Rise and Fall of Therapeutic Hypothermia in Low-Resource Settings: Lessons from the HELIX Trial

Abstract

In the past decade, therapeutic hypothermia using a variety of low-cost devices has been widely implemented in India and other low-and middle-income countries (LMIC) without adequate evidence of either safety or efficacy. The recently reported data from the world’s largest cooling trial (HELIX - hypothermia for encephalopathy in low- and middle-income countries) in LMIC provides definitive evidence of harm of cooling therapy with increase in mortality (number to harm 9) and lack of neuroprotection. Although the HELIX participating centers were highly selected tertiary neonatal intensive care units in South Asia with facilities for invasive ventilation, cardiovascular support, and 3 Tesla magnetic resonance imaging (MRI), and the trial used state-of-the-art automated servo-controlled cooling devices, a therapy that is harmful under such optimal conditions cannot be safe in low-resource settings that cannot even afford servo-controlled cooling devices.The HELIX trial has set a new benchmark for conducting high quality randomized controlled trials in terms of research governance, consent, ethics, follow-up rates, and involvement of parents. The standard care for neonatal encephalopathy in LMIC should remain normothermia, with close attention to prevention of hyperthermia. There is no role for therapeutic hypothermia in LMIC as the efficacy of hypothermia is dependent on the population, and not merely on the level of neonatal intensive care facilities. Future research should explore timings and origins of brain injury and prevention of brain injury in LMIC, with a strong emphasis on academic research capacity building and patient and public engagement.

Pediatric Hypothermia: An Ambiguous Issue

“…below), one may wonder whether neonatology will remain virtually the sole domain of therapeutic hypothermia. This notion has gained further support from a brand-new study suggesting that hypothermic treatment may even do more harm than good, at least under circumstances such as those prevailing in low- and middle-income countries [ 56 , 57 ]. In any case, additional or alternative therapies are currently being sought that modulate the “tertiary” phase of hypoxic–ischemic brain injury so as to promote regenerative (rather than scarring) processes in the damaged neonatal brain [ 58 , 59 , 60 ].…”

Therapeutic hypothermia for neonatal hypoxic ischaemic encephalopathy should not be discontinued in low- and middle-income countries

“…The HELIX study group subsequently wrote a commentary in the Indian Journal of Pediatrics stating that it is time to stop offering TH for neonatal encephalopathy in LMICS, owing to the lack of benefit and increased mortality. [4] These authors argue that the body of research supporting the use of TH was performed in high-income countries (HICs) and that the HELIX study results conclusively show that it is of no benefit in LMICs.…”

Rise and Fall of Therapeutic Hypothermia in Low-Resource Settings: Lessons from the HELIX Trial: Correspondence

“…To the Editor: The review article entitled "Rise and Fall of Therapeutic Hypothermia in Low-Resource Settings: Lessons from the HELIX Trial" [1] is well taken. In the article the key studies upon which Krishnan et al base their opinion are all in press, and are not yet open for reference.…”