Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial

Gluckman, Peter D.; Wyatt, John; Azzopardi, Denis; Ballard, Roberta A.; Edwards, AD; Ferriero, Donna M.; Polin, Richard A.; Robertson, Charlene M.T.; Thoresen, Marianne; Whitelaw, Andrew; Gunn, Alistair J.

doi:10.1016/s0140-6736(05)17946-x

Cited by 1,882 publications

(1,186 citation statements)

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“…6 However, in a controlled trial, hypothermia was only started in 12% of infants within 4 hours of birth. 7 Preclinical studies suggest that some of the loss of efficacy associated with delayed onset of hypothermia can be salvaged by more prolonged cooling. For example, in adult gerbils, 12 hours of hypothermia initiated 1 hour after global ischemia effectively reduced hippocampal injury after 3 minutes, but not 5 minutes, of global ischemia.…”

Section: Introductionmentioning

confidence: 99%

How Long is Too Long for Cerebral Cooling after Ischemia in Fetal Sheep?

Davidson

Wassink

Yuill

et al. 2015

J Cereb Blood Flow Metab

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Therapeutic hypothermia can partially reduce long-term death and disability in neonates after hypoxic-ischemic encephalopathy. The aim of this study was to determine whether prolonging the duration of cooling from 3 days to 5 days could further improve outcomes of cerebral ischemia in near-term fetal sheep. Fetal sheep (0.85 gestation) received 30 minutes bilateral carotid artery occlusion followed by 3 days of normothermia (n = 8), 3 days of hypothermia (n = 8), or 5 days of hypothermia (n = 8) started 3 hours after ischemia. Sham controls received sham ischemia followed by normothermia (n = 8). Cerebral ischemia was associated with profound loss of electroencephalography power and spectral edge, with greater and more rapid recovery in both hypothermia groups (P o0.05). Ischemia was associated with severe loss of neurons in the cortex, hippocampus and thalamus (P o 0.05), with a significant improvement in both hypothermia groups. However, the ischemia-3-day hypothermia group showed greater neuronal survival in the cortex and dentate gyrus compared with ischemia-5-day hypothermia (P o 0.05). Ischemia was associated with induction of iba1-positive microglia, which was attenuated in both hypothermia groups (P o 0.05). Extending the duration of delayed therapeutic hypothermia from 3 to 5 days did not improve outcomes after severe ischemia, and was associated with reduced neuronal survival in some regions.

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Section: Introductionmentioning

confidence: 99%

How Long is Too Long for Cerebral Cooling after Ischemia in Fetal Sheep?

Davidson

Wassink

Yuill

et al. 2015

J Cereb Blood Flow Metab

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“…Finally, in the 1990s laboratory studies demonstrated the benefit of mild hypothermia in dogs after cardiac arrest [14]. In the last decade, pivotal randomized clinical trials have provided direct evidence of a benefit of mild hypothermia to improve neurological outcome after cardiac arrest and perinatal asphyxia [1,2,[4][5][6][7].…”

Section: Historical Aspectsmentioning

confidence: 99%

“…Reduction in temperature is achieved by running 10°C water through a coil of tubing wrapped around the infant's scalp for 72 hours [91]. Other studies have showed improvement in short-term computed tomographic changes [92], neurodevelopment outcome at 18 months [5], or combined outcome of severe disability and death [93]. As with other surface cooling methods, some devices are adjusted manually or automatically via a feedback mechanism [93].…”

Section: Cool Caps For Infantsmentioning

confidence: 99%

“…Until the last decade, management of a newborn with HIE had consisted largely of supportive care. In the last 6 years, 3 large, randomized, placebo-controlled trials have shown that TH initiated within 6 h of birth reduces death and disability in these infants [5][6][7].…”

Section: Perinatal Asphyxiamentioning

confidence: 99%

“…Experts favor the following definitions: mild hypothermia (T c 34°C to 35.9°C), moderate hypothermia (T c 32°C to 33.9°C), moderate-deep hypothermia (T c 30°C to 31.9°C), and deep hypothermia (T c <30°C) [3]. Despite the lack of consensus in terminology, previous studies demonstrated that body temperature does not need to be less than 32°C to achieve neuroprotection [1,2,[4][5][6][7]. In fact, induced hypothermia to temperatures below 32°C has been associated with significant side effects, such as refractory cardiac arrhythmias and coagulopathies that can be very difficult to manage [8,9].…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic Hypothermia for Acute Neurological Injuries

2012

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Therapeutic hypothermia (TH) is the intentional reduction of core body temperature to 32°C to 35°C, and is increasingly applied by intensivists for a variety of acute neurological injuries to achieve neuroprotection and reduction of elevated intracranial pressure. TH improves outcomes in comatose patients after a cardiac arrest with a shockable rhythm, but other off-label applications exist and are likely to increase in the future. This comprehensive review summarizes the physiology and cellular mechanism of action of TH, as well as different means of TH induction and maintenance with potential side effects. Indications of TH are critically reviewed by disease entity, as reported in the most recent literature, and evidence-based recommendations are provided.

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Postasphyxial Hypoxic-Ischemic Encephalopathy in Neonates

Shah¹,

Beyene²,

To³

et al. 2006

Arch Pediatr Adolesc Med

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Objectives:To construct and validate a model and derive a simple rule that is usable in any birth location for the prediction of outcome of term infants with severe asphyxia.Design: Retrospective cohort study. Setting: Regional outborn neonatal intensive care unit.Participants: Infants with postintrapartum asphyxial hypoxic-ischemic encephalopathy (n = 375).Main Exposures: Clinical and laboratory predictors available at age 4 hours. Main Outcome Measures:A logistic regression model was developed and internally validated (with random sampling and based on the year of birth) for severe adverse outcome, which was defined as death or severe disability (severe cerebral palsy, severe developmental delay, sensorineural deafness, or cortical blindness singly or in com bination). A simple prediction rule was derived from 3 variables.Results: Complete data were available for 302 (92%) of the 345 infants with known outcomes (204 infants with severe adverse outcome). Six independent predictors of outcomes were identified. Using the 3 most significant predictors (chest compressions, age at onset of respiration, and base deficit), severe adverse outcome rates were 46% (95% confidence interval, 33%-58%) with none of the 3 predictors, 64% (95% confidence interval, 54%-73%) with any 1 predictor, 76% (95% confidence interval, 66%-85%) with any 2 predictors, and 93% (95% confidence interval, 81%-99%) with all of the 3 predictors present. The internal validations revealed a robust model.Conclusions: This predictive model for neonatal hypoxicischemic encephalopathy provides a sliding scale of probabilities that could be used for prognostication and to design eligibility criteria for decision making including neuroprotective therapy.

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Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial

Cited by 1,882 publications

References 28 publications

How Long is Too Long for Cerebral Cooling after Ischemia in Fetal Sheep?

How Long is Too Long for Cerebral Cooling after Ischemia in Fetal Sheep?

Therapeutic Hypothermia for Acute Neurological Injuries

Postasphyxial Hypoxic-Ischemic Encephalopathy in Neonates

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