Inhalation General anesthetics
A few of inhalation general anesthetics are gases (e.g. nitrous oxide) and some of them are volatile liquid (sevoflurane) which are administered as vapours from calibrated vapourizer. Inhalation general anesthetics are of two types:
- Gases- e.g. Nitrous oxide, Xenon
- Volatile Liquid Anesthetics- e.g. Halothane, Diethyl ether, Isoflurane
Pharmacokinetics of Inhalation General Anesthetics
The anesthetic vapours are carried to the patient in a mixture of nitrous oxide and oxygen or oxygen enriched air. The concentration of an individual gas in a mixture of gases is proportional to its partial pressure. Onset of anesthesia depend on partial pressure of an anesthetic agent in brain which equates with alveolar partial pressure of that agent.
The rate of induction and recovery from anesthesia depend on factors which control the transfer of an inhalation anesthetic agent from the alveoli to the blood, and from there into the brain. These factors are-
- Solubility of the agent in blood– The blood: gas solubility coefficient is defined as relative affinity of an anesthetic agent for blood compared to air. Anesthetic agents having less solubility in blood have less blood: gas solubility coefficient and thus more rapid is the rise in partial pressure in arterial blood.
e.g. Nitrous oxide, desflurane have less blood solubility so they rapidly reach high arterial tension and thus rapid induction of anesthesia. The highly soluble anesthetic agents like diethyl ether show slow induction and slow recovery
- Its density- The lighter the gas, the faster is its diffusion in and out of tissues.
- It’s partial pressure in anesthetic mixture
- The rate of blood flow through the lungs and tissues – Increase in cardiac output results in increase in pulmonary blood flow. More agent is removed from alveoli, slowing the rate of increase in arterial tension and thus slowing the induction.
Inhalation anesthetics are mainly exhaled by pulmonary exhalation, but significant amount of halothane is eliminated also by hepatic metabolism.
The potency of inhalation agents is measured in terms of Minimum Alveolar Concentration (MAC). Anesthesia is produced when anesthetic concentration is brain is ≥ MAC. Usually 0.5 to 2 MAC are required for adequate anesthesia.
Gaseous Anesthetics
Nitrous oxide
Nitrous oxide is colorless inorganic gas with sweet taste. It is most commonly used inhalation anesthetic in dentistry and in emergency center and ambulatory center as well. When used alone, it cannot produce general anesthesia reliably so mostly used in combination with other anesthetics. However, as a single agent it has impressive safety and is excellent for providing minimal to moderate sedation.
Advantages
- By enabling reduced doses of more potent anesthetics, it helps to reduce cost of anesthesia and limits cardiorespiratory side effects.
- Non-inflammable and non-irritant
- Rapid induction and recovery
Disadvantages
- Excitement may be violent.
- When nitrous oxide anesthesia is terminated, nitrous oxide diffuses out of blood in alveoli faster than nitrogen is taken up. This may cause diffusion hypoxia in patients with low cardiopulmonary reserve. It can be countered by administration of 100 % oxygen for 10 minutes.
- May cause hallucination.
- An increase in spontaneous abortions has been reported in the wives of male dentists and in female chairside, dentists’ assistants.
Xenon
Xenon is colorless, odorless inert gas discovered by British chemist in 1898. Xenon possesses properties that make it virtually an ideal anesthetic and is used in critical conditions. The use of xenon as an anesthetic agent is promising.
Advantages
- Xenon is extremely insoluble in blood and other tissues providing rapid induction and quick recovery time.
- It is sufficiently potent to produce surgical anesthesia when used with 30% oxygen.
- It possesses analgesic properties, neuroprotective qualities and cardiovascular stability.
- No effect on pulmonary function, no renal and hepatic toxicity.
Disadvantages
- It is a rare gas that cannot be manufactured and should be extracted from air. So, it has limited availability and is expensive.
Volatile Liquid Anesthetics
The induction and recovery from anesthesia are slower compared to gaseous general anesthetics because of relatively more solubility in blood, cell water and fat.
Halothane
Halothane was introduced into clinical practice in 1956 as new, potent and non-explosive volatile anesthetic agent. It is fluorinated anesthetic with structure similar to chloroform and have sweet, fruity odor.
Advantages
- Non-inflammable and non-irritant.
- Post-operative vomiting infrequent.
- Inhibits pharyngeal and laryngeal reflexes making tracheal intubation easy.
Disadvantages
- Poor anesthetic during fetal intervention
- Poor analgesic
- It has side effects like respiratory depression, hepatic dysfunction, hypotension, intracranial tension, bradycardia, cardiac arrythmia etc.
- Post-operative recovery of mental function is slow.
- Inadequate muscular relaxation for abdominal surgery.
Clinical Use
- Most commonly used in children, in whom preoperative placement of an intravenous catheter can be difficult.
- Used to produce anesthesia along with nitrous oxide and oxygen.
Enflurane
This halogenated volatile liquid anesthetic is non-inflammable with mild sweet odor. It is primarily used for maintenance rather than induction of anesthesia. It produces anesthesia which resemble to that of halothane, except that muscular relaxation is better.
Disadvantages
- Enflurane has side effects like cardiac arrythmia, hypotension.
- It could produce seizures and involuntary muscle activity during deep anesthesia so contraindicated in patients with epilepsy and brain lesions.
Isoflurane
This volatile non-inflammable liquid with pungent odour is related to enflurane. It is considered as ‘near ideal” anesthetic and preferred in neurosurgery.
Advantages
- Rapid induction and recovery of anesthesia
- Good muscle relaxant
- Bronchodilator
- Lack of arrhythmogenic effect and absence of central nervous system excitation.
Disadvantages
- Pungent and respiratory irritant.
- It may cause respiratory depression, reduced arterial blood pressure, uterine relaxation.
Sevoflurane
It is clear, colorless, volatile liquid and is non-inflammable.
Use
- It is widely used for inducing anesthesia in outpatients because of its rapid recovery profile.
- It is well suited for inhalation induction of anesthesia, preferred in children due to its non-irritant nature.
Advantages
- It does not produce tachycardia so may be a preferable agent in patient with myocardial ischemia.
- Non-irritating to airway and is potent bronchodilator.
Disadvantages
- It may increase ICP in patients with poor intracranial compliance.
Desflurane
It is extremely volatile liquid with pungent odour. Induction and recovery from anesthesia are faster than any other volatile anesthetic agents. Due to its irritant nature and chances of causing cough, salivation and bronchospasm it is not preferred as anesthetic.
Diethyl ether
It is colorless volatile liquid with pungent odor.
Advantages
- It can be used during emergency condition without pre-anesthetic medication.
- Diethyl ether can be administered without complicated apparatus.
- It has wide margin of safety.
- Less chances of causing hepatotoxicity, nephrotoxicity and cardiac arrythmia
Disadvantages
- Inflammable and explosive so potentially hazardous
- Slow induction and recovery
- May cause vomiting or nausea due to its irritant nature and may also cause cough.
- May cause convulsion, especially in children.
References
- Ola Dale, Burnell R. Brown. ‘Clinical Pharmacokinetics of the Inhalation Anesthetics’. Clinical Pharmacokinetics. 12:145-167.
- Daniel E. Becker, Morton Rosenberg.’ Nitrous Oxide and Inhalation Anesthetics’. Anesthesia Progress: Winter 2008. 55(4):124-131.
- Philip M, Hopkins MB. Nitrous Oxide: a unique drug of continuing importance for anesthesia. Best Practice and Research Clinical Anesthesiology. 19(3): 381-389.
- Bryan D. Jordan, CRNA, MNA Elizabeth Laura Wright. Xenon as an Anesthetic Agent. AANA Journal ß October 2010 ß. 78(5): 387-392.
- Carl Lynch. Jan Baum, Rob Tenbrik. ‘Xenon anesthesia’. Anaesthiology. 92:865-870
- John P. Bunker, Charles M. Blumenfield. ‘Liver Necrosis after Halothane Anesthesia- Cause or Coincidence?’. The New England Journal of Medicine. 268:531-534.
- Wade JG, Stevens WC. ‘Isoflurane: an anesthetic for the eighties?’. Anesthesia and analgesia. 60(9):666-682.
- Joseph F. Sabik, Renato S. Assad, Frank L. Hanley. ‘Halothane as an anesthetic for fetal surgery’. Journal of Pediatric Surgery. 28(4):542-547.
- Pharmacology and Pharmacotherapeutics book, R.S. Satoskar. Page no- 109-122
- Goodman and GILLMAN’S Manual of Pharmacology and Therapeutics. Page no- 221-241
- A textbook of Clinical Pharmacology and Therapeutics. Page no -145-154.
- https://www.statpearls.com/ArticleLibrary/viewarticle/22065
