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HYPOXIC VENTILATORY DRIVE IN THE DOG UNDER ALTHESIN ANAESTHESIA
Br. J. Anaesth. (1984), 56, 631
HYPOXIC VENTILATORY DRIVE IN THE DOG UNDER ALTHESIN ANAESTHESIA J. H. GAUDY, S. BERGERET, J. F. B O I T I E R A N D F . FERRACCI SUMMARY
Mosso (1904) and Marshall and Rosenfeld (1936) demonstrated that, when the central nervous system (CNS) is depressed in association with the administration of anaesthetic agents, or hypoxia, the administration of oxygen may depress ventilation or even cause apnoea. Since the publication of these studies, Comroe (1965) and Wylie and ChurchillDavidson (1972) stated that the chemoreflexes stimulated by hypoxaemia were not modified by anaesthesia. Weiskopf, Raymond and Severinghaus (1974) reported that, in the dog, halothane induced a decrease in the ventilatory response to hypoxia and this observation was confirmed by many authors using other anaesthetic agents, in animals and man. Recently, Gaudy and colleagues (1982b) demonstrated that, in the dog receiving Althesin anaesthesia, the ventilatory response to hypocapnic hypoxia was not modified during light anaesthesia and was maintained during deep anaesthesia. The scope of the present work was to present evidence concerning the hypoxic stimulus in the dog receiving Althesin anaesthesia with particular regard to the ventilatory effects caused by administration of oxygen. MATERIAL AND METHODS Eight male beagle dogs(mean weight ± S D = 18.34±
J. H. GAUDY,* M . D . ; S . BERGERET, M . D . ; J . F. BOITIER, M . D . ; F .
FERRACCI, M.D.; Laboratoire d'Anesthesiologie, Hdpital Rothschild, 33, boulevard de Pkpus, 75012 Paris, France. * Address for correspondence: Service de Reanimation Chirurgicale Polyvalente, Hdpital Rothschild, 33 bd de Picpus, 75012 Paris, France.
5.2 kg) were starved for 12 h. A vein of a foreleg was cannulated and anaesthesia induced and maintained with Althesin diluted in a saline solution, administered i.v. by an electric pump (Rhone-Poulenc RP 04-PE). Following the induction of anaesthesia, a cuffed tracheal tube was inserted and, to minimi?*; respiratory resistance, the tracheal tube was connected to a Y-shaped tube without any valve, one of the side extensions being connected to a Douglas bag (5 litre) which was supplied with either air or oxygen. The flow of inspired gases was adjusted to exceed the ventilation of the animal to avoid rebreathing. The dogs were placed on a thermostatically controlled heating mattress, the rectal temperature being maintained at 37 °C. A catheter was inserted percutaneously to a femoral artery for the recording of arterial pressure (Statham transducer P 23IA) and the collection of blood samples for the determination of PaOj, Pacch and pH; the determinations were carried out within 5 min of sampling (Instrument Laboratories 313). The concentration of carbon dioxide (FCO2) in the tracheal tube was recorded continuously (Beckman LB2). The spirogram was obtained after integration of the pneumotachographic signal (Fleisch No. 2). The pneumotachograph was calibrated at the beginning and end of each experiment with air, and with oxygen. Systemic arterial pressure, FCO2 and pneumotachogram (flow V and tidal volume VT) were recorded on a polygraph (Beckman DynographR411). As anaesthesia proceeded, the rate of Althesin infusion was adjusted to a level suitable for the maintenance of light anaesthesia, the level of anaes© The Macmillan Press Ltd 1984
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Althesin was administered i. v. to eight dogs, using two different rates of infusion (6.55 ± 2.13(d kg"' min and 12.8O±2.0O/Ukg-1min). Ventilation (Tl, T E , RR, TifTm, V T , V E , V T / T I ) and arterial blood-gas tensions were measured in air and during a 10-min period of 100% oxygen breathing. For both rates of Althesin infusion the ventilatory response to oxygen wai identical: there was significant depression of ventilation (decrease in VE and of the ventilatory drive, V T / T I ) from the 1st min of inhalation lasting up to the 10th min. This decrease in ventilation was more marked and persistent than the decrease noticed in the unanaesthetized dog. We conclude that the hypoxic ventilatory drive persists in the dog under Ahhesin anaesthesia.
BRITISH JOURNAL OF ANAESTHESIA
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TABLE I. Values (mean ± SD) of rau of infusion of Althtsin (pi kg"' min); duration of inspiration (Tl) (s); duration of expiration (TB) respiratory timing (Tl/T^; respiratory rau (RRXb.p.m.); tidal volume(VT)(mlkg'1); mean inspiratory flow(V T/Tl)(ml kg~'s~'); minuU ventilation (VB) (mlkg~'min~'); and arterial blood-gas results during ventilation m air, during light anaesthesia (A) and during dee anaesthtsia (B). P •=• degree of significance observed bttxoetn rau A and rau B
A B P
Althesin Oil kg"1 min)
Ti (*)
TE
VT/TI
VE
Tl[Tm
RR (b.p.m.)
VT
(8)
(ml kg"1)
(ml kg"1*"1)
(ml kg"' min.-')
pH
PacOj (kPa)
P»Oj (kPa)
6.55 2.13 12.80 2.00 0.001
0.76 0.38 1.26 0.26 0.001
1.27 0.78 2.97 1.21 0.01
0.39 0.05 0.31 0.06 0.001
37.6 16.9 15.5 3.8 0.01
11.46 3.99 13.0 4.1 0.05
16.3 4.0 10.3 2.0 0.01
386.5 132.8 193.0 51.0 0.01
7.34 0.06 7.28 0.08 0.01
4.72 1.00 5.95 1.44 0.01
12.02 2.34 10.59 1.34 0.01
was recorded for 1 min before administration of oxygen and for the 10-min period of inhalation. The tidal volume (VT), duration of inspiration (Tl) and duration of expiration (TE) were measured. Respiratory rate (RR) and minute ventilation (V"E) were calculated. Ventilation was also expressed in terms of respiratory timing (Tl/TmJ and mean inspiratory flow ( V T / T I ) which is a measurement of ventilatory drive (Milic-Emili and Grunstein, 1976). Subsequently the rate of Althesin was increased to produce deeper anaesthesia (rate B). Once a steady state was established, the same measurements were
TABLE II. Ventilatory effects of 100% oxygen during an infusion (rate A) of Althesin. Respiratory rau (RR) (b.p.m.); tidal volume (VT) (ml kg'1); minuu ventilation (VB) (ml kg"' min"'); mean inspiratory flow (VT/TI) (ml kg'1 s~'); respiratory riming (Tl/T^,); and arterial blood-gas results. Mean ± SD and differences observed between values in air and values in oxygen Time RR (min) (b.p.m.) Air Oxygen 1
2
3
4
5
10
37.6 16.9 29.3 14.6 P<0.01 29.4 14.3 P<0.01 29.2 12.8 P<0.05 28.7 13.2 P<0.01 29.4 13.2 P<0.01 32.7
VT
VE
(ml kg-') (mlkg-'min-1) 11.5 4.0
10.3 3.6
P<0.01 10.7 3.4
P<0.02 10.8 3.5 n.s. 10.7 3.3 n.s. 10.6 3.7
n.s. 10.6
386.5 132.8 255.9 112.6 P<0.01 265.2 109.4
P<0.01 273.9 107.8 P<0.01 262.3 101.9
P<0.01 268.1 102.6
2.8
3.0
P<0.01 293.9 91.1
D.S.
n.s.
P<0.05
VT/Ti (mlkg-^- 1 ;1 Tl/T r a 16.3 4.0
12.9 3.4
P<0.001 12.9 3.0
P<0.001 13.3 3.4
P<0.0l 12.8 2.9
P<0.01 12.4 3.1 F<0.02 13.5 3.7
J><0.01
0.39 0.05 0.33 0.08 n.s. 0.35 0.37 n.s. 0.35 0.06 n.s. 0.35 0.06 n.s. 0.37 0.07 n.s. 0.36 0.04 n.s.
pH 7.34 0.06
7.31 0.06 n.s.
Pacoj (kPa) 4.72 1.00
Paoj (kPa) 12.02 2.34
5.40 48.90 1.56 15.75 P<0.05P<0.001
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thesia being determined clinically (rate A). Each experiment was carried out, starting after a 45-min period of steady state (45 min being the time required to obtain stable concentrations of Althesin (Sear and Prys-Roberts, 1981). The steady state was determined by noting constant values of Fc&i, systemic arterial pressure, heart rate, respiratory rate, tidal volume and temperature. The air was then replaced by 100% oxygen and this was inhaled for If)min Arterial blood-gas tensions were measured before the administration of oxygen and at the end of the 10th min of oxygen breathing. The spirogram
HYPOXIC VENTILATORY DRIVE
633
TABLE III. Ventilatory effects of 100% oxygen during an infusion (rate B) ofAlthesin. Same abbrtviations as table II
Time
RR
(min) (b.p.m.) Air Oxygen 1 2 3
5 10
193.9 51.0 111.1 30.2 P<0.001 117.9 31.8 P<0.001 122.8 31.8 P<0.001 123.1 32.1 P<0.001 124.2 36.9 P<0.001 132.2 40.5 P<0.001
13.0 4.1 11.0 3.8 P<0.001 11.3 4.0 P<0.01 11.3 3.9 P<0.001 11.2 3.8 P<0.01 11.5 4.0 P<0.001 11.5 3.8 P<0.01
10.3 2.0 7.8 1.3 P<0.001 7.9 1.3 P<0.001 7.8 1.3 P<0.001 7.8 1.4 P<0.001 8.1 1.7 P<0.01 8.3 1.5 P<0.01
Ti/T K»
pH
Paccy (kPa)
(kPa)
0.31 5.95 7.28 10.59 1.44 0.06 0.08 1.34 0.24 0.05 P<0.01 0.25 0.05 P<0.01 0.26 0.06 P<0.05 0.26 0.04 P<0.05 0.26 0.05 P<0.02 0.25 7.21 51.86 7.81 0.05 0.08 11.93 2.10 P<0.01 P<0.001 P<0.01 P<0.001
undertaken, in air, then during and at the end of the 10-min period of oxygen breathing. Student's f test was used on paired groups of observations to analyse the results.
a decrease in respiratory rate, whereas VT increased slightly. The reduction in respiratory rate was caused by an increase of both Tl and T E with a decrease of T I / T E ratio. Concomitantly as anaesthesia became deeper, Pacx>2 increased, while pH RESULTS and Pao2 decreased. A significant difference was Table I shows the two rates of Althesin infusion (A, found between rates A and B for these variables. B), the different variables measured or calculated The administration of oxygen (FlOj = 1.0) was for each rate and the differences observed between followed by an immediate depression of ventilation the two rates. When anaesthesia became deeper (tables II and III). There were no significant differventilation was depressed: VE decreased, caused by ences in the decreases in ventilation expressed as percentage of the value of ventilation in air between rate A and rate B (table IV). The ventilatory depresTABLE IV. Values of minute ventilation expressed in per cent of the sion was partly caused by a decrease in tidal volume values in air (mtan±SD) during the 10-min period of administration °f oxygen during the infusion of Althesin (rates A and B) with the but principally by a reduction in respiratory rate. significances of the differences observed between ventilation in air andThere was a decrease of VT/Tl for the two rates and ventilation in oxygen (A, B). A — B: significance of the differences of Tl/Tm ratio only at rate B. The ventilatory observed between ventilation with oxygen for infusion rates AandB depression (table TV) at 1,2, 3, 4, 5 and 10 min of administration of oxygen was respectively Time (min) 32-28.5-25.7-29-27.1-22% at rate A, and 45.3-39.2-36.3-36.6-36.5 and 35.5% at rate B. 1 10 Hypoventilation produced hypercapnia, observed 68.2 71.5 74.3 71.0 72.9 78.0 at the 10th min. P&Ch increased (without any sig14.6 15.1 11.3 14.0 15.5 15.6 nificant difference in Pac^ between rates A and B). P<0.001 P<0.01 P<0.001P<0.001 P<0.01 P<0.01 57.4 60.8 63.7 63.4 63.5 64.8 14.3 14.0 15.2 13.2 13.2 10.0 P<0.001P<0.001P<0.001P<0.001P<0.001P<0.001
A-B
n.t.
n.s.
n.s.
n.i.
P<0.05
DISCUSSION The ventilatory effects of Althesin anaesthesia observed in the present study were similar to those reported by Gaudy and colleagues (1982a) in dogs.
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4
15.5 3.8 10.9 4.0 P<0.01 11.4 4.2 P<0.02 11.7 4.1 P<0.05 11.8 3.8 P<0.05 11.7 4.0 P<0.05 12.3 4.5 P<0.02
VE VT VT/TI (ml kg"1) (ml kg"1 min"1') (mlkg-'s- ')
634
chemoreflexes to hypoxia might differ according to the anaesthetic agent used (Marshall and Rosenfeld, 1936). The results of the present study emphasize the fact that, in the dog under Althesin anaesthesia, hypoxia is an important stimulus of ventilation. The administration of oxygen entails a decrease in minute ventilation and ventilatory drive (VT/TC) despite hypercapnia and acidosis; the respiratory timing was also modified. The depression of respiration caused by oxygen did not depend on the depth of anaesthesia. For the two rates of anaesthesia under consideration, the depression observed was more marked and persistent than the depression observed by Watt, Dumke and Comroe (1943) in unanaesthetized dogs. This might tend to prove not only that the hypoxic stimulus persists during Althesin anaesthesia, but also that its role is somewhat more prominent than in the awake animal. Comparison of the results of the present study with those reported in the literature, demonstrates that the actions of Althesin on the chemoreflexes sensitive to hypoxia are different from those caused by other anaesthetic agents. The differences exhibited by anaesthetic agents may be caused by the different sites of action of these agents upon the intricate mechanisms of the chemoreceptors. The effects of anaesthetic agents on the peripheral chemoreceptors have caused much controversy. According to Dripps and Dumke (1942), ether and cyclopropane decrease the sensitivity of the peripheral chemoreceptors in the cat and dog. Price and Widdicombe (1962) noted that, in the cat and dog, cyclopropane did not modify the activity of the chemoreceptors, whereas Biscoe and Millar (1968) observed that, in the cat, the activity of the carotid bodies was stimulated by cyclopropane and ether, but was depressed by halothane. This depression by halothane has been observed recently by Davies, Edwards and Lahiri (1982). The activity of the peripheral chemoreceptors can be modified by anaesthetics either directly or indirectly through modifications of the blood supply, blood-gas tensions, innervation or by a modification of the CNS structures involved in the afferent pathways from the chemoreceptors. The possible action on these various mechanisms of Althesin has not been studied. The results observed in the dog under Althesin anaesthesia should not be extrapolated to man without reservation. If these results were corroborated in man, there would be two possible clinical implica-
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During light anaesthesia, ventilation and blood-gas tensions were similar to normal values observed in unanaesthetized dogs (Stahl, 1967; Green, 1979). Deepening of anaesthesia produced ventilatory depression resulting in hypoxia, hypercapnia and acidosis. The significance of the hypoxic stimulus can be demonstrated by administering oxygen (May, 1957; Dejours, 1962) in man during ventilation at rest. In seven unanaesthetized dogs, Watt, Dumke and Comroe (1943) showed that oxygen depressed ventilation: "In each dog there was usually an immediate decrease in minute volume which was ma-irimai at the end of the first minute; the magnitude of this depression varied from 11 to 31 per cent. Minute volume had returned to a normal level by the end of 3 min in 3 dogs, and by the end of 6 min in another, but in 3 dogs, respiration was still 10 to 14 per cent below the control level at the end of the 6th min of O2 inhalation." Anaesthesia modifies the functioning of the respiratory system, and especially the regulation of ventilation (Severinghaus, 1975). It is now accepted that the ventilatory response to carbon dioxide is depressed. Previously, it has been accepted that the sensitivity of the peripheral arterial chemoreceptors to hypoxia was not modified by anaesthetic drugs (Comroe, 1965; Wylie and Churchill-Davidson, 1972). To a certain extent, this was considered as a safety factor, particularly at the time of awakening from anaesthesia. This consideration has been debated further since Weiskopf, Raymond and Severinghaus (1974) demonstrated that, in dogs, halothane decreased the response to hypoxia. The decrease or the abolition of the respiratory response to hypoxia has been noted in animals and in man with other inhalation anaesthetic agents (Yacoub et al., 1976; Hirshman et al.,1977), barbiturates (Hirshman et al., 1975; Gautier, 1976; Smith and Kulp, 1977; Knill, Bright and Manninen, 1978), morphine (Weil et al., 1975), fentanyl (Smith and Kulp, 1977) and diazepam (Smith and Kulp, 1977). Gaudy and colleagues (1982b) reported, in the dog under Althesin anaesthesia, that whereas the response to carbon dioxide was decreased, the ventilatory response to hypocapnic hypoxia was similar to the response to normocapnic hypoxia in unanaesthetized dogs as reported by other authors (Bouverot, Candas and Libert, 1973). The increasing depth of anaesthesia entails a decrease in the response but does not suppress it. Therefore, the effects of anaesthetics on the sensitivity of the
BRITISH JOURNAL OF ANAESTHESIA
HYPOXIC VENTILATORY DRIVE tions: first, under Althesin anaesthesia, the persistence of hypoxic stimulation might increase safety during recovery from anaesthesia and, second, the administration of pure oxygen might induce respiratory depression. ACKNOWLEDGEMENTS
REFERENCES
Biscoc, J. J., and Millar, R. A. (1968). Effects of inhaUtional anaesthetics on carotid body chemoreceptor activity. Br. J. Anaesth., 40,2. Bouverot, P., Candas, V., and Libert, J. P. (1973). Role of the arterial chemoreceptors in ventilatory adaptation to hypoxia of awake dogs and rabbits. Rapir. Phytiol., 17, 209. Comroe, J. H. jr (1965). The peripheral chemorecepton; in Handbook of Physiology, Vol. 2: Rtspiration (eds W. O. Fenn and H. Rahn), chapter23. Washington: American Physiological Society. Davie*, R. O., Edwards, M. W., and Lahiri, S. (1982). Halothane depresses the response of carotid body chemoreceptors to hypoxia and hypcrcapnia in the cat. Anesthesiology, 57, 153. Dejours, P. (1962). Chemoreflexes in breathing. Phytiol. Rtv., 42, 335. Dripps.R. D., and Dumke.P. R. (1942). The effects of narcotics on the balance between central and chemoreceptor control of respiration. / . Pharmacol. Exp. Ther., 135,233. Gaudy, J. H., Dauthier, C , Boitier, J. F., and Ferracci, F. (1982a). Effets ventnatoires de debits croissants d'alfatesine chez le chien. Can. Anaath. Soc. J., 29,600. Ferracci, F., and Boitier, J. F. (1982b). Reponse vcntilfltoire a l*hypercapnie et a lTiypoxie hypocapnique du chien sous differents niveaux d'anesthesie a l'alfattsine. Ann. Franc. Anesth. Rean., 1, 395. Gautier, H. (1976). Pattern of breathing during hypoxia or hypercapnia of the awake or anesthetized cat. Rap. Phytiol., 27,193. Green, C. J. (1979). Animal Anaathaia, lstedn. London: Laboratory Animals. Hirshman, C. A., McCullough, R. E., Cohen, P. J., and Weil, J. V. (1975). Effect of pentobarbitone on hypoxic ventilatory drive in man. Br. J. Anaath., 47, 963. (1977). Depression of hypoxic ventilatory response by halothane, enflurane and tsoflurane in dogs. Br. J. Anaesth., 49, 957. Knill, R. L., Bright, S., and Manninen, P. H. (1978). Hypoxic ventilatory responses during thiopentone sedation and anaesthesia in man. Can. Anaath. Soc. J., 25,366. Marshall, E. K., and Rosenfeld, M. (1936). Depression of respiration by oxygen. / . Pharmacol. Exp. Ther., 57,437. May, P. (1957). L'action immediate de l'oxygene sur la ventilation chez Chomme normal. Htlv. Phytiol. Ada, 15,230. MilJc-EmUi, J., and Gninstcin, M. M. (1976). Drive and timing components of ventilation. O«J.,70(Suppl.I), 131.
Mosso, A. (1904). L'apnee produite par l'oxygene. Arch. Ital. BM., 34,138. Price, H. L. and Widdkombe, J. (1962). Action of cyclopropane on carotid sinus baroreceptors and carotid body chemoreceptors. / . Pharmacol. Exp. Ther., 135,233. Sear, J. W., and Prys-Roberts,C. (1981). Alphadione and minaxolone pharmacokinetics. Ann. Anetth. Franc., 22,142. Severinghaus, J. W. (1975). Ventilation and anesthesia. Dangerous interactions; in Physiological Basis ofAnesthesiology. Theory and Practice (eds W. W. Mushin, J. W. Severinghaus, M. Ticngo and S. Gorini). Padua: Picon Medical Books. Smith, T. C. and Kulp, R. A. (1977). Blunting of the ventilatory responses to hypoxia and hypercapnia by fentanyl, diazepam and pentobarbital in man. Abstr. Sci. Papers. American Society of Anesthesiology Annual Meeting, p. 779. Stahl, W. R. (1967). Scaling of respiratory variables in mammals.
J.Appl. Phytiol., 22,453. Watt, J. G., Dumke, P. R., and Comroe, J. H. jr (1943). Effects of inhalation of 100% and 14% O2 upon respiration of unanesthetized dogs before and after chemoreceptor denervarion. Am. J. Phytiol, 138,610. Weil, J. V., McCullough, R. E., Kline, J. S., and Sodal, I. E. (1975). Diminished ventilatory response to hypoxia and hypercapnia after morphine in normal man. N. Engl. J. Med., 292, 1103. Weiskopf, R. B., Raymond, L. W., and Severinghaus, J. W. (1974). Effects of halothane on canine responses to hypoxia with and without hypercarbia. Anesthesiology, 41, 350. WyUe, W. D., and Churchill-Davidson, H. C. (1972). A Practice of Anaesthesia. London: Lloyd-Luke. Yacoub, O., Doell, D . , Kruger, M. H., and Anthonisen, N. R. (1976). Depression of hypoxic ventilatory response by nitrous oxide. Anesthesiology, 45, 385.
STIMULATION VENTTLATOIRE PAR LTIYPOXIE CHEZ LE CHIEN ANESTHESIE PAR L'ALFATESINE RESUME
De l'alfatesine a etc administree par voie i.v. a hurt chiens, »elon deux debits de perfusion (6,55±2,13ulkg~ 1 inin~ I et 12,80±2,00nlkg~ 1 min~ 1 ). Les parametres ventilatoires ( V T , T E , FR, Tl)Tm, VT, VE, VT/7"I) et les pressions partielles des gaz du sang arterial ont et£ mesures a l'air et pendant une penode de 10 min dc leapiialion en oxygene pur. La response vmtilatoire a l'O2 etait la meme quel que soil le debit de perfusion de l'alfatesine: il y avait une depression significative de la ventilation (diminution de VE et de la commande ventnatoire, VT/ VI) des la premiere minute de ventilation en O? pur et jusqu'a la 10c min. Cette depression etait plus marquee et plus persistante que celle notee chez le chien non anesthesia. Nous en conctuons que la stimulation ventilatoire par l*hypoxie persiste chez le chien anesthesie par l'alfatesine.
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The authors thank. Professor H. Gautier (Laboratoire de Physiologic, Faculty of Medicine Saint-Antoine, Para) for his comments and advice. Supported in part by grants of the Faculty of Medicine SaintAntoine (Paris) and the Anaesthetists' Association of Hdpital Rothschild.
635
636
BRITISH JOURNAL OF ANAESTHESIA HYPOXISCHER ATEMANTRIEB BEI HUNDEN UNTER ALTHESINNARKOSE
IMPULSO VENTILATORIO HIPOXICO EN EL PERRO BAJO ANESTESIA POR ALTESINA SUMARIO
Se administro altesina i.v. a echo peros, al usar do* ritmos de infusion distintos (6,55±2,15/ilkg~ 1 min" 1 y U,S0±2,00tilkg~i min"1). Semidieronlaventilaci6n(Tl, Tn, RR, TilTm, Vt, VB, VT/TI) y las tensmnrs gag-aangre en el aire y durante un periodo de 10 minuto$ de respiration de csigeno al 100%. Para ambos ritmos de infusion de altesina, la respuesta ventilttoria al ozigeno fue identica: no hubo depresion significante de la ventilAcion (descenso del VE y del impuljo ventilatorio, VT/XI) desde el primer minuto de inhalacion que dur6 hasta el lOo. minuto. El descenso en la vendlacioii fue mis marcado y persistente que la disminucion observada en el pei'io no-anestesiado. Concluimos que el impulso vcntilatorio hipozico perdura en el perro bajo anestesia por altesina.
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ZUSAMMHNFASSUNG
Acht Hunde wurden mh Ahhedn bei zwei venchiedeoen Tnfntions geschwindigkeiten (6,55±2,13filkgmin~ 1 und 12,80±2,00Mlkg" 1 mln" 1 ) narfcotisiert. Atmung (Xl/r^,, Tl, Tb, RR, V T , VE, VT/TI) und arterielle Blutgasspannungen wurden bei Luftatmung und wfihrend lOminu tiger Gabe reioen Sauentoffs gemetsen. Bd bdden Inftitioimgeschwindigkrifen von Ahfaedn war die ventilatorische Reiktion aui O2 identisch: et fand tich *in* gignifikante AiymH^prf mion (AbfaU von VB und des ventilatorischen Antrietn VT/TI) von der ersten bis roi T»»hnt«»ti Minute der Oj-Inhalition. Diese Vwiriiutinn«Qhwinii> war betonter und andauemder als die bei nicht narkotisierten Hunden beobachtete Abnahme. Wir tchlieflen daraus, dafi der hypozische Atemantrieb bei Hunden unter Althesin-Karkose weiterbesteht.
HYPOXIC VENTILATORY DRIVE IN THE DOG UNDER ALTHESIN ANAESTHESIA J. H. GAUDY, S. BERGERET, J. F. B O I T I E R A N D F . FERRACCI SUMMARY
Mosso (1904) and Marshall and Rosenfeld (1936) demonstrated that, when the central nervous system (CNS) is depressed in association with the administration of anaesthetic agents, or hypoxia, the administration of oxygen may depress ventilation or even cause apnoea. Since the publication of these studies, Comroe (1965) and Wylie and ChurchillDavidson (1972) stated that the chemoreflexes stimulated by hypoxaemia were not modified by anaesthesia. Weiskopf, Raymond and Severinghaus (1974) reported that, in the dog, halothane induced a decrease in the ventilatory response to hypoxia and this observation was confirmed by many authors using other anaesthetic agents, in animals and man. Recently, Gaudy and colleagues (1982b) demonstrated that, in the dog receiving Althesin anaesthesia, the ventilatory response to hypocapnic hypoxia was not modified during light anaesthesia and was maintained during deep anaesthesia. The scope of the present work was to present evidence concerning the hypoxic stimulus in the dog receiving Althesin anaesthesia with particular regard to the ventilatory effects caused by administration of oxygen. MATERIAL AND METHODS Eight male beagle dogs(mean weight ± S D = 18.34±
J. H. GAUDY,* M . D . ; S . BERGERET, M . D . ; J . F. BOITIER, M . D . ; F .
FERRACCI, M.D.; Laboratoire d'Anesthesiologie, Hdpital Rothschild, 33, boulevard de Pkpus, 75012 Paris, France. * Address for correspondence: Service de Reanimation Chirurgicale Polyvalente, Hdpital Rothschild, 33 bd de Picpus, 75012 Paris, France.
5.2 kg) were starved for 12 h. A vein of a foreleg was cannulated and anaesthesia induced and maintained with Althesin diluted in a saline solution, administered i.v. by an electric pump (Rhone-Poulenc RP 04-PE). Following the induction of anaesthesia, a cuffed tracheal tube was inserted and, to minimi?*; respiratory resistance, the tracheal tube was connected to a Y-shaped tube without any valve, one of the side extensions being connected to a Douglas bag (5 litre) which was supplied with either air or oxygen. The flow of inspired gases was adjusted to exceed the ventilation of the animal to avoid rebreathing. The dogs were placed on a thermostatically controlled heating mattress, the rectal temperature being maintained at 37 °C. A catheter was inserted percutaneously to a femoral artery for the recording of arterial pressure (Statham transducer P 23IA) and the collection of blood samples for the determination of PaOj, Pacch and pH; the determinations were carried out within 5 min of sampling (Instrument Laboratories 313). The concentration of carbon dioxide (FCO2) in the tracheal tube was recorded continuously (Beckman LB2). The spirogram was obtained after integration of the pneumotachographic signal (Fleisch No. 2). The pneumotachograph was calibrated at the beginning and end of each experiment with air, and with oxygen. Systemic arterial pressure, FCO2 and pneumotachogram (flow V and tidal volume VT) were recorded on a polygraph (Beckman DynographR411). As anaesthesia proceeded, the rate of Althesin infusion was adjusted to a level suitable for the maintenance of light anaesthesia, the level of anaes© The Macmillan Press Ltd 1984
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Althesin was administered i. v. to eight dogs, using two different rates of infusion (6.55 ± 2.13(d kg"' min and 12.8O±2.0O/Ukg-1min). Ventilation (Tl, T E , RR, TifTm, V T , V E , V T / T I ) and arterial blood-gas tensions were measured in air and during a 10-min period of 100% oxygen breathing. For both rates of Althesin infusion the ventilatory response to oxygen wai identical: there was significant depression of ventilation (decrease in VE and of the ventilatory drive, V T / T I ) from the 1st min of inhalation lasting up to the 10th min. This decrease in ventilation was more marked and persistent than the decrease noticed in the unanaesthetized dog. We conclude that the hypoxic ventilatory drive persists in the dog under Ahhesin anaesthesia.
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TABLE I. Values (mean ± SD) of rau of infusion of Althtsin (pi kg"' min); duration of inspiration (Tl) (s); duration of expiration (TB) respiratory timing (Tl/T^; respiratory rau (RRXb.p.m.); tidal volume(VT)(mlkg'1); mean inspiratory flow(V T/Tl)(ml kg~'s~'); minuU ventilation (VB) (mlkg~'min~'); and arterial blood-gas results during ventilation m air, during light anaesthesia (A) and during dee anaesthtsia (B). P •=• degree of significance observed bttxoetn rau A and rau B
A B P
Althesin Oil kg"1 min)
Ti (*)
TE
VT/TI
VE
Tl[Tm
RR (b.p.m.)
VT
(8)
(ml kg"1)
(ml kg"1*"1)
(ml kg"' min.-')
pH
PacOj (kPa)
P»Oj (kPa)
6.55 2.13 12.80 2.00 0.001
0.76 0.38 1.26 0.26 0.001
1.27 0.78 2.97 1.21 0.01
0.39 0.05 0.31 0.06 0.001
37.6 16.9 15.5 3.8 0.01
11.46 3.99 13.0 4.1 0.05
16.3 4.0 10.3 2.0 0.01
386.5 132.8 193.0 51.0 0.01
7.34 0.06 7.28 0.08 0.01
4.72 1.00 5.95 1.44 0.01
12.02 2.34 10.59 1.34 0.01
was recorded for 1 min before administration of oxygen and for the 10-min period of inhalation. The tidal volume (VT), duration of inspiration (Tl) and duration of expiration (TE) were measured. Respiratory rate (RR) and minute ventilation (V"E) were calculated. Ventilation was also expressed in terms of respiratory timing (Tl/TmJ and mean inspiratory flow ( V T / T I ) which is a measurement of ventilatory drive (Milic-Emili and Grunstein, 1976). Subsequently the rate of Althesin was increased to produce deeper anaesthesia (rate B). Once a steady state was established, the same measurements were
TABLE II. Ventilatory effects of 100% oxygen during an infusion (rate A) of Althesin. Respiratory rau (RR) (b.p.m.); tidal volume (VT) (ml kg'1); minuu ventilation (VB) (ml kg"' min"'); mean inspiratory flow (VT/TI) (ml kg'1 s~'); respiratory riming (Tl/T^,); and arterial blood-gas results. Mean ± SD and differences observed between values in air and values in oxygen Time RR (min) (b.p.m.) Air Oxygen 1
2
3
4
5
10
37.6 16.9 29.3 14.6 P<0.01 29.4 14.3 P<0.01 29.2 12.8 P<0.05 28.7 13.2 P<0.01 29.4 13.2 P<0.01 32.7
VT
VE
(ml kg-') (mlkg-'min-1) 11.5 4.0
10.3 3.6
P<0.01 10.7 3.4
P<0.02 10.8 3.5 n.s. 10.7 3.3 n.s. 10.6 3.7
n.s. 10.6
386.5 132.8 255.9 112.6 P<0.01 265.2 109.4
P<0.01 273.9 107.8 P<0.01 262.3 101.9
P<0.01 268.1 102.6
2.8
3.0
P<0.01 293.9 91.1
D.S.
n.s.
P<0.05
VT/Ti (mlkg-^- 1 ;1 Tl/T r a 16.3 4.0
12.9 3.4
P<0.001 12.9 3.0
P<0.001 13.3 3.4
P<0.0l 12.8 2.9
P<0.01 12.4 3.1 F<0.02 13.5 3.7
J><0.01
0.39 0.05 0.33 0.08 n.s. 0.35 0.37 n.s. 0.35 0.06 n.s. 0.35 0.06 n.s. 0.37 0.07 n.s. 0.36 0.04 n.s.
pH 7.34 0.06
7.31 0.06 n.s.
Pacoj (kPa) 4.72 1.00
Paoj (kPa) 12.02 2.34
5.40 48.90 1.56 15.75 P<0.05P<0.001
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thesia being determined clinically (rate A). Each experiment was carried out, starting after a 45-min period of steady state (45 min being the time required to obtain stable concentrations of Althesin (Sear and Prys-Roberts, 1981). The steady state was determined by noting constant values of Fc&i, systemic arterial pressure, heart rate, respiratory rate, tidal volume and temperature. The air was then replaced by 100% oxygen and this was inhaled for If)min Arterial blood-gas tensions were measured before the administration of oxygen and at the end of the 10th min of oxygen breathing. The spirogram
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633
TABLE III. Ventilatory effects of 100% oxygen during an infusion (rate B) ofAlthesin. Same abbrtviations as table II
Time
RR
(min) (b.p.m.) Air Oxygen 1 2 3
5 10
193.9 51.0 111.1 30.2 P<0.001 117.9 31.8 P<0.001 122.8 31.8 P<0.001 123.1 32.1 P<0.001 124.2 36.9 P<0.001 132.2 40.5 P<0.001
13.0 4.1 11.0 3.8 P<0.001 11.3 4.0 P<0.01 11.3 3.9 P<0.001 11.2 3.8 P<0.01 11.5 4.0 P<0.001 11.5 3.8 P<0.01
10.3 2.0 7.8 1.3 P<0.001 7.9 1.3 P<0.001 7.8 1.3 P<0.001 7.8 1.4 P<0.001 8.1 1.7 P<0.01 8.3 1.5 P<0.01
Ti/T K»
pH
Paccy (kPa)
(kPa)
0.31 5.95 7.28 10.59 1.44 0.06 0.08 1.34 0.24 0.05 P<0.01 0.25 0.05 P<0.01 0.26 0.06 P<0.05 0.26 0.04 P<0.05 0.26 0.05 P<0.02 0.25 7.21 51.86 7.81 0.05 0.08 11.93 2.10 P<0.01 P<0.001 P<0.01 P<0.001
undertaken, in air, then during and at the end of the 10-min period of oxygen breathing. Student's f test was used on paired groups of observations to analyse the results.
a decrease in respiratory rate, whereas VT increased slightly. The reduction in respiratory rate was caused by an increase of both Tl and T E with a decrease of T I / T E ratio. Concomitantly as anaesthesia became deeper, Pacx>2 increased, while pH RESULTS and Pao2 decreased. A significant difference was Table I shows the two rates of Althesin infusion (A, found between rates A and B for these variables. B), the different variables measured or calculated The administration of oxygen (FlOj = 1.0) was for each rate and the differences observed between followed by an immediate depression of ventilation the two rates. When anaesthesia became deeper (tables II and III). There were no significant differventilation was depressed: VE decreased, caused by ences in the decreases in ventilation expressed as percentage of the value of ventilation in air between rate A and rate B (table IV). The ventilatory depresTABLE IV. Values of minute ventilation expressed in per cent of the sion was partly caused by a decrease in tidal volume values in air (mtan±SD) during the 10-min period of administration °f oxygen during the infusion of Althesin (rates A and B) with the but principally by a reduction in respiratory rate. significances of the differences observed between ventilation in air andThere was a decrease of VT/Tl for the two rates and ventilation in oxygen (A, B). A — B: significance of the differences of Tl/Tm ratio only at rate B. The ventilatory observed between ventilation with oxygen for infusion rates AandB depression (table TV) at 1,2, 3, 4, 5 and 10 min of administration of oxygen was respectively Time (min) 32-28.5-25.7-29-27.1-22% at rate A, and 45.3-39.2-36.3-36.6-36.5 and 35.5% at rate B. 1 10 Hypoventilation produced hypercapnia, observed 68.2 71.5 74.3 71.0 72.9 78.0 at the 10th min. P&Ch increased (without any sig14.6 15.1 11.3 14.0 15.5 15.6 nificant difference in Pac^ between rates A and B). P<0.001 P<0.01 P<0.001P<0.001 P<0.01 P<0.01 57.4 60.8 63.7 63.4 63.5 64.8 14.3 14.0 15.2 13.2 13.2 10.0 P<0.001P<0.001P<0.001P<0.001P<0.001P<0.001
A-B
n.t.
n.s.
n.s.
n.i.
P<0.05
DISCUSSION The ventilatory effects of Althesin anaesthesia observed in the present study were similar to those reported by Gaudy and colleagues (1982a) in dogs.
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4
15.5 3.8 10.9 4.0 P<0.01 11.4 4.2 P<0.02 11.7 4.1 P<0.05 11.8 3.8 P<0.05 11.7 4.0 P<0.05 12.3 4.5 P<0.02
VE VT VT/TI (ml kg"1) (ml kg"1 min"1') (mlkg-'s- ')
634
chemoreflexes to hypoxia might differ according to the anaesthetic agent used (Marshall and Rosenfeld, 1936). The results of the present study emphasize the fact that, in the dog under Althesin anaesthesia, hypoxia is an important stimulus of ventilation. The administration of oxygen entails a decrease in minute ventilation and ventilatory drive (VT/TC) despite hypercapnia and acidosis; the respiratory timing was also modified. The depression of respiration caused by oxygen did not depend on the depth of anaesthesia. For the two rates of anaesthesia under consideration, the depression observed was more marked and persistent than the depression observed by Watt, Dumke and Comroe (1943) in unanaesthetized dogs. This might tend to prove not only that the hypoxic stimulus persists during Althesin anaesthesia, but also that its role is somewhat more prominent than in the awake animal. Comparison of the results of the present study with those reported in the literature, demonstrates that the actions of Althesin on the chemoreflexes sensitive to hypoxia are different from those caused by other anaesthetic agents. The differences exhibited by anaesthetic agents may be caused by the different sites of action of these agents upon the intricate mechanisms of the chemoreceptors. The effects of anaesthetic agents on the peripheral chemoreceptors have caused much controversy. According to Dripps and Dumke (1942), ether and cyclopropane decrease the sensitivity of the peripheral chemoreceptors in the cat and dog. Price and Widdicombe (1962) noted that, in the cat and dog, cyclopropane did not modify the activity of the chemoreceptors, whereas Biscoe and Millar (1968) observed that, in the cat, the activity of the carotid bodies was stimulated by cyclopropane and ether, but was depressed by halothane. This depression by halothane has been observed recently by Davies, Edwards and Lahiri (1982). The activity of the peripheral chemoreceptors can be modified by anaesthetics either directly or indirectly through modifications of the blood supply, blood-gas tensions, innervation or by a modification of the CNS structures involved in the afferent pathways from the chemoreceptors. The possible action on these various mechanisms of Althesin has not been studied. The results observed in the dog under Althesin anaesthesia should not be extrapolated to man without reservation. If these results were corroborated in man, there would be two possible clinical implica-
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During light anaesthesia, ventilation and blood-gas tensions were similar to normal values observed in unanaesthetized dogs (Stahl, 1967; Green, 1979). Deepening of anaesthesia produced ventilatory depression resulting in hypoxia, hypercapnia and acidosis. The significance of the hypoxic stimulus can be demonstrated by administering oxygen (May, 1957; Dejours, 1962) in man during ventilation at rest. In seven unanaesthetized dogs, Watt, Dumke and Comroe (1943) showed that oxygen depressed ventilation: "In each dog there was usually an immediate decrease in minute volume which was ma-irimai at the end of the first minute; the magnitude of this depression varied from 11 to 31 per cent. Minute volume had returned to a normal level by the end of 3 min in 3 dogs, and by the end of 6 min in another, but in 3 dogs, respiration was still 10 to 14 per cent below the control level at the end of the 6th min of O2 inhalation." Anaesthesia modifies the functioning of the respiratory system, and especially the regulation of ventilation (Severinghaus, 1975). It is now accepted that the ventilatory response to carbon dioxide is depressed. Previously, it has been accepted that the sensitivity of the peripheral arterial chemoreceptors to hypoxia was not modified by anaesthetic drugs (Comroe, 1965; Wylie and Churchill-Davidson, 1972). To a certain extent, this was considered as a safety factor, particularly at the time of awakening from anaesthesia. This consideration has been debated further since Weiskopf, Raymond and Severinghaus (1974) demonstrated that, in dogs, halothane decreased the response to hypoxia. The decrease or the abolition of the respiratory response to hypoxia has been noted in animals and in man with other inhalation anaesthetic agents (Yacoub et al., 1976; Hirshman et al.,1977), barbiturates (Hirshman et al., 1975; Gautier, 1976; Smith and Kulp, 1977; Knill, Bright and Manninen, 1978), morphine (Weil et al., 1975), fentanyl (Smith and Kulp, 1977) and diazepam (Smith and Kulp, 1977). Gaudy and colleagues (1982b) reported, in the dog under Althesin anaesthesia, that whereas the response to carbon dioxide was decreased, the ventilatory response to hypocapnic hypoxia was similar to the response to normocapnic hypoxia in unanaesthetized dogs as reported by other authors (Bouverot, Candas and Libert, 1973). The increasing depth of anaesthesia entails a decrease in the response but does not suppress it. Therefore, the effects of anaesthetics on the sensitivity of the
BRITISH JOURNAL OF ANAESTHESIA
HYPOXIC VENTILATORY DRIVE tions: first, under Althesin anaesthesia, the persistence of hypoxic stimulation might increase safety during recovery from anaesthesia and, second, the administration of pure oxygen might induce respiratory depression. ACKNOWLEDGEMENTS
REFERENCES
Biscoc, J. J., and Millar, R. A. (1968). Effects of inhaUtional anaesthetics on carotid body chemoreceptor activity. Br. J. Anaesth., 40,2. Bouverot, P., Candas, V., and Libert, J. P. (1973). Role of the arterial chemoreceptors in ventilatory adaptation to hypoxia of awake dogs and rabbits. Rapir. Phytiol., 17, 209. Comroe, J. H. jr (1965). The peripheral chemorecepton; in Handbook of Physiology, Vol. 2: Rtspiration (eds W. O. Fenn and H. Rahn), chapter23. Washington: American Physiological Society. Davie*, R. O., Edwards, M. W., and Lahiri, S. (1982). Halothane depresses the response of carotid body chemoreceptors to hypoxia and hypcrcapnia in the cat. Anesthesiology, 57, 153. Dejours, P. (1962). Chemoreflexes in breathing. Phytiol. Rtv., 42, 335. Dripps.R. D., and Dumke.P. R. (1942). The effects of narcotics on the balance between central and chemoreceptor control of respiration. / . Pharmacol. Exp. Ther., 135,233. Gaudy, J. H., Dauthier, C , Boitier, J. F., and Ferracci, F. (1982a). Effets ventnatoires de debits croissants d'alfatesine chez le chien. Can. Anaath. Soc. J., 29,600. Ferracci, F., and Boitier, J. F. (1982b). Reponse vcntilfltoire a l*hypercapnie et a lTiypoxie hypocapnique du chien sous differents niveaux d'anesthesie a l'alfattsine. Ann. Franc. Anesth. Rean., 1, 395. Gautier, H. (1976). Pattern of breathing during hypoxia or hypercapnia of the awake or anesthetized cat. Rap. Phytiol., 27,193. Green, C. J. (1979). Animal Anaathaia, lstedn. London: Laboratory Animals. Hirshman, C. A., McCullough, R. E., Cohen, P. J., and Weil, J. V. (1975). Effect of pentobarbitone on hypoxic ventilatory drive in man. Br. J. Anaath., 47, 963. (1977). Depression of hypoxic ventilatory response by halothane, enflurane and tsoflurane in dogs. Br. J. Anaesth., 49, 957. Knill, R. L., Bright, S., and Manninen, P. H. (1978). Hypoxic ventilatory responses during thiopentone sedation and anaesthesia in man. Can. Anaath. Soc. J., 25,366. Marshall, E. K., and Rosenfeld, M. (1936). Depression of respiration by oxygen. / . Pharmacol. Exp. Ther., 57,437. May, P. (1957). L'action immediate de l'oxygene sur la ventilation chez Chomme normal. Htlv. Phytiol. Ada, 15,230. MilJc-EmUi, J., and Gninstcin, M. M. (1976). Drive and timing components of ventilation. O«J.,70(Suppl.I), 131.
Mosso, A. (1904). L'apnee produite par l'oxygene. Arch. Ital. BM., 34,138. Price, H. L. and Widdkombe, J. (1962). Action of cyclopropane on carotid sinus baroreceptors and carotid body chemoreceptors. / . Pharmacol. Exp. Ther., 135,233. Sear, J. W., and Prys-Roberts,C. (1981). Alphadione and minaxolone pharmacokinetics. Ann. Anetth. Franc., 22,142. Severinghaus, J. W. (1975). Ventilation and anesthesia. Dangerous interactions; in Physiological Basis ofAnesthesiology. Theory and Practice (eds W. W. Mushin, J. W. Severinghaus, M. Ticngo and S. Gorini). Padua: Picon Medical Books. Smith, T. C. and Kulp, R. A. (1977). Blunting of the ventilatory responses to hypoxia and hypercapnia by fentanyl, diazepam and pentobarbital in man. Abstr. Sci. Papers. American Society of Anesthesiology Annual Meeting, p. 779. Stahl, W. R. (1967). Scaling of respiratory variables in mammals.
J.Appl. Phytiol., 22,453. Watt, J. G., Dumke, P. R., and Comroe, J. H. jr (1943). Effects of inhalation of 100% and 14% O2 upon respiration of unanesthetized dogs before and after chemoreceptor denervarion. Am. J. Phytiol, 138,610. Weil, J. V., McCullough, R. E., Kline, J. S., and Sodal, I. E. (1975). Diminished ventilatory response to hypoxia and hypercapnia after morphine in normal man. N. Engl. J. Med., 292, 1103. Weiskopf, R. B., Raymond, L. W., and Severinghaus, J. W. (1974). Effects of halothane on canine responses to hypoxia with and without hypercarbia. Anesthesiology, 41, 350. WyUe, W. D., and Churchill-Davidson, H. C. (1972). A Practice of Anaesthesia. London: Lloyd-Luke. Yacoub, O., Doell, D . , Kruger, M. H., and Anthonisen, N. R. (1976). Depression of hypoxic ventilatory response by nitrous oxide. Anesthesiology, 45, 385.
STIMULATION VENTTLATOIRE PAR LTIYPOXIE CHEZ LE CHIEN ANESTHESIE PAR L'ALFATESINE RESUME
De l'alfatesine a etc administree par voie i.v. a hurt chiens, »elon deux debits de perfusion (6,55±2,13ulkg~ 1 inin~ I et 12,80±2,00nlkg~ 1 min~ 1 ). Les parametres ventilatoires ( V T , T E , FR, Tl)Tm, VT, VE, VT/7"I) et les pressions partielles des gaz du sang arterial ont et£ mesures a l'air et pendant une penode de 10 min dc leapiialion en oxygene pur. La response vmtilatoire a l'O2 etait la meme quel que soil le debit de perfusion de l'alfatesine: il y avait une depression significative de la ventilation (diminution de VE et de la commande ventnatoire, VT/ VI) des la premiere minute de ventilation en O? pur et jusqu'a la 10c min. Cette depression etait plus marquee et plus persistante que celle notee chez le chien non anesthesia. Nous en conctuons que la stimulation ventilatoire par l*hypoxie persiste chez le chien anesthesie par l'alfatesine.
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The authors thank. Professor H. Gautier (Laboratoire de Physiologic, Faculty of Medicine Saint-Antoine, Para) for his comments and advice. Supported in part by grants of the Faculty of Medicine SaintAntoine (Paris) and the Anaesthetists' Association of Hdpital Rothschild.
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636
BRITISH JOURNAL OF ANAESTHESIA HYPOXISCHER ATEMANTRIEB BEI HUNDEN UNTER ALTHESINNARKOSE
IMPULSO VENTILATORIO HIPOXICO EN EL PERRO BAJO ANESTESIA POR ALTESINA SUMARIO
Se administro altesina i.v. a echo peros, al usar do* ritmos de infusion distintos (6,55±2,15/ilkg~ 1 min" 1 y U,S0±2,00tilkg~i min"1). Semidieronlaventilaci6n(Tl, Tn, RR, TilTm, Vt, VB, VT/TI) y las tensmnrs gag-aangre en el aire y durante un periodo de 10 minuto$ de respiration de csigeno al 100%. Para ambos ritmos de infusion de altesina, la respuesta ventilttoria al ozigeno fue identica: no hubo depresion significante de la ventilAcion (descenso del VE y del impuljo ventilatorio, VT/XI) desde el primer minuto de inhalacion que dur6 hasta el lOo. minuto. El descenso en la vendlacioii fue mis marcado y persistente que la disminucion observada en el pei'io no-anestesiado. Concluimos que el impulso vcntilatorio hipozico perdura en el perro bajo anestesia por altesina.
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ZUSAMMHNFASSUNG
Acht Hunde wurden mh Ahhedn bei zwei venchiedeoen Tnfntions geschwindigkeiten (6,55±2,13filkgmin~ 1 und 12,80±2,00Mlkg" 1 mln" 1 ) narfcotisiert. Atmung (Xl/r^,, Tl, Tb, RR, V T , VE, VT/TI) und arterielle Blutgasspannungen wurden bei Luftatmung und wfihrend lOminu tiger Gabe reioen Sauentoffs gemetsen. Bd bdden Inftitioimgeschwindigkrifen von Ahfaedn war die ventilatorische Reiktion aui O2 identisch: et fand tich *in* gignifikante AiymH^prf mion (AbfaU von VB und des ventilatorischen Antrietn VT/TI) von der ersten bis roi T»»hnt«»ti Minute der Oj-Inhalition. Diese Vwiriiutinn«Qhwinii> war betonter und andauemder als die bei nicht narkotisierten Hunden beobachtete Abnahme. Wir tchlieflen daraus, dafi der hypozische Atemantrieb bei Hunden unter Althesin-Karkose weiterbesteht.