General anaesthesia: Difference between revisions

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| Name = General anaesthesia
| Image = Ana arbeitsplatz.JPG
| Caption = Equipment used for anaesthesia in the operating theatreroom
| ICD10 =
| ICD9 =
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| OPS301 =
| 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=1308–1315 |doi=10.1111/anae.15459 |pmid=33878803|doi-access=free |pmc=8581983 }}</ref>
| complications = [[Anaesthesia awareness]],<ref name=Budworth2019/> overdose,<ref name=Hewer_1937/> death<ref name=Dewachter2009/>
| approach =
| types =
| recovery time =
| other options =
| outcomes =
| frequency =
}}
'''General anaesthesia''' (UK) or '''general anesthesia''' (US) is a method of medically inducing loss of [[consciousness]] that renders a patient unarousable even with painful stimuli.<ref name=":10">{{cite web | work = American Society of Anesthesiologists. | title = Position on Monitored Anesthesia Care | quote = Approved by the House of Delegates on October 25, 2005, and last amended on October 17, 2018 | url = http://www.asahq.org/~/media/Sites/ASAHQ/Files/Public/Resources/standards-guidelines/position-on-monitored-anesthesia-care.pdf | access-date = 6 November 2022 | archive-url = https://web.archive.org/web/20221111160055/https://www.asahq.org/~/media/sites/asahq/files/public/resources/standards-guidelines/position-on-monitored-anesthesia-care.pdf | archive-date= 2022-11-11 | url-status=dead }}</ref> This effect is achieved by administering either intravenous or inhalational general anaesthetic medications, which often act in combination with an [[analgesic]] and [[neuromuscular blocking agent]]. Spontaneous ventilation is often inadequate during the procedure and intervention is often necessary to protect the airway.<ref name=":10" /> General anaesthesia is generally performed in an [[operating theater]] to allow surgical procedures that would otherwise be intolerably painful for a patient, or in an [[intensive care unit]] or [[emergency department]] to facilitate [[endotracheal intubation]] and mechanical ventilation in critically ill patients. Depending on the procedure, general anaesthesia may be optional or required. Regardless of whether a patient may prefer to be unconscious or not, certain [[pain stimulus|pain stimuli]] could result in involuntary responses from the patient (such as movement or muscle contractions) that may make an operation extremely difficult. Thus, for many procedures, general anaesthesia is required from a practical perspective.
 
A variety of [[General anesthetic|drugs]] may be administered, with the overall goal of achieving [[unconsciousness]], [[amnesia]], [[analgesia]], loss of reflexes of the [[autonomic nervous system]], and in some cases [[paralysis]] of [[skeletal muscle]]s. The optimal combination of anesthetics for any given patient and procedure is typically selected by an [[anesthesiologist|anaesthetist]], or another provider such as a [[nurse anesthetist|nurse anaesthetist]] (depending on local practice and law), in consultation with the patient and the [[surgeon]], dentist, or other practitioner performing the operative procedure.<ref name=":11" />
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In the 20th century, the safety and efficacy of general anaesthesia was improved by the routine use of [[tracheal intubation]] and other advanced [[airway management]] techniques. Significant advances in [[Medical monitor|monitoring]] and new [[anesthetic|anaesthetic agents]] with improved [[Pharmacokinetics|pharmacokinetic]] and [[Pharmacodynamics|pharmacodynamic]] characteristics also contributed to this trend. Finally, standardized training programs for anaesthesiologists and [[nurse anesthetist|nurse anaesthetist]]s emerged during this period.
 
== Purpose and indications ==
'''<big><u>Purpose of general anesthesia</u></big>'''
General anaesthesia has many purposes and routinely used in almost all surgical procedures. An appropriate surgical anesthesia should include the following goals:
 
# Hypnosis/Unconsciousness (loss of awareness)
General anesthesia serves as a critical tool in surgical practice, facilitating procedures by inducing a state of reversible unconsciousness in patients. Its primary objectives encompass ensuring patient safety, comfort, and pain relief throughout the surgical process.
# Analgesia (loss of response to pain)
 
# Amnesia (loss of memory)
'''Induction of unconsciousness'''
# Immobility (loss of motor reflexes)
 
# Paralysis (skeletal muscle relaxation and normal muscle relaxation)<ref name="Hewer_1937">{{cite journal | vauthors = Hewer CL | title = The Stages and Signs of General Anaesthesia | journal = British Medical Journal | volume = 2 | issue = 3996 | pages = 274–276 | date = August 1937 | pmid = 20780832 | doi = 10.1136/bmj.2.3996.274 | pmc = 2087073 }}</ref>
An essential aspect of general anesthesia is the induction of complete unconsciousness, rendering patients oblivious to sensory stimuli and surgical events. This profound state of unawareness is achieved through the administration of pharmacological agents targeting the central nervous system, effectively suppressing consciousness and perception.
 
'''Analgesia and pain control'''
 
In addition to inducing unconsciousness, general anesthesia provides effective analgesia to eliminate intraoperative pain. By interrupting the transmission of nociceptive signals within the nervous system, specialized medications mitigate surgical discomfort, enhancing patient comfort and expediting postoperative recovery.
 
'''Muscle relaxation and facilitation of surgical procedures'''
 
General anesthesia induces muscle relaxation and abolishes reflex responses, optimizing surgical conditions for precise intervention. This relaxation of skeletal muscles assists surgeons in executing procedures with meticulous precision, ensuring optimal outcomes and minimizing the risk of intraoperative complications.
 
'''Overall management of physiological responses'''
 
General anesthesia plays a pivotal role in maintaining physiological stability during surgery, attenuating stress responses and preserving hemodynamic equilibrium. Anesthesiologists vigilantly monitor patients' vital signs and administer medications as necessary to mitigate adverse physiological reactions, promoting procedural safety and minimizing perioperative risks.
 
'''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 |location=Philadelphia, PA}}</ref><ref name=":13">{{Cite book |title=Stoelting's anesthesia and co-existing disease |date=2018 |publisher=Elsevier |isbn=978-0-323-40137-1 |editor-last=Hines |editor-first=Roberta L. |edition=Seventh |location=Philadelphia, PA |editor-last2=Marschall |editor-first2=Katherine E.}}</ref><ref name=":14">{{Cite book |title=Clinical anesthesia |date=2017 |publisher=Wolters Kluwer |isbn=978-1-4963-3700-9 |editor-last=Barash |editor-first=Paul G. |edition=Eighth |location=Philadelphia Baltimore New York London Buenos Aires |editor-last2=Cullen |editor-first2=Bruce F. |editor-last3=Stoelting |editor-first3=Robert K. |editor-last4=Cahalan |editor-first4=Michael K. |editor-last5=Stock |editor-first5=M. Christine |editor-last6=Ortega |editor-first6=Rafael |editor-last7=Sharar |editor-first7=Sam R. |editor-last8=Holt |editor-first8=Natalie F.}}</ref>
 
'''<u><big>Indications for general anesthesia</big></u>'''
 
General anesthesia is employed in a variety of medical situations to ensure patient comfort, safety, and successful procedural outcomes. Understanding the indications for general anesthesia is essential for healthcare providers to make informed decisions and optimize patient care.
 
'''Surgical procedures''': One of the most common indications for general anesthesia is surgical intervention. General anesthesia is utilized across a wide range of surgical specialties, from, on occasion, minor procedures such as dental extractions to major surgeries like cardiac bypass surgery. It allows surgeons to operate on patients without them feeling pain or discomfort, ensuring a smooth and successful procedure.
 
'''Complex non-surgical medical procedures''': Certain medical procedures, such as endoscopies, colonoscopies, and imaging studies, may occasionally require general anesthesia to ensure patient cooperation and comfort. General anesthesia is particularly beneficial in cases where patients need to remain still for an extended period or if the procedure is invasive and potentially uncomfortable.
 
'''Emergency situations''': In emergencies, where immediate intervention is necessary, general anesthesia may be indicated to facilitate life-saving procedures. This could include surgeries to treat traumatic injuries, control bleeding, or relieve acute medical conditions. General anesthesia helps ensure patient stability and safety during critical interventions.
 
'''Pediatric care''': Children often require general anesthesia for various medical procedures, ranging from surgeries to diagnostic tests. Due to their unique physiological and psychological needs, general anesthesia is often preferred to ensure that pediatric patients remain still, pain-free, and cooperative during procedures.
 
'''Obstetric care''': While regional anesthesia techniques like epidurals are more common in obstetrics, there are situations where general anesthesia may be indicated, such as emergency cesarean sections or certain fetal interventions. General anesthesia ensures that the mother remains unconscious and pain-free during these procedures, prioritizing both maternal and fetal well-being.
 
'''Special populations''': Certain patient populations, such as those with intellectual disabilities, severe anxiety, or medical conditions that preclude other anesthesia options, may benefit from general anesthesia. Tailoring anesthesia management to the individual needs of these patients ensures optimal safety, comfort, and procedural success.<ref name=":12" /><ref name=":13" /><ref name=":14" />
 
 
 
 
== Biochemical mechanism of action ==
The [[biochemistry|biochemical]] [[Theories of general anaesthetic action|mechanism of action of general anaesthetics]] is not wellstill understoodcontroversial.<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> Potential

Two molecularnon-exclusionary pharmacologicmechanisms targetsinclude [[Membrane-mediated anesthesia|membrane-mediated]] and direct [[Theories_of_general_anaesthetic_action#Membrane protein hypothesis of general anaestheticsanaesthetic 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> The mostMost volatile anestheticanesthetics hashave 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,. yetA the[[Membrane-mediated exactanesthesia|membrane-mediated]] mechanism remainedthat acould mysteryaccount for overthe activation of an ion channel remained elusive 100until yearsrecently. A study from 2020 demonstrated that inhaled anesthetics ([[chloroform]] and isoflurane) could disruptdisplace [[Phospholipase D|phospholipase D2]] localizationfrom toordered lipid domains in the lipidplasma raftsmembrane, andwhich led to the production of the signaling molecule [[phosphatidic acid]] (PA). SignalingThe moleculessignaling leadmolecule to a cascade of events and eventually activationactivated 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>
 
== Preoperative evaluation ==
Prior to a planned procedure, the anesthesiologist reviews medical records, interviews the patient, and conducts a physical examination to obtain information regarding their medical history and current physical state, and to determine an appropriate anesthetic plan, including what combination of drugs and dosages will likely be needed for the patient's comfort and safety during the procedure. A variety of non-invasive and invasive monitoring devices may be necessary to ensure a safe and effective procedure. Key factors in this evaluation are the patient's age, gender, [[body mass index]], medical and surgical history, current medications, exercise capacity, and fasting time.<ref>{{cite journal | vauthors = Lederman D, Easwar J, Feldman J, Shapiro V | title = Anesthetic considerations for lung resection: preoperative assessment, intraoperative challenges and postoperative analgesia | journal = Annals of Translational Medicine | volume = 7 | issue = 15 | pages = 356 | date = August 2019 | pmid = 31516902 | pmc = 6712248 | doi = 10.21037/atm.2019.03.67 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Izumo W, Higuchi R, Yazawa T, Uemura S, Shiihara M, Yamamoto M | title = Evaluation of preoperative risk factors for postpancreatectomy hemorrhage | journal = Langenbeck's Archives of Surgery | volume = 404 | issue = 8 | pages = 967–974 | date = December 2019 | pmid = 31650216 | pmc = 6935390 | doi = 10.1007/s00423-019-01830-w | doi-access = free }}</ref> Thorough and accurate preoperative evaluation is crucial for the effective safety of the anesthetic plan. For example, a patient who consumes significant quantities of [[Alcoholic beverage|alcohol]] or [[Recreational drug use|illicit drugs]] could be undermedicated during the procedure if they fail to disclose this fact, and this could lead to [[anesthesia awareness|anaesthesia awareness]] or intraoperative [[hypertension]].<ref name=Budworth2019>{{cite journal | vauthors = Budworth L, Prestwich A, Lawton R, Kotzé A, Kellar I | title = Preoperative Interventions for Alcohol and Other Recreational Substance Use: A Systematic Review and Meta-Analysis | journal = Frontiers in Psychology | volume = 10 | pages = 34 | date = 2019-02-04 | pmid = 30778307 | pmc = 6369879 | doi = 10.3389/fpsyg.2019.00034 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Siriphuwanun V, Punjasawadwong Y, Saengyo S, Rerkasem K | title = Incidences and factors associated with perioperative cardiac arrest in trauma patients receiving anesthesia | journal = Risk Management and Healthcare Policy | volume = 11 | pages = 177–187 | date = 2018-10-18 | pmid = 30425598 | pmc = 6201994 | doi = 10.2147/rmhp.s178950 | doi-access = free }}</ref> Commonly used medications can also interact with anaesthetics, and failure to disclose such usage can increase the risk during the operation. Inaccurate timing of last meal can also increase the risk for aspiration of food, and lead to serious complications.<ref name=":11">{{Cite book |title=Miller's anesthesia |date=2020 |publisher=Elsevier |editor=Michael A. Gropper |isbn=978-0-323-61264-7 |edition=Ninth |location=Philadelphia, PA |oclc=1124935549}}</ref>
 
An important aspect of pre-anaesthetic evaluation is an assessment of the patient's [[Respiratory tract|airway]], involving inspection of the mouth opening and visualisation of the soft tissues of the [[Human pharynx|pharynx]].<ref>{{cite journal | vauthors = Mushambi MC, Jaladi S | title = Airway management and training in obstetric anaesthesia | journal = Current Opinion in Anesthesiology | volume = 29 | issue = 3 | pages = 261–267 | date = June 2016 | pmid = 26844863 | doi = 10.1097/ACO.0000000000000309 | s2cid = 27527932 }}</ref> The condition of teeth and location of [[Crown (dentistry)|dental crowns]] are checked, and neck flexibility and head extension are observed.<ref>{{cite journal | vauthors = Rehak A, Watterson LM | title = Institutional preparedness to prevent and manage anaesthesia-related 'can't intubate, can't oxygenate' events in Australian and New Zealand teaching hospitals | journal = Anaesthesia | volume = 75 | issue = 6 | pages = 767–774 | date = June 2020 | pmid = 31709522 | doi = 10.1111/anae.14909 | s2cid = 207944753 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Schieren M, Kleinschmidt J, Schmutz A, Loop T, Staat M, Gatzweiler KH, Wappler F, Defosse J | display-authors = 6 | title = Comparison of forces acting on maxillary incisors during tracheal intubation with different laryngoscopy techniques: a blinded manikin study | journal = Anaesthesia | volume = 74 | issue = 12 | pages = 1563–1571 | date = December 2019 | pmid = 31448404 | doi = 10.1111/anae.14815 | doi-access = free }}</ref> The most commonly performed airway assessment is the Mallampati classification, which evaluates the airway base on the ability to view airway structures with the mouth open and the tongue protruding. Mallampati tests alone have limited accuracy, and other evaluations are routinely performed addition to the Mallampati test including mouth opening, thyromental distance, neck range of motion, and mandibular protrusion. In a patient with suspected distorted airway anatomy, endoscopy or ultrasound is sometimes used to evaluate the airway before planning for the airway management.<ref>{{Cite journal |last1=Roth |first1=Dominik |last2=Pace |first2=Nathan L. |last3=Lee |first3=Anna |last4=Hovhannisyan |first4=Karen |last5=Warenits |first5=Alexandra-Maria |last6=Arrich |first6=Jasmin |last7=Herkner |first7=Harald |date=2018-05-15 |title=Airway physical examination tests for detection of difficult airway management in apparently normal adult patients |journal=The Cochrane Database of Systematic Reviews |volume=5 |issue=5 |pages=CD008874 |doi=10.1002/14651858.CD008874.pub2 |issn=1469-493X |pmc=6404686 |pmid=29761867}}</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 | url = http://www3.interscience.wiley.com/cgi-bin/fulltext/118557949/HTMLSTART | s2cid = 25797363 | archive-url = https://archive.today/20121216135407/http://www3.interscience.wiley.com/cgi-bin/fulltext/118557949/HTMLSTART | archive-date = 2012-12-16 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Dahmani S, Brasher C, Stany I, Golmard J, Skhiri A, Bruneau B, Nivoche Y, Constant I, Murat I | display-authors = 6 | title = Premedication with clonidine is superior to benzodiazepines. A meta analysis of published studies | journal = Acta Anaesthesiologica Scandinavica | volume = 54 | issue = 4 | pages = 397–402 | date = April 2010 | pmid = 20085541 | doi = 10.1111/j.1399-6576.2009.02207.x | s2cid = 205430269 | doi-access = free }}</ref> It reduces postoperative shivering, [[postoperative nausea and vomiting]], and emergence [[delirium]].<ref name=":11" /> However, a randomized controlled trial from 2021 demonstrated that clonidine is less effective at providing anxiolysis and more sedative in children of preschool age. Oral clonidine can take up to 45 minutes to take full effect,<ref>{{Cite journal |last1=Bromfalk |first1=Åsa |last2=Myrberg |first2=Tomi |last3=Walldén |first3=Jakob |last4=Engström |first4=Åsa |last5=Hultin |first5=Magnus |date=November 2021 |editor-last=Cravero |editor-first=Joseph |title=Preoperative anxiety in preschool children: A randomized clinical trial comparing midazolam, clonidine, and dexmedetomidine |journal=Pediatric Anesthesia |language=en |volume=31 |issue=11 |pages=1225–1233 |doi=10.1111/pan.14279 |pmid=34403548 |s2cid=237197251 |issn=1155-5645|doi-access=free }}</ref> The drawbacks of clonidine include [[hypotension]] and [[bradycardia]], but these can be advantageous in patients with hypertension and tachycardia.<ref>{{cite journal | vauthors = Henry RG, Raybould TP, Romond K, Kouzoukas DE, Challman SD | title = Clonidine as a preoperative sedative | journal = Special Care in Dentistry | volume = 38 | issue = 2 | pages = 80–88 | date = March 2018 | pmid = 29364538 | doi = 10.1111/scd.12269 | s2cid = 3875130 }}</ref> Another commonly used alpha-2 adrenergic agonist is dexmedetomidine, which is commonly used to provide a short term sedative effect (<24 hours). [[Dexmedetomidine]] and certain [[atypical antipsychotic]] agents may be also used in uncooperative children.<ref>{{Cite journal |last1=Manning |first1=Alexander N. |last2=Bezzo |first2=Leah K. |last3=Hobson |first3=Jamie K. |last4=Zoeller |first4=Justine E. |last5=Brown |first5=Courtney A. |last6=Henderson |first6=Kristin J. |date=October 2020 |title=Dexmedetomidine Dosing to Prevent Pediatric Emergence Delirium |url=https://pubmed.ncbi.nlm.nih.gov/32990204 |journal=AANA Journal |volume=88 |issue=5 |pages=359–364 |issn=2162-5239 |pmid=32990204}}</ref>
 
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" />
 
[[Melatonin]] has been found to be effective as an anaesthetic premedication in both adults and children because of its [[hypnotic]], [[anxiolytic]], [[Sedation|sedative]], [[Nociception|analgesic]], and [[anticonvulsant]] properties. Recovery is more rapid after premedication with melatonin than with midazolam, and there is also a reduced incidence of post-operative [[Psychomotor agitation|agitation]] and delirium.<ref name="Naguib2007">{{cite journal | vauthors = Naguib M, Gottumukkala V, Goldstein PA | title = Melatonin and anesthesia: a clinical perspective | journal = Journal of Pineal Research | volume = 42 | issue = 1 | pages = 12–21 | date = January 2007 | pmid = 17198534 | doi = 10.1111/j.1600-079X.2006.00384.x | doi-access = free }}</ref> Melatonin has been shown to have a similar effect in reducing perioperative anxiety in adult patients compared to benzodiazepine.<ref>{{cite journal | vauthors = Madsen BK, Zetner D, Møller AM, Rosenberg J | title = Melatonin for preoperative and postoperative anxiety in adults | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | pages = CD009861 | date = December 2020 | issue = 12 | pmid = 33319916 | pmc = 8092422 | doi = 10.1002/14651858.CD009861.pub3 }}</ref>
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== Anesthesia and the brain ==
{{Use dmy dates|date=January 2019}}Anesthesia has little to no effect on brain function, unless there is an existing brain disruption. Barbiturates, or the drugs used to administer anesthesia do not effectaffect auditory brain stem response.<ref>{{Cite journal |last1=Smith |first1=D.I. |last2=Mills |first2=J.H. |date=May 1989 |title=Anesthesia effects: auditory brain-stem response |url=http://dx.doi.org/10.1016/0013-4694(89)90047-3 |journal=Electroencephalography and Clinical Neurophysiology |volume=72 |issue=5 |pages=422–428 |doi=10.1016/0013-4694(89)90047-3 |pmid=2469566 |issn=0013-4694}}</ref> An example of a brain disruption would be a concussion.<ref>{{Cite journal |last1=Rasouli |first1=Mohammed R. |last2=Kavin |first2=Michelle |last3=Stache |first3=Stephen |last4=Mahla |first4=Michael E. |last5=Schwenk |first5=Eric S. |date=February 2020 |title=Anesthesia for the patient with a recently diagnosed concussion: think about the brain! |journal=Korean Journal of Anesthesiology |volume=73 |issue=1 |pages=3–7 |doi=10.4097/kja.19272 |issn=2005-7563 |pmc=7000285 |pmid=31257815}}</ref> It can be risky and lead to further brain injury if anesthesia is used on a concussed person. Concussions create ionic shifts in the brain that adjust the neuronal transmembrane potential. In order to restore this potential more glucose has to be made to equal the potential that is lost. This can be very dangerous and lead to cell death. This makes the brain very vulnerable in surgery. There are also changes to cerebral blood flow. The injury complicates the oxygen blood flow and supply to the brain.
 
== Stages of anaesthesia ==
[[Guedel's classification]], described by [[Arthur Ernest Guedel]] in 1937,<ref name = "Hewer_1937">{{cite journal |vauthors=Hewer CL |date=August 1937 |title=The Stages and Signs of General Anaesthesia |journal=British Medical Journal |volume=2 |issue=3996 |pages=274–276 |doi=10.1136/bmj.2.3996.274 |pmc=2087073 |pmid=20780832}}</ref> describes four stages of anaesthesia. Despite newer anaesthetic agents and delivery techniques, which have led to more rapid onset of—and recovery from—anaesthesia (in some cases bypassing some of the stages entirely), the principles remain.
 
;Stage 1: Stage 1, also known as ''induction'', is the period between the administration of induction agents and loss of consciousness. During this stage, the patient progresses from analgesia without amnesia to analgesia with amnesia. Patients can carry on a conversation at this time, and may complain about visual disturbance.
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[[Acetylcholine]], a natural [[neurotransmitter]] found at the [[neuromuscular junction]], causes muscles to contract when it is released from nerve endings. Muscle paralytic drugs work by preventing acetylcholine from attaching to its receptor. Paralysis of the muscles of respiration—the [[diaphragm (anatomy)|diaphragm]] and [[intercostal muscle]]s of the chest—requires that some form of artificial respiration be implemented. Because the muscles of the [[larynx]] are also paralysed, the airway usually needs to be protected by means of an [[endotracheal tube]].<ref name=":11" />
 
Paralysis is most easily monitored by means of a peripheral nerve stimulator. This device intermittently sends short electrical pulses through the skin over a peripheral nerve while the contraction of a muscle supplied by that nerve is observed. The effects of muscle relaxants are commonly reversed at the end of surgery by [[Cholinesterase inhibitor|anticholinesterase]] drugs, which are administered in combination with muscarinic [[anticholinergic]] drugs to minimize side effects. Examples of skeletal muscle relaxants in use today are [[pancuronium]], [[rocuronium]], [[vecuronium]], [[cisatracurium]], [[atracurium]], [[mivacurium]], and [[succinylcholine]]. Novel neuromuscular blockade reversal agents such as [[sugammadex]] may also be used; it works by directly binding muscle relaxants and removing it from the neuromuscular junction. Sugammadex was approved for use in the United States in 2015, and rapidly gained popularity. A study from 2022 has shown that Sugammadex and neostigmine are likely similarly safe in the reversal of neuromuscular blockade.<ref>{{cite journal | vauthors = Ruetzler K, Li K, Chhabada S, Maheshwari K, Chahar P, Khanna S, Schmidt MT, Yang D, Turan A, Sessler DI | display-authors = 6 | title = Sugammadex Versus Neostigmine for Reversal of Residual Neuromuscular Blocks After Surgery: A Retrospective Cohort Analysis of Postoperative Side Effects | journal = Anesthesia and Analgesia | volume = 134 | issue = 5 | pages = 1043–1053 | date = May 2022 | pmid = 35020636 | doi = 10.1213/ANE.0000000000005842 | s2cid = 245907059 }}</ref>
 
== Maintenance ==
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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 |url=https://pubmed.ncbi.nlm.nih.gov/26516798 |journal=Anesthesia and Analgesia |volume=122 |issue=1 |pages=70–78 |doi=10.1213/ANE.0000000000001009 |issn=1526-7598 |pmid=26516798|s2cid=41023659 |doi-access=free }}</ref>
 
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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Most [[perioperative mortality]] is attributable to [[Complication (medicine)|complications]] from the operation, such as [[Bleeding|haemorrhage]], [[sepsis]], and failure of vital organs. Over the last several decades, the overall anesthesia related mortality rate improved significantly for anesthetics administered. Advancements in monitoring equipment, anesthetic agents, and increased focus on perioperative safety are some reasons for the decrease in perioperative mortality. In the United States, the current estimated anesthesia-related mortality is about 1.1 per million population per year. The highest death rates were found in the geriatric population, especially those 85 and older.<ref>{{Cite journal |last1=Li |first1=Guohua |last2=Warner |first2=Margaret |last3=Lang |first3=Barbara H. |last4=Huang |first4=Lin |last5=Sun |first5=Lena S. |date=April 2009 |title=Epidemiology of Anesthesia-related Mortality in the United States, 1999–2005 |journal=Anesthesiology |volume=110 |issue=4 |pages=759–765 |doi=10.1097/aln.0b013e31819b5bdc |issn=0003-3022 |pmc=2697561 |pmid=19322941}}</ref> A review from 2018 examined perioperative anesthesia interventions and their impact on anesthesia-related mortality. Interventions found to reduce mortality include pharmacotherapy, ventilation, transfusion, nutrition, glucose control, dialysis and medical device.<ref>{{Cite journal |last1=Boet |first1=Sylvain |last2=Etherington |first2=Cole |last3=Nicola |first3=David |last4=Beck |first4=Andrew |last5=Bragg |first5=Susan |last6=Carrigan |first6=Ian D. |last7=Larrigan |first7=Sarah |last8=Mendonca |first8=Cassandra T. |last9=Miao |first9=Isaac |last10=Postonogova |first10=Tatyana |last11=Walker |first11=Benjamin |last12=De Wit |first12=José |last13=Mohamed |first13=Karim |last14=Balaa |first14=Nadia |last15=Lalu |first15=Manoj Mathew |date=2018-11-30 |title=Anesthesia interventions that alter perioperative mortality: a scoping review |journal=Systematic Reviews |volume=7 |issue=1 |pages=218 |doi=10.1186/s13643-018-0863-x |issn=2046-4053 |pmc=6267894 |pmid=30497505 |doi-access=free }}</ref> Interestingly, a randomized controlled trial from 2022 demonstrated that there is no significant difference in mortality between patient receiving handover from one clinician to another compared to the control group.<ref>{{Cite journal |last1=Meersch |first1=Melanie |last2=Weiss |first2=Raphael |last3=Küllmar |first3=Mira |last4=Bergmann |first4=Lars |last5=Thompson |first5=Astrid |last6=Griep |first6=Leonore |last7=Kusmierz |first7=Desiree |last8=Buchholz |first8=Annika |last9=Wolf |first9=Alexander |last10=Nowak |first10=Hartmuth |last11=Rahmel |first11=Tim |last12=Adamzik |first12=Michael |last13=Haaker |first13=Jan Gerrit |last14=Goettker |first14=Carina |last15=Gruendel |first15=Matthias |date=2022-06-28 |title=Effect of Intraoperative Handovers of Anesthesia Care on Mortality, Readmission, or Postoperative Complications Among Adults: The HandiCAP Randomized Clinical Trial |journal=JAMA |volume=327 |issue=24 |pages=2403–2412 |doi=10.1001/jama.2022.9451 |issn=1538-3598 |pmc=9167439 |pmid=35665794}}</ref>
 
Mortality directly related to anaesthetic management is very uncommon but may be caused by [[pulmonary aspiration]] of gastric contents,<ref>{{cite journal | vauthors = Engelhardt T, Webster NR | title = Pulmonary aspiration of gastric contents in anaesthesia | journal = British Journal of Anaesthesia | volume = 83 | issue = 3 | pages = 453–460 | date = September 1999 | pmid = 10655918 | doi = 10.1093/bja/83.3.453 | doi-access = free }}</ref> [[asphyxia]]tion,<ref>{{cite journal | vauthors = Parker RB | title = Maternal death from aspiration asphyxia | journal = British Medical Journal | volume = 2 | issue = 4983 | pages = 16–19 | date = July 1956 | pmid = 13329366 | pmc = 2034767 | doi = 10.1136/bmj.2.4983.16 }}</ref> or [[anaphylaxis]].<ref name=Dewachter2009>{{cite journal | vauthors = Dewachter P, Mouton-Faivre C, Emala CW | title = Anaphylaxis and anesthesia: controversies and new insights | journal = Anesthesiology | volume = 111 | issue = 5 | pages = 1141–1150 | date = November 2009 | pmid = 19858877 | doi = 10.1097/ALN.0b013e3181bbd443 | doi-access = free }}</ref> These in turn may result from malfunction of [[Anaesthetic equipment|anaesthesia-related equipment]] or, more commonly, [[Human reliability|human error]]. In 1984, after a television programme highlighting anaesthesia mishaps aired in the United States, American anaesthesiologist [[Ellison C. Pierce]] appointed the Anesthesia Patient Safety and Risk Management Committee within the [[American Society of Anesthesiologists]].<ref name=Guadagnino2000>{{Cite web|title=Improving anesthesia safety|author=Guadagnino C|publisher=Physician's News Digest, Inc.|location=Narberth, Pennsylvania|year=2000|url=http://physiciansnews.com/spotlight/200wp.html|access-date=8 September 2010|archive-url=https://web.archive.org/web/20100815080827/http://physiciansnews.com/spotlight/200wp.html|archive-date=15 August 2010}}</ref> This committee was tasked with determining and reducing the causes of anaesthesia-related [[Disease#Morbidity|morbidity]] and mortality.<ref name=Guadagnino2000/> An outgrowth of this committee, the Anesthesia Patient Safety Foundation, was created in 1985 as an independent, nonprofit corporation with the goal "that no patient shall be harmed by anesthesia".<ref>{{Cite web|title=Foundation History|author=Stoelting RK|publisher=Anesthesia Patient Safety Foundation|location=Indianapolis, IN|year=2010|url=http://www.apsf.org/about_history.php|access-date=8 September 2010}}</ref>
 
The rare but major complication of general anaesthesia is malignant hyperthermia.<ref>{{cite journal | vauthors = Baldo BA, Rose MA | title = The anaesthetist, opioid analgesic drugs, and serotonin toxicity: a mechanistic and clinical review | journal = British Journal of Anaesthesia | volume = 124 | issue = 1 | pages = 44–62 | date = January 2020 | pmid = 31653394 | doi = 10.1016/j.bja.2019.08.010 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Kim KS, Kriss RS, Tautz TJ | title = Malignant Hyperthermia: A Clinical Review | journal = Advances in Anesthesia | volume = 37 | pages = 35–51 | date = December 2019 | pmid = 31677658 | doi = 10.1016/j.aan.2019.08.003 | s2cid = 207899269 }}</ref> All major hospitalhospitals should have a protocol in place with an emergence drug cart near the OR for this potential complication.<ref>{{cite journal | vauthors = Pollock N, Langtont E, Stowell K, Simpson C, McDonnell N | title = Safe duration of postoperative monitoring for malignant hyperthermia susceptible patients | journal = Anaesthesia and Intensive Care | volume = 32 | issue = 4 | pages = 502–509 | date = August 2004 | pmid = 15675210 | doi = 10.1177/0310057X0403200407 | doi-access = free }}</ref>
 
== See also ==