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1 KoCARC 연구주제발표 Kyuseok Kim, MD. Department of Emergency Medicine Seoul National University Bundang Hospital

4 CPR duration 여러분은 CPR을얼마동안하세요??? 15분? 20분? 30분? 1시간? No guideline Patient-dependent Young age, bystander CPR, Shockable Old age, bystander CPR(-), Asystole

8 Oxygen dose during CPR When supplementary oxygen is available, it may be reasonable to use the maximal feasible inspired oxygen concentration during CPR (Class IIb, LOE C-EO). no RCTs, but observational study Resuscitation, 2013

11 Early Hyperoxemia vs Normoxemia Background ICU에서의 hyperoxemia는좋지않다는연구 CPR시는 FiO2 1.0이좋다 ROSC직후에는? Re-arrest는 myocardium oxygenation이잘안되어서? 따라서 hyperoxemia가좋다? Reperfusion injury to brain은 normoxemia가좋을수도?

12 Early Hyperoxemia vs Normoxemia Population: all ROSC pts Intervention ROSC후 4시간동안 FiO2 1.0 vs SpO % Primary outcome Survival discharge Secondary outcome Early survival (during first 4/24 hours) pattern, 1,3,6 month survival/neurologic outcome (CPC), survival discharge

13 Early Hyperoxemia vs normoxemia Sample size Power 0.8, 유의수준 0.05 Survival discharge 26% 에서 High FIO2 군이 30% 의 outcome차이를보인다가정했을때 (7.8% absolute difference) 군당 540명 ( 전체 1080명 ) 10% 가량의 attrition rate 1200

14 Effect of chest compression depth (4,5,6cm) and hemodynamic change Design: Intervention study Background : 2015 가이드라인에는 5-6cm Population: OHCA patients receiving CPR in ED >18yr, non-traumatic cardiac arrest Intervention: different chest compression depth Outcome: hemodynamic changes (BPs, CPP, EtCO2, S CV O2.. )

15 Intervention: ED도착한 cardiac arrest환자에서 ACLS진행하면서 central cannulation & arterial cannulation을동시시행이후시간별로 chest compression depth를다르게함 ( 이때 Q-CPR을사용하게됨 ) 4cm on Q-CPR (2 분, 8 분, 14 분, 20 분...) => SBP/DBP, EtCO2, CPP, SCVO2 5cm on Q-CPR (4 분, 10 분, 16 분, 22 분...) => SBP/DBP, EtCO2, CPP, SCVO2 6cm on Q-CPR (6 분, 12 분, 18 분, 24 분...) => SBP/DBP, EtCO2, CPP, SCVO2

16 Sample size : 각군별로 23 명씩, 3 군에서 69 명 탈락율을 10% 가정하여 77 명정도의케이스가필요 통계분석 : paired T test (ANOVA) 분석 참고문헌 Ian G. Stiell et al. What is the optimal chest compression depth during out-of-hospital cardiac arrest resuscitation of adult patients? Circulation, 2014:130:

Back-Mask Ventilation Compared With Any Advanced Airway During CPR Either a bag-mask device

inhospital and outof-hospital setting (Class IIb, LOE C-LD).

as the initial advanced airway during CPR (Class IIb, LOE C-LD).

17 Back-Mask Ventilation Compared With Any Advanced Airway During CPR Either a bag-mask device or an advanced airway may be used for oxygenation and ventilation during CPR in both the inhospital and outof-hospital setting (Class IIb, LOE C-LD). For healthcare providers trained in their use, either an SGA device or an ETT may be used as the initial advanced airway during CPR (Class IIb, LOE C-LD).When supplementary oxygen is available, it may be reasonable to use the maximal feasible inspired oxygen concentration during CPR (Class IIb, LOE C-EO).

18 Design Population Inclusion; CPR in ED Exclusion; bleeding, asphyxia Intervention Randomized controlled BVM vs ET intubation during CPR Outcome Primary outcome; sustained ROSC

19 Sample size Sample size ; 427*2 ROSC rate가두군간유의한차이를보이는지참고문헌 ; 30%(ET) vs 40%(BVM) 유의수준 5%, 검정력 80%, 탈락률 20% Hanif MA1, Kaji AH, Niemann JT. Advanced airway management does not improve outcome of out-of-hospital cardiac arrest. Acad Emerg Med Sep;17(9): Limitation 개인실력차이, 인력운영의비효율성

20 Antiarrhythmic Drugs after Resuscitation Lidocaine There is inadequate evidence to support the routine use of lidocaine after cardiac arrest. However, the initiation or continuation of lidocaine may be considered immediately after ROSC from cardiac arrest due to VF/pVT (Class IIb, LOE C-LD). Beta Blocker There is inadequate evidence to support the routine use of a β-blocker after cardiac arrest. However, the initiation or continuation of an oral or intravenous β-blocker may be considered early after hospitalization from cardiac arrest due to VF/pVT (Class IIb, LOE C-LD).

21 Esmolol for refractory VF in OHCA patients

22 Esmolol for refractory VF in OHCA patients Intervention: Arm 1 (placebo): Standard ACLS (ECLS if available) Arm 2: Esmolol 500 mcg/kg bolus 후 100 mcg/kg/min infusion for 1 0 minutes + simultaneous ECLS application if available Outcome: Primary: sustained ROSC (ECLS/non-ECLS) within 20 minutes, tim e to event analysis (competing risk survival analysis) Secondary: Hemodynamic pattern (first 24 hours), early survival (du ring first 1 month) pattern, survival discharge, neurologic outcomes

23 Epinephrine vs. No Epinephrine AHA ERC Standard-dose epinephrine (1 mg every 3 to 5 minutes) may be reasonable for patients in cardiac arrest (Class IIb, LOE B-R). To continue the use of adrenaline during CPR as for Guidelines 2010.

26 JAMA, 2015

28 Standard Dose Epi vs. High-dose Epi AHA ERC High-dose epinephrine is not recommended for routine use in cardiac arrest (Class III: No Benefit, LOE B-R). The optimal dose of adrenaline is not known, and there are no human data supporting the use of repeated doses. In fact, increasing cumulative dose of epinephrine during resuscitation of patients with asystole and PEA is an independent risk factor for unfavourable functional outcome and in-hospital mortality

29 Hemodynamic-directed epinephrine Friess et al. Crit Care Med 2013;41:

30 Subjects and Design Subject Adult (> 18 y) patients undergoing CPR (IHCA, OHCA?, ICU patients?) + Arterial pressure monitoring available during CPR (within 10 min?) Design Group allocation A line access if no a line Standard CPR if arterial line unavailable Hemodynamic group: epinephrine 1mg every 1min to maintain diastolic blood pressure above 25 mmhg Guideline dosing group: epinephrine 1 mg every 3 min Time T0 T30 Arterial line available Discontinue resuscitation attempts if no ROSC The expert panel recommend that rescuers titrate to a diastolic blood pressure > 25 mmhg for adult victims of cardiac arrest. Meaney PA, Bobrow BJ, Mancini ME, et al. Cardiopulmonary resuscitation quality: improving cardiac resuscitation outcomes both inside and outside the hospital: a consensus statement from the American Heart Association. Circulation 2013;128:

31 Main outcomes and Sample size Primary outcome: ROSC Secondary outcomes: survival to hospital discharge, CPC at hospital discharge, dose of epinephrine administered during CPR, duration of CPR, ejection fraction post-arrest Sample size 97 case per group (type I error 0.05, type II error 0.2) Perondi MB, Reis AG, Paiva EF, et al. A comparison of high-dose and standard-dose epinephrine in children with cardiac arrest. New Engla J Med 2004;350:

32 Epinephrine vs. Vasopressin AHA ERC Vasopressin offers no advantage as a substitute for epinephrine in cardiac arrest (Class IIb, LOE B-R). The removal of vasopressin has been noted in the Adult Cardiac Arrest Algorithm We suggest vasopressin should not be used in cardiac arrest instead of adrenaline. Those healthcare professionals working in systems that already use vasopressin may continue to do so because there is no evidence of harm from using vasopressin when compared to adrenaline

33 Epinephrine vs. Epi + Vasopressin AHA Vasopressin in combination with epinephrine offers no advantage as a substitute for standard-dose epinephrine in cardiac arrest (Class IIb, LOE B- R). The removal of vasopressin has been noted in the Adult Cardiac Arrest Algorithm. ERC: No comments

34 Steroid AHA ERC

35 In hospital arrest Epi vs. Epi+Vasopression+steroid(methylprednisolone 40mg) Primary outcome Sustained ROSC and survival discharge with good CPC JAMA 2013

39 VSE for resuscitation of OHCA patients Background VSE (vasopressin, steroid, epinephrine) 는 IHCA에서 Epi단독보다좋은효과를보임 Problems OHCA에서재현된바없음 AVP의효과인지 Steroid의효과인지모름 Population All OHCA pts >18, no prehospital ROSC

40 VSE in OHCA Intervention VSE Vasopressin [20 IU/CPR cycle] Epinephrine [1 mg/cpr cycle] Methylprednisolone [40 mg at first cycle]). 1-cycle approximately lasted 3 minutes Epi단독 Epi+AVP Epi+steroid Epi+AVP+Steroid Primary outcome Primary outcome: sustained ROSC, 6-month CPC 1 or 2 Secondary outcomes: Hemodynamic pattern (first 24 hours), early survi val (during first 1 month) pattern, survival discharge

41 VSE in OHCA Sample size Power 0.8, 유의수준 0.05 Mentzelopoulos et al. good neurologic outcome 13.9% vs 5.1% Placebo군과 Arm 4간의통계적유의미성을확인하기위해서 Arm 1 및 4에최소 전체 174*4=696 (770명) 이필요 만약 Arm 2/3에서 10% 의 good neurologic outcome을가정할때각각그룹당 456명의환자가배정, 전체 1824 (2000명) 명이필요 Mentzelopoulos, S. D., Malachias, S., Chamos, C., Konstantopoulos, D., Ntaidou, T., Papastylianou, A., et al. (2013). Vasopressin, Steroids, and Epinephrine and Neurologically Favorable Survival After In-Hospital Cardiac Arrest. JAMA : the Journal of the American Medical Association, 310(3),

42 Administration of lipid emulsion for myocardial stunning during cardiac arrest Effect on lipophilic agent in intoxication - Anesthetic agent, CCB, BB, glyphosate - For refractory hypotension - For cardiac arrest due to intoxication Corman SL 1, Skledar SJ. Use of lipid emulsion to reverse local anesthetic-induced toxicity. Ann Pharmacother Nov;41(11): Gil HW, Park JS, Park SH, Hong SY. Effect of intravenous lipid emulsion in patients with acute glyphosate intoxication.. Clin Toxicol (Phila) Sep-Oct;51(8): Escajeda JT, Katz KD, Rittenberger JC. Successful treatment of metoprolol-induced cardiac arrest with high-dose insulin, lipid emulsion, and extracorporeal membrane oxygenation. Am J Emerg Med Jan 16 Stephanie K.et al. Intractable cardiac arrest due to lidocaine toxicity successfully resuscitated with lipid emulsion. Crit Care Med 2011; 39: Jeremiah T Escajeda et al. Successful Treatment of Metoprolol-Induced Cardiac Arrest With High-Dose Insulin, Lipid Emulsion, and ECMO. American Journal of Emergency Medicine 33 (2015) 1111.e e4

43 Background Effect on myocardial stunning - (animal study) Increasing BP, PR, RPP - Decreasing size of myocardial infarct - Decreasing reperfusion injury Jingyuan Li, M.D., Ph.D et al. Intralipid, a Clinically Safe Compound, Protects the Heart Against Ischemia-Reperfusion Injury More Efficiently Than Cyclosporine-A. Anesthesiology Oct;117(4): Zuo-Hui Shao et al. Therapeutic hypothermia cardioprotection via Akt- and nitric oxide-mediated attenuation of mitochondrial oxidants Am J Physiol Heart Circ Physiol. 2010;298: H2164 H2173 Jing Li, MD et al. Lipid Emulsion Rapidly Restores Contractility in Stunned Mouse Cardiomyocytes: A Comparison With Therapeutic Hypothermia Dec;42(12):e734-e740

44 Intervention Group 1 (Placebo) ; Crystalloid fluid(0.9% NS or RL) only [500ml loading + 20ml/hr infusion] Group 2 (ILE) ; Smoflipid 20% [500ml loading + 20ml/hr infusion]

45 Outcome Primary outcome ; survival admission Secondary outcome ; survival discharge Sample size Power ; 0.8 P-value ; (648+20% attrition rate)

46 Optimal BP in OHCA pts Background Current guideline은 Sepsis guideline을차용하여 MAP>65을권장함최근 Retrospective study들은 higher MAP 권장최근 Sepsis 연구에서는 MAP 65-70과 80-85가차이가없었음 OHCA 환자군에서는 RCT 없음 Population All adult OHCA patients with sustained ROSC Ameloot, K., Genbrugge, C., Meex, I., Jans, F., Boer, W., Vander Laenen, M., et al. (2015). An observational near-infrared spectroscopy study on cerebral autoregulation in post-cardiac arrest patients: Time to drop "one-size-fits-all" hemodynamic targets?, 90,

48 Optimal BP in OHCA pts Design: Multicenter double blinded RCT using Stratified Randomization Intervention MAP target mmhg group MAP target mmhg group

49 Optimal BP in OHCA pts Primary outcome 6-month CPC 1 or 2 (Whole study population & stratified by the presen ce of underlying hypertension) Secondary outcomes Hemodynamic pattern (first 24 hours), survival discharge, early survival (during first 1 month) pattern, survival discharge Sample size Power 0.8, 유의수준 0.05 Arm 1 vs 2간의절대비율차이가 5% 이상차이가날것이라고가정각그룹별로 817 sustained ROSC 10% attrition rate 1800명

50 Fluid resuscitation in resuscitated card iac arrest patients Background Balanced solution is better than NS Renal function Survival Cardiac arrest 환자군에서연구된바없음 Population Age>18, Non-traumatic, sustained ROSC Exclusion 1) Underlying CRF, 2) Increased creatinine level, 3) Hyperkalemia Intervention Arm 1: 첫 24시간동안의수액투여를 normal saline 사용 Arm 2: 첫 24시간동안의수액투여를 plasmalyte 사용

51 Fluid resuscitation in resuscitated card iac arrest patients Primary outcome: survival discharge Secondary outcome: changes in creatinine level, acidosis and hemodynamic measurements (72 hours), early survival (during first 1 month) pattern, 6/12 month survival/neurologic outcome (CPC)

52 Fluid resuscitation in resuscitated card iac arrest patients Sample size Power 0.8, 유의수준 0.05 Survival discharge 현 26% 보다 30% 의 outcome 차이를보인다가정했을때 (7.8% absolute difference) 군당 540 명 ( 전체 1080 명 ) 10% 가량의 attrition rate 1200 이전 meta-analysis 사망의 odds ratio 가 0.78 control군의 mortality가 0.871로보고, one-sided test를적용 군당 1632명을 enroll, 전체 3264 명이필요 10% attrition rate 3600명 Rochwerg, B., Alhazzani, W., Sindi, A., Heels- Ansdell, D., Thabane, L., Fox- Robichaud, A., et al. (2014). Fluid Resuscitation in Sepsis. Annals of Internal Medicine, 161(5),

54 Primary objective To determine whether TTM between 32.5 C and 33.5 C for 24 h improves neurological outcomes at 6 month after ROSC compared to TTM between 35.5 C and 36.5 C in survivors of nonshockable OHCA. Secondary objectives To determine whether C TTM for 24 h decreases allcause mortality, cognitive function and quality of life at 6 month after ROSC compared to C TTM in survivors of nonshockable OHCA. To assess the safety and harm of C TTM compared to C TTM in survivors of nonshockable OHCA.

57 Procalcitonin-based antibiotics 전향적연구 비열등성연구

58 MRI Diffusion-weighted image, ADC, Just T2 images DWI ADC T-2W Acta Neurol Scand 2004

61 Resuscitation 2013

65 MRI in prognostication in OHCA pts Primary outcome 6-month CPC 1 or 2 Study design Prospective observational Various method비교 Automatic calculation Mean ADC value Low ADC value % All or none Clinical scoring model

66 소아심정지연구 agenda

67 심정지원인에따른국내병원밖소아심정지환자의신경학적예후분석 배경 : 국내소아병원밖심정지환자에대한지역적, 국가 적규모의신경학적예후에대한보고가없는상태임 소아심정지환자의예후에대한구체적이고자세한 평가가필요한시점임. 목적 : 심정지원인별병원밖소아심정지환자의신 경학적예후를분석

68 비심인성병원밖소아심정지환자에서심정지후기도확보까지의시간과 outcome 배경 병원밖소아심정지의상당수는비심인성원인에의하며심폐소생술시성인에비해인공호흡의중요성이상대적으로높음 국내의경우성인 OHCA 환자에서 LMA, intubation, BVM 시행여부에따른심폐소생술결과를비교한연구가있으나소아심정지환자를대상으로한연구는제한되어있음 목적 : 비심인성, 비외상성병원밖소아심정지환자에서심정지에서기도확보여부 / 기도확보시간까지의시간과 outcome 의상관관계확인

69 비심인성병원밖소아심정지환자에서심정지후기도확보까지의시간과 outcome 자료수집 Non-cardiac, non-traumatic causes 의 arrest 소아환자를대상으로 기본인구역학자료, 기도확보여부및기구종류, 전문기도확보시간, 시도횟수등수집 결과지표 primary outcome: 심정지환자의 6 개월및 1 년생존률 6 개월 /1 년신경학적예후 secondary outcome proportion of the patients who were provided central venous catheter (CVC), ventilator care, ECMO, hypothermia, RRT length of stay in ED (hours) & ICU (days)

70 내과적원인에의한소아심정지환자의중환자실입원결과 : PICU vs. GICU 배경 : 소아심정지환자의적절한소생술후처치 (Postresuscitation care) 는환자의최종임상결과와관련이있으며이러한처치는응급실에서완결될수없으며적절한중환자실로의전동이후에시행 목적 : medical causes 를이유로심정지가발생한소아를대상으로각병원에서비교적표준화되어있는 ED care 에더하여 ICU care 의차이가최종 outcome 의차이를알아보고자하였으며이를위하여소아심정지환자를대상으로진행된 ICU care 의종류 / 비율과이에따른 outcome 을비교

71 배경 : 응급실수준과장소에따른소아심정지환자의치료결과 소아환자는연령에따라여러가지다양한크기의장비와다양한용량의약물이필요하다는점등에서성인심정지환자와달리소아환자에익숙한의료진과소아환자에대한준비가잘되어있는응급실에서치료받아야결과가좋을것을예상해볼수있음. 그러나, 아직응급실의수준에따른소아심정지환자의결과를분석한연구는없음. 목적 : 일반응급실과소아응급실에서치료받은소아심정지환자의결과를비교함 일반응급실, 소아구역, 소아응급실에서치료받은소아심정지환자의결과를비교

72 응급실수준과장소에따른소아심정지환자의치료결과 자료수집 - 응급실의특성수집 : 응급의료센터 vs. 권역의료센터 일반 vs. 소아구역 vs. 소아전용여부 연간내원환자수 ( 성인및소아 ) 연간심정지환자수 ( 성인및소아 ) 소아응급인력수준, 교육수준 결과지표 생존입원률 생존퇴원률 6 개월, 12 개월신경학적결과

73 소아 CPR 팀리더수준과 PALS 교육여부에따른소아심정지 outcome 배경 : 전문심폐소생술 (Advanced life support) 은고위험 의료행위이지만소생치료에참여하는의료인력의 수준과치료행위의질적수준에대한연구가부족 심정지환자의치료결과에소생팀수준이미치는결 과를확인하여심정지치료의수준이향상될수있는 과학적근거를마련 목적 : 소생팀리더와팀원의교육수준이병원밖심 정지환자의치료결과에미치는영향을확인

74 소아심정지환아에서 ROSC 후신경학적예후결정인자 S100

<C0CEC5CFBCF6B7C3B1B3C0B0C1F6C4A7BCAD2D28C3D6C1BEC3E2B7C2C8AEC0CE292D312DC3D62E687770>

<C0CEC5CFBCF6B7C3B1B3C0B0C1F6C4A7BCAD2D28C3D6C1BEC3E2B7C2C8AEC0CE292D312DC3D62E687770> 인턴 수련교육 및 진료 지침서 53 15. 심폐소생술 심폐소생술(Cardiopulmonary Resuscitation, CPR)이란 심장이 멎은 사람에게 인 공호흡과 인공순환을 유지하여 주요 장기에 산소를 공급하는 치료 술기이다. 심폐소생술에 관한 표준 가이드라인의 국제화를 위하여 1993년에 미국심장학 회(American Heart Association,