ATTANE — isoflurane liquid
Piramal Critical Care Inc
Federal Law restricts this drug to use by or on the order of a licensed veterinarian.
Not for use in horses intended for food.
Isoflurane, USP, a nonflammable liquid administered by vaporizing, is a general inhalation anesthetic drug. It is l-chloro-2,2,2-trifluoroethyl difluoromethyl ether, and its structural formula is:
Each mL contains 99.9% isoflurane.
Some physical constants are:
Molecular weight 184.5
Boiling point at 760 mm Hg 48.5°C (uncorr.)
Refractive index n20 D 1.2990-1.3005
Specific gravity 25° /25° C 1.496
Vapor pressure in mm Hg** 20° C 238
25° C 295
30° C 367
35° C 450
**Equation for vapor pressure calculation:
A = 8.056
log10 P vap = A + B B = -1664.58
T T = o C + 273.16
Partition coefficients at 37°C:
Partition coefficients at 25°C — rubber and plastic
Conductive rubber/gas 62.0
Butyl rubber/gas 75.0
Polyvinyl chloride/gas 110.0
Butyl acetate/gas ~2.5
Purity by gas chromatography >99.9%
Lower limit of flammability in oxygen or None
nitrous oxide at 9 joules/sec. and 23° C
Lower limit of flammability in oxygen or Greater than useful
nitrous oxide at 900 joules/sec. and 23° C concentration in anesthesia.
MAC (Minimum Alveolar Concentration) is 1.31% in horses1 and 1.28% in dogs.6
Isoflurane is a clear, colorless, stable liquid containing no additives or chemical stabilizers. Isoflurane has a mildly pungent, musty, ethereal odor. Samples stored in indirect sunlight in clear, colorless glass for five years, as well as samples directly exposed for 30 hours to a 2-amp, 115-volt, 60-cycle long wave U.V. light were unchanged in composition as determined by gas chromatography. Isoflurane in one normal sodium methoxide-methanol solution, a strong base, for over six months consumed essentially no alkali, indicative of strong base stability. Isoflurane does not decompose in the presence of soda lime, (at normal operating temperatures) and does not attack aluminum, tin, brass, iron or copper.
Isoflurane is an inhalation anesthetic. Induction and recovery from anesthesia with isoflurane are rapid.2,5 The level of anesthesia may be changed rapidly with isoflurane. Isoflurane is a profound respiratory depressant. RESPIRATION MUST BE MONITORED CLOSELY IN THE HORSE AND DOG AND SUPPORTED WHEN NECESSARY. As anesthetic dose is increased, both tidal volume and respiratory rate decrease.3,6 This depression is partially reversed by surgical stimulation, even at deeper levels of anesthesia.
Blood pressure decreases with induction of anesthesia but returns toward normal with surgical stimulation. Progressive increases in depth of anesthesia produce corresponding decreases in blood pressure; however, heart rhythm is stable and cardiac output is maintained with controlled ventilation and normal PaCO2 despite increasing depth of anesthesia. The hypercapnia which attends spontaneous ventilation during isoflurane anesthesia increases heart rate and raises cardiac output above levels observed with controlled ventilation.3 Isoflurane does not sensitize the myocardium to exogenously administered epinephrine in the dog.
Muscle relaxation may be adequate for intra-abdominal operations at normal levels of anesthesia. However, if muscle relaxants are used to achieve greater relaxation, it should be noted that; ALL COMMONLY USED MUSCLE RELAXANTS ARE MARKEDLY POTENTIATED WITH ISOFLURANE, THE EFFECT BEING MOST PROFOUND WITH THE NONDEPOLARIZING TYPE. Neostigmine reverses the effect of nondepolarizing muscle relaxants in the presence of isoflurane but does not reverse the direct neuromuscular depression of isoflurane.
Attane (isoflurane, USP) is used for induction and maintenance of general anesthesia in horses and dogs.
Attane (isoflurane, USP) is contraindicated in horses and dogs with known sensitivity to isoflurane or to other halogenated agents.
Increasing depth of anesthesia with isoflurane may increase hypotension and respiratory depression. The electroencephalographic pattern associated with deep anesthesia is characterized by burst suppression, spiking, and isoelectric periods.4
Since levels of anesthesia may be altered easily and rapidly, only vaporizers producing predictable percentage concentrations of isoflurane should be used. (see DOSAGE AND ADMINISTRATION)
The action of nondepolarizing relaxants is augmented by isoflurane. Less than the usual amounts of these drugs should be used. If the usual amounts of non-depolarizing relaxants are given, the time for recovery from myoneural blockade will be longer in the presence of isoflurane than in the presence of other commonly used anesthetics.
Not for use in horses intended for food.Keep out of reach of children.
Isoflurane, like some other inhalational anesthetics, can react with desiccated carbon dioxide (CO2 ) absorbents to produce carbon monoxide which may result in elevated levels of carboxyhemoglobin in some patients. Case reports suggest that barium hydroxide lime and soda lime become desiccated when fresh gases are passed through the CO2 absorber canister at high flow rates over many hours or days. When a clinician suspects that CO2 absorbent may be desiccated, it should be replaced before the administration of isoflurane.
Reproduction studies have been performed in mice and rats with no evidence of fetal malformation attributable to isoflurane. Adequate data concerning the safe use of isoflurane in pregnant and breeding horses and dogs have not been obtained.
Hypotension, respiratory depression, and arrhythmias have been reported.
In the event of overdosage, or what may appear to be overdosage, the following action should be taken: Stop drug administration, establish that the airway is clear and initiate assisted or controlled ventilation with pure oxygen as circumstances dictate.
Caution: Operating rooms should be provided with adequate ventilation to prevent the accumulation of anesthetic vapors.
Premedication: A premedication regimen, which may be employed depending upon the patient status, to avert excitement during induction, might include an anticholinergic, a tranquilizer, a muscle relaxant, and a short-acting barbiturate.
Inspired Concentration: The delivered concentration of isoflurane should be known. Isoflurane may be vaporized using a flow-through vaporizer specifically calibrated for isoflurane. Vaporizers delivering a saturated vapor which then is diluted. (eg, Verni-trol(R) vaporizer) also may be used. The delivered concentration from such a vaporizer may be calculated using the formula:
100 PV FV
% isoflurane ————-
FT ( PA -FV )
where: PA = Pressure of atmosphere
PV = Vapor pressure of isoflurane
FV = Flow of gas through vaporizer (mL/min)
FT = Total gas flow (mL/min)
Isoflurane contains no stabilizer. Nothing in the drug product alters calibration or operation of these vaporizers.
Horses: Inspired concentrations of 3.0% to 5.0% isoflurane alone with oxygen following a barbiturate anesthetic induction are usually employed to induce surgical anesthesia in the horse.
Dogs: Inspired concentrations of 2.0% to 2.5% isoflurane alone with oxygen following a barbiturate anesthetic induction are usually employed to induce surgical anesthesia in the dog.
These concentrations can be expected to produce surgical anesthesia in 5 to 10 minutes.
Maintenance: The concentration of vapor necessary to maintain anesthesia is much less than that required to induce it.
Horses: Surgical levels of anesthesia in the horse may be sustained with a 1.5% to 1.8%
concentration of isoflurane in oxygen.
Dogs: Surgical levels of anesthesia in the dog may be sustained with a 1.5% to 1.8%
concentration of isoflurane in oxygen.
The level of blood pressure during maintenance is an inverse function of isoflurane
concentration in the absence of other complicating problems. Excessive decreases, unless
related to hypovolemia, may be due to depth of anesthesia and in such instances may be
corrected by lightening the level of anesthesia.
Recovery from isoflurane anesthesia is typically uneventful.2
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