10/4/18. Objectives. Outline ACLS & Beyond. Circulation - Airway - Breathing. Assess Rhythm for Shockability. ACLS & Beyond CPR. O 2 Monitoring Access

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1 Objectives List recent changes to ACLS guidelines applicable to pharmacists ACLS & Beyond Recognize reversible causes of cardiac arrest and be familiar with their treatments Christa Creech, Pharm.D. PGY-2 Emergency Medicine Pharmacy Resident October 7 th, 2018 Recommend adjunctive therapies for refractory cases of cardiac arrest ACLS = Advanced cardiovascular life support Outline ACLS & Beyond Summary of recent updates to ACLS guidelines ACLS algorithm review Shockable rhythms Non-shockable rhythms Reversible causes of cardiac arrest Other drugs you may encounter during cardiac arrest circumstances Summary of Guideline Updates 2010 à Sequence Airway, breathing, circulation Circulation, airway, breathing Depth & Frequency At least 2 inches & at least 100 compressions inches in adults & no less than 100 but no per minute more than 120 compressions per minute Vasopressin Vasopressin may replace the first or second Vasopressin plus epinephrine provides no dose of epinephrine advantage as a substitute for epinephrine Access & routes of administration Procedural support Next update in 2020 Extracorporeal CPR Insufficient information to recommend routine Extracorporeal CPR may be considered instead use of extracorporeal CPR of regular CPR for reversible cardiac arrest Post-cardiac arrest care Morrison. Circulation. 2010;122(18 Suppl 3):S Comatose patients should be cooled for hours Comatose patients should be cooled for > 24 hours ACLS = Advanced cardiovascular life support Circulation - Airway - Breathing Assess Rhythm for Shockability CPR inches depth for adults compressions per minute O 2 Monitoring Access Avoid excessive ventilation 30:2 compression ventilation ratio Attach monitor Defibrillator Peripheral IV, central IV, IO, ET VF & pvt Asystole & PEA CPR = Cardiopulmonary resuscitation ET = endotracheal Marsch. Swiss Med Wkly. 2013;143:w VF = Ventricular fibrillation pvt = Pulseless ventricular fibrillation PEA = Pulseless electrical activity 1

2 Electricity Versus Pharmacotherapy Some antiarrhythmic drugs have been associated with increased rates of ROSC and hospital admission, but none have yet been proven to increase long-term survival or survival with good neurological outcome. Thus, establishing vascular access to enable drug administration should not compromise the quality of CPR or timely defibrillation, which are known to improve survival. Shockable Rhythm Algorithm Shockable Rhythms VF/pVT s/p 1 shock & 2 min of CPR VF/pVT Shockable Reassess rhythm Not Shockable Shock Shock PEA/Asystole ROSC CPR x 2 minutes IV/IO access CPR x 2 min Epinephrine 1mg every 3-5 minutes Consider advanced airway VF = Ventricular fibrillation pvt = Pulseless ventricular fibrillation CPR = Cardiopulmonary resuscitation PEA = Pulseless electrical activity ROSC= Return of spontaneous circulation CPR = Cardiopulmonary resuscitation VF/pVT s/p 2 shocks & 4 min of CPR Algorithm Drugs Shockable Reassess rhythm Not Shockable Drug Initial Dose Drip MOA 1 mg IV/IO push 1-30 mcg/min Stimulates beta-1, beta-2 and alpha-1 Epinephrine Every 3-5 min adrenergic receptors to produce an increase in cardiac contractility, heart rate, systemic ET: mg every (4 mg/250ml) vascular resistance and blood pressure 3-5 min CPR x 2 min Shock Amiodarone PEA/Asystole Treat reversible causes ROSC Amiodarone 300 mg IV/IO x 1, may repeat 10 min 150 mg 1 mg/min for 6 h à 0.5 mg/min x 18 h 900mg in 500ml of D5W (1.8 mg/ml) Iinhibits adrenergic stimulation, prolongs the action potential, and prolongs the refractory period in myocardial tissue PEA = Pulseless electrical activity ROSC= Return of spontaneous circulation CPR = Cardiopulmonary resuscitation IV = Intravenous D5W = 5% dextrose in water 2

3 What s in your crash cart? Epinephrine PARAMEDIC2 Trial RCT, 8014 patients, out-of-hospital arrest Epinephrine à increased 30-day survival No difference in rate of favorable neurologic outcomes RCT = Randomized controlled trial Perkins. N Engl J Med. 2018; Epinephrine Cumulative Dose of Epinephrine Does the cumulative epinephrine dose impact neurologic outcome after cardiac arrest? Prospective, non-randomized observational propensity analysis Included data from out-of-hospital cardiac arrests Epinephrine associated with increased chance of ROSC before hospital arrival Reduced chance of survival and good functional outcomes 1 month after event Double-blind RCT 534 out-of-hospital cardiac arrests Epinephrine vs. placebo Epinephrine associated with increased chance of ROSC before hospital arrival No significant improvement in survival to hospital discharge Difficult to draw conclusions from the existing data Multiple existing confounders 3 retrospective studies show association of higher cumulative doses and worse neurologic outcome Lack of consistency regarding how much epinephrine is too much RCT = Randomized controlled trial ROSC= Return of spontaneous circulation Hagihara. JAMA. 2012;307(11): Jacobs. Resuscitation. 2011;82(9): Arrich. Resuscitation. 2012;83(3): Laureys. Nat Rev Neurosci. 2005;6(11): Rivers. Chest. 1994;106(5): Behringer. Ann Intern Med. 1998;129(6): Cumulative Dose of Epinephrine Cumulative Dose of Epinephrine Dose Are we giving too much epinephrine? Evidence is not currently strong enough to support implementation of a dose threshold Dose Consider giving guideline recommended dose every 5 minutes Arrich. Resuscitation. 2012;83(3): Rivers. Chest. 1994;106(5): Behringer. Ann Intern Med. 1998;129(6): Arrich. Resuscitation. 2012;83(3): Rivers. Chest. 1994;106(5): Behringer. Ann Intern Med. 1998;129(6):

4 Non-Shockable Rhythm Algorithm Non-Shockable Rhythms Asystole/PEA CPR x 2 min IV/IO access Consider advanced airway PEA = Pulseless electrical activity CPR = Cardiopulmonary resuscitation Non-Shockable Rhythms Reversible Causes CPR x 2 min Asystole/PEA Reassess rhythm Treat Reversible causes VF/pVT ROSC H s Hypoxia, hypovolemia, hydrogen ion, hypo-/hyperkalemia, and hypothermia pneumothorax, tamponade, toxins, thrombosis, and thrombosis CPR = Cardiopulmonary resuscitation VF = Ventricular fibrillation ROSC= Return of spontaneous circulation pvt = Pulseless ventricular fibrillation PEA = Pulseless electrical activity H s Hypoxia Hypovolemia Hypoxia Hydrogen ion (acidosis) O 2 Albuterol RSI Hypo- /hyperkalemia Hypothermia Hypoglycemia RSI = Rapid sequence intubation 4

5 H s Hypovolemia Hypovolemia Hypo- /hyperkalemia Hypoxia Hypothermia Hydrogen ion (acidosis) Hypoglycemia Look for obvious fluid loss Blood Dehydration Severe burns N/V/D Obtain IV access Most important intervention Can also obtain IO if equipment available Fluid challenge At least 2L of isotonic crystalloid +/- pressure bag N/V/D = Nausea/vomiting/diarrhea H s Hydrogen Ion (Acidosis) Hypovolemia Hypo- /hyperkalemia Hypoxia Hypothermia Hydrogen ion (acidosis) Hypoglycemia 10 breaths per minute Respiratory acidosis Metabolic acidosis Sodium bicarbonate 50 meq/50 ml Sodium Bicarbonate H s Why is it given? Prolonged CPR can result in profound acidosis Sodium bicarbonate thought to increase ph to allow better activity of catecholamines in alkaline environment Rapid Push Hypovolemia Hypoxia Hydrogen ion (acidosis) Can result in paradoxical acidosis Will not resolve underlying cause of acidosis Best used for Tricyclic antidepressant overdose Aspirin overdose Wide QRS Hypo- /hyperkalemia Hypothermia Hypoglycemia 5

6 Hypokalemia Hyperkalemia K + - Excessive N/V/D & excessive use of diuretics - Blunted T waves, prominent U waves, and possible wide QRS on EKG - Treat with controlled infusion of KCl - 2 meq per minute for 10 minutes - Followed by 10 meq over 5-10 minutes C B IG K DI Calcium chloride or gluconate -Stabilizes cardiac membranes Beta 2 agonists & Bicarbonate -Shift K + into cells Insulin & Glucose -Shifts K + into cells -Prevent hypoglycemia Kayexalate -Binds K in gut, excretion through feces Dialysis or diuretics -If refractory to all other options KCl = Potassium chloride N/V/D = Nausea/vomiting/diarrhea EKG = Electrocardiography Truhlář. Resuscitation. 2015;95: Tracheal deviation, unequal breath sounds, pulseless, narrow QRS, bradycardia, JVD Needle decompression Chest tube JVD = Jugular vein distention (Cardiac) Signs EKG JVD Muffled heart sounds Tachycardia Narrow QRS Treatment Ultrasound Pericardiocentesis JVD = Jugular vein distention EKG = electrocardiography 6

7 Opioids Pinpoint pupils, respiratory depression Naloxone IN/IV QT prolonging drugs QT C >500 ms Magnesium Sulfate 2g IV bolus Benzodiazepines CNS depression Flumazenil 0.2 mg IV over 30s CNS = Central nervous system IN/IV = Intranasal / intravenous Additional Beta Blockers Bradycardia, hypotension, hypoglycemia Calcium Channel Blockers Hypotension, bradycardia, acidosis, hypoglycemia Serotonergic Drugs Tremor, hyperreflexia, muscle rigidity, hyperthermia, AMS Glucagon, insulin, atropine, catecholamines, calcium, pacing Calcium chloride, insulin, glucagon, catecholamines, methylene blue Supportive care, benzodiazepines cyproheptadine AMS = Altered mental status (Pulmonary) Thrombolytic Therapy Hypotension Tachycardia Narrow QRS Shortness of breath Respiratory Support O2 >90% IV Fluids 500mL-1L NS Wells score & risk of bleeding Thrombolytic Therapy for Pulmonary Emboli Citation Study Design Drug Dose Kurkciyan Ruiz-Bailen Janata Sharifi Case series (6 pts) Case series (23 pts) 100 mg (either two 50 mg boluses OR 15 mg bolus followed by 85 mg over 90 min) 50 mg bolus, repeat 50 mg in 30 min mg/kg bolus (up to 100 mg) 50 mg bolus NS = normal saline Janata. Resuscitation. 2003;57(1): Ruiz-Bailén. Resuscitation. 2001;51(1): Sharifi. Am J Emerg Med. 2016;34(10): Kürkciyan. Arch Intern Med. 2000;160(10):

8 Thrombolytic Therapy for Pulmonary Emboli study (n = 3768) Adult critically ill patients with acute PE treated with systemic alteplase therapy 50 mg (n = 699) vs. 100 mg (n = 3069) Patients that received 50 mg (half-dose) alteplase Similar mortality rates Similar rates of major bleeding Half-dose may provide similar efficacy & improved safety PE = pulmonary embolism Kiser. Crit Care Med. 2018;46(10): Acute MI à Arrest (Coronary) Citation Study Design Drug Dose Lederer Ruiz-Bailen Schreiber Kurkciyan 100 mg (15 mg followed by 85 mg over 90 min) 100 mg (either two 50 mg boluses OR 15 mg bolus followed by 85 mg over 90 min) 100 mg (15 mg followed by 85 mg over 90 min) 100 mg (15 mg followed by 85 mg over 90 min) Morphine 2-4 mg IV every 5-15 minutes Reserve use for patients with an unacceptable level of pain CRUSADE - higher adjusted risk of death Oxygen If <90% No difference in mortality AVOID no reduction in size of infarction Shown to cause direct vasoconstriction of coronaries Nitroglycerin Up to 3 sublingual NTG tablets (1 every 5 minutes) Avoid if hypotensive, or if taken a PDEi within past 24 hours Aspirin 324 mg chewed Significant reduction in 5 week vascular mortality Reduction in nonfatal re-infarction No increase in risk of major bleeding Schreiber. Resuscitation. 2002;52(1): Kurkciyan. J Intern Med. 2003;253(2): MI = Myocardial infarction Lederer. Resuscitation. 2001;50(1): Ruiz-Bailén. Intensive Care Med. 2001;27(6): Meine. Am Heart J. 2005;149(6): Stub. Circulation. 2015;131(24): Thrombolysis Takeaways (PE & MI) The dose of alteplase for cardiac arrest is between 50 and 100 mg given as a bolus +/- an infusion Some studies suggest allowing 15 minutes of CPR for the drug to work Continued CPR is not an absolute contraindication for fibrinolysis Anticoagulants (primarily heparin) were used in most studies with the fibrinolytic PE = pulmonary embolism MI = myocardial infarction CPR = cardiopulmonary resuscitation 8

9 Advanced Life Support Target audience: surgeons in hospitals & trauma centers Removed from H s & but still important be aware of Other Drugs FOR OTHER CIRCUMSTANCES OUTSIDE OF THE H S & T S tic arrests typically due to hypovolemia Copyright by the American College of Surgeons, Chicago, IL Other Drugs Vasopressin No Longer Recommended Magnesium sulfate Vasopressin Recommended for torsades de pointes associated with a long QT interval Magnesium sulfate 1-2 g diluted in 10 ml D 5W IV/IO Previously recommended as a substitute for the first or second dose of epinephrine Thought to sensitize to catecholamines and work at a lower ph than other pressors Recently removed recommendation from new guidelines Small RCT (n = 44) Epinephrine & vasopressin vs. epinephrine + vasopressin + nitroglycerin vs. epinephrine alone The combination(s) did not achieve a higher diastolic blood pressure than epinephrine alone Larger RCT (n = 727) Vasopressin vs. epinephrine No difference in rate of survival at discharge Vasopressin not worse than epinephrine D5W =5% dextrose in water RCT = Randomized controlled trial Ducros. J Emerg Med. 2011;41(5): Ong. Resuscitation. 2012;83(8): Esmolol Esmolol For refractory ventricular fibrillation Excessive catecholamines thought to have harmful effects on myocardium via β-1 receptor agonism Increased myocardial oxygen requirements, worsening ischemic injury, lowering of VF threshold, and worse post-resuscitation myocardial function Antagonism of β-1 receptors theoretically mitigate the above potentially harmful effects of epinephrine while preserving beneficial alpha-receptor actions Case series 6 RVF patients received esmolol 19 RVF control patients Overall 4/6 patients achieved sustained ROSC following a 500 mcg bolus & infusion of esmolol The other 2 patients that received esmolol achieved temporary ROSC Subsequently re-arrested & expired VF = Ventricular fibrillation Evans. Emerg Med J. 2016;33(5): RVF = refractory ventricular fibrillation ROSC = return of spontaneous circulation Driver. Resuscitation. 2014;85(10):

10 MC /4/18 Esmolol Esmolol Conclusions esmolol vs. standard of care Esmolol increased temporary ROSC (67% vs. 42%) Esmolol increased sustained ROSC (67% vs. 32%) Esmolol increased survival to hospital discharge (50% vs. 16%) Esmolol increased survival to discharge with a favorable neurological outcome (50% vs. 11%) Pre- & Post- study following implementation of esmolol for RVF in out-of-hospital cardiac arrest Esmolol bolus of 500 mcg à continuous infusion Esmolol (n = 16) non-esmolol (n = 25) Esmolol group demonstrated a higher rate of temporary ROSC, sustained ROSC, & survival to the intensive care unit ROSC = return of spontaneous circulation Driver. Resuscitation. 2014;85(10): RVF = refractory ventricular fibrillation ROSC = return of spontaneous circulation Lee. Resuscitation. 2016;107: Intraosseous Access & Routes of Administration Proximal tibia Distal tibia Proximal humerus All medications (including blood products) may be safely administered through the IO line Onset & peak drug levels are comparable to IV Important to be mindful of compatibility IO Infusion Pain Management Adult: Typically 40mg Lidocaine Initial dose 120 seconds 2% lidocaine (preservative-free and epinephrine-free) Dwell 60 seconds Infant/Child: Typically 0.5 mg/kg (NOT to exceed 40 mg) 4 minutes total time Rapid Flush Lidocaine ½ initial dose 60 seconds Intracardiac Epinephrine May be asked for during a thoracotomy in traumatic arrest Dosing is the same as in ACLS à 1 mg every 3-5 minutes Both concentrations acceptable 1:10,000 (1 mg/10 ml) 1:1,000 (1 mg/ml) Needle gauge 1.5 inches Injection Directly into chamber of left ventricle as a rapid push ACLS = Advanced cardiovascular life support 10

11 Endotracheal Tube Drug Delivery Stop chest compressions, spray drug down the tube Immediately give 5 manual ventilations to create aerosol Diluents Volume Dose Can affect the rate of absorption of the drug Use saline rather than distilled water The ideal volume for ET drug delivery has not been determined ~10 ml to avoid insufficient absorption or hypoxia Drugs given the ET route should be about times the recommended dose idocaine 2-3 mg/kg pinephrine mg tropine 1-2 mg aloxone mg Procedural Support Duration The duration of actions of drugs given ET is prolonged (depot effect) ET = endotracheal tube Ward. Am J Emerg Med. 1983;1: Pharmacologic Considerations During ECMO Anticoagulation Sedation & Analgesia Paralytics Summary ACLS guidelines Most pharmacy relevant update is the removal of vasopressin from the algorithm Bolus of unfractionated heparin units/kg (max ~ 5000 units) Data does not support the use of anti-thrombin III May be monitored via anti-xa, ACT, or PTT Higher doses typically required Cannulation location can influence goal level of sedation Always use minimum necessary to avoid delirium if possible May be needed if patient is centrally cannulated Long acting paralytic pushes Paralytic infusion Reversible causes of cardiac arrest H s: hypovolemia, hypoxia, hydrogen ion (acidosis), hyper-/hypokalemia, hypothermia, & hypoglycemia : toxins, tamponade, tension pneumothorax, thrombosis (coronary & pulmonary), & trauma Refractory ventricular fibrillation May be treated with esmolol ACT = Activated clotting time PTT = Partial thromboplastin time ELSO. Version Byrnes. ASAIO J. 2014;60(1): ACLS = Advanced cardiovascular life support ACLS & Beyond Christa Creech, Pharm.D. PGY-2 Emergency Medicine Pharmacy Resident October 7 th,