Abstract
Functional hemodynamic parameters, such as stroke volume variation (SVV) and pulse pressure variation (PPV), are useful hemodynamic monitoring tools for the assessment of fluid responsiveness. These parameters are based on heart-lung interaction during positive mechanical pressure ventilation: Cyclic changes of intrathoracic pressure result in a reduced venous return and a decreased cardiac stroke volume after inspiration followed by a restoration of preload and stroke volume after expiration. Hemodynamic monitoring systems based on pulse wave analysis allow an automatic assessment of SVV and—at least for some of the devices—of PPV. Moreover, PPV is being integrated in the standard monitoring in the operating room and the intensive care unit, and the noninvasive plethysmographic assessment of fluid responsiveness has been recently introduced. These developments will result in a broader application of functional hemodynamic parameters in the near future. In contrast to traditional preload parameters (i.e. central venous pressure), SVV and PPV allow the prediction of fluid responsiveness and thus the determination of the actual position on an individual Frank-Starling curve or—in other words—the assessment of an individual preload reserve. Different studies in the last decade were able to prove the validity of this concept. However, to use these functional hemodynamic parameters in daily clinical practice, some limitations have to be considered. Arrhythmia and right heart failure, but also spontaneous breathing of a patient, or small tidal volumes may preclude reliable assessment. Based on these aspects, an ideal area of application of these parameters may be the use during perioperative hemodynamic optimization to improve patient outcome. However, only few studies on goal-directed therapy guided by these parameters have been published so far.
Keywords
hemodynamics; oximetry; plethysmography; pulse; stroke volume;
1. Introduction
Assessment of intravascular volume of critically ill patients in a perioperative setting, and also during the intensive care unit treatment, is a challenging task because direct measurement at the bedside is not possible. Usually, the evaluation is performed by assessment of skin turgor, blood pressure, heart rate, and urine output. However, this clinical assessment is often unspecific and not necessarily reliable.1 Unfortunately, standard pressure preload parameters do not help to solve this problem. Different studies performed in the past years revealed that central venous pressure and also pulmonary capillary wedge pressure may not reflect preload2, 3 nor were they able to discriminate between responders and nonresponders to a fluid trial.4, 5, 6 As a consequence, the so-called volumetric preload parameters, assessed by thermodilution, and echocardiographic preload determination gained importance and allowed an improved preload assessment. It could be shown that global end-diastolic volume measured by transpulmonary thermodilution, right ventricular end-diastolic volume assessed by a modified pulmonary artery catheter, and also left ventricular end-diastolic diameter/volume evaluated by echocardiography were all superior preload variables as compared with central venous pressure and pulmonary capillary wedge pressure.2, 7 However, based on their static nature, assessment of fluid responsiveness is very limited.8
Intravascular fluid administration is typically the first-line intervention for hemodynamic optimization or restoration of hemodynamic stability in a perioperative setting. Basically, the goal is a stroke volume or cardiac output (CO) resulting in a maintained or improved oxygen delivery and organ perfusion. As a result of the difficulties related to the clinical assessment of the intravascular volume status, only 50% of the patients may show an adequate response to fluid loading.1, 5 The consequences can range from minor volume overloading to lung edema with a progressive risk of end-organ underperfusion and decreased peripheral oxygen delivery. On the other hand, several studies demonstrated that hemodynamic optimization using the therapeutic option of fluid administration might have a positive influence on outcome in terms of reduced postoperative complications and a reduced hospital length of stay but also long-term effects.9, 10
Functional hemodynamic parameters, such as stroke volume variation (SVV) and pulse pressure variation (PPV), may be a useful guide for improved fluid administration. The prediction of fluid responsiveness is, obviously, crucial for an adequate management of fluid administration and goal-oriented hemodynamic optimization. It will help to determine the ideal strategy of increasing CO and oxygen delivery.11 Therefore, reliable sensitive and specific variables are required. Different less-invasive hemodynamic monitoring devices primarily based on pulse wave analysis provide SVV and eventually PPV using heart-lung interaction during mechanical positive pressure ventilation, which may be used for this task. The process of integrating PPV into standard clinical monitoring systems has just started. Moreover, noninvasive assessment of fluid responsiveness based on plethysmographic analysis became recently available.
The aim of this article is to describe the underlying physiological principles of the functional hemodynamic parameters SVV and PPV as well as the noninvasive surrogate parameter, to review their potential of adequately predicting fluid responsiveness and their limitations as well as to propose an clinical approach to these functional hemodynamic parameters.
2. Frank-Starling mechanism and heart-lung interactions
The Frank-Starling mechanism describes the curvy-linear relationship between diastolic myocardial distension, that is, preload, and systolic cardiac function12: An increase in myocardial distension typically results in an increased CO. The cardiac function can be primarily improved by intensified diastolic distension in the zone of the ascending limb of the Frank-Starling curve (“preserved preload reserve”). However, the effect on cardiac performance decreases with further efforts to amplify diastolic distension in the zone of the plateau part of the Frank-Starling curve (“reduced preload reserve”). In daily practice, “diastolic filling” is usually used synonymous to “cardiac preload,” and fluid administration as therapeutic intervention in the context of hemodynamic optimization13 is based on the Frank-Starling mechanism (Fig. 1A). Thus, to provide an adequate volume therapy, patients with and without preload reserve, the so-called “responders” and “nonresponders,” have to be identified (Fig. 1B): Responders react with an increase of stroke volume to an increased preload, whereas this effect cannot be observed for nonresponders. In both groups, however, the individual cardiac function for every patient—that is, an individual Frank-Starling curve—can be found (Fig. 1C)14: For a reduced cardiac function, this curve is flatter than that for a preserved left ventricular function.15 The standard preload variables, such as central venous pressure, are not able to discriminate between responders and nonresponders.4 Although they may eventually serve as a surrogate marker of preload, they do not allow an assessment of the cardiac reaction as response to fluid loading.
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The heart-lung interaction is the fundamental mechanism of functional hemodynamic assessment. Intrathoracic pressure variations affect venous return and concomitantly diastolic cardiac filling as well as systolic cardiac performance16: Inspiration of the spontaneously breathing patient results in lung expansion and an increased negative intrapleural pressure. This results in an augmented venous return and subsequently an improved stroke volume. During expiration, intrathoracic pressure increases and lessens this effect. In the mechanically ventilated patient, by contrast, inspiration generates an increased intrathoracic pressure and a reduction of venous return. Preload and—after a delay of three consecutive heart beats, that is, the pulmonary transit time—stroke volume decrease (Fig. 2). This effect can be clinically observed during expiration. On releasing intrathoracic pressure, preload and stroke volume start to increase again. In daily practice, the typical picture of an undulant arterial waveform during mechanical positive pressure ventilation is observed, and the degree of hypovolemia may be correlated with this “wave motion.”5 Based on these observations, the functional hemodynamic variables SVV and PPV can be calculated using dedicated algorithms (Table 1). In the zone of the ascending limb of the Frank-Starling curve (for the responders), intrathoracic pressure variations imposed by mechanical ventilation result in a major variation of stroke volume and, subsequently, in major variation of peripheral arterial pressures, but on the plateau of the Frank-Starling curve (for the nonresponders), only minor variations of stroke volume and of pressure amplitude occur (Fig. 3A). Large variations of stroke volume are represented by large numbers of the functional hemodynamic parameters reflecting the ascending part; small numbers reflect the plateau of the Frank-Starling curve (Fig. 3B).
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3. Assessment of SVV
SVV can be determined from maximal and minimal stroke volumes usually during three cycles of mechanical ventilation (Table 1) at the bedside using different less-invasive hemodynamic monitoring devices typically based on pulse wave analysis.17 Moreover, the recently introduced bioreactance technique allows—apart from cardiac output determination—the assessment of SVV, which has not yet been broadly validated.18 It has to be emphasized that stroke volume measurement and thus SVV assessment is different for different monitoring systems17; therefore, some technical aspects and some inherent limitations of the most used pulse wave analysis systems are addressed in the following.
The PiCCO plus system (Pulsion Medical Systems, Munich, Germany) was the first pulse contour device for CO measurement in clinical practice. It uses a proprietary algorithm based on the assumption that the area under the systolic part of the aortic pressure waveform corresponds to the stroke volume. To align this stroke volume with the actual patient’s stroke volume, calibration by transpulmonary thermodilution is required. Therefore, a dedicated thermistor-tipped catheter, usually introduced through the femoral artery, combined with a central venous catheter for the application of iced-water bolus injections, is used. The thermodilution serves also to adjust for variations of the aortic compliance. Different studies in a variety of clinical settings have been performed in the past years proving the validity of the system with respect to CO measurement.19 Despite all these favorable data, it has to be emphasized that frequent recalibrations for accurate, reliable measurements, especially in situations of rapid hemodynamic changes, may be required.20, 21 The PiCCO plus system allows the simultaneous assessment of SVV and PPV.
The LiDCO plus technique (LiDCO Ltd, London, UK) is usually classified as a pulse contour method, although strictly speaking, it is a pulse power analysis that is based on the principle of mass/power conservation in a system and the assumption that after the correction for compliance and calibration using the lithium dilution method, there is a linear relationship between net power and net flow in the vascular system. Different studies showed a reliable assessment of CO as long as no major hemodynamic changes (alterations of vascular compliance and resistance) occur.17 The LiDCO rapid device, which does not require calibration, may have characteristics comparable to the FloTrac/Vigileo system (Edwards Lifesciences, Irvine, CA, USA). The technique provides continuous SVV and PPV readings.
The FloTrac/Vigileo system requires a specific transducer—the FloTrac sensor—which can be attached to an existing standard arterial line and connected to the Vigileo monitor for continuous CO measurements. In contrast to the PiCCO plus system, the device does not require external calibration: The standard deviation of pulse pressure sampled during a time window of 20 seconds is correlated with the “normal” stroke volume based on an underlying hemodynamic database. Aortic impedance is also estimated from these data, whereas vascular compliance and resistance are determined using arterial waveform analysis. A variety of validation studies in the past years observed an improved performance of the device with a modified software (Generation 2), especially in the perioperative setting.22 However, limited accuracy of measurements in vasoplegic patients under hyperdynamic situations are still of concern,23 and further software modifications addressing the issue are currently being tested (Generation 3). The FloTrac/Vigileo system displays SVV on a continuous basis.
The combination of functional hemodynamic parameters with CO assessment in these minimally invasive hemodynamic monitoring devices facilitates the tracking of the cardiac response during a fluid trial and allows the assessment of fluid responsiveness by alternative maneuvers24, 25 in situations where SVV or PPV may not be reliable. Despite the technical differences of the pulse wave analysis devices, they share the need for an optimal arterial signal quality for valid CO assessment. Moreover, arrhythmias and the use of an intra-aortic balloon pump preclude reliable continuous hemodynamic measurements.
4. Assessment of PPV
PPV was usually manually assessed in the past. PPV is usually determined on three successive respiratory cycles.26 The maximal and the minimal pulse pressures are measured, pulse pressure being the increase from diastolic pressure to systolic pressure (Table 1). It can also be assessed using hemodynamic monitoring devices based on pulse wave analysis, that is, the PiCCO plus and the LiDCO system. Moreover, different algorithms for continuous automated PPV assessment have been recently developed.27, 28, 29 Some of them are being integrated in standard monitoring systems, such as the Philips Intellivue MP70 monitor (Philips, Amsterdam, The Netherlands).30 It can be expected that, in the future, PPV will be broadly available when invasive arterial pressure measurement will be performed. The fact has to be stressed that every manufacturer uses a dedicated computation algorithm, and therefore all the devices providing PPV will require specific validation. From arterial waveform analysis, additional functional parameters can be derived, that is, systolic pressure variation (SPV)31 and the SPV components ∆up and ∆down; these parameters are summarized in Table 2. However, these parameters are not often used in daily clinical practice because they have to be predominantly assessed by manual means. A clear disadvantage of the sole arterial waveform analysis is the lack of CO assessment, which limits a direct control of the fluid-loading effect.
Plethysmographic systolic pressure variation [∆ pulse oxymetric plethysmography (POP)] and plethysmographic variability index (PVI; Massimo Corp, Irvine, CA, USA) allow the completely noninvasive assessment of fluid responsiveness by a pulse oxymetry signal, PVI using a slightly different algorithm than ∆POP (Table 2), the maximal amplitude as denominator instead of an averaged value being applied. These variables can be considered noninvasive surrogate parameters of PPV and, based on their noninvasive nature, a broad application may be possible especially in the perioperative setting when no invasive arterial blood pressure measurement is required.32, 33, 34 Apart from the general limitations of all functional hemodynamic parameters, ∆POP and PVI may be prone to error during low-perfusion conditions with increased vasomotor tone,35 as a result of ambient light or because of movement artifacts.
5. Prediction of fluid responsiveness
In the past years, functional hemodynamic parameters, primarily SVV and PPV,36 and also the noninvasive PPV estimates37 were tested with respect to their capacity of predicting fluid responsiveness in a variety of studies. Most of these studies could demonstrate that the functional hemodynamic parameters were able to discriminate between fluid responders and nonresponders. Typically, functional hemodynamic parameters before a fluid-loading maneuver and the related cardiac responses were recorded. From these test results, receiver-operating characteristic (ROC) curves were plotted to determine the predictive potential and to assess the threshold value of the parameters, which is used for the discrimination of fluid responders and nonresponders. Most of these studies were performed in cardiac surgery patients. Although threshold values of the different parameters revealed in these studies are clinically relevant, they need to be carefully interpreted considering the methodological aspects of these studies: It has to be emphasized that different amounts of fluids were administered, there was no unique definition of the cardiac response, and test variability was neglected in most studies. Moreover, the assessment of ROC curves assumes a “black or white situation,” that is, responder or nonresponder to volume expansion and, unfortunately, the misclassification defined by a sensitivity and specificity level is not considered. This problem may be solved using the gray zone approach that describes a zone between positive and negative test results with different cutoff levels allowing a more appropriate decision making at the bedside.
Prediction of fluid responsiveness using SVV was mainly investigated for the PiCCO plus system,8, 38, 39, 40 but recently, data became available also for the FloTrac/Vigileo41, 42, 43 and the LiDCO monitoring.44, 45 ROC analysis in the different studies showed predominantly a good prediction of fluid responsiveness, and SVV threshold values ranged from 10% to 13%. These findings may primarily be explained by variations of the study design, different patient populations, and eventually measurement errors based on limitations of SVV assessment. Moreover, the different techniques of SVV assessment used by the different devices may have influenced the results of different studies: A direct comparison of SVV assessed by the PiCCO plus and the FloTrac/Vigileo systems revealed a considerable difference of threshold values and a different predictive value.43
Prediction of fluid responsiveness using PPV was assessed with experimental manual methods in most of the studies with positive results published in the past.36 However, there is an increasing number of studies evaluating PPV assessed automatically by algorithms integrated in pulse wave analysis devices or standard monitoring systems.8, 26, 43, 46, 47, 48 ROC analysis for PPV revealed a good predictive capacity for the assessment of fluid responsiveness. In these analyses, the lowest PPV threshold value was 9%, and the maximal level was 17%.
5.1. Comparison of SVV and PPV
From a physiological point of view, SVV may be superior to PPV, because the stroke volume changes induce changes in the arterial pressure waveform, and PPV is thought to be more susceptible to vascular influences than SVV.49 However, most studies comparing SVV and PPV showed no real difference in the ability to predict fluid responsiveness.8, 41, 42, 44 Only in one study, SVV performance was significantly better than that of PPV. In this study, increase of cardiac filling was induced by Trendelenburg positioning, and body tilting may have induced a change in vascular tone.43 Interestingly, a recent meta-analysis on SVV and PPV, including all validation studies published predominantly in the last decade, showed that prediction of fluid responsiveness using PPV was significantly superior to the SVV application.36 It can be argued that this result reflects the fact that all pulse wave analysis techniques use mathematical models and algorithms for the determination of stroke volume. Therefore, functional hemodynamic parameters based on the direct assessment of pulse pressure may be more robust than those using estimates of stroke volume. However, considering the already mentioned methodological issues regarding the available validation studies, this significant difference may be clinically irrelevant.
Prediction of fluid responsiveness by noninvasive parameters, for example, ∆POP and PVI, were also evaluated as predictors of fluid responsiveness. In different studies in patients under general anesthesia, positive results were observed, and a close correlation of invasively assessed functional and plethysmographic parameters could be revealed.50, 51, 52, 53, 54 Conflicting results of these parameters in an intensive care unit setting35 may be related to their inherent limitations, and therefore, these parameters may be primarily useful in a perioperative setting and not necessarily in critically ill patients.
6. Clinical implications and limitations
Despite the fact that functional hemodynamic parameters have proven to reliably predict fluid responsiveness, some specific cardiovascular and respiratory situations may limit a broad clinical application.
6.1. Cardiovascular problems
Arrhythmias can result in an erroneous assessment of SVV and PPV55: During accumulated extrasystoles, absolute arrhythmias and other severe irregularities of heart rate SVV and PPV may be under or overestimated. Right heart insufficiency and cor pulmonale may not allow a correct registration of functional parameters because of pathological ventricular interdependency.56, 57 In a model of hemorrhagic shock in dogs, norepinephrine administration without fluid administration decreased functional hemodynamic parameters, whereas metabolic acidosis worsened. This suggests that norepinephrine may preserve central blood volume by vasoconstricting large-capacitance veins and affecting vascular compliance.58 However, many patients investigated in the various trials were receiving norepinephrine,59, 60 it seems, therefore, that only excessive vasoconstriction should be avoided. Changes of norepinephrine doses should be avoided during the hemodynamic evaluation. Increased intra-abdominal pressure may reduce venous return as a result of caval vein compression and may result in an erroneous assessment of fluid responsiveness. However, so far, only experimental data showed that this situation could interfere with correct functional assessment.61
6.2. Respiratory issues
Positive mechanical pressure ventilation is a prerequisite for adequate dynamic preload assessment. Based on intrathoracic pressure variations of the spontaneously breathing patient, no reliable measurements are possible.62 Supportive positive pressure ventilation may preclude a reliable assessment as a result of an irregular breathing pattern.63 Only an adequate tidal volume sufficiently increases intrathoracic pressure to impede venous return, allowing an accurate preload assessment. Experimental and clinical studies could observe that the different tidal volumes influence functional parameters accordingly. For tidal volumes less than 8 mL/kg, no acceptable prediction of fluid responsiveness is possible in a clinical setting.64 Moreover, low values of functional hemodynamic parameters may not be able to be indicative for nonresponders when driving pressure, which is defined as plateau minus end-expiratory pressure, is less than 20 cmH2O.65 Positive end-expiratory pressure (PEEP) per se does not affect functional hemodynamic assessment. In fact, one of the first studies investigating fluid responsiveness was performed applying different PEEP levels.66 However, changes in PEEP levels may result in corresponding changes of cardiac filling and, thus, in functional hemodynamic parameters. Therefore, a change of respirator settings should be avoided during the assessment of fluid responsiveness. Conflicting results can be found for the prediction of fluid responsiveness during open-chest conditions.67, 68 Yet, it can be assumed for clinical purposes that a change of the intrathoracic pressure ratio during open-chest conditions may impede a reliable assessment. Finally, high respiratory rates and, more specifically, low heart rate to respiratory rate ratios may affect SVVs.69
7. How to assess fluid responsiveness at the bedside?
Based on the clinical implications and limitations of the functional hemodynamic parameters, the following approach may be useful in daily practice to perform a reliable assessment of fluid responsiveness. Initially, a clinical problem that may benefit from fluid administration has to be identified (i.e. signs of tissue hypoperfusion, such as hypotension, oliguria, increased lactate levels, decreased central venous oxygen saturation, low CO): It has to be emphasized that a preserved preload reserve per se is not necessarily an indication for fluid administration. Then, optimal signal quality must be ensured, because a decreased arterial pressure signal quality may impede a reliable assessment. Major limitations (compare previous paragraphs) have to be excluded, and during the assessment, no therapeutic changes regarding norepinephrine administration and ventilator settings should be made. Increased intra-abdominal pressure may require careful interpretation of the dynamic preload variables. Based on these prerequisites, a reliable decision regarding fluid administration can be made. When limitations for the functional hemodynamic parameters by the arterial pressure wave analysis exist, two options should be considered. First, the prediction of fluid responsiveness can be performed by a passive leg-raising test using a CO monitoring system. Different studies were able to demonstrate that a stroke volume increase by head downtilting (Fig. 4) can reliably indicate a preload reserve.70, 71, 72 Second, an end-expiratory pause can be considered in patients under mechanical ventilation. However, only limited data evaluating the validity of this maneuver are actually available.24
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8. Improvement of outcome
Perioperative goal-directed optimization in high-risk patients undergoing major surgery can be considered a sound concept today with positive results in terms of a reduction of hospital stay and postoperative complication rate10; moreover, it may influence long-term outcome.9 The first-line treatment in this concept is intravenous fluid administration, and it is important to realize that crystalloids should be given to replace extracellular losses, whereas colloids should restore intravascular deficits.73 Most of the studies evaluating goal-directed therapy were performed assessing stroke volume and their changes by transesophageal Doppler or pulse wave analysis.10, 74 Although it is evident that only the treatment protocol and not the monitoring device or the parameter monitored per se may influence outcome, it is still important to evaluate if functional hemodynamic parameters can be used for this task, and interestingly, only three studies have been published so far: two studies revealing positive results when PPV or SVV was used in a perioperative fluid management protocol.30, 75 By contrast, in another study, standard and SPV-guided perioperative hemodynamic managements were comparable in terms of outcome.76 Unfortunately, however, in this study, patients with American Society of Anesthesiologists Classification I–III were included, and there was no significant difference in the treatments between the SPV and the control groups.
9. Conclusion
Functional hemodynamic parameters are useful monitoring tools for the assessment of the intravascular volume status in relation to the individual cardiac function based on heart-lung interaction. In contrast to standard preload parameters, SVV, PPV, and their noninvasive surrogates allow a reliable prediction of fluid responsiveness considering their typical limitations. An ideal application of these parameters may be the use during perioperative hemodynamic optimization in order to improve patient outcome.