ACLS Pharmacotherapy Update Jessica Schwenk, Pharm.D. September 14, 2013

Objectives ACLS Guideline Overview Access for Medications in ACLS Introduction Objectives ACLS Guideline Overview Access for Medications in ACLS

Objectives Identify and describe medications used in Advanced Cardiovascular Life Support (ACLS) Understand indications, mechanism of action, dose, administration, and precautions for ACLS medications Recognize place in therapy for medications in updated ACLS algorithms

ACLS Guidelines Developed by American Heart Association Most Recent Released every 5 years Published in Circulation Most Recent 2010 Guidelines for advanced cardiac life support Used comprehensive review of resuscitation literature performed by the International Liaison Committee on Resuscitation (ILCOR) Reviewed continually

Universal cardiac arrest algorithm

ACLS Guidelines First priority Second priority High quality CPR Early defibrillation Second priority Medication administration Advanced airway For drug administration or ventilation Do not interrupt chest compressions Unless bag-mask ventilation is ineffective NO MEDICATION HAS BEEN PROVEN TO INCREASE CHANCES OF SURVIVAL TO HOSPITAL DISCHARGE (human, placebo-controlled study)

Access for Medications in ACLS Intravenous (IV) Route Preferred route Central line not required; can interrupt CPR Medications take 1-2 minutes to reach central circulation Give medications as IV bolus, flush with 20 mL fluid IV preferred unless central line in place Placing central line can interrupt and cause complications—vascular laceration, hematomas, bleeding—can be relative contraindication to fibrinolytic therapy (insertion into non-compressable area of a vein) IV—flush, wait to reach circulation w/ CPR. Possible elevate limb (not studied)

Access for Medications in ACLS Intraosseous (IO) Route Secondary method Safe and effective for administering medications, fluids, and blood as well as drawing blood ALL medications that can be given IV can be given IO Administer medications and flush with at least 20 mL fluid (as with IV administration) IO cannulation provides access to noncollapsible venous plexus in the bone marrow. Time to effectiveness similar to IV Need to apply more pressure with IO administration. Helpful for pediatric codes

Access for Medications in ACLS Endotracheal (ET) Route Not preferred; last resort Medication doses are 2-2.5 times IV/IO doses Optimal dosing not known Medications that can be given ET: epinephrine, vasopressin, lidocaine (atropine, naloxone) Dilute with 5-10 mL SW/NS, administer into ET tube, follow with several positive pressure breaths

Adult cardiac arrest algorithm ACLS Medications Adult cardiac arrest algorithm

Adult cardiac arrest algorithm Medications: Ventricular fibrillation or ventricular tachycardia (VF/VT) Vasopressors: epinephrine, vasopressin Antiarrhythmics: amiodarone Not on algorithm: lidocaine, magnesium Asystole/Pulseless electrical activity (PEA) There is insufficient evidence to support or refute the use of atropine in cardiac arrest to improve survival to hospital discharge.

Adult cardiac arrest algorithm Vasopressor medications Include: epinephrine, norepinephrine, vasopressin Goal: increase coronary and cerebral perfusion Effects: Increase systemic arteriolar vasoconstriction Maintain vascular tone Shunt blood to heart and brain ONLY medications shown to improve ROSC and short term survival Vasoconstriction -> improve perfusion pressure Maintain vascular tone -> decreases arteriolar collapse Guidelines: “use may be considered in adult cardiac arrest”

Adult cardiac arrest algorithm Epinephrine (Adrenaline) MOA: ɑ- and β-receptor agonist ɑ-receptor stimulation restores circulation β-receptor stimulation May lower defibrillation threshold Increases myocardial oxygen demand Adrenergic, non-selective Efficacy due to stimulation of alpha receptors, (a2—a1-agonists such as phenylphrine and methoxamine no advantage over epi/norepi. Probably because a2 receptors more accessible. Also a1 receptors decrease in ischemia) Effect of beta stimulation: unclear beneficial or harmful beta stimulation possibly lowers defibrillation threshold, but increases hearts 02 demand, may increase severity of post-resuscitation myocardial dysfunction

Adult cardiac arrest algorithm Epinephrine Dose and Administration VF, PVT, asystole, PEA IV/IO: 1 mg every 3-5 minutes Concentration 0.1mg/ml (1:10,000 or 1 mg/10ml) Flush with 20 ml NS (central line preferred) ET: 2-2.5 mg every 3-5 minutes Dilute in 5-10 ml SW or NS (use epi 1 mg/ml or 1:1,000)

Vasopressors Vasopressin (antidiuretic hormone) MOA: acts on V1 receptor (among others) to cause vasoconstriction Increases blood pressure and systemic vascular resistance Benefits over epinephrine Not inhibited by metabolic acidosis No β-receptor activity Vasopressin vs. epinephrine for cardiac arrest? No significant difference in ROSC when given 2 doses

Vasopressors Vasopressin Dose and Administration VF, PVT, asystole, PEA IV/IO: 40 units one time (to replace 1st or 2nd dose of epinephrine every 3-5 minutes) 40 Units/2 ml (2 vials of 20 units/ml) Flush with 20 ml NS ET: 80-100 units one time (to replace 1st or 2nd dose of epinephrine every 3-5 minutes) Dilute in 5-10 ml SW or NS

Adult cardiac arrest algorithm Antiarrhythmic medications for cardiac arrest (pulseless VF/VT) include: Amiodarone Not on algorithm: lidocaine, magnesium Goal: increase the fibrillation threshold Prevent development or recurrence of VF and PVT We suggest that antiarrhythmic drugs be considered after a second unsuccessful defibrillation attempt in anticipation of a third shock Previously, also procainamide and bretylium

Adult cardiac arrest algorithm Amiodarone (Cordarone, Pacerone) MOA: Class III antiarrhythmic (potassium channel blocker) Acutely: inhibits α- and β-adrenergic stimulation, blocks calcium channels Side effects (acute): Hypotension, fever, elevated LFTs, confusion, nausea, thrombocytopenia K channel blockers: Prolongs repolarization prolongs action potential and refractory period in myocardial tissue, decreases AV conduction and sinus node function

Adult cardiac arrest algorithm Amiodarone Dose and administration Pulseless VF/VT 300 mg bolus IV/IO, follow with 150 mg in 3-5 minutes Give IV/IO push. If possible dilute in 20-30 ml D5W Amiodarone vial concentration is 50 mg/ml Flush with 20 ml Central line preferred Incompatible with sodium bicarbonate

Other antiarrhythmics Lidocaine (NOT on algorithm for VF/PVT) MOA: Class Ib antiarrhythmic, sodium channel blocker 2010 Guidelines: “There is inadequate evidence to support or refute the use of lidocaine…” in refractory VF/VT Amiodarone beneficial over lidocaine for survival-to-admission May be considered if amiodarone is not available

Other Antiarrhythmics Lidocaine (NOT on algorithm for VF/PVT) Dose and Administration IV/IO: 1-1.5 mg/kg, then 0.5-0.75 mg/kg every 5 to 10 minutes Lidocaine 100 mg/5 ml syringe (20 mg/ml) ET: 2-3 mg/kg in 10 ml NS Monitoring: discontinue if signs of toxicity Sedations, seizures, confusion

Other Antiarrhythmics Magnesium (NOT on algorithm for VF/PVT) Use: suspected hypomagnesemia, Torsades de Pointes Dose and Administration (cardiac arrest) Magnesium 1-2 g IV/IO Magnesium sulfate 50% vials (1 g/2 mL or 0.5 g/ml) Dilute to 10 ml (NS) Administer over 5-20 minutes Monitor: Hypotension, respiratory and CNS depression 15 minutes

Adult bradycardia algorithm (with pulse) ACLS Medications Adult bradycardia algorithm (with pulse)

Adult bradycardia algorithm (with pulse)

Adult bradycardia algorithm (with pulse) Bradycardia is defined conservatively as a heart rate below 60 beats per minute, but symptomatic bradycardia generally entails rates below 50 beats per minute. The 2010 ACLS Guidelines recommend that clinicians not intervene unless the patient exhibits evidence of inadequate tissue perfusion thought to result from the slow heart rate

Adult bradycardia algorithm (with pulse) Medications Atropine Dopamine Epinephrine

Adult bradycardia algorithm (with pulse) Atropine MOA: anticholinergic agent, blocks acetylcholine at M2-receptors of heart Dose and administration 0.5 mg IV/IO bolus, repeat every 3-5 minutes Max 3 mg total dose Atropine syringe 1 mg/10 ml (0.1 mg/ml) Contraindications/Precautions Evidence of a high degree (second degree [Mobitz] type II or third degree) atrioventricular (AV) block May be harmful in cardiac ischemia blocks action of acetylcholine at parasympathetic receptors

Adult bradycardia algorithm (with pulse) Dopamine MOA: adrenergic and dopaminergic receptor agonist, stimulation of β1-recptors increases HR Dose and Administration 2-10 mcg/kg/min IV/IO infusion (up to 20 mcg/kg/min) Titrate to response, increase by 5 mcg/kg/min every 10-30 minutes as needed Premade bags are 200 mg/250 ml D5W (800 mcg/ml) Central line preferred Incompatible with sodium bicarbonate

Adult bradycardia algorithm (with pulse) Epinephrine MOA: adrenergic agonist, stimulation of β1-recptors increases HR Dose and Administration 2-10 mcg/min IV/IO infusion Titrate to response Standard drip 4 mg/250 ml NS or D5W (16 mcg/ml) Central line preferred Incompatible with sodium bicarbonate

Adult tachycardia algorithm (with pulse) ACLS Medications Adult tachycardia algorithm (with pulse)

Adult tachycardia algorithm (with pulse) Medications Regular narrow complex Adenosine Calcium channel blockers or beta blocker Irregular narrow complex Calcium channel blocker or beta blocker Amiodarone

Adult tachycardia algorithm (with pulse) Medications Regular wide complex Adenosine Calcium channel blockers or beta blocker Antiarrhythmics: procainamide, amiodarone, sotolol Irregular wide complex Polymorphic VT, Torsades de Pointes: magnesium

Adult tachycardia algorithm (with pulse) Adenosine Dose and Administration 6-12 mg IV into large proximal vein—fast Flush with 20 mL immediately, elevate limb Extremely short half life May repeat 2nd and 3rd dose of 12 mg Larger doses (18 mg IV) Theophylline or theobromine, caffeine; Smaller doses (3mg IV) Dipyridamole or carbamazepine, transplanted hearts, or into a central vein.

Adult tachycardia algorithm (with pulse) Adenosine Side effects Chest discomfort, dyspnea, and flushing Warn patient! Monitoring Continuous ECG recording during administration If adenosine fails to convert SVT, watch for atrial flutter or a non-reentrant SVT

Adult tachycardia algorithm (with pulse) Diltiazem First choice for acute a-fib with RVR Dose and administration Bolus 15-20 mg IV push over 2 minutes (0.25 mg/kg) Repeat with 20-25 mg IV push over 2 minutes after 15 minutes (0.35 mg/kg) Diltiazem vials 5 mg/ml IV infusion 5-10 mg/hour, titrate up by 5 mg/hour as needed Diltiazem infusion 1 mg/ml Monitor: ECG, blood pressure

Adult tachycardia algorithm (with pulse) Verapamil Dose and administration 2.5-5 mg IV push over 2 minutes Repeat with 5-10 mg over 2 minutes after 15-30 minutes Maximum total dose 20 mg Monitor: ECG, blood pressure

Adult tachycardia algorithm (with pulse) Metoprolol Dose and administration 5 mg IV push over 1 minute for 3 doses every 2-5 minutes Monitor: ECG, blood pressure

Adult tachycardia algorithm (with pulse) Atenolol Dose and administration 5 mg slow IV push over 5 minutes Repeat in 10 minutes Monitor: ECG, blood pressure

Adult tachycardia algorithm (with pulse) Esmolol Dose and administration 500 mcg/kg IV push over 1 minute (may repeat) 10 mg/ml IV infusion 50 mcg/kg/minute for 4 minutes Titrate by 50 mcg/kg/minute at least every 4 minutes Max 200 mcg/kg/min Repeat in 10 minutes Monitor: ECG, blood pressure Another option-labetalol, not FDA approved

Adult tachycardia algorithm (with pulse) Procainamide Class 1a antiarrhythmic (sodium channel blocker) Dose and administration IV infusion 20 mg/min (20 mg/ml in D5W) Alternate dosing: 100 mg IV push over 2 min every 5 min Continue until the arrhythmia is suppressed, or: Hypotension QRS widens 50% beyond baseline Max dose of 17 mg/kg Maintenance infusion 1-3 mg/min (2 mg/ml in D5W) Monitor: ECG, QT interval, pulse, blood pressure ADR: dysrhythmia, systemic lupus erythematosus (up to 30%), hematologic effects, hepatotoxicity Start oral therapy 3-4 hours after infusion stopped/last dose iv Cardiovascular: Cardiac dysrhythmia, Electrocardiogram abnormal, Prolonged QT interval, Torsades de pointes, Ventricular arrhythmia Hematologic: Agranulocytosis (up to 0.5% ), Aplastic anemia (up to 0.5% ), Bone marrow depression (up to 0.5%), Hemolytic anemia (rare ), Neutropenia (up to 0.5% ), Thrombocytopenia (up to 0.5% ) Hepatic: Hepatotoxicity, Liver failure Immunologic: Systemic lupus erythematosus (up to 30% ) Other: Angioedema

Adult tachycardia algorithm (with pulse) Amiodarone Dose and administration 150 mg IV over 10 min, repeat for recurrence Mix in 100 ml D5W (1.5 mg/ml) Follow IV infusion 1 mg/min for 6 hours, then 0.5 mg/min 0.5 mg/min IV for 18 hours Infusion 1.5 mg/ml Max 2.2 g/24 hr Central line preferred Use in-line filter Incompatible with sodium bicarbonate Monitor: ECG, pulse, blood pressure ADR: hyper/hypthyroidism, lupus, vision impairment, renal/liver impairment, pulmonary fibrosis Infuse < or = 15 mg/min to minimize hypotension Cardiovascular: Cardiac dysrhythmia (less than 1% ), Congestive heart failure (1% to 3% ), Prolonged QT interval, Vasculitis, Ventricular arrhythmia Dermatologic: Stevens-Johnson syndrome, Toxic epidermal necrolysis Endocrine metabolic: Hyperthyroidism (1% to 3% ), Hypothyroidism (1% to 3% ), Malignant tumor of thyroid gland, Thyrotoxicosis Hematologic: Thrombocytopenia Hepatic: Liver failure Immunologic: Anaphylaxis, Immune hypersensitivity reaction Musculoskeletal: Low back pain, acute, Lupus erythematosus, Rhabdomyolysis Neurologic: Pseudotumor cerebri, Raised intracranial pressure Ophthalmic: Blindness AND/OR vision impairment level, Optic neuritis, Toxic optic neuropathy Renal: Renal impairment Respiratory: Acute respiratory distress syndrome (2% ), Extrinsic allergic alveolitis, Interstitial pneumonia, Pulmonary fibrosis, Pulmonary toxicity

Adult tachycardia algorithm (with pulse) Magnesium Torsades de Pointes Dose and Administration Magnesium 1-2 g IV Magnesium sulfate 50% vials (1 g/2 mL or 0.5 g/ml) Dilute to 10 ml (NS) Administer over 5-20 minutes Maintenance infusion 0.5-1 g/hour To correct deficiency Monitor: hypotension, respiratory and CNS depression

Extravasation Hyaluronidase (150 units/ml) Inject 0.2 ml subq around the area of the extravasation (5 injections) Amiodarone (hot compress) Calcium (cold compress) Phentolamine (5 mg with 9 ml NS) Inject small amount into blanched area, additional as needed Epineprine (norepinephrine, phenylephrine) Dopamine Vasopressin

What else is in the crash cart?

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