General anaesthesia

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General anaesthesia (UK) or general anesthesia (US) is a method of medically inducing loss of

Attempts at producing a state of general anaesthesia can be traced throughout recorded history in the writings of the ancient

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.^[7]

Two enormous leaps occurred in the late 19th century, which together allowed the transition to modern surgery. An appreciation of the

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.[10]^[11][12]

Indications for General Anesthesia

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.^[10][11][12]

Biochemical mechanism of action

The

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. PLD^null fruit flies were shown to resist anesthesia, the results established a membrane mediated target for inhaled anesthetics.^[19]

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.^[20][21] 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.^[2][22] 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.^[6]

An important aspect of pre-anaesthetic evaluation is an assessment of the patient's

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.[6]

One commonly used premedication is clonidine, an alpha-2 adrenergic agonist.^[27][28] It reduces postoperative shivering, postoperative nausea and vomiting, and emergence delirium.^[6] 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,^[29] The drawbacks of clonidine include hypotension and bradycardia, but these can be advantageous in patients with hypertension and tachycardia.^[30] 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.^[31]

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.^[32] It also provides mild sedation, sympathicolysis, and anterograde amnesia.^[6]

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.^[33] Melatonin has been shown to have a similar effect in reducing perioperative anxiety in adult patients compared to benzodiazepine.^[34]

Another example of anaesthetic premedication is the preoperative administration of

Non-pharmacologic preanaesthetic interventions include playing cognitive behavioral therapy, music therapy, aromatherapy, hypnosis massage, pre-operative preparation video, and guided imagery relaxation therapy, etc.^[36] 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.^[37] Parental presence during premedication and induction of anaesthesia has not been shown to reduce anxiety in children.^[37] 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.^[37]

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 affect auditory brain stem response.^[38] An example of a brain disruption would be a concussion.^[39] 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,^[3] 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.

Stage 2

Stage 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 3

In 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:

1. The eyes roll, then become fixed; eyelid and swallow reflexes are lost. Still have regular spontaneous breathing;
2. Corneal and laryngeal reflexes are lost;
3. 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.
4. Full diaphragm paralysis and irregular shallow abdominal respiration occur.^[40]

Stage 4

Stage 4, also known as overdose, occurs when too much anaesthetic medication is given relative to the amount of surgical stimulation and the patient has severe brainstem or medullary depression, resulting in a cessation of respiration and potential cardiovascular collapse. This stage is lethal without cardiovascular and respiratory support.^[3]

Induction

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

1. Pre-oxygenation or denitrogenation to fill lungs with 100% oxygen to permit a longer period of apnea during intubation without affecting blood oxygen levels
2. Fentanyl for systemic analgesia during intubation
3. Propofol for sedation for intubation
4. Switching from oxygen to a mixture of oxygen and inhalational anesthetic once intubation is complete

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.

Physiologic monitoring

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.^[42]

1. Continuous electrocardiography (ECG or EKG): Electrodes are placed on the patient's skin to monitor heart rate and rhythm. This may also help the anaesthesiologist to identify early signs of heart ischaemia. Typically lead II and V5 are monitored for arrhythmias and ischemia, respectively.
2. Continuous
   hypoxaemia
   ).
3. Blood pressure monitoring: There are two methods of measuring the patient's blood pressure. The first, and most common, is non-invasive blood pressure (NIBP) monitoring. This involves placing a blood pressure cuff around the patient's arm, forearm, or leg. A machine takes blood pressure readings at regular, preset intervals throughout the surgery. The second method is invasive blood pressure (IBP) monitoring, which allows beat to beat monitoring of blood pressure. This method is reserved for patients with significant heart or lung disease, the critically ill, and those undergoing major procedures such as cardiac or transplant surgery, or when large blood loss is expected. It involves placing a special type of plastic cannula in an artery, usually in the wrist (radial artery) or groin (femoral artery).
4. Agent concentration measurement:
   inhalational anaesthetics (e.g., nitrous oxide, isoflurane
   ).
5. Oxygen measurement: Almost all circuits have an alarm in case oxygen delivery to the patient is compromised. The alarm goes off if the fraction of inspired oxygen drops below a set threshold.
6. A circuit disconnect alarm or low pressure alarm indicates failure of the circuit to achieve a given pressure during mechanical ventilation.
7. ventilation
   . MmHg is usually used to allow the provider to see more subtle changes.
8. Temperature measurement to discern hypothermia or fever, and to allow early detection of malignant hyperthermia.
9. anaesthesia awareness
   and of overdose.

Airway management

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.^[43]

Eye management

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.^[44] 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.^[45] 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.

Neuromuscular blockade

Atracurium, for neuromuscular block
- Glycopyrronium bromide

(here under trade name Robinul), reducing secretions

Paralysis, or temporary muscle relaxation with a

endotracheal intubation

.

endotracheal tube.^[6]

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

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.^[47]

Maintenance

The duration of action of intravenous induction agents is generally 5 to 10 minutes, after which spontaneous recovery of consciousness will occur.

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.^[49] 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.^[50][51]

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).[6]

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.^[52]

Other medications are occasionally used to treat side effects or prevent complications. They include

antibiotics are sometimes given to prevent inflammation and infection, respectively.^[6]

Emergence

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

dyspnoea. Responding and following verbal command, is a criterion commonly utilized to assess the patient's readiness for tracheal extubation.^[6]

Postoperative care

Postoperative pain is managed in the

nerve block.^[56][57]

In the recovery unit, many vital signs are monitored, including oxygen saturation,^[58][59] heart rhythm and respiration,^[58][60] blood pressure,^[58] 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.^[61] A number of techniques are used to reduce shivering, such as warm blankets,^[62][63] or wrapping the patient in a sheet that circulates warmed air, called a bair hugger.^[64][65] If the shivering cannot be managed with external warming devices, drugs such as dexmedetomidine,^[66][67] or other α2-agonists, anticholinergics, central nervous system stimulants, or corticosteroids may be used.^[54][68]

In many cases, opioids used in general anaesthesia can cause postoperative

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.^[69]

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.[70]

Perioperative mortality

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.^[71] 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.^[72] 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.^[73]

Mortality directly related to anaesthetic management is very uncommon but may be caused by

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.^[76] This committee was tasked with determining and reducing the causes of anaesthesia-related morbidity and mortality.^[76] 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".^[77]

The rare but major complication of general anaesthesia is malignant hyperthermia.[78]^[79] All major hospitals should have a protocol in place with an emergence drug cart near the OR for this potential complication.^[80]

See also

• Local anaesthesia

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External links

• Chloroform: The molecular lifesaver An article at University of Bristol providing interesting facts about chloroform.
• Australian & New Zealand College of Anaesthetists Monitoring Standard
• Royal College of Anaesthetists Patient Information page