Isoflurane, sold under the trade name Forane among others, is a general anesthetic. It can be used to start or maintain anesthesia. Often another medication is used to start anesthesia due to airway irritation with isoflurane. It is used by inhalation. Isoflurane (isoflurane, USP) is a nonflammable, nonexplosive general inhalation anesthetic agent. Its chemical name is 1-chloro-2,2,2-trifluoroethyl difluoromethyl ether.
Isoflurane has a lower solubility coefficient than that of halothane, so induction and recovery with isoflurane is faster than with halothane. However, isoflurane causes moderate to severe airway irritability if used as an induction agent.
Isoflurane is the most potent of the currently used volatile anesthetics (MAC of 1.15%). Inhalation induction should theoretically be relatively rapid with isoflurane, but it is limited by its pungent odor, which, if induction is allowed to proceed too rapidly, leads to breath holding, laryngospasm, and coughing. This problem is usually overcome by inducing the patient with an intravenous agent prior to administering isoflurane.
Isoflurane is sufficiently potent to provide muscle relaxation adequate for any surgical procedure, but neuromuscular blocking agents are normally used for procedures that require profound muscle relaxation instead of the high concentrations of anesthetic needed to secure muscle relaxation. As with other potent inhalation anesthetics, isoflurane increases the action of the nondepolarizing neuromuscular
Isoflurane is always administered in conjunction with air or pure oxygen. Often nitrous oxide is also used. Although its physical properties imply that anaesthesia can be induced more rapidly than with halothane, its pungency can irritate the respiratory system, negating any possible advantage conferred by its physical properties. It is usually used to maintain a state of general anesthesia which has been induced with another drug, such as thiopentone or propofol.
Induction, Maintenance, and Recovery
Isoflurane is a stable liquid that has a blood:gas partition coefficient of 1.4, which is much higher than both sevoflurane and desflurane. Like the other inhalation agents, the MAC of isoflurane is age-dependent, ranging from 1.3% in preterm infants to 1.7% in infants 6 to 12 months of age and decreasing to 1.6% in children 1 to 5 years old, compared with 1.2% in adults (Cameron et al., 1984; LeDez and Lerman, 1987).
Because of its pungent odor, isoflurane causes coughing and laryngospasm, which precludes its use for inhalation inductions. Isoflurane is resistant to biodegradation, making the incidence of hepatotoxicity and nephrotoxicity minimal (Eger, 1984). The emergence profile is similar to that of halothane.
Like the other inhalation agents, isoflurane produces a dose-dependent respiratory depression, with an increase in respiratory rate and smaller tidal volumes that produce an increase in arterial CO2 pressure. Isoflurane depresses ventilation to a greater extent than halothane, and isoflurane anesthesia requires mechanical ventilation (Eger, 1984). It is also a bronchodilator, with continued effects at higher concentrations (Dikmen et al., 2003).
Isoflurane, in a dose-dependent manner, decreases systemic vascular resistance, resulting in a subsequent drop in the systemic arterial pressure and increase in heart rate, all while maintaining cardiac output (Wolf et al., 1986). Tachycardia is particularly seen in younger patients (Eger, 1984). However, there is no reported increase in the incidence of arrhythmia, and it does not appear to sensitize the myocardium to epinephrine.
Isoflurane produces muscle relaxation and potentiates the intensity and duration of action of pancuronium and to a lesser extent vecuronium and atracurium. This results in the need to adjust dosing of these neuromuscular blockers accordingly.
Animal studies have raised safety concerns of certain general anesthetics, in particular ketamine and isoflurane, in young children. The risk of neurodegeneration was increased in combination of these agents with nitrous oxide and benzodiazepines such as midazolam. Whether these concerns occur in humans is unclear.
Biophysical studies using NMR spectroscopy has provided molecular details of how inhaled anesthetics interact with three amino acid residues (G29, A30 and I31) of amyloid beta peptide and induce aggregation. This area is important as “some of the commonly used inhaled anesthetics may cause brain damage that accelerates the onset of Alzheimer’s disease”
Mechanism of action
Similar to many general anesthetics, the exact mechanism of the action has not been clearly delineated. Isoflurane reduces pain sensitivity (analgesia) and relaxes muscles. Isoflurane likely binds to GABA, glutamate and glycine receptors, but has different effects on each receptor. Isoflurane acts as a positive allosteric modulator of the GABAA receptor in electrophysiology studies of neurons and recombinant receptors. It potentiates glycine receptor activity, which decreases motor function.
It inhibits receptor activity in the NMDA glutamate receptor subtypes. Isoflurane inhibits conduction in activated potassium channels. Isoflurane also affects intracellular molecules. It activates calcium ATPase by increasing membrane fluidity. It binds to the D subunit of ATP synthase and NADH dehydrogenase. General anaesthesia with isoflurane reduces plasma endocannabinoid AEA concentrations, and this could be a consequence of stress reduction after loss of consciousness.