Mean alveolar concentration (MAC) was used as a routine criterion for determining the effectiveness of inhalation anesthetics agents. The definition of MAC is a concentration of an inhalational anesthetics agent that prevents muscular movements in reaction to the surgical stimulation in 50% of individuals.
Effects on the respiratory system
All halogenated anesthetics cause depression of ventilation by reducing tidal volume. All inhalation anesthetics decrease the sensitivity and increase the threshold of the respiratory Centre to CO2. Sevoflurane and isoflurane result in a decrease in airway resistance while desflurane has no significant effect on bronchial tone. (Khan, Hayes, & Buggy, 2014) (Katzung, Masters, & Trevor, 2009)
Effects on cardiovascular system
All halogenated anesthetics decrease cardiac output and mean arterial pressure in a dose-dependent pattern. Desflurane, isoflurane, and sevoflurane primarily reduce systemic vascular resistance and reduce mean arterial pressure. QT interval prolongation may be observed with Sevoflurane and should be administered with caution in QT interval syndrome. Isoflurane has more arrhythmogenic potential than desflurane and isoflurane. (Khan, Hayes, & Buggy, 2014).
| Agent | Heart Rate | Cardiac Output | Systemic Vascular Resistance (SVR) | Mean Arterial Pressure |
|---|---|---|---|---|
| Halothane | Marked Reduction | Decrease | No Effect | Decrease |
| Enflurane | Increase | Marked Reduction | Decrease | Marked Reduction |
| Isoflurane | Increase | Decrease | Decrease | Decrease |
| Desflurane | Increase | No Effect | Decrease | Decrease |
| Sevoflurane | No Effect | No Effect | Decrease | Decrease |
| Nitrous oxide | Increase | Decrease | Increase | No Effect |
| Xenon | Decrease | No Effect | No Effect | No Effect |
Effects on central nervous system
All inhalation anesthetics cause a decrease in cerebral metabolic rate and oxygen consumption. They may also increase intracranial pressure due to cerebral vasodilation. Nitrous Oxide is least likely to increase Cerebral Blood Flow. It also mildly increases the cerebral metabolic rate of O2 (CMRO2), however, coadministration of barbiturates, opiates, or propofol reduce these effects [Petersen KD et al. Anesthesiology 98: 329, 2003]. Desflurane, isoflurane, and Sevoflurane decrease CMRO2. At 0.5 Minimum Alveolar Concentration (MAC) the cerebral metabolic rate of O2 (CMRO2) decreases and cerebral blood flow does not change; above 1 MAC CBF increases due to a more prominent vasodilatory effect. (Kassiri, Ardehali, Rashidi, & Hashemian, 2018) (Khan, Hayes, & Buggy, 2014).
The increase in cerebral blood flow in patients who have elevated intracranial pressure due to brain tumor or head injury is clinically undesirable. Inhaled anesthetics increases CBF, further increases the cerebral blood volume thus cause an increase in ICP. (Katzung, Masters, & Trevor, 2009)
| Agent | Tone | CMRO2 | Cerebral Blood Flow | Intracranial Pressure |
|---|---|---|---|---|
| Nitrous Oxide | Vasodilation | ↑ | ↑ | ↑ |
| Sevoflurane | Vasodilation | ↓ | ↑* | ↑* |
| desflurane | Vasodilation | ↓ | ↑* | ↑* |
| isoflurane | Vasodilation | ↓ | ↑* | ↑* |
*CBF and ICP do not increase until MAC 1.0 because of CMRO2.
Effects on the liver
All inhaled anesthetics decrease blood flow to the liver to some extent. Volatile agents, Sevoflurane, desflurane, and isoflurane are mainly excreted unchanged and only 2-5% of the drug is metabolized.
25% of halothane is metabolized by oxidative phosphorylation. The main metabolite formed is Trifluoroacetic acid (TFA) which binds to a liver protein forming a TFA-protein complex which induces cell-mediated immune response resulting in hepatic necrosis. The risk of hepatitis increases with repeated exposure. (Khan, Hayes, & Buggy, 2014)
Effects on the kidneys
Metabolism of halogenated agents results in the production of fluoride which may cause direct nephrotoxicity. Methoxyflurane is associated with high fluoride levels while with enflurane the serum fluoride level decreases more rapidly than Methoxyflurane. Isoflurane can be used for longer periods without any significant increase in serum fluorides because it is more resistant to defluorination. (Khan, Hayes, & Buggy, 2014)
Dose depended on a decrease in glomerular filtration rate and renal blood flow can impair autoregulation of blood flow in the kidney. (Katzung, Masters, & Trevor, 2009)
Elimination of Inhalation anesthetics:
The same principles of anesthesia are followed in reverse during recovery from inhalation anesthesia. The time of recovery depends on the rate of elimination of anesthetic agent from the central nervous system. The blood Gas partition factor is an important factor that governs the rate of recovery. When the administration of an anesthetic agent is discontinued the alveolar concentration of the drug falls rapidly. Insoluble agents diffuse into the alveolus and are removed from the body through lung ventilation. (Katzung, Masters, & Trevor, 2009)
Inhaled anesthetics agents have low blood: gas partition coefficient and are insoluble in blood and brain and their elimination is faster than more soluble agents. Elimination of desflurane, sevoflurane, and nitrous oxide occurs more rapidly, leading to rapid recovery as compared to halothane and isoflurane. Halothane is more soluble in brain tissues and in blood than nitrous oxide and desflurane; therefore, its elimination slow and recovery is less rapid. (Katzung, Masters, & Trevor, 2009)
20% of the halothane is metabolized while the remaining 80% is eliminated from the body by exhalation. Recent studies suggest that the metabolism of halothane may be as high as 40 to 50%. Initially, halothane is mostly eliminated through exhalation but as the alveolar concertation decreases elimination through metabolism dominates. Enflurane is more resistant to metabolism and only 2 to 5% of the drug is eliminated through hepatic metabolism, however, recent studies show that 8.5% of the drug is hepatically metabolized. Hepatic metabolism of Isoflurane is very low and only 0.2% of the drug metabolized. (Dale & Brown, 2012)
References
Dale, O., & Brown, B. R. (2012, November 04). Clinical Pharmacokinetics of the Inhalational Anaesthetics. Clinical Pharmacokinetic, 145-167. doi:10.2165/00003088-198712030-00001
Kassiri, N., Ardehali, S. H., Rashidi, F., & Hashemian, S. M. (2018). Inhalational anesthetics agents: The pharmacokinetics, pharmacodynamics, and their effects on the human body. 2(3), 173-177.
Katzung, B. G., Masters, S. B., & Trevor, A. J. (2009). Basic & Clinical Pharmacology (11th ed.). The McGraw-Hill Companies. Inc.
Khan, K. S., Hayes, I., & Buggy, D. J. (2014, June). Pharmacology of anesthetic agents II: inhalation anesthetic agents. Continuing Education in Anaesthesia Critical Care & Pain, 14(3), 106-111. doi:https://doi.org/10.1093/bjaceaccp/mkt038.
Eger EI 2nd, Saidman LJ, Brandstater B. Minimum alveolar anesthetic concentration: A standard of anesthetic potency. Anesthesiology 1965;26:756-6.