Effect of VExUS Ultrasound Protocol (Venous Excess Ultrasound) on Perioperative Fluid Management, on the Incidence of Postoperative Pulmonary Complications and Postoperative Acute Kidney Injury in Patients Undergoing Thoracic Surgery

NCT ID: NCT07258875

Last Updated: 2025-12-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

230 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-27

Study Completion Date

2029-11-01

Brief Summary

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This study aims to investigate the effect of a VExUS ultrasound guided protocol of perioperative fluid management within a goal-directed therapy framework, on postoperative respiratory complications, and the occurrence of acute kidney injury (AKI) in patients undergoing thoracic surgery.

Detailed Description

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In thoracic surgery, intraoperative fluid management presents a challenge for anesthesiologists, as patients are at high risk of developing interstitial and alveolar edema of the lungs. A history of pulmonary disease, previous chemotherapy or radiation therapy in the area, one-lung ventilation, surgical manipulation, and ischemia-reperfusion injury can all damage the respiratory epithelium's glycocalyx, the alveolar epithelium, and surfactant, ultimately leading to pulmonary injury. These factors, combined with liberal perioperative fluid management, increase the risk of acute respiratory distress syndrome (ARDS), atelectasis, pneumonia, and ultimately postoperative mortality. Traditionally, a restrictive fluid management strategy is employed intraoperatively, with crystalloid administration at a rate of 1-2 ml/kg/h, ensuring that the perioperative fluid balance does not exceed 1500 ml. This restrictive strategy may increase the risk of hypovolemia, which can lead to tissue hypoperfusion, target organ dysfunction, and acute kidney injury. Within the Enhanced Recovery After Surgery (ERAS) protocols, goal-directed therapy (GDT) for fluid management in thoracic surgery is discussed but not explicitly recommended. Recommendations include avoiding overly restrictive or completely liberal fluid strategies, maintaining euvolemia, and preventing tissue hypoperfusion with balanced use of inotropic agents and fluid administration.

Pulmonary injury is the leading cause of death following thoracic surgery. Pre-existing respiratory disease, surgical manipulation, lung parenchyma resection, and the detrimental effects of one-lung ventilation increase the risk of postoperative respiratory complications. Although overhydration and ventilation with high tidal volumes have been replaced by a restrictive fluid strategy and the application of protective mechanical ventilation, it appears that all factors involved in ventilator-induced lung injury (VILI) also play a harmful role in one-lung ventilation. High strain on the ventilated lung, oxidative stress, surgical trauma, recruitment maneuvers, biological trauma, atelectatic trauma, and ischemia-reperfusion injury are the pathophysiological mechanisms leading to postoperative acute respiratory failure and, in 2-5% of cases, to ARDS.

Postoperative acute kidney injury (AKI) represents 18-47% of in-hospital AKI and is associated with prolonged hospitalization and high morbidity and mortality. Recently, the implementation of new AKI classifications (RIFLE, AKIN, KDIGO) has facilitated its early recognition for immediate preventive measures. Additionally, the detection of two early urinary biomarkers of kidney stress, the tissue inhibitor of metalloproteinases-2 (TIMP-2) and the insulin-like growth factor-binding protein 7 (IGFBP7), has contributed to this. Postoperatively, an increase in serum creatinine by up to 0.5 mg/dL from baseline has been associated with a threefold increase in mortality following cardiac surgery. Potential pathophysiological mechanisms of postoperative AKI include ischemia, inflammation, and toxins. However, in thoracic surgeries, both the hypovolemia of a restrictive fluid administration strategy and overhydration and venous congestion can equally lead to acute kidney injury postoperatively.

The VExUS protocol is a standardized point-of-care ultrasound examination that includes measurements of the inferior vena cava (IVC) diameter, combined with Doppler analysis of waveforms in the hepatic vein, portal vein, and renal veins. From this analysis, the presence of venous congestion-classified as mild or severe-or its absence is determined. A high VExUS score (grade 3) has been strongly associated with the occurrence of acute kidney injury in patients undergoing cardiac surgery and has more recently been linked to elevated right atrial pressure (RAP ≥ 12 mmHg). The protocol includes the following classification:

Grade 0: IVC \< 2 cm Grade 1: IVC ≥ 2 cm, with normal or mildly abnormal waveforms in the hepatic, portal, and renal veins (mild congestion) Grade 2: IVC ≥ 2 cm, with severely altered waveforms in at least one vein (moderate congestion) Grade 3: IVC ≥ 2 cm, with severely altered waveforms in multiple veins (severe congestion).

A single-center clinical study conducted in the Anesthesiology Clinic of the University General Hospital of Heraklion.

Parallel design in two groups.Preoperative assessment, fasting, and premedication according to the routine of the department:

* Discontinuation of fluid intake 2 hours before surgery
* cessation of food intake 6 hours preoperatively
* discontinuation on the day of surgery of ACE inhibitors, angiotensin receptor blockers, thiazide diuretics, and loop diuretics.

Upon entering the operating room, patients will be connected standard ASA monitors: 5 lead ECG, pulse oximetry (SpO2), non-invasive blood pressure measurement. Under local anaesthesia an arterial catheter will be placed for invasive blood pressure measurement and blood gas sampling, along with at least two venous catheters of 16-20 G. Anesthesia and postoperative analgesia management will depend solely on the discretion of the responsible anesthesiologist. After anesthesia induction and double-lumen endotracheal tube placement, patients will be connected to the anesthesia machine, recruitment maneuvers will be performed with PEEP titration, and they will be mechanically ventilated applying the principles of protective mechanical ventilation. The correct placement of the endotracheal tube will be confirmed with fiberoptic bronchoscopy immediately after placement. A urinary catheter will be placed for hourly urine measurement, along with a thermometer.

Intraoperatively, the total administered fluids, hourly urine output, type and dose of vasopressor medications, and blood pressure (SAP, DAP, MAP) will be recorded every 15 minutes (unless a significant change occurs), along with arterial blood gases and lactate.

Protective Mechanical Ventilation of One Lung:

Ventilated lung:

Tidal volume (Vt): 4-5 ml/kg ideal body weight, Appropriate PEEP of 5-15 cmH2O, possible repeat of recruitment maneuver Plateau pressure - PEEP: up to 15 cmH2O, Management of respiratory rate (RR) aiming for permitted mild hypercapnia (PaCO2 = 40-60 mmHg), Modification of the I ratio to avoid air trapping and the emergence of PEEPi, Titration of FiO2 to achieve SpO2 = 88-92%, Protection against hypoxic pulmonary vasoconstriction by avoiding vasodilators, hypoventilation, alkalosis, hypothermia, and if inhaled anesthetics are used, maintaining MAC \< 1, Mechanical ventilation model: Volume Control- Auto Flow on the Perseus A500 and Atlan A350 machines from Drager available in the Anesthesia Clinic.

Non-ventilated lung with SpO2 \< 88%:

Recruitment maneuvers with the use of PEEP if possible, Use of CPAP, FiO2 = 100% and cessation of one lung ventilation.

Control Group:

Intraoperatively patients of the control group will be administered isotonic crystalloids (Lactated Ringer's, Plasma-Lyte) at a rate of 3 mL/kg/h.

VExUS-guided Group:

VExUS Evaluation. The VExUS evaluation will be performed pre- and immediately post-intubation before one-lung ventilation initiation. A trained anesthesiologist (will evaluate the patient according to the VExUS protocol, measuring the IVC diameter and performing Doppler analysis of the hepatic, portal, and renal veins. A VExUS score will be assigned as outlined in the section above.

Ultrasound monitoring will be performed according to the VExUS protocol before positioning the patient in the lateral decubitus position. In patients with VExUS grade 0, a bolus of 250-500 mL (approximately 3 mL/kg) will be administered, followed by the infusion of crystalloids at a rate of 3 mL/kg/h. The inferior vena cava (IVC) diameter will be measured three times: once prior to anesthesia induction, once immediately after intubation, and once before patient emergence from anesthesia. In patients with VExUS grade 1, no bolus will be given, and only a fluid infusion at 3 mL/kg/h will be administered. In patients with VExUS grades 2 and 3, 10 mg of furosemide will be administered intravenously, followed by crystalloids infusion at a rate of 2 mL/kg/h.

In both groups, blood losses will be replaced with a 5% albumin solution at a 1:1 ratio. Transfusion will be administered to maintain hemoglobin levels at 9 mg/dL. Both groups will follow the same multimodal anesthesia-analgesia protocol, with restricted opioid use in accordance with the departmental routine.

Intraoperative hypotension (systolic arterial pressure \< 90 mmHg or a decrease \> 20% from baseline) will be managed with titrated norepinephrine infusion.

Post-Anesthesia Care Unit (PACU)

Control Group:

Fluid administration will continue at a rate of 3 mL/kg/h as per standard practice.

VExUS-guided Group:

VExUS ultrasound will be repeated postoperatively. In patients with VExUS grade 0, a bolus of 250-500 mL (approximately 3 mL/kg) will be administered, followed by the infusion of crystalloids at a rate of 3 mL/kg/h. In patients with grades 1 to 3, 10 mg of intravenous furosemide will be administered, followed by a fluid infusion at 3 mL/kg/h and reassessment.

Patients will be monitored daily for the occurrence of postoperative respiratory complications as defined by the European Society of Anaesthesiology. Preoperative blood gas values (PaO2, PaCO2) will be measured as baseline, and postoperative blood gases will be collected on the 1st and 3rd postoperative days in the PACU. Oxygenation will be assessed using the PaO2/FiO2 ratio, and lactate levels will be measured concurrently.

Additionally, for each patient, estimated glomerular filtration rate (eGFR) using serum creatinine, cystatin C or both will be calculated preoperatively and on the 1st and 3rd postoperative days in PACU. To assess acute kidney injury (AKI), serum creatinine and cystatin C will be measured on the 1st and 3rd postoperative days, and AKI diagnosis and classification will follow KDIGO (Kidney Disease Improving Global Outcomes) criteria.

The following kidney injury biomarkers will also be measured:

Serum cystatin C, Total urine protein and albumin, Urine beta-2 microglobulin, Urine creatinine. Kidney stress biomarkers TIMP-2 and IGFBP7 in urine, as described above, will be measured immediately postoperatively in the PACU.

These biomarkers will also be measured in the PACU and on the 1st and 3rd postoperative days.

Conditions

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Thoracic Surgery With One-lung Ventilation VExUS Fluid Management Acute Kidney Injury Postoperative Pulmonary Complications (PPCs)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

A single-center clinical study conducted in the Anesthesiology Clinic of the University General Hospital of Heraklion.

Parallel design in two groups.
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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standard of care group

Intraoperatively patients of the control group will be administered isotonic crystalloids (Lactated Ringer's, Plasma-Lyte) at a rate of 3 mL/kg/h.Fluid administration will continue at a rate of 3 mL/kg/h as per standard practice in the postanaesthesia care unit( PACU) also.In both groups, blood losses more than 300 ml will be replaced with a 5% albumin solution at a 1:1 ratio. Transfusion will be administered to maintain hemoglobin levels at 9 mg/dL. Both groups will follow the same multimodal anesthesia-analgesia protocol, with restricted opioid use in accordance with the departmental routine.

Intraoperative hypotension (systolic arterial pressure \< 90 mmHg or a decrease \> 20% from baseline) will be managed with titrated norepinephrine infusion.

Group Type PLACEBO_COMPARATOR

Standard of Care (SOC)

Intervention Type OTHER

Intraoperatively patients of the control group will be administered isotonic crystalloids (Lactated Ringer's, Plasma-Lyte) at a rate of 3 mL/kg/h.Fluid administration will continue at a rate of 3 mL/kg/h as per standard practice in the PACU.

vexus guided group

The VExUS evaluation will be performed pre- and immediately post-intubation before one-lung ventilation initiation.

Ultrasound monitoring will be performed according to the VExUS protocol before positioning the patient in the lateral decubitus position. In patients with VExUS grade 0, a bolus of 250-500 mL (approximately 3 mL/kg) will be administered, followed by the infusion of crystalloids at a rate of 3 mL/kg/h. The inferior vena cava (IVC) diameter will be measured three times: once prior to anesthesia induction, once immediately after intubation, and once before patient emergence from anesthesia. In patients with VExUS grade 1, no bolus will be given, and only a fluid infusion at 3 mL/kg/h will be administered. In patients with VExUS grades 2 and 3, 10 mg of furosemide will be administered intravenously, followed by crystalloids infusion at a rate of 2 mL/kg/h.VExUS ultrasound will be repeated postoperatively in the PACU, following the same pattern of intervention.

Group Type ACTIVE_COMPARATOR

Venous Excess Ultrasound

Intervention Type DIAGNOSTIC_TEST

The VExUS protocol is a standardized point-of-care ultrasound examination that includes measurements of the inferior vena cava (IVC) diameter, combined with Doppler analysis of waveforms in the hepatic vein, portal vein, and renal veins. From this analysis, the presence of venous congestion-classified as mild or severe-or its absence is determined. A high VExUS score (grade 3) has been strongly associated with the occurrence of acute kidney injury in patients undergoing cardiac surgery and has more recently been linked to elevated right atrial pressure (RAP ≥ 12 mmHg). The protocol includes the following classification:

* Grade 0: IVC \< 2 cm
* Grade 1: IVC ≥ 2 cm, with normal or mildly abnormal waveforms in the hepatic, portal, and renal veins (mild congestion)
* Grade 2: IVC ≥ 2 cm, with severely altered waveforms in at least one vein (moderate congestion)
* Grade 3: IVC ≥ 2 cm, with severely altered waveforms in multiple veins (severe congestion)

Interventions

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Venous Excess Ultrasound

The VExUS protocol is a standardized point-of-care ultrasound examination that includes measurements of the inferior vena cava (IVC) diameter, combined with Doppler analysis of waveforms in the hepatic vein, portal vein, and renal veins. From this analysis, the presence of venous congestion-classified as mild or severe-or its absence is determined. A high VExUS score (grade 3) has been strongly associated with the occurrence of acute kidney injury in patients undergoing cardiac surgery and has more recently been linked to elevated right atrial pressure (RAP ≥ 12 mmHg). The protocol includes the following classification:

* Grade 0: IVC \< 2 cm
* Grade 1: IVC ≥ 2 cm, with normal or mildly abnormal waveforms in the hepatic, portal, and renal veins (mild congestion)
* Grade 2: IVC ≥ 2 cm, with severely altered waveforms in at least one vein (moderate congestion)
* Grade 3: IVC ≥ 2 cm, with severely altered waveforms in multiple veins (severe congestion)

Intervention Type DIAGNOSTIC_TEST

Standard of Care (SOC)

Intraoperatively patients of the control group will be administered isotonic crystalloids (Lactated Ringer's, Plasma-Lyte) at a rate of 3 mL/kg/h.Fluid administration will continue at a rate of 3 mL/kg/h as per standard practice in the PACU.

Intervention Type OTHER

Other Intervention Names

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VEXUS standard of care

Eligibility Criteria

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Inclusion Criteria

* Adults \>18 years undergoing video assisted thoracic surgery/ lobectomy requiring one-lung ventilation.

Exclusion Criteria

* Refusal to participate.
* Pneumonectomy.
* Young athletes (risk of physiologically large IVC \>2 cm).
* Moderate-severe tricuspid regurgitation, moderate to severe pulmonary hypertension
* Heart failure with reduced ejection fraction, EF\<35%
* Portal hypertension, portal vein thrombosis, or liver cirrhosis.
* Stage 4 or end-stage chronic kidney disease (eGFR \<30 mL/min/1.73 m² or dialysis).
* Transfusion with more than 2 packed red blood cells unit perioperatively (intraoperatively, in the PACU, in the ward)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Crete

OTHER

Sponsor Role lead

Responsible Party

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Alexandros Bogas

Alexandros Bogas Manouselis

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Alexandra Papaioannou, Professor of Anaesthesiology

Role: STUDY_CHAIR

Medical School, University of Crete

Locations

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University General Hospital of Heraklion

Heraklion, Crete, Greece

Site Status RECRUITING

Countries

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Greece

Central Contacts

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Alexandros Bogas Manouselis, Resident of Anaesthesiology

Role: CONTACT

+306947545446

References

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Tarbell JM. Shear stress and the endothelial transport barrier. Cardiovasc Res. 2010 Jul 15;87(2):320-30. doi: 10.1093/cvr/cvq146. Epub 2010 Jun 12.

Reference Type RESULT
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13. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work vexusGroup. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney inter., Suppl. 2012; 2: 1-138.

Reference Type RESULT

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Longino A, Martin K, Leyba K, Siegel G, Gill E, Douglas IS, Burke J. Correlation between the VExUS score and right atrial pressure: a pilot prospective observational study. Crit Care. 2023 May 26;27(1):205. doi: 10.1186/s13054-023-04471-0.

Reference Type RESULT
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Magin JC, Wrobel JR, An X, Acton J, Doyal A, Jia S, Krakowski JC, Schoenherr J, Serrano R, Flynn D, McLean D, Grant SA. Venous Excess Ultrasound (VExUS Grading to Assess Perioperative Fluid Status for Noncardiac Surgeries: a Prospective Observational Pilot Study. POCUS J. 2023 Nov 27;8(2):223-229. doi: 10.24908/pocus.v8i2.16792. eCollection 2023.

Reference Type RESULT
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Beaubien-Souligny W, Rola P, Haycock K, Bouchard J, Lamarche Y, Spiegel R, Denault AY. Quantifying systemic congestion with Point-Of-Care ultrasound: development of the venous excess ultrasound grading system. Ultrasound J. 2020 Apr 9;12(1):16. doi: 10.1186/s13089-020-00163-w.

Reference Type RESULT
PMID: 32270297 (View on PubMed)

Romagnoli S, Ricci Z. Postoperative acute kidney injury. Minerva Anestesiol. 2015 Jun;81(6):684-96. Epub 2014 Jul 24.

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Park M, Yoon S, Nam JS, Ahn HJ, Kim H, Kim HJ, Choi H, Kim HK, Blank RS, Yun SC, Lee DK, Yang M, Kim JA, Song I, Kim BR, Bahk JH, Kim J, Lee S, Choi IC, Oh YJ, Hwang W, Lim BG, Heo BY. Driving pressure-guided ventilation and postoperative pulmonary complications in thoracic surgery: a multicentre randomised clinical trial. Br J Anaesth. 2023 Jan;130(1):e106-e118. doi: 10.1016/j.bja.2022.06.037. Epub 2022 Aug 20.

Reference Type RESULT
PMID: 35995638 (View on PubMed)

Lohser J, Slinger P. Lung Injury After One-Lung Ventilation: A Review of the Pathophysiologic Mechanisms Affecting the Ventilated and the Collapsed Lung. Anesth Analg. 2015 Aug;121(2):302-18. doi: 10.1213/ANE.0000000000000808.

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Arslantas MK, Kara HV, Tuncer BB, Yildizeli B, Yuksel M, Bostanci K, Bekiroglu N, Kararmaz A, Cinel I, Batirel HF. Effect of the amount of intraoperative fluid administration on postoperative pulmonary complications following anatomic lung resections. J Thorac Cardiovasc Surg. 2015 Jan;149(1):314-20, 321.e1. doi: 10.1016/j.jtcvs.2014.08.071. Epub 2014 Sep 18.

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Batchelor TJP, Rasburn NJ, Abdelnour-Berchtold E, Brunelli A, Cerfolio RJ, Gonzalez M, Ljungqvist O, Petersen RH, Popescu WM, Slinger PD, Naidu B. Guidelines for enhanced recovery after lung surgery: recommendations of the Enhanced Recovery After Surgery (ERAS(R)) Society and the European Society of Thoracic Surgeons (ESTS). Eur J Cardiothorac Surg. 2019 Jan 1;55(1):91-115. doi: 10.1093/ejcts/ezy301.

Reference Type RESULT
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Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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18721

Identifier Type: -

Identifier Source: org_study_id

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