Introduction
Arterial hypotension is always a clinical emergency. A sustained decline in arterial pressure, whatever the mechanism that produced it, leads to a decrease in tissue perfusion pressure, organ dysfunction and finally death. Although fluid administration remains the first-choice therapy, the assumption that increasing stroke volume (SV) arterial pressure will also rise is not always true, since the pressure-volume relationship is not easily predictable and depends on the arterial tone. Thus, for the same increase in SV, the increase in arterial pressure will be greater if the arterial tone is higher [
1].
Although systemic vascular resistance (SVR) remains the most common parameter used by clinicians to describe arterial tone, its value only represents the opposition to a mean and constant flow, as it exists mainly at the level of arterioles, where the compensatory mechanisms that control vasomotor tone regulate perfusion pressure within the physiological range [
2,
3]. However, because of the oscillatory nature of arterial pressure and blood flow, this approximation provides not a full characterization of the whole arterial impedance but just a gross oversimplification, ignoring other components such as arterial compliance, characteristic impedance or arterial wave propagation-reflection phenomena [
2,
3].
On the basis of the Windkessel model, the arterial pressure could be described as the result of the interaction between left ventricular SV and the arterial system [
4‐
6]. So, the ability of an arterial vessel to increase pressure with increases in flow is related to arterial stiffness and is a function of the slope of the arterial volume-pressure relationship or arterial elastance (Ea), which could be defined as the ratio of changes in pressure to changes in volume. Arterial elastance therefore could be considered an integrative parameter of overall arterial system behavior [
3,
7].
Recently, Pinsky has advocated the assessment of arterial tone in a dynamic fashion by using cyclic changes in pulse pressure and SV during mechanical ventilation [
1,
8]. He proposed that measuring the ratio of pulse pressure variation (PPV) to stroke volume variation (SVV) during a single positive-pressure breath could provide a functional evaluation of arterial tone. He argues that the functional assessment by dynamic arterial elastance would allow a continuous and immediate estimation of arterial tone at the bedside and could help to predict which patients will show increased arterial pressure with fluid administration [
1,
8].
Since the aim of the cardiovascular system is to maintain not only blood flow but also adequate perfusion pressure [
9], even if a patient is preload-responsive, knowledge of arterial tone is also an important factor in deciding on the appropriate treatment. The purpose of the present study, therefore, was to assess whether dynamic arterial elastance (Ea
dyn), defined as the PPV to SVV ratio, could predict the arterial pressure response after volume loading in hypotensive, preload-dependent patients.
Discussion
The main finding of this study is that Eadyn, defined as the PPV/SVV ratio, efficiently predicted the arterial pressure response to fluid loading in hypotensive, preload-dependent patients with acute circulatory failure.
Since initial hemodynamic resuscitation should be targeted to achieve not only adequate CO but also adequate MAP to guarantee perfusion pressure to all vascular beds [
9,
10], determining whether a patient is preload-dependent only provides half of the answer, because the arterial pressure response to volume administration depends on arterial tone. Thus, for a given SV increase, the greater the arterial tone, the greater the expected boost in arterial pressure [
8].
In our study, only 64% of the hypotensive, preload-dependent patients increased MAP after fluid administration. Neither peripheral vascular resistance, nor the PP/SV ratio, nor the degree of hypotension, defined by the baseline MAP, predicted a subsequent increase in arterial pressure.
Although SVR has traditionally been used to characterize overall arterial tone, this parameter represents primarily the vascular smooth muscle tone at the level of small arteries and arterioles, where a complex system of neurohormonal and local factors adjusts the vessel caliber to protect the capillaries from changes in pressure and to keep capillary perfusion pressure constant [
3]. As SVR is not homogeneously distributed along the arterial vascular tree and essentially provides a quantification of arteriolar vasomotor activity, it has been considered an inappropriate and incomplete assessment of arterial tone [
24]. Not surprisingly, in our study population, fluid administration did not affect SVR in spite of changes in arterial pressure. Moreover, in MAP responder patients, preinfusion SVR did not correlate with volume-induced increases in arterial pressure or changes after fluid administration, suggesting that arterial pressure changes in these patients were not related to arteriolar vasomotor modulation.
Because arterial pressure results from the phasic interaction of blood ejected from the left ventricle and the arterial system, the pulsatile pressure-flow relationship has been used to describe arterial input impedance [
4‐
6]. This relation provides a more comprehensive description of the arterial load faced by the ejecting ventricle, since it incorporates other components of the arterial system, including total arterial compliance, characteristic impedance or the effects of arterial wave reflections, as well as the ratio of mean pressure to mean flow [
3,
7,
25]. Since the evaluation of arterial input impedance requires measuring pressure and flow waves and the application of complex Fourier analysis, the ratio of PP to SV has been proposed as a simple and gross estimation of the pulsatile component of the arterial system and a surrogate measure of the systemic arterial stiffness in clinical practice [
17,
22,
26]. However, in the same way that knowing the values of cardiac preload and CO does not allow the prediction of the response to a fluid challenge, since the response will depend on the slope of the cardiac function curve, the steady-state relationship between pulsatile pressure and pulsatile flow, as measured by the PP/SV ratio, is theoretically variable with different states of arterial tone and influenced by factors such as aging and pathologies such as arterial hypertension [
19,
27,
28]. Therefore, for the same static pressure-flow relationship, the VE-induced increase in arterial pressure should depend on arterial tone; thus, as our results show, prediction of the arterial pressure response by PP/SV should be infeasible [
8].
On the contrary, as Pinsky has pointed out, Ea
dyn represents neither a steady nor pulsatile component of arterial system, but instead a functional measure of central arterial tone [
1,
8]. During mechanical ventilation, swings in intrathoracic pressure induce cyclic changes in left ventricular SV by intermittently varying right ventricular preload. The magnitude of these changes defines the degree of preload dependence of a patient and the position on the Frank-Starling curve, and these changes have been widely used as indicators of fluid responsiveness [
12]. Thus, simultaneous measurements of arterial pulse pressure and left ventricular SV during passive mechanical ventilation should provide an actual assessment of the pressure-volume relationship and an accurate measurement of arterial tone. Ea
dyn, therefore, rather than absolute values of pressure and flow, depicts the actual slope of the pressure-volume relationship using the cyclic changes in left ventricular SV during a single mechanical respiratory cycle. So, Ea
dyn should be interpreted as a functional approach to arterial tone assessment in the same way that preload responsiveness parameters attempt to predict the hemodynamic response to a change in cardiac preload.
According to our results, a patient with an Ea
dyn value <0.89 will not have an increase MAP with volume administration, which pragmatically means that vasopressors should be added along with fluids to increase the patient's CO and MAP. By contrast, an Ea
dyn value >0.89 indicates that fluid loading alone will significantly raise blood pressure, and thus the use of vasoactive drugs can be delayed. These results are in accord with a previous algorithm proposed by Pinsky as part of a functional management protocol based on ventriculoarterial coupling [
1,
8]. According to this algorithm, if a balanced system should present an Ea
dyn close to 1 and changes >20% reflect real variations in arterial elastance, then the normal value for the PPV/SVV ratio should be between 0.8 and 1.2. In our study, Ea
dyn measurement does not represent an online monitoring method (since PPV value was obtained from a
post hoc offline analysis); however, with the current technology available, it might be possible to easily obtain both parameters simultaneously, allowing continuous assessment of Ea
dyn at the bedside.
Interestingly, from a theoretical point of view, the evaluation of Ea
dyn should not necessarily be limited by some of the restrictions imposed on the fluid responsiveness parameters. In particular, the assessment of arterial tone by Ea
dyn could be used in spontaneously breathing patients or in patients with low tidal ventilation, since the relation between PPV and SVV should still be valid under these circumstances [
5]. Furthermore, another potential advantage of the combined evaluation of the preload dependence and arterial tone by Ea
dyn could be the prediction of the expected increase in hydraulic efficiency measured by the cardiac power output. Hypothetically, for the same fluid responsiveness degree, a preload-dependent patient with a higher Ea
dyn value would respond with a more marked increase in MAP, higher CPO, and thus a better improvement in the mechanical efficiency of hydraulic power transfer from the left ventricle to the peripheral circulation [
1]. These assumptions, although physiologically reasonable, require confirmation by further studies.
Some important limitations of our study should be addressed. First, the SVV value was obtained not from the actual arterial blood flow, but from the results of arterial pressure analysis using the Vigileo hemodynamic monitor. Pinsky has already warned against the use of pulse contour-derived SVV to track rapid changes in SV, as occurs during a single mechanical breath [
29,
30]. In this regard, Vigileo-derived SVV has been confirmed as a valuable predictor of fluid responsiveness [
11,
31] and equivalent to SVV measured by transthoracic echocardiography [
15]. However, since SVV is actually the respiratory variation of SD of arterial pressure, as the χ factor is updated only every minute, the possibility of a mathematical coupling cannot be excluded. Also, this study was targeted to a specific group of patients with a preserved preload dependence condition and manifest arterial hypotension, so that extrapolation of our results to other situations should be considered with caution. However, the assessment of arterial tone by Ea
dyn clearly responds to a concrete, often stressful situation with which clinicians must habitually deal in their daily practice. Finally, hemodynamic resuscitation should be aimed not only at restoring blood flow and perfusion pressure but also at maintaining adequate tissue oxygenation. Increasing MAP to a predefined level does not guarantee sufficient oxygenation to all tissues nor can be generalized to all patients [
31]. Furthermore, systemic hypotension is not always present in shock, and restoration of normal arterial blood pressure does not exclude maldistribution of blood flow to vital organs. However, it seems reasonable that an acceptable minimum level of MAP is necessary to avoid further hypoperfusion [
10].
Competing interests
MIMG has received consulting fees from Edwards Lifesciences. AGC and MGR declare that they have no competing interests.
Authors' contributions
MIMG conceived and designed the study, participated in the recruitment of patients, performed the statistical analysis, interpreted the data and drafted the manuscript. AGC participated in the study conception and design, interpreted data and helped draft the manuscript. MGR participated in patient recruitment, data collection, technical support and contributed in the critical review of the manuscript. All of the authors read and approved the final manuscript.