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