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.

Therapeutic moderate hypothermia in newborns with hypoxic-ischemic encephalopathy is rapidly becoming standard clinical practice. We report here 12 cases of subcutaneous fat necrosis among 1239 cases registered with a national registry of newborns treated with moderate whole-body hypothermia. All the infants suffered from perinatal asphyxia and hypoxic-ischemic encephalopathy. Moderate-to-severe hypercalcemia was identified in 8 of 10 infants with blood calcium measurements. In all cases the skin lesions appeared after completion of the cooling treatment. Our data suggest that prolonged moderate hypothermia is an actual risk factor for subcutaneous fat necrosis. Because the lesions often develop several days after birth, physicians need to be aware of this condition as a possible complication in infants treated with moderate hypothermia after asphyxia. Blood calcium levels need to be monitored in affected infants.

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There was limited evidence available to draw any conclusions about the efficacy of PRN versus ATC analgesic administration for the management of postoperative pain in children.