Cardiac Contractility Dapo Odujebe, MD Toxicology Fellow NYC Poison Control Center.

Cardiac ContractilityCardiac Contractility

Dapo Odujebe, MDDapo Odujebe, MDToxicology FellowToxicology Fellow

NYC Poison Control CenterNYC Poison Control Center

OverviewOverview

Review & CasesReview & Cases

Cardiac ElectrophysiologyCardiac Electrophysiology


Cardiac Medications Cardiac Medications

• Overdose ManagementOverdose Management

Questions?Questions?

Case #1Case #1

45-year old woman PMHx s/f depression 45-year old woman PMHx s/f depression presents to the ED after allegedly presents to the ED after allegedly ingesting all of her anti-HTN medication.ingesting all of her anti-HTN medication.

Prescription filled 3 days prior for 30 Prescription filled 3 days prior for 30 tablets of diltiazem CD 240 mg.tablets of diltiazem CD 240 mg.

Patient alert & oriented, mildly diaphoretic Patient alert & oriented, mildly diaphoretic and complaining of generalized weakness.and complaining of generalized weakness.

Case #1Case #1

Vital signs:Vital signs:• BP:BP: 76/36, 76/36, HR:HR: 46, 46, RR:RR: 14, 14, Temp:Temp: 98.6 98.6• pOx:pOx: 100% RA, 100% RA, AccuChk:AccuChk: 154 154

Rest of physical examination is benign.Rest of physical examination is benign.

Patient placed on a cardiac monitor, OPatient placed on a cardiac monitor, O22 via via nasal cannular and IV access established.nasal cannular and IV access established.

Case #1Case #1

What is the next step in her management?What is the next step in her management?

Case #3Case #3

An 86-year old woman presents with increased An 86-year old woman presents with increased confusion and vomiting.confusion and vomiting.

Per family, she’s had increasing weakness, Per family, she’s had increasing weakness, nausea & anorexia over the last 3 days.nausea & anorexia over the last 3 days.

PMHx:PMHx:• hypertensionhypertension• congestive heart failure congestive heart failure

(CHF)(CHF)• diabetes mellitusdiabetes mellitus

Medications:Medications:• hydrochlorothiazidehydrochlorothiazide• digoxindigoxin• furosemidefurosemide• enteric-coated aspirinenteric-coated aspirin• metforminmetformin

Case #3Case #3 In the hospital, she is alert, but oriented only to In the hospital, she is alert, but oriented only to

person. person.

Vital signs are normal, except for a heart rate of Vital signs are normal, except for a heart rate of 46 beats/minute46 beats/minute.. She weighs 143 lbs (65 kg). She weighs 143 lbs (65 kg).

Her physical examination demonstrates:Her physical examination demonstrates:• bibasilar ralesbibasilar rales• irregular S1, S2 with a S3 gallopirregular S1, S2 with a S3 gallop• bilateral LE 2+ pitting edema, up to her shins bilateral LE 2+ pitting edema, up to her shins

Case #3Case #3 ECG:ECG:

• atrial flutter with variable blockatrial flutter with variable block• ventricular rate of 40-50 beats/minute with occasional ventricular rate of 40-50 beats/minute with occasional

premature ventricular contractions (PVCs). premature ventricular contractions (PVCs).

Laboratory results were within limits except:Laboratory results were within limits except:• potassium - 3.2 mEq/Lpotassium - 3.2 mEq/L• creatinine - 1.6 mg/dLcreatinine - 1.6 mg/dL• glucose - 235 mg/dL glucose - 235 mg/dL

Initial digoxin serum concentration (SDC):Initial digoxin serum concentration (SDC):• 3.4 ng/mL (> 6 hours since last dose). 3.4 ng/mL (> 6 hours since last dose).

Case #3Case #3



Actions potentialsActions potentials• SA nodeSA node• Cardiac muscle Cardiac muscle

(atria, ventricles & Purkinje fibers)(atria, ventricles & Purkinje fibers)

ChannelsChannels• CaCa2+2+ channel channel• ββ-adrenergic receptor-adrenergic receptor• NaNa++/K/K++-ATPase-ATPase

Pacemaker Cell CyclePacemaker Cell Cycle

0 mV0 mV

-70 mV-70 mV

-50 mV-50 mV

Phase 0Phase 0

Phase 3Phase 3

Phase 4Phase 4 Phase 4Phase 4

Ca2+

Action potential Action potential (SA Node)(SA Node)

PacemakerPacemaker of the heart of the heart Unstable resting potentialUnstable resting potential

• Exhibits Exhibits automaticityautomaticity• AV node & His-Purkinje system are AV node & His-Purkinje system are

latent pacemakerslatent pacemakers

Phase 1 & 2 are Phase 1 & 2 are not presentnot present in in pacemaker action potentialspacemaker action potentials

Cardiac Muscle Cell CycleCardiac Muscle Cell Cycle

Resting PotentialResting Potential-90 mV-90 mV

0 mV0 mV

+30 mV+30 mV

-70 mV-70 mV

Phase 0Phase 0 Phase 1Phase 1 Phase 2Phase 2

Phase 3Phase 3

Phase 4Phase 4

Ca2+

Na+/K+ ATPase

3 Na3 Na++

2 K2 K++

Representative Cardiac CellRepresentative Cardiac Cell

NaNa++ channel channelNaNa++ channel channelVoltage dependentVoltage dependentL-typeL-type CaCa2+2+ channel channelVoltage dependentVoltage dependentL-typeL-type CaCa2+2+ channel channel NaNa++/K/K++ ATPase ATPaseNaNa++/K/K++ ATPase ATPase

NaNa++/Ca/Ca2+2+ exchangerexchangerNaNa++/Ca/Ca2+2+ exchangerexchanger

SR (Mitochondria)SR (Mitochondria)SR (Mitochondria)SR (Mitochondria)

Heart muscleHeart muscleHeart muscleHeart muscle

KK++ channel(s) channel(s)KK++ channel(s) channel(s)

Na+/Ca2+ Antiporter

Ryanodine receptorRyanodine receptorRyanodine receptorRyanodine receptor

3 Na3 Na++

CaCa2+2+

ββ-adrenergic receptor-adrenergic receptorββ-adrenergic receptor-adrenergic receptor

ContractilityContractility Intrinsic ability of cardiac muscleIntrinsic ability of cardiac muscle

Also called ‘Also called ‘inotropisminotropism’ or ‘’ or ‘inotropyinotropy’’

Related to the intracellular [CaRelated to the intracellular [Ca2+2+]]

Inotropic agentsInotropic agents• positivepositive: : increaseincrease contractility contractility• negativenegative: : decreasedecrease contractility contractility

Factors Increasing ContractilityFactors Increasing Contractility

Increased intracellular [CaIncreased intracellular [Ca2+2+]]• increased heart rateincreased heart rate• cardiac glycosides (e.g. digoxin)cardiac glycosides (e.g. digoxin)

Stimulation of Stimulation of ββ11-adrenergic receptor-adrenergic receptor• sympathomimetic agentssympathomimetic agents• catecholamines catecholamines

Contractility - Other FactorsContractility - Other Factors

ChronotropyChronotropy• rate of contractionrate of contraction• also affected by intracellular [Caalso affected by intracellular [Ca2+2+]]

DromotropyDromotropy• rate of impulse conductionrate of impulse conduction• noted particularly at AV nodenoted particularly at AV node

Cardiac Medications & Cardiac Medications & ReceptorsReceptors

Cardiac MedicationsCardiac Medications

Some examples:Some examples:

• CaCa2+2+ channel antagonists/blockers channel antagonists/blockers

• ββ-adrenergic antagonists/blockers-adrenergic antagonists/blockers

• Cardiac glycosides (digoxin)Cardiac glycosides (digoxin)

CaCa2+2+ Channel Antagonists Channel Antagonists

Calcium ChannelCalcium Channel

Cardiac calcium channelsCardiac calcium channels• L-type calcium channelL-type calcium channel• ryanodine (RyR2) calcium channelryanodine (RyR2) calcium channel

located on the sarcoplasmic reticulumlocated on the sarcoplasmic reticulum

Critical for:Critical for:• conduction velocity (AV node)conduction velocity (AV node)• duration of depolarizationduration of depolarization• cardiac muscle contractioncardiac muscle contraction


Block the L-type calcium channelBlock the L-type calcium channel• negative inotropynegative inotropy in cardiac muscle in cardiac muscle

decrease available intracellular Cadecrease available intracellular Ca2+2+

• negative chronotropynegative chronotropy in pacemaker cells in pacemaker cells• negative dromotropynegative dromotropy at the AV node at the AV node• relaxation of vascular smooth musclerelaxation of vascular smooth muscle

decreased afterloaddecreased afterload decreased systemic blood pressuredecreased systemic blood pressure increased coronary vascular dilatationincreased coronary vascular dilatation

PhentylalkylaminesPhentylalkylamines• e.g. verapamile.g. verapamil

BenzothiazepinesBenzothiazepines• e.g. diltiazeme.g. diltiazem

DihydropyridinesDihydropyridines• e.g. nifedipinee.g. nifedipine

DiarylaminopropylethersDiarylaminopropylethers• e.g. bepridile.g. bepridil

Tetralene DerivativesTetralene Derivatives• e.g. mibefradile.g. mibefradil


Overdose of CCBOverdose of CCB• extension of therapeutic effectsextension of therapeutic effects

Lose their selectivity (mostly)Lose their selectivity (mostly)• Negative inotropy (Negative inotropy (bradycardiabradycardia))• Negative chronotropy (Negative chronotropy (hypotensionhypotension))• Vasodilation (Vasodilation (hypotensionhypotension))• Negative dromotropy (Negative dromotropy (AV blocksAV blocks, , bradybrady))• +/- hyperglycemia (depressed insulin)+/- hyperglycemia (depressed insulin)


CCB = calcium channel blocker

ββ-Adrenergic Antagonists-Adrenergic Antagonists

ββ-Adrenergic Receptors-Adrenergic Receptors

There are 3 known subtypes of There are 3 known subtypes of ββ--adrenergic receptors, namely adrenergic receptors, namely ββ11, , ββ22 & & ββ33..

The human heart has predominantly The human heart has predominantly ββ11 receptors receptors

• ββ22 & & ββ3 3 exist in ‘small’ quantitiesexist in ‘small’ quantities


Stimulation on Stimulation on ββ11 receptors receptors• increases heart rateincreases heart rate• increases contractilityincreases contractility• increases conduction velocityincreases conduction velocity• increases automaticityincreases automaticity

The effect of adrenergic agents on The effect of adrenergic agents on the heart is mediated through a the heart is mediated through a secondary messenger – cAMPsecondary messenger – cAMP


Intracellular cAMP concentrations are Intracellular cAMP concentrations are regulated by 3 components:regulated by 3 components:• adrenergic receptor on the cell surfaceadrenergic receptor on the cell surface• a “G-protein” complexa “G-protein” complex• adenyl cyclase – enzyme synth. cAMPadenyl cyclase – enzyme synth. cAMP

cAMP acts as a secondary messengercAMP acts as a secondary messenger• interacts with protein kinase A to interacts with protein kinase A to

increase phosphorylating activityincrease phosphorylating activity


Protein kinases transfer a phosphate Protein kinases transfer a phosphate group from ATP to serinegroup from ATP to serine

Thereby, phosphorylating various Thereby, phosphorylating various cellular proteinscellular proteins• phospholamban (phospholamban ( activity) activity)• troponin (troponin ( activity) activity)• L-type calcium channels (L-type calcium channels ( activity) activity)


Bers DM. Cardiac excitation-contraction coupling. Nature 2002 415;198 - 205


ββ-Adrenergic antagonists-Adrenergic antagonists• effects similar to blockade of L-type effects similar to blockade of L-type

calcium channelcalcium channel

Clinical effectsClinical effects• decrease contraction (hypotension)decrease contraction (hypotension)• decrease chronotropy (bradycardia)decrease chronotropy (bradycardia)• decrease dromotropy (AV blocks, brady)decrease dromotropy (AV blocks, brady)


Extra-cardiac signs of toxicityExtra-cardiac signs of toxicity• neurological disturbancesneurological disturbances

drowsiness, non-agitated comadrowsiness, non-agitated coma

• dilated pupilsdilated pupils• respiratory depressionrespiratory depression

Treatment of toxicity is based on: Treatment of toxicity is based on: • stimulation of glucagon receptor stimulation of glucagon receptor • restoring intracellular Carestoring intracellular Ca2+2+ stores stores

Overdose ManagementOverdose Management

DecontaminationDecontamination• Emesis not recommendedEmesis not recommended

• Activated charcoal should be consideredActivated charcoal should be considered

• Gastric lavage with 36-40 Fr tubeGastric lavage with 36-40 Fr tube contraindicated in patients w/ bradycardiacontraindicated in patients w/ bradycardia consider particularly in patients a/ SR preps consider particularly in patients a/ SR preps

• Whole bowel irrigationWhole bowel irrigation particularly a/ SR prepsparticularly a/ SR preps


AtropineAtropine• Adult: 0.5 – 1.0 mg IVP (max 3 mg)Adult: 0.5 – 1.0 mg IVP (max 3 mg)

• Children: 0.02 mg/kg IVPChildren: 0.02 mg/kg IVP

• given every 2 – 3 minutesgiven every 2 – 3 minutes

Should be held in patients getting WBI because of Should be held in patients getting WBI because of

anticholinergic effectsanticholinergic effects


Calcium saltsCalcium salts• increases extracellular Caincreases extracellular Ca2+2+

• calcium gluconate: 1 gm = 4.3 mEqcalcium gluconate: 1 gm = 4.3 mEq• calcium chloride: 1 gm = 13.4 mEqcalcium chloride: 1 gm = 13.4 mEq

DoseDose• 10 – 20 mL of 10% CaCl10 – 20 mL of 10% CaCl22• 30 – 60 mL of 10% Ca gluconate30 – 60 mL of 10% Ca gluconate


Dose (cont’d)Dose (cont’d)• effect is transient, redose q15 – 20 minseffect is transient, redose q15 – 20 mins

• in adults, can give 50 mL of 10% CaClin adults, can give 50 mL of 10% CaCl2 2

(5 gm) before having to check a Ca(5 gm) before having to check a Ca2+2+ serum concentrationserum concentration

• (i.e. 150 mL of 10% Ca gluconate)(i.e. 150 mL of 10% Ca gluconate)

• CaClCaCl22 is causes sclerosis of peripheral is causes sclerosis of peripheral

veins and should be given centrallyveins and should be given centrally


GlucagonGlucagon• activates adenyl cyclase directly via activates adenyl cyclase directly via

glucagon receptorglucagon receptor• adult dose: 2-5 mg slowly IVadult dose: 2-5 mg slowly IV• can be repeated every 5-10 minutescan be repeated every 5-10 minutes• total dose should not exceed 10 mgtotal dose should not exceed 10 mg

• follow bolus with an infusion of the dose follow bolus with an infusion of the dose that produced an effectthat produced an effect


CatecholeaminesCatecholeamines• attempt to competitively antagonize attempt to competitively antagonize ββ--

adrenergic antagonist at the receptoradrenergic antagonist at the receptor• no convincing evidenceno convincing evidence• chance of stimulating other receptors in chance of stimulating other receptors in

the required dose to produce competive the required dose to produce competive displacementdisplacement

• if one is used – if one is used – norepinephrinenorepinephrine is is probably the best choiceprobably the best choice


Insulin & GlucoseInsulin & Glucose• growing evidence that used correctly, growing evidence that used correctly,

this increases inotropy and chronotropythis increases inotropy and chronotropy• theory: improved Ca2+ entry & theory: improved Ca2+ entry &

improved myocardial carbohydrate useimproved myocardial carbohydrate use

• Dose:Dose: 0.5 – 1 Unit/kg/hr regular insulin 0.5 – 1 Unit/kg/hr regular insulin• give 0.5 gm/kg/hr dextrose (glu > 100)give 0.5 gm/kg/hr dextrose (glu > 100)• check glucose every 30 mins initiallycheck glucose every 30 mins initially


AmrinoneAmrinone• inhibits breakdown of cAMP by inhibits breakdown of cAMP by

phosphodiasterase IIIphosphodiasterase III• thereby increasing intracellular [] of thereby increasing intracellular [] of

cAMPcAMP

• this increases inotropy and chronotropythis increases inotropy and chronotropy• BUTBUT, causes vasodilation & hypotension, causes vasodilation & hypotension• should be used with a vasopressorshould be used with a vasopressor


Cardiac glycosides Cardiac glycosides (digoxin)(digoxin)

TherapeuticTherapeutic

Digoxin inhibits NaDigoxin inhibits Na++/ K/ K++-ATPase -ATPase

This increases cytosolic CaThis increases cytosolic Ca2+2+ which which increases inotropy.increases inotropy.

Therapeutically:Therapeutically:• digoxin increases automaticitydigoxin increases automaticity• shortens the repolarization intervals of shortens the repolarization intervals of

the atria and ventriclesthe atria and ventricles


Decreases depolarization & conduction Decreases depolarization & conduction through the SA and AV nodes. through the SA and AV nodes.

These changes are reflected on ECG by:These changes are reflected on ECG by:• decrease in ventricular response ratedecrease in ventricular response rate• PR interval prolongationPR interval prolongation• QT interval shorteningQT interval shortening• ST segment & T-wave opposite major QRS forcesST segment & T-wave opposite major QRS forces

scooped ST segment scooped ST segment Both these effects result in the characteristic “digitalis Both these effects result in the characteristic “digitalis

effect”effect”


Some characteristic signs of digoxin therapy and toxicity.Some characteristic signs of digoxin therapy and toxicity.

Digitalis effectDigitalis effect

Atrial flutter with PVCAtrial flutter with PVC

Clinical ToxicityClinical Toxicity

ToxicologicToxicologic

Effects mirror its therapeutic actions.Effects mirror its therapeutic actions.• Bradydysrhythmias Bradydysrhythmias

(from increased VAGAL TONE)(from increased VAGAL TONE)

• Ventricular tachydysrhythmias Ventricular tachydysrhythmias (from myocardial “irritability”)(from myocardial “irritability”)

• Rapid atrial rhythms with slow Rapid atrial rhythms with slow ventricular response ventricular response

(slowed AV conduction)(slowed AV conduction)

3 Na3 Na++

2 K2 K++

Cell ElectrophysiologyCell Electrophysiology


CaCa2+2+

Phase 2Phase 2

CaCa2+2+

CaCa2+2+

CaCa2+2+

CaCa2+2+

CaCa2+2+

CaCa2+2+

CaCa2+2+

3 Na3 Na++

CaCa2+2+

3 [Na3 [Na++]]

2 [K2 [K++]]

Therapeutic & Toxic MoATherapeutic & Toxic MoA


CaCa2+2+

Phase 2Phase 2

CaCa2+2+

CaCa2+2+

CaCa2+2+

CaCa2+2+

CaCa2+2+

CaCa2+2+

CaCa2+2+

= Digoxin= Digoxin

CaCa2+2+

CaCa2+2+

CaCa2+2+

CaCa2+2+

CaCa2+2+CaCa2+2+

CaCa2+2+

CaCa2+2+

CaCa2+2+

CaCa2+2+

CaCa2+2+

CaCa2+2+

CaCa2+2+

CaCa2+2+

CaCa2+2+

CaCa2+2+

CaCa2+2+

CaCa2+2+

CaCa2+2+

CaCa2+2+

CaCa2+2+

CaCa2+2+

Digoxin

NaNa++

K+K+

Signs of ToxicitySigns of Toxicity

MetabolicMetabolic• AcuteAcute: Hyperkalemia is a marker for severe : Hyperkalemia is a marker for severe

poisoningpoisoning Due to blockade of Na+/K+ ATPaseDue to blockade of Na+/K+ ATPase Increases AV blockade and worsens Increases AV blockade and worsens

bradydysrhythmiasbradydysrhythmias

• ChronicChronic: Hypokalemia predisposes the patient : Hypokalemia predisposes the patient to dysrhythmias at lower digoxin levelsto dysrhythmias at lower digoxin levels

Higher resting potential increases Higher resting potential increases automaticityautomaticity

Signs of ToxicitySigns of Toxicity

CardiacCardiac• Acute or chronicAcute or chronic

Increased automaticity with high-degree AV Increased automaticity with high-degree AV blockblock

Any dysrhythmia possible…..Any dysrhythmia possible…..

… … EXCEPT a rapidly conducted EXCEPT a rapidly conducted supraventricular rhythm.supraventricular rhythm.

ElectrocardiogramElectrocardiogram PVCs (most common dysrhythmia)PVCs (most common dysrhythmia)

Classic ECG findings:Classic ECG findings:• Bidirectional ventricular tachycardiaBidirectional ventricular tachycardia

• Atrial tachycardia with variable or slow Atrial tachycardia with variable or slow ventricular responseventricular response

• Accelerated junctional rhythms Accelerated junctional rhythms

Management of ToxicityManagement of Toxicity

The main goal of treatment is to The main goal of treatment is to correct cardiac toxicity. correct cardiac toxicity.

Treatment of cardiac toxicity Treatment of cardiac toxicity usually leads to resolution of CNS usually leads to resolution of CNS and GI symptoms. and GI symptoms.

TreatmentTreatment

DecontaminationDecontamination• Activated charcoal (AC)Activated charcoal (AC)

Adsorbs digoxin wellAdsorbs digoxin well Decrease absorptionDecrease absorption ‘‘Gut dialysis’Gut dialysis’ [Boldy DA. et al. 1985, de Silva HA. et al. 2003, Ibanez C. et al. [Boldy DA. et al. 1985, de Silva HA. et al. 2003, Ibanez C. et al.

1995]1995]

• Multi-dose ACMulti-dose AC Renal failureRenal failure Yellow oleander poisoningYellow oleander poisoning

TreatmentTreatment

DysrhythmiasDysrhythmias• Tachy-Tachy-

Replace KReplace K++ or Mg or Mg++++

Consider Class IB & III antidysrhythmicsConsider Class IB & III antidysrhythmics• amiodarone, lidocaine or phenytoin for ventricular amiodarone, lidocaine or phenytoin for ventricular

dysrhythmiasdysrhythmias AVOID Class IA, IC, II and IV antidysrhythmicsAVOID Class IA, IC, II and IV antidysrhythmics

• particularly procainamide and quinidineparticularly procainamide and quinidine AVOID cardioversion in TOXICITY AVOID cardioversion in TOXICITY

• Brady-Brady- AtropineAtropine AVOID transvenous/internal pacingAVOID transvenous/internal pacing

Management of ToxicityManagement of Toxicity GI decontaminationGI decontamination

• Decrease absorptionDecrease absorption• ‘‘Gut dialysis’Gut dialysis’• [Boldy DA. et al. 1985, de Silva HA. et al. 2003, Ibanez C. et al. [Boldy DA. et al. 1985, de Silva HA. et al. 2003, Ibanez C. et al.

1995]1995]

AtropineAtropine

Correct electrolyte abnormalitiesCorrect electrolyte abnormalities

Consider lidocaine or phenytoinConsider lidocaine or phenytoin• for control of dysrhythmias (if definitive for control of dysrhythmias (if definitive

therapy unavailable)therapy unavailable)

Indications for digoxin-FabIndications for digoxin-Fab Symptomatic bradydysrhythmiasSymptomatic bradydysrhythmias Ventricular dysrhythmiasVentricular dysrhythmias Acute digoxin toxicity & [KAcute digoxin toxicity & [K++] ] >5 mEq/L Ingestion >4 mg - child (or 0.1 mg/kg)Ingestion >4 mg - child (or 0.1 mg/kg) Ingestion >10 mg - healthy adultIngestion >10 mg - healthy adult SDC of ≥10 ng/mL steady stateSDC of ≥10 ng/mL steady state

• 4-6 hours after ingestion4-6 hours after ingestion

SDC of ≥15 ng/mL at any timeSDC of ≥15 ng/mL at any time

Chronic Digoxin ToxicityChronic Digoxin Toxicity

More common and more controversialMore common and more controversial No absolute indication based on serum No absolute indication based on serum

concentrationconcentration Administer digoxin-Fab ifAdminister digoxin-Fab if

• ECG evidence of digoxin toxicityECG evidence of digoxin toxicity

• Unable to tolerate symptoms of toxicityUnable to tolerate symptoms of toxicity

• Unable to clear digoxin (BUN/Creat)Unable to clear digoxin (BUN/Creat)

ManagementManagementEmpiric TherapyEmpiric Therapy

Acute toxicity:Acute toxicity:• Adults: 10 – 20 vialsAdults: 10 – 20 vials• Children: 10 – 20 vialsChildren: 10 – 20 vials

Chronic toxicity:Chronic toxicity:• Adults: 3 – 6 vialsAdults: 3 – 6 vials• Children: 1 – 2 vialsChildren: 1 – 2 vials

****Should be administered IV over 30 minutes Should be administered IV over 30 minutes • via a 0.22-micron membrane filter. via a 0.22-micron membrane filter.

**** Can be given as an IV bolus in a critically ill patient Can be given as an IV bolus in a critically ill patient• (per manufacturer).(per manufacturer).

ManagementManagement

# of vials =# of vials =amt ingested (mg) x 0.8amt ingested (mg) x 0.8

0.50.5

Ingested Dose KnownIngested Dose Known

# of vials =# of vials =SDC (ng/mL) x pt wgt (kg)SDC (ng/mL) x pt wgt (kg)

100100

Serum Drug Concentration (SDC) KnownSerum Drug Concentration (SDC) Known

Things Not To Do!!Things Not To Do!!

CalciumCalcium• ““stone heart” in animal modelsstone heart” in animal models

Transvenous pacingTransvenous pacing• Taboulet Taboulet et al. et al. 19931993• failure rate of 23% and a 17% mortalityfailure rate of 23% and a 17% mortality• increased risk of dysrhythmic deathincreased risk of dysrhythmic death

Case ReviewCase Review

Case #1Case #1

45-year old woman PMHx s/f depression 45-year old woman PMHx s/f depression presents to the ED after allegedly presents to the ED after allegedly ingesting all of her anti-HTN medication.ingesting all of her anti-HTN medication.

Prescription filled 3 days prior for 30 Prescription filled 3 days prior for 30 tablets of diltiazem CD 240 mg.tablets of diltiazem CD 240 mg.

Patient alert & oriented, mildly diaphoretic Patient alert & oriented, mildly diaphoretic and complaining of generalized weakness.and complaining of generalized weakness.

Case #1Case #1

Vital signs:Vital signs:• BP:BP: 76/36, 76/36, HR:HR: 46, 46, RR:RR: 14, 14, Temp:Temp: 98.6 98.6• pOx:pOx: 100% RA, 100% RA, AccuChk:AccuChk: 154 154

Rest of physical examination is benign.Rest of physical examination is benign.

Patient placed on a cardiac monitor, OPatient placed on a cardiac monitor, O22 via via nasal cannular and IV access established.nasal cannular and IV access established.

Case #1Case #1


Case #3Case #3

An 86-year old woman presents with An 86-year old woman presents with increased confusion and vomiting.increased confusion and vomiting.

Per family, she complained of increasing Per family, she complained of increasing weakness, nausea and decreased appetite weakness, nausea and decreased appetite over the last 3 days.over the last 3 days.

She has barely kept any of her She has barely kept any of her medications down, and has not been medications down, and has not been eating.eating.

Case #3Case #3 PMHx:PMHx:

• hypertensionhypertension• congestive heart failure (CHF)congestive heart failure (CHF)• diabetes mellitusdiabetes mellitus

Medications:Medications:• hydrochlorothiazidehydrochlorothiazide• digoxindigoxin• furosemidefurosemide• enteric-coated aspirinenteric-coated aspirin• metforminmetformin

Case #3Case #3

In the hospital, she is alert, but oriented In the hospital, she is alert, but oriented only to person. only to person.

Vital signs are normal, except for a heart Vital signs are normal, except for a heart rate of 46 beats/minuterate of 46 beats/minute.. She weighs 143 lbs She weighs 143 lbs (65 kg).(65 kg).

Her physical examination demonstrates:Her physical examination demonstrates:• bibasilar rales, irregular S1, S2 with an S3 gallopbibasilar rales, irregular S1, S2 with an S3 gallop• bilateral lower extremity 2+ pitting edema up to bilateral lower extremity 2+ pitting edema up to

her shins her shins

Case #3Case #3 ECG:ECG:

• atrial flutter with variable blockatrial flutter with variable block• ventricular rate of 40-50 beats/minute with occasional ventricular rate of 40-50 beats/minute with occasional

premature ventricular contractions (PVCs). premature ventricular contractions (PVCs).

Laboratory results were within limits except:Laboratory results were within limits except:• potassium - 3.2 mEq/Lpotassium - 3.2 mEq/L• creatinine - 1.6 mg/dLcreatinine - 1.6 mg/dL• glucose - 235 mg/dL glucose - 235 mg/dL

Initial digoxin serum concentration (SDC):Initial digoxin serum concentration (SDC):• 3.4 ng/mL (> 6 hours since last dose). 3.4 ng/mL (> 6 hours since last dose).

Case #3Case #3


Digoxin-Fab DoseDigoxin-Fab Dose

Always round UP whatever answer you get.Always round UP whatever answer you get.

# of vials =# of vials =SDC (ng/mL) x pt wgt (kg)SDC (ng/mL) x pt wgt (kg)

100100

Serum Drug Concentration (SDC) KnownSerum Drug Concentration (SDC) Known

= 2.21 vials= 2.21 vials3.4 ng/mL x 65 kg3.4 ng/mL x 65 kg

100100≈≈ 3 vials3 vials

Case #3Case #3

The patient is given 3-vials of digoxin The patient is given 3-vials of digoxin specific antibody fragments (digoxin-Fab).specific antibody fragments (digoxin-Fab).

About 60 minutes after therapy:About 60 minutes after therapy:• her heart rate improved to 85 beats/minuteher heart rate improved to 85 beats/minute• blood pressure remained stableblood pressure remained stable• her ECG demonstratedher ECG demonstrated

rate-controlled atrial fibrillation with no ectopyrate-controlled atrial fibrillation with no ectopy

• Her serum potassium concentration had also Her serum potassium concentration had also improvedimproved

Questions?Questions?

Cardiac Contractility Dapo Odujebe, MD Toxicology Fellow NYC Poison Control Center.

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Transcript of Cardiac Contractility Dapo Odujebe, MD Toxicology Fellow NYC Poison Control Center.