Amy Gutman MD ~ EMS Medical Director

1
Prehospital Therapeutic Hypothermia Post Cardiac
Arrest

• Amy Gutman MD EMS Medical Director
• prehospitalmd_at_gmail.com / www.teaems.com

2
INTRODUCTION

• Therapeutic Hypothermia (TH) is an evidence based
  intervention improving neurologic outcomes
  decreasing mortality in cardiac arrest patients
• Recommended by AHA (2010) ALS Taskforce of
  International Liaison Committee (ILCOR) in 2003
  as a prehospital intervention
• Why cool patients?
• Lower brain temperature in the 1st 24 hours after
  ROSC has positive effects on survival
  neurologic recovery
• Mild hypothermia reduces cerebral metabolic
  demand, decreasing damage from inflammatory
  responses occurring after restoration of cerebral
  perfusion
• One large study showed that for every hour delay
  to onset of cooling, mortality increased by 20!

3
OBJECTIVES

• Definition of Therapeutic Hypothermia (TH)
• Pathophysiology of Hypothermia Cerebral
  Reperfusion Injury
• Indications, Contraindications, Adverse Reactions
  
• Protocol Basics

4
OOHCA EPIDEMIOLOGY

• 295,000 OOHCA annually in the US
• 88 at home / out-of-hospital
• 23 VF
• 31 Bystander CPR
• Median survival all rhythms 8, VF 21
• Prior to hypothermia the best EMS systems had a
  18 survival to hospital discharge (34 VT/VF)
• After hypothermia some systems (i.e. Portland ME)
  increased survival to 30 overall (55 PEA /
  asystole) with a 58 survival to discharge in
  VT/VF subgroup

5
TH NOT JUST FOR OOHCA

• Today we review Therapeutic Hypothermia in OOHCA,
  but TH has many other clinical applications
• Hepatic encephalopathy
• Near hanging
• Neonatal asphyxia
• Elevated ICP, all causes
• Severe SAH with cerebral edema

6
AHA ILCOR POSITION STATEMENTS

• Unconscious VF OOHCA adults with ROSC should be
  cooled to 32-34C for 12-24 hrs
• Possible benefit for other rhythms or in-hospital
  cardiac arrest
• Post-resuscitation treatment
• Induced hypothermia
• Prevention of hyperthermia
• Tight glucose control
• Preventing hypocapnia
• Maintaining elevated MAP

7
AHA / ACC / ILCOR RECOMMENDATIONS FOR OOHCA CARE
8
RECENT CHANGES IN CPR / CCR

• Effective uninterrupted compressions
• Decreased emphasis on ventilation, slower
  ventilatory rates
• ETCO2 to for airway confirmation to guide
  resucitation
• IO for easy / rapid access
• Emphasis on post-resuscitative neurological
  salvage

9
WHY DO PATIENTS DIE AFTER OOHCA?

• 10 Refractory dysrhythmias
• 25 Low cardiac output states
• 10 Infection / sepsis, coagulopathy
• 35 Post Resuscitation Encephalopathy (PRE)
• AKA Cardiac Arrest Associated Brain Injury
  CAABI
• Largest contributor to post resuscitation deaths
  poor neurologic outcomes
• Series of events beginning immediately following
  ROSC brain reperfusion
• Therapeutic hypothermia interventions aimed at
  reducing PRE effects improve patient outcomes,
  hence the concept of neurological salvage

10
APOPTOSIS

• Cells pre-programmed to die after damage /
  ischemic
  injury
• The more cells die, the more ischemia occurs
  due
  to anaerobic metabolism
• Anaerobic metabolism causes increased brain cell
  hyperexitability which worsens brain ischemia
• Brain ischemia leads to cerebral edema, causing
  more cells death
• Blood brain barrier disrupted during
  hypoperfusion / resuscitation causing fluid
  influx into brain, worsening edema increasing
  ischemia
• Therapeutic Hypothermia decreases apoptosis,
  therefore decreasing cerebral injury
  (neuroprotective)

11
POST-RESUSCITATIVE ENCEPHALOPATHY (PRE)

• PRE characterized by metabolic hemodynamic
  derangements similar to severe sepsis
• Initial hypoperfusion insult followed by ROSC
  hyperperfusion
• Key characteristic is the loss of cerebral
  autoregulation causing cerebral inflammation /
  edema, cerebral vasoconstriction, vascular
  sludging / clotting, and a mismatch in supply
  demand of metabolic resources
• Cell injury from O2 free radical formation,
  inflammatory cascade glutamate mediated cell
  death
• PRE leads to Post Resuscitative Syndrome (PRS)

12
POST-RESUSCITATION SYNDROME (PRS)

• Apoptosis can last gt48 hrs after initial ischemic
  events
• Controlled TH neuroprotective by inhibiting
  inflammatory cascade occurring secondary to
  apoptosis cerebral reperfusion
• Neutrophil macrophage functions slow lt35C
• Decreases cerebral metabolic demands 7 for each
  temp degree
• Maintains blood-brain-barrier patency decreasing
  cerebral edema from toxic lipomembranous protein
  fluid influxes

PRS
13
TH IS NOT A NEW CONCEPT!
Anesthesia and Analgesia 195938 (6) 423
14
HYPOTHERMIA DEFINITIONS

• Mild
• 89.6-95F (32-35C)
• Moderate
• 82.4-89.5F (28-32C)
• Severe
• lt82.4F(28C)
• Induced or Therapeutic
• Active body cooling to below normal levels part
  of a multifaceted approach to optimizing
  neurologic resuscitation

15

• So why doesnt EVERY OOHCA patient receive TH?
• Survey of 2,248 EM MDs, intensivists
  cardiologists (UK, US, Finland)
• 74 US 64 of non-US MDs never use hypothermia
• Only 34 of US intensivists used hypothermia
• Rationale?
• Not enough data for non-VF arrests
• Not mandatory in ACLS guidelines
  (recommended)
• Technically difficult

16
CLINICAL STUDIES

• Bernard SA. Treatment of comatose survivors of
  OOHCA with induced hypothermia. NEJM 2002
• 77 patients
• 43 hypothermia, 34 normothermia
• 49 hypothermic pts with good outcomes vs 26
  normothermic pts
• Mild therapeutic hypothermia to improve the
  neurologic outcome after cardiac arrest.
  Hypothermia After Cardiac Arrest Study Group.
  NEJM 2002
• Multi-center trial with 275 patients
• 137 hypothermia, 138 normothermia
• 55 hypothermic pts with good outcomes vs 39
  normothermic pts
• Bernard SA, et al. Induced hypothermia using
  large volume, ice-cold IVF in comatose survivors
  of OOHCA a preliminary report. Resuscitation
  2003
• 22 OOHCA, comatose adults
• LR at 4C at 30ml/kg over 30 min via peripheral
  IV to obtain maintain temp at 33C
• Median temp decreased 1.6C, median MAP increased
  10 mmHg
• No adverse outcomes

17
Wake Forest EMS Study 2011
18
EBM META-ANALYSIS OF TH BENEFITS Polderman.
Lancet 2008, 3711955-1969
19
Summary of Studies
METANALYSIS
Neurologic 50 vs 14
Neurologic 23 vs 7
Survival 50 vs 23
Survival 54 vs 33
Neurologic 49 vs 26
Neurologic 55 vs 39
Survival 48 vs 32
Survival 59 vs 45
20
NNT? NUMBER NEEDED TO TREAT

• Average number of patients who need to be treated
  to prevent one additional bad outcome
• The Bernard meta-analysis study showed the NNT
  for OOHCA patients was 6
• Aspirin therapy in myocardial infarction NNT 25
• Beta blocker in myocardial infarction NNT 42
• Cardiac catherization vs thrombolytics 15

6
21
WHAT ABOUT NON-VF OOHCA PATIENTS?

• Non-VF OOHCA patients receiving TH
• Though evidence growing that TH may have benefits
  in these patients, there is still no AHA / ILCOR
  recommendation for TH in non-VF OOHCA
• Its unclear if data from VF pts (a very
  different type of patient than an asystolic or
  PEA patient) can be extrapolated to non-VF OOHCA
• Do potential benefits outweigh risks?

22
TH METABOLIC CHANGES

• Slows cerebral metabolism rate by 20-28 when
  patient cooled to 33C
• 5-7 reduction for each degree lowered temp
• Decreased O2 consumption CO2 production
• Stabilizes glucose levels
• Decreases myocardial demans

23
TH CARDIOVASCULAR CHANGES

• Decreased CO SV
• Increased SVR SBP
• Response to vasoconstriction
• Sinus bradycardia
• Response to myocardial depression
• Refractory to atropine
• High risk of arrhythmias in moderate cooling
  (lt32C)
• Osborne waves
• Positive deflection notch at junction between QRS
  complex ST segment
• Due to delayed K closing

Osborn Waves
24
PRIOR TO INITIATING TH

• Indications, contraindications
• Primary secondary assessment
• Baseline neuro exam essential to allow for
  comparison when patients are wakened
• Pain/ Sedation management

25
EXAMPLES OF CHECKSHEETS
26
INDICATIONSOnly 10 Patients with OOHCA Meet TH
Criteria

• gt18 years old
• ROSC post cardiac arrest
• Unresponsive (GCSlt8)
• No purposeful movements
• Brainstem reflexes / posturing movements may be
  present
• Secured airway with adequate ventilation (ETI
  preferred)
• SBP 90mmHg (MAP gt80) spontaneously or with
  vasopressors
• SpO2 gt85
• Glucose gt50mg/dl
• Destination hospital must have ability to
  continue hypothermia

27
CONTRAINDICATIONS / EXCLUSIONS

• Cardiac instability / refractory arrhythmia
• Cannot maintain SBP gt90mm Hg
  
  (MAP gt80) despite IVF vasopressors
• Active bleeding / history of coagulopathy
  
  or thrombocytopenia
• Thrombolytic /or fibrinolytics do not preclude
  
  use of hypothermia
• Pregnancy
• Trauma patients
• Environmental hypothermia or initial temperature
  lt32C
• Unclear why, but these patients actually have
  worse outcomes

28
ADVERSE EFFECTS

• Always a riskbenefit question in ALL
  interventions
• One large meta-analysis study found no
  significant differences in complication rates in
  normothermic hypothermic groups except for
  infections (i.e. sepsis, pneumonia)
• Most common
• Respiratory alkalosis
• Neutropenia, sepsis increased pneumonia risk
• Altered clotting cascade platelet function
  (coagulopathy)
• Arrhythmias rarely significant if core temp
  maintained gt30C
• Electrolyte shifts
• Potassium intracellular shift with induction,
  extracellular shifts with warming
• Sodium, Calcium, Magnesium metabolism
  abnormalities
• Fluid shifts with cooling (diuresis) re-warming
  (hypovolemia)
• Changes in drug metabolism, ½ lives elimination

29
3 PHASES TO INDUCE HYPOTHERMIA

• Induction (EMS / ED)
• Rapidly bring temp to 32-34C
• Sedate
• Paralyze to suppress heat production
• Maintenance (ED / CCU / ICU)
• Goal temp 33C for 12-24 hours (optimal duration
  unknown)
• Suppress shivering
• Rewarming (CCU / ICU)
• Most dangerous period hypotension, cerebral
  edema, seizures common
• Goal is to reach normal core temp over 12-24h
• Sedation stopped when normal core temp achieved

Portland, ME 2006
30
TH PROCEDURE
One of the best Hypothermia protocols available
is from Wake County EMS All of Wakes protocols
are high-quality, evidence-based FREE to
reference on-line

• Institute rapid cooling with core temp goal 33C
• Core temp monitoring with a core temp rectal or
  nasal probe
• Acutely cool with either
• Cold (4C) LR IVF (2 L over 30 mins) /- ice
  packs BL to neck, axillae, groin
• If ice-cold fluids unavailable, apply ice packs
  BL to neck, axillae groin
• If pt begins shivering, administer midazolam
  0.1mg/kg in 2 mg increments slow IVP with maximum
  single dose 5 mg
• Document vitals, initial GCS, pupillary response,
  brief neurological exam
• Transport to facility that can maintain
  hypothermia intervention
• If post-arrest ECG indicates STEMI, call med
  control to discuss ED STEMI bypass
• Do not allow core temperature to drop below 33C

Consider reducing by 50 if gt70 years
31
SOME SYSTEMS USE WEIGHT-BASED DOSING
32
ED / CRITICAL CARE TH INDICATIONS

• Less time-dependent than prehospital criteria but
  data shows that the earlier TH started, the
  better the outcomes
• In some non-evidence-based protocols, TH can be
  started up to 8 HOURS post ROSC!
• Encephalopathy present
• Defined as patient unable to follow verbal
  commands
• No life-threatening infection
• No active bleeding or coagulopathy
• Aggressive care warranted desired by patient or
  decision-maker (i.e. no terminal underlying
  disease, DNR / DNI or Hospice)

33
ED / CCU / ICU HYPOTHERMIA PROTOCOL Crit Care Med
200937S211-S222
34
ED / CCU / ICU EXTERNAL COOLING DEVICES

• Many commercially available devices
• External surface cooling systems commonly 1st
  devices utilized while internal devices prepped
  or patient being stabilized
• Servo mechanism varies temp of circulating water
  / air temp to prevent overcooling
• Hydrogel heat exchange pads
• Cold water circulates through plastic suit or
  pads
• RhinoChillTM is a unique device that cools the
  brain through the nose!

35
ED / CCU / ICU INTERNAL COOLING DEVICES

• Invasive (catheter based) systems cool the body
  via circulation of temperature controlled saline
  in central or vena cava IV lines
• Heat exchange catheter in SVC or IVC (plastic or
  metallic heat-exchanger)
• Bladder, esophagus, or central venous/pulmonary
  arterial line monitoring

36
COLD SALINE / ICE STORAGE

• Target IVF temp 36-39F (2-4 C)
• Maintain base IVF stock at 45F
• Many systems use Engels Model 15 Freezer (400)
• 14 quart capacity
• Maintains temps 1-40F
• 3.9 Amp Draw on 12V System
• Fits on floorboard of SUV
• Easier to store ice-packs than ice

37
THOMAS CHILLCORE TM THERAPEUTIC
HYPOTHERMIA INDUCTION KIT (1K)

• Enables immediate scene TH induction
• Keeps IVFs at temps as low as 20F in ambient
  temps of 120F
• Maintains constant set temp /- 1
• Stores 4L IVF
• 3L if stored with Thomas RSI Drug case
• Interior LCD light for low visibility areas
• Exterior Dimensions 19.2 x 15.2 x 7.3
• Interior 11.5 x 9.5 x 3.25
• Durable plastic case with standard 12v vehicle
  power standard, optional 110v

                                                
                         In ambient temperatures
up to 120 F
38
SHIVERING

• Natural response to cold in order to maintain
  core temperature
• Signs in unconscious patient w/ROSC
• Decreased SVO2
• Increased RR
• ECG noise
• Muscle fasciculations / tremors
• Increases systemic metabolic rate
• Increases systemic and cerebral VO2 O2
  consumption 40-90
• Increased CO2 production
• Major cardiac stressor

39
SHIVERING MANAGEMENT

• Sedation
• Midazolam / Versed
• Neuromuscular blockade
• Vecuronium
• Analgesia
• Fentanyl, morphine
• Alpha blockade
• Clonidine, dexmedetomidine
• Antipyretics
• Tylenol rectally
• Focal counterwarming
• Magnesium infusion

40
POST-ROSC BLOOD PRESSURE GOALS

• Retrospective review of 1,234 patients in the
  Brain Resuscitation Clinical Trials (BRCT) II and
  III databases Crit Care Med 199927(S)A29
• Higher SBP at 5, 10, 20 60 mins associated with
  good neurological outcome (controlling for age,
  gender, arrest time, CPR time comorbidities)
• 2 episodes SBP lt100mmHg in 1st 6 hrs associated
  with 3 times greater chance of dying
• Cerebral perfusion concerns balanced against
  risks to the heart
• Blood pressure can be titrated to specific
  hemodynamic endpoints, or to directly measured
  CNS targets (i.e. MAP)

41
DOCUMENTATION

• Utstein data points
• Indications, contraindications
• Time of ROSC
• Time of start of cooling procedure
• Evaluation of cooling procedure
• Notification of receiving center destination and
  alert

42
CLINICAL PEARLS

• Do not delay transport to cool
• Can be done while en-route
• Expose patient but try maintain modesty
• Appropriate airway hemodynamic management
• Dont forget the basics the bigger picture!
• If patient re-arrests, discontinue cooling
  treat per appropriate protocol
• Obtain maintain target core temperature between
  32-34C
• Temp should be monitored prior to initiation at
  receiving ED prior to transfer of care
• Excessive cooling puts patient at risk for
  significant complications

43
TRANSPORT DECISIONS

• OOHCA patients unstable by definition should be
  transported to the nearest hospital that can
  continue TH
• If STEMIgo to a STEMI center, otherwise, go to
  closet regional hospital
• After adjusting for age illness severity
  institutional mortality ranged from 46 to 68
• Annual case volume strongly associated with
  outcome

44
REFERENCES

• Santa Clara County EMS Training Module
  Therapeutic Hypothermia-Chill Out!. 2010
• Wake County EMS Training Module Induced
  Hypothermia. 2011.
• Seder D. MMC Director of Neurocritical Care.
  Post-resuscitation care of the cardiac
  
  arrest survivor. 2010.
• Hypothermia After Cardiac Arrest (HACA) Study
  Group. Mild therapeutic hypothermia
  
  to improve the neurologic outcome
  after cardiac arrest. N Engl J Med. 2002
  346549-56.
• Bernard, SA et al. Treatment of comatose
  survivors of OOHCA with induced hypothermia.
  
  NEJM 2002
  346557-63.
• Yanagawa, Y, et al. Preliminary clinical outcome
  study of mild resuscitative hypothermia
  
  after OOHCA. Resuscitation 1998 3661-66.
• Bernard, SA, et al. Clinical trial of induced
  hypothermia in comatose survivors of OOHCA.
  
  Ann EM. 199730146-53.
• Persse, DE et al. Managing the
  post-resuscitation patient in the field. PEC
  20026114-22.
• AHA Position Statement. Part 7.5
  Postresuscitation Support. Circulation
  200511284-88.
• Kollmar, R. Early effects of acid-base
  management during hypothermia on cerebral infarct
  volume, edema, and cerebral blood flow in acure
  focal cerebral ischemia in rats. Anesthesiology
  200297868-74.
• Sterz F, et al. Hypertension with or without
  hemodilution after cardiac arrest in dogs.
  Stroke. 1990211178-84.
• Kuboyama K, et al. Delay in cooling negates
  beneficial effects of mild resuscitative
  hypothermia after cardiac arrest in dogs. Crit
  Care Med. 1993211348-58.
• Nolan, JP. Therapeutic hypothermia after cardiac
  arrest An advisory statement by the advanced
  life support task force of the international
  liaison committee on resuscitation. Circulation
  2003108118-121.
• Roher MJ. Effect of hypothermia on the
  coagulation cascade. Crit Care Med. 1992 20
  1402-05.
• Valerie CR. Hypothermia induced platelet
  dysfunction Ann Surg. 1987205175-81.
• Holzer M. Hypothermia for neuroprotection after
  cardiac arrest Systematic review and individual
  patient data meta-analysis. Crit Care Med 2005
  33414-18.
• Horstmann et al. Brain atrophy in the aftermath
  of cardiac arrest. Neurology 201074306-312
• www.MIEMSS.org

45
SUMMARYprehospitalmd_at_gmail.com / www.teaems.com

• lt50 patients with ROSC survive very few
  
  survive neurologically intact
• To improve OOHCA patients outcomes,
  
  prehospital critical care clinicians must use
  
  an aggressive paradigm including
  therapeutic
  hypothermia hemodynamic
  support
• Therapeutic Hypothermia requires minimal training
  with few complications, though it has
  significant costs is difficult to do well
• Therapeutic Hypothermia ideally suited to EMS as
  it positively impacts patient outcomes is
  extremely time sensitive
• The impact of great prehospital care does not end
  at the ED door!