1. Dr Lee Wai Chuen Raymond A/C ICU TMH
Joint Anesthesia/ ICU meeting Post cardiac arrest syndrome & Therapeutic hypothermia
Dr Lee Wai Chuen Raymond
A/C ICU TMH

2. Introduction
70% of patients successfully resuscitated die before hospital discharge

3. Introduction main causes of death: irreversible neurological injury
uncontrollable cardiovascular failure
Severe multiple organ dysfunction syndrome

4. Introduction
Dr. Vladimir Negovsky first described a systemic ‘‘post-resuscitation syndrome’’ (Negovsky VA. The second step in resuscitation—–the treatment of the ‘post-resuscitation disease’. Resuscitation. 1972;1:1—7)
“Post-resuscitation” implies end of resuscitation, a new term post-cardiac arrest syndrome is suggested

5. post-cardiac arrest syndrome
Organ injury by
ischaemia & hypoxia during cardiac arrest
reperfusion injury after ROSC
trigger a SIRS or sepsis-like syndrome
unregulated leukocyte production of cytokines
high levels of circulating cytokines, adhesion molecules, plasma endotoxin

6. Early postarrest phase
early interventions might be most effective
intermediate phase
injury pathways are still active
aggressive treatment is typically instituted
Recovery phase
prognostication becomes more reliable
Ultimate outcomes are more predictable

7. post-cardiac arrest syndrome
4 components:
(1) postarrest brain dysfunction
(2) postarrest myocardial dysfunction
(3) systemic ischemia/reperfusion response
(4) Persistent precipitating pathology
individual components are potentially treatable

8. post-cardiac arrest syndrome
Treatment of the global ischaemic brain damage and the dysfunctional heart during the reperfusion phase is the main challenge
The first intervention proved to be clinically effective is therapeutic hypothermia

9. Post resuscitation care
1. Optimising physiology
Body temperature
Blood pressure
Blood glucose
Acid-base status
Electrolytes (potassium)
2. Revascularisation
Thrombolysis
PTCA
CABG
3. Antiarrhythmic therapy
ICD
Beta blockers
Amiodarone
4. Anticonvulsant therapy

10. postarrest brain dysfunction

11. postarrest brain dysfunction
unique vulnerability of the brain
limited tolerance of ischaemia
Unique response to reperfusion
in the hippocampus, cortex, cerebellum, corpus striatum, and thalamus degenerate over hours to days

12. Hypoxic brain injury
Without blood flow, cerebral tissue oxygen tension declines continuously reaching 0 after 2 min
Neuronal energy(ATP) is depleted
Dysfunction of the cell membrane ion pumps → accumulation of calcium in cytosol
Release of excitatory amino acid
ischemia persists, neuronal necrosis throughout the brain
Permanent neurological injury occurs after 5 to 10 mins of no cerebral blood flow state

13. postarrest brain dysfunction
initial reperfusion phase in the first few minutes
often hyperaemic
elevated CPP and impaired autoregulation
Hypertension (MAP >100 mmHg) in the first 5 min after ROSC was not associated with improved neurological outcome
exacerbate brain oedema & reperfusion injury
too much oxygen exacerbate neuronal injury
production of free radicals & mitochondrial injury

14. postarrest brain dysfunction
delayed hypoperfusion in hours to days
hypotension, hypoxaemia, impaired cerebrovascular autoregulation, brain oedema
MAP during the first 2 h after ROSC was positively correlated with neurological outcome
cerebral perfusion varies with CPP instead of being linked to neuronal activity
CPP necessary to maintain optimal cerebral perfusion will vary among individual post-cardiac arrest patients at various time points after ROSC

15. postarrest brain dysfunction
failure of cerebral microcirculatory reperfusion despite adequate CPP (no- reflow phenomenon)
Fixed and/or dynamic no reflow
intravascular thrombosis during cardiac arrest
edema of endothelium, blood cell sludging, leukocyte adhesion
persistent ischaemia & small infarctions
? responsive to thrombolytic therapy
Thrombolysis in Cardiac Arrest (TROICA) trial, tenectaplase did not increase 30-day survival

16. postarrest brain dysfunction
Cerebral edema
limited evidence that brain oedema or elevated ICP directly exacerbates post-cardiac arrest brain injury
early transient brain oedema
rarely associated with clinically relevant increases in ICP
delayed brain oedema, days to weeks after cardiac arrest
due to delayed hyperaemia
likely the consequence of severe ischaemic neurodegeneration

17. postarrest brain dysfunction
Pyrexia
T >39 ◦C in first 72 h post cardiac arrest increased risk of brain death
T >37.8 ◦C was associated with increased in- hospital mortality
Unfavorable outcome increased for every degree Celsius that the peak temperature > 37◦C.
Hyperglycaemia
seizures

18. postarrest brain dysfunction
Management:
avoided hyperventilation: normocarbia
Maintain oxygen saturation 94—98%
hypoxaemia is harmful
hyperoxia ass with worse neurological outcome
production of free radicals & mitochondrial injury
Anticonvulsants: no evidence to support prophylactic anticonvulsant
control of glucose: normoglycaemia

19. Therapeutic hypothermia

20. Therapeutic hypothermia
The Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002;346:549—56
portion of patients with favorable neurological outcome increased by 40%

21. Therapeutic hypothermia
The Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002;346:549—56
mortality
reduced by
26%

22. Therapeutic hypothermia
The Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002;346:549—56
included a small subset of patients with inhospital cardiac arrest

23. Therapeutic hypothermia
Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002;346:557—63

24. Therapeutic hypothermia
Holzer M, Bernard SA, Hachimi-Idrissi S, Roine RO, Sterz F Mu¨ llner M. Hypothermia for neuroprotection after cardiac arrest: systematic review and individual patient data metaanalysis. Crit Care Med 2005;33:414–8
NNT to allow one additional patient with no or only minimal neurological damage is 6

25. Therapeutic hypothermia
Arrich, HolzerM, HerknerH, MüllnerM. Hypothermia for neuroprotection in adults after cardiopulmonary resuscitation. Cochrane Database of Systematic Reviews 2009, Issue 4
patients in the hypothermia group
more likely to reach a best cerebral performance categories score of one or two during hospital stay (RR, 1.55; 95% CI 1.22 to 1.96)
more likely to survive to hospital discharge (RR, 1.35; 95%CI 1.10 to 1.65)

26. Therapeutic hypothermia
growing amount of data from nonrandomized studies reported benefit in comatose survivors of out-of-hospital non-VF arrest and all rhythm arrests

28. Therapeutic hypothermia
therapeutic hypothermia has become more feasible and minimal side effects, it is widely used in the management of anoxic neurological injury whatever the presenting cardiac rhythm and include inhospital cardiac arrest

29. Therapeutic hypothermia
Contraindications:
The patient can follow verbal commands;
More than 8 hrs have elapsed since ROSC;
life-threatening bleeding or infection
Cardiopulmonary collapse is imminent, despite vasopressor or mechanical hemodynamic support;
An underlying terminal condition exists

30. Therapeutic hypothermia
physiological effects
reduces metabolism & cerebral oxygen demands
Metabolism is reduced by 6% to 10% /°C reduction
protection of ATP stores
decrease in apoptosis via
Reduction in calcium overload and glutamate release
Attenuates oxidative stress & lipid peroxidation
direct inhibition of apoptosis
antiapoptotic protein Bcl-is enhanced
proapoptotic factor BAX is suppressed

31. Therapeutic hypothermia
physiological effects
reduction of brain edema and increase cerebral blood flow
Preservation of the blood brain barrier
inhibtion of coagulation cascades & inflammatory reactions improve cerebral reperfusion
inhibiting neutrophil infiltration31 and function
reducing lipid peroxidation and leukotriene production

33. Therapeutic hypothermia
Uncertain areas:
inhospital cardiac arrest
treatment in children
cooling characteristics
“door-to-cool” time
target temperature
cooling rate
duration of hypothermia
cooling methods (external or internal)

34. Cooling methods
Although there are great differences in efficacy and invasiveness among them, it currently not clear whether one particular technique should be preferred to the others.
No studies are available that have compared different cooling devices
the choice of the cooling method was at the physician’s discretion

35. Active surface cooling
0.9°C per hr
1.2°C per hour
Rare but serious skin complications

36. Active surface cooling
Nasopharyngeal evaporative cooling with the Rhino-Chill-device (BeneChill, Inc, San Diego, USA)
spraying a convective coolant into the nasal cavity
cooling basal brain regions
cooling rate 1.4°C per hour
out-of-hospital use

38. Active internal cooling
No preference of choice of fluid
Need muscle
paralysis to avoid shivering
cooling rate of 3.4°C per hour
Compatible with other cooling devices

39. Icy catheter & the CoolGard 3000

40. Icy catheter & the CoolGard 3000
Endovascular cooling via a closed-loop indwelling catheter inserted into the femoral vein
Icy catheter with a CoolGard 3000 system:
temperature monitor, temperature control unit, heat exchange unit, a roller pump
saline circulate through the closed catheter membranes to facilitate steady achievement and maintenance of the desired body temperature
Feedback from a bladder thermister regulates the temperature of sterile saline
providing an extra infusion port to allow for central infusions

41. Active internal cooling
rates of 0.8°C -1.2°C per hour
Limited to the hospital setting
Expensive
delays the induction of hypothermia
complications of central venous
catheterization

42. Active internal cooling
Venovenous cooling
uses a double lumen dialysis catheter inserted in the femoral vein
connected to a heat exchanger for rapid extracorporeal blood cooling
Total liquid ventilation with perflourcarbon
induce hypothermia effectively while allowing oxygenation and ventilation

43. Cooling methods
cooling with the endovascular device or any other cooling method were similar except time to cooling & rewarming rates
water circulating blankets, adherent gel pads, and the intravascular cooling device are more efficient means of induction than ice packs and cold fluids or a surface air- cooling system
intravascular cooling device was the most effective at maintaining temperature

44. Therapeutic hypothermia
3 phases:
Induction
Maintenance
Rewarming
temperature normally decreases within the first hour after ROSC

45. Therapeutic hypothermia
Rapid induction phase:
as early as possible
31% reduction of favorable neurological recovery per 1 hr delay
Active external cooling
Easy and fast
Can be given pre hospital
facilitated by concomitant neuromuscular blockade with sedation to prevent shivering

46. Therapeutic hypothermia
Controlled maintenance phase
external or internal cooling devices, with continuous temperature feedback
avoid significant temperature fluctuation
cooling blankets or pads with water-filled circulating systems
Intravascular cooling catheters
32°C-34°C for 12 to 24 hours
For asphyxia induced cardiac arrest ? Up to 72 hrs

47. Therapeutic hypothermia
Controlled rewarming/Decooling phase
optimal rate of rewarming is not known
≈ 0.25—0.5 ◦C/h or in hrs
avoid an overshoot hyperthermia
Controlled, not passive rewarming
Maintain normothermia of < 37.5°C
associated with electrolyte shifts, vasodilation, “postresuscitation” syndrome
the most challenging period of postarrest care

48. Therapeutic hypothermia
Monitoring:
Continuous Pulse Oximetry:
Peripheral cold-induced vasoconstriction, digital sensory may be inaccurate
forehead lacks sympathetic vasoconstrictive properties-> Forehead sensors

49. Therapeutic hypothermia
Monitoring:
Temperature Source:
continuous feedback to the cooling device is required to maintain the desired temperature range and avoid overcooling
Core temperatures: Esophageal temperature
most practical, very accurate and reliable
Peripheral temperature:
lag behind core temperature
Bladder temperature: depends on adequate urine output

50. therapeutic hypothermia
Complications
Shivering:
occurs between 34°C and 35.5°C
common during induction phase
Sedation, muscle relexant, Magnesium sulphate
increases SVR: reduces cardiac output
Arrhythmias:
Only occur < 31°C
bradycardia (slow AF) is most common

51. therapeutic hypothermia
Complications
Diuresis causing hypovolaemia and electrolyte abnormalities
hypophosphatemia, hypokalaemia, hypomagnesemia and hypocalcemia
Intracellular shifts of electrolyte during hypothermic and rewarming phase
Electrolytes replacement during the maintenance phase but stopped during the rewarming phase
serum amylase may increase
Hyperglycaemia

52. therapeutic hypothermia
Complications
impaired coagulation & increased bleeding
observed with temperatures ≤ 32°C
impair the immune system and increase infection rates
clearance of sedative drugs and neuromuscular blockers is reduced by up to 30%

53. therapeutic hypothermia
these complications can usually be managed by intensive care strategies
The two large randomized clinical trials did not find a significant increase in severe complications when compared with normothermia

54. THE End