The post-arrest TTM Trial:
how do we interpret it, and
where to go from here?
Benjamin S. Abella, MD, MPhil
Clinical Research Director
Center for Resuscitation Science
Department of Emergency Medicine
University of Pennsylvania
Penn post-arrest care program – 11/2013
The TTM Trial – Nielsen et al
Nov 2013
Some disclaimers
The purpose of this short lecture:
To provide interpretation of the recent TTM trial
To hopefully offer some guidance to health care providersWho treat patients after cardiac arrest resuscitation
Disclaimers
1. This slide set does not reflect official opinions of the American Heart Association, or any other guidelines process or organization
2. This slide set reflects the opinions of scholars in the field of resuscitation science
3. This slide set is crafted based on the best knowledge and evidence present in November, 2013
Disclaimers
Importance of post-arrest care
>80%
mortality
~50% neurologic
injury
Post-arrest TTM significantly reduces mortality and injury
cardiac
arrest
~300,000
hospital
discharge
~60,000
long-term
recovery
~30,000
39
38
37
36
Bladder temperature, oC
Temperature dynamics of TTM
Cooling (8-12 hr) Rewarming (24 hr)
Cold (24 hr)
35
34
33
32Bladder temperature,
Time in hours
0 6 12 18 24 28 32 36 40
no cooling
33oC
0 10 20 30 40 50 60 % survival
36%
53%
no cooling 26%
Making sense of the post-arrest trials
HACA
Bernard How canthis be?
% survival
33oC 49%
36oC
33oC
52%
50%
TTM
How canthis be?
Marked differences in “control” group
Nielsen et al HACA study
~37.6oC
~36.0oC ~36.0oC
Bernard et al: ~37.3oC
Large difference in maintenance temperatures
Most important point … and a warning
Current work does not test the same
hypothesis as the HACA, Bernard trials
36oC arm in the trial is still active
management of temperature
Interpreting the evidence: a hypothesis
severe Mild / nonemoderate
Degree of post-arrest injury
Poor outcome
with any TTM
Good outcome
with any TTM
dose of TTM
(33oC v 36oC, e.g.)
affects outcome
Rationale for our TTM approach
Given that:
(1) TTM trial was neutral (no differences in benefit or harms)
(2) Cooling to 33oC is based on extensive laboratory evidence and two RCTs (HACA, 2002; Bernard et al, 2002)and two RCTs (HACA, 2002; Bernard et al, 2002)
(3) We can’t tell who will have significant post-arrest injury based on current technology and clinical factors
(4) the chance to modify neurologic injury is in the acute care ofpost-arrest patients – and we don’t get a second chance
Our recommended approach – Part I
Therefore:
it is reasonable to not change current practice based on the TTM trial, but rather continue to treat comatose post-arrest patients with a TTM goal temperature of 33oC.
However, the TTM trial provides evidence that a more flexible However, the TTM trial provides evidence that a more flexible approach is possible – for patients intolerant of 33oC (marked bradycardia, increased bleeding, marked QT prolongation, e.g.) or for patients that clinicians feel uncomfortable with treating to 33oC for other clinical factors, it is acceptable to treat with higher TTM temperature goals, up to 36oC.
Our recommended approach – Part II
ALL comatose post-arrest patients should at least receive TTM with a maximum temp goal of 36oC – “normothermia” as defined by lack of any temperature control is not supported by the growing body of literature.
In addition to TTM management in the acute phase (12-24 hours of either 33oC or 36oC TTM), all post arrest patients should receive comprehensive best-practice post arrest care, including aggressive avoidance of fever for up to 48-72 hours following rewarming and avoidance of care withdrawal for at least 72 hours post arrest, as supported in the current AHA guidelines and the TTM trial.
Many knowledge gaps remain
Great need for additional clinical trials
in post-arrest care and TTM:
Duration of post-arrest TTM?
Depth of post-arrest TTM for select patients?Depth of post-arrest TTM for select patients?
Optimal injury measurement post-arrest?
Pharmacologic adjuncts to TTM?
Early versus late post-arrest cardiac cath?
For more information
For more information and resources on
TTM, visit our hypothermia resource pages:
https://www.med.upenn.edu/resuscitation/hypothermia/index.shtml