Hypothermia for Neonatal Hypoxic Ischemic Encephalopathy

Obstetrical & Gynecological Survey, 2008

To systematically review the effectiveness, as determined by survival without moderate to severe neurodevelopmental disability in infancy and childhood, and the safety of hypothermia vs normothermia in neonates with postintrapartum hypoxic-ischemic encephalopathy and to perform subgroup analyses based on severity of encephalopathy (moderate or severe), type of hypothermia (systemic or selective head cooling), and degree of hypothermia (moderate [Յ32.0-33.5°C] or mild [Ն33.6°C]). Data Sources: MEDLINE, EMBASE, CINAHL (Cumulative Index for Nursing and Allied Health Literature), the Cochrane Library, abstracts of annual meetings of the Pediatric Academic Societies, and bibliographies of identified articles. Study Selection: Randomized and quasi-randomized controlled trials without language restriction were assessed by 2 reviewers independently and discrepancies were resolved by involving a third reviewer. Quality of the trials was assessed on the basis of concealment of allocation, method of randomization, masking of outcome assessment, and completeness of follow-up. Intervention: Systemic or selective head hypothermia compared with normothermia. Main Outcome Measure: Death or moderate to severe neurodevelopmental disability. Results: Eight studies of acceptable quality were included. The combined outcome of death or neurodevelopmental disability in childhood was reduced in infants receiving hypothermia compared with control infants (4 studies including 497 infants; relative risk, 0.76, 95% confidence interval, 0.65-0.88; number needed to treat, 6; 95% confidence interval, 4-14), as were death and moderate to severe neurodevelopmental disability when analyzed separately. Cardiac arrhythmias and thrombocytopenia were more common with hypothermia; however, they were clinically benign. Conclusions: In neonates with postintrapartum asphyxial hypoxic-ischemic encephalopathy, hypothermia is effective in reducing death and moderate to severe neurodevelopmental disability either in combination or separately and is a safe intervention.

Archives of Pediatrics & Adolescent Medicine, 2007

To systematically review the effectiveness, as determined by survival without moderate to severe neurodevelopmental disability in infancy and childhood, and the safety of hypothermia vs normothermia in neonates with postintrapartum hypoxic-ischemic encephalopathy and to perform subgroup analyses based on severity of encephalopathy (moderate or severe), type of hypothermia (systemic or selective head cooling), and degree of hypothermia (moderate [Յ32.0-33.5°C] or mild [Ն33.6°C]). Data Sources: MEDLINE, EMBASE, CINAHL (Cumulative Index for Nursing and Allied Health Literature), the Cochrane Library, abstracts of annual meetings of the Pediatric Academic Societies, and bibliographies of identified articles. Study Selection: Randomized and quasi-randomized controlled trials without language restriction were assessed by 2 reviewers independently and discrepancies were resolved by involving a third reviewer. Quality of the trials was assessed on the basis of concealment of allocation, method of randomization, masking of outcome assessment, and completeness of follow-up. Intervention: Systemic or selective head hypothermia compared with normothermia. Main Outcome Measure: Death or moderate to severe neurodevelopmental disability. Results: Eight studies of acceptable quality were included. The combined outcome of death or neurodevelopmental disability in childhood was reduced in infants receiving hypothermia compared with control infants (4 studies including 497 infants; relative risk, 0.76, 95% confidence interval, 0.65-0.88; number needed to treat, 6; 95% confidence interval, 4-14), as were death and moderate to severe neurodevelopmental disability when analyzed separately. Cardiac arrhythmias and thrombocytopenia were more common with hypothermia; however, they were clinically benign. Conclusions: In neonates with postintrapartum asphyxial hypoxic-ischemic encephalopathy, hypothermia is effective in reducing death and moderate to severe neurodevelopmental disability either in combination or separately and is a safe intervention.

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.

Journal of Perinatology, 2019

Objective To compare the characteristics and outcomes of neonates with mild hypoxic-ischemic encephalopathy (HIE) who received hypothermia versus standard care. Study design We conducted a retrospective cohort study of neonates ≥35 weeks' gestation and ≥1800 g admitted with a diagnosis of Sarnat stage 1 encephalopathy. We evaluated length of hospital stay, duration of ventilation, evidence of brain injury on MRI, and neonatal morbidities. Results Of 1089 eligible neonates, 393 (36%) received hypothermia and 595 (55%) had neuroimaging. The hypothermia group was more likely to be outborn, born via C-section, had lower Apgar scores, and required extensive resuscitation. They had longer durations of stay (9 vs. 6 days, P < 0.001), respiratory support (3 vs. 2 days, P < 0.001), but lower odds of brain injury on MRI (adjusted odds ratio 0.33, 95% CI: 0.22-0.52) compared with standard care group. Conclusion Despite prolongation of hospital stay, hypothermia may be potentially beneficial in neonates with mild HIE; however, selection bias cannot be ruled out.

Pediatrics &amp; Neonatology, 2017

Therapeutic hypothermia (TH) is a recommended regimen for newborn infants who are at or near term with evolving moderate-to-severe hypoxic ischemic encephalopathy (HIE). The Task Force of the Taiwan Child Neurology Society and the Taiwan Society of Neonatology held a joint meeting in 2015 to establish recommendations for using TH on newborn patients with HIE. Based on current evidence and experts' experiences, this review article summarizes the key points and recommendations regarding TH for newborns with HIE, including: (1) selection criteria for TH, (2) choices of method and equipment for TH, (3) TH before and during transport, (4) methods for temperature maintenance, monitoring, and rewarming, (5) systemic care of patients during TH, including the care of respiratory and cardiovascular systems, management of fluids, electrolytes, and nutrition, as well as sedation and drug metabolism, (6) monitoring and management of seizures, (7) neuroimaging, prognostic factors, and outcomes, and (8) adjuvant therapy for TH.

Pediatrics, 2008

Current Neurology and Neuroscience Reports, 2019

Purpose of review-therapeutic hypothermia reduces death or disability in term and near-term infants with moderate-severe hypoxic-ischemic encephalopathy. Nevertheless, many infants still survive with disability, despite hypothermia, supporting further research into ways to further improve neurologic outcomes. Recent findings-recent clinical and experimental studies have refined our understanding of the key parameters for hypothermic neuroprotection, including timing of initiation, depth, and duration of hypothermia, and subsequent rewarming rate. However, important knowledge gaps remain. There is encouraging clinical evidence from a small phase II trial that combined treatment of hypothermia with recombinant erythropoietin further reduces risk of disability but definitive studies are still needed. Summary-In conclusion, recent studies suggest that current protocols for therapeutic hypothermia are nearoptimal, and that the key to better neurodevelopmental outcomes is earlier diagnosis and initiation of hypothermia after birth. Further research is essential to find and evaluate ways to further improve outcomes after hypoxic-ischemic encephalopathy, including add-on therapies for therapeutic hypothermia and preventing pyrexia during labor and delivery.

JAMA, 2017

Hypothermia initiated at less than 6 hours after birth reduces death or disability for infants with hypoxic-ischemic encephalopathy at 36 weeks&#39; or later gestation. To our knowledge, hypothermia trials have not been performed in infants presenting after 6 hours. To estimate the probability that hypothermia initiated at 6 to 24 hours after birth reduces the risk of death or disability at 18 months among infants with hypoxic-ischemic encephalopathy. A randomized clinical trial was conducted between April 2008 and June 2016 among infants at 36 weeks&#39; or later gestation with moderate or severe hypoxic-ischemic encephalopathy enrolled at 6 to 24 hours after birth. Twenty-one US Neonatal Research Network centers participated. Bayesian analyses were prespecified given the anticipated limited sample size. Targeted esophageal temperature was used in 168 infants. Eighty-three hypothermic infants were maintained at 33.5°C (acceptable range, 33°C-34°C) for 96 hours and then rewarmed. Ei...

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.

2011

To determine the effectiveness and safety of moderate whole-body hypothermia in newborns with hypoxic-ischemic encephalopathy born in hospitals with and without newborn intensive care facilities or complicated hypothermia equipment.