RESPIRATORY FAILURE and CARBON DIOXIDE NARCOSIS by E

2 Postgrad Med J: first published as 10.1136/pgmj.34.387.2 on 1 January 1958. Downloaded from

RESPIRATORY FAILURE AND CARBON DIOXIDE NARCOSIS By E. KEITH WESTLAKE, M.A., M.D., M.R.C.P. Senior Medical Registrar, Middlesex Hospital

All physicians are familiar with the clinical and and the prevailing barometric pressure (B). For biochemical manifestations of cardiac and renal example, when the respiratory quotient is 0.79 and failure, but the syndrome of respiratory failure has the barometric pressure 760 mm., this equation gained recognition more slowly. The primary simplifies to: P02 = 150 - 1.21 x alveolar pCO2. function of the lungs is to maintain a constant Thus at the normal alveolar pCO2 of 40 mm., the exchange ofoxygen and carbon dioxide between the corresponding pO2 will be o02 mm., but if the blood and air. This is achieved by intermittent alveolar pCO2 rises to 80 mm., the alveolar pO0 flushing of the alveoli with inspired air and the must fall to 53 mm. (I50- I.21 x 80). Capillary continuous diffusion of oxygen and carbon dioxide blood leaving the alveoli cannot have an oxygen across the alveolar membrane. In normal indi- tension higher than this figure and the oxygenProtected by copyright. viduals, these processes maintain the mean carbon saturation of arterial blood will therefore be dioxide tension (pCO2) in the alveoli at 40 ± 5 reduced to about 80 per cent. with the appearance mm. Hg. and the oxygen tension (pO2) at Ioo I 5 of central cyanosis. mm. Hg. Respiratory failure may be said to be When the alveolar pCO, is suddenly raised from present when there is inability or failure of the 40 to 80 mm., the volume of carbon dioxide dis- repiratory centre and neuro-muscular mechanism solved in the arterial plasma increases from 2.8 to prevent the alveolar pCO2 rising above, and the vols. per 00oo ml. to 5.6 vols. with consequent fall alveolar pO0 falling below their normal values. in blood pH from 7.4 to 7.I. Renal compensation The level of alveolar pCO, is determined by two for this respiratory acidaemia, with partial restora- variables: (a) the rate of carbon dioxide production of the arterial pH toward normal, is brought tion by the body i.e. the metabolic rate and (b) about over a period of days by increased tubular the adequacy of alveolar ventilation. If the reabsorption of bicarbonate and the excretion of a metabolic rate remains constant, the alveolar highly acid urine (pH 4.6-4.8) containing in- pCO2 will vary inversely with alveolar ventilation. creased amounts of ammonium and chloride ions. http://pmj.bmj.com/ If the latter is halved, the pCO2 will rise to double Thus the biochemical effect of respiratory failure its original level and vice-versa. Similarly, if the is the combination of hypercapnia, hypoxaemia rate of carbon dioxide production is doubled, and acidaemia. alveolar ventilation must increase to the same extent if the alveolar pCO2 is to remain unchanged. Causes of Respiratory Failure Respiratory failure is therefore characterized by failure result from relative underventilation of the alveoli in Respiratory may organic lung disease of the central nervous system (for example, on September 23, 2021 by guest. relation to body metabolism. encephalitis lethargica (Barach and Woodwell, When breathing air, alveolar hypoventilation I92I), bulbo-spinal poliomyelitis (Plum and inevitably causes hypoxaemia (arterial oxygen un- Wolff, I951), motor neurone disease (Feltman saturation) as well as hypercapnia (raised arterial et al., 1952), brain stem haemorrhage) or of the pCOg) since as the level of alveolar pCO, rises, the respiratory muscles (for example, dystrophia alveolar P02 falls. The relationship between the myotonica (Benaim and Worster-Drought, I954), alveolar gas tensions can be appreciated from the myasthenia gravis, dermatomyositis). In general equation derived by Fenn, Rahn and Otis (I946)* medicine, respiratory failure is most commonly and depends on the respiratory quotient (R.Q.) encountered in patients with long standing chest * disease whose is Mean alveolar pO2 = (B - 47) x 0.21 - alveolar ventilatory capacity grossly 0.79 diminished e.g. in chronic bronchitis and emphy- pC02(o.2I + ). sema (Baldwin et al., 1949) and severe kypho- R.Q. scoliosis (Fishman et al., I956). Patients who are WESTLAKE: Failure and Carbon Dioxide Narcosis January 1958 Respiratory 3 Postgrad Med J: first published as 10.1136/pgmj.34.387.2 on 1 January 1958. Downloaded from association with gross obesity (Burwell et al., I956). 90. The Diagnosis of Respiratory Failure OQ ..... Clinical recognition of alveolar hypoventilation may be difficult and the only certain method of diagnosis is the demonstration of a raised level of 65 pCO2. This is most conveniently achieved by 60 analysis of arterial blood since the pCO2 of alveolar air and arterial blood are virtually identical. With practice, samples of arterial blood can be readily obtained by puncture of the brachial artery under 455 local analgesia. Direct determination of both pCO2 and pO2 in arterial blood can be made by the bubble equilibration technique devised by Riley. Jo This method has been extensively used in 0O 25 30 35 40 45 50 5S 60 65 0 75 80 85 90 05 00 respiratory research but is technically too difficult ARTERIAL CO, TENSION for routine use in a biochemical laboratory. arterial can be . Chronic Bronchiti with Cor Pulmonok with However, pCO2 estimated No . accurately or without Emphysma. congestve cardiac by an indirect method. Blood pH, pCO2 and fallure. total content are the FIG. i.-Respiratory failure precipitated by an acute plasma CO2 related by well- chest infection in patients with chronic lung disease. known Henderson-Hasselbalch equation. If any Arterial oxygen saturation and carbon dioxide two of these variables are known, then the third on tension admission with, and recovery from, an can be calculated. Thus, rearranging the equation: Protected by copyright. acute respiratory infection. Single points represent Total patients who died. plasma CO2 content mM/L pCO2 = - 0.03 x (antilog blood pH - 6.09) + i able to maintain a normal alveolar pCO2 when well, Total plasma CO2 content is measured by the frequently develop acute respiratory failure with manometric method of Van Slyke and Neill (1924) severe hypoxaemia and hypercapnia when sub- and blood pH with a glass electrode and pH meter. jected to the stress of a respiratory infection Practical details for measuring blood pH at body (Westlake, 1954). This is illustrated in Fig. i. temperature are to be found in the papers ofWilson In this diagram the arterial oxygen saturation and (1951), Severinghaus, Stupfel and Bradley (1956) pCO2 during the course of an acute respiratory and Wynn and Ludbrook (I957). infection have been plotted as oblique arrows. The six normal subjects i.e. those without previous The Clinical Manifestations of Respiratory black Failure respiratory symptoms (represented by http://pmj.bmj.com/ triangles) were all suffering from extensive lobar The disturbances of blood gas tensions and in pneumonia and in five the pCO2 on admission to blood pH caused by respiratory failure have pro- hospital was lower than that on recovery. This found physiological effects on the brain, cerebral may be taken as the normal response to an acute vessels, heart and lungs and are responsible for the chest infection. In the 39 patients with a previous appearance of certain characteristic signs and history of chest disease (chronic bronchitis, symptoms which may make a bed-side diagnosis emphysema and cor pulmonale), the arterial pCO2 of respiratory failure possible. on admission was higher than on recovery in 37. Mental disturbance in respiratory failure varies on September 23, 2021 by guest. In many instances the initial levels of pCO2 were with its severity. In mild cases the patient may be 30 to 40 mm. higher than those on recovery. euphoric or mildly confused. More severe de- Other factors that may precipitate respiratory grees of hypoxaemia and hypercapnia cause pro- failure in patients with chronic chest disease are gressive deterioration in mental function with severe asthma (Schiller et al., 1951; Sieker and visual and auditory hallucinations, delusions, Hickam, 1956), chest surgery (Bjork and stupor and finally coma. Although disturbed Engstr6m, 1955) and the ill-advised administra- mental function is principally due to cerebral tion of morphine and other drugs which depress anoxia (Simpson, 1957), the effects of hyper- the sensitivity of the respiratory centre (Roussak, capnia and acidaemia on the brain should not be I951; Samuelsson, I952; Wilson, Hoseth and neglected. The effect of breathing Ioo per cent. Dempsey, 1954). In rare instances, chronic oxygen shows that hypoxaemia is only one of the respiratory failure occurs in the absence of either factors concerned since the patient in respiratory pulmonary or neurological disease, usually in failure, although considerably improved, often POSTGRADUATE MEDICAL

4 JOURNAL January 1958 Postgrad Med J: first published as 10.1136/pgmj.34.387.2 on 1 January 1958. Downloaded from remains confused and disorientated despite full (Stone et al., 1953; Fulton, 1953; Flint, 1954). saturation of the arterial blood with oxygen. If The cardiac output is usually normal or even mental disturbance were solely due to hypoxaemia, moderately raised (Ferrer et al., 1950; Mounsey an immediate return to mental clarity would be et al., I952) and this, together with the vasodilator expected. Impaired memory is usual during a effect of hypoxaemia and hypercapnia on the small period of respiratory failure, even in the absence vessels of the limbs, is responsible for the warm of obvious mental disturbance. After recovery extremities and bounding pulse present during from an acute respiratory infection, carefulenquiry episodes of congestive failure-in contrast to con- will often reveal that the patient has complete gestive failure in mitral stenosis, hypertension or amnesia (lasting days or even a week or two) for ischaemic heart disease where the cardiac output the early phase of his illness, although at the time, is low and the extremities cold. As might be he may have appeared alert and rational. Muscular expected, congestive failure is most likely to occur twitching is another common neurological mani- when respiratory failure is severe. From Fig. i, festation of respiratory failure. It consists of it can be seen that of 1 patients with an arterial coarse, irregular, jerky movements of the fingers, oxygen saturation below 55 per cent. and pCO2 arms and facial muscles and, less frequently ofthe above 70 mm., signs of heart failure were absent trunk and legs. Similar movements have been in only three. observed in normal subjects exposed to severe Many of the features of respiratory failure are anoxia. illustrated by the following case history: A 63- A low arterial pO2, high pCO2 and low pH all year-old log sawyer was admitted to hospital on cause dilatation of the cerebral and retinal vessels, January I2, I955. Apart from a chronic 'smoker's' the volume of blood within the skull is increased cough with scanty mucoid sputum he had been in and in consequence the C.S.F. pressure rises. In good health until 1943, when he had a severe 12 attack of acute Since then he had emphysematous patients studied during respi- bronchitis. beenProtected by copyright. ratory infections (Westlake and Kaye, 1954), the subject to repeated exacerbations of winter C.S.F. pressure was above the upper limit of bronchitis with purulent sputum, headache and normal (200 mm.) in ten, and in five subjects it was wheeziness. In 195i, he noticed moderate exer- over 350 mm. The highest pressure recorded was tional dyspnoea but this was not severe enough to 600 mm. Raised intracranial pressure due to interfere with his work. On January 3, I955, respiratory failure is frequently associated with a after walking home in a gale, he felt ill and retired severe throbbing type of headache and in a few to bed. Subsequently his sputum became purulent patients, frank papilloedema appears, with measur- and he complained of anorexia, wheeziness, able swelling of the nerve head, gross dilatation of insomina and severe throbbing headaches. On the retinal veins and flame-shaped haemorrhages. January 7, I955, his practitioner prescribed a Papilloedema as a complication of emphysema was four-day course of aureomycin (o.25 g. six-hourly) first described by Cameron (I933), and although but despite this he continued to deteriorate, and on some authors have attributed the phenomenon to January 9, 1955, was disorientated with rambling raised venous pressure (Beaumont and Hearn, speech and hallucinations. On admission three http://pmj.bmj.com/ 1948), the work of Simpson (1948) leaves no doubt days later he appeared critically ill. There was that the primary cause is cerebral vasodilatation deep cyanosis of the lips and nail beds, the neck consequent to respiratory failure, although in some veins were engorged to the angle of the jaw and he cases raised jugular venous pressure may be a was unable to give any coherent history. Examina- contributory factor. The combination of mental tion of the fundi showed dilated, tortuous veins disturbance, headache and papilloedema may lead with some blurring of the disc margins but no to an erroneous diagnosis of cerebral tumour as in retinal haemorrhages. Heart sounds were normal on September 23, 2021 by guest. the cases reported by Meadows (1947) and Conn with a regular tachycardia, rate Ioo. Blood et al. (1957). pressure I 5/55. Mild sacral oedema was present. While respiratory failure causes cerebral vaso- Respirations were shallow and rapid and on dilatation, it has the opposite effect on the pul- auscultation of the chest coarse rales were audible monary arterioles and the pulmonary artery at both bases with generalized inspiratory and pressure rises (Whitaker, 1954). In patients with expiratory rhonchi. The resting ventilation was pre-existing hypertrophy of the right ventricle 6.25 litres per minute (respiratory rate 40 x tidal (cor pulmonale) the sudden increase in pulmonary air I56 ml.). Analysis of arterial blood confirmed artery pressure that occurs during acute respiratory the clinical diagnosis of severe respiratory failure: infections frequently precipitates heartfailure with oxygen saturation 44 per cent. (PO2 26 mm.), dilatation of the right ventricle, the appearance of pCO2 raised to 88 mm. (more than twice normal) gallop rhythm (best heard over the xiphisternum), and pH reduced to 7.24 (normal range 7.36-7.44). raised venous pressure and peripheral oedema A chest radiograph showed considerable cardiac January 1958 WESTLAKE: Respiratory Failure and Carbon Dioxide Narcosis Postgrad Med J: first published as 10.1136/pgmj.34.387.2 on 1 January 1958. Downloaded from CARBON DIOXIDE NARCOSIS therapy (Barach, 1935; Donald, I949; Comroe, Bahnson and Coates, 1950; Cohn, Carroll and PCO2 pH Riley, 1954; Westlake, Simpson and Kaye, 1955; A | OXYGEN TENT Sieker and Hickam, 1956). A typical example is illustrated in Fig. 2. The patient, a 62-year-old emphysematous man developed an acute pneu- mmpHg mococcal bronchitis with moderately severe --90 respiratory failure: oxygen saturation 64 per cent. --80 pH. (pO2 38 mm.), pCO2 72 mm. and pH. 7.26. On admission to hospital he was rational and orientated but within four hours of being placed in an oxygen --60 7.4-- tent he had lapsed into a semicomatose state with -50 profuse sweating and coarse myoclonic jerking of 7.3- the arms. Arterial blood showed that the pCO2 40 had risen to 105 mm. with fall in pH to 7.I3 --30 (equivalent to the inhalation of 15 per cent. carbon 7.2-- dioxide by a normal subject). Over succeeding 20 days, the arterial pH gradually returned toward 71, normal values and the arterial pCO2 fell to 90 mm. Myoclonicjerking ceased and the patient regained 0 7.4 consciousness but remained unduly drowsy. Mental rte:| Smt-cmm I Cou., ktstn: Throughout the period of oxygen therapy, the HOURS: 0 5 14 24 64 87 112 114 arterial blood remained fully saturated with FIG. 2.-Development of carbon dioxide narcosis during oxygen. Protected by copyright. oxygen therapy. A broad correlation has been established between arterial pCO2, pH and mental state. enlargement but the lung fields were clear. Westlake, Simpson and Kaye (I955) found that Treatment with oxygen, antibiotics, broncho- mental disturbance was usually present when the dilators, nikethamide and corticotrophin resulted arterial pH was less than 7.2 or the pCO2 above in rapid recovery from respiratory failure and dis- 100 mm., and coma when the pH fell below 7.1 or appearance of the signs of right heart failure. the pCO2 rose above 120 mm. Most patients Studies on recovery showed that the arterial blood were conscious and rational if the pH was above was still mildly unsaturated (02 saturation 9I.4 per 7.3 or pCO2 less than 80 mm. These observa- cent.), but that the pCO2 (44 mm.) and pH (7.42) tions have been substantially confirmed by Sieker had returned to normal. The resting ventilation and Hickam (1956). They observed that there was 6.2 litres minute but the tidal was usually no significant abnormality in mental again per larger state if the was less than mm. and the air (310 ml.) now provided adequate alveolar pCO2 90 pH http://pmj.bmj.com/ ventilation. He subsequently returned to work above 7.25. Semi-coma or coma were always ob- and has remained in good health. servedwhen the pCO2 rose above I30 mm. and pH fell below 7.14. In general, the critical level for loss Carbon Dioxide Narcosis of consciousness in carbon dioxide intoxication is In respiratory failure, there is a shift in the at a pH of 7.1-7.14 and pCO2 of I20-130 mm., control of pulmonary ventilation from the medul- although increased susceptibility to the narcotic lary respiratory centre to the peripheral chemo- action of carbon dioxide may be found in individual receptors of the carotid and aortic bodies. With cases. on September 23, 2021 by guest. rising arterial pCO2, the respiratory centre Motor phenomena are common during carbon becomes less and less sensitive to the stimulus dioxide intoxication. They usually consist of fine of carbon dioxide (Scott, 1920; Tenney, 1954; tremors of the fingers, arms and facial muscles Prime and Westlake, 1954; Fishman et al., I955) (Waters, 1937), but severe clonic movements of the and ventilation is increasingly maintained by the limbs and generalized convulsions have been stimulus of hypoxaemia acting via the carotid and observed (Sieker and Hickam, 1956). The C.S.F. aortic chemoreceptors. Breathing high concen- pressure often rises (Davies and Mackinnon, 1949; trations of oxygen abolishes the anoxic stimulus Westlake and Kaye, I954)-despite relief of anoxic to breathing with the inevitable consequence that cerebral vasodilatation-and papilloedema may alveolar and arterial pCO2 levels are raised and make its first appearance during oxygen therapy. arterial pH lowered still further. It is this Carbon dioxide intoxication also causes tachy- phenomenon that is responsible for the develop- cardia, sweating, skin vasodilatation and alterations metnt of carbon dioxide narcosis during oxygen in blood pressure. In the early stage the blood 6 POSTGRADUATE MEDICAL JOURNAL January 1958 Postgrad Med J: first published as 10.1136/pgmj.34.387.2 on 1 January 1958. Downloaded from but more severe of FISHMAN, A. P., BERGOFSKY, E. H., TURINO, G. H. pressure may rise, degrees JAMESON, A. G., and RICHARDS, D. W. (1956), Ibid., hypercapnia and acidaemia are usually associated 14, 935. FISHMAN, A. P., SAMET, P., and COURNAND, A. (1955), with a profound fall in blood pressure. Prolonged Amer. J. Med., 19, 533. narcosis frequently causes death from respiratory FLINT, F. J. (I954), Lancet, ii, 51. FULTON, R. M. (I953), Quart. J. Med., 22, 43. depression. MEADOWS, S. P. (1947), Proc. roy. Soc. Med., 40, 555. MOUNSEY, J. P. D., RITZMANN, L. W., SELVERSTONE, N. J., BRISCOE, W. A., and McLEMORE, G. A. (1952), Brit. BIBLIOGRAPHY Heart ., 14, I53. BALDWIN, E. DE F., COURNAND, A., and RICHARDS, D. W. PLUM, F., and WOLFF, H. G. (i95 ), J. Amer. med. Ass., 146, 4.2. (1949), Medicine, 28, i. PRIME, F. J., and WESTLAKE, E. K. (1954), Clin. Sci., 13, 321. BARACH, A. L. (1935), Anesth. et Analg., 14, 79. ROUSSAK, N. J. (i95s), Lancet, i, 1156. BARACH, A. L., and WOODWELL, M. N. (1921), Arch. int. SAMUELSSON, S. (1952), Cardiologica, 21, 817. Med., 28, 421. SCHILLER, I. W., BEALE, H. D., FRANKLIN, W., LOWELL, BEAUMONT, G. E., and HEARN, J. B. (1948), Brit. med..7., i, 5o. F. C., and HALPERIN, M. H. (i951), J. Allergy, 22, 423. BENAIM, S., and WORSTER-DROUGHT, C. (I954), Med. SCOTT, R. W. (1920), Arch. int. Med., 26, 544. ill. (Lond.), 8, 221. SEVERINGHAUS, J. W., STUPFEL, M., and BRADLEY, A. F. BJORK, V. 0., and ENGSTROM, C. G. (1955), J. thorac. Surg., (1956), J. appl. Physiol., 9, I89. 30, 356. SIEKER, H. O., and HICKAM, J. B. BURWELL, C. S., ROBIN, E. D., WHALEY, R. D., and (1956), Medicine, 35, 389. BICKELMANN, A. G. (I956), Amer. J. Med., 21, 8 I. SIMPSON, T. (1948), Brit. med. J., ii, 639. CAMERON, A. J. (1933), Brit. J. Ophthal., 17, 167. SIMPSON, T. (i957), Lancet, ii, 105. COHN, J. E., CARROLL, D. G., and RILEY, R. L. (1954), STONE, D. J., SCHWARTZ, A., NEWMAN, W., FELTMAN, Amer. J. Med., 17, 447. J. A., and LOVELOCK, F. J. (I953), Amer. J. Med., 14, 14. CONN, H. O., DUNN, J. P., NEWMAN, H. A., and BELKIN, TENNEY, S. M. (I954), J. appl. Physiol., 6, 477. G. A. (I957), Ibid., 22, 524. WATERS, R. M. (I937), New Orleans med. surg. J., 90, 219. COMROE, J. H., BAHNSON, E. R., and COATES, E. O. (1950), WESTLAKE, E. K. (1954), Brit. med. J., ii, IoI2. J. Amer. med. Ass., 143, 1044. WESTLAKE, E. K., and KAYE, M. (1954), I, 302. DAVIES, C. E., and MACKINNON, J. (1949), Lancet, ii, 883. WESTLAKE, E. K., SIMPSON, T., and KAYE, M. (1955), DONALD, K. W. (1949), Ibid., ii, I056. Quart. J. Med., 2, 155. FELTMAN, J. A., NEWMAN, W., SCHWARTZ, A., STONE, WHITAKER, W. (1954), Ibid., 23, 57. D. J., and LOVELOCK, F. J. (1952), J. din. Invest., 31, 762. WILSON, R. H. (1951), J. Lab. clin. Med., 37, 129. FENN, W. O., RAHN, H., and OTIS, A. B. (1946), Amer. J. WILSON, R. H., HOSETH, W., and DEMPSEY, M. E. (1954),Protected by copyright. Physiol., 146, 637. Amer. J. Med., 17, 464. FERRER, M. I., HARVEY, R. M., CATHCART, R. T., WYNN, V., and LUDBROOK, J. (1957), Lancet, i, io68. WEBSTER, C. A., RICHARDS, D. W., and COURNAND, VAN SLYKE, D. D., and NEILL, J. M. (1924), J. biol. Chem., A. (1950), Circulation, I, 161. 6I, 523.

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