1. Dallas 2015 TFQO: Kee-Chong Ng (#COI = 170) EVREV 1: Gene Ong (#COI = 118) EVREV 2: Jos Bruinenberg (#COI = 19) Taskforce: Pediatric Taskforce The Long Term Effects Of Atropine In Intubating Children And Infants (Peds 821)

2. Dallas 2015 COI Disclosure (SPECIFIC to this systematic review) EVREV 1 COI#118 Commercial/industry Nil Potential intellectual conflicts Nil EVREV 2 COI#19 Commercial/industry Nil Potential intellectual conflicts Nil

3. Dallas 2015 2010 Treatment Recommendation “Topic not reviewed in 2010”.

4. Dallas 2015 C2015 PICO Population: Pediatrics & Neonates Intervention: Use of Atropine as premedication in emergency intubation Comparison: No atropine OUTCOMES LEVEL OF IMPORTANCE Likelihood/incidence of cardiac arrestCritical (9) Survival with favorable neurological outcome at survival to  hospital discharge  30 days follow up  90 days follow up  180 days follow up  1 year follow up Critical (8) Likelihood/Incidence of  shock  arrhythmias Important (7)

5. Dallas 2015 Inclusion/Exclusion & Articles Found List Inclusions/Exclusions Inclusion Criteria - atropine, infants and children, emergent intubation, human; Exclusion Criteria - case reports, animals, adults, abstracts, reviews No Articles initially identified = 54 No Finally Included in Evidence Profile tables = 3 observation studies RCTs = 0 Non-RCTs = 3

6. Dallas 2015 2015 Proposed Treatment Recommendations Recommendations from SEERs 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)

7. Dallas 2015 Risk of Bias in studies

8. Dallas 2015 Risk of Bias in studies

9. Dallas 2015 Evidence profile table(s) SURVIVAL IN PICU 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.

10. Dallas 2015 Evidence profile table(s) ARRHYTHMIAS 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.

11. Dallas 2015 Proposed Consensus on Science statements (I) For the critical outcome of survival with favorable neurological outcome, there was no study identified that addressed this for when atropine was used for in-hospital emergent intubation. For the critical outcome of survival to ICU discharge there was very low quality evidence (downgraded for risk of bias & imprecision) from one pediatric observational study of in- hospital emergent intubation (Jones, 2013, 264) of 264 infants and children, supporting the use of atropine pre- intubation for those patients >28 days of life. The use of atropine pre-intubation for neonates was not significantly associated with survival to ICU discharge. (Neonates: propensity score adjusted OR 1.3, 95%CI 0.31–5.1 p=0.74; Older children OR 0.22, 95%CI 0.06–0.85, p = 0.028)

12. Dallas 2015 Proposed Consensus on Science statements (II) For the critical outcome of likelihood/incidence of cardiac arrest there was no study identified that addressed this for when atropine was used for in-hospital emergent intubation For the important outcome of likelihood/incidence of shock or arrhythmias we have identified very low quality evidence (downgraded for risk of bias, inconsistency and imprecision) from two pediatric observational studies. One study of 322 emergent pediatric intubations (Jones, 2013, 289) showed that the use of atropine pre-intubation was significantly associated with a reduced incidence of any dysrhythmia (OR 0.14 95% CI 0.06–0.35) [p value removed for consistency], while the second study of 143 emergent pediatric intubations (Fastle, 2004, 651) failed to find an association between the pre-intubation use of atropine and a reduced incidence of bradycardia (OR 1.11 95% CI 0.22-5.68).

13. Dallas 2015 2015 Proposed Treatment Recommendations Recommendations from SEERs 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)

14. Dallas 2015 Knowledge Gaps There are very few papers that have studied the effects and outcomes of atropine. Further studies, preferably RCTs would help shed light on the effects of atropine when used in emergent intubations in infants and children. Specific research is required particularly for: Survival with neurological outcomes Incidence of Arrhythymias

15. Dallas 2015 Values & Preferences : In making our treatment recommendation, we placed value on causal outcomes from use of atropine. There was only 1 study (low quality of evidence) that showed a higher ICU survival in children > 28 days with while there was unclear evidence on the relationship between use of atropine and arrhythmias. Therefore, due to insufficient and conflicting low quality evidence, we cannot recommend the routine use of atropine in emergent intubation in infants and children until further studies are done.