Hepatectomy, Liver Neoplasms
Conditions
Brief summary
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
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.
Interventions
PROCEDUREPhlebotomy
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.
DEVICECitrated whole blood collection bag
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.
Sponsors
Ottawa Hospital Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Intraoperative Blood Loss, by Measurement of Change in Hemoglobin Levels | 1 week prior to surgery (hemoglobin level), and day two of post-op (hemoglobin again). | 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. |
| Trial Feasibility | through study completion, an average of 2 years | Trial accrual |
Secondary
| Measure | Time frame |
|---|---|
| Perioperative Morbidity (Dindo-Clavien Grade 3b of Higher) and Mortality | Postoperative setting up to 30 days following surgery |
| Blood Product Transfusion Rates | Will be measured in the operating room and in the first postoperative week |
| 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 |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phlebotomy 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.
Phlebotomy: 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.
Citrated whole blood collection bag: 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. | 31 |
| Control Standard of care (low CVP surgery). In this arm, standard anesthesia will be maintained. | 31 |
| Total | 62 |
Baseline characteristics
| Characteristic | Control | Total | Phlebotomy |
|---|---|---|---|
| Age, Continuous | 62 years STANDARD_DEVIATION 11 | 60 years STANDARD_DEVIATION 12.6 | 58 years STANDARD_DEVIATION 14 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Canada | 31 participants | 62 participants | 31 participants |
| Sex: Female, Male Female | 13 Participants | 29 Participants | 16 Participants |
| Sex: Female, Male Male | 18 Participants | 33 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 31 | 1 / 31 |
| other Total, other adverse events | 8 / 31 | 12 / 31 |
| serious Total, serious adverse events | 0 / 31 | 1 / 31 |
Outcome results
Primary
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.
Time frame: 1 week prior to surgery (hemoglobin level), and day two of post-op (hemoglobin again).
Population: incomplete data
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phlebotomy | Total Intraoperative Blood Loss, by Measurement of Change in Hemoglobin Levels | Anaesthetist Estimate | 862 mL |
| Phlebotomy | Total Intraoperative Blood Loss, by Measurement of Change in Hemoglobin Levels | Surgeon Estimate | 761 mL |
| Phlebotomy | Total Intraoperative Blood Loss, by Measurement of Change in Hemoglobin Levels | Calculated EBL | 1116 mL |
| Control | Total Intraoperative Blood Loss, by Measurement of Change in Hemoglobin Levels | Anaesthetist Estimate | 872 mL |
| Control | Total Intraoperative Blood Loss, by Measurement of Change in Hemoglobin Levels | Surgeon Estimate | 872 mL |
| Control | Total Intraoperative Blood Loss, by Measurement of Change in Hemoglobin Levels | Calculated EBL | 1249 mL |
Primary
Trial Feasibility
Trial accrual
Time frame: through study completion, an average of 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phlebotomy | Trial Feasibility | 62 Participants |
Secondary
Blood Product Transfusion Rates
Time frame: Will be measured in the operating room and in the first postoperative week
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phlebotomy | Blood Product Transfusion Rates | Intraoperative | 1 Participants |
| Phlebotomy | Blood Product Transfusion Rates | Postoperative | 5 Participants |
| Phlebotomy | Blood Product Transfusion Rates | Total | 5 Participants |
| Control | Blood Product Transfusion Rates | Total | 4 Participants |
| Control | Blood Product Transfusion Rates | Intraoperative | 1 Participants |
| Control | Blood Product Transfusion Rates | Postoperative | 3 Participants |
Secondary
Change in Physiologic Parameters (Cardiac Index)
Time frame: Will be measured in the operating room
Population: the number analyzed in one or more rows differs from overall number analyzed due to incomplete data
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phlebotomy | Change in Physiologic Parameters (Cardiac Index) | Before transection | 3.5 I per min per m2 |
| Phlebotomy | Change in Physiologic Parameters (Cardiac Index) | transection | 3.5 I per min per m2 |
| Control | Change in Physiologic Parameters (Cardiac Index) | Before transection | 4.2 I per min per m2 |
| Control | Change in Physiologic Parameters (Cardiac Index) | transection | 3.9 I per min per m2 |
Secondary
Changes in Physiologic Parameters (CVP)
Time frame: Will be measured in the operating room
Population: the number analyzed in one or more rows differs from overall number analyzed due to incomplete data
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phlebotomy | Changes in Physiologic Parameters (CVP) | before transection | 8 cmH2O |
| Phlebotomy | Changes in Physiologic Parameters (CVP) | transection | 8 cmH2O |
| Control | Changes in Physiologic Parameters (CVP) | before transection | 7 cmH2O |
| Control | Changes in Physiologic Parameters (CVP) | transection | 7.5 cmH2O |
Secondary
Perioperative Morbidity (Dindo-Clavien Grade 3b of Higher) and Mortality
Time frame: Postoperative setting up to 30 days following surgery
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phlebotomy | Perioperative Morbidity (Dindo-Clavien Grade 3b of Higher) and Mortality | postoperative complications | 10 Participants |
| Phlebotomy | Perioperative Morbidity (Dindo-Clavien Grade 3b of Higher) and Mortality | Major complication | 2 Participants |
| Control | Perioperative Morbidity (Dindo-Clavien Grade 3b of Higher) and Mortality | postoperative complications | 15 Participants |
| Control | Perioperative Morbidity (Dindo-Clavien Grade 3b of Higher) and Mortality | Major complication | 3 Participants |