JULIE M. WATERS RN MS CCRNCLINICAL NURSE EDUCATOR FOR CRITICAL

CAREPROVIDENCE HEALTH CARE

MARCH 2015

Hitting the Target:Does Temperature Management

Matter After Cardiac Arrest?

What do they have in common?

Hit the target every time

Objectives

Describe the impact of thermoregulation in patients after cardiac arrest

Discuss the current state of targeted temperature management in cardiac arrest patients

Identify key principles in the clinical management of patients receiving targeted temperature management

Cardiac Arrest - Dismal

Cardiac Arrest≈300K

Hospital Dischar

ge≈60K

Long Term Recovery

≈30K

80% Mortalit

y50%

NeuroInjury

Cardiac Arrest - Management

Major Goals: Determine and treat the cause of the cardiac arrest

Etiology determines therapy Minimize brain injury Manage cardiovascular dysfunction Manage problems resulting from global ischemia and

reperfusion injury

Baseline Neurological Exam

Determine the likely cause, possible clinical course, and need for interventions

Neurological injury is the most common cause of death in patients with out-of-hospital

cardiac arrest

Consider Targeted Temperature Management for:

Patients who can not follow commands or demonstrate purposeful movement

Definitions for today…..

Controlled Normothermia 36-37.5°C

Temperature Control No higher than 36°C

Therapeutic Hypothermia Decrease core temp to 32-34°C

Targeted Temperature Management (TTM) Maintaining body temp 33-36°C

Historical Perspective

Ancient Greece – Hippocrates1812 Napoleon’s soldiers19th Century “Russian Method of

Resuscitation”

Early Methods of Cooling

Make use of the environment

Pack in ice

Problems with Early Hypothermia

Goal was deep hypothermia (30 C)Duration of cooling varied widely (from 2-10

days)ICUs didn’t exist, monitoring was limitedCooling methods weren’t very reliable

1945: positive effects of TH in severe head injury 1950: improved neuro function in cardiac surgery

with TH Then …………..........

Outcome Hypothermia (n = 43)

Normothermia (n = 34)

Discharge to home or a rehab facility

39% (21/43) 26% (9/34)

Mortality* 51% 68%

* Did not reach statistical significance

Outcome Hypothermia (n = 137)

Normothermia (n = 138)

Positive Neurological

Recovery

55% (75/136) 39% (54/137)

Mortality at 6 months

41% 55%

2010 Updated AHA Guidelines

WHY?.........Ischemia

Perman et al. Clinical Applications of Targeted Temperature Management. Chest 2014; 145(2):386-393.

Abnormal Electrical Depolarization

Blood-Brain Barrier Disruption

Free Oxygen Radical Formation

Neurotransmitter Release

Increased Levels of Excitotoxins

Destabilized Cell Membranes

Mitochondrial Failure

Slide A. Lawrence 2015

Neuronal Damage

Increased temp in the neurologically injured brain or ischemic/anoxic brain…

Cellular Derangements

Cellular Damage

Cell Death

Ischemic Brain Injury

Injury occurs within 4-6 minutes without perfusion

Initial insult followed by a cascade of events

Damage occurs from hours to daysCan be re-triggered by new ischemiaAll processes are temperature dependent

Stimulated by fever Mitigated by hypothermia

Possible Mechanisms of Action

Reduction of cerebral metabolic demand 6-8% for every 1 decrease in temp Reduced 02 and glucose needs more

closely match reduced blood flow Less CO2 and lactate production

Ischemic cell

¯ Oxygen & glucose ¯ ATP

Disruption of Na-K ATP pump

­ Excitatory Neurotransmitt

ers (glutamate)

­ CalciumInflux

Degradation enzymes (carpase,

lipase)

Cellular Apoptosis

Mitochondrial

Dysfunction

X

J. Dirks 2013

ReperfusionInjury

(Inflammatory Response)

↑ Vascular Permeability

(edema)

Disruption of Blood-brain

Barrier

Activation of Coagulation

Microthrombi formation

Cellular Hyperactivity

Temperature in brain

X

J. Dirks 2013

Other Benefits of Hypothermia

Reduction in intracranial pressure

Suppression of epileptic activity

Improved tolerance of recurrent ischemia

Design of Study

International trial - 939 unconscious adults after OHCA targeting either 33°or 36°

Blind study - between 2010-2013 36 ICUs across 10 countries in the EU and AUSAll patients were sedated and ventilated and

had feedback cooling devices All patients had 72 hrs of temp intervention

post ROSC to prevent fever

Summary of Findings

How can this be?

Considerations

All had good post arrest care, 2/3 had angiography, strict rules outlined for prognostication and withdrawal of care

The population included OHCA primary cardiac arrest patients with all rhythms (shockable and nonshockable)80% were Vfib/Vtach and 20% PEA/Asystole

73% of patients received bystander CPR

December 2013

State of the Therapy

All Comatose Post-Arrest Patients

Active control of patient’s temp between 32-36°C

Active avoidance of fever

TTM Recommendations - Patient Specific?

36°C 33°CDuration: 24 hours Duration: 24 hours

Uncomplicated patient with some motor response

Patient with loss of motor response or brainstem reflex

No malignant EEG patterns

Malignant EEG patterns

No evidence of cerebral edema on CT

CT changes suggestive of cerebral

edemaRittenberger JC UpToDate: Post-Cardiac Arrest Management in Adults. Last updated 2/2015

Questions to be Answered

What is the optimal temperature? TTM trial was neutral 33C based on extensive lab evidence and 2 RCTs

What is the optimal duration?What is the optimal injury measurement for post-

arrest? We can’t tell who will have significant post-arrest injury

currentlyHow should we tailor therapy to each patient?

Different presenting rhythms: VF/VT vs PEA/Asystole Different length of down time Severity of presenting illness or comorbiditiesOnly get one shot to modify neurological

injury

Indications and Contraindications

Indications ANY patient not following commands after cardiac

arrestContraindications

Advanced directive against aggressive therapyConsiderations

Active noncompressible bleeding (36°C)

Nielsen trial showed no statistically significant differences in adverse events between 33°C and 36°C

Phases of TTM

1. Induction2. Maintenance3. Rewarming4. Controlled Normothermia

Induction

Temperature Measurement Core Temp 2 Sites Registered Temp + Lag Time = Overshoot

Site of Temperature Measurement

Variation from Core

Temperature

Average Lag Time

Best Practice: Advantage Disadvantage

Pulmonary Artery Catheter

Gold Standard Complex insertion

Esophagus <0.1 C⁰ 5 mins(range 3-10)

Most rapid and accurate reflection of gold standard Temp fluctuates according to depth of probe, accurate placement is key

Bladder <0.2 C⁰ 20 mins(range 10-60)

Easy insertion, low risk dislodgement Accuracy influenced by low U.O., Long lag time, movement of sensor

Rectum <0.3 C⁰ 15 mins(range10-40)

Easy insertion High risk of dislocation, influenced by stool in rectum, long lag time

Rapid Induction is Key at 33°C

35-38 C⁰

33.5 C⁰

FAST

ICEDSALIN

E

ICE PACKS

MEDSCOOLING PADS

Target Temp 36°C

If < 36°C:Controlled rewarm at

0.25°C/ hour

Infusion of Ice-Cold Fluids

Rapidly infuse 30ml/kg (1-3L) of cold (4◦C) isotonic saline via pressure bag

↓ Body temp > 2 ◦C per hour 1L of fluids over 15 minutes can

↓ body temp ≈ 1.0 ◦C Caution in patients with:

Heart failure Severe renal dysfunction Pulmonary edema

If clinically indicated – make the volume cold

Conventional Cooling

Adequate although tricky

DisadvantagesLack of feedback loop makes

maintenance difficultHigh incidence of over coolingExtreme nursing vigilance requiredEffect of temperature fluctuations and

excessive hypothermia on patient outcomes is unknown

Surface Cooling Thermostatically Controlled Devices

DisadvantagesCover patient’s

surface area 40-90%

Risk skin lesionsAdvantages

Easy and fast time to administration

Nurse-driven protocols

Core CoolingIntravascular Cooling Devices

DisadvantagesTime and expertise to initiate

therapyRisk of catheter-related thrombosis

AdvantagesRapid cooling ratesReliable maintenance of core

temperature

Intravascular VS Surface Cooling

Findings: comparable in terms of cooling effectiveness and automatic

temperature feedback controlStudy

Time to device deployment were comparable No significant differences in survival to final

hospital discharge with good neurological function

No difference in rate of shivering No device specific injuries were noted

TФmte O, et al. A comparison of intravascular and surface cooling techniques in comatose cardiac arrest survivors. Crit Care Med 2011; 39(3):443-449.

Thermoregulatory Defenses

BehavioralAutonomic

Vasoconstriction

Shivering

Normal……………. 37°C

Vasoconstriction…..36.5°C

Shivering…..…….35.5°C

Below shivering…..34°C

Threshold

**Still see shivering at 36°C

Shivering

↑ heat production by 600%↑ oxygen consumption 2-3x↑ CO2 production 2-3x↑ metabolic rate 2-5xLinked to ↑risk of morbid cardiac

eventsImpedes induction of TTM and

eliminates possible neuroprotective benefits

Who is likely to shiver?

>60% patients undergoing TTM experience shivering

Young MalesLow Magnesium levels <1.7mg/dLPatients with a difficult-to-

extinguish shivering response had a higher odds of neurological intact survival

How to assess for shivering

Early detectionObserve for piloerectionPalpation of the mandible for

vibrationsIdentifying ECG artifact Resistance to cooling

Objective Indicators

Look for increase in patient’s tempLook at water tempWhat does it indicate the patient is

doing?

Bedside Shivering Assessment Scale*

Score Definition

0 None: no shivering noted on palpation of the masseter, neck, or chest wall

1 Mild: shivering localized to the neck and/or thorax only

2 Moderate: shivering involves gross movement of the upper extremities (in addition to neck and thorax)

3 Severe: shivering involves gross movements of the trunk and upper and lower extremities

*Badjatia N et al, Metabolic impact of shivering during therapeutic temperature modulation: Stroke 2008; 39:3242-3247.

Goal is BSAS ≤ 1

How to combat shivering:Pharmacological &

Nonpharmacological

Surface WarmingSkin temperature influences at least 20% of

the shivering thresholdWorks by countering the feedback loop from

the skin temp to the hypothalamusEffective adjunct in suppressing the

shivering reflexAir-circulating blanket

Insulation of cutaneous thermoregulators on face, hands and feet

Pharmacological

Goal: Pharmacological induction of thermal tolerance

Avoid a cooling-related stress response through pharmacological impairment

Combination of drugs to prevent excessive toxicity

Vasodilation with sedation & analgesiaSedation is importantMonitor efficacy and potency due to

decreased metabolism and elimination of drugs

Miscellaneous Drugs

Acetaminophen Inhibits cyclooxygenase-mediated prostaglandin

synthesis 650-1000mg Q 4-6 H (IV/PO/PR)

Buspirone Acts on 5-HTLA receptor; lowers shiver threshold 20-30mg PO Q 8 H

Magnesium Sulfate Peripheral vasodilation & Facilitates the cooling

process Decreased time to goal temperature Possible direct neuroprotective effects 500mg – 1 gm/hr to reach goal Mg level 3-4mg/dL

Opioids

FENTANYLo 25-50 mcg/hr IV

MORPHINEMEPERIDINE

25-50mg IV Q 1 H One of the most effective anti-shivering

drugs Lowering of the seizure threshold????? Caution in renal failure

Sedation

Dexmedetomidine Dose 0.2-1.5mcg/kg/hr (off-label) Bradycardia & Hypotension

Propofol 50-75 mcg/kg/min Anti-seizure effect Hypotension

Midazolam/Benzodiazepines 2-10 mg/hr Complicates neuro evaluation Less hypotension

Paralytics

Muscles may stop – Brain is still working Advantages

Very effective; quickest method to stop shivering Help achieve goal temp quickly Do not cause hypotension

Considerations May not be able to detect seizure activity

Consider continuous EEG ↑risk of critical illness polyneuromyopathy May mask incomplete sedation Only use as long as needed…….stop/restart TOF does NOT correlate in TH

Combination Agents

Buspirone & MeperidineBuspirone & DexmedetomidineDexmedetomidine & Meperidine

Benefit from combination therapy-

Whether methods or drugs

*Seder DB et al, CCM 2009; 37(7):S211-S222

Columbia Anti-Shivering ProtocolStep Intervention Dose

0 Baseline AcetaminophenBuspironeMagnesium SulfateSkin Counterwarming

650-100mg Q 4-6 h30mg Q 8 h0.5-1 mg/h IV (Goal 3-4 mg/dl)43⁰C/MAX Temp

1 Mild Sedation

Dexmedetomidine OROpioid

0.2-1.5 mcg/kg/hFentanyl starting dose 25mcg/hMeperidine 50-100mg IM or IV

2 Moderate Sedation

Dexmedetomidine AND Opioid

Doses as above

3 Deep Sedation

Propofol 50-75 mcg/kg/min

4 NMB Vecuronium 0.1mg/kg IVChoi HA et al. NeuroCrit Care 2011; 14:389-394.

5.1% of

patients

18% of patients

November 2013

Physiological Impact of Hypothermia

Patients require ICU care to: Maintain hemodynamic stability Ensure adequate oxygenation Correct fluid/electrolyte derangements Prevent complications (infection or bleeding) Deliver safe, controlled cooling and re-

warming Manage shivering

Immunologic:Impaired leukocyte functionCutaneous vasoconstriction

Increased risk of infection if

hypothermia maintained >24

hrs

Systemic Effects of Hypothermia

Hematologic:Depressed clotting

enzyme reactionsImpaired platelet

functionMild

coagulopathy, possible bleeding

Systemic Effects of Hypothermia

Systemic Effects of Hypothermia

HemodynamicSlight increase in contractility (mild hypothermia) then

decrease (moderate-deep)

TH not associated with increased need for vasopressor support

CO = demand

Typical EKG Changes

BradycardiaProlonged PR,

QRS, QTcOsborne waves

(a dome or hump occurring at the R-ST junction (J point) on the ECG)

From: Krantz MJ, Lowery CM. “Giant Osborne Waves in Hypothermia” N Engl J Med 2005; 352:184

Bradycardia usually

well tolerated

33°C

Systemic Effects of Hypothermia

“Cold Diuresis”: Electrolytes:Vasoconstriction increases venous returnIntracellular shifts of electrolytes during

temperature manipulation renal losses due to tubular dysfunction

HypovolemiaLoss of electrolytes(potassium, magnesium,

phosphate)

33°C

Metabolic:Decreased cellular metabolism

O2 & glucose consumption fat metabolism CO2 production

insulin sensitivity

ABGs: O2, CO2, acidosisGlucose: Goal 140-180

mg/dL

Systemic Effects of Hypothermia

Induction Phase

Rapid identification and implementationRapidly cool to 33°CIf <36°C – controlled rewarm at 0.25°C/hr

Maintenance Phase

Maintain target temperature for 24 hours

• Monitor EKG changes• Maintain fluid status• Watch for infection• Monitor for bleeding• Electrolyte monitoring• Monitor for skin breakdown• Avoid hyperglycemia

Rewarming Phase

Rapid rewarming can negate the benefits of TTM

Controlled rate of rewarming to 37°C ≤0.5°C / hour Most suggest 0.25°C / hour

Monitor for Electrolyte abnormalities Cerebral edema Seizures Shivering

Controlled Normothermia Phase

Fever during the first 72 hours after ROSC has been associated with poor outcome

For patients unable to follow commands: maintain normothermia (<37.5°C) for an additional 48 hours after rewarming

Rebound fevers after therapy stopped

Neuroprognostication

Drug clearance is decreased so sedatives may be present 48-72 hours Decisions regarding withdrawal of care must be delayed until adequate clinical exam can be performed Patient’s temperature must be at 35˚C before declaration of brain death can be made

72 hours

Summary

TTM has been shown to improve outcomes in patients after cardiac-arrest

TTM is considered the standard of care for comatose survivors after cardiac-arrest (VF/VT)

TTM is best implemented as a protocol-driven therapy

Shivering must be controlled Stratifying patients based on organ system

dysfunction may be the way to determine 33 vs 36

33°C

36°C

What is my target

temperature?

Questions?

julie.waters@providence.org “The odds of hitting your

target go up dramatically when you aim at it.”

M. Pancoast