Clinical trial NCT05148650: Impact of Balanced Crystalloid and Colloid Infusion on Haemostasis in Healthy Male Volunteers
Official title: Impact of Infusion of Balanced Crystalloid and Colloid Solutions on Haemostasis in Healthy Male Volunteers- a Randomized Controlled Crossover Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Perioperative Hemorrhage
Dilutional Coagulopathy
Keywords: perioperative hemorrhage
fluid therapy
fluid resuscitation
rotational thromboelastometry
goal-directed therapy
dilutional coagulopathy
Lead sponsor: Medical University of Silesia
Sponsor class: OTHER
First posted: 2021-12-08
Enrollment: 25
Sex: MALE
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: The project focuses on perioperative bleeding that requires transfusion of blood products and supplementation of intravascular volume with crystalloids and colloids. The implemented fluid therapy affects coagulation and fibrinolysis, depending on the type of fluid used in an intravenous infusion. Massive haemorrhage significantly impacts the perioperative period and postoperative quality of life and requires individualized therapy, rending the ongoing project relevant from the perspective of the patients.

Detailed description: Perioperative bleeding is a complication that significantly affects postoperative morbidity and quality of life and increases the patient's risk of death. Massive hemorrhage requires individualized therapy, preferably based on international recommendations. It is necessary to transfuse blood and blood products (red blood cells, freshly frozen plasma, platelets, concentrates of coagulation factors) with simultaneous rational supplementation of the intravascular space using crystalloids and colloids. Usually, these are large volumes that are infused over a short time. Proceedings in the operating room and the intensive care unit environment should stabilize the patient's general condition with the lowest possible risk of complications.

However, it has been shown that transfusions are not free from side effects. Transfusions may result not only from "classic" post-transfusion complications (allergic reactions, haemolytic reactions, infections, electrolyte disturbances) but also from iatrogenically generated disorders in the circulatory system (fluid overload), respiratory ( acute lung injury), and hemostasis (risk of hypercoagulability). It is also known that uncontrolled and unbalanced fluid therapy per se may additionally affect the haemodynamic state, haemostasis, and the immune system.

Thromboelastometry (thromboelastography) is becoming the standard of perioperative haemostasis monitoring. It has been documented that it provides more reliable data than standard laboratory tests, such as fibrinogen concentration, activated clotting time (ACT), kaolin-kephalin (aPTT), prothrombin (PT), or INR index. The test can be performed as the so-called point-of-care test (POC), which reduces the waiting time for the result and facilitates goal-directed therapy.

Little is known about the effects of fluid infusion on physiological haemostasis in healthy subjects who do not have a prior bleeding disorder and who are infused with fluids similarly to resuscitation in massive bleeding. Only singular studies in international literature attempted to answer this vital question. Still, the regular progress in the field of fluid therapy makes the obtained data less and less valuable in clinical practice.

Eligibility criteria: Inclusion Criteria:

* Healthy male volunteers aged 18-30 years
* The American Society of Anaesthesiologists Physical Status (ASA PS) I risk class
* Must be able to give informed consent

Exclusion Criteria:

* Female sex
* Blood type O
* A positive history of any acute diseases in the last four weeks
* Chronic diseases
* Any diagnosed haemostatic disorders
* History of anticoagulation
* Any known bleeding diathesis
* Any pharmacotherapy in the previous week
* Participants were informed about the prohibition of drinking alcohol, excessive exercise, and stress on the day before blood sampling

Primary outcomes:
measure: Rotational thromboelastometry (ROTEM) viscoelastic point-of-care coagulation measurements before and after balanced crystalloid infusion
timeFrame: 60 minutes
measure: Rotational thromboelastometry (ROTEM) viscoelastic point-of-care coagulation measurements before and after synthetic colloid infusion
timeFrame: 60 minutes
measure: Standard laboratory tests reporting coagulation status before and after balanced crystalloid infusion
timeFrame: 60 minutes
measure: Standard laboratory tests reporting coagulation status before and after synthetic colloid infusion
timeFrame: 60 minutes
measure: Standard laboratory tests reporting fibrinolysis status before and after balanced crystalloid infusion
timeFrame: 60 minutes
measure: Standard laboratory tests reporting fibrinolysis status before and after synthetic colloid infusion
timeFrame: 60 minutes
Secondary outcomes:
measure: Safety outcomes after crystalloid and colloid infusion
timeFrame: 28 days
Other outcomes:
Locations:
city: Katowice
country: Poland
facility: Department of Anaesthesiology and Intensive Care, Faculty of Medical Sciences in Katowice, Medical University of Silesia in Katowice
state: Silesia
Study officials:
affiliation: Faculty of Medical Sciences in Katowice, Medical University of Silesia
name: Łukasz J Krzych, Professor
role: STUDY_DIRECTOR
affiliation: Faculty of Medical Sciences in Katowice, Medical University of Silesia
name: Agnieszka Wiórek, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wiorek A, Mazur PK, Niemiec B, Krzych LJ. Association between Functional Parameters of Coagulation and Conventional Coagulation Tests in the Setting of Fluid Resuscitation with Balanced Crystalloid or Gelatine: A Secondary Analysis of an In Vivo Prospective Randomized Crossover Study. J Clin Med. 2022 Jul 14;11(14):4065. doi: 10.3390/jcm11144065.