Ruchika Husa, MD

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SCD and Therapeutic Hypothermia

• Ruchika Husa, MD
• OSU Wexner Medical Center

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Clinical Vignette

• Young female found down by coworker in the UCSD
  temporary office building.
• No bystander CPR upon code teams arrival.
• pulseless, non-responsive.

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Post Resuscitation

• Cooled. Full neurologic recovery.
• No baseline ECG abnormalities.
• Cardiac MRI without anatomic abnormalities.
• ICD and discharge after 12 days.

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Objectives

• Evidence behind therapeutic hypothermia
• Patient selection
• Methods of cooling
• Timing of cooling
• Degree of hypothermia
• Duration of hypothermia

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Why should we cool?
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Reperfusion Injury
Reperfusion
Ischemia
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Why should we cool?

• Reperfusion injury
• Necrosis/apoptosis
• Inflammation
• Reactive oxygen species
• Improved defibrillation
• B-blocker effect?

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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.

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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.

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Why should we cool?
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• Entry criteria witnessed cardiac arrest with
  first resuscitation attempt 5-15 min after
  collapse, ROSC (lt60 from collapse), persistent
  coma, VF.
• Exclusion criteria severe cardiogenic shock,
  hypotension (SBP lt90mmHg), persistent
  arrhythmias, primary coagulopathy.
• Approximately 92 of screened participants were
  excluded.

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PROTOCOL

• 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.

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Why should we cool?
Hypothermia After Cardiac Arrest Study Group
(2002) NEJM
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NEUROLOGIC OUTCOME AND MORTALITY AT SIX MONTHS

• OUTCOME NORMOTHERMIA
  HYPOTHERMIA RISK RATIO (95 CI) P VALUE
• 
  no./total no. ()
• Favorable neurologic 54/137 (39)
  75/136 (55) 1.40 (1.081.81) 0.009
• outcome
• Death 6/138 (55)
  56/137 (41) 0.74 (0.580.95)
  0.02

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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.

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Why should we cool?
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Post-Arrest Care

• Cooling
• Emergency PCI
• Good ICU care
• Rehab?

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Post-Arrest Care
Sunde (2007) Resuscitation
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Prognostic factors affecting survival with
favorable outcomes
Prognostic factors Adjusted odds ratio
95 CI Intervention period
4.47 1.6012.52 Age gt70
0.48
0.171.37 Time to ROSC
0.91
0.850.96 Ambulance response time 0.91
0.781.07 Initial VF
1.84
0.3310.41
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Post-Arrest Care
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Prehospital Cooling Issues

• 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?

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When should we cool?

• Cellular approach
• Pre-treatment
• Necrosis/apoptosis
• Inflammation/ROS
• Pragmatic approach
• Intra-arrest
• Prehospital ROSC
• ED
• ICU

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When should we cool?
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When should we cool?
Hypothermia After Cardiac Arrest Study Group
(2002) NEJM
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When should we cool?
Abella (2004) Circulation
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When should we cool?
Kuboyama (1993) Crit Care Med
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When should we cool?
Nozari (2006) Circulation
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When should we cool?
Nozari (2006) Circulation
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Prehospital Hypothermia
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Prehospital Hypothermia
Kim (2007) Circulation
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Prehospital Hypothermia
Kim (2007) Circulation
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Who should we cool?

• All arrest victims?
• Brain doesnt know the rhythm
• Only ventricular fibrillation?
• Evidence-based approach
• Non-VF patients?
• Infection
• CHF
• Bleeding

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Resuscitation - September 2011
Mild therapeutic hypothermia is associated with
favourable outcome in patients after cardiac
arrest with non-shockable rhythms
- 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 1.083.13). -
Mortality was significantly lower in the
hypothermia group (odds ratio 0.56 95
confidence interval 0.340.93).
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Resuscitation - February 2012Does
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.

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Recent trial
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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 33C or
  36C.
• 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

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Nielsen N et al. N Engl J Med 20133692197-2206.
Body Temperature during the Intervention Period.
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Nielsen N et al. N Engl J Med 20133692197-2206.
Probability of Survival through the End of the
Trial.
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Results
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Complications of Hypothermia

• Coagulopathy
• Overshoot?
• Hemodynamic
• Dysrhythmias
• Infectious
• Sepsis, pneumonia
• Electrolyte disturbances

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Who should we cool?
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How should we cool?

• Surface cooling
• Evaporative
• Ice packs/chemical
• Cooling pads
• Internal strategies
• Cooled intravenous fluids
• Intravascular catheters
• Intranasal catheters

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Cooling Catheters
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Surface Cooling
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How cold?

• Official recommendations
• Target temp 32-34o C
• ? 36?C
• Threshold for effect?
• Adverse effects?
• Really cold?
• Different mechanisms

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Deep Hypothermia
20 min Circulatory Arrest
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Deep Hypothermia
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How long?

• Official recommendations
• Inflammatory pattern
• Peak at 72 hours
• Customized
• Depth and duration

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How long?
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Assessing neurologic recovery

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

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Suggested protocol

• OOHCA with ROSC
• Iced saline in EMS or ED
• Cooling catheter ? surface cooling with pads
• Median time from ED arrival to initiation of
  hypothermia lt 30min
• Bladder temp probe
• Avoid shivering
• Aggressively control hyperthermia (fever) post
  rewarming.

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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