Bypass Clear Priming VSD Cardiopulmonary Bypass Circuit Reduce Bypass Associated Inflammation?

Seattle Children's Healthcare System

Status: Not yet enrolling

Conditions: Ventricular Septal Defect

Treatments: Procedure: Clear priming of the bypass pump

Study type: Interventional

Funder types: Other

Identifiers

NCT07393243

STUDY00003941

Details and patient eligibility

About

The purpose of this trial is to study if priming the pump used during cardiac surgery with non-blood fluids instead of donated blood products reduces the inflammation that occurs after heart surgery. The study will focused on pediatric participants who require open heart surgery to repair certain types holes in the heart.

Typically for pediatric patients, the cardiopulmonary bypass pump is "primed" (filled) with donated blood products. This project is going to test if the exposure to these blood products causes inflammation. Patients experience significant inflammation (swelling) after undergoing cardiopulmonary bypass. This inflammation can interfere and slow down the patient's recovery from cardiac surgery. With this project, the investigator are studying if filling the bypass pump with non-blood products reduces the bypass-associated inflammation.

The investigators are also studying if using non-blood fluids to fill the bypass pump reduces bypass associated side effects.

The investigators are also trying to understand how the inflammation starts. The investigators also want to study genetic material called DNA that is collected from a person's blood. Instructions for the body are contained in parts of DNA called genes. Genes determine things like hair and eye color. The investigator hope by studying genes the investigator can learn more about the inflammation that occurs after heart surgery, but the investigators might use participant's genetic information to study other diseases or conditions other the inflammation that occurs after heart surgery.

The investigators will be studying the recovery of 60 participants between 1 month to 18 months of age who require open heart surgery to repair ventricular septal defects (VSDs), a congenital heart defect where there a hole between the lower chambers of the heart.

Participants will:

Allow for information about how the participants recover from surgery to be collected.

Allow blood samples during and after surgery to be collected to understand how the markers of inflammation change between the two groups (blood versus non-blood priming).

Full description

Cardiopulmonary bypass (CPB) is required for surgical correction/palliation of congenital heart defects. Exposure to CPB results in a robust activation of inflammatory responses. It is now well established that exposure to the CPB circuit is associated with an overwhelming, detrimental systemic inflammatory response. The factors associated with this response may be related to the circuit and exposure to the circuit surface, or may be associated with the body's response to surgical trauma, changes in temperature, etc. Multiple pathways have been shown to be mediating this response, including complement activation, leukocyte activation, endotoxin release, release of oxygen-free radicals, nitric oxide, cytokines, platelet-activation factor, arachidonic acid metabolites and endothelins. Activation of these inflammatory pathways has been implicated in the development of some of the major postoperative complications, such as bleeding tendencies, respiratory insufficiency, renal dysfunction, abnormalities in liver function, and, most seriously, multi-organ failure. Multiple pharmacological therapies have been investigated, with a single aim, to modulate this systemic inflammation. The most widely investigated ones have been corticosteroid administration, use of heparin-coated circuits, leukocyte depletion and ultrafiltration. Despite these efforts, the activation of inflammatory pathways in response to CPB remains a significant clinical problem especially in neonates undergoing CPB.

Over the last several years, several centers including Seattle Children's have been pursuing efforts to restrict the administration of blood products during CPB. In some of the recent publications on the topic, the justifications for moving towards "bloodless CPB" include reducing potential infection risks, consideration that blood products are valuable limited resource, and the concerns of certain religious communities. A limitation of these studies is that they do not examine a patient's clinical course or markers of inflammation in depth. CPB patients experience significant post-CPB inflammation - including increased cytokine levels, inflammatory cell infiltration, vascular leak, and multi-organ dysfunction. In children recovering from complicated cardiac surgeries, increased cytokine levels are associated with high mortality and extended intensive care stays. Typically, a blood-containing prime has been used as a method to preserve high hematocrit levels and maintain oxygen delivery. There are several mechanisms by which exposure to blood products can activate inflammation-which include allergic reactions, cytokines in the blood products, or release of proinflammatory proteins from red blood cells. These mechanisms serve as the basis for the hypothesis that "clear prime" CPB patients will have reduced inflammation as compared to standard of care CPB patients.

Since 5/2021, 174 CPB patients have been operated on at Seattle Children's Hospital (SCH) using restrictive blood management. In 90 of these patients, "bloodless" surgery was attempted. These patients received CPB priming with crystalloid fluids only and without any addition of blood products. These crystalloid fluids are same ones used in current standard of care treatment for pediatric cardiac surgery cases. All other aspects of the patients' treatment were the same including the same bypass machines and tubing. 47 of these patients did not receive blood products during the surgery. 35 patients did not receive any blood products during the hospitalization. There were no statistical differences between the median ventilation time and Intensive Care Unit (ICU) length of stay between the patients operated on with such restrictive blood management as compared to patient controls from our center in which blood products were added to CPB prime.

Dr. Bohuta's recent observational study of 99 SCH neonatal cardiac cases using historical controls identified no statistical difference in postoperative seizures, bleeding events, and lactate levels during CPB between patients who received clear prime versus those who received a blood prime. In this same study, both length of stay and postoperative mechanical ventilation time was shorter in the clear prime group. Hematocrit was consistently lower post-operatively for patients in the crystalloid only group, otherwise, there were no unintended consequences/ adverse events identified in the crystalloid only cohort.

Enrollment: 60 estimated patients

Sex: All

Ages: 1 to 18 months old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Weight between 5-10kg
• Age 1-18 months
• Requiring cardiopulmonary bypass as part of clinically indicated surgery
• Surgery performed by Dr. Bohuta or Dr. Greene

Exclusion criteria

• Hemoglobin/hematocrit too low for clear CPB prime (post-dilution Hct <24%)
• Pre-operative ECMO support
• Active infection
• Not clinically appropriate for clear prime (instability, arrhythmias, desaturation, etc.)
• Genetic syndrome
• Pork allergy or family requests pork avoidance

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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60 participants in 2 patient groups

Blood prime

No Intervention group

Description:

The research participants in this arm will undergo their clinically indicated cardiac surgery. The control group will have the bypass pumped primed with mixture of crystalloid solution and blood, which is currently standard of care.

Clear prime

Experimental group

Description:

The research participants in this arm will undergo their clinically indicated cardiac surgery. The experimental group will have the bypass pump primed with mixture of crystalloid solution, non-blood fluids.

Treatment:

Procedure: Clear priming of the bypass pump