I.V. LIGNOCAINE IN REFLEX AND ALLERGIC BRONCHOCONSTRICTION

Br.J. Anaesth. (1980) 52, 873

I.V. LIGNOCAINE IN REFLEX AND ALLERGIC BRONCHOCONSTRICTION H. DOWNES, N. GERBER AND C. A. HIRSHMAN

SUMMARY

The i.v. administration of local anaesthetic agents has been used to treat bronchospasm occurring in both awake (Dos Ghali, Bourdin and Guiot, 1943a, b ; Durieu, De Clercq and Duprez, 1946) and anaesthetized man (Brandus et al., 1970). Lignocaine by this route has been shown to depress the cough reflex in anaesthetized man (Steinhaus and Howland, 1958; Steinhaus and Gaskin, 1963), but parallel effects on pulmonary mechanics were not measured. Moreover, since bronchospasm occurring during anaesthesia may have different causes, the efficacy of lignocaine in treating bronchospasm may depend critically on the nature of the initiating stimulus. Therefore, in dogs anaesthetized with barbiturates, we undertook to test the protection afforded by the i.v. administration of lignocaine against bronchospasm initiated by a chemical irritant (citric acid aerosol, CAA) and by an antigen (ascaris antigen aerosol, AAA). METHODS

Five Basenji-Greyhound (B-G) crossbreed dogs, each about 20 kg, were selected for these experiments on the basis of large and consistent responses during repeated challenges with CAA and AAA. Each dog served as its own control, and on different days, about HALL DOWNES, M.D., PH.D.; NICHOLAS GERBER, M.D.J Department of Pharmacology. CAROL A. HTRSHMAN, M.D.,

Department of Anesthesiology. University of Oregon Health Sciences Center, 3181 S.W. Sam Jackson Park Road, Portland, Oregon 97201, U.S.A. Correspondence to H.D. 0007-0912/80/090873-07 $01.00

1 week apart, was challenged with CAA or AAA, with or without lignocaine treatment. The dogs were not premedicated and were anaesthetized standing, supported by a sung. After the induction of anaesthesia with thiamylal 12 mg kg" 1 i.v., neuromuscular blockade was produced with suxamethonium and the trachea intubated with an 8.5-9 mm cuffed tracheal tube. The lungs were ventilated manually with oxygen 100%. Additional increments of thiamylal and suxamethonium were administered as required. A balloon (Dynasciences, Blue Bell, Pa.) was placed in the oesophagus under direct vision and positioned at the point where recorded end-expiratory pressure was least. The balloon contained 0.8 ml of air. A separate catheter, connected to suction, was placed in the oesophagus to keep it empty of air and liquid. For measurement of pulmonary resistance (Rh) and dynamic compliance (Cdyn), the lungs were ventilated for approximately 30 s with a piston-type ventilator (Harvard Apparatus Company, Millis, Ma.) from which the inspiratory and expiratory valves had been removed. The ventilator was set to deliver a tidal volume of 400 ml at a frequency of 15 b.p.m., and produced a regular sinusoidal flow pattern with a peak inspiratory flow equivalent to 2 jt/x200mls~ 1 . Transpulmonary pressure (Ptp) w a s measured with a differential pressure transducer (Hewlett-Packard 270) connected to the oesophageal balloon and to a needle inserted into the endotracheal tube. Airflow (F) was measured with a calibrated pneumotachograph head (Hewlett-Packard 2107IB) and a differen© Macmillan Publishers Ltd 1980

Downloaded from http://bja.oxfordjournals.org/ at University of Manitoba on August 26, 2015

The protection against bronchospasm afforded by infusions of lignocaine was tested in dogs anaesthetized with thiamylal by challenge with aerosols of citric acid (CAA) or ascaris antigen (AAA). During the infusion of lignocaine, the response to CAA was blocked or markedly attenuated, but AAA still elicited a large increase in pulmonary resistance (.RL)- In untreated dogs, CAA increased Rh from 0.14 ±0.05 (mean±SEM) kPa litre" 1 s to 1.09 ±0.18, whereas in dogs treated with lignocaine, i? L was 0.19 ±0.09 before challenge with CAA and 0.44 ±0.13 after challenge. AAA increased Rh from 0.14 ± 0.06 kPa litre" 1 s to 3.01 ± 0.65 in untreated dogs, and from 0.34 ± 0.10 kPa litre" 1 to 1.85±0.69 in dogs treated with lignocaine. Blood concentrations of lignocaine were 1.5 ± 0.3 and 2.5 ± 0.6 |*g ml" 1 during challenge with CAA and AAA, respectively. We conclude that lignocaine, at blood concentrations which will reduce the risk of cardiac arrhythmia, markedly reduces reflex bronchoconstriction, but has relatively little effect on that initiated by allergic mediators.

874

BRITISH JOURNAL OF ANAESTHESIA by centrifugation, a 25-ml portion of the organic layer was extracted into 2 ml of hydrochloric acid 1 mol litre" 1 . A 1.6-ml aliquot of the acid was neutralized with 2.5 ml of phosphate buffer 4 mol litre" 1 (pH 7.4) in a Reactivial and extracted into chloroform 25 (jditre containing docosane 50 jxg ml" 1 as the internal standard. Samples were analysed on a Hewlett-Packard 5830 gas chromatograph using flame ionization and a 1.75 mx 2 mm (i.d.) glass column packed with 1.5% OV-101 on Gas Chrom Q. The oven temperature was programmed at 10 °C min" 1 from 170 to 250 °C. Standard curves were prepared for each experiment by adding lignocaine to dog blood; correlation coefficients for standard curves varied from 0.991 to 0.998. RL and Cdyn during lignocaine infusions were compared with appropriate controls at each time interval by a paired t test (Steele and Torrie, 1960), at the P> 0.05 level of significance.

Aerosols were delivered by a Hudson 3000 nebulizer driven by compressed oxygen and inserted between the inspiratory limb of a circle anaesthesia system and the tracheal tube. To avoid residual contamination, the circle system was changed after completion of aerosol administration. Ascaris antigen was prepared by Sephadex filtration using the method of Madder, Malley and Amkraut (1971). Ascaris protein, 30 (ig of the purified extract, was placed in 10 ml of water and delivered as an aerosol over a 10-min period. Citric acid aerosols were made up in distilled water and delivered for 2 min. The most reactive animal was challenged with 3 % citric acid and the remaining four animals with 10% citric acid. i? L and Cdyn were measured immediately at the end of the administration of the aerosol and at 5-min intervals for 30 min. During the lignocaine studies, following induction of anaesthesia, a loading dose of lignocaine 1.8 mg kg"1 was administered i.v. over 1 min. Thereafter, maintenance infusion rates of 4-6.5 mg kg" 1 h" 1 were administered throughout the experimental period. At 25 min after the start of the maintenance infusion of lignocaine, baseline values for Rf_ and Cdyn were measured; and at 30 min the dogs were challenged with AAA and CAA. For determination of blood lignocaine concentrations, 2 ml of blood was withdrawn from an indwelling catheter in the cephalic vein and added directly to a tube containing 1-chlorobutane 30 ml and 1 ml of phosphate buffer 0.1 mol litre- 1 (pH 7.4) with 50 units of heparin. After shaking for 10 min followed

RESULTS

In untreated dogs (fig. 1), inhalation of CAA produced large increases in RL and decreases in C dyn , which were maximal at 5 min after completion of the aerosol challenge (7 min after the start). J?L increased from a pre-challenge control of 0.14 ±0.05 (mean±SEM) kPa litre- 1 s to 1.09 ±0.18 at 5 min after challenge, and Cdyn decreased from 1400 ± 270 ml kPa" 1 prechallenge to 520 ± 80 at 5 min after challenge. In individual animals, the change in RL represented a 3- to 14-fold increase. During the infusion of lignocaine (fig. 1), the response to CAA was blocked or markedly attenuated. RL was 0.19 + 0.09 kPa l i t t e r s in the pre-challenge control and 0.44 ± 0.13 at 5 min after challenge, and Cdyn was 1600 ±480 ml kPa" 1 pre-challenge and 1000 + 300 at 5 min after challenge. Four of five dogs showed either no increase in RL or an increase of less than 1.3-fold; in the fifth dog, RL increased by 3.5-fold (compared with a 6-fold increase without lignocaine treatment). In treated compared with untreated dogs, values of i?L after challenge were significantly less during lignocaine infusion throughout the experimental period, and Cdyn during lignocaine infusion was significantly greater for 20 min after challenge. Blood concentrations of lignocaine averaged 1.5 ± 0.3 (Jig ml" 1 at the start of CAA and were maintained at this value for the duration of the experiment (fig. 1). Challenge with AAA elicited large changes in i? L and Cdyn in both untreated and lignocainc-treated

Downloaded from http://bja.oxfordjournals.org/ at University of Manitoba on August 26, 2015

rial pressure transducer (Hewlett-Packard 47304A). Pressure and flow signals were recorded on a HewlettPackard 7754B recorder. Cdyn was calculated by dividing tidal volume by the difference in pressure between points of zero flow. Ptp was measured at the point of maximum inspiratory flow. With the sinusoidal pattern used, this occurred exactly halfway through the inspiratory cycle and corresponded to an inspiratory volume of 200 ml above functional residual capacity. Pulmonary elastic pressure at this point was calculated by dividing 200 ml by compliance. Pressure required to overcome flow resistance (P ro ) was calculated by subtracting elastic pressure from Ptp. Total resistance was then calculated by dividing Pm by instantaneous V at this point. i? L was obtained by subtracting the resistance of the tracheal tube from this value. All volumes were corrected to BTPS. J?L and Cdyn were calculated from a mean of seven consecutive breaths. The electrocardiogram was monitored throughout with a Grass 79 recorder.

875

I.V. LIGNOCAINE IN BRONCHOCONSTRICTION

1.2

0.8

0.4

• — • Response during hgnocaine infusion o—o Control response

LJ'H-

untreated dogs, but RL was significantly less in the lignocaine-treated dogs for the first 10 min after challenge. Blood concentrations of lignocaine averaged 2.5 + 0.6 jig ml" 1 at the start of AAA and were maintained close to this value for the duration of the experiment (fig. 2).

3.0 01

0

20

£

1.0

(A tn

.2

1000

c

^

2000

|

1500

1

500

o •—•Response during lignocaine infusion o ~ o Control response

0L 1000

£

2

J

<3 I 5 o

500

CL

10 Time (mm)

20

30

FIG. 1. Response to CAA in the same dogs, without lignocaine (ligno.) treatment ( O - - O) and during lignocaine infusion ( • — • ) . Each point represents the mean for five dogs and SEM. Time (min) after completion of the aerosol challenge; period of application of the aerosol is indicated by the shaded bar.

8 1

3

•2 2 2

+—^H

0L

20

10

30

(mm)

dogs (fig. 2). These changes were maximal immediately after completion of the aerosol challenge (10 min after its start). In untreated dogs, AAA increased RL from a pre-challenge control of 0.14 +0.06 kPa l i t t e r s to 3.01 ±0.65 immediately after challenge, and decreased Cija from 1746 ±445 ml kPa" 1 prechallenge to 372+ 166 immediately after challenge. During the infusion of hgnocaine, AAA increased RL from a pre-challenge control of 0.34 + 0.10 kPa l i t t e r s to 1.85 + 0.69 immediately after challenge, and decreased Cdyn from 1076 ± 240 ml kPa" 1 prechallenge to 434 ± 123 immediately after challenge. After challenge with AAA, there was no significant difference in Cdyn between lignocaine-treated and

FIG. 2. Response to AAA in the same dogs, without hgnocaine (ligno.) treatment ( O - - O) and during lignocaine infusion ( • — • ) . Each point represents the mean for five dogs and SEM. Time (min) after completion of the aerosol challenge; period of application of the aerosol is indicated by the shaded bar. DISCUSSION

Local anaesthetics have been used sporadically in the treatment of bronchospasm, beginning with cocaine before the turn of the century (Mosler, 1886). Although cocaine was reported to be highly effective in asthma (Potter, 1906), at least in comparison with other treatments then in use, its bronchodilator effects

Downloaded from http://bja.oxfordjournals.org/ at University of Manitoba on August 26, 2015

1500

T

J*

876

blocked or markedly attenuated by atropine. The response to AAA can be attributed to chemical mediators released from sensitized cells on contact with antigen. Such mediators can initiate bronchospasm directly by action on bronchial smooth muscle and indirectly by stimulation of irritant receptors with subsequent reflex bronchospasm (Drazen, 1977). In some dogs, reflex bronchospasm is the major component and the response to AAA can be blocked with atropine (Gold, Kessler and Yu, 1972). This is not true of the B-G dog, since in other studies (in the same animals) pretreatment with large doses of atropine (0.2 mg kg" 1 i.v.) only reduced the response to AAA by about one-third, and Rh was still increased by a factor of six to 26. Lignocaine i.v. could protect against bronchospasm by three general mechanisms: by direct effects on airway smooth muscle, by inhibition of mediator release, and by interruption of reflex arcs. In vitro studies (Weiss, Anderson and O'Brien, 1975; Downes and Loehning, 1977; Weiss, Hargraves and Viswanath, 1978) indicate that the first two mechanisms are possible, given an adequate drug concentration. However, the drug concentrations that produce pronounced effects m vitro are about one-hundred times greater than the blood lignocaine concentrations which can be achieved safely in vivo. Nevertheless, since lignocaine is concentrated in the lung (Sung and Truant, 1954; Keenaghan and Boyes, 1972; Benowitz et al., 1974), possibly in mast cells granules, some effect on mediator release might be achieved with i.v. administration. In our dogs, lignocaine infusions consistently reduced the response to AAA, but the protection was slight and similar to that observed with atropine. Therefore, our studies do not indicate a marked effect of i.v. lignocaine, if any, on mediator release or on smooth muscle response to allergic mediators. Such protection as was observed probably represents interruption of reflex bronchospasm. Since the blood concentrations of lignocaine during challenge with AAA averaged 2.5 p.g ml" 1 (fig. 2), or about midrange of safe antiarhythmic concentrations (Bochner et al., 1978), a large increase in dose is not possible. Although blood concentrations of hgnocaine during challenge with CAA were slightly less (1.5 |zg ml" 1 ), they were adequate to block or markedly reduce the irritant response. Since lignocaine at the concentrations circulating in blood has little or no anticholinergic effect on airway smooth muscle (Downes and Loehning, 1977) or local anaesthetic effect on peripheral nerve (Heavner and de Jong,

Downloaded from http://bja.oxfordjournals.org/ at University of Manitoba on August 26, 2015

may have reflected sympathomimetic rather than anaesthetic actions. This explanation would not apply for procaine, which was given i.v. to treat bronchospasm associated with asthma or pulmonary embolism (Dos Ghali, Bourdin and Guiot, 1943a, b) or during anaesthesia (Brandus et al., 1970), and was an ingredient of commercially produced bronchodilator aerosols (Dautrebande, 1962). These older reports do not include direct measures of drug effect on pulmonary mechanics. More recently, local anaesthetic aerosols have been shown to block a variety of airway reflexes (Jain et al., 1973; Dain, Boushey and Gold, 1975; Cross et al., 1976), presumably by topical anaesthetic effects. Such effects could lessen the reflex component of an asthmatic attack, but lignocaine aerosols frequently elicit bronchoconstriction in patients with reactive airway disease (Miller and Awe, 1975; Weiss and Patwardhan, 1977; Fish and Peterman, 1979). This has been attributed to reflex bronchoconstriction resulting from the irritant effect of lignocaine solution (Miller and Awe, 1975; Fish and Peterman, 1979) or to prostaglandin release and displacement of membrane-bound calcium ion (Weiss and Patwardhan, 1977). Apart from these adverse effects, a portion of the reflex block by local anaesthetic aerosols could represent a systemic effect. I.v. lignocaine, at doses comparable to those used to treat cardiac arrhythmia, has been shown to depress markedly the cough response elicited in anaesthetized patients by mechanical stimulation (Steinhaus and Howland, 1958; Steinhaus and Gaskin, 1963) or in awake patients by inhalation of CAA (Poulton and James, 1979), but parallel effects on RL and Cdyn have not been well documented. Weiss and Patwardhan (1977), studying conscious asthmatic patients with stable disease, noted a slight improvement in FVC and FEVi following i.v. lignocaine, but Loehning, Waltemath and Bergman (1976), studying anaesthetized non-asthmatic subjects, found that i.v. lignocaine did not block the increase in /?L elicited by water aerosols. Both of these studies tested i.v. lignocaine against bronchospasm of relatively mild intensity. In contrast, Brandus and colleagues (1970) reported marked improvement, by clinical standards, following treatment, with i.v. lignocaine, of a case of severe bronchospasm occurring during anaesthesia. In the B-G dog, inhalation of CAA or AAA elicits large changes in pulmonary mechanics of the magnitude seen in severe asthma in man. The response to CAA is primarily reflex bronchospasm and can be

BRITISH JOURNAL OF ANAESTHESIA

I.V. LIGNOCAINE IN BRONCHOCONSTRICTION

877

Downloaded from http://bja.oxfordjournals.org/ at University of Manitoba on August 26, 2015

Dain, D. S., Boushey, H. A., and Gold, W. M. (1975). Inhibition of respiratory reflexes by local anesthetic aerosols in dogs and rabbits. J. Appl. Physiol, 38, 1045. Dautrebande, L. (1962). Microaerosols: Physiology, Pharmacology, Therapeutics, p. 98. New York: Academic Press. Dos Ghali, J., Bourdin, J. S., and Guiot, G. (1943a). La novocaine injectde par voie veineuse dans les dyspnees. Presse Mid., 51, 92. (1943b). Novocaine intraveineuse dans les dyspnees. Rev. Mid. Litgc, 60, 31. Downes, H., and Loehning, R. W. (1977). Local anesthetic contracture and relaxation of airway smooth muscle. Anesthesiology, 47, 430. Drazen, J. M. (1977). Pulmonary physiologic abnormalities in animal models of acute asthma; in Asthma: Physiology, Immunopharmacology, and Treatment, 2nd international symposium (eds L. M. Lichtenstein, and K. F. Austen), p. 250. New York: Academic Press. Durieu, H., De Clercq, F., and Duprez, A. (1946). Traitement de l'asthme par la novocaine intraveineuse. Acta Clin. Belg., 1, 150. Fish, J. E., and Peterman, V. I. (1979). Effects of inhaled lidocaine on airway function in asthmatic subjects. Respiration, 37, 201. Gold, W. M., Kessler, G.-F., and Yu, D. Y. C. (1972). Role ACKNOWLEDGEMENTS of vagus nerves in experimental asthma in allergic dogs. The authors with to thank A. Malley, PH.D. of the Oregon J. Appl. Physiol., 33, 719. Regional Primate Center for purifying the ascaris antigen, Heavner, J. E., and de Jong, R. H. (1974). Lidocaine blockthe Hudson Instrument Company of Temecula, California ing concentrations for B- and C-nerve fibers. Anesthesifor supplying the nebulizer, M. TJII and F. Cetinich for ology, 40, 228. typing the manuscript, B. Bonn for help with chemical assays, and D. R. Morrow for help with animal experiments. Jain, S. K., Trenchard, D., Reynolds, F., Noble, M. I. M., and Guz, A. (1973). The effect of local anaesthesia of the This study was supported by NIH Grant RO1 GM airway on respiratory reflexes in the rabbit. Clin. Sri., 24524 and the Department of Anesthesiology Research and 44, 519. Education Society. Karvonen, S., Jokinen, K., Karvonen, P., and Hollmen, A. (1976). Arterial and venous blood lidocaine concentrations REFERENCES after local anaesthesia of the respiratory tract using an ultrasonic nebulizer. Acta Anaesthesiol. Scand., 20, Benowitz, N., Forsyth, R. P., Melmon, K. L., and Rowland, 156. M. (1974). Lidocaine disposition kinetics in monkey and man. I: Prediction by a perfusion model. Clin. Pharmacol. Keenaghan, J. B., and Boyes, R. N. (1972). The tissue distribution, metabolism, and excretion of lidocaine in Ther., 16, 87. rats, guinea pigs, dogs, and man. J. Pharmacol. Exp. Ther., Bochner, F., Carruthers, G., Kampmann, J., and Steiner, J. 180,454. (1978). Handbook of Clinical Pharmacology, p. 207. Loehning, R. W., Waltemath, C. L., and Bergman, N. A. Boston: Little Brown. (1976). Lidocaine and increased respiratory resistance Boye, N. P., and Bredesen, J. E. (1979). Plasma concentraproduced by ultrasonic aerosols. Anesthesiology, 44, 306. tions of lidocaine during inhalation anaesthesia for fibreoptic bronchoscopy. Scand.J. Respir. Dis., 60, 105. Mackler, B., Malley, A., and Amkraut, A. A. (1971). Antigen-mediated transformation of rhesus lymphocytes Brandus, V., Joffe, S., Benoit, C. V., and Wolff, W. I. in immediate and delayed hypersensitivity. Int. Arch. (1970). Bronchia] spasm during general anaesthesia. Can. Allergy Appl. Immunol., 41, 765. Anaesth. Soc. J., 17, 269. Bromage, P. R., and Robson, J. G. (1961). Concentrations of Miller, W. C , and Awe, R. (1975). Effect of nebulized lidocaine on reactive airways. Am. Rev. Respir. Dis., I l l , lignocaine in the blood after intravenous, intramuscular, 739. epidural and endotracheal administration. Anaesthesia, 16, 461. Mosler (1886). Ueber subcutane Injectionen von Cocainum Salicylicum bei Asthma. Dtsch. Med. Wochenschr., 12, Chu, S. S., Rah, K. H., Brannan, M. D., and Cohen, J. L. 176. (1975). Plasma concentration of lidocaine after endoPelton, D. A., Daly, M., Cooper, P. D., and Conn, A. W. tracheal spray. Anesth. Analg. (Cleve.), 54, 438. (1970). Plasma lidocaine concentrations following topical Cross, B. A., Guz, A., Jain, S. K., Archer, S., Stevens, J., aerosol application to the trachea and bronchi. Can. and Reynolds, F. (1976). The effect of anaesthesia of the airway in dog and man: a study of respiratory reflexes, Anaesth. Soc. J., 17,250. sensations and lung mechanics. CHn. Sri. Molec. Mtd., Potter, S. O. L. (1906). Materia Medico, Pharmacy and 50,439. Therapeutics, p. 587. Philadelphia: Blakiston's Son. 1974) we presume that the site of action is within the central nervous system. In summary, our results indicate that lignocaine at non-toxic blood concentrations significantly reduces the intensity of reflex bronchospasm. Since topical application of lignocaine for intubation or bronchoscopy often results in blood concentrations similar to those achieved here (Bromage and Robson, 1961; Telivuo, 1965; Pelton et al., 1970; Chu et al., 1975; Viegas and Stoelting, 1975; Karvonen et al., 1976; Scott et al., 1976; Smith, 1976; Boye and Bredesen, 1979), topical anaesthesia of the airway may alter pulmonary mechanics by more than local actions. Finally, in the treatment of bronchospasm during anaesthesia, lignocaine i.v. reduces reflex bronchospasm in addition to its antitussive and antiarhythmic effects, but probably has little or no direct action on the release of allergic mediators or on the responsiveness of smooth muscle to such mediators.

878

BRITISH JOURNAL OF ANAESTHESIA

PERFUSION DE LIGNOCAINE CONTRE LA BRONCHOCONSTRICTION REFLEXE ET ALLERGIQUE RESUME

On a teste sur des chiens anesthesies au thiamylal la protection qu'offrent, contre les bronchospasmes, les perfusions de lignocaine par epreuve avec des aerosols d'acide citrique (AAC) ou d'ann'gene ascaricide (AAA). Pendant la perfusion de lignocaine, la reaction a l'AAC a etc bloquec ou nettement attenuee, mais l'AAA a continue a provoquer une forte augmentation de la resistance pulmonaire (i?,_). Chez les chiens non traites, l'AAC a accru la RL de 0,14 ±0,05 (moyenne ± ecart type des moyennes) kPa litre" 1 s a l,09±0,18 tandis que chez les chiens traite» a la lignocaine, la RL a etc de 0,19 ±0,09 avant l'epreuve a l'AAC et de 0,44±0,13 apres l'epreuve. L'AAA a accru la RL de 0,14±0,06 kPa litre"1 s a 3,01 ±0,65 chez les chiens non traites, et de 0,34±0,10 kPa litre"1 s a 1,85 ±0,69 chez les chiens traites a la lignocaine. Les concentrations de lignocaine dans le sang etaient respectivement de 1,5±0,3 et de 2,6±0,6 ng ml" 1 pendant les epreuves a l'AAC et au AAA. Nous en avons conclu

qu'aux concentrations dans le sang permettant de reduire les risques d'arythmie cardiaque, la lignocaine diminue considerablement la bronchoconstriction reflexe, mais qu'elle n'a que tres peu d'effet sur la bronchoconstriction creee par des mediatcurs alergiques. INTRAVENOSES LIGNOCAIN FUR ALLERGISCHE UND REFLEX-BRONCHIALVERENGUNG ZUSAMMENFASSUNG

Schutz gegen Bronchialkrampf durch Lignocain-Infusionen wurde an Hunden getestct, die mit Thiamylal narkotisiert waren, und die mit Zitronensaure (CAA) oder AscaridcsAntigen (AAA) bespruht wurden. Wahrend der Infusion war die Reaktion auf CAA blockicn oder deutlich abgeschwacht, aber AAA fiihrte immer noch zu einem starken Anstieg des Lungenwiderstandes (R^. Bei unbehandelten Hunden wurde RL durch CAA von 0,14±0,05 (mittel± SEM) kPa Liter" 1 s auf 1,09 ±0,18 erhoht, wahrend in den mit Lignocain behandelten Hunden RL vor Reizung durch CAA 0,19 ±0,09 betrug, und 0,44 ±0,13 nach der Reizung. AAA erhohte RL von 0,04±0,06 kPa Liter" 1 s auf 3,01 ± 0,65 bei unbehandelten Hunden, und von 0,34±0,10kPa Liter" 1 s auf 1,85 ±0,69 bei Behandlung mit Lignocain. Lignocain-Blutkonzentrationen betrugen jeweils 1,5±0,3 und 2,6 ± 0,6 |ig ml"' wahrend der Reizung mit CAA und AAA. Wir folgern, dass Lignocain deutlich die Gefahr des Reflex-Bronchialkrampfes verringert, aber relative wenig Wirkung auf den durch Allergie hervorgerufenen Bronchialkrampf hat. LIGNOCAINA EN BRONCOCONSTRICCION ALERGICA Y DE REFLEJO SUMARIO

La protection contra el espasmo bronquial que presentan las infusiones de lignocaina se comprobo en perros anestesiados con tiamilal, en contraposition a los atomizadores de acido cirico (CAA) o de antigeno ascaris (AAA). Durante la infusion de lignocaina, la respuesta a CAA quedo bloqueada o marcadamente atenuada, pero consiguio aun un gran incremento de la resistencia pulmonar (iJJ. En el caso de los perTOS sin tratamiento, CAA incremento la RL desde 0,14±0,05 (media ±desviation tipica) kPa l i t r o ' S hasta 1,09 ±0,18, mientras que para los perros bajo tratamiento con lignocaina, RL fue de 0,19 ±0,09 antes de usar CAA y 0,44 ±0,13 despues de su uso. El uso dc AAA incremento la RL desde 0,14±0,06 kPa litros" 1 hasta 3,01 ±0,65 para los petTOS sin tratamiento, y desde 034 ±0,10 kPa litros" 1 hasta 1,85 ±0,69 en los pen-os tratados con lignocaina. Las concentraciones sanguineas de lignocaina fueron de 1,5 ± 0 3 y de 2,6 ±0,6 jigml" 1 durante el tratamiento con CAA y AAA, respectivamente. La conclusion es, por lo tanto, que la lignocaina, en concentraciones sanguineas que reducen la arritmia cardiaca, reduce de forma acentuada la broncoconstriccion de reflejos, pero ejerce poco efecto, relativamente, sobre la iniciada por los mediadores alcrgicos.

Downloaded from http://bja.oxfordjournals.org/ at University of Manitoba on August 26, 2015

Poulton, T. J., and James, F. M. (1979). Cough suppression by lidocaine. Anesthesiology, 50, 470. Scott, D. B., Littlewood, D. G., Covino, B. G., and Drummond, G. B. (1976). Plasma lignocaine concentrations following endotracheal spraying with an aerosol. Br. J. Anaesth., 48, 899. Smith, R. B. (1976). Uptake of lidocaine from the trachea. Anesthesiology, 44, 269. Steele, R. C , and Torrie, J. (1960). Principles and Procedures of Statistics, 2nd edn, p. 110. New York: McGraw-Hill. Steinhaus, J. E., and Gaskin, L. (1963). A study of intravenous lidocaine as a suppressant of cough reflex. Anesthesiology, 24, 285. Howland, D. E. (1958). Intravenously administered lidocaine as a supplement to nitrous oxide thiobarbiturate anesthesia. Anesth. Analg. (Cleve.), 37, 40. Sung, C.-Y., and Truant, A. P. (1954). The physiological disposition of lidocaine and its comparison in some respects with procaine. J. Pharmacol. Exp. Ther., 112, 432. Telivuo, L. (1965). An experimental study on the absorption of some local anaesthetics through the lower respiratory tract. Ana Anaesthesiol. Seand., (Suppl.) 16, 121. Viegas, O., and Stoelting, R. K. (1975). Lidocaine in arterial blood after laryngotracheal administration. Anesthesiology, 43, 491. Weiss, E. B., Anderson, W. H., and O'Brien, K. P. (1975). The effect of a local anesthetic, lidocaine, on guinea pig trachealis muscle in vitro. Am. Rev. Respir. Dis., 112, 393. Hargraves, W. A., and Viswanath, S. G. (1978). The inhibitory action of lidocaine in anaphylaxis. Am. Rev. Respir. Dis., 117, 859. Patwardhan, A. V. (1977). The response to lidocaine in bronchial asthma. Chest, 72, 429.