Special Feature: Applying Heart-Lung Interactions Physiology to Assess Fluid Responsiveness

By Francisco Baigorri, MD, PhD

Volume expansion is used often in critically ill patients to improve hemodynamics. However, volume expansion may be ineffective or even induce deleterious effects (increasing extravascular lung water). Thus, the detection of an inadequate cardiac preload and fluid responsiveness is a cornerstone of cardiovascular therapy.

A thorough understanding of heart-lung interactions can help us in the decision-making process concerning volume expansion. Respiration can affect global cardiac performance through its effects on the determinants of cardiac function. "The heart works as a pump in the respiratory pump."1 The consequences are affected by the cardiovascular function and intravascular volume status of the individual patient.

The objective of this essay is to briefly review some of the currently available applications of the knowledge about the integrated behavior of the cardiopulmonary system for bedside assessment of fluid responsiveness.

Inspiratory Decrease in Right Atrial Pressure

Theoretical background: It is mainly the change in airway pressure and its transmission to the pleural space that affects cardiac function. The heart acts like a pump, which propels blood from the venous reservoir to the systemic circulation (see Figure 1). Venous return is determined by the pressure gradient from the upstream driving pressure in the venous reservoir (mean circulatory pressure, Pmc) to the right atrium (Pra) and the resistance to venous return (Rv).

Guyton et al2 developed a graphic representation of venous return, which shows the regulation of cardiac output by the vasculature (see Figure 2). The venous return curve intercepts the pressure axis at a Pra, which is equal to Pmc, and the inverse of the slope of the venous return curve is Rv. When Pra is < 0, large veins collapse as they enter the thorax, which prevents a further increase in venous return with further decreases in Pra. As for the cardiac function, since venous return must equal cardiac output in a closed system, the same graphic parameters could be used for both the cardiac function and venous return curves. Therefore, a plot of cardiac output vs. the filling pressures of the right heart, ie, Pra, representing cardiac function, can be superimposed on the same graph as venous return. However, the heart, as with any other pressure chamber in the body, is subjected to the surrounding pressure, ie, pericardial or intrathoracic pressures. Thus, the cardiac function curve must start at a negative value of Pra since the pleural pressure is slightly negative at the end of expiration. The intersection point of both curves will determine the cardiac output and Pra based on the momentary pumping ability of the heart and the characteristics of the circulation. The transmural pressure of the heart in this graph is given by the pressure difference between the Pra with zero cardiac output and the actual Pra.

With a normal breath, pleural pressure falls, which means that the heart becomes negative relative to the rest of the body. This is graphically represented as a left shift of the cardiac function curve (see Figure 3-A). The shift of the cardiac function curve to the left increases the gradient for venous return from Pmc to Pra. Thus, the venous return and cardiac output curves intersect at a higher value of flow.

It is particularly interesting to observe the response when the limits of stretch of the pericardium and ventricle are reached below the plateau of the venous return curve (see Figure 3-B). When this happens, the left shift of the cardiac function curve does not change Pra or cardiac output. In this condition, volume expansion, which would affect the venous return curve by increasing Pmc and therefore shift the venous return curve to the right, will not increase cardiac output.

It would appear, then, that respiratory changes in pleural pressure induce greater changes in Pra when the right ventricle is highly compliant than when it is poorly compliant. In extreme conditions, spontaneous inspiration-associated increases in Pra reflect severe right ventricle failure and are referred to as Kussmaul’s sign.

Available Data: Assuming that, Magder and colleagues3,4 investigated whether the inspiratory decrease in Pra could be used to predict fluid responsiveness in patients with spontaneous breathing activity. They found that it is unlikely that volume loading will increase the cardiac output in a patient who does not have an inspiratory fall in Pra, whereas volume loading will usually increase the cardiac output of patients who have an inspiratory fall in Pra, even if only by 1 mm Hg. Added to that, Magder et al documented that this approach can also be used to predict subsequent changes in cardiac output in response to increasing levels of PEEP in mechanically ventilated subjects.5

However, these studies do not address the issue of left ventricular performance. Let us consider the analysis of how the respiratory changes in left ventricular stroke work to predict fluid responsiveness. Studies on this topic have focused on the effects of positive-pressure ventilation on left ventricular output.

Respiratory Changes in Pulse Pressure

Theoretical Background: Positive-pressure ventilation induces phasic changes in left ventricular stroke volume though similar changes in venous return (see Figure 4). Looking again at Figure 1, systemic venous return decreases due to increases of Pra from the positive-pressure breath. This reduction in venous return will reduce left ventricular filling.

In patients with increased intrathoracic blood volume, systolic pressure can increase transiently during 2 or 3 heartbeats, as a result of the transfer of the pulmonary arterial blood volume into the left atrium increasing left ventricular end-diastolic volume. Later, as systemic venous return decreases, systolic arterial pressure decreases below baseline apneic values.6 Conversely, patients with depressed cardiac contractility and pulmonary vascular congestion often exhibit a "reverse pulsus paradoxus," whereby arterial pressure increases only after a positive pressure-breath.

Ultimately, then, the greater the degree to which the heart’s stroke volume is dependent of this venous return, the greater the change in stroke volume over the breath. However, we should bear in mind that the magnitude of the changes in stroke volume is also a function of the volume of the tidal breath and the subsequent increase in intrathoracic pressure.7

Available Data. Based on this logic, Perel and associates8,9 studied the systolic pressure variation induced by a defined positive-pressure breath in animals made hypovolemic and in heart failure, and in humans. They demonstrated that the variation of the systolic pressure, specifically in the form of the decrease in systolic pressure from an apneic baseline, referred as Ddown, identified hemorrhage and was minimized by fluid resuscitation. It has also been reported in sedated and mechanically ventilated patients with sepsis-induced hypotension10 with a significant relationship between the baseline value of Ddown and the percent increase in stroke volume in response to volume expansion.

However, the systolic pressure depends on diastolic pressure and significant changes in systolic pressure can be observed independent of changes in stroke volume.11 On the other hand, the arterial pulse pressure (systolic minus diastolic pressure) is directly proportional to left ventricular stroke volume. Accordingly, the respiratory changes in pulse pressure have been recently proposed as a better predictor of fluid responsiveness.12,13 A pulse-pressure variation threshold value of 13% allowed discrimination between responder and nonresponder patients with a positive predictive value of 94% and a negative predictive value of 96%.13 Moreover, arterial pulse pressure variation followed a similar response to aortic flow variation, estimated by transesophageal pulsed Doppler echocardiography.14


Neither pulmonary artery occlusion pressure nor Pra predicts with accuracy the response to an intravascular fluid challenge. Spontaneous ventilation and positive-pressure ventilatory therapies often complicate this analysis by dissociating filling pressures from measured intrathoracic vascular pressure because of both increasing intrathoracic pressure and cardiac compression by lung expansion. However, the effects of respiration on cardiocirculatory function, by phasically altering Pra and venous return, may help us to predict fluid responsiveness. On the one hand, available data show that patients with circulatory failure and with spontaneous breathing activity, who do have a respiratory fall in Pra > 1 mm Hg should show an increase in cardiac output after a fluid challenge. On the other, patients under mechanical ventilation and with a systolic pressure variation or pulse pressure variation > 12% will increase cardiac output in response to intravascular volume challenge.


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12. Michard F, et al. Clinical use of respiratory changes in arterial pulse pressure to monitor hemodynamic effects of PEEP. Am J Respir Crit Care Med. 1999; 159:935-939.

13. Michard F, et al. Relation between respiratory changes in arterial pulse pressure and fluid responsiveness in septic patients with acute circulatory failure. Am J Respir Crit Care Med. 2000;162:134-138.

14. Feissel M, et al. Respiratory changes in aortic blood velocity as an indicator of fluid responsiveness in ventilated patients with septic shock. Chest. 2001; 119:867-873.