Chemistry - An inhalant general anesthetic agent, isoflurane occurs as a colorless, nonflammable, stable liquid. It has a characteristic mildly pungent musty, ethereal odor. At 20°C, isoflurane’s specific gravity is 1.496 and vapor pressure is 238 mm Hg.
Storage/Stability/Compatibility - Isoflurane should be stored at room temperature; it is relatively unaffected by exposure to light, but should be stored in a tight, light-resistant container. Isoflurane does not attack aluminum, brass, tin, iron or copper.
Pharmacology - While the precise mechanism that inhalent anesthetics exert their general anesthetic effects is not precisely known, they may interfere with functioning of nerve cells in the brain by acting at the lipid matrix of the membrane. Some key pharmacologic effects noted with isoflurane include: CNS depression, depression of body temperature regulating centers, increased cerebral blood flow, respiratory depression, hypotension, vasodilatation, and myocardial depression (less so than with halothane) and muscular relaxation.
Minimal Alveolar Concentration (MAC; %) in oxygen reported for isoflurane in various species: Dog = 1.5; Cat = 1.2; Horse = 1.31; Human = 1.2. Several factors may alter MAC (acid/base status, temperature, other CNS depressants on board, age, ongoing acute disease, etc.).
Uses/Indications - Isoflurane is an inhalant anesthetic that has some distinct advantages over either halothane or methoxyflurane due to its lessened myocardial depressant and catecholamine sensitizing effects, and the ability to use it safely in patients with either hepatic or renal disease. Isoflurane’s higher cost than either methoxyflurane or halothane is a disadvantage.
Horses may recover more rapidly than with halothane, but be more susceptible to anesthetic associated myopathy.
Pharmacokinetics - Isoflurane is rapidly absorbed from the alveoli. It is rapidly distributed into the CNS and crosses the placenta. The vast majority of the drug is eliminated via the lungs; only about 0.17% is metabolized in liver and only very small amounts of inorganic fluoride is formed.
Contraindications/Precautions/Reproductive Safety - Isoflurane is contraindicated in patients with a history or predilection towards malignant hyperthermia. It should be used with caution (benefits vs. risks) in patients with increased CSF or head injury, or myasthenia gravis.
Some animal studies have indicated that isoflurane may be fetotoxic. Use during pregnancy with caution.
Adverse Effects/Warnings - Hypotension (secondary to vasodilation, not cardiodepression) may occur and is considered to be dose related. Dose-dependent respiratory depression, and GI effects (nausea, vomiting, ileus) have been reported. While cardiodepression generally is minimal at doses causing surgical planes of anesthesia, it may occur. Arrhythmias have also rarely been reported.
Drug Interactions - While isoflurane sensitizes the myocardium to the effects of sympathomimetics less so than halothane, arrhythmias may still result. Drugs included are: dopamine, epinephrine, norepinephrine, ephedrine, metaraminol, etc. Caution and monitoring is advised. Non-depolarizing neuromuscular blocking agents, systemic aminoglycosides, systemic lincomycins should be used with caution with halogenated anesthetic agents as additive neuromuscular blockade may occur. Concomitant administration of succinylcholine with inhalation anesthetics may induce increased incidences of cardiac effects (bradycardia, arrhythmias, sinus arrest and apnea) and in susceptible patients, malignant hyperthermia as well.
Dogs/Cats: (Note: Concentrations are dependent upon fresh gas flow rate; the lower the flow rate, the higher the concentration required.)
a) 5% induction; 1.5 - 2.5% maintenance (Papich 1992)
b) 0.5 - 3 %, inhaled (Hubbell 1994)
CAUTION! Sedative and anesthetic drug dosages for African elephants often vary from those for Asian elephants. Do not assume that the recommendations for one species can be applied to the other. Significant variation may also occur between individual elephants. Higher doses may be needed in wild or excited animals. Unless otherwise specified, doses refer to captive elephants. The information provided here should be used as a guideline only. Consultation with experienced colleagues is advised.
Special Note Concerning the Use of isoflurane: several authors recommend that gas anesthesia be discontinued for a period of time (10-40 minutes) prior to the administration of narcotic antagonists in elephants immobilized with etorphine or carfentanil. The administration of oxygen (with a high flow rate and frequent emptying of the re-breathing bag) facilitates removal of the gas and can prevent ataxia once the narcotic antagonist is given.
a,b) A 2817 kg female Asian elephant was induced with 1.75 mg etorphine IM, followed by 0.75 mg etorphine at 40 minutes. The elephant was intubated with a 30 mm endotracheal tube and maintained with 1.5-2.0% isoflurane. A latex weather balloon was used as a rebreathing bag. Additional etorphine (total additional 1.4 mg) was supplemented IV during the procedure to surgically remove P-3. Thirty minutes prior to the completion of the procedure isoflurane was discontinued, but oxygen continued to flow. Additional etorphine was given intermittently IV (0.4 mg total) during the remaining 45 minutes of recumbency. Naltrexone was given IV and the elephant was standing within 3 minutes (Fowler et.al. 1999 and 2000).
c) See abstract below (Dunlop et.al. 1994).
d) Following induction with 6 mg etorphine and 150 mg atropine IM, followed by 2-4 mg etorphine IV, a 3500 kg African elephant was intubated with a 40 mm (I.D.) cuffed endotracheal tube using a large stomach tube passed through the larynx as a guide. Anesthesia was maintained for 2.5 hrs during each of two procedures. Details of isoflurane % and flow rate not stated. Isoflurane was discontinued and oxygen administered at 120L/min for 40 minutes prior to reversal with 20 mg diprenorphine IV (Dunlop et.al. 1988).
a) Fowler,M.E., Steffey,E.P., Galuppo,L., and Pascoe,J.R. 2000. Facilitation of Asian elephant (Elephas maximus) standing immobilization and anesthesia with a sling. Journal of Zoo and Wildlife Medicine 31:(1):118-123 Abstract: An Asian elephant (Elephas maximus) required general anesthesia for orthopedic foot surgery. The elephant was unable to lie down, so it was placed in a custom-made sling, administered i.m. etorphine hydrochloride in the standing position, and lowered to lateral recumbency. General anesthesia was maintained with isoflurane administered through an endotracheal tube. After surgery, the isoflurane anesthesia was terminated, with immobilization maintained with additional i.v. etorphine. The elephant was lifted to the vertical position, and the immobilizing effects of etorphine were reversed with naltrexone. The suspension system and hoist for the sling were designed specifically for the elephant house.
b) Fowler,M.E., Steffey,E.P., Galuppo,L., and Pascoe,J.R. 1999. Standing immobilization and anesthesia in an Asian elephant (Elephas maximus). Proc. Am. Assoc. Zoo Vet. Pages: 107-110
c) Dunlop,C.I., Hodgson,D.S., Cambre,R.C., Kenny,D.E., and
Martin,H.D. 1994. Cardiopulmonary effects of three prolonged periods of
isoflurane anesthesia in an adult elephant. Journal of the American
Veterinary Medical Association 205:(10):1439-1444
d) Dunlop,C.I., Hodgson,D.S., Cambre,R.C., and Kenney,D. 1988. Prolonged isoflurane anesthesia of an adult elephant on two occasions. Veterinary Surgery 17:(3):167-168
Monitoring Parameters - 1) Respiratory and ventilatory status; 2) Cardiac rate/rhythm; blood pressure (particularly with “at risk” patients; 3) Level of anesthesia
Dosage Forms/Preparations/FDA Approval Status/Withholding Times -
Isoflurane in 100 ml bottles; Aerrane® (Anaquest; Isovet ® (Schering) (Rx) Approved for use in dogs and cats.; IsoFlo® (Abbott) (Rx); Approved for dogs and horses.
Isoflurane in 100 ml bottles;Isoflurane®(Abbott), Forane® (Anaquest); (Rx)
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