Effect of Human Plasma Protein Transfusion With and Without Crystalloids During Major Liver Resection Surgeries

Effect of Human Plasma Protein Transfusion With and Without Crystalloids on Acid Base, Electrolytes and Tissue Perfusion During Major Liver Resection Surgeries

Evaluation of acid-base and electrolyte changes after administration of commonly used colloid solutions (plasma protein fraction contains 5% albumin), and crystalloids (saline 0.9% and lactated ringers solutions) is the primary endpoint of this study. The secondary endpoints are to study dilution acidosis and changes in plasma volume induced by albumin versus crystalloids and their effect on tissue perfusion by randomizing patients into two groups where each group receives intraoperatively one type of the two fluids. Changes in acid-base, electrolytes, and dilution acidosis

Study Overview

• Status: Recruiting
• Conditions: Coagulation; Intravascular; Fluid Electrolyte Disorders
• Intervention / Treatment: Drug: 5% human plasma protein fraction (PPF)

Detailed Description

To compare Between PPF 5% and crystalloids in the management of patients undergoing Liver resection and to conclude if any the benefits of treating those patients with high protein content fluids.

Methodology: Each patient will complete a full medical and surgical history and clinical examination.

Routine examinations will include complete blood picture, kidney function tests (serum urea, creatinine, sodium, and potassium), liver function tests (alanine transaminase, aspartate transaminase, prothrombin time and concentration and international normalized ratio, and serum albumin), random blood sugar, and serum electrolytes (Calcium, Chloride bicarbonate and lactate). Patients will be distributed randomly between two groups using a predetermined computer-generated randomized schedule. Twenty-four of the 48 patients will receive an intraoperative intravenous infusion of 5% human plasma protein fraction PPF, (A group). PPF 5%?Octapharma 5 %? is a colloid solution containing (47.6-52.5% proteins, of which 45.6-52.5 gm/L albumin and 142.5-157.5 mmol/L sodium). The remaining 24 patients will receive an intraoperative intravenous infusion of crystalloids (0.9 % normal saline and/ or Lactated Ringer's solution) (RS group). Fluids will be given targeting euvolemic state which is defined as central venous pressure (CVP) 5-10 mmHg or Stroke volume variation (SVV) of? 13%. Central venous pressure (CVP) CVP of -1 to 1 mmHg or Stroke volume variation (SVV) of 18-21% (12) will be targeted during transaction times.

The transfusion trigger will be Hemoglobin of? 8 gm/dl. Any patient who received additional blood products will be excluded from the study. General anesthesia will be induced using Propofol 2% and fentanyl. The ultrasound-guided central venous catheter will be inserted after induction of anesthesia in the right internal jugular vein. Arterial Cather size 20-gauge will be inserted in the radial artery. All patients will receive inhalational anesthesia using Sevoflurane, targeting MAC 1, and be ventilated using the Drager Xeus machine. Tidal volume of 7ml/Kg and zero PEEP will be used for all patients. All patients will receive furosemide 20-40 mg to maintain good diuresis and control central venous pressure. In addition to this, a 30-45 degree head-up position will be maintained. Arterial blood will be drawn through the radial artery catheter before the start of surgery and fluid infusion (time 0), the start of liver resection (time R), after Liver resection (time AR), and at the end of the procedure (time E). Arterial blood gas parameters (using atrial blood gas analyzer machine) including, pH, K+, Cl-, HCO3-, base deficit, and lactate concentrations will be measured. Hemoglobin, hematocrit concentrations, and albumin will be measured and recorded at time 0, R, AR & E. Intravascular albumin mass will be calculated based on plasma volume (PV) which will be calculated according to Nadler's Formula for calculating total blood volume in adult (TBV) (9, 14): PV = TBV ? (1 ? hematocrit)

• Study Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: yasser Hammad, M.D.; Phone Number: +97433000198; Email: yhammad@hamad.qa
• Study Contact Backup: Name: Nabil Shallik, M.D.; Phone Number: +97455439264; Email: nshallik@hamad.qa

Study Locations

• Qatar
  • Ad Dawhah
    • Doha, Ad Dawhah, Qatar, 3050
      • Recruiting
      • Hamad Medical Corporation
      • Contact: yasser Hammad, M.D.; Phone Number: +974 3300 0198; Email: yhammad@hamad.qa
      • Contact: Nabil Shallik; Phone Number: Shallik +97444393817; Email: nshallik@hamad.qa
      • Sub-Investigator: Nabil Shallik, M.D.
      • Sub-Investigator: Hazem Kassas, M.D.
      • Sub-Investigator: Tarek Tageldin, MBBcH.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18- 70 years old
• Not allergic to PPF5%, NS and RL,
• No morphological or functional cardiac valve/s changes, cardiac ischemia, significant arrhythmias or in failure,
• Patients with normal liver function tests before surgery and has no chronic active liver disease,
• Patients with normal kidney functions.

Exclusion Criteria:

• Patients with cardiac disease,
• Kidney disease,
• Liver dysfunction,
• Those who receive additional blood products other than PRBCs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: (Group A); Twenty-four of the 48 patients will receive an intraoperative intravenous infusion of 5% human plasma protein fraction PPF, (A group). PPF 5% "Octapharma 5 %" is a colloid solution containing (47.6-52.5% proteins, of which 45.6-52.5 gm/L albumin and 142.5-157.5 mmol/L sodium). Fluids will be given targeting euvolemic state which is defined as central venous pressure (CVP) 5-10 mmHg or Stroke volume variation (SVV) of ≤ 13%. Central venous pressure (CVP) CVP of -1 to 1 mmHg or Stroke volume variation (SVV) of 18-21% (12) will be targeted during transaction times. The transfusion trigger will be Hemoglobin of ≤8 gm/dl.	Drug: 5% human plasma protein fraction (PPF); Infusion of 5% human plasma protein fraction PPF. PPF 5% "Octapharma 5 %" is a colloid solution containing (47.6-52.5% proteins, of which 45.6-52.5 gm/L albumin and 142.5-157.5 mmol/L sodium).; Other Names: 5% Human Albumen
No Intervention: (Group RS); 24 patients will receive an intraoperative intravenous infusion of crystalloids (0.9 % normal saline and/ or Lactated Ringer's solution) (RS group). Fluids will be given targeting euvolemic state which is defined as central venous pressure (CVP) 5-10 mmHg or Stroke volume variation (SVV) of ≤ 13%. Central venous pressure (CVP) CVP of -1 to 1 mmHg or Stroke volume variation (SVV) of 18-21% (12) will be targeted during transaction times. The transfusion trigger will be Hemoglobin of ≤8 gm/dl.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Base deficit	The primary end point of the study will be changes in base deficit in the two groups	Intra-operative at the end of the four stages of liver resection
Strong Ion difference	The primary end point of the study will be changes in strong ion difference in the two groups	Intra-operative time at the end of four stages of liver resection
Intra-vascular Albumin content	The primary end point of the study will be changes in intra-vascular albumin mass in the two groups	Intra-operative time at the end of the four stages of liver resection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Kidney functions	Two group comparison on postoperative serum creatinine and urine output at the end of surgery	Urine out put at the end of surgery and postoperative day one serum creatinine
Total blood loss	Comparing the two groups regarding intra-operative blood loss	End of surgery blood loss
Changes in coagulation using Thromboelastogram	Comparing the coagulation of the two groups at the end of resection and end of surgery	At the the end of resection phase and end of surgery
Tissue perfusion index	statistically comparing tissue perfusion index between the two groups at the 4 surgical times	The four intra-operative stages of liver resection

Collaborators and Investigators

• Sponsor: Hamad Medical Corporation
• Investigators: Principal Investigator: Yasser Hammad, M.D., Hamad Medical Corporation - HMC

Publications and helpful links

General Publications

• Nadler SB, Hidalgo JH, Bloch T. Prediction of blood volume in normal human adults. Surgery. 1962 Feb;51(2):224-32. No abstract available.
• Janeway, C. A.
• Greasley L, Russell RJ. Albumin and its role in trauma resuscitation. J R Army Med Corps. 2005 Jun;151(2):65-8. doi: 10.1136/jramc-151-02-01. No abstract available.
• Ashraf S. Hasanin, Fatma M.A. Mahmoud, Hossam M. Soliman. Factors affecting acid base status during hepatectomy in cirrhotic patients. Egyptian Journal of Anesthesia (2013) 29, 305-310).
• Semin Thromb Hemost 1980; 6(2): 85-120 DOI: 10.1055/s-2007-1005097
• Peters T Jr. Serum albumin. Adv Protein Chem. 1985;37:161-245. doi: 10.1016/s0065-3233(08)60065-0. No abstract available.
• Quinlan GJ, Martin GS, Evans TW. Albumin: biochemical properties and therapeutic potential. Hepatology. 2005 Jun;41(6):1211-9. doi: 10.1002/hep.20720. No abstract available.
• Tullis JL. Albumin. 1. Background and use. JAMA. 1977 Jan 24;237(4):355-60 CONTD. doi: 10.1001/jama.237.4.355. No abstract available.
• Liumbruno GM, Bennardello F, Lattanzio A, Piccoli P, Rossettias G; Italian Society of Transfusion Medicine and Immunohaematology (SIMTI). Recommendations for the use of albumin and immunoglobulins. Blood Transfus. 2009 Jul;7(3):216-34. doi: 10.2450/2009.0094-09. No abstract available.
• Pusey C, Dash C, Garrett M, Gascoigne E, Gesinde M, Gillanders K, Wallington T. Experience of using human albumin solution 4.5% in 1195 therapeutic plasma exchange procedures. Transfus Med. 2010 Aug 1;20(4):244-9. doi: 10.1111/j.1365-3148.2010.00999.x. Epub 2010 Mar 11.
• Dill DB, Costill DL. Calculation of percentage changes in volumes of blood, plasma, and red cells in dehydration. J Appl Physiol. 1974 Aug;37(2):247-8. doi: 10.1152/jappl.1974.37.2.247. No abstract available.
• Goodkin DA, Raja RM, Saven A. Dilutional acidosis. South Med J. 1990 Mar;83(3):354-5. doi: 10.1097/00007611-199003000-00029.
• Mathes DD, Morell RC, Rohr MS. Dilutional acidosis: is it a real clinical entity? Anesthesiology. 1997 Feb;86(2):501-3. doi: 10.1097/00000542-199702000-00028. No abstract available.
• 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.
• Norberg A, Rooyackers O, Segersvard R, Wernerman J. Leakage of albumin in major abdominal surgery. Crit Care. 2016 Apr 26;20(1):113. doi: 10.1186/s13054-016-1283-8.

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2019
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): September 1, 2021

Study Registration Dates

• First Submitted: July 28, 2021
• First Submitted That Met QC Criteria: August 30, 2021
• First Posted (Actual): September 5, 2021

Study Record Updates

• Last Update Posted (Actual): September 5, 2021
• Last Update Submitted That Met QC Criteria: August 30, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Human Plasma Protein; Crystalloids; Liver Resection Surgeries
• Additional Relevant MeSH Terms: Plasma Substitutes; Blood Substitutes; Plasma protein fraction
• Other Study ID Numbers: MRC-01-18-256

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: A decision regarding sharing information will be taken at later stage
• IPD Sharing Time Frame: Directly after IRB approval.
• IPD Sharing Access Criteria: Website
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No