Brain Cooling for the Treatment of Perinatal Hypoxic-Ischemic Encephalopathy

from Caring For Our Future, Spring 2005

By Anastasia Achatz, BSN, RN, and Sheila Kaseman, MS, RN

A Research Study in the Neonatal Intensive Care Unit

Neonatal Intensive Care Unit (NICU) at The Children’s Hospital has been involved in an international research study to provide head cooling to term -infants following perinatal asphyxia. The goal is to study prolonged head cooling with mild systemic hypothermia in term newborns who have moderate to severe hypoxic ischemic encephalopathy (HIE). This treatment may improve long-term outcomes of neonatal-encephalopathy.

HIE is a common cause of brain damage in newborns. HIE occurs as a result of an injury to the brain from a combination of systemic hypoxemia and diminished cerebral perfusion that leads to ischemia. The incidence of HIE is 2 percent to 6 percent per 1,000 births (Saugstad, 2001). HIE may occur secondary to prenatal, intrapartum or postnatal insults. Prenatal-intrapartum risk factors include fetal distress, abruptio placentae, placenta previa, maternal hypertension, prematurity, postmaturity, intrauterine growth retardation, prolapsed or nuchal cord, dystocia and precipitate or prolonged labor. Brain injury during the post-birth period usually occurs in infants with a history of severe respiratory distress, persistent pulmonary hypertension, recurrent apnea, hypotension or septic shock (Taeusch, 1998; Vannucci. 2000). HIE can lead to mild to severe neurological dysfunction as well as failure of the neonate’s other organ systems. Perinatal hypoxic-ischemic injury continues to be a major cause of death or later neurodevelopmental sequelae. Experimental and clinical studies have shown that HIE is an evolving process.

Early studies show that mild selective head cooling combined with systemic hypothermia in term newborns after perinatal asphyxia is a safe method of reducing cerebral temperature. These initial studies showed safety and hinted at efficacy (Dunn, Gluckman & Gunn, 1998). Evidence from laboratory animal studies and human babies who have been treated with hypothermia show that damage to the brain can be reduced after this type of injury if the brain temperature is reduced by a few degrees for a period of approximately 72 hours, beginning as soon as possible after birth.

Evidence of Improved Cerebral Outcome

TCH was one of 25 sites in the nation that participated in an initial study from 1999 to 2002. A total of 234 patients were enrolled in this large, multi-site, clinical trial. In the study, 116 of 234 infants from the U.S. , Canada , New Zealand and England were randomly assigned into the experimental, head-cooling group. This study confirmed the safety of this treatment for infants  and identified -significant interest among investigators for continued access to the cooling device.

The benefits of this study included the possibility that infants receiving head cooling will have a lower risk of brain damage or less severe brain damage than if not treated. This pilot study led to a statistically significant improvement (p=0.05) in a mixed group of infants with moderate to severe encephalopathy. In the initial trial protocol, there was strong experimental evidence of improved cerebral outcome, particularly in the moderately affected group of infants when they were tested at 18 months of age (Olympic Medical, 2004).

Given the initial encouraging results and the demonstrated safety of the therapy, a continued-access protocol was initiated while waiting for U.S. Food and Drug Administration’s (FDA) approval for the cooling device. This allowed investigators to offer treatment to eligible infants while more safety data was collected. This international, multi-center, non-randomized, continued-access treatment trial began in January 2004. Adam Rosenberg, MD, and Jan Paisley, MD, are the lead investigators at TCH.

The current treatment trial is called “Brain Cooling for the Treatment of Perinatal Hypoxic-Ischemic Encephalopathy Continued Access Protocol.” Nurses in the NICU who care for the critically ill infants enrolled in the study have read the research protocol, studied the brain cooling equipment and learned procedures to provide appropriate nursing care to these infants.

Olympic Medical Corporation in Seattle is currently conducting the continued-access protocol and has been granted approval to enroll 100 additional babies nationwide. In the continued-access protocol, there is no treatment randomization. Therefore, after receiving parental consent, all infants who meet inclusion criteria undergo the head-cooling protocol. Olympic Medical has furnished the cooling cap system. The FDA has approved continued use of this cooling system for investigational purposes at this time. As of December 2004, the NICU had enrolled 15 of the 48 patients nationwide and continues to enroll patients who meet the study criteria.

For this treatment to be effective, the infant must be enrolled and cooling must begin at six hours of life or less. Doctors at the birth hospital must recognize the potential for HIE based on rapid assessment and arrange for transport to TCH. The transport team is aware of the time limit and therefore works quickly to get the baby to the NICU. Upon arrival in the NICU, the nurses and physicians stabilize and assess the patient and perform an amplitude-integrated electroencephalogram (aEEG).

The aEEG, conducted during the initial assessment of the infant, is a requirement of the study. This aEEG recording is obtained with a cerebral function monitor (CFM). NICU nurses have been trained to perform an aEEG using the CFM. The CFM records a single-channel EEG. It is a representation of the background electrocortical activity of the brain. In addition, electrical seizure activity can be diagnosed. The CFM monitors electrical activity in the infant’s brain using three electrodes attached to the infant’s head. Infants meet the criteria to obtain brain cooling if the aEEG documents seizures or moderate to severe abnormal voltage.

Then the aEEG is analyzed. If the aEEG documents seizures or abnormal voltage and the infant is term (>/=36 weeks), apgar scores from delivery along with cord pH and base deficit are analyzed to determine the infant’s eligibility. If the patient qualifies, parents are asked for consent. After a complete neurological assessment is performed by the attending physician or Dr. Rosenberg, the cooling begins. All of this is completed within 6 hours of birth. If the patient is born at a hospital outside of Denver , this can be quite a challenge!

Infant Closely Monitored

Upon enrollment, the infant is fitted with a cooling cap filled with cool water. The cap is attached to a cooling device that circulates cool water in a temperature-regulated manner. The core rectal temperature of the infant is controlled with this cap and cooling device. An overhead warmer is used to maintain a core rectal temperature at the range of 34.5 C+/-5 C. The infant’s rectal, fontanel and abdominal temperatures are continuously monitored while the cooling occurs for 72 hours. The infant requires close monitoring prior to and throughout the study. The infant continues to be closely monitored as the slow re-warming process begins.

All infants have rectal, abdominal, fontanel and cap temperatures recorded hourly for 12 hours then every four hours until 76 hours after cap placement. Infants are followed with a head ultrasound within the first 24 hours of life. Infants also have complete neurological examinations daily during the head cooling and at seven days of life. Infants also will be followed with an evaluation at 12 to 24 months of life.

Temperatures, extensive lab studies, vital signs, medications, diagnostic studies, procedures and any adverse effects for each patient are followed closely and documented during the study. This data is compiled by NICU nurses and will be analyzed by the Olympic Medical Corporation.   

Infants with HIE who are enrolled in this research study require a high level of nursing and medical care. Other interventions are common in infants with HIE and potential multi-system organ failure following severe perinatal asphyxia. Treatments may be related to respiratory, cardiovascular, metabolic or hematological dysfunction. Treatments for this population often include management of hypotension, electrolyte imbalance, sepsis, seizures, sedation and analgesia. Infants in this population can be critically ill for a few days or a few weeks after removal from the treatment.

A few of the infants with severe HIE, neurological impairment and multi-system injury may not benefit from brain cooling. However, it is rewarding to see the infants admitted with HIE who have been enrolled in this study and have done well clinically. It is exciting to be a major participant in a nationwide research study to provide data on outcomes for newborn infants.

The commitment, expertise and dedication to this study by the physicians, flight team members, nurses and the entire health-care team will have a significant impact on providing clinical evidence for the treatment of HIE. We are proud to be involved in this study and strive to be one of the best NICUs in the nation at treating newborn infants. We look forward to continued involvement in research and the implementation of evidence-based practice for newborn infants.

References

Gunn, A.J., Gluckman, P.D. & Gunn, T.R. (1998). Selective head cooling in newborn infants after perinatal asphyxia: a safety study. Pediatrics, 102(4), 885-892.

Olympic Medical (2004). The Cool-Cap Trial Study.

Taeusch, H.W. & Ballard, R.A. (1998). Avery’s Diseases of the Newborn. W.B. Saunders: Philadelphia.

Vannuccci, R.C. (2000). Hypoxic-ischemic encephalopathy. American Journal of Perinatology 17, 113-120.