The Devil is in the DetailsThe Devil is in the Details R. J. Frascone, MD, FACEPR. J. Frascone, MD, FACEP

Medical Director EMSMedical Director EMS Regions Hospital EMS, St. Paul, Regions Hospital EMS, St. Paul, MNMN Professor of Emergency MedProfessor of Emergency Med University of MinnesotaUniversity of Minnesota

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These trials were studying two These trials were studying two different things, in two very different things, in two very

different waysdifferent ways

The RESQ Trial studied the The RESQ Trial studied the combination of ACD/ITD CPR vs S-combination of ACD/ITD CPR vs S-CPRCPR

ROC PRIMED studied ITD CPR vs S-ROC PRIMED studied ITD CPR vs S-CPRCPR

But,But, The RESQ Trial looked at only The RESQ Trial looked at only

ACD/ITD vs S-CPRACD/ITD vs S-CPR ROC PRIMED looked at two different ROC PRIMED looked at two different

things: Early vs late defibrillation and things: Early vs late defibrillation and ITD CPR vs S-CPR and they did it with ITD CPR vs S-CPR and they did it with a multifactoral approacha multifactoral approach

Both trials were complex, but Both trials were complex, but PRIMED was extraordinarily complexPRIMED was extraordinarily complex

First A ReviewFirst A Review(sorry)(sorry)

Standard CPRStandard CPR

Cardiac Pump TheoryCardiac Pump Theory::Heart squeezed betweenHeart squeezed betweensternum and spine.sternum and spine.

Thoracic Pump TheoryThoracic Pump Theory::Chest acts as bellows.Chest acts as bellows.Compression causesCompression causespositive intrathoracic pressure:positive intrathoracic pressure:

Blood leaves the heart from Blood leaves the heart from higher pressure state higher pressure state (inside the heart) to the (inside the heart) to the lower pressure state lower pressure state (systemic circulation)(systemic circulation)

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Compression Phase

Vacuum develops in the Vacuum develops in the chest, drawing air back chest, drawing air back into the lungs and blood into the lungs and blood back into the heart back into the heart (preload).(preload).

↑ ↑ PRELOADPRELOAD leads to leads to ↑ ↑ CARDIAC OUTPUTCARDIAC OUTPUT

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Chest Wall Recoil Phase

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Inefficiency #1Inefficiency #1 Filling of the heart (preload) is Filling of the heart (preload) is

dependent upon the chest walldependent upon the chest wall’’s ability s ability to recoil during decompression phase.to recoil during decompression phase.

Chest wall recoil may be compromised Chest wall recoil may be compromised by:by: A stiff chestA stiff chest Broken ribsBroken ribs Just doing it wrongJust doing it wrong

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Inefficiency #2Inefficiency #2 Air rushes in through an open airway Air rushes in through an open airway

and wipes out the vacuum weand wipes out the vacuum we’’re re relying on to fill the heart.relying on to fill the heart.

Heart stops filling as soon as vacuum Heart stops filling as soon as vacuum is equalized.is equalized.

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ACD CPRACD CPR

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Metronome Force Gauge

Handle

Suction Cup

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Actively Actively compressingcompressing the the chest, increasing IP pressure chest, increasing IP pressure and thereby forcing blood out and thereby forcing blood out of chestof chest, j, just like s-CPR.ust like s-CPR.

Same position as standard CPRSame position as standard CPR 40 – 50 cm (1 ½ - 240 – 50 cm (1 ½ - 2””))

Soft chest: 65 lbsSoft chest: 65 lbsAverage chest: 90 lbsAverage chest: 90 lbsStiff chest: 110 lbsStiff chest: 110 lbs

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But, unlike S-CPR it actively But, unlike S-CPR it actively decompresses the chestdecompresses the chest,, decreasing IP pressure, decreasing IP pressure, thereby drawing blood into thereby drawing blood into the chest.the chest.

Typically 15-20 lbsTypically 15-20 lbs

ACD-CPR Optimizes Chest Wall ACD-CPR Optimizes Chest Wall RecoilRecoil

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S-CPR ACD-CPR

Does it Work?Does it Work?

Standard or ACD CPR during ACLS only

1.5

1.5 1.4

1.9

2.0

3.2* 2.5*

0

5

10

15

20

25

30

35

40

45

surv

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%)

standard CPR

ACD CPR

* Discharge without neurologic impairment

Standard vs. ACD CPR: Standard vs. ACD CPR: SurvivalSurvival Plaisance, P, Lurie, KG, et al. NEJM. 1999 Aug;341(8):569-575.

Human StudyHuman Study

Standard or ACD CPR during BLS and ACLS

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10152025303540455055

surv

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)

standard CPR

ACD CPR

ACD CPRACD CPRThe Problem is:The Problem is:

Air rushes in through an open airway Air rushes in through an open airway and wipes out the vacuum weand wipes out the vacuum we’’re re relying on to fill the heart.relying on to fill the heart.

Heart stops filling as soon as vacuum Heart stops filling as soon as vacuum is equalized.is equalized.

The SolutionThe Solution

Enter the Impedence Threshold Enter the Impedence Threshold Device Device

(ITD)(ITD)

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Patient can be freely ventilated.

Patient Ventilation

Patient can freely exhale.

Chest Compression

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Air will enter if patient creates at least -10 cmH2O pressure with respiratory

effort.

Spontaneous Breathing

Influx of air is prevented, enhancing the vacuum in the

chest.

Chest Decompression

Greater vacuum (negative pressure) in Greater vacuum (negative pressure) in the chest during chest wall recoil phasethe chest during chest wall recoil phase

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ACD CPR w/ Sham ITD

ACD CPR w/ Facemask + ITD

28Plaisance et al. Crit Care Med 2005;33(5):990-994

ACD CPR w/ ET + ITD Ventilation

Improved Blood PressureImproved Blood Pressure

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mm

Hg

Pirrallo et al. Resuscitation 2005;(66):13-20 and Plaisance et al. Circulation 2000;(101):989-994.

P<0.05 for differences between

S-CPR & S-CPR + ITD, and ACD-CPR & ACD-CPR +

ITD

Many other trials both in animals and human that prove

the effectiveness of the ITD alone or in combination with

ACD

Putting it all Putting it all together together

ACD/ITD CPRACD/ITD CPR in humansin humans

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0 5 10 15 20 25 30

Duration of CPR (minutes)

Without Valve

With Valve

n=10

n=11

n=11

n=9

n=8

n=11n=10

n=10

n=10

n=8

n=10

n=7

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0 5 10 15 20 25

Time (min)

24

n=10

En

d-T

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End

-Tid

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O2

ACD CPR +/ACD CPR +/-- Valve: Valve: EndEnd--Tidal COTidal CO22

Plaisance, P, Lurie, KG, Payen, D. Circ. 2000;101:989-994

Human StudyHuman Study

30

40

50

60

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10 15 20 25

Time (min)

20

30

40

50

60

10 15 20 25 30

Without Valve

With Valve

n=11

n=10 n=10n=10n=10

n=9

n=8

n=8

n=7

Duration of CPR (minutes)

n=10

Dia

stol

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rter

ial P

ress

ure

(mm

Hg)

ACD CPR +/ACD CPR +/-- Valve: Valve: Diastolic Arterial PressureDiastolic Arterial Pressure Plaisance, P, Lurie, KG, Payen, D. Circ. 2000;101:989-994

Dia

sto

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rte

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ress

ure

(mm

Hg)

Human StudyHuman Study

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60

Cor

ona

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(mm

Hg)

10 15 20 25

Time (min)

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50

10 15 20 25 30

Without Valve

With Valve

Duration of CPR (minutes)

n=11

n=10

n=9

n=8

n=7

n=10

n=8

n=10 n=10 n=10

Co

ron

ary

Pe

rfu

sion

Pre

ssu

re (

mm

Hg

)

ACD CPR +/ACD CPR +/-- Valve: Valve: Coronary Perfusion PressureCoronary Perfusion Pressure Plaisance, P, Lurie, KG, Payen, D. Circ. 2000;101:989-994

Human StudyHuman Study

Paris Survival Study:Paris Survival Study: ACD CPR ACD CPR ITD ITD

Prehospital studyPrehospital study 200 patients/arm (ACD vs. ACD/ITV)200 patients/arm (ACD vs. ACD/ITV) ROSC:ROSC:

38.5% - ACD38.5% - ACD 48% - ACD/ITV48% - ACD/ITV

ICU admissionICU admission 28.5% - ACD28.5% - ACD 39.5 – ACD/ITV39.5 – ACD/ITV

24 Hour Survival24 Hour Survival 22% - ACD22% - ACD 32% - ACD/ITV32% - ACD/ITV

The ResQ TrialThe ResQ Trial

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Tom P. Aufderheide, MD; Ralph J. Frascone, MD; Marvin A. Wayne, MD; Brian D. Mahoney, MD; Robert A. Swor, DO; Robert M. Domeier, MD; Michael L. Olinger, MD; Richard G. Holcomb,

PhD; David E. Tupper, PhD; Demetris Yannopoulos, MD; Keith G. Lurie, MD

S-CPR (Control)S-CPR (Control)

ITD + ACD-CPR (Intervention)ITD + ACD-CPR (Intervention)

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Survival to hospital discharge with favorable neurologic function

(measured with a modified Rankin Scale [mRS] ≤ 3), is higher in patients receiving an ITD + ACD-CPR compared to patients receiving Standard CPR (S-

CPR).

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Prospective, randomized, controlled clinical trial with data analyzed on intent to treat basis

Seven US sites (population base: 2.3 million):

46 EMS agencies 4950 EMS providers 25 IRBs Patients assigned, based upon weekly block

randomization, to control or intervention group

Study period: February 2005 – July 2010 All study personnel blinded to aggregate

data

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ResultsResults

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*53% improvementP = 0.019OR 1.58

CI (1.07, 2.36)

*

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44Age at Time of Arrest (years)

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P=1.00 for differences based on gender

Odds ratio for effect of intervention based on

gender: 1.6095% CI (1.10, 2.33)S

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Cumulative Cumulative EnrollmentEnrollment 20062006 20072007 20082008 20092009

ControlControl 55 172172 387387 713713

InterventionIntervention 66 168168 395395 703703

Total Total 1111 340340 782782 14161416

ControlControl

(N = 813)(N = 813)

InterventionIntervention

(N = 840)(N = 840)P-valueP-value

One-Year SurvivalOne-Year Survival 48 (5.9%)48 (5.9%) 74 (8.8%)74 (8.8%) 0.0300.030EmotionalEmotional::

Beck Depression Inventory Beck Depression Inventory (BDI)(BDI)

(Score range: 0 – 63)(Score range: 0 – 63)

5.2 ± 6.35.2 ± 6.3 5.5 ± 5.95.5 ± 5.9 0.8620.862

FunctionalFunctional::

Disability Rating Score (DRS)Disability Rating Score (DRS)(Score range: 0 – 29)(Score range: 0 – 29)

1.4 ± 3.11.4 ± 3.1 2.2 ± 5.72.2 ± 5.7 0.3580.358

CognitiveCognitive::

Cognitive Abilities Screening Cognitive Abilities Screening Instrument (CASI)Instrument (CASI)Score range: (0 – 100)Score range: (0 – 100)

92.9 ± 12.0 92.9 ± 12.0 94.5 ± 4.594.5 ± 4.5 0.4730.473

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Compared to standard CPR, ITD + ACD-CPR Compared to standard CPR, ITD + ACD-CPR resulted in significantly increased survival to resulted in significantly increased survival to hospital discharge with favorable neurological hospital discharge with favorable neurological function (53%). function (53%).

One year after OOHCA, survival rates with similar One year after OOHCA, survival rates with similar neurologic function were also significantly higher neurologic function were also significantly higher in the intervention group (49%). in the intervention group (49%).

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Aufderheide et al. A trial of an impedance threshold device Aufderheide et al. A trial of an impedance threshold device in out-of-hospital cardiac arrest. NEJM 2011365;798-806.in out-of-hospital cardiac arrest. NEJM 2011365;798-806.

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PurposePurpose

To determine if use of an active To determine if use of an active (versus sham) ITD during standard (versus sham) ITD during standard CPR (no ACD used) would improve CPR (no ACD used) would improve rates of hospital discharge with rates of hospital discharge with functional neurological survival in functional neurological survival in adult (modified Rankin Scaleadult (modified Rankin Scale [mRS] [mRS] score ≤3score ≤3)), non-traumatic, out of , non-traumatic, out of hospital cardiac arrestshospital cardiac arrests

Description/Methods 10 sites in US and Canada Prospective, randomized, blinded Subjects: adults with arrest from presumed cardiac etiology 2 x 2 multivariate study design

Analyze Early (30 secs CPR) vs Analyze Later (3 min CPR) Stiell et al. NEJM 2011

Sham vs Active ITD Aufderheide et al. NEJM 2011

Impact of immediate CPR feedback utilizing QCPR device @ three sites

Hostler et al. BJM 2011

Results

ResultsResults Overall results in sham vs active ITD were similar Overall results in sham vs active ITD were similar

(≈6%)(≈6%) November 2, 2009, NIH announced study November 2, 2009, NIH announced study

terminated early (at the 2/3 enrollment point) as it terminated early (at the 2/3 enrollment point) as it was not going to be possible to detect any overall was not going to be possible to detect any overall significant difference between either of the study significant difference between either of the study groups (AnE vs AnL, or sham vs active ITD) even if groups (AnE vs AnL, or sham vs active ITD) even if study continued to 14,000 patients (stopped study continued to 14,000 patients (stopped because of futility)because of futility)

No safety concerns with ITDNo safety concerns with ITD

ConclusionConclusion Compared with standard CPR, Compared with standard CPR,

use of the ITD did not use of the ITD did not significantly improve functional significantly improve functional survival from out-of-hospital survival from out-of-hospital cardiac arrest. cardiac arrest.

When implemented under similar When implemented under similar conditions, routine use of the ITD conditions, routine use of the ITD is not supported. is not supported.

What are the Problems with ROC?

The Devil is in the Details

ProtocolsProtocols Three different BLS protocols Three different BLS protocols ALS protocols per site medical ALS protocols per site medical

directordirector

Various ROC Study ProtocolsVarious ROC Study Protocols

BLS CPR BLS CPR MethodMethod

ITD ITD StudyStudy11

AE vs AL AE vs AL StudyStudy22

QCPRQCPRStudyStudy33

Sites Sites ParticipatinParticipatin

gg

30:2 compression 30:2 compression to ventilation ratioto ventilation ratio

Sham vs Sham vs Active Active

ITDITD

30 secs vs 180 30 secs vs 180 secs secs

of CPR before of CPR before analyze analyze

and shockand shock

Did not Did not participateparticipate

Milwaukee, Milwaukee, WIWI

Dallas, TXDallas, TXSan Diego, San Diego,

CACAPortland, ORPortland, ORBirmingham, Birmingham,

ALALOttawa, CAOttawa, CAToronto, CAToronto, CA

Feedback Feedback ON vs ON vs

Feedback Feedback OFFOFF

Pittsburgh, Pittsburgh, PAPA

Thunder Bay, Thunder Bay, ONON

Continuous chest Continuous chest compressions with compressions with asynchronous asynchronous ventilations @ ventilations @ 10/min10/min

Did not Did not participateparticipate

Vancouver, Vancouver, CACA

Did not Did not participateparticipate

Feedback Feedback ON ON

vs Feedback vs Feedback OFFOFF

Seattle (King Seattle (King County), WACounty), WA57

1Aufderheide et al. NEJM 2011 2Stiell et al. NEJM 2011 3Hostler et al. BMJ 2011

Study ProtocolRespond to scene and determine pulselessness.Perform 1 – 4 simultaneously:1.Review enrollment criteria for AE vs AL study

a) If eligible and in V-Fib, perform either 30 secs or 3 min of CPR prior to analyzing and shocking if indicated.

b) If eligible and in asystole or PEA, or not eligible, perform conventional resuscitation

2.Review enrollment criteria for QCPR studya) If eligible, place QCPR device; then, based upon cluster

randomization, audible and visual feedback either will or will not be given to rescuers.

b) If not eligible, do not place QCPR device and perform conventional resuscitation.

3.Review enrollment criteria for ITD studya) If eligible, select ITD in serialized order and place on patient.b) If not eligible, perform conventional resuscitation.

4.Perform other conventional activities of resuscitation (e.g. airway management, IV/IO, administer medications, defibrillate)

ROC ITD Placement IntervalsROC ITD Placement Intervals

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Device Placement IntervalsDevice Placement IntervalsROC PRIMED StudyROC PRIMED Study

ResQTrial StudyResQTrial Study

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ProblemsProblems Complicated Analyze Early vs Analyze Later & QCPR Complicated Analyze Early vs Analyze Later & QCPR

protocols, multivariate design caused multiple protocols, multivariate design caused multiple problems:problems: ITD placement was very delayed (up to 14 minutes)ITD placement was very delayed (up to 14 minutes) Almost 40% of cases did not have ITD placed within Almost 40% of cases did not have ITD placed within

the planned time interval (under 5 minutes)the planned time interval (under 5 minutes) All the patients who survived in under approximately All the patients who survived in under approximately

4 minutes were not eligible for the ITD4 minutes were not eligible for the ITD Essentially all cases of early use were on asystolic Essentially all cases of early use were on asystolic

patientspatients Treatment protocols were inconsistentTreatment protocols were inconsistent

ResQTrial: Impact of Time to Device ResQTrial: Impact of Time to Device Placement on SurvivalPlacement on Survival

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Time from 911 Call to Randomized CPR Method (min)

Average Time of Device Placement in ResQTrial

(7.1 min)

ACD-CPR + ITDStandard CPR

ROC PRIMEDROC PRIMED

All the patients who survived All the patients who survived in under approximately 4 in under approximately 4

minutes were not eligible for minutes were not eligible for the ITD.the ITD.

The Bottom LineThe Bottom LineTwo Very Different StudiesTwo Very Different Studies

ResQ Trial studied ResQ Trial studied ACD/ITD CombinationACD/ITD Combination

ROC PRIMED studiedROC PRIMED studied ITD AloneITD Alone

In Addition…In Addition…

Early survivors were excluded from getting Early survivors were excluded from getting the ITD (under 4 minutes)the ITD (under 4 minutes)

ITD was used early on probable, non-ITD was used early on probable, non-survivors (asystole)survivors (asystole)

ITD ITD wayway to late for the device to be to late for the device to be successfulsuccessful

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