Without evidence of benefit, an intervention should not be presumed to be beneficial or safe.

- Rogue Medic

Is Earlier Better for Therapeutic Hypothermia? Part I

ResearchBlogging.org
 

When is the right time to begin TH (Therapeutic Hypothermia) to produce the best outcomes?

In the ICU (Intensive Care Unit)?

In the ED (Emergency Department)?

In the ambulance?

While the patient is still pulseless?

This question was asked in 2010.
 


Click on image to make it larger.
 

Favorable outcomes – 47.5% EMS TH vs 52.6% ED TH.

Worse outcome, but not statistically significant.

Discharge to home – 20.3% EMS TH vs 29.3% ED TH.

Worse outcome, but not statistically significant.

Discharge to rehabilitation – 27.1% EMS TH vs 23.3% ED TH.

Worse outcome, because these patients are not well enough to go home, but not statistically significant.

Dead – 52.5% EMS TH vs 46.6% ED TH.

Worse outcome, but not statistically significant.
 

The great tragedy of Science — the slaying of a beautiful hypothesis by an ugly fact. -Thomas Henry Huxley.
 

EMS TH was added to many EMS protocols because of a lack of clear evidence of harm. EMS needed to Just do something.

The results did not support EMS administration of chilled IV (IntraVenous) fluid for prehospital therapeutic hypothermia, but the study was stopped early, because –
 

At the interim analysis of the first 200 patients, the Steering Committee noted that there was no difference in the primary outcome measure and that it was extremely unlikely that such a difference would emerge between the groups. Therefore, the study was stopped because of futility after 234 patients had been enrolled.[1]

 

In other words – We will not let the numbers convince us that there is no benefit, because numbers that do not support a positive effect are futile?

If the data would have indicated a negative effect, but had not reached statistical significance, should we expect the Steering Committee to support continuing the study, or would they support discontinuing the study early to protect the enrolled patients, but leave the question unanswered?

When studies are discontinued early to protect patients, do they discourage further studies?

When studies are discontinued early to protect patients, do they only endanger future patients?

Or does early termination encourage further studies because there is not clear evidence of harm and we want to believe that our interventions are beneficial?
 

What if it works?

Most proposed treatments do not work, so this is just an excuse to continue using something dangerous. What if it works? is the logical fallacy that is used to justify harming patients with alternative medicine.

We should not harm vulnerable patients because of our unreasonable belief in wishful thinking.
 

If it helps just one patient it is worth it.

This is another logical fallacy, because it completely ignores the harm that the treatment causes.

Some patients will improve after almost any treatment – even cyanide.

That means that alternative medicine advocates could should endorse the use of cyanide, because if it helps just one patient . . . .

We need to have unbiased information about the real benefits (if any) and the real harms (if any), before we encourage using anything on vulnerable patients.
 

Is it good to just do something?

Or

Is it good to help patients?

If our responsibility is to help patients, one of the best ways to help patients is to avoid causing harm.

Just doing something, with no evidence of benefit, is causing harm.

How many EMS agencies have prehospital therapeutic hypothermia protocols because of a desire to just do something?

I have been criticized for not being a supporter of treatments that do not have evidence of benefit.

Am I a killjoy, desiring bad outcomes?

No.

I understand that treatment that does not have evidence of benefit is almost always going to do more harm than good.

Just do something?

No.

Just demand valid evidence of improved outcomes.

Footnotes:

[1] Induction of therapeutic hypothermia by paramedics after resuscitation from out-of-hospital ventricular fibrillation cardiac arrest: a randomized controlled trial.
Bernard SA, Smith K, Cameron P, Masci K, Taylor DM, Cooper DJ, Kelly AM, Silvester W; Rapid Infusion of Cold Hartmanns (RICH) Investigators.
Circulation. 2010 Aug 17;122(7):737-42. doi: 10.1161/CIRCULATIONAHA.109.906859. Epub 2010 Aug 2.
PMID: 20679551 [PubMed – indexed for MEDLINE]

Free Full Text from Circulation.

Bernard SA, Smith K, Cameron P, Masci K, Taylor DM, Cooper DJ, Kelly AM, Silvester W, & Rapid Infusion of Cold Hartmanns (RICH) Investigators (2010). Induction of therapeutic hypothermia by paramedics after resuscitation from out-of-hospital ventricular fibrillation cardiac arrest: a randomized controlled trial. Circulation, 122 (7), 737-42 PMID: 20679551

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Comments

  1. I think that there’s an argument to be made for performing an intervention not necessarily because it benefits the patient clinically, but does so logistically. Starting a saline lock and drawing blood samples is an easy example; doesn’t improve patient outcomes because we do it in the field, but expedites care in the ED. In the case of TH, maybe it doesn’t improve outcomes to start it earlier, but when you consider that ED/ICU staff will also be dropping central lines, beginning EGDT, titrating oxygenation, hanging pressors or inserting an IABP, and/or prepping the patient for PCI, it seems like initiating cooling in the field will still benefit the patient, even if it doesn’t result in a statistically significant change in outcome data. Unless we start to see data that starting temp management in the field hurts patients, I think that it’s a worthwhile use of our time in the back of the truck.

    • We have TH in our protocols following ROSC. It was implemented this past February. I’ve had four arrests since then with ROSC and I was faithful to impement it. But I can say honestly that without having the added burden of implementing TH I could have made better use of my time.

      I know that there were some questions regarding the study, but none that really invalidte the finding.

      And while I do support a continuum of care that can be initiated in the ambulance, such as setting up receiving RN’s for easiy blood draws, etc. I feel that if there is an absence of evidence that TH initiated early assures better outcomes, that doing it for the sake of doing something is counter-productive in principle.

      • Will you stop starting IVs as well?

        I’ve found no study that starting an IV in the field improves survival outcomes, and they actually they have a higher risk of iatrogenic infections.

        No evidence that prehospital IV access assures better outcomes. 🙂 Put your money where your mouth is!

        • Ben Dowdy,

          Will you stop starting IVs as well?

          I start IVs to give IV medications.

          I start IVs because I expect the medications to improve outcomes.

          I’ve found no study that starting an IV in the field improves survival outcomes, and they actually they have a higher risk of iatrogenic infections.

          No evidence that prehospital IV access assures better outcomes. 🙂 Put your money where your mouth is!

          I have.

          .

        • I will not stop initiating IV access because the instances where I initiate IV access are either ones where the patient’s condition demanded it, or I had the luxury of time and patient stability to initiate an intervention that began a continuum of care. This particular continuum of care does not result in lower patient survival rates.

          In a patient with a recent ROSC, I rarely have that luxury. I’m shoehorning the intervention in. The patient needs my attention for continuous reassessment, administration of post-arrest medications, airway management, and most importantly, 12-lead acquisition.

          But this discussion is all irrelevant, because as RM points out and as the study indicates, field-initiated TH fairs poorly when compared to hospital initiated TH.

    • Ben Dowdy,

      I think that there’s an argument to be made for performing an intervention not necessarily because it benefits the patient clinically, but does so logistically. Starting a saline lock and drawing blood samples is an easy example; doesn’t improve patient outcomes because we do it in the field, but expedites care in the ED.

      Most of the hospitals I transport to do not accept EMS blood draws.

      Therefore, I do not start many IVs on ALS patients. I start IVs when I expect to give medication through the IV.

      I do have other things to do while the patient is in my care. I am not an IV/lab tech for the ED.

      In the case of TH, maybe it doesn’t improve outcomes to start it earlier, but when you consider that ED/ICU staff will also be dropping central lines, beginning EGDT, titrating oxygenation, hanging pressors or inserting an IABP, and/or prepping the patient for PCI, it seems like initiating cooling in the field will still benefit the patient, even if it doesn’t result in a statistically significant change in outcome data. Unless we start to see data that starting temp management in the field hurts patients, I think that it’s a worthwhile use of our time in the back of the truck.

      You did notice that the survival to discharge was worse with EMS cooling.

      All of the outcomes were worse when the therapeutic hypothermia was initiated by EMS.

      I will eventually write about the editorial (the link is below) that describes the physiological reasons to expect worse outcomes when therapeutic hypothermia is begun by EMS.

      http://circ.ahajournals.org/content/122/7/679.full

      .

  2. One thing that’s always bugged me about the evidence behind therapeutic hypothermia is the real lack of any connection between the onset of cooling and it’s efficacy. You would think that if the theory behind it were valid then there would be a large benefit to starting cooling early as opposed to 4-6 hours post-ROSC, but I haven’t seen a single human study supporting that notion. I have no problem with any places that want to attempt prehospital cooling as part of an experimental setting, but I’ve seen a lot of regions (including my own) that decided to make it standard protocol without any good evidence to back up the practice. It’s not surprising that folks are going to be backpedaling now…

    • Vince D,

      You would think that if the theory behind it were valid then there would be a large benefit to starting cooling early as opposed to 4-6 hours post-ROSC,

      There is – if you are a mouse.

      Human physiology appears to work a bit differently.

      I have no problem with any places that want to attempt prehospital cooling as part of an experimental setting, but I’ve seen a lot of regions (including my own) that decided to make it standard protocol without any good evidence to back up the practice. It’s not surprising that folks are going to be backpedaling now…

      I completely agree.

      The editorial (by Lance Becker, MD) that accompanied this paper is free and does an excellent job of explaining the many possible reasons for worse outcomes with early therapeutic hypothermia.

      http://circ.ahajournals.org/content/122/7/679.full

      .

  3. Lets all consider a few questions….No evidence for pre-hospital cooling? What body of evidence did ILCOR, ERC and AHA use a basis for making their recommendations? Animal studies? Of course, doesn’t a lot of research start there? Human studies? Of course, there are studies that show early cooling is neuroprotective….take for instance Sendelbach in Resuscitation 82, where the data showed a five minute delay in cooling resulted in a 6% chance for a poor neuro outcome. Cooling for TBI has been around a long time. Several Chinese studies exist showing better outcomes. Is it the same as cardiac arrest? No. Is it relevant? Yes. Becker does a great job at discussing the challenges of infusing chilled saline. More questions, as Bernard found that patients only had a 0.8C drop at ED arrival, did the brain reach mild TH at all? Many studies (I.e. Kim) reference the use of saline and bladder temp. what is the brain temp? Nobody knows. If the brain is warmer than the core normally, what about in cardiac arrest where the brain is injured due to the ischemic effects? Is a 1.2C core drop sufficient? Lastly, rewarming is a major issue and since the max infused volume is 2L, how long will it last? Not long, and definitely not long enough for the systemic systems to reach target temperature. So, could the issue be the “method” of using chilled saline and the known issues or side effects, or any type of pre-hospital cooling? Looks to me like the evidence is clear that it’s the method. Check out the November issue of JEMS.

    • The AHA states chilled fluids are to be used as an adjunct, and yet it seems to be the primary method of pre-hospital cooling. The AHA cites studies that have small populations or do not look for anything such as outcomes, only to see if it dropped the temperature.

      There really are several issues at stake here.
      Is the actual cooling component of therapeutic hypothermia beneficial or is the benefit derived from simply not letting people get too hot ( febrile ) ? Has there been a study of TH vs enforced normo-thermia?

      how should patients be cooled? Are all methods equal? Are chilled fluids the BEST method, especially pre-hospital? ( hint: no)

      If you have not read the Targeted Temperature Management study, stop right now and go read it:
      http://www.nejm.org/doi/full/10.1056/NEJMoa1310519
      It may be a game changer, then again it may not be.

      • Brian,

        Thanks for your input. I have a few questions…please tell us where the AHA recommended chilled saline as an adjunct. Not sure where that is coming from. The AHA typically does not recommend a product or method. It would help the community to know what you are referring to.

        • The AHA does not specifically recommend any one method of cooling over another… From part 9:

          “Although there are multiple methods for inducing hypothermia, no single method has proved to be optimal. Feedback-controlled endovascular catheters and surface cooling devices are available.47–49 Other techniques (eg, cooling blankets and frequent application of ice bags) are readily available and effective but may require more labor and closer monitoring. As an adjunct, iced isotonic fluid can be infused to initiate core cooling but must be combined with a follow-up method for maintenance of hypothermia.50–52”. – http://circ.ahajournals.org/content/122/18_suppl_3/S768.full

          So the AHA is pretty vague on how or even when to do it? When the guidelines were written this was possibly the best answer. Now it appears that chilled fluids have some evidence of worse outcomes than other methods of inducing hypothermia.

          I don’t want to steal roguemedics thunder on this but …..http://jama.jamanetwork.com/article.aspx?articleid=1778673

  4. Do you have any knowledge of whether this was controlled for the mental state of the pt. arriving at the hospital? For example, does it simply matter that TH be initiated before return of consciousness? Before intensive thinking? I’m comparing this to some of the recovery used for TBI and wondering if there are any correlations.

    • Garrett,

      Do you have any knowledge of whether this was controlled for the mental state of the pt. arriving at the hospital? For example, does it simply matter that TH be initiated before return of consciousness? Before intensive thinking? I’m comparing this to some of the recovery used for TBI and wondering if there are any correlations.

      These are the criteria listed in the study.

      Patients were eligible for enrollment if they were assessed by paramedics as having all the following: OHCA with an initial cardiac rhythm of VF, return of spontaneous circulation, systolic blood pressure >90 mm Hg, cardiac arrest time >10 minutes, age ≥15 years, and intravenous access available. Patients were excluded if they were not intubated, were dependent on others for activities of daily living before the cardiac arrest event, were already hypothermic (temperature <34°C), or were women who were obviously pregnant.

      http://circ.ahajournals.org/content/122/7/737.full

      I would expect that patients who woke up would not be sedated and treated, but these appear to be limited to patients who have been pulseless for more than 10 minutes, so waking up quickly is not likely.

      There does not appear to be an attempt to awaken the patients at all to assess for level of consciousness, since this would be counterproductive.

      The neurological outcomes were excellent in both groups.

      Only one patient was discharged to a nursing home and that comatose patient was not in the EMS cooling group.

      http://circ.ahajournals.org/content/122/7/737/T3.expansion.html

      Most outcomes of cardiac arrest studies show greater percentages of patients with severe neurological disabilities.

      .

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