1. Dominique Biarent Hôpital Universitaire des Enfants Urgences et Soins Intensifs

2. Consensus on Sciences and Treatment Recommendations http://www.c2005.org/presenter.jhtml?identifier=3022512 Your Guide to the 2005 International CoSTR Conference What is the purpose of the evidence evaluation process? The endpoint of this process is the preparation of the International Consensus on CPR and ECC Science with Treatment Recommendations.

3. What is the purpose of the International CoSTR Conference? ILCOR is conducting systematic reviews and updates of scientific evidence supporting ECC treatment recommendations. More than 300 CPR and ECC scientific topics will undergo evidence-based review scientific topics This process represents the most comprehensive, systematic review of the resuscitation literature to date

4. Who's in charge? ILCOR - the International Liaison Committee on Resuscitation. includes 7 international resuscitation organizations American Heart AssociationAmerican Heart Association (AHA), European Resuscitation CouncilEuropean Resuscitation Council (ERC), Heart and Stroke Foundation of CanadaHeart and Stroke Foundation of Canada (HSFC), Resuscitation Council of Southern Africa (RCSA), AustraliaAustralia and New Zealand Council on Resuscitation (ANZCOR),New Zealand InterAmerican Heart FoundationInterAmerican Heart Foundation (IAHF). Japan Resuscitation CouncilJapan Resuscitation Council JRC : international observer to ILCOR. China (Ministry of Health) : international observer to the C2005 Conference.

5. C2005 Evidence Evaluation Worksheets C2005 Evidence Evaluation Worksheets « Vasopressine leads to better outcome from pediatric cardiac arrest than epinephrine »

6. Level of Evidence (LOE)

7. Rating

8. Direction

9. Search Strategy Vasopressin and cardiac arrest, children, ventricular fibrillation, resuscitation, asystole and children (MeSH term and textwords) Pubmed 244 hits (19 Aug 2004) Embase141 hits (19 Aug 2004) Cochrane Library 1 hit (15 Aug 2004) Update 24 Jan 2005 : 1 hit

10. Supporting evidence table denotes key article Q u al it y o f E vi d e n c e Excellent Wenzel 2004 ABC (Nolan 2004 ) Mayr 2001 AE Voelckel 2002 E Good Lindner 1997 A Ito 2004 E Lindner 1992 E Lindner 1996a E Fair Morris 1997 E Lindner 1996b ABCD Mann 2002 ABCD Voelckel 2000b B Paradis 1993 E 12345678 Level of Evidence A = Return of spontaneous circulationC = Survival to hospital discharge B = Survival of eventC = Survival to hospital discharge D = Intact neurological survival²E = Other endpoint Quality of Evidence Supporting evidence Vasopressin leads to better outcome from paediatric cardiac arrests than epinephrine Underlined: peds

11. denotes key article Quality of Evidence Neutral/opposing evidence table Excellent Stiell 2001 ABCD Kono 2002 AB Voelckel, 2000c AE Good Biondi- Zoccai 2003A Fair Voelckel 2000b A 12345678 Level of Evidence A = Return of spontaneous circulationC = Survival to hospital discharge B = Survival of eventC = Survival to hospital discharge D = Intact neurological survival²E = Other endpoint Neutral / Opposing evidence Vasopressin leads to better outcome from paediatric cardiac arrests than epinephrine Neutral/opposing evidence table

12. Wenzel V, Krismer AC, Arntz HR, Sitter H, Stadlbauer KH, Lindner KH. A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation. N Engl J Med 2004;350(2):105-13. LOE1 excellent RCT (intention to treat) 1189 patients (no children) Similar rate of survival to hospital admission for VF /PEA Better survival for asystolic patients treated with vasopressin In absence of ROSC with study drug, additional epinephrine improved survival in VP group not in EPI group

13. Wenzel 2004 AVPEPIRR–CI 95% VF H admission H discharge 46.2 % 17.8 % 43% 19.2% 0.9 (0.6-1.3) (p0.48) 1.1 (0.7-1.8) (p0.7) PEA H admission H discharge 33.7% 5.9 % 30.5% 8.6 % 0.8 (0.5-1.8) (p0.65) 1.4 (0.5-4.7) (p0.47) ASYSTOLE H admission H discharge H discharge after epi 29% 4.7% 3.8% 20.3% 1.5% 0 0.6 (0.4-0.9) (p0.02*) 0.3 (0.1-1.0) (p0.04*) (p0.008*) Additional epinephrine w/o ROSC H discharge Intact neurol 6.2 % 10/40 1.7 % 4/10 0.3 (0.1-0.6) (p0.002*) (ns)

14. Voelckel WG, Lurie KG, McKnite S, et al. Comparison of epinephrine and vasopressin in a pediatric porcine model of asphyxial cardiac arrest. Crit Care Med 2000;28(12):3777-83. Paediatric piglet model of asphyxial arrest Epi or VP+Epi : higher myocardial BF VP+Epi : higher cerebral BF ROSC Epi 6/6* VP+Epi 5/6 VP 1/6 Limitation : use of high dose Epi (200 mcg/kg)

15. Voelckel WG, Lurie KG, McKnite S, et al. Effects of epinephrine and vasopressin in a piglet model of prolonged ventricular fibrillation and cardiopulmonary resuscitation. Crit Care Med 2002;30(5):957-62. Paediatric piglet model of prolonged VF (8 min + 20 min CPR), Combination VP (0.8 IU/kg) +Epi (45  g/kg) : higher left ventricular myocardial blood flow than VP or Epi alone VP+Epi and VP alone : higher cerebral blood flow than Epi alone ROSC ns VP + Epi 6/6 VP5/6 Epi 2/6.

16. Mann K, Berg RA, Nadkarni V. Beneficial effects of vasopressin in prolonged pediatric cardiac arrest: a case series. Resuscitation 2002;52(2):149-56.  6 long lasting CA in 4 children after > 2 doses adrenaline  VP as rescue therapy  3 ROSC (>1h)  1 withdrawal therapy (>24 h)  1 survivor

17. High dose versus low dose adrenaline Author A « High dose of adrenaline is harmful in children with in-hospital and out-of- hospital cardiac arrest » Search strategies 209 articles excluded 40 articles analysed : 25 human and 15 animal model studies Author B « The recommended resuscitation dose of adrenaline for children (0.01 mg/kg) should be increased Search strategies Age less than 18 years 5 articles met full criteria

18. Goetting MG, Paradis NA. High dose epinephrine in refractory pediatric cardiac arrest. Crit Care Med. 1989;17:1258-62 7 children received 0.2 mg/kg adre : 6 ROSC Compared to 20 historic controls (SDE): no ROSC LOE 5 (fair) Goetting MG, Paradis NA. High-dose epinephrine improves outcome from pediatric cardiac arrest. Ann Emerg Med. 1991;20:22-6. Prospective intervention group versus historic control group (20 in each). HDE : 14 ROSC (70%), 8 long term survival, 3 intact LOE 3 Refractory CA is > 2 doses of adrenaline

20. No difference in survival at discharge LOE1 (excellent)

21. Compression / Ventilation Ratio Author A A universal compression- ventilation ratio should be used for infants and children irrespective of their age, etiology of arrest and number of rescuers Search strategies 9 articles Author B Scientific evidence supports the superiority of a 5:1 CV ratio in children rather than the 15:2 CV ratio recommended for adults Search strategies 20 articles used for discussion 9 articles in grid

22. In children Metabolic rates, CO2 production, ventilatory needs are higher in the non- arrest setting Pediatric CA are precipitated by asphyxia or shock In-hospital HCP are accustomed to a 5:1 rather than 15:2 time to BLS in asphyxial CA vs Time to defibrillation in VF are crucial

23. Rescue breathing is critically important for asphyxial arrest (inadequate O2 content and high CO2 in the lungs at the time of CA) but not necessary for VF VF has a normal O2 / CO2 content in lungs and hyperventilation is deleterious BLS not necessary fort short duration VF BLS crucial for prolonged duration VF

24. Evidence Of Science Manikin studies or animal studies (LOE 6) Mathematical model (LOE 6)

25. Berg RA, Sanders AB et al. Adverse hemodynamic effects of interrupting chest compressions for rescue breathing during cardiopulmonary resuscitation for VF cardiac arrest. Circ 2001;104:2465-2470 Interrupting CC for rescue breathing decreases mean coronary perfusion, LV blood flow & number of compression in swine.

26. Dorph E, Wik L, Steen PA. Effectiveness of ventilation-compression ratios 1:5 and 2:15 in simulated single rescuer paediatric resuscitation. Resuscitation. 2002;54:259-64 1 lay rescuer – child sized manikin – 2 ratios 5:1 or 15:2 Same minute ventilation; Better compression with 15:2

27. C/V ratios 5:110:215:2 Tidal volume 121117115 Breaths/min 181712 MV 2.22.01.4 Total compressions/min 87.978.983.7 % effective chest compression 84.6 Kinney SB, Tibballs J. An analysis of the efficacy of bag-valve-mask ventilation and chest compression during different compression–ventilation ratios in manikin- simulated paediatric resuscitation. Resuscitation 2000;43:115-120.

28. J. L. Greingor. Quality of cardiac massage with ratio compression–ventilation 5/1 and 15/2. Resuscitation 2002; 55:263-267 Mean number of correct compression Ratio 5/1Ratio 15/2 Min 15859 Min 25541 Min 35340 Min 46047 Min 55634

29. Optimum C/V ratios in pediatric basic life support 5 + AGE for Pro 5 + AGE/2 for LAY Babbs CF, Nadkarni V. Optimizing chest compression to rescue ventilation ratios during one- rescuer CPR by professionals and lay persons: children are not just little adults. Resuscitation 2004;61:173-81.

30. Oxygen delivery function of C/V ratio (a)professionally trained rescuers (2 rescue breaths in 5 s) (b)lay rescuers, (2 rescue breaths in 16 s) Babbs CF, Kern KB. Optimum compression to ventilation ratios in CPR under realistic, practical conditions: a physiological and mathematical analysis. Resuscitation. 2002 Aug;54(2):147-57. Blood flow DO2 Blood flow DO2 Alv O2

31. Optimal combined flow/DO2

32. For 10 000 simulations OPTIMAL RATIO between 30:2 and 50:2

33. Simplicity of teaching is crucial Do we need an universal ratio?

35. Number of shocks that failed to terminate the initial VF episode for monophasic weight- based and attenuated adult biphasic shocks in the 4, 14 and 24 kg weight categories. * P<0.01. Biphasic defibrillation

36. Berg RA, Chapman FW et al Attenuated adult biphasic shocks compared with weight-based monophasic shocks in a swine model of prolonged pediatric ventricular fibrillation.Resuscitation 2004, 61:189-197 ROSC and 4 & 24 h survival

37. Ventricular function

38. Automated External Defibrillator (AED) Evaluates the victim’s ECG Determines if a “shockable” rhythm is present Charges the “appropriate” dose When activated by operator, delivers a shock Provides synthetised voice prompts to assist the operator

39. AED in children? Experience limited Recommended (Class IIb) for children older than 1 year in the pre-hospital setting (circulation 2003) Remember: –Most arrests in children are respiratory in origin –The most frequent arrest rhythms are Asystole and PEA –Prompt defibrillation is the definitive treatment for VF and pulseless VT –Basic life support sequence

40. Conclusion Ongoing process Evidence of science Guidelines Courses Evidence Based Medicine