toby (total body hypothermia): a study of treatment for perinatal asphyxia

Conditions: Asphyxia Neonatorum; Hypoxia; Encephalopathy; Seizures

Summary: hypothesis: prolonged whole body cooling in term infants with perinatal asphyxial encephalopathy reduces death and severe neurodevelopmental disability. this study aims to determine whether whole body cooling to 33-34°c is a safe treatment that improves survival, without severe neurological or neurodevelopmental impairments at 18 months, of term infants suffering perinatal asphyxial encephalopathy.

this is a multicentre prospective randomised controlled trial to determine whether a reduction of body temperature by 3-4°c following perinatal asphyxia improves survival without neurodevelopmental disability. full term infants will be randomised within 6 hours of birth to either a control group with the rectal temperature kept at 37 ± 0.2°c or to whole body cooling with the rectal temperature kept at 33.5 ± 0.5°c for 72 hours followed by slow rewarming. the outcome will be assessed at 18 months of age by survival and neurological and neurodevelopmental testing. eligibility criteria: term infants less than 6 hours after birth with moderate or severe perinatal asphyxia (a combination of clinical and eeg criteria). exclusion criteria: infants expected to be 6 hours of age at the time of randomisation or infants with major congenital abnormalities. intervention: intensive care with whole body cooling versus intensive care without whole body cooling (babies are cooled to 33.5°c for 72 hours) main outcomes: death and severe neurodevelopmental impairment at 18 months of age secondary outcomes: cerebral thrombosis or haemorrhage, persistent hypotension, pulmonary hypertension, abnormal coagulation, arrhythmia and sepsis in the neonatal period. neurological impairments at 18 months number of patients required: 236. on 30th november 2006, when recruitment closed, 325 babies had been recruited.

Eligibility criteria:
inclusion criteria the infant will be assessed sequentially by criteria a, b and c listed below: a. infants =\>36 completed weeks gestation admitted to the neonatal intensive care unit (nicu) with at least one of the following: * apgar score of =\<5 at 10 minutes after birth * continued need for resuscitation, including endotracheal or mask ventilation, at 10 minutes after birth * acidosis within 60 minutes of birth (defined as any occurrence of umbilical cord, arterial or capillary ph \<7.00) * base deficit =\>16 mmol/l in umbilical cord or any blood sample (arterial, venous or capillary) within 60 minutes of birth infants that meet criteria a will be assessed for whether they meet the neurological abnormality entry criteria (b) by trained personnel: b. moderate to severe encephalopathy, consisting of altered state of consciousness (lethargy, stupor or coma) and at least one of the following: * hypotonia * abnormal reflexes including oculomotor or pupillary abnormalities * absent or weak suck * clinical seizures infants that meet criteria a \& b will be assessed by amplitude-integrated electroencephalogram (aeeg) (read by trained personnel): c. at least 30 minutes duration of amplitude integrated eeg recording that shows abnormal background aeeg activity or seizures. there must be one of the following: * normal background with some seizure activity * moderately abnormal activity * suppressed activity * continuous seizure activity exclusion criteria * infants expected to be \> 6 hours of age at the time of randomisation * major congenital abnormalities, such as diaphragmatic hernia requiring ventilation, or congenital abnormalities suggestive of chromosomal anomaly or other syndromes that include brain dysgenesis

Keywords: hypoxia ischaemia encephalopathy neonatal hypothermia perinatal cooling whole/total body