INHALATION ANESTHESIA

James O.Stevens, D.V.M., Ph.D. Associate Director for Research Services.

The curtailment of manufacture of methoxyflurane (Metofane) by the manufacturer has caused a problem for researchers using this inhalant anesthetic for rodents. The alternatives, isoflurane and halothane, are available and can be used in lieu of methoxyflurane but each poses problems for the animals that were not presented with the use of methoxyflurane. Although the O A! conducted a series of hands"on wor#shops for those research personnel who must switch anesthetics, many individuals were unable to attend these wor#shops. $e will schedule more wor#shops if necessary to allow researchers gain experience using the alternative inhalant anesthetics for rodent anesthesia. %n addition to the wor#shop, % have prepared a primer on inhalation anesthesia prefaced by the critical essentials of general anesthesia for your information and it is presented below. SURGERY, PAIN PERCEPTION AND ANESTHESIA: To carry out surgical procedures on animals, pain perception must be completely suppressed. This can be achieved either by general anesthesia, which produces loss of consciousness, or by local or regional anesthesia. $hile different agents can appear to provide similar levels of hypnosis (sleep), the degree of intraoperative analgesia produced can vary with the agent. %t is important to ensure that an anesthetic regimen is selected that provides an appropriate degree of intra"operative analgesia. %f an anesthesia is being induced simply to provide humane restraint while non"painful procedures are carried out, then only light anesthesia, with little pain suppression, will be re&uired. 'onversely, if potentially painful surgical procedures are to be underta#en, then deep anesthesia, with complete suppression of pain perception, is necessary. GENERAL ANESTHESIA: (eneral anesthesia involves the re&uired features of loss of consciousness, analgesia, suppression of reflex activity and muscle relaxation. Often a single drug can produce all aspects of general anesthesia or it can be achieved by a combination of agents, each ma#ing a contribution to the overall effect. The latter approach has the advantage that undesirable side effects can often be minimi)ed. The side effects of anesthetics are usually dose dependant. (iving several drugs in combination, at relatively low doses, often results in less effect on ma*or body systems than that following anesthesia with single anesthetic agents. The best anesthetic regimens, including those involving inhalant anesthetics, usually involve an initial tran&uili)ation and+or muscle relaxation followed by general anesthesia using an anesthetic drug. ,uch multiple agents are not generally or se&uentially used for rodent anesthesia where general anesthesia using inhalant anesthetics may routinely be induced using only the anesthetic agent. There are distinct advantages and disadvantages of this type of regimen as noted below. ADMINISTRATION BY INHALATION: %nhalant anesthetics may be supplied to the patient either by anesthetic machines using face mas#s or endotracheal tubes or by using enclosed chambers containing anesthetic vapors. Anesthesia machines are designed to supply oxygen, anesthetic gases and volatile anesthetic agents to the animal. The gases

pass through a vapori)er which is designed for use with a particular volatile anesthetic agent. -lowmeters and calibrated vapori)ers on the machines control anesthetic vapor and oxygen levels. .reathing circuits on machines may be open or closed. A widely used breathing circuit is an open facemas#, which is a simple and convenient way of delivering anesthetic gases to an animal. /xpired gases pass around the edges of the mas#s and, depending upon the gas flow rate, rebreathing of exhaled gas can be minimi)ed and dilution of the anesthetic gases by breathing room air can be avoided. ,uch an apparatus should always be used in a scavenging hood. The most serious disadvantage in using a simple open circuit (besides the safety issue for the surgeon) is that it is not possible to assist ventilation artificially in case of emergency. .oth semi" closed and T"piece breathing circuits have been developed. The T"piece circuit was developed and intended to provide a circuit of low resistance and little dead space for use on infants. %t has been used widely on small animals such as rabbits and cats where it is connected directly to an endotracheal tube or close"fitting mas#. Occluding the 0exhaust1 end, which is fitted with a reservoir, controls ventilation. 'losed breathing circuits are systems in which expired carbon dioxide is absorbed in a soda lime canister. 2se of such circuits should be limited to experienced anesthetists. This system has routinely been used for larger animals but has now been adapted for use in anestheti)ing small animals and rodents where an inline, sealable chamber is utili)ed to place the animal. $hen controlled breathing, anesthetic machines are not available, the 0drop method1 using a bell *ar techni&ue may be used. /&uipment ranges from the classic glass bell or desiccation *ar with tight fitting lid, to plastic chambers with clear lids or a&uaria. All chambers should have bottom screens, which separate the anesthetic soa#ed media (cotton balls or gau)e) from the animal in order to prevent contact with the irritating anesthetic agent. Ade&uate scavenging (chemical fume hood, charcoal filtered safety hood, hood connected to house exhaust) must be used to prevent unintentional exposure of humans and animals to waste anesthetic gases. %nhalant anesthetic agents are poured onto the media and the chamber is closed to allow the anesthetic to vapori)e inside the chamber (34 minutes). An animal is then place into the chamber where it becomes anestheti)ed as it inhales the volati)ed anesthetic. After removal of the animal from the chamber, one may administer additional anesthetic during a procedure by placing an anesthetic soa#ed gau)e or cotton containing nose cone over the face of the animal. -or rats and mice, a 54"67 cc syringe barrel may be used for the nose cone. 2nless ade&uate scavenging is available, this method of prolonging inhalant anesthesia is not recommended. INHALANT ANESTHETICS: Many inhalant anesthetics are available for use in animals. One of the most widely used for rodent anesthesia is methoxyflurane (Metofane). 8owever, this agent is no longer manufactured and halothane and isoflurane are being used as replacements. Methoxyflurane has been the preferred agent when using the bell *ar techni&ue because room temperature and pressures permit a 59 concentration to easily develop. This concentration of methoxyflurane is safe, whereas, lethal concentrations of halothane and isoflurane develop under identical conditions. The potency of each anesthetic agent is indicated by its, minimum alveolar concentration

(MA') value. This value, most commonly referred to simply as MA', is the alveolar concentration of an anesthetic re&uired to bloc# the response to a specified stimulus in the animals. The lower the MA' value, the lower the concentration re&uired, so the more potent the anesthetic. %nformation concerning the range of concentrations of the different inhalation anesthetics which are re&uired for induction and maintenance of anesthesia are given below. SPECIFIC AGENTS:
a. b. c. Halothane: Des !a"le e##e$ts: 8alothane is easy to vapori)e, and induction and recovery are rapid (:"5 minutes). %t is a potent anesthetic, is non"irritant and is neither flammable nor explosive. Un%es !a"le e##e$ts: 8alothane has a depressant effect on the cardiovascular system. Moderate hypotension is produced at surgical levels of anesthesia because of a reduction in cardiac output and peripheral vasodilation. A dose"dependant depression of respiration also occurs. ,ome hepatic metabolism of halothane occurs and mar#ed liver microsomal en)yme induction may follow anesthesia. S&e$ al $o''ents: The desirable effects listed above ma#e halothane an excellent agent for maintaining anesthesia in most species. %t should be administered using a calibrated vapori)er since dangerously high concentrations can be attained if a simple apparatus is used. Although recovery is usually rapid, it may be considerably delayed following prolonged, deep anesthesia. Iso#l(!ane: Des !a"le e##e$ts: %soflurane produces very rapid induction and recovery from anesthesia and the depth of anesthesia can be altered easily and rapidly. %t is non"irritant, non" exploxive and non"flammable. Un%es !a"le e##e$ts: %soflurane produces slightly more severe respiratory depression than does halothane, but slightly less depression of the cardiovascular system. %ts pungent odor has been reported to cause breath"holding during induction in children, but this does not appear to be a significant problem in most species, with the exception of the rabbit.

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S&e$ al $o''ents: The main advantage of using isoflurane in experimental animals is that it undergoes minimal biotransformation and is almost completely eliminated in exhaled air. This suggests that there will be little effect on liver microsomal en)ymes and, hence, little interference in drug metabolism or toxicology studies. This characteristic, together with the rapid induction and recovery from anesthesia, has led to the widespread adoption of isoflurane in many research establishments.

Metho)+#l(!ane: Des !a"le e##e$ts: Methoxyflurane is non"irritant, non"flammable and non" explosive in air or oxygen. %t has a potent analgesic effect and has some post"operative analgesic action. Un%es !a"le e##e$ts: Methoxyflurane produces some respiratory and cardiovascular system depression, but generally less than halothane at comparable depths of anesthesia. Metabolism of methoxyflurane results in fluoride ion release, which may cause renal damage. The significance of this ha)ard in animals is small except following prolonged periods of anesthesia. S&e$ al $o''ents: .ecause of the slow rate of induction with methoxyflurane, in larger species it is best used for maintenance of anesthesia following induction with short"acting in*ectable agents. %n small animals, it can safely be used in anesthetic chambers, where its slow

induction and the low vapor concentration produced can be an advantage in reducing the ris# of inadvertent overdose. %t is an excellent agent for inducing and maintaining anesthesia in neonatal animals.

!eferences;
-lec#nell, <. (:==6). 0 aboratory Animal Anesthesia; A practical %ntroduction for !esearch $or#ers and Technicians1, >nd /dition, Academic <ress, ?ew @or#. ,harp, <./. and a!egina, M.'. (:==A). 0The aboratory !at1 /d; M. A. ,uc#ow, '!' <ress, .oca !atan, ?ew @or#.

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