HAEMODYNAMIC EFFECTS OF PULMONARY VENTILATION

Br. J. Anaesth. (1975), 47, 761 HAEMODYNAMIC EFFECTS OF PULMONARY VENTILATION C. M. CONWAY As the heart is located within the thoracic cavity, changes in the thorax will affect cardiac performance. During inspiration, a gradient has to be developed across the lungs, being positive at the mouth or trachea relative to the pleural space. In spontaneous ventilation, this gradient is generated by an initial reduction in pleural below atmospheric, and the subatmospheric intrathoracic so produced plays an important part in the maintenance of venous return. Inspiration during intermittent positive ventilation (IPPV) is initiated by increasing tracheal above atmospheric. As expiration is usually passive in both modes of ventilation, mean intrathoracic will thus be greater during IPPV than during spontaneous ventilation. The effective filling of the heart is determined by the difference between intra-atrial and intrathoracic s. During normal quiet spontaneous ventilation, mean intrapleural is some 4-5 cm H 2 O below atmospheric, increasing about 3 cm H 2 O above this mean value during expiration, and decreasing a similar amount below mean during inspiration. Deep inspiration may produce intrapleural s 50-60 cm H 3 O below atmospheric. Because of these intrathoracic changes, cardiac performance fluctuates during each respiratory cycle. Greater fluctuations occur in venous return to the right atrium than in left ventricular output, as the pulmonary circulation partially damps fluctuations in left ventricular inflow. If the chest is opened, intrathoracic increases to atmospheric value and right atrial must increase by about 4 mm Hg to maintain filling and therefore the same output as with an intact chest wall (Fermoso, Richardson and Guyton, 1964). An enhanced subatmospheric within the thorax may occur during active hyperventilation, or in negative breathing, and will improve cardiac filling and cardiac performance. Of greater clinical importance are the homeostatic mechanisms C. M. CONWAY, M.B., B.S., F.F.A.R.C.S., Magill Department of Anaesthetics, Westminster Medical School, London SW1P 2AP. which oppose the potentially deleterious cardiovascular effects of an increased intrathoracic during EPPV. Normal response to an increased intrathoracic Although the application of high intrathoracic s will produce dramatic cardiovascular effects in most anaesthetized patients, marked reductions in cardiac output and mean systemic arterial are uncommon during routine clinical use of IPPV. Thus Prys-Roberts and colleagues (1967) were unable to demonstrate consistent changes in cardiac output when mean inflation was changed during anaesthesia and IPPV. The importance of the applied waveform in limiting cardiovascular effects of IPPV was established by Cournand and his colleagues (1948), who showed that minimal changes in cardiac output occurred during positive breathing when relatively rapid inflation, rapid deflation and inspiratory/expiratory ratio in the order of 1:2 were used. Whilst Command's studies were performed on conscious volunteers breathing from patienttriggered ventilators, the importance of a prolonged expiratory time during IPPV is now well established. The inspiratory/cxpiratory ratio is of far greater importance in limiting deleterious cardiovascular effects of IPPV than is the shape of the ventilating waveform. Bergman (1963, 1967) and Watson (1962) were unable to detect significant differences in lung function when different flow waveforms were used, other than changes attributable to altered mean intrathoracic ; and Adams and his colleagues (1970) could show no significant changes in cardiorespiratory function when four different waveforms were used with the same inspiratory/expiratory ratio. The cardiovascular responses to a sustained increase in intrathoracic in terms of the Valsalva manoeuvre have been extensively studied. IPPV may be considered as a series of short, repeated Valsalva manoeuvres. Hamilton, Woodbury and Harper (1936) divided the response to a sustained increase in intrathoracic into four phases (fig. 1). The transient increase in arterial

BRITISH JOURNAL OF ANAESTHESIA 762 development of a tachycardia and an increase in systemic vascular resistance. The overshoot in the final phase is the result of the ejection of a restored stroke volume into a still constricted circulation. In response to this transient hypertension there is a baroreceptor-mediated bradycardia. The compensatory powers of the circulatory system are such that, in normal, conscious individuals, mean systemic arterial is rarely reduced below preexisting values during the manoeuvre. Some decrease in systemic commonly occurs when a Valsalva response is evoked during anaesthesia, possibly because of a greater intra-abdominal pooling of blood (Sharpey-Schafer, 1965). Opie, Spalding and Smith (1961) have shown that, in clinical practice, mean intrathoracic s during IPPV he in the range of + 0.5 to + 2.5 cm H 5 O. Watson, Smith and Spalding (1961) showed that right atrial filling was unchanged during Valsalva manoeuvres performed on artificially ventilated subjects until mean oesophageal increased to 3-5 cm H 2 O, and for mean arterial to decrease required mean intrathoracic to increase above 5 cm H,O. These values of mean intrathoracic are rarely attained during clinical IPPV. These workers also suggested that, during IPPV, constriction of venous capacitance vessels was normally the main factor in limiting cardiovascular reactions to increased intrathoracic. At high inflating s, arteriolar constriction also occurred, as indicated by some overshoot of arterial at the end of each inspiration. «3 0-180. iiii&xafclii 11 ;.aa:.u!;ri.!--;!«e 1 min FIG. 1. The four stages of the Valsalva response, elicited from an anaesthetized ventilated patient. The traces from above downward show tracheal, high aortic and heart rate with an inverted scale. (From Blackburn et al., 1973.) at the onset of increased airway, and the decrease at its release, are direct reflections of the effects of changes in alveolar on pulmonary capillary Wood volume and left ventricular inflow. During phase n, the reduction in venous return causes a decrease in stroke volume, the effects of which are limited by the rapid Abnormal responses to increased intrathoracic The ability of the cardiovascular system to counteract the effects of an increased mean intrathoracic depends on the integrity of compensating reflexes. If these reflexes are absent or impaired, cardiac output and systemic arterial may decrease continuously when intrathoracic is increased, whilst restoration of intrathoracic to normal will often produce a slow recovery of arterial with no overshoot (fig. 2). The classical "blocked" Valsalva response is seen when the nervous pathways by which compensating reflexes act are interrupted, as in high spinal cord transection or severe polyneuritis. Compensation for increased airway may be impaired or absent in hypovolaemia (Maloney et al., 1953; Virtue, Caranna and Takaoka, 1961),

HAEMODYNAMIC EFFECTS OF PULMONARY VENTILATION 763 tion on gas exchange within the lungs severely limits its clinical application. The use of positive end-expiratory s has recently become popular in the ventilatory treatment of many respiratory disorders associated with impaired arterial oxygenation. A potential danger of such therapy is that the 200 increased mean intrathoracic so produced may cause reductions in cardiac output, which by 200 limiting oxygen supply to the tissues can outweigh the advantages of any improvement in arterial oxygenation (Uzawa and Ashbough, 1969; King, Jones and Patakas, 1973). Controlled hypotension is commonly induced with drugs such as ganglion blocking and betaadrenergic blocking agents which can affect the reflex responses to increased intrathoracic. Blackburn and colleagues (1973) showed that nor1 min mal responses to a Valsalva manoeuvre could commonly be elicited under light general anaesthesia in young healthy patients, even after the adminifig. 2. Blocked Valsalva response in a supine patient who stration of ganglion blocking and beta-adrenergic had received pentolinium 8 mg and was being ventilated blocking drugs. Doses of these drugs sufficient to with nitrous oxide, oxygen and 1% methoxyflurane. produce or potentiate clinical hypotension only produce partial pharmacological blockade. When sympathetic blockade (Sarnoff, Hardenbergh and the depth of anaesthesia was increased with either Whittenberger, 1948; Price, Conner and Dripps, halothane or methoxyflurane, an increasing propor1954), spinal anaesthesia (Sarnoff, Maloney and tion of their subjects showed blocked Valsalva Whittenberger, 1950), and moderate to deep responses. These workers also showed that the general anaesthesia (Price et al., 1951; Scott, Slaw- response to a Valsalva manoeuvre during clinically son and Taylor, 1969; Corbett, 1969). induced hypotension could be influenced by posmean intrathoracic during IPPV will be ture, presumably due to excessive pooling of blood a function of the duration of inspiration as com- in the lower portion of the body and a reduction pared with expiration, and the mean s dur- in effective circulating blood volume (fig. 3). The ing the two phases of respiration. Mean technique of deliberate hypotension which these will increase as the relative duration of inspiration workers studied relied on the interaction of a series is prolonged, and a high mean will also of factors general anaesthesia, ganglion and betabe produced if expiratory s are maintained adrenergic blockade, posture and maintained inabove atmospheric. Cournand and his co-workers creased airway to decrease arterial pres(1948) demonstrated the deleterious effects on sure. The level of mean intrathoracic cardiac output of their so-called "Type II" wave- offers, in these circumstances, a fine controlling form, in which inspiratory time exceeds expiratory mechanism over systemic arterial. time and a positive is applied during expiration. Conversely, application of a subarmo- Aberrant responses to increased intrathoracic spheric during expiration, by decreasing mean intrathoracic, will oppose reductions When a Valsalva manoeuvre is performed in a in cardiac output during IPPV. The use of a sub- patient in congestive failure, cardiac output and atmospheric phase during expiration has been systemic arterial may increase. The classic widely advocated in the past as a method of oppo- "top hat" or "square wave" response seen under sing untoward cardiovascular effects of clinical these circumstances is the result of an improvement IPPV, and most available ventilators have facilities in cardiac output consequent upon cardiac filling for application of such a "negative" phase. How-. This response only occurs in marked cases ever, the detrimental effects of this form of ventila- of congestive failure, when venous engorgement is

BRITISH JOURNAL OF ANAESTHESIA 764 PULSE Bnta/mln seen in its most marked form during the ventilator treatment of status asthmaticus, when s of 80-100 cm HjO may need to be applied to the airways to produce adequate ventilation. Under these circumstances, so long as high airways s are necessary to produce normal ventilatory exchange and therefore normal variations in intrathoracic, no deleterious cardiovascular effects will occur. Conversely, in the presence of severe restrictive lung disease, the high alveolar s necessary to cause lung expansion may have marked effects on cardiac performance. Arterial mmhg - -- PROPRANOLOL L Arterial mmhg PENTOUMim Arterial mmhg FIG. 3. Serial Valsalva responses in a 23-year-old patient anaesthetized with nitrous oxide, oxygen and phenoperidinc 1 mg. Left-hand column, supine; right-hand column, 30 degree head-up. Top row, postinduction; middle row, after propranolol 1.5 mg; bottom row, after propranolol 1.5 mg and pentolinium 7.5 mg (From Blackburn et al., 1973.) sufficient to prevent great veins from collapsing as intrathoracic increases. The pooling of blood outside the thorax, and consequent reduction in cardiac filling, permits the heart to work at a more effective point on its ventricular function curve. For this reason, IPPV often produces marked improvement in cardiac performance when initiated in patients in congestive failure. A second variant of the Valsalva response consists of a failure of increased airway to influence cardiac function, and is seen in patients with severe obstructive airways disease. For a applied at the upper airway to influence the circulation, it must be transmitted to the pulmonary capillaries. Any increase in airways resistance will increase the gradient across the airways and modify the acting on the pulmonary capillary bed. An absent Valsalva response is IPPV and pulmonary blood flow Under normal conditions, there are considerable differences of structure and function between the pulmonary and systemic circulatory systems. The systemic circulation is a high- system, whilst pulmonary artery is normally in the region of 20 mm Hg systolic. The pulmonary circulation can be considered as a series system with a single vascular bed, whilst the systemic system consists of a large number of parallel resistive elements. Control over the systemic circulation is such that marked alterations in the distribution of blood flow can be produced readily in response to a large number of differing stimuli. In the pulmonary circulation, whilst some autoregulation of blood flow can occur in response to changing oxygen concentrations, gravity is the major factor affecting distribution of blood within the lungs. Isotope scanning techniques have shown that, in the upright situation, blood flow increases progressively from the apex to the base of the lungs. West and his colleagues have given an elegant and widely accepted explanation of the influence of gravitational effects on the regional distribution of blood flow within the lungs. In the simplest form of the model they proposed (West, 1966), the lung was divided into three zones determined by the relative magnitudes of pulmonary arterial, venous and alveolar s. Zone 1 is at the uppermost or gravitationally least dependent portion of the lung, where pulmonary artery is less than alveolar and blood flow is absent. Below this, in zone 2, arterial exceeds alveolar, but alveolar is greater than pulmonary venous. This produces a situation in which flow is a function of the arterial-alveolar hydrostatic difference, and a reduction in this gradient leads to collapse of the venous end of the capillaries. Thus the vessels in zone 2 behave

HAEMODYNAMIC EFFECTS OF PULMONARY VENTILATION 765 as does the resistance in a Starling heart-lung preparation. Zone 3 consists of the most dependent parts of the lungs, where venous exceeds alveolar and flow depends on the arteriovenous hydrostatic difference. Zone 1 at the uppermost part of the lung, together with the uppermost part of zone 2, contains ventilated but unperfused alveoli which constitute alveolar deadspace. It has been well established that, during IPPV, there is an increased deadspace to tidal volume ratio, almost entirely caused by an increased alveolar deadspace (Campbell, Nunn and Peckett, 1958). Whilst VD/VE ratios normally have values lower than 0.3, Cooper (1967) showed that during anaesthesia and IPPV, much higher values were present. He gave an approximate formula relating deadspace to age in patients with normal lungs as: VD/VE%=33 + (Age/3) An attractive explanation of the increased physiological deadspace seen during IPPV, based on West's model, is that increased intra-alveolar during IPPV alters the balance, between alveolar, arterial and venous s within the lung. The increased alveolar during IPPV will tend to increase that area of the lung in which alveoli are being ventilated and not perfused (zone 1 and the upper portion of zone 2), and divert more blood to zone 3 at the most dependent part of the lung. A similar increase in alveolar deadspace can occur if pulmonary artery and pulmonary blood flow are reduced, as in haemorrhage (Freeman and Nunn, 1963), myocardial infarction (McNichol et al., 1964) and during deliberate hypotension (Eckenhoff et al., 1963). Here again, reduced perfusion of the upper parts of the lung would explain the phenomenon of increased deadspace. In the absence of undue alteration of the distribution of ventilation, and if alveolar ventilation is increased to maintain a normal arterial Pco I3 the large increase in deadspace produced by IPPV will not necessarily be associated with any increased venous admixture (West, 1974). However, as IPPV is often associated with alterations in regional pulmonary ventilation, tending to divert gas away from the dependent and towards the upper portions of the lung, marked ventilation-perfusion inequality, indicated by both an increased physiological deadspace and an increased venous admixture, can occur during clinical IPPV. REFERENCES Adams, A. P., Economides, A. P., Finlay, W. E. I., and Sykes, M. K. (1970). The effects of variations of inspiratory flow waveform on cardiorespiratory function during controlled ventilation in normo-, hypoand hypervolaemic dogs. Br. J. Anaesth., 42, 818. Bergman, N. A. (1963). Effect of different breathing patterns on alveolar-arterial gradient in dogs. J. Appl. Physiol., 18, 1049. (1967). Effects of varying respiratory waveforms on gas exchange. Anesthesiology, 28, 390. Blackburn, J. P., Conway, C M., Davies, R. M., Endcrby, G. E. H., Edridge, A. W., Leigh, J. M., Lindop, M. J., Phillips, G. D., and Strickland, D. A. P. (1973). Valsalva responses and systolic time intervals during anaesthesia and induced hypotension. Br. J. Anaesth., 45, 704. Campbell, E. J. M., Nunn, J. F., and Peckett, B. W. (1958). A comparison of artificial ventilation and spontaneous respiration with particular reference to ventilation-blood flow relationships. Br. J. Anaesth., 30, 166 Cooper, E. A. (1967). Physiological deadspace in passive ventilation. Anaesthesia, 22, 199. Corbett, J. L. (1969). Some aspects of the autonomic nervous system in health and disease. D.Phil, thesis, University of Oxford. Cournand, A., Motley, H. L., Werko, L., and Richards, D. W. (1948). Physiological studies on the effects of intermittent positive breathing on cardiac output in man Am. J. PhysioL, 152, 162. Eckenhoff, J. E., Enderby, G. E. H., Larson, A., Edridge, A., and Judevine, D. E. (1963). Pulmonary gas exchange during deliberate hypotension. Br. J. Anaesth., 35, 750. Fermoso, J. D., Richardson, T. Q., and Guyton, A. C. (1964). Mechanism of decrease in cardiac output caused by opening the chest. Am. J. Physiol., 207, 1112. Freeman, J., and Nunn, J. F. (1963). Ventilation-perfusion relationships after haemorrhage. Clin, Set., 24, 135. Hamilton, W. F., Woodbury, R. A., and Harper, H. T. (1936). Physiologic relationships between intrathoracic, intraspinal and arterial s. JA.MA., 147, 1201. King, E. G., Jones, R. L., and Patakas, D. A. (1973). Evaluation of positive end-expiratory therapy in the adult respiratory distress syndrome. Can. Anaesth. Soc. J., 20, 546. McNichol, M. W., Kirby, B. J., Everest, M. S., Freedman, S., and Bhoola, K. D. (1964). Circulatory and respiratory studies in myocardial infarction and cardiogenic shock. Lancet, 2, 1180. Maloney, J. V., Elam, J. O., Handford, S. W., Balk, G. A., Eastwood, D. W., Brown, E. S., and Ten Pas, R. H. (1953). Importance of negative phase in mechanical ventilators. JA.MA., 152, 212. Opie, L. H., Spalding, J. M. K., and Smith, A. C. (1961). Intrathoracic during intermittent positive respiration. Lancet, 1, 911. Price, H. L., Conner, E. H., and Dripps, R. D. (1954). Some respiratory and circulatory effects of mechanical respirators. J. Appl. Physiol., 6, 517. King, B. D., Elder, J. D., Libien, B. H., and Dripps, R. D. (1951). Circulatory effects of raised airway during cyclopropane anesthesia in man. J. Clin. Invest., 30, 1243. Prys-Roberts, C, Kelman, G. R., Greenbaum, R., and Robinson, R. H. (1967). Circulatory influences of artificial ventilation during nitrous oxide anaesthesia in man. II: Results; the relative influence of mean intrathoracic and arterial carbon dioxide tension. Br. J. Anaesth., 39, 533.

766 BRITISH JOURNAL OF ANAESTHESIA Sarnoff, S. J., Hardenbergh, E., and Whittenberger, J. L. (1948). Mechanism of the arterial response to the Valsalva test: the basis for its use as an indicator of the intactness of the sympathetic outflow. Am. J. Physiol, 154, 316. Maloney, J. K., and Whittenberger, J. L. (1950). Electrophrenic respiration. V: Effect on the circulation of electrophrenic respiration and positive breathing during the respiratory paralysis of high spinal anesthesia. Ann. Surg., 132, 921. Scott, D. B., Slawson, K. B., and Taylor, S. H. (1969). The circulatory effects of the Valsalva manoeuvre during anaesthesia and thoracotomy. Cardiovasc. Res.. 3, 331. Sharpey-Schafer, E. P. (1965). Effect of respiratory acts on the circulation; in Handbook of Physiology. Section 2, Circulation, Vol. 3, p. 1875. Washington, D.C.: Am. Physiol. Soc. Uzawa, T., and Ashbough, D. G. (1969). Continuous positive breathing in acute hemorrhagic pulmonary edema. J. Appl. Physiol., 26, 427. Virtue, R. W, Caranna, L. J., and Takaoka, K. (1961). The respiratory patterns and cardiac output. Br. J. Anaesth., 33, 77. Watson, W. E. (1962). Observations on physiological deadspace during intermittent positive respiration. Br. J. Anaesth., 34, 502. Smith, A. C, and Spalding, J. M. K. (1962). Transmural central venous during intermittent positive respiration. Br. J. Anaesth., 34, 278. West, J. B. (1966). Regional differences in blood flow and ventilation in the lung; in Advances in Respiratory Physiology (ed. C. G. Caro), p. 198. London: Edward Arnold. (1974). Ventilation Blood Flow and Gas Exchange. 2nd edn., p. 72. London: Blackwell.