ICU Physiology in 1,000 Words: Stroke Volume Variation and the Concept of Dose-Response

Stroke Volume Variation and the Concept of Dose-Response

Jon-Emile S. Kenny M.D.

Awareness of the undulating pattern of an arterial line tracing is high amongst health professionals in the intensive care unit; certainly this is an aftereffect of a cacophony of studies and reviews pertaining to pulse pressure variation and fluid responsiveness in the operating room and ICU.  But what exactly is the genesis of pulse pressure variation?  What are its limitations and why do these limitations exist?

Functional hemodynamic monitoring

Functional hemodynamic monitoring [FHM] assesses the functional state of the cardiovascular system by measuring a response to a defined stress [1].  The measured response may be either a ‘venous-side’ [e.g. venae cavae diameter change] or an ‘arterial-side’ [e.g. stroke volume variation (SVV)] variable [2]; the defined stress is often a change in intra-thoracic pressure [ITP].  A commonly queried hemodynamic state is whether cardiac output will rise in response to a volume challenge. The general principle involved in FHM is a dose-response relationship similar to basic pharmacology.  Importantly, if one alters the dose of a medication and observes a different clinical response, the change in response may be due to the altered dose.  Similarly, because the diagnostic characteristics of SVV were derived in the context of a specific, predefined stress applied to the cardiovascular system [e.g. ITP change], observing a change in ‘response’ of SVV will be confounded by a change in the ‘dose’ of ITP.

Intra-thoracic pressure

In the passive, ventilated patient – one not generating any respiratory effort – the change in ITP is related directly to the ventilator-applied tidal volume and indirectly to the compliance of the chest wall [3-5].  Thus, the ITP experienced by the cardiovascular system will increase with higher tidal volume and/or lower chest wall compliance [e.g. obesity, ascites, chest wall edema, etc.], and vice versa [4].  If a patient generates his or her own inspiratory effort with the ventilator or bears down against it, the change in ITP is, essentially, unpredictable.  Such fluctuations in ITP will confound any measured cardiovascular response such as SVV.  It is the reason why studies of FHM included patients who were completely passive with the ventilator and receiving relatively high tidal volumes [8-10 mL/Kg] [6-8].

Intra-thoracic pressure and cardiovascular physiology

Cardiac output is determined at the cross-roads of venous return and cardiac function.  These two physiological phenomenon may be plotted simultaneously to generate the Guyton Diagram [9, 10].  The intersection of venous return and cardiac function defines the operating point of the cardiovascular system; the operating point determines the central venous pressure [on the x-axis] and cardiac output [on the y-axis] [11].  A passive, mechanical breath [i.e. an increase in ITP] favors a right shift of the cardiac function curve relative to the venous return curve.  Consequently, if the operating point lies upon the ascending [volume-responsive] portion of the cardiac function curve, an increase in ITP transiently reduces right ventricular output.  By contrast, if the operating point intersects the plateau of the cardiac function curve [volume-unresponsive], an increase in ITP will not diminish cardiac output.  While this physiology applies to the right ventricle, 2-3 cardiac cycles later, the right heart output is experienced by the left heart – a delay imposed by the pulmonary transit time.  Therefore, the physiological stress of an increase in ITP may be assayed by beat-to-beat evaluation of left ventricular SVV; the magnitude of SVV is suggestive of where upon the cardiac function curve the venous return curve intersects [12] and, consequently, alludes to volume responsiveness.

The physiology of left ventricular stroke volume variation

Because aortic pulse pressure [aortic systolic pressure – aortic diastolic pressure] directly relates to left ventricular stroke volume [as a function of central aortic compliance], pulse pressure variation (PPV) is frequently used as a surrogate of left ventricular SVV [12].  Deflections in pulse pressure during a single, mechanical respiratory cycle are referenced to an end-expiratory baseline.  In the patient passive with the ventilator, a mechanical breath causes an in initial increase in systolic blood pressure referred to as reverse pulsus paradoxus, dUP [or delta UP] and is the consequence of multiple mechanisms. 

Firstly, there may be direct transmission of the increased ITP to the aorta and arterial tree [13], secondly mechanical insufflation of the lungs in a passive patient favors each of the following: improved left ventricular compliance via reduction of right ventricular volume [14], reduced left ventricular afterload [15] and, most prominently, an increase in pulmonary venous return and therefore LV preload [16, 17].  As many of these variables are not related to volume responsiveness, dUP is felt to be a poor marker of fluid responsiveness [18].  By contrast, during mechanical expiration, an inspiratory reduction in RV output reaches the left ventricle.  This is reflected as an expiratory reduction in aortic systolic pressure and is referred to as dDown [or delta DOWN].

Caveats and considerations

Firstly, in the initial clinical FHM studies, the patients were assumed to have essentially normal chest wall compliance, all received relatively large tidal volumes and all were completely passive with the ventilator.  These parameters, in effect, standardized the ‘dose’ of ITP.  As a consequence, PPV performs poorly in patients generating spontaneous inspiratory effort [19-22], when smaller tidal volumes are applied [23, 24], or when there are abnormalities in chest wall compliance [4, 25, 26].

Secondly, the primary mechanism of SVV as a marker of fluid responsiveness is the result of an inspiratory reduction in right ventricular output that is transmitted to the left ventricle during mechanical expiration [12, 18]; this is because small changes in ITP affect large changes in venous return [27, 28].  However, increasing lung volume also afterloads the right heart such that diminished right heart output may not reflect preload reserve, but instead afterload sensitivity.  As such, reduced pulmonary compliance and pulmonary arterial hypertension may accentuate afterload sensitivity and diminish SVV and PPV as predictors of fluid responsiveness [29-34].  Additionally, if the left ventricle is afterload sensitive [e.g. systolic heart failure], ITP can unload the heart, facilitate dUP and create PPV [4, 35-37]. 

The predictive value of SVV and PPV is also impaired in patients with cardiac arrhythmia [SVV due to variable diastole length], and excessive respiratory rate [38]. Finally, means of FHM that vary the venous return function may reduce some of the aforementioned uncertainty.  Passive leg raising and the end-expiratory occlusion test are two such methods which outperform those that rely on ITP change as the cardiovascular stress in both in patients breathing spontaneously and with arrhythmia [29, 39].

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References:

1. Pinsky, M.R. and D. Payen, Functional hemodynamic monitoring. Crit Care, 2005. 9(6): p. 566-72.

2. Broccard, A.F., Cardiopulmonary interactions and volume status assessment. J Clin Monit Comput, 2012. 26(5): p. 383-91.

3. Pinsky, M.R., Recent advances in the clinical application of heart-lung interactions. Curr Opin Crit Care, 2002. 8(1): p. 26-31.

4. Mesquida, J., H.K. Kim, and M.R. Pinsky, Effect of tidal volume, intrathoracic pressure, and cardiac contractility on variations in pulse pressure, stroke volume, and intrathoracic blood volume. Intensive Care Med, 2011. 37(10): p. 1672-9.

5. Jardin, F., et al., Influence of lung and chest wall compliances on transmission of airway pressure to the pleural space in critically ill patients. Chest, 1985. 88(5): p. 653-8.

6. 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(1): p. 134-8.

7. Barbier, C., et al., Respiratory changes in inferior vena cava diameter are helpful in predicting fluid responsiveness in ventilated septic patients. Intensive Care Med, 2004. 30(9): p. 1740-6.

8. Vieillard-Baron, A., et al., Superior vena caval collapsibility as a gauge of volume status in ventilated septic patients. Intensive Care Med, 2004. 30(9): p. 1734-9.

9. Guyton, A.C., Determination of cardiac output by equating venous return curves with cardiac response curves. Physiol Rev, 1955. 35(1): p. 123-9.

10. Magder, S., Bench-to-bedside review: An approach to hemodynamic monitoring - Guyton at the bedside. Crit Care, 2012. 16(5): p. 236.

11. Feihl, F. and A.F. Broccard, Interactions between respiration and systemic hemodynamics. Part I: basic concepts. Intensive Care Med, 2009. 35(1): p. 45-54.

12. Michard, F. and J.L. Teboul, Using heart-lung interactions to assess fluid responsiveness during mechanical ventilation. Crit Care, 2000. 4(5): p. 282-9.

13. Denault, A.Y., et al., Determinants of aortic pressure variation during positive-pressure ventilation in man. Chest, 1999. 116(1): p. 176-86.

14. Mitchell, J.R., et al., RV filling modulates LV function by direct ventricular interaction during mechanical ventilation. Am J Physiol Heart Circ Physiol, 2005. 289(2): p. H549-57.

15. Buda, A.J., et al., Effect of intrathoracic pressure on left ventricular performance. N Engl J Med, 1979. 301(9): p. 453-9.

16. Brower, R., et al., Effect of lung inflation on lung blood volume and pulmonary venous flow. J Appl Physiol (1985), 1985. 58(3): p. 954-63.

17. Scharf, S.M., et al., Hemodynamic effects of positive-pressure inflation. J Appl Physiol Respir Environ Exerc Physiol, 1980. 49(1): p. 124-31.

18. Magder, S., Clinical usefulness of respiratory variations in arterial pressure. Am J Respir Crit Care Med, 2004. 169(2): p. 151-5.

19. Soubrier, S., et al., Can dynamic indicators help the prediction of fluid responsiveness in spontaneously breathing critically ill patients? Intensive Care Med, 2007. 33(7): p. 1117-24.

20. Heenen, S., D. De Backer, and J.L. Vincent, How can the response to volume expansion in patients with spontaneous respiratory movements be predicted? Crit Care, 2006. 10(4): p. R102.

21. Magder, S., Predicting volume responsiveness in spontaneously breathing patients: still a challenging problem. Crit Care, 2006. 10(5): p. 165.

22. Monnet, X., et al., Passive leg raising predicts fluid responsiveness in the critically ill. Crit Care Med, 2006. 34(5): p. 1402-7.

23. De Backer, D., et al., Pulse pressure variations to predict fluid responsiveness: influence of tidal volume. Intensive Care Med, 2005. 31(4): p. 517-23.

24. Renner, J., et al., Stroke volume variation during hemorrhage and after fluid loading: impact of different tidal volumes. Acta Anaesthesiol Scand, 2007. 51(5): p. 538-44.

25. Jacques, D., et al., Pulse pressure variation and stroke volume variation during increased intra-abdominal pressure: an experimental study. Crit Care, 2011. 15(1): p. R33.

26. Duperret, S., et al., Increased intra-abdominal pressure affects respiratory variations in arterial pressure in normovolaemic and hypovolaemic mechanically ventilated healthy pigs. Intensive Care Med, 2007. 33(1): p. 163-71.

27. Fessler, H.E., et al., Effects of Positive End-Expiratory Pressure on the Gradient for Venous Return. American Review of Respiratory Disease, 1991. 143(1): p. 19-24.

28. Jellinek, H., et al., Influence of positive airway pressure on the pressure gradient for venous return in humans. J Appl Physiol (1985), 2000. 88(3): p. 926-32.

29. Monnet, X., et al., Passive leg-raising and end-expiratory occlusion tests perform better than pulse pressure variation in patients with low respiratory system compliance. Crit Care Med, 2012. 40(1): p. 152-7.

30. Wyler von Ballmoos, M., et al., Pulse-pressure variation and hemodynamic response in patients with elevated pulmonary artery pressure: a clinical study. Crit Care, 2010. 14(3): p. R111.

31. Daudel, F., et al., Pulse pressure variation and volume responsiveness during acutely increased pulmonary artery pressure: an experimental study. Crit Care, 2010. 14(3): p. R122.

32. Magder, S., Further cautions for the use of ventilatory-induced changes in arterial pressures to predict volume responsiveness. Critical Care, 2010. 14(5).

33. Venus, B., L.E. Cohen, and R.A. Smith, Hemodynamics and intrathoracic pressure transmission during controlled mechanical ventilation and positive end-expiratory pressure in normal and low compliant lungs. Crit Care Med, 1988. 16(7): p. 686-90.

34. Mahjoub, Y., et al., Assessing fluid responsiveness in critically ill patients: False-positive pulse pressure variation is detected by Doppler echocardiographic evaluation of the right ventricle. Crit Care Med, 2009. 37(9): p. 2570-5.

35. Grace, M.P. and D.M. Greenbaum, Cardiac performance in response to PEEP in patients with cardiac dysfunction. Crit Care Med, 1982. 10(6): p. 358-60.

36. Rasanen, J., P. Nikki, and J. Heikkila, Acute myocardial infarction complicated by respiratory failure. The effects of mechanical ventilation. Chest, 1984. 85(1): p. 21-8.

37. Pizov, R., Y. Ya'ari, and A. Perel, The arterial pressure waveform during acute ventricular failure and synchronized external chest compression. Anesth Analg, 1989. 68(2): p. 150-6.

38. De Backer, D., et al., Influence of Respiratory Rate on Stroke Volume Variation in Mechanically Ventilated Patients. Anesthesiology, 2009. 110(5): p. 1092-1097.

39. Marik, P.E., X. Monnet, and J.L. Teboul, Hemodynamic parameters to guide fluid therapy. Ann Intensive Care, 2011. 1(1): p. 1.