Use of ‘tidal volume challenge’ to improve the reliability of pulse pressure variation
© Myatra et al. 2017
Published: 21 March 2017
This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2017. Other selected articles can be found online at http://ccforum.com/series/annualupdate2017. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.
Studies have shown that only about 50% of unstable critically ill patients will actually respond positively to a fluid challenge . Uncorrected hypovolemia may result in inappropriate administration of vasopressor infusions, which may in turn affect tissue oxygenation, leading to organ dysfunction and death [2, 3]. On the other hand, excessive fluid loading is associated with increased complications, mortality and duration of intensive care unit (ICU) stay [4, 5]. Thus, it is important to identify fluid responders to know who can benefit from fluid administration and to avoid fluid overload in those who are not fluid responsive. However, identifying which patients will respond to volume expansion presents a daily challenge in ICUs today.
Dynamic changes in arterial waveform‐derived variables during mechanical ventilation, such as systolic pressure variation (SPV), pulse pressure variation (PPV) and stroke volume variation (SVV), have proven to be superior to traditionally used static indices, such as central venous pressure (CVP) and pulmonary artery occlusion pressure (PAOP), to predict fluid responsiveness [1, 6–8]. Of these indices, PPV and SVV are commonly used in clinical practice, with PPV being more reliable and having a higher level of evidence [7, 9, 10].
Heart‐lung interactions during mechanical ventilation: physiological principles underlying PPV and SVV
The PPV is calculated as the difference between the maximal and the minimal pulse pressure value over one ventilator cycle divided by their average value . It can be automatically calculated by newer hemodynamic monitors. The SVV is derived from the arterial pressure waveform analysis and is automatically calculated by calibrated and uncalibrated pulse contour analysis cardiac output monitors. The principle mechanisms underlying how these parameters work are based on heart‐lung interactions during mechanical ventilation .
Intermittent positive‐pressure ventilation produces cyclic changes in the loading conditions of both the ventricles. The intrathoracic and transpulmonary pressures increase during inspiration leading to variable changes in the loading conditions of both the ventricles. Increase in intrathoracic pressures during mechanical insufflation decreases venous return and in turn decreases the right ventricular (RV) preload, whereas an increase in transpulmonary pressure increases RV afterload resulting in decreased RV stroke volume, which will be at its lowest at the end of inspiration [11–16]. At the same time, an increase in the intrathoracic and transpulmonary pressures results in decreased LV afterload and a transient increase in LV preload due to squeezing out of alveolar blood, leading to increased LV stroke volume, which will be at its maximum at the end of inspiration . The reduction in RV stroke volume during inspiration leads to decreased LV filling after a lag period of two to three heart beats due to the pulmonary transit time . This leads to decreased LV stroke volume, which will be its lowest during expiration.
Thus, intermittent positive‐pressure ventilation produces cyclic changes in LV stroke volume, which is maximum during inspiration and lowest during expiration. The magnitude of change in LV stroke volume, or of its surrogates, such as pulse pressure, will be magnified when the patient is preload‐dependent. Therefore, a high PPV value should be associated with preload responsiveness and a low PPV value with preload unresponsiveness (Fig. 1). A threshold value greater than 12–13% has been reported to be highly predictive of volume responsiveness [7, 9, 10].
Comparison of dynamic changes of arterial waveform‐derived variables during mechanical ventilation (SPV, PPV and SVV)
Comparison of predictive value of variables used to determine fluid responsiveness in mechanically ventilated patients in three systematic reviews
Types of studies
AUC (95% confidence interval)
Marik et al. 
variable tidal volume
ICU and OR patients
Hong et al. 
variable tidal volume
Only ICU patients
Yang and Du 
tidal volume > 8 ml/kg
Only ICU patients
Limitations with the use of PPV to predict fluid responsiveness
Limitations with the use of pulse pressure variation (PPV) to predict fluid responsiveness
Mechanisms for failure
Type of error
Spontaneous breathing activity
Irregular variations in intrathoracic pressure and thus the variation in stroke volume cannot correlate with preload dependency
(may occasionally be false negative depending on the type of breathing)
The variation in stroke volume is related more to the irregularity in diastole than to the heart‐lung interactions
Mechanical ventilation using low tidal volume (<8 ml/kg)
The small variations in intrathoracic pressure due to the low tidal volume are insufficient to produce significant changes in the intrathoracic pressure
Low lung compliance
The transmission of changes in alveolar pressure to the intrathoracic structures is attenuated
No change in intrathoracic pressure during the respiratory cycle
Increased intra‐abdominal pressure
Threshold values of PPV will be elevated
Low HR/RR ratio < 3.6 (severe bradycardia or high frequency ventilation)
If the RR is very high, the number of cardiac cycles per respiratory cycle may be too low to allow variation in stroke volume
Using a ‘tidal volume challenge’ to overcome the limitations associated with PPV during low tidal volume ventilation
Several studies have shown that PPV does not reliably predict fluid responsiveness during low tidal volume ventilation [25, 33–37]. De Backer et al.  showed that PPV was a reliable predictor of fluid responsiveness, provided that the tidal volume was at least 8 ml/kg predicted body weight (PBW). During low tidal volume ventilation, PPV may indicate a non‐responsive status even in responders as the tidal volume might be insufficient to produce a significant change in the intrathoracic pressure [38, 39]. However, Freitas et al.  showed that PPV was a reliable marker of fluid responsiveness in septic patients with acute respiratory distress syndrome (ARDS) during low tidal volume ventilation using a lower cut‐off value of 6.5%.
Among the limitations with use of PPV during controlled mechanical ventilation in the ICU, the use of low tidal volume is the most common. Today the indications for use of low tidal volume in ICU are expanding [41, 42]. Two multicenter studies [18, 19] showed that the number of ICU patients in whom PPV was suitable for use was very low, with as many as 72–87% of the patients on controlled mechanical ventilation being unsuitable for use of this parameter, because of the use of low tidal volume ventilation. Two recent studies [43, 44] that used the ‘gray zone’ approach to investigate the clinical value of PPV, included several patients ventilated with low tidal volume. Biais et al. , in a subgroup analysis, showed that the gray zone was larger in patients ventilated with a low tidal volume than in patients with a tidal volume of at least 8 ml/kg PBW. These studies may mislead one to conclude that PPV has limited clinical value .
The ‘tidal volume challenge’ is a novel test proposed to improve the reliability of PPV during low tidal volume ventilation . The test involves transiently increasing tidal volume from 6 ml/kg PBW to 8 ml/kg PBW for one minute and observing the change in PPV (∆PPV6–8) from baseline (PPV6) to that at 8 ml/kg PBW (PPV8). In a recent study testing the tidal volume challenge , 30 sets of measurements were recorded in 20 patients with acute circulatory failure receiving low tidal volume ventilation using volume assist‐control ventilation and without spontaneous breathing activity. Fluid responsiveness was defined as an increase in thermodilution cardiac output > 15% after giving a fluid bolus after reducing tidal volume back to 6 m/kg PBW. As expected, the PPV6 could not predict fluid responsiveness, with an AUROC of 0.69. Importantly, there was a significant increase in PPV (∆PPV6–8), following the tidal volume challenge only in fluid responders. The ∆PPV6–8 discriminated responders from non‐responders with an AUROC of 0.99 (sensitivity 94% and specificity 100%) with a cut off value of 3.5% . The tidal volume challenge thus improved the reliability of PPV in predicting fluid responsiveness in patients receiving low tidal volume ventilation. Similar results were also seen using SVV (∆SVV6–8) obtained from a pulse contour analysis cardiac output device with an AUROC of 0.97 (sensitivity 88% and specificity 100%) with a cut off value of 2.5% . The change in PPV after giving a fluid bolus (∆PPVfb) also accurately confirmed fluid responsiveness with an AUROC of 0.98 (sensitivity 94% and specificity 100%) with a cut off value of 1.5%.
How to perform and interpret the tidal volume challenge
This test is performed to assess fluid responsiveness in patents in shock, ventilated using low tidal volume without spontaneous breathing activity. The PPV is noted from the bedside monitor at baseline (tidal volume 6 ml/kg PBW). The tidal volume is then transiently increased from 6 ml/kg PBW to 8 ml/kg PBW for one minute. The PPV is recorded at 8 ml/kg PBW and the tidal volume is reduced back to 6 ml/kg PBW. The ∆PPV6–8 after performing the tidal volume challenge is recorded. A ∆PPV6–8 greater than 3.5% predicts fluid responsiveness with high accuracy.
PPV is unreliable in patients with low lung compliance, especially in patients with ARDS . In these patients, airway pressure transmission is reduced, such that the cyclic changes in intrathoracic pressure may be attenuated even with marked changes in alveolar pressure . Monnet et al.  showed that the predictive value of PPV was related to the compliance of the respiratory system and if the compliance was < 30 ml/cmH2O, PPV was less accurate in predicting fluid responsiveness. In our study, although the median compliance of the respiratory system was < 30 ml/cmH2O (25 [23–33]) during low tidal volume ventilation, it increased to > 30 ml/cmH2O (32 [24–40]) after the tidal volume challenge. Thus, the tidal volume challenge may help identify responders even when compliance of the respiratory system is low in patients receiving low tidal volume ventilation with recruitable lungs. This needs to be confirmed in an adequately powered study. Whether this approach will also work in patients who do not increase compliance of the respiratory system after giving a tidal volume challenge needs to be tested. Whether PPV will be reliable during spontaneous breathing attempts after giving a tidal volume challenge or in other situations where the use of PPV is limited also needs to be tested.
Advantages of using the tidal volume challenge
Use of a tidal volume challenge increases the reliability of PPV to predict fluid responsiveness during low tidal volume ventilation, which is now common practice in the ICU. It is a simple test that can be performed easily at the bedside. Importantly, observing the changes in PPV (obtained from a simple bedside hemodynamic monitor) during this test does not require a cardiac output monitor, making this test applicable even in resource‐limited settings. The ∆PPVfb accurately confirms fluid responsiveness. Thus, a combination of ∆PPV6–8 with ∆PPVfb can help predict and thereafter confirm fluid responsiveness when continuous cardiac output monitoring is unavailable.
Limitations of the tidal volume challenge
The tidal volume challenge may not be able to overcome the other limitations associated with the use of PPV, such as spontaneous breathing, cardiac arrhythmias, open chest, and raised intra-abdominal pressure and needs to be evaluated in these settings. Alternative techniques, such as PLR or end‐expiratory occlusion, when applicable, may be considered in these situations.
The PPV is a dynamic parameter that can be easily recorded from a bedside monitor and reliably predicts preload responsiveness. In addition, it does not require continuous cardiac output monitoring or any other tools or maneuvers to be performed. One of the major limitations with its use in patients receiving controlled mechanical ventilation is that it is unreliable during low tidal volume ventilation, which is now widely practiced in ICU patients. Discarding this useful parameter would, however, be like throwing the baby out with the bathwater. This major limitation can be easily overcome by using the ‘tidal volume challenge’ a simple bedside test, following which PPV can reliably predict fluid responsiveness. Whether this test may also have the potential to overcome other limitations associated with the use of PPV needs to be further studied. Alternative methods to assess preload responsiveness may be required to overcome the other limitations with the use of PPV.
The publication charges will be funded by the Division of Clinical Research of the Hôpitaux universitaires Paris-Sud (Assistance Publique-Hôpitaux de Paris).
Availability of data and materials
SNM, XM and JLT contributed equally to the writing of this manuscript. All authors read and approved the final manuscript.
SNM has no competing interests. XM and JLT are members of the Medical Advisory Board of Pulsion Medical Systems.
Consent for publication
Ethics approval and consent to participate
- Michard F, Teboul JL. Predicting fluid responsiveness in ICU patients: a critical analysis of the evidence. Chest. 2002;121:2000–8.View ArticlePubMedGoogle Scholar
- Murakawa K, Kobayashi A. Effects of vasopressors on renal tissue gas tensions during hemorrhagic shock in dogs. Crit Care Med. 1998;16:789–92.View ArticleGoogle Scholar
- Pinsky MR, Brophy P, Padilla J, Paganini E, Pannu N. Fluid and volume monitoring. Int J Artif Organs. 2008;31:111–26.PubMedGoogle Scholar
- Wiedemann HP, Wheeler AP, Bernard GR, et al. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006;354:2564–75.View ArticlePubMedGoogle Scholar
- Acheampong A, Vincent JL. A positive fluid balance is an independent prognostic factor in patients with sepsis. Crit Care. 2015;19:251.View ArticlePubMedPubMed CentralGoogle Scholar
- Michard F, Boussat S, Chemla D, 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;162:134–8.View ArticlePubMedGoogle Scholar
- Marik PE, Cavallazzi R, Vasu T, Hirani A. Dynamic changes in arterial waveform derived variables and fluid responsiveness in mechanically ventilated patients. A systematic review of the literature. Crit Care Med. 2009;37:2642–7.View ArticlePubMedGoogle Scholar
- Perel A, Pizov R, Cotev S. Respiratory variations in the arterial pressure during mechanical ventilation reflect volume status and fluid responsiveness. Intensive Care Med. 2014;40:798–807.View ArticlePubMedGoogle Scholar
- Hong JQ, He HF, Chen ZY, et al. Comparison of stroke volume variation with pulse pressure variation as a diagnostic indicator of fluid responsiveness in mechanically ventilated critically ill patients. Saudi Med J. 2014;35:261–8.PubMedGoogle Scholar
- Yang X, Du B. Does pulse pressure variation predicts fluid responsiveness in critically ill patients: a critical review and meta-analysis. Crit Care. 2014;18:650.View ArticlePubMedPubMed CentralGoogle Scholar
- Michard F, Teboul JL. Using heart lung interactions to assess fluid responsiveness during mechanical ventilation. Crit Care. 2000;4:282–9.View ArticlePubMedPubMed CentralGoogle Scholar
- Morgan BC, Martin WE, Hornbein TF, Crawford EW, Guntheroth WG. Hemodynamic effects of intermittent positive pressure ventilation. Anesthesiology. 1966;27:584–90.View ArticlePubMedGoogle Scholar
- Jardin F, Delorme G, Hardy A, Auvert B, Beauchet A, Bourdarias JP. Reevaluation of hemodynamic consequences of positive pressure ventilation: emphasis on cyclic right ventricular afterloading by mechanical lung inflation. Anesthesiology. 1990;72:966–70.View ArticlePubMedGoogle Scholar
- Permutt S, Wise RA, Brower RG. How changes in pleural and alveolar pressure cause changes in afterload and preload. In: Scharf SM, Cassidy SS, editors. Heart-Lung Interactions in Health and Disease. New York: Marcel Dekker; 1989. p. 243–50.Google Scholar
- Jardin F, Farcot JC, Gueret P, Prost JF, Ozier Y, Bourdarias JP. Cyclic changes in arterial pulse during respiratory support. Circulation. 1983;68:266–74.View ArticlePubMedGoogle Scholar
- Scharf SM, Brown R, Saunders N, Green LH. Hemodynamic effects of positive-pressure inflation. J Appl Physiol. 1980;49:124–31.PubMedGoogle Scholar
- Berkenstadt H, Margalit N, Hadani M, et al. Stroke volume variation as a predictor of fluid responsiveness in patients undergoing brain surgery. Anesth Analg. 2001;92:984–9.View ArticlePubMedGoogle Scholar
- Mahjoub Y, Lejeune V, Muller L, et al. Evaluation of pulse pressure variation validity criteria in critically ill patients: a prospective observational multicentre point prevalence study. Br J Anaesth. 2014;112:681–5.View ArticlePubMedGoogle Scholar
- Fischer MO, Mahjoub Y, Boisselier C, et al. Arterial pulse pressure variation suitability in critical care: A French national survey. Anaesth Crit Care Pain Med. 2015;34:23–8.View ArticlePubMedGoogle Scholar
- Benes J, Zatloukal J, Kletecka J, Simanova A, Haidingerova L, Pradl R. Respiratory induced dynamic variations of stroke volume and its surrogates as predictors of fluid responsiveness: applicability in the early stages of specific critical states. J Clin Monit Comput. 2013;28:225–31.View ArticlePubMedGoogle Scholar
- Monnet X, Marik P, Teboul JL. Passive leg raising for predicting fluid responsiveness: a systematic review and meta-analysis. Intensive Care Med. 2016;42:1935–47.View ArticlePubMedGoogle Scholar
- Monnet X, Teboul JL. Passive leg raising. Intensive Care Med. 2008;34:659–63.View ArticlePubMedGoogle Scholar
- Monnet X, Teboul JL. Passive leg raising: five rules, not a drop of fluid! Crit Care. 2015;19:18.View ArticlePubMedPubMed CentralGoogle Scholar
- Monnet X, Osman D, Ridel C, Lamia B, Richard C, Teboul JL. Predicting volume responsiveness by using the end-expiratory occlusion in mechanically ventilated intensive care unit patients. Crit Care Med. 2009;37:951–6.View ArticlePubMedGoogle Scholar
- Monnet X, Bleibtreu A, Ferré A, 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;40:152–7.View ArticlePubMedGoogle Scholar
- Silva S, Jozwiak M, Teboul JL, Persichini R, Richard C, Monnet X. End-expiratory occlusion test predicts preload responsiveness independently of positive end-expiratory pressure during acute respiratory distress syndrome. Crit Care Med. 2013;41:1692–701.View ArticlePubMedGoogle Scholar
- Guerin L, Monnet X, Teboul JL. Monitoring volume and fluid responsiveness: From static to dynamic indicators. Best Pract Res Clin Anaesthesiol. 2013;27:177–85.View ArticlePubMedGoogle Scholar
- De Backer D, Pinsky MR. Can one predict fluid responsiveness in spontaneously breathing patients? Intensive Care Med. 2007;33:1111–3.View ArticlePubMedGoogle Scholar
- Muller L, Toumi M, Bousquet PJ, et al. An increase in aortic blood flow after an infusion of 100 ml colloid over 1 minute can predict fluid responsiveness: the mini-fluid challenge study. Anesthesiology. 2011;115:541–7.View ArticlePubMedGoogle Scholar
- Vieillard-Baron A, Chergui K, Rabiller A, et al. Superior vena caval collapsibility as a gauge of volume status in ventilated septic patients. Intensive Care Med. 2004;30:1734–9.View ArticlePubMedGoogle Scholar
- Feissel M, Michard F, Faller JP, Teboul JL. The respiratory variation in inferior vena cava diameter as a guide to fluid therapy. Intensive Care Med. 2004;30:1834–7.View ArticlePubMedGoogle Scholar
- Michard F, Chemla D, Teboul JL. Applicability of pulse pressure variation: how many shades of grey? Crit Care. 2015;19:144.View ArticlePubMedPubMed CentralGoogle Scholar
- De Backer D, Heenen S, Piagnerelli M, Koch M, Vincent J. Pulse pressure variations to predict fluid responsiveness: influence of tidal volume. Intensive Care Med. 2005;31:517–23.View ArticlePubMedGoogle Scholar
- Vallée F, Richard JC, Mari A, et al. Pulse pressure variations adjusted by alveolar driving pressure to assess fluid responsiveness. Intensive Care Med. 2009;35:1004–10.View ArticlePubMedGoogle Scholar
- Lakhal K, Ehrmann S, Benzekri-Lefèvre D, et al. Respiratory pulse pressure variation fails to predict fluid responsiveness in acute respiratory distress syndrome. Crit Care. 2011;15:R85.View ArticlePubMedPubMed CentralGoogle Scholar
- Lansdorp B, Lemson J, vanPutten MJ, de Keijzer A, van der Hoeven JG, Pickkers P. Dynamic indices do not predict volume responsiveness in routine clinical practice. Br J Anaesth. 2012;108:395–401.View ArticlePubMedGoogle Scholar
- Reuter DA, Bayerlein J, Goepfert MS, et al. Influence of tidal volume on left ventricular stroke volume variation measured by pulse contour analysis in mechanically ventilated patients. Intensive Care Med. 2003;29:476–80.View ArticlePubMedGoogle Scholar
- Teboul JL, Monnet X. Pulse pressure variation and ARDS. Minerva Anestesiol. 2013;79:398–407.PubMedGoogle Scholar
- Pinsky MR. Using ventilation-induced aortic pressure and flow variation to diagnose preload responsiveness. Intensive Care Med. 2004;30:1008–10.View ArticlePubMedGoogle Scholar
- Freitas FG, Bafi AT, Nascente AP, et al. Predictive value of pulse pressure variation for fluid responsiveness in septic patients using lung-protective ventilation strategies. Br J Anaesth. 2013;110:402–8.View ArticlePubMedGoogle Scholar
- Serpa Neto A, Cardoso SO, Manetta JA, et al. Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome: a meta-analysis. JAMA. 2012;308:1651–9.View ArticlePubMedGoogle Scholar
- Futier E, Pereira B, Jaber S. Intraoperative low-tidal-volume ventilation. N Engl J Med. 2013;369:1862–3.View ArticlePubMedGoogle Scholar
- Cannesson M, Le Manach Y, Hofer C, et al. Assessing the diagnostic accuracy of pulse pressure variations for the prediction of fluid responsiveness: a “gray zone” approach. Anesthesiology. 2011;115:231–41.View ArticlePubMedGoogle Scholar
- Biais M, Ehrmann S, Mari A, et al. Clinical relevance of pulse pressure variations for predicting fluid responsiveness in mechanically ventilated intensive care unit patients: the grey zone approach. Crit Care. 2014;18:587.View ArticlePubMedPubMed CentralGoogle Scholar
- Myatra SN, Prabu NR, Divatia JV, Monnet X, Kulkarni AP, Teboul JL. The changes in pulse pressure variation or stroke volume variation after a “tidal volume challenge” reliably predict fluid responsiveness during low tidal volume ventilation. Crit Care Med. 2017;45:415–21.View ArticlePubMedGoogle Scholar
- Teboul JL, Pinsky MR, Mercat A, et al. Estimating cardiac filling pressure in mechanically ventilated patients with hyperinflation. Crit Care Med. 2000;28:3631–6.View ArticlePubMedGoogle Scholar