prospective Studies
Insulin
/ administration & dosage
Delirium
/ prevention & control
Cardiac Surgical Procedures
/ adverse effects
Middle Aged
Incidence
Elective Surgical Procedures
Randomized Controlled Trials as Topic
Postoperative Complications
/ prevention & control
Female
Male
Treatment Outcome
Length of Stay
Hospital Mortality
4 a’s Test
Cardiac surgery
Delirium
Intranasally administered insulin
Journal
Trials
ISSN: 1745-6215
Titre abrégé: Trials
Pays: England
ID NLM: 101263253
Informations de publication
Date de publication:
27 Aug 2024
27 Aug 2024
Historique:
received:
14
04
2024
accepted:
21
08
2024
medline:
28
8
2024
pubmed:
28
8
2024
entrez:
27
8
2024
Statut:
epublish
Résumé
Delirium, marked by acute cognitive decline, poses a life-threatening issue among older individuals, especially after cardiac surgery, with prevalence ranging from 15 to 80%. Postoperative delirium is linked to increased morbidity and mortality. Although clinical trials suggest preventability, there is limited research on intranasal insulin (INI) for cardiac surgery-related delirium. INI has shown promise in managing cognitive disorders. It rapidly elevates brain hormone levels, enhancing memory even in non-impaired individuals. While effective in preventing delirium in gastrointestinal surgery, its impact after cardiac surgery remains understudied, especially for middle-aged patients. This is a prospective randomized, double-blind, single-center controlled trial. A total of 76 eligible participants scheduled for elective on-pump cardiac surgery will be enrolled and randomly assigned in a 1:1 ratio to either receive Intranasally administered insulin (INI) or intranasally administered normal saline. The primary outcome of our study is the incidence of postoperative delirium (POD). Secondary outcomes include duration of ICU, postoperative hospital length of stay, all in-hospital mortality, the change in MMSE scores pre- and post-operation, and incidence of postoperative cognitive dysfunction at 1 month, 3 months, and 6 months after operation. Moreover, we will subjectively and objectively evaluate perioperative sleep quality to investigate the potential impact of nasal insulin on the development of delirium by influencing sleep regulation. Our study will aim to assess the impact of intranasal administration of insulin on the incidence of postoperative delirium in middle-aged patients undergoing on-pump elective cardiac surgery. If intranasal insulin proves to be more effective, it may be considered as a viable alternative for preventing postoperative delirium. ChiCTR ChiCTR2400081444. Registered on March 1, 2024.
Sections du résumé
BACKGROUND
BACKGROUND
Delirium, marked by acute cognitive decline, poses a life-threatening issue among older individuals, especially after cardiac surgery, with prevalence ranging from 15 to 80%. Postoperative delirium is linked to increased morbidity and mortality. Although clinical trials suggest preventability, there is limited research on intranasal insulin (INI) for cardiac surgery-related delirium. INI has shown promise in managing cognitive disorders. It rapidly elevates brain hormone levels, enhancing memory even in non-impaired individuals. While effective in preventing delirium in gastrointestinal surgery, its impact after cardiac surgery remains understudied, especially for middle-aged patients.
METHOD
METHODS
This is a prospective randomized, double-blind, single-center controlled trial. A total of 76 eligible participants scheduled for elective on-pump cardiac surgery will be enrolled and randomly assigned in a 1:1 ratio to either receive Intranasally administered insulin (INI) or intranasally administered normal saline. The primary outcome of our study is the incidence of postoperative delirium (POD). Secondary outcomes include duration of ICU, postoperative hospital length of stay, all in-hospital mortality, the change in MMSE scores pre- and post-operation, and incidence of postoperative cognitive dysfunction at 1 month, 3 months, and 6 months after operation. Moreover, we will subjectively and objectively evaluate perioperative sleep quality to investigate the potential impact of nasal insulin on the development of delirium by influencing sleep regulation.
DISCUSSION
CONCLUSIONS
Our study will aim to assess the impact of intranasal administration of insulin on the incidence of postoperative delirium in middle-aged patients undergoing on-pump elective cardiac surgery. If intranasal insulin proves to be more effective, it may be considered as a viable alternative for preventing postoperative delirium.
TRIAL REGISTRATION
BACKGROUND
ChiCTR ChiCTR2400081444. Registered on March 1, 2024.
Identifiants
pubmed: 39192373
doi: 10.1186/s13063-024-08417-x
pii: 10.1186/s13063-024-08417-x
doi:
Substances chimiques
Insulin
0
Types de publication
Journal Article
Clinical Trial Protocol
Langues
eng
Sous-ensembles de citation
IM
Pagination
565Subventions
Organisme : Development Program of China
ID : 2018YFC0117200
Organisme : the National Natural Science Foundation of China
ID : 82171265
Informations de copyright
© 2024. The Author(s).
Références
Inouye SK. Delirium in older persons. New Engl J Med. 2006;354(11):1157–65.
doi: 10.1056/NEJMra052321
pubmed: 16540616
Fong TG, Tulebaev SR, Inouye SK. Delirium in elderly adults: diagnosis, prevention and treatment. Nat Rev Neurol. 2009;5(4):210–20.
doi: 10.1038/nrneurol.2009.24
pubmed: 19347026
pmcid: 3065676
Djaiani G, et al. Dexmedetomidine versus Propofol Sedation Reduces Delirium after Cardiac Surgery: A Randomized Controlled Trial. Anesthesiology. 2016;124(2):362–8.
doi: 10.1097/ALN.0000000000000951
pubmed: 26575144
Inouye SK, et al. A multicomponent intervention to prevent delirium in hospitalized older patients. New Engl J Med. 1999;340(9):669–76.
doi: 10.1056/NEJM199903043400901
pubmed: 10053175
Marcantonio ER, et al. Reducing delirium after hip fracture: a randomized trial. J Am Geriatr Soc. 2001;49(5):516–22.
doi: 10.1046/j.1532-5415.2001.49108.x
pubmed: 11380742
Reger MA, et al. Effects of intranasal insulin on cognition in memory-impaired older adults: modulation by APOE genotype. Neurobiol Aging. 2006;27(3):451–8.
doi: 10.1016/j.neurobiolaging.2005.03.016
pubmed: 15964100
Craft S, et al. Effects of Regular and Long-Acting Insulin on Cognition and Alzheimer’s Disease Biomarkers: A Pilot Clinical Trial. J Alzheimers Dis. 2017;57(4):1325–34.
doi: 10.3233/JAD-161256
pubmed: 28372335
pmcid: 5409050
Avgerinos KI, et al. Intranasal insulin in Alzheimer’s dementia or mild cognitive impairment: a systematic review. J Neurol. 2018;265(7):1497–510.
doi: 10.1007/s00415-018-8768-0
pubmed: 29392460
pmcid: 6465964
Fan LW, et al. Rapid transport of insulin to the brain following intranasal administration in rats. Neural Regen Res. 2019;14(6):1046–51.
doi: 10.4103/1673-5374.250624
pubmed: 30762017
pmcid: 6404510
Benedict C, et al. Intranasal insulin improves memory in humans: superiority of insulin aspart. Neuropsychopharmacol. 2007;32(1):239–43.
doi: 10.1038/sj.npp.1301193
Benedict C, et al. Differential sensitivity of men and women to anorexigenic and memory-improving effects of intranasal insulin. J Clin Endocr Metab. 2008;93(4):1339–44.
doi: 10.1210/jc.2007-2606
pubmed: 18230654
Huang Q, et al. Repeated Preoperative Intranasal Administration of Insulin Decreases the Incidence of Postoperative Delirium in Elderly Patients Undergoing Laparoscopic Radical Gastrointestinal Surgery: A Randomized, Placebo-Controlled, Double-Blinded Clinical Study. Am J Geriat Psychiat. 2021;29(12):1202–11.
doi: 10.1016/j.jagp.2021.02.043
Ely EW, et al. Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Crit Care Med. 2001;29(7):1370–9.
doi: 10.1097/00003246-200107000-00012
pubmed: 11445689
Chang Y, et al. Diagnostic accuracy of the “4 A’s Test” delirium screening tool for the postoperative cardiac surgery ward. J Thorac Cardiov Sur. 2023;165(3):1151-1160.e8.
doi: 10.1016/j.jtcvs.2021.05.031
Maldonado JR. Delirium pathophysiology: An updated hypothesis of the etiology of acute brain failure. Int J Geriatr Psych. 2018;33(11):1428–57.
doi: 10.1002/gps.4823
Duarte AI, Moreira PI, Oliveira CR. Insulin in central nervous system: more than just a peripheral hormone. J Aging Res. 2012;2012:384017.
doi: 10.1155/2012/384017
pubmed: 22500228
pmcid: 3303591
Born J, et al. Sniffing neuropeptides: a transnasal approach to the human brain. Nat Neurosci. 2002;5(6):514–6.
doi: 10.1038/nn0602-849
pubmed: 11992114
Novak V, et al. MemAID: Memory advancement with intranasal insulin vs. placebo in type 2 diabetes and control participants: a randomized clinical trial. J Neurol. 2022;269(9):4817–35.
doi: 10.1007/s00415-022-11119-6
pubmed: 35482079
pmcid: 9046533