Heart Lung Interactions

Transcription

1 Section 11 Respiratory Disorders Chapter 101 Heart Lung Interactions Michael R. Pinsky INTRODUCTION Perhaps the most obvious and least understood aspect of cardiopulmonary disease is the profound and intimate relation between cardiac and pulmonary dysfunction. Heart lung interactions go in both directions: they include the effect of the circulation on ventilation wherein acute ventricular failure causes hypoxemia and ischemic respiratory failure; and the effect of ventilation on circulation where hyperinflation can induce tamponade and spontaneous inspiration acute heart failure. Although, most references to heart lung interactions usually refer to the effect of ventilation on the circulation, the opposite interactions also exist and are relevant to the bedside clinician. Since the initial publication of this chapter in the 4th edition of this textbook in 2009 few new advances in our understanding of heart lung interactions have evolved, but several new applications of those principles have entered into clinical practice. Those changes are reflected in this version of the chapter. Heart lung interactions can be grouped into interactions that involve three basic concepts that usually coexist (1,2). First, spontaneous ventilation is exercise, requiring O2 and blood flow, thus placing demands on cardiac output, and producing CO2, adding additional ventilatory stress on CO2 excretion. Second, inspiration increases lung volume above resting endexpiratory volume. Thus, some of the hemodynamic effects of ventilation are due to changes in lung volume and chest wall expansion. Third, spontaneous inspiration decreases intrathoracic pressure (ITP); whereas positive- pressure ventilation increases ITP. Thus the differences between spontaneous ventilation and positive-pressure ventilation primarily reflect the differences in ITP swings and the energy n ecessary to produce them. THE EFFECTS OF CARDIOVASCULAR DYSFUNCTION ON VENTILATION Cardiogenic shock can induce hydrostatic pulmonary edema, causing, or worsening if extant, acute hypoxic respiratory failure. Furthermore, circulatory shock, by limiting blood flow to the respiratory muscles, can induce respiratory muscle failure and respiratory arrest. These points underscore a fundamental aspect of ventilation, namely that it is exercise, and like any form of exercise, it must place a certain metabolic demand on the cardiovascular system (3). If cardiovascular reserve is limited, this metabolic demand may exceed the heart s ability to deliver O2 to meet the increased metabolic activity a ssociated with spontaneous ventilation. Thus, ventilatordependent patients with cardiovascular insufficiency may not be able to wean from mechanical ventilation because the metabolic demand is too great. Failure to wean from mechanical ventilation often reflects cardiovascular insufficiency. Becuase the increased stress only occurs during the weaning trial, such insufficiency may not be apparent prior to weaning attempts. Under conditions of normal cardiovascular conditions, respiratory muscle blood flow is not the limiting factor determining maximal ventilatory effort even with marked respiratory efforts. Although ventilation normally requires less than 5% of total O2 consumption (3), if the work of breathing is increased, such as in pulmonary edema, pulmonary fibrosis, or bronchospasm, the work cost of breathing can increase to 25% of total O2 consumption (3 6). If cardiac output (CO) is limited, then blood flow to all organs- including the respiratory muscles may be compromised, inducing both tissue hypoperfusion and lactic acidosis (7 10). Under these severe heart failure conditions, respiratory muscle failure may develop despite high central neuronal drive (11). Supporting spontaneous ventilation by the use of mechanical ventilation will reduce O2 consumption, resulting in an increased SvO2 for a constant CO and arterial O2 content (CaO2). Thus, intubation and mechanical ventilation in patients in severe heart failure will not only decrease the work of breathing, but increased the available O2 delivery to other vital organs, decreasing serum lactate levels. These cardiovascular benefits are not limited to intubated patients but can also be seen with noninvasive ventilation mask continuous positive airway pressure (CPAP) (12). Ventilator-dependent patients who fail to wean during spontaneous breathing trials often have impaired baseline cardiovascular performance that may be apparent (13). More commonly, however, the patients develop overt signs of heart failure only during spontaneous breathing trials. The heart failure presentation can be dramatic, with the acute development of pulmonary edema (13,14), myocardial ischemia (15 18), tachycardia, and gut ischemia (19). Because breathing is exercise, all subjects will increase their CO in response to a spontaneous breathing trial. However, those that subsequently fail to wean demonstrate a reduction in mixed venous O2, consistent with a failing cardiovascular response to an increased metabolic demand (20). Importantly, the increased work of breathing may come from the endotracheal tube flow resistance (21). Thus, some subjects who fail a spontaneous breathing trial may actually be able to breathe on their own if extubated. Clearly, weaning from mechanical ventilatory support is a cardiovascular stress test. Numerous studies have 1265 LWBK1580_C101_p indd 1265

2 1266 Section 11 Respiratory Disorders documented weaning-associated ischemic ECG changes and thallium cardiac blood flow scan-related signs of ischemia in both subjects with known coronary artery disease (15) and those with normal coronaries (17,18). Using this same logic in reverse, placing patients with severe heart failure and/or ischemia on mechanical ventilatory support by either intubation and ventilation (22) or noninvasive CPAP (23) often reverses myocardial ischemia. Since weaning from artificial ventilatory support is cardiovascular stress, if a subject has reduced cardiovascular reserve, then their ability to wean may be impaired. Several recent studies have documented that they could predict which patients would fail a spontaneous breathing trial by indirect measures of their baseline cardiovascular reserve. Gruartmoner et al. (24) used the microvascular reoxygenation rate measured by noninvasive near infrared spectroscopy on the thenar eminence following a total blood pressure cuff hand vascular occlusion as a measure of cardiovascular reserve: a delayed reoxygenation rate reflecting impaired reserve. They showed that those patients with a delayed reoxygenation rate failed to wean from mechanical ventilation significantly more often than those with a normal reoxygenation rate. Similarly, Dres et al. (25) measured the ability of a ventilated patient to increase their CO by at least 10% in response to a passive leg-raising maneuver, as a measure of cardiovascular reserve. They showed that patients who could not increase their blood flow were more likely to not successfully wean from mechanical ventilation. HEMODYNAMIC EFFECTS OF VENTILATION AND VENTILATORY MANEUVERS Ventilation can profoundly alter cardiovascular function. The specific response seen will be dependent on myocardial reserve, circulating blood volume, blood flow distribution, autonomic tone, endocrinologic responses, lung volume, ITP, and the surrounding pressures for the remainder of the circulation (26,27). Relevant to this issue is the relation between airway pressure (Paw) and ITP: the transpulmonary pressure. Paw is relatively easy to measure (28,29), whereas ITP is not. Positive-pressure ventilation-induced increases in Paw do not necessarily equate to proportional increases in ITP. The primary determinants of the hemodynamic responses to ventilation are due to changes in ITP and lung volume (30), not Paw. The relation between Paw, ITP, pericardial pressure (Ppc) and lung volume varies with spontaneous ventilatory effort, lung and chest wall compliance. Lung expansion during positivepressure inspiration pushes on the surrounding structures distorting them and causing their surface pressures to increase, increasing lateral wall, diaphragmatic, juxtacardiac pleural pressure (Ppl) and Ppc (31). Only lung and thoracic compliance determine the relation between end-expiratory Paw and lung volume in the sedated and paralyzed patient. However, if a ventilated patient actively resist lung inflation or sustains expiratory muscle activity at end-inspiration, then end-inspiratory Paw will exceed resting Paw for that lung volume. Similarly, if the patient activity prevents full exhalation by expiratory breaking, then for the same end-expiratory Paw, lung volume may be higher than predicted from end-expiratory Paw values. At end-expiration, if the respiratory system is at rest, Paw equals alveolar pressure and lung volume is at functional residual capacity (FRC). If incomplete exhalation occurs, then alveolar pressure will exceed Paw. The difference between measured Paw and alveolar pressure is called intrinsic PEEP. Finally, if chest wall compliance decreases, as may occur with increased abdominal pressure, both Paw and ITP will increase for the same tidal breath. Since the heart is fixed within a cardiac fossa and cannot displace in any direction, juxtacardiac Ppl will increase more than lateral chest wall or diaphragmatic Ppl during inspiration. Ppc is the outside pressure to LV intraluminal ventricular pressure determining LV filling. Ppc and ITP may not be similar, nor increase by similar amounts with the application of positive Paw, if the pericardium acts as a limiting membrane (32,33). With pericardial restraint, as in tamponade, Ppc exceeds juxtacardiac Ppl (34). With progressive increases in PEEP, juxtacardiac Ppl will increase toward Ppc levels, whereas Ppc will initially remain constant. Once these two pressures equalize, further increases in PEEP by increasing lung volume will increase both juxtacardiac Ppl and Ppc in parallel. Thus, if pericardial volume restraint exists, as may occur with acute cor pulmonale or tamponade, then juxtacardiac Ppl will underestimate Ppc. The presence of lung parenchymal disease, airflow obstruction, and extra-pulmonary processes that directly alter chest wall diaphragmatic contraction or intra-abdominal pressure may also alter these interactions. Static lung expansion occurs as Paw increases because the transpulmonary pressure (Paw relative to ITP) increases. If lung injury induces alveolar flooding or increased pulmonary parenchyma stiffness, then greater increases in Paw will be required to distend the lungs to a constant end-inspiratory volume (9,31,35). Thus, the primary determinants of the increase in Ppl and Ppc during positive-pressure ventilation are lung volume change and chest wall compliance, not Paw change (36). Since acute lung injury (ALI) is often nonhomogeneous, with aerated areas of the lung displaying normal specific compliance, increases in Paw above approximately 30 cm H 2 O will overdistend these aerated lung units (37). Vascular structures that are distended will have a greater increase in their surrounding pressure than collapsible structures that do not distend (38). Despite this nonhomogeneous alveolar distention, if tidal volume is kept constant, then Ppl increases equally, independent of the mechanical properties of the lung (35,39,40). Thus, under constant tidal volume conditions, changes in peak and mean Paw will reflect changes in the mechanical properties of the lungs and patient coordination, but may not reflect changes in ITP. Thus, one cannot predict the amount of change in ITP or Ppc that will occur in a given patient as PEEP is varied. Accordingly, assuming some constant fraction of Paw transmission to the pleural surface as a means of calculating the effect of increasing Paw on ITP is inaccurate and potentially dangerous if used to assess transmural intrathoracic vascular pressures. However, if the patient has a pulmonary artery catheter in situ, then one can estimate end-expiratory ITP. The ability to measure on-peep intrathoracic vascular pressures by calculating the airway pressure transmission index to the pleural space (41) or by briefly removing PEEP while these pressures are directly measured (40) has been shown to be accurate under a variety of clinical conditions. The ratio of end-inspiratory to end-expiratory pulmonary artery diastolic pressure (reflecting ITP changes) to Paw (reflecting alveolar LWBK1580_C101_p indd 1266

3 chapter 101 Heart Lung Interactions 1267 pressure changes) defines the pulmonary transmission index. If one assumes that lung compliance is linear over the given tidal volume, then the product of this transmission index and PEEP represents the end-expiratory ITP. HEMODYNAMIC EFFECTS OF CHANGES IN LUNG VOLUME Changing lung volume alters autonomic tone, pulmonary vascular resistance and, at high lung volumes, compresses the heart in the cardiac fossa, limiting absolute cardiac volumes analogous to cardiac tamponade. However, unlike tamponade where Ppc selectively increases in excess of Ppl, with hyperinflation both juxtacardiac Ppl and Ppc increase together. Autonomic Tone Cyclic changes in lung volume induce cyclic changes in autonomic inflow. The lungs are richly enervated with integrated somatic and autonomic fibers that originate, traverse through, and end in the thorax. These neuronal pathways mediate many homeostatic processes through the autonomic nervous system that alter both instantaneous cardiovascular function and steady-state cardiovascular status (42,43). Lung inflation to normal tidal volumes (<8 ml/kg) induces parasympathetic withdrawal, increasing heart rate. This inspiration-induced cardioacceleration is referred to as respiratory sinus arrhythmia (44). The presence of respiratory sinus arrhythmia connotes normal autonomic control (45), and is used in diabetics with peripheral neuropathy to assess peripheral dysautonomia (46). Inflation to larger tidal volumes (>15 ml/kg) decreases heart rate by a combination of both increased vagal tone (47) and sympathetic withdrawal. The sympathetic withdrawal also creates arterial vasodilation (42,48 52). This inflation vasodilatation response induces expiration-associated reductions in LV contractility in healthy volunteers (53), and in ventilator-dependent patients with the initiation of high-frequency ventilation (42) or hyperinflation (50). Humeral factors, including compounds blocked by cyclooxygenase inhibition (54), released from pulmonary endothelial cells during lung inflation may also induce this depressor response (55 57). However, these interactions do not appear to grossly alter cardiovascular status (58). Although overdistention of aerated lung units in patients with ALI may induce such cardiovascular depression, unilateral lung hyperinflation (unilateral PEEP) does not appear to influence systemic hemodynamics (59). Thus, these cardiovascular effects are of uncertain clinical significance. Ventilation also compresses the right atrium and, through this mechanical effect, alters control of intravascular fluid balance. Both positive-pressure ventilation and sustained hyperinflation decrease right atrial stretch, stimulating endocrinologic responses that induce fluid retention. Plasma norepinephrine, plasma rennin activity (60,61), and atrial natriuretic peptide (62) increase during positive-pressure ventilation owing to right atrial collapse. Potentially, one of the benefits of the use of nasal CPAP in patients with CHF is to decrease plasma atrial natriuretic peptide activity in parallel with improvements in blood flow (63,64). Thus, some of the observed benefit of CPAP therapy in heart failure patients may be mediated through humoral mechanisms. Pulmonary Vascular Resistance Right ventricular (RV) ejection performance is much more limited by changes in ejection pressure than is LV ejection performance, because the right ventricle has thin walls that cannot distribute increased wall stress. Sudden increases in pulmonary vascular resistance, if associated with increases in pulmonary arterial pressure, can induce cardiovascular collapse. In this context, changing lung volume changes pulmonary vascular resistance. The mechanisms inducing these changes are often complex, often conflicting, and include both humoral and mechanical interactions. Increasing lung volume occurs because transpulmonary pressure increases. For example, although obstructive inspiratory efforts, as occur during obstructive sleep apnea, are usually associated with increased RV afterload, the increased afterload is due primarily to either increased vasomotor tone (hypoxic pulmonary vasoconstriction) or backward LV failure, and not lung volume induced changes in pulmonary vascular resistance (65,66). However, RV afterload increases with obstructive sleep apnea; since RV afterload can be defined as the maximal RV systolic wall stress during contraction (67), it is a function of the maximal product of the RV free wall radius of curvature (a function of end-diastolic volume) and transmural pressure (a function of systolic RV pressure) during ejection (68). Systolic RV pressure equals transmural pulmonary artery pressure (Ppa). Increases in transmural Ppa impede RV ejection (69), decreasing RV stroke volume (70), and inducing RV dilation and passive impedance to venous return (54,56). If not relieved quickly, acute cor pulmonale rapidly develops (71). Furthermore, if RV dilation and RV pressure overload persist, RV free wall ischemia and infarction can develop (72). Importantly, rapid fluid challenges in the setting of acute cor pulmonale can precipitate profound cardiovascular collapse due to excessive RV dilation, RV ischemia, and compromised LV filling. The pulmonary vasculature constricts if alveolar PO 2 (P A O 2 ) decreases below 60 mmhg (73). This process of hypoxic pulmonary vasoconstriction is mediated, in part, by variations in the synthesis and release of nitric oxide by endothelial nitric oxide synthase localized on pulmonary vascular endothelial cells and in part by an NAD/NADH voltage-dependent calcium channel in the pulmonary vasculature. Hypoxic pulmonary vasoconstriction, by reducing pulmonary blood flow to hypoxic lung regions, minimizes shunt blood flow. However, if generalized alveolar hypoxia occurs then pulmonary vasomotor tone increases, increasing pulmonary vascular resistance and impeding RV ejection (67). Importantly, at low lung volumes, alveoli spontaneously collapse as a result of loss of interstitial traction and closure of the terminal airways. This collapse causes both absorption atelectasis and alveolar hypoxia. Patients with acute hypoxemic respiratory failure have small lung volumes and are prone to spontaneous alveolar collapse (74,75). Therefore, pulmonary vascular resistance is often increased in patients with acute hypoxemic respiratory failure due to small lung volumes and atelectasis (e.g., ALI). Mechanical ventilation may reduce pulmonary vasomotor tone and pulmonary artery pressure, decreasing RV afterload by many related processes. First, hypoxic pulmonary vasoconstriction can be inhibited if O 2 -enriched inspired gas increases P A O 2 (76 79) or if the mechanical breaths and PEEP, by recruiting collapsed alveolar units, increases P A O 2 in those local alveoli (30,80 82). Second, mechanical ventilation often LWBK1580_C101_p indd 1267

4 1268 Section 11 Respiratory Disorders reverses respiratory acidosis by increasing alveolar ventilation, which itself stimulates pulmonary vasoconstriction (79). Finally, decreasing central sympathetic output by sedation during mechanical ventilation will also reduce vasomotor tone (59,83,84). Increases in lung volume directly increase pulmonary vascular resistance by compressing the alveolar vessels (74,81,82). The actual mechanisms by which this occurs have not been completely resolved, but appear to reflect differential extraluminal pressure gradient induced vascular compression. The pulmonary circulation can be conceptually viewed as existing in two distinct compartments based on the pressure outside, either alveolar pressure (alveolar vessels) or extra-alveolar or ITP (extra-alveolar vessels) (81). The small pulmonary arterioles, venules, and alveolar capillaries sense alveolar pressure as their surrounding pressure, whereas the large pulmonary arteries and veins, as well as the heart and intrathoracic great vessels of the systemic circulation, sense interstitial pressure or ITP as their surrounding pressure. Since alveolar pressure minus ITP is the transpulmonary pressure, and increasing lung volume requires transpulmonary pressure to increase, such increases in lung volume must increase the extraluminal pressure gradient from extra-alveolar vessels to alveolar vessels. Increases in lung volume progressively increase alveolar vessel resistance, becoming measurable above FRC (Fig ) (77,85). Since the intraluminal pressure in the pulmonary arteries is generated by RV ejection relative to ITP, but the outside pressure of the alveolar vessels is alveolar pressure, if transpulmonary pressure exceeds intraluminal pulmonary arterial pressure, then the pulmonary vasculature will collapse where extra-alveolar vessels pass into alveolar loci, reducing the vasculature cross-sectional area and increasing pulmonary vascular resistance. Hyperinflation can create significant pulmonary hypertension and may precipitate acute RV failure (acute cor pulmonale) (86) and RV ischemia (72) especially in patients prone to hyperinflation (e.g., COPD). Thus, PEEP may increase pulmonary vascular resistance if it induces lung overdistention (87). Similarly, if lung volumes are reduced, Pulmonary vascular resistance Hypoxic pulmonary vasoconstriction Alveolar compression Total PVR Alveolar vessels Extra-alveolar vessels RV FRC TLC Lung volume Figure Schematic diagram of the relation between changes in lung volume and pulmonary vascular resistance, where the extraalveolar and alveolar vascular components are separated. Note that pulmonary vascular resistance is minimal at resting lung volume or functional residual capacity (FRC). As lung volume increases toward total lung capacity (TLC) or decreases toward residual volume (RV), pulmonary vascular resistance also increases. However, the increase in resistance with hyperinflation is due to increased alveolar vascular resistance, whereas the increase in resistance with lung collapse is due to increased extra-alveolar vessel tone. increasing lung volume back to baseline levels by the use of PEEP decreases pulmonary vascular resistance by reversing hypoxic pulmonary vasoconstriction (88). Relevant to these findings, Vieillard-Baron et al. (89) reviewed their echocardiographic studies for all patients with acute respiratory distress syndrome (ARDS) on mechanical ventilation with PEEP before and after the era of protective lung ventilation, and found the incidence of acute right heart syndrome to be approximately 40% before protective lung ventilation, decreasing to approximately 25% afterward. Thus, protective lung ventilation by minimizing overdistention may limit acute cor pulmonale but does not eliminate it in ARDS patients. Ventricular Interdependence Although LV preload must eventually be altered by changes in RV output, because the two ventricles are in series, changes in RV end-diastolic volume can also alter LV preload by altering LV diastolic compliance by the mechanism of ventricular interdependence (90). Ventricular interdependence functions through two separate processes. First, increasing RV enddiastolic volume will induce an intraventricular septal shift into the LV, decreasing LV diastolic compliance (91). Thus, for the same LV filling pressure, RV dilation will decrease LV end-diastolic volume and, therefore, CO. Second, if pericardial restraint limits absolute biventricular filling, then RV dilation will increase Ppc without septal shift (2,92). This ventricular interaction is believed to be the major determinant of the phasic changes in arterial pulse pressure and stroke volume seen in tamponade, and is referred to as pulsus paradoxus. Pulsus paradoxus can be demonstrated during loaded spontaneous inspiration in normal subjects as an inspiration-associated decrease is pulse pressure. Maintaining a constant rate of venous return, either by volume resuscitation (93) or vasopressor infusion (29) will minimize hyperinflation-induced cardiac compression. Hyperinflation-Induced Cardiac Compression As lung volume increases, the heart is compressed between the expanding lungs (94), increasing juxtacardiac ITP. This compressive effect of the inflated lungs can be seen with either spontaneous (95) or positive-pressure induced hyperinflation (5,40,96 98). As described above, both Ppc and ITP are increased and no pericardial restraint exists. This decrease in apparent LV diastolic compliance (93) was previously misinterpreted as impaired LV contractility, because LV stroke work for a given LV end-diastolic pressure or pulmonary artery occlusion pressure is decreased (99,100). However, when such patients are fluid resuscitated to return LV end-diastolic volume to its original level, both LV stroke work and CO also returned to their original levels (93,101) despite the continued application of PEEP (102). HEMODYNAMIC EFFECTS OF CHANGES IN INTRATHORACIC PRESSURE The heart within the thorax is a pressure chamber within a pressure chamber. Therefore, changes in ITP will affect the LWBK1580_C101_p indd 1268

5 chapter 101 Heart Lung Interactions 1269 pressure gradients for both systemic venous return to the RV and systemic outflow from the LV, independent of the heart itself. Increases in ITP, by increasing right atrial pressure and decreasing transmural LV systolic pressure, will reduce the pressure gradients for venous return and LV ejection, decreasing intrathoracic blood volume. Using the same argument, decreases in ITP will augment venous return and impede LV ejection and increase intrathoracic blood volume; everything else follows from these simple truths. Venous Return LV pressure (mmhg) RV volume (ml) Blood flows back from the systemic venous reservoirs into the right atrium through low pressure low resistance venous conduits (103). Right atrial pressure is the backpressure for venous return; ventilation alters both right atrial pressure and venous reservoir pressure. It is these changes in right atrial and venous capacitance vessel pressure that induce most of the observed cardiovascular effects of ventilation. Pressure in the upstream venous reservoirs is called mean systemic pressure and is, itself, a function of blood volume, peripheral vasomotor tone, and the distribution of blood within the vasculature (104). Usually mean systemic pressure does not change rapidly during positive-pressure ventilation, whereas right atrial pressure does owing to concomitant changes in ITP. Thus, variations in right atrial pressure represent the major factor determining the fluctuation in pressure gradient for systemic venous return during ventilation (105,106). The positive-pressure inspiration increases in right atrial pressure, decreases the pressure gradient for venous return, decreasing RV filling (70) and RV stroke volume (70,105, ). During normal spontaneous inspiration, the opposite occurs (2,29,70,71,109,112,116,117). The detrimental effect of positive-pressure ventilation on CO can be minimized by either fluid resuscitation to increase mean systemic pressure (29,107,118,119) or by keeping both mean ITP and swings in lung volume as low as possible. Accordingly, prolonging expiratory time, decreasing tidal volume, and avoiding PEEP all minimize this decrease in systemic venous return to the RV (4,26,105, ,120). However, if positive-pressure ventilation-induced increases in right atrial pressure always proportionally decreased venous return, then most patients would display profound cardiovascular insufficiency when placed on mechanical ventilator support and especially so when given increased levels of PEEP. Fortunately, when lung volumes increase, the diaphragm descends, compressing the abdominal compartment and increasing intra-abdominal pressure (121,122). Since a large proportion of venous blood exists in intra-abdominal vasculature, it is pressurized as well, increasing mean systemic pressure. Accordingly, the pressure gradient for venous return is often not reduced by PEEP (118). Inspiration-induced abdominal pressurization by diaphragmatic descent is probably the primary mechanism by which the decrease in venous return is minimized during positive-pressure ventilation ( ). However, laparotomy, by abolishing the inspiration-associated increases in intra-abdominal pressure, makes surgery patients especially sensitive to mechanical ventilation and is one of the reasons why abdominal surgery patients often leave the operating room many liters positive. Spontaneous inspiratory efforts usually increase venous return because of the combined decrease in right atrial LV volume (ml) Figure Schematic diagram of the effect of increasing right ventricular (RV) volumes on the left ventricular (LV) diastolic pressure volume (filling) relationship. Note that increasing RV volumes decrease LV diastolic compliance, such that a higher filling pressure is required to generate a constant end-diastolic volume. (Adapted from Taylor RR, Covell JW, Sonnenblick EH, Ross J Jr. Dependence of ventricular distensibility on filling the opposite ventricle. Am J Physiol. 1967;213: ) pressure (2,28, ) and increase in intra-abdominal pressure (121,122), described above. However, this augmentation of venous return is limited (129,130) because as ITP decreases below atmospheric pressure, central venous pressure also becomes subatmospheric, collapsing the great veins as they enter the thorax and creating a flow-limiting segment (103). Ventricular Interdependence Since spontaneous inspiration increases RV filling, it will also directly alter LV diastolic compliance by the process of ventricular interdependence. Increasing RV volume decreases LV diastolic compliance, while decreasing RV volume increases LV diastolic compliance, although the positive-pressure ventilation effect of increased LV diastolic compliance is usually minimal (Fig ) (90, ). However, the spontaneous inspiration-induced RV volume increase reduces the LV diastolic compliance and is the primary cause for the inspiration-associated decrease in LV stroke volume and pulse pressure (89,91,134,135). If the pulse pressure change is greater than 10 mmhg, or 10% of the mean pulse pressure, then it is referred to as pulsus paradoxus (2). Since spontaneous inspiratory efforts can also occur during positive-pressure ventilation, the use of ventilation-associated pulse pressure variation (PPV) during positive-pressure ventilation can reflect ventricular interdependence. Presently, positive-pressure induced changes in pulse pressure and LV stroke volume have been advocated to be a useful parameter of preload-responsiveness (136). However, in order to assess volume responsiveness using PPV, it is essential that no spontaneous inspiratory efforts be present. These points are discussed in greater detail in the next section. Changes in ITP can directly and indirectly alter LV afterload by altering both LV end-diastolic volume and ejection pressure. LV ejection pressure can be estimated as arterial pressure relative to ITP. Since baroreceptor mechanisms located in the extrathoracic carotid body maintain arterial pressure constant relative to atmosphere, if arterial pressure were to remain constant as ITP increased, then transmural LV pressure and thus LWBK1580_C101_p indd 1269

6 1270 Section 11 Respiratory Disorders LV afterload would decrease. Similarly, if transmural arterial pressure were to remain constant as ITP decreased then LV wall tension would increase (137). Thus, under steadystate conditions, increases in ITP decrease LV afterload and decreases in ITP increase LV afterload (138,139). The spontaneous inspiration-associated decrease in ITP-induced increase in LV afterload is one of the major mechanisms thought to be operative in the wean-induced LV ischemia described in the first part of this chapter, since increased LV afterload must increase myocardial O 2 consumption (MVO 2 ). Thus, spontaneous ventilation not only increases global O 2 demand by its exercise component (3 5), but also increases MVO 2. Profoundly negative swings in ITP commonly occur during forced spontaneous inspiratory efforts in patients with bronchospasm and obstructive breathing. This condition may rapidly deteriorate into acute heart failure and pulmonary edema (65), as has been described for airway obstruction (asthma, upper airway obstruction, vocal cord paralysis) or stiff lungs (interstitial lung disease, pulmonary edema, and ALI), as these swings may selectively increase LV afterload and may be the cause of the LV failure and pulmonary edema (1,51,65,66) seen, especially if LV systolic function is already compromised (13,140). Clearly, weaning from mechanical ventilation is a selective LV stress test (137,141,142). Similarly, improved LV systolic function is observed in patients with severe LV failure placed on mechanical ventilation (142). The improvement in LV functional seen with positivepressure ventilation in subjects with severe heart failure is selflimited, because venous return also decreases, limiting total blood flow. However, the effect of removing large negative swings of ITP on LV performance will also act to reduce LV afterload, but will not be associated with a change in venous return because, until ITP becomes positive, venous return remains constant. Thus, removing negative ITP swings on LV afterload will selectively reduce LV afterload in a fashion analogous to increasing ITP, but without the effect on CO (23,29,103, ). This concept has been validated to be a very important clinical approach for patients with obstructive sleep apnea. For example, the cardiovascular benefits of positive airway pressure in nonintubated patients can be seen with CPAP therapy for heart failure patients (146,147). Even low levels of CPAP, if they inhibit airway obstruction, will be beneficial (148,149). Prolonged nighttime nasal CPAP can selectively improve respiratory muscle strength, as well as LV contractile function if the patients have pre-existent heart failure (150,151); these benefits are associated with reductions of serum catecholamine levels (152). Furthermore, CPAP therapy now forms the fundamental first step in the management of acute cardiogenic pulmonary edema, because it both abolishes the negative swings in ITP during inspiration while sustaining alveolar oxygenation, and it does this from the very first breath it delivers (153,154). USING HEART LUNG INTERACTIONS TO DIAGNOSE CARDIOVASCULAR INSUFFICIENCY Since the cardiovascular response to positive-pressure breathing is determined by the baseline cardiovascular state, ventilation-associated changes in arterial pulse pressure and stroke volume should be inferential for dynamic changes in venous return and the responsiveness of the heart to these transient and cyclic changes in preload (155). Both arterial pulse pressure (diastole to systole) and systolic pressure variations during positive-pressure ventilation nicely describe preload-responsiveness, with threshold values of greater than 10% variability compared to mean values in a patient on 8 ml/kg or more, adapted to the ventilation and without dysrhythmias (136). This technique can be modified to assess stroke volume variation (SVV) (156) and has profound clinical potential as newer monitoring devices allow for the bedside display of both PPV and SVV. In subjects on controlled mechanical ventilation, a PPV of more than 13% or an SVV of more than 10% accurately predict preloadresponsiveness. Since a primary cardiovascular management decision in shock is whether or not to give intravascular fluids to increase blood flow (157), knowing if a patient is volume responsive before giving fluids will both prevent overhydration of nonresponsive patients and aid in monitoring the response to fluid resuscitation in responsive ones. This approach has been termed functional hemodynamic monitoring because it uses a repetitive known physiologic perturbation to drive a readout physiologic signal defining cardiovascular reserve. This application of heart lung interactions has been validated in many prospective clinical trials, reviewed in a meta-analysis (158). This practical application of heart lung interactions is now commonplace. Importantly, a basic understanding of the principles described in this chapter is an essential part of the training of acute care physicians. For example, the ITP-induced PPV and SVV, caused by the positive pressure breath, would be inaccurate if tidal volume were to vary from breath to breath. Similarly, if chest wall compliance were to decrease, owing to increased intraabdominal pressure limiting diaphragmatic descent, then the accuracy of these measures would also decline. Many functional hemodynamic monitoring approaches take advantage of these dynamic transients to measure either the capacity of the ventricles to fill as the pressure gradient for ventricular filling changes, or for the ventricles to proportionally eject this varying amount of volume (159). As described above, both spontaneous and positive-pressure breathing, by altering the pressure gradients for venous return to the right ventricle, can be used to assess both right and left ventricular preload reserve (160). For dynamic changes in venous return to alter LV stroke volume or arterial pulse pressure, then both RV and LV preload reserve need to be present. Dynamic venous flow changes during spontaneous and positive-pressure ventilation identify RV preload reserve, and can be measured indirectly by the dynamic changes in inferior vena caval (161), superior vena caval (162), and internal jugular venous diameters (163). Threshold values above 10% to 15% change in diameter define volume-responsiveness. Because both SVV and PPV sensitivity degrade during spontaneous ventilation, low tidal volume ventilation, severe cor pulmonale and other extremes of physiology (164), alterative tests have been proposed. Specifically, performing passive legraising maneuvers to transiently increase venous return while concomitantly monitoring transient changes in left-sided CO is very sensitive and specific predictor of volume responsiveness under most conditions (165). It also becomes inaccurate when intra-abdominal hypertension exists because the pressure gradient for venous return is altered less (166). LWBK1580_C101_p indd 1270

7 chapter 101 Heart Lung Interactions 1271 Key Points Spontaneous ventilation is exercise. Failure to wean may connote cardiovascular insufficiency. Weaning is a cardiovascular stress test. Breathing loads both the heart and lungs. Changes in lung volume alter autonomic tone, pulmonary vascular resistance, and at high lung volumes compress the heart in the cardiac fossa in a fashion analogous to cardiac tamponade. Low lung volumes increase pulmonary vasomotor tone by stimulating hypoxic pulmonary vasoconstriction. High lung volumes increase pulmonary vascular resistance by increasing transpulmonary pressure. Spontaneous inspiration and spontaneous inspiratory efforts decrease intrathoracic pressure. Increasing venous return. Increasing LV afterload. Positive-pressure ventilation increases intrathoracic pressure. Decreasing venous return. The decrease in venous return is mitigated by the associated increase in intra-abdominal pressure. Decreasing LV afterload. Abolishing negative swings in ITP selectively reduces LV afterload without reducing venous return. Acknowledgments Supported in part by the NIH grants HL074316, HL HL07820, and NR References 1. Bromberger-Barnea B. Mechanical effects of inspiration on heart functions: a review. Fed Proc. 1981;40: Wise RA, Robotham JL, Summer WR. Effects of spontaneous ventilation on the circulation. Lung. 1981;159: Roussos C, Macklem PT. The respiratory muscles. N Engl J Med. 1982; 307: Grenvik A. Respiratory, circulatory and metabolic effects of respiratory treatment. Acta Anaesthesiol (19 Suppl): Shuey CB, Pierce AK, Johnson RL. An evaluation of exercise tests in chronic obstructive lung disease. J Appl Physiol. 1969;27: Stock MC, David DW, Manning JW, Ryan ML. Lung mechanics and oxygen consumption during spontaneous ventilation and severe heart failure. Chest. 1992;102: Kawagoe Y, Permutt S, Fessler HE. Hyperinflation with intrinsic PEEP and respiratory muscle blood flow. J Appl Physiol (1985). 1994;77: Aubier M, Vires N, Sillye G, et al. Respiratory muscle contribution to lactic acidosis in low cardiac output. Am Rev Respir Dis. 1982;126: Frazier SK, Stone KS, Schertel ER, et al. A comparison of hemodynamic changes during the transition from mechanical ventilation to T-piece, pressure support, and continuous positive airway pressure in canines. Biol Res Nurs. 2000;1: Magder S, Erian R, Roussos C. Respiratory muscle blood flow in oleic acid-induced pulmonary edema. J Appl Physiol. 1986;60: Vires N, Sillye G, Rassidakis A, et al. Effect of mechanical ventilation on respiratory muscle blood flow during shock. Physiologist. 1980;23: Baratz DM, Westbrook PR, Shah K, Mohsenifar Z. Effects of nasal continuous positive airway pressure on cardiac output and oxygen delivery in patients with congestive heart failure. Chest. 1992;102: Lemaire F, Teboul JL, Cinoti J, et al. Acute left ventricular dysfunction during unsuccessful weaning from mechanical ventilation. Anesthesiology. 1988;69: Richard C, Teboul JL, Archambaud F, et al. Left ventricular dysfunction during weaning in patients with chronic obstructive pulmonary disease. Intensive Care Med. 1994;20: Hurford WE, Lynch KE, Strauss HW, et al. Myocardial perfusion as assessed by thallium-201 scintigraphy during the discontinuation of mechanical ventilation in ventilator-dependent patients. Anesthesiology. 1991;74: Abalos A. Leibowitz AB, Distefano D, et al. Myocardial ischemia during the weaning period. Am J Crit Care. 1992;1: Chatila W, Ani S, Guaglianone D, et al. Cardiac ischemia during weaning from mechanical ventilation. Chest. 1996;109: Srivastava S, Chatila W, Amoateng-Adjepong Y, et al. Myocardial ischemia and weaning failure in patients with coronary disease: an update. Crit Care Med. 1999;27: Mohsenifar Z, Hay A, Hay J, et al. Gastric intramural ph as a predictor of success or failure in weaning patients from mechanical ventilation. Ann Intern Med. 1993;119: Jabran A, Mathru M, Dries D, Tobin MJ. Continuous recordings of mixed venous oxygen saturation during weaning from mechanical ventilation and the ramifications thereof. Am J Respir Crit Care Med. 1998; 158: Straus C, Lewis B, Isebey D, et al. Contribution of the endotracheal tube and the upper airway to breathing workload. Am J Respir Crit Care Med. 1998;157: Rasanen J, Nikki P, Heikkila J. Acute myocardial infarction complicated by respiratory failure: the effects of mechanical ventilation. Chest. 1984;85: Rasanen J, Vaisanen IT, Heikkila J, et al. Acute myocardial infarction complicated by left ventricular dysfunction and respiratory failure: the effects of continuous positive airway pressure. Chest. 1985;87: Gruartmoner G, Mesquida J, Masip J, et al. Tissue oxygen saturation (StO 2 ) during weaning from mechanical ventilation: an observational study. Eur Respir J. 2014;43: Dres M, Teboul JL, Anguel N, et al. Passive leg raising performed before a spontaneous breathing trial predicts weaning-induced cardiac dysfunction. Intensive Care Med. 2015;41: Cournaud A, Motley HL, Werko L, et al. Physiologic studies of the effect of intermittent positive pressure breathing on cardiac output in man. Am J Physiol. 1948;152: Tyberg JV, Grant DA, Kingma I, et al. Effects of positive intrathoracic pressure on pulmonary and systemic hemodynamics. Respir Physiol. 2000;119: Milic-Emili J, Mead J, Turner JM, Glauser EM. Improved method for assessing the validity of the esophageal balloon technique. J Appl Physiol. 1964;19: Braunwald E, Binion JT, Morgan WL Jr, Sarnoff SJ. Alterations in central blood volume and cardiac output induced by positive pressure breathing and counteracted by metraminol (Aramine). Circ Res. 1957;5: Whittenberger JL, McGregor M, Berglund E, Borst HG. Influence of state of inflation of the lung on pulmonary vascular resistance. J Appl Physiol. 1960;15: Novak RA, Matuschak GM, Pinsky MR. Effect of ventilatory frequency on regional pleural pressure. J Appl Physiol. 1988;65: Kingma I, Smiseth OA, Frais MA, et al. Left ventricular external constraint: relationship between pericardial, pleural and esophageal pressures during positive end-expiratory pressure and volume loading in dogs. Ann Biomed Eng. 1987;15: Tsitlik JE, Halperin HR, Guerci AD, et al. Augmentation of pressure in a vessel indenting the surface of the lung. Ann Biomed Eng. 1987; 15: Pinsky MR, Guimond JG. The effects of positive end- expiratory pressure on heart-lung interactions. J Crit Care. 1991;6: Romand JA, Shi W, Pinsky MR. Cardiopulmonary effects of positive pressure ventilation during acute lung injury. Chest. 1995;108: O Quinn RJ, Marini JJ, Culver BH, et al. Transmission of airway pressure to pleural pressure during lung edema and chest wall restriction. J Appl Physiol. 1985;59: Gattinoni L, Mascheroni D, Torresin A, et al. Morphological response to positive end-expiratory pressure in acute respiratory failure. Intensive Care Med. 1986;12: Globits S, Burghuber OC, Koller J, et al. Effect of lung transplantation on right and left ventricular volumes and function measured by magnetic resonance imaging. Am J Respir Crit Care Med. 1994;149: Scharf SM, Ingram RH Jr. Effects of decreasing lung compliance with oleic acid on the cardiovascular response to PEEP. Am J Physiol. 1977; 233:H635 H Pinsky MR, Vincent JL, DeSmet JM. Estimating left ventricular filling pressure during positive end-expiratory pressure in humans. Am Rev Respir Dis. 1991;143: LWBK1580_C101_p indd 1271

8 1272 Section 11 Respiratory Disorders 41. Teboul JL, Pinsky MR, Mercat A, et al. Estimating cardiac filling pressure in mechanically ventilated patients with hyperinflation. Crit Care Med. 2000;28: Glick G, Wechsler AS, Epstein DE. Reflex cardiovascular depression produced by stimulation of pulmonary stretch receptors in the dog. J Clin Invest. 1969;48: Painal AS. Vagal sensory receptors and their reflex effects. Physiol Rev. 1973;53: Anrep GV, Pascual W, Rossler R. Respiratory variations in the heart rate. I. The reflex mechanism of the respiratory arrhythmia. Proc R Soc Lond B Biol Sci. 1936;119: Taha BH, Simon PM, Dempsey JA, et al. Respiratory sinus arrhythmia in humans: an obligatory role for Vagal feedback from the lungs. J Appl Physiol (1985). 1995;78: Bernardi L, Calciati A, Gratarola A, et al. Heart rate-respiration relationship: computerized method for early detection of cardiac autonomic damage in diabetic patients. Acta Cardiol. 1986;41: Persson MG, Lonnqvist PA, Gustafsson LE. Positive end-expiratory pressure ventilation elicits increases in endogenously formed nitric oxide as detected in air exhaled by rabbits. Anesthesiology. 1995;82: Cassidy SS, Eschenbacher WI, Johnson RL Jr. Reflex cardiovascular depression during unilateral lung hyperinflation in the dog. J Clin Invest. 1979;64: Daly MB, Hazzledine JL, Ungar A. The reflex effects of alterations in lung volume on systemic vascular resistance in the dog. J Physiol. 1967; 188: Shepherd JT. The lungs as receptor sites for cardiovascular regulation. Circulation. 1981;63: Stalcup SA, Mellins RB. Mechanical forces producing pulmonary edema in acute asthma. N Engl J Med. 1977;297: Vatner SF, Rutherford JD. Control of the myocardial contractile state by carotid chemo- and baroreceptor and pulmonary inflation reflexes in conscious dogs. J Clin Invest. 1978;63: Karlocai K, Jokkel G, Kollai M. Changes in left ventricular contractility with the phase of respiration. J Auton Nerv Syst. 1998;73: Said SI, Kitamura S, Vreim C. Prostaglandins: release from the lung during mechanical ventilation at large tidal ventilation. J Clin Invest. 1972; 51:83a. 55. Bedetti C, Del Basso P, Argiolas C, Carpi A. Arachidonic acid and pulmonary function in a heart-lung preparation of guinea-pig: modulation by PCO 2. Arch Int Pharmacodyn Ther. 1987;285: Berend N, Christopher KL, Voelkel NF. Effect of positive end- expiratory pressure on functional residual capacity: role of prostaglandin production. Am Rev Respir Dis. 1982;126: Pattern MY, Liebman PR, Hetchman HG. Humorally mediated decreases in cardiac output associated with positive end-expiratory pressure. Microvasc Res. 1977;13: Berglund JE, Halden E, Jakobson S, Svensson J. PEEP ventilation does not cause humorally mediated cardiac output depression in pigs. Intensive Care Med. 1994;20: Fuhrman BP, Everitt J, Lock JE. Cardiopulmonary effects of unilateral airway pressure changes in intact infant lambs. J Appl Physiol Respir Environ Exerc Physiol. 1984;56: Payen DM, Brun-Buisson CJ, Carli PA, et al. Hemodynamic, gas exchange, and hormonal consequences of LBPP during PEEP ventilation. J Appl Physiol. 1987;62: Frage D, de la Coussaye JE, Beloucif S, et al. Interactions between hormonal modifications during PEEP-induced antidiuresis and antinatriuresis. Chest. 1995;107: Frass M, Watschinger B, Traindl O, et al. Atrial natrituretic peptide release in response to different positive end-expiratory pressure levels. Crit Care Med. 1993;21: Wilkins MA, Su XL, Palayew MD, et al. The effects of posture change and continuous positive airway pressure on cardiac natriuretic peptides in congestive heart failure. Chest. 1995;107: Shirakami G, Magaribuchi T, Shingu K, et al. Positive end-expiratory pressure ventilation decreases plasma atrial and brain natriuretic peptide levels in humans. Anesth Analg. 1993;77: Fletcher EC, Proctor M, Yu J, et al. Pulmonary edema develops after recurrent obstructive apneas. Am J Respir Crit Care Med. 1999;160: Chen L, Shi Q, Scharf SM. Hemodynamic effects of periodic obstructive apneas in sedated pigs with congestive heart failure. J Appl Physiol. 2000;88: Maughan WL, Shoukas AA, Sagawa K, Weisfeldt ML. Instantaneous pressure-volume relationships of the canine right ventricle. Circ Res. 1979; 44: Sibbald WJ, Driedger AA. Right ventricular function in disease states: pathophysiologic considerations. Crit Care Med. 1983;11: Piene H, Sund T. Does pulmonary impedance constitute the optimal load for the right ventricle? Am J Physiol. 1982;242:H154 H Pinsky MR. Determinants of pulmonary arterial flow variation during respiration. J Appl Physiol. 1984;56: Theres H, Binkau J, Laule M, et al. Phase-related changes in right ventricular cardiac output under volume-controlled mechanical ventilation with positive end-expiratory pressure. Crit Care Med. 1999;27: Johnston WE, Vinten-Johansen J, Shugart HE, Santamore WP. Positive end-expiratory pressure potentates the severity of canine right ventricular ischemia-reperfusion injury. Am J Physiol. 1992;262:H168 H Madden JA, Dawson CA, Harder DR. Hypoxia-induced activation in small isolated pulmonary arteries from the cat. J Appl Physiol. 1985;59: Hakim TS, Michel RP, Chang HK. Effect of lung inflation on pulmonary vascular resistance by arterial and venous occlusion. J Appl Physiol. 1982;53: Quebbeman EJ, Dawson CA. Influence of inflation and atelectasis on the hypoxic pressure response in isolated dog lung lobes. Cardiovas Res. 1976;10: Brower RG, Gottlieb J, Wise RA, et al. Locus of hypoxic vasoconstriction in isolated ferret lungs. J Appl Physiol. 1987;63: Hakim TS, Michel RP, Minami H, Chang K. Site of pulmonary hypoxic vasoconstriction studied with arterial and venous occlusion. J Appl Physiol. 1983;54: Marshall BE, Marshall C. A model for hypoxic constriction of the pulmonary circulation. J Appl Physiol. 1988;64: Marshall BE, Marshall C. Continuity of response to hypoxic pulmonary vasoconstriction. J Appl Physiol. 1980;49: Dawson CA, Grimm DJ, Linehan JH. Lung inflation and longitudinal distribution of pulmonary vascular resistance during hypoxia. J Appl Physiol Respir Environ Exerc Physiol. 1979;47: Howell JB, Permutt S, Proctor DF, et al. Effect of inflation of the lung on different parts of the pulmonary vascular bed. J Appl Physiol. 1961; 16: West JB, Dollery CT, Naimark A. Distribution of blood flow in isolated lung: relation to vascular and alveolar pressures. J Appl Physiol. 1964;19: Fuhrman BP, Smith-Wright DL, Kulik TJ, Lock JE. Effects of static and fluctuating airway pressure on the intact, immature pulmonary circulation. J Appl Physiol. 1986;60: Thorvalson J, Ilebekk A, Kiil F. Determinants of pulmonary blood volume: effects of acute changes in airway pressure. Acta Physiol Scand. 1985;125: Lopez-Muniz R, Stephens NL, Bromberger-Barnea B, et al. Critical closure of pulmonary vessels analyzed in terms of Starling resistor model. J Appl Physiol. 1968;24: Block AJ, Boyson PG, Wynne JW. The origins of cor pulmonale, a hypothesis. Chest. 1979;75: Vieillard-Baron A, Loubieres Y, Schmitt JM, et al. Cyclic changes in right ventricular output impedance during mechanical ventilation. J Appl Physiol. 1999;87: Canada E, Benumnof JL, Tousdale FR. Pulmonary vascular resistance correlated in intact normal and abnormal canine lungs. Crit Care Med. 1982;10: Vieillard-Baron A, Schmitt JM, et al. Acute cor pulmonale in acute respiratory distress syndrome submitted to protective ventilation: incidence, clinical implications, and prognosis. Crit Care Med. 2001;29: Taylor RR, Corell JW, Sonnenblick EH, Ross J Jr. Dependence of ventricular distensibility on filling the opposite ventricle. Am J Physiol. 1967;213: Brinker JA, Weiss I, Lappe DL, et al. Leftward septal displacement during right ventricular loading in man. Circulation. 1980;61: Takata M, Harasawa Y, Beloucif S, Robotham JL. Coupled vs. uncoupled pericardial restraint: effects on cardiac chamber interactions. J Appl Physiol. 1997;83: Marini JJ, Culver BN, Butler J. Mechanical effect of lung distention with positive pressure on cardiac function. Am Rev Respir Dis. 1980; 124: Butler J. The heart is in good hands. Circulation. 1983;67: Cassidy SS, Wead WB, Seibert GB, Ramanathan M. Changes in left ventricular geometry during spontaneous breathing. J Appl Physiol. 1987;63: Hoffman EA, Ritman EL. Heart lung interaction: effect on regional lung air content and total heart volume. Ann Biomed Eng. 1987;15: LWBK1580_C101_p indd 1272