general anaesthesia general anaesthesia 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. 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. 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. general anaesthesiaequipment used for anaesthesia in the operating theatremeshd000768medlineplus007410 a variety of 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 muscles. the optimal combination of anesthetics for any given patient and procedure is typically selected by an anaesthetist, or another provider such as a nurse anaesthetist (depending on local practice and law), in consultation with the patient and the surgeon, dentist, or other practitioner performing the operative procedure. history attempts at producing a state of general anaesthesia can be traced throughout recorded history in the writings of the ancient sumerians, babylonians, assyrians, egyptians, greeks, romans, indians, and chinese. during the middle ages, scientists and other scholars made significant advances in the eastern world, while their european counterparts also made important advances. the renaissance saw significant advances in anatomy and surgical technique. however, despite all this progress, surgery remained a treatment of last resort. largely because of the associated pain, many patients chose certain death rather than undergo surgery. although there has been a great deal of debate as to who deserves the most credit for the discovery of general anaesthesia, several scientific discoveries in the late 18th and early 19th centuries were critical to the eventual introduction and development of modern anaesthetic techniques. two enormous leaps occurred in the late 19th century, which together allowed the transition to modern surgery. an appreciation of the germ theory of disease led rapidly to the development and application of antiseptic techniques in surgery. antisepsis, which soon gave way to asepsis, reduced the overall morbidity and mortality of surgery to a far more acceptable rate than in previous eras. concurrent with these developments were the significant advances in pharmacology and physiology which led to the development of general anaesthesia and the control of pain. on 14 november 1804, hanaoka seishū, a japanese surgeon, became the first person on record to successfully perform surgery using general anaesthesia. 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 monitoring and new anaesthetic agents with improved pharmacokinetic and pharmacodynamic characteristics also contributed to this trend. finally, standardized training programs for anaesthesiologists and nurse anaesthetists emerged during this period. purpose 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) analgesia (loss of response to pain) amnesia (loss of memory) immobility (loss of motor reflexes) paralysis (skeletal muscle relaxation and normal muscle relaxation) biochemical mechanism of action the biochemical mechanism of action of general anaesthetics is not well understood. theories need to explain the function of anaesthesia in animals and plants. 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 networks and arousal circuits linked with unconsciousness, and some anesthetics potentially able to activate specific sleep-active regions. potential molecular pharmacologic targets of general anaesthetics are gabaa,and nmda glutamate receptors. general anesthesia was hypothesized to either enhance the inhibitory transmission or reduce the excitatory transmission of neuro signaling. most volatile anesthetic has been found to be a gabaa agonist, although the site of action on the receptor remains unknown. ketamine is a non-competitive nmda receptor antagonist. the chemical structure and properties of anesthetics suggest they could target the plasma membrane, yet the exact mechanism remained a mystery for over 100 years. a study from 2020 demonstrated that inhaled anesthetics (chloroform and isoflurane) could disrupt phospholipase d2 localization to the lipid rafts and led to production of the signaling molecule phosphatidic acid (pa). signaling molecules lead to a cascade of events and eventually activation twik-related k+ channels (trek-1). pldnull fruit flies were shown to resist anesthesia, the results established a membrane mediated target for inhaled anesthetics. 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. thorough and accurate preoperative evaluation is crucial for the effective safety of the anesthetic plan. for example, a patient who consumes significant quantities of alcohol or illicit drugs could be undermedicated during the procedure if they fail to disclose this fact, and this could lead to anaesthesia awareness or intraoperative hypertension. 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. an important aspect of pre-anaesthetic evaluation is an assessment of the patient's airway, involving inspection of the mouth opening and visualisation of the soft tissues of the pharynx. the condition of teeth and location of dental crowns are checked, and neck flexibility and head extension are observed. 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. premedication 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. one commonly used premedication is clonidine, an alpha-2 adrenergic agonist. it reduces postoperative shivering, postoperative nausea and vomiting, and emergence delirium. 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, the drawbacks of clonidine include hypotension and bradycardia, but these can be advantageous in patient with hypertension and tachycardia. 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. 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 preoperative anxiety, including separation anxiety in children. it also provides mild sedation, sympathicolysis, and anterograde amnesia. melatonin has been found to be effective as an anaesthetic premedication in both adults and children because of its hypnotic, anxiolytic, sedative, 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 agitation and delirium. melatonin has been shown to have a similar effect in reducing perioperative anxiety in adult patients compared to benzodiazepine. another example of anaesthetic premedication is the preoperative administration of beta adrenergic antagonists, which reduce the burden of arrhythmias after cardiac surgery. however, evidence also has shown an association of increased adverse events with beta-blockers in non-cardiac surgery. anaesthesiologists may administer one or more antiemetic agents such as ondansetron, droperidol, or dexamethasone to prevent postoperative nausea and vomiting. nsaids are commonly used analgesic premedication agent, and often reduce need for opioids such as fentanyl or sufentanil. also gastrokinetic agents such as metoclopramide, and histamine antagonists such as famotidine. non-pharmacologic preanaesthetic interventions include playing cognitive behavioral therapy, music therapy, aromatherapy, hypnosis massage, pre-operative preparation video, and guided imagery relaxation therapy, etc. these techniques are particularly useful for children and patients with intellectual disabilities. minimizing sensory stimulation or distraction by video games may help to reduce anxiety prior to or during induction of general anaesthesia. larger high-quality studies are needed to confirm the most effective non-pharmacological approaches for reducing this type of anxiety. parental presence during premedication and induction of anaesthesia has not been shown to reduce anxiety in children. it is suggested that parents who wish to attend should not be actively discouraged, and parents who prefer not to be present should not be actively encouraged to attend. anesthesia and the brain 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 effect auditory brain stem response. an example of a brain disruption would be a concussion. 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, 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 1stage 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. stage 2stage 2, also known as the excitement or delirium stage, is the period following loss of consciousness and marked by excited and delirious activity. during this stage, the patient's respiration and heart rate may become irregular. in addition, there may be uncontrolled movements, vomiting, suspension of breathing, and pupillary dilation. because the combination of spastic movements, vomiting, and irregular respiration may compromise the patient's airway, rapidly acting drugs are used to minimize time in this stage and reach stage 3 as fast as possible. stage 3in stage 3, also known as surgical anaesthesia, the skeletal muscles relax, vomiting stops. respiratory depression and cessation of eye movements are the hallmarks of this stage. the patient is unconscious and ready for surgery. this stage is divided into four planes: the eyes roll, then become fixed; eyelid and swallow reflexes are lost. still have regular spontaneous breathing; corneal and laryngeal reflexes are lost; the pupillary light reflex is lost; and the process is marked by complete relaxation of abdominal and intercostal muscles. ideal level of anesthesia for most surgeries. full diaphragm paralysis and irregular shallow abdominal respiration occur. stage 4stage 4, also known as overdose, occurs when too much anaesthetic medication is given relative to the amount of surgical stimulation and the patient has