Evidence that therapeutic hypothermia should be continued for 72 hours

Davidson, John B.; Battin, Malcolm; Gunn, Alistair J.

doi:10.1136/archdischild-2018-315844

Cited by 6 publications

(2 citation statements)

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“…Rapid rewarming is associated with caspase cleavage and histological brain injury . In contrast, slower rewarming over 24 hours was associated with improved electrographic EEG power in a sheep model . Of note, the preclinical studies had different durations of TH, making it difficult to disentangle the effect of longer duration of neuroprotective therapy from the specific effects of the rate of temperature elevation during rewarming …”

Section: Discussionmentioning

confidence: 99%

Association Between Increased Seizures During Rewarming After Hypothermia for Neonatal Hypoxic Ischemic Encephalopathy and Abnormal Neurodevelopmental Outcomes at 2-Year Follow-up

et al. 2021

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IMPORTANCECompared with normothermia, hypothermia has been shown to reduce death or disability in neonatal hypoxic ischemic encephalopathy but data on seizures during rewarming and associated outcomes are scarce. OBJECTIVE To determine whether electrographic seizures are more likely to occur during rewarming compared with the preceding period and whether they are associated with abnormal outcomes in asphyxiated neonates receiving hypothermia therapy. DESIGN, SETTING, AND PARTICIPANTSThis prespecified nested cohort study of infants enrolled in the Optimizing Cooling (OC) multicenter Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network trial from December 2011 to December 2013 with 2 years' follow-up randomized infants to either 72 hours of cooling (group A) or 120 hours (group B). The main trial included 364 infants. Of these, 194 were screened, 10 declined consent, and 120 met all predefined inclusion criteria. A total of 112 (90%) had complete data for death or disability. Data were analyzed from January 2018 to January 2020.INTERVENTIONS Serial amplitude electroencephalography recordings were compared in the 12 hours prior and 12 hours during rewarming for evidence of electrographic seizure activity by 2 central amplitude-integrated electroencephalography readers blinded to treatment arm and rewarming epoch. Odds ratios and 95% CIs were evaluated following adjustment for center, prior seizures, depth of cooling, and encephalopathy severity. MAIN OUTCOMES AND MEASURESThe primary outcome was the occurrence of electrographic seizures during rewarming initiated at 72 or 120 hours compared with the preceding 12-hour epoch. Secondary outcomes included death or moderate or severe disability at age 18 to 22 months. The hypothesis was that seizures during rewarming were associated with higher odds of abnormal neurodevelopmental outcomes.RESULTS A total of 120 newborns (70 male [58%]) were enrolled (66 in group A and 54 in group B). The mean (SD) gestational age was 39 (1) weeks. There was excellent interrater agreement (κ, 0.99) in detection of seizures. More infants had electrographic seizures during the rewarming epoch compared with the preceding epoch (group A, 27% vs 14%; P = .001; group B, 21% vs 10%; P = .03). Adjusted odd ratios (95% CIs) for seizure frequency during rewarming were 2.7 (1.0-7.5) for group A and 3.2 (0.9-11.6) for group B. The composite death or moderate to severe disability outcome at 2 years was significantly higher in infants with electrographic seizures during rewarming (relative risk [95% CI], 1.7 [1.25-2.37]) after adjusting for baseline clinical encephalopathy and seizures as well as center.CONCLUSIONS AND RELEVANCE Findings that higher odds of electrographic seizures during rewarming are associated with death or disability at 2 years highlight the necessity of electroencephalography monitoring during rewarming in infants at risk.

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Section: Discussionmentioning

confidence: 99%

Association Between Increased Seizures During Rewarming After Hypothermia for Neonatal Hypoxic Ischemic Encephalopathy and Abnormal Neurodevelopmental Outcomes at 2-Year Follow-up

et al. 2021

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“…Treating all such cases would increase the numbers of infants being separated from their parents, receiving invasive treatments such as central lines, invasive respiratory support, sedation and delayed oral feeding. There is no established prognostic method by which clinicians can determine if it is possible to stop cooling before 72 hours [63], and so hypothermia should be continued for 3 days. Supporting this concept, in one case series of 10 infants with mild HIE in whom hypothermia was stopped early because of rapid clinical improvement, neural injury on magnetic resonance imaging was seen in half and disability at 2 years of age in 2 infants [64].…”

Section: Other Populations: Should We Cool Infants With Mild Hie?mentioning

confidence: 99%

Therapeutic Hypothermia in Neonatal Hypoxic-Ischemic Encephalopathy

Wassink

Davidson

Dhillon

et al. 2019

Curr Neurol Neurosci Rep

108

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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.

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