Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy: a nested substudy of a randomised controlled trial (original) (raw)
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Moderate hypothermia in neonatal encephalopathy: Efficacy outcomes
Pediatric Neurology, 2005
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°C) vs normothermia (37°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.
Archives of Disease in Childhood - Fetal and Neonatal Edition, 2018
ObjectiveTo examine the effect of therapeutic hypothermia on MR biomarkers and neurodevelopmental outcomes in babies with mild hypoxic-ischaemic encephalopathy (HIE).DesignNon-randomised cohort study.SettingEight tertiary neonatal units in the UK and the USA.Patients47 babies with mild HIE on NICHD neurological examination performed within 6 hours after birth.InterventionsWhole-body cooling for 72 hours (n=32) or usual care (n=15; of these 5 were cooled for <12 hours).Main outcome measuresMRI and MR spectroscopy (MRS) within 2 weeks after birth, and a neurodevelopmental outcome assessment at 2 years.ResultsThe baseline characteristics in both groups were similar except for lower 10 min Apgar scores (p=0.02) in the cooled babies. Despite this, the mean (SD) thalamic NAA/Cr (1.4 (0.1) vs 1.6 (0.2); p<0.001) and NAA/Cho (0.67 (0.08) vs 0.89 (0.11); p<0.001) ratios from MRS were significantly higher in the cooled group. Cooled babies had lower white matter injury scores than no...
Archives of Disease in Childhood-fetal and Neonatal Edition, 2019
Objective To evaluate the neuroprotective effect of therapeutic hypothermia (TH) induced by phase changing material (PCM) on MRI biomarkers in infants with hypoxic-ischaemic encephalopathy (HIE) in a lowresource setting. Design Open-label randomised controlled trial. Setting One neonatal intensive care unit in a tertiary care centre in India. Patients 50 term/near-term infants admitted within 5 hours after birth with predefined physiological criteria and signs of moderate/severe HIE. Interventions Standard care (n=25) or standard care plus 72 hours of hypothermia (33.5°C±0.5°C, n=25) induced by PCM. Main outcome measures Primary outcome was fractional anisotropy (FA) in the posterior limb of the internal capsule (PLIC) on neonatal diffusion tensor imaging analysed according to intention to treat. Results Primary outcome was available for 22 infants (44%, 11 in each group). Diffusion tensor imaging showed significantly higher FA in the cooled than the non-cooled infants in left PLIC and several white matter tracts. After adjusting for sex, birth weight and gestational age, the mean difference in PLIC FA between groups was 0.026 (95% CI 0.004 to 0.048, p=0.023). Conventional MRI was available for 46 infants and demonstrated significantly less moderate/severe abnormalities in the cooled (n=2, 9%) than in the noncooled (n=10, 43%) infants. There was no difference in adverse events between groups. Conclusions This study confirmed that TH induced by PCM reduced brain injury detected on MRI in infants with moderate HIE in a neonatal intensive care unit in India. Future research should focus on optimal supportive treatment during hypothermia rather than looking at efficacy of TH in low-resource settings. Trial registration number CTRI/2013/05/003693.
Safety study of hypothermia for treatment of hypoxic-ischemic brain damage in term neonates
KEY WORDS hypothermia; hypoxic-ischemic brain damage; newborn ABSTRACT AIM: To investigate safety and efficacy of mild hypothermia by selective head cooling in term neonates with hypoxic-ischemic brain damage (HIBD). METHODS: Fifty term neonates with Apgar scores ≤5 at 5 min, and/or evidence of encephalopathy within 6 h after birth, were randomized to either noncooling, normothermia (NORM, n=27), or mild hypothermia group (HYPO, n=23), in which head cooling was induced by circulating water for 72 h. Neurodevelopment outcome was assessed at 6 month. RESULTS: The heart rates of the HYPO at 24, 48, and 72 h after treatment dropped to 96±12, 85±9, and 96±16, whereas that of the NORM to 123±10, 125±13 and 121±19, respectively (P<0.05). There was no difference regarding ejection fraction (EF), stroke volume (SV) and cardiac output CO) between the two groups [(0.61±0.04) vs (0.58±0.06), (2.3±0.5) vs (2.4±0.4) mL/kg, (256±54) vs (277±42) mL⋅kg -1 ⋅min -1 , respectively]. D-dimmer and β 2 MG were elevated in both groups. The neuron specific enolase (NSE) level of CSF was (26.2±10.8) mg/L in the HYPO and (34.6±17.1) mg/L in the NORM (P<0.05). Glutamic acid (GA) was lower in the HYPO [(2.4±0.8) vs (2.9±1.1) mmol/L, P<0.05]. The neurodevelopment outcome of the patients at 6 mo showed that 18 of 23 patients in the HYPO (78.3 %) were considered to have a normal developmental quotient (DQ) compared with 19 of 27 (70.4 %) in the NORM. CONCLUSION:
Use of therapeutic hypothermia in neonates with hypoxic ischemic encephalopathy: a literature review (Atena Editora), 2023
Objectives: Expose basic concepts of the existing literature on induced hypothermia in newborns who evolved with hypoxic-ischemic encephalopathy. Methods: A narrative literature review was carried out based on 22 articles, from February to April 2023, prioritizing articles published in the last 5 years. The articles were taken from the Lilacs, Pubmed, Scielo, Embase and Scopus databases. Results: Hypoxic-ischemic encephalopathy (HIE) consists of a series of cellular and molecular alterations resulting from a severe anoxic brain injury that occurred in the neonatal period. Current research reveals that even the condition in its mild form is not benign. Therapeutic Hypothermia (TH) is the most effective technique indicated for the management of newborns (NB) admitted to the Neonatal Intensive Care Unit (NICU) who present neuropathies secondary to asphyxia, accompanied by clinical signs of Hypoxic-Ischemic Encephalopathy. The therapy consists of exposing the newborn at term or late preterm to a temperature of 33.5º C from the first 6 hours of life and, over 72 hours of cooling, gradually rewarming the patient. Total body hypothermia, when compared with the control group to identify the outcome of neurological abnormalities, contributed to a 17% reduction. Concomitantly with these data, found at 18 months of age, there was also a 21% reduction in the risk of cerebral palsy and a 22% reduction in moderate or severe disability. Conclusion: It has been shown that induced hypothermia can be effective in reducing mortality and neurodevelopmental failures in these newborns.
Whole-Body Hypothermia for Neonates With Hypoxic-Ischemic Encephalopathy
… England Journal of …, 2005
Hypothermia is protective against brain injury after asphyxiation in animal models. However, the safety and effectiveness of hypothermia in term infants with encephalopathy is uncertain. methods We conducted a randomized trial of hypothermia in infants with a gestational age of at least 36 weeks who were admitted to the hospital at or before six hours of age with either severe acidosis or perinatal complications and resuscitation at birth and who had moderate or severe encephalopathy. Infants were randomly assigned to usual care (control group) or whole-body cooling to an esophageal temperature of 33.5°C for 72 hours, followed by slow rewarming (hypothermia group). Neurodevelopmental outcome was assessed at 18 to 22 months of age. The primary outcome was a combined end point of death or moderate or severe disability. results Of 239 eligible infants, 102 were assigned to the hypothermia group and 106 to the control group. Adverse events were similar in the two groups during the 72 hours of cooling. Primary outcome data were available for 205 infants. Death or moderate or severe disability occurred in 45 of 102 infants (44 percent) in the hypothermia group and 64 of 103 infants (62 percent) in the control group (risk ratio, 0.72; 95 percent confidence interval, 0.54 to 0.95; P=0.01). Twenty-four infants (24 percent) in the hypothermia group and 38 (37 percent) in the control group died (risk ratio, 0.68; 95 percent confidence interval, 0.44 to 1.05; P=0.08). There was no increase in major disability among survivors; the rate of cerebral palsy was 15 of 77 (19 percent) in the hypothermia group as compared with 19 of 64 (30 percent) in the control group (risk ratio, 0.68; 95 percent confidence interval, 0.38 to 1.22; P=0.20). conclusions Whole-body hypothermia reduces the risk of death or disability in infants with moderate or severe hypoxic-ischemic encephalopathy.
BMJ, 2010
of physiology, 4 Henry Halliday, professor of perinatal medicine, 5,6 Edmund Juszczak, head of trials , 3 Malcolm Levene, professor of paediatrics and child health, 7,8 Brenda Strohm, trial coordinator, 3 Marianne Thoresen, professor of neonatal neuroscience, 9 Andrew Whitelaw, professor of neonatal medicine, 9 Denis Azzopardi, clinical reader in neonatal medicine 1,2 ABSTRACT Objective To determine whether moderate hypothermia after hypoxic-ischaemic encephalopathy in neonates improves survival and neurological outcome at 18 months of age. Design A meta-analysis was performed using a fixed effect model. Risk ratios, risk difference, and number needed to treat, plus 95% confidence intervals, were measured. Data sources Studies were identified from the Cochrane central register of controlled trials, the Oxford database of perinatal trials, PubMed, previous reviews, and abstracts. Review methods Reports that compared whole body cooling or selective head cooling with normal care in neonates with hypoxic-ischaemic encephalopathy and that included data on death or disability and on specific neurological outcomes of interest to patients and clinicians were selected. Results We found three trials, encompassing 767 infants, that included information on death and major neurodevelopmental disability after at least 18 months' follow-up. We also identified seven other trials with mortality information but no appropriate neurodevelopmental data. Therapeutic hypothermia significantly reduced the combined rate of death and severe disability in the three trials with 18 month outcomes (risk ratio 0.81, 95% confidence interval 0.71 to 0.93, P=0.002; risk difference −0.11, 95% CI −0.18 to −0.04), with a number needed to treat of nine (95% CI 5 to 25). Hypothermia increased survival with normal neurological function (risk ratio 1.53, 95% CI 1.22 to 1.93, P<0.001; risk difference 0.12, 95% CI 0.06 to 0.18), with a number needed to treat of eight (95% CI 5 to 17), and in survivors reduced the rates of severe disability (P=0.006), cerebral palsy (P=0.004), and mental and the psychomotor developmental index of less than 70 (P=0.01 and P=0.02, respectively). No significant interaction between severity of encephalopathy and treatment effect was detected. Mortality was significantly reduced when we assessed all 10 trials (1320 infants; relative risk 0.78, 95% CI 0.66 to 0.93, P=0.005; risk difference −0.07, 95% CI −0.12 to −0.02), with a number needed to treat of 14 (95% CI 8 to 47). Conclusions In infants with hypoxic-ischaemic encephalopathy, moderate hypothermia is associated with a consistent reduction in death and neurological impairment at 18 months.