PEEP application and breathing pattern influence ecographic IVC collapsibility in normal subjects

Paola Campodonico(1), Andrea Duca(2), Valentina Rosti(2), Chiara Travierso(2), Anna Maria Brambilla(3) and Roberto Cosentini(2)
1) Ospedale Sn Paolo, Savona, Italy
2) Emergenza ad Alta Specializzazione – ASST – Papa Giovanni XXIII, Bergamo, Italy
3) Emergency Medicine Department, IRCCS Fondazione Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy


Volemia evaluation is fundamental in ED critical patients. Bedside ultrasound is an useful and non-invasive method to determine volemic status, including patients with acute respiratory failure treated with Non-Invasive Mechanical Ventilation. AIM. The aim of our study was to evaluate the whether PEEP application during Non-Invasive Mechanical Ventilation influences Inferior Vena Cava measurement and collapsibility to evaluate the volemia in normal subjects.
We measured Inferior Vena Cava Collapsibility Index (IVC-CI) with three different PEEP value application (0, 5 an 10 cm H2O), each at two different respiratory rates, 15 and 30 breaths per minute. For each subject 6 different measures were performed.
We enrolled 40 normal subjects, 15 males, with a mean age of 31.8 ± 10,4 years. We observed that the increase of PEEP from 0 to 10 cmH2O lead to a significant IVC-CI reduction (from 32,4 ± 13,5 to 25,1 ± 12,7, p = 0,03), and similarly from 5 to 10 cmH2O (from 30,5 ± 15.1 to 25.1 ± 12.7, p = 0,02). Conversely, the increase of PEEP from 0 to 5 cmH2O did not determine a significant decrease of IVC-CI (from 32,4 ± 13,5 to 30,5 ± 15.1, p = 0,326). The increase of respiratory rate from 16 to 30 bpm lead to a significant increase of IVC-CI at all PEEP levels (PEEP 0, 32.4 ± 13.4 vs 42.8 ± 15.9, p = 0.001; PEEP 5, 30.5 ±15.1 vs 42.8 15.9, p = 0.001; PEEP 10, 25.1 ± 12.7 vs 38.8 ± 17.6, p = 0.001).
One results show that in normal subjects IVC-CI is significantly affected by both Non-Invasive Mechanical Ventilation application and respiratory rate. In fact, higher PEEP application (10 cmH2O) determine decrees of IVC-CI, whereas higher respiratory rate (30 bpm) induce a significant increase of IVC-CI.
Our data suggest that in normal subjects the ultrasound evaluation of volemia by IVC-CI must be evaluated according to PEEP application and breathing pattern. These data should be confirmed in the ED patients with acute respiratory failure in order to further explore the validity of volemia evaluation in the critical population.


The assessment of the intravascular volume status of patients admitted to the Emergency
Department (ED) is essential not only for the diagnosis and treatment but also to improve patient’s monitoring.
The optimization of intravenous fluid and diuretic therapy is a paramount in the critically ill patients with cardiovascular insufficiency; it has the double objective of ensuring an adequate tissue perfusion and preventing or treating the interstitial-alveolar imbibition. Basing on the Frank-Starling law, there is a linear correlation between the ventricular end diastolic volume (pre-load) and the volume of blood pumped from the left ventricle per beat (stroke volume) that is to say more blood arrives to the heart, higher is the stroke volume. Fluid therapy should be based on the so called fluid responsiveness, that is the ability of the heart to increase the stroke volume in response to fluid administration. Fluid responsiveness depends on the personal Frank-Starling curve of the patient and on the part of the curve where the patient’s heart is working at the moment of the evaluation. If it is in the flat part of the curve, as in heart failure happens, the increase of pre-load does not produce a proportional increase of the stroke volume; in this situation, liquid overload is going to increase the interstitial-alveolar oedema instead of stroke volume, with negative effects on the hemodynamic conditions and gas exchanges.
Central venous pressure (CVP) measured by a central venous catheter is commonly used in clinical practice to assess fluid responsiveness . Nevertheless, recent studies showed that CVP is not a good indicator of circulating volume and is not accurate in predicting the fluid responsiveness (1-2-3).
Another method to predict fluid responsiveness is the fluid challenge: a small amount of fluid is given to the patient in a short period of time and then the hemodynamic response is assessed.
This procedure can expose the patient to an excessive amount of fluid without benefits (4-5).
The ultrasound (US) of the inferior vena cava (IVC) is easy to learn and to reproduce (6). Some studies showed a good correlation between the diameter of the IVC, the volemia and the CVP (7-8-9). In fact, during inspiration phase, when the intrathoracic pressure becomes negative, the collapsibility index of the IVC (CI) correlates to CVP: the higher is the CI value, the lower is CVP (10-16). The reduction in the intrathoracic pressure during inspiration leads to three different effects: the increase in the diastolic filling, the increase in the vascular bed capacity and the reduction of the vascular resistances. Big respiratory variations of IVC diameter (>40%) have been shown to predict good response to fluid challenge (12) Studies on the accuracy of CI in patients in spontaneous breathing have been published (12).
There are only few studies (17, 18) on the relationship between non invasive ventilation (NIV) and CI. We conducted a pilot study in a population of healthy volunteers to assess the possible interference of NIV on the assessment of volemia using CI, at different levels of PEEP and respiratory rates.

Matherial And Methods

We enrolled healthy volunteers, with no medical history, of age >=18. Exclusion criteria: difficult ultrasound assessment due to obesity or meteorism; known chronic diseases.


We applied the following protocol to assess how the application of a positive end respiratory
pressure (PEEP) could affect the respiratory variations of the ICV (CI) at different respiratory rates:
• subject supine with the seat-back reclined of 45 degrees: the IVC was visualized using a subxifoideal approach with a convex probe 5 MHZ in B- mode
• using M-mode, we measured maximum and minimum diameter of IVC on one single respiratory cycle 2-3 cm from the outlet in the right atrium
• The CI was calculated with the following formula:
CI = [(Dmax – Dmin)/Dmax] x 100
CI value is expressed as a percentage.
We repeated these measurements with different levels of PEEP (PEEP 0, PEEP 5 and PEEP 10) and respiratory rates (RR 16, RR 30) – see Table 1
I scan  0  16 bpm
II scan  0  30 bpm
III scan  5  16 bpm
IV scan  5  30 bpm
V scan  10  16 bpm
VI scan  10  30 bpm
Table 1. Schedule of US scanning according to PEEP and Respiratory Rate
For every combination of PEEP and RR the maximum and minimum diameter of ICV was recorded as the medium value of two subsequent measurements in two different respiratory cycles. PEEP was given through a CPAP system with a venturimeter. The interface used was a CPAP Starmed Helmet.

Statistical Analysis

We used SPSS to analyze the data. According to the results of the Kolmogorov-Smirnov test the distribution was normal, so parametric statistic was used (student t test).


We enrolled 40 healthy subjects: 15 males (37,5%) and 25 women (62,5%). The mean age was 31,8 ± 10,42. Within subjects with normal respiratory rate (RR=16), there was a significant reduction of IVC-CI values with the increase in PEEP from 0 to 10 cmH2O (from 32,4 ± 13,5 to 25,1 ± 12,7, p = 0,007). Similarly, there was a significant decrease in IVC-CI values increasing SCAN PEEP RR I scan 0 16 bpm II scan 0 30 bpm III scan 5 16 bpm IV scan 5 30 bpm V scan 10 16 bpm VI scan 10 30 bpm PEEP from 5 to 10 cmH2O (IVC-CI = 30,5 ± 15,069 vs 25,1 ± 12,7, p = 0,02). Changing PEEP from 0 to 5 cmH2O, however, was not correlated with a significant decrease of IVCCI values (32,40 ± 1 13,513 vs 30,48 ± 15,069; p = 0,401). Evaluating subjects breathing at a higher respiratory rate (RR=30), we found no significant difference within IVC-CI values increasing the PEEP from 0 to 10 cmH2O. Comparing subjects with different respiratory rates and same PEEP, we found a significant increase in IVC-CI values concomitant with an increase in respiratory rate from 16 to 30 breaths per minute: 32,4 vs 42,8 in the PEEP=0 group (p < 0,001), 30,5 vs 41,8 in the PEEP=5cmH2O group (p <0,001) and 25,1 vs 38,8 in the PEEP=10 cmH2O group p < 0,001).
Within our population, males had mean IVC-CI values higher than females in the group with PEEP=5 cmH2O and RR 16/min and in the group with PEEP=10cmH2O and RR 30/ min (see Table 4).
I scan  0  16 bpm
II scan  0  30 bpm
III scan  5  16 bpm
IV scan  5  30 bpm
V scan  10  16 bpm
VI scan  10  30 bpm
Table 1. Schedule of US scanning according to PEEP and Respiratory Rate
RR (bpm) PEEP
16 0 32,4 13,5
16 5 30,5 15,1
16 10 25,1 12,7
30 0 42,8 15,9
30 5 41,8 15,1
30 10 38,8 17,1
Table 2. IVC Collapsibility Index (IVC-CI) according to respiratory rate (RR) and breaths per minute (bpm)
 P value Table  
  RR 16 RR 30
PEEP 0 vs PEEP 5 p 0,401 p 0,706
PEEP 0 vs PEEP 10 p 0,003  p 0,126
PEEP 5 vs PEEP 10 p 0,002   p 0,134
Table 3. P values according of Delta IVC-CI according to PEEP and RR
    Male Female p value
RR16   ZEEP 35,80 (±14,042) 30,36 (±13,044) 0,235
PEEP5 39,73 (±17,998) 24,92 (±9,712) 0,009
PEEP10 30,2 (±15,373) 22,08 (±9,870) 0,085
RR30   ZEEP 45,47 (±17,283) 41,16 (±15,126) 0,424
PEEP5 48,13 (±17,217) 38,00 (±12,573) 0,064
PEEP10 47,60 (±15,449) 33,52 (±16,882) 0,011
Table 4. IVC-CI mean values Males vs Females


Our study shows that in healthy volunteers in spontaneous breathing, the increase of PEEP reduces the CI. The same effect is described in mechanically ventilated patients (12-15-27). There was a statistically significant difference in reduction of CI between groups with PEEP 10 and PEEP 0 (p=0.007) and with PEEP 10 and PEEP 5 (p=0.002); no significant difference was found between groups with PEEP 0 and PEEP 5. The reduction of CI during NIV can produce an underestimation of the response to fluid therapy; this is true particularly at higher levels of PEEP (17,18). CI is less influenced by lower level of PEEP (PEEP 5); this result can be attributed not only to the lower intrathoracic pressure, but also to the protocol of the study. Measurements with PEEP 10 were executed short after measurements with PEEP 5, therefore it is possible that the measurements with PEEP 10 were influenced in part by the period of time at PEEP 5. There was also a statistically significant difference of the CI comparing normal RR and higher RR at all levels of PEEP. Therefore, respiratory rate and thus mechanical respiratory pattern seems to be another important factor influencing CI (26-30). There is a technical limitation in this measurement due to the movement of the blood vessel toward the US probe, in particular when the respiratory excursions increase (high RR). We can speculate that patients with a higher RR and an augmented alveolar ventilation (resulting in hypocapnia) can create the greater negative intrathoracic pressure with consequent higher values of CI. On the other hand, patients experiencing respiratory muscles impairment due to muscular exhaustion are not capable of augmenting their alveolar ventilation anymore (resulting in hypercapnia). This second type of patients are not able to generate enough negative intrathoracic pressure; thus, their CI will be reduced. (29,30) We found also a higher CI in men than in women. This can be explained by the higher muscular component and the higher lung capacity in men. According to the results of our study, there are two adjunctive variables in patients suffering from respiratory failure and treated with NIV that can interfere with the assessment of CI: the PEEP and the respiratory pattern. This can induce to a more difficult interpretation of CI as a marker of fluid responsiveness.
This is consistent with the recently published study from Via et al (25), that identify the following as factors possibly altering the interpretation of fluid responsiveness:
  • spontaneous respiration that creates ICV variations that are not predictable – higher respiratory efforts that can produce markedly negative intrathoracic pressure and thus induce ICV collapsibility without fluid responsiveness
  • a superficial respiratory pattern, with small variations of intrathoracic pressure, can create no or small ICV collapsibility even in presence of fluide responsiveness


Using US to assess volemic status in critically ill patients is not easy. When interpreting US measurements of IVC there are different factors that must be taken into account, in particular NIV and respiratory pattern. IVC-CI must always be combined with data from the echocardiography. More studies are needed to better understand how to interpret IC in the context of NIV and respiratory failure. These data should be confirmed in the ED patients with acute respiratory failure in order to further explore the validity of volemia evaluation in the critical population. Conflict of Interest: The authors declare that they have no conflict of interest.


  1. Marik PE, Cavallazzi R. Does the central venous pressure predict fluid responsiveness? An updated meta-analysis and a plea for some common sense. Crit Care Med. 2013 Jul;41(7):1774-81.
  2. Boyd JH, Forbes J, Nakada TA, Walley KR, Russell JA. Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit Care Med. 2011 Feb;39(2):259-65.
  3. Marik PE, Lemson J. Fluid responsiveness: an evolution of our understanding. Br J Anaesth. 2014 Apr;112(4):617-20.
  4. Yunfan Wu,1 Shusheng Zhou,1 Zhihua Zhou,2 and Bao Liu. A 10-second fluid challenge guided by transthoracic echocardiography can predict fluid responsiveness. Critical Care 2014 May 27.
  5. Frederic Michard, and Jean-Louis Teboul. Predicting Fluid Responsiveness in ICU Patients. A Critical Analysis of the Evidence. Critical Care Review. Chest 2002.
  6. Gómez Betancourt, Moreno-Montoya , Barragán González, Ovalle, Bustos Martínez Learning process and improvement of point-of-care ultrasound technique for subxiphoid visualization of the inferior vena cava. Crit Ultrasound J. 2016
  7. Citilcioglu S, Sebe A, Ay MO, Icme F, Avci A, Gulen M, Sahan M, Satar S. The relationship between inferior vena cava diameter measured by bedside ultrasonography and central venous pressure value. Pak J Med Sci. 2014 Mar;30(2):310-5
  8. Prekker ME, Scott NL, Hart D, Sprenkle MD, Leatherman JW. Point-of-care ultrasound to estimate central venous pressure: a comparison of three techniques. Crit Care Med. 2013 Mar;41(3):833-41.
  9. Zengin S, Al B, Genc S, Yildirim C, Ercan S, Dogan M, Altunbas G. Role of inferior vena cava and right ventricular diameter in assessment of volume status: a comparative study: ultrasound and hypovolemia. Am J Emerg Med. 2013 May;31(5):763-7
  10. Zhang Z, Xu X, Ye S, Xu L. Ultrasonographic measurement of the respiratory variation in the inferior vena cava diameter is predictive of fluid responsiveness in critically ill patients: systematic review and meta-analysis. Ultrasound Med Biol. 2014 May;40(5):845-53.
  11. Vieillard-Baron A1, Chergui K, Rabiller A, Peyrouset O, Page B, Beauchet A, Jardin F. Superior vena caval collapsibility as a gauge of volume status in ventilated septic patients. Intensive Care Med. 2004 Sep;30(9):1734-9
  12. Muller L, Bobbia X, Toumi M, Louart G, Molinari N, Ragonnet B, Quintard H, Leone M, Zoric L, Lefrant JY; AzuRea group. Respiratory variations of inferior vena cava diameter to predict fluid responsiveness in spontaneously breathing patients with acute circulatory failure: need for a cautious use. Crit Care. 2012 Oct 8;16(5):R188.
  13. Feissel M1, Michard F, Faller JP, Teboul JL. The respiratory variation in inferior vena cava diameter as a guide to fluid therapy. Intensive Care Med. 2004 Sep;
  14. Airapetian N, Maizel J, Alyamani O, et al. Does inferior vena cava respiratory variability predict fluid responsiveness in spontaneously breathing patients? Crit Care. 2015 Nov 13;19:400
  15. Daniele Dossi, Silvia Monte, Manfred Pfaender. Variazioni respiratorie del diametro cavale in respiro spontaneo vs ventilazione meccanica
  16. Stawicki SP, Braslow BM, Panebianco NL, Kirkpatrick JN, Gracias VH, Hayden GE, Dean AJ. Intensivist use of hand-carried ultrasonography to measure IVC collapsibility in estimating intravascular volume status: correlations with CVP. J Am Coll Surg. 2009
  17. Juhl-Olsen P, Frederiksen CA, Sloth E. Ultrasound assessment of inferior vena cava collapsibility is not a valid measure of preload changes during triggered positive pressure ventilation: a controlled cross-over study. Ultraschall Med. 2012 Apr;33(2):152-9
  18. Zanobetti M, Prota A, Coppa A, et al. Can non-invasive ventilation modify central venous pressure? Comparison between invasive measurement and ultrasonographic evaluation. Intern Emerg Med. 2016 Nov 22. [Epub ahead of print]
  19. Bagheri-Hariri S1, Yekesadat M1, Farahmand S2,3, Arbab M4, Sedaghat M5, Shahlafar N6, Takzare A7, Seyedhossieni-Davarani S1, Nejati A. The impact of using RUSH protocol for diagnosing the type of unknown shock in the emergency department. Emerg Radiol. 2015 Oct;22(5):517-20
  20. Coen D1, Cortellaro F2, Pasini S2, Tombini V2, Vaccaro A2, Montalbetti L2, Cazzaniga M2, Boghi D2. Towards a less invasive approach to the early goal-directed treatment of septic shock in the Emergency Department. Am J Emerg Med. 2014 Jun
  21. Abu-Zidan FM. Optimizing the value of measuring inferior vena cava diameter in shocked patients. World J Crit Care Med. 2016 Feb 4;5(1):7-11
  22. Manno E, Navarra M, Faccio L, Motevallian M, Bertolaccini L, Mfochivè A, Pesce M, Evangelista A. Deep impact of ultrasound in the intensive care unit: the “ICU-sound” protocol. Anesthesiology. 2012 Oct;117(4):801-9
  23. Mitaka C1, Nagura T, Sakanishi N, Tsunoda Y, Amaha K. Two-dimensional echocardiographic evaluation of inferior vena cava, right ventricle, and left ventricle during positive-pressure ventilation with varying levels of positive end-expiratory pressure. Crit Care Med. 1989 Mar;17(3):205-10
  24. Kelly CR, Higgins AR, Chandra S. Noninvasive Positive-Pressure Ventilation. N Engl J Med. 2015 Sep 24;373(13):1279
  25. Keenan SP1, Sinuff T, Cook DJ, Hill NS. Which patients with acute exacerbation of chronic obstructive pulmonary disease benefit from noninvasive positive-pressure ventilation? A systematic review of the literature. Ann Intern Med. 2003 Jun 3;138(11):861-70
  26. Via G, Tavazzi G. Ten situations where inferior vena cava ultrasound may fail to accurately predict fluid responsiveness: a physiologically based point of view. Intensive Care Med. 2016 Jul
  27. Barbier C1, Loubières Y, Schmit C, Hayon J, Ricôme JL, Jardin F, Vieillard-Baron A. Respiratory changes in inferior vena cava diameter are helpful in predicting fluid responsiveness in ventilated septic patients. Intensive Care Med. 2004 Sep
  28. Dipti A1, Soucy Z, Surana A, Chandra S. Role of inferior vena cava diameter in assessment of volume status: a meta-analysis. Am J Emerg Med. 2012 Oct
  29. Blehar DJ1, Resop D, Chin B, Dayno M, Gaspari R. Inferior vena cava displacement during respirophasic ultrasound imaging. Crit Ultrasound J. 2012 Aug 6;4(1):18
  30. Gignon L1, Roger C, Bastide S, Alonso S, Zieleskiewicz L, Quintard H, Zoric L, Bobbia X, Raux M, Leone M, Lefrant JY, Muller L. Influence of Diaphragmatic Motion on Inferior Vena Cava Diameter Respiratory Variations in Healthy Volunteers. Anesthesiology. 2016