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Whole-body cooling in neonatal encephalopathy using phase changing material
  1. Sudhin Thayyil1,
  2. Seetha Shankaran2,
  3. Angie Wade3,
  4. Frances M Cowan4,
  5. Manju Ayer5,
  6. Karayapally Satheesan5,
  7. Ceebi Sreejith5,
  8. Hannah Eyles6,
  9. Andrew M Taylor7,
  10. Alan Bainbridge6,
  11. Ernest B Cady6,
  12. Nicola J Robertson1,
  13. David Price5,
  14. Guhan Balraj5
  1. 1Academic Neonatology, Institute for Women's Health, University College London, London, UK
  2. 2Department of Neonatal-Perinatal Medicine, Wayne State University School of Medicine, Children's Hospital of Michigan and Hutzel Women's Hospital, Detroit, USA
  3. 3Department of Paediatric Epidemiology and Biostatistics, Institute of Child Health, University College London, London, UK
  4. 4Department of Paediatrics, Imperial College, London, UK
  5. 5Department of Neonatal Medicine, Institute of Maternal and Child Health, Calicut Medical College, Kerala, India
  6. 6Department of Medical Physics and Bioengineering, University College London Hospitals NHS Foundation Trust, London, UK
  7. 7Centre for Cardiovascular Imaging, Institute of Cardiovascular Science, University College London, London, UK
  1. Correspondence to Dr Sudhin Thayyil, Academic Neonatology, Institute for Women's Health, University College London, 74 Huntley Street, London WC1E 6AU, UK; s.thayyil{at}

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Whole body cooling improves outcomes after neonatal encephalopathy (NE) in high-income countries1; however, effective low technology cooling devices suitable for use in low and middle-income countries (LMIC) is lacking.2 Although cooling using ice is effective in tertiary neonatal units, dangerous temperature fluctuations may occur if continuous temperature monitoring and nursing support is not available.2 Phase changing materials (PCM) are made of salt hydride, fatty acid, and esters or paraffin, and melt at a set point; in the process they can store or release large amounts of energy (figure 1). We examined the feasibility of administering whole body cooling using PCM.

Figure 1

Whole-body cooling by phase changing material. (A) Heat exchange in phase changing material (PCM). When in contact with a warm object, PCM (melting point 32°C) absorbs heat and slowly melts, thus reducing the temperature of the object. (B) Structure of the cooling mattress made of PCM. 

We randomly (Minimisation software; Simin, UCL) allocated 33 infants with NE (Thompsons encephalopathy score >5) aged <6 h, admitted to the neonatal unit at Calicut Medical College, Kerala, India, to whole-body cooling by a PCM mattress, or to standard care, after informed parent consent. The institutional review boards at Calicut Medical College and the ethics committee at University College London approved the study.

Mean (SD) birth weight and gestation of the standard-care (n=16) and the cooled infants (n=17) were 2890 (467) g; 38.9 (0.8) weeks and 2977 (402) g; 38.0 (1.2) weeks, respectively. Mean (SD) rectal temperature at randomisation was 35.2 (1.2)°C in the cooled infants and 35.2 (1.3) °C in the standard-care infants. The rectal temperature was 33.5 (0.3) °C during cooling and 36.4 (0.5) °C for standard-care (mean difference −2.8°C (95% CI −2.9°C to −2.7°C, p<0.001)). SD of the hourly measurements was on average 0·52°C in the cooled group and 0·54°C in the standard-care group (figure 2).

Figure 2

Temperature profile. Individual and mean rectal temperatures in the standard-care (red) and cooled (blue) infants, and the ambient temperature (black; ±2SD) until 80 h after randomisation.

The median (IQR) cooling induction time was 30 (10–90) minutes and rewarming took 10.3 (6.5–15.4) hours at a rate of 0.24 (0.2–0.4)°C/hour. The mean heart rate was significantly lower during cooling (123 vs 113) beats per minute; diff −10 (95% CI −15 to −5 beats per minute, p<0.001); however, respiratory rate, blood pressure, oxygen saturation, serum electrolytes, glucose, platelet counts, liver enzymes or coagulation profile were unchanged. Blood culture positive sepsis was seen in three (18%) cooled infants, but in none of the standard-care infants. Clinical seizures were noted in seven (44%) standard-care and eight (47%) cooled infants. Two (13%) standard-care and four (24%) cooled infants died; the neurological examination at discharge was abnormal in six (43%) standard-care and eight (62%) cooled infants.

PCM cooling was effective only when the ambient temperature was <28°C, and required close temperature monitoring by the nursing staff. Despite these limitations, PCM may be an effective, low technology cooling device suitable for use in some LMIC neonatal units. Clearly our study was not powered to examine any clinical outcomes, and further evidence from large clinical trials are required before cooling is offered as a therapy after NE in LMIC.3 Once such multicountry LMIC trial (HELIX—Hypothermia for Encephalopathy In Low Income countries) is expected to start recruiting in the near future.4


ST is supported by a Clinician Scientist award from the National Institute of Health Research (NIHR) and AMT is supported by a senior research fellowship from NIHR.



  • Contributors ST conceived the idea, designed the study along with SS, and GB, analysed the data, drafted the manuscript, and had the final responsibility for all aspects of the study. MA, KS and CS recruited the cases, collected data and performed neurological assessments. AW advised on randomisation and supervised the data analysis. All authors contributed towards manuscript development and approved the final draft for publication. The study is compliant with the TRUST (Transparent Research Audit System) guidelines for ensuring research quality and integrity.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Ethics Committee, University College London.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Clinical No NCT01138176