chapter 101chapter 101 heart–lung interactions 1267 pressure changes) defines the pulmonary...

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Section 11 RespiRatoRy DisoRDeRs

Chapter

101Heart–Lung interactionsMichael R. Pinsky

intRoDUction

Perhaps the most obvious and least understood aspect of car-diopulmonary 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 end-expiratory volume. Thus, some of the hemodynamic effects of ventilation are due to changes in lung volume and chest wall expansion. Third, spontaneous inspiration decreases intra-thoracic pressure (ITP); whereas positive- pressure ventilation increases ITP. Thus the differences between spontaneous ven-tilation and positive-pressure ventilation primarily reflect the differences in ITP swings and the energy necessary 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 fail-ure. 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 associated with spontaneous ventilation. Thus, ventilator-dependent patients with cardiovascular insufficiency may not be able to wean from mechanical ventilation because the meta-bolic 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 deter-mining maximal ventilatory effort even with marked respira-tory 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 respi-ratory 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 sponta-neous 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 venti-lation 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 devel-opment of pulmonary edema (13,14), myocardial ischemia (15–18), tachycardia, and gut ischemia (19). Because breath-ing is exercise, all subjects will increase their CO in response to a spontaneous breathing trial. However, those that subse-quently 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

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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 isch-emia 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 car-diovascular 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. Gruart-moner 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 circu-lation (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 venti-lation 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 positive-pressure inspiration pushes on the surrounding structures dis-torting them and causing their surface pressures to increase, increasing lateral wall, diaphragmatic, juxtacardiac pleural pressure (Ppl) and Ppc (31). Only lung and thoracic compli-ance 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 expi-ratory 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 vol-ume 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 dis-place 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 obstruc-tion, and extra-pulmonary processes that directly alter chest wall–diaphragmatic contraction or intra-abdominal pres-sure 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 alveo-lar 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 dur-ing 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 H2O 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 trans-mission 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 vascu-lar 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 pres-sures 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

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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 hyperin-flation both juxtacardiac Ppl and Ppc increase together.

autonomic tone

Cyclic changes in lung volume induce cyclic changes in auto-nomic 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 arrhyth-mia (44). The presence of respiratory sinus arrhythmia con-notes 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–vaso-dilatation response induces expiration-associated reductions in LV contractility in healthy volunteers (53), and in venti-lator-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 car-diovascular status (58). Although overdistention of aerated lung units in patients with ALI may induce such cardiovascu-lar 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 bal-ance. Both positive-pressure ventilation and sustained hyperin-flation decrease right atrial stretch, stimulating endocrinologic responses that induce fluid retention. Plasma norepinephrine, plasma rennin activity (60,61), and atrial natriuretic pep-tide (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 improve-ments in blood flow (63,64). Thus, some of the observed ben-efit 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 pul-monary 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 exam-ple, 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 vasoconstric-tion) 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 isch-emia 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 PO2 (PAO2) decreases below 60 mmHg (73). This process of hypoxic pul-monary 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 cal-cium channel in the pulmonary vasculature. Hypoxic pulmo-nary vasoconstriction, by reducing pulmonary blood flow to hypoxic lung regions, minimizes shunt blood flow. However, if generalized alveolar hypoxia occurs then pulmonary vaso-motor tone increases, increasing pulmonary vascular resis-tance 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 alveo-lar 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 vasomo-tor tone and pulmonary artery pressure, decreasing RV after-load by many related processes. First, hypoxic pulmonary vasoconstriction can be inhibited if O2-enriched inspired gas increases PAO2 (76–79) or if the mechanical breaths and PEEP, by recruiting collapsed alveolar units, increases PAO2 in those local alveoli (30,80–82). Second, mechanical ventilation often

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reverses respiratory acidosis by increasing alveolar ventila-tion, 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 vas-cular 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 extralu-minal 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 arteri-oles, 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 pres-sure gradient from extra-alveolar vessels to alveolar vessels. Increases in lung volume progressively increase alveolar ves-sel resistance, becoming measurable above FRC (Fig. 101.1) (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 pul-monary 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,

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 echocardio-graphic 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 approxi-mately 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 alter-ing LV diastolic compliance by the mechanism of ventricular interdependence (90). Ventricular interdependence functions through two separate processes. First, increasing RV end- diastolic 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 pha-sic changes in arterial pulse pressure and stroke volume seen in tamponade, and is referred to as pulsus paradoxus. Pulsus par-adoxus can be demonstrated during loaded spontaneous inspi-ration 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 hyperinfla-tion (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 misin-terpreted 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 vol-ume 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

Lung volume

Pul

mon

ary

vasc

ular

res

ista

nce

FRC RV TLC

Total PVR

Alveolarvessels

Extra-alveolarvessels

Hypoxicpulmonary

vasoconstriction

Alveolarcompression

FiGURe 101.1 schematic diagram of the relation between changes in lung volume and pulmonary vascular resistance, where the extra-alveolar 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 resis-tance, whereas the increase in resistance with lung collapse is due to increased extra-alveolar vessel tone.

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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, decreas-ing 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

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 pres-sure 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, decreas-ing RV filling (70) and RV stroke volume (70,105,107–115). 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 (4,26,105,109–113,120).

However, if positive-pressure ventilation-induced increases in right atrial pressure always proportionally decreased venous return, then most patients would display profound cardiovas-cular insufficiency when placed on mechanical ventilator sup-port 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 vascu-lature, it is pressurized as well, increasing mean systemic pres-sure. Accordingly, the pressure gradient for venous return is often not reduced by PEEP (118). Inspiration-induced abdom-inal pressurization by diaphragmatic descent is probably the primary mechanism by which the decrease in venous return is minimized during positive-pressure ventilation (123–128). 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

pressure (2,28,110–112) and increase in intra-abdominal pres-sure (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 ven-tricular 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. 101.2) (90,131–134).

However, the spontaneous inspiration-induced RV volume increase reduces the LV diastolic compliance and is the pri-mary cause for the inspiration-associated decrease in LV stroke volume and pulse pressure (89,91,134,135). If the pulse pres-sure 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 ven-tilation 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 sponta-neous 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 pres-sure. 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 con-stant as ITP increased, then transmural LV pressure and thus

RV volume (mL)

20

10

0LV p

ress

ure

(mm

Hg)

LV volume (mL)

0 10 20 30 40

50 35 20 0

FiGURe 101.2 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 disten-sibility on filling the opposite ventricle. Am J Physiol. 1967;213:711–718.)

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LV afterload would decrease. Similarly, if transmural arte-rial pressure were to remain constant as ITP decreased then LV wall tension would increase (137). Thus, under steady-state conditions, increases in ITP decrease LV afterload and decreases in ITP increase LV afterload (138,139). The sponta-neous 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 O2 consumption (MVO2). Thus, sponta-neous ventilation not only increases global O2 demand by its exercise component (3–5), but also increases MVO2.

Profoundly negative swings in ITP commonly occur dur-ing forced spontaneous inspiratory efforts in patients with bronchospasm and obstructive breathing. This condition may rapidly deteriorate into acute heart failure and pulmo-nary edema (65), as has been described for airway obstruc-tion (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). Simi-larly, improved LV systolic function is observed in patients with severe LV failure placed on mechanical ventilation (142).

The improvement in LV functional seen with positive-pressure ventilation in subjects with severe heart failure is self-limited, 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 (23,29,103,143–145). This concept has been validated to be a very important clinical approach for patients with obstruc-tive 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 fail-ure (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 sustain-ing 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 arte-rial pulse pressure (diastole to systole) and systolic pres-sure 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 pro-found 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 preload-responsiveness. 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 moni-toring 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 inter-actions 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 chap-ter is an essential part of the training of acute care physi-cians. 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 intra-abdominal 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 proportion-ally 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 diam-eters (163). Threshold values above 10% to 15% change in diameter define volume-responsiveness.

Because both SVV and PPV sensitivity degrade during spon-taneous ventilation, low tidal volume ventilation, severe cor pulmonale and other extremes of physiology (164), alterative tests have been proposed. Specifically, performing passive leg-raising maneuvers to transiently increase venous return while concomitantly monitoring transient changes in left-sided CO is very sensitive and specific predictor of volume responsive-ness under most conditions (165). It also becomes inaccurate when intra-abdominal hypertension exists because the pres-sure gradient for venous return is altered less (166).

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AcknowLeDGMentSSupported in part by the NIH grants HL074316, HL120877 HL07820, and NR013912.

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• Spontaneous ventilation is exercise.• Failure to wean may connote cardiovascular

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• Changes in lung volume alter autonomic tone, pul-monary 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

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• 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.

key Points

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chapter 101chapter 101 heart–lung interactions 1267 pressure changes) defines the pulmonary...

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