An early clinical score predicting an abnormal amplitude-integrated electroencephalogram (aEEG) or moderate-severe hypoxic ischemic encephalopathy (HIE) may allow rapid triage of infants for therapeutic hypothermia. We aimed to determine if early clinical examination could predict either an abnormal aEEG at age 6 hours or moderate-severe HIE presenting within 72 hours of birth.

OBJECTIVE. Several trials suggest that hypothermia is beneficial in selected infants with hypoxic-ischemic encephalopathy. However, the cooling methods used required repeated interventions and were either expensive or reported significant temperature variation. The objective of this pilot study was to describe the use, efficacy, and physiologic impact of an inexpensive servo-controlled cooling fan blowing room-temperature air. PATIENTS AND METHODS. A servo-controlled fan was manufactured and used to cool 10 infants with hypoxic-ischemic encephalopathy to a rectal temperature of 33°C to 34°C. The infants were sedated with phenobarbital, but clonidine was administered to some infants if shivering or discomfort occurred. A servo-controlled radiant warmer was used simultaneously with the fan to prevent overcooling. The settings used on the fan and radiant warmer differed slightly between some infants as the technique evolved. RESULTS. A rectal temperature of 34°C was achieved in a median time of 58 minutes. Overcooling did not occur, and the mean temperature during cooling was 33.6°C ± 0.2°C. Inspired oxygen requirements increased in 6 infants, and 5 infants required inotropic support during cooling, but this was progressively reduced after 1 to 2 days. Dehydration did not occur. Five infants shivered when faster fan speeds were used, but 4 of the 5 infants had hypomagnesemia. Shivering was controlled with clonidine in 4 infants, but 1 infant required morphine. CONCLUSIONS. Servo-controlled fan cooling with room-temperature air, combined with servo-controlled radiant warming, was an effective, simple, and safe method of inducing and maintaining rectal temperatures of 33°C to 34°C in sedated infants with hypoxic-ischemic encephalopathy. After induction of hypothermia, a low fan speed facilitated accurate temperature control, and warmer-controlled rewarming at 0.2°C increments every 30 minutes resulted in more appropriate rewarming than when 0.5°C increments every hour were used.

Background: Neonatal encephalopathy (NE) due to suspected hypoxic-ischemic encephalopathy (HIE), referred to as NESHIE, is a clinical diagnosis in late preterm and term newborns. It occurs as a result of impaired cerebral blood flow and oxygen delivery during the peripartum period and is used until other causes of NE have been discounted and HIE is confirmed. Therapeutic hypothermia (TH) is the only evidence-based and clinically approved treatment modality for HIE. However, the limited efficacy and uncertain benefits of TH in some low- to middle-income countries (LMICs) and the associated need for intensive monitoring have prompted investigations into more accessible and effective stand-alone or additive treatment options. Data sources: This review describes the rationale and current evidence for alternative treatments in the context of the pathophysiology of HIE based on literatures from Pubmed and other online sources of published data. Results: The underlining mechanisms of neurotoxic effect, current clinically approved treatment, various categories of emerging treatments and clinical trials for NE are summarized in this review. Melatonin, caffeine citrate, autologous cord blood stem cells, Epoetin alfa and Allopurinal are being tested as potential neuroprotective agents currently. Conclusion: This review describes the rationale and current evidence for alternative treatments in the context of the pathophysiology of HIE. Neuroprotective agents are currently only being investigated in high- and middle-income settings. Results from these trials will need to be interpreted and validated in LMIC settings. The focus of future research should therefore be on the development of inexpensive, accessible monotherapies and should include LMICs, where the highest burden of NESHIE exists. Graphical

Objectives: There are few population-based studies of hypoxic ischemic encephalopathy (HIE) in sub-Saharan Africa, and the published criteria that are used to define and grade HIE are too variable for meaningful comparisons between studies and populations. Our objectives were (1) to investigate how the incidence of HIE in our region varies with different criteria for intrapartum hypoxia and (2) to determine how encephalopathy severity varies with different grading systems. Method: We reviewed the records of infants with a diagnosis of HIE born between September 2008 and March 2009 in public facilities in the Southern Cape Peninsula, South Africa. The incidence of HIE was calculated according to four definitions of intrapartum hypoxia and graded according to three methods. Results: Depending on which defining criteria were applied, the incidence of HIE varied from 2.3 to 4.3 per 1000 live births, of mild HIE ranged from 0.4 to 1.3 per 1000 live births, and of moderate-severe HIE ranged from 1.5 to 3.7 per 1000 live births. Ninety-seven of the 110 (88%) infants reviewed had at least one intrapartum-related abnormality. Only 62 (56%) infants had a blood gas performed in the first hour of life. Conclusion: The incidence and grade of HIE can vary more than 2-fold in the same population, depending on which defining criteria are used. Consensus definitions are needed for benchmarking.

This study describes and evaluates a simple method of neuroprotective hypothermia for infants with hypoxic-ischaemic encephalopathy (HIE). Five term infants with HIE were cooled by applying soft, cold gel bags to the head. A radiant warmer, set to 34°C, servo-controlled the temperature measured at a probe between the infant’s back and the mattress. The infants’ heads were shielded from the warmer. After 72 h, the infants were re-warmed by 0.2°C per hour, by adjusting the radiant warmer. A rectal temperature of 34°C was attained in a median time of 45 min. Mean rectal temperatures during cooling were 33.9 ± 0.3°C. There was good correlation between insulated back temperatures and deep rectal temperatures (r = 0.76). There were no major or irreversible adverse events during cooling. This method of cooling achieved rectal temperatures within the target range of 33–34°C and re-warming was effective.