Liver Tumor; SurgeryNCT06905015
Stroke Volume Variation Versus Central Venous Pressure Guidance for Reducing Perioperative Blood Loss During Open Liver Resection, A Non-inferiority Randomized Controlled Trial
A study testing High SVV-guided fluid management and Low CVP-guided fluid management in people with Liver Tumor; Surgery and Primary Liver Tumor, Metastatic Liver, run by Chiang Mai University at 1 site in Thailand.
Trial summary
Liver resection is a major surgery that can be associated with significant intraoperative blood loss and blood transfusion. Among high-volume centers, median intraoperative blood loss ranges between 300-800 ml. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Liver Tumor; Surgery, Primary Liver Tumor, Metastatic Liver, Primary Liver Cancer
- What is being tested?
- High SVV-guided fluid management and Low CVP-guided fluid management
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteThailand
- Study dates
- 25 Nov 2024to 26 Sep 2026
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All genders, age 18 to 70 years old
- American Society of Anesthesiologists (ASA) physical status classification of I-III
- The patients who scheduled in elective open liver resection and diagnosed Hepatocellular Carcinoma, Cholangiocarcinoma, Liver metastasis, and Benign malignant tumor.
Who cannot join
- Pregnancy
- Active cardiac conditions (unstable coronary syndromes, decompensated heart failure, significant arrhythmias, severe valvular disease, active coronary artery disease within 6 months prior surgery)
- History of significant cerebrovascular disease (Patients with clinically significant stroke/CVA within 6 months prior surgery, severe carotid stenosis)
- Renal dysfunction (GFR < 60 ml/min/1.73 m²)
- Abnormal coagulation parameters (INR >1.5 not on warfarin and/or platelet count <100,000)
- Preoperative autologous blood donation
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- Tumor size > 10 cm.
- Previous liver resection
- Withdrawal criteria:
- Unresectable tumor
- Persistent intraoperative hypotension that cannot be corrected with vasopressors.
- Cardiac arrest during operation
- Low central venous pressure (CVP < 5 mmHg) or high stroke volume variation (SVV >13%) cannot be achieved before and during liver parenchymal transection.
Trial locations and contacts
1 site in 1 country.
Thailand1 site
Department of Anesthesiology, Faculty of Medicine, Chiang Mai University
Chiang Mai, Chiangmai, 50200
About this study
Official title: Comparison the Effectiveness of Stroke Volume Variation Versus Central Venous Pressure Guidance for Reducing Perioperative Blood Loss During Open Liver Resection: A Prospective, Double-Blinded, Noninferiority, Randomized Controlled Study
Liver resection is a major surgery that can be associated with significant intraoperative blood loss and blood transfusion. Among high-volume centers, median intraoperative blood loss ranges between 300-800 ml. Excessive blood loss is a strong independent predictor of worsened postoperative outcomes, increasing morbidity and mortality rates by 20%-35%. Additionally, perioperative allogeneic blood transfusions are associated with deleterious outcomes, including tumor recurrence and increased rates of complications and death.
The liver is a highly vascular organ with minimal vascular resistance, receiving up to 25% of cardiac output and pooling 20% of the splanchnic blood. Hepatic veins are a common source of venous hemorrhage. The pressure in the hepatic veins is directly correlated with the pressure in the vena cava and reducing cardiac preload results in decreased hepatic vein congestion. Therefore, low central venous pressure anesthesia (typically below 5 mmHg) can reduce the pressure gradient for retrograde venous bleeding, facilitate the outflow of blood from hepatic veins, and decrease blood volume and pressure in the liver. This anesthetic method is the standard technique to minimize blood loss during liver resection.
Read more
Central venous pressure was the static parameter used to indicate the right ventricular end-diastolic volume index (RVEDI) and was believed to be correlated with volume status. Despite this, central venous pressure did not reliably predict preload responsiveness due to the curvilinear shape of the ventricular pressure-volume curve, which indicates a poor relationship between ventricular filling pressure and volume. Additionally, the placement of a central venous catheter could lead to serious complications such as arterial cannulation, pneumothorax, and infection.
Arterial waveform analysis is dynamic hemodynamic monitoring based on the interaction between the heart and lungs in patients with mechanical ventilation. Stroke volume variation (SVV) is one aspect of arterial pressure waveform analysis and is a less invasive alternative technique for guiding preload status and fluid management in patients undergoing major abdominal surgery.
In liver resection, several anesthetic methods are used to achieve low central venous pressure (CVP < 5 mmHg) during the liver parenchymal dissection phase. These methods include intraoperative volume restriction, administration of venodilators or vasodilators, the use of forced diuresis with furosemide, and the implementation of hypovolemic phlebotomy. As mentioned, central venous pressure is a static hemodynamic monitoring parameter and poorly correlates with volume status. Recently, stroke volume variation has been recognized as a good parameter to predict volume status and fluid responsiveness in patients undergoing liver resection. However, no previous publications have studied the efficacy of stroke volume variation monitoring compared with central venous pressure monitoring to reduce perioperative blood loss during open liver resection.
The study aimed to compare the efficacy of maintaining high stroke volume variation versus low central venous pressure in reducing perioperative blood loss during the liver transection phase in open liver resection.
Read the detailed description
Bleeding is the most common and concerning complication in liver resection because it affects overall complications. Nowadays, there are numerous surgical and anesthetic techniques to decrease blood loss and the need for blood transfusion during liver resection. Surgical strategies include the use of temporary hepatic vascular occlusion techniques, infrahepatic inferior vena caval clamping, and multiple parenchymal transection techniques to minimize intraoperative blood loss and blood transfusion.
Low central venous pressure (CVP < 5 mmHg) is the main anesthetic technique to reduce blood loss and transfusion requirements. Low CVP decreases the impedance for blood flow through the hepatic venous system into the inferior vena cava, resulting in reduced retrograde venous bleeding during parenchymal resection. Low CVP anesthesia can be achieved by several methods such as restrictive intravenous fluid infusion, administration of diuretics and systemic nitroglycerin, reducing mechanical ventilation, and the application of epidural anesthesia.
Nowadays, stroke volume variation (SVV) monitoring, obtained using the FloTrac-Vigileo system (Edwards Lifesciences®, Irvine, CA, USA), is a minimally invasive technique for hemodynamic monitoring that utilizes arterial pressure waveform analysis. This system offers several benefits such as sensitivity, convenience, and real-time application. It is used to assess volume status and enable optimal fluid management under positive pressure ventilation in high-risk surgical patients. Moreover, arterial pressure waveform analysis is superior to central venous pressure monitoring in terms of predicting volume responsiveness. Several studies have shown the benefits of SVV guidance during the intraoperative period in mechanically ventilated patients, including improved hemodynamic stability, decreased serum lactate levels, a lower incidence of postoperative complications, and shortened hospital stays. However, the reliability of arterial waveform analysis is influenced by certain conditions, such as tidal volume greater than 8 ml/kg, normal right ventricular function, absence of cardiac arrhythmias, and normal respiratory mechanics.
Perioperative fluid management is a crucial aspect of anesthesia for liver resection and is divided into two phases: the "fluid-restrictive" phase during parenchymal transection and the "resuscitative" phase after the completion of liver resection. In the first phase, intraoperative fluid administration can be restricted, and vasopressors may be administered to maintain hemodynamic stability. However, the optimal balance of fluid volumes and vasopressors is unclear. In the second phase, liberal fluid administration should be employed for resuscitation to reduce the risk of postoperative organ hypoperfusion, oliguria, and metabolic acidosis.
The utilization of stroke volume variation (SVV) for guiding fluid therapy in liver resection has been reported. Central venous pressure (CVP) monitoring was found to correlate significantly with SVV values during liver resection, demonstrating that a CVP of 3 mmHg correlated with an SVV of 13%, while a CVP of -1 to 1 mmHg corresponded to an SVV of 18-21%. Maintaining a high stroke volume variation of 10-20% as the target value during the restrictive phase has been shown to result in significantly lower amounts of intraoperative blood loss compared to patients maintained with a central venous pressure of less than 5 mmHg. Moreover, previous publications have shown that a high SVV (SVV 10-20%) compared to a low SVV (SVV <10%) reduces blood loss during liver resection. Additionally, goal-directed therapy (GDT) using the stroke volume variation parameter can guide the resuscitative phase during liver transection, potentially preventing excessive fluid administration after liver resection and helping to maintain a balanced fluid status postoperatively.
Objective
The purpose of this study is to compare the efficacy of maintaining high stroke volume variation versus low central venous pressure in minimizing perioperative blood loss during open liver resection. The primary and secondary objectives are as follows:
- Conditions
- Liver Tumor; Surgery, Primary Liver Tumor, Metastatic Liver, Primary Liver Cancer, Liver Resection, Benign Liver Tumor
- Being tested
- High SVV-guided fluid management, Low CVP-guided fluid management
- Keywords
- Stroke volume variation, central venous pressure, open liver resection, blood loss
- Medical subject headings
- Carcinoma, Hepatocellular, Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High SVV-guided fluid managementOther
Before and during parenchymal transection, the attending anesthesiologist used stroke volume variation to guide fluid management and maintained SVV between 13% and 20%. The CVP display was concealed from the attending anesthesiologist during this phase. If SVV exceeded 20%, balanced crystalloid was administered in the minimum amount required to reduce SVV to 20% or lower. Hemodynamic instability was treated according to the prespecified study protocol.
Low CVP-guided fluid managementOther
Before and during parenchymal transection, the attending anesthesiologist used central venous pressure to guide fluid management and maintained CVP below 5 mmHg. The SVV display was concealed from the attending anesthesiologist during this phase. Hemodynamic instability was treated according to the prespecified study protocol.
| Study group | Role | What they receive |
|---|---|---|
| High SVV group, Intervention name: High stroke volume variation-guided fluid management | Experimental | Before and during parenchymal transection, the attending anesthesiologist used SVV to guide fluid management and maintained SVV between 13% and 20%. The CVP display was concealed from the anesthesiologist during this phase. If SVV exceeded 20%, balanced crystalloid was administered in the minimum amount required to reduce SVV to 20% or lower. Hemodynamic instability was treated according to the prespecified study protocol. Receives: Other: High SVV-guided fluid management |
| Low CVP group, Intervention name: Low central venous pressure-guided fluid management | Active comparator | Before and during parenchymal transection, the attending anesthesiologist used central venous pressure to guide fluid management and maintained a CVP of less than 5 mmHg. The SVV display was concealed from the anesthesiologist during this phase. Hemodynamic instability was treated according to the prespecified study protocol. Receives: Other: Low CVP-guided fluid management |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total intraoperative blood loss
Total intraoperative blood loss
Total blood loss, measured in milliliters, from skin incision to completion of surgery. Blood loss will be evaluated by an outcome assessor who was blinded to group allocation, by subtracting irrigation fluid volume from the total suction-canister volume and adding blood loss determined by weighing surgical sponges and gauze before and after use, assuming that a 1-g increase in weight corresponded to 1 mL The treatment effect was defined as the mean difference between groups (high-SVV minus low-CVP). The prespecified noninferiority margin in study protocol was 210 mL. The study had two co-primary blood-loss outcomes. Overall noninferiority required both total intraoperative blood loss and parenchymal transection blood loss to satisfy the noninferiority criterion.
Measured: From skin incision to completion of surgery
Blood loss during parenchymal transection
Blood loss, measured in milliliters, during the liver parenchymal transection phase. Blood loss will be evaluated by an outcome assessor who was blinded to group allocation, by subtracting irrigation fluid volume from the total suction-canister volume and adding blood loss determined by weighing surgical sponges and gauze before and after use, assuming that a 1-g increase in weight corresponded to 1 mL The treatment effect was defined as the mean difference between groups (high-SVV minus low-CVP). The prespecified noninferiority margin in study protocol was 210 mL. The study had two co-primary blood-loss outcomes. Overall noninferiority required both total intraoperative blood loss and parenchymal transection blood loss to satisfy the noninferiority criterion.
Measured: From the beginning to completion of liver parenchymal transection
Secondary outcomes (30)
Intraoperative packed red cell transfusion
Number and proportion of participants receiving allogeneic packed red cells and number of units transfused
Measured: From induction of anesthesia to completion of surgery
Intraoperative transfusion of other blood products
Number and proportion receiving fresh frozen plasma, platelets, cryoprecipitate, or other recorded blood products
Measured: From induction of anesthesia to completion of surgery
Postoperative packed red cell transfusion
Number and proportion receiving packed red cells and number of units transfused
Measured: From completion of surgery through 72 postoperative hours
Postoperative transfusion of other blood products
Number and proportion receiving fresh frozen plasma, platelets, cryoprecipitate, or other blood products
Measured: From completion of surgery through 72 postoperative hours
Hepatic surgical field bleeding score Surgical-field bleeding assessed by the blinded operating surgeon using the prespecified hepatic surgical field bleeding scale; higher scores indicate greater bleeding During parenchymal transection
Surgical-field bleeding assessed by the blinded operating surgeon using the prespecified hepatic surgical field bleeding scale; higher scores indicate greater bleeding
Measured: During parenchymal transection
End-of-surgery serum lactate
Serum lactate concentration measured after post-transection fluid resuscitation
Measured: At the end of surgery
Serum lactate on postoperative day 1
Serum lactate concentration measured in mmol/L
Measured: Postoperative day 1
Serum lactate on postoperative day 3
Serum lactate concentration measured in mmol/L
Measured: Postoperative day 3
Serum lactate on postoperative day 5
Serum lactate concentration measured in mmol/L
Measured: Postoperative day 5
Postoperative acute kidney injury
Incidence and worst stage of acute kidney injury according to KDIGO criteria
Measured: During the index hospitalization, up to postoperative day 30
Posthepatectomy liver failure
Incidence and severity grade of posthepatectomy liver failure according to ISGLS criteria
Measured: From postoperative day 5 through postoperative day 30
Major postoperative morbidity
Complications classified as Clavien-Dindo grade IIIa or higher
Measured: Within 30 days after surgery
Comprehensive Complication Index
Overall postoperative morbidity summarized on the 0-100 Comprehensive Complication Index scale
Measured: Within 30 days after surgery
Intensive care unit admission
Number and proportion of participants requiring postoperative ICU admission
Measured: During the index hospitalization
Length of intensive care unit stay
Number of days spent in the ICU after surgery
Measured: During the index hospitalization
Length of hospital stay
Number of days from the date of surgery to hospital discharge
Measured: During the index hospitalization
Reoperation
Unplanned reoperation related to the index liver resection
Measured: Within 30 days after surgery
In-hospital mortality
Death occurring during the index hospitalization
Measured: During the index hospitalization
30-day mortality
Death from any cause
Measured: Within 30 days after surgery
Postoperative coagulopathy
Presence of postoperative coagulopathy according to the prespecified INR and/or platelet criteria (Postoperative INR >1.5 and/or platelet count < 100,000)
Measured: POD 1 -5
Cardiovascular complications
At least one prespecified postoperative cardiovascular complication
Measured: Within 30 days
Respiratory complications
At least one prespecified postoperative respiratory complication
Measured: Within 30 days
Gastrointestinal complications
At least one prespecified postoperative gastrointestinal complication
Measured: Within 30 days
Infectious complications
At least one prespecified postoperative infectious complication
Measured: Within 30 days
End-of-surgery hyperlactatemia
Serum lactate >2 mmol/L
Measured: At the end of surgery
Hyperlactatemia on POD1
Serum lactate >2 mmol/L
Measured: Postoperative day 1
Hyperlactatemia on POD3
Serum lactate >2 mmol/L
Measured: Postoperative day 3
Hyperlactatemia on POD5
Serum lactate >2 mmol/L
Measured: Postoperative day 5
Intraoperative metabolic acidosis
Presence of metabolic acidosis according to the prespecified laboratory definition
Measured: During the operation
Reoperation
Reoperation occuring during the index hospitalization
Measured: During the index hospitalization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2025
- Study start25 Nov 2024
- Primary completion26 Aug 2026
- Study completion26 Sep 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Liver Tumor; SurgeryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel-group randomized controlled noninferiority trial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chiang Mai University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Warangkana Lapisatepun, MD PhD, Chiang Mai University
- Investigators
- Warangkana Lapisatepun, MD. PhD., Principal investigator, Chiang Mai University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06905015
- Sponsor's protocol ID
- ANE-2567-0300
- Status last verified
- Oct 2026
- First submitted
- 25 Mar 2025
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified data from the study will be made available upon reasonable request to other researchers for further analysis and validation, in alignment with data sharing principles and participant confidentiality.
Publications
Dunki-Jacobs EM, Philips P, Scoggins CR, McMasters KM, Martin RC 2nd. Stroke volume variation in hepatic resection: a replacement for standard central venous pressure monitoring. Ann Surg Oncol. 2014 Feb;21(2):473-8. doi: 10.1245/s10434-013-3323-9. Epub 2013 Oct 23.
PubMed 24150192