Head cooling, started within 6 hours of birth and continued for 72 hours, appears to improve later neurodevelopmental outcomes in neonates with moderate hypoxic-ischemic encephalopathy, reported Peter D. Gluckman, M.D., of the University of Auckland and his associates in the “CoolCap” study.
This is the first large randomized trial to be published on the technique of selective head cooling for this disorder. The method uses a “relatively low-tech” fitted cap through which cold water (initially 8°C–12°C) circulates. The concurrent use of a radiant heater above the neonate's abdomen, which is controlled to maintain the rectal temperature at 34°C–35°C, ensures that only mild systemic hypothermia occurs while the brain is cooled.
At least four other large studies of this technique in the United States, United Kingdom, and Germany are planned for the next year or two, and if they bear out the CoolCap results “we shall soon have the first useful treatment for hypoxic-ischemic encephalopathy,” Richard Cooke, M.D., said in an editorial comment accompanying the CoolCap findings (Lancet 2005;365:632-4).
According to the CoolCap investigators, neonatal encephalopathy is a progressive syndrome that begins with the initial insult to the brain but continues after resuscitation. At birth, many affected infants “show initial transient recovery of cerebral oxidative metabolism followed by secondary deterioration with cerebral energy failure 6-15 hours after birth.
This delay offers the potential for therapeutic intervention.
“The severity of this secondary deterioration is closely correlated with neurodevelopmental outcome at 1 and 4 years of age. … Essentially, experimental hypothermia is effective only if it is started in [this] latent phase, before the onset of secondary deterioration,” Dr. Gluckman and his associates noted (Lancet 2005;365:663-70).
In their study, 234 term neonates with acute encephalopathy were treated from 1999 to 2002 at 25 perinatal centers in New Zealand, the United States, and the United Kingdom. All had experienced perinatal hypoxia or ischemia, showed abnormal results on neurological examination, and had an abnormal amplitude-integrated EEG (aEEG). The researchers used this last criterion to screen out infants with mild encephalopathy, who would be expected to have a normal prognosis.
All subjects had a 10-minute Apgar score of 5 or less; required continued ventilation or had severe acidosis; showed lethargy, stupor, or coma; and showed hypotonia, abnormal reflexes, an absent or weak sucking reflex, and/or seizures. Infants were excluded from the study if encephalopathy occurred together with major congenital abnormalities, head trauma, or severe growth restriction.
The neonates were randomly assigned to receive either head cooling (116 subjects) or conventional treatment (118 subjects). No cases of ventricular arrhythmia occurred with the cooling treatment, and no other adverse effects were noted except for mild, transient edema beneath the cooling cap.
At 18 months of age, 218 of the subjects were available for neurological exam, visual and auditory assessment, and neurodevelopmental assessment. “Of 108 cooled infants, about half had an unfavorable outcome, compared with two-thirds of control infants,” the investigators said, noting that this result did not achieve statistical significance.
However, head cooling had no effect at all on the subgroup of 46 neonates with the most severe aEEG changes. When that group was removed from the analysis, outcomes were highly significantly better in the cooled infants, who showed a greater than 50% reduction in severe neuromotor disability.
Only six such infants would need to be treated for one to show clear benefit, Dr. Gluckman and his associates said.