THERAPEUTIC HYPOTHERMIA FOR CARDIAC ARREST

USING PERFORMANCE TARGETS

Raghu Loganathan, MD, FCCP

Director, Medical ICU & Stroke Center

March 2010

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Disclosures

• Nothing extraordinary in the case reports

• Use 2 case studies to describe successful implementation of a new protocol

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Cardiac Arrest Epidemiology

Out of Hospital cardiac arrests

• 64% of all arrests• 2 to 9% survive to discharge• 1/ 3rd of survivors have

irreversible cognitive dysfunction

In-hospital cardiac arrests

• 36 % of all arrests• 18% survive to

discharge

ILCOR 2008 Circulation 2008; 118:2452-83

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MILD THERAPUETIC HYPOTHERMIA CLINCIAL STUDIES

• RCT’s– Bernard S et al – NEJM 2002; 346(8)– Holtzer M et al – NEJM 2002; 346 (8)– Idrissi et al – NEJM 2001

• Other Designs– Benson D et al – Anaes Analg 1959; vol 38– Bernard S et al – Ann Emerg Med 1997; 33(2)– Bernard S et al – Resuscitation 2003; 56(1)

• Meta-analysis– Holtzer M et al – Crit Care Med 2005; 33(2)

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Summary of Landmark Trials

HACA (European)

Bernard (Australian)

Initial rhythm VF or VT VF

Pre ED Cooling No Yes

Target Temp 32 to 33 C 33 C

Hypothermia patients 136 43

Standard Rx Patients 137 34

Hypothermia duration 24 hours 12 hours

Morbidity Reduction ARR 16%, NNT 6 ARR 16%, NNT 4

Mortality Reduction ARR 14%, NNT 6 ARR 17%, NNT 6

Adverse events (sepsis, arrhythmias & Bleeding)

NS NS

HACA study group, NEJM, 2002 & Bernard SA, NEJM 2002

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MILD THERAPEUTIC HYPOTHERMIAFDNY initiative

• Less than 15% hospitals are currently using hypothermia in US

• Designated hypothermia centers– Cardiac arrests triaged by EMS

• Model based on STEMI/ PCI centers & Stroke Centers

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Case Study -1

• 69 year old male progressively dyspenic for 5 days• EMS found him cyanotic• Initial PEA, followed by asystole and V fib• Intubated on the field • Downtime 26 minutes

PMH: HTN, COPD, CAD, Morbid Obesity

• Arrived in ED comatose, GCS 3T

• PAP 54 on ventilator

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Case Study -1

• Cold saline: 4.5 liters started within 5 minutes

• Surface cooling in 25 minutes

• Central line placed 30 minutes

• Initial Lactate was 9.3, ScVo2 65%

• Baseline Temp was 37.2

• Target temp reached in 3.4 hours– Double vests used in series

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Case Study -1

• EKG: no STEMI

• Mild elevation of troponins

• ECHO showed depressed EF (30%) with wall motion abnormalities

• CXR showed lower lobe infiltrates

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Case Study -1

• Posturing with de-cerebrating signs noted at 5 hours

• TH continued with sedation and paralytics for shivering

• Re-warming after 24 hours• EEG showed diffuse slowing, no seizures• No clinical response when sedation was stopped• Day 3; spontaneous eye opening and followed

some commands• Day 6 Able to follow more commands

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Case Study -1

• Day 9: Unable to extubate transferred to vent floor

• Day 17 Trach done

• Day 23 weaned off Trach

• Day 25 discharged to SNF

• March 25th: Trach de-cannulated, ambulating and functioning at baseline

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Case Study : 2

• 72 year old male well known to Lincoln BIBEMS• ESRD, Known asthma, Known CAD • EMS called for respiratory distress, “noted to

hypotensive and dyspneic and went into cardiac arrest”

• “Wide QRS on 3 lead” placed on NRB• Subsequently “patient agonal, PEA on monitor, 3

blocks from hospital, CPR started immediately”

• ED arrival 10 minutes later: CPR continued• Intubated in ED, various rhythms, 2 doses of

epinephrine and atropine given

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Case Study : 2• Post intubation, noted to be “de-cerebrating” by ED

attending

• ROSC at 25 minutes: BP 143/ 76, RR 20 at set rate and Pulse 67

• MICU called for therapeutic hypothermia– Unresponsive to deep stimuli, comatose

• Hypothermia initiated 40 mins after ROSC• Myoclonic jerks observed day 1• 36 hours into protocol: patient opens eyes

and following simple commands

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Who to Cool?Inclusion Criteria

• Post-cardiac arrest: defined as absence of pulses requiring chest compressions, regardless of location or presenting rhythm

• Any Initial rhythm (VF/VT, asystole or PEA)

• ROSC within 30 minutes to a SBP > 90 mmHg (with or without vasoactive meds)

• Patient is comatose (unable to follow commands/ GCS < 6) upon arrival to the hospital in the absence of sedation

• Time at start of cooling is within 4 hours after ROSC

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Who to Cool?Exclusion Criteria

• Another reason to be comatose

• Purposeful response to verbal commands or noxious stimuli after ROSC and prior to initiation of hypothermia

• Absent brainstem function not explained by treatment with sedatives, paralytics or anti-cholinergic agents

• A known terminal illness preceding arrest

• ? Pregnancy ( Case report showing benefit)

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Who to Cool?Exclusion Criteria

• Pre-existing DNR and / or DNI code status and patient not intubated as part of resuscitation efforts

• Multi-organ system failure, refractory shock requiring high doses of vasopressors (MAP<60 on 2 or more vasopressor agents), severe persistent hypoxia, acidosis or co-morbidities with minimal chance of meaningful survival independent of neurological status

• Uncontrolled bleeding to coagulopathy

• Recurrent VF or refractory VT in spite of appropriate therapy should generate consideration of emergent referral for cardiac catheterization          

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Typical Cooling and Rewarming Protocol

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How to Cool?ICU Notification

• Once eligibility for induced hypothermia is determined, call MICU/ Stroke attending ASAP

• Obtain 2 large bore IV lines

• Obtain baseline temperature

• Infusion of approximately 2 to 3 liters (for 70 kg individual) of normal saline refrigerated at 4-5 °C

– Can safely and reliably lower core body temperature by 3-4 °C when infused over 50 minutes.

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COOLING PROTOCOL• Obtain laboratory tests ASAP:

– Beta HCG on all women of childbearing age– Arterial blood gas– CBC/ platelets / PT / PTT/INR, Fibrinogen– Electrolyte “panel 7”, plus iCa / Mg / Phos , Cl-, Glucose– Amylase, Lipase, LFTs, , Lactate, CPK-MB, CK, Troponin– Blood Cultures, Urine Cultures, Urinalysis

• Toxicology screen if appropriate

• 12 lead EKG, Chest X-ray

• Placement of urinary catheter with temperature sensor

• Insertion of Central Line Catheter (subclavian or IJ)

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HYPOTHERMIA BUNDLE

TIME ZERO RETURN OF SPONTANEUOUS CIRCULATION (ROSC)

10 MINUTES COMPLETE SCREENING & NOTIFY ICU ATTENDING

15 MINUTES • “HYPOTHERMIA LABS” TO BE SENT OUT• START COLD SALINE

30 MINUTES PLACE CENTRAL LINE IN SUBCLAVIAN

PLACE TEMP SENSING FOLEY

45 MINUTES START SURFACE COOLING

4 HOURS ACHIEVE TARGET TEMP OF 32 C

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GAYMAR III Not selling this product

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14 PATIENTS COOLED

58 cardiac arrest patients to ED

22 patients in ED with ROSC

12 INPATIENTS COOLED

18 INPATIENTS screened

January 2009 to February 2010

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Clinical Characteristics• 26 patients cooled

• Rhythm:– Vtach/ Vfib = 3 patients– Asystole/ PEA = 18– Mixed (VF with asystole/ PEA) = 5 patients

• Average APACHE II = 26 (predicted death rate of 64%)

• 22/ 26 had 100% compliance with hypothermia bundle

• Average ICU days on vent 7.03 days

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OUTCOMES• 26 patients cooled• 11/ 26 (42.3%) survived to hospital discharge • 10/ 26 (38.4%) had “good outcomes”

CPS category

Description Number

1 Conscious and alert with normal function or only slight disability

8

2 Conscious and alert with moderate disability 2

3 Conscious with severe disability 1

4 Comatose or persistent vegetative state 0

5 Brain dead or death from other causes 15

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OUTCOMES BY RHYTHM

Rhythm Cooled Survived

VF/ V-tach 3 1 (33.3%)

Asystole / PEA 18 8 (44.4%)

Mixed (VF/ V-tach and asytole / PEA)

5 2 (40%)

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Summary of Studies Neurologic 50% vs 14%

Survival

50% vs 23%

Neurologic23% vs 7%

Survival54% vs 33%

Neurologic49% vs 26%

Survival48% vs 32%

Neurologic55% vs 39%

Survival59% vs 45%

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Does Rhythm Matter?

• Data from RCTs”– Suggest VF and VT

• Combination of rhythms during a cardiac arrest event

• Underlying mechanisms of brain injury are same

• Multiple observational trials on asystolic rhythm have shown benefit

Who to Cool ?

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Who to cool? Do Circumstances of Arrest Adequately Predict Outcome?

Practice Parameters: Prediction of outcome in comatose survivors after cardiopulmonary resuscitation, NEUROLOGY 2006;67:203–210

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Complications

HACA study group, NEJM, 2002

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SUMMARY

• Screening of patients:– Judgement improves with time– Rhythm alone should not exclude patients

• Most have combined rhythms• Information on initial rhythm not always available

• Use of bundles helps with rapid implementation and achieving target temp– Performance targets helps

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FUTURE DIRECTIONS

• Phase 2 FDNY hypothermia– Cool Enroute to hospital

• MCA ischemic Infarcts

• Traumatic brain injury

• SAH patients with increased ICP

• Hepatic encephalopathy

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Old CPR

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HYPOTHERMIA