Phlebotomy to Prevent Blood Loss in Major Hepatic Resections

Study Overview
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Brief Summary
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Major liver resection is associated with substantial intraoperative blood loss. Blood loss in elective liver surgery is a significant factor of perioperative morbidity and mortality, as well as possibly long-term oncologic outcome. The purpose of this study is to use whole blood phlebotomy to decrease the central venous pressure, resulting in a state of relative hypovolemia. It is hypothesized that this intervention will lead to a decrease in blood loss at the time of liver resection.

Detailed Description
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Major liver resection is associated with significant intraoperative blood loss. Blood loss in elective liver surgery is a key determinant of perioperative morbidity and mortality, as well as possibly long-term oncologic outcome. Whole blood phlebotomy is a simple intervention, whose aim is to decrease the central venous pressure yielding a state of relative hypovolemia and thus lead to decreased blood loss. Small studies, mostly from the liver transplant literature, would suggest that phlebotomy with controlled hypovolemia can result in decreased blood loss and blood transfusion. Since blood loss is an important issue in liver surgery, and the benefits of phlebotomy and controlled hypovolemia are unknown in liver resection patients, a rigorously conducted trial in a representative population of patients undergoing liver resection is warranted, and feasible. In this proposal, it is hypothesized that by the use of phlebotomy and controlled hypovolemia, it is possible to decrease blood loss and blood transfusions. To test this hypothesis the investigators plan to randomly allocate participants to phlebotomy plus standard of care or to standard of care. Participants will be those patients undergoing elective major liver resection at the Ottawa Hospital for any indication. The primary outcome will be intraoperative blood loss. Secondary outcomes will include transfusion requirements, perioperative morbidity and mortality, safety, physiologic parameters, and feasibility elements. A total of 62 patients will be randomized. The efficacy of phlebotomy in terms of blood loss prevention will be assessed.

Official Title
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The PRICE Trial: Phlebotomy Resulting in Controlled Hypovolemia to Prevent Blood Loss in Major Hepatic Resections

Conditions
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Liver Neoplasms, Hepatectomy

Intervention / Treatment
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* Procedure: Phlebotomy
* Device: Citrated whole blood collection bag


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any patient being considered for a major elective liver resection will be considered for trial enrollment. Patients who are undergoing a concurrent additional abdominal or thoracic procedure (eg. colonic resection) will also be included. Exclusion Criteria: Age <18 years Pregnancy Refusal of blood products Active cardiac conditions: unstable coronary syndromes, decompensated heart failure (NYHA functional class IV; worsening or new-onset heart failure), significant arrhythmias, severe valvular disease History of significant cerebrovascular disease Renal dysfunction (patients with an estimated GFR <60 mL/min) Abnormal coagulation parameters (INR >1.5 not on warfarin and/or platelets count <100 X109/L ) Evidence of hepatic metabolic disorder (bilirubin >35 umol/L) Presence of active infection Preoperative autologous blood donation Hemoglobin <100 g/L

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phlebotomy<br>For patients randomized to phlebotomy, the intervention will consist of the standard of care (low CVP surgery), plus whole blood phlebotomy. Blood will be collected in citrated whole blood collection bag. | Procedure: Phlebotomy<br>* A central venous catheter will be inserted for every patient to measure central venous pressure, as is the standard of care in elective liver surgery. Strict aseptic technique will be maintained. A total volume of whole blood of 7-10 mL per kg of body weight will be removed, as tolerated. The volume of removed blood will not be replaced by intravenous fluid administration. Collected blood will be transfused back at the end of the liver parenchymal transection, or within 8 hours of collection.<br>Device: Citrated whole blood collection bag<br>* Transfusion Medicine will send the requested number of whole blood collection bags labelled with the patient's name and MRN. These whole blood collection bags are used in standard practice for collection of whole blood.<br>|
| No Intervention: Control<br>Standard of care (low CVP surgery). In this arm, standard anesthesia will be maintained. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Intraoperative Blood Loss, by Measurement of Change in Hemoglobin Levels | Intraoperative blood loss is notoriously difficult to measure. It is suggested that calculation of blood loss using preoperative and postoperative hemoglobin levels in most consistently accurate. In order to minimize the risk of bias associated with any one method of intraoperative measurement of blood loss, three methods will be used independently. In the operating room, all blood and fluid aspirated from the abdomen will be measured accurately using graduated suction containers. As well, the amount of irrigation fluid will be carefully monitored and recorded. Finally, the weight of all surgical sponges will be measured. This information will be used by the surgeon and anesthesiologist to independently visually estimate blood loss, as is commonly done in clinical practice. In parallel, intraoperative blood loss will also be calculated based on an equation. | 1 week prior to surgery (hemoglobin level), and day two of post-op (hemoglobin again). | 
| Trial Feasibility | Trial accrual | through study completion, an average of 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Product Transfusion Rates |  | Will be measured in the operating room and in the first postoperative week | 
| Perioperative Morbidity (Dindo-Clavien Grade 3b of Higher) and Mortality |  | Postoperative setting up to 30 days following surgery | 
| Changes in Physiologic Parameters (CVP) |  | Will be measured in the operating room | 
| Change in Physiologic Parameters (Cardiac Index) |  | Will be measured in the operating room |