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Update on Targeted Temperature Management
1. Kristopher R. Maday, MS, PA-C, CNSC
University of Alabama at Birmingham
Pegasus Emergency Group
Is It Still “Cool” to Cool or Is It “Hot” to Not
2.
3.
4. • Discuss history of hypothermia in acute
cardiac events
• Evaluate the advantages/disadvantages of
hypothermia in post-arrest management
• Critically evaluate current literature
regarding temperature end-points
• Discuss future trends of TTM
9. 1960s - Dr. Peter Safar
Acierno LJ. Clin. Cardiol. 2007;30:52-54.
10. 1971 - Dr. Brian Barrat-Boyes of New Zealand
Barratt-Boyes BG. Circulation. 1971;43(Suppl 5):25-30.
11. Late 1970s
1980s
85o F (29oC) for days
Mild hypothermia
Numerous complications
Less complications
12. • 1980 - Annals of Internal Medicine
– 2 case reports of hypothermic immersions
Sekar TS. Arch Intern Med. 1980;140(6):775-779.
13.
14. • Lowers tissue oxygen requirements
• Decreases cerebral metabolism and edema
• Improved tolerance to ischemia
• Decreases reperfusion inflammatory
cascade
Young RSK. JAMA. 1980;244:1233-1235 Globus MY. J Neurochem. 1995;65(4):1704-1711Busto R. Stroke. 1989;28(8):1113-1114
15. HACA Trial
• 275 patients
• 32-34o C vs
normothermia for 24 hr
• Primary Outcome
– Neurologic function at 6
months
Bernard Trial
• 77 patients
• 33o vs 37o for 12 hr
• Primary Outcome
– Favorable discharge
location
HACA Investigators. NEJM. 2002;346(8):549-556. Bernard SA. NEJM. 2002;346(8):557-563.
16. HACA Investigators. NEJM. 2002;346(8):549-556. Bernard SA. NEJM. 2002;346(8):557-563.
Trials Criteria Mortality
Good Neurologic
Outcomes
HACA
VT/VF rhythm
Resuscitation within 15min
ROSC within 60min
32-34o for 24hr
Control – 55%
Hypothermia –
41%
Control – 39%
Hypothermia –
55%
Bernard
VF with persistent coma
33o within 2hr for 12hr
Control – 68%
Hypothermia –
51%
Control – 26%
Hypothermia –
49%
33. • 939 patients in 36 ICU across Europe and
Australia
• ***ALL RHYTHMS***
• 2 study groups
• Protocol
• Outcomes
– Primary – All cause mortality
– Secondary – Neurologic status
Nielson N. NEJM. 2013;369:2197-2206
34. Nielson N. NEJM. 2013;369:2197-2206
Outcome 33o Group 36o Group HR/RR (95% CI) P-value
Primary Outcome
Death at end of trial 235/473 (50%) 225/466 (48%) 1.06 (0.89-1.28) 0.51
Secondary outcome
Neurologic function at 180d
CPC of 3-5 251/469 (54%) 242/464 (52%) 1.02 (0.88-1.16) 0.78
MRS of 4-6 245/469 (52%) 239/464 (52%) 1.01 (0.89-1.14) 0.87
Death at 180d 226/473 (48%) 220/466 (47%) 1.01 (0.87-1.15) 0.92
Primary Outcome
No difference in all-cause mortality
Secondary Outcome
No difference in neurologic status
Shorter ICU and hospital stays in 36o group
35. 1. 24 hours at 36o C
2. 12 hours at 37o C
3. 36 hours at 37.5o C (de-sedate)
4. 36 hours at whatever (no sedation)
Prognosticate after 108 hours following ROSC
36. • 33o is not better than 36o
• Not just for VT/VF
• Easier on smaller hospitals
• Decreased hospital LOS
37. • What temperature is best?
• When to start cooling?
• Duration of cooling?
• Any complications with 36o?
Advocated packing wounded soldiers with snow or ice to staunch bleeding
Recommended placing typhoid fever patients in cold baths
Neurosurgeons in the 1930s-1950s experimented with hypothermia to stop cancer cells from multplying and to help with a bloodless field during surgery
University of Pittsburgh
Widely credited as the Father of CPR and included hypothermia in the recommendations after a patient’s heart was re-started
1st to report hypothermia with cardiac arrest in neonates too small for conventional cardiopulonary bypass
Theory of the times was the cooler the brain, the less oxyegn it needed. This lead to temperatures as low as 85o and patients were maintained there for up to 5 days. This lead to dysrhythmias, infection, and bleeding
Excitement with hypthermia waned because of this.
IN the 1980s, Dr. Safar’s lab began animal studies using milder forms of hypthermia and showed that these animals made a good recovery with less complications.
Research continued through the 1990s with some success, but no real practical advancements
25min and 6min complete neurologic recovery
Hypothesis from these case reports is that the hypothermia protected the brain from hypoxic injury
Extends the time a patient can be without circulation
Metabolism reduced 5-10% per degree Celsius of core temperature
For ever 1o degree over 37, risk of unfavorabel neurologic recovery increases with OR 2.26
2 landmark publications in NEJM
HACA (Hypothermia After Cardiac Arrest) – VT/VF, resus began with in 15min of collapse and ROSC within 60min, 32-34o for 24hr and passive rewarming
mean time to 32-34o was 8hr
Bernard – VF with persistant coma, intiating TH within 2hr, 33o for 12hr
Favorable Discharge Location – Home or acute rehab vs LTAC or death
HACA (Hypothermia After Cardiac Arrest) – VT/VF, resus began with in 15min of collapse and ROSC within 60min, 32-34o for 24hr and passive rewarming
mean time to 32-34o was 8hr
Bernard – VF with persistant coma, intiating TH within 2hr, 33o for 12hr
Favorable Discharge Location – Home or acute rehab vs LTAC or death
1 degree per hours and that is debatable
Artic sun external cooling system
33o in in average time of 80 minutes
8 degree per hour
VELOCITY Trial of 2014 showed no benefit
1 degree per hour
Zoll bought out Phillips
ASAP after ROSC…no benefit if started after 6 hours
Only patients with persistant coma
Ideally reach goal within 4 hours
From the time of cooling inititation until the start of rewarming
ASAP after ROSC…no benefit if started after 6 hours
Deep sedation and paralytics
Begin only after 72hr of normothermia
Best predictors of poor outcomes neuronspecific enolase (NSE), somatosensory-evoked potentials (SEPs)
Begin only after 72hr of normothermia
Best predictors of poor outcomes neuronspecific enolase (NSE), somatosensory-evoked potentials (SEPs)
Cardiac – bradycardia, prolonged QT, hypotension
Infectious Disease - decreased immune function
Renal – hypokalemia, cold diuresis
Hematology – coagulopathy, decreased platelet function
Endocrine – dysglycemias from sporadic insulin release
Methodolicgical masterpiece
Randomized to 33 or 36 after 20min of ROSC with a GCS < 8
Maintained for 28hr with gradual rewarming to 37o and avoidance of pyrexia for 72hr
After 72hr those still comatose underwent neurological prognostication
Cerebral Performance Category Modified Rankin Score
1 – minimal disability 0-no symptoms
2 – moderate 1-no clinical signficant symptoms
3 – severe (requires assistantce) 2-slight diability
4- coma or vegetative state 3-moderate
5-brain death 4-mod/severe (requires assisatnce)
5-bedridden
6-brain death
Dr. Stephan Bernard’s hospital
33o may be beneficial for non-shockable rhythyms
When to start prehospital, during CPR, after ROSC