Delayed Rewarming for Neuroprotection in Infants Following Cardiopulmonary Bypass Surgery

This is an unblinded, single center, randomized study of infants with congenital heart disease undergoing cardiopulmonary bypass surgery, randomized to either the delayed rewarming intervention or to the standard of care (strict normothermia).

Study Overview

• Status: Completed
• Conditions: Post-Op Complication
• Intervention / Treatment: Other: Strict normothermia; Device: Delayed Rewarming

Detailed Description

Control Group:

The congenital heart surgery will be performed according to usual practice with the degree of intra-operative hypothermia determined by the cardiothoracic surgeon based on the anticipated complexity of the case. Following completion of the surgical procedure, the infant will be rapidly rewarmed on CPB at a rate of 0.2 to 0.3°C per minute to a normothermic temperature of 36.5°C. Infants in this group will be given a single weight-based 15 mg/kg dose of intravenous Tylenol in the operating room (OR) by the anesthesiologist as the chest is being closed. The infant will be transported to the Pediatric Intensive Care Unit (PICU) for routine post-operative monitoring. If the infant develops a fever, ice packs will be applied to the axilla and groin per usual routine and removed once the fever has abated.

Experimental group:

Partial rewarming will occur on CPB to 35°C. During the last hour of surgery, the infant's temperature will be maintained at 35°C while the chest is closed by using a BairHugger and lowering the room temperature. Transfusions of packed red blood cells, fresh frozen plasma and cryoprecipitate will not be automatically warmed. Infants will be given a single 15 mg/kg dose of IV Tylenol in the OR. The infant will be transported to the PICU at 35°C and placed on the temperature-regulating blanket. The infant will be incrementally rewarmed with increases in temperature of 0.3°C every 2 hours for 6 hours, then 0.2°C every 2 hours for 6 hours to the goal temperature of 36.5°C. Once the infant is stable, EEG will be performed for 48 hours to screen for seizures. The PI will interpret the EEG every 6-8 hours. The infant will remain on the blanket at 36.5°C for another 12 hours. The blanket and esophageal temperature probe will then be removed a total of 24 hours after surgery was completed.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maine
    • Portland, Maine, United States, 04102
      • Maine Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 6 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of congenital heart disease requiring congenital heart surgery on bypass
2. Age less than 6 months at the time of surgery
3. Intra-operative hypothermia less than or equal to 35°C

Exclusion Criteria:

1. Concern for underlying coagulation disorder such as hemophilia
2. Death in the operating room
3. Inability to wean of cardiopulmonary bypass at conclusion of surgery

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Strict Normothermia; Patients will be rewarmed to 36.5 degrees centigrade in the operating room and maintained here by conventional means in the PICU.	Other: Strict normothermia
Experimental: Delayed Rewarming; Patient will be rewarmed to 35.0 degrees centigrade in the operating room, then slowly rewarmed to normal physiologic temperature over 12 hours by using a servo-controlled cooling blanket. Normothermia will be maintained by the cooling blanket for an additional 12 hours.	Device: Delayed Rewarming; Use of the servo-controlled cooling blanket for delayed rewarming to target temperature.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infants With Elevated s100b and NSE	In a population of infants with congenital heart disease undergoing cardiopulmonary bypass surgery, does delayed rewarming administered during the 12 hours after surgery, compared to standard care, decrease brain injury as measured by levels of serum biomarkers of brain injury, s100b and neuron specific enolase during the four days after surgery?	4 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	In a population of infants with congenital heart disease undergoing cardiopulmonary bypass surgery, is there evidence for increased frequency of severe, moderate or other adverse events in the delayed rewarming group compared to the standard of care group?	4 days

Collaborators and Investigators

• Sponsor: Alexa Craig
• Collaborators: MaineHealth
• Investigators: Principal Investigator: Alexa K Craig, MD, MSc, Assistant Professor of Pediatrics

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2016
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): May 1, 2019

Study Registration Dates

• First Submitted: January 24, 2017
• First Submitted That Met QC Criteria: January 26, 2017
• First Posted (Estimate): January 30, 2017

Study Record Updates

• Last Update Posted (Actual): July 13, 2020
• Last Update Submitted That Met QC Criteria: June 30, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Therapeutic Hypothermia
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications
• Other Study ID Numbers: IRB 4489; 4KL2TR001063-04 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO