Criteria
Judgeme
nts
○ No
○
Probably
no
Problem
Is there a
problem
priority?
○
Uncertain
●
Probably
yes
○ Yes
○ Varies
Additional
considerat
ions
Research evidence
What we knew: The mortality of post cardiac arrest patients is
high. Post arrest management has the potential to improve
survival and neurologic outcomes. Hyperventilation (leading to
hypocapnia) reduces cerebral blood flow and is associated
with worse outcomes in children following stroke or traumatic
brain injury and hypoxic ischemic injury in neonates.
Alternatively, hypercapnia can increase cerebral blood flow
which could increase intracranial pressure and worsen
metabolic acidosis. Alternatively, mild hypercapnia improves
cerebral perfusion and may have neuro-protective effects
after brain injury in animal studies.
What is added with this review: The prevalence of dyscarbia
during the first hours after ROSC is high: up to 55% of the
total of patients included in the reviewed studies (36.2%
hypercapneic and 25% hypocapneic). The 2 studies selected
have been published recently (2012, 2013), are observational
and only include non-traumatic patients suffering both in and
out-of- hospital cardiac arrest. The Del Castillo study reports a
negative association between hypocapnia and outcome and a
negative association with hypercapnia and outcome, whereas
the Bennett reported no association between ventilation
status and outcome.
What is added from the adult taskforce on ventilation strategy
post cardiac arrest: All studies are observational, recent
(2012-2014), and only include non-traumatic cardiac arrest
patients. All studies showed a trend or worse outcomes with
hypocapnia and hypercapnia.
○ No
included
studies
What is
the
overall
certainty
of this
evidence?
Benefits
& harms
of the
options
● Very
Outcome
low
○ Low
○
Relative
importance
○ High
Survival with Favorable
neurological/functional
outcome at discharge in
pediatric patients
CRITICAL
○
Survival to hospital discharge
in pediatric patients
IMPORTANT
Moderate
Is there
important
uncertaint
y about
how much
people
value the
main
The relative importance or values of the main outcomes
of interest:
Certainty of
the
evidence
(GRADE)
⨁◯◯◯
VERY LOW
⨁◯◯◯
VERY LOW
Important
uncertaint
y or
Summary of findings: normocapnia
variability
○
Possibly
important
Outcome
Without
ventilati
With
ventilati
Differe
nce
Relati
ve
Criteria
outcomes
?
Judgeme
nts
uncertaint
y or
variability
on to
on to
hypercap hypercap
nia
nia
○
Probably
no
important
uncertaint
y of
variability
● No
important
uncertaint
y of
variability
○ No
known
undesirab
le
Additional
considerat
ions
Research evidence
Survival with
Favorable
neurological/fun
ctional outcome
at discharge in
pediatric
patients
Survival to
hospital
discharge in
pediatric
patients
474 per
1000
669 per
1000
(95%
CI)
effect
(RR)
(95%
CI)
359 per
1000
(235 to
551)
114
fewer
per
1000
(from
77 more
to 239
fewer)
RR
0.758
7
(0.495
3 to
1.162
2)
320 per
1000
(178 to
575)
349
fewer
per
1000
(from
95
fewer to
491
fewer)
RR
0.478
(0.266
2 to
0.858
2)
With
ventilati
on to
hypocap
nia
Differe
nce
(95%
CI)
Relati
ve
effect
(RR)
(95%
CI)
140
fewer
per
1000
(from 68
more to
268
fewer)
RR
0.703
7
(0.433
4 to
1.142
6)
○ No
●
Probably
no
Are the
desirable
anticipate
d effects
large?
○
Uncertain
○
Probably
yes
○ Yes
○ Varies
Are the
undesirab
le
anticipate
d effects
small?
○ No
○
Probably
no
○
Uncertain
●
Probably
yes
Outcome
Without
ventilati
on to
hypocap
nia
Survival with
Favorable
neurological/func
tional outcome at
discharge in
pediatric patients 474 per
(assessed with:
1000
PCPC 1-2 or no
change with
baseline pre-CA)Bennett, CCM,
2013
333 per
1000
(205 to
541)
Criteria
Judgeme
nts
○ Yes
○ Varies
○ No
○
Are the
desirable
effects
large
relative to
undesirab
le effects?
Additional
considerat
ions
Research evidence
Survival to
hospital
discharge in
pediatric
patients- Del
Castillo,
Resuscitation,
2012
669 per
1000
556 per
1000
(305 to
1010)
114
fewer
per
1000
(from
341
more to
364
fewer)
RR
0.829
8
(0.456
3 to
1.508
9)
Probably
no
●
Uncertain
○
N.B. Del Castillo did not study survival with favourable
neurological outcome at discharge. Bennett does not present
the data on survival to hospital discharge by ventilation
category thus is not included in this RR calculation.
Probably
yes
○ Yes
○ Varies
○ No
○
Probably
no
Are the
resources
required
small?
○
Uncertain
○
Probably
yes
● Yes
○ Varies
Resource
use
Is the
increment
al cost
small
relative to
the net
benefits?
○ No
○
Probably
no
●
Uncertain
○
Probably
yes
The additional resources required would be possibly more
frequent blood gases (depending on institution baseline) and
adjustments on the ventilator.
Pre-hospital monitoring of ventilation after ROSC is desirable,
especially if the pre-hospital time is long. The equipment
necessary to monitor ventilation is not frequently available for
pre-hospital providers. In the in-hospital setting this
monitoring is a standard of care.
Criteria
Judgeme
nts
Research evidence
○ Yes
○ Varies
○
Increased
Depending on the ability to do blood gas monitoring and make
ventilator changes.
○
Equity
What
would be
the
impact on
health
inequities
?
Probably
increased
●
Uncertain
○
Probably
reduced
○
Reduced
○ Varies
○ No
○
Acceptab
ility
Is the
option
acceptabl
e to key
stakehold
ers?
Probably
no
○
Uncertain
●
Probably
yes
○ Yes
○ Varies
○ No
○
Feasibilit
y
Is the
Probably
option
feasible to no
implemen
t?
Uncertain
○
●
Probably
It would likely be acceptable to stakeholders to monitor pCO2,
as this is currently the standard of care in the hospital setting.
Monitoring EtCO2 is becoming the standard in pre-hospital
settings as a surrogate marker for quality of CPR and
detection of ROSC and thus it may be acceptable to continue
to monitor EtCO2 until arrival to a hospital, even though the
evidence is of low quality.
Additional
considerat
ions
Criteria
Judgeme
nts
Additional
considerat
ions
Research evidence
yes
○ Yes
○ Varies
Recommendation
Should ventilation to hypercapnia vs. normocapnia be used for infants and
children with ROSC after cardiac arrest in any setting?
Balance of
consequences
Undesirable
consequences
clearly
outweighdesirable
consequences in
most settings
Undesirable
consequences
probably
outweigh
desirable
consequences in
most settings
The balance
between
desirable and
undesirable
consequences is
closely balanced
or uncertain
Desirable
consequences
probably
outweigh
undesirable
consequences in
most settings
Desirable
consequences
clearly outweigh
undesirable
consequences in
most settings
○
○
●
○
○
Type of
recommendation
Recommendation
We recommend against
offering this option
We suggest not
offering this option
We suggest
offering this
option
We recommend
offering this option
○
●
○
○
We suggest maintaining pCO2 with normal physiological range (30-50mmHg) as part of a
post ROSC bundle of care (weak recommendation, very low quality of evidence).
Part A. Hypercapnia vs. Normocapnia
Justification
For the critical outcome of survival to hospital discharge with favorable/functional
neurological outcome in pediatric patients (assessed with PCPC 1-2 or no change with
baseline pre-CA), we have identified very low quality evidence from one observational
study [Bennett, 2013, 1534] of 195 pediatric in and out-of-hospital cardiac arrest
survivors to at least 6 hours post-arrest (down-graded for indirectness, imprecision and
serious risk of bias) showing no benefit of hypercapnia (> 50 mmHg) (Relative Risk of
survival to hospital discharge with favorable/functional neurological outcome is 0.7587, CI
0.4953 to 1.1622).
For the important outcome of survival to hospital discharge in pediatric patients we have
identified very low quality evidence from one observational study [Del Castillo, 2012,
1456] of 223 pediatric patients suffering an in-hospital cardiac arrest (down-graded for
inconsistency, indirectness, imprecision and serious risk of bias). This study showed worse
outcome with hypercapnia (≥ 50 mmHg) (Relative Risk of survival to hospital discharge is
0.478, CI 0.2662 to 0.8582).
Part B. Hypocapnia vs. Normocapnia
For the critical outcome of survival to hospital discharge with favorable/functional
neurological outcome in pediatric patients (assessed with PCPC 1-2 or no change with
baseline pre-CA), we have identified very low quality evidence from one observational
study [Bennett, 2013, 1534] of 195 pediatric in and out-of-hospital cardiac arrest
survivors to at least 6 hours post-arrest (down-graded for indirectness, imprecision and
serious risk of bias) showing no benefit of hypocapnia (< 30 mmHg) (Relative Risk of
survival to hospital discharge with favorable/functional neurological outcome 0.7037, CI
0.4334 to 1.1426).
For the important outcome of survival to hospital discharge in pediatric patients we have
identified very low quality evidence from one observational study [Del Castillo, 2012,
1456] of 223 pediatric suffering an in-hospital cardiac arrest (down-graded for
inconsistency, indirectness, imprecision and serious risk of bias) showing no benefit of
hypocapnia (< 30 mmHg) (Relative Risk of survival to hospital discharge is 0.8298, CI
0.4563 to 1.5089).
There were no subgroups analyzed in the two pediatric studies.
Subgroup
considerations
Patients being treated with therapeutic hypothermia would require temperature corrected
interpretation of blood gases to avoid excessive hypocapnia.
Patients with lung injury may benefit from less aggressive respiratory ventilation targets
and a strategy of "permissive hypercapnia" to minimize risk of ventilator-induced lung
injury.
Acceptability: current recommendations are to consider performing blood gas analysis
every 10 to 15 minutes after establishing initial mechanical ventilator settings and make
appropriate adjustments. If we were to institute pCO2 targets, this would align with this
2010 ILCOR recommendation. Targets may be acceptable in the pre-hospital setting
where EtCO2 detectors are in use. The evidence may not be strong enough to institute
EtCO2 detectors for the sole purpose of targeting normocapnia in the pre-hospital setting.
Implementation
considerations
Feasibility: Achieving pCO2 targets may be difficult (as evidenced in Roberts's CCM 2014
study) but in all patients who are intubated and can have blood gas analyses, it is feasible
to target pCO2. Aiming to avoid hypocapnia could result in hypercapnia. The long term
consequences of hypercapnia are more unclear than they are for hypocapnia.
Time frame: No study went beyond 24h. Duration of targeted pCO2 would depend on
patient's condition and their ability to control their own CO2 (pressure supported
ventilation vs mandatory ventilatory strategies)
Accountability: In most cases, the most responsible physician will be accountable to the
targets in the in-hospital setting.
Monitoring and
evaluation
Research
possibilities
Studies need to look at both mean PCO2 (temperature corrected where appropriate), and
variability of PCO2. The more values the better and all must have temporal correlation.
No analysis should be performed without adjusting for age, Utstein criteria, prescribed
ventilation, comorbidities (e.g. lung disease), oxygenation, cooling. Degree of dyscarbia
should be reported and analyzed.
Currently, a multicenter RCT in adult population has been started to evaluate a strategy
of normocapnia versus mild hypercapnia during the first 24h. Similar studies would be
desirable in the pediatric population. The available studies are observational and very
heterogeneous regarding patients, methodology and outcomes. Additional research
evaluating the balance between lung protection parameters and permissive hypercapnia
versus standard ventilatory parameters and normocapnia may be interesting, as
respiratory etiology is common among the pediatric population. It would also be
interesting to determine which is the most desirable method of evaluating PaCO2 during
hypothermia in pediatric patients (ph-stat or alpha-stat).