Implementation and Conduct of Therapeutic Hypothermia for Perinatal Asphyxial Encephalopathy in the UK – Analysis of National Data

Abstract

Background Delay in implementing new treatments into clinical practice results in considerable health and economic opportunity costs. Data from the UK TOBY Cooling Register provides the opportunity to examine how one new effective therapy for newborn infants suspected of suffering asphyxial encephalopathy – therapeutic hypothermia- was implemented in the UK. Methodology/Principal Findings We analysed returned data forms from inception of the Register in December 2006 to the end of July 2011. Data forms were received for 1384 (67%) of the 2069 infants registered. The monthly rate of notifications increased from median {IQR} 18 {15–31} to 33 {30–39} after the announcement of the results of the recent TOBY trial, and to 50 {36–55} after their publication. This rate further increased to 70 {64–83} following official endorsement of the therapy, and is now close to the expected numbers of eligible infants. Cooling was started at 3.3 {1.5–5.5} hours after birth and the time taken to achieve the target 33–34°C rectal temperature was 1 {0–3} hours. The rectal temperature was in the target range in 83% of measurements. From 2006 to 2011 there was evidence of extension of treatment to slightly less severely affected infants. 278 of 1362 (20%) infants died at 2.9 {1.4–4.1} days of age. The rates of death fell slightly over the period of the Register and, at two years of age cerebral palsy was diagnosed in 22% of infants; half of these were spastic bilateral. Factors independently associated with adverse outcome were clinical seizures prior to cooling (p<0.001) and severely abnormal amplitude integrated EEG (p<0.001). Conclusions/Significance Therapeutic hypothermia was implemented appropriately within the UK, with significant benefit to patients and the health economy. This may be due in part to participation by neonatal units in clinical trials, the establishment of the national Register, and its endorsement by advisory bodies.

High-Dose Erythropoietin and Hypothermia for Hypoxic-Ischemic Encephalopathy: A Phase II Trial

“…18,19 However, these trials used alternative dosing regimens and did not include the use of hypothermia. In countries where therapeutic hypothermia has become a standard of care, [20][21][22] novel neuroprotective agents should be evaluated together with hypothermia. 23 Epo is commercially available, easy to administer, and has a good safety profile in newborns.…”

Therapeutic Hypothermia in Asphyxiated Neonates with Hypoxic-ischemic Encephalopathy: A single-center Experience from its First Application in Saudi Arabia

“…Several factors may delay initiation of treatment as late recognition of eligible patients and/ or, need for transfer. Data analysis between December 2006 and July 2011on the implementation-conduction of therapeutic hypothermia in the United Kingdom showed that 2.2 % of the neonates suffering asphyxial encephalopathy had cooling commenced more than 12 hours after birth [12] . Furthermore, in a retrospective review of neonates referred to a regional tertiary center in Canada, 44% of the patients had cooling initiated after 6 hours of age [24] .…”

“…In Europe, therapeutic hypothermia is already achieved in several countries as well. This because the participation of some medical centers in clinical trials such as: TOBY; in the United Kingtom, neo.nEURO; in Germany and in several European countries , while in others its use is expanding rapidly [11][12][13][14][15] .…”

Recent Information on the Pathogenesis and Treatment of Hypoxic-Ischemic Brain Lesions in Newborns

“…Ранее метаанализ управля-емой гипотермии в первые 6 ч жизни среди 1440 ново-рожденных (13 исследований) показал значительное снижение риска смертности, умеренных и тяжелых нерв-но-психических расстройств, развития церебрального паралича, тяжелых зрительных и когнитивных нарушений на сроках до 12 мес [82]. Метод внедрен в клиническую практику ряда стран, в частности Великобритании [83], где уже подведены первые экономические результаты, согласно которым внедрение признано эффективным, исходы ГИП в целом улучшаются примерно на 15% [84]. Подтверждений эффективности гипотермии при перина-тальных поражениях другого генеза, например инфекци-онного, в экспериментах пока не получено [85].…”