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| OtherCodes =
| Specialty = [[Anesthesiology|Anaesthetics]]
| uses = Facilitating surgery, [[terminal sedation]]<ref name="Takla2021">{{cite journal |last1=Takla |first1=A |last2=Savulescu |first2=J |last3=Wilkinson |first3=DJC |last4=Pandit |first4=JJ |title=General anaesthesia in end-of-life care: extending the indications for anaesthesia beyond surgery. |journal=Anaesthesia |date=October 2021 |volume=76 |issue=10 |pages=
| complications = [[Anaesthesia awareness]],<ref name=Budworth2019/> overdose,<ref name=Hewer_1937/> death<ref name=Dewachter2009/>
| approach =
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'''Psychosocial Considerations and Anxiety Management in Surgery'''
Addressing psychosocial concerns and managing anxiety are integral components of perioperative care, particularly in patients facing challenges with stress tolerance or immobility. General anesthesia may be warranted for individuals with movement disorders, while elective use can alleviate anxiety in patients with learning disabilities or severe apprehension. Implementing a patient-centered approach, interdisciplinary collaboration, and comprehensive support are essential strategies for optimizing patient experience and surgical outcomes.<ref name=":12">{{Cite book |title=Miller's anesthesia |date=2020 |publisher=Elsevier |isbn=978-0-323-59604-6 |editor-last=Gropper |editor-first=Michael A. |edition=Ninth
'''<u><big>Indications for General Anesthesia</big></u>'''
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The [[biochemistry|biochemical]] [[Theories of general anaesthetic action|mechanism of action of general anaesthetics]] is still controversial.<ref>{{cite journal | vauthors = Jevtovic-Todorovic V | title = General Anesthetics and Neurotoxicity: How Much Do We Know? | journal = Anesthesiology Clinics | volume = 34 | issue = 3 | pages = 439–451 | date = September 2016 | pmid = 27521190 | pmc = 5477636 | doi = 10.1016/j.anclin.2016.04.001 }}</ref> Theories need to explain the function of anaesthesia in animals and plants.<ref>{{cite news| vauthors = Frazier J |title=Plants, Like People, Succumb to Anesthesia|url=https://blogs.scientificamerican.com/artful-amoeba/plants-like-people-succumb-to-anesthesia-video/|access-date=26 January 2018|work=[[Scientific American]]|date=26 January 2018}}</ref> To induce unconsciousness, anaesthetics have myriad sites of action and affect the [[central nervous system]] (CNS) at multiple levels. General anaesthesia commonly interrupts or changes the functions of CNS components including the [[cerebral cortex]], [[thalamus]], [[reticular activating system]], and [[spinal cord]]. Current theories on the anaesthetized state identify not only target sites in the CNS but also [[neural network]]s and arousal circuits linked with unconsciousness, and some anesthetics potentially able to activate specific sleep-active regions.<ref>{{Cite journal |last1=Moody |first1=Olivia A. |last2=Zhang |first2=Edlyn R. |last3=Vincent |first3=Kathleen F. |last4=Kato |first4=Risako |last5=Melonakos |first5=Eric D. |last6=Nehs |first6=Christa J. |last7=Solt |first7=Ken |date=2021-05-01 |title=The Neural Circuits Underlying General Anesthesia and Sleep |journal=Anesthesia and Analgesia |volume=132 |issue=5 |pages=1254–1264 |doi=10.1213/ANE.0000000000005361 |issn=1526-7598 |pmc=8054915 |pmid=33857967}}</ref>
Two non-exclusionary mechanisms include [[Membrane-mediated anesthesia|membrane-mediated]] and direct [[Theories_of_general_anaesthetic_action#Membrane protein hypothesis of general anaesthetic action|protein-mediated]] anesthesia. Potential protein-mediated molecular targets are [[gamma-Aminobutyric acid|GABA<sub>A</sub>]],and [[Glutamic acid|NMDA glutamate]] receptors. General anesthesia was hypothesized to either enhance the inhibitory transmission or reduce the excitatory transmission of neuro signaling.<ref>{{Cite journal |last=Lambert |first=David G. |date=2020-05-01 |title=Mechanisms of action of general anaesthetic drugs |url=https://www.anaesthesiajournal.co.uk/article/S1472-0299(20)30028-X/abstract |journal=Anaesthesia & Intensive Care Medicine |language=English |volume=21 |issue=5 |pages=235–237 |doi=10.1016/j.mpaic.2020.02.006 |issn=1472-0299}}</ref> Most volatile anesthetics have been found to be a GABA<sub>A</sub> [[agonist]], although the site of action on the receptor remains unknown.<ref>{{Cite journal |last1=Woll |first1=Kellie A. |last2=Zhou |first2=Xiaojuan |last3=Bhanu |first3=Natarajan V. |last4=Garcia |first4=Benjamin A. |last5=Covarrubias |first5=Manuel |last6=Miller |first6=Keith W. |last7=Eckenhoff |first7=Roderic G. |date=August 2018 |title=Identification of binding sites contributing to volatile anesthetic effects on GABA type A receptors |journal=The FASEB Journal |volume=32 |issue=8 |pages=4172–4189 |doi=10.1096/fj.201701347R |doi-access=free |issn=0892-6638 |pmc=6044061 |pmid=29505303}}</ref> [[Ketamine]] is a non-competitive [[NMDA receptor antagonist]].<ref>{{Cite journal |last1=Zhang |first1=Youyi |last2=Ye |first2=Fei |last3=Zhang |first3=Tongtong |last4=Lv |first4=Shiyun |last5=Zhou |first5=Liping |last6=Du |first6=Daohai |last7=Lin |first7=He |last8=Guo |first8=Fei |last9=Luo |first9=Cheng |last10=Zhu |first10=Shujia |date=August 2021 |title=Structural basis of ketamine action on human NMDA receptors |url=https://pubmed.ncbi.nlm.nih.gov/34321660 |journal=Nature |volume=596 |issue=7871 |pages=301–305 |doi=10.1038/s41586-021-03769-9 |issn=1476-4687 |pmid=34321660|bibcode=2021Natur.596..301Z |s2cid=236496390 }}</ref>
The chemical structure and properties of anesthetics, as first noted by [[Theories_of_general_anaesthetic_action#Lipid solubility-anaesthetic potency correlation (the Meyer-Overton correlation)|Meyer and Overton]], suggest they could target the plasma membrane. A [[Membrane-mediated anesthesia|membrane-mediated]] mechanism that could account for the activation of an ion channel remained elusive until recently. A study from 2020 demonstrated that inhaled anesthetics ([[chloroform]] and isoflurane) could displace [[Phospholipase D|phospholipase D2]] from ordered lipid domains in the plasma membrane, which led to the production of the signaling molecule [[phosphatidic acid]] (PA). The signaling molecule activated TWIK-related K+ channels (TREK-1), a channel involved in anesthesia. PLD<sup>null</sup> fruit flies were shown to resist anesthesia, the results established a membrane mediated target for inhaled anesthetics.<ref>{{cite journal | vauthors = Pavel MA, Petersen EN, Wang H, Lerner RA, Hansen SB | title = Studies on the mechanism of general anesthesia | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 117 | issue = 24 | pages = 13757–13766 | date = June 2020 | pmid = 32467161 | pmc = 7306821 | doi = 10.1073/pnas.2004259117 | bibcode = 2020PNAS..11713757P | doi-access = free }}</ref>
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Prior to administration of a general anaesthetic, the anaesthetist may administer one or more drugs that complement or improve the quality or safety of the anaesthetic or simply provide anxiolysis. Premedication also often has mild sedative effects and may reduce the amount of anaesthetic agent required during the case.<ref name=":11" />
One commonly used premedication is [[clonidine]], an [[Alpha-adrenergic agonist#α2 agonists|alpha-2 adrenergic agonist]].<ref>{{cite journal | vauthors = Bergendahl H, Lönnqvist PA, Eksborg S | title = Clonidine in paediatric anaesthesia: review of the literature and comparison with benzodiazepines for premedication | journal = Acta Anaesthesiologica Scandinavica | volume = 50 | issue = 2 | pages = 135–143 | date = February 2006 | pmid = 16430532 | doi = 10.1111/j.1399-6576.2006.00940.x
Benzodiazepines are the most commonly used class of drugs for premedication. The most commonly utilized benzodiazepine is [[Midazolam]], which is characterized by a rapid onset and short duration. Midazolam is effective in reducing [[Preoperational anxiety|preoperative anxiety]], including [[Separation anxiety disorder|separation anxiety]] in children.<ref>{{Cite journal |last=El Batawi |first=Hisham Yehia |date=2015 |title=Effect of preoperative oral midazolam sedation on separation anxiety and emergence delirium among children undergoing dental treatment under general anesthesia |journal=Journal of International Society of Preventive & Community Dentistry |volume=5 |issue=2 |pages=88–94 |doi=10.4103/2231-0762.155728 |issn=2231-0762 |pmc=4415335 |pmid=25992332 |doi-access=free }}</ref> It also provides mild sedation, sympathicolysis, and anterograde amnesia.<ref name=":11" />
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{{anchor|tci}}
In the 1990s, a novel method of maintaining anaesthesia was developed in [[Glasgow]], Scotland. Called [[target controlled infusion]] (TCI), it involves using a computer-controlled syringe driver (pump) to infuse propofol throughout the duration of surgery, removing the need for a volatile anaesthetic and allowing pharmacologic principles to more precisely guide the amount of the drug used by setting the desired drug concentration. Advantages include faster recovery from anaesthesia, reduced incidence of postoperative nausea and vomiting, and absence of a trigger for [[malignant hyperthermia]]. At present, TCI is not permitted in the United States, but a syringe pump delivering a specific rate of medication is commonly used instead.<ref>{{Cite journal |last1=Absalom |first1=Anthony R. |last2=Glen |first2=John Iain B. |last3=Zwart |first3=Gerrit J. C. |last4=Schnider |first4=Thomas W. |last5=Struys |first5=Michel M. R. F. |date=January 2016 |title=Target-Controlled Infusion: A Mature Technology
Other medications are occasionally used to treat side effects or prevent complications. They include [[antihypertensives]] to treat high blood pressure; [[ephedrine]] or [[phenylephrine]] to treat low blood pressure; [[salbutamol]] to treat [[asthma]], [[laryngospasm]], or [[bronchospasm]]; and [[epinephrine]] or [[diphenhydramine]] to treat allergic reactions. [[Glucocorticoids]] or [[antibiotics]] are sometimes given to prevent inflammation and infection, respectively.<ref name=":11" />
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