Goldstein, H. Induced Hypothermia for Hypoxic-Ischaemic Encephalopathy – Part 2, Don't Forget the Bubbles, 2015. Available at:
Consider and identify hypoxic ischaemic encephalopathy early
Cooling improves mortality rates without additional adverse neurodevelopmental outcomes at 18 months
If the child fits the FEAST criteria during or soon after resus, they might be a candidate for cooling
Neonates must only be actively cooled in a tertiary neonatal centre
Use your local guidelines and discuss with a neonatologist early
It’s 2am and you (the Paeds Reg), have been called to the Birth Suite. After some significant resuscitation, you’ve taken the neonate to the Special Care Nursery. Read part 1 here.
Baby is still working hard to breathe but hasn’t moved much otherwise. She’s really grunting away on the CPAP.
You discuss the baby with tertiary centre for retrieval & consideration of cooling. The neonatologist advises to turn off the overhead heater.
What’s the evidence for cooling in HIE?
A 2007 Cochrane review found that, when started within 6 hours of birth, 72 hours of moderate hypothermia reduced the rate of death and disability at 18 months of age, for neonates with moderate to severe HIE. At that stage, the data was considered inadequate and incomplete with respect to data or neurodevelopment outcomes in survivors. The question also remained whether the benefits of hypothermia were attenuated by the severity of encephalopathy.
This was further updated in Edwards et al’s 2010 meta-analysis in the BMJ. Their total analysis included ten trials (~1300 patients) for mortality, and a subset of 767 patients for whom neurodevelopmental outcomes at 18 months were available. This subset comprised three large trials completed after the 2007 meta analysis.
With regard to the primary outcome of neurodevelopment, the analysis was strongly about in favour of cooling to prevent death or disability by 18 months, with a NNT of 9.
Note well that cooling (aka therapeutic hypothermia) needs tertiary level care; a good example of this is a small study from Uganda (included in the Edwards et al meta-analysis), in which the outcomes for cooled babies with HIE were significantly worse than those not cooled. The implication here is that without adequate monitoring, experienced personnel and appropriate equipment, any benefit of therapeutic hypothermia is rapidly lost.
More recently, the Cochrane Review has been, well, reviewed; an analysis of this paper comprises the Part 3 of this series.
The new Dad has been by his baby daughter’s side through all of this, and soon after your call with the NICU Team, Mum arrives.
What do you tell them?
The BeBoP group provides a nice printout for parents, available here.
Some of the good explainers I’ve heard are short and simple. It’s good to start right back at the start. Both BeBoP and The Queensland Maternity & Neonatal Guidelines program recommend the explainers below:
|Criteria||Advice for parents|
|What does the treatment entail?||Your baby will receive cooling therapy in addition to standard intensive care support. Your baby's temperature will be slowly lowered and kept between 33 to 34u00b0C for 72 hours. Cooling will be achieved by exposing your baby to the ambient air temperature and subsequently by specialised cooling equipment. Your babyu2019s temperature and other vital signs will be closely monitored throughout the process. If your baby shows any signs of discomfort during cooling he/she will be prescribed medication to reduce this. After 72 hours of cooling, your baby will be gradually rewarmed to a temperature of 37C.|
|Treatment||In the past there were no treatments to reduce the severity of brain injury in these newborn babies. Recent research has shown that cooling these babies reduces the secondary brain injury, increases the chances of survival and reduces the severity of possible long-term disability.|
|Prognosis||Approximately 30 to 60% of those babies who survive after this degree of damage to their brain may develop long-term disabilities. These disabilities include cerebral palsy and severe learning difficulties.|
|Consequences||This can result in brain damage from direct injury and also from ongoing changes that begin around six hours after the injury. These secondary changes are known to increase the amount of brain injury that occurs.|
|Incidence||About 1-3 in 1000 newborn babies suffer from the effects of reduced blood flow or oxygen supply to their brain around the time of birth.|
|Resuscitation||Your baby needed significant resuscitation at birth to help him/her breathe. He/she appears to have suffered from the effects of lack of oxygen and blood supply to the brain.|
More recently, I’ve begun to mention a protocol. The idea that this is common enough and that there’s been some forethought and research in the area can provide another kind of reassurance to parents. It helps set expectations and frame your decision making, in the subacute phase.
Whilst waiting for the retrieval team, the baby has 5 minutes of cycling movements of both legs. You think it’s a seizure.
Seizures and other complications
Apnoeas, lip smacking, rowing of the arms or cycling of the legs can be subtle signs of seizures in neonates. It’s important to have a low threshold for suspicion of seizures, and experienced nurse keeping an eye on the baby. A full description of the management of seizures associated with HIE is (just) outside the scope of this post, but they can notoriously hard to control.
It’s also worth considering some of the other complications of delivery that may be arising concurrently with an hypoxic-ischaemic type presentation; urgent delivery may be facilitated by vacuum extraction, with an increased risk of subgaleal haemorrhage
With current levels of care & investigation, prognostication is multimodal. A 2009 review of outcomes based on Sarnat stage (clinical examination) identified that: stage 1 HIE has a normal neurological outcome in >90% of cases whereas stage 3 has poor neurologic outcome in almost all cases. In between, the incidence of poor outcomes ranges from 30-60%. In addition to high Sarnat stage clinical exam findings, the presence of seizures, an persistently abnormal EEG, MRI changes (particularly on MR spectroscopy) all augur a poor prognosis.
HIE is a poorly understood pathophysiologic process, that can lead to long term disability or death. Identifying the features of HIE early in the piece (either during resuscitation, but specifically within 6 hours) can be important to facilitating cooling. When there’s a long neonatal resus for a flat baby, make sure you think of HIE and the FEAST.
Hypoxic-Ischemic Encephalopathy; A Review for the Clinician Escobar, et al. JAMA Pediatr. 2015;169(4):397-403. doi:10.1001/jamapediatrics.2014.3269. http://archpedi.jamanetwork.com/article.aspx?articleid=2118582
Edwards, D et al. Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data. BMJ 2010;340:c363 doi:10.1136/bmj.c363 http://www.bmj.com/content/340/bmj.c363
Walston, F et al East of England Perinatal Networks: Guidelines for Management of Infants with Suspected Hypoxic Ischaemic Encephalopathy (HIE). Published 28/2/2012.
De Paoli A (Ed.) Royal Hobart Hospital Clinical Guidelines – Cooling for Neonatal Hypoxic Ischaemic Encephalopathy (HIE) – Guideline.
Davies, Cartwright & Inglis. “Pocket notes on Neonatology 2E.” 2008. Elsevier. (3rd Ed available as iPhone application)
Ambalavanan, N & Carlo, W A. (Chapter Authors) 93.5 Hypoxic-Ischemic Encephalopathy; Nelson’s Textbook of Pediatrics 18th Edition. https://expertconsult.inkling.com/read/nelson-pediatrics-kliegman-behrman-19th/chapter-93/93-5-hypoxic-ischemic
Battin, M. Auckland District Health Board Newborn Services Clinical Guideline – Cooling Overview. Feb 2010.
Ballot DE. Cooling for newborns with hypoxic ischaemic encephalopathy: RHL commentary (last revised: 1 October 2010). The WHO Reproductive Health Library; Geneva: World Health Organization. http://apps.who.int/rhl/newborn/cd003311_ballotde_com/en/