ACLS & Beyond Christa Creech, Pharm.D. PGY-2 Emergency Medicine Pharmacy Resident October 7 th, 2018 Objectives List recent changes to ACLS guidelines applicable to pharmacists Recognize reversible causes of cardiac arrest and be familiar with their treatments Recommend adjunctive therapies for refractory cases of cardiac arrest ACLS = Advanced cardiovascular life support 1
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 Access & routes of administration Procedural support ACLS = Advanced cardiovascular life support 2010 2015 Sequence Summary of Guideline Updates Airway, breathing, circulation At least 2 inches & at least 100 compressions per minute Depth & Frequency Circulation, airway, breathing 2-2.5 inches in adults & no less than 100 but no more than 120 compressions per minute 2010 à 2015 Next update in 2020 Vasopressin may replace the first or second dose of epinephrine Insufficient information to recommend routine use of extracorporeal CPR Vasopressin Extracorporeal CPR Vasopressin plus epinephrine provides no advantage as a substitute for epinephrine Extracorporeal CPR may be considered instead of regular CPR for reversible cardiac arrest Morrison. Circulation. 2010;122(18 Suppl 3):S665-75. Comatose patients should be cooled for 12-24 hours Post-cardiac arrest care Comatose patients should be cooled for > 24 hours 2
Circulation - Airway - Breathing CPR O 2 Monitoring Access 2-2.5 inches depth for adults 100-120 compressions per minute Avoid excessive ventilation 30:2 compression ventilation ratio Attach monitor Defibrillator Peripheral IV, central IV, IO, ET IV = intravenous CPR = Cardiopulmonary resuscitation IO = intraosseous ET = endotracheal Marsch. Swiss Med Wkly. 2013;143:w13856. Assess Rhythm for Shockability VF & pvt Asystole & PEA VF = Ventricular fibrillation pvt = Pulseless ventricular fibrillation PEA = Pulseless electrical activity 3
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 4
Shockable Rhythms VF/pVT Shock CPR x 2 minutes IV/IO access VF = Ventricular fibrillation pvt = Pulseless ventricular fibrillation IV = intravenous CPR = Cardiopulmonary resuscitation IO = intraosseous VF/pVT s/p 1 shock & 2 min of CPR Shockable Reassess rhythm Not Shockable Shock PEA/Asystole ROSC CPR x 2 min Epinephrine 1mg every 3-5 minutes Consider advanced airway PEA = Pulseless electrical activity ROSC= Return of spontaneous circulation CPR = Cardiopulmonary resuscitation 5
VF/pVT s/p 2 shocks & 4 min of CPR Shockable Reassess rhythm Not Shockable Shock PEA/Asystole ROSC CPR x 2 min Amiodarone Treat reversible causes PEA = Pulseless electrical activity ROSC= Return of spontaneous circulation CPR = Cardiopulmonary resuscitation Algorithm Drugs Drug Initial Dose Drip MOA Epinephrine 1 mg IV/IO push Every 3-5 min ET: 2-2.5 mg every 3-5 min 1-30 mcg/min (4 mg/250ml) Stimulates beta-1, beta-2 and alpha-1 adrenergic receptors to produce an increase in cardiac contractility, heart rate, systemic vascular resistance and blood pressure 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 IV = Intravenous IO = intraosseous D5W = 5% dextrose in water 6
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; 7
Epinephrine Prospective, non-randomized observational propensity analysis Included data from 417188 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 RCT = Randomized controlled trial ROSC= Return of spontaneous circulation 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 Hagihara. JAMA. 2012;307(11):1161-8. Jacobs. Resuscitation. 2011;82(9):1138-43. Cumulative Dose of Epinephrine Does the cumulative epinephrine dose impact neurologic outcome after cardiac arrest? Difficult to draw conclusions from the existing data 3 retrospective studies show association of higher cumulative doses and worse neurologic outcome Multiple existing confounders Lack of consistency regarding how much epinephrine is too much Arrich. Resuscitation. 2012;83(3):333-7. Laureys. Nat Rev Neurosci. 2005;6(11):899-909. Rivers. Chest. 1994;106(5):1499-507. Behringer. Ann Intern Med. 1998;129(6):450-6. 8
Cumulative Dose of Epinephrine Are we giving too much epinephrine? Dose Evidence is not currently strong enough to support implementation of a dose threshold Arrich. Resuscitation. 2012;83(3):333-7. Rivers. Chest. 1994;106(5):1499-507. Behringer. Ann Intern Med. 1998;129(6):450-6. Cumulative Dose of Epinephrine Dose Consider giving guideline recommended dose every 5 minutes Arrich. Resuscitation. 2012;83(3):333-7. Rivers. Chest. 1994;106(5):1499-507. Behringer. Ann Intern Med. 1998;129(6):450-6. 9
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 IV = intravenous IO = intraosseous 10
Non-Shockable Rhythms Reassess rhythm Asystole/PEA VF/pVT ROSC CPR x 2 min Treat Reversible causes CPR = Cardiopulmonary resuscitation ROSC= Return of spontaneous circulation VF = Ventricular fibrillation pvt = Pulseless ventricular fibrillation PEA = Pulseless electrical activity Reversible Causes H s Hypoxia, hypovolemia, hydrogen ion, hypo-/hyperkalemia, and hypothermia T s Tension pneumothorax, tamponade, toxins, thrombosis (pulmonary), and thrombosis (coronary) 11
H s Hypovolemia Hypoxia Hydrogen ion (acidosis) Hypo- /hyperkalemia Hypothermia Hypoglycemia Hypoxia O 2 Albuterol RSI RSI = Rapid sequence intubation 12
H s Hypovolemia Hypoxia Hydrogen ion (acidosis) Hypo- /hyperkalemia Hypothermia Hypoglycemia Hypovolemia 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 IV = intravenous IO = intraosseous N/V/D = Nausea/vomiting/diarrhea 13
H s Hypovolemia Hypoxia Hydrogen ion (acidosis) Hypo- /hyperkalemia Hypothermia Hypoglycemia Hydrogen Ion (Acidosis) 10 breaths per minute Respiratory acidosis Metabolic acidosis Sodium bicarbonate 50 meq/50 ml 14
Sodium Bicarbonate 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 Can result in paradoxical acidosis Will not resolve underlying cause of acidosis Best used for Tricyclic antidepressant overdose Aspirin overdose Wide QRS H s Hypovolemia Hypoxia Hydrogen ion (acidosis) Hypo- /hyperkalemia Hypothermia Hypoglycemia 15
Hypokalemia 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 KCl = Potassium chloride N/V/D = Nausea/vomiting/diarrhea EKG = Electrocardiography Truhlář. Resuscitation. 2015;95:148-201. Hyperkalemia 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 16
T s Tension Pneumothorax Tamponade (cardiac) Toxins Thrombosis (pulmonary) Thrombosis (coronary) Trauma Tension Pneumothorax Tracheal deviation, unequal breath sounds, pulseless, narrow QRS, bradycardia, JVD Needle decompression Chest tube JVD = Jugular vein distention 17
T s Tension Pneumothorax Tamponade (cardiac) Toxins Thrombosis (pulmonary) Thrombosis (coronary) Trauma Tamponade (Cardiac) Signs EKG Treatment JVD Muffled heart sounds Tachycardia Narrow QRS Ultrasound Pericardiocentesis JVD = Jugular vein distention EKG = electrocardiography 18
T s Tension Pneumothorax Tamponade (cardiac) Toxins Thrombosis (pulmonary) Thrombosis (coronary) Trauma Toxins 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 19
Additional Toxins 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 T s Tension Pneumothorax Tamponade (cardiac) Toxins Thrombosis (pulmonary) Thrombosis (coronary) Trauma 20
Thrombosis (Pulmonary) Thrombolytic Therapy Hypotension Tachycardia Respiratory Support O2 >90% Narrow QRS Shortness of breath IV Fluids 500mL-1L NS Wells score & risk of bleeding IV = intravenous NS = normal saline Thrombolytic Therapy for Pulmonary Emboli Citation Study Design Drug Dose Kurkciyan et al. Retrospective cohort Alteplase 100 mg (either two 50 mg boluses OR 15 mg bolus followed by 85 mg over 90 min) Ruiz-Bailen et al. Case series (6 pts) Alteplase 50 mg bolus, repeat 50 mg in 30 min Janata et al. Retrospective cohort Alteplase 0.6-1.0 mg/kg bolus (up to 100 mg) Sharifi et al. Case series (23 pts) Alteplase 50 mg bolus Janata. Resuscitation. 2003;57(1):49-55. Ruiz-Bailén. Resuscitation. 2001;51(1):97-101. Sharifi. Am J Emerg Med. 2016;34(10):1963-1967. Kürkciyan. Arch Intern Med. 2000;160(10):1529-1535. 21
Thrombolytic Therapy for Pulmonary Emboli Retrospective cohort 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):1617-1625. T s Tension Pneumothorax Tamponade (cardiac) Toxins Thrombosis (pulmonary) Thrombosis (coronary) Trauma 22
Acute MI à Arrest Citation Study Design Drug Dose Lederer et al. Retrospective cohort Alteplase 100 mg (15 mg followed by 85 mg over 90 min) Ruiz-Bailen et al. Retrospective cohort Alteplase 100 mg (either two 50 mg boluses OR 15 mg bolus followed by 85 mg over 90 min) Schreiber et al. Retrospective cohort Alteplase 100 mg (15 mg followed by 85 mg over 90 min) Kurkciyan et al. Retrospective cohort Alteplase 100 mg (15 mg followed by 85 mg over 90 min) Schreiber. Resuscitation. 2002;52(1):63-69. Kurkciyan. J Intern Med. 2003;253(2):128-135. MI = Myocardial infarction Lederer. Resuscitation. 2001;50(1):71-76. Ruiz-Bailén. Intensive Care Med. 2001;27(6):1050-1057. Thrombosis (Coronary) Morphine Oxygen Nitroglycerin Aspirin 2-4 mg IV every 5-15 minutes Reserve use for patients with an unacceptable level of pain CRUSADE - higher adjusted risk of death If <90% No difference in mortality AVOID no reduction in size of infarction Shown to cause direct vasoconstriction of coronaries Up to 3 sublingual NTG tablets (1 every 5 minutes) Avoid if hypotensive, or if taken a PDEi within past 24 hours 324 mg chewed Significant reduction in 5 week vascular mortality Reduction in nonfatal re-infarction No increase in risk of major bleeding Meine. Am Heart J. 2005;149(6):1043-9. Stub. Circulation. 2015;131(24):2143-50. 23
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 T s Tension Pneumothorax Tamponade (cardiac) Toxins Thrombosis (pulmonary) Thrombosis (coronary) Trauma 24
Trauma Advanced Trauma Life Support Target audience: surgeons in hospitals & trauma centers Removed from H s & T s but still important be aware of Traumatic arrests typically due to hypovolemia Copyright 1996-2018 by the American College of Surgeons, Chicago, IL 60611-3295 Other Drugs FOR OTHER CIRCUMSTANCES OUTSIDE OF THE H S & T S 25
Other Drugs Magnesium sulfate Vasopressin Recommended for torsades de pointes associated with a long QT interval Magnesium sulfate 1-2 g diluted in 10 ml D 5 W 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 IV = intravenous IO = intraosseous D 5 W =5% dextrose in water Vasopressin No Longer Recommended 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 RCT = Randomized controlled trial Larger RCT (n = 727) Vasopressin vs. epinephrine No difference in rate of survival at discharge Vasopressin not worse than epinephrine Ducros. J Emerg Med. 2011;41(5):453-9. Ong. Resuscitation. 2012;83(8):953-60. 26
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 VF = Ventricular fibrillation Evans. Emerg Med J. 2016;33(5):367-8. Esmolol 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 RVF = refractory ventricular fibrillation ROSC = return of spontaneous circulation Driver. Resuscitation. 2014;85(10):1337-41.. 27
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%) ROSC = return of spontaneous circulation Driver. Resuscitation. 2014;85(10):1337-41.. Esmolol Pre- & Post-cohort 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 RVF = refractory ventricular fibrillation ROSC = return of spontaneous circulation Lee. Resuscitation. 2016;107:150-5.. 28
Access & Routes of Administration Intraosseous 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 IV = intravenous IO = intraosseous 29
MC-002864 IO Infusion Pain Management 2% lidocaine (preservative-free and epinephrine-free) Adult: Typically 40mg Infant/Child: Typically 0.5 mg/kg (NOT to exceed 40 mg) Lidocaine Initial dose 120 seconds Dwell 60 seconds Rapid Flush Lidocaine ½ initial dose 60 seconds 4 minutes total time 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 18-22 gauge 1.5 inches Injection Directly into chamber of left ventricle as a rapid push ACLS = Advanced cardiovascular life support 30
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 2-1.5 times the recommended dose idocaine 2-3 mg/kg pinephrine 2-2.5 mg tropine 1-2 mg aloxone 0.8-5 mg Duration The duration of actions of drugs given ET is prolonged (depot effect) ET = endotracheal tube Ward. Am J Emerg Med. 1983;1:71-82. Procedural Support 31
Pharmacologic Considerations During ECMO Anticoagulation Sedation & Analgesia Paralytics Bolus of unfractionated heparin 50-100 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 ACT = Activated clotting time PTT = Partial thromboplastin time ELSO. Version 1.4. 2017. Byrnes. ASAIO J. 2014;60(1):57-62. Summary ACLS guidelines Most pharmacy relevant update is the removal of vasopressin from the algorithm Reversible causes of cardiac arrest H s: hypovolemia, hypoxia, hydrogen ion (acidosis), hyper-/hypokalemia, hypothermia, & hypoglycemia T s: toxins, tamponade (cardiac), tension pneumothorax, thrombosis (coronary & pulmonary), & trauma Refractory ventricular fibrillation May be treated with esmolol ACLS = Advanced cardiovascular life support 32
ACLS & Beyond Christa Creech, Pharm.D. PGY-2 Emergency Medicine Pharmacy Resident October 7 th, 2018 33