Question ID : Peds 821 – “The Long Term Effects Of Atropine In Intubating Children And Infants” : ILCOR DATA COLLECTION
ILCOR Data Collection Form for Intervention Questions
Intervention Group
First Author Year
Jones P et al 2013
Jones P et al
2013
RCT or Non-RCT
Intervention
Measured
Outcome Measured
Loss to Follow-up?
Intervention or
Control?
Number with
Outcome
Atropine for
Non RCT
emergent RSI
(Prospective, intubation in
ICU survival
cohort)
critically ill paediatric
patients
No loss to follow
up. N=333; Noninclusions 56 (27,
extreme urgency,
17 ICT antenatal
positioning, 12
unclear); Excluded
13 (11 poor quality
tracing, 1 start
unclear, 1
prematurely
terminated)
Atropine for
Non RCT
emergent RSI
(Prospective,
intubation in
cohort)
critically ill paediatric
patients
No loss to follow
up. N=414; Noninclusions 60 (27,
extreme urgency,
17 ICT antenatal
positioning, 16
unclear); Excluded
7 bradyarrhythmias
27 (11 no heart rate
data, 15 no
arrhythmia data, 1
start unclear); 5 Preintubation non
sinus rhythm were
excluded
Arrhythmias
9 ICU deaths in
atropine
group; 115
survived at ICU
discharge
-
Control Group
Total
Number
Number with
Outcome
124
22 ICU deaths
in no atropine
group; 118
survived at ICU
discharge
152
Dichotomous Data
45 bradyarrhythmias
Total
Number
Notes relevant to the outcome
140
OR (ICU crude mortality) = 0.4198 95%CI (0.1854 to 0.9502); RR (ICU crude
mortality) = 0.4619 95%CI (0.221-0.9651), NNT = 11 95% CI (164-6); Subgroup
analysis suggest neonates (≤28 days old) - OR and RR (crude and adjusted for
illness) were not statistically significant. Paediatric patients > 28 days in this
study appear to have improved RR and OR for ICU survival when atropine was
given for emrgency RSI
125
RR 0.174 95%CI(0.0809 to 0.3741); OR 0.14 [95%CI, 0.06–0.35], p < 0.001;
Subgroup analysis shows greater sigbnificance when patient was >28 days of
age. Factors of interest associated with arrhythmias include: 1) Age (months)
– only univariate analysis showed significance OR 1.02 (1.00–1.04); p= 0.02;
multivariate analysis not significant; 2) Atropine – both in univariate OR 0.17
(0.07–0.39); p= <0.0001 and multivariate analysis OR 0.14 (0.06–0.34); p <.0001
1
Use of Atropine compared to no-atropine as Premedication for Emergency intubation in infants and Children
Bibliography (systemic reviews)
Quality Assessment
No of Participants
(Studies)
Followup
Summary of findings
Risk of
Bias
Inconsistency
Indirectness
Imprecision
Publication
bias
Overall quality
of evidence
Atropine
No Atropine
OR
(95%
CI)
RR
(95%
CI)
ARR
(95% CI)
124
140
0.42
(0.190.95)
Atropine
No Atropine
OR
(95% CI)
RR
(95% CI)
0.23 (0.120.45)
0.2 (0.1 -0.4)
Survival to ICU Discharge -Critical Outcome
264
(1 non RCT,
observational study
1
)
No of Participants
(Studies)
Followup
Serious
Not serious
Not serious
Serious
none
Risk of
Bias
Inconsistency
Indirectness
Imprecision
Publication
bias
Overall quality
of evidence
0.46
(0.220.97)
0.085
(0.060.16)
Incidence of Arrhythymias (Bradyarrhythmias) – Important outcome
220
(2 non RCT,
observational
studies 2,3)
Serious
Serious
Not serious
Serious
none
220
245
2
Appendix A : Subgroup Analysis of the 3 studies
Use of Atropine compared to no-atropine as Premedication for Emergency intubation in infants and Children
Quality Assessment
Survival to ICU Discharge -Critical Outcome
Subgroup analysis
Summary of findings
Atropine
No Atropine
OR (95% CI)
RR (95% CI)
(Subgroup Analysis)
1a) Neonates (Crude survival)
79
74
1b) Non-neonates (Crude survival)
45
66
2a) Neonates (Propensity scored)
79
74
1.4
(0.41-4.78)
0.24
(0.08-0.78)
-
2b) Non-neonates (Propensity scored)
45
66
1.43
(0.39-5.31)
0.19
(0.05-0.69)
2.4
(0.56-10.4)
0.24
(0.06-0.96)
Incidence of Arrhythymias (Bradyarrhythmias) – Important outcome
Atropine
Survival to ICU Discharge -Critical Outcome
(Subanalysis of the 2 studies)
P Jones 2
RK Fastle 3
152
68
-
ARR (95% CI)
-0.02
(-.11 -0.07)
0.21
(0.06-0.33)
-
No Atropine
OR (95% CI)
RR (95% CI)
170
75
0.17 (0.08 - 0.37)
1.10 (0.23-5.21)
0.14 (0.06–0.35)
1.11 (0.22-5.68)
1.P Jones, MJ Peters, NP da Costa, T Kurth, C Alberti, K Kessous, N Lode, S Dauger. Atropine for critical care intubation in a cohort of 264 children and reduced mortality unrelated to effects on
bradycardia. PLoS ONE 2013; 8 (2): e57478.
2. P Jones, S Dauger, I Denjoy, NP da Costa, C Alberti, R Boulkedid, MJ Peters. The effect of atropine on rhythm and conduction disturbances during 322 critical care intubations. Pediatr Crit Care
Med Jul--2013; 14 (6): e289-97.
3. RK Fastle, MG Roback. Pediatric rapid sequence intubation: Incidence of reflex bradycardia and effects of pretreatment with atropine. Pediatr. Emerg. Care 2004; 20 (10): 651-655.
3
Question ID : Peds 821 – “The Long Term Effects Of Atropine In Intubating Children And Infants” : GRADE GRID
In infants and children requiring emergent tracheal intubation (P), does the use of atropine as a pre-medication (I), compared with when compared to not using atropine
(C), change Survival with Favorable neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year, survival to hospital discharge, incidence of
arrhythmias, the likelihood of cardiac arrest, the likelihood of shock (O)?
Benefits & harms of the options
Problem
Criteria
Is there a
problem
priority?
Judgement
s
 Probably
yes
Research evidence
Additional
consideration
s
1) Outcome : Survival
There were no outcome studies published on survival with good neurological outcomes
ICU survival : Only 1 Non-RCT –prospective, cohort study
Jones et al 2013. Prospective cohort study (n= 264). Atropine for critical care intubation in a cohort of 264 children and reduced
mortality unrelated to effects on bradycardia.
OR (ICU crude mortality) = 0.4198 95%CI (0.1854 to 0.9502)
RR (ICU crude mortality) = 0.4619 95%CI (0.221-0.9651), ARR 0.085 95% CI (0.06-0.162), NNT = 11 95% CI (164-6)
What is
the overall
certainty
of this
evidence?
 Low
Subgroup analysis :
Age: Neonates – not significant
OR ICU crude mortality for neonates: 1.4 CI 95% 0.39-5.3;
RR ICU crude mortality for neonates= 1.4051 95% CI (0.4128-4.7821),ARR: -0.022 95% CI(-0.108-0.065), NNT = -46 95% CI (-9-15)
OR Adjusted ICU mortality for neonates: OR for neonates: 1.3 95%CI (0.31-5.1)
Age: >28 days – highly significant
OR Crude ICU mortality for >28days old: 0.017 CI 95% 0.06-0.75
RR crude ICU mortality >28days old = 0.2444 95% CI (0.0765-0.7814),; ARR: 0.206 95% CI(0.061-0.332), NNT = 4 95% CI (16-3)
OR Adjusted ICU mortality for >28 days old: 0.22 95%CI (0.06-0.85)
There was also no clinically significant adverse events associated with atropine use.
4
In infants and children requiring emergent tracheal intubation (P), does the use of atropine as a pre-medication (I), compared with when compared to not using atropine
(C), change Survival with Favorable neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year, survival to hospital discharge, incidence of
arrhythmias, the likelihood of cardiac arrest, the likelihood of shock (O)?
Criteria
Judgement
s
Research evidence
Additional
consideration
s
Risk of Bias :
Is there
important
uncertaint
y about
how much
people
value the
main
outcomes?
 Possibly
important
uncertainty
or variability
Conclusions:
For this single study, the use of atropine for emergent intubation in paediatric patients (overall) was associated with ICU mortality RR
of 0.4619 95%CI (0.221-0.9651). On subgroup analysis, patients >28 days old appear to have statistically significant association with
improved ICU survival rates when atropine is used during emergent intubation with RR of ICU mortality 0.2444 95% CI (0.0765-0.7814).
However N = 111. Limited recommendations can be made on the effects of atropine and its influence on ICU mortality based on this
single cohort study; however atropine was associated with statistically significant ICU survival especially if >28 days of age.
5
In infants and children requiring emergent tracheal intubation (P), does the use of atropine as a pre-medication (I), compared with when compared to not using atropine
(C), change Survival with Favorable neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year, survival to hospital discharge, incidence of
arrhythmias, the likelihood of cardiac arrest, the likelihood of shock (O)?
Criteria
Judgement
s
Research evidence
Additional
consideration
s
2) Outcome: Arrhythmias
3 studies of which only 2 can be analysed:
1)
Jones et al 2013. Prospective, cohort study (N=322): The effect of atropine on rhythm and conduction disturbances during 322
critical care intubations.
2) Fastle RK et al 2004. Retrospective, cohort study (N= 143). Pediatric rapid sequence intubation: incidence of reflex bradycardia
and effects of pretreatment with atropine.
3) Sing RF et al. 1996. Retrospective, epidemiological study (N=40). Out-of-hospital rapid-sequence induction for intubation of the
pediatric patient.
Due to low quality of study and lack of availability of details for Sing RF et al, only 2 studies are analysed.
1) Jones et al. 2013 (N=322)
Outcome: Development of bradyarrhythmias or conduction/heart blocks
RR 0.174 95%CI(0.0809 to 0.3741); OR 0.14 [95%CI, 0.06–0.35], p < 0.001
Factors associated with arrhythmias include
a)Age (months) – only univariate analysis showed significance OR 1.02 (1.00–1.04); p= 0.02; multivariate analysis not significant
b)Atropine – both in univariate OR 0.17 (0.07–0.39); p= <0.0001 and multivariate analysis OR 0.14 (0.06–0.34); p <.0001
c) Etomidate – only multivariate analysis showed significance OR 5.29 (1.07–26.2); p=0.04; univariate analysis not significant
2) Fastle RK et al 2004 (N=143)
Outcome: Development of bradycardia
RR 1.3061 95%CI (0.1235-13.8165); OR 1.1077 95%CI (0.2159-5.6824)
3) Combining both studies: (N=465)
RR 0.2320 95%CI (0.1203-0.4473); z=4.362 (p<0.0001)
OR 0.1954 95%CI (0.0962 -0.3969), z=4.516 (p<0.0001)
Risk of Bias :
6
In infants and children requiring emergent tracheal intubation (P), does the use of atropine as a pre-medication (I), compared with when compared to not using atropine
(C), change Survival with Favorable neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year, survival to hospital discharge, incidence of
arrhythmias, the likelihood of cardiac arrest, the likelihood of shock (O)?
Criteria
Judgement
s
Research evidence
Additional
consideration
s
Conclusions:
2 Non- RCTs were included for analysis and review for the effect of atropine on the development of bradycardias during emergency
intubations in critically ill infants and children.
Due to the weighted effects of Jones et al, it would appear that atropine may be associated with a decreased occurrence of
bradyarrhythmias during emergency intubations in critically ill infant and children.
7
In infants and children requiring emergent tracheal intubation (P), does the use of atropine as a pre-medication (I), compared with when compared to not using atropine
(C), change Survival with Favorable neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year, survival to hospital discharge, incidence of
arrhythmias, the likelihood of cardiac arrest, the likelihood of shock (O)?
Criteria
Judgement
s
Research evidence
Additional
consideration
s
However, there was no direct clinical consequence attributable to the development of these bradyarrhythmias noted in both papers.
There were also no clinically significant adverse events associated with atropine use.
The relative importance or values of the main outcomes of interest :
Summary of Findings :
8
In infants and children requiring emergent tracheal intubation (P), does the use of atropine as a pre-medication (I), compared with when compared to not using atropine
(C), change Survival with Favorable neurological/functional outcome at discharge, 30 days, 60 days, 180 days AND/OR 1 year, survival to hospital discharge, incidence of
arrhythmias, the likelihood of cardiac arrest, the likelihood of shock (O)?
Criteria
Judgement
s
Research evidence
Additional
consideration
s
9
RECOMMENDATIONS
Should atropine vs no-atropine be used as a premedication in infants and children for emergency intubation?
Balance of
Consequences
Type of Recommendation
Recommendation
Justification /
Subgroup considerations
Undesirable consequences
clearly outweigh desirable
consequences in most
settings
Undesirable consequences
probably outweigh
desirable consequences in
most settings
We recommend against offering
this option
The balance between
desirable and undesirable
consequences is closely
balanced or uncertain
We suggest not offering this
option
Desirable consequences
probably outweigh
undesirable consequences
in most settings
We suggest offering this
option
Desirable consequences
clearly outweigh
undesirable consequences
in most settings
We recommend offering this
option
There is insufficient evidence for the routine use of atropine as a premedication for emergent intubation in infants and children.
(Weak recommendation, Very low quality of evidence)
Thus far, there has only been 1 prospective 2 year observational study involving 264 patients. In this study, atropine use was
associated with a significant difference in the survival of the older children but not in neonates.
There were 2 non-RCT trials involving a total of 465 patients which seem to suggest that atropine may be associated with a
decreased occurrence of the development of bradyarrhythmias/conduction blocks during emergency RSI intubations in critically ill
paediatric patients. However both studies suggest that there was no direct clinical consequence (haemodynamics) of the
arrhythmias.
10