Peds 814: In infants and children during cardiac arrest (P), does the presence of any specific intra-arrest prognostic factors (I), compared with the
absence of these factors (C), change survival to 180 days with good neurological outcome, survival to 60 days with good neurological outcome, survival
to hospital discharge with good neurological outcome, survival to 30 days with good neurological outcome, Survival only at discharge, 30 days, 60 days,
180 days AND/OR 1 year (O)?
Summary of evidence:
No randomized clinical trials were found. The initial search strategy (detailed in SEERS) generated 6476 abstracts. After screening the papers from the
search strategy and excluding repeated studies, studies done in another language than English, studies with mixed adult and pediatric populations or
OOHCA and IHCA when the data could not be analyzed separately, publications before the year of 2000 (guidelines then were different) and papers that
reported exclusively cases with trauma, drowning populations or SIDS (these are populations with known different prognostics related to cardiac
arrest): 22 papers were reviewed to determine which intra-arrest prognostic factors could be assessed from the published data. Therapeutic
interventions were not reviewed as part of this work, as a number of these were assessed in other PICO questions. Duration of CPR, age, and initial
arrest rhythm were selected as being most amenable to assessment from published data. We selected 5 studies for out of hospital cardiac arrest
(OOHCA), one of the studies was determined to be not applicable to the PICO question and was excluded after assessment of risk of bias.
1.
2.
3.
4.
5.
Young2004 157. Subsequent analysis of randomized study comparing airway interventions in OOHCA, 601 patients, data from 1994-97 (older
CPR guidelines with different compression:ventilation ratios). Setting: USA. Subjects: age < 12 years or smaller than 40kg. Total number of
cases: age: 601/601; rhythm: 548/601; duration: not available (NA); survival to discharge: 596. No multivariate analysis performed. For
survival to discharge, shorter CPR duration and older age were associated with survival.
Lopez-Herce2005 807. Reanalysis of a published 2004 report limiting data to OOHCA, Observational study of 95 children with respiratory
arrest or OOHCA, data from 1998-1999. Setting: multicenter in Spain. Subjects: age: 7 days to 16 years. Total number of cases: age: 95/95;
rhythm: 83/95; duration: 94/95, 78 had cardiac arrest. Outcomes of survival to discharge and one year survival were not available for all
factors selected. Multivariate analysis showed best predictor of mortality was duration of resuscitation of > 20 minutes. Mortality was higher
for infants. Mortality was higher for asystole, PEA, and slow rhythms vs. VF.
Tham2005 289. Retrospective study of OOHCA, 85 patients with only 4 survivors. Setting: Single center in Singapure. Subjects: does not define
age group for “children.” Only significant finding was shorter duration of CPR associated with survival. This non-RCT was not included on our
GRADE evaluation due to the imprecision of definitions, missing data, and very low number of survivors making comparison between groups
problematic.
Atkins2009 1484. Prospective observation study from Resuscitation Outcomes Consortium, from 2005-2007. Setting: Multicentric USA and
Canada. Subjects: age less than 20 years with OOHCA; trauma excluded. Total of 624 patients, not all data available for all patients: age:
621/624; rhythm: 469/624; duration: not available (NA). Age > 12 months was associated with survival; VF/VT rhythm was associated with
survival compared to combined PEA/asystole.
Moler2011 141. Retrospective analysis of OOHCA data collected for future hypothermia trial from 2003 to 2004. Setting: 15 sites PECARN.
Subjects: ages: 24 hours to 18 years. Total of 138 patients, but not all data available for all variables for selected variables: age: 137/138;
rhythm: 138/138; duration: 69/138. Patients were less likely to survive is they had non-VF rhythms or had longer duration of CPR.
Moderate/large
effect size
Publication bias
Study
Limitations
Imprecision
Number of
participants
Indirectness
Potential prognostic factor
Odds Ratio
(95%
Number of confidence
studies
interval)
Inconsistentency
Potential Prognostic Factor: Age
Overall
quality
Survival to discharge (Important)
Very low
Age > 1 year (Young2004)
601
1A
Non-RCT
1.3 (0.8 -2.1)
Very
SeriousB
Not
Not
Serious Serious
Not
Not
Serious Serious
Age > 1 year (Atkins2009)
621
1C
Non-RCT
2.7 (1.3-5.7)
Not serious
Not
Not
Serious Serious
SeriousD
Not
Serious
Low
Moderate
⨁⨁◯◯
effect size
Age > 1 year (Moler2011)
137
1E
Non-RCT
1.4 (0.8-2.4)
Very
SeriousF
Not
Not
Serious Serious
SeriousG
Not
Serious
No
A:
Young2004 157.
No control for confounders and data from 1994-1997.
C: Atkins2009 1484.
D: Wide confidence interval.
E: Moler2011 141.
F: No control for confounders and data from 2003-2004.
G: Small number of events.
B:
No
⨁◯◯◯
Very low
⨁◯◯◯
Moderate/large
effect size
Publication bias
Imprecision
Number of
participants
Indirectness
Potential prognostic factor
Relative Risk
(95%
Number of confidence Study
studies
interval)
Limitations
Inconsistentency
Potential Prognostic Factor: Rhythm
Overall
quality
Survival to discharge (Important)
Very low
VF/VT compared to Asystole/PEA
548
(Young2004)
1H
Non-RCT
1.3 (0.5-3.0)
Very SeriousI
Not
Not
Serious Serious
Not
Not
Serious Serious
VF/VT compared to Asystole/PEA
417
(Atkins2009)
1J
Non-RCT
4.0 (1.8-8.9)
SeriousK
Not
Not
Serious Serious
SeriousL
Not
Serious
Moderate Very low
effect size ⨁◯◯◯
VF/VT compared to Asystole/PEA
91
(Moler2011)
1M
Non-RCT
2.7 (1.3-5.6)
Very
SeriousN
Not
Not
Serious Serious
SeriousO
Not
Serious
Moderate Very low
effect size ⨁◯◯◯
H:
No
⨁◯◯◯
Young2004 157
No control for confounders and data from 1994-1997.
J: Atkins2009 1484.
K: Loss of follow up in 156 cases out of 624 (25%) and rhythm not determined in 51 subjects (more than the total number of subjects in the VF/VT
group).
L: Large confidence interval.
M: Moler2011 141.
N: No control for confounders and data from 2003-2004. Asystole at any time during the arrest was more common in nonsurvivors than in survivors
(67% vs 26%, p<0.01).
O: Small number of events and wide confidence interval.
I:
Moderate/large
effect size
Publication bias
Imprecision
Number of
participants
Indirectness
Potential prognostic factor
Relative Risk
(95%
Number of confidence Study
studies
interval)
Limitations
Inconsistentency
Potential Prognostic Factor: Duration of Resuscitation
Overall
quality
Survival to discharge (Important)
Young2004 157
601
Non-RCT
Moler2011 141
138
Non-RCT
63
1S
Non-RCT
Survivors:
median 16
(IQR 1030)min,
nonsurvivors:
median 36
(29-48)min.P
Survivors:
median 18.5
(3.5-28.5)min
and
nonsurvivors:
41 (24-54)
min. p<0.01
Very
SeriousQ
Not
Not
Serious Serious
Very
SeriousR
Not
Not
serious Serious
Very
SeriousT
Not
Not
Not serious SeriousU
Serious
Serious
Very Low
NA
Not
Serious
NA
NA
Not
Serious
NA
⨁◯◯◯
Very Low
⨁◯◯◯
Survival 1 year (important)
Duration < 20 minutes
(Lopez-Herce2005)
6.6 (2.9-14.9)
Large
Very low
⨁◯◯◯
P:
Not statistically significant. Longest duration of CPR in a survivor: 56 minutes, longest duration of CPR in a survivor with good neurologic outcome 42
minutes (31 minutes of CPR in ED and 11 minutes before hospital arrival).
Q: No control for confounders and data from 1994-1997.
R: 50% loss of follow up for the duration of resuscitation data (information on 69 subjects).
S: Lopez-Herce2005 807.
T: Lopez-Herce2005 807 included both respiratory and cardiac arrests and data is from 1998-1999.
U: Small number of events, large confidence interval.
Consensus on Science
For the important outcome of survival to discharge in OOHCA, we found one low quality observational study (Atkins 2009:1484; 621 OOHCA subjects,
downgraded for serious imprecision and upgraded for moderate effect size) that found that age >1 year was significantly associated with improved
outcome (Relative Risks 2.7(1.3-5.7). Two very low quality observational studies (Young 2004:157; 601 OOHCA subjects, downgraded for very serious
risk of bias) (Moler 2011:141; 137 OOHCA subjects, downgraded for very serious risk of bias and serious imprecision) showed an insignificant trend
toward improved outcomes in patients >1 year (Relative Risk: Young 1.3 (0.8-2.1), Moler 1.4 (0.8-2.4)
For the important outcome of survival to discharge, we found two very low quality observational studies (Atkins 2009:1484, 417 OOHCA subjects,
downgraded for serious risk of bias and serious imprecision and upgraded for moderate effect size) (Moler 2011:141, 91 OOHCA subjects, downgraded
for very serious risk of bias and serious imprecision and upgraded for moderate effect size) that found VF/VT as an initial rhythm was significantly
associated with improved outcome compared to the combined rhythm group of PEA/asystole with Relative Risks of: Atkins 4.0(1.8-8.9) and Moler 2.7
(1.3-5.6). One observational study (Young 2004:157; 548 OOHCA subjects, downgraded for very serious risk of bias) demonstrated a trend toward
improved survival in the VF/VT group that did not achieve statistical significance (Relative Risk 1.3(0.5-3.0)).
For the important outcome of survival to discharge and survival to one year we have identified very low quality evidence from three observational
studies (Young 2004:157; 601 OOHCA subjects, downgraded for very serious risk of bias) (Moler 2011:41; 138 OOHCA subjects, downgraded for very
serious risk of bias) (Lopez-Herce 2005:807, 63 OOHCA subjects, downgraded for very serious risk of bias and serious imprecision and upgraded for
large effect size) showing a higher likelihood of survival with shorter duration of CPR. CPR for less than 20 minutes was associated with improved one
year survival in one study (Relative Risk 6.6; CI 2.9-14.9, Lopez) while median durations of 16 (IQR 10-30) and 19 (IQR3.5-28.5) minutes were
associated with survival to hospital discharge in two studies (Young, Moler).
We did not identify enough evidence to address the critical outcomes of survival to 180 days with good neurological outcome, survival to 60 days with
good neurological outcome, survival to hospital discharge with good neurological outcome.
We did not identify enough evidence to address the important outcomes of survival only at 30 days, 60 days, 180 days nor survival to 30 days with good
neurological outcome.
Treatment Recommendation
For pediatric patients in OOHCA treated with standard CPR (without extracorporeal rescue), the published data are so limited in number and quality
that confidence in effect estimates is very low. As a result, the task force feels that any recommendation to identify a maximum length for attempted CPR
is speculative.
Knowledge gaps
Large prospective studies correlating risk factors to event survival and longer-term survival, particularly with neurological outcomes, are needed to
predict successful resuscitation for children in OOHCA and guide decisions on termination of resuscitation. Studies need to be performed in time frames
that maintain similar resuscitation protocols to reduce the risk of bias from changing treatment strategies.