954
Editorial Desflurane: the dawn of a new era? In the 1950's, a new generation of inhalational anaesthetics was synthesized and introduced into clinical practice. These anaesthetics, the methyl ethyl halogenated ethers, differed from their predecessors in that they combined two important attributes: (1) nonflammability and (2) absence of anaesthetic toxicity.I Development of this series of anaesthetics continued until 1981, with the release of isoflurane for clinical use. In common with many of the anaesthetics in this series, isoflurane possessed many desirable characteristics: it was nonflammable, produced modest cardiorespiratory depression, resisted degradation, and was neither hepatotoxic nor nephrotoxic. I Its most important characteristic was its low solubility in blood and tissues which facilitated a more rapid wash-in and wash-out of anaesthetic than any other halogenated ether anaesthetic at the time. However, in comparison to nitrous oxide and cyclopropane, the pharmacokinetics of isoflurane were less desirable, t Since an halogenated ether anaesthetic with a pharmacokinetic profile similar to nitrous oxide and cyclopropane would be highly desirable for rapid induction and recovery from anaesthesia, the search continued for an ultra rapid-acting halogenated ether anaesthetic. One such anaesthetic which was developed was desflurane. Desflurane (difluoromethyi l-fluoro,2,2,2-trifluoroethyl ether) is a polyfluorinated methyl ethyl ether compound that is identical in chemical structure to isoflurane except for the substitution of fluoride for chloride at the ot ethyl carbon. Substitution of this single atom radically alters its physical properties in comparison to the other ether anaesthetics. First, the boiling point of desflurane (23.5 ~ C) is one-half that of other ether anaesthetics and therefore its high vapour pressure (664 mmHg) precludes the use of a traditional vaporizer. Second, the extensive fluorination and molecular symmetry of this anaesthetic renders it resistant to microsomal enzyme systems and hydrolysis in soda-lime absorbers. Third, it has very low blood and tissue solubilities. These characteristics distinguish desflurane from the remainder of the halogenated ether inhalational anaesthetics. The low boiling point of desflurane, however, poses a serious problem for its delivery. If desflurane is administered with a conventional vaporizer, it may boil and
CAN ! ANAESTH 1991 / 3 8 : 8 / pp954-7
quickly produce a very high inspired concentration. This high inspired concentration, however, will be short-lived since vaporization of desflurane will rapidly cool the liquid within the vaporizer and reduce its vapour pressure. To maintain a stable inspired concentration of desflurane, a heated and pressurized vaporizer has been designed. This vaporizer will be the only vaporizer that requires electricity to maintain a constant concentration of anaesthetic in the effluent. If this vaporizer loses electrical power, then the temperature of the liquid desflurane will gradually decrease as desflurane vaporizes. This will be followed immediately by a decrease in the inspired concentration of desflurane. In light of this potential difficulty, it seems prudent that a vaporizer capable of delivering a second anaesthetic be immediately available whenever desflurane is used. The solubility of desflurane in blood and tissues may be one of its most important attributes. Its solubility in blood is 0.42, similar to that of nitrous oxide and cyclopropane.2 Despite the similarity in solubility, the wash-in profile of desflurane is slightly slower than that of nitrous oxide. 3 The slower wash-in of desflurane when compared with nitrous oxide may be attributed to the greater inspired concentration of nitrous oxide and the lower tissue solubility of nitrous oxide when compared with desflurane. 4 Two prerequisites facilitate a rapid induction of anaesthesia by inhalation: (1) a low solubility in blood and tissues and (2) absence of irritant effects on the respiratory tract. Previous studies established the low solubility of desflurane in blood and tissues. In a preliminary study of adults who were given MAC and sub-MAC desflurane, desflurane failed to elicit airway reflex responses, s The authors of that study suggested that "this property" (referring to its lack of pungency and irritation and its low solubility) "would be of particular value in paediatric anaesthesia." However, recent studies in infants and children who were anaesthetized with desflurane established conclusively that desflurane irritates the respiratory tract in this age group .6.7 In studies undertaken at several institutions, induction of anaesthesia with desflurane resulted in a high incidence of coughing, breathholding, mild laryngospasm and arterial oxygen desaturation.
EDITORIAL
Neither nitrous oxide nor premedication ameliorated these complications. As a result of this experience, desflurane is not recommended for induction of anaesthesia in infants and children. The low solubility of desflurane in blood and tissues does, however, offer advantages during both maintenance of and emergence from anaesthesia. During maintenance, increases or decreases in the inspired concentration of desflurane are rapidly reflected in the end-tidal or alveolar concentration of desflurane. This facilitates rapid and precise control of the depth of anaesthesia. When anaesthesia is discontinued, the alveolar concentration of desflurane decreases precipitously. 3 This is associated with a rapid recovery of consciousness. In comparative trials with isoflurane and halothane, recovery from desflurane anaesthesia is more rapid and more complete than from either of these two inhalationai anesthetics. 6's'9 However, Ghouri et al. noted that the concomitant use of intravenous agents could negate any advantage of desflurane over isoflurane for earlier discharge from hospital, s In our experience, children's recovery from desflurane anaesthesia was rapid and complete. 7 This means that there are no residual anaesthetic effects (i.e., analgesia) at extubation, and that analgesics should be given either before emergence or immediately upon extubation whenever desflurane is used. It was also our impression that the children were fully awake and alert a very short period after discontinuation of desflurane. The quality of recovery is similar to that observed after propofol anaesthesia. The potency of an inhalational anaesthetic is inversely related to its lipid solubility. This relationship holds true for a wide range of anaesthetics. Desflurane has a very low lipid solubility (oil/gas partition coefficient of 18.7) 2 and consequently has a low potency, that is, the MAC is high. The MAC of desflurane in young adults is 7.25% ~~ and MAC increases with decreasing age reaching a zenith in infants 6-12 months of age (9.9%). J t The low potency of desflurane poses several difficulties. High concentrations must be administered to maintain an adequate anaesthetic depth. As a result, the maximum safe concentration of nitrous oxide is reduced. Futhermore, to deliver these high concentrations of desflurane, large volumes of desflurane must be vaporized and this requires frequent replenishment of the vaporizer. These difficulties though, are unlikely to limit the use of desflurane in clinical practice. The physiological effects of desflurane are currently under investigation. Preliminary data indicate that the cardiovascular, ~2 respiratory 13 and electroencephalographic ~4 effects of desflurane in adults are similar to those of isoflurane. Although small differences between desflurane and the other ether inhalational anaesthetics
955
may exist, these are not likely to determine the future role of this drug. Like isoflurane, desflurane resists degradation. 3 With isoflurane anaesthesia, the risk of nephrotoxicity and hepatotoxicity has been virtually eliminated. Nephrotoxicity, for example, is most unlikely since the in vivo metabolism of isoflurane is minimal (0.2%). Given this extremely low likelihood of nephrotoxicity after isoflurane anaesthesia, what is the risk of organ toxicity after desflurane anaesthesia? Metabolism of desflurane is one tenth (0.02%) that of isoflurane. 15 Since isoflurane is almost devoid of organ toxicity, the risk of organ toxicity with an anaesthetic with an even smaller rate of degradation than isoflurane is moot. The role ofdesflurane in clinical anaesthesia remains to be established. As an induction agent, desflurane has been found to be wanting. For maintenance and recovery, it is marginally superior to isoflurane. Only with a large clinical experience will we determine whether desflurane is an improvement over inhalational anaesthetics that are currently available. The search for a relatively insoluble inhalational anaesthetic that will ensure a rapid and pleasant induction of anaesthesia continues.
Le desflurane: le d6but d'une nouvelle g6n6ration Dans les ann6es 1950, une nouvelle g6n6ration d'anesth6siques gazeux fut synth6tis6e et introduite dans notre pratique clinique. Ces anesth6siques, les 6thers halog6n6s de methyl ethyl 6taient diff6rents de leurs pr6d6cesseurs car ils combinaient deux attributs importants : !) la non-inflammabilit6 et 2) l'absence de toxicit6 anesth6sique, t Le d6veloppement de cette s6rie d'anesth6siques a continu6 jusqu'en 1981 avec la mise au march6 de i'isoflurane pour l'utilisation clinique, lndentique avec plusieurs gaz anesth6siques de cette s6rie, l'isoflurane poss6de plusieurs caract6ristiques souhaitables : il est non-inflammable, produit une d6pression cardiorespiratoire modeste, r6siste/~ la d6gradation, et n'est ni h6patotoxique ni n6phrotoxique, i Sa caract6ristique la plus importante 6tant sa basse solubilit6 dans le sang et les tissus ce qui facilite une captation et un lavage anesth6sique plus rapide que les autres anesth6siques halog6n6s
956 base d'~ther. Cependant, comparativement au protoxyde d'azote et au cyclopropane, la pharmacocin6tique de I'isoflurane est moins id6ale.I Etant donn6 qu'un anesth6sique d'6ther halog6n6 avec un profil pharmacocin6tique similaire au protoxyde d'azote et le cyclopropane serait fortement souhaitable pour une induction et un r6veil rapides de I'anesth6sie, la recherche pour un anesth6sique halog6n6 d'6ther/i action ultra rapide s'est poursuivie. Le desflurane en est un exemple. Les desflurane (difluoromethyl l-fluoro,2,2,2-trifluoroethyl 6ther) est un compos6 de methyl ethyl 6ther polyfluor6 qui est identique quant :~ la structure chimique /~l'isoflurane ~ i'exception de la substitution du fluor pour le chlore au niveau du carbone alpha ethyl. La substitution de cet atome unique alt~re radicalement ses propri6t6s physiques en comparaison avec les autres anesth6siques d'6ther. Premi6rement, le point d'6bullition du desflurane (23.5 ~ C) est ia moiti6 des autres anesth6siques d'6ther et par cons6quent sa pression de vapeur ~lev6e (664 mmHg) ne permet pas l'utilisation d'un vaporisateur traditionnel. Deuxi~mement, la fluorination extensive et la sym6trie mol6culaire de cet anesth6sique le rend r6sistant aux syst6mes enzymatiques microsomiaux et ~t l'hydrolyse darts I'absorbeur de chaux-sod6e. Troisi6mement, il pr6sente des coefficients de solubilit6 tr6s basses dans le sang et les tissues. Ces caract6ristiques le distinguent des autres anesth6siques halog6n6s ~ base d'6ther. Le point d'6bullition bas du desflurane cependant, am6ne un probl6me s~rieux Iors de son administration. Si le desflurane est administr6 avec un vaporisateur conventionnel, il peut bouillir et produire rapidement des concentrations inspir6es tr6s ~lev6es. Ces concentrations inspir6es 61ev6es cependant, seront de courte dur6e car la vaporisation refroidira rapidement le liquide :~ I'int6rieur du vaporisateur et r6duira sa pression de vapeur. Afin de maintenir une concentration inspir6e stable, un vaporisateur pressuris6 et chauff6 a 6t6 conqu. Ce vaporisateur serait le seul vaporisateur qui requiert de l'61ectricit6 afin de maintenir une concentration constante d'anesth6sique darts ie circuit. Si ce vaporisateur perd sa puissance 61ectrique, alors la temp6rature du desflurane liquide diminuera graduellement au fur et ~ mesure que le desflurane se vaporise. Ceci sera suivi imm6diatement par une diminution de la concentration inspir6e. En vue de cette difficult6 potentielle, il apparait prudent que des vaporisateurs capables de d~livrer un autre anesth6sique soient imm~diatement disponibles quand le desflurane est utilis6. La solubilit6 du desflurane dans le sang et tissus peut ~tre une de ses plus importantes caract6ristiques. Sa solubilit6 clans le sang est de 0,42, similaire :~ celle du protoxyde d'azote et du cyclopropane. 2 Malgr6 la similitude dans la solubilit6, le profil de captation du desflurane
CANADIAN
JOURNAL
OF ANAESTHESIA
est plus lent que celui du protoxyde d'azote. 3 La captation lente du desflurane lorsque compar6 au protoxyde d'azote pourrait ~tre attribu6e ~ la plus grande concentration inspir6e de protoxyde d'azote et la plus basse solubilit6 tissulaire du protoxyde d'azote comparativement au desflurane. 4 Deux pr6requis facilitent l'induction rapide de l'anesth6sie par des agents gazeux: 1) une faible solubilit6 dans le sang et tissues et 2) l'absence d'effets irritants sur les voies a~riennes. Des ~tudes pr6alables ont 6tabli la basse solubilit~ du desflurane dans le sang et tissus. Dans une 6tude pr~liminaire chez les adultes ayant requ du desflurane h des concentrations ~gales ou inf6rieures ~ son MAC, le desflurane n'a pas provoqu6 de r~flexes des voies a6riennes.S Les auteurs de cette 6tude sugg~rent que (le manque d'irritation et sa base solubilit6)
Editorial Desflurane: the dawn of a new era? In the 1950's, a new generation of inhalational anaesthetics was synthesized and introduced into clinical practice. These anaesthetics, the methyl ethyl halogenated ethers, differed from their predecessors in that they combined two important attributes: (1) nonflammability and (2) absence of anaesthetic toxicity.I Development of this series of anaesthetics continued until 1981, with the release of isoflurane for clinical use. In common with many of the anaesthetics in this series, isoflurane possessed many desirable characteristics: it was nonflammable, produced modest cardiorespiratory depression, resisted degradation, and was neither hepatotoxic nor nephrotoxic. I Its most important characteristic was its low solubility in blood and tissues which facilitated a more rapid wash-in and wash-out of anaesthetic than any other halogenated ether anaesthetic at the time. However, in comparison to nitrous oxide and cyclopropane, the pharmacokinetics of isoflurane were less desirable, t Since an halogenated ether anaesthetic with a pharmacokinetic profile similar to nitrous oxide and cyclopropane would be highly desirable for rapid induction and recovery from anaesthesia, the search continued for an ultra rapid-acting halogenated ether anaesthetic. One such anaesthetic which was developed was desflurane. Desflurane (difluoromethyi l-fluoro,2,2,2-trifluoroethyl ether) is a polyfluorinated methyl ethyl ether compound that is identical in chemical structure to isoflurane except for the substitution of fluoride for chloride at the ot ethyl carbon. Substitution of this single atom radically alters its physical properties in comparison to the other ether anaesthetics. First, the boiling point of desflurane (23.5 ~ C) is one-half that of other ether anaesthetics and therefore its high vapour pressure (664 mmHg) precludes the use of a traditional vaporizer. Second, the extensive fluorination and molecular symmetry of this anaesthetic renders it resistant to microsomal enzyme systems and hydrolysis in soda-lime absorbers. Third, it has very low blood and tissue solubilities. These characteristics distinguish desflurane from the remainder of the halogenated ether inhalational anaesthetics. The low boiling point of desflurane, however, poses a serious problem for its delivery. If desflurane is administered with a conventional vaporizer, it may boil and
CAN ! ANAESTH 1991 / 3 8 : 8 / pp954-7
quickly produce a very high inspired concentration. This high inspired concentration, however, will be short-lived since vaporization of desflurane will rapidly cool the liquid within the vaporizer and reduce its vapour pressure. To maintain a stable inspired concentration of desflurane, a heated and pressurized vaporizer has been designed. This vaporizer will be the only vaporizer that requires electricity to maintain a constant concentration of anaesthetic in the effluent. If this vaporizer loses electrical power, then the temperature of the liquid desflurane will gradually decrease as desflurane vaporizes. This will be followed immediately by a decrease in the inspired concentration of desflurane. In light of this potential difficulty, it seems prudent that a vaporizer capable of delivering a second anaesthetic be immediately available whenever desflurane is used. The solubility of desflurane in blood and tissues may be one of its most important attributes. Its solubility in blood is 0.42, similar to that of nitrous oxide and cyclopropane.2 Despite the similarity in solubility, the wash-in profile of desflurane is slightly slower than that of nitrous oxide. 3 The slower wash-in of desflurane when compared with nitrous oxide may be attributed to the greater inspired concentration of nitrous oxide and the lower tissue solubility of nitrous oxide when compared with desflurane. 4 Two prerequisites facilitate a rapid induction of anaesthesia by inhalation: (1) a low solubility in blood and tissues and (2) absence of irritant effects on the respiratory tract. Previous studies established the low solubility of desflurane in blood and tissues. In a preliminary study of adults who were given MAC and sub-MAC desflurane, desflurane failed to elicit airway reflex responses, s The authors of that study suggested that "this property" (referring to its lack of pungency and irritation and its low solubility) "would be of particular value in paediatric anaesthesia." However, recent studies in infants and children who were anaesthetized with desflurane established conclusively that desflurane irritates the respiratory tract in this age group .6.7 In studies undertaken at several institutions, induction of anaesthesia with desflurane resulted in a high incidence of coughing, breathholding, mild laryngospasm and arterial oxygen desaturation.
EDITORIAL
Neither nitrous oxide nor premedication ameliorated these complications. As a result of this experience, desflurane is not recommended for induction of anaesthesia in infants and children. The low solubility of desflurane in blood and tissues does, however, offer advantages during both maintenance of and emergence from anaesthesia. During maintenance, increases or decreases in the inspired concentration of desflurane are rapidly reflected in the end-tidal or alveolar concentration of desflurane. This facilitates rapid and precise control of the depth of anaesthesia. When anaesthesia is discontinued, the alveolar concentration of desflurane decreases precipitously. 3 This is associated with a rapid recovery of consciousness. In comparative trials with isoflurane and halothane, recovery from desflurane anaesthesia is more rapid and more complete than from either of these two inhalationai anesthetics. 6's'9 However, Ghouri et al. noted that the concomitant use of intravenous agents could negate any advantage of desflurane over isoflurane for earlier discharge from hospital, s In our experience, children's recovery from desflurane anaesthesia was rapid and complete. 7 This means that there are no residual anaesthetic effects (i.e., analgesia) at extubation, and that analgesics should be given either before emergence or immediately upon extubation whenever desflurane is used. It was also our impression that the children were fully awake and alert a very short period after discontinuation of desflurane. The quality of recovery is similar to that observed after propofol anaesthesia. The potency of an inhalational anaesthetic is inversely related to its lipid solubility. This relationship holds true for a wide range of anaesthetics. Desflurane has a very low lipid solubility (oil/gas partition coefficient of 18.7) 2 and consequently has a low potency, that is, the MAC is high. The MAC of desflurane in young adults is 7.25% ~~ and MAC increases with decreasing age reaching a zenith in infants 6-12 months of age (9.9%). J t The low potency of desflurane poses several difficulties. High concentrations must be administered to maintain an adequate anaesthetic depth. As a result, the maximum safe concentration of nitrous oxide is reduced. Futhermore, to deliver these high concentrations of desflurane, large volumes of desflurane must be vaporized and this requires frequent replenishment of the vaporizer. These difficulties though, are unlikely to limit the use of desflurane in clinical practice. The physiological effects of desflurane are currently under investigation. Preliminary data indicate that the cardiovascular, ~2 respiratory 13 and electroencephalographic ~4 effects of desflurane in adults are similar to those of isoflurane. Although small differences between desflurane and the other ether inhalational anaesthetics
955
may exist, these are not likely to determine the future role of this drug. Like isoflurane, desflurane resists degradation. 3 With isoflurane anaesthesia, the risk of nephrotoxicity and hepatotoxicity has been virtually eliminated. Nephrotoxicity, for example, is most unlikely since the in vivo metabolism of isoflurane is minimal (0.2%). Given this extremely low likelihood of nephrotoxicity after isoflurane anaesthesia, what is the risk of organ toxicity after desflurane anaesthesia? Metabolism of desflurane is one tenth (0.02%) that of isoflurane. 15 Since isoflurane is almost devoid of organ toxicity, the risk of organ toxicity with an anaesthetic with an even smaller rate of degradation than isoflurane is moot. The role ofdesflurane in clinical anaesthesia remains to be established. As an induction agent, desflurane has been found to be wanting. For maintenance and recovery, it is marginally superior to isoflurane. Only with a large clinical experience will we determine whether desflurane is an improvement over inhalational anaesthetics that are currently available. The search for a relatively insoluble inhalational anaesthetic that will ensure a rapid and pleasant induction of anaesthesia continues.
Le desflurane: le d6but d'une nouvelle g6n6ration Dans les ann6es 1950, une nouvelle g6n6ration d'anesth6siques gazeux fut synth6tis6e et introduite dans notre pratique clinique. Ces anesth6siques, les 6thers halog6n6s de methyl ethyl 6taient diff6rents de leurs pr6d6cesseurs car ils combinaient deux attributs importants : !) la non-inflammabilit6 et 2) l'absence de toxicit6 anesth6sique, t Le d6veloppement de cette s6rie d'anesth6siques a continu6 jusqu'en 1981 avec la mise au march6 de i'isoflurane pour l'utilisation clinique, lndentique avec plusieurs gaz anesth6siques de cette s6rie, l'isoflurane poss6de plusieurs caract6ristiques souhaitables : il est non-inflammable, produit une d6pression cardiorespiratoire modeste, r6siste/~ la d6gradation, et n'est ni h6patotoxique ni n6phrotoxique, i Sa caract6ristique la plus importante 6tant sa basse solubilit6 dans le sang et les tissus ce qui facilite une captation et un lavage anesth6sique plus rapide que les autres anesth6siques halog6n6s
956 base d'~ther. Cependant, comparativement au protoxyde d'azote et au cyclopropane, la pharmacocin6tique de I'isoflurane est moins id6ale.I Etant donn6 qu'un anesth6sique d'6ther halog6n6 avec un profil pharmacocin6tique similaire au protoxyde d'azote et le cyclopropane serait fortement souhaitable pour une induction et un r6veil rapides de I'anesth6sie, la recherche pour un anesth6sique halog6n6 d'6ther/i action ultra rapide s'est poursuivie. Le desflurane en est un exemple. Les desflurane (difluoromethyl l-fluoro,2,2,2-trifluoroethyl 6ther) est un compos6 de methyl ethyl 6ther polyfluor6 qui est identique quant :~ la structure chimique /~l'isoflurane ~ i'exception de la substitution du fluor pour le chlore au niveau du carbone alpha ethyl. La substitution de cet atome unique alt~re radicalement ses propri6t6s physiques en comparaison avec les autres anesth6siques d'6ther. Premi6rement, le point d'6bullition du desflurane (23.5 ~ C) est ia moiti6 des autres anesth6siques d'6ther et par cons6quent sa pression de vapeur ~lev6e (664 mmHg) ne permet pas l'utilisation d'un vaporisateur traditionnel. Deuxi~mement, la fluorination extensive et la sym6trie mol6culaire de cet anesth6sique le rend r6sistant aux syst6mes enzymatiques microsomiaux et ~t l'hydrolyse darts I'absorbeur de chaux-sod6e. Troisi6mement, il pr6sente des coefficients de solubilit6 tr6s basses dans le sang et les tissues. Ces caract6ristiques le distinguent des autres anesth6siques halog6n6s ~ base d'6ther. Le point d'6bullition bas du desflurane cependant, am6ne un probl6me s~rieux Iors de son administration. Si le desflurane est administr6 avec un vaporisateur conventionnel, il peut bouillir et produire rapidement des concentrations inspir6es tr6s ~lev6es. Ces concentrations inspir6es 61ev6es cependant, seront de courte dur6e car la vaporisation refroidira rapidement le liquide :~ I'int6rieur du vaporisateur et r6duira sa pression de vapeur. Afin de maintenir une concentration inspir6e stable, un vaporisateur pressuris6 et chauff6 a 6t6 conqu. Ce vaporisateur serait le seul vaporisateur qui requiert de l'61ectricit6 afin de maintenir une concentration constante d'anesth6sique darts ie circuit. Si ce vaporisateur perd sa puissance 61ectrique, alors la temp6rature du desflurane liquide diminuera graduellement au fur et ~ mesure que le desflurane se vaporise. Ceci sera suivi imm6diatement par une diminution de la concentration inspir6e. En vue de cette difficult6 potentielle, il apparait prudent que des vaporisateurs capables de d~livrer un autre anesth6sique soient imm~diatement disponibles quand le desflurane est utilis6. La solubilit6 du desflurane dans le sang et tissus peut ~tre une de ses plus importantes caract6ristiques. Sa solubilit6 clans le sang est de 0,42, similaire :~ celle du protoxyde d'azote et du cyclopropane. 2 Malgr6 la similitude dans la solubilit6, le profil de captation du desflurane
CANADIAN
JOURNAL
OF ANAESTHESIA
est plus lent que celui du protoxyde d'azote. 3 La captation lente du desflurane lorsque compar6 au protoxyde d'azote pourrait ~tre attribu6e ~ la plus grande concentration inspir6e de protoxyde d'azote et la plus basse solubilit6 tissulaire du protoxyde d'azote comparativement au desflurane. 4 Deux pr6requis facilitent l'induction rapide de l'anesth6sie par des agents gazeux: 1) une faible solubilit6 dans le sang et tissues et 2) l'absence d'effets irritants sur les voies a~riennes. Des ~tudes pr6alables ont 6tabli la basse solubilit~ du desflurane dans le sang et tissus. Dans une 6tude pr~liminaire chez les adultes ayant requ du desflurane h des concentrations ~gales ou inf6rieures ~ son MAC, le desflurane n'a pas provoqu6 de r~flexes des voies a6riennes.S Les auteurs de cette 6tude sugg~rent que (le manque d'irritation et sa base solubilit6)
