Phlebotomy to Prevent Blood Loss in Major Hepatic Resections

Liver Neoplasms Clinical Trial

— PRICE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02548910
• Other study ID #: 3588
• Status: Completed
• Phase: N/A
• Start date: April 2016
• Est. completion date: March 2018

Study information

• Verified date: February 2021
• Source: Ottawa Hospital Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: March 2018
• Est. primary completion date: March 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hepatectomy
• Liver Neoplasms

Intervention

Procedure:
• 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.

Device:
• 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.

Locations

Country	Name	City	State
Canada	The Ottawa Hospital - General Campus	Ottawa	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Ottawa Hospital Research Institute

Country where clinical trial is conducted

Canada, 

References & Publications (10)

Alkozai EM, Lisman T, Porte RJ. Bleeding in liver surgery: prevention and treatment. Clin Liver Dis. 2009 Feb;13(1):145-154. doi: 10.1016/j.cld.2008.09.012. — View Citation

Andreou A, Aloia TA, Brouquet A, Dickson PV, Zimmitti G, Maru DM, Kopetz S, Loyer EM, Curley SA, Abdalla EK, Vauthey JN. Margin status remains an important determinant of survival after surgical resection of colorectal liver metastases in the era of modern chemotherapy. Ann Surg. 2013 Jun;257(6):1079-88. doi: 10.1097/SLA.0b013e318283a4d1. — View Citation

Hashimoto T, Kokudo N, Orii R, Seyama Y, Sano K, Imamura H, Sugawara Y, Hasegawa K, Makuuchi M. Intraoperative blood salvage during liver resection: a randomized controlled trial. Ann Surg. 2007 May;245(5):686-91. — View Citation

Huntington JT, Royall NA, Schmidt CR. Minimizing blood loss during hepatectomy: a literature review. J Surg Oncol. 2014 Feb;109(2):81-8. doi: 10.1002/jso.23455. Epub 2013 Oct 4. Review. — View Citation

Jarnagin WR, Gonen M, Fong Y, DeMatteo RP, Ben-Porat L, Little S, Corvera C, Weber S, Blumgart LH. Improvement in perioperative outcome after hepatic resection: analysis of 1,803 consecutive cases over the past decade. Ann Surg. 2002 Oct;236(4):397-406; discussion 406-7. — View Citation

Massicotte L, Perrault MA, Denault AY, Klinck JR, Beaulieu D, Roy JD, Thibeault L, Roy A, McCormack M, Karakiewicz P. Effects of phlebotomy and phenylephrine infusion on portal venous pressure and systemic hemodynamics during liver transplantation. Transplantation. 2010 Apr 27;89(8):920-7. doi: 10.1097/TP.0b013e3181d7c40c. — View Citation

McNally SJ, Revie EJ, Massie LJ, McKeown DW, Parks RW, Garden OJ, Wigmore SJ. Factors in perioperative care that determine blood loss in liver surgery. HPB (Oxford). 2012 Apr;14(4):236-41. doi: 10.1111/j.1477-2574.2011.00433.x. Epub 2012 Feb 28. — View Citation

Poon RT, Fan ST, Lo CM, Liu CL, Lam CM, Yuen WK, Yeung C, Wong J. Improving perioperative outcome expands the role of hepatectomy in management of benign and malignant hepatobiliary diseases: analysis of 1222 consecutive patients from a prospective database. Ann Surg. 2004 Oct;240(4):698-708; discussion 708-10. — View Citation

Sima CS, Jarnagin WR, Fong Y, Elkin E, Fischer M, Wuest D, D'Angelica M, DeMatteo RP, Blumgart LH, Gönen M. Predicting the risk of perioperative transfusion for patients undergoing elective hepatectomy. Ann Surg. 2009 Dec;250(6):914-21. — View Citation

Spolverato G, Ejaz A, Kim Y, Hall BL, Bilimoria K, Cohen M, Ko C, Pitt H, Pawlik TM. Patterns of care among patients undergoing hepatic resection: a query of the National Surgical Quality Improvement Program-targeted hepatectomy database. J Surg Res. 2015 Jun 15;196(2):221-8. doi: 10.1016/j.jss.2015.02.016. Epub 2015 Mar 19. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	1 week prior to surgery (hemoglobin level), and day two of post-op (hemoglobin again).
Primary	Trial Feasibility	Trial accrual	through study completion, an average of 2 years
Secondary	Blood Product Transfusion Rates		Will be measured in the operating room and in the first postoperative week
Secondary	Perioperative Morbidity (Dindo-Clavien Grade 3b of Higher) and Mortality		Postoperative setting up to 30 days following surgery
Secondary	Changes in Physiologic Parameters (CVP)		Will be measured in the operating room
Secondary	Change in Physiologic Parameters (Cardiac Index)		Will be measured in the operating room