This article needs additional citations for verification. (February 2015)
General anaesthesia or general anesthesia (see spelling differences) is a medically induced coma with loss of protective reflexes, resulting from the administration of one or more general anaesthetic agents. It is generally performed in an operating theater to allow surgical procedures that would otherwise be intolerably painful for the patient, or in an intensive care unit or emergency department to facilitate mechanical ventilation in critically ill patients.
A variety of drugs may be administered, with the overall aim of ensuring unconsciousness, amnesia, analgesia, loss of reflexes of the autonomic nervous system, and in some cases paralysis of skeletal muscles. The optimal combination of drugs for any given patient and procedure is typically selected by an anaesthetist, or another provider such as an intensivist, anaesthetist practitioner, physician assistant, or nurse anaesthetist (depending on local practice), in consultation with the patient and the surgeon, dentist, or other practitioner performing the operative procedure.
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 doctor, became the first person 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.
General anaesthesia has many purposes, including:
- 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 actionEdit
This section needs to be updated.(February 2021)
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. Common areas of the central nervous system whose functions are interrupted or changed during general anaesthesia include 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 loops whose interruption is linked with unconsciousness. Potential pharmacologic targets of general anaesthetics are GABA, glutamate receptors, voltage-gated ion channels, and glycine and serotonin receptors.
Prior to a planned procedure, the anesthesiologist reviews medical records and/or interviews the patient to determine the best combination of drugs and dosages and the degree to which monitoring will be required to ensure a safe and effective procedure. Key factors in this evaluation are the patient's age, body mass index, medical and surgical history, current medications, and fasting time. Thorough and accurate answering of the questions is important so that the anaesthetist can select the proper drugs and procedures. For example, a patient who consumes significant quantities of alcohol or illicit drugs could be undermedicated if they fail to disclose this fact, and this could lead to anaesthesia awareness or intraoperative hypertension. Commonly used medications can interact with anaesthetics, and failure to disclose such usage can increase the risk to the patient.
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.
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.
One commonly used premedication is clonidine, an alpha-2 adrenergic agonist. Clonidine premedication reduces the need for anaesthetic induction agents, for volatile agents to maintain general anaesthesia, and for postoperative analgesics. It also reduces postoperative shivering, postoperative nausea and vomiting, and emergence delirium. In children, clonidine premedication is at least as effective as benzodiazepines and has less serious side effects. However, oral clonidine can take up to 45 minutes to take full effect, and drawbacks include hypotension and bradycardia.
Midazolam, a benzodiazepine characterized by a rapid onset and short duration, is effective in reducing preoperative anxiety, including separation anxiety in children. Dexmedetomidine and certain atypical antipsychotic agents may be used in uncooperative children.
Melatonin has been found to be effective as an anaesthetic premedication in both adults and children because of its hypnotic, anxiolytic, sedative, antinociceptive, and anticonvulsant properties. Unlike midazolam, melatonin does not impair psychomotor skills or hinder recovery. 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 premedication also reduces the required induction dose of propofol and sodium thiopental.
Another example of anaesthetic premedication is the preoperative administration of beta adrenergic antagonists to reduce the incidence of postoperative hypertension, cardiac dysrhythmia, or myocardial infarction. Anaesthesiologists may administer an antiemetic agent such as ondansetron, droperidol, or dexamethasone to prevent postoperative nausea and vomiting, or subcutaneous heparin or enoxaparin to reduce the incidence of deep vein thrombosis. Other commonly used premedication agents include opioids such as fentanyl or sufentanil, gastrokinetic agents such as metoclopramide, and histamine antagonists such as famotidine.
Non-pharmacologic preanaesthetic interventions include playing relaxing music, massage, and reducing ambient light and noise levels in order to maintain the sleep-wake cycle. 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.
Stages of anaesthesiaEdit
Guedel's classification, introduced 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 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.
- Stage 2
- Stage 2, also known as the excitement 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 occurs, and eye movements slow and then stop. The patient is unconscious and ready for surgery. This stage is divided into four planes:
- The eyes roll, then become fixed;
- Corneal and laryngeal reflexes are lost;
- The pupils dilate and light reflex is lost;
- Intercostal paralysis and shallow abdominal respiration occur.
- 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.
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.
As an example sequence of induction drugs:
- Pre-oxygenation to fill lungs with oxygen to permit a longer period of apnea during intubation without affecting blood oxygen levels
- Fentanyl for systemic analgesia for intubation
- Propofol for sedation for intubation
- Switching from oxygen to a mixture of oxygen and inhalational anesthetic
Laryngoscopy and intubation are both very stimulating and 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.
- 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.
- Continuous pulse oximetry (SpO2): A device is placed, usually on a finger, to allow for early detection of a fall in a patient's haemoglobin saturation with oxygen (hypoxaemia).
- 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. 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).
- Agent concentration measurement: anaesthetic machines typically have monitors to measure the percentage of inhalational anaesthetic agents used as well as exhalation concentrations. These monitors include measuring oxygen, carbon dioxide, and inhalational anaesthetics (e.g., nitrous oxide, isoflurane).
- 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.
- A circuit disconnect alarm or low pressure alarm indicates failure of the circuit to achieve a given pressure during mechanical ventilation.
- Capnography measures the amount of carbon dioxide exhaled by the patient in percent or mmHg, allowing the anaesthesiologist to assess the adequacy of ventilation. MmHg is usually used to allow the provider to see more subtle changes.
- Temperature measurement to discern hypothermia or fever, and to allow early detection of malignant hyperthermia.
- Electroencephalography, entropy monitoring, or other systems may be used to verify the depth of anaesthesia. This reduces the likelihood of anaesthesia awareness and of overdose.
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.
General anaesthesia reduces the tonic contraction of the orbicularis oculi muscle, causing lagophthalmos, or incomplete eye closure, in 59% of patients. 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.
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. 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, the natural neurotransmitter at the neuromuscular junction, causes muscles to contract when it is released from nerve endings. Muscle relaxants 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. Novel neuromuscular blockade reversal agents such as sugammadex may also be used. Examples of skeletal muscle relaxants in use today are pancuronium, rocuronium, vecuronium, cisatracurium, atracurium, mivacurium, and succinylcholine.
The duration of action of intravenous induction agents is generally 5 to 10 minutes, after which spontaneous recovery of consciousness will occur. In order to prolong unconsciousness for the required duration (usually 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 medication (usually propofol) through an intravenous catheter. Inhaled agents are frequently supplemented by intravenous analgesic agents, such as opioids (usually fentanyl or a fentanyl derivative) and sedatives (usually propofol or midazolam). With propofol-based anaesthetics, however, supplementation by inhalation agents is not required. 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.
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 (usually within 1 to 30 minutes, 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.
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. 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.
Hospitals strive for pain-free awakening from anaesthesia. Although not a direct result of general anaesthesia, postoperative pain is managed in the anaesthesia recovery unit 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. Sometimes, opioid medication is administered by the patient themselves using a system called a patient controlled analgesic. 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. If the patient becomes too sleepy or sedated, he or she makes 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.
Postanesthetic shivering is common. Apart from causing discomfort and exacerbating pain, shivering has been shown to increase oxygen consumption, catecholamine release, cardiac output, heart rate, blood pressure, and intraocular pressure. A number of techniques are used to reduce shivering, such as warm blankets, or wrapping the patient in a sheet that circulates warmed air, called a bair hugger. If the shivering cannot be managed with external warming devices, drugs such as dexmedetomidine, or other α2-agonists, anticholinergics, central nervous system stimulants, or corticosteroids may be used.
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 reduce the severity and duration of ileus.
Most perioperative mortality is attributable to complications from the operation, such as haemorrhage, sepsis, and failure of vital organs. Current estimates of perioperative mortality in procedures involving general anaesthesia range from one in 53 to one in 5,417. However, a 1997 Canadian retrospective review of 2,830,000 oral surgical procedures in Ontario between 1973 and 1995 reported only four deaths in cases in which an oral and maxillofacial surgeon or a dentist with specialized training in anaesthesia administered the general anaesthetic or deep sedation. The authors calculated an overall mortality rate of 1.4 per 1,000,000.
Mortality directly related to anaesthetic management is very uncommon but may be caused by pulmonary aspiration of gastric contents, asphyxiation, or anaphylaxis. These in turn may result from malfunction of anaesthesia-related equipment or, more commonly, human error. A 1978 study found that 82% of preventable anaesthesia mishaps were the result of human error. In a 1954 review of 599,548 surgical procedures at 10 hospitals in the United States between 1948 and 1952, 384 deaths were attributed to anaesthesia, for an overall mortality rate of 0.064%. 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. 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".
As with perioperative mortality rates in general, mortality attributable to the management of general anaesthesia is controversial. Estimates of the incidence of perioperative mortality directly attributable to anaesthesia range from one in 6,795 to one in 200,200.
- Jevtovic-Todorovic V (September 2016). "General Anesthetics and Neurotoxicity: How much do we know?". Anesthesiology Clinics. Anesthesiol Clin. 34 (3): 439–51. doi:10.1016/j.anclin.2016.04.001. PMC 5477636. PMID 27521190.
- Frazier, Jennifer (26 January 2018). "Plants, Like People, Succumb to Anesthesia". Scientific American. Retrieved 26 January 2018.
- Schneider G (2007). "The Search for Structures and Mechanisms Controlling Anesthesia-induced Unconsciousness". Anesthesiology. 107 (2): 195–198. doi:10.1097/01.anes.0000271869.27956.d1. PMID 17667560.
- Li X, Pearce RA (February 2000). "Effects of halothane on GABA(A) receptor kinetics: evidence for slowed agonist unbinding". The Journal of Neuroscience. 20 (3): 899–907. doi:10.1523/JNEUROSCI.20-03-00899.2000. PMC 6774186. PMID 10648694.
- Harrison NL, Simmonds MA (February 1985). "Quantitative studies on some antagonists of N-methyl D-aspartate in slices of rat cerebral cortex". British Journal of Pharmacology. 84 (2): 381–91. doi:10.1111/j.1476-5381.1985.tb12922.x. PMC 1987274. PMID 2858237.
- Lederman D, Easwar J, Feldman J, Shapiro V (August 2019). "Anesthetic considerations for lung resection: preoperative assessment, intraoperative challenges and postoperative analgesia". Annals of Translational Medicine. 7 (15): 356. doi:10.21037/atm.2019.03.67. PMC 6712248. PMID 31516902.
- Izumo W, Higuchi R, Yazawa T, Uemura S, Shiihara M, Yamamoto M (October 2019). "Evaluation of preoperative risk factors for postpancreatectomy hemorrhage". Langenbeck's Archives of Surgery. 404 (8): 967–974. doi:10.1007/s00423-019-01830-w. PMC 6935390. PMID 31650216.
- Budworth L, Prestwich A, Lawton R, Kotzé A, Kellar I (4 February 2019). "Preoperative Interventions for Alcohol and Other Recreational Substance Use: A Systematic Review and Meta-Analysis". Frontiers in Psychology. 10: 34. doi:10.3389/fpsyg.2019.00034. PMC 6369879. PMID 30778307.
- Siriphuwanun V, Punjasawadwong Y, Saengyo S, Rerkasem K (18 October 2018). "Incidences and factors associated with perioperative cardiac arrest in trauma patients receiving anesthesia". Risk Management and Healthcare Policy. 11: 177–187. doi:10.2147/rmhp.s178950. PMC 6201994. PMID 30425598.
- Mushambi MC, Jaladi S (June 2016). "Airway management and training in obstetric anaesthesia". Current Opinion in Anesthesiology. 29 (3): 261–7. doi:10.1097/ACO.0000000000000309. PMID 26844863. S2CID 27527932.
- Rehak A, Watterson LM (November 2019). "Institutional preparedness to prevent and manage anaesthesia-related 'can't intubate, can't oxygenate' events in Australian and New Zealand teaching hospitals". Anaesthesia. 75 (6): 767–774. doi:10.1111/anae.14909. PMID 31709522. S2CID 207944753.
- Schieren M, Kleinschmidt J, Schmutz A, Loop T, Staat M, Gatzweiler KH, et al. (December 2019). "Comparison of forces acting on maxillary incisors during tracheal intubation with different laryngoscopy techniques: a blinded manikin study". Anaesthesia. 74 (12): 1563–1571. doi:10.1111/anae.14815. PMID 31448404.
- Bergendahl H, Lönnqvist PA, Eksborg S (February 2006). "Clonidine in paediatric anaesthesia: review of the literature and comparison with benzodiazepines for premedication". Acta Anaesthesiologica Scandinavica. 50 (2): 135–43. doi:10.1111/j.1399-6576.2006.00940.x. PMID 16430532. S2CID 25797363. Archived from the original on 16 December 2012.
- Dahmani S, Brasher C, Stany I, Golmard J, Skhiri A, Bruneau B, et al. (April 2010). "Premedication with clonidine is superior to benzodiazepines. A meta analysis of published studies". Acta Anaesthesiologica Scandinavica. 54 (4): 397–402. doi:10.1111/j.1399-6576.2009.02207.x. PMID 20085541. S2CID 205430269.
- Rosenbaum A, Kain ZN, Larsson P, Lönnqvist PA, Wolf AR (September 2009). "The place of premedication in pediatric practice". Pediatric Anesthesia. 19 (9): 817–28. doi:10.1111/j.1460-9592.2009.03114.x. PMID 19691689. S2CID 7743205.
- Cox RG, Nemish U, Ewen A, Crowe MJ (December 2006). "Evidence-based clinical update: does premedication with oral midazolam lead to improved behavioural outcomes in children?". Canadian Journal of Anaesthesia. 53 (12): 1213–9. doi:10.1007/BF03021583. PMID 17142656.
- Bozkurt P (June 2007). "Premedication of the pediatric patient - anesthesia for the uncooperative child". Current Opinion in Anesthesiology. 20 (3): 211–5. doi:10.1097/ACO.0b013e328105e0dd. PMID 17479023. S2CID 25446995.
- Naguib M, Gottumukkala V, Goldstein PA (January 2007). "Melatonin and anesthesia: a clinical perspective". Journal of Pineal Research. 42 (1): 12–21. doi:10.1111/j.1600-079X.2006.00384.x. PMID 17198534.
- Mencía SB, López-Herce JC, Freddi N (May 2007). "Analgesia and sedation in children: practical approach for the most frequent situations" (PDF). Jornal de Pediatria. 83 (2 Suppl): S71-82. doi:10.2223/JPED.1625. PMID 17530139.
- Manyande A, Cyna AM, Yip P, Chooi C, Middleton P (July 2015). "Non-pharmacological interventions for assisting the induction of anaesthesia in children" (PDF). The Cochrane Database of Systematic Reviews (7): CD006447. doi:10.1002/14651858.CD006447.pub3. PMID 26171895.
- Hewer CL (August 1937). "The Stages and Signs of General Anaesthesia". British Medical Journal. 2 (3996): 274–6. doi:10.1136/bmj.2.3996.274. PMC 2087073. PMID 20780832.
- Booth AW, Vidhani K, Lee PK, Thomsett CM (March 2017). "SponTaneous Respiration using IntraVEnous anaesthesia and Hi-flow nasal oxygen (STRIVE Hi) maintains oxygenation and airway patency during management of the obstructed airway: an observational study". British Journal of Anaesthesia. 118 (3): 444–451. doi:10.1093/bja/aew468. PMC 5409133. PMID 28203745.
- Contractor S, Hardman JG (2006). "Injury during anaesthesia". Continuing Education in Anaesthesia, Critical Care & Pain. 6 (2): 67–70. doi:10.1093/bjaceaccp/mkl004.
- Nair PN, White E (2014). "Care of the eye during anaesthesia and intensive care". Anaesthesia & Intensive Care Medicine. 15: 40–43. doi:10.1016/j.mpaic.2013.11.008.
- Baker, Jason Joe; Öberg, Stina; Rosenberg, Jacob (2017). "Loss of Smell and Taste After General Anesthesia". A & A Case Reports. 9 (12): 346–348. doi:10.1213/XAA.0000000000000612.
- Elterman KG, Mallampati SR, Kaye AD, Urman RDPostoperative alterations in taste and smell. Anesth Pain Med. 2014;4:e18527
- Basics of Anesthesia, 5th Edition Authors: Robert K. Stoelting & Ronald D. Miller ISBN 978-0-443-06801-0
- Lopez, M. B. (2018). "12.1.2018". Romanian Journal of Anaesthesia and Intensive Care. 25 (1): 73–81. doi:10.21454/rjaic.7518.251.xum. PMC 5931188. PMID 29756066.
- Rajpal S, Gordon DB, Pellino TA, Strayer AL, Brost D, Trost GR, et al. (April 2010). "Comparison of perioperative oral multimodal analgesia versus IV PCA for spine surgery". Journal of Spinal Disorders & Techniques. 23 (2): 139–45. doi:10.1097/BSD.0b013e3181cf07ee. PMID 20375829. S2CID 5319313.
- Schnabel A, Reichl SU, Weibel S, Zahn PK, Kranke P, Pogatzki-Zahn E, Meyer-Frießem CH (October 2019). Cochrane Anaesthesia Group (ed.). "Adductor canal blocks for postoperative pain treatment in adults undergoing knee surgery". The Cochrane Database of Systematic Reviews. 2019 (10). doi:10.1002/14651858.CD012262.pub2. PMC 6814953. PMID 31684698.
- Sharma A, Goel AD, Sharma PP, Vyas V, Agrawal SP (October 2019). "The Effect of Transversus Abdominis Plane Block for Analgesia in Patients Undergoing Liver Transplantation: A Systematic Review and Meta-Analysis". Turkish Journal of Anaesthesiology and Reanimation. 47 (5): 359–366. doi:10.5152/tjar.2019.60251. PMC 6756312. PMID 31572985.
- Olsen RM, Aasvang EK, Meyhoff CS, Dissing Sorensen HB (October 2018). "Towards an automated multimodal clinical decision support system at the post anesthesia care unit". Computers in Biology and Medicine. 101: 15–21. doi:10.1016/j.compbiomed.2018.07.018. PMID 30092398.
- Petersen C, Wetterslev J, Meyhoff CS (August 2018). "Perioperative hyperoxia and post-operative cardiac complications in adults undergoing non-cardiac surgery: Systematic review protocol". Acta Anaesthesiologica Scandinavica. 62 (7): 1014–1019. doi:10.1111/aas.13123. PMID 29664117.
- Orbach-Zinger S, Bizman I, Firman S, Lev S, Gat R, Ashwal E, et al. (October 2019). "Perioperative noninvasive cardiac output monitoring in parturients undergoing cesarean delivery with spinal anesthesia and prophylactic phenylephrine drip: a prospective observational cohort study". The Journal of Maternal-Fetal & Neonatal Medicine. 32 (19): 3153–3159. doi:10.1080/14767058.2018.1458835. PMID 29683007. S2CID 5039625.
- Mahajan RP, Grover VK, Sharma SL, Singh H (March 1987). "Intraocular pressure changes during muscular hyperactivity after general anesthesia". Anesthesiology. 66 (3): 419–21. doi:10.1097/00000542-198703000-00030. PMID 3826703.
- Shaw CA, Steelman VM, DeBerg J, Schweizer ML (May 2017). "Effectiveness of active and passive warming for the prevention of inadvertent hypothermia in patients receiving neuraxial anesthesia: A systematic review and meta-analysis of randomized controlled trials". Journal of Clinical Anesthesia. 38: 93–104. doi:10.1016/j.jclinane.2017.01.005. PMC 5381733. PMID 28372696.
- Alderson P, Campbell G, Smith AF, Warttig S, Nicholson A, Lewis SR (June 2014). Cochrane Anaesthesia, Critical and Emergency Care Group (ed.). "Thermal insulation for preventing inadvertent perioperative hypothermia". The Cochrane Database of Systematic Reviews (6): CD009908. doi:10.1002/14651858.CD009908.pub2. PMID 24895945.
- Stanger R, Colyvas K, Cassey JG, Robinson IA, Armstrong P (August 2009). "Predicting the efficacy of convection warming in anaesthetized children". British Journal of Anaesthesia. 103 (2): 275–82. doi:10.1093/bja/aep160. PMID 19541677.
- Wagner K, Swanson E, Raymond CJ, Smith CE (June 2008). "Comparison of two convective warming systems during major abdominal and orthopedic surgery". Canadian Journal of Anaesthesia. 55 (6): 358–63. doi:10.1007/BF03021491. PMID 18566199.
- Zhang J, Zhang X, Wang H, Zhou H, Tian T, Wu A (22 August 2017). "Dexmedetomidine as a neuraxial adjuvant for prevention of perioperative shivering: Meta-analysis of randomized controlled trials". PLOS ONE. 12 (8): e0183154. Bibcode:2017PLoSO..1283154Z. doi:10.1371/journal.pone.0183154. PMC 5567500. PMID 28829798.
- Zhang X, Wang D, Shi M, Luo Y (April 2017). "Efficacy and Safety of Dexmedetomidine as an Adjuvant in Epidural Analgesia and Anesthesia: A Systematic Review and Meta-analysis of Randomized Controlled Trials". Clinical Drug Investigation. 37 (4): 343–354. doi:10.1007/s40261-016-0477-9. PMID 27812971. S2CID 5512397.
- English W (2002). "Post-operative shivering, causes, prevention and treatment (letter)". Update in Anaesthesia (15). Archived from the original on 29 May 2011. Retrieved 8 September 2010.
- Leslie JB, Viscusi ER, Pergolizzi JV, Panchal SJ (2011). "Anesthetic Routines: The Anesthesiologist's Role in GI Recovery and Postoperative Ileus". Advances in Preventive Medicine. 2011: 976904. doi:10.4061/2011/976904. PMC 3168940. PMID 21991449.
- Kim KS, Kriss RS, Tautz TJ (December 2019). "Malignant Hyperthermia: A Clinical Review". Advances in Anesthesia. 37: 35–51. doi:10.1016/j.aan.2019.08.003. PMID 31677658. S2CID 207899269.
- Baldo BA, Rose MA (October 2019). "The anaesthetist, opioid analgesic drugs, and serotonin toxicity: a mechanistic and clinical review". British Journal of Anaesthesia. 124 (1): 44–62. doi:10.1016/j.bja.2019.08.010. PMID 31653394.
- Pollock N, Langtont E, Stowell K, Simpson C, McDonnell N (August 2004). "Safe duration of postoperative monitoring for malignant hyperthermia susceptible patients". Anaesthesia and Intensive Care. 32 (4): 502–9. doi:10.1177/0310057X0403200407. PMID 15675210.
- Lagasse RS (December 2002). "Anesthesia safety: model or myth? A review of the published literature and analysis of current original data". Anesthesiology. 97 (6): 1609–17. doi:10.1097/00000542-200212000-00038. PMID 12459692. S2CID 32903609.
- Arbous MS, Meursing AE, van Kleef JW, de Lange JJ, Spoormans HH, Touw P, et al. (February 2005). "Impact of anesthesia management characteristics on severe morbidity and mortality". Anesthesiology. 102 (2): 257–68, quiz 491–2. doi:10.1097/00000542-200502000-00005. hdl:1874/12590. PMID 15681938.
- Nkansah PJ, Haas DA, Saso MA (June 1997). "Mortality incidence in outpatient anesthesia for dentistry in Ontario". Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 83 (6): 646–51. doi:10.1016/S1079-2104(97)90312-7. PMID 9195616.
- Engelhardt T, Webster NR (September 1999). "Pulmonary aspiration of gastric contents in anaesthesia". British Journal of Anaesthesia. 83 (3): 453–60. doi:10.1093/bja/83.3.453. PMID 10655918.
- Parker RB (July 1956). "Maternal death from aspiration asphyxia". British Medical Journal. 2 (4983): 16–9. doi:10.1136/bmj.2.4983.16. PMC 2034767. PMID 13329366.
- Dewachter P, Mouton-Faivre C, Emala CW (November 2009). "Anaphylaxis and anesthesia: controversies and new insights". Anesthesiology. 111 (5): 1141–50. doi:10.1097/ALN.0b013e3181bbd443. PMID 19858877.
- Cooper JB, Newbower RS, Long CD, McPeek B (December 1978). "Preventable anesthesia mishaps: a study of human factors". Anesthesiology. 49 (6): 399–406. doi:10.1097/00000542-197812000-00004. PMID 727541.[permanent dead link]
- Beecher HK, Todd DP (July 1954). "A study of the deaths associated with anesthesia and surgery: based on a study of 599, 548 anesthesias in ten institutions 1948-1952, inclusive". Annals of Surgery. 140 (1): 2–35. doi:10.1097/00000658-195407000-00001. PMC 1609600. PMID 13159140.
- Guadagnino C (2000). "Improving anesthesia safety". Narberth, Pennsylvania: Physician's News Digest, Inc. Archived from the original on 15 August 2010. Retrieved 8 September 2010.
- Stoelting RK (2010). "Foundation History". Indianapolis, IN: Anesthesia Patient Safety Foundation. Retrieved 8 September 2010.
- Cottrell, J.E. (2003). "Uncle Sam, Anesthesia-Related Mortality and New Directions: Uncle Sam Wants You!". ASA Newsletter. 67 (1). Archived from the original on 31 July 2010. Retrieved 8 September 2010.
- Chloroform: The molecular lifesaver An article at University of Bristol providing interesting facts about chloroform.
- In detail about General anesthesia
- Australian & New Zealand College of Anaesthetists Monitoring Standard
- Royal College of Anaesthetists Patient Information page