Therapeutic Hypothermia After Pediatric Cardiac Arrest (THAPCA)

1. Therapeutic Hypothermia After Pediatric Cardiac Arrest (THAPCA) A Clinician Education Module

2. Purpose: To educate clinicians about pediatric cardiac arrest and to describe the THAPCA study. Objectives: At the end of this presentation, you will have increased knowledge of: Cardiac arrest in children; Temperature control as a treatment intervention in children post cardiac arrest; and The purpose of the Therapeutic Hypothermia After Pediatric Cardiac Arrest (THAPCA) study. Objectives

3. About 16,000 children suffer from cardiac arrest each year in the United States.1 Survival rates in children are around 27% after in-hospital cardiac arrest and 5% to 10% after out-of-hospital cardiac arrest.1 Cardiac arrest in children outside of the hospital is often caused by events like near drowning.  Such events typically lead to severe hypoxia and, if of sufficient duration, lead to cardiac arrest.  In-hospital pediatric cardiac arrest occurs associated with a variety of conditions; for example, acquired or congenital heart disease with or without surgery for these conditions.  Low cardiac output, pulmonary hypertension, hypoxia, and arrhythmias are some of the potential causes leading to cardiac arrest.  If enough hypoxic and ischemic injury occurs secondary to a cardiac arrest, then death or long term brain damage may occur. Successful resuscitation in children with full cardiac arrest without long term brain damage is low, especially in out-of-hospital arrests, primarily because of the length of time the child is hypoxic and subsequent tissue damage and metabolic acidosis. Pediatric Cardiac Arrest 1 Topjian AA, Berg RA, Nadkarni VM. Pediatric cardiopulmonary resuscitation: advances in science, techniques, and outcomes. Pediatrics. 2008; 122(5): 1086-98.

4. The medical community agrees that better treatments are needed for children resuscitated after cardiac arrest. The THAPCA study is investigating whether body temperature control improves outcomes in children after cardiac arrest. There have been previous hypothermia studies in animals, adults with cardiac arrest, and newborn babies with perinatal asphyxia, but NOT in children with cardiac arrest. It is notknown whether temperature control results in better outcomes for children after cardiac arrest. Purpose of THAPCA Study

5. Enrolling patients: Age 2 days through 17 years; Suffered an unplanned cardiac arrest no more than 6 hours prior to enrollmentwith CPR lasting at least 2 minutes with return of circulation for at least 20 minutes; and Need for mechanical ventilation About 900 children will be enrolled during a 6-year study period at more than 30 clinical centers Study Participants

6. Body temperature control may protect the brain from injury after cardiac arrest. If the study shows positive outcomes, body temperature control may become the standard practice for pediatric cardiac arrest cases. Potential Benefits

7. Two possible treatments (randomized with 50/50 chance) Hypothermia: body temperature is reduced to 89-93°F (32-34°C) for 48 hrs Normothermia: body temperature will be kept in a normal range 96-99°F (36.0-37.5°C) for 48 hrs Study Procedures • Temperature control blanket • Temperature monitors in esophagus and bladder or rectum • ECMO machine may be used to maintain temperature • Medication to alleviate pain and discomfort and/or prevent shivering

8. Study Procedures

9. Increased chance of infection Cultures of blood and urine will be done at least every other day If positive or doctor thinks an infection may be occurring, antibiotics will be ordered as judged by care team Increased risk of bleeding Blood counts and coagulation tests at least once a day Will be treated as indicated by the medical care team If too much bleeding occurs, will stop cooling and re-warm the child to a normal temperature Risk of cooling too much Could result in life-threatening irregular heart rhythms Will watch the child’s temperature at 2 places (esophagus and bladder or rectum), use a cooling unit that has an automatic temperature safety system built in, and nursing staff will monitor the child’s temperature continuously Risks of Hypothermia

10. Increased risk of blood and chemistry changes Measure blood potassium at least every 6-12 hours and blood glucose levels at least every 6-12 hours Blood potassium may decrease a small amount and require extra potassium to be administered Blood glucose levels may be increased after cardiac arrest and may be more increased during body cooling Doctor may remove some of the glucose from the IV fluids or give insulin to lower the glucose level Minor increase of laboratory values done to check the condition of the pancreas (amylase and lipase) Risks of Hypothermia

11. Risk of sedation Usual practice to sedate children who require mechanical ventilation because this therapy is uncomfortable More sedation than usual may be administered to stop the child from shivering in order to keep the temperature in the correct range Extra sedation for a period of 2-3 days not believed to be harmful Risk of surviving with brain injury Significant number of children having cardiac arrest will survive with brain injury regardless of whether they are in this study or not Likely that some children in the study receiving either temperature therapy will have brain injury Risks of Hypothermia and Normothermia

12. Ensuring Safety During Study • The child’s safety is the top priority, and if there are any concerns for the child’s well-being, he or she will be removed from the study. • While in the study, the child’s safety will be monitored with the following tests: • Blood tests done at least every 12 hours • Blood and urine samples to watch for infection • Chest x-rays for position of the temperature probe placed in the child’s throat • Temperature monitoring for 5 days • Cultures to check for infection for 7 days • Routine urine pregnancy test for females over age 11

13. As you are a caregiver for a child with cardiac arrest, the THAPCA team requests that you: Stay informed regarding the THAPCA trials Recognize eligible patients and refer them to the THAPCA study team Remain objective if parents ask questions about enrolling their child in the study Help parents understand that the purpose of the trial is to determine if body temperature control is beneficial in children with cardiac arrest, and this is not yet known. Your Role as Caregiver

14. Your Role as Caregiver • If a parent asks how their child will be treated if not enrolled in the study: • Answer: We will provide the standard of care for our institution for any child not enrolled on the study • If a parent asks if their child can be treated with hypothermia without being enrolled in the study: • Answer: No, we are not doing hypothermia outside of the study, because we do not know if there is benefit, and there may be dangers associated with the use of hypothermia

15. Caregiver surveys Within the first 12-24 hours: 60 minute surveys to assess how the child was doing developmentally before the cardiac arrest At Day 28: a phone call to determine the vital status of the patient At 3 months and 12 months after cardiac arrest: 1 hour phone surveys about how the child and family are doing since the cardiac arrest Patient follow-up appointments At 12 months after cardiac arrest: patient follow-up appointments at the hospital including a neurologic exam and psychologic/ rehabilitative assessment, taking approximately 4 to 5 hours Follow-up

16. Parent may take child out of study at any time No harm to child No penalty or loss of benefits Researchers may take child out of study at any time Possible reasons include not in child’s best interest to stay in study, parent provides false information, or study is suspended or canceled Ending the Study

17. Research-related laboratory specimens, evaluation forms, surveys, and reports will be identified by a coded number Information about child may be obtained, used, and shared for many reasons Assure proper, safe, and ethical study procedures Analyze results of study Confidentiality

18. Study Details

19. Presentation developed by the Emergency Medical Services for Children (EMSC) National Resource Center with the help of the THAPCA resource team and Data Coordinating Center at the University of Utah. Acknowledgements

20. Contact Information Please use the contact information below to: • Obtain more information about the study • Ask a question about the study procedures or treatments • Talk about study-related costs to the parent or the health plan • Report an illness, injury, or other problem • Express a concern about the study www.thapca.org