A T R O P I N E P R E M E D I C A T I O N A N D A R T E R I A L O X Y G E N T E N S I O N

C. M. CONWAY and J. P. PAYNE

In a study of hypoxaemia following anaesthesia and controlled ventilation, Conway and Payne (1964) noted that not only did hypoxaemia occur post- operatively, but that during the course of surgery arterial oxygen tensions were lower than predicted values in spite of evidence of hyperventilation, and that hypoxaemia was also present in a small group of patients from whom blood samples had been taken before surgery. These patients had been pre- medicated with atropine but no other drugs had been given. Subsequently, Tomlin, Conway and Payne (1964) showed that a group of patients pre- medicated with atropine had a significantly lower arterial oxygen saturation than a comparable group of unpremedicated patients.

Other workers have failed to find an action of atropine upon arterial oxygen tension. Because of these conflicting results the work previously reported has been extended. Additional studies were undertaken to investigate the effect of atropine upon arterial oxygen tension in more detail to ascertain whether any action could be modified by altering the route of administration, and to ascertain whether any action of atropine upon arterial oxygen tension was related to the age of the subject.

METHODS

Studies have been carried out on 66 patients admitted to hospital for elective surgical procedures. All these patients were clinically free from respira- tory and cardiovascular disease.

In each patient two arterial blood samples were obtained, the first before premedication with atropine, and the second sample just before induction of anaesthesia, approximately one hour later. All samples were taken with the subjects supine and at rest.

Luton and Dunstable Hospital, Bedfordshire, and Research Department of Anaesthetics, Royal College of Surgeons of England, Lincoln’s Inn Fields, London, W.C. 2, England.

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Each blood sample was taken into a 5-ml syringe, the dead space of which was filled with heparin (10 mg/ml). Oxygen tension was measured polaro- graphically with a Clark electrode, and carbon dioxide tension was measured by a C0,-sensitive electrode. Duplicate analyses were performed on all samples. The oxygen and carbon dioxide electrodes were calibrated with known gas mixtures analysed on a Haldane apparatus. The blood-gas difference of the oxygen electrode was checked by frequent tonometry.

RESULTS

In 36 patients 0.6 mg of atropine was given by one of three different routes and the effects upon blood-gas tension measured. In 10 patients given intra- venous atropine a fall in arterial oxygen tension of 0.2 mm Hg was observed. 15 patients given intramuscular atropine showed a mean fall in oxygen tension of 2.1 mm Hg and 11 patients given subcutaneous atropine had an oxygen tension fall of 7.6 mm Hg. The duration of action of atropine was comparable in all groups and there was no significant change in carbon dioxide tension.

A further 30 patients were given 0.6 mg atropine subcutaneously. This series consisted of 12 males and 18 females, with ages ranging from 21 to 68 years (mean, 43.8 years). Before atropine the mean arterial oxygen tension was 9 1.8 mm Hg and there was an inverse correlation between arterial oxygen tension and age which could be expressed by the equation PaO, = 102.2-0.24 (age) (r = -0.71). After atropine the mean arterial oxygen tension was 87.2 mm Hg and the regression equation relating arterial oxygen tension to age was given by PaO, = 104.1-0.385 (age) (r = -0.66). The change inarterial oxygen tension could be related to age by the equation PaO, = 1.88-0.15 (age) (r = -0.41). Patients under 40 years of age had a mean oxygen tension fall of 1.9 mm Hg; those aged 40 and over had a mean oxygen tension fall of 6.4 mm Hg. The overall mean fall was 4.6 mm Hg. Before atropine there was no significant difference in arterial oxygen tension between males (mean PaO, = 91.75 mm Hg) and famales (mean value 91.88 mm Hg); following atropine there was a slightly greater fall in arterial oxygen tension in males (mean fall 5.42 mm Hg) than in females (mean fall 4.11 mm Hg), which was statistically significant (0.05 > P > 0.025).

D I S C U S S I O N

The first part of this study demonstrates that atropine given subcutaneously can cause a fall in arterial oxygen tension in otherwise healthy individuals, but that such an effect on arterial oxygen tension is not seen when atropine is given either intravenously or intramuscularly.

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Daly, Ross and Behnke (1963) studied the effects of atropine on pulmonary vascular function and showed that 2 mg intravenous atropine caused a rise in physiological dead space and in compliance within 10 minutes of administra- tion; no change in arterial oxygen saturation was observed. They also showed that atropine causes a redistribution of blood away from the lungs and reduces the volume of blood available for gas exchange. Rotman (1964), from studies on the action of atropine on pulmonary diffusing capacity in man, similarly concluded that the fall in diffusing capacity produced by atropine was com- patible with a shift of blood away from the lungs. Nunn and Bergman (1964) found no significant effects of intravenous atropine on arterial oxygen tension or on the magnitude of the alveolar-arterial oxygen difference when breathing 100 yo oxygen, air, or 1 1 yo oxygen. They found greater changes in physiological dead space than could be accounted for by the increase in anatomical dead space, and concluded that atropine increases the degree of regional relative over-ventilation but not the degree of regional relative overperfusion.

Halmigyi and his associates (1964) have demonstrated an effect of atropine upon the ventilation-perfusion ratio of experimental animals. They found that, in animals rendered hypoxaemic by the instillation of fluid into the lung, atropine restored compliance without causing a proportional rise in arterial oxygen saturation, and that in animals breathing 11% oxygen in nitrogen the administration of atropine caused a marked increase in venous admixture. From this and other evidence they postulated the presence of a local homeostatic reflex by which perfusion is regulated in response to ventilation, and inferred that atropine blocks this reflex, rendering the pulmonary circulation passive.

The action of subcutaneous atropine on arterial oxygen tension reported in this paper is unlikely to be due to an effect of atropine upon the nervous or local reflex regulation of the pulmonary circulation. Were such a mechanism operative, it would be expected that the effects of atropine would be greatest when high peak blood levels were attained, as after intravenous or intramuscular administration. The fact that an action of atropine on arterial oxygen tension was seen only after subcutaneous administration is more in favour of a mechani- cal mode of action, perhaps in relation to surfactant or to the increased tenacity of secretions.

The second part of this study demonstrates that the magnitude of the fall in arterial oxygen tension produced by atropine is inversely proportional to the age of the subject, being relatively insignificant in young patients but of more significance in older patients. I t has been previously shown (Conway, Payne and Tomlin, 1965) that in healthy patients awaiting surgery there is an inverse correlation between arterial oxygen tension and age, described by the regression equation PaO, = 102.5-0.22 (age). The regression equation relating age to arterial oxygen tension before atropine in the present paper does not differ significantly from either the above equation or that derived by Raine and Bishop (1963) in healthy volunteers.

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After atropine there is a significant increase in the slope of the equation relating PaO, to age. Nunn (1965) has shown that postoperative hypoxaemia is related to age, and study of his data shows that the lines relating age to postoperative arterial oxygen tension have a markedly greater slope than normal, associated with a lower intercept. The regression lines derived by Nunn are virtually parallel to but lower than that derived from the present study relating age to arterial oxygen tension after atropine. This implies that although atropine may not be the cause of postoperative hypoxaemia it cer- tainly exacerbates the condition in the elderly.

R E F E R E N C E S

CONWAY, C. M., and PAYNE, J. P. (1964): Hypoxaemia associated with anaesthesia and controlled respiration. Lancet. i, 12.

DALY, W. J., Ross, J. C., and BEHNKE, R. H. (1963) : The effect ofchanges in the pulmonary vascular bad produced by atropine, pulmonary engorgement and positive pressure breathing on diffusing and mechanical properties of the lung. J. Clin. Invest. 42, 1083.

H A L M ~ Y I , D. F., COLEBATCH, H. J. H., STARZECKI, B., and HORNER, G. J. (1964) : Pul- monary alveolar-vascular reflex. J. Appl. Physiol. 19, 105.

NUNN, J. F. (1965) : Influence of age and other factors on hypoxaemia in the postoperative period. Lancet. ii, 466.

NUNN, J. F., and BERGMANN, N. A. (1964): The effect of atropine upon pulmonary gas exchange. Brit. J. Anaesth. 36, 68.

RAINE, J. M., and BISHOP, J. M. (1963) : Alveolar arterial differences in oxygen tension and physiological dead space in normal man. J. Appl. Physiol. 18, 284.

ROTMAN, H. H. (1964) : Effect of atropine on pulmonary diffusing capacity in man. Brit. J. Anaesth. 36, 74.

TOMLIN, P. J., CONWAY, C. M., and PAYNE, J. P. (1964): Hypoxaemia due to atropine. Lancet. i, 14.