Pump Work: The “C” in CPR: Evidence on Epinephrine and Chest

CompressionsMyra H. Wyckoff, MD

Associate Professor of Pediatrics

UT Southwestern Medical Center at Dallas

Disclosures

I am not on any speakers bureaus

I do not intend to discuss unapproved uses of a commercial product

I received a manikin from Laerdal for cardiac compression research

I have a translational research grant funded by Ikaria

Audience Response Question

In the past year, have you been in the delivery room when chest compressions were administered to a newborn?

1=Yes

2=No

Goal of Compressions

Generate sufficient O2 delivery to the coronary and cerebral circulation while waiting for a definitive restoration of a cardiac rhythm by pharmacologic intervention (such as Epi)

Coronary perfusion is a determinant of return of spontaneous circulation (ROSC) and cerebral perfusion is a determinant of neurologic outcome

Compressions withMinimal Diastolic BP

Aorta

Heart

Compressions with Diastolic BP

Aorta

Heart

Coronary Perfusion Pressure

ATPATP

ATPα-adrenergic effects

of epinephrine or uninterrupted compressions

lead to Aortic DBP

CoronaryArteries

Coronary Perfusion Pressure=Aortic DBP – Right Atrial DBP

Adequate Diastolic Blood Pressure is Critical to the Success of CPR

ETCO2 74 61 1632 47 0MA

P (

mm

Hg

)

4080120

30 s Simulated DPSS 30 s PPV

12

Epi 0.01 mg/kg

13 14 15 19 32

30 s compressions 3:1 ROSC

ETCO2

Coronary Perfusion Pressure=Aortic DBP – Right Atrial DBP

Indications For Cardiac Compressions During Neonatal CPR: NRP 6th ed.

30 s of provide warmth, position, suction (if needed), dry and stimulate

30-60 s of EFFECTIVE assisted ventilation (focus on MRSOPA steps to achieve this first including an advanced airway)

Chest Compressions are indicated when the heart rate remains below 60 bpm despite

Note: Because chest compressions are likely to compete with effective ventilation, rescuers are encouraged to ensure that assisted ventilation is delivered optimally BEFORE initiation of chest compressions

Copyright ©2010 American Academy of Pediatrics

Mnemonic for remembering the six steps for improving efficacy of positive-pressure

ventilation

Techniques for Achieving Effective Ventilation

(MR. SOPA)

2011 6th ed. NRP Cardiac Compression Guidelines

Compress to depth of 1/3 AP diameter of chest Compress the lower 1/3 of the sternum

Use 2-thumb technique rather than 2-finger technique

3:1 compressions to ventilation ratio for asphyxial arrest

Coordinate compressions and ventilations to avoid simultaneous delivery

Avoid frequent interruptions in compressions

Administer Neonatal Compressions at a Depth of 1/3 the AP Diameter of the Chest

Braga et al. Pediatrics 2009– CT estimates of chest dimensions (n=20, age < 3 mo)– 1/3 AP diameter depth compressions estimated to be

more appropriate than 1/2 AP diameter due to concern for internal structural damage

Maher et al. Resuscitation 2009– No difference in diastolic blood pressure (the main

determinant of coronary perfusion pressure) between 1/3 and1/2 AP Diameter compressions (n=6, age 2wk – 7 mo cardiac surgery patients)

Administer Compressions at a Depth of 1/3 the AP Diameter

of the Chest

Meyer et al. Resuscitation 2010– Neonates (n=54, age<28 d)– Mathematical modeling

based upon neonatal chest CT scan dimensions

– 1/3 AP chest depth should be more effective than ¼ compression depth, and safer than 1/2 AP compression depth

Administer Neonatal Compressions Over Lower

1/3 of Sternum

Orlowski et al. Ann Emerg Med 1986– Heart lies under lower 1/3 of sternum in > 67% of

children (n=187, age < 17yrs ) as noted on CXR– Significantly better MAP achieved with compressions

administered over lower 1/3 compared to mid sternum (n=10, age 1 mo – 3 yrs).

Philips et al. Lancet 1986– Heart under lower 1/3 of sternum in 87% of infants

(n=55, age 27 wks EGA - 13 mo post-term)

Use Two-Thumb Method Rather than Two-Finger Method for Neonatal Cardiac

Compressions

2 small human neonate case series (3 infants)—Two-Thumb Method achieved superior MAP, DBP

2 randomized animal trials—Two-Thumb Method achieved superior MAP, CPP

3 manikin studies-only one using NRP Guidelines— Two-Thumb superior depth of compression with less fatigue

? ?

2-Thumb Method Provides Superior Depth and Less

Variability During Neonatal CPR

Coefficient of Variation (CV) = standard deviation/mean *100

20/21 subjects achieved greater depth of compression with the Two Thumb Method vs Two Finger Method (p=0.00005)

20/21 subjects achieved less variability with the Two Thumb Method vs Two Finger Method (p=0.00005)

Cristman et al. ADC 2011

Two Thumb(n=21)

Two Finger(n=21)

p value

1. Depth of Compression (mm) 29.6±5.3 24.4±5.8 0.0022. Variability in Compression Depth (CV) 5.9±3.0 9.5±3.2 <0.0014. Number of Compressions per min 193±28 198±33 NS

Proper Finger Placement with Two-Thumb vs Two-Finger

*P <0.001 TT vs TF Proper Placement

# of

sub

ject

s

*

Cristman et al. ADC 2011

Sounds good but….. Won’t the two-finger technique be needed

at least briefly so that the compressors hands are not blocking access to the umbilical cord for emergent umbilical venous line placement?

Head of Bed Compressions Allows Continuous Two-thumb Technique

Once an airway is established and secured, move the provider giving compressions to head of bed

Potential Advantages:– Arms are in a more natural position– Umbilical access is more readily available while

continuing Two-thumb technique– More space for person giving meds at the patient’s side

Audience Response Question

In the past year, have you been practicing delivering compressions from the head of the bed?

1=Yes

2=No

Audience Response Question

For those that have been practicing or actually performing giving compressions from the head of the bed…have you found this technique helpful?

1=Yes

2=No

3=Undecided

Efficacy and Fatigue: Side versus Head of the Bed Compressions

Side of the Bed

Head of the Bed

p value

1. Depth of Compression (mm) 24.1 ± 3.8 24.3 ± 3.8 NS

2. Variability in Compression Depth (CV) 15.7 15.9 NS

3. % Compressions with full recoil 85% 86% NS

4. Number of Compressions per min 100 ± 17 106 ± 17 NS

5. Total number of compressions 814 ± 308 979 ± 280 0.003

6. Time giving compressions (sec) 480 ± 162 551 ± 123 0.009

Coefficient of Variation (CV) = standard deviation/mean *100

Sparks et al. PAS Abstract 2011

Compressor Drop-off

*p=0.016

# of

Sub

ject

s C

ompr

essi

ng

MinutesSparks et al. PAS Abstract 2011

What is the Optimal Compression to Ventilation Ratio For Neonatal

CPR?

In Adult V-fib Cardiac Arrest…

Immediately after the cardiac arrest:– Aortic oxygen and carbon dioxide concentrations are

close to pre-arrest state– When compressions are initiated, this is the blood that

will be flowing to the coronaries – The problem is the lack of flow and not so much the

content of the blood

Ventilation from chest compressions and gasping seems to provide adequate ventilation and oxygenation for resuscitation in the short term

Coronary Perfusion Pressure is Enhanced by Continuous Cardiac Compressions

Compared to Pausing for Breaths in 30:2 CC+V ratio in an Adult V-fib Arrest

Ewy GA et al. Circulation 2007

Continuous 30:2 CC+V

Coronary Perfusion Pressure=Aortic DBP – Right Atrial DBP

2 Breath

s

CPP CPP

30 Co

mp

ression

s

Asphyxia-induced Cardiac Arrest is Different…..

At arrest, there is significant hypoxemia, hypercarbia, and acidemia

This promotes maximal systemic vasodilation and very low diastolic blood pressure

Piglet studies of CPR for asphyxial arrests show that in addition to compressions rescue breathing is critical to achieve return of spontaneous circulation

Comparison of CCC vs 15:2 CC+V in Model of Asystole Due to Acute Asphyxia (Clamped ETT)

CCC(n=10)

CC + V(n=10)

Baseline (before asphyxia)

Arterial pH 7.42 ± 0.02 7.42 ± 0.01

Arterial pCO2 (mmHg) 42 ± 1 43 ± 1

After 1 min of CPR

Arterial pH 7.17 ± 0.04 7.20 ± 0.03

Arterial pCO2 (mmHg) 77 ± 11 68 ± 5

ROSC obtained in < 2 min, n (%)* 4 (40%) 10 (100%)

Berg RA et al. Circulation 2000

*p 0.01

Extended Series of Compressions to Ventilations: 3:1 vs 15:2 In Neonatal

Piglet Model of Asphyxial Arrest

3:1(n=9)

15:2(n=9)

P value

Cardiac Compression/min 58 ± 7 75 ± 5 <0.001

Increase in DBP during compression cycles (mmHg)

4.8 ± 2.6 7.1 ± 2.8 0.004

Number of animals with no ROSC

2 2 NS

Time to ROSC (sec)* 150 (140-180) 195 (145-358) NS

Solevåg et al. ADC 2011

DBP=Diastolic Blood Pressure, ROSC=return of spontaneous circulation* Median (25th-75th %tile)

Should we continue to coordinate the compressions

and ventilations?

CPR Coordination Methods

Synchronized: Chest compressions and ventilations are given in cycles alternating between the two in a specific ratio

Simultaneous: Chest compressions and ventilations are given at the same time at a specific rate per minute

Asynchronous: Chest compressions and ventilations are delivered independently of one another – each has its own target rate per minute

Synchronized 3:1 Compression to Ventilation CPR

One… and…

Two… and…

and…

and…Three…

Breathe…

Ventilation

HeartCompressor’s hands

Synchronized 3:1 Compression to Ventilation CPR

One… and…

Two… and…

and…

and…Three…

Breathe…

Ventilation

HeartCompressor’s hands

Simultaneous Compression and Ventilation CPR

Ventilation

HeartCompressor’s hands

Simultaneous Compression and Ventilation CPR

Ventilation

HeartCompressor’s hands

Asynchronous Compression and Ventilation CPR

Ventilation

HeartCompressor’s hands

120 compressions and 30 breaths per minute

Asynchronous Compression and Ventilation CPR

Ventilation

HeartCompressor’s hands

120 compressions and 30 breaths per minute

What Does NRP Currently Say About Asynchronization?

“Avoid giving a compression and a ventilation simultaneously, because one will decrease the efficacy of the other.”

2 activities must be coordinated, with one ventilation interposed after every third compression

Should provide a total of 30 breaths and 90 compressions per minute

What evidence is used to substantiate the current

recommendations?

Simultaneous Method – 2 Studies

Designed to look at the possibility of better cardiac output by increasing the intrathoracic pressure using simultaneous compressions and ventilations– Both use a cardiac arrest model

When compared to 5:1 synchronized compressions, simultaneous CPR:– Did not enhance cerebral and myocardial perfusion

– Resulted in higher PCO2 values raising the concern that this technique might limit ventilation

Berkowitz et al. Ped Res 1989Hou SH et al. Japan Circ J 1994

PaCO2 and pH During 5:1 CC+V vs Simultaneous CPR

5:1 CC+V

Simultaneous

Hou SH et al. Japan Circ J 1994

Limited Applicability

The simultaneous compression groups do not represent what we want to do in the DR– High PIP (60 cm H2O) for ventilations

– Compression rate of 60 bpm– Would not attempt the simultaneous events since we

are not trying to utilize higher intrathoracic pressure to enhance cardiac output

There are no published studies of asynchronous compressions in neonates or neonatal models of profound asphyxia

Asynchronized vs Synchronized Compressions

ACCn=6

NRPn=5

p value

1. Failures to achieve ROSC 1 1 NS

2. Time to ROSC (min)5.5 ± 2.2

n=56.3 ± 3.9

n=4NS

3. Need for Epinephrine 2/6 2/5 NS

4. Minute Vent (MV) during CPR (L/min) 1.3 ± 0.5 1.9 ± 0.9 NS

5. MV per kg during CPR (L/kg/min) 0.6 ± 0.2 0.8 ± 0.3 NS

6. DBP during CPR (mmHg) 6.7 ± 4.2 4.8 ± 3.4 NS

Wyckoff et al. Unpublished data

Arterial pCO2 During CPR

p = NS (ANOVA)

What can we do to interrupt compressions less?

For Starters…. Be aware of the many pauses in circulation that can inadvertently

come up during CPR and help your team stay focused on optimizing perfusion

Continue compressions for at least 45-60s before interrupting to auscultate for heart rate

If at all possible, assign the role of auscultation for heart rate to a team member that is not responsible for compressions or ventilations– Takes longer than 6 seconds to put on stethoscope to determine the

heart rate and get hands back into position

Be aware that pulse oximetry will likely not pick up during this time or the heart rate may reflect the compression rate

End-tidal CO2 (ETCO2) Monitoring During CPR

Quantitative ETCO2 monitoring is a non-invasive tool that has been shown to predict and demonstrate ROSC during experimental and human cardiac arrest

Used to monitor cardiac output and efficacy of CPR in adults where low ETCO2 levels indicate —poor cardiac output (r=0.82 Idris et al, 1994)—poor cardiac perfusion pressure (r=.91 Sanders et al, 1985)—predict low rates of ROSC (Kern et al, 1989)

ETCO2 Detection During Asystole

No blood flow: CO2 can’t get to lungs

Constant ventilationBlows off CO2 left in lungs

Build up of lactate in tissues/decreased CO2 production

Decreased ETCO2 reading

ETCO2 Detection with Return of Spontaneous Circulation

Increased blood flow: CO2 can now get to lungs

Constant ventilationblows off CO2

Increased CO2 production in tissues

Markedly increased ETCO2 reading

ROC Curve for ETCO2 Detection of Audible Heart Rate

1 - Specificity

0.0 0.2 0.4 0.6 0.8 1.0

Se

nsi

tivity

0.0

0.2

0.4

0.6

0.8

1.0

End-Tidal CO2 value

5678

910

11,1213

14

15

16

ETCO2 > 14 mmHg Predicts Return of Spontaneous Circulation

ETCO2 74 61 1632 47 0MA

P (

mm

Hg

)

4080120

30 s Simulated DPSS 30 s PPV

12

Epi 0.01 mg/kg

13 14 15 19 32

30 s compressions 3:1 ROSC

ETCO2

Chalak et al. Pediatric Research 2011

Audience Response Question

In the past year, have you been in the delivery room when epinephrine was given to a newborn?

1=Yes

2=No

Adequate Diastolic Blood Pressure is Critical to the Success of CPR

ETCO2 74 61 1632 47 0MA

P (

mm

Hg

)

4080120

30 s Simulated DPSS 30 s PPV

12

Epi 0.01 mg/kg

13 14 15 19 32

30 s compressions 3:1 ROSC

ETCO2

Coronary Perfusion Pressure=Aortic DBP – Right Atrial DBP

2011 NRP Epinephrine Guidelines

Epinephrine (1:10,0000 solution) should be administered intravenously at 0.01 to 0.03 mg/kg per dose.

Umbilical line placement should be a priority if epinephrine is needed as endotracheal delivery is unreliable.

While access is being obtained, a higher dose (0.05 to 0.1 mg/kg) of endotracheal epinephrine may be given but the safety and efficacy of this practice have not been evaluated.

Can We Do It Better? Is 1/3 the AP diameter really the optimal depth of

compression clinically?

Are there other ergonomic changes that could be made to optimize compressions?

Is coordination of compressions and ventilations really necessary ?

Would use of ETCO2 to predict return of adequate heart rate during cardiac compressions lead to less interruptions and better outcomes?

Is a heart rate less than 60 bpm the optimal time to initiate compressions?

Two Changes You MayWish to Make in Your Practice

Intubate to optimize ventilation prior to initiation of compressions

Once the airway is secure, perform compressions from the head of the bed

This will allow you to use the more effective two-thumb technique for cardiac compressions at all times, even while umbilical access is being obtained

Ackowledgments

Thanks to the AAP for several of the drawings and photos used for illustration