Cardiac arrest temperature management

[sluggs]

After the article in NEJM from June 17, "Hypothermia vs Normothermia..." is there anything left for holding a patient's post-arrest temperature to 32-34 or 36 post arrest?
So much has evolved since the initial 32-34 study, including the 36 study, some data showing no benefit to cooling in-hospital arrest, then Hyperion. Now we have this!
What should practice be now? Cool patients under 65 years of age who have had shockable arresting rhythms? Just top patients out at normothermia until they declare themselves? Anybody have good explanations for the disparities in results or think that they are not disparities?
I have been following this forever, and trying to guide institutions to "best practices", but it seems like the nihilists carry the day now!?!?
Some thoughts?

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[SurfingDoctor]

We do targeted temps, ie don’t let the patients be febrile. Typically it’s just cooling blankets and ice packs. I’ve never felt inclined to give chilled IVF outside of heat stroke.

I will say, I don’t try to actively warm patients with CA who come in hypothermic, just a gradual normothermia.

But then again, the data in pediatrics was always equivocal for out of hospital CA, so the therapeutic hypothermia never really caught on (outside of the neonates).

We also have the same normothermic goal for in hospital CA. There has been a significant push for ECPR, and they never get cooled. They also typically die or have a poor outcome anyway though, excluding the CVICU were the outcomes are slightly better.

 

[Siggy]

We recently had an email discussion among the attendings at one of my sites in regards to TTM goals. Here was my overall thoughts on the current situation:



General post arrest care thoughts:

• I think any focus on mortality with TTM is misplaced. The goal with post arrest care should be improved outcome (modified Rankin score/neurologically intact discharge) instead of improved mortality. I don't necessarily think we do anyone any favors with trach/peg/LTAC outcomes. However when it comes to studies, mortality is an easy button outcome.
• It's often impossible to guess outcomes early on. In my brief experience, too many people want to throw in the towel on post arrest patients too early. I've seen "extended downtime" (how much should we trust downtime reports that have gone through multiple people) have good outcomes and extremely brief arrests have poor outcomes. Of course pre-arrest status matters and most patients will do poorly, but I think it's worth the effort to try to salvage the rare salvageable patient.
• Expanding on the above, official AHA/ECC recommendation is no prognosis for 72 hours after arrest or 72 hours after the completion of a 33 degree C TTM run (class of evidence 2a benefit >>risk, LOE 2-NR (moderate quality, non-randomized).
• AHA/ECC also recommends against using myoclonic jerks for prognostication (class of evidence 3: risks >benefit, LOE 2-NR) (I'm definitely guilty of this).
• So the question becomes "Who is salvageable, and when do we know that they're salvageable?" Given that the period of maximum recovery is about 3-6 months post arrest, I don't feel comfortable trying to prognosticate an outcome 2 hours post arrest short of poor pre-arrest function OR significant imaging findings.

So... thoughts on TTM:

• Older studies show benefit, more recent larger, more robust studies seem to show no difference for 33 vs 37 degrees C.
• I agree that likely the benefit is avoiding fever more so than inducing hypothermia
• EMCrit/IBCC recommends scheduled APAP, however given the amount of ischemic hepatitis, I'm concerned about adding insult to injury. Maybe Ofirmev would be better (given lack of first pass metabolism), but cost would be an issue.
• The benefit of TTM, regardless of temp goal, is that it is a proactive management strategy rather than a reactive strategy.
• If we forego starting TTM on everyone post arrest, then we need to be aggressive at starting it if the temperature starts to go up. Similarly, we should be using continuous core temperature monitoring on all post arrest patients regardless of whether we're actively cooling them or not.

EMCrit/IBCC editorial on post arrest TTM: Post-cardiac arrest management Recommends against 33 degrees C. Recommends aggressive anti fever measures including empiric, scheduled APAP dosing.

Effects of in-hospital low targeted temperature after out of hospital cardiac arrest: A systematic review with meta-analysis of randomized clinical trials. 2015: Effects of in-hospital low targeted temperature after out of hospital cardiac arrest: A systematic review with meta-analysis of randomized clinical trials - PubMed. 6 studies, 1,418 patients. Low T was associated with good neurologic performance at hospital discharge compared with in-hospital high or not targeted temperature.

Targeted Temperature Management at 33 Versus 36 Degrees: A Retrospective Cohort Study (2020): Targeted Temperature Management at 33 Versus 36 Degrees: A Retrospective Cohort Study - PubMed. Single center urban hospital, before/after analysis. 782 patients. No mortality difference, however improved neuro intact discharge level with 33 degrees. odds ratio, 1.79; 95% CI, 1.09-2.94

TTM 1 (2013): Targeted temperature management at 33°C versus 36°C after cardiac arrest - PubMed 36 hospitals, Europe and Australia, 939 patients, no change in outcome. hazard ratio with a temperature of 33°C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51

TTM 2 (2021): (other attending's initial email) 1,850 patients, international multicenter trial, no change in outcome. Improvement in mRS: 1.00; 95% CI, 0.92 to 1.09

 

[Radetzky]

The early trials were small and underpowered and everyone jumped on the bandwagon because it seemed to make some physiological sense (eg cold water drowning having good outcomes). I’m not aware of any robust studies that have ever showed benefit. The same pattern occurs over and over again. Early enthusiasm due to poor statistics, followed by a dose of reality.

 

[vector2]

TTM2 is methodologically strong and essentially definitive. I think it's silly to do anything other than fever avoidance after their trial results were released.

 

[bigdan]

Vector -

I know we’ll never get a study in this patient cohort that checks all the boxes to exactly match our patient groups...but the TTM2 patients had 80% bystander CPR. And like 40% of the patients had STEMI. Most of our OHCA are “found down” and rarely get a sniff at the Cath Lab.

There are a few holdouts in the TTM world that are urging some discretion before declaring hypothermia dead. I will continue to cool for the prolonged no-flow/low-flow cases.

 

[Hamhock]

• EMCrit/IBCC recommends scheduled APAP, however given the amount of ischemic hepatitis, I'm concerned about adding insult to injury. Maybe Ofirmev would be better (given lack of first pass metabolism), but cost would be an issue.

Siggy - great post to share. Here's a small nitpick that I am a bit hesitant to post. The cost of Ofirmev relative to enteral acetaminophen shouldn't enter into this discussion. It's like avoiding isolyte in septic shock (in favor of abnormal saline) due to cost.
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SDN - I still "cool" to 36 for the same reason I often tell the nurses the MAP floor is 70 or 75. When the floor is 70, I often see MAPs as low as 67. When the floor is 65, I often see MAPs of 58 for too long.

I also keep my TTM device 'ordered' for more than the 'cooling' period. Without great evidence, I admit, I feel that fever hurts neurologic outcome.

HH

 

[Siggy]

Siggy - great post to share. Here's a small nitpick that I am a bit hesitant to post. The cost of Ofirmev relative to enteral acetaminophen shouldn't enter into this discussion. It's like avoiding isolyte in septic shock (in favor of abnormal saline) due to cost.
---------------------
SDN - I still "cool" to 36 for the same reason I often tell the nurses the MAP floor is 70 or 75. When the floor is 70, I often see MAPs as low as 67. When the floor is 65, I often see MAPs of 58 for too long.

I also keep my TTM device 'ordered' for more than the 'cooling' period. Without great evidence, I admit, I feel that fever hurts neurologic outcome.

HH

While I would agree, I'm still having to sacrifice my first born (or write a clear justification in the order) for pharmacy to approve Ofirmev. It doesn't matter how much I want to order something if I can't get it past the pharmacist.

Now if I can just get them to approve Olumient for SARS-CoV-2 because of the ACT-II, COV-Barrier, and the updated NIH guidance. It's sad when pharmacists put dollars above patients lives.

 

[vector2]

Vector -

I know we’ll never get a study in this patient cohort that checks all the boxes to exactly match our patient groups...but the TTM2 patients had 80% bystander CPR. And like 40% of the patients had STEMI. Most of our OHCA are “found down” and rarely get a sniff at the Cath Lab.

There are a few holdouts in the TTM world that are urging some discretion before declaring hypothermia dead. I will continue to cool for the prolonged no-flow/low-flow cases.

Indeed, I think we need to make sure we keep in mind TTM2 inclusion and exclusion criteria and their cohort characteristics before we generalize the findings to literally every cardiac arrest we run across regardless of that individual pt's clinical picture

"

Population​

• Inclusion:
  • Out-of-hospital cardiac arrest of presumed cardiac or unknown cause
  • Sustained ROSC: >20 minutes of circulation without need for chest compressions
  • Unconscious: as defined by the FOUR score motor response <4 and not able to obey verbal command
  • No limitations to management in place
  • Inclusion must be no later than 180 minutes after ROSC
• Exclusion:
  • Unwitnessed cardiac arrest with initial rhythm asystole
  • Temperature on admission < 30°C
  • On ECMO prior to ROSC
  • Suspected pregnancy
  • Intracranial bleed
  • Severe COPD with long-term home O2

"

 

[Radetzky]

Ok, but what was the evidence that cooling is beneficial in the first place? A few statistically problematic and underpowered trials. It’s not reversing something if there’s no solid evidence to begin with

 

[Siggy]

Ok, but what was the evidence that cooling is beneficial in the first place? A few statistically problematic and underpowered trials. It’s not reversing something if there’s no solid evidence to begin with

There are a lot of things that are standard of care with no solid evidence behind it. See spinal immbolization and kayexalate.