HIE and Hypothermia therapy

[sjbrott]

Is anyone trying hypothermia, systemic or cranial, to minimize the effects of HIE? Candidates for this form of therapy must first be placed on aEEG to determine if any brain activity is present. Sustained cranial or systemic hypothermia needs to be initiated by 6 hours from birth to be effective.

[Stefan Johansson]

Is anyone trying hypothermia, systemic or cranial, to minimize the effects of HIE? Candidates for this form of therapy must first be placed on aEEG to determine if any brain activity is present. Sustained cranial or systemic hypothermia needs to be initiated by 6 hours from birth to be effective.

Hypothermia is a hot issue ;) - we participated in the UK-based TOBY-trial and now "post-TOBY" the Swedish Neonatal Society is discussing if/how/when hypothermia should be considered a treatment option. I saw the draft of clinical guidelines just the other day, will report when it is official!

[hehady]

Hypothermia may be the only hope for asphyxiated infants. The evidence from 2 large RCTs supports the use of selective head cooling and total body hypothermia, However the evidence is not that clear and it is premature to recommend brain cooling until results of more trials like the TOBY trial are published and a metanalysis completed.

1- CooLCAP trial ( Gluckman PD, Wyatt JS, Azzopardi D, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy:
multicentre randomised trial. Lancet 2005;365:663-70).

234 term infants with moderate to severe neonatal encephalopathy and abnormal amplitude integrated electroencephalography (aEEG) were randomly assigned to either head cooling for 72 h, within 6 h of birth, with rectal temperature maintained at 34–35°C (n=116), or conventional care (n=118). Primary outcome was death or severe disability at 18 months. Analysis was by intention to treat. We examined in two predefined subgroup analyses the effect of hypothermia in babies with the most severe aEEG changes before randomisation—ie, severe loss of background amplitude, and seizures—and those with less severe changes.
Findings In 16 babies, follow-up data were not available. Thus in 218 infants (93%), 73/110 (66%) allocated conventional care and 59/108 (55%) assigned head cooling died or had severe disability at 18 months (odds ratio
0·61; 95% CI 0·34–1·09, p=0·1). After adjustment for the severity of aEEG changes with a logistic regression model, the odds ratio for hypothermia treatment was 0·57 (0·32–1·01, p=0·05). No difference was noted in the
frequency of clinically important complications. Predefined subgroup analysis suggested that head cooling had no effect in infants with the most severe aEEG changes (n=46, 1·8; 0·49–6·4, p=0·51), but was beneficial in infants
with less severe aEEG changes (n= 172, 0·42; 0·22–0·80, p=0·009).
Interpretation These data suggest that although induced head cooling is not protective in a mixed population of infants with neonatal encephalopathy, it could safely improve survival without severe neurodevelopmental disability in infants with less severe aEEG changes.


2- NICDH Whole Body Hypothermia Trail (Shankaran S, Laptook AR, Ehrenkranz RA, et al. Whole-body hypothermia for neonates with hypoxic–ischemic encephalopathy.N Engl J Med 2005;353:1574-84.

Of 239 eligible infants, 102 were assigned to the hypothermia group and 106 to the control group. Adverse events were similar in the two groups during the 72 hours of cooling. Primary outcome data were available for 205 infants. Death or moderate or severe disability occurred in 45 of 102 infants (44 percent) in the hypothermia group and 64 of 103 infants (62 percent) in the control group (risk ratio, 0.72; 95 percent confidence interval, 0.54 to 0.95; P=0.01). Twenty-four infants (24 percent) in the hypothermia
group and 38 (37 percent) in the control group died (risk ratio, 0.68; 95 percent confidence interval, 0.44 to 1.05; P=0.08). There was no increase in major disability among survivors; the rate of cerebral palsy was 15 of 77 (19 percent) in the hypothermia group as compared with 19 of 64 (30 percent) in the control group (risk ratio, 0.68; 95 percent confidence interval, 0.38 to 1.22; P=0.20). Conclusions Whole-body hypothermia reduces the risk of death or disability in infants with moderate or severe hypoxic–ischemic encephalopathy.

In developing countries economic methods for cooling like ice bags, electric fan may be used, however, the problem will be the availability of aEEG machines which are expensive, yet, very crucial for the selection of infants in hypothermia trials.
We had difficulty in enrolling infants in multicenter trials because of that.

Any suggestions for some research group that can provide us with aEEG and we can paricipate in a RCT that looks at economic methods of head cooling that can be applied in developing countires (where the problem of asphyxia is more common and number of babies who can benifit is larger)

[javiergv]

it´s easy, safe and logic. Decrease the severity of the injury... why not?

[cihanber]

which device do you use for coolcap ? is it commercial.

[Linus Olson]

Dear all I have been involved in some of the swedish studies and are doing research in the field I will try to answer all the question ´s from my knowledge during next week Best regards Linus Olson

[sjbrott]

Earlier this year the US Federal Drug Admin (FDA) recentently approved the Olympic Neonatal Cool Cap. The effectiveness will be followed through the Vermont Oxford Network.

Note: Total body cooling including the Cool Cap has been having better results to date.

[cihanber]

thanks a lot sjbrott ,
is there any web adress or source to look at this things and to buy coolcap or blanket ?

[j.micallef]

Hypothermia is a hot issue ;) - we participated in the UK-based TOBY-trial and now "post-TOBY" the Swedish Neonatal Society is discussing if/how/when hypothermia should be considered a treatment option. I saw the draft of clinical guidelines just the other day, will report when it is official!
Hi Stefan
I was wondering wether you are treating asphyxiated infants with hypothermia outside of a controlled trial?
Have the Swedish "post-TOBY" guidelines been published yet?
best regards
John

[Stefan Johansson]

Hi Stefan
I was wondering wether you are treating asphyxiated infants with hypothermia outside of a controlled trial?

The answer is yes, there are now guidelines for cooling, but all treated infants are included in an observational study. I don't have the guidelines at hand right now, but pathol CFM is NOT included as a criteria.

Personally I feel more research is needed on this technique and thaht CFM seems to be a reasonable inclusion criteria. But I can also understand that one may argue that the treatment works, although I think the scientific evidence is a bit weak so far.

[Linus Olson]

Dear all
In sweden we have as mentioned by Stefan Johansson been running Cooling studies with Toby guidlines as a base for the new Swedish Guidlines.

We are now in most places recruting children that is forfilling the old criterias of Toby but with the extention that CFM is not a must but a should if you have a CFM at the clinic. The Arguments for not having it as a mandatory at the inclusion are a few. Here is one of them : In sweden we wanted to be able to start as soon as possible with the cooling. And if you have a transport "issue" (from a local hospital to the speciallity clinic) and you are monitoring the childs temperature and other important vital parameters, you the can start cooling the child during transport and then at the speciallity clinic exclude the child if the CFM shows othervise. We will then not have a child that miss the 6 Hour start of cooling limit due to rules. Though I belief all clinics in sweden will try to monitor with a CFM if possible already from start since this is common sense.

[Linus Olson]

Swedish cooling.
In sweden we are using at nearly all places the Tecotherm 200 whole body cooling system, we have not closed our boarders to other inventions or ideas but since the Tecotherm was used in TOBY we have kept using it. Olympics Cool cap has been considered in at a few sites but the price and the support have not been what we have wanted so far. ( But I am hopeful that this text will put these issues to a thing from the past or a historic event will happen when both the olympic and the Tec compamy in germany will say now we will give great support.) There have also been arguments that the mother/father comes closer to the child and is not so frightend by the equipment as if the child has a cap with cooling fluid running throw it.

We are now developing and doing research in sweden for a safe new method that will be able to use in the transport situation, in remote locations or in the local hospital in the time before a transport to the speciallity cliic, and hopefully all over the world. Since this is a research project we will have to get the results before clinical trials can start but the results are really promissing.

[adnamn]

Realy the initial data are promising,as it was pointed by my colleguues.My q.is how to apply the hole body cooling in yours centers?
how to measeures the temp.?

[rajunarasimhan]

Hi there,
Here in the UK, many neonatal units are providing hypothermia therapy as per the TOBY guidelines but without the need for aEEG criteria. These babies are then entered into the TOBY register for followup purposes.