THERAPEUTIC HYPOTHERMIA FOR CARDIAC ARREST USING PERFORMANCE TARGETS

Raghu Loganathan, MD, FCCP Director, Medical ICU & Stroke Center March 2010

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

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ILCOR 2008 Circulation 2008; 118:2452-83

MILD THERAPUETIC HYPOTHERMIA

CLINCIAL STUDIES
RCTs
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)
Initial rhythm VF or VT

Bernard (Australian)
VF

Pre ED Cooling Target Temp Hypothermia patients Standard Rx Patients Hypothermia duration Morbidity Reduction Mortality Reduction
Adverse events (sepsis, arrhythmias & Bleeding)
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No 32 to 33 C 136 137 24 hours

ARR 16%, NNT 6

Yes 33 C 43 34 12 hours
ARR 16%, NNT 4

ARR 14%, NNT 6

NS

ARR 17%, NNT 6

NS

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

MILD THERAPEUTIC HYPOTHERMIA FDNY 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

RLPAP 54 on ventilator

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
RLTime at start of cooling is within 4 hours after ROSC

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 anticholinergic agents A known terminal illness preceding arrest RL? Pregnancy ( Case report showing benefit)

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 comorbidities 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 RL

Aa

Typical Cooling and Rewarming Protocol

Aa

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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

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

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 RLInsertion of Central Line Catheter (subclavian or IJ)

HYPOTHERMIA BUNDLE
TIME ZERO RETURN OF SPONTANEUOUS CIRCULATION (ROSC)

10 MINUTES
15 MINUTES

30 MINUTES

45 MINUTES 4 HOURS
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COMPLETE SCREENING & NOTIFY ICU ATTENDING HYPOTHERMIA LABS TO BE SENT OUT START COLD SALINE PLACE CENTRAL LINE IN SUBCLAVIAN PLACE TEMP SENSING FOLEY START SURFACE COOLING ACHIEVE TARGET TEMP OF 32 C

GAYMAR III
Not selling this product

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January 2009 to February 2010

58 cardiac arrest patients to ED

22 patients in ED with ROSC

18 INPATIENTS screened

14 PATIENTS COOLED

12 INPATIENTS COOLED

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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

RL Average ICU days on vent 7.03 days

OUTCOMES
26 patients cooled 11/ 26 (42.3%) survived to hospital discharge 10/ 26 (38.4%) had good outcomes
CPS category Description
Conscious and alert with normal function or only slight disability Conscious and alert with moderate disability Conscious with severe disability Comatose or persistent vegetative state Brain dead or death from other causes

Number

1 2 3 4 5

8 2 1 0 15

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OUTCOMES BY RHYTHM

Rhythm
VF/ V-tach

Cooled
3

Survived
1 (33.3%)

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

18
5

8 (44.4%)
2 (40%)

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Summary of Studies

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%

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

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Practice Parameters: Prediction of outcome in comatose survivors after cardiopulmonary resuscitation, NEUROLOGY 2006;67:203210

Complications

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HACA study group, NEJM, 2002

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
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