1. Dallas 2015 TFQO: Allan de Caen COI #38 EVREV 1: Tia Raymond COI #153; EVREV 2: Jonathan Egan COI #44 Taskforce: Peds The role of invasive vascular monitoring for titrating CPR (PICO ID# Peds 826)

2. Dallas 2015 COI Disclosure (specific to this systematic review) EVREV 1 Tia Raymond COI #153; Commercial/industry none Potential intellectual conflicts none EVREV 2 Jonathan Egan COI #44 Commercial/industry none Potential intellectual conflicts none

3. Dallas 2015 2010 CoSTR Topic not reviewed in 2010.

4. Dallas 2015 C2015 PICO Population: Infants and children undergoing CPR Intervention: using invasive hemodynamic monitoring to titrate to a specific systolic/diastolic BP Comparison: not using invasive hemodynamic monitoring to titrate to a specific systolic/diastolic BP Outcomes: survival with good neurological outcome at discharge (7-Critical), 60 days (7-Critical), 180 days (9-Critical) survival only at discharge (5-Important) ROSC (5-Important)

5. Dallas 2015 Inclusion/Exclusion & Articles Found Inclusions 2 /Exclusions 591 No human studies were identified Animal studies were included We did not include studies without a concurrent comparator group or studies that did not report invasive hemodynamic parameters Number of Articles Finally Evaluated: 2 recent RCTs in animals

6. Dallas 2015 2015 Proposed Treatment Recommendations Due to limited animal data only we can not recommend for or against the use of invasive hemodynamic monitoring in children and infants to titrate to a specific systolic/diastolic BP during CPR (weak recommendation, very low quality of evidence).

7. Dallas 2015 Risk of Bias in studies RCT bias assessment StudyYearDesign Total Patients Population Industry Funding Allocation: Generation Allocation: Concealment Blinding: Participants Blinding: Assessors Outcome: Complete Outcome: Selective Other Bias Sutton 2013RCT19 Animal (3-mo swine)PartlyLowHighLowHighLowHigh Friess 2013RCT24 Animal (3-mo swine)UnclearLowHighLowHighLowHigh

8. Dallas 2015 Key data from key studies Reference: Sutton, 2013, 696. P: 19 female 3-mo swine with 7 min asphyxia, followed by induction of VF randomized to 1 of 3 resuscitation strategies I: RCT C: Hemodynamic directed care (CPP-20): CC depth to target SBP 100mmHg and titration of vasopressors to target CPP > 20mmHg vs. Depth 33 (D33) target CC depth 33mm with standard AHA epi dosing vs. Depth 51 (D51) target CC depth 51mm with standard AHA epi dosing  All animals received manual CPR guided by audiovisual feedback for 10mins prior to first shock

9. Dallas 2015 Key data from key studies O: 45-min survival higher CPP-20 (6/6) vs. D33 (1/7) vs. D51 (1/6); p=0.002 CPP higher in CPP-20 vs. D33 (p=0.011) and D51 (p=0.04) CPP higher in survivors vs. non-survivors (p<0.01) Vasopressor total doses and # shocks not different Reference: Sutton, 2013, 696.

10. Dallas 2015 Key data from key studies Reference: Freiss, 2013, 2698. P: 24 female 3-mo swine with 7 min untreated VF arrest, randomized to 1 of 3 resuscitation strategies I: RCT C: Hemodynamic directed care (CPP-20): CC depth to target SBP 100mmHg and titration of vasopressors to target CPP > 20mmHg vs. Depth 33 (D33) target CC depth 33mm with standard AHA epi dosing vs. Depth 51 (D51) target CC depth 51mm with standard AHA epi dosing  All animals received manual CPR guided by audiovisual feedback for 10mins prior to first shock

11. Dallas 2015 Key data from key studies O: 45-min survival higher CPP-20 (8/8) vs. D33 (1/8) vs. D51 (3/8); p=0.002 CPP higher in CPP-20 vs. D33 (p=0.004) and D51 (p=0.006) CPP higher in survivors vs. non-survivors (p<0.01) Vasopressor total doses and # shocks not different Reference: Freiss, 2013, 2698.

12. Dallas 2015 Evidence profile table Quality assessment№ of patientsEffect QualityImportance № of studies Study design Risk of bias Inconsistenc y IndirectnessImprecisionOther Using invasive hemodynamic monitoring to titrate to SBP Not using invasive hemodynamic monitoring to titrate to SBP Relative (95% CI) Absolute (95% CI) Survival to 180 days with good neurologic outcome (follow up: range 180 days) 0 CRITICAL Survival to 60 days with good neurologic outcome (follow up: range 60 days) 0 CRITICAL Survival to hospital discharge with good neurologic outcome (follow up: range 1 day) 0 CRITICAL Author(s) : Tia Raymond, Jonathan Eagan Date : 22 Jan 2015 Question : Does using invasive vascular monitoring to titrate to a specific SBP/DBP in infants and children undergoing CPR improve outcome compared to not using invasive vascular monitoring? Settings : Cardiac arrests Bibliography (systematic reviews) : 1. Sutton, Resuscitation, 2013 2. Freiss, CCM, 2013.

13. Dallas 2015 Evidence profile table Quality assessment№ of patientsEffect QualityImportance № of studies Study design Risk of bias Inconsistenc y IndirectnessImprecisionOther Using invasive hemodynamic monitoring to titrate to SBP Not using invasive hemodynamic monitoring to titrate to SBP Relative (95% CI) Absolute (95% CI) Survival to hospital discharge (follow-up range 0.03 days) 2RCTsserious 1 serious 2 very seriousserious 2 Publication bias strongly suspected Strong association all plausible residual confounding would reduce the demonstrated effect 14/14 (100%)6/29 (20.7%) RR 4.833 (2.370 to 9.856) 207 fewer per 1000 ⨁ ◯◯◯ VERY LOW IMPORTANT ROSC (follow-up range 0.03 days) 2RCTsserious 1 serious 2 very serious serious 2 Publication bias strongly suspected Strong association all plausible residual confounding would reduce the demonstrated effect 2 14/14 (100%) 7/29 (24.1%) RR 4.143 (2.173 to 7.898) 241 fewer per 1000 ⨁ ◯◯◯ VERY LOW IMPORTANT Author(s) : Tia Raymond, Jonathan Eagan Date : 22 Jan 2015 Question : Does using invasive vascular monitoring to titrate to a specific SBP/DBP in infants and children undergoing CPR improve outcome compared to not using invasive vascular monitoring? Settings : Cardiac arrests in children Bibliography (systematic reviews) : 1. Sutton, Resuscitation, 2013 2. Freiss, CCM, 2013.

14. Dallas 2015 Proposed Consensus on Science statements We did not identify any evidence to address the critical outcome of “survival to 180 days and good neurological outcome”. We did not identify any evidence to address the critical outcome of “survival to 60 days and good neurological outcome”. We did not identify any evidence to address the critical outcome of “survival to hospital discharge and good neurological outcome”.

15. Dallas 2015 Proposed Consensus on Science statements For the critical outcome of “survival to hospital discharge” we identified very low quality evidence (downgraded for risk of bias, inconsistency, indirectness and imprecision) from 2 animal RCTs enrolling 43 patients showing an associated pooled effect of 80% with the intervention (Sutton, 2013, 696; Friess, 2013, 2698). For the important outcome of “ROSC” we identified very low quality evidence (downgraded for risk of bias, inconsistency, indirectness and imprecision) from 2 animal RCTs enrolling 43 patients showing an associated pooled effect of 76% with the intervention (Sutton, 2013, 696; Friess, 2013, 2698).

16. Dallas 2015 Draft Treatment Recommendations Due to limited animal data only we can not recommend for or against the use of invasive hemodynamic monitoring in children and infants to titrate to a specific systolic/diastolic BP during CPR (weak recommendation, very low quality of evidence).

17. Dallas 2015 Knowledge Gaps The data available to assess this question is unblinded and from animal studies only. Given the suggestion of an effect in these studies, comparable prospective clinical studies should be considered in humans.

18. Dallas 2015 Next Steps Consideration of interim statement Person responsible Due date