Ruchika Husa, MD

OSU Wexner Medical Center

SCD and Therapeutic SCD and Therapeutic HypothermiaHypothermia

2

Clinical Vignette

• Young female found down by coworker in the UCSD temporary office building.

• No bystander CPR upon code teams arrival.

• pulseless, non-responsive.

2

00:45

Shock 1

02:45

Shock 2

05:30

Shock 3

08:30

Shock 4

10:30

Shock 5

11:45

Shock 6

ROSC

Intubation

4

Post Resuscitation

• Cooled. Full neurologic recovery.

• No baseline ECG abnormalities.

• Cardiac MRI without anatomic abnormalities.

• ICD and discharge after 12 days.

4

Objectives

• Evidence behind therapeutic hypothermia

• Patient selection

• Methods of cooling

• Timing of cooling

• Degree of hypothermia

• Duration of hypothermia

Why should we cool?

7

Reperfusion Injury

300 10 20

Reperfusion

Ischemia

• Reperfusion injury

• Necrosis/apoptosis

• Inflammation

• Reactive oxygen species

• Improved defibrillation

• B-blocker effect?

Why should we cool?

10

Historic perspective

• Open heart surgeries: moderate hypothermia (28C to 32C) used since the 1950s to protect the brain during intra-op global ischemia.

• Successful use of hypothermia after SCD described in 1950s but subsequently abandoned due to lack of evidence.

10

11

Cont.

• Guideline 2000 for CPR and Emergency Cardiovascular care did not include therapeutic hypothermia after arrest.

• In 2002 the results of 2 prospective randomized trials lead to addition of this recommendation to the guidelines.

11

Why should we cool?

13

• Entry criteria: witnessed cardiac arrest with first resuscitation attempt 5-15 min after collapse, ROSC (<60 from collapse), persistent coma, VF.

• Exclusion criteria: severe cardiogenic shock, hypotension (SBP <90mmHg), persistent arrhythmias, primary coagulopathy.

• Approximately 92% of screened participants were excluded.

14

• In European study, patients were cooled using a special mattress and ice packs. Target temp 32℃ to 34℃ for 24 hours. Rewarming over 8 hours.

• Australian study used cold packs in the field. Target temp 33℃ for 12 hours. Rewarming over 6 hours.

PROTOCOL

Hypothermia After Cardiac Arrest Study Group (2002) NEJM

Why should we cool?

16

OUTCOME NORMOTHERMIA HYPOTHERMIA RISK RATIO (95% CI)* P VALUE†

no./total no. (%)

• Favorable neurologic 54/137 (39) 75/136 (55) 1.40 (1.08–1.81) 0.009

outcome

• Death 6/138 (55) 56/137 (41) 0.74 (0.58–0.95) 0.02

16

NEUROLOGIC OUTCOME AND MORTALITY AT SIX MONTHS

17

ALS Task Force recommendation in 2002• Unconscious adult patients with

spontaneous circulation after out-of-hospital cardiac arrest should be cooled to 32℃ to 34℃ for 12-24 hours when initial rhythm was ventricular fibrillation.

• Such cooling may be beneficial for other rhythms or in-hospital cardiac arrest.

Why should we cool?

• Cooling

• Emergency PCI

• Good ICU care

• Rehab?

Post-Arrest Care

Post-Arrest Care

Sunde (2007) Resuscitation

21

Prognostic factors affecting survival with favorable outcomes

Prognostic factors Adjusted odds ratio 95% CI

Intervention period 4.47 1.60—12.52

Age >70 0.48 0.17—1.37

Time to ROSC 0.91 0.85—0.96

Ambulance response time 0.91 0.78—1.07

Initial VF 1.84 0.33—10.41

Post-Arrest Care

• Does post-arrest cooling in the field really make that much difference?

• Should we be cooling during arrest?

• Does cooling distract from other tasks?

• Are there patients with complications from cooling that cannot be identified in the field?

Prehospital Cooling Issues

• Cellular approach

• Pre-treatment

• Necrosis/apoptosis

• Inflammation/ROS

• Pragmatic approach

• Intra-arrest

• Prehospital ROSC

• ED

• ICU

When should we cool?

When should we cool?

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

Necrosis

Apoptosis

Days

When should we cool?

Hypothermia After Cardiac Arrest Study Group (2002) NEJM

When should we cool?

Abella (2004) Circulation

When should we cool?

Kuboyama (1993) Crit Care Med

When should we cool?

Nozari (2006) Circulation

When should we cool?

Nozari (2006) Circulation

Prehospital Hypothermia

Prehospital Hypothermia

Kim (2007) Circulation

Prehospital Hypothermia

Kim (2007) Circulation

• All arrest victims?

• Brain doesn’t know the rhythm

• Only ventricular fibrillation?

• Evidence-based approach

• Non-VF patients?

• Infection

• CHF

• Bleeding

Who should we cool?

35

Mild therapeutic hypothermia is associated with favourable outcome in patients after cardiac arrest with non-shockable rhythms

Resuscitation - September 2011

- Retrospective analysis of adult cardiac arrest survivors suffering a witnessed out-of-hospital cardiac arrest with asystole or pulseless electric activity as the first documented rhythm.

- Patients who were treated with mild therapeutic hypothermia were more likely to have good neurological outcomes, odds ratio of 1.84 (95% confidence interval: 1.08–3.13).

- Mortality was significantly lower in the hypothermia group (odds ratio: 0.56; 95% confidence interval: 0.34–0.93).

36

Resuscitation - February 2012

Does therapeutic hypothermia benefit adult cardiac arrest patients presenting with non-shockable initial rhythms?: A systematic review and meta-analysis of randomized and non-randomized studies.

• TH is associated with reduced in-hospital mortality for adults patients resuscitated from non-shockable CA.

• However, most of the studies had substantial risks of bias and quality of evidence was very low.

• Further high quality randomized clinical trials would confirm the actual benefit of TH in this population.

36

Recent trial

37

Trial design• Randomized 950 unconscious adults after out-

of-hospital cardiac arrest of presumed cardiac cause (irrespective of initial rhythm) to targeted temperature management at either 33°C or 36°C.

• The primary outcome was all-cause mortality through the end of the trial.

• Secondary outcomes included a composite of poor neurologic function or death at 180 days

38

Body Temperature during the Intervention Period.

Nielsen N et al. N Engl J Med 2013;369:2197-2206.

Probability of Survival through the End of the Trial.

Nielsen N et al. N Engl J Med 2013;369:2197-2206.

Results

41

Complications of Hypothermia

• Coagulopathy

• Overshoot?

• Hemodynamic

• Dysrhythmias

• Infectious

• Sepsis, pneumonia

• Electrolyte disturbances

Who should we cool?

44

45

How should we cool?• Surface cooling

• Evaporative

• Ice packs/chemical

• Cooling pads

• Internal strategies

• Cooled intravenous fluids

• Intravascular catheters

• Intranasal catheters

Cooling Catheters

Surface Cooling

How cold?

• Official recommendations

• Target temp 32-34o C

• ? 36◦C

• Threshold for effect?

• Adverse effects?

• Really cold?

• Different mechanisms

50

Deep Hypothermia

20 min Circulatory

Arrest

Deep Hypothermia

How long?

• Official recommendations

• Inflammatory pattern

• Peak at 72 hours

• Customized

• Depth and duration

How long?

55

Assessing neurologic recovery

• New thoughts on longer waiting time prior to withdrawal of care.

55

• OOHCA with ROSC

• Iced saline in EMS or ED

• Cooling catheter surface cooling with pads

• Median time from ED arrival to initiation of hypothermia < 30min

• Bladder temp probe

• Avoid shivering

• Aggressively control hyperthermia (fever) post rewarming.

Suggested protocol

57

58

59

60

61

Parting Thoughts

• More patients should be closely monitored for hyperthermia

• The complications of hypothermia should be anticipated, not avoided

• Future research may help clarify the optimal “dose” and duration of hypothermia