Although therapeutic hypothermia (TH) is the standard of care for hypoxic ischaemic encephalopathy in high-income countries, the safety and efficacy of this therapy in low-income and middle-income countries (LMICs) is unknown. We aimed to describe the feasibility of TH using a low-cost servo-controlled cooling device and the short-term outcomes of the cooled babies in LMIC.
Design We recruited babies with moderate or severe hypoxic ischaemic encephalopathy (aged <6 hours) admitted to public sector tertiary neonatal units in India over a 28-month period. We administered whole-body cooling (set core temperature 33.5°C) using a servo-controlled device for 72 hours, followed by passive rewarming. We collected the data on short-term neonatal outcomes prior to hospital discharge.
Results Eighty-two babies were included—61 (74%) had moderate and 21 (26%) had severe encephalopathy. Mean (SD) hypothermia cooling induction time was 1.7 hour (1.5) and the effective cooling time 95% (0.08). The mean (SD) hypothermia induction time was 1.7 hour (1.5 hour), core temperature during cooling was 33.4°C (0.2), rewarming rate was 0.34°C (0.16°C) per hour and the effective cooling time was 95% (8%). Twenty-five (51%) babies had gastric bleeds, 6 (12%) had pulmonary bleeds and 21 (27%) had meconium on delivery. Fifteen (18%) babies died before discharge from hospital. Heart rate more than 120 bpm during cooling (P=0.01) and gastric bleeds (P<0.001) were associated with neonatal mortality.
Conclusions The low-cost servo-controlled cooling device maintained the core temperature well within the target range. Adequately powered clinical trials are required to establish the safety and efficacy of TH in LMICs.
Clinical trial registration number NCT01760629.
- brain injury
- low and middle-income
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VO and J contributed equally.
Contributors VO analysed and interpreted the data and wrote the initial drafts of the manuscript. KK, NE, MS and KC assisted in the study design and supervised the recruitment and data collection in Chennai. JS, NB and PBan led the recruitment at Bangalore. MC and RS assisted in the data collection and interpretation of data. JMo, KD and SM assisted in the study design and supervised the recruitment and data collection in Mumbai. SB and VM assisted in the study design and supervised the recruitment and data collection in Pondicherry. VM and MN assisted in the study design and supervised the recruitment and data collection in Calicut. PJL, PM, GA and JMe assisted in the data interpretation and preparation of the manuscript. PM undertook the statistical analysis. SR, SS and ST (chief investigator) conceived the idea, designed the study and interpreted the data. All authors contributed to the development of the manuscript and approved the final version for publication.
Funding This study was funded by the Gates and Melinda Foundation and Weston Garfield Foundation. The study was coordinated by the Centre for Perinatal Neuroscience at Imperial College London, which receives funding from the NIHR Imperial Biomedical Research Centre.
Competing interests None declared.
Patient consent Obtained from the parents/guardian.
Ethics approval University College London Research Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.
Collaborators Wayne State University, USA: SS; Imperial College London, UK: GA, MC, Jethro Herberg, PJL, JMe, PM, VO, RS, ST; Stats Consultancy, Amersham, UK: PBas; Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh: Arjun Chandra Dey, Sanjoy Kumer Dey, Mohammed Tariqul Islam, Ismat Jahan, Mohammed Abdul Mannan, Sadeka Chowdhury Moni, Kamrul Hasan Shabuj, Mohammod Shahidullah; National Institute of Neurosciences & Hospital, Dhaka, Bangladesh: Mohammed Nazrul Islam, Mst. Nazmun Nahar; Maulana Azad Medical College, New Delhi, India: Ashish Jain, SR; Lokmanya Tilak Municipal Medical College, Sion, Mumbai, India: SM, JMo, KD, Swapnil Bhiskar; Institute of Child Health, Egmore, Madras Medical College, Chennai, India: Rema Chandramohan, KC, JK, MS, NE, Monica Sebastian, Padmesh Vadekepad; Indira Gandhi Institute of Child Health, Bangalore, India: NB, PB, Usha Kantharajanna, Sowmya Krishnappa, JS, Niranjan Hunsanhalli Shivanna; Institute of Obstetrics & Gynaecology, Madras Medical College, Chennai, India: Arasar Seeralar, Vinayagam Prakash, Mythilli Babu, Mohamed Sajjid; Barnard Institute of Radiology, Madras Medical College, Chennai, India: Babu Peter Sathyanathan, R Ravi; Jawaharlal Nehru Institute of Postgraduate Medical Education and Research, Pondicherry, India: SB, VB; Institute of Maternal and Child Health, Government Medical College, Calicut, India: VM, MN; University of Kelaniya, Sri Lanka: Kalpani Chathurangika, Sanjeewa Munasinghe, Radika Karunaratne Shaman Rajindrajith, Ranmali Rodrigo, Samanmali Sumanasena, Jithangi Wanigasinghe; Sree Avittom Thirunal Hospital, Thiruvananthapuram, India Radhika Ajit, Sobha Kumar, Ashwathy Nair.
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