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Therapeutic hypothermia - who, what, when, where, how?

Todd Fraser on 26-04-2011

Two recent publications raise the issue of therapeutic hypothermia. In march 2011, Dumas et al published a large retrospective review of outcomes from cardiac arrest. While not a randomised trial, the results reflect outcomes produced in 2 large randomised controlled trials in the early 2000s. In a prespecified group with a shockable initial rhythm, patients were almost twice as likely to have a good neurological outcome when cooled. Interestingly, the group with a 'non-shockable' rhythm did worse. A second study by Tomte, comparing surface with invasive cooling, found little difference in outcomes, but was too small to detect meaningful differences. A number of questions come to mind : 1) Why is therapeutic hypothermia not universally adopted? A number of surveys still indicate that there is some relucance to administer this therapy. 2) What is the best method of cooling? To my knowledge, the only RCTs that have demonstrated mortality benefit used surface cooling. While head to head studies have compared time-to-target temperatures etc, none have examined the safety and important outcomes of invasive techniques (such as cold saline, cooling catheters etc). Is it appropriate to substitute one for the other? 3) Who benefits from hypothermia? There is great temptation to apply this therapy to other groups who were not included in the available studies - for example near drownings, hangings etc. The study by Tomte seems to caution against this assumption. Both papers are available in the Journal Club


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Todd Fraser wrote 01-29-2012 12:18:51 pm
I've just added a paper to the journal club that brings early hypothermia into question.



Todd Fraser wrote 05-27-2011 06:13:57 pm
It appears hypothermia after traumatic brain injury may be set for another hit - I'm told the Cool Kids trial, examining the effect of hypothermia in children with severe brain injury, has been stopped early. It will be interesting to see what comes of the interim analysis.



Todd Fraser wrote 06-05-2011 01:16:11 pm
New guidelines have been released by a combined panel representing 5 international critical care societies. The recommendations were hardly a ringing endorsement of hypothermia outside the context of out-of-hospital cardiac arrest with VF/VT as the primary rhythm. I've put the guidelines in the journal club.



alexander browne wrote 07-28-2011 08:33:22 pm
I find it hard to believe that cooling strategies that have proved harmful in other situations: (TBI comatose patients, anoxic brain injury) are suddenly better for the OOHCA clinical situation.

I suppose we have little else to offer. My feeling is that, like stroke centres, we now give these patients a better standard of general care despite cooling them, and they have better outcomes because of that fact.

TBI: VERY EARLY HYPOTHERMIA INDUCTION IN PATIENTS WITH SEVERE BRAIN INJURY (THE NATIONAL ACUTE BRAIN INJURY STUDY: HYPOTHERMIA II): A RANDOMISED TRIAL: CONCLUSIONS: Early initiation of hypothermia did not improve outcomes in patients with severe brain injury. Clifton, G.L., et al, Lancet Neurol 10(2):131, February 2011



Jo Butler wrote 07-29-2011 12:45:35 pm
What do you mean when you say that it hasn't been found to be of benefit in anoxic brain injury? Two trials published simultaneously in the NEJM demonstrated you were 50% more likely to go to home or rehab than the control group. There aren't too many interventions that can claim that. Certainly not adrenaline by the looks of things!

I guess they are just different pathologies.

I'm quite happy to do it for OOHCA. The groups I'm still unclear on are near drownings, near hangings, OD with hypoxic brain injury but not arrest.... My inclination is that we should do it, other prognostic indicators aside...



Jo Butler wrote 06-12-2011 07:07:36 pm
We've used hypothermia for years and have found far fewer complications than we expected (occult sepsis, electrolyte imbalance, coagulopathy etc). We use the Arctic Sun cooling pads, and while we have had some problems with overshoot, it seems pretty effective. We've treated drownings, hangings etc, and can't see a good reason they are fundamentally different from sudden VF arrest.

Cool Kids is a bit of a concern though - it will be interesting to hear the reasons for terminating it.



Alex McKenzie wrote 06-13-2011 10:03:50 am
I'm not convinced that you can assume that IV ice cold saline is going to be harmless - the idea of giving 2-3L of saline to a patient who has just recovered from a cardiac arrest, particularly those with a PEA-type arrest where the heart itself may be damaged, seems cavalier to me.

Until these "non-inferiority" trials are performed and there is better evidence, I'll stick to surface cooling thanks very much.



alexander browne wrote 08-05-2011 03:43:57 pm
Concerning the NEJM articale I have issues with...surrogate endpoints (neuro scores); it wasn't powered for mortality, it was a 2ndary outcome, and the 2002 study was small. I just think we are doing a better job at caring for these patients now, and studies have born this out too, and cooling patients may or may not be part of that.
IMPROVING OUTCOME AFTER OUT-OF-HOSPITAL CARDIAC ARREST BY STRENGTHENING WEAK LINKS OF THE LOCAL CHAIN OF SURVIVAL: QUALITY OF ADVANCED LIFE SUPPORT AND POST-RESUSCITATION CARE
Lund-Kordahl, I., et al, Resuscitation 81(4):422, April 2010



Alex McKenzie wrote 08-05-2011 08:33:49 pm
Not sure I agree Alex. I don't think a good neuro outcome is a surrogate, its a valuable endpoint in its own right. Both trials included this as their primary endpoint. The results of a number of trials are consistently in favour of its use, supported by a Cochrane meta-analysis.

While mortality isn't improved, I'm not sure this matters. Turning vegetative survivors into neurologically favourable survivors is a very good outcome.



AlexB from New Zealand wrote 02-05-2014 07:01:02 pm
Hate to say I told you so. In 2011 I wrote

"I find it hard to believe that cooling strategies that have proved harmful in other situations: (TBI comatose patients, anoxic brain injury) are suddenly better for the OOHCA clinical situation.

I suppose we have little else to offer. My feeling is that, like stroke centres, we now give these patients a better standard of general care despite cooling them, and they have better outcomes because of that fact."

I reckon that's why cooling was better. Better management and care within the first 24 hours.



Blair from Australia wrote 02-09-2014 10:59:57 am
Yes, but that doesn't explain the results in the 2 initial cooling trials. There's no reason why the "better care" was only in the cooling group and not the control group in those studies.



Mark from Australia wrote 02-21-2014 04:41:36 pm
I spoke to one of the guys who authored one of the original studies. His view is that the usual care group contained several patients who became quite hyperthermic. The interpretation is thus that while cooling is probably harmless (and of no enormous benefit), cooking is definitely bad.
Of course the other reason might simply be that the two earlier studies (altogether only about 160 patients from memory) may have found a chance effect (Type 1 error).



 

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