| General anaesthesia | |
| Specialty: | Anaesthetics |
| Uses: | Facilitating surgery, terminal sedation[1] |
| Complications: | Anaesthesia awareness, overdose, death |
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.[2] 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. 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 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 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.
See main article: History of general anesthesia.
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.[3]
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.[4] 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.[5]
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.
General anaesthesia has many purposes and is routinely used in almost all surgical procedures. An appropriate surgical anesthesia should include the following goals:
Instead of receiving continuous deep sedation, such as via benzodiazepines, dying patients may choose to be completely unconscious as they die.[1]
The biochemical mechanism of action of general anaesthetics is still controversial.[7] Theories need to explain the function of anaesthesia in animals and plants.[8] 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 anaesthetics potentially able to activate specific sleep-active regions.[9]
Two non-exclusionary mechanisms include membrane-mediated and direct protein-mediated anesthesia. Potential protein-mediated molecular targets are GABAA,and NMDA glutamate receptors. General anesthesia was hypothesized to either enhance the inhibitory transmission or reduce the excitatory transmission of neuro signaling.[10] Most volatile anesthetics have been found to be a GABAA agonist, although the site of action on the receptor remains unknown.[11] Ketamine is a non-competitive NMDA receptor antagonist.[12]
The chemical structure and properties of anesthetics, as first noted by Meyer and Overton, suggest they could target the plasma membrane. A 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 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. PLDnull fruit flies were shown to resist anesthesia, the results established a membrane mediated target for inhaled anesthetics.[13]
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.[14] [15] 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.[16] [17] 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.[18]
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.[19] The condition of teeth and location of dental crowns are checked, and neck flexibility and head extension are observed.[20] [21] 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.[22]
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.[23] [24] 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,[25] The drawbacks of clonidine include hypotension and bradycardia, but these can be advantageous in patients with hypertension and tachycardia.[26] 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.[27]
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.[28] 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.[29] Melatonin has been shown to have a similar effect in reducing perioperative anxiety in adult patients compared to benzodiazepine.[30]
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.[31] 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.[32] 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.[33] 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 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 affect auditory brain stem response.[34] An example of a brain disruption would be a concussion.[35] 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.
Guedel's classification, described by Arthur Ernest Guedel in 1937,[6] 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.
General anaesthesia is usually induced in an operating theatre or in a dedicated anaesthetic room adjacent to the theatre. General anaesthesia may also be conducted in other locations, such as an endoscopy suite, intensive care unit, radiology or cardiology department, emergency department, ambulance, or at the site of a disaster where extrication of the patient may be impossible or impractical.
Anaesthetic agents may be administered by various routes, including inhalation, injection (intravenous, intramuscular, or subcutaneous), oral, and rectal. Once they enter the circulatory system, the agents are transported to their biochemical sites of action in the central and autonomic nervous systems.
Most general anaesthetics are induced either intravenously or by inhalation. Commonly used intravenous induction agents include propofol, sodium thiopental, etomidate, methohexital, and ketamine. Inhalational anaesthesia may be chosen when intravenous access is difficult to obtain (e.g., children), when difficulty maintaining the airway is anticipated, or when the patient prefers it. Sevoflurane is the most commonly used agent for inhalational induction, because it is less irritating to the tracheobronchial tree than other agents.[37]
As an example sequence of induction drugs:
Laryngoscopy and intubation are both very stimulating. The process of induction blunts the response to these maneuvers while simultaneously inducing a near-coma state to prevent awareness.
Several monitoring technologies allow for a controlled induction of, maintenance of, and emergence from general anaesthesia. Standard for basic anesthetic monitoring is a guideline published by the ASA, which describes that the patient's oxygenation, ventilation, circulation and temperature should be continually evaluated during anesthetic.[38]
See main article: Airway management. Anaesthetized patients lose protective airway reflexes (such as coughing), airway patency, and sometimes a regular breathing pattern due to the effects of anaesthetics, opioids, or muscle relaxants.To maintain an open airway and regulate breathing, some form of breathing tube is inserted after the patient is unconscious.To enable mechanical ventilation, an endotracheal tube is often used, although there are alternative devices that can assist respiration, such as face masks or laryngeal mask airways.Generally, full mechanical ventilation is only used if a very deep state of general anaesthesia is to be induced for a major procedure, and/or with a profoundly ill or injured patient.That said, induction of general anaesthesia usually results in apnea and requires ventilation until the drugs wear off and spontaneous breathing starts.In other words, ventilation may be required for both induction and maintenance of general anaesthesia or just during the induction.However, mechanical ventilation can provide ventilatory support during spontaneous breathing to ensure adequate gas exchange.
General anaesthesia can also be induced with the patient spontaneously breathing and therefore maintaining their own oxygenation which can be beneficial in certain scenarios (e.g. difficult airway or tubeless surgery). Spontaneous ventilation has been traditionally maintained with inhalational agents (i.e. halothane or sevoflurane) which is called a gas or inhalational induction. Spontaneous ventilation can also be maintained using intravenous anaesthesia (e.g. propofol). Intravenous anaesthesia to maintain spontaneous respiration has certain advantages over inhalational agents (i.e. suppressed laryngeal reflexes) however it requires careful titration. Spontaneous Respiration using Intravenous anaesthesia and High-flow nasal oxygen (STRIVE Hi) is a technique that has been used in difficult and obstructed airways.[39]
See main article: Eye injuries during general anaesthesia. General anaesthesia reduces the tonic contraction of the orbicularis oculi muscle, causing lagophthalmos (incomplete eye closure) in 59% of people.[40] In addition, tear production and tear-film stability are reduced, resulting in corneal epithelial drying and reduced lysosomal protection. The protection afforded by Bell's phenomenon (in which the eyeball turns upward during sleep, protecting the cornea) is also lost. Careful management is required to reduce the likelihood of eye injuries during general anaesthesia.[41] Some of the methods to prevent eye injury during general anesthesia includes taping the eyelids shut, use of eye ointments, and specially designed eye protective goggles.
Paralysis, or temporary muscle relaxation with a neuromuscular blocker, is an integral part of modern anaesthesia. The first drug used for this purpose was curare, introduced in the 1940s, which has now been superseded by drugs with fewer side effects and, generally, shorter duration of action.[42] Muscle relaxation allows surgery within major body cavities, such as the abdomen and thorax, without the need for very deep anaesthesia, and also facilitates endotracheal intubation.
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 and intercostal muscles 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.
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 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.[43]
The duration of action of intravenous induction agents is generally 5 to 10 minutes, after which spontaneous recovery of consciousness will occur.[44] In order to prolong unconsciousness for the duration of surgery, anaesthesia must be maintained. This is achieved by allowing the patient to breathe a carefully controlled mixture of oxygen and a volatile anaesthetic agent, or by administering intravenous medication (usually propofol). Inhaled anaesthetic agents are also frequently supplemented by intravenous analgesic agents, such as opioids (usually fentanyl or a fentanyl derivative) and sedatives (usually propofol or midazolam). Propofol can be used for total intravenous anaesthetia (TIVA), therefore supplementation by inhalation agents is not required.[45] General anesthesia is usually considered safe; however, there are reported cases of patients with distortion of taste and/or smell due to local anesthetics, stroke, nerve damage, or as a side effect of general anesthesia.[46] [47]
At the end of surgery, administration of anaesthetic agents is discontinued. Recovery of consciousness occurs when the concentration of anaesthetic in the brain drops below a certain level (this occurs usually within 1 to 30 minutes, mostly depending on the duration of surgery).
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.[48]
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.
Emergence is the return to baseline physiologic function of all organ systems after the cessation of general anaesthetics. This stage may be accompanied by temporary neurologic phenomena, such as agitated emergence (acute mental confusion), aphasia (impaired production or comprehension of speech), or focal impairment in sensory or motor function. Shivering is also fairly common and can be clinically significant because it causes an increase in oxygen consumption, carbon dioxide production, cardiac output, heart rate, and systemic blood pressure. The proposed mechanism is based on the observation that the spinal cord recovers at a faster rate than the brain. This results in uninhibited spinal reflexes manifested as clonic activity (shivering). This theory is supported by the fact that doxapram, a CNS stimulant, is somewhat effective in abolishing postoperative shivering.[49] Cardiovascular events such as increased or decreased blood pressure, rapid heart rate, or other cardiac dysrhythmias are also common during emergence from general anaesthesia, as are respiratory symptoms such as dyspnoea. Responding and following verbal command, is a criterion commonly utilized to assess the patient's readiness for tracheal extubation.
Postoperative pain is managed in the anaesthesia recovery unit (PACU) with regional analgesia or oral, transdermal, or parenteral medication. Patients may be given opioids, as well as other medications like non steroidal anti-inflammatory drugs and acetaminophen.[50] Sometimes, opioid medication is administered by the patient themselves using a system called a patient controlled analgesic.[51] The patient presses a button to activate a syringe device and receive a preset dose or "bolus" of the drug, usually a strong opioid such as morphine, fentanyl, or oxycodone (e.g., one milligram of morphine). The PCA device then "locks out" for a preset period to allow the drug to take effect, and also prevent the patient from overdosing. If the patient becomes too sleepy or sedated, they make no more requests. This confers a fail-safe aspect that is lacking in continuous-infusion techniques. If these medications cannot effectively manage the pain, local anesthetic may be directly injected to the nerve in a procedure called a nerve block.[52] [53]
In the recovery unit, many vital signs are monitored, including oxygen saturation,[54] [55] heart rhythm and respiration,[56] blood pressure, and core body temperature.
Postanesthetic shivering is common. Apart from causing discomfort and exacerbating pain, shivering has been shown to increase oxygen consumption, catecholamine release, risk for hypothermia, and induce lactic acidosis.[57] A number of techniques are used to reduce shivering, such as warm blankets,[58] [59] or wrapping the patient in a sheet that circulates warmed air, called a bair hugger.[60] [61] If the shivering cannot be managed with external warming devices, drugs such as dexmedetomidine,[62] [63] or other α2-agonists, anticholinergics, central nervous system stimulants, or corticosteroids may be used.[64]
In many cases, opioids used in general anaesthesia can cause postoperative ileus, even after non-abdominal surgery. Administration of a μ-opioid antagonist such as alvimopan immediately after surgery can help accelerate the timing of hospital discharge, but does not reduce the development of paralytic ileus.[65]
Enhanced Recovery After Surgery (ERAS) is a society that provides up-to-date guidelines and consensus to ensure continuity of care and improve recovery and peri-operative care. Adherence to the pathway and guidelines has been shown to associate with improved post-operative outcomes and lower costs to the health care system.[66]
See main article: Perioperative mortality. Most perioperative mortality is attributable to complications from the operation, such as 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.[66] 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.[67] 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.[68]
Mortality directly related to anaesthetic management is very uncommon but may be caused by pulmonary aspiration of gastric contents,[69] asphyxiation,[70] or anaphylaxis.[71] These in turn may result from malfunction of anaesthesia-related equipment or, more commonly, 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.[72] This committee was tasked with determining and reducing the causes of anaesthesia-related morbidity and mortality. 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".[73]
The rare but major complication of general anaesthesia is malignant hyperthermia.[74] [75] All major hospitals should have a protocol in place with an emergence drug cart near the OR for this potential complication.[76]
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