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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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RLAa
Aa
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