The median effective concentration of propofol with different doses of esketamine during gastrointestinal endoscopy in elderly patients: A randomized controlled trial

Hua Yang, Qian Zhao, Hai-Yan Chen, Wen Liu, Tong Ding, Bin Yang, Jin-Chao Song, Hua Yang, Qian Zhao, Hai-Yan Chen, Wen Liu, Tong Ding, Bin Yang, Jin-Chao Song

Abstract

Aims: Propofol may result in hypotension, bradycardia and loss of protective reflexes, especially in elderly patients, while esketamine, a N-methyl-D-aspartate receptor antagonist, has analgesic, anaesthetic and sympathomimetic properties and is known to cause less cardiorespiratory depression. We hypothesized that esketamine may reduce the median effective concentration (EC50 ) of propofol and coadministration is less likely to produce hypotension during gastrointestinal endoscopy in elderly patients.

Methods: Ninety elderly patients, aged 65-89 years, undergoing gastrointestinal endoscopy were randomly assigned into 3 groups: SK0 (control) group (0 mg/kg esketamine); SK0.25 group (0.25 mg/kg esketamine); and SK0.5 group (0.5 mg/kg esketamine). Anaesthesia was achieved by plasma target-controlled infusion of propofol with different bolus doses of esketamine. The EC50 of propofol for gastrointestinal endoscopy was determined by using the up-and-down method of Dixon. The initial plasma target concentration is 2.5 μg/mL and the adjacent concentration gradient is 0.5 μg/mL. Cardiovascular variables were also measured.

Results: Propofol EC50 s and its 95% confidence interval for gastrointestinal endoscopy in elderly patients were 3.69 (2.59-4.78), 2.45 (1.85-3.05) and 1.71 (1.15-2.27) μg/mL in the SK0, SK0.25 and SK0.5 groups, respectively (P < .05). The average percent change from baseline mean arterial pressure was -19.7 (7.55), -15.2 (7.14) and -10.1 (6.73), in the SK0, SK0.25 and SK0.5 groups, respectively (P < .001).

Conclusion: Combination medication of propofol with esketamine reduced the propofol EC50 during gastrointestinal endoscopy in elderly patients compared with administration of propofol without esketamine. Increasing doses of SK with propofol are less likely to produce hypotension with shorter recovery time.

Keywords: EC50; elderly patients; esketamine; propofol.

© 2021 British Pharmacological Society.

References

REFERENCES

    1. Ferreira AO, Cravo M. Sedation in gastrointestinal endoscopy: Where are we at in 2014? World J Gastrointest Endosc. 2015;7(2):102-109.
    1. Moon SH. Sedation regimens for gastrointestinal endoscopy. Clin Endosc. 2014;47(2):135-140.
    1. Fanti L, Gemma M, Agostoni M, et al. Target Controlled Infusion for non-anaesthesiologist propofol sedation during gastrointestinal endoscopy: The first double blind randomized controlled trial. Dig Liver Dis. 2015;47(7):566-571.
    1. Song JC, Lu ZJ, Jiao YF, et al. Etomidate Anesthesia during ERCP Caused More Stable Haemodynamic Responses Compared with Propofol: A Randomized Clinical Trial. Int J Med Sci. 2015;12(7):559-565.
    1. Angsuwatcharakon P, Rerknimitr R, Ridtitid W, et al. Cocktail sedation containing propofol versus conventional sedation for ERCP: a prospective, randomized controlled study. BMC Anesthesiol. 2012;12(1):20.
    1. Jung M, Hofmann C, Kiesslich R, Brackertz A. Improved sedation in diagnostic and therapeutic ERCP: propofol is an alternative to midazolam. Endoscopy. 2000;32(03):233-238.
    1. Kongkam P, Rerknimitr R, Punyathavorn S, et al. Propofol infusion versus intermittent meperidine and midazolam injection for conscious sedation in ERCP. J Gastrointestin Liver Dis. 2008;17(3):291-297.
    1. Eberl S, Preckel B, Bergman JJ, van Dieren S, Hollmann MW. Satisfaction and safety using dexmedetomidine or propofol sedation during endoscopic oesophageal procedures: A randomised controlled trial. Eur J Anaesthesiol. 2016 Sep;33(9):631-637.
    1. Faigel DO, Baron TH, Goldstein JL, et al. Guidelines for the use of deep sedation and anesthesia for GI endoscopy. Gastrointest Endosc. 2002Nov;56(5):613-617.
    1. Li S, Yu F, Zhu H, Yang Y, Yang L, Lian J. The median effective concentration (EC50) of propofol with different doses of fentanyl during colonoscopy in elderly patients. BMC Anesthesiol. 2016;16(1):24.
    1. Saad Z, Hibar D, Fedgchin M, et al. Effects of Mu-Opiate Receptor Gene Polymorphism rs1799971 (A118G) on the Antidepressant and Dissociation Responses in Esketamine Nasal Spray Clinical Trials. Int J Neuropsychopharmacol. 2020;23(9):549-558.
    1. Jonkman K, van Rijnsoever E, Olofsen E, et al. Esketamine counters opioid-induced respiratory depression. Br J Anaesth. 2018;120(5):1117-1127.
    1. Eberl S, Koers L, van Hooft J, et al. The effectiveness of a low-dose esketamine versus an alfentanil adjunct to propofol sedation during endoscopic retrograde cholangiopancreatography: A randomised controlled multicentre trial. Eur J Anaesthesiol. 2020;37(5):394-401.
    1. Wang J, Huang J, Yang S, et al. Pharmacokinetics and Safety of Esketamine in Chinese Patients Undergoing Painless Gastroscopy in Comparison with Ketamine: A Randomized, Open-Label Clinical Study. Drug des Devel Ther. 2019;13:4135-4144.
    1. Absalom AR, Mani V, De Smet T, et al. Pharmacokinetic models for propofol--defining and illuminating the devil in the detail. Br J Anaesth. 2009 Jul;103(1):26-37.
    1. Hanley C, Zerbolio DJ. Developmental changes in five illusions measured by the up-and-down method. Child Dev. 1965;36(2):437-452.
    1. Manolaraki MM, Theodoropoulou A, Stroumpos C, et al. Remifentanil compared with midazolam and pethidine sedation during colonoscopy: a prospective, randomized study. Dig Dis Sci. 2008;53(1):34-34, 40.
    1. Pace NL, Stylianou MP. Advances in and limitations of up-and-down methodology: a précis of clinical use, study design, and dose estimation in anesthesia research. Anesthesiology. 2007;107(1):144-152.
    1. Fu F, Chen X, Feng Y, Shen Y, Feng Z, Bein B. Propofol EC50 for inducing loss of consciousness is lower in the luteal phase of the menstrual cycle. Br J Anaesth. 2014;112(3):506-513.
    1. Scheller MS, Saidman LJ, Partridge BL. MAC of sevoflurane in humans and the New Zealand white rabbit. Can J Anaesth. 1988;35(2):153-156.
    1. Rampil IJ, Lockhart SH, Zwass MS, et al. Clinical characteristics of desflurane in surgical patients: minimum alveolar concentration. Anesthesiology. 1991;74(3):429-433.
    1. Levitt C, Wei H. Supraglotic pulsatile jet oxygenation and ventilation during deep propofol sedation for upper gastrointestinal endoscopy in a morbidly obese patient. J Clin Anesth. 2014;26(2):157-159.
    1. Wehrmann T, Kokabpick S, Lembcke B, Caspary WF, Seifert H. Efficacy and safety of intravenous propofol sedation during routine ERCP: a prospective, controlled study. Gastrointest Endosc. 1999;49(6):677-683.
    1. Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy, Lichtenstein DR, Jagannath S, et al. Sedation and anesthesia in GI endoscopy. Gastrointest Endosc. 2008;68(5):815-826.
    1. Claeys MA, Gepts E, Camu F. Haemodynamic changes during anaesthesia induced and maintained with propofol. Br J Anaesth. 1988;60(1):3-9.
    1. Gragasin FS, Davidge ST. The effects of propofol on vascular function in mesenteric arteries of the aging rat. Am J Physiol Heart Circ Physiol. 2009;297(1):H466-H474.
    1. Memtsoudis SG, The AH, Heerdt PM. Autonomic mechanisms in the age-related hypotensive effect of propofol. Anesth Analg. 2005;100(1):111-115.
    1. John AD, Sieber FE. Age associated issues: geriatrics. Anesthesiol Clin North America. 2004;22(1):45-58.
    1. You AH, Kim JY, Kim DH, Suh J, Han DW. Effect of remifentanil and midazolam on ED95 of propofol for loss of consciousness in elderly patients: A randomized, clinical trial. Medicine (Baltimore). 2019;98(16):e15132.
    1. Dahaba AA, Zhong T, Lu HS, et al. Geographic differences in the target-controlled infusion estimated concentration of propofol: bispectral index response curves. Can J Anaesth. 2011;58(4):364-370.
    1. Irwin MG, Hui TW, Milne SE, et al. Propofol effective concentration 50 and its relationship to bispectral index. Anaesthesia. 2002;57(3):242-248.
    1. Mortero RF, Clark LD, Tolan MM, Metz RJ, Tsueda K, Sheppard RA. The effects of small-dose ketamine on propofol sedation: respiration, postoperative mood, perception, cognition, and pain. Anesth Analg. 2001;92(6):1465-1469.
    1. Vallejo MC, Romeo RC, Davis DJ, et al. Propofol-ketamine versus propofol-fentanyl for outpatient laparoscopy: comparison of postoperative nausea, emesis, analgesia, and recovery. J Clin Anesth. 2002;14(6):426-431.
    1. Eberl S, Koers L, van Hooft JE, et al. Sedation with propofol during ERCP: is the combination with esketamine more effective and safer than with alfentanil? Study protocol for a randomized controlled trial. Trials. 2017;18(1):472.
    1. Trapani G, Altomare C, Liso G, et al. Propofol in anesthesia. Mechanism of action, structure-activity relationships, and drug delivery. Curr Med Chem. 2000 Feb;7(2):249-271.
    1. Orser BA, Bertlik M, Wang LY, MacDonald JF. Inhibition by propofol (2,6 di-isopropylphenol) of the N-methyl-D-aspartate subtype of glutamate receptor in cultured hippocampal neurones. Br J Pharmacol. 1995 Sep;116(2):1761-1768.
    1. Doherty T, Wajs E, Melkote R, Miller J, Singh JB, Weber MA. Cardiac Safety of Esketamine Nasal Spray in Treatment-Resistant Depression: Results from the Clinical Development Program. CNS Drugs. 2020;34(3):299-310.
    1. Kamp J, van Velzen M, Aarts L, Niesters M, Dahan A, Olofsen E. Stereoselective ketamine effect on cardiac output: a population pharmacokinetic/pharmacodynamic modelling study in healthy volunteers. Br J Anaesth. 2021 Jul;127(1):23-31.
    1. Vaessen HHB, Knuttel FM, van Breugel JMM, et al. Moderate-to-deep sedation technique, using propofol and ketamine, allowing synchronised breathing for magnetic resonance high-intensity focused ultrasound (MR-HIFU) treatment for uterine fibroids: a pilot study. J Ther Ultrasound. 2017;5(1):8.

Source: PubMed

Подписаться