OBJECTIVES: To determine the neurodevelopmental outcome of infants treated with head cooling with systemic hypothermia after hypoxic-ischemic encephalopathy. STUDY DESIGN: Infants >/=37 weeks' gestation, who had an umbilical artery pH </=7.09 or Apgar score </=6 at 5 minutes, plus clinical encephalopathy. Infants with major congenital abnormalities were excluded. TRIAL DESIGN: Infants were allocated to either no cooling (rectal temperature = 37.0 +/- 0.2 degrees C, n = 15), or, sequentially, to head cooling accompanied by different levels of systemic hypothermia, including minimal cooling, rectal temperature 36.5 degrees C to 36 degrees C (n = 6), and mild cooling, to either 35.9 degrees C to 35.5 degrees C (n = 6), 35 +/- 0.5 degrees C (n = 6) or 34.5 +/- 0.5 degrees C (n = 7). Head cooling was accomplished by circulating cooled water through a coil of tubing wrapped around the head for up to 72 hours. Survivors were followed up with regular neurologic examination by a neonatologist until 18 months of age, then with blinded developmental testing using the revised Bayley Scales. RESULTS:A total of 40 term infants were enrolled from 2 to 5 hours after birth. The control and the cooled groups were not significantly different for gestation, birth weight, Apgar score, and initial pH. There were 6 early neonatal deaths (3 normothermic and 3 cooled), and 1 death in infancy associated with severe spastic cerebral palsy in a normothermic infant. Six normothermic, 1 minimally cooled, and 4 mildly cooled infants had early stage 1 encephalopathy; all but 1 had a good outcome. Among infants with early stage 2 or 3 encephalopathy, an adverse outcome was found in 4 of 9 normothermic infants (44%) and 4 of 5 minimally cooled infants (80%), whereas in the combined mildly cooled groups, an adverse outcome was found in 4 of 15 infants (26%, odds ratio 0.46 [0.08, 2.56] vs normothermia). CONCLUSIONS: The present study supports the safety of hypothermia, with no evidence of late adverse effects in any infant. Among infants with moderate to severe encephalopathy at enrollment, there was a tendency toward better outcome. These results emphasize the relatively wide range of outcomes using purely clinical criteria for enrollment. Therapeutic hypothermia should not be used outside of stringent, multicenter trials.
RCT Entities:
OBJECTIVES: To determine the neurodevelopmental outcome of infants treated with head cooling with systemic hypothermia after hypoxic-ischemicencephalopathy. STUDY DESIGN:Infants >/=37 weeks' gestation, who had an umbilical artery pH </=7.09 or Apgar score </=6 at 5 minutes, plus clinical encephalopathy. Infants with major congenital abnormalities were excluded. TRIAL DESIGN:Infants were allocated to either no cooling (rectal temperature = 37.0 +/- 0.2 degrees C, n = 15), or, sequentially, to head cooling accompanied by different levels of systemic hypothermia, including minimal cooling, rectal temperature 36.5 degrees C to 36 degrees C (n = 6), and mild cooling, to either 35.9 degrees C to 35.5 degrees C (n = 6), 35 +/- 0.5 degrees C (n = 6) or 34.5 +/- 0.5 degrees C (n = 7). Head cooling was accomplished by circulating cooled water through a coil of tubing wrapped around the head for up to 72 hours. Survivors were followed up with regular neurologic examination by a neonatologist until 18 months of age, then with blinded developmental testing using the revised Bayley Scales. RESULTS: A total of 40 term infants were enrolled from 2 to 5 hours after birth. The control and the cooled groups were not significantly different for gestation, birth weight, Apgar score, and initial pH. There were 6 early neonatal deaths (3 normothermic and 3 cooled), and 1 death in infancy associated with severe spastic cerebral palsy in a normothermic infant. Six normothermic, 1 minimally cooled, and 4 mildly cooled infants had early stage 1 encephalopathy; all but 1 had a good outcome. Among infants with early stage 2 or 3 encephalopathy, an adverse outcome was found in 4 of 9 normothermic infants (44%) and 4 of 5 minimally cooled infants (80%), whereas in the combined mildly cooled groups, an adverse outcome was found in 4 of 15 infants (26%, odds ratio 0.46 [0.08, 2.56] vs normothermia). CONCLUSIONS: The present study supports the safety of hypothermia, with no evidence of late adverse effects in any infant. Among infants with moderate to severe encephalopathy at enrollment, there was a tendency toward better outcome. These results emphasize the relatively wide range of outcomes using purely clinical criteria for enrollment. Therapeutic hypothermia should not be used outside of stringent, multicenter trials.
Authors: A David Edwards; Peter Brocklehurst; Alistair J Gunn; Henry Halliday; Edmund Juszczak; Malcolm Levene; Brenda Strohm; Marianne Thoresen; Andrew Whitelaw; Denis Azzopardi Journal: BMJ Date: 2010-02-09
Authors: Susan E Jacobs; Marie Berg; Rod Hunt; William O Tarnow-Mordi; Terrie E Inder; Peter G Davis Journal: Cochrane Database Syst Rev Date: 2013-01-31
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Authors: Wolfram Burkhardt; Hans Proquitté; Susann Krause; Roland R Wauer; Mario Rüdiger Journal: Intensive Care Med Date: 2004-01-14 Impact factor: 17.440