Blood Warming for Premature Birth

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: University of South Carolina

Disqualifiers: Neurological abnormalities, Major brain hemorrhage

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 4 hours per transfusion

140 Participants Needed

Trial Summary

What is the purpose of this trial?

Background/significance: Over 100,000 early preterm infants are born annually in the United States and suffer morbidity and mortality during hospitalization in a neonatal intensive care unit. One such condition is hypothermia. Hypothermia has been defined as a contributor of neonatal morbidity by The World Health Organization. Another acute morbidity is anemia in preterm infants due to the prematurity and frequent laboratory testing. Anemia requires correction with a packed red blood cells (PRBC) transfusion. Researchers have previous noted hypothermia during PRBC transfusions in preterm infants. Objective: To use a commercial blood warmer in the neonatal intensive care setting to prevent hypothermic body temperatures (\<36.5°C) in very preterm infants during PRBC transfusions. Process: Based on a completed national survey of neonatal intensive care nurses and PRBC transfusion practices and personal NICU experience, we designed this randomized control trial in 140 very preterm infants in a Southeastern, level III neonatal intensive care unit. Outcomes: Very preterm infants (\<32 weeks gestational age) receiving PRBC transfusions warmed by the commercial blood warmer will have a lower incidence of central body hypothermia post transfusion (temperatures \<36.5C), compared to infants receiving PRBC transfusions by standard of care. Very preterm infants (\<32 weeks gestational age) receiving PRBC transfusions warmed by the commercial blood warmer will have a higher post transfusion mean abdominal skin body temperature when compared to infants receiving PRBC transfusions by standard of care. Hypothesis : The results of this trial could show that very preterm infants experience hypothermia during PRBC transfusions, and thus provide the evidence to support the need for warmed PRBC transfusions in very preterm infants nationwide.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether participants need to stop taking their current medications.

What data supports the effectiveness of the Ranger blood warmer treatment for premature birth?

Research shows that the Ranger blood warmer is effective at warming blood quickly and maintaining body temperature better than some other devices, especially at higher flow rates. This suggests it could help prevent hypothermia in situations like premature birth where maintaining body temperature is crucial. ^{1 2 3 4 5}

How does the Ranger blood warmer treatment differ from other treatments for premature birth?

The Ranger blood warmer is unique because it is specifically designed to warm blood products to prevent hypothermia during transfusions, which is particularly important for premature infants who are more susceptible to temperature fluctuations. Unlike other treatments, it focuses on maintaining the temperature of blood products during transfusion, potentially reducing the risk of hypothermia-related complications. ^{1 2 5 6 7}

Eligibility Criteria

This trial is for very preterm infants born at less than 32 weeks gestational age who are admitted to the neonatal intensive care unit and need a blood transfusion within their first month of life. It excludes those with major brain damage or certain neurological abnormalities, as these can affect body temperature regulation.

Inclusion Criteria

My newborn was in intensive care and received a blood transfusion within the first month.

Any infant born at PRISMA Health Richland hospital

Less than 32 weeks gestational age by obstetrical dating as indicated in the electronic medical chart

Exclusion Criteria

My infant has major brain issues affecting body temperature control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PRBC transfusions with or without the use of a blood warming device

4 hours per transfusion

1 visit (in-person) per transfusion

Monitoring

Participants are monitored for temperature data post-transfusion

24 hours post-transfusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

Treatment Details

Interventions

• Ranger blood warmer

Trial Overview The study tests if using a commercial blood warmer during packed red blood cell transfusions can prevent hypothermia in very preterm infants. The trial randomly assigns participants to receive either warmed transfusions or standard care, aiming to compare body temperatures post-transfusion.

Participant Groups

Group I: Intervention Active Control 1 Intervention

Intervention group: Once a nurse receives the PRBC from the Blood Bank, the nurse will obtain a specialized tubing and use a commercial PRBC warming device, the Ranger blood warmer (3M Healthcare, Oakdale, Minnesota) to deliver the PRBC transfusion to the infant. The unit contains highly responsive aluminum heating plates that distribute heat quickly, which responds to flow changes with even and consistent heat. The plate temperature is monitored 4 times per second and is accurate within 1°C (3M Healthcare, Oakdale, Minnesota). The Ranger blood warmer meets the American Association of Blood Bank (AABB) guidelines for warming blood. All times and information associated with the PRBC transfusion will be recorded on the bedside study document. The transfusion will be given over 4 hours, per the clinician's orders. The infant will end study participation 24 hours after the PRBC transfusion is complete to verify that all temperature data have been received and are valid.

Group II: Standard care Active Control 1 Intervention

Standard care/Control group: The nurse will receive the PRBC transfusion from the Blood Bank. As standard care, there are no deliberate procedures for warming PRBC transfusions in this NICU. The syringe of blood may sit outside the incubator for some time and as such, will warm to the environmental ambient temperature while transfusing into the infant using a standard pump. The transfusion will be given over 4 hours, per the clinician's orders. The bedside nurse will document transfusion start and stop times, and route, on the study document at the bedside. The infant will end study participation 24 hours after the PRBC transfusion is complete to verify that all temperature data have been received and are valid.

Ranger blood warmer is already approved in United States for the following indications:

Approved in United States as Ranger blood warmer for:

• Prevention of hypothermia in preterm infants during PRBC transfusions

Who Is Running the Clinical Trial?

University of South Carolina

Lead Sponsor

Trials

233

Recruited

122,000+

Prisma Health-Midlands

Collaborator

Trials

24

Recruited

2,800+

The Gerber Foundation

Collaborator

Trials

45

Recruited

6,200+

Findings from Research

In a study comparing four portable blood warming devices, all devices outperformed the control in warming blood products at clinically relevant flow rates, with the °M Warmer showing the most significant temperature increases across all tested flow rates.

Importantly, the study found no link between the warming performance of any device and the rates of haemolysis, indicating that these devices can safely warm blood without causing damage to the red blood cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of portable blood-warming devices under simulated pre-hospital conditions: a randomised in-vitro blood circuit study. Weatherall, A., Gill, M., Milligan, J., et al.[2019]

Using a blood warmer set at 41.5°C with compression sleeves at pressures of 150 or 300 mmHg does not cause hemolysis in packed red blood cells, indicating safety in this aspect.

However, the blood warmer is ineffective at reaching the desired temperature, with outlet temperatures only reaching 37.1°C at 150 mmHg and 33.7°C at 300 mmHg, suggesting a risk of hypothermia during massive transfusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pressure Infusion Cuff and Blood Warmer during Massive Transfusion: An Experimental Study About Hemolysis and Hypothermia. Poder, TG., Pruneau, D., Dorval, J., et al.[2019]

In a study of 24 pediatric cardiac surgical patients, forced-air warming was found to be 21% faster than radiant warming in rewarming patients with moderate hypothermia, particularly when their core temperature was below 33 degrees Celsius.

Both warming methods were effective, but forced-air warming provided a significantly greater rewarming rate, suggesting it may be the preferred method for quickly restoring normothermia in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of forced air warming after pediatric cardiac surgery employing hypothermic circulatory arrest without cardiopulmonary bypass. Guvakov, DV., Cheung, AT., Weiss, SJ., et al.[2019]

The Hotline blood warmer delivered warmer packed red blood cells (RBCs) and saline at slower flow rates (1-4 L/h), but did not show a clinically significant advantage in mean body temperature (MBT) changes compared to the Ranger.

At higher flow rates (>4 L/h), the Ranger outperformed the Hotline by warming RBCs and saline more effectively and causing smaller decreases in MBT, suggesting that the Ranger is the better choice for rapid infusions of cold blood products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Flow rates and warming efficacy with Hotline and Ranger blood/fluid warmers. Horowitz, PE., Delagarza, MA., Pulaski, JJ., et al.[2022]

Warming packed red blood cells (RBCs) to 41.5°C using an infusion pump is effective in preventing hypothermia during transfusions, but high flow rates can increase haemolysis from 0.2% to 2.1%.

Using a syringe to hold warmed blood resulted in lower final temperatures (as low as 33.1°C), indicating that infusion pumps should be used cautiously at high flow rates to avoid potential complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of warming and flow rate conditions of blood warmers on red blood cell integrity. Poder, TG., Pruneau, D., Dorval, J., et al.[2018]

The new high-efficiency pediatric blood warmer (System 250TM) significantly outperformed the conventional warmer by achieving higher output temperatures (33.6°C vs. 24.6°C) at a flow rate of 225 ml/min, making it more effective for warming blood in infants and children during massive transfusions.

However, the performance of the System 250TM deteriorated at flow rates above 250 ml/min, highlighting the need to limit flow rates to ensure adequate warming, as it cooled down to only 24.2°C at 400 ml/min.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of a new high-efficiency blood warmer for children. Presson, RG., Haselby, KA., Bezruczko, AP., et al.[2019]

Using an inline blood warmer during neonatal transfusions can safely deliver blood products at near-physiologic temperatures (around 37°C) without causing any detectable damage to the blood components, such as hemolysis or platelet dysfunction.

In a simulated model, the inline warmer effectively increased the temperature of cold-stored blood products from about 4.2°C to 32.6°C at the patient during a rapid 30-minute infusion, suggesting potential benefits in reducing transfusion-associated hypothermia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Warming blood products for transfusion to neonates: In vitro assessments. Hulse, W., Bahr, TM., Fredrickson, L., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Comparison of portable blood-warming devices under simulated pre-hospital conditions: a randomised in-vitro blood circuit study. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Pressure Infusion Cuff and Blood Warmer during Massive Transfusion: An Experimental Study About Hemolysis and Hypothermia. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Effectiveness of forced air warming after pediatric cardiac surgery employing hypothermic circulatory arrest without cardiopulmonary bypass. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Flow rates and warming efficacy with Hotline and Ranger blood/fluid warmers. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Effect of warming and flow rate conditions of blood warmers on red blood cell integrity. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Evaluation of a new high-efficiency blood warmer for children. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Warming blood products for transfusion to neonates: In vitro assessments. [2021]