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RESPIRATORY ACIDOSIS IN BRONCHIAL ASTHMA
632
the Council has a long row to hoe before it need worry about the detailed implementation of its new and ambitious plans.
NO HELP FOR THE SMOKER
Clearly
RESPIRATORY ACIDOSIS IN BRONCHIAL ASTHMA
MEASURES applied in acute bronchial asthma include administration of sympathomimetic agents, intravenous aminophylline, and adrenal steroids, removal of secretions from the airways by means of bronchoscopy or tracheostomy, and application of assisted respiration. Blumenthal et al. 1 suggested that in some instances the correction of respiratory acidosis may be important, and now Mithoefer et awl. report 6 cases in which this measure produced relief after standard treatment (short of suction and assisted respiration) had failed. All 6 patients had severe unremitting bronchospasm and were shown by blood-gas analysis and pH measurements to have associated respiratory acidosis. Relief was obtained only when the pH was restored to near-normal values by intravenous administration of sodium bicarbonate. In chronic obstructive airways disease acidosis may stimulate respiration, and correction of acidosis lead to a fall in ventilation 4; but in the asthmatic subjects of Mithoefer et al.-even in those with associated chronic respiratory disease-the decisive response was a distinct diminution in airways resistance and the net effect an increase in alveolar ventilation and a fall in arterial carbon-dioxide tension. Acidosis has been shown to lessen, by a direct hydrogenion effect,5 both contractileand relaxation2 responses to adrenaline; and Blumenthal et al.1thought that the relief from bronchospasm which they noted in suitable asthmatic cases treated by the intravenous administration of an alkalinising solution (sodium lactate) resulted from the elimination of this action. Experimental work, however, has cast doubt on the significance of this acidotic depression of the adrenaline response,5 and Mithoefer et al. do not believe that there is as yet a convincing rationale for the striking therapeutic results they obtained. They recommend that, when patients with status asthmaticus have failed to respond to standard treatment, the arterial C02 level and the pH should be measured and, if significant respiratory acidosis is revealed, 90 mEq. of sodium bicarbonate (100 ml. of 0-3 M solution) be administered intravenously over a five-minute period. The measurements should then be repeated and further doses of 44-90 mEq. given at five to ten minute intervals until the pH has returned to a near-normal value or until the clinical condition has improved. So far, they have had no experience of the procedure in children. They point out that, since renal loss of chloride is part of the compensatory mechanism for respiratory acidosis,’ metabolic alkalosis associated with hypochloraemia may occur when the carbon-dioxide tension is lowered,8 and administration of chloride may be indicated. Potassium depletion may also demand correction.99 Blumenthal, J. S., Brown, E. B., Campbell, G. S. Ann. Allergy, 1956, 14, 506. 2. Blumenthal, J. S., Blumenthal, M. N., Brown, E. B., Campbell, G. S., Prasad, A. Dis. Chest, 1961, 39, 516. 3. Mithoefer, J. C., Runser, R. H., Karetzky, M. S. New Engl. J. Med. 1965, 272, 1200. 4. Luchsinger, P. C. Ann. N.Y. Acad. Sci. 1961, 92, 743. 5. Tenney, S. M. Am. J. Physiol. 1956, 187, 341. 6. Tenney, S. M. Anesthesiology, 1960, 21, 674. 7. Polak, A., Haynie, G. D., Hays, R. M., Schwartz, W. B. J. clin. Invest. 1961, 40, 1223. 8. Schwartz, W. B., Hays, R. M., Polak, A., Haynie, G. D. ibid. p. 1238. 9. Refsum, H. E. Scand. J. clin Lab. Invest. 1962, 14, 545. 1.
SCANT
from antismoking clinics and campaigns be taken for granted, and indeed failure of persuasion alone was predictable. In combating an irrational craving, appeals to reason are unlikely to meet with much response. Effective and legitimate means of reinforcing them have, however, still to be found. Lobeline has been said to be helpful in the first cigarettefree days in reducing symptoms of withdrawal and so tiding the smoker over the shock of abstention. But Scott et al.1 could find no evidence of this benefit. The case recently made out for the drug by Golledge2 however, establishes nothing so well as the extraordinary difficulty of establishing anything in an antismoking clinic. Golledge set out to conduct a double-blind trial of lobeline as an aid to stopping smoking. He was running his clinic single-handed and only 36 smokers were invited to attend: only 32 came, and only 27 persevered with the At these meetings, course of four weekly meetings. films, charts, and posters were displayed. Each smoker was given a supply of white tablets containing either lobeline or a placebo preparation, and each was asked to record the number of tablets he took and the number of cigarettes he smoked each day. Of 15 subjects taking lobeline, 11 had stopped smoking after twenty-eight days, compared with 6 of 12 taking the placebo. The difference is not signicant and the figures are small. They were, nevertheless, arrived at only with difficulty. What, for instance, in the treatment of nicotine addiction, constitutes success ? The man who cuts his daily consumption of cigarettes from sixty to six must be felt to have achieved something; but he has not regained his independence. How, in any analysis of results, should he figure" ? " Percentage reduction in cigarette consumption is a measure which perhaps conveys more than it seems
success
to
ought. Golledge also had difficulty with lackadaisical attenders at his clinic. Where the subject’s will and inclination are so much at variance, consistency can hardly be expected. Golledge lost trace of 10 of his 32 subjects before the trial was complete; after extended inquiry only 5 were subsequently found. 9 of the 10 proved to have been taking the placebo, and this Golledge liked to feel was significant since, in general, lack of interest complements lack of success.
Once a trial or course of treatment is over, however, there is nothing to induce either those who have managed to stop smoking or those who have failed to contact the clinic for follow-up. The assessment of success in the longer run must be difficult and frustrating. Golledge, in his trial of lobeline, did not attempt it; and, indeed, in the testing of a drug intended only to facilitate withdrawal, follow-up is hardly relevant. But withdrawal, however painlessly achieved, is itself a waste of time if it has to be
repeated too often. Sooner
later
know whether antismoking propaganda is having any real success. How he is to be answered is not yet apparent. The campaign of persuasion seems perfectly to reconcile doing nothing and doing everything about the established dangers of cigarette-smoking. A Government in two minds about the wisdom of reducing cigarette sales could have lighted on no more obscure or unexceptionable or
someone
will
want to
compromise. Scott, G. W., Cox, A. G. C., Maclean, K. S., Price, T. M. L., Southwell, N. Lancet, 1962, i, 54. 2. Golledge, A. H. Med. Offr, 1965, 117, 59. 1.
the Council has a long row to hoe before it need worry about the detailed implementation of its new and ambitious plans.
NO HELP FOR THE SMOKER
Clearly
RESPIRATORY ACIDOSIS IN BRONCHIAL ASTHMA
MEASURES applied in acute bronchial asthma include administration of sympathomimetic agents, intravenous aminophylline, and adrenal steroids, removal of secretions from the airways by means of bronchoscopy or tracheostomy, and application of assisted respiration. Blumenthal et al. 1 suggested that in some instances the correction of respiratory acidosis may be important, and now Mithoefer et awl. report 6 cases in which this measure produced relief after standard treatment (short of suction and assisted respiration) had failed. All 6 patients had severe unremitting bronchospasm and were shown by blood-gas analysis and pH measurements to have associated respiratory acidosis. Relief was obtained only when the pH was restored to near-normal values by intravenous administration of sodium bicarbonate. In chronic obstructive airways disease acidosis may stimulate respiration, and correction of acidosis lead to a fall in ventilation 4; but in the asthmatic subjects of Mithoefer et al.-even in those with associated chronic respiratory disease-the decisive response was a distinct diminution in airways resistance and the net effect an increase in alveolar ventilation and a fall in arterial carbon-dioxide tension. Acidosis has been shown to lessen, by a direct hydrogenion effect,5 both contractileand relaxation2 responses to adrenaline; and Blumenthal et al.1thought that the relief from bronchospasm which they noted in suitable asthmatic cases treated by the intravenous administration of an alkalinising solution (sodium lactate) resulted from the elimination of this action. Experimental work, however, has cast doubt on the significance of this acidotic depression of the adrenaline response,5 and Mithoefer et al. do not believe that there is as yet a convincing rationale for the striking therapeutic results they obtained. They recommend that, when patients with status asthmaticus have failed to respond to standard treatment, the arterial C02 level and the pH should be measured and, if significant respiratory acidosis is revealed, 90 mEq. of sodium bicarbonate (100 ml. of 0-3 M solution) be administered intravenously over a five-minute period. The measurements should then be repeated and further doses of 44-90 mEq. given at five to ten minute intervals until the pH has returned to a near-normal value or until the clinical condition has improved. So far, they have had no experience of the procedure in children. They point out that, since renal loss of chloride is part of the compensatory mechanism for respiratory acidosis,’ metabolic alkalosis associated with hypochloraemia may occur when the carbon-dioxide tension is lowered,8 and administration of chloride may be indicated. Potassium depletion may also demand correction.99 Blumenthal, J. S., Brown, E. B., Campbell, G. S. Ann. Allergy, 1956, 14, 506. 2. Blumenthal, J. S., Blumenthal, M. N., Brown, E. B., Campbell, G. S., Prasad, A. Dis. Chest, 1961, 39, 516. 3. Mithoefer, J. C., Runser, R. H., Karetzky, M. S. New Engl. J. Med. 1965, 272, 1200. 4. Luchsinger, P. C. Ann. N.Y. Acad. Sci. 1961, 92, 743. 5. Tenney, S. M. Am. J. Physiol. 1956, 187, 341. 6. Tenney, S. M. Anesthesiology, 1960, 21, 674. 7. Polak, A., Haynie, G. D., Hays, R. M., Schwartz, W. B. J. clin. Invest. 1961, 40, 1223. 8. Schwartz, W. B., Hays, R. M., Polak, A., Haynie, G. D. ibid. p. 1238. 9. Refsum, H. E. Scand. J. clin Lab. Invest. 1962, 14, 545. 1.
SCANT
from antismoking clinics and campaigns be taken for granted, and indeed failure of persuasion alone was predictable. In combating an irrational craving, appeals to reason are unlikely to meet with much response. Effective and legitimate means of reinforcing them have, however, still to be found. Lobeline has been said to be helpful in the first cigarettefree days in reducing symptoms of withdrawal and so tiding the smoker over the shock of abstention. But Scott et al.1 could find no evidence of this benefit. The case recently made out for the drug by Golledge2 however, establishes nothing so well as the extraordinary difficulty of establishing anything in an antismoking clinic. Golledge set out to conduct a double-blind trial of lobeline as an aid to stopping smoking. He was running his clinic single-handed and only 36 smokers were invited to attend: only 32 came, and only 27 persevered with the At these meetings, course of four weekly meetings. films, charts, and posters were displayed. Each smoker was given a supply of white tablets containing either lobeline or a placebo preparation, and each was asked to record the number of tablets he took and the number of cigarettes he smoked each day. Of 15 subjects taking lobeline, 11 had stopped smoking after twenty-eight days, compared with 6 of 12 taking the placebo. The difference is not signicant and the figures are small. They were, nevertheless, arrived at only with difficulty. What, for instance, in the treatment of nicotine addiction, constitutes success ? The man who cuts his daily consumption of cigarettes from sixty to six must be felt to have achieved something; but he has not regained his independence. How, in any analysis of results, should he figure" ? " Percentage reduction in cigarette consumption is a measure which perhaps conveys more than it seems
success
to
ought. Golledge also had difficulty with lackadaisical attenders at his clinic. Where the subject’s will and inclination are so much at variance, consistency can hardly be expected. Golledge lost trace of 10 of his 32 subjects before the trial was complete; after extended inquiry only 5 were subsequently found. 9 of the 10 proved to have been taking the placebo, and this Golledge liked to feel was significant since, in general, lack of interest complements lack of success.
Once a trial or course of treatment is over, however, there is nothing to induce either those who have managed to stop smoking or those who have failed to contact the clinic for follow-up. The assessment of success in the longer run must be difficult and frustrating. Golledge, in his trial of lobeline, did not attempt it; and, indeed, in the testing of a drug intended only to facilitate withdrawal, follow-up is hardly relevant. But withdrawal, however painlessly achieved, is itself a waste of time if it has to be
repeated too often. Sooner
later
know whether antismoking propaganda is having any real success. How he is to be answered is not yet apparent. The campaign of persuasion seems perfectly to reconcile doing nothing and doing everything about the established dangers of cigarette-smoking. A Government in two minds about the wisdom of reducing cigarette sales could have lighted on no more obscure or unexceptionable or
someone
will
want to
compromise. Scott, G. W., Cox, A. G. C., Maclean, K. S., Price, T. M. L., Southwell, N. Lancet, 1962, i, 54. 2. Golledge, A. H. Med. Offr, 1965, 117, 59. 1.