IM Board IM Board Prep FunPrep Fun

Toxicology Toxicology

Kurt Kleinschmidt, MD, Kurt Kleinschmidt, MD,

FACEP, FACMTFACEP, FACMT

Professor of Professor of

Emergency MedicineEmergency Medicine

Division Chief & Division Chief &

Program DirectorProgram Director

Medical ToxicologyMedical Toxicology

UTSW Medical CenterUTSW Medical Center

• Drug overdoseDrug overdose• Hazardous exposure to chemical productsHazardous exposure to chemical products

– Pesticides; heavy metals Pesticides; heavy metals – Household productsHousehold products– Toxic gasesToxic gases– Toxic alcoholsToxic alcohols– Other industrial chemicals Other industrial chemicals

• Drug Abuse management & MRO Drug Abuse management & MRO • EnvenomationsEnvenomations• Food-borne toxins, such as botulism; marine toxins Food-borne toxins, such as botulism; marine toxins

(e.g. paralytic shellfish toxin; ciguatoxin). (e.g. paralytic shellfish toxin; ciguatoxin). • Plants and mushrooms. Plants and mushrooms. • Independent medical examinations Independent medical examinations

Problems Evaluated By ToxicologistsProblems Evaluated By Toxicologists

Board CertificationBoard Certification

• American Board Medical Specialties RecognizedAmerican Board Medical Specialties Recognized• First ABMS exam 2000First ABMS exam 2000• Toxicology is a Dependent “Sub-Board”Toxicology is a Dependent “Sub-Board”

– Emergency Medicine (Administrative)Emergency Medicine (Administrative)– Preventive MedicinePreventive Medicine– PediatricsPediatrics

• Approximately 50 examinees every Approximately 50 examinees every otherother year year• Total Boarded < 400Total Boarded < 400

Which physicians can become Which physicians can become medical toxicologists?medical toxicologists?

• Emergency MedicineEmergency Medicine

• Preventive and Preventive and Occupational MedicineOccupational Medicine

• PediatricsPediatrics

• Internal MedicineInternal Medicine

• Family MedicineFamily Medicine

• PsychiatryPsychiatry

• NeurologyNeurology

> 50%> 50%

> 95%> 95%

North Texas Poison CenterNorth Texas Poison Center

Division of Toxicology ≠ Poison Center(But we do share much)

ToxidromesToxidromes

• Collection of symptoms characteristic for Collection of symptoms characteristic for specific agent groupsspecific agent groups

• Many different agents can cause “a” Many different agents can cause “a” toxidrometoxidrome

• Management of any one toxidrome…Management of any one toxidrome…

– Is the sameIs the same

– No matter the agentNo matter the agent

ToxidromesToxidromesSympathomimeticSympathomimetic Cocaine, Amphetamines, Cocaine, Amphetamines,

Decongestants, CaffeineDecongestants, Caffeine

AnticholinergicAnticholinergic 11stst-Generation antihistamines, -Generation antihistamines, Neuroleptics, Tricyclics Neuroleptics, Tricyclics

CholinergicCholinergic Carbamates, Carbamates, OrganophosphatesOrganophosphates

OpioidOpioid Codeine, Morphine, Codeine, Morphine, HydrocodoneHydrocodone

Sedative-HypnoticSedative-Hypnotic Benzos, Barbs, EthanolBenzos, Barbs, Ethanol

SerotonergicSerotonergic Too many to list…Too many to list…

AdrenalMedulla

EpiEpi NENE

NN

VasoconstrictionVasoconstriction↑↑ Urethral Urethral Sphincter ToneSphincter ToneMydriasisMydriasis

DiaphoresisDiaphoresis MM

α α

TachycardiaTachycardiaVasodilationVasodilationBronchodilationBronchodilationMetabolicMetabolic↓ ↓ K+K+↓ ↓ PO4PO4↓ ↓ pHpH↑↑ GlucoseGlucose↑↑ WBCWBC

ββNENE

NENE

NN

NNAChACh DDiarrhea iarrhea

UUrinationrinationMMiosisiosisBBronchospasmronchospasmBBronchorrhearonchorrheaEEmesismesisLLacrimationacrimationSSalivationalivation

NN

MMAChACh

AChACh

AChACh

AChACh

AChACh

ANSANSParsympatheticParsympatheticSympatheticSympathetic

AnticholinergicsAnticholinergicsHot as a hareHot as a hare HyperthermiaHyperthermia

Mad as a hatterMad as a hatter Delirium / AgitationDelirium / Agitation

Dry as a boneDry as a bone Skin; Muc Membranes DrySkin; Muc Membranes Dry

Red as a beetRed as a beet Skin flushedSkin flushed

TachycardiaTachycardia

Hypoactive Bowel SoundsHypoactive Bowel Sounds

Bladder Urine RetentionBladder Urine Retention

But which are the most

Sensitive?

Anticholinergic vs. SympathomimeticAnticholinergic vs. Sympathomimetic

SympathoSympatho Anti-CholAnti-Chol

HRHR ↑ ↑ ↑ ↑BPBP ↑ ↑ ↑ ↑PupilsPupils ↑ ↑ ↑ ↑MentalMental AgitatedAgitated AgitatedAgitated

BladderBladder Nml Nml Nml or Nml or ↑↑Bowel SoundsBowel Sounds NmlNml Nml or Nml or ↓↓SkinSkin WetWet Dry**Dry**

CholinergicsCholinergicsMuscarinicMuscarinic

““DUMBELS”DUMBELS”• DiarrheaDiarrhea• UrinationUrination• MiosisMiosis• BronchorrheaBronchorrhea• BronchospasmBronchospasm• EmesisEmesis• LacrimationLacrimation• SalivationSalivation

NicotinicNicotinic

““M, T, W, tH, F”M, T, W, tH, F”• MydriasisMydriasis• TremorTremor• WeakWeak• HypertensionHypertension• FasciculationsFasciculations

What agents affect these receptors?What agents affect these receptors?Organophosphates (Insecticides)Organophosphates (Insecticides)Carbamates (Insecticides)Carbamates (Insecticides)Nerve agentsNerve agents

OpioidOpioidThe ToxidromeThe Toxidrome

• Mental status depressedMental status depressed

• MiosisMiosis

• Respirations depressedRespirations depressed

Not always clear…Coingestants…Not always clear…Coingestants…Hypoxic Brain damage may already be presentHypoxic Brain damage may already be presentNarcan is a poor diagnostic toolNarcan is a poor diagnostic tool

Serotonergic ExcessSerotonergic Excess

Class Drugs

AntidepressantsMonoamine oxidase inhibitors (MAOIs), TCAs, SSRIs, SNRIs, bupropion, nefazodone, trazodone mirtazapine

Opioids tramadol, meperidine, dextromethorphan

CNS stimulants MDMA, MDA, phentermine, methamphetamine, cocaine

5-HT1 agonists triptans

Psychedelics 5-Methoxy-diisopropyltryptamine, LSD

Serotonergic ExcessSerotonergic Excess

• ClinicalClinical– Tremor Tremor

– ↑ ↑ DTRs / ClonusDTRs / Clonus– TachycardiaTachycardia– Agitation or Agitation or

diaphoresisdiaphoresis• Differential DxDifferential Dx

– NMSNMS– LithiumLithium– SympathomimeticsSympathomimetics– Malignant HyperthermiaMalignant Hyperthermia

6 Acetaminophen Cases6 Acetaminophen CasesAll are 40 y/o Males who took 15 grams…All are 40 y/o Males who took 15 grams…

• 2 hrs before arrival2 hrs before arrival– One vomitingOne vomiting– One notOne not

• 8 hrs before arrival8 hrs before arrival– One vomitingOne vomiting– One notOne not

• 15 hrs before arrival15 hrs before arrival

– One vomitingOne vomiting– One notOne not

Start antidote before getting a level?Start antidote before getting a level?PO or IV?PO or IV?Duration of therapy?Duration of therapy?Role of repeat levels?Role of repeat levels?

Acetaminophen Case ContinuedAcetaminophen Case Continued

• 2 hrs before arrival2 hrs before arrival– One vomitingOne vomiting– One notOne not

• 8 hrs before arrival8 hrs before arrival– One vomitingOne vomiting– One notOne not

• 15 hrs before arrival15 hrs before arrival– One vomitingOne vomiting– One notOne not

Start antidote before getting a level?No

PO or IV?If toxic level, go IV

Duration of therapy?If IV, Bolus + 20 hours

Role of repeat levels?None

Start antidote before getting a level?Start antidote before getting a level?PO or IV?PO or IV?Duration of therapy?Duration of therapy?Role of repeat levels?Role of repeat levels?

Acetaminophen Case ContinuedAcetaminophen Case Continued

• 2 hrs before arrival2 hrs before arrival– One vomitingOne vomiting– One notOne not

• 8 hrs before arrival8 hrs before arrival– One vomitingOne vomiting– One notOne not

• 15 hrs before arrival15 hrs before arrival– One vomitingOne vomiting– One notOne not

Start antidote before getting a level?Yes

PO or IV?If Vomiting, go IV If Not Vomiting, go PO (?)

Duration of therapy?If IV, Bolus + 20 hours

If PO, typically 24-36 hrsRole of repeat levels?

None

Start antidote before getting a level?Start antidote before getting a level?PO or IV?PO or IV?Duration of therapy?Duration of therapy?Role of repeat levels?Role of repeat levels?

• If treated within 8 hrsIf treated within 8 hrs– No pts → Liver FailureNo pts → Liver Failure

– Some patients → HepatitisSome patients → Hepatitis

• Toxicity Defined – AST > 1000Toxicity Defined – AST > 1000

Acetaminophen Case ContinuedAcetaminophen Case Continued

• 2 hrs before arrival2 hrs before arrival– One vomitingOne vomiting– One notOne not

• 8 hrs before arrival8 hrs before arrival– One vomitingOne vomiting– One notOne not

• 15 hrs before arrival15 hrs before arrival– One vomitingOne vomiting– One notOne not

Start antidote before getting a level?Yes (?)

PO or IV?If Vomiting, go IV If Not Vomiting, go PO (?)

Duration of therapy?If IV, typically 36 hrs**

If PO, typically 36 hrsRole of repeat levels?

None

Start antidote before getting a level?Start antidote before getting a level?PO or IV?PO or IV?Duration of therapy?Duration of therapy?Role of repeat levels?Role of repeat levels?

Duration based upon LFTs. Note that Acetadote use is likely BEYOND 21 hours

Besides vomiting, conditions Besides vomiting, conditions where IV route is preferred?where IV route is preferred?

PregnancyPregnancyLiver FailureLiver Failure

Lets talk…BioavailabilityLets talk…Bioavailability

LithiumLithium• Your body thinks it is sodium…and treats it as suchYour body thinks it is sodium…and treats it as such• ClinicalClinical

– NeuromuscularNeuromuscular – tremor; ↑ DTRs (very sensitive) – tremor; ↑ DTRs (very sensitive)– Chronic Neuro Sequelae #1 Concern. Chronic Neuro Sequelae #1 Concern.

• Include cerebellar issues; memory deficits, NM weak, personality Include cerebellar issues; memory deficits, NM weak, personality change, tremors. change, tremors.

• DecontaminationDecontamination– Charcoal – No role (like all monovalent cations)Charcoal – No role (like all monovalent cations)– Whole Bowel Irrigation Whole Bowel Irrigation

• Fluids and Electrolytes - Key - Restore volume if there is depletion, Fluids and Electrolytes - Key - Restore volume if there is depletion, otherwise Lithium elimination is slowedotherwise Lithium elimination is slowed

• Dialysis - Dialysis - Ideal for dialysis - (1) small, (2) not protein bound, and (3) small Ideal for dialysis - (1) small, (2) not protein bound, and (3) small volume of distributionvolume of distribution; BUT…Li; BUT…Li++ is mainly intracellular and it diffuses slowly is mainly intracellular and it diffuses slowly across cell membranes (needs serial HD treatments)across cell membranes (needs serial HD treatments)– Indication - Severe neurotoxicity i.e. AMS, those with ARF, Level > 4.0 Indication - Severe neurotoxicity i.e. AMS, those with ARF, Level > 4.0

mEq/L (Acute) or 2.5 mEq/L (Chronic). mEq/L (Acute) or 2.5 mEq/L (Chronic).

Distribution Clinical MomentsDistribution Clinical MomentsLithiumLithium

• Normal Level: 0.6-1.2 mEq/LNormal Level: 0.6-1.2 mEq/L

• Which is clinically worse for a patient?Which is clinically worse for a patient?

– Level 4.2 mEq/LLevel 4.2 mEq/L

– Level 2.2 mEq/LLevel 2.2 mEq/L

It all depends…It all depends…Acute vs Chronic ExposureAcute vs Chronic ExposureAgent with slow distributionAgent with slow distribution

Distribution Clinical MomentsDistribution Clinical Moments - Lithium - Lithium

FastFast

SlowSlow

Stomach and IntestinesStomach and Intestines

Blood and Blood and some organs (Liver)some organs (Liver)

BrainBrain

AcuteAcute ChronicChronic

4.24.2 2.22.2

0.20.2 2.22.2

AbsorptionAbsorption

DistributionDistribution

Common SalicylatesCommon Salicylates

Alka-Seltzer

Alka-Seltzer

AnacinAnacin

ExcedrinExcedrin

Bismuth subsalicylate Bismuth subsalicylate (Pepto Bismol)(Pepto Bismol)

Cold Cold PreparationsPreparations

AspirinAspirin

KeratolyticKeratolyticAgentsAgents

Oil of Oil of WintergreenWintergreen

Clinical Signs and SymptomsClinical Signs and Symptoms

Salicylate Toxidrome (Acute)Salicylate Toxidrome (Acute)• Shortness of Breath (Hyperpnea, Tachypnea)Shortness of Breath (Hyperpnea, Tachypnea)• N/V & stomach upsetN/V & stomach upset• Tinnitus and/or Hearing changeTinnitus and/or Hearing change• DizzyDizzy• DiaphoresisDiaphoresis

My great clinical moment…My great clinical moment…

Can be easy to miss

More Clinical Signs and SymptomsMore Clinical Signs and Symptoms• CNSCNS

– AMS (Cerebral edema, Hypoglycemia)AMS (Cerebral edema, Hypoglycemia)– SeizuresSeizures

• HyperthermiaHyperthermia

• Non-Cardiogenic Pulmonary EdemaNon-Cardiogenic Pulmonary Edema

• Metabolic Acidosis & Resp AlkalosisMetabolic Acidosis & Resp Alkalosis

• CoagulopathyCoagulopathy

• Liver failureLiver failure

• Renal failureRenal failure

Multiorgan!Multiorgan!

Often confused with Sepsis Often confused with Sepsis and/or other conditionsand/or other conditions

LaboratoryLaboratory

• Anion-Gap Metabolic AcidosisAnion-Gap Metabolic Acidosis• Plasma Salicylate LevelsPlasma Salicylate Levels

– Serial levelsSerial levels – Useless without clinical courseUseless without clinical course

Significance of Salicylate LevelSignificance of Salicylate Level

Urine EliminationUrine Elimination

BloodBlood

BrainBrain

Level will Level will ↓↓ Clinically - Clinically - GoodGood

Level will Level will ↓↓Clinically - Clinically - BadBad

Assessment:

Assessment:

Level + Clinical

Level + Clinical

““Well, Mrs. Johnson…”Well, Mrs. Johnson…”

TreatmentTreatment

• Absorption:Absorption: CharcoalCharcoal → ↓ → ↓ AbsorptionAbsorption

• Distribution: Distribution: Not a targetNot a target

• Metabolism and EliminationMetabolism and Elimination

– Multidose Activated CharcoalMultidose Activated Charcoal

– Ion Trapping (Sodium Bicarbonate)Ion Trapping (Sodium Bicarbonate)

– HemodialysisHemodialysis

Ion TrappingIon Trapping

Brain BloodRenal Tubule

HA HA ↑ ↓↑ ↓

HH+ + + A+ A--

Diurese it outDiurese it out

HA HA ↑ ↓↑ ↓

HH+ + + A+ A--

HA HA ↑ ↓↑ ↓

HH+ + + A+ A--

Ion TrappingIon Trapping

Brain BloodRenal Tubule

HA HA ↑ ↑ ↓↓

HH+ + + A+ A--

Diurese it outDiurese it out

HA HA ↑↑ ↓ ↓

HH+ + + A+ A--

HA HA ↑↑ ↓ ↓

HH+ + + A+ A--

A weak acid in an alkaline environmentA weak acid in an alkaline environmentAlkalinize the urineAlkalinize the urine

HemodialysisHemodialysisItems amendable to dialysisItems amendable to dialysis• SmallSmall• Non-chargedNon-charged• Low Volume of Distribution Low Volume of Distribution

(Agent mostly in the blood)(Agent mostly in the blood)Indications with SalicylatesIndications with Salicylates• Renal failure (the # 1 indication)Renal failure (the # 1 indication)• Metabolic acidosis (persistent)Metabolic acidosis (persistent)• Cerebral or Pulmonary edemaCerebral or Pulmonary edema• Really nasty, horrid, ugly high levelsReally nasty, horrid, ugly high levels

Pitfalls in Salicylate Management Pitfalls in Salicylate Management • Failure to be scaredFailure to be scared• Failure to know that symptoms Failure to know that symptoms

can be delayedcan be delayed• Ruling out toxicity using Ruling out toxicity using

serum level alone serum level alone • Failure to alkalinize the urine due Failure to alkalinize the urine due

to inadequate K+ levelto inadequate K+ level• Failure to Dialyze in the really Failure to Dialyze in the really

sick ones!!!!!!!!!!!!!!!!!!!!!!!!!sick ones!!!!!!!!!!!!!!!!!!!!!!!!!

Continue therapy until Continue therapy until symptoms are gonesymptoms are gone

• Sodium Bicarb Sodium Bicarb for Ion Trappingfor Ion Trapping

• Multiple Dose Multiple Dose Activated Activated

CharcoalCharcoal

CyanideCyanide• Cyanide Salts: Ingest Cyanide Salts: Ingest → → CN-salt + stomach Acid CN-salt + stomach Acid →→

HCN HCN →→ Absorbed Absorbed →→ Die Die• HCN Gas: HCN Gas: Inhale Inhale →→ Mucosal absorption Mucosal absorption →→ Die Die

Burn...Burn...Plastics (Polyacrylonitriles, Polyacrylamides)Plastics (Polyacrylonitriles, Polyacrylamides)Foam (Polyurethane)Foam (Polyurethane)Varnishes and Paints (Polyurethane)Varnishes and Paints (Polyurethane)Wool and SilkWool and Silk

FireFire

Smoke Smoke with with HCNHCN

Formed when combine an acid with the salt; thus keep pH high, no gas will be created

Cyanide PathophysiologyCyanide Pathophysiology

Binds ferric ion in Binds ferric ion in Cytochrome Cytochrome OxidaseOxidase

CNCNCyt a3++Cyt a3++Cyt a3+++Cyt a3+++

OO22 2H2H22OO

Oxidative Oxidative PhosphorylationPhosphorylation

X

X

Can NOT use OCan NOT use O22

CNSCNSLOCLOCSeizuresSeizures

Body Ischemia Body Ischemia Severe Met acidosisSevere Met acidosis

Cyanide DiagnosisCyanide Diagnosis

HistoryHistoryLaboratoryLaboratory• Cyanide LevelCyanide Level: : Back next weekBack next week• Lactate:Lactate: Back next hourBack next hour

Cyanide DiagnosisCyanide Diagnosis

Blood GasBlood Gas• Supporting CNSupporting CN

– Severe metabolic acidosis*****Severe metabolic acidosis*****– Arterial-venous OArterial-venous O22 gradient gradient ↓ ↓ (?) (?)

– Venous OVenous O22 ↑↑ (?) (?)

• Smoke “clouds” the picture Smoke “clouds” the picture – Hypoxia…Hypoxia… AsphyxiantsAsphyxiants Pulmonary irritants Pulmonary irritants

COCO CN CN – Lactate…Lactate… Hypoxia Hypoxia Hypoperfusion Hypoperfusion

Severe Met Acidosis (Tox Related)Inhibitors / Uncouples Oxid PhosphToxic Alcohols

Detoxification – The OldDetoxification – The Old

CNCN

HH22SS

COCO

NitriteNitrite

Thiosulfate (S)Thiosulfate (S)

Lilly Cyanide KitLilly Cyanide KitAmyl Nitrite PearlsAmyl Nitrite PearlsSodium Nitrite (300 mg)Sodium Nitrite (300 mg)Sodium Thiosulfate (12.5 g)Sodium Thiosulfate (12.5 g)

Cyt a3++Cyt a3++ Cyt a3+++Cyt a3+++

OO22 2H2H22OO

Oxidative Oxidative PhosphorylationPhosphorylation

Oxy-HgOxy-Hg

Met-HgMet-Hg

CyanoMet-HgCyanoMet-Hg

CNCN RhodaneseRhodanese + S+ S

SCN (Thiocyanate)SCN (Thiocyanate)

Eliminated

ATP

NitritesNitritesSide Effects Side Effects

– Vasodilation Vasodilation →→ Hypotension Hypotension– MethemoglobinemiaMethemoglobinemia →→ ↓↓OO22 Carrying Capacity Carrying Capacity

• Create a “toxicity” to cure another “toxicity”Create a “toxicity” to cure another “toxicity”• Another issue in smoke inhalation setting Another issue in smoke inhalation setting

Carbon Monoxide also Carbon Monoxide also →→ “Dys-hemoglobinemia” “Dys-hemoglobinemia”

→→ ↓↓OO22 Carrying Capacity Carrying Capacity

Sodium Thiosulfate Sodium Thiosulfate is quite benignis quite benign

NormalHemoglobin

HydroxocobalaminHydroxocobalaminfor for

CyanideCyanide(CN)(CN)

Recycling of HydroxycobalaminRecycling of Hydroxycobalamin

CobalaminCobalamin

OHOH

CNCN

CNCN

CobalaminCobalamin OHOH--++ ++(Vitamin B(Vitamin B1212))

HH++

CNCN

CobalaminCobalamin ThiosulfateThiosulfate CobalaminCobalamin

OHOH

ThiocyanateThiocyanateRhodanaseRhodanaseHH22OO

++ ++++++(Vitamin B(Vitamin B1212))

Alcohols that in significant amounts Alcohols that in significant amounts typically cause specific end organ typically cause specific end organ damage if not managed appropriatelydamage if not managed appropriately

Toxic AlcoholsToxic AlcoholsDefinedDefined

These include:These include:

• Ethylene GlycolEthylene Glycol

• MethanolMethanol

Do NOT include:Do NOT include:

• IsopropanolIsopropanol

• EthanolEthanol

Alcohol DehydrogenaseAlcohol Dehydrogenase

Aldehyde DehydrogenaseAldehyde Dehydrogenase

Metabolism of Ethylene GlycolMetabolism of Ethylene Glycol

PyridoxinePyridoxine

ThiamineThiamine

GlycineGlycine

OxalateOxalate

FormateFormate

αα-Hydroxy- -Hydroxy- ββ-Ketoadipate-Ketoadipate

GlyoxylateGlyoxylate

Ethylene glycolEthylene glycol

GlycoaldehydeGlycoaldehyde

GlycolateGlycolate

FolateFolate

AlcoholAlcohol DehydrogenaseDehydrogenase

Metabolism of Metabolism of MethanolMethanolMethanolMethanol

FormaldehydeFormaldehyde

FormateFormate

COCO22 + H + H22OO

The IssuesThe Issues

• Ethylene GlycolEthylene Glycol ARFARF

• MethanolMethanol BlindnessBlindness

• IsopropanolIsopropanol Tummy upsetTummy upset

OsmolesOsmolesWhat is Normal?What is Normal?

65%65%

-2-2

300 “Normal” people300 “Normal” people

-2 -2 ±± 6 6

95%95%

1010-14-14

2.5%2.5%

97.5%97.5%

97.5% 97.5% population population gap < 10gap < 10

ManagementManagement

Ethylene GlycolEthylene Glycol

GlycoaldehydeGlycoaldehyde

MethanolMethanol

FormaldehydeFormaldehyde

Alcohol DehydrogenaseAlcohol Dehydrogenase

EthanolFomepizole

ManagementManagement Hemodialysis Hemodialysis

• SymptomaticSymptomatic

• Significant metabolic acidosis (?)Significant metabolic acidosis (?)

– pH < 7.1pH < 7.1

– One that can’t easily correct One that can’t easily correct

• Ethylene glycol or methanol levels Ethylene glycol or methanol levels

– > 25 mg/dL > 25 mg/dL

– > 50 mg/dL> 50 mg/dL

• Renal compromiseRenal compromise

?

Indications:

Symptomspresent

Often done Often done after symptoms after symptoms have begunhave begun

Sodium BicarbonateSodium Bicarbonate

For TCAs and Other For TCAs and Other Sodium Channel Blockers Sodium Channel Blockers

•It’s the It’s the sodiumsodium that counts that counts

•Boluses (Boli?) – the way to goBoluses (Boli?) – the way to go

•You follow your “efficacy” thru – QRS!!!You follow your “efficacy” thru – QRS!!!

•QRS corrects rapidly (minutes)QRS corrects rapidly (minutes)

• The big questions – Is there a correlation between…The big questions – Is there a correlation between…– QRS ≥ 100 ms & TCA concentration > 1000 ng/mLQRS ≥ 100 ms & TCA concentration > 1000 ng/mL

– Development of seizures or Development of seizures or ventricular dysrhythmias and ventricular dysrhythmias and • QRS ≥ 100 ms QRS ≥ 100 ms • TCA concentration > 1000 ng/mL TCA concentration > 1000 ng/mL

NEJM 1985313:474-9

Figure 1Figure 1Correlation between the Correlation between the max Limb Lead QRS max Limb Lead QRS Duration and the Duration and the Occurrence of Seizures of Occurrence of Seizures of Ventricular Arrhythmias.Ventricular Arrhythmias.Each circle denotes 1 of the Each circle denotes 1 of the 49 study patients.49 study patients.

Vs. Sodium Bicarbonate Vs. Sodium Bicarbonate with Salicylateswith Salicylates

• It’s the bicarbonate that countsIt’s the bicarbonate that counts

• Done as an infusion.Done as an infusion.

• You will cause hypokalemiaYou will cause hypokalemia

• You monitor “efficacy” via – urine pH You monitor “efficacy” via – urine pH (want it high to trap)(want it high to trap)