Pilot Study of Treatment With Whole Body Hypothermia for Neonatal Encephalopathy

Azzopardi, Denis; Robertson, Nicola J.; Cowan, Frances; Rutherford, Mary; Rampling, M.W.; Edwards, AD

doi:10.1542/peds.106.4.684

Cited by 243 publications

(117 citation statements)

References 33 publications

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“…[131][132][133] Although none of these studies were powered or designed to evaluate neurological outcome, there is some suggestion of improved outcomes. 127,134,135 For example, in a controlled study of head cooling among infants with early stage 2 or 3 encephalopathy, mild systemic hypothermia was associated with a trend to reduced cerebral palsy in survivors (odds ratio 0.46 [0.08, 2.56] vs normothermia).…”

Section: Phase I and Ii Studiesmentioning

confidence: 99%

“…157,158 There are no systematic data from large animals. The clinical studies of therapeutic hypothermia have empirically chosen to rewarm infants at no more than 0.5°C per h, 128,130,132 however, it remains possible that rewarming still more slowly might be beneficial. Further, there is some evidence that worsening of intracranial pressure during rewarming in adult patients with head injury may be able to be avoided by an extremely slow rewarming schedule, although it is still not known whether this improves long-term outcomes.…”

Section: How Long Should Cooling Be Continued?mentioning

confidence: 99%

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Hypothermic neuroprotection

Gunn

Thoresen

2006

NeuroRX

212

128

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Summary:The possibility that hypothermia during or after resuscitation from asphyxia at birth, or cardiac arrest in adults, might reduce evolving damage has tantalized clinicians for a very long time. It is now known that severe hypoxia-ischemia may not necessarily cause immediate cell death, but can precipitate a complex biochemical cascade leading to the delayed neuronal loss. Clinically and experimentally, the key phases of injury include a latent phase after reperfusion, with initial recovery of cerebral energy metabolism but EEG suppression, followed by a secondary phase characterized by accumulation of cytotoxins, seizures, cytotoxic edema, and failure of cerebral oxidative metabolism starting 6 to 15 h post insult. Although many of the secondary processes can be injurious, they appear to be primarily epiphenomena of the 'execution' phase of cell death. Studies designed around this conceptual framework have shown that moderate cerebral hypothermia initiated as early as possible before the onset of secondary deterioration, and continued for a sufficient duration in relation to the severity of the cerebral injury, has been associated with potent, long-lasting neuroprotection in both adult and perinatal species. Two large controlled trials, one of head cooling with mild hypothermia, and one of moderate whole body cooling have demonstrated that post resuscitation cooling is generally safe in intensive care, and reduces death or disability at 18 months of age after neonatal encephalopathy. These studies, however, show that only a subset of babies seemed to benefit. The challenge for the future is to find ways of improving the effectiveness of treatment.

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Section: Phase I and Ii Studiesmentioning

confidence: 99%

Section: How Long Should Cooling Be Continued?mentioning

confidence: 99%

Hypothermic neuroprotection

Gunn

Thoresen

2006

NeuroRX

212

128

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“…38 Initial pilot studies in human newborns described reproducible approaches to both selective head and whole-body hypothermic therapy and confirmed the feasibility of such therapies. [39][40][41][42][43][44] Although these studies noted mild physiological changes in cardiovascular status and the potential for minor permutations in coagulation measurements, they showed that these changes were not clinically significant, that both methods of cooling were practical and that there were no major short-term consequences or complications to either method of cooling. On the basis of these pilot studies, larger clinical trials in newborns (described below) have been performed.…”

Section: Therapeutic Hypothermiamentioning

confidence: 98%

Hypothermia for the treatment of infants with hypoxic–ischemic encephalopathy

Pfister

Soll

2010

J Perinatol

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“…However, this procedure does not seem to be fully protective in the injured brain, as it does not induce the neuronal repair that is essential for normal neurodevelopment. The clinical data have merely demonstrated that mild hypothermia is not harmful in infants with perinatal asphyxia, but there was no obvious benefit (Gunn, Gluckman et al 1998;Azzopardi, Robertson et al 2000).…”

Section: Hypothermiamentioning

confidence: 99%