Xenon and Cooling Therapy in Babies at High Risk of Brain Injury Following Poor Condition at Birth
Xenon and Cooling Therapy in Babies at High Risk of Brain Injury Following Poor Condition at Birth
This study examines the effect of inhaled xenon gas in the treatment of newborn infants with
 hypoxic-ischemic encephalopathy (HIE) in combination with cooling, which is the standard
 treatment for this condition. The hypothesis is that the xenon + cooling combination will
 produce better neuroprotection than the standard treatment of cooling alone.
Infants will be eligible for for the trial if the St Michael's hospital standard inclusion
 criteria for cooling and additional inclusion criteria for xenon administration are met.

 St Michael's hospital standard inclusion criteria for standard hypothermia treatment of 72
 hrs:

 A: Neonates born at greater than 36 weeks gestation (estimated or clinical assessment) with
 at least ONE of the following:

 1. Apgar score of ≤5 at ten minutes after birth

 2. Continued need for resuscitation, including tracheal or mask ventilation, at ten
 minutes after birth

 3. Acidosis, defined as either umbilical cord pH or any arterial, venous or capillary pH
 within 60 minutes of birth less < 7.00

 4. Base deficit ≥16 mmol/L in umbilical cord blood sample or any blood sample within 60
 minutes of birth (arterial or venous blood).

 If the infant meets criterion A then assess for neurological abnormality using criterion B
 and C (by trained personnel):

 B: Moderate or Severe encephalopathy as evidenced by any of the following:

 1. Altered state of consciousness (reduced or absent responses or pathological
 irritability and hyper responsive and at least ONE or more of the following:

 2. Hypotonia

 3. Abnormal reflexes including oculomotor or pupillary abnormalities

 4. Absent or weak suck

 5. Clinical seizures, as recorded by trained personnel

 And

 C: At least 30 minutes duration of amplitude-integrated electroencephalography (aEEG)
 recording that shows abnormal background aEEG activity. The decision to cool is based on
 the worst 30 min section of the aEEG, not the best [35] or seizures (clinical or
 electrical) thus meeting ONE of the following:

 1. Normal background with some (> 5 min) electrical seizure activity

 2. Moderately abnormal activity (upper margin of trace >10μV and lower margin <5μV)

 3. Suppressed activity (upper margin of trace <10μV and lower margin of trace <5μV)

 4. Definite seizure activity

 Additional inclusion criteria for xenon:

 Before being considered for additional inhaled xenon therapy via the breathing gas mixture,
 the infant would need to meet further additional entry criteria (all must be met):

 1. Intubated, ventilated, sedated, being cooled

 2. ≤ 5 hours old

 3. Any seizures under control

 4. Weight > 2nd centile for gestational age

 5. Stable cardiovascular parameters; Mean arterial pressure >40mmHg.

 6. Oxygen requirement via mechanical ventilator ≤ 40%.

 7. Positive End Expiratory Pressure (PEEP) requirement ≤ 8cm H2O

 8. Arterial (preferable)/capillary/venous pCO2 within acceptable range (<7kPa)

 9. Postnatal age ≤ 5 hours

 10. Absence of major congenital abnormalities, imperforate anus and in particular any
 bowel obstruction, congenital abnormalities suggestive of chromosomal anomaly or other
 syndromes that include brain dysgenesis. Congenital syndromes affecting the brain
 should be excluded when diagnosed.

 Exclusion criteria for cooling in the CoolXenon3 study:

 1. Infants expected to be greater than 3 hours of age at the time of starting cooling
 treatment.

 2. Futility. Where prognosis is considered to be hopeless e.g. no cardiac output for 20
 minutes.