Abstract
Aging is a physiological condition involving progressive degenerative modifications and loss of functionality in all organ systems. In general, aged patients are frail and sensitive to anesthesia and surgery. Clinical practice indicates that being more sensitive to anesthetic drugs and more susceptible to the side effects, elderly requires usually lower doses to reach the clinical anesthesia. This is mainly associated with the significant changes in pharmacokinetics (and pharmacodynamics) occurring with advancing age. However, how the dose–response relationship is affected by age should be better defined. This chapter focuses on the main changes that physiologically occur with age, how these changes affect organs and systems, and their impact on anesthetic care. The agents used in general anesthesia are discussed in detail with particular emphasis on aspects concerning the dose, safety, and efficacy of their use in the elderly. Moreover, we highlight some recent preclinical evidence on the use of general anesthetics in aged animals.
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References
Nigam Y, Knight J, Bhattacharya S, Bayer A (2012) Physiological changes associated with aging and immobility. J Aging Res 2012:468469. https://doi.org/10.1155/2012/468469
Zaugg M, Lucchinetti E (2000) Respiratory function in the elderly. Anaesthesiol Clin North Am 18:47–58
Tajiri K, Shimizu Y (2013) Liver physiology and liver diseases in the elderly. World J Gastroenterol 19(46):8459–8467
Le Couteur DG, McLean AJ (1998) The aging liver: drug clearance and an oxygen diffusion barrier hypothesis. Clin Pharmacokinet 34:359–373
Magnusson KR (1998) The aging of the NMDA receptor complex. Front Biosci 3:e70–e80
Magnusson KR, Nelson SE, Young AB (2002) Age-related changes in the protein expression of subunits of the NMDA receptor. Brain Res Mol Brain Res 99(1):40–45
Reidenberg MM, Levy M, Warner H et al (1978) Relationship between diazepam dose, plasma level, age, and central nervous system depression. Clin Pharmacol Ther 23:371–374
Swift CG, Ewen JM, Clarke P, Stevenson IH (1985) Responsiveness to oral diazepam in the elderly: relationship to total and free plasma concentrations. Br J Clin Pharmacol 20:111–118
Castleden CM, George CF, Marcer D, Hallett C (1977) Increased sensitivity to nitrazepam in old age. Br Med J 1:10–12
Cascella M, Bimonte S (2017) The role of general anesthetics and the mechanisms of hippocampal and extra-hippocampal dysfunctions in the genesis of postoperative cognitive dysfunction. Neural Regen Res 12(11):1780–1785
Cascella M (2015) Anesthesia awareness. Can midazolam attenuate or prevent memory consolidation on intraoperative awakening during general anesthesia without increasing the risk of postoperative delirium? Korean J Anesthesiol 68(2):200–202
Cascella M, Schiavone V, Muzio MR, Cuomo A (2016) Consciousness fluctuation during general anesthesia: a theoretical approach to anesthesia awareness and memory modulation. Curr Med Res Opin 32(8):1351–1359
Fredman B, Lahav M, Zohar E, Golod M, Paruta I, Jedeikin R (1999) The effect of midazolam premedication on mental and psychomotor recovery in geriatric patients undergoing brief surgical procedures. Anesth Analg 89:1161–1166
Kruijt Spanjer M, Bakker NA, Absalom AR (2011) Pharmacology in the elderly and newer anaesthesia drugs. Best Pract Res Clin Anaesthesiol 25:355–365
Kirmeier E, Eriksson LI, Lewald H, et al; POPULAR Contributors (2019) Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study. Lancet Respir Med 7(2):129–140
Scott JC, Stanski DR (1987) Decreased fentanyl and alfentanil dose requirements with age: a simultaneous pharmacokinetic and pharmacodynamic evaluation. J Pharmacol Exp Ther 240:159–166
Sakai EM, Connolly LA, Klauck JA, Parker CJ, Hunter JM, Snowdon SL (1992) Effect of age, sex and anaesthetic technique on the pharmacokinetics of atracurium. Br J Anaesth 69:439–434
Heavner JE, Kaye AD, Lin BK et al (2003) Recovery of elderly patients from two or more hours of desflurane or sevoflurane anaesthesia. Br J Anaesth 91(4):502–506
Claeys MA, Gepts E, Camu F (1988) Haemodynamic changes during anaesthesia induced and maintained with propofol. Br J Anaesth 60:3–9
Phillips AT, Deiner S, Mo Lin H et al (2015) Propofol use in the elderly population: prevalence of overdose and association with 30-day mortality. Clin Ther 37(12):2676–2685
Reich DL, Hossain S, Krol M (2005) Predictors of hypotension after induction of general anesthesia. Anesth Analg 101(3):622–628
Avidan MS, Searleman AC, Storandt M, Barnett K, Vannucci A, Saager L et al (2009) Long-term cognitive decline in older subjects was not attributable to noncardiac surgery or major illness. Anesthesiology 111:964–970
Ehlenbach WJ, Hough CL, Crane PK, Haneuse SJ, Carson SS, Curtis JR, Larson EB (2010) Association between acute care and critical illness hospitalization and cognitive function in older adults. JAMA 303:763–770
Cascella M, Muzio MR, Bimonte S, Cuomo A, Jakobsson JG (2018) Postoperative delirium and postoperative cognitive dysfunction: updates in pathophysiology, potential translational approaches to clinical practice and further research perspectives. Minerva Anestesiol 84(2):246–260
Erden IA, Altinel S, Saricaoglu F et al (2012) Effect of intra-articular injection of levobupivacaine on articular cartilage and synovium in rats. Anaesthesist 61:420–423
Maione S, Palazzo E, Guida F et al (2013) New insights on neuropathic pain mechanisms as a source for novel therapeutical strategies. In: Souayah N (ed) Peripheral neuropathy – a new insight into the mechanism, evaluation and management of a complex disorder. IntechOpen. https://doi.org/10.5772/55276
Chemonges S, Shekar K, Tung KP et al (2014) Optimal management of the critically ill: Anaesthesia, monitoring, data capture, and point-of-care technological practices in ovine models of critical care. Biomed Res Int 2014:468309. https://doi.org/10.1155/2014/468309
D’Aniello A, Luongo L, Romano R et al (2017) D-aspartic acid ameliorates painful and neuropsychiatric changes and reduces β-amyloid Aβ1-42peptide in a long lasting model of neuropathic pain. Neurosci Lett 651:151–158
Boccella S, Guida F, Palazzo E et al (2018) Spared nerve injury as a long-lasting model of neuropathic pain. Methods Mol Biol 1727:373–378
Paddleford R (2000) Small animals anesthesia. Masson, Milano-Cremona
Kushi A, Sasai H, Koizumi H, Takeda N, Yokoyama M, Nakamura M (1998) Obesity and mild hyper-insulinemia found in neuropeptide Y-Y1 receptor-deficient mice. Proc Natl Acad Sci U S A 26:15659–15664
Naveilhan P, Canals JM, Arenas E, Ernfors P (2001) Distinct roles of the Y1 and Y2 receptors on neuropeptide Y-induced sensitization to sedation. J Neurochem 78(6):1201–1207
Flecknell PA (1989) Laboratory animal anaesthesia. Academic Press, San Diego
Zeller W, Meier G, Bürki K, Panoussis B (1998) Adverse effects of tribromoethanol as used in the production of transgenic mice. Lab Anim 32(4):407–413
Weinberger J, Nicklas WJ, Berl S (1976) Mechanism of action of anticonvulsants. Role of the differential effects on the active uptake of putative neurotransmitters. Neurology 26(2):162–166
Bennett B (2000) Congenic strain developed for alcohol- and drug-related phenotypes. Pharmacol Biochem Behav 67:671–681
Christensen SC, Johnson TE, Markel PD et al (1996) Quantitative trait locus analyses of sleep-times induced by sedative-hypnotics in LSXSS recombinant inbred strains of mice. Alcohol Clin Exp Res 20:543–550
Burianova J, Ouda L, Profant O, Syka J (2009) Age-related changes in GAD levels in the central auditory system of the rat. Exp Gerontol 44(3):161–169
de Villers-Sidani E, Alzghoul L, Zhou X, Simpson KL, Lin RC, Merzenich MM (2010) Recovery of functional and structural age-related changes in the rat primary auditory cortex with operant training. Proc Natl Acad Sci U S A 107(31):13900–13905
Ling LL, Hughes LF, Caspary DM (2005) Age-related loss of the GABA synthetic enzyme glutamic acid decarboxylase in rat primary auditory cortex. Neuroscience 132(4):1103–1113
Magnusson KR et al (2002) Age-related changes in the protein expression of subunits of the NMDA receptor. Brain Res Mol Brain Res 99(1):40–45
Alves HN, da Silva AL, Olsson IA, Orden JM, Antunes LM (2010) Anesthesia with intraperitoneal propofol, medetomidine, and fentanyl in rats. J Am Assoc Lab Anim Sci 49(4):454–459
Kiliç N, Henke J (2004) Comparative studies on the effects of S(+)-ketamine-medetomidine and racemic ketamine-medetomidine in mice. YYÜ Vet Fak Derg 15:15–17
Xie Z, Culley DJ, Dong Y, Zhang G, Zhang B, Moir RD, Frosch MP, Crosby G, Tanzi RE (2008) The common inhalation anesthetic isoflurane induces caspase activation and increases amyloid beta-protein level in vivo. Ann Neurol 64(6):618–627
Bianchi SL, Tran T, Liu C, Lin S, Li Y, Keller JM et al (2008) Brain and behavior changes in 12-month-old Tg2576 and nontransgenic mice exposed to anesthetics. Neurobiol Aging 29:1002–1010
Eckenhoff RG, Johansson JS, Wei H et al (2004) Inhaled anesthetic enhancement of amyloid-beta oligomerization and cytotoxicity. Anesthesiology 110(2):427–430
Chen G, Chen KS, Knox J, Inglis J, Bernard A, Martin SJ et al (2000) A learning deficit related to age and betaamyloid plaques in a mouse model of Alzheimer’s disease. Nature 408:975–979
Rosenholm M, Paro E, Antila H, Võikar V (2017) Repeated brief isoflurane anesthesia during early postnatal development produces negligible changes on adult behavior in male mice. PLoS One 12(4):e0175258. https://doi.org/10.1371/journal.pone.0175258
de Klaver MJ, Manning L, Palmer LA, Rich GF (2002) Isoflurane pretreatment inhibits cytokine-induced cell death in cultured rat smooth muscle cells and human endothelial cells. Anesthesiology 97:24–32
Gray JJ, Bickler PE, Fahlman CS, Zhan X, Schuyler JA (2005) Isoflurane neuroprotection in hypoxic hippocampal slice cultures involves increases in intracellular Ca2+ and mitogen-activated protein kinases. Anesthesiology 102(3):606–615
Xie Z, Xu Z (2013) General anesthetics and β-amyloid protein. Prog Neuropsychopharmacol Biol Psychiatry 47:140–146
Loop T, Dovi-Akue D, Frick M et al (2005) Volatile anesthetics induce caspase-dependent, mitochondria-mediated apoptosis in human T lymphocytes in vitro. Anesthesiology 102:1147–1157
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Guida, F. et al. (2020). Pharmacological Considerations for the Use of General Anesthetics in the Elderly. In: Cascella, M. (eds) General Anesthesia Research. Neuromethods, vol 150. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9891-3_8
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DOI: https://doi.org/10.1007/978-1-4939-9891-3_8
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