Resuscitation

83 (2012) 813–

818

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at

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Resuscitation

j o

u

r n

a l

h o m

e p a g e

:

w w w . e l s e v i e r . c o m / l o c a t e / r e s u s c i t a t i o n

Clinical

paper

Factors

complicating

interpretation

of

capnography

during

advanced

life

support

in

cardiac

arrest—A

clinical

retrospective

study

in

575

patients

夽

Bård

E.

Heradstveit

a

,

∗

,

Kjetil

Sunde

b

,

Geir-Arne

Sunde

a

,

Tore

Wentzel-Larsen

c

,

d

,

e

,

Jon-Kenneth

Heltne

a

,

f

a

Department

of

Anaesthesia

and

Intensive

Care,

Haukeland

University

Hospital,

Bergen,

Norway

b

Surgical

Intensive

Care

Unit

Ullevål,

Department

of

Anaesthesiology,

Division

of

Critical

Care,

Oslo

University

Hospital,

Oslo,

Norway

c

Centre

for

Clinical

Research,

Haukeland

University

Hospital,

Bergen,

Norway

d

Centre

for

Child

and

Adolescent

Mental

Health,

Eastern

and

Southern

Norway,

Oslo,

Norway

e

Norwegian

Centre

for

Violence

and

Traumatic

Stress

Studies,

Oslo,

Norway

f

Department

of

Medical

Sciences,

University

of

Bergen,

Bergen,

Norway

a

r

t

i

c

l

e

i

n

f

o

Article

history:

Received

21

November

2011

Received

in

revised

form

7

February

2012

Accepted

15

February

2012

Keywords:
Cardiac

arrest

Outcome
Capnography
Capnometry
Advanced

life

support

Pulmonary

embolism

Prognostics

a

b

s

t

r

a

c

t

Background:

End

tidal

carbon

dioxide

(ETCO

2

)

monitoring

during

advanced

life

support

(ALS)

using

capnography,

is

recommended

in

the

latest

international

guidelines.

However,

several

factors

might

com-

plicate

capnography

interpretation

during

ALS.

How

the

cause

of

cardiac

arrest,

initial

rhythm,

bystander

cardiopulmonary

resuscitation

(CPR)

and

time

impact

on

the

ETCO

2

values

are

not

completely

clear.

Thus,

we

wanted

to

explore

this

in

out-of-hospital

cardiac

arrested

(OHCA)

patients.

Methods:

The

study

was

carried

out

by

the

Emergency

Medical

Service

of

Haukeland

University

Hospital,

Bergen,

Norway.

All

non-traumatic

OHCAs

treated

by

our

service

between

January

2004

and

December

2009

were

included.

Capnography

was

routinely

used

in

the

study,

and

these

data

were

retrospectively

reviewed

together

with

Utstein

data

and

other

clinical

information.

Results:

Our

service

treated

918

OHCA

patients,

and

capnography

data

were

present

in

575

patients.

Capnography

distinguished

well

between

patients

with

or

without

return

of

spontaneous

circulation

(ROSC)

for

any

initial

rhythm

and

cause

of

the

arrest

(p

<

0.001).

Cardiac

arrests

with

a

respiratory

cause

had

significantly

higher

levels

of

ETCO

2

compared

to

primary

cardiac

causes

(p

<

0.001).

Bystander

CPR

affected

ETCO

2

-recordings,

and

the

ETCO

2

levels

declined

with

time.

Conclusions:

Capnography

is

a

useful

tool

to

optimise

and

individualise

ALS

in

cardiac

arrested

patients.

Confounding

factors

including

cause

of

cardiac

arrest,

initial

rhythm,

bystander

CPR

and

time

from

cardiac

arrest

until

quantitative

capnography

had

an

impact

on

the

ETCO

2

values,

thereby

complicating

and

limiting

prognostic

interpretation

of

capnography

during

ALS.

© 2012 Elsevier Ireland Ltd. All rights reserved.

1.

Introduction

The

partial

pressure

of

end

tidal

carbon

dioxide

(ETCO

2

)

esti-

mates

alveolar

carbon

dioxide

(CO

2

)

tension,

and

reflects

its

production,

transport

to,

and

elimination

from

the

lungs;

hence

it

generally

reflects

cardiac

output.

1,2

Alteration

in

one

of

these

fac-

tors

will

affect

the

measurement.

The

technique

was

first

described

during

anaesthesia

in

the

1950s,

3

in

order

to

verify

correct

tube

夽 A

Spanish

translated

version

of

the

summary

of

this

article

appears

as

Appendix

in

the

final

online

version

at

doi:10.1016/j.resuscitation.2012.02.021

.

∗ Corresponding

author.

Tel.:

+47

55976850;

fax:

+47

55974955.

E-mail

addresses:

[e-mail]

(B.E.

Heradstveit),

[e-mail]

(K.

Sunde),

[e-mail]

(G.-A.

Sunde),

[e-mail]

(T.

Wentzel-Larsen),

[e-mail]

(J.-K.

Heltne).

placement.

Monitoring

of

ETCO

2

during

cardiopulmonary

resusci-

tation

(CPR)

was

first

described

by

Kalenda,

who

used

ETCO

2

as

a

guide

to

the

efficacy

of

CPR.

A

drop

in

ETCO

2

was

an

indicator

for

when

to

change

the

person

providing

chest

compressions,

due

to

inadequate

compression

efficacy.

4

This

was

later

followed

by

studies

reporting

its

use

during

CPR

in

experimental

models.

1,5

The

positive

correlation

between

ETCO

2

and

outcome

of

cardiac

arrest

in

patients

has

been

well

described

in

several

studies,

5–11

and

a

significant

increase

in

ETCO

2

during

CPR

has

been

associated

with

return

of

spontaneous

circulation

(ROSC).

12,13

The

2010

guidelines

from

European

Resuscitation

Council

(ERC)

now

encourage

the

use

of

capnography

to

guide

CPR

during

Advanced

Life

Support

(ALS).

14

Interpretation

of

ETCO

2

during

resuscitation

from

cardiac

arrest

is

still

challenging

and

has

several

pitfalls.

Especially

the

cause

of

the

arrest

seems

to

have

impact

on

the

ETCO

2

,

and

recent

studies

have

described

higher

ETCO

2

in

asphyxial

arrests

compared

with

arrests

of

cardiac

aetiology.

15,16

Further,

the

influence

of

bystander

0300-9572/$

–

see

front

matter ©

2012 Elsevier Ireland Ltd. All rights reserved.

doi:

10.1016/j.resuscitation.2012.02.021

814

B.E.

Heradstveit

et

al.

/

Resuscitation

83 (2012) 813–

818

CPR

may

impact

on

ETCO

2

as

well

as

variations

over

time,

but

this

has

not

been

documented

in

clinical

studies.

Thus,

the

aims

of

the

study

were

to

document

levels

of

ETCO

2

in

patients

with

out-of-hospital

cardiac

arrest

(OHCA).

We

hypothe-

sised

that

although

capnography

will

give

valuable

feedback

to

the

ALS

providers,

initial

heart

rhythm,

cause

of

the

arrest,

presence

of

bystander

CPR

and

time

dependency

will

limit

and

complicate

its

interpretation.

2.

Material

and

methods

2.1.

Ethics

This

retrospective

study

was

carried

out

at

the

Emergency

Med-

ical

Service

(EMS),

Haukeland

University

Hospital,

Norway.

The

Privacy

Protection

Supervisor

approved

the

study

and

the

Regional

Committees

for

Medical

Research

Ethics

had

no

objections.

The

need

of

an

informed

consent

from

the

patients

or

the

families

was

waived.

2.2.

Organisation

Our

region

has

a

population

of

approximately

470,000

peo-

ple

(15,000

km

2

).

Since

1988,

the

Helicopter

Emergency

Medical

Service

(HEMS)

at

Haukeland

University

Hospital

has

assisted

the

decentralised

ambulances

treating

cardiac

arrests.

The

paramedics

are

trained

in

ALS

and

are

yearly

certified.

The

HEMS

is

served

by

an

anaesthesiologist

by

helicopter

or

rapid

response

car.

Regarding

cardiac

arrest,

the

emergency

dispatch

centre

provides

telephone

guided

CPR

to

lay

people

if

the

patient

is

unconscious

with

abnor-

mal

breathing.

In

parallel,

both

the

nearest

ambulance

and

the

HEMS

are

immediately

despatched

for

initiation

of

ALS.

Local

first-responders

providing

basic

life

support

with

defibrillation

(fire-fighters)

are

also

despatched,

who

may

arrive

at

the

patient

before

the

ambulance/HEMS.

2.3.

ALS

treatment

All

patients

in

the

present

study

were

treated

accord-

ing

to

the

current

international

guidelines

with

our

national

adjustments.

17–19

Both

the

ambulances

and

the

HEMS

were

equipped

with

Lifepak

®

12

Defibrillator

(Physio-Control

Inc.,

Red-

mond,

WA,

USA),

while

the

first

responders

used

the

fully

automatic

Lifepak

CR

®

(Physio-Control).

To

permit

continuous

chest

com-

pressions,

the

patients

had

airways

secured

with

a

supraglottic

laryngeal

tube

(LTS-D,

VBM

Medizintechnik

GmbH,

Germany)

by

the

paramedics,

or

endotracheal

tube

by

the

anaesthesiologists.

The

first

responders

used

mouth-to-mouth

ventilation

with

a

pocket

mask.

All

patients

were

manually

ventilated

according

to

the

cur-

rent

guidelines.

17–19

ALS

drugs

were

used

according

to

national

guidelines,

17–19

and

no

bicarbonate

buffer

was

administered

dur-

ing

the

study

period.

If

ROSC

did

not

occur

and

the

resuscitation

attempt

was

deemed

to

be

futile

by

the

attending

doctor,

ALS

was

terminated

on

the

scene.

In

the

presence

of

profound

hypothermia,

or

in

other

special

circumstances,

patients

were

transported

with

ongoing

CPR

to

Haukeland

University

Hospital.

2.4.

Capnography

use

The

HEMS

has

routinely

used

waveform

capnography

in

all

intu-

bated

patients

since

1999.

Initially,

the

purpose

of

capnography

was

to

verify

correct

tracheal

tube

placement.

However,

in

cardiac

arrest

patients,

we

also

used

it

as

a

surrogate

marker

of

circulation.

20

ETCO

2

-monitoring

was

performed

using

a

mainstream

sensor,

using

single

beam,

non-dispersive

infrared

absorption,

ratio-

metric

measurements

(Tidal

Wave

®

,

Philips

Respironics,

The

Netherlands).

Recording

of

ETCO

2

-values

were

initiated

upon

the

arrival

of

the

HEMS,

and

after

placement

of

a

secured

airway,

and

were

continuously

observed

by

the

treating

anaesthesiologist.

2.5.

Study

design

and

data

collection

All

patients

with

ALS

initiated

non-traumatic

cardiac

arrest

treated

at

our

HEMS

between

January

2004

and

December

2009

were

included

in

the

study.

Pre-hospital

data

were

recorded

accord-

ing

to

the

Utstein

model.

21

Time

records

from

the

dispatch

centre

supplemented

ambulance

records

regarding

response

times.

In

cases

where

the

exact

time

of

cardiac

arrest

was

unknown,

the

time

was

estimated

based

on

the

current

information

available.

In

patients

with

unknown

arrest

time

of

over

60

min,

all

response

times

were

increased

by

60

min.

In

patients

with

ROSC

admitted

to

hospital,

the

cause

of

arrest

was

determined

based

on

hospital

records

and

all

available

information.

Patients

were

classified

in

four

categories;

cardiac,

respiratory,

pulmonary

embolism

(PE)

and

unknown.

Based

on

the

initial

heart

rhythm,

patients

were

classified

in

three

groups;

ventricular

fibrillation/pulseless

ventricular

tachycardia

(VF/VT),

asystole

(AS)

or

pulseless

electric

activity

(PEA).

For

those

pro-

nounced

dead

at

the

scene,

the

anaesthesiologist

stated

the

assumed

cause

of

the

arrest

according

to

the

Utstein-criteria.

This

assumption

was

based

on

previous

medical

history,

comparative

information

from

family,

witnesses

and

bystanders

and

all

avail-

able

clinical

or

environmental

data

or

signs.

21

For

example,

a

PE

was

decided

as

the

cause

of

the

arrest

if

a

clinical

suspicion

of

a

deep

vein

thrombosis

(presumably

with

initial

AS

or

PEA)

was

present.

Those

patients

with

an

unclear

cause

of

the

arrest

were

grouped

as

“unknown”

in

order

to

have

as

clean

groups

as

possible.

Patients

who

gained

ROSC

before

arrival

of

HEMS,

patients

transported

to

the

hospital

with

ongoing

resuscitation

(hypother-

mic

patients

or

other

special

circumstances),

and

patients

with

unknown

initial

heart

rhythm

were

excluded

from

the

study.

ETCO

2

were

recorded

after

the

HEMS

crew

arrived

at

the

patient

as

previously

described.

After

one

minute

of

normal

ventilation,

the

average,

minimal

and

maximal

values

in

the

following

15

min

of

ALS

(or

until

ROSC

if

it

occurred

before

15

min)

were

recorded

manually

by

the

anaesthesiologist.

The

Tidal

Wave

®

capnograph

has

no

automatic

recording

of

data,

and

the

average

value

dur-

ing

these

15

min

was

not

an

average

in

a

strict

sense,

but

was

based

on

the

anaesthesiologist’s

judgement.

ETCO

2

measurements

were

then

analysed

based

upon

the

initial

heart

rhythm,

cause

of

the

arrest

and

presence

of

bystander

CPR,

and

further

classified

depending

on

ROSC

or

no

ROSC.

Association

of

ETCO

2

related

to

bystander

CPR,

time

of

measurement,

initial

rhythms

and

cause

of

the

arrest

were

also

classified.

Other

factors

that

may

influence

ETCO

2

like

epinephrine,

quality

of

CPR

and

ventilation

data

were

not

available.

2.6.

Statistics

All

numbers

are

presented

as

mean

±

SD.

Continuous

data

were

compared

using

independent

samples

t-tests.

Linear

regression

analysis

was

used

to

determine

the

relationship

of

average

mea-

surement

on

ETCO

2

with

bystander

CPR,

time

of

measurement,

rhythm

and

cause

of

the

arrest.

Regression

analysis

used

all

obser-

vations

where

average

ETCO

2

was

known.

Since

some

covariates

from

different

patients

were

missing,

the

regression

analysis

was

run

using

multiple

imputation,

a

well

described

general

procedure

to

use

as

much

information

as

possible.

22

In

this

procedure,

several

completed

data

sets

(200

in

our

case)

are

constructed

and

analyses

from

these

completed

data

sets

are

combined.

Some

continuous

covariates

were

entered

nonlinearly,

when

deviations

from

a

linear

relationship

was

suspected.

A

p-value

<0.05

was

considered

B.E.

Heradstveit

et

al.

/

Resuscitation

83 (2012) 813–

818

815

significant.

The

R

(The

R

Foundation

for

Statistical

Computing,

Vienna,

Austria)

packages

rms

and

Hmisc

were

used

for

regression

analysis,

imputation

and

assessment

of

which

covariates

that

should

be

entered

nonlinearly.

SPSS

version

17-18

(IBM

SPSS,

Somers,

NY,

USA)

was

used

for

presentation

of

the

data

and

for

other

statistical

analyses.

3.

Results

A

total

of

918

patients

received

ALS

after

OHCA

during

the

study

period.

Patient

flow

chart

with

included

and

excluded

patients

is

shown

in

Fig.

1

.

Of

724

eligible

patients,

ETCO

2

recordings

were

present

in

575

(82%)

patients

who

were

included

in

the

final

study.

Patients

with

ETCO

2

measurements

did

not

differ

from

the

miss-

ing/excluded

group

regarding

gender,

age,

initial

heart

rhythm,

response

times

or

outcome.

All

baseline

characteristics

are

pre-

sented

in

Table

1

.

Data

only

relates

to

patients

in

whom

a

clear

airway

and

controlled

ventilation

were

established

and

confirmed

by

capnography

before

data

collection

started.

Additionally

all

tube

placements

were

confirmed

by

signs

of

effective

ventilation.

Among

the

575

included,

232

patients

(40%)

gained

ROSC

and

were

transported

to

the

hospital.

For

all

initial

heart

rhythms

and

dif-

918

98 ROSC

before

HEMS arrival

ALS after

OCHA

194

HEMS arrival

38 Transport

with ALS

194

Excluded

19 Traumatic

arrests

724

Eligible patients

11 Special

circumstances

149

ETCO

2

not record

ed

575

Include

d patie

nts

Fig.

1.

Included

and

excluded

patients

– flow

chart.

Table

1

Baseline

characteristics

in

study

population

(n

=

575).

Variable

Mean

±

SD

Age

(year)

60.7

±

17.8

Female/male

145/430

Witnessed

414

(72%)

Bystander

CPR

438

(76%)

Arrest-CPR

(min)

8.6

±

15.4

Arrest-ACLS

(min)

14.7

±

16.9

Arrest-CO

2

recording

(min)

22.5

±

17.5

Admitted

hospital

with

ROSC

232

(40%)

Any

ROSC

(%)

286

(50%)

Termination

of

resuscitation

(min)

a

43.3

±

22.3

Cause

of

the

arrest

Cardiac

336

(58%)

Respiratory

117

(20%)

Pulmonary

embolism

12

(2%)

Unknown/other

110

(19%)

Initial

rhythm

Ventricular

fibrillation

195

(34%)

Ventricular

tachycardia

3

(1%)

Asystole

266

(46%)

Pulseless

electrical

activity

111

(19%)

CPR,

cardio

pulmonary

resuscitation;

ACLS,

advanced

cardiac

life

support.

a

Time

between

arrest

and

termination

of

resuscitation.

Table

2

Average

ETCO

2

(kPa)

during

CPR

in

patients

with

or

without

ROSC,

regarding

the

cause

of

the

arrest.

Cause

Overall

ETCO

2

,

mean

±

SD

ROSC,
mean

±

SD

No-ROSC,
mean

±

SD

p-Value

a

Cardiac

2.8

±

1.3

3.4

±

1.2

2.4

±

1.2

<0.001

Respiratory

3.5

±

2.2

4.5

±

2.2

2.3

±

1.5

<0.001

Pulmonary

embolism

1.7

±

1.1

2.2

±

1.0

0.9

±

0.5

0.023

Unknown/Other

2.0

±

1.2

2.7

±

1.0

1.3

±

1.1

<0.001

a

Contrast

between

ROSC

and

no-ROSC

using

independent

samples

t-test.

Table

3

ETCO

2

(kPa)

in

patients

presenting

asystole

with

respiratory

and

cardiac

causes

to

the

arrest.

ETCO

2

Cardiac

cause,

mean

±

SD

Respiratory

cause,

mean

±

SD

p-Value

a

Average

2.3

±

1.4

3.5

±

2.3

<0.001

Min.

1.5

±

1.0

2.4

±

2.0

<0.001

Max.

3.4

±

2.3

5.1

±

3.5

<0.001

a

Contrast

between

cardiac

and

respiratory

causes

using

independent

samples

t-test.

ferent

causes,

ETCO

2

were

significantly

higher

in

those

achieving

ROSC

compared

to

those

not

achieving

ROSC

(

Tables

2

and

3

).

3.1.

ETCO

2

and

different

causes

There

were

significant

differences

in

ETCO

2

depending

on

the

cause

of

the

arrest

(p

<

0.001)

(

Table

2

),

with

respiratory

arrests

hav-

ing

increased

levels

compared

to

primary

cardiac

caused

arrests.

Furthermore,

a

significantly

lower

level

of

ETCO

2

was

present

in

patients

with

PE

compared

to

patients

with

respiratory

and

car-

diac

causes,

regardless

of

ROSC

or

not

(

Table

2

).

Patients

with

ROSC

and

PE,

had

similar

values

as

patients

without

ROSC

and

all

other

causes

(and

actually

tended

to

be

even

lower)

(

Table

2

).

In

patients

with

initial

asystole,

the

minimum,

maximum

and

average

ETCO

2

were

characteristically

higher

among

those

patients

with

respira-

tory

compared

to

cardiac

causes

(p

<

0.001)

(

Table

3

).

More

patients

gained

ROSC

in

the

respiratory

compared

to

the

cardiac

group,

49%

vs.

15%.

3.2.

ETCO

2

and

different

initial

rhythms

Initial

VF/VT

was

present

in

198

patients

(34%),

AS

in

266

patients

(46%),

and

PEA

in

111

(19%)

patients

(

Table

4

).

Regression

analysis

did

reveal

differences

in

the

ETCO

2

with

respect

to

initial

rhythms

(p

=

0.004).

Within

each

rhythm,

there

were

significant

contrasts

between

patients

with

and

without

ROSC

(

Table

4

).

In

the

presence

of

ROSC,

patients

with

initial

asystole

had

the

highest

ETCO

2

,

and

PEA

the

lowest,

whereas

in

absence

of

ROSC,

patients

with

initial

VF/VT

had

the

highest

levels

(

Table

4

).

Table

4

Average

ETCO

2

(kPa)

during

CPR

in

patients

with

or

without

ROSC,

regarding

the

initial

heart

rhythm.

Initial

heart

rhythm

ETCO

2

ROSC,
mean

±

SD

No-ROSC,
mean

±

SD

p-Value

a

VF/VT

(n

=

198)

Average

3.4

±

1.1

2.8

±

1.2

<0.001

Min.

2.6

±

1.0

1.8

±

0.9

<0.001

Max.

5.1

±

2.2

4.3

±

1.9

0.009

AS

(n

=

266)

Average

4.1

±

2.1

2.0

±

1.3

<0.001

Min.

2.9

±

1.8

1.4

±

1.0

<0.001

Max.

5.9

±

3.3

3.0

±

2.1

<0.001

PEA

(n

=

111)

Average

3.1

±

1.5

2.2

±

1.3

0.001

Min.

2.2

±

1.4

1.3

±

1.0

<0.001

Max.

4.4

±

2.5

3.1

±

1.9

0.003

a

Contrast

between

ROSC

and

No-ROSC

using

independent

samples

t-test.

816

B.E.

Heradstveit

et

al.

/

Resuscitation

83 (2012) 813–

818

Time of onset CPR (min)

(a)

(b)

A

v

er

age endt

idal

C

O

2 (

k

P

a

)

2.0

2.5

3.0

3.5

4.0

4.5

60

50

40

30

20

10

0

Time of measurement (min)

Average endtidal CO2 (kPa)

0

1

2

3

4

80

60

40

20

0

Fig.

2.

(a)

End

tidal

CO

2

and

time

of

onset

bystander

CPR

after

the

arrest,

adjusted

for

time

of

measurement,

initial

rhythms

and

cause

of

the

arrest

(estimated

values

with

95%

CI).

(b)

Measurement

of

end

tidal

CO

2

at

different

times

after

the

arrest,

adjusted

for

bystander

CPR,

initial

rhythms

and

cause

of

the

arrest

(estimated

values

with

95%

CI).

3.3.

ETCO

2

and

bystander

CPR

The

impact

of

bystander

CPR

affected

the

ETCO

2

significantly

(p

=

0.003).

Initiation

of

bystander

CPR

within

four

minutes

after

the

cardiac

arrest

resulted

in

higher

values

of

ETCO

2

while

CPR

started

later

resulted

in

lower

values

(

Fig.

2

a).

Over

time,

the

trend

was

decreasing

values

of

ETCO

2

.

3.4.

ETCO

2

and

time

of

measurement

The

average

ETCO

2

was

significantly

affected

by

the

time

of

recording

after

the

arrest

(p

=

0.037),

and

the

values

declined

with

delayed

measurement

(

Fig.

2

b).

4.

Discussion

In

the

present

study

we

have

documented

that

several

factors

complicate

the

interpretation

of

ETCO

2

during

ALS.

Although

ETCO

2

differs

well

between

patients

with

and

without

ROSC,

there

is

no

clear

generalised

cut-off

value

determining

whether

ROSC

will

be

achieved

or

not.

Several

confounding

factors

such

as

cause

of

the

arrest,

initial

rhythm,

bystander

CPR

and

changes

over

time

from

arrest

until

ETCO

2

recordings

seem

to

influence

this.

Patients

with

respiratory

causes

and

initial

AS

had

in

general

higher

levels

of

ETCO

2

than

those

with

a

primary

cardiac

cause.

Similarly,

Grmec

et

al.

have

previously

reported

higher

ETCO

2

immediately

after

intubation

in

patients

with

asphyxial

compared

to

primary

cardiac

arrests.

15

Lah

et

al.

from

the

same

group

demon-

strated

that

this

difference

normalised

within

three

to

five

minutes

after

initiation

of

ALS.

16

They

also

reported

that

the

initial

ETCO

2

could

not

be

used

as

a

prognostic

factor

due

to

these

aetiology

differences.

16

We

speculate

that

capnography

for

CPR

guidance

during

ALS

is

easier

to

interpret

in

patients

with

cardiac

causes

than

in

patients

with

asphyxial

arrests.

The

higher

ETCO

2

in

patients

with

asphyxial

arrests

are

presum-

ably

not

due

to

better

cardiac

output,

but

due

to

CO

2

accumulation

in

the

tissue

and

venous

blood

due

to

asphyxia

and

absence

of

ventilation.

15

This

assumption

introduces

the

possibility

for

con-

founding

in

the

presence

of

bystander

CPR,

which

affected

the

ETCO

2

.

First,

we

found

increased

ETCO

2

with

onset

of

CPR

within

the

first

four

minutes

after

the

cardiac

arrest.

Thereafter,

the

ETCO

2

seemed

to

decrease

with

delayed

onset

of

CPR

beyond

four

minutes.

Survival

after

cardiac

arrest

depends

on

time

from

arrest

until

CPR

and

successful

defibrillation,

17,18,23

and

thereby

reduces

with

later

onset

of

bystander

CPR.

24,25

Besides

the

hypoxic

component,

this

can

also

be

related

to

development

of

stone

heart

with

thickening

of

the

myocardium

and

decrease

in

left

ventricular

volume.

This

has

been

demonstrated

in

untreated

cardiac

arrest

in

pigs.

26

Our

data

confirm

that

delayed

initiation

of

CPR

leads

to

lower

ETCO

2

.

This

might

be

explained

by

less

effective

chest

compressions

due

to

development

of

stone

heart.

The

reported

delay

between

time

of

arrest

and

ETCO

2

-recording

may

seem

long,

but

can

partly

be

explained

by

the

fact

that

also

unwitnessed

arrests

were

included.

An

interesting

result

in

our

study

was

the

low

levels

of

ETCO

2

in

patients

with

PE.

ETCO

2

in

PE

patients

are

characteristically

lower

because

of

diminished

pulmonary

perfusion

and

increased

alveolar

dead

space,

and

consequently

decreased

CO

2

elimination

capability.

27–28

Low

ETCO

2

and

clinical

suspicion

of

PE,

might

there-

fore

be

an

indication

for

trombolysis

during

ongoing

ALS,

since

individually

adjusted

treatment

with

fibrinolytics

for

these

patients

previously

can

be

successful.

29

Only

12/575

patients

in

the

present

study

had

a

PE

confirmed

as

the

cause

of

their

arrest.

This

is

far

less

than

previously

reported,

30

and

emphasizes

the

fact

that

PE

is

difficult

to

diagnose

in

cardiac

arrest.

Low

ETCO

2

combined

with

a

non-shockable

rhythm

can

be

suspectible

of

PE.

In

clinical

studies,

ETCO

2

>

2.4

kPa

after

20

min

has

been

shown

to

predict

ROSC,

and

values

<1.3

kPa

have

been

associated

with

no

ROSC.

15,16

Our

data

demonstrates

that

such

cut-off

values

must

be

used

with

caution.

Too

many

confounding

factors

impact

on

the

actual

ETCO

2

.

Importantly,

cut-off

values

from

observational

studies

are

only

based

on

the

actual

dataset,

and

cannot

be

gen-

eralised

to

other

systems.

Strict

use

of

cut-off

values

in

patient

treatment

will

lead

to

treatment

withdrawal

based

on

self-fulfilling

prophecy.

Furthermore,

the

compression

site

on

sternum

might

presumably

affect

haemodynamics

and

thereby

cardiac

output

and

ETCO

2

,

as

recently

shown

in

a

clinical

study.

31

This

fits

well

with

our

impression

that

levels

of

ETCO

2

in

each

patient

varied

depend-

ing

on

the

rescuer

performing

chest

compressions.

Thus,

since

B.E.

Heradstveit

et

al.

/

Resuscitation

83 (2012) 813–

818

817

both

compression

site

and

quality

of

chest

compressions

impact

on

the

ETCO

2

,

this

should

be

acknowledged

by

ALS-providers

during

interpretation

of

capnography.

With

ETCO

2

-guided

resusci-

tation

it

is

thereby

possible

to

encourage

the

rescuers

to

maximise

quality

of

CPR

and

to

change

the

person

providing

compres-

sions

when

the

ETCO

2

drops,

thereby

optimising

CPR

for

each

patient.

The

major

limitation

in

the

present

study

is

the

method

used

for

ETCO

2

recordings.

The

anaesthesiologist

on

scene

observed

the

ETCO

2

continuously

during

the

first

15

min

after

arrival

on

scene,

and

registered

manually

the

values

without

any

further

validation

of

these

data.

Since

the

Tidal

Wave

®

capnograph

had

no

auto-

matic

recording,

the

registered

minimum,

maximum

and

average

ETCO

2

from

each

patient

were

based

on

the

anaesthesiologists’

judgement.

Such

observation

might

lead

to

recording

errors

and

bias,

but

since

this

was

a

non-interventional

study,

the

registered

data

should

only

have

been

prone

to

recording

error.

Due

to

the

interesting

finding

of

the

time

variation

and

difference

between

causes

and

initial

rhythms,

future

studies

should

link

every

ETCO

2

to

time

during

the

resuscitation

procedure.

The

method

used

for

ETCO

2

recordings

should

be

improved

and

optimised

for

better

data

management

and

scientific

and

valid

interpretation.

Further,

the

patients

were

manually

ventilated,

and

although

this

was

done

or

observed

by

an

experienced

anaesthesiologist

we

have

no

data

on

quality

of

ventilations.

However,

the

impact

of

ventilation

may

be

of

minor

importance

in

a

low

flow

state

like

cardiac

arrest.

20

Pulmonary

flow,

generated

from

cardiac

output

achieved

through

chest

compressions,

is

more

important

in

this

situation.

Another

limitation

is

how

cause

of

death

was

determined

in

the

field

in

patients

without

ROSC.

We

have

no

autopsy

data,

and

the

uncer-

tainty

involved

in

these

causes

may

also

hide

undiagnosed

PE.

Consequently,

the

number

of

unknown

causes

is

high.

Finally,

epinephrine

impacts

on

cardiac

output

and

ETCO

2

during

ALS,

32

but

unfortunately

we

have

no

data

on

epinephrine

use

in

the

present

study.

Our

patients

received

epinephrine

following

guide-

line

recommendations.

17–19

5.

Conclusion

Capnography

is

a

useful

tool

to

optimise

and

individualise

ALS

in

cardiac

arrested

patients.

However,

confounding

factors

including

cause

of

arrest,

initial

rhythm,

bystander

CPR

and

time

from

cardiac

arrest

until

quantitative

capnography

had

an

impact

on

ETCO

2

val-

ues,

thereby

complicating

and

limiting

prognostic

interpretation

of

capnography

during

ALS.

Role

of

the

funding

source

Bård

E.

Heradstveit

is

a

fellow

research

of

The

Regional

Centre

for

Emergency

Medical

Research

and

Development

(RAKOS,

Sta-

vanger/Norway).

The

RAKOS

had

no

influence

on

the

topic,

study

design

or

interpretation

of

the

data.

Conflict

of

interest

statement

There

are

no

conflicts

of

interest.

Acknowledgements

The

study

was

supported

by

a

research

grant

from

the

Regional

Centre

for

Emergency

Medical

Research

and

Development

(RAKOS,

Stavanger/Norway).

MD

Ivar

Austlid

provided

supportive

infor-

mation

to

the

registration,

and

MD

Brian

Burns

made

valuable

comments

to

the

manuscript.

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