Article

Moderate hypothermia to treat perinatal asphyxial encephalopathy.

Division of Clinical Sciences and Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, Imperial College London, London, United Kingdom.
New England Journal of Medicine (Impact Factor: 54.42). 10/2009; 361(14):1349-58. DOI: 10.1056/NEJMoa0900854
Source: PubMed

ABSTRACT Whether hypothermic therapy improves neurodevelopmental outcomes in newborn infants with asphyxial encephalopathy is uncertain.
We performed a randomized trial of infants who were less than 6 hours of age and had a gestational age of at least 36 weeks and perinatal asphyxial encephalopathy. We compared intensive care plus cooling of the body to 33.5 degrees C for 72 hours and intensive care alone. The primary outcome was death or severe disability at 18 months of age. Prespecified secondary outcomes included 12 neurologic outcomes and 14 other adverse outcomes.
Of 325 infants enrolled, 163 underwent intensive care with cooling, and 162 underwent intensive care alone. In the cooled group, 42 infants died and 32 survived but had severe neurodevelopmental disability, whereas in the noncooled group, 44 infants died and 42 had severe disability (relative risk for either outcome, 0.86; 95% confidence interval [CI], 0.68 to 1.07; P=0.17). Infants in the cooled group had an increased rate of survival without neurologic abnormality (relative risk, 1.57; 95% CI, 1.16 to 2.12; P=0.003). Among survivors, cooling resulted in reduced risks of cerebral palsy (relative risk, 0.67; 95% CI, 0.47 to 0.96; P=0.03) and improved scores on the Mental Developmental Index and Psychomotor Developmental Index of the Bayley Scales of Infant Development II (P=0.03 for each) and the Gross Motor Function Classification System (P=0.01). Improvements in other neurologic outcomes in the cooled group were not significant. Adverse events were mostly minor and not associated with cooling.
Induction of moderate hypothermia for 72 hours in infants who had perinatal asphyxia did not significantly reduce the combined rate of death or severe disability but resulted in improved neurologic outcomes in survivors. (Current Controlled Trials number, ISRCTN89547571.)

2 Bookmarks
 · 
142 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In 1993, Przyklenk and colleagues made the intriguing experimental observation that ‘brief ischemia in one vascular bed also protects remote, virgin myocardium from subsequent sustained coronary artery occlusion’ and that this effect ‘…. may be mediated by factor(s) activated, produced, or transported throughout the heart during brief ischemia/reperfusion’. This seminal study laid the foundation for the discovery of ‘remote ischemic conditioning’ (RIC), a phenomenon in which the heart is protected from the detrimental effects of acute ischemia/reperfusion injury (IRI), by applying cycles of brief ischemia and reperfusion to an organ or tissue remote from the heart. The concept of RIC quickly evolved to extend beyond the heart, encompassing inter-organ protection against acute IRI. The crucial discovery that the protective RIC stimulus could be applied non-invasively, by simply inflating and deflating a blood pressure cuff placed on the upper arm to induce cycles of brief ischemia and reperfusion, has facilitated the translation of RIC into the clinical setting. Despite intensive investigation over the last 20 years, the underlying mechanisms continue to elude researchers. In the 8th Biennial Hatter Cardiovascular Institute Workshop, recent developments in the field of RIC were discussed with a focus on new insights into the underlying mechanisms, the diversity of non-cardiac protection, new clinical applications, and large outcome studies. The scientific advances made in this field of research highlight the journey that RIC has made from being an intriguing experimental observation to a clinical application with patient benefit.
    Archiv für Kreislaufforschung 12/2014; 110(1). · 5.96 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Automated analysis and grading of the neonatal EEG has a potential to assist clinical decision making for neonates with hypoxic-ischemic encephalopathy. This paper proposes a method to grade the degree of abnormality in hour-long segments of neonatal EEG. The HMM-based speaker diarization approach is employed to segment and cluster the neonatal EEG into homogeneous states. Several features are proposed to characterize the resultant state sequence to provide a single measure for a complete hour-long EEG recording. These features aim at capturing both the statistics of the state durations (e.g. average state duration, average number of segments), and any patterns contained in the sequentiality of the obtained states (e.g. permutation entropy, entropy rate). Statistical analysis indicates that the proposed features contain discriminative information for the task of automated neonatal EEG grading. Unlike other studies, the developed framework of the EEG 'diarization' provides an easy and intuitive interpretation of the computed features, which is a clinically important aspect.
    ICASSP 2014 - 2014 IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP); 05/2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We examined two potential biomarkers of brain damage in hypoxic-ischemic encephalopathy (HIE) neonates: glial fibrillary acidic protein (GFAP; a marker of gliosis) and ubiquitin C-terminal hydrolase L1 (UCH-L1; a marker of neuronal injury). We hypothesized that the biomarkers would be measurable in cord blood of healthy neonates and could serve as a normative reference for brain injury in HIE infants. We further hypothesized that higher levels would be detected in serum samples of HIE neonates and would correlate with brain damage on magnetic resonance imaging (MRI) and later developmental outcomes.? Serum UCH-L1 and GFAP concentrations from HIE neonates (n = 16) were compared to controls (n = 11). The relationship between biomarker concentrations of HIE neonates and brain damage (MRI) and developmental outcomes (Bayley-III) was examined using Pearson correlation coefficients and a mixed model design. Both biomarkers were detectable in cord blood from control subjects. UCH-L1 concentrations were higher in HIE neonates (p < 0.001), and associated with cortical injury (p < 0.055) and later motor and cognitive developmental outcomes (p < 0.05). The temporal change in GFAP concentrations during (from birth to 96 h of age) predicted motor developmental outcomes (p < 0.05) and injury to the basal ganglia and white matter. Ubiquitin C-terminal hydrolase L1 and GFAP should be explored further as promising serum biomarkers of brain damage and later neurodevelopmental outcomes in neonates with HIE.
    Frontiers in Neurology 12/2014; 5:273.

Full-text (2 Sources)

Download
73 Downloads
Available from
May 28, 2014