Science Driving the Future of Resuscitation: ACLS

Paris Hotel and Casino Las Vegas, Nevada Science Driving the Future of Resuscitation: ACLS Joseph P. Ornato, MD, FACP, FACC, FACEP Professor & Chairman, Dept. of Emergency Medicine Professor, Internal Medicine (Cardiology) Virginia Commonwealth University Health System Operational Medical Director Richmond Ambulance Authority Richmond Fire & EMS Henrico County Division of Fire Richmond, VA

Disclosure Information Joseph P. Ornato, MD, FACP, FACC, FACEP Science Driving the Future of Resuscitation: ACLS FINANCIAL DISCLOSURE: Cardiac Co-Chair & Consultant: NIH Resuscitation Outcomes Consortium (ROC) American Editor, Resuscitation Advisory Board, Key Technologies, Inc. (Transnasal Cooling Device) UNLABELED/UNAPPROVED USES DISCLOSURE: Transnasal cooling devices

Intra-arrest hot topics Airway management Role of ACLS drugs Extracorporeal Membrane Oxygenation CPR (ecpr) Intra-arrest therapeutic hypothermia

AHA Guidelines Grading

Airway Management During CPR performed by providers trained in its use, the supraglottic airway is a reasonable alternative to bag-mask ventilation (Class IIa, LOE B) and endotracheal intubation (Class IIa, LOE A). For healthcare professionals trained in its use, the esophagealtracheal tube is an acceptable alternative to both bag-mask ventilation (Class IIa, LOE C) or endotracheal intubation (Class IIa, LOE A) for airway management in cardiac arrest. For healthcare professionals trained in its use, the laryngeal tube may be considered as an alternative to bag-mask ventilation (Class IIb, LOE C) or endotracheal intubation for airway management in cardiac arrest (Class IIb, LOE C). For healthcare professionals trained in its use, the laryngeal mask airway is an acceptable alternative to bagmask ventilation (Class IIa, LOE B) or endotracheal intubation (Class IIa, LOE C) for airway management in cardiac arrest.

Prehospital airway management in cardiac arrest - CARES McMullan J et al. Resuscitation 2014; 85:617-22 10,691 out-of-hospital cardiac arrests in the CARES registry Frequency of use ET= 5,591 (52%) SGA= 3,110 (30%) BVM= 1,929 (18%) Survival to DC intact ET= 5.4% SGA= 6.7% BVM= 18.6% BVM pts more likely to be: VF or VT initially EMS witnessed Bystander AED Propensity matched, adjusted for confounders Survival to discharge intact Survival by Airway Management Strategy Survival to discharge Survival to admission Sustained ROSC -1 0 1 2 3 4 5 6 Favors SGA or ET 1.45 1.01 Favors BVM Odds Ratio [95% CI] 3.53 4.19

Prehospital airway management in cardiac arrest - CARES McMullan J et al. Resuscitation 2014; 85:617-22 Survival by Advanced Airway Type 10,691 out-of-hospital cardiac arrests in the Survival to discharge 1.66 CARES registry neurologically intact Frequency of use 1.72 ET= 5,591 (52%) Survival to discharge SGA= 3,110 (30%) 1.43 BVM= 1,929 (18%) Survival to admission Survival to DC intact ET= 5.4% 1.38 SGA= 6.7% Sustained ROSC Propensity matched, adjusted for confounders -1-0.5 0 0.5 1 1.5 2 2.5 3 Favors SGA Odds Ratio [95% CI] Favors ET

ET intubation vs. supraglottic airway in cardiac arrest - ROC Wang HE et al. Resuscitation 2012; 83:1061-6 Survival by Advanced Airway Type 10,455 adult out-ofhospital 0.84 cardiac arrest in Resuscitation Airway or respiratory complications Outcomes Consortium 1.78 (ROC) registry ROSC Not a randomized trial 1.74 Frequency of use Survival to 24 hrs ET= 8,487 (81%) SGA= 1,968 (19%) 1.40 Survival to DC Survival to DC intact neurologically intact ET= 4.7% SGA= 3.9% -1-0.5 0 0.5 1 1.5 2 2.5 3 Favors SGA Odds Ratio [95% CI] Favors ET

ACLS Drugs It is reasonable to consider administering a 1 mg dose of IV/IO epinephrine every 3 to 5 minutes during adult cardiac arrest (Class IIb, LOE A). Amiodarone may be considered for VF or pulseless VT unresponsive to CPR, defibrillation, and a vasopressor therapy (Class IIb, LOE B). Lidocaine may be considered if amiodarone is not available (Class IIb, LOE B).

Benefit of each link in the chain of survival Stiell I et al. N Engl J Med 2004;351:647-56 5,638 OOH-CA patients 17 cities in Ontario, CA Sequential addition of each link in the chain of survival Outcome= survival to hospital discharge Variable Age <75 yr Early Access Adjusted Odds Ratio [95% CI] Adjusted Odds Ratio [95% CI] 1.6 [1.2, 2.3] 4.4 [3.1, 6.4] Early CPR 3.7 [2.5, 5.4] Early DF 3.4 [1.4, 8.4] Early ACLS 1.1 [0.8, 1.5] ccv 0.1 1.0 10.0 Survival worse Survival better ccv

ACLS meds vs. no ACLS drugs in Oslo Olasveengen TM et al. JAMA 2009; 301:2222-9 No drugs 851 OOH-CA cases Randomized to ACLS with vs. without drugs EMS response time interval= 10 min Initial VF= 33% Byst witn= 65% Byst CPR= 63% MD on unit= 37% 50% 40% 30% 20% 10% 0% 40% 25% ROSC 32% 21% Admitted to hospital Drugs p>.001 p>.001 p>.002 p>.61 p>.53 30% 20% Admitted to ICU 11% 9% Discharged 10% 8% Alive at 1 year

Prehospital randomized trial of no epinephrine vs. epinephrine Jacobs I et al. Resuscitation 2011;82(9):1138-43 534 out-of-hospital cardiac arrest patients Randomized to receive no epinephrine vs. epinephrine during resuscitation Perth, Australia 30% 25% 20% 15% 10% 5% 0% p <0.001 8% No epinephrine 24% p <0.001 13% Epinephrine 25% p =.15 2% 4% ROSC Admitted Discharged

Prehospital epinephrine use & survival in Japan Hagihara A et al. JAMA 2012; 307:1161-8 417,188 OOH-CA cases EMS skills: CPR AED IV Give epi 1 mg q4min x 3 Epinephrine vs. no epinephrine by EMS 3.7% of patients received epinephrine Model ROSC Unadjusted Adjusted for propensity Adjusted for propensity and selected variables Adjusted for all covariates 1 month survival Unadjusted Adjusted for propensity Adjusted for propensity and selected variables Adjusted for all covariates CPC 1 or 2 Unadjusted Adjusted for propensity Adjusted for propensity and selected variables Adjusted for all covariates OPC 1 or 2 Unadjusted Adjusted for propensity Adjusted for propensity and selected variables Adjusted for all covariates Favors No No Prehospital Epinephrine Favors Prehospital Epinephrine Odds Ratio [95% CI]

Antiarrhythmic drugs for VF/pVT American Heart Association 2010 ACLS Guidelines Amiodarone or lidocaine (each is a class Iib may be considered recommendation for shock-refractory VF/VT) Amiodarone and lidocaine may have other adverse effects Neither drug has been proven (or tested adequately) to improve survival to discharge Unproven therapies may be... Beneficial Inconsequential (make no difference) Harmful The only way to know if lidocaine or amiodarone work is to compare either against placebo

Amiodarone vs. lidocaine OOH-CA ARREST Trial ALIVE Trial Persistent or recurrent VF/VT Continue CPR Intubate at once Obtain IV access Epi 1 mg IV q 3-5 min DF 360 J 30-60 sec after med dose Pattern drug-shock, drug-shock Amio 300 mg DF 360 J within 30-60 sec Placebo IIb medications Lidocaine Bretylium Mg sulfate Procainamide (Na bicarb) N= 348 Amio vs. Lido Toronto EMS 911-1 st DF = 12±7 min 911-drug = 25±8 min Survival to Admission 70% 60% 50% 40% 30% 20% 10% N= 504 44% 34% Amiodarone 300 mg 49% 39% 17% 12% Placebo 64% 41% 38% 33% Admission 25% 20% 15% 10% 5% 0% 23% Amio p<.004 11% Lido 0% All patients VF Asys or PEA ROSC No ROSC Kudenchuk P et al. N Engl J Med 1999; 341:871-8 Dorian P et al. N Engl J Med. 2002 Mar 21;346(12):884-90

NIH Resuscitation Outcomes Consortium (ROC) Amiodarone vs. Lidocaine vs. Placebo Study (ALPS) N= SYRINGE # AMIODARONE KIT LIDOCAINE KIT PLACEBO KIT 1 Amiodarone 150 mg (3 cc) Lidocaine 60 mg (3 cc) Placebo (3 cc) 2 Amiodarone 150 mg (3 cc) Lidocaine 60 mg (3 cc) Placebo (3 cc) 3 Amiodarone 150 mg (3 cc) Lidocaine 60 mg (3 cc) Placebo (3 cc)

Extra Corporeal Membrane Oxygenation (ECMO) CPR (ecpr) In settings where ecpr is readily available, it may be considered when the time without blood flow is brief and the condition leading to the cardiac arrest is reversible (e.g., accidental hypothermia drug intoxication) or amenable to heart transplantation (eg, myocarditis) or revascularization (e.g., acute myocardial infarction) (Class IIb, LOE C).

Extra Corporeal Membrane Oxygenation (ECMO) CPR (ecpr) Lack of randomized trials Available data is from small case series and observational reports Most are retrospective Age 18-83 (median= 56) years Duration of CPR 20-90 + minutes Initial rhythm Typical exclusion criteria IHCA vs. OHCA Survival 20-33%

ECPR associated with hypothermia and normoxia in refractory cardiac arrest Fagnoul D et al. Resuscitation 2013;84:1519-24 Collapse to ECPR 58 min [45-70] Survivors 41 min [39-58] Non-survivors 60 min [55-77] p=0.059 ALL had mechanical chest compression ALL had intra arrest hypothermia Tight P a O 2 & P a CO 2 management PCI on ECMO for suspected ischemia

ecpr for patients with OHCA of cardiac origin: A propensity matched study Maekawa K et al. Crit Care Med 2013;41:1186-1196 Sopporo, Japan Witnessed OHCA of cardiac origin Failed CPR >20 min Primary Endpoint: Neuro Intact Survival 3-months post-arrest Log-rank p= 0.018 ecpr (n= 48, PCI 40%) Manual CPR (n= 48, PCI 5%) Hazard Ratio [95% CI] Adjusted Hazard Ratio [95% CI] p Pre-existing arrhythmia 0.33 [0.10-1.06] 0.59 [0.15-2.13] 0.42 Atropine administration (+1 mg) 1.55 [1.16-2.07] 1.28 [0.92-1.77] 0.14 Duration of CPR (+10 min) 1.18 [0.98-1.42] 1.08 [0.85-1.34] 0.52 Pupil diameter on hospital arrival (+1 mm) 1.56 [1.26-1.93] 1.39 [1.09-1.78] 0.007 Breathing spontaneously on hospital arrival 0.28 [0.11-0.71] 0.42 [0.14-1.28] 0.13 Shockable rhythm on hospital arrival 0.39 [0.20-0.77] 0.84 [0.36-1.99] 0.69 Initial lactate level (+1 mmol/l) 1.05 [0.99-1.12] 1.03 [0.96-1.10] 0.40

Two year survival and neurological outcome of IHCA patients rescued by ecpr Shin TG, et al. International Journal Cardiol 2013;168:3434-3430 ecpr ecpr increased 2-year survival 2.4 fold compared to CCPR NNT: 7 patients over 2 years Best candidates: < 65 years CPR duration < 35 min Potentially reversible causes

Intra-Arrest Hypothermia In summary, we recommend that comatose (ie, lack of meaningful response to verbal commands) adult patients with ROSC after out-of-hospital VF cardiac arrest should be cooled to 32 C to 34 C (89.6 F to 93.2 F) for 12 to 24 hours (Class I, LOE B). Induced hypothermia also may be considered for comatose adult patients with ROSC after in-hospital cardiac arrest of any initial rhythm or after out-of-hospital cardiac arrest with an initial rhythm of pulseless electric activity or asystole (Class IIb, LOE B).

Randomized Trial of Prehospital Induction of Hypothermia in OOH-CA with Rapid Infusion of 4ºC Saline Kim et. al. JAMA 2014; 311:45-52 80% 70% 60% Cooled p=.69 62% 64% Not Cooled N= 1,359 Median times from 911 call to ROSC = 25-30 min Survival to Discharge 50% 40% 30% 20% 18% p=.30 16% 10% 0% VF Not VF 50% 40% Cooled Not Cooled 41% p=.0001 Mean temp change NS vs control VF= -1.1 ºC Non-VF= -1.2 ºC Survival to Discharge 30% 20% 10% 26% p=.008 21% 30% 0% Rearrest Pulm Edema on CXR

Intra-arrest hypothermia Nozari et al. Circulation, 2006; 113: 2690-96 17 dogs VF cardiac arrest No flow 3 min, 7 min BLS before ALS Randomized to early vs. delayed intra-arrest hypothermia to 34 ºC 10 min 20 min

Intra-arrest hypothermia Nozari et al. Circulation, 2006; 113: 2690-96 17 dogs VF cardiac arrest No flow 3 min, 7 min BLS before ALS Randomized to early vs. delayed intra-arrest hypothermia to 34 ºC Early Hypothermia Delayed Hypothermia OPC-1 (normal) OOOO O OPC-2 (mildly impaired) OPC-3 (moderately impaired OPC-4 (severely impaired) O O O OPC-5 (death) O OOOOOOOO

Design of the Rapid Infusion of cold Normal SalinE by paramedics during CPR (RINSE trial) Deasy C et al. BMC Emergency Medicine. 2011;11:17 Australian pre-hospital randomized clinical trial During CPR, infuse up to 2L of 4 C saline rapidly IV Primary outcome: survival to d/c Secondary outcomes: ROSC, survival to admission, temp on ED arrival, 12 month quality of life in survivors

External Head/Neck Cooling Callaway C et al. Resuscitation 2002;52:159-65 27 OOH-CA pts randomized to usual care vs. ice bags on head & neck during resuscitation Monitored nasopharyngeal & esophageal temp

Comparison between transnasal head cooling begun during CPR and surface cooling after resuscitation in a pig model of cardiac arrest Guan J, Barbut D, Wang H, et al. Critical Care Medicine.2008:36(11) Suppl:S428-S433

Selective Brain Cooling ( Rhinochill ) Non-invasive Intranasal PFC spray delivered through nasal prongs Can be initiated early Ambulance or ED Very rapid cooling Upper airways designed for heat exchange Preferential brain cooling Brain-core gradient

Intra-arrest transnasal cooling Castren et al. Circulation 2010;122(7):729-36 194 out-of-hospital cardiac arrest patients 15 sites, 5 European countries Pts randomized to prehospital nasal cooling or no prehospital nasal cooling Standard therapeutic hypothermia used after hospital arrival

Transnasal cooling with dehumidified high flow air Harikrishna Tandri H, Zviman M, Srinivas MR, et al. Circulation 2012; 126:A1 18 adult pigs Intubated, mechanically ventilated Core body temp in R atrium Brain temp of frontal, parietal, occipital lobes using thermocouples Rate of temp cooling measured at 80L/min transnasal dehumidified air flow MR thermography showed uniform global brain cooling

Intra-arrest hot topics summary Airway management Role of ACLS drugs Extracorporeal Membrane Oxygenation CPR (ecpr) Intra-arrest therapeutic hypothermia