toxic bradycardia and hypotension alyssa reed, r1 thanks to dr mark yarema
TRANSCRIPT
Toxic Toxic Bradycardia Bradycardia
and and HypotensionHypotension
Alyssa Reed, R1Alyssa Reed, R1
Thanks to Dr Mark Yarema
CASECASE
It is 330 am when the paramedics patch to It is 330 am when the paramedics patch to tell you they are on scene with a man who tell you they are on scene with a man who has a pulse of 45 and SBP of 80has a pulse of 45 and SBP of 80
What medical conditions could cause this? What medical conditions could cause this?
Medical Causes of Medical Causes of BradycardiaBradycardia
MIMI
Sick Sinus SyndromeSick Sinus Syndrome
HyperkalemiaHyperkalemia
HypothermiaHypothermia
Increased ICPIncreased ICP
VasovagalVasovagal
Physiologic (athletes)Physiologic (athletes)
CASE CONTINUED…CASE CONTINUED…
The patient arrives. Vitals are unchanged The patient arrives. Vitals are unchanged after 2L N/S and 2 mg of atropine. He is after 2L N/S and 2 mg of atropine. He is obtunded but breathing spontaneously. His obtunded but breathing spontaneously. His wife says he has a history or atrial wife says he has a history or atrial fibrillation, angina, hypertension and fibrillation, angina, hypertension and depression. The paramedics found a lot of depression. The paramedics found a lot of pill bottles beside him and suspect an pill bottles beside him and suspect an overdose. They left the bottles behind. overdose. They left the bottles behind.
What medications cause bradycardia?What medications cause bradycardia?
TOXIC BRADYCARDIATOXIC BRADYCARDIA Beta BlockersBeta Blockers
Calcium Channel BlockersCalcium Channel Blockers
Cardiac glycosides (digoxin)Cardiac glycosides (digoxin)
Cholinergic agents Cholinergic agents
Clonidine/Imidazolines (alpha2 agonists)Clonidine/Imidazolines (alpha2 agonists)
Opioids/Sedative HypnoticsOpioids/Sedative Hypnotics
Phenylpropanolamine (alpha1 agonists)Phenylpropanolamine (alpha1 agonists)
Sodium channel blockersSodium channel blockers
Can we eliminate any of these based on clinical presentation? Can we eliminate any of these based on clinical presentation?
TOXIC BRADYCARDIATOXIC BRADYCARDIA
Beta BlockersBeta Blockers
Calcium Channel BlockersCalcium Channel Blockers
Cardiac glycosides (digoxin)Cardiac glycosides (digoxin)
Cholinergic agents Cholinergic agents
Clonidine/Imidazolines (alpha2 agonists)Clonidine/Imidazolines (alpha2 agonists)
Opioids/Sedative HypnoticsOpioids/Sedative Hypnotics
Phenylpropanolamine (alpha1 agonists)Phenylpropanolamine (alpha1 agonists)
Sodium channel blockersSodium channel blockers
THE “BIG FOUR”THE “BIG FOUR”
Beta BlockersBeta Blockers
Calcium Channel BlockersCalcium Channel Blockers
Cardiac GlycosidesCardiac Glycosides
Sodium Channel BlockersSodium Channel Blockers
Maybe put in some physiology and table Maybe put in some physiology and table 17.11 page 393 of lilly17.11 page 393 of lilly
CASECASE
40M brought by EMS after an OD. Drug 40M brought by EMS after an OD. Drug unknown. Pulse is 50 and SBP is 90.unknown. Pulse is 50 and SBP is 90.
Which of the four do you think is most likely Which of the four do you think is most likely responsible? responsible?
Na Channel BlockersNa Channel Blockers
Class IA Class IA AntiarrhythmicsAntiarrhythmics• QuinidineQuinidine• ProcainamideProcainamide• DisopyramideDisopyramide
Class IC Class IC AntiarrhythmicsAntiarrhythmics• FlecainideFlecainide• PropafenonePropafenone
CocaineCocaine
TCAsTCAs Diltiazem/Diltiazem/
VerapamilVerapamil PropranololPropranolol CarbamazepineCarbamazepine
PresentationPresentation
QRS wideningQRS widening
HypotensionHypotension
SeizuresSeizures
Altered Mental StatusAltered Mental StatusMembrane Stabilizing ActivityMembrane Stabilizing ActivityDecreased perfusionDecreased perfusion
ManagementManagement
Sodium BicarbonateSodium Bicarbonate 50ml = 50mEq = 1ampule50ml = 50mEq = 1ampule IndicationsIndications
11 QRS > 100msQRS > 100ms
22 Persistent hypotension despite adequate Persistent hypotension despite adequate fluid resusfluid resus
33 DysrhythmiasDysrhythmias DosingDosing• Bolus 3 ampsBolus 3 amps• 3 amps in a bag of D5W and infuse and 3 amps in a bag of D5W and infuse and
2-3x maintenance2-3x maintenance
Hypertonic SalineHypertonic Saline
CASECASE
A 55M is brought in by the paramedics with A 55M is brought in by the paramedics with a pulse of 40 and SBP of 78. His BG is 18. He a pulse of 40 and SBP of 78. His BG is 18. He is AOx3.is AOx3.
He has a history of “heart problems” and no He has a history of “heart problems” and no other medical historyother medical history
K 4.0 K 4.0
Which of the “big four” is likely responsible? (see Which of the “big four” is likely responsible? (see next ECG to help eliminate)next ECG to help eliminate)
Beta Blockers Calcium Channel Blockers
Vitals HypotensiveBradycardic
HypotensiveBradycardicTachycardic
Mental Status Depressed Preserved
Blood Glucose Low-Normal High
Calcium Channel Calcium Channel BlockersBlockers
All block L-type calcium channelsAll block L-type calcium channels Heart*Heart*• Contractile TissueContractile Tissue• Pacemaker cellsPacemaker cells
Vascular Smooth Muscle*Vascular Smooth Muscle* Endocrine (including beta pancreatic Endocrine (including beta pancreatic
cells)cells) RetinaRetina Skeletal muscleSkeletal muscle
Put in a pic of the channels and Put in a pic of the channels and depolarizationdepolarization
1) Myocyte depolzn triggers opening of LTCC
2) Causes release of stored Ca from SR
3) Contract
Calcium Channel Calcium Channel BlockersBlockers
2 Major Clasess2 Major Clasess DihydropyridinesDihydropyridines• Preferentially block L-type calcium Preferentially block L-type calcium
channels in the vasculaturechannels in the vasculature• Potent vasodilators with little negative Potent vasodilators with little negative
effect upon cardiac contractillity or effect upon cardiac contractillity or conductionconduction
Non-dihydropyridinesNon-dihydropyridines• Preferentially block L-type calcium Preferentially block L-type calcium
channels in the myocardiumchannels in the myocardium• Negative inotropic effects and decrease Negative inotropic effects and decrease
AV node conductionAV node conduction
CCB OD PresentationCCB OD Presentation HypotensionHypotension
Bradydysrhythmias (or reflex tachycardia)Bradydysrhythmias (or reflex tachycardia)
Normal mental statusNormal mental status
HyperglycemiaHyperglycemia disruption of fatty acid metabolism creating disruption of fatty acid metabolism creating
relative insulin resistance and decreased relative insulin resistance and decreased release of insulin from β panc cellsrelease of insulin from β panc cells
Pulmonary EdemaPulmonary Edema Heart failure + vasodilation and extravasationHeart failure + vasodilation and extravasation
IleusIleus Decreased smooth muscle function in bowelDecreased smooth muscle function in bowel
CCB OD DxCCB OD Dx
No urine or serum test readily availableNo urine or serum test readily available
ECGECG
CXRCXR
Lytes (including Ca, Mg)Lytes (including Ca, Mg)
Blood GlucoseBlood Glucose
ABGABG
What are some of the ECG findings/rhythms in CCB OD?
CCB OD and the ECGCCB OD and the ECG
BradysrhythmiasBradysrhythmias• AV block of all degreesAV block of all degrees• Sinus arrestSinus arrest• AV dissociationAV dissociation• Junctional rhythmJunctional rhythm• AsystoleAsystole
Reflex Sinus TachReflex Sinus Tach• Nifedipine ODNifedipine OD
OD General ApproachOD General Approach
1.1. ABCsABCs
2.2. GI DecontaminationGI Decontamination• Activated charcoal (50G in adult, 1g/kg in Activated charcoal (50G in adult, 1g/kg in
peds)peds)• Gastric LavageGastric Lavage• Whole Bowel Irrigation (polyethylene Whole Bowel Irrigation (polyethylene
glycol 2L/hr adults, 500cc/hr peds)glycol 2L/hr adults, 500cc/hr peds)
3.3. Enhanced EliminationEnhanced Elimination• HemodialysisHemodialysis
4.4. AntidotesAntidotes
5.5. Supportive careSupportive care
CCB OD MxCCB OD Mx
HYPOTENSIONHYPOTENSION• Fluids Fluids • CalciumCalcium• GlucagonGlucagon• PressorsPressors
BRADYCARDIABRADYCARDIA• AtropineAtropine• CalciumCalcium• GlucagonGlucagon• PacerPacer
AtropineAtropine
Given routinely to symptomatic Given routinely to symptomatic bradycardic patientsbradycardic patients
Often ineffectiveOften ineffective
AdultsAdults: 0.5-1 mg IV Q3min to a max : 0.5-1 mg IV Q3min to a max of 3mgof 3mg
PedsPeds: 0.02mg/kg IV with a min dose : 0.02mg/kg IV with a min dose of 0.1mg and a max of 1mg of 0.1mg and a max of 1mg
Calcium Calcium
CALCIUM CHLORIDECALCIUM CHLORIDE• 10% solution10% solution• 1g/10ml1g/10ml• 1g = 13.6 mEq1g = 13.6 mEq• Central lineCentral line• DoseDose: 1g over 10 : 1g over 10
min (10cc) Q15 to min (10cc) Q15 to a max of 6 g and a max of 6 g and can infuse 1-2g/hr can infuse 1-2g/hr if responsiveif responsive
CALCIUM CALCIUM GLUCONATEGLUCONATE• 10% solution10% solution• 1g/10ml1g/10ml• 1g = 4.5 mEq1g = 4.5 mEq• Peripheral linePeripheral line• DoseDose: 3g (30cc) : 3g (30cc)
over 10 minover 10 min
GlucagonGlucagon Increases intracellular levels of cAMPIncreases intracellular levels of cAMP• Opens Ca channelsOpens Ca channels
Animal modelsAnimal models• increase in heart rateincrease in heart rate• Little effect on MAPLittle effect on MAP
Bolus: 5mg over 1-2 min, to max of 15mg Bolus: 5mg over 1-2 min, to max of 15mg (this is diluted in 10cc N/S)(this is diluted in 10cc N/S)
Maintenance: infusion of response dose Maintenance: infusion of response dose mg/hrmg/hr
Vomiting and aspiration riskVomiting and aspiration risk
Phenol toxicity Phenol toxicity
PressorsPressors
Q: What would be the ideal properties of a pressor in CCB Q: What would be the ideal properties of a pressor in CCB tox? tox?
A: Direct-acting agent with +chronotropy, inotropy, A: Direct-acting agent with +chronotropy, inotropy, and vasoconstrictive effectsand vasoconstrictive effects
Q: What would you use? Q: What would you use?
A: Norepinenphrine is initial choice A: Norepinenphrine is initial choice
Dopamine not because indirect effects and little Dopamine not because indirect effects and little alpha alpha
Can increase pulmonary edema and ischemic Can increase pulmonary edema and ischemic vascular dz and renal failure vascular dz and renal failure
Insulin and GlucoseInsulin and Glucose CJEM 2006 Prediger and YaremaCJEM 2006 Prediger and Yarema
Systematic review of 13 papersSystematic review of 13 papers 20 cases of CCB OD (17 adult, 3 pediatric)20 cases of CCB OD (17 adult, 3 pediatric) Most effective at treating hypotension Most effective at treating hypotension
(n=15)(n=15) 3 patients converted to sinus from AV block3 patients converted to sinus from AV block Dosing and length of treatment varied Dosing and length of treatment varied
widelywidely AE: asymptomatic hypoglycemia AE: asymptomatic hypoglycemia
(n=8),hypokalemia (n=4)(n=8),hypokalemia (n=4) Conclusion: HDIG is safe and effective Conclusion: HDIG is safe and effective
treatment of CCB overdose treatment of CCB overdose
Insulin and Glucose Insulin and Glucose
The heart usually metabolizes free fatty acids The heart usually metabolizes free fatty acids but in shock state it needs glucosebut in shock state it needs glucose
In CCB OD cardiac glucose uptake is impaired In CCB OD cardiac glucose uptake is impaired b/cb/c1.1. Decreased insulin release (calcium mediated)Decreased insulin release (calcium mediated)
2.2. CCB toxicity induces a state of insulin CCB toxicity induces a state of insulin resistance (myocardium and rest of body)resistance (myocardium and rest of body)
3.3. Acidosis and low perfusion limits glycolysis and Acidosis and low perfusion limits glycolysis and carbohydrte delivery to the heart carbohydrte delivery to the heart
Insulin acts as a pressorInsulin acts as a pressor Improved glucose delivery and uptake to the Improved glucose delivery and uptake to the
heart and improving cardiac performanceheart and improving cardiac performance
Insulin and GlucoseInsulin and Glucose Disrupt state of carbohydrate dependence Disrupt state of carbohydrate dependence
and insulin resistance and insulin resistance
Animal modelsAnimal models• Improved survival with Improved survival with
hyperinsulinemia/euglycemia compared to hyperinsulinemia/euglycemia compared to calcium, pressors and glucagoncalcium, pressors and glucagon
• Positive inotropic effects Positive inotropic effects
Bolus: 0.1U/kg IV of regular insulin Bolus: 0.1U/kg IV of regular insulin
Infusion: 0.2-0.5 U/kg/hrInfusion: 0.2-0.5 U/kg/hr
Glucose: 25-50 g of dextrose at beginning or Glucose: 25-50 g of dextrose at beginning or can infuse at 0.5 g/kg/hr can infuse at 0.5 g/kg/hr
Other TherapiesOther Therapies Phosphodiesterase InhibitorsPhosphodiesterase Inhibitors• Amrinone , milrinoneAmrinone , milrinone• Increase cAMP by preventing degradation Increase cAMP by preventing degradation
of it by phosphodiesterase enzymeof it by phosphodiesterase enzyme• May exacerbate hypotensionMay exacerbate hypotension• ICU setting with pulmonary artery ICU setting with pulmonary artery
cathetercatheter
Sodium BicarbonateSodium Bicarbonate• Prolonged QRS or lactic acidosisProlonged QRS or lactic acidosis• 1amp= 50mEq1amp= 50mEq• Put 3 amps in 1L D5W and infuse and Put 3 amps in 1L D5W and infuse and
two times maintenancetwo times maintenance
Invasive MxInvasive Mx
Transvenous pacingTransvenous pacing• Does not counteract negative Does not counteract negative
inotropic effectsinotropic effects• Successful capture may not Successful capture may not
correct hypotensioncorrect hypotension
Intraaortic balloon pumpIntraaortic balloon pump
Cardiopulmonary bypassCardiopulmonary bypass
SummarySummary Block L-type channelsBlock L-type channels• Vascular smooth muscleVascular smooth muscle• Cardiac muscle cells and pacemaker cellsCardiac muscle cells and pacemaker cells
Hypotension, brady or tachy, preserved Hypotension, brady or tachy, preserved mental status, hyperglycemicmental status, hyperglycemic
MxMx• Early WBIEarly WBI• Fluids/atropineFluids/atropine• CalciumCalcium• GlucagonGlucagon• PressorsPressors• Insulin and glucoseInsulin and glucose
CASECASE
50F brought in by EMS. Patient is altered. 50F brought in by EMS. Patient is altered. T= 37, P= 50, RR= 12, SBP= 74, O2=90%RA, T= 37, P= 50, RR= 12, SBP= 74, O2=90%RA, BG 3.5BG 3.5
Hx of “heart problems” and hypertensionHx of “heart problems” and hypertension
Which of the big four do you suspect? Which of the big four do you suspect?
Beta ReceptorsBeta ReceptorsBeta 1Beta 1
Primarily in the heartPrimarily in the heart Increase 1) heart rate, 2) contractility, and Increase 1) heart rate, 2) contractility, and
3) AV conduction3) AV conduction Decrease AV node refractoriness Decrease AV node refractoriness
Beta 2Beta 2 Primarily in bronchial and peripheral Primarily in bronchial and peripheral
smooth musclesmooth muscle Also in liver, uterus, heartAlso in liver, uterus, heart Vasodilation, bronchodilation, Vasodilation, bronchodilation,
gluconeogenesis, glycogenolysis gluconeogenesis, glycogenolysis Beta 3Beta 3
Adipose tissue and heartAdipose tissue and heart Thermogenesis Thermogenesis
Beta BlockersBeta Blockers
Structurally resemble isoproterenol (pure β Structurally resemble isoproterenol (pure β agonist)agonist)
Competitively inhibit endogenous Competitively inhibit endogenous catecholamines (ex. Epinephrine) at the B-catecholamines (ex. Epinephrine) at the B-receptorreceptor
These catecholamines normally bind to the These catecholamines normally bind to the receptor and result in activation of adenyl receptor and result in activation of adenyl cyclase, resulting in cAMPcyclase, resulting in cAMP
cAMP augments:cAMP augments:1.1. InotropyInotropy (myocardial contraction) (myocardial contraction)
2.2. DromotropyDromotropy (cardiac conduction) (cardiac conduction)
3.3. Chronotropy Chronotropy (heart rate)(heart rate)
Clinical PresentationClinical Presentation
BradycardiaBradycardia HypotensionHypotension UnconsciousnessUnconsciousness Respiratory Respiratory
arrest or arrest or insufficiencyinsufficiency
Hypoglycemia Hypoglycemia (uncommon in (uncommon in adults)adults)
Seizures (esp. Seizures (esp. propranolol)propranolol)
Symptomatic Symptomatic BronchospasmBronchospasm
VT or VFVT or VF Mild hyperK Mild hyperK
Rosen’s Table 150-8
βB PropertiesβB Properties
1.1. Membrane-Stabilizing Activity (MSA)Membrane-Stabilizing Activity (MSA)• Inhibition of myocardial fast sodium channelsInhibition of myocardial fast sodium channels• Can result in wide QRS and other Can result in wide QRS and other
dysrhythmiasdysrhythmias
2.2. LipophilicityLipophilicity• High lipid solubility= rapidly cross BBBHigh lipid solubility= rapidly cross BBB• Cause altered LOC (independent of Cause altered LOC (independent of
hypoperfusion)hypoperfusion)
3.3. Intrinsic Sympathomimetic Activity (ISA)Intrinsic Sympathomimetic Activity (ISA) Partial agonist effect at beta receptor sitePartial agonist effect at beta receptor site Cause less bradycardia and hypotension Cause less bradycardia and hypotension DO NOT completely protect DO NOT completely protect
Noncardioselective βBNoncardioselective βB
MSA Lipophilic ISA ½ life (hr) Comments
Propranolol ++ + - 4 Most deaths
Nadolol - - - 10-20 Dialyzable
Labetalol + - - 4-6 α blocker too
Sotalol - + - 7-18 Class III/II
Rosen’s Table 150-3
Cardioselective βBCardioselective βB
MSE Lipohilic ISA ½ life (hr) Comments
Metoprolol - + - 3-4
Atenolol - - - 5-8 Dialyzable
Esmolol - - - 0.13
Acebutolol ++ + + 2-4 QT long
Rosen’s Table 150-3
βB OD and the ECGβB OD and the ECG
Increased PR Increased PR from decreased from decreased conduction velocity down AV nodeconduction velocity down AV node
BradycardiaBradycardia from decreased from decreased automaticity within SA nodeautomaticity within SA node
Ventricular tachydysrhythmiasVentricular tachydysrhythmias with with MSA βBMSA βB
Wide QRS Wide QRS with MSA βBwith MSA βB
QT prolongation QT prolongation with sotalol ODwith sotalol OD
βB OD MxβB OD Mx
HYPOTENSIONHYPOTENSION• FluidsFluids• GlucagonGlucagon• EpinephrineEpinephrine• IsoproterenolIsoproterenol
BRADYCARDIA*BRADYCARDIA*• AtropineAtropine• GlucagonGlucagon• PacemakerPacemaker• EpinephrineEpinephrine• IsoproterenolIsoproterenol
* Only tx if third degree block or symptomatic
AtropineAtropine
Symptomatic bradycardia onlySymptomatic bradycardia only
Adults: O.5-1mg IV to a max of 3mgAdults: O.5-1mg IV to a max of 3mg
Peds: 0.02mg/kg with a min of 0.1mg Peds: 0.02mg/kg with a min of 0.1mg and max of 1mgand max of 1mg
Poor effect on improving bradycardia Poor effect on improving bradycardia and hypotension and hypotension
GlucagonGlucagon
Remember glucagon activates adenylate Remember glucagon activates adenylate cyclase at a site independent from beta-cyclase at a site independent from beta-adrenergic sitesadrenergic sites• Increases cAMP= increases intracellular Increases cAMP= increases intracellular
Ca= increasing contractility Ca= increasing contractility
Considered first line (“antidotal”) Considered first line (“antidotal”)
DoseDose• 2-5mg (50mcg/kg in peds) diluted in 2-5mg (50mcg/kg in peds) diluted in
10cc N/S over 1-2 min to a max of 15mg10cc N/S over 1-2 min to a max of 15mg• Maintenance: response dose in mg/hrMaintenance: response dose in mg/hr
ATP cAMP
Gs
Beta blocker Beta blocker “antidotes” “antidotes”
Phosphodiesterase
AMP
Amrinone
GlucagonCatecholaminepressors
InsulinInsulin
Animal models show promiseAnimal models show promise• Improved cardio and hemodynamic Improved cardio and hemodynamic
parameters and decreased mortalityparameters and decreased mortality
No definite dosing regimenNo definite dosing regimen• Regular insulin infusion starting at Regular insulin infusion starting at
0.1U/kg/hr combined with glucose at 0.1U/kg/hr combined with glucose at 1g/kg/hr1g/kg/hr
• Check glucose levels every 30-60minCheck glucose levels every 30-60min• Less than in CCB OD (0.2-0.5U/kg/hr Less than in CCB OD (0.2-0.5U/kg/hr
after a bolus)after a bolus)
OthersOthers
CalciumCalcium• Shown to reverse hypotension in animal and Shown to reverse hypotension in animal and
human modelshuman models• Dosing: see CCB OD section (Calcium chloride Dosing: see CCB OD section (Calcium chloride
vs. gluconate) vs. gluconate)
PressorsPressors• Epinephrine and norepinephrine have both Epinephrine and norepinephrine have both
been used been used • Poor outcomesPoor outcomes
IsoproterenolIsoproterenol• Should be ideal because B1 and B2 agonist Should be ideal because B1 and B2 agonist
effectseffects• However, can worsen hypotensionHowever, can worsen hypotension
OthersOthers Phosphodiesterase InhibitorsPhosphodiesterase Inhibitors• Inhibit breakdown of cAMP by Inhibit breakdown of cAMP by
phosphodiesterasesphosphodiesterases• Case reports onlyCase reports only• Use only after other therapies have failedUse only after other therapies have failed
Sodium BicarbonateSodium Bicarbonate• Safe adjunctSafe adjunct• Use if QRS wideUse if QRS wide• 1-2mEq/kg IV push1-2mEq/kg IV push
MagnesiumMagnesium• Ventricular arrhythmiasVentricular arrhythmias• Sotalol OD Sotalol OD
OthersOthers
Intravenous pacingIntravenous pacing• Profound bradycardiaProfound bradycardia• Frequently cannot captureFrequently cannot capture• Can increase heart rate without a Can increase heart rate without a
corresponding increase in perfusioncorresponding increase in perfusion
Intraaortic balloon pumpIntraaortic balloon pump• Successful case reports in failed Successful case reports in failed
pharmacological tx of propranolol and pharmacological tx of propranolol and atenolol ODatenolol OD
HemodialysisHemodialysis• Nadolol, sotalol, atenolol Nadolol, sotalol, atenolol
SummarySummary
BETA BLOCKER ODBETA BLOCKER OD
1. GI Decontamination1. GI Decontamination
2. Atropine/Fluids2. Atropine/Fluids
3. Glucagon3. Glucagon
4. Calcium4. Calcium
5. Insulin/Glucose5. Insulin/Glucose
6. Pressors (with 6. Pressors (with caution)caution)
7. Phosphodiesterase 7. Phosphodiesterase inhibitorsinhibitors
8. Invasive tx8. Invasive tx
CCB ODCCB OD
1. GI decontamination1. GI decontamination
2. Atropine/Fluids2. Atropine/Fluids
3. Calcium3. Calcium
4. Glucagon4. Glucagon
5. Insulin/glucose5. Insulin/glucose
6. Pressors (with 6. Pressors (with caution)caution)
7. Invasive tx7. Invasive tx
CASECASE
55M brought in by EMS. Pulse is 45, SBP is 55M brought in by EMS. Pulse is 45, SBP is 95. Patient complaint of nausea and 95. Patient complaint of nausea and vomiting for several days and difficulty vomiting for several days and difficulty seeing for the last day. seeing for the last day.
Hx: HTN, AfibHx: HTN, Afib
Na-K ATPase Na-K ATPase InhhibitorsInhhibitors
DigoxinDigoxin, Digitoxin, Ouabain, Foxglove, Lilly , Digitoxin, Ouabain, Foxglove, Lilly of the valley, oleanderof the valley, oleander
2 desired effects of Digoxin2 desired effects of Digoxin
1.1. Improve the contractility of the failing heartImprove the contractility of the failing heart• By blocking the Na-K ATPase pump and By blocking the Na-K ATPase pump and
ultimately increasing intracellular Ca ultimately increasing intracellular Ca which increases the force of which increases the force of contractioncontraction
2.2. Prolong the refractory period of the AV node Prolong the refractory period of the AV node in pts with SVTin pts with SVT• By enhancing vagal tone and reducing By enhancing vagal tone and reducing
sympathetic activitysympathetic activity
Clinical PresentationClinical Presentation ACUTEACUTE
Few initial signs Few initial signs and symptomsand symptoms
Cardiac Cardiac instabilityinstability
HyperKHyperK
CHRONICCHRONIC FatigueFatigue VisionVision• Blurred visionBlurred vision• Color Color
disturbancesdisturbances GIGI• Abdo painAbdo pain• DiarrheaDiarrhea• Nausea/Nausea/
VomitingVomiting CNSCNS• HeadacheHeadache• DizzinessDizziness• ConfusionConfusion
* Usually preserve BP and not significantly hypotensive like βB and CCBs
DiagnosisDiagnosis
ECGECG
ElectrolytesElectrolytes
Serum digoxin levelSerum digoxin level Measure at least 6 hrs after last dose Measure at least 6 hrs after last dose
(time needed to reach steady state)(time needed to reach steady state) False + elevated levels (no SSx)False + elevated levels (no SSx)• Pregnant womenPregnant women• Chronic renal failure or hepatobiliary Chronic renal failure or hepatobiliary
dz dz False – normal levels (sig SSx) False – normal levels (sig SSx) • Foxglove or oleander ingestionFoxglove or oleander ingestion
Increased vagal tone.
Increased automaticity
Digoxin and the ECGDigoxin and the ECG
What are common digoxin toxic arrhythmias?
Dig Tox and the ECGDig Tox and the ECG
NONSPECIFICNONSPECIFIC PVCs PVCs 11st,st, 2 2ndnd (type 1), 3 (type 1), 3rdrd
degree AV blockdegree AV block Sinus bradycardiaSinus bradycardia Sinus tachycardiaSinus tachycardia Sinoatrial block or Sinoatrial block or
arrestarrest Afib with slow Afib with slow
ventricular ventricular responseresponse
Junctional escape Junctional escape rhythmrhythm
AV dissociationAV dissociation Ventricular Ventricular
bigeminy and bigeminy and trigeminytrigeminy
VTach/VFibVTach/VFib Torsades de Torsades de
pointespointes
Dig Tox and the ECGDig Tox and the ECG
MORE SPECIFICMORE SPECIFIC Afib with slow, regular ventricular Afib with slow, regular ventricular
rate (AV dissociation)rate (AV dissociation) Nonparoxysmal junctional Nonparoxysmal junctional
tachycardia (70-130 bpm)tachycardia (70-130 bpm) Atrial tachycardia with block (150-Atrial tachycardia with block (150-
200 bpm)200 bpm) Bidirectional VTachBidirectional VTach
Dig Tox and the ECGDig Tox and the ECG
Very rarely seeVery rarely see Mobitz Type II blockMobitz Type II block Afib or Aflutter with rapid Afib or Aflutter with rapid
ventricular responseventricular response Unimorphic VtachUnimorphic Vtach
Potassium and Dig Potassium and Dig ToxicityToxicity
Acute ToxicityAcute Toxicity• Correlates with hyperkalemiaCorrelates with hyperkalemia• K level determines prognosis and K level determines prognosis and
treatmenttreatment
Chronic ToxicityChronic Toxicity• K normal or lowK normal or low• Slow rise over time allows kidneys to Slow rise over time allows kidneys to
balancebalance• Patients often also on diuretic which Patients often also on diuretic which
reduce the K levelreduce the K level
Potassium and acute Potassium and acute digoxin toxicitydigoxin toxicity
3
8
5
7
6
4
SurvivedDied
Bismuth, C., et al. Hyperkalemia in acute digitalis poisoning: prognostic significance and therapeutic implications. Clin Toxicol 1973; 6:153.
K<5.0, 0% mortalityK 5-5.5, 50% mortalityK>5.5 100% mortality
Predisposing FactorsPredisposing Factors
Advanced ageAdvanced age WomenWomen Renal InsufficiencyRenal Insufficiency Heart DiseaseHeart Disease• Congenital Heart Congenital Heart
DzDz• Ischemic heart Ischemic heart
DzDz• CHFCHF• MyocarditisMyocarditis
AlkalosisAlkalosis HypothyroidismHypothyroidism
Electrolyte ImbalanceElectrolyte Imbalance• Hypo or hyper kalemiaHypo or hyper kalemia• HypomagnesemiaHypomagnesemia• HypercalcemiaHypercalcemia
Sympathomimetic DrugsSympathomimetic Drugs Cardiotoxic CoingestantsCardiotoxic Coingestants• BBBB• CCBCCB• Tricyclic Tricyclic
antidepressantsantidepressants Drug InteractionsDrug Interactions• Quinidine, amiodaroneQuinidine, amiodarone• ErythromycinErythromycin
Management of Dig Management of Dig ToxicityToxicity
GI DecontaminationGI Decontamination
Electrolyte CorrectionElectrolyte Correction
BradycardiasBradycardias
Ventricular DysrhythmiasVentricular Dysrhythmias
Fab FragmentsFab Fragments
GI DecontaminationGI Decontamination
Digoxin is absorbed effectively by Digoxin is absorbed effectively by activated charcoalactivated charcoal Within one hour of ingestionWithin one hour of ingestion 50g for adults50g for adults 1g/kg for peds 1g/kg for peds
No improvement in outcome has No improvement in outcome has been provenbeen proven
Electrolyte CorrectionElectrolyte Correction KK
Hypo: in chronic tox want to replace (goals of Hypo: in chronic tox want to replace (goals of 3.5 to 4mEq/L)3.5 to 4mEq/L)• Oral repletion preferredOral repletion preferred• Don’t replace in acuteDon’t replace in acute
Hyper: in acute tox want to reduce itHyper: in acute tox want to reduce it• Insulin glucoseInsulin glucose• Beta agonistBeta agonist• Sodium bicarbonateSodium bicarbonate• NOTNOT Calcium Calcium
MgMg• Hypomag often reportedHypomag often reported• Replace with 2-4g magnesium sulfate Replace with 2-4g magnesium sulfate
BradycardiasBradycardias
AtropineAtropine• Reverses dig induced vagal toneReverses dig induced vagal tone• More effective than in other cardiac More effective than in other cardiac
drug toxicity (acute toxicity)drug toxicity (acute toxicity)• 0.5mg-1mg to a max of 3mg Q2-3 min 0.5mg-1mg to a max of 3mg Q2-3 min
PacingPacing• If fail atropine treatmentIf fail atropine treatment• Catheter may induce ventricular Catheter may induce ventricular
dysrhythmiasdysrhythmias• External pacing safer but not as External pacing safer but not as
effectiveeffective
Ventricular Ventricular DysrhythmiasDysrhythmias
Vagal ManeuversVagal Maneuvers• NO!!! Can cause asystole and cardiac arrest NO!!! Can cause asystole and cardiac arrest
PhenytoinPhenytoin• SafeSafe• May enhance AV conductionMay enhance AV conduction• Load with 10-15mg/kg Infuse at 25-Load with 10-15mg/kg Infuse at 25-
50mg/min50mg/min
LidocaineLidocaine• SafeSafe• Load with 1-3mg/kg Infuse at 1-4mg/minLoad with 1-3mg/kg Infuse at 1-4mg/min
Fab FragmentsFab Fragments
Digibind™Digibind™
Purified from sheepPurified from sheep
Rapidly bind to digoxin in the Rapidly bind to digoxin in the tissuestissues
Efflux of intracellular digoxin Efflux of intracellular digoxin
Further binding of free digoxinFurther binding of free digoxin
Renally excretedRenally excreted
Indications for Indications for Digibind™Digibind™
1.1. Vetricular dysrhythmiasVetricular dysrhythmias
2.2. Severe bradycardia unresponsive to Severe bradycardia unresponsive to atropineatropine
3.3. Serum K > 5 mEq/L (acute ingestion)Serum K > 5 mEq/L (acute ingestion)
4.4. Serum digoxin levelSerum digoxin level >10 mmol/L at any time>10 mmol/L at any time >12.5 mmol/L 6 hours after ingestion >12.5 mmol/L 6 hours after ingestion
5.5. Acute Ingestion of > 10mg (4mg peds)Acute Ingestion of > 10mg (4mg peds)
6.6. Presence of a digoxin-toxic rhythm in the Presence of a digoxin-toxic rhythm in the setting of an elevated digoxin levelsetting of an elevated digoxin level
Effectiveness of Effectiveness of DigibindDigibind
Antman, EM, et al. Antman, EM, et al. CirculationCirculation 1990 1990 N=150 (cases of life-threatening digitalis tox)N=150 (cases of life-threatening digitalis tox) ResultsResults• 80% complete resolution of all signs and 80% complete resolution of all signs and
symptomssymptoms• 10% improved10% improved• 10% showed no response10% showed no response• Median time to initial response was 19 min Median time to initial response was 19 min • Time to complete response was 88 minTime to complete response was 88 min• 54% of cardiac arrest patients survived 54% of cardiac arrest patients survived
hospitalizationhospitalization
Nonresponders to Nonresponders to DigibindDigibind
1.1. Underlying heart disease (that Underlying heart disease (that causes some of the causes some of the manifestations)manifestations)
2.2. Too low a dose of FabToo low a dose of Fab
3.3. Moribund on presentationMoribund on presentation
4.4. Co-ingestion of other cardiac toxic Co-ingestion of other cardiac toxic drugsdrugs
Dosing of DigibindDosing of Digibind
Given IV over 30 minutesGiven IV over 30 minutes Unless arrested, then give as a bolusUnless arrested, then give as a bolus
Vials of Fab= (Dig level ng/ml x Mass Vials of Fab= (Dig level ng/ml x Mass kg)/ 100kg)/ 100
Always round upAlways round up
Example: how many vials would you need for Example: how many vials would you need for a 70kg woman with a digoxin level of 3 and a 70kg woman with a digoxin level of 3 and frequent PVCs?frequent PVCs?Vials= (3 x 70) / 100 = 2.1 so you would give 3
What if you don’t know the dig level right away???
Dosing of DigibindDosing of Digibind
ACUTEACUTE Stable- 5 vialsStable- 5 vials Unstable- 15 vialsUnstable- 15 vials
CHRONICCHRONIC Stable- 1 vialStable- 1 vial Unstable- 4 vialsUnstable- 4 vials
*1 vial costs approx 400$*1 vial costs approx 400$
Summary- Acute vs Summary- Acute vs ChronicChronic
CHRONICCHRONIC
1.1. Higher mortalityHigher mortality
2.2. K normal or lowK normal or low
3.3. Ventricular Ventricular dysrhythmias more dysrhythmias more commoncommon
4.4. Usually elderly Usually elderly patientspatients
5.5. Often need Fab Often need Fab fragment therapyfragment therapy
6.6. Underlying heart dz Underlying heart dz increases morbidity increases morbidity and mortalityand mortality
ACUTEACUTE
1.1. Lower mortalityLower mortality
2.2. K normal or highK normal or high
3.3. Bradycardia and AV Bradycardia and AV block more commonblock more common
4.4. Usually younger Usually younger patientspatients
5.5. Often do well Often do well without Fab without Fab fragment therapyfragment therapy
6.6. Absence of heart dz Absence of heart dz decreases morbidity decreases morbidity and mortalityand mortality
Bradycardia and Bradycardia and HypotensionHypotension
Sodium channel blockersSodium channel blockers Wide QRS. Wide QRS. Rx = bicarbonateRx = bicarbonate
DigoxinDigoxin Blocks, increased automaticity. Blocks, increased automaticity. Rx = digibind.Rx = digibind.
Calcium channel blockersCalcium channel blockers Increased glucose, preserved mental status Increased glucose, preserved mental status Rx - Calcium, pressors, insulin / glucoseRx - Calcium, pressors, insulin / glucose
Beta blockersBeta blockers Altered mental status, normal glucoseAltered mental status, normal glucose Rx - Glucagon, insulin / glucose, pressorsRx - Glucagon, insulin / glucose, pressors