25 Volume 55 July 1962 565 Section of Medicine President A M Cooke DM Meeting March 27 1962 Respiratory Failure Dr C M Fletcher (Department of Medicine, Postgraduate Medical School, Hammersmith) Definition and Classification of the Causes of Respiratory Failure Normal respiratory function keeps the arterial blood almost fully oxygenated and the arterial carbon dioxide pressure within a narrow range, both at rest and on the most extreme exertion. We can therefore define respiratory failure in terms of arterial blood gases as 'a fall in arterial oxygen saturation or a rise in arterial carbon dioxide pressure beyond the normal range'. We must, however, exclude three factors which may cause alterations in blood gases in the absence of respiratory failure. These are: (1) Anatomical shunting of blood past the lungs as in a right-to-left shunt in the heart. (2) Metabolic alkalosis in which, when compensated, the arterial pco2 is increased. (3) Lowering of the ambient oxygen tension, as at high altitude. Oxygen saturation rather than oxygen tension is used in this definition because it is so much easier to measure, and because it is related to the clinical sign of cyanosis. It is because we use saturation that we must base our definition on either a fall in oxygen saturation or a rise in arterial pco2 in order to define respiratory failure because the oxygen saturation and pco2 behave quite differently in the two main types of respiratory failure (Table 1). Table I Main types of respiratory failure (1) Alveolar underventilation - ventilatory failure pco, increased 0, saturation slightly reduced (2) Impaired alveolar-arterial gas erchange 0, saturation decreased (especially on exercise) pco, normnal or decreased The arterial pco2 is directly proportional to the rate of CO2 production in the body and inversely proportional to alveolar ventilation: Arterial PCO2 a CO2 production Alveolar ventilation Since, at rest, the rate of CO2 production is constant, alveolar underventilation due to ventilatory failure produces a direct and proportional increase in alveolar and hence arterial pco2. A rise in alveolar pco2 results in an arithmetically equivalent fall in alveolar P02. Thus a rise of alveolar pco2 from, say, 40 to 60 must be associated with a fall of alveolar P02 from 100 to 80. Because of the shape of the oxygen dissociation curve this would only produce a small and almost undetectable change of arterial oxygen saturation. Thus, alveolar underventilation can be quite severe with little change in arterial oxygen saturation. In the other main type of respiratory failure - impaired alveolar-arterial gas exchange - there is, in effect, a reduction of the alveolar surface ava-ilable for gas exchange. This may be either a direct reduction of total perfused alveolar surface or may be just a relative underventilation of some parts of the lungs. Either of these disturbances may seriously interfere with oxygen uptake, particularly on exercise, so that arterial desaturation results. But CO2 exchange may continue normally because of the much greater diffusibility of CO2 than of oxygen or because of increased ventilation of the adequately ventilated parts of the lung. This will compensate for the inadequate elimination of CO2 from the badly ventilated alveoli, but it cannot compensate for the desaturated blood returning from these underventilated parts of the lung, for even the most extreme overventilation of the more normal parts of the lung cannot raise the saturation of blood leaving it above 100 %. When this fully saturated blood is admixed with the shunted blood, the mixture is desaturated as it reaches the systemic arteries. Thus, in this group the arterial blood is desaturated but the arterial PCO2 is normal or even lower than normal.
566 Proceedings ofthe Royal Society ofmedicine 26 Table 2 Causes of alveolar underventilation or ventilatory failure (1) Obstructive Bronchitis Asthma Emphysema Strangulation (2) Restrictive Kyphoscoliosis (Obesity) (Pleural thickening) (3) Neuromuscular impairment Poliomyelitis Neuritis Curare (4) Lack of respiratory drive Sedative drugs and poisons Idiopathic hypoventilation Terminal states The causes of alveolar underventilation are listed in Table 2. First there is a group of conditions leading to generalized airway obstruction. These are by far the most frequent clinical causes of respiratory failure. The next group are conditions that restrict the movement of the thorax and increase the work of breathing. Obesity and pleural thickening seldom cause respiratory failure in the absence of some other disease of the respiratory apparatus. Thirdly, there are conditions in which the thoracic movements are weakened by neurological or muscular diseases, and fourthly, conditions in which the respiratory centre ceases to respond normally to the stimulus of a raised arterial pco2. When the arterial pco2 is high enough (levels over 100 mm Hg) it acts itself as a depressant of the respiratory centre and thus the well-known vicious circle of respiratory failure may be initiated. Table 3 Causes of impaired alveolar-arterial gas exchange (1) Pulmonary fibrosis and granulomatoses e.g. Sarcoidosis Idiopathic interstitial fibrosis Asbestosis (2) Severe emphysema (3) Pulmonary edema (4) Chronic obstructive pulmonary vascular disease e.g. Idiopathic and thromboembolic pulmonary hypertension (5) Anatomical loss offunctioning lung e.g. Pneumonectomy Pleural effusion Masive collapse Conditions in which alveolar-arterial gas exchange is impaired are listed in Table 3. The first group are those conditions which are commonly said to be associated with 'alveolar-capillary block' which is often thought to be due to thickening of the alveolar membrane. There is very little histological justification for this idea and it is probable that in all of them the most important factor is reduction in the total alveolar bed available for gas exchange by obliteration of large numbers of alveoli. But there is also shunting of blood through alveoli with inadequate ventilation and compensatory overventilation of the more normal parts of the lung. Emphysema has been put into a group by itself. In it there is not only destruction of effective lung tissue but also gross disturbance of ventilation-perfusion ratios. When associated with bronchitis, emphysema is also associated with alveolar underventilation, but it seems that in the idiopathic or primary type of emphysema the arterial PCO2 is often normal, arterial desaturation occurring at first only on exercise but later at rest, and only terminally is there alveolar underventilation. Pulmonary cedema is probably the cause of arterial desaturation in many cases of left ventricular failure. This is probably not because cedematous fluid lines the alveoli, increasing the effective thickness of the alveolar walls, but rather because large numbers of alveoli are underventilated, owing to oedema, but are still perfused. The cause of arterial desaturation in chronic obstructive pulmonary vascular disease is rather obscure, but it certainly occurs in severe cases and is presumably due to large areas of lung being rendered avascular and thus unavailable for oxygen exchange. Anatomical loss of functioning lung by surgical removal, collapse with or without effusion, or pneumonia is an uncommon cause of respiratory failure. When cyanosis occurs in pulmonary collapse and pneumonia it is probably due to an effective shunt through unaerated lung, but these conditions seldom cause respiratory failure in the absence of other respiratory disease. The most severe cases of respiratory failure are those associated with both underventilation and impaired alveolar-arterial gas exchange. This is the usual situation encountered in the cases of advanced emphysema and bronchitis which fill our medical wards every winter. Dr E J Moran Campbell (Department of Medicine, Postgraduate Medical School, London) Respiratory Failure: Simple Bedside Tests of Lung Function I shall follow Dr C M Fletcher's terminology and discuss the diagnosis first of respiratory failure with CO2 retention (i.e. ventilatory failure), and secondly of respiratory failure without CO2 retention.
27 Section of Medicine 567 VENTILATORY FAILURE In brief, the diagnosis and assessment of the adequacy of ventilation requires measurement of the blood CO2 tension (pco2), but I will approach the subject by considering first of all the assessment of ventilatory capacity. Evidence of Ventilatory Capacity (1) Due to airways obstruction: Clinical signs: Diffuse airways obstruction, particularly if it is chronic, causes inflation of the lungs. This leads to an enlargement of the chest and a flattening of the diaphragm. These mechanical changes in the thoracic cage lead to certain physical signs. There is a 'paradoxical' movement of the costal margin during breathing, so that the costal margin moves inwards instead of outwards during inspiration. Secondly, there is a tracheal tug with each inspiration due to the traction of the diaphragm on the base of the mediastinum and pericardium. The heart is to be seen, felt, and heard close to the mid-line and very often in the epigastrium rather than in its usual position. Percussion may show depression of the liver dullness and obliteration of the cardiac dullness. There are the usual stethoscopic signs of wheezing, but if the obstruction is due to mechanical trapping rather than narrowing of the airways by disease in their walls, the wheezing may be very slight. Although the measurement of chest expansion is very unreliable when comparing different observers, it may have a small place when used by an individual in a standard way. Simple tests: The 'match' test. The patient is asked to take a deep breath and, with his mouth wide open, to try and blow out a lighted match. A normal subject can usually do this at a distance of 3 or 4 or more inches, but a patient with diffuse airways obstruction may be unable to do it even when the match is close to the mouth. I prefer to measure the 'forced expiratory time'. I ask the patient to take a deep breath in and then blow out as hard as he can and keep blowing until he can get no more air out or until he is forced to take another breath. A normal person can empty his chest and air stops coming out after three or four seconds. A patient with diffuse airways obstruction may be unable to empty his chest in eight or ten seconds, and in fact has to take another breath before he has finished emptying his chest. Tests using portable equipment: The Wright peak flow meter is a very useful, simple and portable instrument for assessing the ventilatory capacity. It does not really measure the absolute peak flow but the maximum flow that is sustained over a period of 0 01 sec. This probably makes it more useful than a machine which measures the true peak flow. The Vitalor is a dry spirometer working on the bellows principle, which gives a recording of the forced expiratory spirogram on a card from which it is very easy to obtain the forced expired volume in one second. This is probably the most generally useful measurement in following the progress or comparing severity of airways obstruction. Laboratory procedures: Under this heading I have put simple spirometry, although it is really so simple as to be perfectly practicable at the bedside. With a recording spirometer one can obtain the vital capacity, the forced vital capacity, forced expired volume in one second or some other interval of time, and the maximum breathing capacity. This is not the place to discuss these tests in detail but I would recommend measuring both the forced expired volume in one second and the forced vital capacity. (2) Due to 'restriction': Ventilatory failure due to conditions such as kyphoscoliosis, obesity or muscular paralysis, which cause restrictive reduction of ventilatory capacity is rare. The match test and the forced expiratory time and the peak flow as measured with the Wright machine are relatively normal. The forced expired volume in one second is reduced but it remains a normal proportion of the vital capacity. That is to say, the subjects can expel more than 75% of the air in their lungs within one second. Ventilatory Failure The clinical diagnosis of ventilatory failure is very unreliable. The condition implies carbon dioxide retention which causes tachycardia, rise in the blood pressure, sweating, warm extremities, twitching, confusion and coma. Unfortunately, however, these physical signs are not specific and may be present in ill patients due to other causes such as fever or anoxia. Because of the S-shape of the oxygen dissociation curve, arterial desaturation, cyanosis and anoxia do not occur until the ventilation is reduced to about half normal, and cyanosis is a particularly unreliable physical sign. Laboratory procedures: In most hospitals it is possible to measure the CO2 content or alkali reserve of the venous blood and this can give a clue to the presence of CO2 retention provided it has been present for a sufficient time for a secondary metabolic alkalosis to have developed. Un-
568 Proceedings ofthe Royal Society ofmedicine fortunately, however, in acute situations this may not have occurred and these measurements may be within normal limits. They can be very misleading if there is a combined respiratory and metabolic acidosis, because under these circumstances measurements of the total CO2 or alkali reserve may be quite normal. With improvements in modern ph meters it is now possible to measure the arterial CO2 tension in a number of ways. Provided the equipment has been set up and checked, all that is required is to take an arterial blood sample anaerobically and the arterial CO2 tension can usually be measured in less than half an hour. The rebreathing method for measuring mixed venous pco2: The rebreathing method for measuring CO2 tension overcomes many of the laboratory problems associated with blood pco2 measurement and also takes the measurement from the laboratory back into the wards. It can justifiably be included among the simple bedside tests. The principles underlying this method are as follows: Mixed venous CO2 tension is measured because in the resting subject the arteriovenous PCO2 difference, which depends upon the cardiac output, is small and relatively constant and the mixed venous pco2 depends upon ventilation as much as does the arterial PCO2 and can be used to indicate whether or not ventilation is adequate. The essence of the technique consists of having the patient rebreathe from a small bag containing a CO2 mixture. The contents of the bag and of the lungs mix with each other and the resulting CO2 mixture is titrated by the blood running through the lungs until itis in equilibrium. This equilibrium persists until blood is recirculated round the body and returned to the lungs with its CO2 tension further increased. If a rapid CO2 analyser is available this equilibration process can be observed and checked. If an analyser is not available the equilibration can be guaranteed by using a two-stage procedure. In the first stage the subject rebreathes an oxygen mixture from a small bag for about a minute and a half. During this time he excretes CO2 into the bag until it is somewhat above the CO2 tension in the mixed venous blood. There is then a rest period of two or three minutes to allow any retained CO2 to be blown off and in the second stage the subject rebreathes from the bag for twenty to forty seconds. During this period the equilibration with the incoming mixed venous blood is completed and the bag can then be analysed by any simple method of measuring CO2 in gas mixtures. The rebreathing method enables the CO2 tension of the mixed venous blood to be measured in about ten minutes without elaborate equipment. RESPIRATORY FAILURE WITHOUT C02 RETENTION 28 This definition implies a reduced arterial oxygen tension or saturation with a normal or reduced arterial carbon dioxide tension. I must therefore take it that one has been able to exclude CO2 retention either on very good clinical evidence or on the basis of measurements of CO2 tension. Clinical diagnosis: It is most important to reiterate that anoxia must be sought through evidence of disturbed nervous function. It is not by itself an important cause of breathlessness. The manifestations of anoxia are protean and vary from mild disturbances of consciousness, resembling alcoholic intoxication, to abrupt unconsciousness, convulsions and death within a few minutes. In ordinary clinical practice it usually presents as confusion, drowsiness, disturbed sleep and twitching. Some of these patients do not find anoxia unpleasant and they may not be grateful when their anoxia is relieved. Cyanosis: Cyanosis is a blue colour. It is difficult to see. Most books suggest that it implies the presence of 5 g of reduced hemoglobin to 100 ml of blood. This piece of physiological cant is carried on from book to book, despite the fact that many very good studies have shown that the ability to perceive cyanosis is very variable and in many patients an indistinguishable blue colour can be caused by thickness of pigmentation of the mucous membranes, even in the mouth. Nevertheless, as it is the best sign we have of arterial desaturation, we are forced to make use of it and it can in fact be made much more reliable by the use of two simple procedures. The first is to give the patient oxygen to breathe. The arterial desaturation of patients with pulmonary disease is so sensitive to oxygen that a few breaths of it, even in relatively low concentration, will make it disappear within a minute. Therefore, when in doubt give the patient oxygen. If the blue colour does not improve then it is not due to arterial desaturation. The second method is to exercise the patient. If a patient has sufficiently severe generalized lung disease to prevent him saturating his blood at rest, he will be even less able to maintain the saturation during exercise. So that if he is able to exercise at all it will lead to an intensification of the cyanosis and this can be prevented by the use of oxygen. Bedside Tests Oximetry: Although it is not certain how accurate modern percutaneous oximeters are at measuring absolute saturation, they can be used to record changes in saturation. Thus the oximeter can be used to see the effects of oxygen breathing and of exercise.
29 Section of Medicine 569 The arterial oxygen saturation can, of course, be measured quite accurately on arterial blood. Apart from the classical Van Slyke method, there are now excellent and convenient spectrophotometric methods. The interpretation of a measurement of arterial saturation, however, is not quite as simple as it is usually thought to be, for the following reasons: (1) The arterial oxygen saturation depends upon all aspects of respiratory physiology and must be related to the level of alveolar ventilation, the respiratory quotient and even the barometric pressure before we can think in terms of the alveolar-capillary membrane. (2) The S-shape ofthe dissociation curve means that a reduction in the partial pressure of oxygen in the alveolar air and arterial blood does not result in a fall of saturation below the conventionally accepted normal range, until there is a very severe disturbance. For example, alveolar ventilation must be reduced to almost half normal before the arterial saturation falls below 90 %; and the volume of blood passing through the lungs without being oxygenated must be about 30% of the total pulmonary blood flow before arterial saturation falls below 90 %. Having indicated these difficulties one can nevertheless summarize by saying that respiratory failure due to diseases affecting the alveolar-capillary membrane and the uptake of gases from the alveolar air are characterized by a normal or low pco2 and a low arterial oxygen saturation. The arterial oxygen saturation can be easily increased by breathing oxygen and decreased by exercise. I do not often pursue these diagnoses of respiratory failure without CO2 retention as far as I have indicated because the observation of the patient at exercise with and without oxygen enables the clinical diagnosis to be reached without arterial blood measurements. Nevertheless the interpretation of the clinical observations requires the same understanding of physiology as the interpretation of the arterial blood gas measurements. In fact, one requires a better knowledge of physiology if one is going to rely on the physical signs and not make the measurements. Dr T Simpson (Chase Farml Hospital, Enfield) Management Acute Respiratory Failure The chronic bronchitic/emphysematous patient is always liable to fall ill from a chest infection. These infections do not present much difficulty until the disease is advanced when respiratory failure, with all its consequences, will occur. The respiratory failure may come on suddenly as a result of acute asphyxia due to bronchial 35 blockage but more commonly it is part of a general cerebral depression due to hypoxia and hypercapnia which in turn is due to inadequate alveolar ventilation. The mechanical blockage in the bronchial tree is more often at a low level out of reach of the bronchoscope and sucker. Relief of the chest infection must be the first objective. If we could determine at once the infecting organism and give the appropriate antibiotic our troubles would be much less. This is often impossible and we must concentrate on the treatment of the respiratory failure. The aim is to establish oxygenation without mental depression, and certain steps must be taken: (1) Relief of the severe hypoxia, because unrelieved it will cause inevitable changes in the heart, brain, kidneys and liver. Oxygen should be given at a low flow rate. Full saturation of the arterial blood should not be the aim. (2) If in spite of this, drowsiness and semi-coma occur, respiratory stimulants such as amiphenazole or prethcamide should be used. Both are very effective intravenously but less so intramuscularly and not at all by mouth. Repeated hourly injections may be necessary. Infusions should be avoided since they only add to the burden of hypervolemia. (3) If these measures fail, intermittent positive pressure respiration should be tried if the patient can co-operate. Control can be maintained by estimating the arterial ph. (4) If this fails, a tracheotomy with or without positive pressure respiration is necessary. Tracheotomy makes severe demands on the medical and nursing staff and is therefore to be avoided, if at all possible, in the less well equipped and staffed hospitals where these patients are usually seen. It is sensible to set up an emphysema clinic and keep a watch on the bad risk cases, those who have a high or rising pco2. If they fall ill they should be admitted at once. In this way simple measures may be effective and tracheotomy avoided. Chronic Respiratory Failure This condition is unfortunately difficult to treat and the only satisfactory drug is dichlorphenamide; the dose is one tablet in the morning, increasing to a maximum of four. Incapacitating headache and parxsthesixe may preclude its use, but these complications are not common. After using the drug arterial CO2 tension falls, there is slight acidosis and the maximum breathing capacity increases. However, the magnitude of these changes is not proportionate to the marked improvement. The proof of the value of this drug is that patients who have been taken off it by their general practitioners return to the clinic to ask for its resumption.