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Pulmonary Function Testing: An Approach to the Thoracic Surgical Patient
Pulmonary Function Testing: An Approach to the Thoracic Surgical Patient EDWIN J. KROEKER, M.D.
THE CLINICAL ASSESSMENT by the clinician and surgeon of pulmonary function in the thoracic surgical patient is usually sufficient to determine the operative risk and to arrive at a reasonable prediction of postoperative disability. In certain selected patients, however, the pulmonary function tests to be outlined may be of value in quantitating these factors more precisely. In addition, the physiological approach to the problems of all thoracic surgical patients may improve the management in the preoperative and postoperative periods. The primary function of the lung is gas exchange. Oxygen is absorbed by the blood, carbon dioxide is excreted and a delicate balance of the hydrogen ion concentration of the blood is maintained. The alveolus (Fig. 1) is the final common path where venous blood and environmental air meet to accomplish these processes. For effective gas exchange the alveolus must be adequately ventilated with air, evenly distributed throughout the lung. Diffusion across the gas-blood barrier must occur readily and the alveolar capillaries must have an adequate and even blood supply. Alveolar ventilation with air is accomplished by the pumping action of the lung-thoracic cage bellows. Like the cardiac output of blood, alveolar ventilation has a constant resting level of 4 liters per minute for a cardiac output of 5 liters per minute. 6 Although the lung has the advantage of a greater reserve (it can increase its resting ventilation ten times, while the heart can increase its resting output only four times), it has the disadvantage of having to move air through the nonrespiratory tracheobronchial tree-the anatomical "dead space." This is approximately 150 cc., or 1 cc. per pound of body weightY· 32 Were it not for the dead space, the exact measurement of which requires complicated gas dilution techniques, the problem of measuring alveolar ventilation (Fig. 2) would simply be that of measuring the minute ventilation from the spirogram (tidal volume times respiratory rate per minute). If the estimated dead space ventilation were subtracted from the minute
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(0)
VENTI LATION (b)
DISTRIBUTION (No obStruction and normal elasticity)
Partial pressure C02 02 4Omm. Hg
IOOmm.Hg
Alveolar mArnhn;';A"'C~IQQz:r:s::l1r
(d)
PERFUSION Fig.!. The alveolus, indicating the factors concerned with external respiration.
ventilation (dead space times the respiratory rate per minute) the amount of alveolar ventilation per minute would be approximated. Indirect but valuable information as to the ability of the lung-thoracic cage bellows to maintain adequate alveolar ventilation is obtained from the maximal stress tests. These include: (1) Vital capacity (Fig. 2) is the maximal respiratory excursion of the lung-thoracic cage bellows and measures all the air an individual is capable of moving in a single breath. This is the total lung capacity excluding the residual volume. (2) Timed vital capacity is the volume of air mentioned above plotted against time (that is, the spirogram). Normally, 70 per cent of the total should be exhaled in the first second and 95 per cent after three seconds. Any volume moved after three seconds can probably not be used for alveolar ventilation. The maximal mid expiratory flow rate is a variant of the above. 25 (3) The maximal breathing capacity is the total amount of air a patient can pump with maximal respiratory effort. This is usually measured for 15 seconds on a spirographic tracing or the air is collected
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2. Spirogram, illustrating subdivisions of lung volumes. Volume is represented on the ordinate and time on the abscissa. The primary "volume" subdivisions do not overlap and always equal total lung capacity. The "capacity" subdivisions always include two or more primary "volumes."
in a Douglas bag and measured in a tissot spirometer. The results are expressed in liters per minute at body temperature. This is considered by many as the best over-all test of the function of the lung-thoracic cage bellows. RESTRICTIVE VENTILATORY INSUFFICIENCY
Alveolar ventilation may be reduced by conditions restricting the function of the lung-thoracic cage bellows (Fig. 1, a). These include impairment of central control of respiration, local paralysis or weakness of thoracic cage muscles including the diaphragm, pathologic changes in thoracic cage or deformities, primary pleural lesions which trap the lung and prevent its expansion, loss of lung tissue after operation or as a result of disease, space-occupying pulmonary lesions, either focal (neoplasm) or diffuse (interstitial fibrosis). In this group of restrictive ventilatory insufficiencies the vital capacity is reduced often proportionate to the amount of pathologic alteration as compared with predicted normal values. The timed vital capacity is normal; that is, although the vital capacity is reduced, this amount of air can be exhaled rapidly. By and large, the maximal breathing capacity is not reduced or at least not to the same extent as the vital capacity. In other words, patients can compensate for the decrease in vital capacity by increasing the rate of respiration. This relationship has been expressed in a ratio called the air velocity index: l4 per cent of predicted maximal breathing capacity per cent of predicted vital capacity
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Table 1.
J.
Tests of Pulmonary Functions ,7,ls." RESTRICTIVEVENTILATORY
FUNCTION STUDIED
KROEKER
TEST
NORMAL VALUE
DEFECT
OBSTRUCTIVEDISTRIBUTIVEVENTILATORY DEFECT
Maximal tidal volume
Vital capacity
Normal
Timed vital capacity
100% (=20) of predicted value 1 sec. volume 70 % or more of total
Decreased
Maximal Volume = speed of Time ventila tion
Normal
Decreased
Maximal breathing capacity
100% (=20) of predicted value*
Normal
Decreased
Increased (larger than 1)
Decreased (smaller than 1)
Normal
Increased
Air velocity index % of predicted MBCt % of predicted VC Intrapulmonary gas mixing
Maximal breathing capacity Vital capacity Nitrogen wash-out time
Less than 2.5% end expiratory nitrogen after min. 7 of breathing oxygen
* Predicted maximal breathing capacity for males: [86.5-(0.52 X age)] X body surface area in square meters; for females: [71.3-(0.47 X age)] X body surface area in square meters. t MBC - Maximal breathing capacity VC - Vital capacity If this ratio is larger than 1, the insufficiency is classified as being restrictive; if smaller than 1, it is considered to be obstructive in nature (Table 1). OBSTRUCTIVE AND DISTRIBUTIVE VENTILATORY INSUFFICIENCY
Alveolar ventilation may also be impaired in a group of conditions in which the lung-thoracic cage bellows seem adequate but in which bronchial obstruction or uneven elasticity with poor air distribution, or both, are limiting factors (Fig. 1, b). The common diseases in this group include bronchial asthma, pulmonary emphysema and chronic bronchitis. In this group of obstructive ventilatory insufficiencies the vital capacity is usually normal, or only slightly reduced. The timed vital capacity and maximal breathing capacity are markedly reduced and consequently the air velocity index is smaller than 1. The slowing of the timed vital capacity is the result of several factors, the most obvious being bronchiolar narrowing by bronchospasm or bronchial edema causing an actual stenotic obstruction to the outflow of air during expiration. To evaluate the bronchospastic component it is well to perform this test before and after the inhalation of a nebulized bronchodilating drug. If marked improvement occurs after the use of a bronchodilator this would tend to indicate that intensive treatment might improve pulmonary function before operation. However, we know
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that actual obstruction of the smaller bronchioles can occur by virtue of their delicate unsupported structure whenever the intrapleural pressure exceeds the atmospheric pressurel3 (Fig. 3). In the static stage with no air flow the pressure in the alveolus is equal to the atmospheric pressure and the retractive elastic forces of the lung are in equilibrium with the thoracic cage (intrapleural pressure) elastic forces. In the dynamic state when air flow occurs along the bronchiole, the intrapleural pressure is balanced by the retractive forces of the lung plus the intra-alveolar pressure. During inspiration (Fig. 3, a) with an increased stretching of the lung and a negative alveolar pressure, the intrapleural pressure is always negative. During expiration (Fig. 3, b) the intrapleural pressure remains negative wltil the intra-alveolar pressure exceeds the retractive elastic forces of the lung. When the intrapleural pressure becomes positive, that is, greater than atmospheric, it tends to collapse the unsupported bronchiole. If the retractive forces of the lung are diminished as in emphysema, this may occur at a relatively low rate of air flow. Thus, the loss of elasticity alone with a decrease of the negative intrapleural pressure might cause a slowing of the timed vital capacity. In
Fig. 3. Forces involved in ventilation of the alveolus. a, Pressure exerted on the unsupported bronchiole is intrapleural pressure. During inspiration this is always negative relative to atmospheric pressure, and the bronchiole remains patent. b, During expiration in patients with reduced retractive force of the lung (emphysema) the intrapleural pressure may become positive relative to atmospheric pressure and cause collapse of the unsupported bronchiole. The air in the alveolus is then trapped despite additional pressure that may be applied by the thoracic cage bellows.
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addition, any loss of elasticity reduces the driving force of expiration and results in a slowing of the timed vital capacity. The phenomenon of air trapping is common in the obstructive group of respiratory insufficiencies. This is best seen on a spirogram after several vital capacity measurements. Normally, the tidal volume immediately returns to the resting base line. When air trapping is present it takes several respiratory cycles for the breathing pattern to return to its resting base line. 28 The two stage vital capacity may be useful in measuring the amount of air trapping. The patient is instructed to take as deep a breath as possible after a normal expiration (the point of fwictional residual capacity), then after a short time interval of normal breathing the patient is instructed to expire maximally after a normal respiratory cycle (Fig. 2). The total respiratory excursion of these maneuvers is greater than the one stage vital capacity and the difference represents the amount of air trapping. If the two stage vital capacity is smaller than the one stage, we should suspect malingering or inadequate instruction of the patient. The reduction in the maximal breathing capacity is, in large measure, the result of air trapping. With each succeeding breath the patient seems to blow up like a bullfrog and eventually has to pause in the maneuver to decompress his lungs. In addition, it must be remembered that at a respiratory rate of 40 per minute and allowing equal time for inspiration and expiration, only the one second or less vital capacity can be brought into play. Although poor gas distribution is not found exclusively in the obstructive group of respiratory insufficiencies (it may be present in the restrictive defect of the trapped lung) it is so common in this group that it must be included in the discussion. For adequate alveolar ventilation each alveolus must get its share of the total ventilation. If an alveolus is not ventilated but has a normal blood flow, no gas exchange can occur and the net effect is similar to an anatomical right to left shunt (Fig. 1, d) when venous blood goes directly to the arterial side without being exposed to gas exchange in the alveolus. This is a physiological right to left shunt of blood flow through nonaerated alveoli which is normally less than 2 per cent of the total blood flow. Contrarily, if an alveolus is ventilated but has no blood flow, this results in an increase of the physiological dead space and is a wasted effort on the part of the respiratory machine,33 just as the right to left shunt is a wasted effort on the part of the circulatory system. The nitrogen wash-out time is the best known test employed to quantitate impaired mixing but requires more expensive equipment which may not be available in the smaller hospitals. Normally, after 100 per cent oxygen is breathed for seven minutes an end expiratory gas sample should contain less than 2.5 per cent nitrogen. 22 An increase in the percentage of nitrogen suggests that mixing is uneven and the nitrogen originally in the alveoli has not been "washed out" even after breathing oxygen for seven minutes.
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PULMONARY DIFFUSION DEFECTS
Given adequate alveolar ventilation with normal distribution and normal gas tensions within the alveolus (Fig. 1, c), diffusion of oxygen across the gas-blood barrier of alveolar membrane, interstitial tissue, capillary endothelium, plasma, red blood cell membrane and intracellular fluid must occur for combination with hemoglobin. Normally, these spaces are exceedingly thin and a large diffusion reserve is present. However, changes might occur to alter the characteristics of the gasblood barrier and consequently limit the diffusion of oxygen. Acutely this may occur in pulmonary edema with intra-alveolar and interstitial edema, subacutely in the Hamman-Rich syndrome with alveolar and interstitial thickening, and chronically in any of the interstitial pulmonary fibroses. As diffusion is also dependent on the total alveolar capillary bed area it may be interfered with by reducing this drastically. Excretion of carbon dioxide from the blood into the alveolus is probably never interfered with by virtue of its great solubility in saline solution (20 to 25 times that of oxygen 33) and the specific action of carbonic anhydrase releasing carbon dioxide from the red blood cell. 10 However, when the alveolus is reached, this advantage that carbon dioxide enjoys ends and its removal from here to the exterior is dependent entirely on adequate alveolar ventilation. The assumption that the partial pressure of carbon dioxide in the arterial blood is in equilibrium with the partial pressure of the carbon dioxide in the alveolus provides us with a useful clinical tool to evaluate the adequacy of alveolar ventilation. Although the normal alveolar partial pressure of carbon dioxide varies from 35 to 45 mm. of mercury (elevated with hypoventilation of sleep and decreased with hyperventilation of emotion), the figure usually accepted as normal is 40 'mm. of mercury. The partial pressure of arterial carbon dioxide can be measured directly by techniques not generally available but indirectly in the following way. The measurement of the carbon dioxide content and the hydrogen ion concentration (pH) of arterial blood can be determined by standard methods. Using these data the partial pressure of carbon dioxide is calculated from suitable nomograms. S4 Any pulmonary insufficiency (with the possible exception of diffusion defects) will eventually lead to alveolar hypoventilation and an increase in the alveolar and arterial partial pressures of carbon dioxide. The measurement of the arterial partial pressure of oxygen is presently not generally available nor does it lend itself to the estimation of alveolar ventilation because we cannot assume that the end capillary partial pressure of oxygen is in equilibrium with the alveolar partial pressure of oxygen. The oxygen saturation of hemoglobin is readily measurable but is normal over a wide range of partial pressures of oxygen because of the sigmoid-shaped oxygen hemoglobin dissociation curve. Practically speak-
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ing, the measurement of the arterial oxygen saturation can be very helpful in gauging respiratory effectiveness, especially as cyanosis in normal subjects is ordinarily not detectable until the saturation has fallen to 85 per cent. In normal subjects arterial oxygen saturation does not change with exercise. Diffusing capacity actually increases with exercise as measured by the carbon monoxide method. 26 In the obstructive group of respiratory insufficiencies arterial oxygen saturation may be somewhat reduced at rest owing to the physiological right to left shunt of blood through poorly aerated alveoli as discussed, while compensatory alveolar hyperventilation in the early stages allows the partial pressure of carbon dioxide to remain normal or only slightly elevated. On exercise, the oxygen saturation may drop even farther but it is not unusual for it to rise with exercise j presumably the greater respiratory effort of exercise may then ventilate adequately previously unventilated areas. In the more advanced diffusion problems (early diffusion difficulties require evaluation by the carbon monoxide method) the arterial oxygen saturation will show a precipitous drop with exercise. Blood flowing through the alveoli at the resting rate of 5 liters per minute may still be normally saturated even though a significant oxygen gradient exists between the alveolus and end capillary blood due to the diffusion defect. The sigmoid-shaped oxygen hemoglobin dissociation curve indicates that a significant drop in partial pressure of oxygen in the blood is necessary before a decrease in oxygen saturation occurs. However, if we double the rate of blood flow with exercise, diminishing the time the red blood cell spends in the capillary by one-half, there is not enough time for saturation to occur and marked arterial oxygen desaturation is present. In an effort to overcome the gas-blood diffusion barrier, the patient with a diffusion defect hyperventilates to increase the partial pressure of oxygen in the alveolus. The exact nature of the reflex causing hyperventilation is unknown. The partial pressure of oxygen in the alveolus can be raised only slightly, however, and is limited in that air contains only 20 per cent oxygen. The hyperventilation does cause a lowering of the partial pressure of carbon dioxide in the alveolus and consequently in the arterial blood. This combination of marked arterial desaturation of blood on exercise with low arterial partial pressures for carbon dioxide at rest is pathognomonic of a pulmonary diffusion defect. If the patient breathes 100 per cent oxygen for 10 to 15 minutes the arterial oxygen saturation will return to normal if the desaturation is pulmonary in origin. The partial pressure of oxygen in the alveolus (at sea level) with breathing of 100 poc cent oxygen approaches 667 mm. of mercury and this is a sufficient driving force to saturate completely the arterial blood even in severe diffusion defects. Also, it will penetrate sufficiently into the poorly aerated alveoli to correct the physiological right to left shunts. If there is an appreciable anatomical right to left
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shunt (pulmonary arteriovenous fistula reversing ductus arteriosus or intracardiac septal defect) where the shunted blood does not come near an alveolus (Fig. 1, d) the arterial saturation will not return to normal. PULMONARY PERFUSION DEFECTS
The pulmonary circulation (Fig. 1, d) is an integral part of pulmonary function and the even distribution of blood to the alveoli, like the even distribution of air to the alveoli, is necessary for normal respiratory function. Pulmonary hypertension is a common complication of pulmonary insufficiency and has been ascribed to arteriolar pathology or arteriolar tone (increased by hypoxia) and decrease in the pulmonary capillary bed, and is aggravated by increase in blood viscosity secondary to polycythemia. The presence of pulmonary hypertension greatly increases the surgical risk even of minor procedures, such as right cardiac catheterization. Although we have learned to evaluate pulmonary hypertension clinically, this is admittedly more difficult in the emphysematous patient and right heart catheterization may rarely be necessary to clarify the problem. This should then be combined with balloon occlusion of the branch of the pulmonary artery on the side contemplated for resection, noting any increase in pressure or change in cardiac output with occlusion as, strangely enough, an initial elevation of pulmonary artery pressure may not be aggravated by unilateral right or left pulmonary artery occlusion. If no significant increase occurs the patient may be exercised as it has been shown that a significant rise in pressure with a combination of these procedures increases the surgical risk. 36 Presumably, unilateral occlusion of the pulmonary artery in the emphysematous patient with only mild pulmonary arterial hypertension seldom causes a significant rise in pulmonary artery pressure at rest, whereas in granulomatous (fibrosis) conditions, pressure is more consistently elevated after unilateral occlusion. 3s Burton's3 concept of the critical closing or opening pressure of small blood vessels which act in an all-or-none manner may have a special application in the pulmonary circulation. 3s Certainly, the pulmonary capillary suspended in space, so to speak, and subjected to changes of intrapleural and intrapulmonary pressures is in a strategic position to cause great changes in vascular resistance. Some basic studies regarding these aspects of the pulmonary circulation have been carried out and more are eagerly awaited. BRONCHOSPIROMETRY
Evaluation of the pulmonary function of each lung individually by the method of differential bronchospirometry has been invaluable in documenting functional changes after lobectomy and segmental resections37 for bronchiectasis, phrenic clysis,39 pleural decortication,31, 42 pulmonary
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collapse procedures27 or even simple thoracotomyP Clinically, th greatest usefulness of bronchospirometry is in the evaluation of th patient with moderate pulmonary insufficiency who is being considere for surgical resection. If the diseased lung contributes only slightly to the over-all pulmonary function it may be removed with impunity al though prognostication of the maximal function of the remaining lung i most difficult. It is especially valuable in patients with pleural or dia phragmatic conditions inasmuch as an almost normally appearing lun radiologically may have practically no function or, on the other hand severe parenchymal disease as judged by the roentgenogram may b consistent with surprisingly good function. 8. 9 In patients considered fo pleural decortication it is valuable in measuring the percentage o ventilation of the involved lung in order to decide whether improvemen might be expected from operation. The oxygen uptake of the involve lung, presumably measuring the blood flow, has been of poor prognosti value as in one series the patients with the poorest oxygen uptake ha the greatest postoperative improvement. 31 Recently it has been advo cated that patients who have had thoracotomies previously and who ar being considered for this procedure on the contralateral side should hav differential bronchospirometry preoperatively as ill-advised operation of this nature have resulted in postoperative respiratory insufficiency.4 PULMONARY COMPLIANCE
A discussion of pulmonary function is probably incomplete withou mentioning the elastic forces of the lung and chest wall. Elastic factor related to diastolic blood flow in the arterial system have long bee recognized and widely investigated. 1s . 23. 41 The importance of the elasti components of the thorax and lung, especially in the expiratory phase o respiration, has also been recognized 24 . 29 but investigated compara tively recently. Confusion of terminology and blurred concepts hav arisen, however. Elasticity has been defined as the property of materials which enable them to resist deformation..by an external force or tension. 4 By definitio then, a material of high elasticity resists deformation, for example stretching by a large force. Thus, glass or steel has a much higher elas ticity than rubber. The term "elastance" has been used and applies th above classical concepts to the elastic components of the lung. 2 As th physical concepts mentioned above are the opposite of popular usag and conception, the term "compliance" was mtroduced. Compliance defined as the volume change in the lungs per unit of pressure change,1 volume . . that is, relatIOnshIp. Burton4 suggested that the term "dis pressure tensibility" be used for volume elastic changes, and this indeed can b used interchangeably with compliance.
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The tenn "volume" adds another dimension to the ordinary concept of a linear unit of stretch per unit of force, as with an ordinary rubber band. The absolute value of our volume/pressure relationship will depend on the initial volume. For example, if 200 cc. of air is injected into each of two rubber balloons of identical structure, except that one has a deflated capacity of 5 cc. and the other of 50 cc., the pressure in the smaller will be much higher than in the larger balloon. Thus, decrease in compliance or distensibility values following pneumonectomy must be interpreted with this in mind. During inspiration (from the point of functional residual capacity where elastic forces of the lung are balanced by the elastic forces of the chest wall in the relaxed state) elastic energy is stored in the system by virtue of muscular action, the amount depending on the end inspiratory volume and the compliance or distensibility of the system (Fig. 2). Expiration has always been termed passive as it does not require muscular effort at the actual moment of occurrence. This tenn is unfortunate as it masks the dynamic factors of pressure flow relationships that are involved. The pressure flow relationships in the lungs and the work of breathing30 (pressure times volume) and its relation to dyspnea are discussed in recent texts and reviews. 6, 16, 22 THE POOR RISK THORACIC SURGICAL PATIENT
Knowing the various factors necessary for external respiration and their measurement, the decision must be made as to whether a particular patient with some respiratory impairment on exertion can tolerate a specific thoracic surgical procedure and also what his postoperative respiratory disability may be. Dyspnea at rest is not compatible with life except for a few months. IS Cardiorespiratory failure has been reported as the commonest cause of death in all pulmonary resections and occurs much more frequently in patients over 60 years of age. 1 , 19, 3S Although every patient must be considered individually I have found some simple and admittedly unsophisticated and inaccurate calculations useful. Alveolar ventilation at rest is approximately 4 liters per minute in a 150 pound normal man whose cardiac output is 5 liters per minute. Assuming an anatomical dead space of 150 cc. and a respiratory rate of 20 per minute, an additional 3 liters of dead space ventilation must be added. Thus, the minute ventilation at rest is approximately 7 liters per minute. With moderate exercise, such as might cause a doubling of the cardiac output, the minute ventilation will also have to double-to 14 liters per minute. Dyspnea is usually present if the ventilation while walking exceeds 40 per cent of the maximal breathing capacity, but is frequently present much sooner. Thus, assuming all other factors to be normal (which they never are in pulmonary disease), a maximal breathing capacity of 25 to 30 liters per minute would be needed for moderate
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exertion with comfort. Ventilation while walking at the standard speed of 180 feet per minute is often much higher than 14 liters per minute in the patient with pulmonary disease. Although the ventilation during walking in itself has been found to be a poor indication of tolerance to a thoracic surgical procedure,15 it does indicate a decrease in efficiency of respiration in the diseased lungs. Thus, it would seem advisable to hope for at least a maximal breathing capacity of 40 liters per minute in our hypothetical patient after operation. Actually, in Gaensler'sl5 group of 460 patients who had pulmonary function tests prior to surgical procedures for tuberculosis, all but one death occurred in the group with maximal breathing capacities of less than 50 per cent of the predicted normal. If the patients were too ill to undergo the basic pulmonary function studies they were considered too ill to undergo operation. No one particular test should be used as a criterion of operability. Bronchospirometry, as mentioned, may show that the lung on the operative side contributes little or nothing to the total ventilation. THE POSTOPERATIVE THORACIC PATIENT
The surgeon, with the help of the internist and, in doubtful cases, with the help of some of the function tests described, having made the decision to operate, now faces the critical operative and postoperative periods, a full discussion of which are beyond the scope of this presentation. A reduction in alveolar ventilation with an increase of the partial pressure of carbon dioxide in the alveolus and in the arterial blood must be avoided. 21 In one small series5 all the deaths occurred in those patients in whom the partial pressure of carbon dioxide was over 45 mm. of mercury 24 hours after operation. In these cases the partial pressure of carbon dioxide also increased significantly two days prior to death. As mentioned previously, the partial pressure of carbon dioxide can be determined by measuring the hydrogen ion concentration (pH) and the carbon dioxide content of the arterial blood-measurements now commonly available in most hospitals-and the partial pressure of carbon dioxide can be read from a suitable nomogram. If the partial pressure of carbon dioxide is high indicating reduced alveolar ventilation, tracheotomy should be considered. This procedure ordinarily reduces dead space by one-half and in a 150 pound man with a dead space of approximately 150 cc. and a postoperative respiratory rate of 30 per minute, this could add (30 times 75) over 2 liters to the alveolar ventilation. With a normal alveolar ventilation at rest of 4 liters per minute, this means an addition of 50 per cent. Oxygen therapy will overcome any postoperative diffusion or distribution defect but will aggravate alveolar hypoventilation by removing the added stimulus to respiration provided by the emergency chemoreceptor mechanism
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(carotid body) which responds to anoxia. If tracheotomy alone does not restore the partial pressure of arterial carbon dioxide to normal, mechanical aids to respiration must be used. Gastric suction or postoperative vomiting, by the loss of hydrochloric acid so induced, can cause metabolic alkalosis and reduce the central stimulus to respiration, thus increasing the alveolar hypoventilation. Excess sedation will also decrease the central stimulus to respiration 20 and contribute to alveolar hypoventilation causing an increase in the partial pressure of carbon dioxide in the alveolus and the arterial blood. SUMMARY
Table 1 is a simplified approach at relating specific tests of pulmonary function to specific ventilatory defects. Although no one particular test of pulmonary function is diagnostic of a particular defect of function, and although pulmonary disease usually affects multiple respiratory functions, it is helpful to classify the major steps of external respiration as shown in Figure 1. The determination of the partial pressure of carbon dioxide in the arterial blood, especially in the critically ill patient, may be of great help in evaluating the adequacy of alveolar ventilation. Studies of the arterial oxygen saturation and the partial pressure of carbon dioxide during the physiological states of rest and exercise and the breathing of 100 per cent oxygen may also be of diagnostic value especially when a defect in alveolar-capillary diffusion exists. REFERENCES 1. Adams, W. E.: Problems in pulmonary resection for primary lung tumor in aged. J. Am. Geriat. Soc. 2: 440-449 (July) 1954. 2. Bader, M. E. and Bader, R. A.: Editorial. The work of breathing. Am. J. Med. 18: 851-854 (June) 1955. 3. Burton, A. C.: On the physical equilibrium of small blood vessels. Am. J. Physiol. 164-: 319-329 (Feb.) 1951. 4. Burton, A. C.: Relation of structure to function of tissues of wall of blood vessels. Physiol. Rev. 34-: 6HHi42 (Oct.) 1954. 5. Clowes, G. H., Jr., Alichniewicz, A., Del Guercio, L. R. and Gillespie, D.: The relationship of postoperative acidosis to pulmonary and cardiovascular function. J. Thor. Cardiov. Surg. 39: 1-25 (Jan.) 1960. 6. Comroe, J. H., Jr.: The Lung: Clinical Physiology and Pulmonary Function Tests. Chicago, Illinois, Year Book Publishers, 1955,219 pp. 7. Dittmer, D. S. and Grebe, R. M., editors: Handbook of Respiration. Philadelphia, W. B. Saunders Company, 1958, 403 pp. 8. Donald, K. W.: Bronchospirometry. Postgrad. M. J. 28: 171-178 (March) 1952. 9. Fleming, H. A. and West, L. R.: Appreciation of bronchospirometry as a method of investigation based on 125 cases. Thorax 9: 273-284 (Dec.) 1954. 10. Forster. R. E.: Exchange of gases between alveolar air and pulmonary capillary blood: pulmonary diffusing capacity. Physiol. Rev. 37: 391-452 (Oct.) 1957. 11. Fowler, W. S.: Lung function studies; respiratory dead space. Am. J. Physiol. 154-: 405-416 (Sept.) 1948. 12. Frank, N. R., Mead, J., Siebens, A. A. and Storey, C. F.: Measurements of pulmonary compliance in 70 healthy young adults. J. Appl. Physiol. 9: 38-42 (July) 1956.
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13. Fry, D. L., Ebert, R. V., Stead, W. W. and Brown, C. C.: Mechanics of pulmonary ventilation in normal subjects and in patients with emphysema. Am. J. Med. 16: 80-97 (Jan.) 1954. 14. Gaensler, E. A.: Medical progress; clinical pulmonary physiology. New England J. Med. 252: 177-184 (Feb. 3); 221-228 (Feb. 10); 264-271 (Feb. 17) 1955. 15. Gaensler, E. A. et al.: Role of pulmonary insufficiency in mortality and invalidism following surgery for pulmonary tuberculosis. J. Thoracic Surg. 29: 163184 (Feb.) 1955. 16. Gordon, B. L.: Clinical Cardiopulmonary Physiology. 2nd Ed. New York, Grune & Stratton, 1960, 1001 pp. 17. Gorlin, R., Knowles, J. H. and Storey, C. F.: Effects of thoracotomy on pulmonary function; patients with localized pulmonary disease. J. Thoracic Surg. 34: 242-249 (Aug.) 1957. 18. Hales, S.: Haemastatics. 2nd Ed. London, 1740, pp. 22-23. Quoted by Kroeker, reference 23. 19. Hepper, N. G. and Bernatz, P. E.: Thoracic surgery in the aged. Dis. Chest 37: 298-303 (March) 1960. 20. Holford, F. D. and Mithoefer, J. C.: The effect of morphine on respiration in the aged. S. CLIN. NORTH AMERICA 40: 907-916 (Aug.) 1960. 21. Hood, R. M. and Beall, A. C., Jr.: Hypoventilation, hypoxia and acidosis occurring in the acute postoperative period. J. Thoracic Surg. 36: 729-743 (Nov.) 1958. 22. Knowles, J. H.: Respiratory Physiology and Its Clinical Application. Cambridge, Massachusetts, Harvard University Press, 1959,256 pp. 23. Kroeker, E. J.: Comparison of Central and Peripheral Arterial Pressure Pulses in Man. Thesis, University of Minnesota, 1954, 142 pp. 24. Laennec, R. H. T.: A Treatise on the Diseases of the Chest and on Mediate Auscultation. 3rd Ed., translated by J. Forbes. London, Thomas & George Underwood, 1829, 724 pp. 25. Leuallen, E. C. and Fowler, W. S.: Maximum midexpiratory flow. Am. Rev. Tuberc. 72: 783-800 (Dec.) 1955. 26. Lewis, B. M., Lin, T. H., Noe, F. E. and Komisaruk, R.: The measurement of pulmonary capillary blood volume and pulmonary membrane diffusing capacity in normal subjects; the effects of exercise and position. J. Clin. Invest. 37: 1061-1070 (July) 1958. 27. Lindahl, T.: Spirometric and bronchospirometric studies in 5-rib thoracoplasties. Thorax 9: 285-290 (Dec.) 1954. 28. Meneely, G. R.: Pulmonary function testing; a special exhibit from the Section on Diseases of the Chest of the American Medical Association. Dis. Chest 31: 125-154 (Feb.) 1957. 29. Otis, A. B.: Work of breathing. Physiol. Rev. 34: 449-458 (July) 1954. 30. Otis, A. B., Fenn, W. O. and Rahn, H.: Mechanics of breathing in man. J. Appl. Physiol. 2: 592-607 (May) 1950. 31. Patton, W. E., Watson, T. R., Jr. and Gaensler, E. A.: Pulmonary function before and at intervals after surgical decortication of lung. Surg. Gynec. & Obst. 95: 477-496 (Oct.) 1952. 32. Radford, E. P., Ferris, B. G. and Kriete, B. C.: Clinical use of a nomogram to estimate proper ventilation during artificial respiration. New England J. Med. 251: 877-883 (Nov. 25) 1954. 33. Riley, R. L.: Pulmonary gas exchange. Am. J. Med. 10: 210-220 (Feb.) 1951. 34. Singer, R. B. and Hastings, A. B.: Improved clinical method for the estimation of disturbances of the acid-base balance of human blood. Medicine 27: 223242 (May) 1948. 35. Shields, T. W.: Factors influencing the morbidity and mortality in the older aged patient undergoing pulmonary surgery. Surg. Gynec. & Obst. 111: 598-602 (Nov.) 1960. 36. Sloan, H., Morris, J. D., Figley, M. and Lee, R.: Temporary unilateral occlusion of pulmonary artery in preoperative evaluation of thoracic patients; preliminary report. J. Thoracic Surg. 30: 591-597 (Nov.) 1955.
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37. Smith, G. A., Siebens, A. A. a.nd Storey, C. F.: Preoperative and postoperative cardiopulmonary function studies in patients with bronchiectasis. Am. Rev. Tuberc. 69: 869-914 (June) 1954. 38. Soderholm, B.: The pulmonary blood flow in pulmonary tuberculosis and the effect of unilateral occlusion of the pulmonary artery. In: Pulmonary Circulation: An International Symposium, 1958, Sponsored by the Chicago Heart Association, edited by W. R. Adams and I. Veith, New York, Grune & Stratton, 1959, pp. 139-146. 39. Vacarezza, R. F., Soubrie, A. and Rey, J. C.: Functional examination of each lung before and after paralysis of phrenic nerve. Dis. Chest 14: 580-584 (July-Aug.) 1948. 40. Wells, R. E., Taylor, W. J., Black, H. and Harken, D. E.: Pulmonary function in the selection of patients for open heart surgery. Proc. New England Cardiovasc. Soc. 18: 31, 1959-1960. 41. Wezler, K. and Boger, A.: Die Dynamik des arteriellen Systems. Der arterielle Blutdruck und seine Komponenten. Ergebnisse der Physiologie 41: 292-606, 1939. 42. Wright, G. W., Yee, L. B., Filley, G. F. and Stranahan, A.: Physiologic observations concerning decortication of lung. J. Thoracic Surg. 18: 372-384 (June) 1949.
THE CLINICAL ASSESSMENT by the clinician and surgeon of pulmonary function in the thoracic surgical patient is usually sufficient to determine the operative risk and to arrive at a reasonable prediction of postoperative disability. In certain selected patients, however, the pulmonary function tests to be outlined may be of value in quantitating these factors more precisely. In addition, the physiological approach to the problems of all thoracic surgical patients may improve the management in the preoperative and postoperative periods. The primary function of the lung is gas exchange. Oxygen is absorbed by the blood, carbon dioxide is excreted and a delicate balance of the hydrogen ion concentration of the blood is maintained. The alveolus (Fig. 1) is the final common path where venous blood and environmental air meet to accomplish these processes. For effective gas exchange the alveolus must be adequately ventilated with air, evenly distributed throughout the lung. Diffusion across the gas-blood barrier must occur readily and the alveolar capillaries must have an adequate and even blood supply. Alveolar ventilation with air is accomplished by the pumping action of the lung-thoracic cage bellows. Like the cardiac output of blood, alveolar ventilation has a constant resting level of 4 liters per minute for a cardiac output of 5 liters per minute. 6 Although the lung has the advantage of a greater reserve (it can increase its resting ventilation ten times, while the heart can increase its resting output only four times), it has the disadvantage of having to move air through the nonrespiratory tracheobronchial tree-the anatomical "dead space." This is approximately 150 cc., or 1 cc. per pound of body weightY· 32 Were it not for the dead space, the exact measurement of which requires complicated gas dilution techniques, the problem of measuring alveolar ventilation (Fig. 2) would simply be that of measuring the minute ventilation from the spirogram (tidal volume times respiratory rate per minute). If the estimated dead space ventilation were subtracted from the minute
557
558
EDWIN
t
J.
KROEKER
(0)
VENTI LATION (b)
DISTRIBUTION (No obStruction and normal elasticity)
Partial pressure C02 02 4Omm. Hg
IOOmm.Hg
Alveolar mArnhn;';A"'C~IQQz:r:s::l1r
(d)
PERFUSION Fig.!. The alveolus, indicating the factors concerned with external respiration.
ventilation (dead space times the respiratory rate per minute) the amount of alveolar ventilation per minute would be approximated. Indirect but valuable information as to the ability of the lung-thoracic cage bellows to maintain adequate alveolar ventilation is obtained from the maximal stress tests. These include: (1) Vital capacity (Fig. 2) is the maximal respiratory excursion of the lung-thoracic cage bellows and measures all the air an individual is capable of moving in a single breath. This is the total lung capacity excluding the residual volume. (2) Timed vital capacity is the volume of air mentioned above plotted against time (that is, the spirogram). Normally, 70 per cent of the total should be exhaled in the first second and 95 per cent after three seconds. Any volume moved after three seconds can probably not be used for alveolar ventilation. The maximal mid expiratory flow rate is a variant of the above. 25 (3) The maximal breathing capacity is the total amount of air a patient can pump with maximal respiratory effort. This is usually measured for 15 seconds on a spirographic tracing or the air is collected
559
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2. Spirogram, illustrating subdivisions of lung volumes. Volume is represented on the ordinate and time on the abscissa. The primary "volume" subdivisions do not overlap and always equal total lung capacity. The "capacity" subdivisions always include two or more primary "volumes."
in a Douglas bag and measured in a tissot spirometer. The results are expressed in liters per minute at body temperature. This is considered by many as the best over-all test of the function of the lung-thoracic cage bellows. RESTRICTIVE VENTILATORY INSUFFICIENCY
Alveolar ventilation may be reduced by conditions restricting the function of the lung-thoracic cage bellows (Fig. 1, a). These include impairment of central control of respiration, local paralysis or weakness of thoracic cage muscles including the diaphragm, pathologic changes in thoracic cage or deformities, primary pleural lesions which trap the lung and prevent its expansion, loss of lung tissue after operation or as a result of disease, space-occupying pulmonary lesions, either focal (neoplasm) or diffuse (interstitial fibrosis). In this group of restrictive ventilatory insufficiencies the vital capacity is reduced often proportionate to the amount of pathologic alteration as compared with predicted normal values. The timed vital capacity is normal; that is, although the vital capacity is reduced, this amount of air can be exhaled rapidly. By and large, the maximal breathing capacity is not reduced or at least not to the same extent as the vital capacity. In other words, patients can compensate for the decrease in vital capacity by increasing the rate of respiration. This relationship has been expressed in a ratio called the air velocity index: l4 per cent of predicted maximal breathing capacity per cent of predicted vital capacity
560
EDWIN
Table 1.
J.
Tests of Pulmonary Functions ,7,ls." RESTRICTIVEVENTILATORY
FUNCTION STUDIED
KROEKER
TEST
NORMAL VALUE
DEFECT
OBSTRUCTIVEDISTRIBUTIVEVENTILATORY DEFECT
Maximal tidal volume
Vital capacity
Normal
Timed vital capacity
100% (=20) of predicted value 1 sec. volume 70 % or more of total
Decreased
Maximal Volume = speed of Time ventila tion
Normal
Decreased
Maximal breathing capacity
100% (=20) of predicted value*
Normal
Decreased
Increased (larger than 1)
Decreased (smaller than 1)
Normal
Increased
Air velocity index % of predicted MBCt % of predicted VC Intrapulmonary gas mixing
Maximal breathing capacity Vital capacity Nitrogen wash-out time
Less than 2.5% end expiratory nitrogen after min. 7 of breathing oxygen
* Predicted maximal breathing capacity for males: [86.5-(0.52 X age)] X body surface area in square meters; for females: [71.3-(0.47 X age)] X body surface area in square meters. t MBC - Maximal breathing capacity VC - Vital capacity If this ratio is larger than 1, the insufficiency is classified as being restrictive; if smaller than 1, it is considered to be obstructive in nature (Table 1). OBSTRUCTIVE AND DISTRIBUTIVE VENTILATORY INSUFFICIENCY
Alveolar ventilation may also be impaired in a group of conditions in which the lung-thoracic cage bellows seem adequate but in which bronchial obstruction or uneven elasticity with poor air distribution, or both, are limiting factors (Fig. 1, b). The common diseases in this group include bronchial asthma, pulmonary emphysema and chronic bronchitis. In this group of obstructive ventilatory insufficiencies the vital capacity is usually normal, or only slightly reduced. The timed vital capacity and maximal breathing capacity are markedly reduced and consequently the air velocity index is smaller than 1. The slowing of the timed vital capacity is the result of several factors, the most obvious being bronchiolar narrowing by bronchospasm or bronchial edema causing an actual stenotic obstruction to the outflow of air during expiration. To evaluate the bronchospastic component it is well to perform this test before and after the inhalation of a nebulized bronchodilating drug. If marked improvement occurs after the use of a bronchodilator this would tend to indicate that intensive treatment might improve pulmonary function before operation. However, we know
Pulmonary Function Testing
561
that actual obstruction of the smaller bronchioles can occur by virtue of their delicate unsupported structure whenever the intrapleural pressure exceeds the atmospheric pressurel3 (Fig. 3). In the static stage with no air flow the pressure in the alveolus is equal to the atmospheric pressure and the retractive elastic forces of the lung are in equilibrium with the thoracic cage (intrapleural pressure) elastic forces. In the dynamic state when air flow occurs along the bronchiole, the intrapleural pressure is balanced by the retractive forces of the lung plus the intra-alveolar pressure. During inspiration (Fig. 3, a) with an increased stretching of the lung and a negative alveolar pressure, the intrapleural pressure is always negative. During expiration (Fig. 3, b) the intrapleural pressure remains negative wltil the intra-alveolar pressure exceeds the retractive elastic forces of the lung. When the intrapleural pressure becomes positive, that is, greater than atmospheric, it tends to collapse the unsupported bronchiole. If the retractive forces of the lung are diminished as in emphysema, this may occur at a relatively low rate of air flow. Thus, the loss of elasticity alone with a decrease of the negative intrapleural pressure might cause a slowing of the timed vital capacity. In
Fig. 3. Forces involved in ventilation of the alveolus. a, Pressure exerted on the unsupported bronchiole is intrapleural pressure. During inspiration this is always negative relative to atmospheric pressure, and the bronchiole remains patent. b, During expiration in patients with reduced retractive force of the lung (emphysema) the intrapleural pressure may become positive relative to atmospheric pressure and cause collapse of the unsupported bronchiole. The air in the alveolus is then trapped despite additional pressure that may be applied by the thoracic cage bellows.
562
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KROEKER
addition, any loss of elasticity reduces the driving force of expiration and results in a slowing of the timed vital capacity. The phenomenon of air trapping is common in the obstructive group of respiratory insufficiencies. This is best seen on a spirogram after several vital capacity measurements. Normally, the tidal volume immediately returns to the resting base line. When air trapping is present it takes several respiratory cycles for the breathing pattern to return to its resting base line. 28 The two stage vital capacity may be useful in measuring the amount of air trapping. The patient is instructed to take as deep a breath as possible after a normal expiration (the point of fwictional residual capacity), then after a short time interval of normal breathing the patient is instructed to expire maximally after a normal respiratory cycle (Fig. 2). The total respiratory excursion of these maneuvers is greater than the one stage vital capacity and the difference represents the amount of air trapping. If the two stage vital capacity is smaller than the one stage, we should suspect malingering or inadequate instruction of the patient. The reduction in the maximal breathing capacity is, in large measure, the result of air trapping. With each succeeding breath the patient seems to blow up like a bullfrog and eventually has to pause in the maneuver to decompress his lungs. In addition, it must be remembered that at a respiratory rate of 40 per minute and allowing equal time for inspiration and expiration, only the one second or less vital capacity can be brought into play. Although poor gas distribution is not found exclusively in the obstructive group of respiratory insufficiencies (it may be present in the restrictive defect of the trapped lung) it is so common in this group that it must be included in the discussion. For adequate alveolar ventilation each alveolus must get its share of the total ventilation. If an alveolus is not ventilated but has a normal blood flow, no gas exchange can occur and the net effect is similar to an anatomical right to left shunt (Fig. 1, d) when venous blood goes directly to the arterial side without being exposed to gas exchange in the alveolus. This is a physiological right to left shunt of blood flow through nonaerated alveoli which is normally less than 2 per cent of the total blood flow. Contrarily, if an alveolus is ventilated but has no blood flow, this results in an increase of the physiological dead space and is a wasted effort on the part of the respiratory machine,33 just as the right to left shunt is a wasted effort on the part of the circulatory system. The nitrogen wash-out time is the best known test employed to quantitate impaired mixing but requires more expensive equipment which may not be available in the smaller hospitals. Normally, after 100 per cent oxygen is breathed for seven minutes an end expiratory gas sample should contain less than 2.5 per cent nitrogen. 22 An increase in the percentage of nitrogen suggests that mixing is uneven and the nitrogen originally in the alveoli has not been "washed out" even after breathing oxygen for seven minutes.
Pulmonary Function Testing
563
PULMONARY DIFFUSION DEFECTS
Given adequate alveolar ventilation with normal distribution and normal gas tensions within the alveolus (Fig. 1, c), diffusion of oxygen across the gas-blood barrier of alveolar membrane, interstitial tissue, capillary endothelium, plasma, red blood cell membrane and intracellular fluid must occur for combination with hemoglobin. Normally, these spaces are exceedingly thin and a large diffusion reserve is present. However, changes might occur to alter the characteristics of the gasblood barrier and consequently limit the diffusion of oxygen. Acutely this may occur in pulmonary edema with intra-alveolar and interstitial edema, subacutely in the Hamman-Rich syndrome with alveolar and interstitial thickening, and chronically in any of the interstitial pulmonary fibroses. As diffusion is also dependent on the total alveolar capillary bed area it may be interfered with by reducing this drastically. Excretion of carbon dioxide from the blood into the alveolus is probably never interfered with by virtue of its great solubility in saline solution (20 to 25 times that of oxygen 33) and the specific action of carbonic anhydrase releasing carbon dioxide from the red blood cell. 10 However, when the alveolus is reached, this advantage that carbon dioxide enjoys ends and its removal from here to the exterior is dependent entirely on adequate alveolar ventilation. The assumption that the partial pressure of carbon dioxide in the arterial blood is in equilibrium with the partial pressure of the carbon dioxide in the alveolus provides us with a useful clinical tool to evaluate the adequacy of alveolar ventilation. Although the normal alveolar partial pressure of carbon dioxide varies from 35 to 45 mm. of mercury (elevated with hypoventilation of sleep and decreased with hyperventilation of emotion), the figure usually accepted as normal is 40 'mm. of mercury. The partial pressure of arterial carbon dioxide can be measured directly by techniques not generally available but indirectly in the following way. The measurement of the carbon dioxide content and the hydrogen ion concentration (pH) of arterial blood can be determined by standard methods. Using these data the partial pressure of carbon dioxide is calculated from suitable nomograms. S4 Any pulmonary insufficiency (with the possible exception of diffusion defects) will eventually lead to alveolar hypoventilation and an increase in the alveolar and arterial partial pressures of carbon dioxide. The measurement of the arterial partial pressure of oxygen is presently not generally available nor does it lend itself to the estimation of alveolar ventilation because we cannot assume that the end capillary partial pressure of oxygen is in equilibrium with the alveolar partial pressure of oxygen. The oxygen saturation of hemoglobin is readily measurable but is normal over a wide range of partial pressures of oxygen because of the sigmoid-shaped oxygen hemoglobin dissociation curve. Practically speak-
564
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KROEKER
ing, the measurement of the arterial oxygen saturation can be very helpful in gauging respiratory effectiveness, especially as cyanosis in normal subjects is ordinarily not detectable until the saturation has fallen to 85 per cent. In normal subjects arterial oxygen saturation does not change with exercise. Diffusing capacity actually increases with exercise as measured by the carbon monoxide method. 26 In the obstructive group of respiratory insufficiencies arterial oxygen saturation may be somewhat reduced at rest owing to the physiological right to left shunt of blood through poorly aerated alveoli as discussed, while compensatory alveolar hyperventilation in the early stages allows the partial pressure of carbon dioxide to remain normal or only slightly elevated. On exercise, the oxygen saturation may drop even farther but it is not unusual for it to rise with exercise j presumably the greater respiratory effort of exercise may then ventilate adequately previously unventilated areas. In the more advanced diffusion problems (early diffusion difficulties require evaluation by the carbon monoxide method) the arterial oxygen saturation will show a precipitous drop with exercise. Blood flowing through the alveoli at the resting rate of 5 liters per minute may still be normally saturated even though a significant oxygen gradient exists between the alveolus and end capillary blood due to the diffusion defect. The sigmoid-shaped oxygen hemoglobin dissociation curve indicates that a significant drop in partial pressure of oxygen in the blood is necessary before a decrease in oxygen saturation occurs. However, if we double the rate of blood flow with exercise, diminishing the time the red blood cell spends in the capillary by one-half, there is not enough time for saturation to occur and marked arterial oxygen desaturation is present. In an effort to overcome the gas-blood diffusion barrier, the patient with a diffusion defect hyperventilates to increase the partial pressure of oxygen in the alveolus. The exact nature of the reflex causing hyperventilation is unknown. The partial pressure of oxygen in the alveolus can be raised only slightly, however, and is limited in that air contains only 20 per cent oxygen. The hyperventilation does cause a lowering of the partial pressure of carbon dioxide in the alveolus and consequently in the arterial blood. This combination of marked arterial desaturation of blood on exercise with low arterial partial pressures for carbon dioxide at rest is pathognomonic of a pulmonary diffusion defect. If the patient breathes 100 per cent oxygen for 10 to 15 minutes the arterial oxygen saturation will return to normal if the desaturation is pulmonary in origin. The partial pressure of oxygen in the alveolus (at sea level) with breathing of 100 poc cent oxygen approaches 667 mm. of mercury and this is a sufficient driving force to saturate completely the arterial blood even in severe diffusion defects. Also, it will penetrate sufficiently into the poorly aerated alveoli to correct the physiological right to left shunts. If there is an appreciable anatomical right to left
Pulmonary Function Testing
565
shunt (pulmonary arteriovenous fistula reversing ductus arteriosus or intracardiac septal defect) where the shunted blood does not come near an alveolus (Fig. 1, d) the arterial saturation will not return to normal. PULMONARY PERFUSION DEFECTS
The pulmonary circulation (Fig. 1, d) is an integral part of pulmonary function and the even distribution of blood to the alveoli, like the even distribution of air to the alveoli, is necessary for normal respiratory function. Pulmonary hypertension is a common complication of pulmonary insufficiency and has been ascribed to arteriolar pathology or arteriolar tone (increased by hypoxia) and decrease in the pulmonary capillary bed, and is aggravated by increase in blood viscosity secondary to polycythemia. The presence of pulmonary hypertension greatly increases the surgical risk even of minor procedures, such as right cardiac catheterization. Although we have learned to evaluate pulmonary hypertension clinically, this is admittedly more difficult in the emphysematous patient and right heart catheterization may rarely be necessary to clarify the problem. This should then be combined with balloon occlusion of the branch of the pulmonary artery on the side contemplated for resection, noting any increase in pressure or change in cardiac output with occlusion as, strangely enough, an initial elevation of pulmonary artery pressure may not be aggravated by unilateral right or left pulmonary artery occlusion. If no significant increase occurs the patient may be exercised as it has been shown that a significant rise in pressure with a combination of these procedures increases the surgical risk. 36 Presumably, unilateral occlusion of the pulmonary artery in the emphysematous patient with only mild pulmonary arterial hypertension seldom causes a significant rise in pulmonary artery pressure at rest, whereas in granulomatous (fibrosis) conditions, pressure is more consistently elevated after unilateral occlusion. 3s Burton's3 concept of the critical closing or opening pressure of small blood vessels which act in an all-or-none manner may have a special application in the pulmonary circulation. 3s Certainly, the pulmonary capillary suspended in space, so to speak, and subjected to changes of intrapleural and intrapulmonary pressures is in a strategic position to cause great changes in vascular resistance. Some basic studies regarding these aspects of the pulmonary circulation have been carried out and more are eagerly awaited. BRONCHOSPIROMETRY
Evaluation of the pulmonary function of each lung individually by the method of differential bronchospirometry has been invaluable in documenting functional changes after lobectomy and segmental resections37 for bronchiectasis, phrenic clysis,39 pleural decortication,31, 42 pulmonary
566
EDWIN
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KROEKER
collapse procedures27 or even simple thoracotomyP Clinically, th greatest usefulness of bronchospirometry is in the evaluation of th patient with moderate pulmonary insufficiency who is being considere for surgical resection. If the diseased lung contributes only slightly to the over-all pulmonary function it may be removed with impunity al though prognostication of the maximal function of the remaining lung i most difficult. It is especially valuable in patients with pleural or dia phragmatic conditions inasmuch as an almost normally appearing lun radiologically may have practically no function or, on the other hand severe parenchymal disease as judged by the roentgenogram may b consistent with surprisingly good function. 8. 9 In patients considered fo pleural decortication it is valuable in measuring the percentage o ventilation of the involved lung in order to decide whether improvemen might be expected from operation. The oxygen uptake of the involve lung, presumably measuring the blood flow, has been of poor prognosti value as in one series the patients with the poorest oxygen uptake ha the greatest postoperative improvement. 31 Recently it has been advo cated that patients who have had thoracotomies previously and who ar being considered for this procedure on the contralateral side should hav differential bronchospirometry preoperatively as ill-advised operation of this nature have resulted in postoperative respiratory insufficiency.4 PULMONARY COMPLIANCE
A discussion of pulmonary function is probably incomplete withou mentioning the elastic forces of the lung and chest wall. Elastic factor related to diastolic blood flow in the arterial system have long bee recognized and widely investigated. 1s . 23. 41 The importance of the elasti components of the thorax and lung, especially in the expiratory phase o respiration, has also been recognized 24 . 29 but investigated compara tively recently. Confusion of terminology and blurred concepts hav arisen, however. Elasticity has been defined as the property of materials which enable them to resist deformation..by an external force or tension. 4 By definitio then, a material of high elasticity resists deformation, for example stretching by a large force. Thus, glass or steel has a much higher elas ticity than rubber. The term "elastance" has been used and applies th above classical concepts to the elastic components of the lung. 2 As th physical concepts mentioned above are the opposite of popular usag and conception, the term "compliance" was mtroduced. Compliance defined as the volume change in the lungs per unit of pressure change,1 volume . . that is, relatIOnshIp. Burton4 suggested that the term "dis pressure tensibility" be used for volume elastic changes, and this indeed can b used interchangeably with compliance.
Pulmonary Function Testing
567
The tenn "volume" adds another dimension to the ordinary concept of a linear unit of stretch per unit of force, as with an ordinary rubber band. The absolute value of our volume/pressure relationship will depend on the initial volume. For example, if 200 cc. of air is injected into each of two rubber balloons of identical structure, except that one has a deflated capacity of 5 cc. and the other of 50 cc., the pressure in the smaller will be much higher than in the larger balloon. Thus, decrease in compliance or distensibility values following pneumonectomy must be interpreted with this in mind. During inspiration (from the point of functional residual capacity where elastic forces of the lung are balanced by the elastic forces of the chest wall in the relaxed state) elastic energy is stored in the system by virtue of muscular action, the amount depending on the end inspiratory volume and the compliance or distensibility of the system (Fig. 2). Expiration has always been termed passive as it does not require muscular effort at the actual moment of occurrence. This tenn is unfortunate as it masks the dynamic factors of pressure flow relationships that are involved. The pressure flow relationships in the lungs and the work of breathing30 (pressure times volume) and its relation to dyspnea are discussed in recent texts and reviews. 6, 16, 22 THE POOR RISK THORACIC SURGICAL PATIENT
Knowing the various factors necessary for external respiration and their measurement, the decision must be made as to whether a particular patient with some respiratory impairment on exertion can tolerate a specific thoracic surgical procedure and also what his postoperative respiratory disability may be. Dyspnea at rest is not compatible with life except for a few months. IS Cardiorespiratory failure has been reported as the commonest cause of death in all pulmonary resections and occurs much more frequently in patients over 60 years of age. 1 , 19, 3S Although every patient must be considered individually I have found some simple and admittedly unsophisticated and inaccurate calculations useful. Alveolar ventilation at rest is approximately 4 liters per minute in a 150 pound normal man whose cardiac output is 5 liters per minute. Assuming an anatomical dead space of 150 cc. and a respiratory rate of 20 per minute, an additional 3 liters of dead space ventilation must be added. Thus, the minute ventilation at rest is approximately 7 liters per minute. With moderate exercise, such as might cause a doubling of the cardiac output, the minute ventilation will also have to double-to 14 liters per minute. Dyspnea is usually present if the ventilation while walking exceeds 40 per cent of the maximal breathing capacity, but is frequently present much sooner. Thus, assuming all other factors to be normal (which they never are in pulmonary disease), a maximal breathing capacity of 25 to 30 liters per minute would be needed for moderate
568
EDWIN
J.
KROEKER
exertion with comfort. Ventilation while walking at the standard speed of 180 feet per minute is often much higher than 14 liters per minute in the patient with pulmonary disease. Although the ventilation during walking in itself has been found to be a poor indication of tolerance to a thoracic surgical procedure,15 it does indicate a decrease in efficiency of respiration in the diseased lungs. Thus, it would seem advisable to hope for at least a maximal breathing capacity of 40 liters per minute in our hypothetical patient after operation. Actually, in Gaensler'sl5 group of 460 patients who had pulmonary function tests prior to surgical procedures for tuberculosis, all but one death occurred in the group with maximal breathing capacities of less than 50 per cent of the predicted normal. If the patients were too ill to undergo the basic pulmonary function studies they were considered too ill to undergo operation. No one particular test should be used as a criterion of operability. Bronchospirometry, as mentioned, may show that the lung on the operative side contributes little or nothing to the total ventilation. THE POSTOPERATIVE THORACIC PATIENT
The surgeon, with the help of the internist and, in doubtful cases, with the help of some of the function tests described, having made the decision to operate, now faces the critical operative and postoperative periods, a full discussion of which are beyond the scope of this presentation. A reduction in alveolar ventilation with an increase of the partial pressure of carbon dioxide in the alveolus and in the arterial blood must be avoided. 21 In one small series5 all the deaths occurred in those patients in whom the partial pressure of carbon dioxide was over 45 mm. of mercury 24 hours after operation. In these cases the partial pressure of carbon dioxide also increased significantly two days prior to death. As mentioned previously, the partial pressure of carbon dioxide can be determined by measuring the hydrogen ion concentration (pH) and the carbon dioxide content of the arterial blood-measurements now commonly available in most hospitals-and the partial pressure of carbon dioxide can be read from a suitable nomogram. If the partial pressure of carbon dioxide is high indicating reduced alveolar ventilation, tracheotomy should be considered. This procedure ordinarily reduces dead space by one-half and in a 150 pound man with a dead space of approximately 150 cc. and a postoperative respiratory rate of 30 per minute, this could add (30 times 75) over 2 liters to the alveolar ventilation. With a normal alveolar ventilation at rest of 4 liters per minute, this means an addition of 50 per cent. Oxygen therapy will overcome any postoperative diffusion or distribution defect but will aggravate alveolar hypoventilation by removing the added stimulus to respiration provided by the emergency chemoreceptor mechanism
Pulmonary Function Testing
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(carotid body) which responds to anoxia. If tracheotomy alone does not restore the partial pressure of arterial carbon dioxide to normal, mechanical aids to respiration must be used. Gastric suction or postoperative vomiting, by the loss of hydrochloric acid so induced, can cause metabolic alkalosis and reduce the central stimulus to respiration, thus increasing the alveolar hypoventilation. Excess sedation will also decrease the central stimulus to respiration 20 and contribute to alveolar hypoventilation causing an increase in the partial pressure of carbon dioxide in the alveolus and the arterial blood. SUMMARY
Table 1 is a simplified approach at relating specific tests of pulmonary function to specific ventilatory defects. Although no one particular test of pulmonary function is diagnostic of a particular defect of function, and although pulmonary disease usually affects multiple respiratory functions, it is helpful to classify the major steps of external respiration as shown in Figure 1. The determination of the partial pressure of carbon dioxide in the arterial blood, especially in the critically ill patient, may be of great help in evaluating the adequacy of alveolar ventilation. Studies of the arterial oxygen saturation and the partial pressure of carbon dioxide during the physiological states of rest and exercise and the breathing of 100 per cent oxygen may also be of diagnostic value especially when a defect in alveolar-capillary diffusion exists. REFERENCES 1. Adams, W. E.: Problems in pulmonary resection for primary lung tumor in aged. J. Am. Geriat. Soc. 2: 440-449 (July) 1954. 2. Bader, M. E. and Bader, R. A.: Editorial. The work of breathing. Am. J. Med. 18: 851-854 (June) 1955. 3. Burton, A. C.: On the physical equilibrium of small blood vessels. Am. J. Physiol. 164-: 319-329 (Feb.) 1951. 4. Burton, A. C.: Relation of structure to function of tissues of wall of blood vessels. Physiol. Rev. 34-: 6HHi42 (Oct.) 1954. 5. Clowes, G. H., Jr., Alichniewicz, A., Del Guercio, L. R. and Gillespie, D.: The relationship of postoperative acidosis to pulmonary and cardiovascular function. J. Thor. Cardiov. Surg. 39: 1-25 (Jan.) 1960. 6. Comroe, J. H., Jr.: The Lung: Clinical Physiology and Pulmonary Function Tests. Chicago, Illinois, Year Book Publishers, 1955,219 pp. 7. Dittmer, D. S. and Grebe, R. M., editors: Handbook of Respiration. Philadelphia, W. B. Saunders Company, 1958, 403 pp. 8. Donald, K. W.: Bronchospirometry. Postgrad. M. J. 28: 171-178 (March) 1952. 9. Fleming, H. A. and West, L. R.: Appreciation of bronchospirometry as a method of investigation based on 125 cases. Thorax 9: 273-284 (Dec.) 1954. 10. Forster. R. E.: Exchange of gases between alveolar air and pulmonary capillary blood: pulmonary diffusing capacity. Physiol. Rev. 37: 391-452 (Oct.) 1957. 11. Fowler, W. S.: Lung function studies; respiratory dead space. Am. J. Physiol. 154-: 405-416 (Sept.) 1948. 12. Frank, N. R., Mead, J., Siebens, A. A. and Storey, C. F.: Measurements of pulmonary compliance in 70 healthy young adults. J. Appl. Physiol. 9: 38-42 (July) 1956.
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13. Fry, D. L., Ebert, R. V., Stead, W. W. and Brown, C. C.: Mechanics of pulmonary ventilation in normal subjects and in patients with emphysema. Am. J. Med. 16: 80-97 (Jan.) 1954. 14. Gaensler, E. A.: Medical progress; clinical pulmonary physiology. New England J. Med. 252: 177-184 (Feb. 3); 221-228 (Feb. 10); 264-271 (Feb. 17) 1955. 15. Gaensler, E. A. et al.: Role of pulmonary insufficiency in mortality and invalidism following surgery for pulmonary tuberculosis. J. Thoracic Surg. 29: 163184 (Feb.) 1955. 16. Gordon, B. L.: Clinical Cardiopulmonary Physiology. 2nd Ed. New York, Grune & Stratton, 1960, 1001 pp. 17. Gorlin, R., Knowles, J. H. and Storey, C. F.: Effects of thoracotomy on pulmonary function; patients with localized pulmonary disease. J. Thoracic Surg. 34: 242-249 (Aug.) 1957. 18. Hales, S.: Haemastatics. 2nd Ed. London, 1740, pp. 22-23. Quoted by Kroeker, reference 23. 19. Hepper, N. G. and Bernatz, P. E.: Thoracic surgery in the aged. Dis. Chest 37: 298-303 (March) 1960. 20. Holford, F. D. and Mithoefer, J. C.: The effect of morphine on respiration in the aged. S. CLIN. NORTH AMERICA 40: 907-916 (Aug.) 1960. 21. Hood, R. M. and Beall, A. C., Jr.: Hypoventilation, hypoxia and acidosis occurring in the acute postoperative period. J. Thoracic Surg. 36: 729-743 (Nov.) 1958. 22. Knowles, J. H.: Respiratory Physiology and Its Clinical Application. Cambridge, Massachusetts, Harvard University Press, 1959,256 pp. 23. Kroeker, E. J.: Comparison of Central and Peripheral Arterial Pressure Pulses in Man. Thesis, University of Minnesota, 1954, 142 pp. 24. Laennec, R. H. T.: A Treatise on the Diseases of the Chest and on Mediate Auscultation. 3rd Ed., translated by J. Forbes. London, Thomas & George Underwood, 1829, 724 pp. 25. Leuallen, E. C. and Fowler, W. S.: Maximum midexpiratory flow. Am. Rev. Tuberc. 72: 783-800 (Dec.) 1955. 26. Lewis, B. M., Lin, T. H., Noe, F. E. and Komisaruk, R.: The measurement of pulmonary capillary blood volume and pulmonary membrane diffusing capacity in normal subjects; the effects of exercise and position. J. Clin. Invest. 37: 1061-1070 (July) 1958. 27. Lindahl, T.: Spirometric and bronchospirometric studies in 5-rib thoracoplasties. Thorax 9: 285-290 (Dec.) 1954. 28. Meneely, G. R.: Pulmonary function testing; a special exhibit from the Section on Diseases of the Chest of the American Medical Association. Dis. Chest 31: 125-154 (Feb.) 1957. 29. Otis, A. B.: Work of breathing. Physiol. Rev. 34: 449-458 (July) 1954. 30. Otis, A. B., Fenn, W. O. and Rahn, H.: Mechanics of breathing in man. J. Appl. Physiol. 2: 592-607 (May) 1950. 31. Patton, W. E., Watson, T. R., Jr. and Gaensler, E. A.: Pulmonary function before and at intervals after surgical decortication of lung. Surg. Gynec. & Obst. 95: 477-496 (Oct.) 1952. 32. Radford, E. P., Ferris, B. G. and Kriete, B. C.: Clinical use of a nomogram to estimate proper ventilation during artificial respiration. New England J. Med. 251: 877-883 (Nov. 25) 1954. 33. Riley, R. L.: Pulmonary gas exchange. Am. J. Med. 10: 210-220 (Feb.) 1951. 34. Singer, R. B. and Hastings, A. B.: Improved clinical method for the estimation of disturbances of the acid-base balance of human blood. Medicine 27: 223242 (May) 1948. 35. Shields, T. W.: Factors influencing the morbidity and mortality in the older aged patient undergoing pulmonary surgery. Surg. Gynec. & Obst. 111: 598-602 (Nov.) 1960. 36. Sloan, H., Morris, J. D., Figley, M. and Lee, R.: Temporary unilateral occlusion of pulmonary artery in preoperative evaluation of thoracic patients; preliminary report. J. Thoracic Surg. 30: 591-597 (Nov.) 1955.
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37. Smith, G. A., Siebens, A. A. a.nd Storey, C. F.: Preoperative and postoperative cardiopulmonary function studies in patients with bronchiectasis. Am. Rev. Tuberc. 69: 869-914 (June) 1954. 38. Soderholm, B.: The pulmonary blood flow in pulmonary tuberculosis and the effect of unilateral occlusion of the pulmonary artery. In: Pulmonary Circulation: An International Symposium, 1958, Sponsored by the Chicago Heart Association, edited by W. R. Adams and I. Veith, New York, Grune & Stratton, 1959, pp. 139-146. 39. Vacarezza, R. F., Soubrie, A. and Rey, J. C.: Functional examination of each lung before and after paralysis of phrenic nerve. Dis. Chest 14: 580-584 (July-Aug.) 1948. 40. Wells, R. E., Taylor, W. J., Black, H. and Harken, D. E.: Pulmonary function in the selection of patients for open heart surgery. Proc. New England Cardiovasc. Soc. 18: 31, 1959-1960. 41. Wezler, K. and Boger, A.: Die Dynamik des arteriellen Systems. Der arterielle Blutdruck und seine Komponenten. Ergebnisse der Physiologie 41: 292-606, 1939. 42. Wright, G. W., Yee, L. B., Filley, G. F. and Stranahan, A.: Physiologic observations concerning decortication of lung. J. Thoracic Surg. 18: 372-384 (June) 1949.