Selective cerebral hypothermia for term infants following hypoxic ischaemic injury

Abstract

Perinatal hypoxic ischaemic injury is an important cause of both neonatal death and long-term disability. The sequence of resuscitation followed by a latent phase then a secondary cascade of injury is well documented. This thesis covers key steps toward the utilization of selective hypothermia as an intervention during the latent phase to ameliorate the secondary injury and improve subsequent outcome. The technique was shown to be both feasible and well tolerated. Specifically, a rectal temperature of 35 °C and 34.5 °C, in term infants with neonatal encephalopathy, was not associated with an excessive requirement for cardio-respiratory support. Although a decrease in heart rate occurred during cooling, this was expected and there was no significant change in blood pressure during either the cooling or rewarming phase. Additional reassuring findings were that neither major electrolyte disturbance; hypoglycaemia or haematological changes, including excessive haemorrhage, were observed during hypothermia. The study of neurodevelopmental outcome established that selective cerebral hypothermia was not associated with late adverse effects and, in infants with moderate to severe encephalopathy, the combined cooled groups demonstrated a trend towards better outcome. These data confirmed the potential for selective cerebral hypothermia to provide neuroprotection following perinatal asphyxia. In further chapters cerebral CT scan was confirmed as a helpful adjunct to clinical staging in predicting neurodevelopmental outcome and important clinical experience was reported including rebound seizures following rewarming; sclerema neonatorum associated with hypothermia; and abnormal flow in the superior sagittal sinus, associated with perinatal asphyxia. Lastly a review of infants assessed but not recruited to the CoolCap trial based on aEEG criteria was performed. As these aEEG criteria could be applied to future clinical use it was considered important to ensure large numbers of infants with potential to benefit were not excluded from intervention Neurodevelopmental status for those infants excluded by the aEEG criteria was largely favourable but a small number had adverse outcome and the majority manifested short term morbidity. In conclusion, the work presented in this thesis suggests that intervention with selective hypothermia offers the potential to change disease progression and improve subsequent outcome following perinatal asphyxia at term.