Resuscitation

83 (2012) 1425–

1426

Contents

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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

Editorial

Optimizing

oxygenation

and

ventilation

after

cardiac

arrest

in

“little

adults”

In

this

issue

of

the

journal,

del

Castillo

et

al.

1

report

the

find-

ings

of

the

Iberoamerican

Pediatric

Cardiac

Arrest

Network

on

the

timely

topic

of

oxygenation

after

cardiac

arrest

in

children.

Recent

studies

on

the

potential

deleterious

consequences

of

hyperoxia

in

adults

after

cardiac

arrest

2,3

have

brought

considerable

attention

to

this

aspect

of

patient

management

and

have

created

controversy.

4,5

In

this

exploratory

study

in

223

infants

and

children

between

1

month

and

18

years

of

age,

the

authors

once

again

demonstrate

that

pediatric

patients

are

not

little

adults.

Contrasting

a

recent

report

in

adults,

they

reported

no

association

between

hyperoxia

(defined

as

either

a

PaO

2

>

300

mmHg,

or

a

ratio

of

PaO

2

to

FiO

2

>

300)

after

restoration

of

spontaneous

circulation

(ROSC)

and

mortality

rate.

Acute

and/or

sub-acute

(24

hour)

hyperoxia

(PaO

2

>

300

mmHg)

after

ROSC

were

rarely

seen

and

represented

only

8.5%

and

1.7%

of

cases,

respectively.

In

contrast,

hypercapnia

or

hypocapnea

after

ROSC

were

common

and

both

were

significantly

associated

with

mortality—versus

normocapnea.

Finally,

more

than

66%

of

the

chil-

dren

had

a

non-cardiac

cause

for

their

arrest,

and

more

than

35%

had

a

pre-existing

respiratory

illness

as

the

arrest

etiology.

We

have

learned

the

lesson

that

children

are

not

little

adults

on

many

occasions

in

medicine,

and

the

field

of

resuscitation

medicine

has

produced

some

of

the

most

striking

examples

in

this

regard.

For

example,

we

know

that

after

asphyxial

cardiac

arrest

in

children

there

is

marked

superiority

of

conventional

cardiopul-

monary

resuscitation

(CPR)

when

compared

to

compression

only

CPR

6

—importantly

contrasting

the

adult

findings.

7

Well

known

to

most

of

the

readership

of

this

journal

is

the

fact

that

pediatric

cardiopulmonary

arrest

commonly

results

from

non-cardiac

eti-

ologies,

specifically

asphyxia—contrasting

the

cardiac

etiology

in

adults.

8,9

As

mentioned

above,

that

fact

was

again

demonstrated

in

the

current

report

of

del

Castillo

et

al.

1

In

2006,

Vereczki

et

al.

10

published

an

important

pre-clinical

report

in

an

adult

dog

model

of

ventricular

fibrillation

(VF)

car-

diac

arrest

showing

that

acute

hyperoxia

during

resuscitation

led

to

increased

neuronal

death

and

poor

outcomes.

Mechanisms

such

as

nitration

of

key

mitochondrial

enzymes

like

pyruvate

dehydro-

genase

or

selective

oxidation

of

mitochondrial

caridolipin

with

subsequent

triggering

of

apoptosis

may

be

deleterious

in

this

regard.

11,12

There

is

a

well

known

predisposition

of

the

developing

brain

to

injury

from

oxidative

stress

related

in

part

to

the

age-

dependent

relative

lack

of

glutathione

peroxidase.

13

This

creates

special

vulnerability

in

infants

to

hydrogen

peroxide

when

it

is

pro-

duced.

These

concerns

have,

for

decades,

been

the

basis

of

limiting

hyperoxia

in

the

field

of

neonatology.

One

might,

thus,

anticipate

that

this

biochemical

risk

factor

would

greatly

increase

the

dele-

terious

consequences

of

exposure

of

the

brain

to

hyperoxia

after

cardiopulmonary

arrest

in

pediatrics—to

a

level

above

that

seen

in

adult

resuscitation

medicine.

However,

in

children,

we

see

from

the

current

report

that

hyperoxia

was

a

fairly

uncommon

occurrence.

This

is

likely

in

part

due

to

the

excellent

treatment

delivered

by

the

caregivers

of

these

patients.

It

could

also

result

in

part

from

the

fact

that

over

35%

of

these

children

had

lung

disease

as

an

underlying

cause

for

the

arrest,

and

the

ability

to

generate

arterial

hyperoxia

may

have

been

blunted,

as

reflected

by

the

fact

that

many

patients

needed

a

high

FiO

2

to

achieve

normal

arterial

oxygenation.

This

is

certainly

not

surprising,

but

highlights

again

the

fact

that

asphyx-

ial

cardiopulmonary

arrest

is

a

unique

form

of

cardiac

arrest

that

has

its

own

unique

panoply

of

important

associated

factors.

For

example,

during

the

recent

deliberations

of

the

international

com-

mittee

addressing

guidelines

for

the

management

of

brain-directed

therapy

in

the

resuscitation

of

cardiopulmonary

arrest

in

drown-

ing

victims,

it

was

clear

that

approaches

such

as

the

use

of

room

air

in

resuscitation

could

be

deleterious

to

some

patients

given

the

pulmonary

morbidity

commonly

seen

in

drowning

victims.

14

How-

ever,

it

is

important

to

recognize,

that

the

question

of

potential

deleterious

effects

of

hyperoxia

on

mortality

or

reperfusion

injury

in

brain

or

heart

after

ROSC

in

children

was

not

really

tested

in

this

study,

given

its

rare

occurrence

in

this

dataset.

Thus,

the

possibility

that

pediatric

patients

could

exhibit

increased

risk

for

reoxygena-

tion

injury

in

the

setting

of

hyperoxia

has

not

yet

been

adequately

examined.

In

contrast

to

hyperoxia,

alterations

in

arterial

PaCO

2

,

defined

as

<30

mmHg

or

>50

mmHg

were

common

after

asphyxial

cardiopul-

monary

arrest

in

children,

having

been

seen

in

41%

of

the

patients

overall,

and

in

over

13%

and

27%

of

children,

respectively.

In

addi-

tion,

both

of

these

arterial

blood

gas

abnormalities

were

associated

with

mortality

with

odds

ratios

of

3.27

and

2.71,

respectively.

The

potential

effects

of

hypocapnea

in

resuscitation

are

com-

plex;

particularly

so

after

asphyxial

cardiopulmonary

arrest.

For

example,

overventilation

has

been

shown

to

adversely

impact

car-

diac

output

during

CPR.

15

Similarly

hypocapnea

has

been

suggested

to

produce

cerebral

vasoconstriction

and

exacerbate

cerebral

hypoperfusion

after

ROSC.

This

phenomenon

is

well

described

in

traumatic

brain

injury.

16

Delayed

hypoperfusion

after

ROSC

may,

as

first

reported

by

Snyder

et

al.

17

in

classic

studies,

be

important,

and

potentially

exacerbated

by

hypocapnea.

However,

hypocap-

nea

could

also

confer

potential

benefit

by

normalizing

arterial

pH,

a

phenomenon

that

is

seen

with

sodium

bicarbonate

in

some,

but

not

all

studies.

18

It

is

also

possible

that

the

association

between

hypocapnea

and

poor

outcome

could

simply

reflect

overwhelming

injury

with

severe

metabolic

depression

and

resultant

reduced

CO

2

production,

particularly

in

brain.

0300-9572/$

–

see

front

matter ©

2012 Published by Elsevier Ireland Ltd.

http://dx.doi.org/10.1016/j.resuscitation.2012.09.004

1426

Editorial

/

Resuscitation

83 (2012) 1425–

1426

The

association

between

hypercapnea

and

mortality

is

also

interesting

and

potentially

complex

in

the

setting

of

resuscitation

after

asphyxial

cardiopulmonary

arrest.

Whether

the

hypercapnea

has

a

cause

and

effect

on

mortality

or

whether

the

relationship

rep-

resents

an

epiphenomenon

is

unclear.

Greater

than

10%

of

patients

had

both

hypercapnea

and

hypoxemia,

and

thus

could

represent

a

high

risk

subgroup

with

significant

lung

disease

after

ROSC.

This

may

also

be

the

case

for

the

patients

with

isolated

hyper-

capnea,

which

has

been

shown

to

have

adverse

effects

even

on

resuscitation

from

experimental

VF

cardiac

arrest.

19

In

addition

to

simply

reflecting

lung

disease

or

large

functional

dead

space

from

low

cardiac

output

after

ROSC,

hypercapnea

could

potentially

con-

tribute

to

acute

post-resuscitation

cerebral

hyperemia,

the

impact

of

which

has

never

been

understood.

Consistent

with

this

possi-

bility,

although

blood

pressure

autoregulation

of

cerebral

blood

flow

is

likely

disturbed

after

clinically

relevant

asphyxial

cardiac

arrest,

20

it

is

likely

that

CO

2

reactivity

of

the

cerebral

circulation

is

intact—given

that

it

is

well

known

to

be

much

more

difficult

to

attenuate.

21

The

status

of

blood

pressure

autoregulation

of

CBF

and

CO

2

reactivity,

and

their

impact

on

outcome

inpatients

merit

additional

study

in

the

field

of

resuscitation.

Delayed

hypercap-

nea

at

24

h

after

ROSC

was

seen

in

∼10%

of

children

and

whether

this

contributed

to

deleterious

mechanisms

such

as

intracranial

hypertension,

brain

swelling,

or

herniation

is

unclear.

Similarly,

hypercapnea

after

ROSC

could

also

exacerbate

pulmonary

hyper-

tension

in

some

infants

and

children

and

reduce

cardiac

output.

Information

on

parameters

such

as

cardiac

output

and

mixed

venous

saturation

might

have

been

further

informative.The

con-

trasting

findings

of

del

Castillo

et

al.

1

and

the

aforementioned

prior

reports

in

adults

may

not

simply

reflect

differences

between

cardiac

arrest

in

children

and

adults.

They

may

reflect

important

differ-

ences

between

cardiopulmonary

arrests

of

asphyxial

vs.

cardiac

origins,

whether

in

children

or

adults.

However,

the

key

clinical

studies

published

to

date

in

adults

have

not

specifically

addressed

the

impact

of

hyperoxia

(or

alterations

in

PaCO

2

)

in

adults

in

asphyxial

cardiac

arrest

victims.

2–4

In

any

case,

del

Castillo

et

al.

1

once

again

demonstrate

that

cardiac

arrest

in

infants

and

children

represents

a

unique

entity

and

that

the

impact

of

various

therapeutic

interventions

must

be

specifically

examined

in

that

setting.

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Bouma

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1991;9:

S333–48.

Patrick

M.

Kochanek

a

,

b

,

∗

a

Safar

Center

for

Resuscitation

Research,

University

of

Pittsburgh

School

of

Medicine,

Pittsburgh,

PA,

United

States

b

Department

of

Critical

Care

Medicine,

University

of

Pittsburgh

School

of

Medicine,

Pittsburgh,

PA,

United

States

Hülya

Bayır

a

,

b

,

c

,

d

a

Safar

Center

for

Resuscitation

Research,

University

of

Pittsburgh

School

of

Medicine,

Pittsburgh,

PA,

United

States

b

Department

of

Critical

Care

Medicine,

University

of

Pittsburgh

School

of

Medicine,

Pittsburgh,

PA,

United

States

c

Department

of

Environmental

and

Occupational

Health,

University

of

Pittsburgh

School

of

Medicine,

Pittsburgh,

PA,

United

States

d

Pittsburgh

Center

for

Free

Radical

and

Antioxidant

Health,

University

of

Pittsburgh

School

of

Medicine,

Pittsburgh,

PA,

United

States

∗

Corresponding

author

at:

Safar

Center

for

Resuscitation

Research,

University

of

Pittsburgh

School

of

Medicine,

3434

Fifth

Avenue,

Pittsburgh,

PA

15260,

United

States.

Tel.:

+1

412

3831900;

fax:

+1

412

624

0943.

E-mail

address:

[e-mail]

(P.M.

Kochanek)

5

September

2012