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

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

3. 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

4. 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

5. Universal cardiac arrest algorithm

6. 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)

7. 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)

8. 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

9. Access for Medications in ACLS
Endotracheal (ET) Route
Not preferred; last resort
Medication doses are 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

10. Adult cardiac arrest algorithm
ACLS Medications
Adult cardiac arrest algorithm

15. 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.

16. 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”

17. 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

18. 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: mg every 3-5 minutes
Dilute in 5-10 ml SW or NS (use epi 1 mg/ml or 1:1,000)

19. 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

20. 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: units one time (to replace 1st or 2nd dose of epinephrine every 3-5 minutes)
Dilute in 5-10 ml SW or NS

21. 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

22. 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

23. 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 ml D5W
Amiodarone vial concentration is 50 mg/ml
Flush with 20 ml
Central line preferred
Incompatible with sodium bicarbonate

24. 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

25. Other Antiarrhythmics
Lidocaine (NOT on algorithm for VF/PVT)
Dose and Administration
IV/IO: mg/kg, then 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

26. 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

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

29. Adult bradycardia algorithm (with pulse)

30. 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

31. Adult bradycardia algorithm (with pulse)
Medications
Atropine
Dopamine
Epinephrine

32. 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

33. 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 minutes as needed
Premade bags are 200 mg/250 ml D5W (800 mcg/ml)
Central line preferred
Incompatible with sodium bicarbonate

34. 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

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

38. 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

39. 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

40. 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.

41. 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

42. Adult tachycardia algorithm (with pulse)
Diltiazem
First choice for acute a-fib with RVR
Dose and administration
Bolus mg IV push over 2 minutes (0.25 mg/kg)
Repeat with 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

43. 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 minutes
Maximum total dose 20 mg
Monitor: ECG, blood pressure

44. 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

45. 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

46. 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

47. 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

48. 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

49. 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 g/hour
To correct deficiency
Monitor:
hypotension, respiratory and CNS depression

50. 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

51. What else is in the crash cart?

52. References
ACLS Provider Manual Supplementary Material (2012). American Heart Association Web site. Available at: Accessed August 13, 2013.
Barletta, JF. Cardiopulmonary resuscitation. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, editors. Pharmacotherapy. A Pathophysiologic Approach. 6th ed. New York (NY): McGraw Hill;2005:
Bauman JL, Schoen MD. Arrhythmias. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, editors. Pharmacotherapy. A Pathophysiologic Approach. 6th ed. New York (NY): McGraw Hill;2005:
DRUGDEX® System [Internet database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically.
Hazinski MF, Nolan JP, Billi JE, et al International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation 2010;122:e1-330.
Lacy CF, Armstrong LL, Goldman MP, Lance LL. Lexi-Comp’s Drug Information Handbook. 17th ed. Hudson (OH): Lexi-Comp;2008.
Ponzer CN, Advanced cardiac life support (ACLS) in adults. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2013.