Have a case:

Stat CS for maternal abruption and decels

Term baby. Poor tone and resp effort. Suspected blood aspiration. Needed PPV and 100% FiO2 for hypoxia. Intubated in DR.

Cord gases pH 7.22 BE -8

Baby H/H: 18/50

Baby gas 7.18 / -8 at ~50 min of life

Started having clinical seizures at 12 HOL. Electrical seizures on EEG. Normal HUS. 

Would you start late therapeutic hypothermia? Did not meet mod/severe sarnat encephalopathy on exam but was hypotonic, was intubated, and required prolonged resuscitation. TH is often fairly well tolerated and there's not much else to do.

2017 Laptook paper suggests potential benefit with late cooling. The baby had a perinatal event and clinical signs of possible HIE but no acidosis. Could be stroke or other. Some papers looking retrospectively at cooled infants who went on to have perinatal stroke had seizure reduction with TH.

So far has received phenobarb, keppra, fospheny for refractory seizures. 

Thanks for sharing this (not uncommon!) clinical scenario. Will be interesting to follow the discussion.

Actually, this topic will be one of the interactive lecture sessions on the #99nicuMeetup in Vienna next year , one of the real experts in this field has semi-confirmed.

I find this tricky myself, I like to stick to our guidelines. In practise, we typically handle a case like this with an inter-collegial discussion (sometimes also involving our neighbouring level-3 NICU) and reach consensus how to act that way. In this case, I think the jury would be out for some time before deciding. What we'd decide in this case, an open question in my view.

Just for the purpose of recall.(Cochrane 2013, Jacobs)

Evidence of peripartum asphyxia, with each enrolled infant satisfying at least one of the following criteria:
i) Apgar score of 5 or less at 10 minutes;
ii) mechanical ventilation or resuscitation at 10 minutes;
iii) cord pH < 7.1, or an arterial pH < 7.1 or base deficit of 12 or more within 60 minutes of birth.
AND

Evidence of encephalopathy according to Sarnat staging (Sarnat 1976; Finer 1981):
i) Stage 1 (mild): hyperalertness, hyper-reflexia, dilated pupils, tachycardia, absence of seizures;
ii) Stage 2 (moderate): lethargy, hyper-reflexia, miosis, bradycardia, seizures, hypotonia with weak suck and Moro;
iii) Stage 3 (severe): stupor, flaccidity, small to mid position pupils that react poorly to light, decreased stretch reflexes, hypothermia and absent Moro.

AND abnormal standard EEG or aEEG findings(this in addition to above as in NeoNeuro Network RCT by Simburner, Germany).

Evidence

Laptook etal. Effect of therapeutic hypothermia initiated after 6hours of age on death or disability among newborns with Hypoxic-ischemic encephalopathy, Jama 2017 October 24;318(16): 1550-1560.

•Randomized clinical trial

•April 2008 –june 2016

•Moderate or severe HIE enrolled at 6-24 hours after birth.

•Twenty one US neonatal research network centers

•There were 168 participants and 83 were randomly assigned to hypothermia and 85 to noncooling.

Results

76% probability of any reduction in death or disability.(Biasian Statistics and analysis)
64% probability of at least 2% less death or disability at 18 to 22 months. 
Hypothermia initiated at 6 to 24 hours after birth may have benefit but there is uncertainty in its effectiveness.

Gist: TH can be tried for its benefit though not greater than that of starting early but with due consideration of parents participation and Consultant in decision making.
 

This is not an uncommon dilemma. We have developed a one paged trigger/ assessment tool for babies who meet criteria for monitoring for moderate or severe encephalopathy. It seems to work most times and one of our fellows is conducting an audit to see if we miss any babies with this tool. 

Based on this case, it sounds like the baby would have met criteria for clinical monitoring for moderate or severe HIE i.e. prolonged resuscitation and possibly Apgar scores? but not pH or BE related values and we would have then assessed this baby hourly for the first 6 hours of life for clinical signs of moderate or severe encephalopathy. TH would have been started as per the trigger tool thresholds.

The problem comes when these babies don't meet clinical criteria for moderate or severe HIE and clinical monitoring is ceased and then go on to have seizures some time later - as is seen in this case. The current trend in our unit would be to not cool them at the 12hr mark but I have personally cooled a baby who did not meet criteria for moderate or severe encephalopathy in the 1st 6hrs but then went on to have seizures at ~8hrs of life. We would just optimise other medical intervention and use anti-convulsants (levetiracetam, topiramate and midazolam or lignocaine) to treat seizure burden.

I'm not sure if that helps!

Cheers

Richard

HIE trigger tool.pdf

There has been a recent narrative review of cooling outside of "standard" criteria here: https://www.sciencedirect.com/science/article/abs/pii/S1355184118301595

I agree with above comments- I think given need for resuscitation at 10 mins (ventilated) and evidence of encephalopathy on clinical assessment (+/1 aEEG/CFAM) then we would have cooled on admission. 

We generally do not cool > 6 hrs but have on occasions, including late preterms. We had an interesting situation a few years ago where a baby ended up being resuscitated after an unplanned extubation (ex-preterm, difficult to get chest movement, difficult to intubate, long period of bradycardia and poor oxygenation) and there was a decision made to cool. 

What happened in your case?

I think it's fairly reasonable to attribute the baby's seizures at 12 hours to an etiology other than HIE. The cord gas is ok and also the gas at 1 hour can be attributed to the resuscitation YES. But it could be also respiratory as you have not mentioned the PCo2.

 

And again regarding the gas at 1 hour of life... It's not that acidotic to start cooling ( Looking at the CPS statement of 7.15)

 

I think guidelines are made for those situations ...to help when things get blurry. Sticking to it as is the right thing for me until an alternative approach has established evidence behind it.

On 11/27/2019 at 7:16 AM, richmaus said:

This is not an uncommon dilemma. We have developed a one paged trigger/ assessment tool for babies who meet criteria for monitoring for moderate or severe encephalopathy. It seems to work most times and one of our fellows is conducting an audit to see if we miss any babies with this tool. 

Based on this case, it sounds like the baby would have met criteria for clinical monitoring for moderate or severe HIE i.e. prolonged resuscitation and possibly Apgar scores? but not pH or BE related values and we would have then assessed this baby hourly for the first 6 hours of life for clinical signs of moderate or severe encephalopathy. TH would have been started as per the trigger tool thresholds.

The problem comes when these babies don't meet clinical criteria for moderate or severe HIE and clinical monitoring is ceased and then go on to have seizures some time later - as is seen in this case. The current trend in our unit would be to not cool them at the 12hr mark but I have personally cooled a baby who did not meet criteria for moderate or severe encephalopathy in the 1st 6hrs but then went on to have seizures at ~8hrs of life. We would just optimise other medical intervention and use anti-convulsants (levetiracetam, topiramate and midazolam or lignocaine) to treat seizure burden.

I'm not sure if that helps!

Cheers

Richard

HIE trigger tool.pdf 91.49 kB · 26 downloads

What about outborns?

Do you have special protocol for referrals or for aEEG evaluation ?
Do you use other criteria than those for hypothermia inclusion (lower thresold)?
Do you use other tools (further ABG; telemedecine, ...)?

It seems to me that we sometimes miss opportunities for cooling when babies are in referring units and that the neurologic evaluation (according Sarnat or Thompson score) is made by less experienced people. aEEG is sometimes not available there and you don't have access to the clinical status of the patient.

last case:
spontanous labour, term baby, vaginal delivery, meconium stained liquid
APGAR 1-5-7 - Mask ventilation less than 5 min (no intubation, no chest compression)
cord gas 6.92 BE -20 lact 14
mild resp distress - CPAP
according to physician : no sign of encephalopathy (thompson score 1 - sarnat 1)
seizures at 10 hour of life - pheno/pheny/keppra/midazolam
bilateral basal ganglia lesion on MRI

but unfortunatly not referred for hypothermia...

thanks for your experiences

Hi Antoine 

Thank you for the reply. Yes - outborn infants will always remain a problem for us, as we have many referral centres that look after newborn babies and refer to our tertiary centre for ongoing management.

I live in Brisbane, Queensland and the state of Queensland has an area of 1.853 million square kilometres. It is nearly five times the size of Japan, seven times the size of Great Britain and two and half times the size of Texas. The states total population is just over 5 million. We only have 4 NICU's in the state that are capable of providing therapeutic hypothermia for moderate or severe HIE.

We do have a state wide guideline, online for HIE which includes flow charts, policies and educational tools (which includes the HIE trigger tool) in order that peripheral centres can up-skill themselves with regards to management of a baby suspected of having moderate or severe HIE and therefore refer then early in their postnatal course (https://www.health.qld.gov.au/qcg/publications). Outside the 4 level 6 NICU's scattered throughout the state (3 of them are in the SE corner of the state) no other facility that delivers newborn babies has the capability of doing aEEG monitoring so that is not an option for us. 

We have recently improved our TeleHealth service so that we are able to dial in to these peripheral centres and we are able to see these babies that we are getting calls about whether we should cool them or not - which is not the same as examining them ourselves - but is better than just getting the information over the phone. The retrieval service is managed medically by a level 6 Neonatologist, 24/7 and so this has definitely helped in the situation where there is a questionable neurological examination  - again this is only dedicated to the first 6hrs of life as it was in the original cooling trials (see attached).

With regards to the above-mentioned case, if a baby like that was delivered in our level 6 hospital, then it would have been commenced on the HIE trigger tool because of the cord gas results (pH 7.0 and BE > -12) and would have had hourly clinical monitoring for moderate or severe HIE using the Sarnat scoring system. If the baby did not meet clinical criteria for moderate or severe HIE in the first 6 hrs then we would have stopped these hourly assessments and if the baby was otherwise systemically well (no respiratory support and planned to established feeding) then it would have been discharged to the postnatal ward. So the outcome may have unfortunately been the same as it was in this case! We certainly do see these cases in our hospital from time to time. 

The questions therefore arise:

1.  Could there be benefit of therapeutic hypothermia for babies with mild HIE? (One could argue that this baby would have been diagnosed with mild/ stage 1 HIE based on the information provided in the case - I have attached some interesting information from Terrie India and her group out of Boston, USA, regarding this topic)

2. Is there benefit from initiating cooling beyond the 6hr time frame that was introduced after the original cooling studies were performed? (I have attached a nice RCT attached looking at this!)

Sorry, I know this probably doesn't answer your questions but we have a similar problem here to. I think getting more information on these 2 questions will be very helpful when trying to manage a baby like this one.

I hope everyone is managing OK with the current COVID-19 pandemic. Keep safe!

Best wishes 

Richard

 

Whole-body hypothermia for term and near-term newborns with HIE.pdf Selective head cooling with mild systemic hypothermia after neonatal encephalopathy - a multicentre randomised trial.pdf

Due to limitations of upload size I haven't been able to upload all of the articles.

This is the title of the article from Terrie Inder's group: 

"Should therapeutic hypothermia be offered to babies with mild neonatal encephalopathy in the first 6 h after birth?"

This is the title of the article regarding cooling for moderate or severe HIE after 6hrs of life:

"Effect of Therapeutic Hypothermia Initiated After 6 Hours of Age on Death or Disability Among Newborns With Hypoxic-Ischemic Encephalopathy A Randomized Clinical Trial"

thank you for your reply.

despite feeling powerlessness i'm not alone 

 

stay safe, stay strong!