An anesthetic (American) (or anaesthetic, (British English) see spelling differences) is a drug that causes anesthesia—reversible loss of sensation. Anesthetics contrast with analgesics (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 anesthetics, 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.
Each of the local anesthetics have the suffix "-caine" in their names.
- lidocaine (also known as Lignocaine)
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, benzocaine, tetracaine) are generally unstable in solution and fast-acting, and allergic reactions are common.
Amide local anesthetics (e.g., lidocaine, prilocaine, bupivicaine, levobupivacaine, ropivacaine, mepivacaine, dibucaine and etidocine) 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.
- Nitrous oxide
- Xenon (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 anaesthetic agent currently in use meets all these requirements, nor can any anaesthetic agent be considered safe. There are inherent risks and drug interactions that are specific to each and every patient. 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.
Intravenous agents (non-opioid)
While there are many drugs that can be used intravenously to produce anesthesia or sedation, the most common are:
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 dreaming, extracorporeal experiences, and illusions." 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.
Neonatal and infant neurotoxicity concerns
Concerns have been raised as to the safety of general anesthetics, in particular ketamine 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 in these animals. 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:
The following agents have longer onset and duration of action and are frequently used for post-operative pain relief:
- diacetyl morphine, (Diamorphine, also known as heroin, not available in U.S.)
- Meperidine, also called pethidine in the UK, New Zealand, Australia and other countries
- Oxycodone, (not available intravenously in U.S.)
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 intubation or surgery by paralyzing skeletal muscle.
- Depolarizing muscle relaxants
- Non-depolarizing muscle relaxants
- 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 hyperthermia, 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.
- Non-depolarizing Muscle Relaxants
- Histamine release e.g. Atracurium & Mivacurium
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.
Intravenous reversal agents
- Flumazenil, reverses the effects of benzodiazepines
- Naloxone, reverses the effects of opioids
- Neostigmine, helps reverse the effects of non-depolarizing muscle relaxants
- Sugammadex, new agent that is designed to bind Rocuronium therefore terminating its action
- Hendrickx, JF.; Eger, EI.; Sonner, JM.; Shafer, SL. (Aug 2008). "Is synergy the rule? A review of anesthetic interactions producing hypnosis and immobility.". Anesth Analg 107 (2): 494–506. doi:10.1213/ane.0b013e31817b859e. PMID 18633028.
- Krøigaard, M.; Garvey, LH.; Menné, T.; Husum, B. (Oct 2005). "Allergic reactions in anaesthesia: are suspected causes confirmed on subsequent testing?". Br J Anaesth 95 (4): 468–71. doi:10.1093/bja/aei198. PMID 16100238.
- Townsend, Courtney (2004). Sabiston Textbook of Surgery. Philadelphia: Saunders. Chapter 17 – Anesthesiology Principles, Pain Management, and Conscious Sedation. ISBN 0-7216-5368-5.
- Miller, Ronald (2005). Miller's Anesthesia. New York: Elsevier/Churchill Livingstone. ISBN 0-443-06656-6.
- Garfield, JM, Garfield, FB, Stone, JG, Hopkins, D, Johns, LA (1972). ": A comparison of psychologic responses to ketamine and thiopental-nitrous oxide-halothane anesthesia". Anesthesiology 36 (4): 329–338. doi:10.1097/00000542-197204000-00006. PMID 5020642.
- Mellon, RD.; Simone, AF.; Rappaport, BA. (Mar 2007). "Use of anesthetic agents in neonates and young children.". Anesth Analg 104 (3): 509–20. doi:10.1213/01.ane.0000255729.96438.b0. PMID 17312200.
- Wang, C.; Slikker, W. (Jun 2008). "Strategies and experimental models for evaluating anesthetics: effects on the developing nervous system.". Anesth Analg 106 (6): 1643–58. doi:10.1213/ane.ob013e3181732c01. PMID 18499593.
- Istaphanous, GK.; Loepke, AW. (Jun 2009). "General anesthetics and the developing brain.". Current Opinion in Anesthesiology 22 (3): 368–73. doi:10.1097/ACO.0b013e3283294c9e. PMID 19434780.
- Philbin, DM, Rosow, CE, Schneider, RC, Koski, G, D'ambra, MN (1990). ": Fentanyl and sufentanil anesthesia revisited: how much is enough?". Anesthesiology 73 (1): 5–11. doi:10.1097/00000542-199007000-00002. PMID 2141773.
- Streisand JB, Bailey PL, LeMaire L, Ashburn MA, Tarver SD, Varvel J, Stanley TH: Fentanyl-induced rigidity and unconsciousness in human volunteers. Incidence, duration, and plasma concentrations. Anesthesiology 1993; 78:629–634.