Therapeutic hypothermia: from lab to NICU.

The possibility of a therapeutic role for cerebral hypothermia during or after resuscitation from perinatal asphyxia has been a long-standing focus of research. However, early studies had limited and contradictory results. It is now known that severe hypoxia-ischemia may not cause immediate cell death, but may precipitate a complex biochemical cascade leading to the delayed development of neuronal loss. These phases 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 from 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. This conceptual framework allows a better understanding of the experimental parameters that determine effective hypothermic neuroprotection, including the timing of initiation of cooling, its duration and the depth of cooling attained. Moderate cerebral hypothermia initiated in the latent phase, between one and as late as 6 h after reperfusion, and continued for a sufficient duration in relation to the severity of the cerebral injury, has been consistently associated with potent, long-lasting neuroprotection in both adult and perinatal species. The results of the first large multicentre randomized trial of head cooling for neonatal encephalopathy and previous phase I and II studies now strongly suggest that prolonged cerebral hypothermia is both generally safe - at least in an intensive care setting - and can improve intact survival up to 18 months of age. Both long-term followup studies and further large studies of whole body cooling are in progress.

The effect of methadone treatment on the quantity and quality of human fetal movement.

OBJECTIVE: To evaluate the effect of daily maternal methadone maintenance treatment on the quality and quantity of fetal movement. METHODS: At 34-37 weeks gestation, real-time ultrasound recordings were obtained from 17 methadone treated and 17 non-opioid-dependent mothers at two time points relative to the methadone mothers' daily dose of methadone. The first observation was just prior to the mother taking her daily dose (Time A) and the second was 1-h postdose (Time B). The incidence and pattern of fetal breathing movements (FBMs), fetal trunk movements (FTMs) and total fetal activity (TFA) were obtained from these ultrasounds. RESULTS: A time by group effect was found for measures of FBM and TFA, Fs(1,32)=6.06 and 4.94, P<0.05. At Time A and Time B for these measures t-tests showed no difference in the incidence of FBM (47.9% vs. 55.4%) and TFA (56% vs. 64%) at Time A between the methadone and comparison groups; however, at Time B the incidence of FBM (16.6% vs. 53.5%) and TFA (27% vs. 65%) was decreased for the methadone group. In addition, there was a between-group difference for two qualitative measures of fetal breathing. A slower rate of fetal breathing (40.3 vs. 47.2 breaths/min) and fewer FBMs per breathing episode (51.7 vs. 92.4) were found for the methadone group regardless of time since the mothers' daily dose. CONCLUSION: Taken together these results suggest that daily maternal methadone maintenance treatment altered both quantitative and qualitative measures of fetal activity that have been found to be related to normal fetal development.

Treatment of term infants with head cooling and mild systemic hypothermia (35.0 degrees C and 34.5 degrees C) after perinatal asphyxia.

OBJECTIVE: To assess the safety of selective head cooling in birth-asphyxiated term newborn infants while maintaining the rectal temperature at 35.0 degrees C or 34.5 degrees C. METHODS: Twenty-six term infants with Apgar