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Antiarrhythmic Drugs. Paul Miller, Pharm.D. Emergency Clinical Pharmacy Specialist St. Elizabeth Health Center August 2012. Overview. Brief arrhythmia pathophysiology review Antiarrhythmic medications Mechanism Use Dosing Clinical pearls Use in the Emergency Department Discussion.

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Antiarrhythmic drugs

Antiarrhythmic Drugs

Paul Miller, Pharm.D.

Emergency Clinical Pharmacy Specialist

St. Elizabeth Health Center

August 2012


  • Brief arrhythmia pathophysiology review

  • Antiarrhythmic medications

    • Mechanism

    • Use

    • Dosing

    • Clinical pearls

  • Use in the Emergency Department

  • Discussion

Arrhythmia pathophysiology
Arrhythmia pathophysiology

  • “Arrhythmias result from abnormalities of impulse initiation or impulse conduction, or a combination of both”1

Impulse formation disturbances
Impulse formation disturbances

  • Can be no pathological change in pacemaker sites

    • Sinus Bradycardia (<60bpm) – slowed SA node impulse formation

    • Sinus Tachycardia (>100bpm) – rapid SA node impulse formation

  • Ectopic focus

    • Impulse generated outside SA node

    • Electrolyte disturbances, ischemia, excessive myocardial stretch, drugs, toxins

Williams & Wilkins, 2011

Conduction abnormalities
Conduction abnormalities

  • Most common conduction abnormalities involve conduction blocks (Heart block)

    • Usually caused by localized or regional hypoxia from decreased coronary blood flow

    • Hypoxia decreases action potential amplitude and rate of depolarization (phase 0 slope)

    • Areas of conduction block can lead to reentry circuits (major cause of ventricular and supraventricular tachyarrhythmia's)

Williams & Wilkins, 2011

Sa and av node action potentials
SA and AV node action potentials

  • Pacemaker cells

  • No true resting potential (phase 4)

  • Unlike other cells, the depolarizing current enters the cell via slow Ca++ currents, rather than Na currents

  • Slow response action potentials

Williams & Wilkins, 2011

Sa and av node action potentials1
SA and AV node action potentials

Williams & Wilkins, 2011

Non pacemaker action potentials
Non-pacemaker action potentials

  • Atrial myocytes, ventricular myocytes and Purkinje cells

  • Rapid depolarization “fast response”

  • Phase 0 – Na

  • Phase 1 – K

  • Phase 2 – Ca

  • Phase 3 – K

Williams & Wilkins, 2011

Conversion to pacemaker cells
Conversion to pacemaker cells

  • Non-pacemaker cells can undergo spontaneous depolarizations under certain conditions

  • Hypoxia causes membrane depolarization, which closes fast Na channels

  • Inward Ca++ current can initiate spontaneous action potentials and automaticity

  • Mechanism for ectopic beats and arrhythmias seen in ischemic heart disease patients

Williams & Wilkins, 2011

Assessment question
Assessment question

  • Slow Ca++ channels are responsible for membrane depolarization in which type of tissue/cells?

  • A. Ventricular myocytes

  • B. Atrial myocytes

  • C. SA/AV nodal cells

  • D. Skeletal muscle cells

Effective refractory period erp
Effective Refractory Period (ERP)

  • Period of time a new action potential can NOT be initiated

  • Protective mechanism to limit rapid successive depolarization (and HR)

  • Many antiarrhythmic drugs alter the ERP

  • Altering (prolonging) the ERP can be effective for abolishing reentry currents

Williams & Wilkins, 2011


  • Most common mechanism for most tachyarrhythmia's

  • For reentry to occur, 3 conditions must be met

    • Unidirectional block

    • Critical timing

    • Length of block matches refractory period

Williams & Wilkins, 2011


Williams & Wilkins, 2011

Global reentry svt and wpw
Global Reentry (SVT and WPW)

Williams & Wilkins, 2011

Assessment question1
Assessment Question

  • What are the 3 requirements for a reentry circuit to occur?

Assessment question2
Assessment Question

  • What are the 3 requirements for a reentry circuit to occur?

  • 1. Unidirectional block

  • 2. Critical timing

  • 3. Length of block matches refractory period

Antiarrhythmic drug classification
Antiarrhythmic drug classification

  • Vaughan Williams

    • Class I – Na channel Blockers

    • Class II – Beta Blockers

    • Class III – K channel blockers

    • Class IV – Ca channel blockers

  • Miscellaneous

    • Atropine, Adenosine, Digoxin, Electrolytes (Mag, K),

Williams & Wilkins, 2011

Class i na channel blockers
Class I – Na Channel Blockers

  • !a: Quinidine, Procainamide, Disopyramide

  • 1b: lidocaine, mexiletine

  • 1c: Flecainide, Propafenone,

  • All block fast sodium channels responsible for depolarization (phase 0) of non-nodal action potentials

    • Decreased slop of phase 0

  • Remember: non-nodal = Atrial and ventricular myocytes and purkinje cells

    • Nodal cells cells of the SA node and AV node (depolarization occurs by Cachannels)

Williams & Wilkins, 2011

Class i na channel blockers1
Class I – Na Channel Blockers

  • By decreasing slope of phase 0, Class I drugs can interrupt conduction in reentry circuits (a good thing)

  • Differences in Na channel blockade and ERP

    • Class 1a: Moderate blockade

      • Increase ERP

    • Class 1b: Weak

      • Decrease ERP

    • Class 1c: Strong

      • No change ERP

Williams & Wilkins, 2011

Class ia
Class Ia

Williams & Wilkins, 2011

Class 1a procainamide
Class 1a: Procainamide

  • Stable monomorphic ventricular tachycardia

    • Dose: 100mg IV every 5 minutes until arrhythmia controlled, hypotension occurs, further QRS widening, up to total 17mg/kg

    • Then start infusion 1-4mg/min.

  • Note: Not recommended for Vfib or hemodynamically unstable Vtachdue to long administration times and unknown efficacy

  • If known hepatic impairment, reduce dose by half

  • After conversion to sinus rhythm, possible tachycardia from anticholinergic effects after prolonged administration

Coyle, 1992

Class ia1
Class Ia

  • Quinidine rarely used due to newer more effective treatments

  • Disopyramide

    • Oral Class 1a antiarrhythmic

    • Only used for last line therapy due to adverse effects and newer more effective treatment

    • Negative inotropic effects. Do not use in patients with LVEF < 40%

    • Strong anticholinergic activity

Coyle, 1992

Class 1b
Class 1b

Williams & Wilkins, 2011

Lidocaine class 1b
Lidocaine – Class 1b

  • Weak inhibitor of fast sodium channels in non-nodal cardiac myocytes

    • Decreases ERP

  • Hemodynamically stable Vtach

    • 1-1.5mg/kg (usually 100mg syringe) IV x 1 bolus, then continuous infusion 1-4mg/min (usually 1mg/min)

    • Can repeat 0.5-0.75mg/kg bolus as necessary.

  • Usually second line to amiodarone

  • Caution lidocaine toxicity with prolonged infusions

  • Consider use for Vfib refractory to shock and amiodarone

Dorian 2002

Mexiletine class 1b
Mexiletine – Class 1b

  • Orally active analog of Lidocaine

  • Not used for termination of active ventricular arrhythmia, should use IV lidocaine

  • Most commonly used to prevent serious ventricular arrhythmias in patients with pacemaker

  • Can load 400mg PO, then 200mg every 8 hours (if converting from IV procainamide) or start at 200mg every 8 hours (if converting from IV lidocaine)

  • Start 6-8 hours after stopping IV lidocaine

Williams & Wilkins, 2011

Class 1c
Class 1c

Williams & Wilkins, 2011


  • Oral Class 1c anti-arrhythmic

  • No utility in the ER

  • Contraindicated in CAD (CAST trial)

  • BEERS list for anti-cholinergic effects

  • Used to prevent life threatening ventricular arrhythmias or PSVT.

  • Also used as “Pill-in-the-pocket”

    • 200mg PO x1 (<70kg), 300mg PO x1 (>70kg) for palpitations

    • Reduced ER visits by 94% (Alboni 2004)

    • Only for select patients with infrequent paroxysmal Afib

Alboni 2004


  • Oral class 1c antiarrhythmic

  • Prevent recurrence of Afib

    • 225mg PO q12 hr

  • Pharmacologic cardioversion (unlabeled use)

    • 600mg PO x 1 dose

    • To prevent rapid AV conduction, patients should be initiated on beta blocker or non-DHP calcium channel blocker prior to initiating therapy

  • Also a BEERS medication

Williams & Wilkins, 2011

Class ii antiarrhythmics beta blockers
Class II antiarrhythmics – Beta-Blockers

  • MOA: Bind to beta-adrenergic receptors and block the activity of epinephrine and norepinephrine

  • Inhibits normal sympathetic effects through these receptors

  • “Partial Agonists”

    • Provide some background sympathetic activity while preventing normal enhanced sympathetic activity

    • “intrinsic sympathomimetic activity” (ISA)

    • Membrane stabilizing activity (MSA) (ex. Metoprolol)

Williams & Wilkins, 2011

Beta blockers

  • First generation = non-selective

    • Block both Beta-1 and Beta-2 adrenergic receptors

  • Second generation = relative Beta-1 selectivity

    • Cardioselective

    • Beta-1 selectivity overcome by higher doses

  • Third generation = additional alpha blocking properties

    • Vasodilation effects through alpha-1 blockade

    • Mainly used for HTN

Williams & Wilkins, 2011

Beta blockers1
Beta Blockers

  • Actions on cardiac tissue

  • Block beta receptors in nodal tissue, conducting system, and contracting myocytes

  • Predominantly beta-1 receptors in cardiac tissue

  • Beta-2 receptors more predominant in airway smooth muscle

    • Caution COPD and asthma

Williams & Wilkins, 2011

Beta blockers for arrhythmia
Beta-blockers for arrhythmia

  • Normal sympathetic influences on cardiac electrical activity

  • Increased SA node automaticity (pacemaker activity) – increased sinus rate

  • Increased conduction velocity at AV node

  • By decreasing conduction velocity beta-blockers abort reentry circuits

  • Beta-blockers also affect non-pacemaker action potentials

    • Increase APD and ERP

    • Again effective for treating reentry circuits

Williams & Wilkins, 2011


  • Selective beta-1 blocker

  • Decreases rate of depolarization in nodal tissue

  • Afib, SVT rate control: 2.5-5mg IVP every 3-5 minutes up to maximum 15mg in 15 minutes

  • Only use if hemodynamically stable

  • Caution decompensated heart failure

  • Contraindicated Wolff Parkinson White (WPW) syndrome

Williams & Wilkins, 2011

Other beta blockers
Other beta blockers

  • Labetalol

    • Beta-1 and beta-2 blockade and alpha-1 blockade

    • Solely used for HTN, not arrhythmia

  • Other selective beta-1 blockers similar to metoprolol, however metoprolol primary class II anti-arrhythmic.

  • Why not Sotalol? Actually classified as Class III anti-arrhythmic

Williams & Wilkins, 2011

Class iii anti arrhythmics
Class III anti-arrhythmics

  • K+ channel Blockers

  • K+ channels responsible for cell repolarization

  • Work both in nodal and non-nodal tissue

  • After Na+ and Ca++ channels are activated, K+ channels begin to open

    • Allows K+ to leave cell, causing membrane potential repolarization

    • Repolarize fast response action potentials in non-nodal tissue

    • Repolarize slow response action potentials in nodal tissue

Williams & Wilkins, 2011

Class iii anti arrhythmics1
Class III anti-arrhythmics

Williams & Wilkins, 2011

Class iii anti arrhythmics2
Class III anti-arrhythmics

  • Blocking K+ channels slows or delays membrane repolarization

  • Increased action potential duration (APD)

  • And increased effective refractory period (ERP)

  • On the EKG, this will prolong QT interval

    • Classic effect of all class III anti-arrhythmics

    • Prolongs the time the cell is not excitable

  • By increasing the ERP – very useful for terminating reentry mechanisms

Williams & Wilkins, 2011


  • Uses: Vtach, Vfib, rate control in Afib/flutter

  • Has activity of all Classes of antiarrhythmics, mostly K+ blockade

  • Extremely long T1/2 – 45-60 DAYS!

  • Lots of drug interactions including Warfarin

  • Warfarin adjustments needed for up to several months

  • Lots of side effects

Williams & Wilkins, 2011

Amiodarone side effects
Amiodarone side effects

  • Lungs

    • Interstitial pneumonitis

    • Pulmonary fibrosis

  • Thyroid (iodine component)

    • Structurally similar to T4

  • Eyes

    • Corneal deposits in 90% of patients after 6 months

    • Usually asymptomatic

  • GI/Liver toxicity

  • Skin – UV sensitivity

  • Hands/Feet – neuropathy

Williams & Wilkins, 2011

Amiodarone dosing
Amiodarone dosing

  • Stable Vtach: 150mg/100mL over 10 minutes followed by continuous infusion 1mg/min x 6hrs then 0.5mg/min

  • SVT: 150mg/100mL over 10 minutes

  • Afib RVR: 150mg/100mL over 10 minutes, then 1mg/min

  • Vfib /pulseless vtach(ACLS) refractory to defibrillation: 300mg IV push, may repeat 150mg Iv push after 3-5min. If ROSC occurs, initiate continuous infusion

  • If they are Pulseless, then Push it!

Williams & Wilkins, 2011


  • Structurally very similar to amiodarone without iodine

  • Developed as alternative to amiodarone

  • Lacks side effects of amiodarone (pulmonary thyroid)

  • Increased mortality in patients with heart failure (ANDROMEDA 2007)

  • PALLAS trial 2011 – double risk of cardiovascular death in patients with permanent Afib.

Williams & Wilkins, 2011

Sotalol betapace
Sotalol (Betapace)

  • Non-selective beta blocker, also K+ channel blocker

  • Dual action – prolongs both PR interval and QTc interval

  • Use for stable Vtach (unlabeled) and prevention of Afib

  • Dose: (Stable monomorphic Vtach) 1.5mg/kg over 5 minutes (ACLS 2010)

  • Must monitor renal function and QTc

Williams & Wilkins, 2011

Dofetilide tikosyn
Dofetilide (Tikosyn)

  • Oral Class III anti-arrhythmic

  • Dose related increases in QTc

  • Must be initiated in hospital with constant EKG monitoring

  • Remember! Drug interactions and QTc prolongation!

    • Avelox, Zofran, Geodon all contraindicated

  • Renally cleared

  • Must be T.I.P.S. certified to prescribe

Williams & Wilkins, 2011

Class iv anti arrhythmics
Class IV anti-arrhythmics

  • Ca++ channel blockers

  • Only non-dihydropyridine Ca++ channel blockers

  • Diltiazem and Verapamil

  • Block Ca++ channels in cardiac Nodal tissue, also causes peripheral vasodilation

  • Slows conduction through AV node, increases time needed for each beat, decreased myocardial oxygen demand, effective for reentry supraventricular tachycardias

  • Negative inotropic effects

  • Contraindicated in decompensated heart failure

Williams & Wilkins, 2011

Diltiazem cardizem
Diltiazem (Cardizem)

  • Use: Angina, HTN, rate control in Afib/flutter, PSVT

  • Dose (Afib rvr): 0.25mg/kg IV slow push (ACLS recommends 15-20mg)

    • 10mg often used, but is a wussy dose!

  • May repeat 0.35mg/kg (ACLS recommends 20-25mg) after 15 min

  • Initiate infusion at 10mg/hr

  • Titrate to desired HR (15mg/hr max)

  • Many patients respond to 5mg/hr

Williams & Wilkins, 2011

Diltiazem cardizem1
Diltiazem (Cardizem)

  • Only for hemodynamically stable patients

  • Contraindicated SBP<90, cardiogenic shock, administration within 2 hours of IV beta blocker

  • Also contraindicated in Afib/flutter associated with accessory bypass tract (WPW)

  • Conversion to PO

    • Oral dose (mg/day) = [rate(mg/hr)x3 +3] x 10

    • 3mg/hr = 120mg/day

    • 5mg/hr = 180mg/day

    • 7mg/hr= 240mg/day

    • 11mg/hr = 360mg/day

Williams & Wilkins, 2011

Assessment question3
Assessment Question

  • Which VW class antiarrhythmic slow conduction velocity and depolarization in Non-Nodal tissue (Ventricular/Atrial myocytes, Purkinje cells)?

  • A. Class I

  • B. Class II

  • C. Class III

  • D. Class IV

Assessment question4
Assessment Question

  • Before prescribing Avelox (moxifloxacin), what antiarrhythmic should you make sure the patient is NOT taking?

Assessment question5
Assessment Question

  • Before prescribing Avelox (moxifloxacin), what antiarrhythmic should you make sure the patient is NOT taking?

  • Answer: Tikosyn (dofetilide)

  • Why?

Miscellaneous anti arrhythmics
Miscellaneous anti-arrhythmics

  • Digoxin

  • Adenosine

  • Magnesium, Potassium salts

  • Atropine


  • Cardiac glycoside derived from foxglove plant (Digitalis purpurea)

  • Inhibits Na+/K+-ATPase

  • Increases intracellular Ca++

  • Causes Increased Contractility

  • Decreased SA node firing

  • Reduced conduction velocity in AV node

  • Digoxin can cause virtually any type of arrhythmia EXCEPT rapid atrial tachyarrhythmia's

Williams & Wilkins, 2011


  • Williams & Wilkins, 2011

Digoxin dosing
Digoxin Dosing

  • Rate control (Afib): 0.25-0.5mg IV x1

  • Administer slowly over at least 5min

  • T1/2 ~ 35-40hrs (prolonged in renal disease)

  • May take 45min-1hr for rate control

  • Preferred for hypotensive patients

  • Can use in conjunction with other agents

Williams & Wilkins, 2011


  • Very short half life = 10 seconds!

  • Administration is key

    • Proximal vein, rapid administration

  • Use for PSVT

  • MOA: Causes inhibition of L-type calcium channels (remember AV node)

    • Reduces HR and conduction velocity particularly in AV node

  • Dose (peripheral line): 6mg rapid IVP, may repeat 12mg in 1 min, then 12mg in 1min

    • If Central Line, heart transplant, on dipyridamoleor carbamazepine: initial dose 3mg (ACLS 2010)

  • Contraindicated WPW, asthma?

Williams & Wilkins, 2011

Magnesium and potassium
Magnesium and Potassium

  • Hypomagnesaemia and hypo/hyperkalemia can precipitate arrhythmias

  • Vtach, Vfib, SVT, Afib/flutter, atrial tachyarrhythmia's

  • Can also potentiate digoxin toxicity

  • Magnesium 2g IV, slow push (torsade's)

  • Replace K+ as necessary

    • Max infusion rate 20meq/hr (10meq/hr at SEHC) peripherally

    • 40meq/hr central line (20meq/hr at SEHC)

Williams & Wilkins, 2011


  • Vagus nerves that innervate the heart (parasympathetic) release acetylcholine (Ach)

  • Ach binds and activates muscarinic (M2) receptors in the SA and AV node

  • Leads to decreased rate of phase 4 depolarization (thus decreased firing rate)

  • Atropine blocks these effects, increasing phase 4 depolarization (thus increasing firing rate)

  • Primary use for atropine is bradycardia

Williams & Wilkins, 2011


  • Bradycardia: 0.5mg IV q 3-5min, max dose 3mg

  • Will not work for transplant (no vagal innervation)

  • Atropine and ACLS???ds

Atropine and acls
Atropine and ACLS

  • Atropine completely removed from ACLS algorithm in 2010 guidelines

  • Retrospective analysis shows overall no benefit

  • Possibly worse outcomes (decreased ROSC, increased mortality) in fast PEA

  • Trend toward increased ROSC in Slow PEA (<50) and asystole (not significant)

  • Definitely no mortality benefit

  • Would still recommend as last resort in Slow PEA (my personal recommendation)

  • Dose: 1mg iv/io q3-5min, max 3mg

Assessment question6
Assessment Question

  • A patient with known WPW syndrome presents with stable SVT. What is the drug of choice?

  • A. Adenosine

  • B. Metoprolol

  • C. Digoxin

  • D. Procainamide

Anti arrhythmic conclusions
Anti-arrhythmic Conclusions

  • Anti-Arrhythmics are Pro-arrhythmic

  • Class 1c antiarrhythmics increase mortality in patients with CAD and asymptomatic, non-life threatening ventricular arrhythmias (PVCs) - CAST

  • Reentry is the mechanism responsible for most tachyarrhythmia's

  • Altering conduction velocity (and thus ERP) is effective to abolish reentry

  • Proper dosing and administration is key to effectively manage arrhythmias


  • Lippincott Williams & Wilkins: Cardiovascular Physiology Concepts, Second Edition. 2011

  • Hollman A (February 1992). "Procaine and procainamide". Br Heart J 67 (2): 143

  • Coyle JD, Lima JJ.  ”procainamide”. In a applied pharmacokinetics: Principles of therapeutic drug monitoring. 3rd ed. Applied Therapeutics:1992

  • Dorian P, et al. “Amiodarone as Compared with Lidocaine for Shock-Resistant Ventricular Fibrillation,” N Engl J Med 2002, 346(12)

  • Alboni P, et al. “Outpatient Treatment of Recent-Onset Atrial Fibrillation With the “Pill-in-the-Pocket” Approach,” N Engl J Med, 2004, 351(23)

  • ACC/AHA ACLS guidelines, 2010 focused update

Hemodynamics vasopressors and inotropes

Hemodynamics, Vasopressors and Inotropes

Paul Miller, Pharm.D.

Emergency Clinical Pharmacy Specialist

St Elizabeth Health Center

August 2012


  • Brief hemodynamics/shock pathophysiology review

  • Vasopressors and Inotropes

    • MOA

    • Use

    • Dosing

    • Clinical Pearls

  • Use in the Emergency Department

  • Discussion


  • Decreased perfusion > Hypoxia > vital end organ damage

  • Cellular effects

    • Ion pump dysfunction

    • Ion leakage

    • Edema

    • pH

  • Systemic effects

    • Stimulation of inflammatory and anti-inflammatory cascades

    • Serum pH

    • Endothelial dysfunction

    • Cardiac dysfunction

Mullner 2004

Physiology review
Physiology review

  • Tissue perfusion determined by CO and SVR

  • CO = SV x HR

  • SV Preload, contractility, afterload

  • SVR Vessel length/diameter, viscosity (Hg/Hct)

  • Decreased CO, SVR or both = tissue hypoperfusion

  • Compensatory mechanisms exist (but overcome)

Mullner 2004

Types of shock
Types of shock

  • Cardiogenic (Pump problem) – heart failure

  • Hypovolemic (Possible pipe problem) – trauma

  • Distributive (Pipe problem) – sepsis

Cardiogenic shock
Cardiogenic shock

  • Decreased CO

  • SVR increases to compensate

  • PCWP is increased

  • Cardiac index usually < 2.5

Mullner 2004

Hypovolemic shock
Hypovolemic shock

  • Intravascular volume loss

  • Decreased CO

  • Increased SVR to compensate

  • PCWP decreased

  • Fluid resuscitation beyond scope of this lecture

Mullner 2004

Distributive shock
Distributive shock

  • SVR severely decreased

  • CO usually increases

  • PCWP low or normal

  • Causes:

    • Sepsis, SIRS (burns), Addisonian crisis, anaphylaxis, toxic shock, myxedema coma

Mullner 2004

Vasopressor and inotrope mechanisms
Vasopressor and Inotrope mechanisms

  • Alpha receptors

    • Alpha 1 stimulation in peripheral vascular walls cause vasoconstriction

  • Beta receptors

    • Beta 1 stimulation increases inotropy and chronotropy

    • Beta 2 stimulation causes vasodilation

  • Dopamine receptors

    • Present in renal, splanchnic, coronary

    • Stimulation causes vasodilation

  • Direct Vasoconstriction (vasopressin)

  • Phosphodiesteraseinhibition (increased inotropy)

Mullner 2004

Norepinephrine levophed
Norepinephrine (Levophed)

  • Acts primarily on Alpha-1 (vasoconstriction), some beta-1 activity

  • Reflex bradycardic effect from increased MAP – offset by small beta-1 activity  HR usually remains stable or may increase slightly

  • Preferred agent for septic shock

  • Careful dosing!

Allwood, 1993

Norepinephrine dosing
Norepinephrine Dosing

  • Can be dosed in mcg/min OR mcg/kg/min

    • CAUTION!!!!!!

  • Start at 5-10mcg/min (not mcg/kg/min)

    • Sepsis – order 16mg/250mL infusion (non-fluid restricted)

    • Cardiogenic shock – order 32mg/250mL infusion (fluid restricted)

  • Titrate by 5-10mcg/min every 3-5min to desired MAP

  • Up to 3mcg/kg/min have been used (210mcg/min in 70kg pt)

    • Don’t be scared to titrate

  • Obtain central access ASAP for administration

  • Extravasation may cause necrosis – use phentolamine (alpha blocker)

Allwood, 1993

Dopamine intropin
Dopamine (Intropin)

  • Dose determines pharmacologic effect!

  • 1-2mcg/kg/min – primarily acts on dopamine receptors in renal, splanchnic, coronary, cerebral vasculature – VASODILATION

    • Renal dose – possible increase in urine output

    • Clinical significance unknown – don’t use for sole purpose of increasing urine output

    • Hypotension usually results from these low doses

Allwood, 1993

Dopamine intropin1
Dopamine (Intropin)

  • 2-5mcg/kg/min

    • Combination dopamine activity and beta stimulation

    • Increased CO balanced by slight vasodilation

    • variable effects on BP

  • 5-10mcg/kg/min

    • Mostly Beta-1 adrenergic stimulation, some alpha stimulation

    • Increases CO (inotropy, mild chronotropy)

    • Usually increased BP

Allwood, 1993

Dopamine intropin2
Dopamine (Intropin)

  • >10mcg/kg/min

  • Predominant effect is alpha-1 stimulation

  • Vasoconstriction – increased SVR and MAP

  • Dopamine doses >2mcg/kg/min is very pro-arrhythmic

  • Changing doses of Dopamine similar to changing drugs

    • Be cognoscente of this for different indications

  • CHF – doses > 10mcg/kg/min may increase SVR and worsen CO

  • Sepsis – doses <10mcg/kg/min may cause vasodilation and worsen tissue perfusion

Allwood, 1993

Norepinephrine vs dopamine
Norepinephrine vs. Dopamine

  • Surviving sepsis campaign

  • Norepinephrine or Dopamine recommended first line agents

    • Norepinephrine is preferred

  • Consider Dopamine for concurrent cardiac failure

  • Tissue hypoperfusion should be corrected with fluid resuscitation BEFORE initiating vasopressors – even in patients with HF (Remember pump or pipes?)

Martin, 1993

Norepinephrine vs dopamine1
Norepinephrine vs Dopamine

  • NEJM march 2010 – Norepinephrine vs Dopamine for shock

  • 1679 patients randomized to Norepi or Dopamine for all types of shock

  • Primary outcome – Death at 28 days

  • Overall no difference in rate of death at 28 days

  • More arrhythmic events in Dopamine patients

  • Subgroup – cardiogenic shock – Increased mortality in dopamine group vs norepinephrine

    • Attributed to fatal arrhythmic events in dopamine group

    • Not a prospective trial – interpret with caution

Martin, 1993

Assessment question7
Assessment Question

  • 30mL/kg fluid bolus is contraindicated in sepsis patients with a history of Congestive Heart Failure?

  • True

  • False

Phenylephrine neo synephrine
Phenylephrine (Neo-Synephrine)

  • Pure alpha-1 agonist

  • Minimal effect on chronotropy or inotropy

  • Commonly used in trauma – increase tissue perfusion

  • Dose: Initiate infusion at 100mcg/min, titrate by 20-40mcg/min q5-10min

    • Up to 9mcg/kg/min may be required for septic shock

    • Can initiate bolus of 100-500mcg while preparing infusion

Mullner, 2004

Epinephrine adrenalin
Epinephrine (Adrenalin)

  • Potent Alpha and Beta adrenergic agonist

  • At low doses, primarily beta -1 stimulation, some beta -2 agonist

    • Increased CO, possibly decreased SVR (Caution Sepsis)

  • At higher doses, peripheral alpha-1 activity overcomes beta-2 activity

    • Increased SVR (along with increased CO)

  • Very pro-arrhythmic

  • May induce coronary ischemia (caution severe CAD)

Mullner, 2004

Epinephrine adrenalin1
Epinephrine (Adrenalin)

  • Uses: Cardiac arrest, anaphylaxis, second line for septic shock

  • Dosing

  • Cardiac arrest: 1mg IV/IO q3-5min (0.1mg/ml, 1:10,000)

    • Not an antiarrhythmic

    • Purpose: peripheral vasoconstriction to increasing cardiac and vital organ perfusion

    • Do not use 1mg/ml (1:1,000), must dilute (premade syringes)

    • If known beta blocker overdose – may need higher doses (0.2mg/kg)

    • No IV/IO access, give 2mg endotracheal

      • May falsely decrease ETCO2 – use alternative methods to verify tube placement

Mullner, 2004

Epinephrine dosing cont
Epinephrine Dosing Cont.

  • Septic/Cardiogenic Shock

    • Initiate infusion 2-10mcg/min, titrate by 2-5mcg/min q 5-10min to MAP > 65

  • Anaphylaxis

    • 0.3mg IM (Epipen) (1:1000)

    • Note: IM preferred to SQ for more rapid systemic absorption (ACLS 2010)

    • Can repeat as needed q5min for 2 doses

    • If refractory, 0.1mg (1:10,000) IV

    • If repeated doses are necessary, initiate IV infusion

  • Bronchodilation (Asthma)

    • 0.3-0.5mg SQ q 20min, max 3 doses (slower absorption, avoid tachycardia)

    • Consider IM/IV administration for severe symptoms

Mullner, 2004

Dobutamine dobutrex
Dobutamine (Dobutrex)

  • Inotrope, not a vasopressor

  • Purely beta-1 and beta-2 agonist activity

  • Increases contraction (inotropy) and HR (chronotropy)

    • Increased CO, decreased left ventricular filling pressure

  • Beta 2 agonism causes vasodilation and decreased SVR

  • Reflex vasodilation results from increased CO

Mullner, 2004

Dobutamine dobutrex1
Dobutamine (Dobutrex)

  • Use: severe refractory HF and cardiogenic shock

  • Caution in severely volume depleted HF patients

    • Peripheral vasodilation may overcome modest increase in CO

    • May worsen BP in septic shock

  • Decompensated HF: initiate 2.5-10mcg/kg/min, max 40mcg/kg/min

  • If hypotension worsens, re-evaluate cause for shock, consider adding vasopressor (norepinephrine)

Mullner, 2004

Isoproterenol isuprel
Isoproterenol (Isuprel)

  • Inotrope, no vasopressor activity

  • Beta-1 and beta-2 agonist

  • Beta-1 effects are mostly chronotropic, less inotropic activity (as opposed to dobutamine)

  • Beta-2 agonism causes vasodilation and decrease in MAP

  • Use in hypotensive patients is usually avoided

  • Dose:

    • Bradyarrhythmia / AV block: 2-10mcg/min

Mullner, 2004

Assessment question8
Assessment Question

  • When you see acute decompensated HF, you should automatically think of Dopamine

  • True

  • False

Vasopressin pitressin
Vasopressin (Pitressin)

  • Antidiuretic hormone analog

  • MOA: Direct vasoconstrictor without inotropic or chronotropic effects

  • Only approved FDA use is Diabetes insipidus, however can be used in vasodilatory shock, variceal hemorrhage, and cardiac arrest

  • Vasodilatory shock: initiate .01-.03units/min, typical dose .04units/min (max?)

  • Only initiate as addition to catecholamine therapy – may decrease requirements of other agents (ex. tachycardia)

  • Do not abruptly withdraw (rebound hypotension)

    • Reduce dose by 0.01units/min every 30 minutes

Mullner, 2004

Vasopressin pitressin1
Vasopressin (Pitressin)

  • ACLS 2010 algorithm

  • Can substitute single dose of vasopressin for 1st or 2nd dose of epinephrine during cardiac arrest

  • 40units IV/IO/ET x 1 dose

  • No documented benefits reported, just stick with epinephrine!

  • Consider only as last line agent for variceal bleeding

    • Octreotide more effective

    • Higher vasopressin doses increase coronary ischemic events

Mullner, 2004

Push dose pressors
Push Dose Pressors?

  • Why?

    • Short term reversible hypotension

    • Post RSI

    • Procedural sedation

  • Provides temporary fix while waiting for infusion

Push dose pressors in the er
Push Dose Pressors in the ER?

  • The evidence…..not so good

  • “Anesthesia does it all the time”

  • “Dr. Smith does it a loves it”

  • “It makes sense, right?”

  • “I saw it on greys anatomy”

Push dose pressors in the er1
Push Dose Pressors in the ER?

  • Textbook references?

  • Tintinalli's: No Information

  • Rosen’s: “Propofol commonly results in a transient drop in systolic and diastolic blood pressure, which usually responds to fluid administration and is well tolerated in healthy adults.”

  • Miller’s Anesthesia: “[Phenylephrine] commonly used ... as in hypotension that may accompany spinal anesthesia. It may be given in bolus doses of 40-100mcg or by infusion…”

Push dose pressors in the er2
Push Dose Pressors in the ER?

  • Which drugs?

  • Epinephrine or phenylephrine have been reported

    • Epinephrine: alpha and beta agonist

    • Phenylephrine: alpha agonist

  • Phenylephrine preferred agent

Push dose pressors in the er3
Push Dose Pressors in the ER?

  • Phenylephrine

  • Preparation

    • Inject 10mg/mL phenylephrine into 100mL NS bag

    • Draw up 10mL of final solution – 100mcg/mL

  • Give 0.5-1mL as needed until continuous infusion arrives or transient hypotension resolves

  • Max dose 500mcg (or 5mL)

Push dose pressors conclusions
Push Dose Pressors Conclusions

  • Not great evidence for use in the ER

  • Can we extrapolate evidence from anesthesia to ER/Critical care?

  • MAP and SVR increase with phenylephrine

    • May be detrimental in CAD

    • Benefit vs risk?

  • Requires careful dilution and preparation

    • “Adds another hole to the Swiss cheese of errors in the ER”

Push dose pressors conclusions1
Push Dose Pressors conclusions

  • Who are we treating?

  • Us or the patient?

Non adrenergic agents
Non-adrenergic Agents

  • Phosphodiesterase inhibitors (PDE)

  • Inamrinone and Milrinone

  • Positive inotropic and vasodilatory actions

  • Lower incidence of arrhythmia vs dobutamine

  • Limited use due to vasodilatory effects

Mullner, 2004

Pde inhibitors
PDE inhibitors

  • Phosphodiesterases break down cAMP

  • Milrinone and Inamrinone inhibit phosphodiesterase type-3

  • Leads in decreased breakdown of cAMP (increased cAMP)

  • Increased phosphorylation of Ca++ channels increases Ca++ influx

  • Results in increased contractility

Mullner, 2004

Pde inhibitor dosing
PDE inhibitor dosing

  • Milrinone: Initiate 0.2-0.4mcg/kg/min IV infusion, typical dose 0.5mcg/kg/min

  • Needs adjustment in renal dysfunction

  • Use limited to HF refractory to dobutamine, palliation of symptoms in end stage HF, Inotropic support with ventricular assist device (VAD)

  • Inamrinone: 0.75mg/kg IV bolus, followed by 5-10mcg/kg/min

  • Not much utility in the ER

Mullner, 2004

Adverse effects
Adverse Effects

  • Numerous adverse effects from vasopressors and inotropes

  • Limb ischemia

  • Coronary ischemia

  • Arrhythmia

  • Hyperglycemia (impaired pancreatic function)

  • Shock liver

  • Renal failure

Mullner, 2004

Assessment question9
Assessment Question

  • A patient presents via EMS in PEA. After 2 rounds of proper ACLS, you get a weak pulse, and a pressure of 85/45, HR=35. What is your next choice for drug therapy?

Assessment question10
Assessment Question

  • A patient presents via EMS in PEA. After 2 rounds of proper ACLS, you get a weak pulse, and a pressure of 85/45, HR=35. What is your next choice for drug therapy?

  • Answer: Atropine 0.5mg IV

  • Remember: atropine still first line for bradycardia, not in cardiac arrest any more.


  • Assessment of volume status and fluid resuscitation is key

  • Pump or pipe problem?

  • Different doses produce different pharmacologic effects (dopamine)

  • Careful with push dose pressors, not much evidence

  • Proper administration and intense monitoring required for all patients


  • Müllner M, Urbanek B, Havel C, et al. Vasopressors for shock. Cochrane Database Syst Rev 2004

  • AHLQUIST RP. A study of the adrenotropic receptors. Am J Physiol 1948; 153:586.

  • ALLWOOD MJ, COBBOLD AF, GINSBURG J. Peripheral vascular effects of noradrenaline, isopropylnoradrenaline and dopamine. Br Med Bull 1963; 19:132

  • Practice parameters for hemodynamic support of sepsis in adult patients in sepsis. Task Force of the American College of Critical Care Medicine, Society of Critical Care Medicine. Crit Care Med 1999; 27:639.

  • Moran JL, O'Fathartaigh MS, Peisach AR, et al. Epinephrine as an inotropic agent in septic shock: a dose-profile analysis. Crit Care Med 1993; 21:70.

  • Calvin JE, Driedger AA, Sibbald WJ. Does the pulmonary capillary wedge pressure predict left ventricular preload in critically ill patients? Crit Care Med 1981; 9:437.

  • Packman MI, Rackow EC. Optimum left heart filling pressure during fluid resuscitation of patients with hypovolemic and septic shock. Crit Care Med 1983; 11:165.

  • Lherm T, Troché G, Rossignol M, et al. Renal effects of low-dose dopamine in patients with sepsis syndrome or septic shock treated with catecholamines. Intensive Care Med 1996; 22:213.

  •  Martin C, Papazian L, Perrin G, et al. Norepinephrine or dopamine for the treatment of hyperdynamic septic shock? Chest 1993; 103:1826.

Thank you
Thank you!

  • Presented by Paul Miller, Pharm.D.

  • Emergency Clinical Pharmacy Specialist

  • St Elizabeth Health Center

  • August 2012

  • [email protected]

  • 330-480-3667