Therapeutic Hypothermia
John S. Burr, MD, FCCP
Illinois Heart and Lung Associates
Advocate Medical Group
Therapeutic Hypothermia
• No relevant disclosures
Therapeutic Hypothermia
• Mild hypothermia by definition
• Also known as Targeted Temperature
Management (TTM)
• What we originally knew about hypothermia
came from cases of accidental hypothermia
• Mammalian diving reflex is an example of
prolonged brain survival in hypothermia
Accidental Hypothermia
• Unintentional decline in core temperature below 35°C
Mild Hypothermia
90-95 F
32.2-35 C
Moderate Hypothermia
82.4-90 F
28-32.2 C
Severe Hypothermia
<82.4 F
<28 C
• Mild Hypothermia is used therapeutically to
decrease risk, increase benefits
Danzl D and Pozos R. NEJM, 1994;331:1756-1760
Accidental Hypothermia
Danzl D and Pozos R. N Engl J Med 1994;331:1756-1760
Therapeutic Hypothermia
• Post Cardiac Arrest: VF/VT
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Ischemic and Hemorrhagic Stroke
Traumatic Brain Injury
Spinal Cord Injury
Acute Liver Failure: cerebral edema
Newborn hypoxic / ischemic encephalopathy
Limiting infarct size in MI in non arrest patient
Miscellaneous: CO poisoning, hanging, near
drowning, choking.
Therapeutic Hypothermia
• Randomized trials supporting therapeutic
hypothermia in cardiac arrest
– Bernard, SA et al., NEJM, Vol 346, No. 8, pp 557563, Feb 21, 2002. Australian Study (smaller)
– Holzer, M et al., NEJM, Vol. 346, No. 8, pp 549556, Feb 21, 2002. Austrian Study (larger)
Therapeutic Hypothermia
• Melbourne, Australia- Bernard, et al.
– N=77 patient recruited with strict inclusion criteria
over 33 months. Men>18, Women>50, VF arrest,
coma from other than circulatory arrest excluded
– Persistent shock after resuscitation excluded
– Cold packs to head/chest to cool within 2 hours
from arrest and maintained for 12 hours
– 49% Hypothermia and 26% Normothermia group
with good neurological outcome.
NEJM, Vol. 346, No. 8, 557-563
Therapeutic Hypothermia
• Melbourne, Australia- Bernard, et al.
– Differences in sex between groups: 58% male in
Hypothermia and 79% male in Normothermia
– Bystander CPR: 49% Hypothermia 71%
Normothermia (might skew to diminish effect)
– Lidocaine IV used in all and SG catheter
– No mortality difference in this study, just
improved neurological outcome
NEJM, Vol. 346, No. 8, 557-563
Therapeutic Hypothermia
NEJM, Vol. 346, No. 8, 557-563
Therapeutic Hypothermia
• Vienna, Austria- Holzer et. al.
– N=275, recruitment criteria more strict,
recruitment time period not mentioned
– 92% screened not eligible: generalizable?
– VF/pulseless VT, Witnessed arrest, Down < 15 min
– ROSC (return of spontaneous circulation) < 1 hour
– Age 18-75, excluded: pregnancy, TM < 30 C, preexisting coma prior to arrest, hypotension, rearrest after EMS arrival, response to verbal
commands (GCS too high), pre-existing coag.
NEJM, Vol. 346, No. 8, p 549-556
Therapeutic Hypothermia
• Vienna, Austria- Holzer et. al.
– Cooling different: cold air mattress
• Time average to target temp 8 hours
• 19/136 patients target not reached (14%)
– Hypothermia 75/136 (55%) good neuro outcome
– Normothermia 54/137 (39%) good outcome
– Mortality (H) 41% vs (N) 55%
• There is consensus based on aspects of both trials to
guide patient selection for therapeutic hypothermia
NEJM, Vol. 346, No. 8, p 549-556
Therapeutic Hypothermia
• Both studies ROSC < 60 min- average 20-25
• Australian study cooled at beginning with cold
packs to head and torso
• Austrian trial ROSC to cooling 105 minutes
with IQR (65-192)
• Similar target temperature, 12 hr vs 24 hr
• VF/VT arrest with reasonable parameters for
ROSC and reduced presenting mental status
Therapeutic Hypothermia
• Miracle Max (Billy Crystal) summarizes:
• Efforts at cerebral salvage- appropriate patient
Therapeutic Hypothermia
• Who to cool?
– Adults resuscitated with ROSC from witnessed
arrest of presumed cardiac etiology
– Initial rhythm VF/pulseless VT
– May also benefit but more study needed: ROSC
from other initial rhythms: asystole, PEA,
?resuscitation from in-hospital cardiac arrest
– Patients who do not have absolute criteria for
avoiding hypothermia
Therapeutic Hypothermia
• Who NOT to Cool: Absolute
– Patients with TM temp <30 C (all dead)
– Patients who already have coma prior to arrest
– Patients with Glascow coma score > 7 (mostly
alive with relatively preserved neurological
function)
– Terminally ill or have advanced malignancy
– Obviously DNR excluded
Therapeutic Hypothermia
Therapeutic Hypothermia
• Who NOT to Cool: Relative
– > 15 min to initiation of BLS
– Time to ROSC of > 60 minutes
– Time from arrest to initiation of cooling > 6 hrs
– Hemodynamic instability SBP > 90 without pressor
– Intracranial pathology until assessment/imaging
– Inappropriate for ICU: multi-organ dysfunction,
severe sepsis, comorbidity decreasing survival
– Traumatic full arrest: coagulopathy, hemorrhage
Therapeutic Hypothermia
• Who NOT to Cool: Relative
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Pregnancy: risks/benefits discussed with OB
Extremes of age
Bleeding ongoing or inherited coagulopathy
Surgery < 48 hrs before or major trauma to spleen or
liver
Sepsis is reason for arrest
QT prolongation
Prolonged hypoxemia, SaO2 < 85% for > 15 minutes
after ROSC
Thrombocytopenia < 50K, initial asystole, coma (med)
Therapeutic Hypothermia
• Physiologic changes during hypothermia
– Brain injury during arrest and salvage by cooling
– Cardiovascular effects
– Respiratory effects
– Renal effects
– Musculoskeletal
– Immune system and infection
– Endocrine/Metabolic/Hematologic
Therapeutic Hypothermia
• After BLS and ACLS to ROSC: BE COOL
Therapeutic Hypothermia
Therapeutic Hypothermia
• By multiple mechanisms proposed above,
cooling prevents spread of already existing
anoxic/ischemic neural injury, limiting damage
and thereby treat post-resuscitation disease
• Current target of 33 C, mild hypothermia, has
less risk than severe hypothermia of causing
other systemic side effects
• The temperature of benefit may be 36 C ?
NEJM 2013; 369: 2197-2206
Therapeutic Hypothermia
Overall goal of post-resuscitation cooling
Therapeutic Hypothermia
• Cardiovascular effects:
– Decreased HR and increased BP (increased SVR)
– Cardiac output decreased (SV decreased, diuresis)
– CVP maintained by venocontriction
– Increased SvO2 despite CO due to decreased
peripheral oxygen extraction from cellular
respiration. Myocardial O2 extraction also so
myocardial oxygenation improves despite
decreased coronary blood flow
Therapeutic Hypothermia
• Electrical changes during decreased temp:
– Increased PR, QRS, QTc but Osborn waves rare at
mild hypothermia. AF, VF, Asystole more common
when <30 C but most common <28 C
Therapeutic Hypothermia
• Respiratory Effects
– Decreased RR and Minute Ventilation (but on
ventilator is whatever you set)
– Increased serum gas solubility for O2/CO2 so if
ABG not temp corrected overestimate PaCO2 by
about 10 mm and O2 by about 20 mm Hg (shoot
for PaO2 85-100 mm Hg if not temp corrected)
– Left shift of O2/Hemoglobin dissociation so less
O2 delivery but again, less cellular respiration
unless shivering starts to increase metabolism
Therapeutic Hypothermia
• Renal and electrolyte changes
– Volume loss due to cold diuresis: venocontriction
then increased ANP, decreased ADH leading to
polyuria. Also decreased concentration capability
from decreased ion pump activity in Loop of Henle
– Decreased serum levels of electrolytes: K, Mg, P
• Increased urine flow with renal tubular dysfunction
• Intracellular movement of K, Mg, P
– Electrolytes move back out during re-warming
Therapeutic Hypothermia
• Musculoskeletal effects:
– Shivering leads to increased oxygen consumption
which lead to increased temperature, increased
work of breathing, HR, increased myocardial O2
demand
– Antagonizes efforts to maintain cooling so must be
controlled by counter-warming or pharmacy
including sedation with or without paralytics
Therapeutic Hypothermia
• Immune and infectious problems:
– Immune/inflammatory suppression two-edged
sword in that cerebral complication reduced while
increased susceptibility to infection
– Increased pneumonia risk with cooling >> 24 hrs
– Increased wound infection with decreased WBC
function, skin vasoconstriction, and pressure and
irritation from cooling pad contact
Therapeutic Hypothermia
• Endocrine/Metabolic considerations:
– Decreased metabolic rate 8% per degree C
– Drug levels increased due to decreased hepatic
clearance ( enzyme function, blood and bile flow)
– Hyperglycemia from decreased insulin sensitivity
and secretion
• Hematologic:
– Hct (concentration), Plt function, coag function,
but the risk of spontaneous bleeding is low
Therapeutic Hypothermia
• Selection of candidate: evidence covered as
above: out of hospital arrest VF/VT with GCS 7
or less and no contraindications
• Physiologic consideration in hypothermia,
most importantly brain salvage, covered
• We will now turn toward practical
considerations in implementing hypothermia
as therapy in ICU
Therapeutic Hypothermia
• Team Approach to management
– MD: ER, Cardiology, Neurology, Critical Care
– Nursing: ER, Cath Lab, CC nurses, clinical nurse
specialists/educators, nurse managers
– Respiratory Therapy
– Pharmacy and Laboratory support
– Pre-hospital care by EMS personnel
Therapeutic Hypothermia
• Pre-hospital attempts to cool in the field: ice
bags (in Australian study), iced saline, cool air
evaporative cooling: no convincing evidence
(yet) that superior to cooling on ER arrival
Reindeer nasal cooling
Post arrest cool dry air
Circulation. 2010;122:737-742
Therapeutic Hypothermia
• General Care on Arrival:
– Communication between ER, Cardiology/Cath Lab,
Critical Care
– Head CT, 12 Lead EKG, Labs: CBC/BMP/Troponin,
Lactate, coags
– If STEMI, cath lab if deemed appropriate
– Three phased hypothermia protocol: complex
longitudinal care so ICU bundle/caremap
Therapeutic Hypothermia
• Initiation of Cooling
– Patient assessment for protocol and start in ED or
cath lab. If not comatose, decide if appropriate.
• Maintenance
– Decrease and maintain temperature at goal with
ongoing supportive care: manage shivering
• Re-Warming
– 24 hours after cooling initiated with slow
controlled rise in temperature and monitoring
Therapeutic Hypothermia
Numerous methods to maintain hypothermia: surface and catheter based common
Polderman, KH, Intensive Care Medicine, 2004
Therapeutic Hypothermia
Core Cooling
Therapeutic Hypothermia
Blanket Cooler
Therapeutic Hypothermia
Surface Cooling
Therapeutic Hypothermia
Overview of Process
Therapeutic Hypothermia
• Equipment as above and– Arterial line important with hemodynamic change
– Central line for drug and pressor delivery.
Australian study used PA catheters but most
studies did not uniformly insert
– Temperature monitoring by PA cath, esophageal
probe, caution with bladder temp only if patient
oliguric/anuric, rectal temp
– Sedation, Treat shivering, paralysis vs skin
counter-warming, EEG if available
Therapeutic Hypothermia
• Continuous assessment
– Metabolic disturbances, arrhythmias, Glucose
level, Sedation and Pain level, Shivering, Seizure,
Skin Breakdown, Infection/fever, Bleeding
– Temperature by core method with back up
– IVF to replace diuretic losses, sedation and
analgesia, NM blocker vs counter-warming
– Vasopressor may be needed MAP >80 preferred
for CPP
– IV insulin if needed for hyperglycemia
Therapeutic Hypothermia
• Sedation deeper if NM blockade, consider BIS
monitoring although accuracy based on
evidence is questioned at < 35 C
• The importance of shivering is the increased
metabolic heat production slows/impairs
target temp acquisition
• Shivering early signs decreased SvO2,
increased RR, facial tensing, noise on EKG,
palpable muscle fasciculation of face or chest
Therapeutic Hypothermia
• Shivering:
– Optimize sedation and analgesia
– Bair Hugger Device for counter warming can
decrease shivering
– Paralytic IVP if above ineffective
– Paralytic infusion only if above ineffective
– Deep sedation for paralysis if needed and periodic
assessment of TOF (train of four) which is
assessed prior and during infusion
Therapeutic Hypothermia
• Fever can be commonly secondary to
aspiration pneumonia/itis from arrest
• Cultures, WBC with diff, empiric coverage for
source
• Add Tylenol to antibiotics to prevent
hyperthermia from undoing your hard work
Therapeutic Hypothermia
• Skin breakdown is higher risk with peripheral
vasoconstriction and pressure from cooling
pads if used
• Every 2 hours with turning do skin survey
• Care in applying cooling device on areas of
fragile skin or wound
Therapeutic Hypothermia
• Slow re-warming starts 24 hours after the
onset of the cooling phase (not when TT
reached)
• Rewarming should proceed no faster than
0.25 C or 0.5 F per hour averaged over 4 hrs
• Goal 36.5 to 37 C with temperature (clamping)
maintained normo-thermic for 48 hours.
Therapeutic Hypothermia
• While cool replace K, Mg, P to LLN as needed
and discontinue replacement while rewarming
• If using paralytic, discontinue when 36 C
• Watch for hypotension secondary to
peripheral vasodilation and replace
intravascular volume with additional
crystalloid as need
Therapeutic Hypothermia
• Careful selection of appropriate candidate
• Mindfulness of physiologic changes of
hypothermia
• Reach goal temperature as soon as possible and
maintain 24 h with slow rewarming
• Shivering and Fever need to be controlled to help
protect the brain
• After arrest, hypothermia allows more people to
go back to independent living with good cognitive
function
Case of VF Arrest
• 53 yo female went to work with vague CP
• Arrest near cafeteria at work, AED delivered
shock, intubated in field, CPR for PEA (but no
epinephrine given), given versed for agitation
then placed on propofol drip in ER
• At the time critical care called patient was
unresponsive on propofol drip
• Should she be chilled or continue current
care?
Thank You
The Importance of Bedside Assessment