anesthesia

The anesthesia (from ancient Greek ναρκώδης narkōdēs “solidified”) or general anesthesia , colloquially also general anesthesia and less often general anesthesia , is a form of anesthesia , the aim of which is to completely switch off the patient's consciousness and pain sensation in order to carry out diagnostic or therapeutic interventions ( operations ) can and create optimal conditions for this for both the patient and the doctor. For this purpose, one or more anesthetics ( general anesthetics ) are administered that work in the central nervous system , possibly also active ingredients to relax the skeletal muscles. The patient cannot be awakened, in contrast to local and regional anesthesia procedures ("partial anesthesia"), in which the pain is eliminated by blocking nerve fibers only in individual regions of the body.

General anesthesia is usually carried out under planned circumstances as part of an operation, but is also used for interventional procedures and for procedures in veterinary medicine . For endotracheal intubation for airway management in emergency and intensive care medicine , anesthesia can also be used; sedation is then sufficient to continue ventilation therapy .

In the middle of the 19th century, starting in Boston in 1846, inhalation anesthesia as general anesthesia in the current sense was performed for the first time, but only through the development of modern anesthesia machines , methods of airway management , easily controllable anesthetics and technical monitoring procedures as well as the establishment of the field of anesthesiology , With the training of specialized doctors and the development of guidelines and algorithms, general anesthesia achieved its status as a low-risk routine procedure, which only enables painful interventions in the body's integrity to the extent and widespread that it is today. Just like an operation, anesthesia is a medical intervention into the body's integrity (and thus legally a bodily harm ), which requires the patient to be prepared and informed accordingly and given his / her consent .

The person performing anesthesia is referred to as an anesthetist or anesthetist , formerly (without special academic training for the field) as an anesthetist ; anyone who deals scientifically with anesthesia as an anesthesiologist .

Anesthesia workstation for performing anesthesia

Overview

Components and definitions of general anesthesia

There is no generally accepted definition of the state of general anesthesia. This consists of different dimensions, which was already reflected in the naming of the ether application in the 19th century. Anesthesia is made up of the ancient Greek ἀν- “un-, not” and αἴσϑησις “perception”.

Anesthesia is borrowed from ancient Greek νάρκωσις , nárkōsis and has been traceable in German since the 18th century. Related words in Greek are the verb ναρκάειν , narkáein , "numb", "freeze" and the noun νάρκη , nárkē , "paralysis", "drowsiness".

The two terms emphasize different aspects that an anesthetic with ether produced, on the one hand the absence of unpleasant sensations, on the other hand the immobility that made an operation possible. The terms general anesthesia and general anesthesia are now largely used synonymously as a description.

Today, most authors differentiate between the dimensions of general anesthesia , the elimination of consciousness (mental component), elimination of pain ( analgesia , sensory component) and immobility (motor component, possibly as muscle relaxation ). Usually this goes hand in hand with the dampening of vegetative reactions (reflex component to pain stimuli: rise in blood pressure, accelerated heart rate) and a loss of memory ( amnesia ). Whether and to what extent each of these components is required for the implementation is controversial. For example, a slight movement of the patient under general anesthesia does not necessarily interfere with operations on other body regions.

On this basis, modern attempts at definition define general anesthesia as drug-induced unconsciousness during which the patient cannot be awakened, even by pain impulses ("General Anesthesia is a drug-induced loss of consciousness during which patients are not arousable, even by painful stimulation", American Society of Anesthesiologists ). Another formulation defines general anesthesia as a ( iatrogenic ) induced, reversible (reversible) insensitivity of the entire organism with the aim of making an intervention possible.

Demarcation

The boundary between general anesthesia and (anal) sedation is fluid. This also dampens the functions of the central nervous system, but the patient can be awakened. However, sedation and anesthesia also differ in terms of impairment of respiratory function and circulation (see table). The deeper the sedation, the more it can be assumed that these vital functions will be impaired. As a consequence, as the depth of sedation increases, more extensive measures must be taken through monitoring and, if necessary, stabilization, such as the administration of oxygen using a mask ( insufflation ). In general anesthesia, the maximum form of this spectrum, the respiratory function must be completely taken over and, under certain circumstances, measures to stabilize the circulation with appropriate means (infusions, circulation-supporting medication) must be used.

Overview of the Sedation-Anesthesia Continuum (American Society of Anesthesiologists)
	slight sedation	deep sedation	General anesthesia
Responsiveness	awakenable	can be awakened with stimulation or pain stimulus	not awakenable
Airway management	unnecessary	possibly necessary	usually necessary
own breathing	sufficient	possibly reduced	usually no longer available
Cardiovascular system	usually not affected	usually not affected	possibly impaired

The premedication before anesthesia / surgery causes a slight sedation, but the main goal is the anti-anxiety effect (anxiolysis).

In local and regional anesthesia procedures, blocking nerve fibers enables pain to be switched off in individual regions of the body; In contrast to general anesthesia, consciousness is not affected, breathing and circulatory function are unchanged.

Hypnosis techniques are used to achieve a trance characterized by altered alertness and relaxation . The various qualities of general anesthesia are not achieved. There are indications that the use of hypnosis as a pain therapy method or in combination with anesthesia methods ( hypno anesthesia ) has positive effects on the outcome of operations . However, there is no good evidence of effectiveness; the data available so far are based on very different studies with small case numbers, so that a final assessment is not possible.

pharmacology

The distinguishable qualities of modern general anesthesia are brought about by different drugs, which are called anesthetics . Every combination of the substance groups by means of injection and breathing air is called balanced anesthesia .

In the case of anesthetics that are administered intravenously, a distinction is made between different groups of active substances:

• Hypnotics : The loss of consciousness results from the injection of sleeping pills such as propofol , thiopental , methohexital , etomidate or substances from the group of benzodiazepines . The main focus of action of these substances is the GABA _A receptor , the most important inhibitory receptor in the central nervous system , which exerts its effect by influencing the permeability for chloride ions. The receptor in the thalamus has a special function in inducing and maintaining sleep . The hypnotics have no significant pain-relieving effect and only a minor muscle-relaxing effect.

• Analgesics : Highly effective painkillers, usually opioids such as fentanyl , sufentanil , remifentanil or alfentanil, are used, the primary target of which is the various opioid receptors , the analgesic effect being mainly caused by influencing the permeability for calcium ions. Just like ketamine (acting on the NMDA receptor ), which is an alternative, opioids also have a consciousness-depressing effect in higher doses. Analgesics and hypnotics also suppress memory ( amnesia ) and dampen vegetative functions.

• Muscle relaxants : Muscle relaxation occurs through muscle relaxants such as rocuronium , ( cis- ) atracurium , mivacurium , vecuronium or succinylcholine . They block the neuromuscular transmission of stimuli to the nicotinic acetylcholine receptors of the motor endplate , which causes reversible paralysis. There is no effect on the central nervous system, which is why there is no analgesic or consciousness-suppressing effect. Muscle relaxation makes endotracheal intubation easier for the anesthetist in order to secure the airway, as the intubation conditions are significantly improved and damage to the larynx is reduced. It does not have to be continued during the course of anesthesia for all types of operations, but is usually required for interventions in the abdominal cavity.

Inhalation anesthetics such as sevoflurane , isoflurane , desflurane or nitrous oxide are supplied through the breath. The corridors mainly cause a loss of consciousness, besides a slight muscle relaxation and pain relief. Laughing gas, on the other hand, has a strong analgesic effect, but has only a slight hypnotic and no muscle-relaxing effect. The earliest substances for inhalation anesthesia were nitrous oxide, diethyl ether ("ether") and chloroform .

The Neuroleptanalgesia as a combination of neuroleptics with painkillers has as an alternative to general anesthesia today only of historical significance.

The effects of anesthetics on the GABA _A receptor are now held responsible as an important molecular mechanism, particularly for loss of consciousness.

Mechanisms of action theories

The complex effects on a number of receptors and ion channels , as well as on other modifications of synaptic signal transmission , which also exist to varying degrees for the individual anesthetics, are held responsible for the various dimensions of anesthesia . Are involved in addition to the above GABA _A - and NMDA receptor and opioid receptors and receptors for other neurotransmitters , and the sodium and potassium channels in the cell membranes of nerve cells . The anatomical sites of action in the central nervous system are mainly the cerebral cortex , the spinal cord and the thalamus . The anesthetics, especially the inhalation anesthetics, have very complex effects on these receptors, which are still the subject of research in their entirety and interaction. In addition to the direct effects on the receptors and channels made up of proteins , an unspecific effect on the lipid components of the central nervous system was assumed in the past for inhalation anesthetics (according to the Meyer-Overton hypothesis ) , but this is less important today. Ultimately, however, it cannot be completely ruled out and an involvement in the anesthetic effects is still being discussed. A comprehensive anesthesia theory that can be explained by the known mechanisms is therefore not yet available.

Indications and contraindications

application areas

Appendectomy ( appendectomy ) with an opening of the abdominal cavity, which would not be possible without general anesthesia

The classic area of ​​application for general anesthesia is to create a tolerance for an operation . Painful interventions in the body's integrity were only made possible in today's extent and spread through the development of modern general anesthesia. Various medical disciplines ( surgical disciplines , obstetrics , psychiatry , interventional radiology ) are currently performing such interventions on all body regions for therapeutic and sometimes diagnostic purposes ( sampling ). After modern anesthesia began 150 years ago, anesthesia has emerged as a specialized field.

In the 20th century, there were further indications for performing general anesthesia in emergency and intensive care medicine . It is used in particular when securing the airways by means of endotracheal intubation , as otherwise defensive reflexes make it difficult to insert the ventilation hose ( tube ). Stress reduction and a reduction in oxygen demand as well as uncontrollable seizures in emergency medicine are indications for induction of anesthesia. Sedation with adequate analgesia is usually sufficient to continue ventilation. The objective of sedating patients so deeply that they are in an anesthesia-like state during the entire ventilation period has increasingly been abandoned in recent years. Deep sedation or even accompanying neuromuscular blockade is only reserved for a few special indications. Exceptions are inadequate ventilation in the event of difficulties in adapting the patient to mechanical ventilation , intracranial pressure symptoms with the risk of entrapment or a reduction in oxygen consumption in the case of impending hypoxia .

Differences in the various areas of application arise primarily from the urgency of the implementation: In a planned operation, general anesthesia can be carried out under controlled conditions on informed, evaluated, fasted, premedicated patients. In emergency medicine, the patient's medical history ( anamnesis ) is often not known, the patient must be viewed as not sober and the local, temporal and personal conditions are often unfavorable. As a result, the effect of the anesthetic on the circulatory stability of injured or acutely ill patients can be more difficult to assess than would be the case with planned interventions.

Contraindications

Contraindications (contraindications) to the implementation of general anesthesia are, for example, refusal by the patient, serious previous illnesses, conditions with a lack of sobriety or pregnancy. The contraindications are to be viewed as relative if a life-threatening or indispensable surgical procedure or an airway security has to be carried out. Under these circumstances, side effects and possible complications must then be taken into account and, if necessary, managed with extended monitoring and therapeutic measures.

Alternatives to general anesthesia exist for some of the operations in locally effective local anesthesia procedures . In these, the targeted application of local anesthetics provokes a temporary, reversible function inhibition of nerves , which leads to insensitivity and freedom from pain in certain parts of the body without impairing consciousness. A distinction is made between surface anesthesia, infiltration anesthesia and conduction anesthesia ( regional anesthesia method ) of peripheral or spinal cord-related nerves. Using local anesthesia procedures, problems of general anesthesia can be avoided in certain patient groups, for example those with a predisposition to postoperative nausea or malignant hyperthermia (sau). The range of applications for these methods is limited, however. For example, interventions in the body cavities (abdominal and chest cavity, skull) usually have to be carried out under general anesthesia.

Monitoring the patient

Extended monitoring during general anesthesia

Monitoring the patient is a core task of the anesthetist. The direct monitoring of body functions is known as monitoring . This is done using the doctor's examination methods , apparatus monitoring and laboratory tests carried out continuously or intermittently ( point-of-care testing ). The aim of monitoring is to ensure the safety of the patient, to recognize critical situations and to enable the general anesthesia to be controlled.

The extent of the monitoring is adapted to the patient's state of health and the extent of the intervention. A standardized anesthesia device (in accordance with EN 740 ) with the option of monitoring ECG , non-invasive blood pressure measurement , monitoring of blood oxygen content ( pulse oximetry ), monitoring of CO ₂ exhalation ( capnometry ) and measurement of inhalation anesthetic concentrations are essential basic monitoring . Various other methods are also available that can be used if necessary: ​​temperature monitoring, monitoring of muscle relaxation ( relaxometry ), measurement of central venous pressure , invasive blood pressure measurement , blood gas analysis , pulse contour analysis methods , transesophageal echocardiography , neuromonitoring, etc.

execution

General anesthesia is now performed in most cases by administering anesthetics from various groups of active ingredients. The medication can be administered through a vein ( intravenously ) or through the air ( by inhalation ). In total intravenous anesthesia (TIVA), the drugs are administered intravenously only, mostly using syringe pumps . Reasons for this include contraindications to anesthetic gases, a lack of options for gas suction, or a tendency to severe postoperative nausea.

Simultaneous use of regional anesthesia is known as combination anesthesia , which saves anesthetics and allows effective pain therapy to be carried out after the operation . This is practiced for abdominal ( laparotomy ) or thoracotomy ( thoracotomy ) in combination with an epidural catheter or for bone surgery, usually in combination with a peripheral pain catheter .

In most countries, anesthesia is carried out by a specialist doctor , the anesthetist . In Germany, he is supported by an anesthesia nurse who also often has a defined specialist training. The implementation by an assistant doctor in further training must always be carried out under the direct supervision of a specialist, whereby eye or phone contact must exist between the two (“specialist standard”). In other countries, such as the USA or Sweden, the implementation is in the hands of non-medical anesthesiologists ( Nurse Anesthesists , in Sweden Anestesisjuksköterskor , in Switzerland Swiss certified anesthesiologist HF ), an anesthesiologist for several patients is available for complications. However, the practice of general anesthesia is viewed by the jurisprudence and specialist societies in Germany as a medical task, the transfer of which is not possible in key aspects.

Preparations

Preliminary talk and clarification

Anamnesis and physical examination form the basis of the preliminary discussion, whereby the anesthetist gets an idea of ​​the patient's state of health. In the case of previous illnesses, he may request further examinations in order to assess them and, if necessary, treat them. These can be laboratory tests or a 12-lead ECG lead , ergometry , echocardiography or lung function test . The patient's long-term medication may be changed before the procedure, especially for anticoagulant drugs .

The patient must consent to the performance of general anesthesia as a medical intervention in the body's integrity , if he is able to do so. In the case of adults who are unable to make a decision, this must be done by a legitimate representative, who can be a court-appointed supervisor or an authorized representative appointed by the patient by means of a health care proxy. In the case of children, the legal guardians agree. In Germany, children up to the age of 14 are considered incapable of giving consent ; from 14 to 18 years of age they can give their own consent if the informing doctor has the impression that they have sufficient psychosocial maturity. In order for the patient to have an overview of the scope of his consent and to be able to give legally effective consent ( informed consent ), the anesthetist must provide a medical explanation of the risks and alternatives to general anesthesia. This must be done in good time, usually at least the day before. For interventions performed on an outpatient basis, information and consent are permitted on the day of the operation. In the case of emergency interventions or in the emergency medical service, the doctor can initiate general anesthesia in accordance with the presumed patient's wishes even if prior clarification was not possible.

sobriety

Before a planned procedure, you must abstain from food in order to avoid the gastric contents flowing back or vomiting and their penetration into the lungs ( aspiration ) during induction of anesthesia, as the anesthetics block the esophagus (closure force of the upper esophageal sphincter) and the patient's protective reflexes (Coughing, swallowing, choking). The professional societies recommend a fasting of six hours for solid foods, for clear liquids such as water or coffee with less than a fifth of milk two hours are sufficient to ensure that the stomach is emptied. Children should be breastfed four hours before the procedure. By administering a clear, carbohydrate-containing oral solution , which is still not routine, possibly can be reduced thirst, anxiety and postoperative nausea.

Various pre-existing conditions can lead to a delay in gastric passage, in other patient groups there is no sobriety in principle. In these cases, a modified, rapid induction of anesthesia ( Rapid Sequence Induction , see below) is carried out with the aim of reducing the risk of aspiration.

smoking ban

The intake of nicotine has various negative effects on the body and thus increases the risk of complications in the cardiovascular and pulmonary system during an operation. Wound infections can occur more frequently. According to current knowledge, there does not seem to be an increased risk of stomach problems or aspiration during anesthesia, as the gastric sphincter normalizes five to eight minutes after the last smoking. A planned operation therefore does not have to be postponed due to recent nicotine consumption. However, smoking should be stopped as early as possible before surgery. Just a few hours improve the oxygen content of the blood by reducing the carbon monoxide in the blood. The assumption that if you were forced to abstain from nicotine shortly before the operation caused stress, which itself leads to complications, seems to be unfounded according to the latest findings.

Preparation and induction of anesthesia

If necessary, premedication is administered on the morning of the operation for planned interventions , the main goal of which is an anxiolytic effect ( anxiolysis ). Today, benzodiazepines are mainly used as tablets or juice ( per os ). In addition, if there are special risks, other means are prescribed, for example to reduce gastric acid production or to prevent allergic reactions. For children, rectal (administration through the anus) or nasal administration (atomization with special syringes) of the active ingredients is possible. The previously practiced intramuscular premedication (injection into a skeletal muscle) is no longer common. In addition, local anesthesia of the skin with a plaster or a cream ( lidocaine / prilocaine mixture, product name EMLA ) is often performed in the area of ​​the planned venipuncture (back of the hand, elbow) in children .

Preoxygenation with a tight-fitting ventilation mask before induction of anesthesia

The patient's identity, procedure, and other items on the WHO Surgical Safety Checklist are checked prior to induction of anesthesia .

The intravenous induction ( induction ) of general anesthesia takes place after the monitoring measures have been implemented and an access route to the infusion has been placed . This is usually a peripheral venous catheter , possibly a central venous catheter in the case of an intensive care patient, and in an emergency it may be an intraosseous access . By holding a ventilation mask in front of the patient, oxygen is supplied (see the following section on airway management and ventilation ). After intravenous administration of an analgesic and a hypnotic, the patient falls asleep. By stopping the respiratory drive, it is necessary to secure the airways and ventilation. The choice and dosage of the active ingredients is made in relation to the type and duration of airway protection and the operation as well as the patient's age, weight and previous illnesses. If endotracheal intubation is performed or the patient is operated on in the abdominal cavity, a muscle relaxant is also administered during induction.

Alternatively, anesthesia can be induced by inhalation , by inhaling an inhalation anesthetic through a mask. This is mainly used in children who cannot tolerate the puncture of a vein while awake despite previous premedication. After the anesthetic gas has been flooded in, a venous access is established and the general anesthesia is completed with injected anesthetics in the sense of a balanced anesthesia.

The rapid sequence induction (RSI) is a special type of anesthesia. It is used when the patient is at increased risk of pulmonary aspiration , which is the penetration of stomach contents into the airways. The RSI is used for non-fasting patients, advanced pregnancy , illnesses or injuries to the gastrointestinal tract and emergency patients with injuries . The purpose of RSI is to keep the time span from loss of consciousness (with the suspension of protective reflexes such as swallowing and coughing) to securing the airway from rising stomach contents by means of endotracheal intubation as short as possible ( rapid sequence induction : "rapid induction of anesthesia") . For this purpose, various processes of induction of anesthesia are modified: the upper body can be positioned differently, a constant suction facility can be kept ready or fast-acting muscle relaxants such as succinylcholine or rocuronium can be used. Previously, a pressure on the larynx (was Krikoiddruck according Sellick ) exerted. However, the usefulness of an RSI, especially cricoid pressure, is controversial. According to the standards of evidence-based medicine , a reduction in the aspiration rate or mortality from it has not been proven.

Airway management and ventilation

The administration of the hypnotic and analgesic reduces or eliminates the patient's respiratory drive, and the use of muscle relaxants also switches off the respiratory muscles. To ensure that the body, especially the brain, is supplied with oxygen, the patient's airway must be secured. In order to gain time for this, an enrichment of oxygen in the body is carried out beforehand by holding a mask ( pre-oxygenation ). After the airway has been secured, the patient is ventilated with the anesthesia machine , usually with a controlled form of ventilation. Depending on the procedure, different variants of airway management are carried out:

(Endotracheal) tube

Laryngeal mask with a tube for a nasogastric tube

• In the case of short, uncomplicated interventions, oxygen may only be supplied with a ventilation mask and bag (mask anesthesia).
• For major interventions, the classic method of securing the airway ( gold standard ) is endotracheal intubation , in which a ventilation hose ( tube ) is inserted through the mouth and larynx (alternatively via the nose or via a tracheostoma ) into the trachea ( intubation anesthesia , ITN, rarely also called intubation anesthesia ). This is usually done with a direct view of the vocal folds (direct laryngoscopy) , for which the epiglottis is lifted with a laryngoscope . As the tube is sealed by an inflatable block cuff in the windpipe, this procedure largely provides protection against aspiration of stomach contents. Intubation is used for interventions in the body cavities or for corresponding risks to the patient, in particular it is absolutely necessary for rapid sequence induction . In cases where difficult intubation is to be expected, the tube can be inserted endoscopically under fiberoptic control . For interventions in the chest there are double lumen tubes with which separate ventilation of the lungs is possible.
• For superficial interventions and patients without risk factors, the larynx mask (LMA) has been used as an alternative since the 1980s . This is placed in the patient's throat so that its opening is in front of the entrance to the larynx. The seal is made by a plastic bead. Complications of intubation such as injuries to teeth or soft tissue are largely avoided when using the laryngeal mask, but the protection against aspiration is less. There are different variants of the laryngeal mask, for example with the option of inserting an additional gastric tube or inserting an endotracheal tube through the mask. Alternatives are the laryngeal tube and the combined tube , which in principle function in the same way.

Maintenance of anesthesia

Anesthesia machine vaporizer with inhalation anesthetics

Maintaining general anesthesia is often done as balanced anesthesia . For this purpose, a general anesthetic (e.g. by continuously adding inhalation anesthetics to the breath) is administered in combination with single doses or continuous doses of analgesics and muscle relaxants via the venous access. In the case of total intravenous anesthesia , on the other hand, maintenance takes place exclusively through continuous administration of anesthetic, usually using syringe pumps. Pure inhalation anesthesia (with the addition of laughing gas) is possible, but not very common.

The anesthetist reacts to changes in the operation during anesthesia; if there is a strong pain stimulus, the analgesia must be deepened. The assessment of the depth of anesthesia and control of the medication administration is carried out using clinical parameters (blood pressure, heart rate, lacrimation, sweating, pupil size, pupil reflex, movement reactions) and possibly using monitoring systems that measure and display electrical brain activity ( electroencephalography , acoustic evoked potentials ), or by measuring the concentration of inhalation anesthetics in the exhaled air. Every patient who has been given a muscle relaxant is monitored using relaxometry .

The anesthetist is responsible for maintaining the elementary body functions ( breathing , circulation , metabolism , fluid , electrolyte and acid-base balance , coagulation system ) of the patient for the duration of the entire procedure. At the same time, he performs diagnostics and treatment of complications that may result from surgery, anesthesia procedures and previous illnesses of the patient. By infusion therapy blood loss and fluid deficits of patients are compensated and may transfused blood component . Furthermore, all important drugs for the treatment of various complications (including circulatory disorders, narrowing of the bronchi, allergies) are available.

Anesthesia diversion

After completing the procedure, the general anesthesia is diverted. In order to discharge the anesthesia , the anesthetist stops supplying the anesthetics and the patient wakes up after the active substances have been broken down or exhaled. The prerequisite is that muscle relaxants are largely broken down ( adequate neuromuscular function ). If necessary, their effect can be canceled ( antagonized ). Adequate analgesia should also be ensured. The patient should be normothermic and the checklist should have gone through the main points at the sign out before leaving the operating room. After the patient has started to breathe adequately spontaneously and defensive reflexes are present (swallowing, coughing), the tube or larynx mask is removed ( extubation ). Both agitated awakening (emergence delirium) and delayed awakening behavior are possible.

Post-operative monitoring

Monitoring a patient in the recovery room

The postoperative monitoring following the operation and anesthesia is carried out in the recovery room for routine interventions , before the patient is released to the normal ward or home for outpatient interventions . Seriously ill or injured patients may be admitted to an intensive care unit , possibly with continued ventilation and sedation. The recovery room is usually supervised by one or more anesthesia nurses and must be equipped with appropriate monitoring devices. An anesthetist is also present or on call to intervene in the event of complications.

The patient remains in the recovery room until he is fully awake again, is in full possession of his protective reflexes and no respiratory and circulatory complications are to be expected. The vital parameters (blood pressure, pulse, breathing) as well as excretions ( urine , stool ) and drainage systems are monitored . A central therapeutic goal in the postoperative phase is pain therapy with painkillers or the continuation of regional anesthesia procedures. The nausea caused by pain relief and the effects of general anesthesia is treated here as well as other postoperative problems.

Problems and Risks

"There should be no deaths due to anaesthesia."

"There should be no deaths from anesthesia."

- Sir Robert Reynolds Macintosh : 1949 (first professor of anesthesiology in Europe)

When assessing complications in the course of an operation, the effects of the operation, problems with performing anesthesia and previous illnesses of the patient must be taken into account. It is not always possible to make a clear distinction between these factors. The mortality rate from the sum of these factors is summarized as perioperative mortality , although the recorded period is not uniformly defined perioperatively (“as part of an operation”). Figures on the incidence of complications and mortality from surgery vary widely. The causes are a lack of uniform definitions, different study populations and different observation periods.

The mortality during an operation (perioperative mortality) correlates with the health status of the patient, which is expressed by the ASA status . For a largely healthy patient (ASA 1–2) this is statistically 0.05–0.5%, while it is significantly higher for patients with severe previous illnesses (4.40% for ASA-3 patients, up to 25% at ASA 4). The risk of complications also increases with age. The mortality ( mortality ) or permanent damage ( morbidity ) primarily caused by the anesthetic procedure make up only a small proportion of these cases. In large, retro or prospective studies it is now 0.001 to 0.014% (1–14 / 100,000 anesthetic procedures), compared to around 0.037% in 1954. In a patient without significant previous illnesses, the mortality rate is 0.4 / 100,000 anesthesia performed. A mathematical slight increase in the complication rates in recent years is due to the disproportionate increase in surgical interventions in very old or multimorbid patients .

The reduction in the risk over the last decades is improved monitoring capabilities, mainly routine use of pulse oximetry and capnography , and the development and establishment of systematic error reduction measures ( Specialist Standard , policies and guidelines , algorithms , simulator training , of The Helsinki Declaration for Patient Safety in Anaesthesiology with attributed to the use of checklists , lived error culture ). There are large variations in risk rates around the world; in developing countries they are many times higher.

Problems with securing the airway, inadequate care during anesthesia, inadequate treatment of cardiovascular complications, mix-up of medications and errors in preoperative assessment and patient preparation are the main causes of anesthesia-related mortality. The majority of these would be potentially avoidable.

Breathing disorders, problems with securing the airway

Difficulties or impossibility of securing the airway ("difficult airway securing") are an important reason for the anesthesia-related mortality in the context of a surgical procedure. For such cases, algorithms have been developed which can be used to control the situation. A distinction is made between expected difficulties, which were recognized in the preliminary discussion, and unexpectedly difficult airway management.

Mastering difficult intubation using a video laryngoscope

If problems are expected, it is possible to insert a tube with a flexible device endoscopically controlled and under vision ( fiber-optic awake intubation ). This happens when spontaneous breathing is maintained (with local anesthesia of the throat and slight sedation of the patient) in order to ensure the oxygen supply. In the event of unexpected problems with ventilation or intubation, a number of aids (other laryngoscope blades, video laryngoscope, laryngeal mask, laryngeal tube, combitube, etc.) are available to help you cope with the situation. If the patient cannot be supplied with oxygen, the surgical opening of the airways ( cricothyrotomy ) is the last option .

Under an aspiration means the penetration of foreign bodies into the lower respiratory tract. When performing anesthesia, it usually involves vomited or regurgitated food components and secretions from the stomach. This can lead to an obstruction of the airways, which can lead to pneumonia and acute lung failure . Attempts are made to reduce the risk of aspiration in endangered patients by modifying the induction of anesthesia (see above). After aspiration, the foreign materials are sucked endoscopically from the trachea and bronchi, as far as possible, and the patient is ventilated with pure oxygen. As a result, antibiotic therapy may be necessary. Most aspirations are benign; fatal outcomes are rare.

Under a bronchospasm is an acute narrowing of the bronchi , which is caused by a spasm of smooth muscle. Patients with previous lung diseases ( bronchial asthma , COPD , infections of the respiratory tract, nicotine abuse ) and a tendency to allergic reactions are at risk of bronchospasm . Manipulation in securing the airway or (too) shallow anesthesia can be the trigger. Increased ventilation pressures are necessary, the patient's exhalation is prolonged, and wheezing and humming over the lungs can often be auscultated . The treatment is carried out through an anesthetic deepening. Further therapy with bronchodilator agents (such as β2-sympathomimetics ) may be necessary. If an allergic reaction is suspected, it must be treated accordingly.

A laryngospasm is a spasmodic condition of the larynx muscles, so that the glottis is closed and breathing is no longer possible. Such a situation usually occurs during anesthesia discharge, when the tube is removed and there are secretions or blood residues in front of the larynx entrance, for example after interventions in ear, nose and throat medicine such as tonsillectomy . Laryngospasm can also develop during shallow anesthesia with a laryngeal mask or during anesthesia diversion in children. Oxygen deficiency ( hypoxia ) with cyanosis can quickly develop. The patient's breathing efforts are spasmodic and frustran a swing respiration occurs. Sometimes the resistance of the vocal folds can still be overcome with mask ventilation and oxygen can be supplied. Secretions must be aspirated from the throat area. If the laryngospasm does not resolve, it may be necessary to inject a fast-acting muscle relaxant ( succinylcholine ), which allows the muscles of the larynx to relax.

Cardiovascular disorders

The anesthetics inhibit the vegetative regulation of the blood vessels , in particular the arterioles , to varying degrees , which results in a widening of the vessels ( vasodilation ) and a drop in blood pressure ( hypotension ). The heart's beating power is also reduced (negative inotropy ). While this has little effect on healthy patients, pre-existing conditions of the cardiovascular system or a lack of fluids often have significant effects on blood pressure. The anesthetist therefore closely monitors the blood pressure, either with non-invasive blood pressure measurement at short intervals or by means of a pressure probe inserted into an artery (invasive blood pressure measurement), which enables continuous monitoring in real time for high-risk patients. The therapy of the drop in blood pressure is carried out by balancing the fluid balance by means of infusion as well as with vasoconstricting substances ( catecholamines ) such as noradrenaline , cafedrine-theodrenaline ( akrinor ) or ephedrine .

Cardiac arrhythmias are common during anesthesia, but only lead to serious complications in a very small number of patients and must then be treated with specific antiarrhythmic drugs or electrotherapy . Isolated extrasystoles often occur , even in patients with healthy heart.

An intraoperative myocardial infarction is feared , which can occur with pre-existing coronary artery disease due to stress on the body from surgical stress, blood loss and reduced blood flow to the heart muscle due to tachycardia or a drop in blood pressure. In the worst case, it can lead to cardiac arrest that requires resuscitation . To avoid this, a sufficient depth of anesthesia serves to dampen the vegetative nervous system and at the same time maintain sufficient arterial blood pressure. Pre-existing therapy for heart disease patients with beta blockers or acetylsalicylic acid (ASA) is generally continued today, although the latter has a slightly higher risk of bleeding. Exceptions in individual cases are interventions with the risk of uncontrollable bleeding, such as interventions inside the skull , the eye or the prostate .

In the worst case, various causes lead to cardiovascular arrest, which necessitates immediate resuscitation measures. Every time anesthesia is carried out, all human and material resources must therefore be available to adequately carry out advanced life support .

Intraoperative wakefulness

Awareness monitoring ( Bispectral Index Scale , BIS)

As intraoperative awareness ( awareness ) perceptions are referred to the patient during general anesthesia to which in retrospect a reminder there. Mostly these are individual words or sentences that were uttered in the presence of the patient. However, in some cases, pain, fear, panic, helplessness are also perceived. Although the majority of patients do not find awareness events to be stressful in retrospect, in individual cases there are also illnesses that require treatment and even post-traumatic stress disorder .

The frequency of awareness is given as 0.1–0.2%. Factors related to anesthesia that increase the risk of being awake are the use of muscle relaxants , difficult intubation with a prolonged phase of securing the airway, and shallow anesthesia due to previous cardiac diseases, patients with dehydration (injuries, blood loss during surgery) or technical defects, for example a pump malfunction when performing intravenous anesthesia . Operations with an increased risk of intraoperative wakefulness can be found in traumatology , cardiac surgery and obstetrics . Patient-related risk factors are abuse of alcohol , benzodiazepines or other psychotropic drugs as well as experiences of previous awareness , female gender and obesity .

In addition to observing the patient, technical monitoring systems are used to exclude wakefulness. These devices analyze the extent to which the electrical brain activity is suppressed (using electroencephalography ) or the patient's acoustic perception ability ( acoustic evoked potentials ). This raw data is analyzed by a computer and converted into dimensions. The effectiveness and the benefit (reduction of conscious memories, especially those with consequences that require treatment) are, however, controversial. The use of such devices is therefore not part of routine monitoring in all clinics and is not unreservedly recommended by specialist societies.

Allergic reaction

Allergic reactions during general anesthesia are rare events, the frequency of occurrence is given as 1: 3,500 to 1: 20,000. They are mostly caused by medication, in about 70% of the cases by muscle relaxants ( succinylcholine , rocuronium , atracurium ), in 10% by other anesthetics ( propofol , thiopental , opioids , local anesthetics) and in 8% by antibiotics , mostly β-lactams . In around 12% of the cases, latex in gloves or catheters is the allergen. Pathophysiologically, these are type 1 reactions according to Coombs and Gell , in which messenger substances such as histamine, leukotrienes and prostaglandins are released after allergen exposure and IgE- mediated binding to mast cells ; in addition, non-IgE-mediated reactions also play a role ( anaphylactoid reaction ).

The clinical picture is very variable and includes reddening of the skin ( urticaria ), narrowing of the bronchi ( bronchoconstriction ) and, in extreme cases, the breakdown of the circulatory system due to anaphylactic shock . The treatment includes, if possible, the interruption of the allergen supply as well as aggressive infusion and drug therapy ( adrenaline , corticosteroids , H ₁ and H ₂ antihistamines ). The triggering substance can be identified retrospectively through allergy tests (skin tests, serological examinations). The most important prophylactic measure is a careful review of the medical history prior to general anesthesia.

Malignant hyperthermia

The malignant hyperthermia is a rare life-threatening disease that occurs as a complication of general anesthesia in appearance. By administering triggering substances ( trigger : inhalation anesthetics and the muscle relaxant succinylcholine ), a metabolic derangement in the skeletal muscles is caused with a corresponding genetic predisposition at 1: 20,000 to 1: 60,000 anesthesia .

The symptoms are very variable and include stiff muscles, a racing heart, an increased production of carbon dioxide (CO ₂ ) and a rise in temperature up to hyperacidity of the body as well as metabolic and organ failure, which ultimately lead to death. Malignant hyperthermia can be effectively treated by immediately interrupting the supply of inhalation anesthetics and treating with the active ingredient dantrolene . With the introduction of dantrolene, the mortality rate could be reduced significantly - to below 5% - in the past.

If a predisposition to malignant hyperthermia is suspected, the in vitro contracture test and molecular biological methods are available to clarify this. In such cases, general anesthesia can also be carried out without triggering substances. If appropriate for the procedure, regional anesthesia procedures can also be used safely for patients at risk of MH.

Post-operative problems

Postoperative nausea and vomiting

Postoperative nausea and vomiting are side effects of general anesthesia that occur after awakening. The abbreviation PONV is also used in German-speaking countries for the English. used postoperative nausea and vomiting . The frequency ( incidence ) with normal balanced anesthesia in a mixed patient collective is 20–30%. Statistical risk factors for postoperative nausea are female gender, the occurrence during previous anesthesia or a known tendency to travel sickness , non-smoking status and a high need for opioid pain relievers following pain therapy. The therapy consists of the administration of a single antiemetic or a combination of several active substances. For this purpose include antihistamines , such as dimenhydrinate , neuroleptics such as droperidol , a 5-HT ₃ antagonist , a tropane alkaloid such as scopolamine , the corticosteroid dexamethasone or metoclopramide in question, whose effectiveness is well documented. The frequency and intensity of postoperative nausea and vomiting can be effectively reduced prophylactically by choosing a suitable anesthetic method. Avoiding inhalation anesthetics and nitrous oxide and instead administering propofol as part of purely intravenous anesthesia leads to a significant reduction in PONV. The risk-adapted prophylactic administration of antiemetics is also effective.

Hypothermia and postoperative tremors

As postanesthetic shivering ( shivering ) is called an involuntary, not suppressible tremors . On the one hand, the body tries to compensate for heat losses ( hypothermia ) that have arisen during the course of the operation, but on the other hand, other causes can also be responsible for the tremors. It occurs in 5-60 percent of patients. In addition to subjective discomfort, this can trigger complications of the cardiovascular system in previously ill patients. Treatment involves intravenous administration of clonidine or the opioid pethidine and external warming. As with any anesthesia, perioperative efforts are always made to prevent a drop in body temperature for other reasons. This is done through active prewarming prior to anesthesia and the warming up of infusions and rinsing solutions, heat pads and hot air blowers. Likewise, only a low fresh gas flow is used in general anesthesia in order to reduce the loss of heat through ventilation . The core body temperature of the patient is monitored by a temperature probe during interventions over half an hour of anesthesia.

Disorders of the cognitive brain functions

Disorders of the brain functions after an operation mostly affect older people. The postoperative delirium , which is noticeable hours to days after the intervention with disorders of consciousness, attention and orientation, is differentiated from the postoperative cognitive dysfunction , in which problems of the ability to remember, learn and concentrate arise after days / weeks to months . The causes of these disorders are not clear, current concepts describe the development as the sum of external influences (surgery, anesthesia, pain, effects of complications and previous illnesses, foreign environment), with individual resilience . However, the frequency of cognitive disorders in regional anesthesia procedures is comparable to general anesthesia.

The postoperative delirium (or delirium ) falls by disturbances of consciousness and attention and perception ( memory , orientation ) on. Psychomotor restlessness, sleep disorders and thinking disorders ( delusions, etc.) can also occur. The symptoms are extremely variable, even in the same person in the course of the disease. A hyperactive form, which is often easy to recognize and diagnose, is distinguished from the hypoactive form and a mixed form, which are often not recognized. The incidence in older patients is 5–15%, after hip operations and in cardiac surgery it is significantly higher (up to 60%). The consequences of delirium are a prolonged stay in hospital, an increased need for care and a higher mortality rate over time.

Anesthesia in veterinary medicine

In veterinary medicine, anesthesia differs in a number of ways from that performed in human medicine. There is no separate department for veterinary anesthesia at any of the five veterinary training centers in Germany; there are only a few federal states with a specialist veterinarian . Most surgical procedures do not have a separate anesthetist and the anesthesia is initiated and monitored by the operating veterinarian. The obligation to anesthetize in painful interventions is regulated by Section 5 of the Animal Welfare Act . In wild and zoo animals, dogs and cats, anesthesia can also be necessary for less painful interventions such as x-ray examinations , the insertion of a stomach tube, tartar removal, clipping, etc., if an animal does not tolerate such procedures.

A number of factors influence the performance of general anesthesia:

• Animal species differences : In veterinary practice, not only different animal species, but representatives of different vertebrate classes are presented. There are considerable differences here in the physiology , the pharmacokinetics of the anesthetics, the accessibility to blood vessels, intubation and the reaction to various manipulations. But even within a species there are sometimes considerable race differences.
• Pharmaceutical regulations : While active ingredients for human medicine can also be used in small animal medicine under certain conditions (→ therapy emergency ), only active ingredients approved for these animal species may be used in food-producing animals .
• Technical requirements : Many resident veterinarians do not have anesthesia and monitoring devices.
• Costs : Since animal health or operation insurance is rarely available, costs also play a not insignificant role. In addition to the actual anesthesia, if it is carried out, the monitoring of the vital functions will also be billed separately according to GOT.

In veterinary medicine, injection anesthesia are often combined with inhalation anesthesia. Mixtures of different active compounds are used predominantly, most often a combination of ketamine with a Thiazinderivat as xylazine ( Hellabrunner mixture ) or medetomidine (antagonized with the α ₂ -adrenoceptor - agonists Atipemazol), as well as propofol, optionally additionally benzodiazepines and opioids . Muscle relaxants are also used in veterinary medicine.

Inhalation anesthesia is mainly used in birds, pets and horses and is the method of choice for longer interventions and high-risk patients. Spontaneous breathing is predominantly used; controlled ventilation is usually only carried out for very long interventions, in thoracic surgery and in the event of anesthetic incidents. The only approved inhalation anesthetic is isoflurane .

Historical aspects

Mandrakes from the herbal book Gart der Gesundheit, printed in 1485

Antiquity to the Middle Ages

For the first time in literature, probably around 3500 BC. Chr., Mentioned is an "anesthetic for surgical purposes" in the Bible (Genesis 2.21). In ancient Greece, medicines called Nepenthes are said to have made surgical interventions possible, which could have been opium preparations. The Indian doctor Charaka described the intoxication of alcohol to induce numbness during operations. However, higher percentage alcoholic narcotics have only been available since the distillation of spirits by Taddeo Alderotti in the 13th century AD.

For centuries, major surgical interventions were considered to be measures in extreme emergency situations with a high mortality rate. Bleeding, infection and severe pain severely restricted its use. In order to be able to operate on the patient at all, he was painstakingly fixed with aids or shackles. In the course of time, plant extracts were also administered in all cultures to relieve pain, such as henbane , hellebore , opium poppy capsules , hemp and coca leaves as well as various alcoholic beverages. Even Hippocrates to v to 450th Have already carried out inhalation anesthesia using herbal vapors and the Chinese doctor Bian Que passed on oral anesthesia using alcohol and hemp extract (the Chinese doctor Hua Tuo , who died in 220 AD, also used alcohol with hemp extract).

In the medieval herbal medicine played Mandrake a special role, one placed with legends and myths associated plant, the analgesic effect was described in ancient times. Together with other substances (especially poppy sap, henbane and water hemlock as well as "hellebore" and arsenic compounds from the 13th century), mandrake has been used since the 9th century (as evidenced by the Bamberg antidotarium published by Henry Ernest Sigerist in 1923, around 880 ). used in "sleeping sponges" ( Spongia somnifera ), which, soaked with the extracts, were held in front of the patient's mouth and nose to "inhale" and the active ingredients were then absorbed in the digestive tract. In a Codex Monte Cassino from Italy from the 9th century, there is an instruction according to which sponges are dipped in an infusion of opium, thorn apple, mulberry juice, hand, mandragora and monkshood and then dried in order to be anesthetized when they are re-moistened Vapors from it causing inhalers. Sleeping sponge anesthesia was also described by the Salernitan doctor Copho (11th / 12th century) and by Ugo Borgognoni (13th century), Guy de Chauliac , Heinrich von Pfalzpaint and Hans von Gersdorff . Other methods of pain relief included ligating extremities or compressing the carotid arteries , which led to fainting.

All of these methods, which in principle were used up into the 18th century, were often ineffective and dangerous for the patient. The French surgeon Guy de Chauliac had already reported complications ( rush of blood , asphyxia and death) after the administration of anesthetics around 1300 . The lack of reliable methods of eliminating pain prevented the development of more complex surgical procedures.

Modern times

Around 1547 Paracelsus recommended the therapeutic use of ether for painful suffering. However, nothing is known about the use for inhalation anesthesia in humans of the drowsy effects he observed in chickens around 1540 of the diethyl ether produced by the Wittenberg physician and pharmacologist Valerius Cordus or first described as a synthetic product in 1546 before 1841. The substance, which was still called “sweet vitriol” at that time, was only given the name ether after 1729 (based on the spiritus vini aethereus by the German chemist August Sigmund Frobenius ). The fact that Ramon Lull discovered the anesthetic ether (sulfur or saltpeter ether, oleum vitrioli dulce ) in Spain as early as the 13th century cannot be proven from the sources. The Italian Giambattista della Porta published in 1562/1589 ( De soporiferis medicamentis in: Magiae naturalis , Volume 2, Chapter 20) on sleep sponge "inhalation anesthesia" with various soporific agents.

On October 13, 1804, the Japanese doctor Hanaoka Seishū performed anesthesia with a sleeping potion comparable to the formulations of the medieval sleep sponge anesthesia during a breast cancer operation.

Substances that form the basis of modern anesthesia were isolated as early as the 18th century. In 1772 Joseph Priestley discovered the laughing gas (nitrous oxide) that he had synthesized and in 1806 Friedrich Sertürner succeeded in isolating the morphine . Although the analgesic effect of these substances was recognized, for example by Humphry Davy that of the laughing gas that he also used for the treatment of toothache in 1798 (in the Pneumatic Institute ) and that he proposed for use in operations in 1800, there was no regular use in medicine. The observation that opium introduced into the bloodstream of dogs can numb them, however, was made by the inventor of intravenous injection Christopher Wren in 1665. One of the pioneers of intravenous anesthesia was Pierre-Cyprien Oré, who modified the syringe von Pravaz first used the chloral hydrate introduced by Oskar Liebreich in 1869 as an intravenous anesthetic for anesthetic purposes in people in 1872 .

Henry Hill Hickman (1800–1830) from Shifnal in Shropshire was able to show in 1824 that inhaled carbon dioxide gets into the bloodstream and thus laid the scientific foundation for modern inhalation anesthesia.

Development of modern general anesthesia

Daguerreotype of the procedure recreated for the photographers Southworth & Hawes in the operating room in Boston, which later became known as the “ Ether Dome ”.

In January 1842, the chemistry student William E. Clarke (1819–1898) administered ether to a patient of the dentist Elijah Pope to relieve pain during tooth extraction. The doctor Crawford Williamson Long had also used ether to eliminate pain during surgical interventions on March 30, 1842 and removed a tumor from a patient's neck painlessly, using a towel soaked with ether for anesthesia. But he failed to publish it. Horace Wells , a dentist from Hartford (Connecticut) , USA, observed on December 10, 1844 the analgesic effect of nitrous oxide by chance in an application made by Gardner Quincy Colton for the entertainment of the public, as it was common at fairs at that time. He used it successfully in tooth extractions from 1844 , but a public demonstration at Massachusetts General Hospital in Boston in 1845 failed, and the patient screamed in pain.

The birth of modern anesthesia today is October 16, 1846, when the American dentist William Thomas Green Morton , after having been made aware of the possibility of anesthesia with sulfur ether by Charles Thomas Jackson , at the Massachusetts General Hospital of Harvard University ( Boston ) enabled the removal of a hemangioma on the neck of the patient Gilbert Abbot by inhaling ether fumes ( diethyl ether ) ("Ethereal Day of Boston"). Even if the patient moved during the procedure and made noises, he could not remember the procedure and did not report any pain, so that the implementation was considered successful. Morton is therefore attributed to the first publicly documented performance of general anesthesia. The presiding surgeon, John Collins Warren , said, “ Gentlemen, this is no humbug ! ”Carried away.

As a result, interest in the new method quickly spread in the scientific world, thanks mainly to the publications of Henry Jacob Bigelow . However, many skeptical surgeons expressed themselves critically, they viewed the "Yankee invention" as "cream puff egg" and "fraternization with quacking" and found that "... the ether that kills pain also kills life". The advocates of anesthesia prevailed, however, and knowledge about anesthesia, starting in England, spread rapidly in Europe over the next few years.

The first successful ether anesthesia in Germany was performed on January 24th, 1847 by Heinrich E. Weikert and Carl FE Obenaus in Leipzig.

Ether drip mask with interchangeable cloths according to Schimmelbusch

In the following decades, in addition to ether, other narcotics such as nitrous oxide and chloroform , known since 1831 and introduced as an anesthetic by James Young Simpson in 1847, were used. For this purpose, a wide variety of devices were developed for applying the substances, from drip masks (such as the Schimmelbusch mask, which was developed for hygienic considerations in the context of aseptics and introduced in 1890 as an ether drip mask (for ether drip anesthesia ) ) to the first simple anesthetic devices. Further anesthetics introduced in 1848 were the alcohol-chloroform-ether mixture (ACE) by the Englishman Thomas Nunneley and the chloroethyl by the German Heyfelder . Cyclopropane , discovered by the Austrian chemist August Freund in 1882 , was also used in humans after it was introduced to anesthesia in the USA in November 1928 by the chemist George HW Lucas, supported by the Canadian pharmacologist Velyien E. Henderson (1877-1945) first used in 1930 by Ralph M. Waters and Erwin R. Schmidt, who introduced this application with their publication published in 1934) for a time as a narcotic. Isopropyl chloride has been used since its introduction by Hans Killian in 1939. The similar to chloroform Trilen (trichlorethylene) was from 1941, introduced in England by C. Langton Hewer, often for several years using next nitrous oxide.

A gas inhaler designed in England by James Watt for Thomas Beddoes in 1795 and the laughing gas inhaler designed by Humphry Davy and presented in 1799 are part of the fundamentals of controllable anesthetic delivery via the airways .

The rectal ether anesthesia to be administered via the rectum, described by the Russian surgeon Nikolai Pirogoff in 1847, has not caught on.

Airway management methods such as the endotracheal intubation developed in Great Britain and the USA and first carried out in Germany in 1869 by Friedrich Trendelenburg (via a tracheotomy ) made it possible to completely take over the respiratory function and to precisely dose the anesthetic gases. The Scot William Macewen established in 1878 the peroral (carried out through the mouth) introduction of the ventilation hose (tube). Intubation anesthesia was a prerequisite for the development of interventions in the body cavities, which are otherwise hardly possible. A direct view of the larynx during endotracheal intubation was first made possible by the laryngoscope constructed in 1895 by the German ear, nose and throat doctor Alfred Kirstein .

Developments in the 20th Century

In the 20th century, a large number of technical processes and procedures were developed that made performing general anesthesia a largely safe routine procedure. In their entirety, they enable operations that are routine surgical procedures today, but were not yet possible with simple ether drip anesthesia.

To avoid or reduce the undesirable side effects of anesthesia, patients are usually given premedication prior to anesthesia . This type of pretreatment began around 1900 when the German doctor Schneiderlein first proposed the administration of morphine and scopolamine.

One of the first scientific theories about the mode of action of narcotics and also a step in the direction of modern anesthesiology was the lipid theory established in 1901 by Hans Horst Meyer and Ernst Overton .

From 1923 (WE Brown) on, ethene, which was discovered in the 18th century, was used for ethylene anesthesia for a while and in 1918 by Arno B. Luckhardt as anesthetically effective. Also in 1923, the Würzburg gynecologist Carl Joseph Gauß and the Heidelberg pharmacologist Hermann Wieland (1885–1929) introduced narcylene anesthesia using ethyne . Both substances were inhaled.

Sleeping pills from the group of barbiturates have been used to induce anesthesia intravenously since the beginning of the 20th century . The first barbiturate, veronal, was available from 1903 after synthesis by the German chemist and Nobel Prize winner Emil Fischer . The German doctor Hellmut Weese introduced the barbiturate Evipan in 1932 . The intravenous ether anesthesia, first successfully used by Ludwig Burkhardt in Würzburg in 1909, and the intravenous narcotic Hedonal , which the Russians Nicholas Krawkow and Sergei Fedoroff had developed for the first time in 1909 , as well as that in 1926 by the surgeon Otto Butzengeiger and Fritz Eichholtz , did not gain acceptance introduced Avertin and the Pernocton , introduced by Richard Bumm in 1927 as an intravenous narcotic, disappeared from the market. Propanidide ( Epontol ), introduced in Germany in 1963 by R. Hiltmann, H. Wollweber, W. Wirth and F. Hoffmeister, was one of the first short-acting intravenous narcotics . Remifentanil was introduced in Germany in 1996 .

From 1910 Maximilian Neu, with the help of Rudolf Gottlieb and Walter Madelung in Germany, had a modern gas mixer , a nitrous oxide-oxygen anesthesia machine with rotameter , available and in 1914 Richard Foregger had an anesthesia machine with a flow meter (a water flow meter ) constructed. To remove the anesthetic system used for the first time Dennis E. Jackson (1878-1980) in 1915 to be any common today anesthesia machine (and also oscillating or circulating in the "circle part," exhaled by the patient carbon dioxide rebreathers ) belonging carbon dioxide absorber. (Henry) Edmund Boyle (1875–1941) constructed a nitrous oxide-oxygen-ether anesthetic machine in 1917 in England. In 1924 Ralph M. Waters introduced a "pendulum system" and in 1930 a "circle system" constructed from 1928 by Brian C. Sword and Richard von Foregger was made known. The first permanent anesthesia system in Germany was designed by Hans Killian at the University Clinic in Freiburg im Breisgau, where it was installed with gas tanks, oxygen, carbon dioxide and a triple suction pump.

The anesthesia machines for ventilation and the administration of anesthetics via the airways were developed from simple drip masks to the rebreathing machines with circular parts that are common today . In these, the breathing air circulates between the device and the patient, while only a small amount of fresh gas is added, which reduces heat and fluid losses and the consumption of anesthetic gas. Monitoring, which initially only consisted of simple pulse keying, now includes a large number of parameters.

Modern anesthesia monitor with a large number of monitored parameters

While intubation (generally via the mouth or, more rarely, the nose) quickly established itself in the United States and the United Kingdom after endotracheal anesthesia was widely introduced by Ivan Magill and Stanley Rowbotham (1890-1979) in 1920 it was initially viewed critically in continental Europe. Despite scientific advocates such as Franz Kuhn , who had already published his monograph on peroral intubation in 1911, it was vigorously rejected by surgeons such as Ferdinand Sauerbruch, among others , which led to the Anglo-Saxon countries taking the lead in developing modern anesthesia.

Complete muscle relaxation , which is often necessary in the context of anesthesia (when inserting the ventilation tube and many operations, especially abdominal surgery) , is made possible in modern anesthesia by using certain medications administered through the vein. After Arthur Läwen had already made his first clinical trials for the use of curare in 1910 and this muscle relaxant was used by the Canadian anesthetists on January 23, 1942 with the use of Tubocurare (in the preparation Intocostrin from Squibb ) during an appendectomy under cyclopropan anesthesia at the Homoepathic Hospital of Montreal Harold R. Griffith and G. Enid Johnson had been introduced into clinical practice, the Italian pharmacologist Daniel Bovet discovered between 1946 and 1950 the muscle-relaxing effects of flaxedil (gallamine) and the succinylcholine that is still used today (developed in 1951 by Franz Theodor von Brücke , Otto Mayrhofer and M. Hassfurther in Austria the muscle relaxation with succinylcholine chloride and S. Thesleff in Sweden succinylcholine iodide). In 1992, Mivacurium , the first short-acting, non-depolarizing muscle relaxant approved for clinical use, was introduced. Rocuronium was introduced in 1995, about a year later Cis-Atracurium .

The inhalation anesthetic halothane , which offers advantages over ether, chloroform and other substances, was synthesized by Charles Suckling, J. Raventos and Michael Johnstone in England, tested pharmacologically and used clinically for the first time on January 20, 1956 by Johnstone in Manchester. Methoxyflurane ( penthrane ) was made known as another inhalation anesthetic in the USA in 1960 by JF Artusio and A. Van Poznak. Later, sevoflurane (Japan, 1990; since 1996, also in Germany), desflurane , add (from 1995 in Germany, USA, 1991).

Instead of causing a generally deep anesthesia inhalation anesthesia was in Belgium by P. mouth empty and J. De Castro in 1959 to avoid potential adverse effects of pure inhalation anesthesia, the Neuroleptanalgesia introduced. Here, a neuroleptic and a strong pain reliever are injected. The use of ketamine , which largely allows the protective reflexes to persist when creating a so-called dissociative anesthesia , has been part of the anesthesiological repertoire since its introduction ( e.g. as ketalar ) by G. Chen, G. Corssen and EF Domino in 1965.

The practice of anesthesia (who worked as anesthetists around 1920 - for example chaplains in the Juliusspital Würzburg ) experienced a professionalization in the second half of the 20th century as part of the establishment of the anesthesiology department . Together with a large number of technical developments and their routine clinical use (sensitive monitoring procedures such as pulse oximetry and capnometry, short-acting and easily controllable anesthetics, various instruments for coping with difficult airway management) and the establishment of guidelines, algorithms, simulator training, checklists, etc., general anesthesia reached their current status as a relatively low-risk routine procedure.

literature

• Georg Laux: General anesthesia. In: Rossaint, Werner, Zwissler (ed.): Die Anästhesiologie. General and special anesthesiology, pain therapy and intensive care medicine. 2nd Edition. Springer, Berlin 2008, ISBN 978-3-540-76301-7 , pp. 593-614.
• Hans Walter Striebel: The anesthesia: Basics and practice. 2nd Edition. Schattauer, 2010, ISBN 978-3-7945-2636-9 .
• Ludwig Brandt: Illustrated history of anesthesia. Wissenschaftliche Verlagsgesellschaft, Stuttgart 1997, ISBN 3-8047-1501-X .
• Richard J. Kitz, Leroy D. Vandam: A History and the Scope of Anesthetic Practice. In: Ronald D. Miller (Ed.): Anesthesia. 3 volumes, Churchill Livingstone, New York / Edinburgh / London / Melbourne 1981, 2nd edition ibid. 1986, ISBN 0-443-08328-2 , Volume 1, pp. 3–25.

Web links

Wiktionary: anesthesia  - explanations of meanings, word origins, synonyms, translations

• Ulf Glade: History of Anesthesia. The history of anesthesia from antiquity to the year 2000 .

Individual evidence

1. ↑ Kluge: Etymological dictionary of the German language. 24th edition
2. ↑ ^{a b} B. W. Urban, M. Bleckwenn: Concepts and correlations relevant to general anesthesia . In: Br J Anaesth. 2002 Jul; 89 (1), pp. 3-16. (Review: PMID 12173238 )
3. ↑ ^{a b c} H. A. Adams, E. Kochs, C. Krier: Today's anesthesia methods - attempt at a system. In: Anaesthesiology, Intensive Care Medicine, Emergency Medicine, Pain Therapy. Volume 36, 2001, pp. 262-267. doi: 10.1055 / s-2001-14470 , PMID 11413694 .
4. ^ I. Rundshagen: Intraoperative alertness. In: Anästh Intensivmed. 2009 50, pp. 296-308. Review.
5. ↑ ^{a b} Continuum of depth of sedation, definition of general anesthesia, and levels of sedation / analgesia. American Society of Anesthesiologists Standards, Guidelines, and Statements, October 27, 2004.
6. ^ GH Montgomery, D David, G Winkel, JH Silverstein, DH Bovbjerg: The effectiveness of adjunctive hypnosis with surgical patients: a meta-analysis. In: Anesth Analg. , 2002 Jun; 94 (6), pp. 1639-1645, PMID 12032044 .
7. ↑ AH Wobst: Hypnosis and surgery: past, present, and future . In: Anesth Analg. 2007 May; 104 (5), pp. 1199-1208. Review. PMID 17456675 .
8. ↑ Richard J. Kitz, Leroy D. Vandam (1986), pp. 4-8 ( The Rise of Inhalation Anesthesia ).
9. ↑ Striebel: The anesthesia: Basics and practice. 2010, pp. 108-203.
10. ^ NP Franks: Molecular targets underlying general anesthesia. In: Br J Pharmacol . 2006 Jan; 147 Suppl 1, pp. S72-81. Review. PMID 16402123 .
11. ↑ VS Eckle, C. Hucklenbruch, SM Todorovic: What do we know about anesthetic mechanisms? Unconsciousness, immobility, and amnesia. In: Anaesthesiologist. 2009 Nov; 58 (11), pp. 1144-1149. PMID 19760252 . PMC 2823130 (free full text)
12. ↑ ^{a b} Ellinger, Osswald, Genzwürker (ed.): Course book emergency medicine. Deutscher Ärzte-Verlag, 2007, ISBN 978-3-7691-0519-3 , pp. 623ff.
13. ↑ ^{a b} Equipment of the anesthesiological workstation. Update of the guidelines of the German Society for Anesthesiology and Intensive Care Medicine and the Professional Association of German Anesthesiologists. Anästh Intensivmed 36 (1995) pp. 250-254.
14. ^ W. Buhre, R. Rossaint: Perioperative management and monitoring in anaesthesia. In: Lancet. 2003 Nov 29; 362 (9398), pp. 1839-1846. Review. PMID 14654324 .
15. ↑ Standards for basic anesthetic monitoring. American Society of Anesthesiologists, October 25, 2005.
16. ↑ Admissibility and limits of the parallel procedures in anesthesiology ("Münster Declaration II 2007"). In: Anästh Intensivmed. 2007; 48: 000-000 ( full text )
17. ^ M. Andreas: Delegation of medical activities to non-medical staff. In: Anästhesiol Intensivmed. 2008, 11, pp. 593-601.
18. ↑ B. Zwissler u. a. Preoperative evaluation of adult patients before elective, non-cardiac surgery. DGAInfo; Supplement No. 8 - 2010. Joint recommendation of the German Society for Anaesthesiology and Intensive Care Medicine, the German Society for Internal Medicine and the German Society for Surgery. In: Anästh Intensivmed. 2010, 11: pp. 788-796.
19. ↑ Rossaint, Werner, Zwissler (Ed.): Die Anästhesiologie. General and special anesthesiology, pain therapy and intensive care medicine. 2nd Edition. Springer, Berlin 2008, ISBN 978-3-540-76301-7 , pp. 1720-1726.
20. ↑ A. Ng, G. Smith: Gastroesophageal reflux and aspiration of gastric contents in anesthetic practice . In: Anesth Analg. 2001 Aug; 93 (2), pp. 494-513. Review. PMID 11473886 .
21. ↑ German Society for Anaesthesiology and Intensive Care Medicine (DGAI) and Professional Association of German Anesthetists (BDA): Preoperative sobriety requirement for elective interventions. In: Anaesthesiol Intensivmed. 2004; 45, p. 722.
22. ↑ American Society of Anesthesiologists Task Force on Preoperative Fasting: Practice guidelines for preoperative fasting and the use of pharmacologic agents to reduce the risk of pulmonary aspiration: application to healthy patients undergoing elective procedures. In: Anesthesiology. 1999, 90, pp. 896-905.
23. ^ ^{A b c} G. Weiß, M. Jacob: Preoperative sobriety 2008. In: Anaesthesist. 2008, 57, pp. 857-872 Review.
24. ^ Opinion on preoperative abstinence from nicotine * K. Waurick · H. Van Aken, resolution of the DGAI Executive Committee of March 7, 2013, Anästh Intensivmed 2013; 54: 488 Aktiv Druck & Verlag GmbH
25. ↑ D. Steinmann, HJ Priebe: Krikoiddruck. In: Anaesthesiologist. 2009 Jul; 58 (7), pp. 695-707. Review. PMID 19554271 ; on this: A. Timmermann, C. Byhahn: Cricoid pressure: protective handle or established nonsense? (Editorial). In: Anaesthesiologist. 2009 Jul; 58 (7), pp. 663-664. PMID 19547935 .
26. ↑ DT Neilipovitz, ET Crosby: No evidence for Decreased incidence of aspiration after rapid sequence induction . In: Can J Anaesth. 2007 Sep; 54 (9), pp. 748-764. Review. PMID 17766743 .
27. ↑ ^{a b c} Airway Management. Guideline of the German Society for Anaesthesiology and Intensive Care Medicine. In: Anästh Intensivmed. 45 (2004), pp. 302-306.
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29. ^ GN Schmidt, J. Müller, P. Bischoff: Measurement of the depth of anesthesia. In: Anaesthesiologist. 2008 Jan; 57 (1), pp. 9-30, 32-36. Review. PMID 18209969
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32. ↑ JM Hunter: The recovery period . In: Br J Anaesth. 2005 Jul; 95 (1), pp. 1-2. PMID 15941733 .
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36. ↑ ^{a b c} R.S. Lagasse: Anesthesia safety: model or myth? A review of the published literature and analysis of current original data . In: Anesthesiology. 2002 Dec; 97 (6), pp. 1609-1617. Review. PMID 12459692
37. ^ ^{A b c} A. Lienhart, Y. Auroy, F. Péquignot, D. Benhamou, J. Warszawski, M. Bovet, E. Jougla: Survey of anesthesia-related mortality in France. In: Anesthesiology. 2006 Dec; 105 (6), pp. 1087-1097. PMID 17122571 .
38. ↑ MS Arbous, DE Grobbee, JW van Kleef, JJ de Lange, HH Spoormans, P. Touw u. a .: Mortality associated with anesthesia: a qualitative analysis to identify risk factors. Anaesthesia 2001; 56 (12), pp. 1141-1153. PMID 11736769 .
39. ↑ Y. Kawashima, S. Takahashi, M. Suzuki, K. Morita, K. Irita, Y. Iwao, N. Seo, K. Tsuzaki, S. Dohi, T. Kobayashi, Y. Goto, G. Suzuki, A Fujii, H. Suzuki, K. Yokoyama, T. Kugimiya: Anesthesia-related mortality and morbidity over a 5-year period in 2,363,038 patients in Japan. In: Acta Anaesthesiol Scand. 2003 Aug; 47 (7), pp. 809-817. PMID 12859300
40. ↑ Striebel: The anesthesia: Basics and practice. 2010, p. 804 f.
41. ↑ Striebel: The anesthesia: Basics and practice. 2010, p. 802 f.
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43. ↑ ^{a b c} U Linstedt, H Wulf: EEG measurement to avoid awareness - benefit or luxury? Anesthesiol Intensivmed Emergency Med Schmerzther. 2008 May; 43 (5): 384-91. PMID 18464217
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45. ↑ Practice Advisory for Intraoperative Awareness and Brain Function Monitoring. A Report by the American Society of Anesthesiologists Task Force on Intraoperative Awareness. In: Anesthesiology. 2006; 104, pp. 847-864. PMID 16571982
46. ↑ DL Hepner, MC Castells: Anaphylaxis during the perioperative period . In: Anesth Analg. 2003 Nov; 97 (5), pp. 1381-1395. Review. PMID 14570656 .
47. ↑ PM Mertes, MC Laxenaire: Allergy and anaphylaxis in anesthesia. In: Minerva Anestesiol. 2004 May; 70 (5), pp. 285-291. Review. PMID 15181405 minervamedica.it  ( Page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice. (PDF; 60 kB).  
48. ↑ H. Rosenberg, M. Davis, D. James, N. Pollock, K. Stowell: Malignant hyperthermia. In: Orphanet J Rare Dis. 2007 Apr 24; 2, p. 21. Review. PMID 17456235 .
49. ↑ Recommendation for the therapy of malignant hyperthermia. Decision of the DGAI Executive Committee. (revised version 2008) ( PDF, 108 kB )
50. ↑ Robert M. Knapp: Prophylaxis for PONV etherweb.bwh.harvard.edu (PDF; 7.1 MB).
51. ↑ D. Rüsch, LH Eberhart, J. Wallenborn, P. Ill people: Nausea and vomiting after operations under general anesthesia: an evidence-based overview of risk assessment, prophylaxis and therapy . In: Dtsch Arztebl Int. 2010 Oct; 107 (42), pp. 733-741. PMID 21079721 .
52. ^ LH Eberhart, F. Döderlein, G. Eisenhardt, Peter Kranke, DI Sessler, A. Torossian, H. Wulf, AM Morin: Independent risk factors for postoperative shivering . Anesth Analg. 2005 Dec; 101 (6): 1849-57. PMID 16301273 .
53. ↑ P. Alfonsi: Postanaesthetic shivering. Epidemiology, pathophysiology and approaches to prevention and management.  ( Page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice. (PDF) In: Minerva Anestesiol. 2003 May; 69 (5), pp. 438-442. Review. PMID 12768180 .  
54. ↑ Peter Kranke, LH Eberhart, Norbert Roewer, MR Tramèr: Pharmacological treatment of postoperative shivering: a quantitative systematic review of randomized controlled trials . In: Anesth Analg. 2002 Feb; 94 (2), pp. 453-460. PMID 11812718 .
55. ↑ ^{a b} J.H. Silverstein, M. Timberger, DL Reich, S. Uysal: Central nervous system dysfunction after noncardiac surgery and anesthesia in the elderly . In: Anesthesiology. 2007 Mar; 106 (3), pp. 622-628. Review. PMID 17325520 .
56. ^ CD Hanning: Postoperative cognitive dysfunction . In: Br J Anaesth. 2005 Jul; 95 (1), pp. 82-87. Review. PMID 15640305 .
57. ↑ M. Coburn, A. Fahlenkamp, ​​N. Zoremba, G. Schaelte: Postoperative cognitive dysfunction: incidence and prophylaxis. In: Anaesthesiologist. 2010; 59, pp. 177-185. PMID 20084351 .
58. ↑ GL Bryson, A. Wyand: Evidence-based clinical update: general anesthesia and the risk of delirium and postoperative cognitive dysfunction . In: Can J Anaesth. 2006 Jul; 53 (7), pp. 669-677. Review. PMID 16803914 .
59. ↑ ^{a b} T.N. Robinson, B. Eiseman: PMC 2546478 (free full text) Postoperative delirium in the elderly: diagnosis and management. In: Clin Interv Aging. 2008; 3 (2), pp. 351-355. Review. PMID 18686756 .
60. ↑ CL Wu, W. Hsu, JM Richman, SN Raja: Postoperative cognitive function as an outcome of regional anesthesia and analgesia. In: Reg Anesth Pain Med. 2004; 29, pp. 257-268. PMID 15138912 .
61. ↑ ^{a b c} Wolf Erhardt: Anesthesia and analgesia in small and domestic animals as well as in birds, reptiles, amphibians and fish . Schattauer Verlag 2004, ISBN 3-7945-2057-2 .
62. ↑ ^{a b} Martin Kramer: Compendium of General Veterinary Surgery. Schlütersche 2004, ISBN 3-87706-743-3 , p. 144.
63. ↑ Michaele Alef, Gerhard Schmidt-Oechtering: Practice of inhalation anesthesia . Enke 2003, ISBN 3-8304-1015-8 .
64. ^ Rudolf Frey , Otto Mayrhofer , with the support of Thomas E. Keys and John S. Lundy: Important data from the history of anesthesia. In: R. Frey, Werner Hügin , O. Mayrhofer (Ed.): Textbook of anesthesiology and resuscitation. Springer, Heidelberg / Basel / Vienna 1955; 2nd, revised and expanded edition. With the collaboration of H. Benzer. Springer-Verlag, Berlin / Heidelberg / New York 1971. ISBN 3-540-05196-1 , pp. 13-16, here: p. 13.
65. ↑ Brandt: Illustrated history of anesthesia. Pp. 15-28.
66. ^ Rudolf Frey, Otto Mayrhofer: Important dates from the history of anesthesia. 1971, p. 13.
67. ↑ Gundolf Keil: Treatise on sleep-making pieces according to the Arabic way (Ars somnifera). In: Author's Lexicon . 2nd edition, Volume 9, Col. 997 f.
68. ↑ Wolfgang Wegner: Treatise on sleep-making pieces according to the Arabic way. In: Werner E. Gerabek, Bernhard D. Haage, Gundolf Keil, Wolfgang Wegner (eds.): Enzyklopädie Medizingeschichte. De Gruyter, Berlin / New York 2005, ISBN 3-11-015714-4 , p. 1407.
69. ^ Theodor Husemann : The sleep sponges and other methods of general and local anesthesia in the Middle Ages. A contribution to the history of surgery. In: German journal for surgery. Volume 42, 1896, pp. 517-596.
70. ↑ Christoph Weißer: Sleeping sponge. In: Werner E. Gerabek, Bernhard D. Haage, Gundolf Keil, Wolfgang Wegner (eds.): Enzyklopädie Medizingeschichte. Walter de Gruyter, Berlin and New York 2005, ISBN 3-11-015714-4 , p. 1299 f.
71. ^ Jürgen Müller : Pharmaca diabolica and Pocula amatoria. On the cultural history of the Solanaceae alkaloids atropine and scopolamine. In: Würzburg medical historical research. Volume 17, 1998, pp. 361-373, here: pp. 364 f.
72. ^ Rudolf Frey, Otto Mayrhofer: Important dates from the history of anesthesia. 1971, p. 13.
73. ↑ Axel W. Bauer : Copho. In: Lexicon of the Middle Ages . Volume 3, Munich / Zurich 1995, Col. 214.
74. ↑ Rudolf Creutz: The Magister Copho and his position in the high salerno. In: Sudhoff's archive. Volume 33, 1941, pp. 249-338.
75. ^ Gundolf Keil: Copho [Kopho]. In: Werner E. Gerabek u. a. (Ed.): Encyclopedia of medical history. De Gruyter, Berlin / New York 2005, ISBN 3-11-015714-4 , p. 271.
76. ↑ Cophonis Ars medendi. In: Salvatore de Renzi, Charles Victor Daremberg , August Wilhelm Henschel (ed.): Collectio Salernitana: ossia documenti inediti, e trattati di medicina appartenenti alla scuola medica Salernitana . 5 volumes, Tipografia del Filiatre-Sebezio, Naples 1852-1859; Reprint Bologna 1967 (= Biblioteca di storia della medicina. II, 1–5). Volume 4, pp. 415-438.
77. ^ Rudolf Frey, Otto Mayrhofer: Important dates from the history of anesthesia. 1971, p. 13.
78. ^ Bernhard Dietrich Haage: Medical Literature of the Teutonic Order in the Middle Ages. In: Würzburg medical history reports. Volume 9, 1991, pp. 217-231, here: pp. 224 f.
79. ↑ Brandt: Illustrated history of anesthesia. Pp. 29-35.
80. ^ Rudolf Frey, Otto Mayrhofer: Important dates from the history of anesthesia. 1971, p. 13.
81. ^ Rudolf Frey, Otto Mayrhofer: Important dates from the history of anesthesia. 1971, p. 13.
82. ^ Richard J. Kitz, Leroy D. Vandam: A History and the Scope of Anesthetic Practice. Volume 1, 1986, p. 4.
83. ^ Rudolf Frey, Otto Mayrhofer: Important dates from the history of anesthesia. 1971, p. 13 f.
84. ↑ Akira Hori, The first general anesthetic: 1804 in Japan , Dtsch Arztebl 1991; 88 (47): A-4151. Retrieved August 14, 2016.
85. ^ Rudolf Frey, Otto Mayrhofer: Important dates from the history of anesthesia. 1971, p. 14.
86. ↑ Brandt: Illustrated history of anesthesia. P. 49 f.
87. ↑ Ken True: The Age of Science: Sir Christopher Wren (1632-1723) .
88. ^ Richard J. Kitz, Leroy D. Vandam: A History and the Scope of Anesthetic Practice. 1986, pp. 4 and 11.
89. ^ Rudolf Frey, Otto Mayrhofer: Important dates from the history of anesthesia. 1971, p. 14.
90. ^ Richard J. Kitz, Leroy D. Vandam: A History and the Scope of Anesthetic Practice. In: Ronald D. Miller (Ed.): Anesthesia. 3 volumes, Churchill Livingstone, New York / Edinburgh / London / Melbourne 1981, 2nd edition ibid. 1986, ISBN 0-443-08328-2 , Volume 1, pp. 3–25, here: pp. 6–8.
91. ↑ Christoph Weißer: Anesthesia. In: Werner E. Gerabek, Bernhard D. Haage, Gundolf Keil, Wolfgang Wegner (eds.): Enzyklopädie Medizingeschichte . De Gruyter, Berlin 2005, ISBN 3-11-015714-4 , p. 54 f., Here: p. 54.
92. ^ RP Haridas: Photographs of Early Ether Anesthesia in Boston: The Daguerreotypes of Albert Southworth and Josiah Hawes. In: Anesthesiology. 2010 Jul; 113 (1), pp. 13-26. PMID 20526183 .
93. ↑ Ken True: Pioneer: Dr William E Clarke .
94. ^ Rudolf Frey, Otto Mayrhofer: Important dates from the history of anesthesia. 1971, p. 14.
95. ^ Richard J. Kitz, Leroy D. Vandam (1986), p. 6.
96. ↑ ^{a b c} Brandt: Illustrated history of anesthesia. Pp. 52-65.
97. ↑ ^{a b} L. Brandt, K.-H. Krauskopf: 150 years Anesthesia: "A discovery in surgery." . In: Dtsch Arztebl. 1996; 93 (45), pp. A-2957 / B-2293 / C-2089.
98. ^ Rudolf Frey, Otto Mayrhofer: Important dates from the history of anesthesia. 1971, p. 14.
99. ^ Robert Hirst: From Out of the Primordial Soup: A Brief History of Anesthesia. In: The Internet Journal of Anesthesiology. 2005; Volume 10, Number 1.
100. ↑ Brandt: Illustrated history of anesthesia. Pp. 67–77 (citations p. 67)
101. ↑ Brandt: Illustrated history of anesthesia. Pp. 78-96.
102. ^ Betty J. Bamforth: Cyclopropane Anesthesia: Its Introduction at Wisconson. In: J. Ruprecht, MJ van Lieburg, JA Lee, W. Erdmann (eds.): Anaesthesia. Essays on Its History. Springer, Berlin / Heidelberg 1985, ISBN 978-3-540-13255-4 , chapter 4.19.
103. ↑ Rudolf Frey, Werner Hügin, Otto Mayrhofer (Ed.): Textbook of Anaesthesiology. Springer, Berlin / Göttingen / Heidelberg 1955; Reprint Berlin / Heidelberg, ISBN 978-3-662-01557-5 , pp. 344–346 ( cyclopropane )
104. ↑ Cyclopropane anesthesia. In: Journal of the American Medical Association. 103 (13): 975-983.
105. ↑ G. Döderlein: Round table discussion: The possibilities to take away fear and pain from the woman giving birth. In: H. Runge, H. Naujoks (Ed.): Negotiations of the German Society for Gynecology. Thirty-first meeting held in Heidelberg from September 18 to 22, 1956. (= Archive for Gynecology. Volume 189). Scientific part. Springer, Berlin / Heidelberg 1957, ISBN 978-3-642-53808-7 , pp. 311-335, here: p. 327.
106. ^ Rudolf Frey, Otto Mayrhofer: Important dates from the history of anesthesia. 1971, p. 14 f.
107. ^ Thomas Beddoes, James Watt: Considerations on the Medicinal Use, and on the Production of Factitious Aires. J. Johnson, Bristol 1795.
108. ↑ Thomas E. Keys: The history of surgical anesthesia. Springer, Berlin / Heidelberg 1968, ISBN 978-3-540-04040-8 , p. 34 f.
109. ^ Rudolf Frey, Otto Mayrhofer: Important dates from the history of anesthesia. 1971, p. 14.
110. ↑ Andreas Vesalius made animal experiments with ventilation via endotracheal intubation as early as 1542 . Cf. Rudolf Frey, Otto Mayrhofer: Important data from the history of anesthesia. 1971, p. 13.
111. ^ Rudolf Frey, Otto Mayrhofer: Important dates from the history of anesthesia. 1971, p. 14.
112. ^ Rudolf Frey, Otto Mayrhofer: Important dates from the history of anesthesia. 1971, p. 14.
113. ↑ Ulf Glade: History of anesthesia .
114. ↑ www.researchgate.net: Arno B. Luckhardt .
115. ^ Rudolf Frey, Otto Mayrhofer: Important dates from the history of anesthesia. 1971, p. 15.
116. ^ Rudolf Frey, Otto Mayrhofer: Important dates from the history of anesthesia. 1971, p. 14 f.
117. ↑ www.gv-solas.de: Statement by the “Anesthesia and Analgesia” Committee of GV-SOLAS on the use of tribromoethanol (TBE, Avertin®, E107, Renarcol®, Byk 250) in laboratory animals. Historical background and area of ​​application . (PDF)
118. ↑ Richard Bumm: Intravenous anesthesia with barbituric acid derivatives. In: Results of surgery and orthopedics. Volume 29, 1936, pp. 372-414, here: p. 374.
119. ↑ Alan Dronsfield, Pete Ellis, John Prin: From Waterloo to thiopentone. The Early Chemical History of Intravenous Anesthesia. In: RSC Historical Group Newsletter. No. 67, Winter 2015, pp. 10–12.
120. ^ Rudolf Frey, Otto Mayrhofer: Important dates from the history of anesthesia. 1971, p. 15 f.
121. ↑ Michael Heck, Michael Fresenius: Repetitorium Anaesthesiologie. Preparation for the anesthesiological specialist examination and the European diploma in anesthesiology. 3rd, completely revised edition. Springer, Berlin / Heidelberg / New York et al. 2001, ISBN 3-540-67331-8 , p. 804.
122. ^ The Wood Library Museum: Jackson CO2 absorber .
123. ↑ See also Ulf Gade: History of Anesthesia .
124. ^ Rudolf Frey, Otto Mayrhofer: Important dates from the history of anesthesia. 1971, p. 15.
125. ↑ Josef Haupt: The history of the Dräger anesthetic machines. Volume I. 1970; 1st revised version, ed. from Drägerwerk AG, Rosenbauer and Solbach, Hamburg 1996, ISBN 3-926762-14-4 , p. 31 f. and 51.
126. ↑ Hans Killian: There is only God behind us. Sub umbra dei. A surgeon remembers. Kindler, Munich 1957; here: Licensed edition as Herder paperback (= Herder library. Volume 279). Herder, Freiburg / Basel / Vienna 1975, ISBN 3-451-01779-2 , pp. 87 f.
127. ↑ Gail McLachlan: Sir Ivan Magill KCVO, DSc, MB, BCh, BAO, FRCS, FFARCS (Hon), FFARCSI (Hon), DA, (1888-1986). In: Ulster Medical Journal. Volume 77, No. 3, 2008, pp. 146–152, PMC 2604469 (free full text)
128. ^ Rudolf Frey, Otto Mayrhofer: Important dates from the history of anesthesia. 1971, cited here: p. 15.
129. ^ Franz Kuhn: The oral intubation. A guide to learning and performing the method with rich casuistry. With a foreword by Geh. Council Prof. Dr. O. Hildebrand, Berlin. Kassel 1911; New print Karger, Basel, ISBN 978-3-318-02903-1 .
130. ↑ Brandt: Illustrated history of anesthesia. Pp. 163-169.
131. ↑ Harold R. Griffith, G. Enid Johnson: The use of curare in general anesthesia. In: Anesthesiology. 3, 1942, pp. 418-420.
132. ↑ Michael Heck, Michael Fresenius: Repetitorium Anaesthesiologie. Preparation for the anesthesiological specialist examination and the European diploma in anesthesiology. 3rd, completely revised edition. Springer, Berlin / Heidelberg / New York et al. 2001, ISBN 3-540-67331-8 , p. 803.
133. ↑ Erich Kirchner: Preliminary remark. In: Wolfgang Seitz (Ed.): Clinic of muscle relaxation. 50 years after Griffith and Johnson. 1994, p. 1.
134. ^ Rudolf Frey, Otto Mayrhofer: Important dates from the history of anesthesia. 1971, p. 15.
135. ^ SJ Basta: Clinical pharmacology of mivacurium chloride: a review. In: Journal of Clinical Anesth. 4 (2), March-April 1992, pp. 153-163.
136. ↑ Michael Heck, Michael Fresenius: Repetitorium Anaesthesiologie. Preparation for the anesthesiological specialist examination and the European diploma in anesthesiology. 3rd, completely revised edition. Springer, Berlin / Heidelberg / New York et al. 2001, ISBN 3-540-67331-8 , p. 804.
137. ^ Rudolf Frey, Otto Mayrhofer: Important dates from the history of anesthesia. 1971, p. 15.
138. ↑ Michael Heck, Michael Fresenius: Repetitorium Anaesthesiologie. Preparation for the anesthesiological specialist examination and the European diploma in anesthesiology. 2001, p. 804.
139. ^ Rudolf Frey, Otto Mayrhofer: Important dates from the history of anesthesia. 1971, p. 15.
140. ↑ Ernst Kern : Seeing - Thinking - Acting of a surgeon in the 20th century. ecomed, Landsberg am Lech 2000, ISBN 3-609-20149-5 , p. 280.

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