Anaesthetic drugs
Encyclopedia
An anesthetic is a drug that causes anesthesia
—reversible loss of sensation. They contrast with analgesic
s (painkillers), which relieve pain without eliminating sensation. These drugs are generally administered to facilitate surgery
. A wide variety of drugs are used in modern anesthetic practice. Many are rarely used outside of anesthesia, although others are used commonly by all disciplines. Anesthetics are categorized into two classes: general anesthetics, which cause a reversible loss of consciousness, and local anesthetic
s, which cause a reversible loss of sensation for a limited region of the body while maintaining consciousness. Combinations of anesthetics are sometimes used for their synergistic and additive therapeutic effects. Adverse effects, however, may also be increased.
Local anesthetics are agents that prevent transmission of nerve impulses without causing unconsciousness. They act by binding to fast sodium channels from within (in an open state). Local anesthetics can be either ester
or amide
based.
Ester local anesthetics (e.g., procaine, amethocaine, cocaine) are generally unstable in solution and fast-acting, and allergic reactions are common.
Amide local anesthetics (e.g., lidocaine, prilocaine, bupivicaine, levobupivacaine, ropivacaine, mepivacaine and dibucaine) are generally heat-stable, with a long shelf life (around 2 years). They have a slower onset and longer half-life than ester anesthetics, and are usually racemic
mixtures, with the exception of levobupivacaine (which is S(-) -bupivacaine) and ropivacaine (S(-)-ropivacaine). These agents are generally used within regional and epidural or spinal techniques, due to their longer duration of action, which provides adequate analgesia for surgery, labor, and symptomatic relief.
Only preservative
-free local anesthetic agents may be injected intrathecal
ly.
Volatile agents are specially formulated organic liquids that evaporate readily into vapors, and are given by inhalation for induction and/or maintenance of general anesthesia. Nitrous oxide and xenon are gases at room temperature rather than liquids, so they are not considered volatile agents. The ideal anesthetic vapor or gas should be non-flammable, non-explosive, and lipid-soluble. It should possess low blood gas solubility, have no end-organ (heart, liver, kidney) toxicity or side-effects, should not be metabolized, and should not be an irritant to the respiratory pathways of the patient.
No anesthetic agent currently in use meets all these requirements. The agents in widespread current use are isoflurane
, desflurane
, sevoflurane
, and nitrous oxide. Nitrous oxide is a common adjuvant
gas, making it one of the most long-lived drugs still in current use. Because of its low potency, it cannot produce anesthesia on its own but is frequently combined with other agents. Halothane, an agent introduced in the 1950s, has been almost completely replaced in modern anesthesia practice by newer agents because of its shortcomings. Partly because of its side effects, enflurane never gained widespread popularity.
In theory, any inhaled anesthetic agent can be used for induction of general anesthesia. However, most of the halogenated anesthetics are irritating to the airway, perhaps leading to coughing, laryngospasm and overall difficult inductions. For this reason, the most frequently used agent for inhalational induction is sevoflurane . All of the volatile agents can be used alone or in combination with other medications to maintain anesthesia (nitrous oxide is not potent enough to be used as a sole agent).
Volatile agents are frequently compared in terms of potency, which is inversely proportional to the minimum alveolar concentration
. Potency is directly related to lipid solubility. This is known as the Meyer-Overton hypothesis
. However, certain pharmacokinetic properties of volatile agents have become another point of comparison. Most important of those properties is known as the blood: gas partition coefficient. This concept refers to the relative solubility of a given agent in blood. Those agents with a lower blood solubility (i.e., a lower blood–gas partition coefficient; e.g., desflurane) give the anesthesia provider greater rapidity in titrating the depth of anesthesia, and permit a more rapid emergence from the anesthetic state upon discontinuing their administration. In fact, newer volatile agents (e.g., sevoflurane, desflurane) have been popular not due to their potency (minimum alveolar concentration), but due to their versatility for a faster emergence from anesthesia, thanks to their lower blood–gas partition coefficient.
The two barbiturates mentioned above, thiopental and methohexital, are ultra-short-acting, and are used to induce and maintain anesthesia. However, though they produce unconsciousness, they provide no analgesia (pain relief) and must be used with other agents. Benzodiazepines can be used for sedation
before or after surgery and can be used to induce and maintain general anesthesia. When benzodiazepines are used to induce general anesthesia, midazolam is preferred. Benzodiazepines are also used for sedation during procedures that do not require general anesthesia. Like barbiturates, benzodiazepines have no pain-relieving properties. Propofol is one of the most commonly used intravenous drugs employed to induce and maintain general anesthesia. It can also be used for sedation during procedures or in the ICU
. Like the other agents mentioned above, it renders patients unconscious without producing pain relief. Because of its favorable physiological effects, "etomidate has been primarily used in sick patients". Ketamine is infrequently used in anesthesia because of the unpleasant experiences that sometimes occur on emergence from anesthesia, which include "vivid dream
ing, extracorporeal experiences, and illusion
s." However, like etomidate it is frequently used in emergency settings and with sick patients because it produces fewer adverse physiological effects. Unlike the intravenous anesthetic drugs previously mentioned, ketamine produces profound pain relief, even in doses lower than those that induce general anesthesia. Also unlike the other anesthetic agents in this section, patients who receive ketamine alone appear to be in a cataleptic
state, unlike other states of anesthesia that resemble normal sleep
. Ketamine-anesthetized patients have profound analgesia but keep their eyes open and maintain many reflexes.
and isoflurane
in neonates and young children due to significant neurodegeneration
. The risk of neurodegeneration is increased in combination of these agents with nitrous oxide and benzodiazepines such as midazolam. This has led to the FDA and other bodies to takes steps to investigate these concerns. These concerns have arisen from animal studies involving rats and non-human primates. Research has found that anesthetics which enhance GABA or block NMDA can precipitate neuronal cell death. The developing central nervous system is most vulnerable to these potential neurotoxic effects during the last trimester of pregnancy and shortly after birth. Melatonin, a free oxygen radical scavenger and indirect antioxidant is known to reduce the toxicity of a range of drugs has been found in a rat study to reduce the neurotoxicity of anesthetic agents to the early developing brain. Recent research in animals has found that all sedatives and anesthetics cause extensive neurodegeneration in the developing brain. There is also some evidence in humans that surgery and exposure to anesthetics in the early developmental stages causes persisting learning deficits.
The following agents have longer onset and duration of action and are frequently used for post-operative pain relief:
or surgery by paralyzing skeletal muscle.
Another potentially disturbing complication where neuromuscular blockade is employed is 'anesthesia awareness
'. In this situation, patients paralyzed may awaken during their anesthesia, due to an inappropriate decrease in the level of drugs providing sedation and/or pain relief. If this fact is missed by the anesthesia provider, the patient may be aware of his surroundings, but be incapable of moving or communicating that fact. Neurological monitors are increasingly available that may help decrease the incidence of awareness. Most of these monitors use proprietary algorithms monitoring brain activity via evoked potentials. Despite the widespread marketing of these devices many case reports exist in which awareness under anesthesia has occurred despite apparently adequate anesthesia as measured by the neurologic monitor.
Anesthesia
Anesthesia, or anaesthesia , traditionally meant the condition of having sensation blocked or temporarily taken away...
—reversible loss of sensation. They contrast with analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
s (painkillers), which relieve pain without eliminating sensation. These drugs are generally administered to facilitate surgery
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
. A wide variety of drugs are used in modern anesthetic practice. Many are rarely used outside of anesthesia, although others are used commonly by all disciplines. Anesthetics are categorized into two classes: general anesthetics, which cause a reversible loss of consciousness, and local anesthetic
Local anesthetic
A local anesthetic is a drug that causes reversible local anesthesia, generally for the aim of having local analgesic effect, that is, inducing absence of pain sensation, although other local senses are often affected as well...
s, which cause a reversible loss of sensation for a limited region of the body while maintaining consciousness. Combinations of anesthetics are sometimes used for their synergistic and additive therapeutic effects. Adverse effects, however, may also be increased.
Local anesthetics
Each of the local anesthetics have the suffix "-caine" in their names.- procaineProcaineProcaine is a local anesthetic drug of the amino ester group. It is used primarily to reduce the pain of intramuscular injection of penicillin, and it was also used in dentistry. Owing to the ubiquity of the trade name Novocain, in some regions procaine is referred to generically as novocaine...
- amethocaine
- cocaineCocaineCocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
- lidocaineLidocaineLidocaine , Xylocaine, or lignocaine is a common local anesthetic and antiarrhythmic drug. Lidocaine is used topically to relieve itching, burning and pain from skin inflammations, injected as a dental anesthetic or as a local anesthetic for minor surgery.- History :Lidocaine, the first amino...
(also known as Lignocaine) - prilocainePrilocainePrilocaine is a local anesthetic of the amino amide type first prepared by Claes Tegner and Nils Lofgren. In its injectable form , it is often used in dentistry. It is also often combined with lidocaine as a preparation for dermal anesthesia , for treatment of conditions like paresthesia...
- bupivacaineBupivacaineBupivacaine is a local anaesthetic drug belonging to the amino amide group. AstraZeneca commonly markets it under various trade names, including Marcain, Marcaine, Sensorcaine and Vivacaine.-Indications:...
- levobupivacaineLevobupivacaineLevobupivacaine is a local anaesthetic drug belonging to the amino amide group. It is the S-enantiomer of bupivacaine. Levobupivacaine hydrochloride is commonly marketed by Abbott under the trade name Chirocaine.-Clinical use:...
- ropivacaineRopivacaineRopivacaine is a local anaesthetic drug belonging to the amino amide group. The name ropivacaine refers to both the racemate and the marketed S-enantiomer...
- mepivacaineMepivacaineMepivacaine is a local anesthetic of the amide type. Mepivacaine has a reasonably rapid onset and medium duration of action and is marketed under various trade names including Carbocaine and Polocaine.Mepivacaine became available in the United States in the 1960s.Mepivacaine is used in any...
- dibucaine
Local anesthetics are agents that prevent transmission of nerve impulses without causing unconsciousness. They act by binding to fast sodium channels from within (in an open state). Local anesthetics can be either ester
Ester
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
or amide
Amide
In chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...
based.
Ester local anesthetics (e.g., procaine, amethocaine, cocaine) are generally unstable in solution and fast-acting, and allergic reactions are common.
Amide local anesthetics (e.g., lidocaine, prilocaine, bupivicaine, levobupivacaine, ropivacaine, mepivacaine and dibucaine) are generally heat-stable, with a long shelf life (around 2 years). They have a slower onset and longer half-life than ester anesthetics, and are usually racemic
Racemic
In chemistry, a racemic mixture, or racemate , is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule. The first known racemic mixture was "racemic acid", which Louis Pasteur found to be a mixture of the two enantiomeric isomers of tartaric acid.- Nomenclature :A...
mixtures, with the exception of levobupivacaine (which is S(-) -bupivacaine) and ropivacaine (S(-)-ropivacaine). These agents are generally used within regional and epidural or spinal techniques, due to their longer duration of action, which provides adequate analgesia for surgery, labor, and symptomatic relief.
Only preservative
Preservative
A preservative is a naturally occurring or synthetically produced substance that is added to products such as foods, pharmaceuticals, paints, biological samples, wood, etc. to prevent decomposition by microbial growth or by undesirable chemical changes....
-free local anesthetic agents may be injected intrathecal
Intrathecal
Intrathecal is an adjective that refers to something introduced into or occurring in the space under the arachnoid membrane of the brain or spinal cord...
ly.
Inhaled agents
- DesfluraneDesfluraneDesflurane is a highly fluorinated methyl ethyl ether used for maintenance of general anesthesia. Like halothane, enflurane and isoflurane, it is a racemic mixture of and optical isomers...
- EnfluraneEnfluraneEnflurane is a halogenated ether that was commonly used for inhalational anesthesia during the 1970s and 1980s. Developed by Ross Terrell in 1963, it was first used clinically in 1966....
- HalothaneHalothaneHalothane is an inhalational general anesthetic. Its IUPAC name is 2-bromo-2-chloro-1,1,1-trifluoroethane. It is the only inhalational anesthetic agent containing a bromine atom; there are several other halogenated anesthesia agents which lack the bromine atom and do contain the fluorine and...
- IsofluraneIsofluraneIsoflurane is a halogenated ether used for inhalational anesthesia. Together with enflurane and halothane, it replaced the flammable ethers used in the pioneer days of surgery. Its name comes from being a structural isomer of enflurane, hence they have the same empirical formula...
- MethoxyfluraneMethoxyfluraneMethoxyflurane is a halogenated ether that was in clinical use as an volatile inhalational anesthetic from its introduction by Joseph F. Artusio et al in 1960 until around 1974. It was first synthesized in the late 1940s by William T...
- Nitrous oxideNitrous oxideNitrous oxide, commonly known as laughing gas or sweet air, is a chemical compound with the formula . It is an oxide of nitrogen. At room temperature, it is a colorless non-flammable gas, with a slightly sweet odor and taste. It is used in surgery and dentistry for its anesthetic and analgesic...
- SevofluraneSevofluraneSevoflurane , also called fluoromethyl hexafluoroisopropyl ether, is a sweet-smelling, nonflammable, highly fluorinated methyl isopropyl ether used for induction and maintenance of general anesthesia. Together with desflurane, it is replacing isoflurane and halothane in modern anesthesiology...
- XenonXenonXenon is a chemical element with the symbol Xe and atomic number 54. The element name is pronounced or . A colorless, heavy, odorless noble gas, xenon occurs in the Earth's atmosphere in trace amounts...
(rarely used)
Volatile agents are specially formulated organic liquids that evaporate readily into vapors, and are given by inhalation for induction and/or maintenance of general anesthesia. Nitrous oxide and xenon are gases at room temperature rather than liquids, so they are not considered volatile agents. The ideal anesthetic vapor or gas should be non-flammable, non-explosive, and lipid-soluble. It should possess low blood gas solubility, have no end-organ (heart, liver, kidney) toxicity or side-effects, should not be metabolized, and should not be an irritant to the respiratory pathways of the patient.
No anesthetic agent currently in use meets all these requirements. The agents in widespread current use are isoflurane
Isoflurane
Isoflurane is a halogenated ether used for inhalational anesthesia. Together with enflurane and halothane, it replaced the flammable ethers used in the pioneer days of surgery. Its name comes from being a structural isomer of enflurane, hence they have the same empirical formula...
, desflurane
Desflurane
Desflurane is a highly fluorinated methyl ethyl ether used for maintenance of general anesthesia. Like halothane, enflurane and isoflurane, it is a racemic mixture of and optical isomers...
, sevoflurane
Sevoflurane
Sevoflurane , also called fluoromethyl hexafluoroisopropyl ether, is a sweet-smelling, nonflammable, highly fluorinated methyl isopropyl ether used for induction and maintenance of general anesthesia. Together with desflurane, it is replacing isoflurane and halothane in modern anesthesiology...
, and nitrous oxide. Nitrous oxide is a common adjuvant
Adjuvant
An adjuvant is a pharmacological or immunological agent that modifies the effect of other agents, such as a drug or vaccine, while having few if any direct effects when given by itself...
gas, making it one of the most long-lived drugs still in current use. Because of its low potency, it cannot produce anesthesia on its own but is frequently combined with other agents. Halothane, an agent introduced in the 1950s, has been almost completely replaced in modern anesthesia practice by newer agents because of its shortcomings. Partly because of its side effects, enflurane never gained widespread popularity.
In theory, any inhaled anesthetic agent can be used for induction of general anesthesia. However, most of the halogenated anesthetics are irritating to the airway, perhaps leading to coughing, laryngospasm and overall difficult inductions. For this reason, the most frequently used agent for inhalational induction is sevoflurane . All of the volatile agents can be used alone or in combination with other medications to maintain anesthesia (nitrous oxide is not potent enough to be used as a sole agent).
Volatile agents are frequently compared in terms of potency, which is inversely proportional to the minimum alveolar concentration
Minimum alveolar concentration
Minimum alveolar concentration or MAC is a concept used to compare the strengths, or potency, of anaesthetic vapours; in simple terms, it is defined as the concentration of the vapour in the lungs that is needed to prevent movement in 50% of subjects in response to surgical stimulus...
. Potency is directly related to lipid solubility. This is known as the Meyer-Overton hypothesis
Minimum alveolar concentration
Minimum alveolar concentration or MAC is a concept used to compare the strengths, or potency, of anaesthetic vapours; in simple terms, it is defined as the concentration of the vapour in the lungs that is needed to prevent movement in 50% of subjects in response to surgical stimulus...
. However, certain pharmacokinetic properties of volatile agents have become another point of comparison. Most important of those properties is known as the blood: gas partition coefficient. This concept refers to the relative solubility of a given agent in blood. Those agents with a lower blood solubility (i.e., a lower blood–gas partition coefficient; e.g., desflurane) give the anesthesia provider greater rapidity in titrating the depth of anesthesia, and permit a more rapid emergence from the anesthetic state upon discontinuing their administration. In fact, newer volatile agents (e.g., sevoflurane, desflurane) have been popular not due to their potency (minimum alveolar concentration), but due to their versatility for a faster emergence from anesthesia, thanks to their lower blood–gas partition coefficient.
Intravenous agents (non-opioid)
While there are many drugs that can be used intravenously to produce anesthesia or sedation, the most common are:- BarbiturateBarbiturateBarbiturates are drugs that act as central nervous system depressants, and can therefore produce a wide spectrum of effects, from mild sedation to total anesthesia. They are also effective as anxiolytics, as hypnotics, and as anticonvulsants...
s- AmobarbitalAmobarbitalAmobarbital is a drug that is a barbiturate derivative. It has sedative-hypnotic and analgesic properties. It is a white crystalline powder with no odor and a slightly bitter taste. It was first synthesized in Germany in 1923...
(trade nameTrade nameA trade name, also known as a trading name or a business name, is the name which a business trades under for commercial purposes, although its registered, legal name, used for contracts and other formal situations, may be another....
: Amytal) - MethohexitalMethohexitalMethohexital, also called methohexitone, is a drug which is a barbiturate derivative. It is classified as short-acting, and has a rapid onset of action...
(trade name: Brevital) - ThiamylalThiamylalThiamylal is a barbiturate derivative invented in the 1950s. It has sedative, anticonvulsant and hypnotic effects, and is used as a strong but short acting sedative. Thamylal is still in current use, primarily for induction in surgical anaesthesia or as an anticonvulsant to counteract side...
(trade name: Surital) - ThiopentalSodium thiopentalSodium thiopental, better known as Sodium Pentothal , thiopental, thiopentone sodium, or Trapanal , is a rapid-onset short-acting barbiturate general anaesthetic...
(trade name: Penthothal, referred to as thiopentone in the UK)
- Amobarbital
- Benzodiazepines
- DiazepamDiazepamDiazepam , first marketed as Valium by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms , restless legs syndrome, alcohol withdrawal,...
- LorazepamLorazepamLorazepam is a high-potency short-to-intermediate-acting 3-hydroxy benzodiazepine drug that has all five intrinsic benzodiazepine effects: anxiolytic, amnesic, sedative/hypnotic, anticonvulsant, antiemetic and muscle relaxant...
- MidazolamMidazolamMidazolam is a short-acting drug in the benzodiazepine class developed by Hoffmann-La Roche in the 1970s. The drug is used for treatment of acute seizures, moderate to severe insomnia, and for inducing sedation and amnesia before medical procedures. It possesses profoundly potent anxiolytic,...
- Diazepam
- EtomidateEtomidateEtomidate is a short acting intravenous anaesthetic agent used for the induction of general anaesthesia and for sedation for short procedures such as reduction of dislocated joints, tracheal intubation and cardioversion...
- KetamineKetamineKetamine is a drug used in human and veterinary medicine. Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist...
- PropofolPropofolPropofol is a short-acting, intravenously administered hypnotic agent. Its uses include the induction and maintenance of general anesthesia, sedation for mechanically ventilated adults, and procedural sedation. Propofol is also commonly used in veterinary medicine...
The two barbiturates mentioned above, thiopental and methohexital, are ultra-short-acting, and are used to induce and maintain anesthesia. However, though they produce unconsciousness, they provide no analgesia (pain relief) and must be used with other agents. Benzodiazepines can be used for sedation
Sedation
Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure...
before or after surgery and can be used to induce and maintain general anesthesia. When benzodiazepines are used to induce general anesthesia, midazolam is preferred. Benzodiazepines are also used for sedation during procedures that do not require general anesthesia. Like barbiturates, benzodiazepines have no pain-relieving properties. Propofol is one of the most commonly used intravenous drugs employed to induce and maintain general anesthesia. It can also be used for sedation during procedures or in the ICU
Intensive Care Unit
thumb|220px|ICU roomAn intensive-care unit , critical-care unit , intensive-therapy unit/intensive-treatment unit is a specialized department in a hospital that provides intensive-care medicine...
. Like the other agents mentioned above, it renders patients unconscious without producing pain relief. Because of its favorable physiological effects, "etomidate has been primarily used in sick patients". Ketamine is infrequently used in anesthesia because of the unpleasant experiences that sometimes occur on emergence from anesthesia, which include "vivid dream
Dream
Dreams are successions of images, ideas, emotions, and sensations that occur involuntarily in the mind during certain stages of sleep. The content and purpose of dreams are not definitively understood, though they have been a topic of scientific speculation, philosophical intrigue and religious...
ing, extracorporeal experiences, and illusion
Illusion
An illusion is a distortion of the senses, revealing how the brain normally organizes and interprets sensory stimulation. While illusions distort reality, they are generally shared by most people....
s." However, like etomidate it is frequently used in emergency settings and with sick patients because it produces fewer adverse physiological effects. Unlike the intravenous anesthetic drugs previously mentioned, ketamine produces profound pain relief, even in doses lower than those that induce general anesthesia. Also unlike the other anesthetic agents in this section, patients who receive ketamine alone appear to be in a cataleptic
Catalepsy
Catalepsy is also a term used by hypnotists to refer to the state of making a hypnotised subject's arm, leg or back rigid. "Arm catalepsy" is often a pre-hypnotic test performed prior to an induction into a full trance.-Causes:...
state, unlike other states of anesthesia that resemble normal sleep
Sleep
Sleep is a naturally recurring state characterized by reduced or absent consciousness, relatively suspended sensory activity, and inactivity of nearly all voluntary muscles. It is distinguished from quiet wakefulness by a decreased ability to react to stimuli, and is more easily reversible than...
. Ketamine-anesthetized patients have profound analgesia but keep their eyes open and maintain many reflexes.
Neonatal and infant neurotoxicity concerns
Concerns have been raised as to the safety of general anesthetics, in particular ketamineKetamine
Ketamine is a drug used in human and veterinary medicine. Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist...
and isoflurane
Isoflurane
Isoflurane is a halogenated ether used for inhalational anesthesia. Together with enflurane and halothane, it replaced the flammable ethers used in the pioneer days of surgery. Its name comes from being a structural isomer of enflurane, hence they have the same empirical formula...
in neonates and young children due to significant neurodegeneration
Neurodegeneration
Neurodegeneration is the umbrella term for the progressive loss of structure or function of neurons, including death of neurons. Many neurodegenerative diseases including Parkinson’s, Alzheimer’s, and Huntington’s occur as a result of neurodegenerative processes. As research progresses, many...
. The risk of neurodegeneration is increased in combination of these agents with nitrous oxide and benzodiazepines such as midazolam. This has led to the FDA and other bodies to takes steps to investigate these concerns. These concerns have arisen from animal studies involving rats and non-human primates. Research has found that anesthetics which enhance GABA or block NMDA can precipitate neuronal cell death. The developing central nervous system is most vulnerable to these potential neurotoxic effects during the last trimester of pregnancy and shortly after birth. Melatonin, a free oxygen radical scavenger and indirect antioxidant is known to reduce the toxicity of a range of drugs has been found in a rat study to reduce the neurotoxicity of anesthetic agents to the early developing brain. Recent research in animals has found that all sedatives and anesthetics cause extensive neurodegeneration in the developing brain. There is also some evidence in humans that surgery and exposure to anesthetics in the early developmental stages causes persisting learning deficits.
Intravenous opioid analgesic agents
While opioids can produce unconsciousness, they do so unreliably and with significant side effects. So, while they are rarely used to induce anesthesia, they are frequently used along with other agents such as intravenous non-opioid anesthetics or inhalational anesthetics. Furthermore, they are used to relieve pain of patients before, during, or after surgery. The following opioids have short onset and duration of action and are frequently used during general anesthesia:- AlfentanilAlfentanilAlfentanil is a potent but short-acting synthetic opioid analgesic drug, used for anaesthesia in surgery. It is an analogue of fentanyl with around 1/4 the potency of fentanyl and around 1/3 of the duration of action, but with an onset of effects 4x faster than fentanyl...
- Fentanyl
- RemifentanilRemifentanilRemifentanil is a potent ultra short-acting synthetic opioid analgesic drug. It is given to patients during surgery to relieve pain and as an adjunct to an anaesthetic. Remifentanil is used for sedation as well as combined with other medications for use in general anesthesia...
- SufentanilSufentanilSufentanil is a powerful synthetic opioid analgesic drug, approximately 5 to 10 times more potent than its analog, fentanyl. Sufentanil is marketed for use by specialist centres under different trade names, such as Sufenta and Sufentil...
(Not available in the UK)
The following agents have longer onset and duration of action and are frequently used for post-operative pain relief:
- BuprenorphineBuprenorphineBuprenorphine is a semi-synthetic opioid that is used...
- ButorphanolButorphanolButorphanol is a morphinan-type synthetic opioid analgesic developed by Bristol-Myers. Brand name Stadol was recently discontinued by the manufacturer. It is now only available in its generic formulations, manufactured by Novex, Mylan, Apotex and Ben Venue Laboratories. Butorphanol is most...
- Diamorphine, (diacetyl morphine, also known as heroin, not available in U.S.)
- HydromorphoneHydromorphoneHydromorphone, a more common synonym for dihydromorphinone, commonly a hydrochloride is a very potent centrally-acting analgesic drug of the opioid class. It is a derivative of morphine, to be specific, a hydrogenated ketone thereof and, therefore, a semi-synthetic drug...
- LevorphanolLevorphanolLevorphanol is an opioid medication used to treat severe pain. It is the levorotatory stereoisomer of the synthetic morphinan and a pure opioid agonist, first described in Germany in 1948 as an orally active morphine-like analgesic...
- Meperidine, also called pethidine in the UK, New Zealand, Australia and other countries
- MethadoneMethadoneMethadone is a synthetic opioid, used medically as an analgesic and a maintenance anti-addictive for use in patients with opioid dependency. It was developed in Germany in 1937...
- MorphineMorphineMorphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
- NalbuphineNalbuphineNalbuphine is a semi-synthetic opioid used commercially as an analgesic under a variety of trade names, including Nubain. It is noteworthy in part for the fact that at low dosages, it is found much more effective by women than by men, and may even increase pain in men, leading to its...
- OxycodoneOxycodoneOxycodone is an opioid analgesic medication synthesized from opium-derived thebaine. It was developed in 1916 in Germany, as one of several new semi-synthetic opioids in an attempt to improve on the existing opioids: morphine, diacetylmorphine , and codeine.Oxycodone oral medications are generally...
, (not available intravenously in U.S.) - OxymorphoneOxymorphoneOxymorphone or 14-Hydroxydihydromorphinone is a powerful semi-synthetic opioid analgesic first developed in Germany circa 1914, patented in the USA by Endo Pharmaceuticals in 1955 and introduced to the United States market in January 1959 and other countries around the same time...
- PentazocinePentazocinePentazocine is a synthetically prepared prototypical mixed agonist-antagonist narcotic drug of the benzomorphan class of opioids used to treat moderate to moderately severe pain...
Muscle relaxants
Muscle relaxants do not render patients unconscious or relieve pain. Instead, they are sometimes used after a patient is rendered unconscious (induction of anesthesia) to facilitate intubationIntubation
Tracheal intubation, usually simply referred to as intubation, is the placement of a flexible plastic or rubber tube into the trachea to maintain an open airway or to serve as a conduit through which to administer certain drugs...
or surgery by paralyzing skeletal muscle.
- Depolarizing muscle relaxants
- Succinylcholine (also known as suxamethonium in the UK, New Zealand, Australia and other countries, "Celokurin" or "celo" for short in Europe)
- DecamethoniumDecamethoniumDecamethonium is a depolarizing muscle relaxant or neuromuscular blocking agent, and is used in anesthesia to induce paralysis.- Pharmacology :...
- Non-depolarizing muscle relaxants
- Short acting
- MivacuriumMivacuriumMivacurium chloride is a short-duration non-depolarizing neuromuscular-blocking drug or skeletal muscle relaxant in the category of non-depolarizing neuromuscular-blocking drugs, used adjunctively in anesthesia to facilitate endotracheal intubation and to provide skeletal muscle relaxation during...
- RapacuroniumRapacuroniumRapacuronium is a rapidly acting, non-depolarizing neuromuscular blocker formerly used in modern anaesthesia, to aid and enable endotracheal intubation, which is often necessary to assist in the controlled ventilation of unconscious patients during surgery and sometimes in intensive care...
- Mivacurium
- Intermediate acting
- AtracuriumAtracuriumAtracurium besylate is a neuromuscular-blocking drug or skeletal muscle relaxant in the category of non-depolarizing neuromuscular-blocking drugs, used adjunctively in anesthesia to facilitate endotracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical...
- CisatracuriumCisatracuriumCisatracurium is a neuromuscular-blocking drug or skeletal muscle relaxant in the category of non-depolarizing neuromuscular-blocking drugs, used adjunctively in anesthesia to facilitate endotracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation...
- RocuroniumRocuroniumRocuronium is an aminosteroid non-depolarizing neuromuscular blocker or muscle relaxant used in modern anaesthesia, to facilitate endotracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation.Introduced in 1994, rocuronium has...
- VecuroniumVecuroniumVecuronium is a muscle relaxant in the category of non-depolarizing blocking agents. Vecuronium bromide is indicated as an adjunct to general anesthesia, to facilitate endotracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation...
- Atracurium
- Long acting
- AlcuroniumAlcuroniumAlcuronium is a peripherally acting muscle relaxant in the curare alkaloid family. It is a semi-synthetic substance derived from toxiferine.- Effects :...
- Doxacurium
- GallamineGallamineGallamine triethiodide is a non-depolarising muscle relaxant. It acts by combining with the cholinergic receptor sites in muscle and competitively blocking the transmitter action of acetylcholine. Gallamine triethiodide has a parasympatholytic effect on the cardiac vagus nerve which causes...
- MetocurineMetocurineMetocurine is a muscle relaxant through neuromuscular blockade.It is excreted entirely through the kidneys and therefore should not be used in patients with renal failure....
- PancuroniumPancuroniumPancuronium is a muscle relaxant with various purposes. It is the second of three drugs administered during most lethal injections in the United States.- Mode of action :...
- Pipecuronium
- TubocurarineTubocurarineTubocurarine is a neuromuscular-blocking drug or skeletal muscle relaxant in the category of non-depolarizing neuromuscular-blocking drugs, used adjunctively in anesthesia to provide skeletal muscle relaxation during surgery or mechanical ventilation...
- Alcuronium
- Short acting
Adverse effects
- Depolarizing Muscle Relaxants i.e. Suxamethonium
- Hyperkalemia – A small rise of 0.5 mmol/l occurs normally, this is of little consequence unless potassium is already raised such as in renal failure
- Hyperkalemia – Exaggerated potassium release in burn patients (occurs from 24 hours after injury, lasting for up to 2 years), neuromuscular disease and paralyzed (quadraplegic, paraplegic) patients. The mechanism is reported to be through upregulation of acetylcholine receptors in those patient populations with increased efflux of potassium from inside muscle cells. May cause life threatening arrhythmia
- Muscle aches, commoner in young muscular patients who mobilize soon after surgery
- Bradycardia, especially if repeat doses are given
- Malignant hyperthermiaMalignant hyperthermiaMalignant hyperthermia or malignant hyperpyrexia is a rare life-threatening condition that is usually triggered by exposure to certain drugs used for general anesthesia; specifically, the volatile anesthetic agents and the neuromuscular blocking agent, succinylcholine...
, a potentially life threatening condition in susceptible patients - Suxamethonium Apnea, a rare genetic condition leading to prolonged duration of neuromuscular blockade, this can range from 20 minutes to a number of hours. Not dangerous as long as it is recognized and the patient remains intubated and sedated, there is the potential for awareness if this does not occur.
- Anaphylaxis
- Non-depolarizing Muscle Relaxants
- Histamine release e.g. Atracurium & Mivacurium
- Anaphylaxis
Another potentially disturbing complication where neuromuscular blockade is employed is 'anesthesia awareness
Anesthesia awareness
Anesthesia awareness, or unintended intra-operative awareness occurs during general anesthesia, on the operating table, when the patient has not been given enough of the general anesthetic or analgesic to render the patient unconscious during general anesthesia...
'. In this situation, patients paralyzed may awaken during their anesthesia, due to an inappropriate decrease in the level of drugs providing sedation and/or pain relief. If this fact is missed by the anesthesia provider, the patient may be aware of his surroundings, but be incapable of moving or communicating that fact. Neurological monitors are increasingly available that may help decrease the incidence of awareness. Most of these monitors use proprietary algorithms monitoring brain activity via evoked potentials. Despite the widespread marketing of these devices many case reports exist in which awareness under anesthesia has occurred despite apparently adequate anesthesia as measured by the neurologic monitor.
Intravenous reversal agents
- FlumazenilFlumazenilFlumazenil is a benzodiazepine antagonist available for injection only, and the only benzodiazepine receptor antagonist on the market today.It was first introduced in 1987 by Hoffmann-La Roche under the trade name Anexate, but only approved by...
, reverses the effects of benzodiazepines - NaloxoneNaloxoneNaloxone is an opioid antagonist drug developed by Sankyo in the 1960s. Naloxone is a drug used to counter the effects of opiate overdose, for example heroin or morphine overdose. Naloxone is specifically used to counteract life-threatening depression of the central nervous system and respiratory...
, reverses the effects of opioids - NeostigmineNeostigmineNeostigmine is a parasympathomimetic that acts as a reversible acetylcholinesterase inhibitor.- Synthesis :Neostigmine was first synthesized by Aeschlimann and Reinert in 1931....
, helps reverse the effects of non-depolarizing muscle relaxants - SugammadexSugammadexSugammadex is an agent for reversal of neuromuscular blockade by the agent rocuronium in general anaesthesia. It is the first selective relaxant binding agent and was discovered at the Newhouse research site in Scotland. . These scientists who discovered Sugammadex worked for the pharmaceutical...
, new agent that is designed to bind Rocuronium therefore terminating its action