Respiratory Variation of Superior Vena Cava in Transthoracic View as a Fluid Responsiveness Predictor

Association of Respiratory Variation of Superior Vena Cava in Transthoracic View and Fluid Responsiveness in Critically Ill Patients

Fluid evaluation is relevant in critical care. Cardiac ultrasound is the first line of evaluation in hemodynamic characterization of patients in shock, to tailor therapy.

Fluid responsiveness predictors allow to better decide when to administer fluids, and transesophagic view of superior vena cava is an effective one. Recently a transthoracic view of the superior vena cava has been described.

The investigators aim to evaluate if the variations of superior vena cava can predict fluid responsiveness in critically il, ventilated patients.

Hypothesis: Respiratory variations of superior vena cava diameter, evaluated with transthoracic ultrasound, can predict fluid responsiveness

Study Overview

• Status: Recruiting
• Conditions: Shock
• Intervention / Treatment: Diagnostic test: Superior vena cava transthoracic evaluation

Detailed Description

Prospective evaluation of diameter variability of the superior vena cava by transthoracic echocardiography as fluid responsiveness predictor in critically ill patients:

Background Fluid administration is frequent in critically ill patients, particularly during reanimation and its empirical use is recommended as an initial step during this phase.

However, even though excess fluid administration is associated to negative outcomes fluid use is still being empirical and with scarce application of responsiveness predictors before its indication.

Different measurements or maneuvers exist, that allow clinicians to predict if a patient would present a positive fluid response, usually defined as cardiac output increasing 15% when infusing 500ml of crystalloids, and application of these predictive parameters could have clinical benefits on outcomes by avoiding inappropriate fluid administration.

As for the variables used, different types stand out. In general, flow or pressure variations originated in cardiothoracic interaction, auto-infusion and reduced fluid test evaluations such as the "mini" o "micro" fluid tests, in addition venous diameter variations in ultrasound evaluation with variable accuracy depending on the context. However, cardiothoracic interaction variables might have false positive results when right ventricular failure is present, given the cyclic increment on its afterload induced by positive pressure ventilation, reducing right ventricle stroke volume limiting its application in established or unknown and probable right heart failure if and advanced hemodynamic monitoring has not been performed to rule it out.

In this context, venous evaluations and reduced volume fluid test have advantages, and particularly in patients in shock under positive pressure ventilation, superior vena cava variation, being a better predictor than inferior vena cava. However, traditionally, superior vena cava can only be observed with transesophageal echocardiography and that can be a limitation in resource limited settings. Recently a new transthoracic acoustic window has been described, using a vertical left parasternal approach that allows evaluation of the superior vena cave, and initially, this approach shows a good correlation with the transesophageal measurement, and acceptable feasibility in the pilot study patients.

In this way, it can be postulated as possible, to evaluate if the variability of superior vena cava diameter on a transthoracic approach can be used as a fluid responsiveness predictor in critically ill patients on positive pressure ventilation.

Hypothesis Superior vena cava diameter respiratory variation evaluated with transthoracic ultrasound can predict fluid responsiveness in critically ill patients in positive pressure ventilation.

Objective To evaluate if superior vena cava respiratory diameter variation is associated with fluid responsiveness, when compared with the mini fluid infusion of 100ml evaluated with expiratory left ventricle outflow tract velocity time integral (LVOT-VTI) before and after fluid administration.

Methods

After evaluation, inclusion and exclusion criteria checking:

A basal echocardiography is performed, main pattern and clinical data are recorded (age, sex, weight, height, main diagnosis, secondary diagnosis, length of stay, surgical procedures, sequential organ failure assesment (SOFA) score, renal replacement therapy), respiratory (ventilator mode, tidal volume, respiratory rate, positive end expiratory pressure (PEEP), plateau pressure, peak inspiratory pressure, autoPEEP, fraction of inspired oxygen (FiO2), I:E relation, total inspiratory time), hemodynamic data from unit monitors. (cardiac rate, systolic pressure, diastolic pressure, mean pressure, central venous pressure) and closest laboratory to evaluation (lactate, venous oxygen saturation (ScVO2), arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), pH, base excess (BE), bicarbonate (HCO3), carbon dioxide (CO2) arterio-venous difference, )

• Superior vena cava evaluation, Respiratory variation observed in M mode and measured. Registry of expiratory and inspiratory diameter (evaluated in the same cardiac cycle phase)
• Using Apical 5 chamber view, basal LVOT-VTI would be obtained, 3 measurements in regular rhythms and 5 measurements in irregular rhythms such as atrial fibrillation. 100 ml will be infused without changing the view and end-expiratory LVOT-VTI would be obtained a minute after infusion in the same fashion as before.
• Considering ultrasound evaluation is part of standard patient care, informed consent was waived by the ethical board.
• For analysis, the proportion of variation in superior vena cava (SVC) and VTI variation would be calculated as percentage.
• All values will be registered in a google drive table and then included in microsoft excel for coding and analyzed with Stata 12.
• Fluid responsiveness will be defined as 10% increase in VTI with the "mini bolus" fluid test, considering the minimal detectable change.
• For analysis, receiver operator curve (ROC) statistic will be done in Stata 12.
• Summary variables of the population will be presented.
• For diagnostic evaluation, the tool "roctab" for receiver operating characteristic curve will be used, obtaining cut off values, sensitivity, specificity and gray area in addition to traditional area under curve (AUC). A dichotomic value for simple orientation will be selected with an ideally balanced sensitivity and specificity for general use. Linear correlation will be explored to detect a continuous relation between SVC variation and VTI increase.
• Window success will be recorded and proportion will be analysed during the months of the study to check for performance improvements that might be expected as a learning curve effect.
• Additional data might allow post hoc analysis including window feasibility in association with clinical variables and
• After the ultrasound evaluation, the result of the 100ml test will be informed to the treating physician.
• Sample size:

Considering a possible 50% loss with inadequate acoustic window, 100 evaluated patients would achieve at least 48 included to obtain AUC 0.7. (estimating 24 to be responders and 24 not responders)

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Diego Ugalde, md; Phone Number: +56974197896; Email: diegougaldecastillo@gmail.com

Study Locations

• Chile
  • Región Metropolitana
    • Santiago, Región Metropolitana, Chile, 8380420
      • Recruiting
      • Hospital Clínico Universidad de Chile
      • Contact: Diego Ugalde, md; Phone Number: +56974197896; Email: diegougaldecastillo@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Ventilated critically ill patients with hemodynamic instability hospitalized in the intensive care unit.

Description

Inclusion Criteria:

• Patients >18 years,
• Hospitalized in the Intensive Care Unit (ICU) with length of stay under 7 days
• Under positive pressure ventilation with no inspiratory effort,
• With hemodynamic instability (defined as abnormal peripheral perfusion or increased blood lactic or vasopressor infusion of norepinephrine >0.1 ug/kg/min to achieve adequate mean arterial pressure)

Exclusion Criteria:

• Spontaneous ventilatory effort
• Lack of venous access
• Carrier of carbapenemase or clostridium difficile
• Lack of adequate superior vena cava (SVC) window (not allowing M-mode during both respiratory phases)
• Severe aortic regurgitation
• Impossibility to measure LVOT-VTI
• Extracorporeal membrane oxygenation.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fluid responsiveness	An increase of 10% or more in the left ventricle velocity time integral value (average of 3 in regular rhythms or 5 in irregular rhythms) measured with cardiac ultrasound in 5 chambers apical view after the infusion of 100ml bolus of intravenous crystalloid solution.	1 minute

Collaborators and Investigators

• Sponsor: University of Chile

Publications and helpful links

General Publications

• Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-377. doi: 10.1007/s00134-017-4683-6. Epub 2017 Jan 18.
• 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 Mar;37(3):951-6. doi: 10.1097/CCM.0b013e3181968fe1.
• Monnet X, Marik P, Teboul JL. Passive leg raising for predicting fluid responsiveness: a systematic review and meta-analysis. Intensive Care Med. 2016 Dec;42(12):1935-1947. doi: 10.1007/s00134-015-4134-1. Epub 2016 Jan 29.
• Muller L, Toumi M, Bousquet PJ, Riu-Poulenc B, Louart G, Candela D, Zoric L, Suehs C, de La Coussaye JE, Molinari N, Lefrant JY; AzuRea Group. 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 Sep;115(3):541-7. doi: 10.1097/ALN.0b013e318229a500.
• Malbrain MLNG, Van Regenmortel N, Saugel B, De Tavernier B, Van Gaal PJ, Joannes-Boyau O, Teboul JL, Rice TW, Mythen M, Monnet X. Principles of fluid management and stewardship in septic shock: it is time to consider the four D's and the four phases of fluid therapy. Ann Intensive Care. 2018 May 22;8(1):66. doi: 10.1186/s13613-018-0402-x.
• Monnet X, Marik PE, Teboul JL. Prediction of fluid responsiveness: an update. Ann Intensive Care. 2016 Dec;6(1):111. doi: 10.1186/s13613-016-0216-7. Epub 2016 Nov 17.
• Cecconi M, Hofer C, Teboul JL, Pettila V, Wilkman E, Molnar Z, Della Rocca G, Aldecoa C, Artigas A, Jog S, Sander M, Spies C, Lefrant JY, De Backer D; FENICE Investigators; ESICM Trial Group. Fluid challenges in intensive care: the FENICE study: A global inception cohort study. Intensive Care Med. 2015 Sep;41(9):1529-37. doi: 10.1007/s00134-015-3850-x. Epub 2015 Jul 11. Erratum In: Intensive Care Med. 2015 Sep;41(9):1737-8. multiple investigator names added.
• Biais M, Ehrmann S, Mari A, Conte B, Mahjoub Y, Desebbe O, Pottecher J, Lakhal K, Benzekri-Lefevre D, Molinari N, Boulain T, Lefrant JY, Muller L; AzuRea Group. Clinical relevance of pulse pressure variations for predicting fluid responsiveness in mechanically ventilated intensive care unit patients: the grey zone approach. Crit Care. 2014 Nov 4;18(6):587. doi: 10.1186/s13054-014-0587-9.
• Jardin F, Dubourg O, Bourdarias JP. Echocardiographic pattern of acute cor pulmonale. Chest. 1997 Jan;111(1):209-17. doi: 10.1378/chest.111.1.209. No abstract available.
• Messina A, Dell'Anna A, Baggiani M, Torrini F, Maresca GM, Bennett V, Saderi L, Sotgiu G, Antonelli M, Cecconi M. Functional hemodynamic tests: a systematic review and a metanalysis on the reliability of the end-expiratory occlusion test and of the mini-fluid challenge in predicting fluid responsiveness. Crit Care. 2019 Jul 29;23(1):264. doi: 10.1186/s13054-019-2545-z.
• Reuter DA, Chappell D, Perel A. The dark sides of fluid administration in the critically ill patient. Intensive Care Med. 2018 Jul;44(7):1138-1140. doi: 10.1007/s00134-017-4989-4. Epub 2017 Nov 11. No abstract available.
• Acheampong A, Vincent JL. A positive fluid balance is an independent prognostic factor in patients with sepsis. Crit Care. 2015 Jun 15;19(1):251. doi: 10.1186/s13054-015-0970-1.
• Bednarczyk JM, Fridfinnson JA, Kumar A, Blanchard L, Rabbani R, Bell D, Funk D, Turgeon AF, Abou-Setta AM, Zarychanski R. Incorporating Dynamic Assessment of Fluid Responsiveness Into Goal-Directed Therapy: A Systematic Review and Meta-Analysis. Crit Care Med. 2017 Sep;45(9):1538-1545. doi: 10.1097/CCM.0000000000002554.
• Vistisen ST, Juhl-Olsen P. Where are we heading with fluid responsiveness research? Curr Opin Crit Care. 2017 Aug;23(4):318-325. doi: 10.1097/MCC.0000000000000421.
• Michard F. Toward Precision Hemodynamic Management. Crit Care Med. 2017 Aug;45(8):1421-1423. doi: 10.1097/CCM.0000000000002458. No abstract available.
• Vignon P, Repesse X, Begot E, Leger J, Jacob C, Bouferrache K, Slama M, Prat G, Vieillard-Baron A. Comparison of Echocardiographic Indices Used to Predict Fluid Responsiveness in Ventilated Patients. Am J Respir Crit Care Med. 2017 Apr 15;195(8):1022-1032. doi: 10.1164/rccm.201604-0844OC.
• Wu Y, Zhou S, Zhou Z, Liu B. A 10-second fluid challenge guided by transthoracic echocardiography can predict fluid responsiveness. Crit Care. 2014 May 27;18(3):R108. doi: 10.1186/cc13891.
• Vieillard-Baron A, Naeije R, Haddad F, Bogaard HJ, Bull TM, Fletcher N, Lahm T, Magder S, Orde S, Schmidt G, Pinsky MR. Diagnostic workup, etiologies and management of acute right ventricle failure : A state-of-the-art paper. Intensive Care Med. 2018 Jun;44(6):774-790. doi: 10.1007/s00134-018-5172-2. Epub 2018 May 9.
• Jardin F, Dubourg O, Margairaz A, Bourdarias JP. Inspiratory impairment in right ventricular performance during acute asthma. Chest. 1987 Nov;92(5):789-95. doi: 10.1378/chest.92.5.789.
• Ugalde D, Haruel PA, Godement M, Prigent A, Vieillard-Baron A. Transthoracic echocardiography to evaluate the superior vena cava in critically ill patients: window description and pilot study. Intensive Care Med. 2019 Jul;45(7):1052-1054. doi: 10.1007/s00134-019-05621-1. Epub 2019 Apr 25. No abstract available.
• Jozwiak M, Mercado P, Teboul JL, Benmalek A, Gimenez J, Depret F, Richard C, Monnet X. What is the lowest change in cardiac output that transthoracic echocardiography can detect? Crit Care. 2019 Apr 11;23(1):116. doi: 10.1186/s13054-019-2413-x.

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2021
• Primary Completion (Estimated): November 1, 2023
• Study Completion (Estimated): March 1, 2024

Study Registration Dates

• First Submitted: December 28, 2021
• First Submitted That Met QC Criteria: January 14, 2022
• First Posted (Actual): January 27, 2022

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 78/20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Probably database will be available if asked once completed.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No