Parmenides

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https://en.wikipedia.org/wiki/Anaxagoras

Parmenides
Bust of Parmenides discovered at Velia, thought to have been partially modeled on a Metrodorus bust.
Born	c. late 6th century BC Elea, Magna Graecia
Died	c. 5th century BC
Era	Pre-Socratic philosophy
Region	Western philosophy
School	Eleatic school
Main interests	Ontology, poetry, cosmology
Notable ideas	Monism, truth/opinion distinction

Parmenides of Elea (/pɑːrˈmɛnɪdiːz ... ˈɛliə/; Greek: Παρμενίδης ὁ Ἐλεάτης; fl. late sixth or early fifth century BC) was a pre-Socratic Greek philosopher from Elea in Magna Graecia.

Parmenides was born in the Greek colony of Elea, from a wealthy and illustrious family. His dates are uncertain; according to doxographer Diogenes Laërtius, he flourished just before 500 BC, which would put his year of birth near 540 BC, but in the dialogue Parmenides Plato has him visiting Athens at the age of 65, when Socrates was a young man, c. 450 BC, which, if true, suggests a year of birth of c. 515 BC. He is thought to have been in his prime (or "floruit") around 475 BC.

The single known work by Parmenides is a poem whose original title is unknown but which is often referred to as On Nature. Only fragments of it survive. In his poem, Parmenides prescribes two views of reality. The first, the Way of "Aletheia" or truth, describes how all reality is one, change is impossible, and existence is timeless and uniform. The second view, the way of "Doxa", or opinion, describes the world of appearances, in which one's sensory faculties lead to conceptions which are false and deceitful.

Parmenides has been considered the founder of ontology and has, through his influence on Plato, influenced the whole history of Western philosophy. He is also considered to be the founder of the Eleatic school of philosophy, which also included Zeno of Elea and Melissus of Samos. Zeno's paradoxes of motion were developed to defend Parmenides' views. In contemporary philosophy, Parmenides' work has remained relevant in debates about the philosophy of time.

Biography

Parmenides was born in Elea (called Velia in Roman times), a city located in Magna Graecia. Diogenes Laertius says that his father was Pires, and that he belonged to a rich and noble family. Laertius transmits two divergent sources regarding the teacher of the philosopher. One, dependent on Sotion, indicates that he was first a student of Xenophanes, but did not follow him, and later became associated with a Pythagorean, Aminias, whom he preferred as his teacher. Another tradition, dependent on Theophrastus, indicates that he was a disciple of Anaximander.

Chronology

Everything related to the chronology of Parmenides—the dates of his birth and death, and the period of his philosophical activity—is uncertain.

Date of birth

All conjectures regarding Parmenides' date of birth are based on two ancient sources. One comes from Apollodorus and is transmitted to us by Diogenes Laertius: this source marks the Olympiad 69th (between 504 BC and 500 BC) as the moment of maturity, placing his birth 40 years earlier (544 BC – 540 BC). The other is Plato, in his dialogue Parmenides. There Plato composes a situation in which Parmenides, 65, and Zeno, 40, travel to Athens to attend the Panathenaic Games. On that occasion they meet Socrates, who was still very young according to the Platonic text.

The inaccuracy of the dating from Apollodorus is well known, who chooses the date of a historical event to make it coincide with the maturity (the floruit) of a philosopher, a maturity that he invariably reached at forty years of age. He tries to always match the maturity of a philosopher with the birth of his alleged disciple. In this case Apollodorus, according to Burnet, based his date of the foundation of Elea (540 BC) to chronologically locate the maturity of Xenophanes and thus the birth of his supposed disciple, Parmenides. Knowing this, Burnet and later classicists like Cornford, Raven, Guthrie, and Schofield preferred to base the calculations on the Platonic dialogue. According to the latter, the fact that Plato adds so much detail regarding ages in his text is a sign that he writes with chronological precision. Plato says that Socrates was very young, and this is interpreted to mean that he was less than twenty years old. We know the year of Socrates' death (399 BC) and his age—he was about seventy years old–making the date of his birth 469 BC. The Panathenaic games were held every four years, and of those held during Socrates' youth (454, 450, 446), the most likely is that of 450 BC, when Socrates was nineteen years old. Thus, if at this meeting Parmenides was about sixty-five years old, his birth occurred around 515 BC.

However, neither Raven nor Schofield, who follows the former, finds a dating based on a late Platonic dialogue entirely satisfactory. Other scholars directly prefer not to use the Platonic testimony and propose other dates. According to a scholar of the Platonic dialogues, R. Hirzel, Conrado Eggers Lan indicates that the historical has no value for Plato. The fact that the meeting between Socrates and Parmenides is mentioned in the dialogues Theaetetus (183e) and Sophist (217c) only indicates that it is referring to the same fictional event, and this is possible because both the Theaetetus and the Sophist are considered after the Parmenides. In Soph. 217c the dialectic procedure of Socrates is attributed to Parmenides, which would confirm that this is nothing more than a reference to the fictitious dramatic situation of the dialogue. Eggers Lan proposes a correction of the traditional date of the foundation of Elea. Based on Herodotus I, 163–167, which indicates that the Phocians, after defeating the Carthaginians in naval battle, founded Elea, and adding the reference to Thucydides I, 13, where it is indicated that such a battle occurred in the time of Cambyses II, the foundation of Elea can be placed between 530 BC and 522 BC So Parmenides could not have been born before 530 BC or after 520 BC, given that it predates Empedocles. This last dating procedure is not infallible either, because it has been questioned that the fact that links the passages of Herodotus and Thucydides is the same. Nestor Luis Cordero also rejects the chronology based on the Platonic text, and the historical reality of the encounter, in favor of the traditional date of Apollodorus. He follows the traditional datum of the founding of Elea in 545 BC, pointing to it not only as terminus post quem, but as a possible date of Parmenides' birth, from which he concludes that his parents were part of the founding contingent of the city and that he was a contemporary of Heraclitus. The evidence suggests that Parmenides could not have written much after the death of Heraclitus.

Timeline relative to other Presocratics

Beyond the speculations and inaccuracies about his date of birth, some specialists have turned their attention to certain passages of his work to specify the relationship of Parmenides with other thinkers. It was thought to find in his poem certain controversial allusions to the doctrine of Anaximenes and the Pythagoreans (fragment B 8, verse 24, and frag. B 4), and also against Heraclitus (frag .B 6, vv.8–9), while Empedocles and Anaxagoras frequently refer to Parmenides.

The reference to Heraclitus has been debated. Bernays's thesis that Parmenides attacks Heraclitus, to which Diels, Kranz, Gomperz, Burnet and others adhered, was discussed by Reinhardt, whom Jaeger followed.

Guthrie finds it surprising that Heraclitus would not have censured Parmenides if he had known him, as he did with Xenophanes and Pythagoras. His conclusion, however, does not arise from this consideration, but points out that, due to the importance of his thought, Parmenides splits the history of pre-Socratic philosophy in two; therefore his position with respect to other thinkers is easy to determine. From this point of view, the philosophy of Heraclitus seems to him pre-Parmenidean, while those of Empedocles, Anaxagoras and Democritus are post-Parmenidean.

Anecdotes

Plutarch, Strabo and Diogenes—following the testimony of Speusippus—agree that Parmenides participated in the government of his city, organizing it and giving it a code of admirable laws.

Detail of the pedestal found in Velia. Greek inscriptions were made only in capital letters, and without spaces. Read as follows: ΠΑ[ ]ΜΕΝΕΙΔΗΣ ΠΥΡΗΤΟΣ ΟΥΛΙΑΔΗΣ ΦΥΣΙΚΟΣ

Archaeological discovery

In 1969, the plinth of a statue dated to the 1st century AD was excavated in Velia. On the plinth were four words: ΠΑ[Ρ]ΜΕΝΕΙΔΗΣ ΠΥΡΗΤΟΣ ΟΥΛΙΑΔΗΣ ΦΥΣΙΚΟΣ. The first two clearly read "Parmenides, son of Pires." The fourth word φυσικός (fysikós, "physicist") was commonly used to designate philosophers who devoted themselves to the observation of nature. On the other hand, there is no agreement on the meaning of the third (οὐλιάδης, ouliadēs): it can simply mean "a native of Elea" (the name "Velia" is in Greek Οὐέλια), or "belonging to the Οὐλιος" (Ulios), that is, to a medical school ( the patron of which was Apollo Ulius). If this last hypothesis were true, then Parmenides would be, in addition to being a legislator, a doctor. The hypothesis is reinforced by the ideas contained in fragment 18 of his poem, which contains anatomical and physiological observations. However, other specialists believe that the only certainty we can extract from the discovery is that of the social importance of Parmenides in the life of his city, already indicated by the testimonies that indicate his activity as a legislator.

Visit to Athens

Plato, in his dialogue Parmenides, relates that, accompanied by his disciple Zeno of Elea, Parmenides visited Athens when he was approximately sixty-five years old and that, on that occasion, Socrates, then a young man, conversed with him. Athenaeus of Naucratis had noted that, although the ages make a dialogue between Parmenides and Socrates hardly possible, the fact that Parmenides has sustained arguments similar to those sustained in the Platonic dialogue is something that seems impossible. Most modern classicists consider the visit to Athens and the meeting and conversation with Socrates to be fictitious. Allusions to this visit in other Platonic works are only references to the same fictitious dialogue and not to a historical fact.

On Nature

Parmenides' sole work, which has only survived in fragments, is a poem in dactylic hexameter, later titled On Nature. Approximately 160 verses remain today from an original total that was probably near 800. The poem was originally divided into three parts: an introductory proem that contains an allegorical narrative which explains the purpose of the work, a former section known as "The Way of Truth" (aletheia, ἀλήθεια), and a latter section known as "The Way of Appearance/Opinion" (doxa, δόξα). Despite the poem's fragmentary nature, the general plan of both the proem and the first part, "The Way of Truth" have been ascertained by modern scholars, thanks to large excerpts made by Sextus Empiricus and Simplicius of Cilicia. Unfortunately, the second part, "The Way of Opinion", which is supposed to have been much longer than the first, only survives in small fragments and prose paraphrases.

Introduction

The introductory proem describes the narrator's journey to receive a revelation from an unnamed goddess on the nature of reality. The remainder of the work is then presented as the spoken revelation of the goddess without any accompanying narrative.

The narrative of the poet's journey includes a variety of allegorical symbols, such as a speeding chariot with glowing axles, horses, the House of Night, Gates of the paths of Night and Day, and maidens who are "the daughters of the Sun" who escort the poet from the ordinary daytime world to a strange destination, outside our human paths. The allegorical themes in the poem have attracted a variety of different interpretations, including comparisons to Homer and Hesiod, and attempts to relate the journey towards either enlightenment or darkness, but there is little scholarly consensus about any interpretation, and the surviving evidence from the poem itself, as well as any other literary use of allegory from the same time period, may be too sparse to ever determine any of the intended symbolism with certainty.

The Way of Truth

In the Way of Truth, an estimated 90% of which has survived, Parmenides distinguishes between the unity of nature and its variety, insisting in the Way of Truth upon the reality of its unity, which is therefore the object of knowledge, and upon the unreality of its variety, which is therefore the object, not of knowledge, but of opinion. This contrasts with the argument in the section called "the way of opinion", which discusses that which is illusory.

The Way of Opinion

In the significantly longer, but far worse preserved latter section of the poem, Way of Opinion, Parmenides propounds a theory of the world of seeming and its development, pointing out, however, that, in accordance with the principles already laid down, these cosmological speculations do not pretend to anything more than mere appearance. The structure of the cosmos is a fundamental binary principle that governs the manifestations of all the particulars: "the aether fire of flame" (B 8.56), which is gentle, mild, soft, thin and clear, and self-identical, and the other is "ignorant night", body thick and heavy. Cosmology originally comprised the greater part of his poem, explaining the world's origins and operations. Some idea of the sphericity of the Earth also seems to have been known to Parmenides.

Legacy

As the first of the Eleatics, Parmenides is generally credited with being the philosopher who first defined ontology as a separate discipline distinct from theology. His most important pupil was Zeno, who appears alongside him in Plato's Parmenides where they debate dialectic with Socrates. The pluralist theories of Empedocles and Anaxagoras and the atomist Leucippus, and Democritus have also been seen as a potential response to Parmenides' arguments and conclusions. Parmenides is also mentioned in Plato's Sophist and Theaetetus. Later Hellenistic doxographers also considered Parmenides to have been a pupil of Xenophanes. Eusebius, quoting Aristocles of Messene, says that Parmenides was part of a line of skeptical philosophy that culminated in Pyrrhonism for he, by the root, rejects the validity of perception through the senses whilst, at any rate, it is first through our five forms of senses that we become aware of things and then by faculty of reasoning. Parmenides' proto-monism of the One also influenced Plotinus and Neoplatonism.

General anaesthetic

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/General_anaesthetic

General anaesthetics (or anesthetics, see spelling differences) are often defined as compounds that induce a loss of consciousness in humans or loss of righting reflex in animals. Clinical definitions are also extended to include an induced coma that causes lack of awareness to painful stimuli, sufficient to facilitate surgical applications in clinical and veterinary practice. General anaesthetics do not act as analgesics and should also not be confused with sedatives. General anaesthetics are a structurally diverse group of compounds whose mechanisms encompasses multiple biological targets involved in the control of neuronal pathways. The precise workings are the subject of some debate and ongoing research.

General anesthetics elicit a state of general anesthesia. It remains somewhat controversial regarding how this state should be defined. General anesthetics, however, typically elicit several key reversible effects: immobility, analgesia, amnesia, unconsciousness, and reduced autonomic responsiveness to noxious stimuli.

Mode of administration

General anaesthetics can be administered either as gases or vapours (inhalational anaesthetics), or as injections (intravenous anaesthetics or even intramuscular). All of these agents share the property of being quite hydrophobic (i.e., as liquids, they are not freely miscible—or mixable—in water, and as gases they dissolve in oils better than in water). It is possible to deliver anaesthesia solely by inhalation or injection, but most commonly the two forms are combined, with an injection given to induce anaesthesia and a gas used to maintain it.

Inhalation

General anesthetics are frequently administered as volatile liquids or gases.

Inhalational anaesthetic substances are either volatile liquids or gases, and are usually delivered using an anaesthesia machine. An anaesthesia machine allows composing a mixture of oxygen, anaesthetics and ambient air, delivering it to the patient and monitoring patient and machine parameters. Liquid anaesthetics are vapourised in the machine.

Many compounds have been used for inhalation anaesthesia, but only a few are still in widespread use. Desflurane, isoflurane and sevoflurane are the most widely used volatile anaesthetics today. They are often combined with nitrous oxide. Older, less popular, volatile anaesthetics, include halothane, enflurane, and methoxyflurane. Researchers are also actively exploring the use of xenon as an anaesthetic.

Injection

Injectable anaesthetics are used for the induction and maintenance of a state of unconsciousness. Anaesthetists prefer to use intravenous injections, as they are faster, generally less painful and more reliable than intramuscular or subcutaneous injections. Among the most widely used drugs are:

• Propofol
• Etomidate
• Barbiturates such as methohexital and thiopentone/thiopental
• Benzodiazepines such as midazolam
• Ketamine is used in the UK as "field anaesthesia", for instance in road traffic incidents or similar situations where an operation must be conducted at the scene or when there is not enough time to move to an operating room, while preferring other anaesthetics where conditions allow their use. It is more frequently used in the operative setting in the US.

Benzodiazepines are sedatives and are used in combinations with other general anaesthetics 

Mechanism of action

Induction and maintenance of general anesthesia, and the control of the various physiological side effects is typically achieved through a combinatorial drug approach. Individual general anesthetics vary with respect to their specific physiological and cognitive effects. While general anesthesia induction may be facilitated by one general anesthetic, others may be used in parallel or subsequently to achieve and maintain the desired anesthetic state. The drug approach utilized is dependent upon the procedure and the needs of the healthcare providers.

It is postulated that general anaesthetics exert their action by the activation of inhibitory central nervous system (CNS) receptors, and the inactivation of CNS excitatory receptors. The relative roles of different receptors is still under debate, but evidence exists for particular targets being involved with certain anaesthetics and drug effects.

Below are several key targets of general anesthetics that likely mediate their effects:

GABA_A receptor agonists

• GABA_A receptors are chloride channels that hyperpolarize neurons and function as inhibitory CNS receptors. General anesthetics that agonize them are typically used to induce a state of sedation and/or unconsciousness. Such drugs include propofol, etomidate, isoflurane, benzodiazepines (midazolam, lorazepam, diazepam), and barbiturates (sodium thiopental, methohexital).

NMDA receptor antagonists

• Ketamine, an NMDA receptor antagonist, is used primarily for its analgesic effects and in an off-label capacity for its anti-depressant effects. This drug, however, also alters arousal and is often used in parallel with other general anesthetics to help maintain a state of general anesthesia. Administration of ketamine alone leads to a dissociative state, in which a patient may experience auditory and visual hallucinations. Additionally, the perception of pain is dissociated from the perception of noxious stimuli. Ketamine appears to bind preferentially to the NMDA receptors on GABAergic interneurons, which may partially explain its effects.

Two-pore potassium channels (K_2Ps) activation

• Two-pore potassium channels (K_2Ps) modulate the potassium conductance that contributes to the resting membrane potential in neurons. Opening of these channels therefore facilitates a hyperpolarizing current, which reduces neuronal excitability. K_2Ps have been found to be affected by general anesthetics (esp. halogenated inhalation anesthetics) and are currently under investigation as potential targets. The K_2P channel family comprises six subfamilies, which includes 15 unique members. 13 of these channels (excluding TWIK-1 and TWIK-2 homomers) are affected by general anesthetics. While it has not been determined that general anesthetics bind directly to these channels, nor is it clear how these drugs affect K_2P conductance, electrophysiological studies have shown that certain general anesthetics result in K_2P channel activation. This drug-elicited channel activation has been shown to be dependent upon specific amino-acids within certain K_2P channels (i.e. TREK-1 and TASK channels). In the case of TREK-1, activation was shown through an anesthetic perturbation to membrane lipid clusters and activation of phospholipase D2; direct binding of anesthetics to purified reconstituted TREK-1 had no effect on conductance. The effects of certain general anesthetics are less pronounced in K_2P knock-out mice, as compared to their wild-type counterparts. Cumulatively, TASK-1, TASK-3, and TREK-1 are particularly well supported as playing a role in the induction of general anesthesia.

Others

• Opioid receptor agonists are primarily utilized for their analgesic effects. These drugs, however, can also elicit sedation. This effect is mediated by opioid actions on both opioid and acetylcholine receptors. While these drugs can lead to decreased arousal, they do not elicit a loss of consciousness. For this reason, they are often used in parallel with other general anesthetics to help maintain a state of general anesthesia. Such drugs include morphine, fentanyl, hydromorphone, and remifentanil.
• Administration of the alpha2 adrenergic receptor agonist dexmedetomidine leads to sedation that resembles non-REM sleep. It is used in parallel with other general anesthetics to help maintain a state of general anesthesia, in an off-label capacity. Notably, patients are easily aroused from this non-REM sleep state.
• Dopamine receptor antagonists have sedative and antiemetic properties. Previously, they were used in parallel with opioids to elicit neuroleptic anesthesia (catalepsy, analgesia, and unresponsiveness). They are no longer used in the context, because patients experiencing neuroleptic anesthesia were frequently aware of the medical procedures being performed, but could not move or express emotion. Such drugs include haloperidol and droperidol.

See also: Theories of general anaesthetic action

Stages of anesthesia

During administration of an anesthetic, the receiver goes through different stages of behavior ultimately leading to unconsciousness. This process is accelerated with intravenous anesthetics, so much so that it is negligible to consider during their use. The four stages of anesthesia are described using Guedel's signs, signifying the depth of anesthesia. These stages describe effects of anesthesia mainly on cognition, muscular activity, and respiration.

Stage I - Analgesia

The receiver of the anesthesia primarily feels analgesia followed by amnesia and a sense of confusion moving into the next stage.

Stage II - Excitement

Stage II is often characterized by the receiver being delirious and confused, with severe amnesia. Irregularities in the patterns of respiration are common at this stage of anesthesia. Nausea and vomiting are also indicators of Stage II anesthesia. Struggling and panic can sometimes occur as a result of delirium.

Stage III - Surgical Anesthesia

Normal breathing resumes at the beginnings of Stage III. Nearing the end of the stage, breathing ceases completely. Indicators for stage III anesthesia include loss of the eyelash reflex as well as regular breathing. Depth of stage III anesthesia can often be gauged by eye movement and pupil size.

Stage IV - Medullary Depression

No respiration occurs in stage IV. This is shortly followed by circulatory failure and depression of the vasomotor centers. Death is common at this stage of anesthesia if no breathing and circulatory support is available.

Physiological side effects

Aside from the clinically advantageous effects of general anesthetics, there are a number of other physiological consequences mediated by this class of drug. Notably, a reduction in blood pressure can be facilitated by a variety of mechanisms, including reduced cardiac contractility and dilation of the vasculature. This drop in blood pressure may activate a reflexive increase in heart rate, due to a baroreceptor-mediated feedback mechanism. Some anesthetics, however, disrupt this reflex.

Patients under general anesthesia are at greater risk of developing hypothermia, as the aforementioned vasodilation increases the heat lost via peripheral blood flow. By and large, these drugs reduce the internal body temperature threshold at which autonomic thermoregulatory mechanisms are triggered in response to cold. (On the other hand, the threshold at which thermoregulatory mechanisms are triggered in response to heat is typically increased.)

Anesthetics typically affect respiration. Inhalational anesthetics elicit bronchodilation, an increase in respiratory rate, and reduced tidal volume. The net effect is decreased respiration, which must be managed by healthcare providers, while the patient is under general anesthesia. The reflexes that function to alleviate airway obstructions are also dampened (e.g. gag and cough). Compounded with a reduction in lower esophageal sphincter tone, which increases the frequency of regurgitation, patients are especially prone to asphyxiation while under general anesthesia. Healthcare providers closely monitor individuals under general anesthesia and utilize a number of devices, such as an endotracheal tube, to ensure patient safety.

General anesthetics also affect the chemoreceptor trigger zone and brainstem vomiting center, eliciting nausea and vomiting following treatment.

Pharmacokinetics

Intravenous general anesthetics

Induction

Intravenously delivered general anesthetics are typically small and highly lipophilic molecules. These characteristics facilitate their rapid preferential distribution into the brain and spinal cord, which are both highly vascularized and lipophilic. It is here where the actions of these drugs lead to general anesthesia induction.

Elimination

Following distribution into the central nervous system (CNS), the anesthetic drug then diffuses out of the CNS into the muscles and viscera, followed by adipose tissues. In patients given a single injection of drug, this redistribution results in termination of general anesthesia. Therefore, following administration of a single anesthetic bolus, duration of drug effect is dependent solely upon the redistribution kinetics.

The half-life of an anesthetic drug following a prolonged infusion, however, depends upon both drug redistribution kinetics, drug metabolism in the liver, and existing drug concentration in fat. When large quantities of an anesthetic drug have already been dissolved in the body's fat stores, this can slow its redistribution out of the brain and spinal cord, prolonging its CNS effects. For this reason, the half-lives of these infused drugs are said to be context-dependent. Generally, prolonged anesthetic drug infusions result in longer drug half-lives, slowed elimination from the brain and spinal cord, and delayed termination of general anesthesia.

Inhalational general anesthetics

Minimal alveolar concentration (MAC) is the concentration of an inhalational anesthetic in the lungs that prevents 50% of patients from responding to surgical incision. This value is used to compare the potencies of various inhalational general anesthetics and impacts the partial-pressure of the drug utilized by healthcare providers during general anesthesia induction and/or maintenance.

Induction

Induction of anesthesia is facilitated by diffusion of an inhaled anesthetic drug into the brain and spinal cord. Diffusion throughout the body proceeds until the drug's partial pressure within the various tissues is equivalent to the partial pressure of the drug within the lungs. Healthcare providers can control the rate of anesthesia induction and final tissue concentrations of the anesthetic by varying the partial pressure of the inspired anesthetic. A higher drug partial pressure in the lungs will drive diffusion more rapidly throughout the body and yield a higher maximum tissue concentration. Respiratory rate and inspiratory volume will also affect the promptness of anesthesia onset, as will the extent of pulmonary blood flow.

The partition coefficient of a gaseous drug is indicative of its relative solubility in various tissues. This metric is the relative drug concentration between two tissues, when their partial pressures are equal (gas:blood, fat:blood, etc.). Inhalational anesthetics vary widely with respect to their tissue solubilities and partition coefficients. Anesthetics that are highly soluble require many molecules of drug to raise the partial pressure within a given tissue, as opposed to minimally soluble anesthetics which require relatively few. Generally, inhalational anesthetics that are minimally soluble reach equilibrium more quickly. Inhalational anesthetics that have a high fat:blood partition coefficient, however, reach equilibrium more slowly, due to the minimal vascularization of fat tissue, which serves as a large, slowly-filling reservoir for the drug.

Elimination

Inhaled anesthetics are eliminated via expiration, following diffusion into the lungs. This process is dependent largely upon the anesthetic blood:gas partition coefficient, tissue solubility, blood flow to the lungs, and patient respiratory rate and inspiratory volume. For gases that have minimal tissue solubility, termination of anesthesia generally occurs as rapidly as the onset of anesthesia. For gases that have high tissue solubility, however, termination of anesthesia is generally context-dependent. As with intravenous anesthetic infusions, prolonged delivery of highly soluble anesthetic gases generally results in longer drug half-lives, slowed elimination from the brain and spinal cord, and delayed termination of anesthesia.

Metabolism of inhaled anesthetics is generally not a major route of drug elimination.

Anesthesia

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Anesthesia

 

Anesthesia
Pronunciation	/ˌænɪsˈθiːziə, -siə, -ʒə/
MeSH	E03.155
MedlinePlus	anesthesia
eMedicine	1271543

Anesthesia or anaesthesia is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prevention of pain), paralysis (muscle relaxation), amnesia (loss of memory), and unconsciousness. An individual under the effects of anesthetic drugs is referred to as being anesthetized.

Anesthesia enables the painless performance of procedures that would otherwise cause severe or intolerable pain in a non-anesthetized individual, or would otherwise be technically unfeasible. Three broad categories of anesthesia exist:

• General anesthesia suppresses central nervous system activity and results in unconsciousness and total lack of sensation, using either injected or inhaled drugs.
• Sedation suppresses the central nervous system to a lesser degree, inhibiting both anxiety and creation of long-term memories without resulting in unconsciousness.
• Regional and local anesthesia, which blocks transmission of nerve impulses from a specific part of the body. Depending on the situation, this may be used either on its own (in which case the individual remains fully conscious), or in combination with general anesthesia or sedation.
  • Local anesthesia is simple infiltration by the clinician directly onto the region of interest (e.g. numbing a tooth for dental work).
  • Peripheral nerve blocks use drugs targeted at peripheral nerves to anesthetize an isolated part of the body, such as an entire limb.
  • Neuraxial blockade , mainly epidural and spinal anesthesia, can be performed in the region of the central nervous system itself, suppressing all incoming sensation from nerves supplying the area of the block.

In preparing for a medical or veterinary procedure, the clinician chooses one or more drugs to achieve the types and degree of anesthesia characteristics appropriate for the type of procedure and the particular patient. The types of drugs used include general anesthetics, local anesthetics, hypnotics, dissociatives, sedatives, adjuncts, neuromuscular-blocking drugs, narcotics, and analgesics.

The risks of complications during or after anesthesia are often difficult to separate from those of the procedure for which anesthesia is being given, but in the main they are related to three factors: the health of the individual, the complexity and stress of the procedure itself, and the anaesthetic technique. Of these factors, the individual's health has the greatest impact. Major perioperative risks can include death, heart attack, and pulmonary embolism whereas minor risks can include postoperative nausea and vomiting and hospital readmission. Some conditions, like local anesthetic toxicity, airway trauma or malignant hyperthermia, can be more directly attributed to specific anesthetic drugs and techniques.

Medical uses

The purpose of anesthesia can be distilled down to three basic goals or endpoints:

• hypnosis (a temporary loss of consciousness and with it a loss of memory. In a pharmacological context, the word hypnosis usually has this technical meaning, in contrast to its more familiar lay or psychological meaning of an altered state of consciousness not necessarily caused by drugs—see hypnosis).
• analgesia (lack of sensation which also blunts autonomic reflexes)
• muscle relaxation

Different types of anesthesia affect the endpoints differently. Regional anesthesia, for instance, affects analgesia; benzodiazepine-type sedatives (used for sedation, or "twilight anesthesia") favor amnesia; and general anesthetics can affect all of the endpoints. The goal of anesthesia is to achieve the endpoints required for the given surgical procedure with the least risk to the subject.

The anesthetic area of an operating room

To achieve the goals of anesthesia, drugs act on different but interconnected parts of the nervous system. Hypnosis, for instance, is generated through actions on the nuclei in the brain and is similar to the activation of sleep. The effect is to make people less aware and less reactive to noxious stimuli.

Loss of memory (amnesia) is created by action of drugs on multiple (but specific) regions of the brain. Memories are created as either declarative or non-declarative memories in several stages (short-term, long-term, long-lasting) the strength of which is determined by the strength of connections between neurons termed synaptic plasticity. Each anesthetic produces amnesia through unique effects on memory formation at variable doses. Inhalational anesthetics will reliably produce amnesia through general suppression of the nuclei at doses below those required for loss of consciousness. Drugs like midazolam produce amnesia through different pathways by blocking the formation of long-term memories.

Nevertheless, a person can have dreams during anesthetic or have consciousness of the procedure despite having no indication of it under anesthetic. It is estimated that 22% of people dream during general anesthesia and 1–2 cases per 1000 have some consciousness termed "awareness during general anesthesia". It is unknown whether non-human animals have dreams during general anesthesia.

Techniques

Anesthesia is unique in that it is not a direct means of treatment; rather, it allows the clinician to do things that may treat, diagnose, or cure an ailment which would otherwise be painful or complicated. The best anesthetic, therefore, is the one with the lowest risk to the patient that still achieves the endpoints required to complete the procedure. The first stage in anesthesia is the pre-operative risk assessment consisting of the medical history, physical examination and lab tests. Diagnosing an animal's pre-operative physical status allows the clinician to minimize anesthetic risks. A well completed medical history will arrive at the correct diagnosis 56% of the time which increases to 73% with a physical examination. Lab tests help in diagnosis but only in 3% of cases, underscoring the need for a full history and physical examination prior to anesthetics. Incorrect pre-operative assessments or preparations are the root cause of 11% of all adverse anesthetic events.

Safe anesthesia care depends greatly on well-functioning teams of highly trained healthcare workers. The medical specialty centred around anesthesia is called anesthesiology, and doctors specialised in the field are termed anesthesiologists. Additional healthcare professionals involved in anesthesia provision have varying titles and roles depending on the jurisdiction, and include anesthetic nurses, nurse anesthetists, anesthesiologist assistants, anaesthetic technicians, anaesthesia associates, operating department practitioners and anesthesia technologists. International standards for the safe practice of anesthesia, jointly endorsed by the World Health Organization and the World Federation of Societies of Anaesthesiologists, highly recommend that anesthesia should be provided, overseen or led by anesthesiologists, with the exception of minimal sedation or superficial procedures performed under local anesthesia. A trained, vigilant anesthesia provider should continually care for the patient; where the provider is not an anesthesiologist, they should be locally directed and supervised by an anesthesiologist, and in countries or settings where this is not feasible, care should be led by the most qualified local individual within a regional or national anesthesiologist-led framework. The same minimum standards for patient safety apply regardless of the provider, including continuous clinical and biometric monitoring of tissue oxygenation, perfusion and blood pressure; confirmation of correct placement of airway management devices by auscultation and carbon dioxide detection; use of the WHO Surgical Safety Checklist; and safe onward transfer of the patient's care following the procedure.

ASA physical status classification system

ASA class	Physical status
ASA 1	Healthy person
ASA 2	Mild systemic disease
ASA 3	Severe systemic disease
ASA 4	Severe systemic disease that is a constant threat to life
ASA 5	A moribund person who is not expected to survive without the operation
ASA 6	A declared brain-dead person whose organs are being removed for donor purposes
E	Suffix added for patients undergoing emergency procedure

One part of the risk assessment is based on the patient's health. The American Society of Anesthesiologists has developed a six-tier scale that stratifies the patient's pre-operative physical state. It is called the ASA physical status classification. The scale assesses risk as the patient's general health relates to an anesthetic.

The more detailed pre-operative medical history aims to discover genetic disorders (such as malignant hyperthermia or pseudocholinesterase deficiency), habits (tobacco, drug and alcohol use), physical attributes (such as obesity or a difficult airway) and any coexisting diseases (especially cardiac and respiratory diseases) that might impact the anesthetic. The physical examination helps quantify the impact of anything found in the medical history in addition to lab tests.

Aside from the generalities of the patient's health assessment, an evaluation of specific factors as they relate to the surgery also need to be considered for anesthesia. For instance, anesthesia during childbirth must consider not only the mother but the baby. Cancers and tumors that occupy the lungs or throat create special challenges to general anesthesia. After determining the health of the patient undergoing anesthesia and the endpoints that are required to complete the procedure, the type of anesthetic can be selected. Choice of surgical method and anesthetic technique aims to reduce risk of complications, shorten time needed for recovery and minimize the surgical stress response.

General anesthesia

Further information: General anaesthesia, General anesthetic, and Inhalational anesthetic

 

A vaporizer holds a liquid anesthetic and converts it to gas for inhalation (in this case sevoflurane)

 

A patient receiving anesthesia through inhalation

Anesthesia is a combination of the endpoints (discussed above) that are reached by drugs acting on different but overlapping sites in the central nervous system. General anesthesia (as opposed to sedation or regional anesthesia) has three main goals: lack of movement (paralysis), unconsciousness, and blunting of the stress response. In the early days of anesthesia, anesthetics could reliably achieve the first two, allowing surgeons to perform necessary procedures, but many patients died because the extremes of blood pressure and pulse caused by the surgical insult were ultimately harmful. Eventually, the need for blunting of the surgical stress response was identified by Harvey Cushing, who injected local anesthetic prior to hernia repairs. This led to the development of other drugs that could blunt the response leading to lower surgical mortality rates.

The most common approach to reach the endpoints of general anesthesia is through the use of inhaled general anesthetics. Each anesthetic has its own potency which is correlated to its solubility in oil. This relationship exists because the drugs bind directly to cavities in proteins of the central nervous system, although several theories of general anesthetic action have been described. Inhalational anesthetics are thought to exact their effects on different parts of the central nervous system. For instance, the immobilizing effect of inhaled anesthetics results from an effect on the spinal cord whereas sedation, hypnosis and amnesia involve sites in the brain. The potency of an inhalational anesthetic is quantified by its minimum alveolar concentration (MAC). The MAC is the percentage dose of anesthetic that will prevent a response to painful stimulus in 50% of subjects. The higher the MAC, generally, the less potent the anesthetic.

Syringes prepared with medications that are expected to be used during an operation under general anesthesia maintained by sevoflurane gas:
– Propofol, a hypnotic
– Ephedrine, in case of hypotension
– Fentanyl, for analgesia
– Atracurium, for neuromuscular blockade
– Glycopyrronium bromide (here under trade name "Robinul"), reducing secretions

The ideal anesthetic drug would provide hypnosis, amnesia, analgesia, and muscle relaxation without undesirable changes in blood pressure, pulse or breathing. In the 1930s, physicians started to augment inhaled general anesthetics with intravenous general anesthetics. The drugs used in combination offered a better risk profile to the subject under anesthesia and a quicker recovery. A combination of drugs was later shown to result in lower odds of dying in the first seven days after anesthetic. For instance, propofol (injection) might be used to start the anesthetic, fentanyl (injection) used to blunt the stress response, midazolam (injection) given to ensure amnesia and sevoflurane (inhaled) during the procedure to maintain the effects. More recently, several intravenous drugs have been developed which, if desired, allow inhaled general anesthetics to be avoided completely.

Equipment

Further information: Instruments used in anesthesiology and Anaesthetic machine

The core instrument in an inhalational anesthetic delivery system is an anesthetic machine. It has vaporizers, ventilators, an anesthetic breathing circuit, waste gas scavenging system and pressure gauges. The purpose of the anesthetic machine is to provide anesthetic gas at a constant pressure, oxygen for breathing and to remove carbon dioxide or other waste anesthetic gases. Since inhalational anesthetics are flammable, various checklists have been developed to confirm that the machine is ready for use, that the safety features are active and the electrical hazards are removed. Intravenous anesthetic is delivered either by bolus doses or an infusion pump. There are also many smaller instruments used in airway management and monitoring the patient. The common thread to modern machinery in this field is the use of fail-safe systems that decrease the odds of catastrophic misuse of the machine.

Monitoring

An anesthetic machine with integrated systems for monitoring of several vital parameters.

Patients under general anesthesia must undergo continuous physiological monitoring to ensure safety. In the US, the American Society of Anesthesiologists (ASA) has established minimum monitoring guidelines for patients receiving general anesthesia, regional anesthesia, or sedation. These include electrocardiography (ECG), heart rate, blood pressure, inspired and expired gases, oxygen saturation of the blood (pulse oximetry), and temperature. In the UK the Association of Anaesthetists (AAGBI) have set minimum monitoring guidelines for general and regional anesthesia. For minor surgery, this generally includes monitoring of heart rate, oxygen saturation, blood pressure, and inspired and expired concentrations for oxygen, carbon dioxide, and inhalational anesthetic agents. For more invasive surgery, monitoring may also include temperature, urine output, blood pressure, central venous pressure, pulmonary artery pressure and pulmonary artery occlusion pressure, cardiac output, cerebral activity, and neuromuscular function. In addition, the operating room environment must be monitored for ambient temperature and humidity, as well as for accumulation of exhaled inhalational anesthetic agents, which might be deleterious to the health of operating room personnel.

Sedation

Further information: Sedation

Sedation (also referred to as dissociative anesthesia or twilight anesthesia) creates hypnotic, sedative, anxiolytic, amnesic, anticonvulsant, and centrally produced muscle-relaxing properties. From the perspective of the person giving the sedation, the patient appears sleepy, relaxed and forgetful, allowing unpleasant procedures to be more easily completed. Sedatives such as benzodiazepines are usually given with pain relievers (such as narcotics, or local anesthetics or both) because they do not, by themselves, provide significant pain relief.

From the perspective of the subject receiving a sedative, the effect is a feeling of general relaxation, amnesia (loss of memory) and time passing quickly. Many drugs can produce a sedative effect including benzodiazepines, propofol, thiopental, ketamine and inhaled general anesthetics. The advantage of sedation over a general anesthetic is that it generally does not require support of the airway or breathing (no tracheal intubation or mechanical ventilation) and can have less of an effect on the cardiovascular system which may add to a greater margin of safety in some patients.

Regional anesthesia

Further information: Conduction anesthesia

 

Sonography guided femoral nerve block

 

Backflow of cerebrospinal fluid through a spinal needle after puncture of the arachnoid mater during spinal anesthesia

When pain is blocked from a part of the body using local anesthetics, it is generally referred to as regional anesthesia. There are many types of regional anesthesia either by injecting into the tissue itself, a vein that feeds the area or around a nerve trunk that supplies sensation to the area. The latter are called nerve blocks and are divided into peripheral or central nerve blocks.

The following are the types of regional anesthesia:

• Infiltrative anesthesia: a small amount of local anesthetic is injected in a small area to stop any sensation (such as during the closure of a laceration, as a continuous infusion or "freezing" a tooth). The effect is almost immediate.
• Peripheral nerve block: local anesthetic is injected near a nerve that provides sensation to particular portion of the body. There is significant variation in the speed of onset and duration of anesthesia depending on the potency of the drug (e.g. Mandibular block, Fascia Iliaca Compartment Block).
• Intravenous regional anesthesia (also called a Bier block): dilute local anesthetic is infused to a limb through a vein with a tourniquet placed to prevent the drug from diffusing out of the limb.
• Central nerve block: Local anesthetic is injected or infused in or around a portion of the central nervous system (discussed in more detail below in spinal, epidural and caudal anesthesia).
• Topical anesthesia: local anesthetics that are specially formulated to diffuse through the mucous membranes or skin to give a thin layer of analgesia to an area (e.g. EMLA patches).
• Tumescent anesthesia: a large amount of very dilute local anesthetics are injected into the subcutaneous tissues during liposuction.
• Systemic local anesthetics: local anesthetics are given systemically (orally or intravenous) to relieve neuropathic pain.

A 2018 Cochrane review found moderate quality evidence that regional anesthesia may reduce the frequency of persistent postoperative pain (PPP) from 3 to 18 months following thoracotomy and 3 to 12 months following caesarean. Low quality evidence was found 3 to 12 months following breast cancer surgery. This review acknowledges certain limitations that impact its applicability beyond the surgeries and regional anesthesia techniques reviewed.

Nerve blocks

Further information: Nerve block

When local anesthetic is injected around a larger diameter nerve that transmits sensation from an entire region it is referred to as a nerve block or regional nerve blockade. Nerve blocks are commonly used in dentistry, when the mandibular nerve is blocked for procedures on the lower teeth. With larger diameter nerves (such as the interscalene block for upper limbs or psoas compartment block for lower limbs) the nerve and position of the needle is localized with ultrasound or electrical stimulation. Evidence supports the use of ultrasound guidance alone, or in combination with peripheral nerve stimulation, as superior for improved sensory and motor block, a reduction in the need for supplementation and fewer complications. Because of the large amount of local anesthetic required to affect the nerve, the maximum dose of local anesthetic has to be considered. Nerve blocks are also used as a continuous infusion, following major surgery such as knee, hip and shoulder replacement surgery, and may be associated with lower complications. Nerve blocks are also associated with a lower risk of neurologic complications compared to the more central epidural or spinal neuraxial blocks.

Spinal, epidural and caudal anesthesia

Further information: Neuraxial blockade and History of neuraxial anesthesia

Central neuraxial anesthesia is the injection of local anesthetic around the spinal cord to provide analgesia in the abdomen, pelvis or lower extremities. It is divided into either spinal (injection into the subarachnoid space), epidural (injection outside of the subarachnoid space into the epidural space) and caudal (injection into the cauda equina or tail end of the spinal cord). Spinal and epidural are the most commonly used forms of central neuraxial blockade.

Spinal anesthesia is a "one-shot" injection that provides rapid onset and profound sensory anesthesia with lower doses of anesthetic, and is usually associated with neuromuscular blockade (loss of muscle control). Epidural anesthesia uses larger doses of anesthetic infused through an indwelling catheter which allows the anesthetic to be augmented should the effects begin to dissipate. Epidural anesthesia does not typically affect muscle control.

Because central neuraxial blockade causes arterial and venous vasodilation, a drop in blood pressure is common. This drop is largely dictated by the venous side of the circulatory system which holds 75% of the circulating blood volume. The physiologic effects are much greater when the block is placed above the 5th thoracic vertebra. An ineffective block is most often due to inadequate anxiolysis or sedation rather than a failure of the block itself.

Acute pain management

Nociception (pain sensation) is not hard-wired into the body. Instead, it is a dynamic process wherein persistent painful stimuli can sensitize the system and either make pain management difficult or promote the development of chronic pain. For this reason, preemptive acute pain management may reduce both acute and chronic pain and is tailored to the surgery, the environment in which it is given (in-patient/out-patient) and the individual.

Pain management is classified into either pre-emptive or on-demand. On-demand pain medications typically include either opioid or non-steroidal anti-inflammatory drugs but can also make use of novel approaches such as inhaled nitrous oxide or ketamine. On demand drugs can be administered by a clinician ("as needed drug orders") or by the patient using patient-controlled analgesia (PCA). PCA has been shown to provide slightly better pain control and increased patient satisfaction when compared with conventional methods. Common preemptive approaches include epidural neuraxial blockade or nerve blocks. One review which looked at pain control after abdominal aortic surgery found that epidural blockade provides better pain relief (especially during movement) in the period up to three postoperative days. It reduces the duration of postoperative tracheal intubation by roughly half. The occurrence of prolonged postoperative mechanical ventilation and myocardial infarction is also reduced by epidural analgesia.

Risks and complications

See also: Patient safety

Risks and complications as they relate to anesthesia are classified as either morbidity (a disease or disorder that results from anesthesia) or mortality (death that results from anesthesia). Quantifying how anesthesia contributes to morbidity and mortality can be difficult because an animal's health prior to surgery and the complexity of the surgical procedure can also contribute to the risks.

Anesthesia-related deaths by ASA status

Prior to the introduction of anesthesia in the early 19th century, the physiologic stress from surgery caused significant complications and many deaths from shock. The faster the surgery was, the lower the rate of complications (leading to reports of very quick amputations). The advent of anesthesia allowed more complicated and life-saving surgery to be completed, decreased the physiologic stress of the surgery, but added an element of risk. It was two years after the introduction of ether anesthetics that the first death directly related to the use of anesthesia was reported.

Morbidity can be major (myocardial infarction, pneumonia, pulmonary embolism, kidney failure/chronic kidney disease, postoperative cognitive dysfunction and allergy) or minor (minor nausea, vomiting, readmission). There is usually overlap in the contributing factors that lead to morbidity and mortality between the health of the animals, the type of surgery being performed and the anesthetic. To understand the relative risk of each contributing factor, consider that the rate of deaths totally attributed to the patient's health is 1:870. Compare that to the rate of deaths totally attributed to surgical factors (1:2860) or anesthesia alone (1:185,056) illustrating that the single greatest factor in anesthetic mortality is the health of the patient. These statistics can also be compared to the first such study on mortality in anesthesia from 1954, which reported a rate of death from all causes at 1:75 and a rate attributed to anesthesia alone at 1:2680. Direct comparisons between mortality statistics cannot reliably be made over time and across countries because of differences in the stratification of risk factors, however, there is evidence that anesthetics have made a significant improvement in safety but to what degree is uncertain.

Rather than stating a flat rate of morbidity or mortality, many factors are reported as contributing to the relative risk of the procedure and anesthetic combined. For instance, an operation on a person who is between the ages of 60–79 years old places the patient at 2.3 times greater risk than someone less than 60 years old. Having an ASA score of 3, 4 or 5 places the person at 10.7 times greater risk than someone with an ASA score of 1 or 2. Other variables include age greater than 80 (3.3 times risk compared to those under 60), gender (females have a lower risk of 0.8), urgency of the procedure (emergencies have a 4.4 times greater risk), experience of the person completing the procedure (less than 8 years experience and/or less than 600 cases have a 1.1 times greater risk) and the type of anesthetic (regional anesthetics are lower risk than general anesthetics). Obstetrical, the very young and the very old are all at greater risk of complication so extra precautions may need to be taken.

On 14 December 2016, the Food and Drug Administration issued a Public Safety Communication warning that "repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in children younger than 3 years or in pregnant women during their third trimester may affect the development of children's brains." The warning was criticized by the American College of Obstetricians and Gynecologists, which pointed out the absence of direct evidence regarding use in pregnant women and the possibility that "this warning could inappropriately dissuade providers from providing medically indicated care during pregnancy." Patient advocates noted that a randomized clinical trial would be unethical, that the mechanism of injury is well-established in animals, and that studies had shown exposure to multiple uses of anesthetic significantly increased the risk of developing learning disabilities in young children, with a hazard ratio of 2.12 (95% confidence interval, 1.26–3.54).

Recovery

The immediate time after anesthesia is called emergence. Emergence from general anesthesia or sedation requires careful monitoring because there is still a risk of complication. Nausea and vomiting are reported at 9.8% but will vary with the type of anesthetic and procedure. There is a need for airway support in 6.8%, there can be urinary retention (more common in those over 50 years of age) and hypotension in 2.7%. Hypothermia, shivering and confusion are also common in the immediate post-operative period because of the lack of muscle movement (and subsequent lack of heat production) during the procedure. Furthermore, the rare manifestation in the post-anesthetic period may be the occurrence of functional neurological symptom disorder (FNSD).

Postoperative cognitive dysfunction (also known as POCD and post-anesthetic confusion) is a disturbance in cognition after surgery. It may also be variably used to describe emergence delirium (immediate post-operative confusion) and early cognitive dysfunction (diminished cognitive function in the first post-operative week). Although the three entities (delirium, early POCD and long-term POCD) are separate, the presence of delirium post-operatively predicts the presence of early POCD. There does not appear to be an association between delirium or early POCD and long-term POCD. According to a recent study conducted at the David Geffen School of Medicine at UCLA, the brain navigates its way through a series of activity clusters, or "hubs" on its way back to consciousness. Dr. Andrew Hudson, an assistant professor in anesthesiology states, "Recovery from anesthesia is not simply the result of the anesthetic 'wearing off,' but also of the brain finding its way back through a maze of possible activity states to those that allow conscious experience. Put simply, the brain reboots itself."

Long-term POCD is a subtle deterioration in cognitive function, that can last for weeks, months, or longer. Most commonly, relatives of the person report a lack of attention, memory and loss of interest in activities previously dear to the person (such as crosswords). In a similar way, people in the workforce may report an inability to complete tasks at the same speed they could previously. There is good evidence that POCD occurs after cardiac surgery and the major reason for its occurrence is the formation of microemboli. POCD also appears to occur in non-cardiac surgery. Its causes in non-cardiac surgery are less clear but older age is a risk factor for its occurrence.

History

Main articles: History of general anesthesia and History of neuraxial anesthesia

 

See also: Hua Tuo

 

Hua Tuo

The first attempts at general anesthesia were probably herbal remedies administered in prehistory. Alcohol is one of the oldest known sedatives and it was used in ancient Mesopotamia thousands of years ago. The Sumerians are said to have cultivated and harvested the opium poppy (Papaver somniferum) in lower Mesopotamia as early as 3400 BCE. The ancient Egyptians had some surgical instruments, as well as crude analgesics and sedatives, including possibly an extract prepared from the mandrake fruit.

In China, Bian Que (Chinese: 扁鹊, Wade–Giles: Pien Ch'iao, c. 300 BCE) was a legendary Chinese internist and surgeon who reportedly used general anesthesia for surgical procedures.Despite this, it was the Chinese physician Hua Tuo whom historians considered the first verifiable historical figure to develop a type of mixture of anesthesia, though his recipe has yet to be fully discovered.

Throughout Europe, Asia, and the Americas, a variety of Solanum species containing potent tropane alkaloids was used for anesthesia. In 13th-century Italy, Theodoric Borgognoni used similar mixtures along with opiates to induce unconsciousness, and treatment with the combined alkaloids proved a mainstay of anesthesia until the 19th century. Local anesthetics were used in Inca civilization where shamans chewed coca leaves and performed operations on the skull while spitting into the wounds they had inflicted to anesthetize. Cocaine was later isolated and became the first effective local anesthetic. It was first used in 1859 by Karl Koller, at the suggestion of Sigmund Freud, in eye surgery in 1884. German surgeon August Bier (1861–1949) was the first to use cocaine for intrathecal anesthesia in 1898. Romanian surgeon Nicolae Racoviceanu-Piteşti (1860–1942) was the first to use opioids for intrathecal analgesia; he presented his experience in Paris in 1901.

The "soporific sponge" ("sleep sponge") used by Arabic physicians was introduced to Europe by the Salerno school of medicine in the late 12th century and by Ugo Borgognoni (1180–1258) in the 13th century. The sponge was promoted and described by Ugo's son and fellow surgeon, Theodoric Borgognoni (1205–1298). In this anesthetic method, a sponge was soaked in a dissolved solution of opium, mandragora, hemlock juice, and other substances. The sponge was then dried and stored; just before surgery the sponge was moistened and then held under the patient's nose. When all went well, the fumes rendered the individual unconscious.

Sir Humphry Davy's Researches chemical and philosophical: chiefly concerning nitrous oxide (1800), pp. 556 and 557 (right), outlining potential anesthetic properties of nitrous oxide in relieving pain during surgery.

The most famous anesthetic, ether, may have been synthesized as early as the 8th century, but it took many centuries for its anesthetic importance to be appreciated, even though the 16th century physician and polymath Paracelsus noted that chickens made to breathe it not only fell asleep but also felt no pain. By the early 19th century, ether was being used by humans, but only as a recreational drug.

Meanwhile, in 1772, English scientist Joseph Priestley discovered the gas nitrous oxide. Initially, people thought this gas to be lethal, even in small doses, like some other nitrogen oxides. However, in 1799, British chemist and inventor Humphry Davy decided to find out by experimenting on himself. To his astonishment he found that nitrous oxide made him laugh, so he nicknamed it "laughing gas". In 1800 Davy wrote about the potential anesthetic properties of nitrous oxide in relieving pain during surgery, but nobody at that time pursued the matter any further.

On 14 November 1804, Hanaoka Seishū, a Japanese doctor, became the first person to successfully perform surgery using general anesthesia. Hanaoka learned traditional Japanese medicine as well as Dutch-imported European surgery and Chinese medicine. After years of research and experimentation, he finally developed a formula which he named tsūsensan (also known as mafutsu-san), which combined Korean morning glory and other herbs.

Hanaoka's success in performing this painless operation soon became widely known, and patients began to arrive from all parts of Japan. Hanaoka went on to perform many operations using tsūsensan, including resection of malignant tumors, extraction of bladder stones, and extremity amputations. Before his death in 1835, Hanaoka performed more than 150 operations for breast cancer. However, this finding did not benefit the rest of the world until 1854 as the national isolation policy of the Tokugawa shogunate prevented Hanaoka's achievements from being publicized until after the isolation ended. Nearly forty years would pass before Crawford Long, who is titled as the inventor of modern anesthetics in the West, used general anesthesia in Jefferson, Georgia.

Long noticed that his friends felt no pain when they injured themselves while staggering around under the influence of diethyl ether. He immediately thought of its potential in surgery. Conveniently, a participant in one of those "ether frolics", a student named James Venable, had two small tumors he wanted excised. But fearing the pain of surgery, Venable kept putting the operation off. Hence, Long suggested that he have his operation while under the influence of ether. Venable agreed, and on 30 March 1842 he underwent a painless operation. However, Long did not announce his discovery until 1849.

Contemporary re-enactment of Morton's 16 October 1846, ether operation; daguerrotype by Southworth & Hawes

 

Morton's ether inhaler

Horace Wells conducted the first public demonstration of the inhalational anesthetic at the Massachusetts General Hospital in Boston in 1845. However, the nitrous oxide was improperly administered and the person cried out in pain. On 16 October 1846, Boston dentist William Thomas Green Morton gave a successful demonstration using diethyl ether to medical students at the same venue. Morton, who was unaware of Long's previous work, was invited to the Massachusetts General Hospital to demonstrate his new technique for painless surgery. After Morton had induced anesthesia, surgeon John Collins Warren removed a tumor from the neck of Edward Gilbert Abbott. This occurred in the surgical amphitheater now called the Ether Dome. The previously skeptical Warren was impressed and stated, "Gentlemen, this is no humbug." In a letter to Morton shortly thereafter, physician and writer Oliver Wendell Holmes, Sr. proposed naming the state produced "anesthesia", and the procedure an "anesthetic".

Morton at first attempted to hide the actual nature of his anesthetic substance, referring to it as Letheon. He received a US patent for his substance, but news of the successful anesthetic spread quickly by late 1846. Respected surgeons in Europe including Liston, Dieffenbach, Pirogov, and Syme quickly undertook numerous operations with ether. An American-born physician, Boott, encouraged London dentist James Robinson to perform a dental procedure on a Miss Lonsdale. This was the first case of an operator-anesthetist. On the same day, 19 December 1846, in Dumfries Royal Infirmary, Scotland, a Dr. Scott used ether for a surgical procedure. The first use of anesthesia in the Southern Hemisphere took place in Launceston, Tasmania, that same year. Drawbacks with ether such as excessive vomiting and its explosive flammability led to its replacement in England with chloroform.

Discovered in 1831 by an American physician Samuel Guthrie (1782–1848), and independently a few months later by Frenchman Eugène Soubeiran (1797–1859) and Justus von Liebig (1803–1873) in Germany, chloroform was named and chemically characterized in 1834 by Jean-Baptiste Dumas (1800–1884). In 1842, Dr Robert Mortimer Glover in London discovered the anaesthetic qualities of chloroform on laboratory animals.

In 1847, Scottish obstetrician James Young Simpson was the first to demonstrate the anesthetic properties of chloroform on humans and helped to popularize the drug for use in medicine. This first supply came from local pharmacists, James Duncan and William Flockhart, and its use spread quickly, with 750,000 doses weekly in Britain by 1895. Simpson arranged for Flockhart to supply Florence Nightingale. Chloroform gained royal approval in 1853 when John Snow administered it to Queen Victoria when she was in labor with Prince Leopold. For the experience of child birth itself, chloroform met all the Queen's expectations; she stated it was "delightful beyond measure". Chloroform was not without fault though. The first fatality directly attributed to chloroform administration was recorded on 28 January 1848 after the death of Hannah Greener. This was the first of many deaths to follow from the untrained handling of chloroform. Surgeons began to appreciate the need for a trained anesthetist. The need, as Thatcher writes, was for an anesthetist to "(1)Be satisfied with the subordinate role that the work would require, (2) Make anesthesia their one absorbing interest, (3) not look at the situation of anesthetist as one that put them in a position to watch and learn from the surgeons technique (4) accept the comparatively low pay and (5) have the natural aptitude and intelligence to develop a high level of skill in providing the smooth anesthesia and relaxation that the surgeon demanded" These qualities of an anesthetist were often found in submissive medical students and even members of the public. More often, surgeons sought out nurses to provide anesthesia. By the time of the Civil War, many nurses had been professionally trained with the support of surgeons.

John Snow of London published articles from May 1848 onwards "On Narcotism by the Inhalation of Vapours" in the London Medical Gazette. Snow also involved himself in the production of equipment needed for the administration of inhalational anesthetics, the forerunner of today's anesthesia machines.

Alice Magaw, born in November 1860, is often referred to as "The Mother of Anesthesia". Her renown as the personal anesthesia provider for William and Charles Mayo was solidified by Mayo's own words in his 1905 article in which he described his satisfaction with and reliance on nurse anesthetists: "The question of anaesthesia is a most important one. We have regular anaesthetists [on] whom we can depend so that I can devote my entire attention to the surgical work." Magaw kept thorough records of her cases and recorded these anesthetics. In her publication reviewing more than 14,000 surgical anesthetics, Magaw indicates she successfully provided anesthesia without an anesthetic-related death. Magaw describes in another article, "We have administered an anesthetic 1,092 times; ether alone 674 times; chloroform 245 times; ether and chloroform combined 173 times. I can report that out of this number, 1,092 cases, we have not had an accident". Magaw's records and outcomes created a legacy defining that the delivery of anesthesia by nurses would serve the surgical community without increasing the risks to patients. In fact, Magaw's outcomes would eclipse those of practitioners today.

The first comprehensive medical textbook on the subject, Anesthesia, was authored in 1914 by anesthesiologist Dr. James Tayloe Gwathmey and the chemist Dr. Charles Baskerville. This book served as the standard reference for the specialty for decades and included details on the history of anesthesia as well as the physiology and techniques of inhalation, rectal, intravenous, and spinal anesthesia.

Of these first famous anesthetics, only nitrous oxide is still widely used today, with chloroform and ether having been replaced by safer but sometimes more expensive general anesthetics, and cocaine by more effective local anesthetics with less abuse potential.

Society and culture

Further information: Anesthesia provision in the United States, Anesthesiologist, and Nurse anesthetist

Almost all healthcare providers use anesthetic drugs to some degree, but most health professions have their own field of specialists in the field including medicine, nursing and dentistry.

Doctors specializing in anaesthesiology, including perioperative care, development of an anesthetic plan, and the administration of anesthetics are known in the US as anesthesiologists and in the UK, Canada, Australia, and NZ as anaesthetists or anaesthesiologists. All anesthetics in the UK, Australia, New Zealand, Hong Kong and Japan are administered by doctors. Nurse anesthetists also administer anesthesia in 109 nations. In the US, 35% of anesthetics are provided by physicians in solo practice, about 55% are provided by anesthesia care teams (ACTs) with anesthesiologists medically directing certified registered nurse anesthetists (CRNAs) or anesthesiologist assistants, and about 10% are provided by CRNAs in solo practice. There can also be anesthesiologist assistants (US) or physicians' assistants (anaesthesia) (UK) who assist with anesthesia.

Special populations

There are many circumstances when anesthesia needs to be altered for special circumstances due to the procedure (such as in cardiac surgery, cardiothoracic anesthesiology or neurosurgery), the patient (such as in pediatric anesthesia, geriatric, bariatric or obstetrical anesthesia) or special circumstances (such as in trauma, prehospital care, robotic surgery or extreme environments).