Cooling for neonatal encephalopathy in 2010 (original) (raw)
Acta Paediatrica, 2009
Although selective or whole body cooling combined with optimal intensive care improves outcomes following neonatal encephalopathy in high-income countries, the safety and efficacy of cooling in low-and middle-income countries is not known. Objective: We performed a systematic review and meta-analysis of all published randomised or quasi-randomised controlled trials of cooling therapy for neonatal encephalopathy in low-and middle-income countries. Results: Seven trials, comprising a total of 567 infants were included in the meta-analysis. Most study infants had mild (15%) or moderate encephalopathy (48%) and did not receive invasive ventilation (88%). Cooling devices included watercirculating cooling caps, frozen gel packs, ice, water bottles, and phase-changing material. No statistically significant reduction in neonatal mortality was seen with cooling (risk ratio: 0.74, 95% confidence intervals: 0.44 to 1.25). Data on other neonatal morbidities and long-term neurological outcomes were insufficient. Cooling therapy was not associated with a statistically significant reduction in neonatal mortality in low-and middle-income countries although the confidence intervals were wide and not incompatible with results seen in highincome countries. The apparent lack of treatment effect may be due to the heterogeneity and poor quality of the included studies, inefficiency of the low technology cooling devices, lack of optimal neonatal intensive care, sedation and ventilatory support, overuse of oxygen, or may be due to the intrinsic difference in the population, for example higher rates of perinatal infection, obstructed labor, intrauterine growth retardation and maternal malnutrition. Evaluation of the safety and efficacy of cooling in adequately powered randomised controlled trials is required before cooling is offered in routine clinical practice in low-and middle-income countries.
PLoS ONE, 2012
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 33-34uC 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.
Clinics in Perinatology, 2008
The entry criteria in the two large published trials, 1-5 the CoolCap trial 2 and National Institute of Child Health and Human Development (NICHD) trial, 3 recruited infants of similar severity (moderate and severe encephalopathy). As such, the percentages of poor outcome in the untreated arm in the two trials were 66% and 62%, respectively. A series of feasibility studies undertaken in New Zealand 5 and the United Kingdom 6 led to the CoolCap trial, which recruited 235 infants. These studies combined selective head cooling (SHC; circulating cold water in a cap fitted around the head) with mild body hypothermia to 34.5 C rectal temperature, using a protocol that was then applied in the CoolCap trial (and, later, the Whole Body Hypothermia for Perinatal Asphyxial Encephalopathy [TOBY] trial). 7 In the United States, the NICHD used total body hypothermia by means of two cooling blankets, reducing infant temperatures to a rectal temperature of 33.5 C in its 2005 trial (n 5 204). 3 Currently, we are awaiting the outcome of 650 randomized infants from three international studies, with the largest being the United Kingdom-led TOBY trial (Primary Investigator: Dennis Azzopardi) 6,7 with 325 infants recruited. Two other trials were stopped prematurely because of lack of equipoise among the participants: the Australian Infant Cooling Evaluation (ICE) trial (n 5 204, Primary Investigator: Sue Jacobs) and the European, induced hypothermia in asphyxiated newborns trial (Neo nEuro Network) (n 5 121, Primary Investigator: George Simbrunner). Many centers have decided to delay introducing hypothermia treatment into their protocols until these
Therapeutic hypothermia in mild neonatal encephalopathy: a national survey of practice in the UK
Archives of Disease in Childhood - Fetal and Neonatal Edition, 2017
Although major cooling trials (and subsequent guidelines) excluded babies with mild encephalopathy, anecdotal evidence suggests that cooling is often offered to these infants. We report a national survey on current cooling practices for babies with mild encephalopathy in the UK. From 74 neonatal units contacted, 68 were cooling centres. We received 54 responses (79%) and included 48 (five excluded due to incomplete data and one found later not to offer cooling). Of these, 36 centres (75%) offered cooling to infants with mild encephalopathy. Although most of the participating units reported targeting 33–34°C core temperature, seven (19%) considered initiating cooling beyond 6 hours of age and 13 (36%) discontinued cooling prior to 72 hours. Babies were ventilated for cooling in two (6%) units and 13 (36%) sedated all cooled babies. Enteral feeding was withheld in 15 (42%) units and reduced below 25% of requirements in eight (22%) units. MRI and neurodevelopmental outcome evaluation w...
BMC Pediatrics, 2008
Background: A hypoxic-ischaemic insult occurring around the time of birth may result in an encephalopathic state characterised by the need for resuscitation at birth, neurological depression, seizures and electroencephalographic abnormalities. There is an increasing risk of death or neurodevelopmental abnormalities with more severe encephalopathy. Current management consists of maintaining physiological parameters within the normal range and treating seizures with anticonvulsants.
Should neonatal encephalopathy now be treated with cooling
The use of selective and systemic induced mild hypothermia for the treatment of neonatal encephalopathy has been the subject of several randomised controlled trials over recent years. The largest of these, the TOBY Study, has recently completed recruitment. This article discusses the current status of hypothermia and how its use might evolve in the near future.
2017
Therapeutic hypothermia is recommended for moderate and severe neonatal encephalopathy, but is being applied to a wider range of neonates than originally envisaged. To examine the clinical use of therapeutic hypothermia, data collected during the first 3 years (2012–2014) of the Baby Cooling Registry of Japan were analysed. Of 485 cooled neonates, 96.5% were ≥36 weeks gestation and 99.4% weighed ≥1,800 g. Severe acidosis (pH < 7 or base deficit ≥16 mmol/L) was present in 68.9%, and 96.7% required resuscitation for >10 min. Stage II/III encephalopathy was evident in 88.3%; hypotonia, seizures and abnormal amplitude-integrated electroencephalogram were observed in the majority of the remainder. In-hospital mortality was 2.7%; 90.7% were discharged home. Apgar scores and severity of acidosis/encephalopathy did not change over time. The time to reach the target temperature was shorter in 2014 than in 2012. The proportion undergoing whole-body cooling rose from 45.4% to 81.6%, whil...
Therapeutic hypothermia for mild neonatal encephalopathy: a systematic review and meta-analysis
Archives of Disease in Childhood - Fetal and Neonatal Edition, 2018
ObjectivesTo examine if therapeutic hypothermia reduces the composite outcome of death, moderate or severe disability at 18 months or more after mild neonatal encephalopathy (NE).Data sourceMEDLINE, Cochrane database, Scopus and ISI Web of Knowledge databases, using ‘hypoxic ischaemic encephalopathy’, ‘newborn’ and ‘hypothermia’, and ‘clinical trials’ as medical subject headings and terms. Manual search of the reference lists of all eligible articles and major review articles and additional data from the corresponding authors of selected articles.Study selectionRandomised and quasirandomised controlled trials comparing therapeutic hypothermia with usual care.Data extractionSafety and efficacy data extracted independently by two reviewers and analysed.ResultsWe included the data on 117 babies with mild NE inadvertently recruited to five cooling trials (two whole-body cooling and three selective head cooling) of moderate and severe NE, in the meta-analysis. Adverse outcomes occurred i...
Early Human Development, 2008
Recent evidence suggests that the current ILCOR guidelines regarding hypothermia for the treatment of neonatal encephalopathy need urgent revision. In 2005 when the current ILCOR guidelines were finalised one large (CoolCap trial, n = 235) and one small RCT (n = 67), in addition to pilot trials, had been published, and demonstrated that therapeutic hypothermia after perinatal asphyxia was safe. The CoolCap trial showed a borderline overall effect on death and disability at 18 months of age, but significant improvement in a large subset of infants with less severe electroencephalographic changes. Based on this and other available evidence, the 2005 ILCOR guidelines supported post-resuscitation hypothermia in paediatric patients after Abbreviations: ILCOR, International Liaison Committee on Resuscitation; aEEG, amplitude integrated EEG. ଝ A Spanish translated version of the summary of this article appears as Appendix in the final online version at