Year: 2018
Type: article
Abstract: Commentary on: Laptook AR, Shankaran S, Tyson JE, Munoz B, Bell EF, Goldberg RN, et al. Effect of therapeutic hypothermia initiated after 6 hours of age on death or disability among newborns with hypoxic-ischemic encephalopathy: a randomized clinical trial. JAMA 2017; 318:1550–60. PMID 29067428. Hypoxic-ischaemic encephalopathy (HIE), also known as neonatal encephalopathy, affects an estimated 1–3 term infants per 1000 live births and leads to significant long-term morbidity and mortality 1. Several clinical trials evaluating the use of therapeutic hypothermia (TH), cooling the core body temperature to 33–34°C for 72 hours, initiated within six hours of birth, have demonstrated benefit with decreased moderate-severe disability or death at 18–22 months 2. As such, TH for infants with HIE has become standard of care. While animal studies have demonstrated superior treatment effect with early cooling initiated prior to six hours of age 3, not all eligible infants undergo initiation of TH within this ideal timeframe. This randomised clinical trial by Laptook et al. 4 enroled infants who met clinical or laboratory criteria for TH, but who were between six hours and 24 hours of age at the time of randomisation. Infants underwent whole-body cooling to a goal core temperature of 33.5°C (range 33–34°C) for 96 hours. This longer cooling time, compared to the standard 72 hours, was chosen due to previous data suggesting that longer hypothermia was necessary for neuroprotection, although this has been recently refuted 5. The results of this study suggest that the benefit of beginning hypothermia more than six hours of age is much less than starting it earlier, which is supported by preclinical data. However, despite most of the patients being more than 12 hours of age at randomisation, there was still a small benefit to TH, indicated by Bayesian analysis, despite an increased seizure burden in the TH group at randomisation. Combined with the lack of increased serious in-hospital adverse effects in the treatment group (no difference in hypotension, coagulopathy or seizures, although possible increase in hypoglycaemia in TH group), and the significant risk for moderate-severe neurodevelopmental disability after HIE, the small potential benefit purported by this trial should prompt NICUs to consider initiation of TH beyond six hours of age. It is important to note that reasons for lack of initiation of early TH are many and while not specifically stated in this population, may include prolonged transport distance from referring hospital to a tertiary care centre capable of cooling and under-recognition of clinical encephalopathy after birth, among others 6. The difficulty in translating preclinical pharmacologic interventions for neonatal ischaemia has prompted a discussion to expand the inclusion criteria for hypothermia after HIE. Among these groups are infants initiated beyond six hours of life, mild encephalopathy, preemies and neonatal stroke 7. While others have evaluated non-standard TH 7, this is the only randomised clinical trial to date to evaluate the effectiveness of this practice. While trials such as that reviewed here may be difficult to design and fund, it is certainly the better course of action to let randomly controlled clinical trials guide clinical care than to practice medicine by anecdote or trial and error. Much hope remains though that new therapeutic options to augment TH are on the horizon 8. Hence, the concerted efforts of researchers and funding agencies to discover novel strategies to treat acquired neonatal brain injury must continue in earnest. https://ebneo.org/2018/04/does-late-therapeutic-hypothermia-reduce-risk-of-death-or-disability/ Supported by the National Institutes of Health 5T32HD007186-37 (SLB) and 1K08NS097586 (RMD). None.
Source: Acta Paediatrica
DOI: 10.1111/apa.14334
Authors: Stephanie L. Bourque, Robert M. Dietz
Institution: University of Colorado Anschutz
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2802094616