ANESTHESIOLOGY FAST REVIEW

ANESTHESIOLOGY_FAST_REVIEWKAPAK1-0-25

GENERAL ANESTHESIA MAIN PRINCIPLES

Berrak Sebil Aydın

Zonguldak Karadeniz Ereğli State Hospital, Department of Anesthesiology and Reanimation, Zonguldak, Türkiye

Aydın BS. General Anesthesia Main Principles. In: Kazancı D, editor. Anesthesiology Fast Review. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.187-198.

ABSTRACT

  • General anesthesia is a comprehensive term encompassing a range of behavioral endpoints, such as amnesia, immobility, and unconsciousness.
  • Consciousness is defined by both wakefulness and awareness; anesthetics can cause loss of awareness by disrupting the connections between cortical and thalamocortical networks.
  • General anesthetics have significant effects on various brain regions and receptor populations. However, a detailed understanding of the anesthetic mechanism of action of these drugs is still lacking.
  • In general, anesthetics produce widespread neurodepression in the central nervous system by enhancing inhibitory transmission and blocking excitatory transmission.
  • With the development of cellular electrophysiology and molecular biology techniques, tools for analyzing the components of the lipid membrane have led to greater acceptance of proteins, particularly receptors and ion channels, as potential targets of anesthetic effects in recent years.
  • The most well-known target of general anesthetics is the GABAA receptor. Particularly due to advancements in genetic engineering, the ways in which various behavioral response patterns are selectively related to GABAA receptor subunits in specific brain regions have been gradually revealed.
  • Considering the serious adverse effects that may arise during anesthesia, a deeper understanding of the mechanisms of action of general anesthetics will allow for the development of safer and more effective anesthesia alternatives.

Keywords: Anesthesia; Anesthetics; Molecular mechanisms of pharmacological action; Ion channels; Consciousness

Referanslar

  1. Kopp Lugli A, Yost CS, Kindler CH. Anaesthetic mechanisms: Update on the challenge of unravelling the mystery of anaesthesia. Eur J Anaesthesiol. 2009; 26: 807-20. [Crossref]  [PubMed]  [PMC]
  2. Diao S, Ni J, Shi X, Liu P, Xia W. Mechanisms of action of general anesthetics. Front Biosci. 2014; 19: 747-57. [Crossref]  [PubMed]
  3. Eger EI, Sonner JM. Anaesthesia defined (gentlemen, this is no humbug). Best Pract Res Clin Anaesthesiol. 2006; 20: 23-9. [Crossref]  [PubMed]
  4. Noreika V, Jylhankangas L, Moro L, Valli K, Kaskinoro K, Aantaa R, et al. Consciousness lost and found: subjective experiences in an unresponsive state. Brain and Cogn. 2011; 77: 327-34. [Crossref]  [PubMed]
  5. Koch C, Greenfield S. How does consciousness happen? Sci Am. 2007; 297: 76-83. [Crossref]  [PubMed]
  6. Klafta JM, Roizen MF, Michael F. Current understanding of patients' attitudes toward and preparation for anesthesia: a review. Anesth Analg. 1996; 83: 1314-21. [Crossref]  [PubMed]
  7. Nicolelis MA, Chapin JK. Spatiotemporal structure of somatosensory responses of many neuron ensembles in the rat ventral posterior medial nucleus of the thalamus. J Neurosci. 1994;14:3511-32. [Crossref]  [PubMed]  [PMC]
  8. Nicolelis MA, Ghazanfar AA, Stambough CR, Oliveira LM, Laubach M, Chapin JK, et al. Simultaneous encoding of tactile information by three primate cortical areas. Nat Neurosci. 1998;1:621-30. [Crossref]  [PubMed]
  9. Urban BW. Current assessment of targets and theories of anaesthesia. Br J Anaesth. 2002;89:167-83. [Crossref]  [PubMed]
  10. Mashour GA. Consciousness unbound: Toward a paradigm of general anesthesia. Anesthesiology. 2004;100:428-33. [Crossref]  [PubMed]
  11. Gugino LD, Chabot RJ, Prichep LS, John ER, Formanek V, Aglio LS. Quantitative EEG changes associated with loss and return of consciousness in healthy adult volunteers anaesthetized with propofol or sevoflurane. Br J Anaesth. 2001;87:421-8. [Crossref]  [PubMed]
  12. John ER. The neurophysics of consciousness. Brain Res Rev. 2002;39:1-28. [Crossref]  [PubMed]
  13. Fiset P, Paus T, Daloze T, Plourde G, Meuret P, Bonhomme V, et al. Brain mechanisms of propofol-induced loss of consciousness in humans: a positron emission tomographic study. J Neurosci. 1999;19:5506-13. [Crossref]  [PubMed]  [PMC]
  14. Katoh T, Suguro Y, Nakajima R, Kazama T, Ikeda K. Blood concentration of sevoflurane and isoflurane on recovery from anaesthesia. Br J Anaesth. 1992;69:259-62. [Crossref]  [PubMed]
  15. Alkire MT, Pomfrett CJD, Haier RJ, Gianzero MV, Chan CM, Jacobsen BP, et al. Functional brain imaging during anesthesia in humans: effects of halothane on global and regional cerebral glucose metabolism. Anesthesiology. 1999;90:701-9. [Crossref]  [PubMed]
  16. Hughes SW, Crunelli V. Thalamic mechanisms of EEG alpha rhythms and their pathological implications. Neuroscientist. 2005;11:357-72. [Crossref]  [PubMed]
  17. Alkire MT, Haier RJ, Fallon JH. Toward a unified theory of narcosis: brain imaging evidence for a thalamocortical switch as the neurophysiologic basis of anesthetic-induced unconsciousness. Conscious Cogn. 2000;9:370-86. [Crossref]  [PubMed]
  18. Vijayan S, Ching S, Purdon PL, Brown EN, Kopell NJ. Thalamocortical mechanisms for the anteriorization of alpha rhythms during propofol-induced unconsciousness. J Neurosci. 2013;33:11070-5. [Crossref]  [PubMed]  [PMC]
  19. Samra SK, Vanderzant CW, Domer PA, Sackellares JC. Differential effects of isoflurane on human median nerve somatosensory evoked potentials. Anesthesiology. 1987;66:29-35. [Crossref]  [PubMed]
  20. Kochs E, Stockmanns G, Thornton C, Nahm W, Kalkman CJ. Wavelet analysis of middle latency auditory evoked responses: calculation of an index for detection of awareness during propofol administration. Anesthesiology. 2001;95:1141-50. [Crossref]  [PubMed]
  21. Neumann MA, Eger E II, Weiskopf RB. Solubility of volatile anesthetics in bovine white matter, cortical gray matter, thalamus, hippocampus, and hypothalamic area. Anesth Analg. 2005;100:1003-6. [Crossref]  [PubMed]
  22. Brown EN, Lydic R, Schiff ND. General anesthesia, sleep, and coma. N Engl J Med. 2010;363:2638-50. [Crossref]  [PubMed]  [PMC]
  23. Ma J, Shen B, Stewart LS, Herrick IA, Leung LS. The septohippocampal system participates in general anesthesia. J Neurosci. 2002;22:1-6. [Crossref]  [PubMed]  [PMC]
  24. Simon W, Hapfelmeier G, Kochs E, Zieglgansberger W, Rammes G. Isoflurane blocks synaptic plasticity in the mouse hippocampus. Anesthesiology. 2001;94:1058-65. [Crossref]  [PubMed]
  25. Alkire MT, Gruver R, Miller J, McReynolds JR, Hahn EL, Cahill L. Neuroimaging analysis of an anesthetic gas that blocks human emotional memory. Proc Natl Acad Sci. 2008;105:1722-7. [Crossref]  [PubMed]  [PMC]
  26. Iselin-Chaves IA, Willems SJ, Jermann FC, Forster A, Adam SR, Van der Linden M. Investigation of implicit memory during isoflurane anesthesia for elective surgery using the process dissociation procedure. Anesthesiology. 2005;103:925-33. [Crossref]  [PubMed]
  27. Kungys G, Kim J, Jinks S, Atherley RJ, Antognini JF. Propofol produces immobility via action in the ventral horn of the spinal cord by a GABAergic mechanism. Anesth Analg. 2009;108:1531-7. [Crossref]  [PubMed]  [PMC]
  28. Desborough JP. The stress response to trauma and surgery. Br J Anaesth. 2000;85:109-17. [Crossref]  [PubMed]
  29. Bandeiras C, Serro AP, Luzyanin K, Fernandes A, Saramago B. Anesthetics interacting with lipid rafts. Eur J Pharm Sci. 2013;48:153-65. [Crossref]  [PubMed]
  30. Cheng G, Kendig JJ. Pre and postsynaptic volatile anaesthetic actions on glycinergic transmission to spinal cord motor neurons. Br J Pharmacol. 2002;136:673-84. [Crossref]  [PubMed]  [PMC]
  31. Franks NP. General anaesthesia: from molecular targets to neuronal pathways of sleep and arousal. Nat Rev Neurosci. 2008;9:370-86. [Crossref]  [PubMed]
  32. Zhou C, Liu J, Chen XD. General anesthesia mediated by effects on ion channels. World J Crit Care Med. 2012;1:80-93. [Crossref]  [PubMed]  [PMC]
  33. Farrant M, Nusser Z. Variations on an inhibitory theme: phasic and tonic activation of GABAA receptors. Nature Rev Neurosci. 2005;6:215-29. [Crossref]  [PubMed]
  34. McCartney MR, Deeb TZ, Henderson TN, Hales TG. Tonically active GABAA receptors in hippocampal pyramidal neurons exhibit constitutive GABA-independent gating. Mol Pharmacol. 2007;71:539-48. [Crossref]  [PubMed]
  35. Nishikawa K, Jenkins A, Paraskevakis I, Harrison NL. Volatile anesthetic actions on the GABAA receptors: contrasting effects of α1(S270) and β2(N265) point mutations. Neuropharmacology. 2002;42:337-45. [Crossref]  [PubMed]
  36. Krasowski MD, Harrison NL. The actions of ether, alcohol and alkane general anaesthetics on GABAA and glycine receptors and the effects of TM2 and TM3 mutations. Br. J. Pharmacol. 2000;129:731-43. [Crossref]  [PubMed]  [PMC]
  37. Collinson N, Kuenzi FM, Jarolimek W, Maubach KA, Cothliff R, Sur C, et al. Enhanced learning and memory and altered GABAergic synaptic transmission in mice lacking the alpha 5 subunit of the GABAA receptor. J Neurosci. 2002;22:5572-80. [Crossref]  [PubMed]  [PMC]
  38. Rudolph U, Möhler H. Analysis of GABAA receptor function and dissectıon of the pharmacology of benzodiazepines and general anesthetics through mouse genetics. Annu Rev Pharmacol Toxicol. 2004;44:475-98. [Crossref]  [PubMed]
  39. Sonner JM, Antognini JF, Dutton RC, Flood P, Gray AT, Harris RA, et al. Inhaled anesthetics and immobility: mechanisms, mysteries, and minimum alveolar anesthetic concentration. Anesth Analg. 2003;97:718-40. [Crossref]  [PubMed]
  40. Ishizawa Y. Mechanisms of anesthetic actions and the brain. J Anesth. 2007;21:187-99. [Crossref]  [PubMed]
  41. Li XT, Dyachenko V, Zuzarte M, Putzke C, Preisig-Muller R, Isenberg G, et al. The stretch-activated potassium channel TREK-1 in rat cardiac ventricular muscle. Cardiovasc Res. 2006;69:86-97. [Crossref]  [PubMed]
  42. Dickinson R, Peterson BK, Banks P, Simillis C, Martin JCS, Valenzuela CA, et al. Competitive inhibition at the glycine site of the N-methyl-D-aspartate receptor by the anesthetics xenon and isoflurane: evidence from molecular modelingand electrophysiology. Anesthesiology. 2007;107:756-67. [Crossref]  [PubMed]
  43. Flood P, Sonner JM, Gong D, Coates KM. Isoflurane hyperalgesia is modulated by nicotinic inhibition. Anesthesiology. 2002;97:192-8. [Crossref]  [PubMed]
  44. Minami K, Minami M, Harris RA. Inhibition of 5-hydroxytryptamine type 2A receptor-induced currents by n-alcohols and anesthetics. J Pharmacol Exp Ther. 1997;281:1136-43. [Crossref]  [PubMed]
  45. Dahmani S, Rouelle D, Gressens P, Mantz J. Effects of dexmedetomidine on hippocampal focal adhesion kinase tyrosine phosphorylation in physiologic and ischemic conditions. Anesthesiology. 2005;103:969-77. [Crossref]  [PubMed]
  46. Liu C, Cotten JF, Schuyler JA, Fahlman CS, Au JD, Bickler PE, et al. Protective effects of TASK-3 (KCNK9) and related 2P K channels during cellular stress. Brain Res. 2005;1031: 164-73. [Crossref]  [PubMed]
  47. Heurteaux C, Guy N, Laigle C, Blondeau N, Duprat F, Mazzuca M, et al. TREK-1, a K+ channel involved in neuroprotection and general anesthesia. EMBO J. 2004;23:2684-95. [Crossref]  [PubMed]  [PMC]
  48. Rasmussen LS, Johnson T, Kuipers HM, Kristensen D, Siersma VD, Villa P. Does anaesthesia cause postoperative cognitive dysfunction? A randomised study of regional versus general anaesthesia in 438 elderly patients. Acta Anaesthesiol Scand. 2003;47:260-6. [Crossref]  [PubMed]