Inhalation anesthetic
Inhalation anesthetics (also known as inhalation anesthetics ) are medicinal substances that can be absorbed by inhalation and are used in anesthesia to maintain and also induce anesthesia . Inhalation anesthetics are administered as gases or vaporized liquids by means of a vaporizer via a ventilation mask , a laryngeal mask or an endotracheal tube as breathing gas mixtures ( gas mixtures ). The aim of using inhalation anesthetics is to temporarily switch off consciousness and reflexes.
Substance groups
Volatile anesthetics and the gases N 2 O ( laughing gas , nitrous oxide) and (to a lesser extent) xenon are used as inhalation anesthetics . Substances used previously, such as chloroform and diethyl ether , are generally no longer of any significance today due to their toxicity or risk of explosion.
Gases
Laughing gas has an analgesic effect (relieves pain), but less deactivates consciousness (hypnotic). In order to achieve an effective concentration of 70% it must be given together with pure oxygen . In modern anesthesia , the effect of nitrous oxide is by adding other anesthetic optimized. It is advantageous that the gas Toggle rapidly under anesthesia and down flooded . The diffusion of laughing gas into air-filled body cavities can be problematic. The medical use of nitrous oxide as an anesthetic has declined sharply in recent years.
Xenon is a modern alternative, but it is not yet widespread, particularly for economic reasons.
Volatile anesthetics
Volatile anesthetics are anesthetics that are administered via a vaporizer of the anesthesia machine . Historically, diethyl ether and chloroform were important as the first volatile anesthetics. Nowadays, in the western world, mainly flurans such as isoflurane , sevoflurane and desflurane are used. The bromine-containing halothane is generally no longer used in Europe and the USA.
Flurans are characterized by low molecular weight, high vapor pressure and low boiling point . They contain an ether bridge as a functional group. Flurans are halogenated several times. This is why they are also called "halo ethers". They have very good hypnotic and low-level analgesic properties , as well as, to varying degrees, low muscle-relaxing properties. Mononesthesia for painful interventions is therefore not recommended for humans; the corridors should then be combined with analgesics (so-called balanced anesthesia ). All volatile anesthetics lead, depending on the dose, to loss of consciousness, respiratory depression and a decrease and / or cessation of reflex activity. Hallways are colorless and non-flammable. Their odor is pungent and they are irritating to the upper respiratory tract , only sevoflurane has a mild, allegedly pleasant odor and is the only volatile anesthetic that is also suitable for induction of anesthesia with a mask. They are inert and relatively stable to light. They do not interact with metals or plastics, but can partially dissolve plastics or their additives.
The flurans include enflurane , isoflurane , sevoflurane and desflurane, as well as methoxyflurane . They are commercially available as liquids. The largest suppliers of Fluranen are Abbott Laboratories and Baxter Healthcare. To enable easy identification, Flurane containers are provided with a color code: enflurane orange, isoflurane violet, sevoflurane yellow and desflurane blue.
Mechanism of action
Inhalation anesthetics are believed to affect numerous target structures. The inhalation anesthetics used in anesthesia are characterized by high lipophilicity . In addition, the chemically inert noble gas xenon also has an anesthetic effect. Therefore, the effect of inhalation anesthetics is explained in particular with their lipophilicity and a non-specific interaction with components of the cell membrane (see Meyer-Overton hypothesis ).
In addition to this membrane modulation, there are also interactions with hydrophobic parts of ion channels , which are responsible for the transmission of stimuli. Specific interactions with cell membrane components, such as receptors ( GABA-A receptor , 5-HT3 receptor , NMDA receptor , mACh receptor ), are also discussed.
In addition to the anesthetic effect, volatile anesthetics and xenon also have protective effects, e.g. B. on heart muscle tissue (pharmacological preconditioning). For example, patients who underwent heart surgery had a lower mortality rate when they were anesthetized with anesthetic gases compared to patients with anesthesia with only intravenous drugs (TIVA). This is attributed to a heart-protecting effect (cardioprotection).
Pharmacokinetics
Inhalation anesthetics differ in their physicochemical properties, such as the vapor pressure , the oil-gas distribution coefficient and the blood-gas distribution coefficient. The vapor pressure and the blood-gas partition coefficient determine the uptake by the lungs, while the oil-gas partition coefficient allows a prediction of the anesthetic potency. The minimum alveolar concentration (MAC) is used as the unit of measurement for the effectiveness of an inhalation anesthetic .
The following Mac 50 values apply :
- Halothane 0.8%;
- Isoflurane 1.2%;
- Sevoflurane 1.7%;
- Enflurane 1.7%;
- Desflurane 6.0%;
- Nitrous oxide 105%.
- Xenon 71%
Blood solubility
Inhalation anesthetics have the great advantage of being precisely controllable, as they can flood in and out quickly. They are added to the inspiratory gas mixture ( oxygen / compressed air or oxygen / nitrous oxide ) and inhaled by the patient. They pass into the blood from the alveoli of the lungs. The speed at which this transfer takes place depends on the one hand on the inspiratory concentration (the higher the concentration in the alveolar air, the higher the concentration gradient between alveolar air and blood and therefore the faster the transfer into the blood), and on the other hand on the solubility of the Anesthetic in the blood (the more soluble, the slower the rise in the partial pressure in the blood, see also Henry's Law ). The ratio of the concentration of the anesthetic in the blood to the concentration in the alveolar air is called the blood / gas coefficient . A coefficient of 1 means that when the partial pressures between the two compartments blood and air are equalized, the same concentration prevails in both compartments. The higher this coefficient, the more soluble the anesthetic is in the blood, i.e. the more anesthetic has to pass into the blood until the partial pressures are equalized. The result is a slow influx of the anesthetic, i.e. falling asleep more slowly (or deepening the anesthesia). On the other hand, if the coefficient is significantly lower than 1, this indicates poor solubility. The partial pressure rises rapidly, which is referred to as "rapid influx" of the anesthesia, accompanied by rapid falling asleep or deepening of the anesthesia. In the same way, a poorly soluble gas (with a low blood / gas partition coefficient) will quickly drain away as soon as the alveolus is flushed with an anesthetic-free air mixture (during anesthesia diversion). Desflurane has the lowest blood / gas coefficient of all currently used volatile anesthetics and is therefore the fastest to flood on and off. However, the duration of the previous anesthesia also plays a role in the elimination time, since the longer the exposure time, an accumulation in the body, mainly in the fatty tissue, takes place.
Fat solubility
The volatile anesthetic is distributed with the blood in the patient's body and is released to different tissues because there is a concentration gradient here too. The enrichment in lipophilic, i.e. fatty structures, is interesting for the effect of the anesthetics. The primary site of action, the central nervous system / brain, largely consists of fatty structures. Therefore, good fat solubility of a volatile anesthetic requires rapid accumulation in the brain and thus a rapid onset of action . The oil / gas coefficient (analogous to the distribution coefficient ) is used as a measure of fat solubility . A volatile anesthetic is more potent, the higher the oil / gas coefficient.
Side effects
Side effects of inhalation anesthetics vary depending on the substance. Malignant hyperthermia is a serious undesirable effect of all inhalation anesthetics (with the exception of nitrous oxide and xenon) . Since flurans in particular promote postoperative nausea and vomiting and (in the case of isoflurane dose-dependent) lead to an increase in intracranial pressure , total intravenous anesthesia is preferred in the case of known postoperative nausea and vomiting or in patients prone to travel sickness and in patients with increased intracranial pressure .
literature
- Karsten Michael: Pharmacological Knowledge - Inhalation Anesthetics. In: Franz-Josef Kretz, Frank Teufel (Ed.): Anesthesia and intensive medicine. Springer Medicine, Heidelberg 2006, ISBN 3-540-62739-1 , pp. 19-28.
Individual evidence
- ↑ C. Uhlig, T. Bluth, K. Schwarz, S. Deckert, L. Heinrich, J. Schmitt, T. Koch: Effects of general anesthesia with volatile anesthetics on lethality . In: Anästh Intensivmed . tape 57 , 2016, p. 394-442 .
- ↑ E. Eger 2nd, C. Lundgren, S. Miller, W. Stevens: Anesthetic potencies of sulfur hexafluoride, carbon tetrafluoride, chloroform and Ethrane in dogs: correlation with the hydrate and lipid theories of anesthetic action. In: Anestesiology. 30, 1969, pp. 129-135.
- ↑ Reinhard Larsen: Anesthesia and intensive medicine in cardiac, thoracic and vascular surgery. (1st edition 1986) 5th edition. Springer, Berlin / Heidelberg / New York et al. 1999, ISBN 3-540-65024-5 , pp. 1-16; here: p. 3.