Targeted temperture management (Therapeutic hypothermia)

1. THERPEUTIC HYPOTHERMIA
DR. ASWIN R. M.

2. Introduction
Mechanism
History
Recommendations
Methods
Treatment Goals & protocols

3. TARGETED TEMPERATURE
MANAGEMENT
 Previously known as Therapeutic
hypothermia or Protective hypothermia
 Specific body temperature x specific duration of
time
 To prevent Ischemia related injury to brain
 After a cardiac arrest or other causes of ischemia
 Concept very old
 But accepted treatment only since last 15 years

4. MECHANISM OF TTM
 Cardiact arrest f/b ROSC - 2 types of brain injury
ISCHEMIC INJURY
• Depletion of glucose and ATP
• Anaerobic glycolysis
• Cells lose structural integrity
• Mitochondrial damage
• Increaesd intracellular
Calcium
• Release of excitatoxic
neurotransmitters –
glutamate , aspartate
• APOPTOSIS
REPEFUSION INJURY
• Free radicals
• Inflammatory processes
activated
• ( TNF , IL-1 & other cytokines)
• Endothelial dysfunction,
• Vasomotor dysregulation,
• Edema,
• Tissue-level hypoxia despite
adequate arterial oxygenation
• NEUROLOGICAL DAMAGE.

5. EFFECTS OF HYPOTHERMIA
 Decreases metabolic demand - 1 degree fall in temperature
decreases O2 consumption by 6%
 Attenuation and/or reversibility of ischemic depolarization of the
central nervous system (CNS)
 leading to membrane stabilization, electrolyte redistribution, and
normalization of intracellular water concentration and
intracellular pH (stabilization of the blood-brain barrier)
 Reduces release of excitatory amino acids
 Attenuation of lipid peroxidation & oxygen free radical production
 Restoration of calcium modulation
 Inhibition of deleterious signaling mechanisms, such as apoptotic
signaling
 Inhibition of deleterious inflammatory products (ie, cytokines,
interleukins, arachidonic acid cascade end products)
 Inhibition of cytoskeletal breakdown
 Decreases ICP.

6. HISTORY
 First description of cold as treatment modality -
Edwin Smith Papyrus, an ancient Egyptian
treatise on medicine and surgery ,5000 years ago
 Hippocrates advised snow and ice packing to
reduce hemorrhage in the wounded
 Total body cooling was used for tetanus
treatment in the fourth- and fifth-century
 Late 1700s, Dr James Currie Scottish physician -
first systematic experiments on humans to
determine the effects of various methods of
cooling upon body temperature, pulse, and
respiration.
 1803 - Russian method of packing in ice
 Baron de Larrey, Napoleon’s chief surgeon
observed that wounded soldiers kept closer to a
fire died faster than those who were neglected.

7. HISTORY
 Dr Temple Fay -credited with reintroducing
therapeutic hypothermia to modern day
medicine
 In his famous experiment in 1938
 Used induced hypothermia to relieve
pain from metastatic breast cancer
(32°C for 24 hours).
 Invented one of the earliest “cooling
blankets”
 Advised the same for traumatic brain
injury
 1950s - Bigelow and colleagues
documented positive physiological effects
of hypothermia on the brain during
cardiac surgery in animals
 Late 1950s to 1960 was common practice
in neurosurgical procedures

8. HISTORY
 1958 - The first clinical trial of hypothermia in the
treatment of comatose patients following cardiac arrest
was published
 50% survival for patients (6 of 12) managed with
hypothermia at 33°C compared to 14% (1 of 7) of
patients in the normothermic group
 1964 - became a part of the first published algorithm on
heart–lung resuscitation
 Advocated cooling patients within 30 minutes of the
return of spontaneous circulation if there were no
signs of central nervous system recovery.
 Further interests declined due to side effects until it
became evident that even mild hypothermia has
potential benefits
 1990s - again became common practice

9. 2002 – 2 RCTS
 In 2002 - 2 landmark RCTs were published in NEJM
by independent researchers in Europe & Australia.

10. BERNARD et al
 Melbourne
 77 Patients randomized to Hypothermia (33°C for 12 h) &
Normothermia group
 Demonstrated that 49% of hypothermia-treated patients
survived versus 26% of control patients, with odds ratio
(OR) = 5.25 in benefit of hypothermia.
THE HYPOTHERMIA AFTER CARDIAC ARREST STUDY GROUP
TRIAL (HACA TRIAL)
 9 centres in five European countries
 Demonstrated better neurological outcomes in the
treated group
 275 were randomly assigned to the hypothermia (32–
34°C for 24 h) & normothermia group
 Observed Increased recovery (55% vs 39% in the control)
as well as lower 6-month mortality (41% vs 55%).

11. In 2003
ILCOR (International Liaison Committee on Resuscitation ) endorsed
the use of targeted temperature management following cardiac arrest.

12. AHA GUIDELINES
Recommendations 2005 2010 2015
OHCA-VF/p-VT IIa Class I, LOE B Class I, LOE B
Non VF OHCA IIb Class IIb, LOE B Class I, LOE C
IHCA IIb Class IIb, LOE B Class I, LOE C
Temperature &
Duration
Strength of evidence
32-34°C
12-24 hrs
Poor
32-34°C
12-24 hrs
Poor
32-36°C
24 hrs
Class I LOE B
Active rewarming of
spontaneous mild
hypothermia (> 33°C)
Class III, LOE C Class III, LOE C Class III, LOE C

13. 2015 AHA ACLS
 Comatose (ie, lack of meaningful response to verbal
commands) adult patients with ROSC after cardiac arrest
have TTM
 Class I, LOE B for VF/pVT OHCA
 Class I, LOE C for non-VF/pVT (ie, “nonshockable”) & in-
hospital cardiac arrest).
 Selecting and maintaining a constant temperature between
32ºC and 36ºC during TTM. (Class I, LOE B)
 Specific Feature of individual patient will determine the
target tempertaure
 It is reasonable that TTM be maintained for at least 24 hours
after achieving target temperature. (Class IIa, LOE C)

14. 2015 AHA ACLS
 Recommends against the routine prehospital cooling of
patients after ROSC with rapid infusion of cold intravenous
fluids. (Class III: No Benefit, LOE A)
 It may be reasonable to actively prevent fever in comatose
patients after TTM. (Class IIb, LOE C)
 Hemodynamically stable patients with spontaneous mild
hypothermia (>33°C) after resuscitation from cardiac arrest
should not be actively rewarmed

15. AAN RECOMMENDATIONS
“Reducing brain injury after cardiopulmonary resuscitation,”
American Academy of Neurology (AAN) guideline May 10, 2017

16. IDEAL TEMPERATURE 34 VS 36 °C
 ILCOR , 2005 & 2010 AHA guielines recommended a
target temperature of 32 – 34 °C
 The 2015 guideline revised the target temperatures
of 32-36 °C, which only some institutions have
adopted so far
 This was following a large RCT in 2013 & a
subsequent meta analysis in 2015 which confirmed
the results
 In 2015 ILCOR adopted the term targeted
temperature management (TTM).

17. 2013
 950 OHCA patients
 Randomised to 33 & 36 °C
 Primary outcome – all
cause mortality
 Secondary outcome -
composite of poor
neurologic function or
death at 180 days
 Hypothermia at a targeted
temperature of 33°C did
not confer a benefit as
compared with 36°C

18. COOLING METHODS
SURFACE
INTERNAL (CORE)
COMBINATION

19. SURFACE COOLING
• ICE PACKS
• EXTERNAL
EVAPORATIVE
COOLING
• COOLING BLANKETS
• HEAT-EXCHANGE
DEVICES
• SURFACE COOLING
HELMETS
CORE COOLING
• COLD IV FLUIDS
• NASAL,GASTRIC,
PERITONEAL LAVAGE
• CATHETER BASED
TECHNIQUES
• INTERNAL
EVAPORATIVE
COOLING

20. SURFACE COOLING WITH
ICE PACKS
 Inexpensive but messy
 Appropriate way to initiate cooling.
 Less than optimal in the rate of
cooling and temperature
maintenance.
 Ice packs placed in anatomic areas
with large heat-exchange capability
(the head, neck, axillae, and groin)
 Replaced when the ice packs have
substantially melted.
 In addition to ice packs 
evaporative cooling with fans also
used.
 Average temperature drop -
moderately slow and highly variable
 0.03°0.98°Celcius per hour.

21. NEWER SURFACE
COOLING SYSTEMS
 Works by circulating cold fluid or cold air through
blankets or pads that are wrapped around the
patient
 The temperature of the circulating fluids can be
adjusted
 Cooling blankets
 Surface cooling pads
 Many of them has auto feed back mechanism to
adjust the temperature of the circulating fluids.

22. COOLING BLANKETS
 Curewrap™ with CritiCool by MTRE, Yavne, Israel
 Kool-Kit® with Blanketrol III by Cincinnati
 Sub-Zero, Cincinnati
 Conventional surface cooling blankets are also suboptimal
because of poor surface contact with the patient’s skin.
 Combination with ice packs are effective at rapidly cooling
patients and are fair at maintaining target temperature
 Once target temperature is achieved , ice packs removed &
blanket used for maintenance

23. SURFACE COOLING PADS
 Better heat exchange due to conducting gels
 Superior cooling rate than cooling blankets.
 InnerCool STX Philips ,Netherlands (non adhesive
surface pads)
 Artic Sun® by Medivance, Louisville (adhesive pads)
 EMCOOLS cooling system Vienna, Austria –
adhesive non-invasive HypoCarbon® pads with a
carbon-based cooling gel and provides cooling rates
of 3.5°C/h.

24. Artic Sun® Cooling system

25. SURFACE COOLING
ADVANTAGES
 Ease of application and rapid initiation of treatment.
 Most devices has computerized auto-feedback mechanisms -
Set target temperature and the system modifies the coolant
temperature using the feedback from patient’s skin and core
temperature sensors.
DISADVANTAGES
 Rare risk of skin burns and skin irritation
 The initiation of hypothermia varies between different
devices and can range from 2–8 hours.
 Shivering is more commonly seen with surface systems than
with other systems which may necessitate the use of muscle
relaxants & sedatives

26. SURFACE COOLING HELMET
 Contains a solution of
aqueous glycerol that
facilitates heat exchange.
 Although this method
works, it may be slower
than other methods.

27. INTERNAL(CORE) COOLING
COLD INFUSIONS
CATHETER BASED TECHNIQUES
TRANSNASAL EVAPOARTIVE COOLING

28. COLD INFUSIONS
 4°Celcius
 Saline or Ringer Lactate
 30 mL/KG (2 L)
 Given over 30-60 mins
 Temperature reduction upto
2.5°C
 Given through peripheral line
or femoral Vein.
 Not to be given by subclavian
or internal jugular vein

29. CATHETER BASED CORE COOLING
 Uses endovascular heat-exchange catheters.
 Placed into central vein (Femoral , IJV ,Subclavian)
 Heat exchange occurs between cooled saline that
passes through the heat-exchange portion of the
catheter and the blood that flows over the outer
surface of the catheter.
 2 devices currently available on the market:
 Thermoguard XP temperature management
system (Zoll)
 InnerCool RTx with Accutrol catheter (Philips).

30. Thermogaurd XP

31. CATHETER BASED CORE COOLING
ADVANTAGES
 Has computerized temperature control with an auto-feedback
mechanism.
 Faster cooling (1.46 -1.59°C/h) and precise temperature control
during all 3 stages
 Fewer incidences of failure to reach target temperature than other
systems
 Less overcooling than other systems.
 Less shivering compared to surface devices.
 Sedation & paralysis not required
DISADVANTAGES
 There was no difference in outcome when compared to surface
cooling systems
 Added risk of catheter-related bloodstream infection, venous
thrombosis and complications related to insertion of intravascular
lines

32. TRANS NASAL
EVAPORATIVE COOLING
 RhinoChill device –battery-operated device composed of a
control unit, coolant bottle and a transnasal cooling catheter
 Two 10 cm long nasal catheter prongs inserted
 Perfluro carbon coolant mixture in sprayed into the nasal cavity.
 Cerebral hypothermia is induced by
 Evaporation of coolant into skull cavity
 Conduction - Rapid cooling of skull base
 Convection - Cooling of blood in adjacent blood vessels
 The coolant that is expelled by the lungs in gas form is inert and
nontoxic.

33. TRANS NASAL
EVAPORATIVE COOLING
ADVANTAGES
 Portable & simple -Can be used by nonmedical
personnel in the field
 Rapid intiation of therapeutic hypothermia
 Continue maintaining the temperature while the
patient is actively resuscitated transported.
 Enables brain cooling even in the absence of blood
circulation.
DISADVANTAGES
 Minor – Epistaxis , Cold injury nose

34. OTHER METHODS
CRRT
 Some positive reports for continuous renal replacement therapy
(CRRT) for induction and maintenance of hypothermia
Selective brain cooling by hypothermic retrograde jugular vein flush
 Relevant in conditions where whole body hypothermia may be
detrimental.
Intrapulmonary perflurochemical fluids
 For induction and maintenance of hypothermia and also to
support gas exchange
The esophageal route
 Also being investigated,
 Because of the close proximity of the esophagus to blood flow
from the heart and great vessels

35. TTM
Patient Selection
Contraindications
Treatment Goals
Patient preparation
Stages of Procedure
Side effects & how to manage

36. INCLUDED PATIENTS
 Post cardiac arrest
 ROSC within 60 mins
 Duration of arrest <6 hrs
 Maximum down time 15 mins
 Able to maintain a systolic blood pressure >90 mm
Hg (with or without pressors)
 Patient with GCS < 3

37. CONTRAINDICATIONS
 Not maintaining MAP 65 mmHg 30 mins after ROSC
 Recent major surgery within 14 days -
 Hypothermia may increase the risk of infection and bleeding.
 Systemic infection/sepsis -
 Hypothermia may inhibit immune function and is associated with a
small increase in risk of infection.
 Coma from other causes (drug intoxication, preexisting coma
prior to arrest)
 Known bleeding diathesis or with active ongoing bleeding -
 Inappropriate for patients with DNR order
 Not recommended for an isolated respiratory arrest.
 Reccurrent arrhythmia
 Intrcranial Haemorrhage
 Frank pulmonary edema

38. 3 STAGES
INTIATION
• Intentional change from current temperature to lower
temperature
MAINTAINENCE
• Maintenance of target temperature for specific time
duration
REWARMING
• Temperature increased at a slower & specific rate to a
normothermic target

39. TREATMENT GOAL
 24 hours X 32ºC-36ºC.
 Intiate at the earliest. Each 1 hr delay - increases
mortality by 20 %.
 Achieve the target temperature as quickly as possible.
 Most cases - achieved within 3-4 hours of initiating
cooling.
 Rewarming - 24 hours after the time of initiation of
cooling (not from the time the target temperature is
achieved).
 More evidence is needed to define the optimal duration
of hypothermia treatment in humans

40. PATIENT PREPERATION
 Should be initiated in the emergency department.
 Can be continued while doing PCI.
 Continuous core Temperature measurement is done
 Foleys Catheter with probe commonly used (but adequate
urine output required) . Otherwise esophageal or rectal.
 Most ideal - PA probe.
 Place an early arterial line -
 Vasoconstriction will make placing the line later difficult
 Surface cooling methods- sedation , analgesia and chemical
paralysis is usually necessary.
 Use of endovascular cooling can negate the need for
paralysis
 Buspirone and meperidine - lower the shivering threshold
 DVT prophylaxis

41. INTIATION
A combination of surface and internal cooling is
usually used
2 cooling blankets (to sandwich) or Heat-exchange
Pads
Pack the patient in ice (groin, chest, axillae, and sides
of neck) Avoid packing on top of the chest - impair
chest wall motion.
Use additional measures as needed to bring the
patient to a temperature between 32ºC and 34ºC.
Continuous cardiac monitor, with particular
attention to arrhythmia detection and hypotension ,
regular O2 saturation measurement

42. MAINTENANCE &
SUPPORTIVE TREATMENT
 Feedback mechanisms used to modulate the amount of
cooling provided.
 MAP goal > 80 mm Hg is preferred
 Norepinephrine at 0.01 mcg/kg/min starting dose and
titrated to a MAP greater than 80 mm Hg.
 Practice standard neuroprotective strategies such as placing
the head of the bed at 30º
 Monitor the patient for arrhythmias
 Osborn waves often seen.
 Heart rate < 40 bpm is frequent
 Arrhythmia & bleeding – rewarming to be intiated.
 Investigations
 CBC RFT LFT Blood sugar electrolytes troponin level, ABG,
APTT PT-INR at baseline
 Glucose, K+, and ABG every 6 hours

43. MAINTENANCE &
SUPPORTIVE TREATMENT
 Cooling – Decreases K+ , Increases Blood sugar
 K+ < 3.5 mEq/L should be treated
 Hyperglycemia delitirous – no guideline but strict
control recommended
 Normocarbia advised (35-45 mm Hg for PaCO2)
 Avoid hypoxia & hyperoxia (SPO2> 94% recommended)
 Skin checked every 2-6 hours for thermal injury
 Regularly temperature check with a secondary
temperature monitoring device .
 No nutrition during all 3 phases.
 Avoid fever

44. CONTROLLED REWARMING
 Most critical
 Peripheral Vasodilatation - hypotension.
 Recommended speed -0.3ºC-0.5ºC every hour.
 Approximately 8-12 hours required .
 Remove cooling blankets (and ice if still in use).
 Cooling Pads & Catheter based devices may be set
at 35°C
 Increase the water temperature by 0.5°C every 1-2
hours until a stable core body temperature of 36°C
has been reached for 1 hour.

45. CONTROLLED REWARMING
 Maintain the paralytic agent and sedation until the
patient’s temperature reaches 36°C.
 Discontinue the paralytic agent first. The sedation
may be discontinued at the practitioner’s
discretion.
 Monitor the patient for hypotension secondary to
vasodilatation related to rewarming.
 Discontinue potassium infusions.
 The goal after rewarming is normothermia (ie,
avoidance of hyperthermia)

46. PHYSIOLOGIC EFFECTS AND
COMPLICATIONS
All complications infrequent
 Shivering
 Arrhythmias
 Hyperglycemia
 Electrolyte disorders
 Coagulopathy
 Alterations in drug metabolism
 Risk of Infections
 Cold diuresis

47. Shivering management
 Shivering - body’s attempt at maintaining temperature
 Major concern when trying to achieve a hypothermic state.
 Shivering is uncomfortable, and generates heat and is
therefore counterproductive to targeted temperature
management.
 Meperidine (50 mg IV q 6 hrs)
 Buspirone (30 mg po q 8 hrs)
 Sedation (midazolam, fentanyl, propofol, lorazepam)
 Neuromuscular blocker (vecuronium 0.1 mg/kg bolus;
cisatracurium infusion 0.15 mg/kg bolus followed by 1-10
mcg/kg/min infusion)
 Neuromuscular blocker can hide seizure activity,
 Rapid on off sedation medications are preferable to permit
serial neurological assessment.

48. More experience needed…
OTHER INDICATIONS
 TBI -Shown to be effective in traumatic brain injury with high ICP.
 Refractory intracranial hypertension in new born
 Acute stroke
PREHOSPITAL COOLING
 Originally thought to improve outcomes,
 To date, no cooling manoeuvres begun in the prehospital period have
improved neurologic recovery or mortality in several trials
 One study noted - increased pulmonary oedema and repeat cardiac
arrest with 2 L of cold intravenous fluids.
COOLING VARIABLES
 Timing of the initiation of cooling, cooling technique, rate, depth, and
length of cooling and rewarming all have some effect on mortality and
morbidity
 These variables are not well studied & no head to head comparisons
 Might be having different levels of importance on the basis of clinical
indications.

49. SUMMARY
 Cool early (in the emergency department).
 Use any cooling method but temperature strictly
monitored & for induction combination of methods
required.
 Patients can continue to be cooled during percutaneous
coronary intervention (PCI).
 Tight glycemic control, vigilance for signs of infection,
maintain perfusion, and use pressors if necessary
 Practice standard neuroprotective strategies
 Rewarming should be slow.
 Predict and be proactive regarding management of
complications from ROSC and hypothermia

50. THANK YOU