Article

Moderate hypothermia in neonatal encephalopathy: Efficacy outcomes

Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina, United States
Pediatric Neurology (Impact Factor: 1.5). 02/2005; 32(1):11-7. DOI: 10.1016/j.pediatrneurol.2004.06.014
Source: PubMed

ABSTRACT Therapeutic hypothermia holds promise as a rescue neuroprotective strategy for hypoxic-ischemic injury, but the incidence of severe neurologic sequelae with hypothermia is unknown in encephalopathic neonates who present shortly after birth. This study reports a multicenter, randomized, controlled, pilot trial of moderate systemic hypothermia (33 degrees C) vs normothermia (37 degrees C) for 48 hours in neonates initiated within 6 hours of birth or hypoxic-ischemic event. The trial tested the ability to initiate systemic hypothermia in outlying hospitals and participating tertiary care centers, and determined the incidence of adverse neurologic outcomes of death and developmental scores at 12 months by Bayley II or Vineland tests between normothermic and hypothermic groups. Thirty-two hypothermic and 33 normothermic neonates were enrolled. The entry criteria selected a severely affected group of neonates, with 77% Sarnat stage III. Ten hypothermia (10/32, 31%) and 14 normothermia (14/33, 42%) patients expired. Controlling for treatment group, outborn infants were significantly more likely to die than hypoxic-ischemic infants born in participating tertiary care centers (odds ratio 10.7, 95% confidence interval 1.3-90). Severely abnormal motor scores (Psychomotor Development Index < 70) were recorded in 64% of normothermia patients and in 24% of hypothermia patients. The combined outcome of death or severe motor scores yielded fewer bad outcomes in the hypothermia group (52%) than the normothermia group (84%) (P = 0.019). Although these results need to be validated in a large clinical trial, this pilot trial provides important data for clinical trial design of hypothermia treatment in neonatal hypoxic-ischemic injury.

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    • "Many centres had introduced this practice already in 2007 when the UK lead TOBY trial had finished recruiting. These recommendations on how to administer TH, and to whom, were based on a large number of preclinical studies, pilot [1,4e7] and smaller clinical studies [8], in addition to the first three large trials: CoolCap, NICHD and TOBY [9e11]. Before discussing " who should we cool?, " it is important to define " who did we cool? "
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    ABSTRACT: Three ongoing challenges have arisen after the introduction of therapeutic hypothermia (TH) as standard of care for term newborns with moderate or severe perinatal asphyxia: (i) to ensure that the correct group of infants are cooled; (ii) to optimize the delivery of TH and intensive care in relation to the severity of the encephalopathy; (iii) to systematically follow up the long-term efficacy of TH using comparable outcome data between centers and countries. This review addresses the entry criteria for TH, and discusses potential issues regarding patient selection, and management of TH: cooling mild, moderate, and very severe perinatal asphyxia, cooling longer or deeper, and/or starting with a greater delay. This includes cooling of patients outside of standard trial entry criteria, such as after postnatal collapse, premature infants, those with infection, and infants with metabolic, chromosomal or surgical diagnoses in addition to perinatal asphyxia. Copyright © 2015. Published by Elsevier Ltd.
    Seminars in Fetal and Neonatal Medicine 02/2015; 20(2). DOI:10.1016/j.siny.2015.01.002 · 3.13 Impact Factor
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    • "Hypoxic–ischemic encephalopathy is the most common cause of brain injury in term newborns. Therapeutic hypothermia is currently the only existing treatment to minimize brain injury in these newborns, with decreased death and disability rates at 12–18 months and beyond (Azzopardi et al., 2009; Eicher et al., 2005a, b; Gluckman et al., 2005; Jacobs et al., 2007; Shankaran et al., 2005; Shankaran et al., 2012). However , some newborns still develop brain injury despite this treatment (Barks, 2008; Higgins et al., 2006; Higgins and Shankaran, 2009). "
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    ABSTRACT: Arterial spin labeling (ASL) perfusion-weighted imaging (PWI) by magnetic resonance imaging (MRI) has been shown to be useful for identifying asphyxiated newborns at risk of developing brain injury, whether or not therapeutic hypothermia was administered. However, this technique has been only rarely used in newborns until now, because of the challenges to obtain sufficient signal-to-noise ratio (SNR) and spatial resolution in newborns.
    Clinical neuroimaging 12/2014; 6. DOI:10.1016/j.nicl.2014.08.010 · 2.53 Impact Factor
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    • "Hypoxic–ischemic encephalopathy (HIE) remains the most common cause of brain injury in term newborns. Induced hypothermia is currently the only existing treatment to minimize brain injury in these newborns, with decreased death and disability rates at 12–18 months and beyond (Azzopardi et al., 2009; Eicher et al., 2005; Gluckman et al., 2005; Jacobs et al., 2007; Shankaran et al., 2005, 2012). However, some newborns still develop brain injury despite this treatment (Barks, 2008; Higgins and Shankaran, 2009; Higgins et al., 2006). "
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    ABSTRACT: BACKGROUND: The measurement of brain perfusion may provide valuable information for assessment and treatment of newborns with hypoxic-ischemic encephalopathy (HIE). While arterial spin labeled perfusion (ASL) magnetic resonance imaging (MRI) provides noninvasive and direct measurements of regional cerebral blood flow (CBF) values, it is logistically challenging to obtain. Near-infrared spectroscopy (NIRS) might be an alternative, as it permits noninvasive and continuous monitoring of cerebral hemodynamics and oxygenation at the bedside. OBJECTIVE: The purpose of this study is to determine the correlation between measurements of brain perfusion by NIRS and by MRI in term newborns with HIE treated with hypothermia. DESIGN/METHODS: In this prospective cohort study, ASL-MRI and NIRS performed during hypothermia were used to assess brain perfusion in these newborns. Regional cerebral blood flow values (CBF), measured from 1-2 MRI scans for each patient, were compared to mixed venous saturation values (SctO2) recorded by NIRS just before and after each MRI. Analysis included groupings into moderate versus severe HIE based on their initial background pattern of amplitude-integrated electroencephalogram. RESULTS: Twelve concomitant recordings were obtained of seven neonates. Strong correlation was found between SctO2 and CBF in asphyxiated newborns with severe HIE (r = 0.88; p value = 0.0085). Moreover, newborns with severe HIE had lower CBF (likely lower oxygen supply) and extracted less oxygen (likely lower oxygen demand or utilization) when comparing SctO2 and CBF to those with moderate HIE. CONCLUSIONS: NIRS is an effective bedside tool to monitor and understand brain perfusion changes in term asphyxiated newborns, which in conjunction with precise measurements of CBF obtained by MRI at particular times, may help tailor neuroprotective strategies in term newborns with HIE.
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