General anaesthesia

Attempts at producing a state of general anesthesia 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, which correspond roughly to what is sometimes referred to as the Islamic Golden Age, scientists and other scholars made significant advances in science and medicine in the Muslim world and Eastern world, while their European counterparts also made important advances.

The European 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 with surgical disorders 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 anesthesia, it is generally agreed that certain scientific discoveries in the late 18th and early 19th centuries were critical to the eventual introduction and development of modern anesthetic techniques.

Two "quantum 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 anesthesia and the control of pain.

In the 20th century, the safety and efficacy of general anesthesia was improved by the routine use of tracheal intubation and other advanced airway management techniques. Significant advances in monitoring and new anesthetic agents with improved pharmacokinetic and pharmacodynamic characteristics also contributed to this trend. Finally, standardized training programs for anesthesiologists and nurse anesthetists emerged during this period.

General anaesthesia has many purposes including:

1. Analgesia — loss of response to pain,
2. Amnesia — loss of memory,
3. Immobility — loss of motor reflexes,
4. Hypnosis — loss of consciousness,
5. Skeletal muscle relaxation.

The biochemical mechanism of action of general anaesthetics is not yet well understood. To induce unconsciousness, anaesthetics affect the GABA and NMDA systems. For example, halothane is a GABA agonist,^[1] and ketamine is an NMDA receptor antagonist.^[2]

Prior to planned operation or procedure, the anaesthetist reviews the medical record 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 of 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 anaesthetic drugs and procedures. For example, a patient who consumes significant quantities of alcohol or illicit drugs could be undermedicated if s/he fails to disclose this fact. This in turn could then lead to anaesthesia awareness or dangerously high blood pressure.^{[citation needed]} Commonly used medications (e.g., sildenafil) can interact with anaesthesia drugs; failure to disclose such usage can also increase the risk to the patient.^{[citation needed]} There are some situations (where patients are on a certain medication and must undergo a given procedure) in which local anaesthesiaorregional anaesthesia can be given, but instead general anaesthesia is chosen, though this is not extremely common due to the fact that general anaesthesia is by nature more dangerous and the agents used react with many more medications.

An important aspect of the preanaesthetic evaluation is that 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 and caps are checked, neck flexibility and head extension observed. If a tracheal tube is indicated and airway management is deemed difficult, then alternative methods of tracheal intubation, such as fibreoptic intubation, may be required as part of the anaesthetic management.

Anaesthesiologists may prescribe or administer a premedication prior to administration of a general anaesthetic. Anaesthetic premedication consists of a drug or combination of drugs that serve to complement or otherwise improve the quality of the anaesthetic.

One example of this is the preoperative administration of clonidine, an alpha-2 adrenergic agonist. Clonidine premedication reduces the need for anaesthetic induction agents^{[citation needed]}, as well as the need for volatile anaesthetic agents during maintenance of general anaesthesia,^{[citation needed]} and the need for postoperative analgesics.^{[citation needed]} Clonidine premedication also reduces postoperative shivering^{[citation needed]}, postoperative nausea and vomiting and emergence delirium.^{[citation needed]} In children, clonidine premedication is at least as effective as benzodiazepines, in addition to having a more favourable side effect profile.^{[citation needed]} It also reduces the incidence of post-operative delirium associated with sevoflurane anaesthesia.^{[citation needed]} As a result clonidine has become a popular agent for anaesthetic premedication.^[3][4] Drawbacks of oral clonidine include the fact that it can take up to 45 minutes to take full effect,^[5] hypotension and bradycardia.^{[citation needed]}

Midazolam, a benzodiazepine characterized by a rapid onset and short duration relative to other benzodiazepines, is effective in reducing preoperative anxiety, including separation anxiety associated with separation of children from their parents and induction of anaesthesia.^[6] Dexmedetomidine and certain atypical antipsychotic agents are other drugs that are used in particular in very uncooperative children.^[7]

Melatonin has been found to be effective as an anaesthetic premedication in both adults and children due to its hypnotic, anxiolytic, sedative, antinociceptive, and anticonvulsant properties. Unlike midazolam, melatonin does not impair psychomotor skills or adversely affect the quality of recovery. Recovery is more rapid after melatonin premedication than with midazolam, and there is also a reduced incidence of post-operative agitation and delirium.^[8] Melatonin premedication also reduces the required induction dose of propofol and thiopental.^[8]

Another example of anaesthetic premedication is the preoperative administration of beta adrenergic antagonists to reduce the incidence of postoperative hypertension, cardiac dysrhythmiaormyocardial infarction.^{[citation needed]} One may choose to administer an antiemetic agent such as droperidolordexamethasone to reduce the incidence of postoperative nausea and vomiting,^{[citation needed]} or subcutaneous heparinorenoxaparin to reduce the incidence of deep vein thrombosis.^{[citation needed]} Other commonly used premedication agents include opioids such as fentanylorsufentanil, 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.^[9] These techniques are particularly useful for paediatric and mentally retarded patients. Other options for children who refuse or cannot tolerate pharmacologic premedication include interventions by clowns and child life specialists. Minimizing sensory stimulation or distraction by video games may also help to reduce anxiety prior to or during induction of general anaesthesia.^[10]

The four stages of anaesthesia were described in 1937.^[11] Despite newer anaesthetic agents and delivery techniques, which have led to more rapid onset and recovery from anaesthesia, with greater safety margins, the principles remain.

Stage 1

Stage 1 anaesthesia, also known as the "induction", is the period between the initial administration of the 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 anaesthesia, also known as the "excitement stage", is the period following loss of consciousness and marked by excited and delirious activity. During this stage, respirations and heart rate may become irregular. In addition, there may be uncontrolled movements, vomiting, breath holding, and pupillary dilation. Since the combination of spastic movements, vomiting, and irregular respirations may lead to airway compromise, rapidly acting drugs are used to minimize time in this stage and reach stage 3 as fast as possible.

Stage 3

Stage 3, "surgical anaesthesia". During this stage, the skeletal muscles relax, and the patient's breathing becomes regular. Eye movements slow, then stop, and surgery can begin. It has been divided into 4 planes:

1. eyes initially rolling, then becoming fixed
2. loss of corneal and laryngeal reflexes
3. pupils dilate and loss of light reflex
4. intercostal paralysis, shallow abdominal respiration

Stage 4

Stage 4 anaesthesia, also known as "overdose", is the stage where too much medication has been given relative to the amount of surgical stimulation and the patient has severe brain stem or medullary depression. This results in a cessation of respiration and potential cardiovascular collapse. This stage is lethal without cardiovascular and respiratory support.

Induction of general anaesthesia is usually conducted in a medical facility, most commonly in an operating room. However, general anaesthesia may also be conducted in many other locations, such as an endoscopy suite, radiologyorcardiology 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, intramuscularorsubcutaneous), oral, and rectal. After administration by one or more of these routes, the agents gain access to the blood. Once in the circulatory system, they are transported to their biochemical sites of action in the central and autonomic nervous systems, where they exert their pharmacologic effects.

Most general anaesthetics today are induced either with a needle, by intravenous injection, or by breathing a volatile anaesthetic through an anaesthetic circuit (inhalational induction). Onset of anaesthesia is faster with intravenous injection than with inhalation, taking about 10–20 seconds to induce total unconsciousness.^{[citation needed]} This has the advantage of avoiding the excitatory phase of anaesthesia (see above), and thus reduces complications related to induction of anaesthesia.^{[citation needed]} Commonly used intravenous induction agents include propofol, sodium thiopental, etomidate, and ketamine. An inhalational induction may be chosen by the anaesthesiologist where intravenous access is difficult to obtain, where difficulty maintaining the airway is anticipated, or due to patient preference (e.g., children). Sevoflurane is currently the most commonly used agent for inhalational induction, because it is less irritating to the tracheobronchial tree than other volatile anaesthetic agents.^{[citation needed]}

Monitoring involves the use of several technologies to allow for a controlled induction of, maintenance of and emergence from general anaesthesia.

1. Continuous Electrocardiography (ECG): The placement of electrodes that monitor heart rate and rhythm. This may also help the anaesthetist to identify early signs of heart ischaemia.
2. Continuous pulse oximetry (SpO2): The placement of this device (usually on one of the fingers) allows for early detection of a fall in a patient's haemoglobin saturation with oxygen (hypoxaemia).
3. Blood Pressure Monitoring (NIBP or IBP): There are two methods of measuring the patient's blood pressure. The first, and most common, is called non-invasive blood pressure (NIBP) monitoring. This involves placing a blood pressure cuff around the patient's arm, forearm or leg. A blood pressure machine takes blood pressure readings at regular, preset intervals throughout the surgery. The second method is called invasive blood pressure (IBP) monitoring. This method is reserved for patients with significant heart or lung disease, the critically ill, major surgery such as cardiac or transplant surgery, or when large blood losses are expected. The invasive blood pressure monitoring technique involves placing a special type of plastic cannula in the patient's artery - usually at the wrist or in the groin.
4. Agent concentration measurement - Common anaesthetic machines have monitors to measure the per cent of inhalational anaesthetic agent used (e.g. sevoflurane, isoflurane, desflurane, halothane etc.). The monitors also usually measure nitrous oxide and oxygen percentages and could give a MAC level.
5. Low oxygen alarm - Almost all circuits have a backup alarm in case the oxygen delivery to the patient becomes compromised. This warns if the fraction of inspired oxygen drops lower than minimum alarm setting and allows the anaesthetist to take immediate remedial action.
6. Circuit disconnect alarm or low pressure alarm indicates failure of circuit to achieve a given pressure during mechanical ventilation.
7. Carbon dioxide measurement (capnography)- measures the amount of carbon dioxide expired by the patient's lungs in per cent or mmHg, mmHg is usually used to allow the anaesthesia provider to see more subtle changes in CO2. It allows the anaesthetist to assess the adequacy of ventilation
8. Temperature measurement to discern hypothermiaorfever, and to aid early detection of malignant hyperthermia.
9. EEG or other system to verify depth of anaesthesia may also be used. This reduces the likelihood that a patient will be mentally awake, although unable to move because of the paralytic agents. It also reduces the likelihood of a patient receiving significantly more amnesic drugs than actually necessary to do the job.

With the loss of consciousness caused by general anaesthesia, there is loss of protective airway reflexes (such as coughing), loss of airway patency and sometimes loss of a regular breathing pattern due to the effect of anaesthetics, opioids, or muscle relaxants. To maintain an open airway and regulate breathing within acceptable parameters, some form of "breathing tube" is inserted in the airway after the patient is unconscious. To enable mechanical ventilation, an endotracheal tube is often used (intubation), although there are alternative devices such as face masks or laryngeal mask airways.

"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, e.g. abdomen and thorax without the need for very deep anaesthesia, and is also used to facilitate endotracheal intubation. Acetylcholine, the natural neurotransmitter substance 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, i.e. the diaphragm and intercostal muscles of the chest requires that some form of artificial respiration be implemented. As the muscles of the larynx are also paralysed, the airway usually needs to be protected by means of an endotracheal tube. Monitoring of paralysis is most easily provided 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 termination of surgery by anticholinesterase drugs. Examples of skeletal muscle relaxants in use today are pancuronium, rocuronium, vecuronium, atracurium, mivacurium, and succinylcholine.

The duration of action of intravenous induction agents is in general 5 to 10 minutes, after which time spontaneous recovery of consciousness will occur. In order to prolong anaesthesia for the required duration (usually the duration of surgery), anaesthesia must be maintained. Usually this is achieved by allowing the patient to breathe a carefully controlled mixture of oxygen, nitrous oxide, and a volatile anaesthetic agent or by having a carefully controlled infusion of medication, usually propofol, through an intravenous catheter. The inhalation agents are transferred to the patient's brain via the lungs and the bloodstream, and the patient remains unconscious. Inhaled agents are frequently supplemented by intravenous anaesthetics, such as opioids (usually fentanyl or a fentanyl derivative) and sedative-hypnotics (usually propofol or midazolam), though, for a propofol-based anaesthetic, supplementation by inhalation agents is not required. At the end of surgery, the volatile or intravenous anaesthetic 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 upon the duration of surgery). In the 1990s, a novel method of maintaining anaesthesia was developed in Glasgow, UK. Called TCI (target controlled infusion), this 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 infusion of the drug. Purported advantages include faster recovery from anaesthesia, reduced incidence of post-operative nausea and vomiting, and absence of a trigger for malignant hyperthermia. At present, TCI is not permitted in the United States.^{[citation needed]} Other medications will occasionally be given to anaesthetized patients to treat side-effects or prevent complications. These medications include antihypertensives to treat high blood pressure, drugs like ephedrine and phenylephrine to treat low blood pressure, drugs like salbutamol to treat asthma or laryngospasm/bronchospasm, and drugs like epinephrineordiphenhydramine to treat allergic reactions. Sometimes glucocorticoidsorantibiotics are given to prevent inflammation and infection, respectively.

Emergence is the process of return to baseline physiologic function of all organ systems after the cessation of administration of general anaesthetic agent(s). This stage of general anaesthesia may be accompanied by certain unusual but temporary neurologic phenomena, such as delirium (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 since it results in 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.^[12] Cardiovascular events such as increasedordecreased blood pressure, rapid heart rate or other cardiac dysrhythmias are also common during emergence from general anaesthesia, as are respiratory symptoms such as dyspnoea.

The anaesthesia should conclude with a pain-free awakening and a management plan for postoperative pain relief. This may be in the form of regional analgesia, oral, transdermal, or parenteral medication. Minor surgical procedures are amenable to oral pain relief medications such as paracetamol and NSAIDs such as ibuprofen. Moderate levels of pain require the addition of mild opiates such as tramadol. Major surgical procedures may require a combination of modalities to confer adequate pain relief. Parenteral methods include patient-controlled analgesia (PCA) involving a strong opiate such as morphine, fentanyl, or oxycodone. Here, to activate a syringe device, the patient presses a button and receives a preset dose or "bolus" of the drug (e.g., one milligram of morphine). The PCA device then "locks out" for a preset period, e.g. 5 minutes, to allow the drug to take effect. If the patient becomes too sleepy or sedated, he or she make no more morphine requests. This confers a fail-safe aspect that is lacking in continuous-opiate infusion techniques. Shivering is a frequent occurrence in the post-operative period. Apart from causing discomfort and exacerbating post-operative pain, shivering has been shown to increase oxygen consumption, catecholamine release, cardiac output, heart rate, blood pressure, and intra-ocular pressure. There is a number of techniques used to reduce this occurrence, such as increasing the ambient temperature in theatre, using conventional or forced warm air blankets, and using warmed intravenous fluids.^[13]

In many cases, opioids used in general anaesthesia can cause post-operative ileus even in non-abdominal surgery. Administration of a μ-opioid antagonist such as alvimopan immediately after recovery can help reduce the severity and duration of ileus.^[14]

Most perioperative mortality is attributable to complications from the operation (such as haemorrhage, sepsis, and failure of vital organs. This also may include memory loss or slowing down of the thought processes) or pre-existing medical conditions.^{[citation needed]} Most current estimates of perioperative mortality range from 1 death in 53 anaesthetics to 1 in 5,417 anaesthetics.^[15][16] However, a 1997 Canadian retrospective review of 2,830,000 oral surgical procedures in Ontario between 1973–1995 reported only four deaths in cases in which either 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.^[17] The largest and most recent study of postoperative mortality was published in 2010. In this review of 3.7 million elective open surgical procedures performed on inpatients at 102 hospitals in the Netherlands during 1991–2005, postoperative mortality from all causes was observed in 67,879 patients, for an overall rate of 1.85%.^[18] The wide disparity between the results of these studies may be the result of differences in operational definitions and reporting sources.^[15]

Mortality directly related to anaesthetic management is significantly less common, and may include such causes as pulmonary aspiration of gastric contents,^[19] asphyxiation^[20] and anaphylaxis.^[21] 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.^[22] In a 1954 review of 599,548 surgical procedures at 10 hospitals in the United States between 1948–1952, 384 deaths were attributed to anaesthesia, for an overall mortality rate of 0.064%.^[23] In 1984, after a television programme highlighting anaesthesia mishaps aired in the United States, American anaesthesiologist Ellison C. Pierce appointed a committee called the Anesthesia Patient Safety and Risk Management Committee of the American Society of Anesthesiologists.^[24] This committee was tasked with determining and reducing the causes of peri-anaesthetic morbidity and mortality.^[24] An outgrowth of this committee, the Anesthesia Patient Safety Foundation was created in 1985 as an independent, nonprofit corporation with the vision that "that no patient shall be harmed by anesthesia".^[25] As with perioperative mortality rates in general, the current mortality attributable to the management of general anaesthesia is controversial.^[26] The incidence of perioperative mortality that is directly attributable to anaesthesia ranges from 1 in 6,795 to 1 in 200,200 anaesthetics.^[15]

• Local anesthesia

• Chloroform: The molecular lifesaver An article at University of Bristol providing interesting facts about chloroform.
• General anesthesia: General anesthesia is a treatment that puts you into a deep sleep
• Australian & New Zealand College of Anaesthetists Monitoring Standard
• Royal College of Anaesthetists Patient Information page