Therapeutic hypothermia:

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www.resuscitation-research.org
  Therapeutic hypothermia Who, when and
how to cool?
Kjetil Sunde Ulleval University Hospital
Oslo, Norway
COI No conflicts
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What is the optimal treatment after ROSC?

• Early decision if active treatment. Consider
  anoxia time, time
• to ROSC, cause of arrest, general condition,
  ethical aspects

- if awake, adequate keep them awake!
- if comatose early optimization of
hemodynamics and oxygenation and focus on
optimal vital organ perfusion ? goaldirected,
standardized intensive care treatment
with mechanical ventilation

• Treat the cause of arrest as early as possible
• - revascularization if indicated (the majority
  have CHD)

• As early as possible therapeutic hypothermia
• - fast induction, steady and stable maintenance
• - slow, controlled rewarming

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So, I would rephrase the question Who, when,
and how should we treat actively after primary
succesful resuscitation after cardiac arrest?

• get the patient to the right place
• with the right people and a standardized
• post resuscitation care protocol!

? independent of initial rhythm........!!!!!!
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Post cardiac arrest syndrome a reperfusion
injury!

• primary (before CPR) and secondary ischemic
  damage (during CPR/after ROSC)

Apoptosis
Coagulation-disorder, microcirculation ?
Inflammation, Ca-changes, blood-brain barrier,
lipid peroxidation
- free radicals
(Lactate production)
M.G. Angelos et al Academic Emergency Medicine
2001, 8909
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Hypothermia physiological effects
Awake patients Tp 30-35 ?C generate heath,
shivering, periph. vasoconstr.,
muscle activity ?, oxygen demand ?,
metabolism ?

• physiological effects to increase the
  temperature!

Tp lt 30 ?C shivering ?, metabolism ?,
increased risks for
arrhythmias cardiac arrest
Tp 30 - 31 ?C reduced consciousness, coma
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Hypothermia physiological effects
Controlled therapeutic hypothermia
Metabolic effects 30-35 ?C Oxygen demand
CO2 production ?
Metabolism ?
Cardiovascular effects 36-35 ?C
Tachycardia lt 35 ?C Bradycardia lt 35 ?C
May slightly increase BP, but coma, heavy
sedation and
myocard-dysfunction reduce
BP.................and CO and CI ? with TH lt 32
?C Mild arrhythmias in some patients lt
33 ?C EKG-changes increased PR-and
QT-intervall, wider
QRS-complex 28-30 ?C Increased risk for
tachyarrhythmias, starts
frequently with atrial fibrillation
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Hypothermia physiological effects
Renale effects lt 35 ?C Diuresis ?,
tubular dysfunction
Hematological effects lt 35 ?C Blood
plates and white blood cells ?,
reduced function
Electrolyts/blood sugar lt 35 ?C OBS
electrolyte (Potassium, Phosphate, Mg, Ca)
and blood sugar disorders!
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Optimal treatment during reperfusion with mild
therapeutic hypothermia
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Results UUH from 1.9.03 25.06.07
All patients treated after OHCA at Ulleval
University Hospital with cardiac Etiology
180 patients admitted to ICU

• 56 of all patients survive with favourable
  outcome

• 94 of all survivors have a neurological
  favourable
• outcome

? similar data from Stavanger, Lausanne, Lund,
Uppsala, Helsingborg, Copenhagen, Wienna,
Ljublana, University Hospital Ambroise
Paré.....
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Therapeutic hypothermia for revived non-VF
cardiac arrests at UUH, Oslo

• The same standardized treatment protocol, n58

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Prognostication in cooled patients

• Confirmed by others
• Sunde et al 2007
• Hovdenes et al 2007
• Skulec et al 2008

Oddo et al, Crit Care Med, in press
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Hypothermia Network (2004-07) n 1108 patients
Outcome (6-months) for TH treated group
according to initial rhythm, n931
Quality of CPR!

• 101 patients with a time to ROSC
• of more than 40 minutes (range 40-240 min)
• with an overall good outcome of 27 .

Nielsen et al, Abstract Resuscitation
2008, Ghent
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Prognostic factors

• Clinical signs

- persisting coma after discontinuation of
sedatives - no signs of breathing - absence
of pupillary light reflexes, corneal reflexes
- seizures - no motor responce to pain
? no clinical absolute predictive signs the
first two days after the arrest!
Edgren et al, Lancet 1993
? Madl et el, Crit Care Med 2000 experienced
physicians agreed correctly in only 52 of
the patients after
reviewing clinical data
24 hrs post arrest
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Hypothermia Network (2004-07), TH in children
(n14)

• median of 15 years (range 3-17),
• out of hospital arrests, 10 witnessed,
• VT/VF 6, asystole 6, PEA 2
• time from cardiac arrest to CPR 8 minutes
• time to ROSC 18.5 minutes.
• the first registered core temperature on
  admission was 34.5 ?C.

• at follow-up after six months CPC 1
  10 (71)
• 
  CPC 5 (dead) 4
• five of the survivors (all CPC 1) had initial
  asystole/PEA

Nielsen et al, Abstract Resuscitation
2008, Ghent
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TH and newborn-asphyxia
Shankaran S et al. Whole-body TH N Engl J Med.
2005 3531574 -1584.
Gluckman PD et al. Selective head cooling Lancet
2005 365663 - 670

• Further trials to determine the appropriate
  method, including comparison
• of whole body with selective head cooling
  with mild systemic hypothermia,
• are required.

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Future!

• We do not know
• The optimal target temperature (32-37 C/h) ?

• Duration 12 h 24h - 48 h 72h?

• Rewarming how fast? 0.3 - 0.5 C/h?

• Methods of cooling?
• ? Internal vs external cooling ?
• ? Fast vs late ?
• ? Intra arrest cooling vs post ROSC cooling ?
• ? Selective head cooling vs total body cooling?
  
• Or combination, perhaps fast head cooling
  during CPR,
• followed by total body cooling ?

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Main challenge Implementation

• Carefully plan a well-defined implementation
  plan
• chaired by a charismatic strong
• leader with accessibility
• and skills to change

- identify and beat the barriers!

• define and select important
• collaborators from different
• fields (doctors, nurses)

- financial and institutional support
- a continuous process evaluation with feedback
and research
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Therapeutic hypothermia must be part of our daily
life activities....
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But TH cant, unfortunately, solve everything....