Critical Care ToxicologyCritical Care Toxicology

Division of Critical Care Division of Critical Care MedicineMedicine

University of AlbertaUniversity of Alberta

ObjectivesObjectives

Approach to the poisoned patientApproach to the poisoned patient General treatment strategiesGeneral treatment strategies Common Poisonings in the ICUCommon Poisonings in the ICU Toxicology literatureToxicology literature

EpidemiologyEpidemiology Approximately 2.4million exposures reported Approximately 2.4million exposures reported

per year in the U.S. (2004)per year in the U.S. (2004) True incidence unknownTrue incidence unknown 91% - single substance exposures91% - single substance exposures 12.8% required ICU admission12.8% required ICU admission 7.0% required non-critical care7.0% required non-critical care 1183 fatalities (0.05%)1183 fatalities (0.05%) 50.6% of fatal cases were multi-substance 50.6% of fatal cases were multi-substance

exposuresexposures

Immediate StabilizationImmediate Stabilization

AAirway with cervical spine controlirway with cervical spine control LOC, emesis, evidence of traumaLOC, emesis, evidence of trauma

BBreathingreathing Oxygen, ventilation if respiratory suppressionOxygen, ventilation if respiratory suppression

CCirculationirculation IVs, fluid resuscitationIVs, fluid resuscitation Cardiac monitorCardiac monitor

DDecontaminationecontamination EEnhance eliminationnhance elimination FFind an antidoteind an antidote

Important historical Important historical informationinformation

Often incomplete, unreliable or unobtainableOften incomplete, unreliable or unobtainable What was ingested, how much and whenWhat was ingested, how much and when What was the patient doing when they What was the patient doing when they

became illbecame ill Past medical historyPast medical history Information from family, friends, EMSInformation from family, friends, EMS Pill containers – pill countPill containers – pill count May need to contact pharmacyMay need to contact pharmacy

Toxicological Physical ExamToxicological Physical Exam CNSCNS – level of arousal, GCS, – level of arousal, GCS, pupilspupils, ,

behavior, neurological exambehavior, neurological exam CVSCVS – rate, rhythm – rate, rhythm RespResp – pattern, depth, wheezing – pattern, depth, wheezing GIGI – bowel sounds, distention – bowel sounds, distention SkinSkin – color, temp, signs of trauma – color, temp, signs of trauma OdorsOdors

ToxidromesToxidromes

SympathomimeticsSympathomimetics CholinergicCholinergic AnticholinergicAnticholinergic OpiateOpiate Sedative hypnoticSedative hypnotic Withdrawal (EtOH, BDZ, opiates)Withdrawal (EtOH, BDZ, opiates)

Laboratory investigationsLaboratory investigations

General labs: CBC, lytes, BUN, Cr, General labs: CBC, lytes, BUN, Cr, glucose, ABG, anion gapglucose, ABG, anion gap

Special laboratory investigation Special laboratory investigation indicated in following casesindicated in following cases Intentional ingestionIntentional ingestion Substance unknownSubstance unknown Potential for moderate to severe toxicityPotential for moderate to severe toxicity

Laboratory investigationsLaboratory investigations

Labs considered essential and available Labs considered essential and available within 4 hrs:within 4 hrs: EtOH,EtOH, acetaminophen acetaminophen, salicylate, digoxin, , salicylate, digoxin,

carbamazepine, phenobarb, phenytoin, valproate, carbamazepine, phenobarb, phenytoin, valproate, theophyllinetheophylline

Labs available through referral center:Labs available through referral center: Methanol, ethylene glycol, isopropyl alcohol, iron, Methanol, ethylene glycol, isopropyl alcohol, iron,

lithiumlithium

Tox screen – generally does not contribute to Tox screen – generally does not contribute to patient managementpatient management

Additional TestsAdditional Tests

ECG – ECG – TCA or other cardiotoxic drugs, TCA or other cardiotoxic drugs, arrhythmias, ischemiaarrhythmias, ischemia

Radiology Radiology CXR – aspiration, noncardiogenic CXR – aspiration, noncardiogenic

pulmonary edemapulmonary edema Abdominal films useful in screening for Abdominal films useful in screening for

ingestions of radio-opaque materialsingestions of radio-opaque materials What substances are visible on AXR?What substances are visible on AXR?

AntidotesAntidotes

If after stabilization a toxin is If after stabilization a toxin is identified, there may be a specific identified, there may be a specific antidoteantidote

There are approximately 18 There are approximately 18 antidotes commonly stored in antidotes commonly stored in tertiary care centers in N. Americatertiary care centers in N. America

AntidotesAntidotesantidoteantidote poisonpoison

AcetylcysteinAcetylcysteinee

acetaminophenacetaminophen

Crotalid Crotalid Antivenin Antivenin

Crotalid snake Crotalid snake bitebite

atropineatropine Carbamate or Carbamate or organophosphateorganophosphate

Ca gluconate Ca gluconate or Ca or Ca chloridechloride

CCB or hydrogen CCB or hydrogen fluoridefluoride

Cyanide kitCyanide kit cyanidecyanide

DeferoxaminDeferoxaminee

IronIron

Digoxin Digoxin immune Fabimmune Fab

Digoxin, digitoxinDigoxin, digitoxin

Dimercaprol Dimercaprol (BAL)(BAL)

Arsenic, mercury, Arsenic, mercury, leadlead

antidoteantidote poisonpoison

EthanolEthanol MeOH, Et glycolMeOH, Et glycol

FlumazenilFlumazenil BDZBDZ

FomepizoleFomepizole MeOH, Et glycolMeOH, Et glycol

GlucagonGlucagon ΒΒ-blocker, CCB-blocker, CCB

Methylene Methylene blueblue

methemoglobinmethemoglobin

NaloxoneNaloxone opioidsopioids

PhysostigminPhysostigminee

anticholinergicanticholinergic

PralidoximePralidoxime organophosphatorganophosphatee

PyridoxinePyridoxine isoniazidisoniazid

Sodium Sodium bicarbonatebicarbonate

TCA, cocaine, TCA, cocaine, salicylatesalicylate

Gastrointestinal Gastrointestinal DecontaminationDecontamination

AACT/EAPCCT Position statement on AACT/EAPCCT Position statement on gastrointestinal decontaminationgastrointestinal decontamination Clinical Toxicology 2004, 2005Clinical Toxicology 2004, 2005

IpecacIpecac Gastric LavageGastric Lavage Whole bowel irrigation Whole bowel irrigation Single dose activated charcoalSingle dose activated charcoal CatharticsCathartics

IpecacIpecac

Emetic – both peripherally and central actingEmetic – both peripherally and central acting >90% effective>90% effective Dose: 30cc PO >5yrs, 15cc 1-5yrs, 10cc 6-12 moDose: 30cc PO >5yrs, 15cc 1-5yrs, 10cc 6-12 mo IndicationsIndications

None, reallyNone, really consider in the out of hospital toxic ingestionconsider in the out of hospital toxic ingestion

ContraindicationsContraindications Unprotected or anticipated unprotected airwayUnprotected or anticipated unprotected airway Hydrocarbons, causticsHydrocarbons, caustics Debilitated patientsDebilitated patients

ComplicationsComplications Diarrhea, lethargy/drowsiness, prolonged vomitingDiarrhea, lethargy/drowsiness, prolonged vomiting

Gastric LavageGastric Lavage 36-40 Fr NG, sequential instillation and 36-40 Fr NG, sequential instillation and

removal of small volumes of isotonic fluidremoval of small volumes of isotonic fluid IndicationsIndications

Recent ingestion (<1-2 hr)Recent ingestion (<1-2 hr) Substance exceeds adsorptive capacity of Substance exceeds adsorptive capacity of

initial AC dosinginitial AC dosing Agents not adsorbed by ACAgents not adsorbed by AC Substances likely to form concretions Substances likely to form concretions

after overdoseafter overdose Substantial risk of toxicity, or Substantial risk of toxicity, or LOC LOC

requiring intubation (ASA, chloroquine, requiring intubation (ASA, chloroquine, colchicine, TCA, CCBs)colchicine, TCA, CCBs)

Gastric LavageGastric Lavage

ContraindicationsContraindications Unprotected airwayUnprotected airway CorrosivesCorrosives HydrocarbonsHydrocarbons Risk of GI bleed or perforationRisk of GI bleed or perforation

ComplicationsComplications Aspn pneumonia, laryngospasm, Aspn pneumonia, laryngospasm,

hypoxia, mechanical injury, hypoxia, mechanical injury, fluid/electrolyte imbalancesfluid/electrolyte imbalances

Whole bowel irrigationWhole bowel irrigation

PEG via NG at 1-2 L/h (500cc/h in peds) until PEG via NG at 1-2 L/h (500cc/h in peds) until effluent cleareffluent clear

IndicationsIndications Potentially toxic ingestion of SR or EC prepPotentially toxic ingestion of SR or EC prep Ingested packets of illicit drug (stuffers, Ingested packets of illicit drug (stuffers,

packers)packers) Substances not adsorbed by ACSubstances not adsorbed by AC Iron ingestionsIron ingestions

Whole bowel IrrigationWhole bowel Irrigation

ContraindicationsContraindications Bowel perforation or obstructionBowel perforation or obstruction GI bleed GI bleed IleusIleus Unprotected airwayUnprotected airway Hemodynamic instabilityHemodynamic instability Intractable vomitingIntractable vomiting

ComplicationsComplications Nausea, vomiting, aspiration, crampsNausea, vomiting, aspiration, cramps

Activated CharcoalActivated Charcoal 1g/kg PO or NG1g/kg PO or NG IndicationsIndications

Within 1 hour of ingestionWithin 1 hour of ingestion Nearly all suspected toxic ingestions Nearly all suspected toxic ingestions exceptexcept May be considered more than 1 hour after ingestion but May be considered more than 1 hour after ingestion but

insufficient data to support or exclude useinsufficient data to support or exclude use ContraindicationsContraindications

Unprotected airwayUnprotected airway When AC therapy may increase risk and severity of When AC therapy may increase risk and severity of

aspirationaspiration Intestinal obstructionIntestinal obstruction GI tract not anatomically intact (Boerhaave’s…)GI tract not anatomically intact (Boerhaave’s…)

ComplicationsComplications Aspiration, emesisAspiration, emesis

Enhancing eliminationEnhancing elimination

Multiple dose activated charcoal Multiple dose activated charcoal Alkalinization Alkalinization Hemodialysis Hemodialysis HemoperfusionHemoperfusion

Multiple Dose Activated Multiple Dose Activated CharcoalCharcoal

Improves elimination of drugs with enterohepatic Improves elimination of drugs with enterohepatic circulationcirculation

Initial dose of 1g/kg, then 1/4 - 1/2 g/kg q1hInitial dose of 1g/kg, then 1/4 - 1/2 g/kg q1h Consider only if life-threatening amount of:Consider only if life-threatening amount of:

CarbamazepineCarbamazepine PhenobarbitalPhenobarbital DapsoneDapsone QuinineQuinine TheophyllineTheophylline

May also increase elimination of :May also increase elimination of : amitriptyline, propoxyphene, digitoxin, digoxin, disopyramide, amitriptyline, propoxyphene, digitoxin, digoxin, disopyramide,

nadolol, phenylbutazone, phenytoin, piroxicam, sotalolnadolol, phenylbutazone, phenytoin, piroxicam, sotalol

Contraindications same as for single dose ACContraindications same as for single dose AC

AlkalinizationAlkalinization

Enhances elimination of weak bases by Enhances elimination of weak bases by ion trappingion trapping

Useful for:Useful for: Salicylate, phenobarbital, chlorpropamide, Salicylate, phenobarbital, chlorpropamide,

methotrexate, myoglobinmethotrexate, myoglobin NaHCONaHCO3 3 1-2 mEq/kg IV Q3-4H1-2 mEq/kg IV Q3-4H Aim for Urine pH 7-8Aim for Urine pH 7-8 Must replace K in order to achieve Must replace K in order to achieve

alkaline urinealkaline urine

HemodialysisHemodialysis

Blood passed across membrane with Blood passed across membrane with countercurrent dialysate flowcountercurrent dialysate flow

Toxins removed primarily by diffusionToxins removed primarily by diffusion

Properties required:Properties required: Molecular weight < 500 daltonsMolecular weight < 500 daltons High water solubilityHigh water solubility Low or saturable plasma protein bindingLow or saturable plasma protein binding Low Vd (<1L/kg)Low Vd (<1L/kg) Low endogenous clearance(<4ml/min/kg)Low endogenous clearance(<4ml/min/kg)

HemoperfusionHemoperfusion

Blood passed through extracorporeal Blood passed through extracorporeal circuit containing ACcircuit containing AC

Toxins removed by adsorptionToxins removed by adsorption

Properties required:Properties required: Low Vd <1L/kgLow Vd <1L/kg Low endogenous clearance <4cc/min/kgLow endogenous clearance <4cc/min/kg Absorbable to ACAbsorbable to AC

Substances amenable to Substances amenable to hemodialysishemodialysis

LET ME SAV PLET ME SAV P LLithiumithium EEthylene glycolthylene glycol TTheophyllineheophylline

MEMEthanolthanol

SSalicylatesalicylates AAtenololtenolol VValproic acidalproic acid

PPotassiumotassium

AcetaminophenAcetaminophen

Common overdoseCommon overdose Normally 90% metabolized by glucuronidation Normally 90% metabolized by glucuronidation

and sulfation, 5-10% metabolized by cytP450 and sulfation, 5-10% metabolized by cytP450 to NAPQIto NAPQI

In overdose glutathione stores are depleted In overdose glutathione stores are depleted NAPQI accumulates and directly damages NAPQI accumulates and directly damages liver, kidneys…liver, kidneys…

↑ ↑ susceptibility in alcoholics, malnourished b/c susceptibility in alcoholics, malnourished b/c upregulated cytP450 and upregulated cytP450 and ↓ ↓ glutathione storesglutathione stores

Acetaminophen – Acetaminophen – clinical clinical presentationpresentation

Stage 1: Pre-injury period– 0-24h Stage 1: Pre-injury period– 0-24h Asymptomatic or minor N+VAsymptomatic or minor N+V

Stage 2: Acute liver injury– 24-48h Stage 2: Acute liver injury– 24-48h RUQ pain, RUQ pain, ↑AST/ALT, PTT, INR, bili +/- ↑Cr↑AST/ALT, PTT, INR, bili +/- ↑Cr

Stage 3: Maximal liver injury – 48-96h Stage 3: Maximal liver injury – 48-96h marked hepatic dysfnmarked hepatic dysfnfulminant hepatic failure, fulminant hepatic failure,

encephalopathy, coagulopathy, hypoglycemia, encephalopathy, coagulopathy, hypoglycemia, acidosis, renal failureacidosis, renal failure

Stage 4: Recovery period - 4-14 daysStage 4: Recovery period - 4-14 days Resolution of hepatic dysfunction and recoveryResolution of hepatic dysfunction and recovery

Acetaminophen – treatment Acetaminophen – treatment

N-acetylcysteine (NAC) – 20 hr IV N-acetylcysteine (NAC) – 20 hr IV protocolprotocol

Mechanism of action:Mechanism of action: Glutathione precursorGlutathione precursor Glutathione substituteGlutathione substitute Substrate for sulfationSubstrate for sulfation Non-specific free radical binderNon-specific free radical binder

Rumack-Matthew Rumack-Matthew NomogramNomogram

AcetaminophenAcetaminophen Obtain serum level at 4hrs post ingestion and use Obtain serum level at 4hrs post ingestion and use

Rumack-Matthew nomogramRumack-Matthew nomogram If 8 -24 hrs, or unknown time of ingestion draw level If 8 -24 hrs, or unknown time of ingestion draw level

and start IV NACand start IV NAC Efficacy of NAC decreases with time if administered Efficacy of NAC decreases with time if administered

> 8 hrs post ingestion> 8 hrs post ingestion No documented fatalities if given within 8 hrsNo documented fatalities if given within 8 hrs

If over 24 hrs and acetaminophen level If over 24 hrs and acetaminophen level undetectable, AST and INR normal – no treatment undetectable, AST and INR normal – no treatment requiredrequired

If INR > 2 after completion of 20hr protocol, If INR > 2 after completion of 20hr protocol, continue infusion until INR < 2continue infusion until INR < 2

Acetaminophen – transplant Acetaminophen – transplant criteriacriteria

King’s College Hospital CriteriaKing’s College Hospital Criteria Metabolic acidosis persisting after Metabolic acidosis persisting after

resuscitation – pH <7.3 or lactate > resuscitation – pH <7.3 or lactate > 3.03.0

All 3 of below within 24hrsAll 3 of below within 24hrs Progressive coagulopathy – INR >6.5Progressive coagulopathy – INR >6.5 Hepatic encephalopathy – Grade 3 -4Hepatic encephalopathy – Grade 3 -4 Renal failure – Cr >300Renal failure – Cr >300

ASAASA

Toxic dose – 200 mg/kg in single Toxic dose – 200 mg/kg in single ingestion (40-45 x 325mg tab)ingestion (40-45 x 325mg tab)

Pts with chronic ingestion may have Pts with chronic ingestion may have serious toxicity with remarkably low serious toxicity with remarkably low serum salicylate concentrationsserum salicylate concentrations

Mortality rate: Mortality rate:

acute salicylate intoxicationacute salicylate intoxication 1%1%

chronic salicylate intoxicationchronic salicylate intoxication 25%25%

ASA – preparationsASA – preparations Aspirin 325 mg/ tab; 500 mg/ tab Aspirin 325 mg/ tab; 500 mg/ tab Enteric coated aspirin; 325 mg/ tab Enteric coated aspirin; 325 mg/ tab Children's aspirin 80 mg Children's aspirin 80 mg Oil of Wintergreen (100 % Methyl Oil of Wintergreen (100 % Methyl

salicylate)salicylate)7000 mg/ 5 ml 7000 mg/ 5 ml Ben Gay® (20 % methyl salicylate)6000 mg/ Ben Gay® (20 % methyl salicylate)6000 mg/

30 ml 30 ml Pepto Bismol (Bismuth subsalicylate)650 mg/ Pepto Bismol (Bismuth subsalicylate)650 mg/

60 ml60 ml Herbal products contain various amountsHerbal products contain various amounts

ASA – clinical featuresASA – clinical features

Initial SxInitial Sx Hearing loss, tinnitusHearing loss, tinnitus

Significant toxicitySignificant toxicity Hyperventilation, N & V, dehydration, Hyperventilation, N & V, dehydration,

hyperthermia, altered LOChyperthermia, altered LOC Serious toxicitySerious toxicity

Pulmonary edema, cerebral edema, renal Pulmonary edema, cerebral edema, renal failure, rhabdomyolysis, seizures, coma, failure, rhabdomyolysis, seizures, coma, deathdeath

ASA – clinical featuresASA – clinical features

Acid Base disturbanceAcid Base disturbance1.1. Resp. alkalosisResp. alkalosis - direct stimulation of medulla - direct stimulation of medulla

2.2. Compensatory metabolic acidosisCompensatory metabolic acidosis – renal – renal HCOHCO33 loss loss

3.3. Inhibition Krebs cycle enzymesInhibition Krebs cycle enzymes - - lactate, lactate, pyruvate pyruvate anion gap metabolic acidosisanion gap metabolic acidosis

4.4. Uncoupling of oxidative phosphorylationUncoupling of oxidative phosphorylation - - tissue glycolysis and BMR tissue glycolysis and BMR hypo/hyperglycemia, hyperpyrexiahypo/hyperglycemia, hyperpyrexia

ASA - treatmentASA - treatment1. Prevent further salicylate absorption1. Prevent further salicylate absorption Gastric decontaminationGastric decontamination

Activated charcoalActivated charcoal Whole bowel irrigationWhole bowel irrigation

2. Correct fluid deficits and acid-base 2. Correct fluid deficits and acid-base abnormalitiesabnormalities

Volume resuscitation Volume resuscitation Careful not to over resuscitate to prevent Careful not to over resuscitate to prevent

precipitation of pulmonary/cerebral edemaprecipitation of pulmonary/cerebral edema Must replace KMust replace K++

ASA -treatmentASA -treatment

3. Enhance elimination3. Enhance elimination Ion trappingIon trapping

Alkalinize urine: 3 amps NaHCOAlkalinize urine: 3 amps NaHCO33 in 1L in 1L D5W D5W Run @ 250cc/h to urine pH 7.5 -8.0Run @ 250cc/h to urine pH 7.5 -8.0

Urine salicylate clearance is directly Urine salicylate clearance is directly proportional to urine flow rate, but more proportional to urine flow rate, but more importantly, it is importantly, it is logarithmicallylogarithmically proportional to proportional to urine pHurine pH

ASA - treatmentASA - treatment Hemodialysis Hemodialysis Toxic level (>3 mmol/L) and:Toxic level (>3 mmol/L) and:

CNS toxicity – sz, coma, deliriumCNS toxicity – sz, coma, delirium ARDSARDS Renal failureRenal failure Severe acid-base or electrolyte abnormalitySevere acid-base or electrolyte abnormality CoagulopathyCoagulopathy Unstable or deteriorating vital signsUnstable or deteriorating vital signs CHFCHF

Acute level > 7mmol/LAcute level > 7mmol/L Chronic level > 4 mmol/LChronic level > 4 mmol/L

Cardiac drugs – clinical Cardiac drugs – clinical presentationpresentation

Calcium channel blockersCalcium channel blockers Bradycardia and hypotensionBradycardia and hypotension Awake and alertAwake and alert HyperglycemiaHyperglycemia Narrow QRSNarrow QRS May get reflex tachycardia with May get reflex tachycardia with

dihydropyridinesdihydropyridines

Cardiac drugs – clinical Cardiac drugs – clinical presentationpresentation

Beta BlockersBeta Blockers Bradycardia and hypotensionBradycardia and hypotension Depressed LOCDepressed LOC HypoglycemiaHypoglycemia

Cardiac drugsCardiac drugs

DigoxinDigoxin Variable HR +/- hypotensionVariable HR +/- hypotension GI and visual symptomsGI and visual symptoms HyperkalemiaHyperkalemia Characteristic ECG findingsCharacteristic ECG findings

Enhanced automaticity and slowed AV Enhanced automaticity and slowed AV conductionconduction

Multiple PVCs – ventricular dysrhythmiasMultiple PVCs – ventricular dysrhythmias

Cardiac drugs - treatmentCardiac drugs - treatment Calcium channel blockersCalcium channel blockers

IV CaCl or Ca gluconate,IV CaCl or Ca gluconate, Fluids, pressors, pacing, IABPFluids, pressors, pacing, IABP Insulin/glucose - 10-20 units IV, then 0.2-1 Insulin/glucose - 10-20 units IV, then 0.2-1

U/kg/h, with D5W or D10W infusionU/kg/h, with D5W or D10W infusion

Beta blockersBeta blockers IV glucagon - 5-10 mg over 1 min, then 1-10 IV glucagon - 5-10 mg over 1 min, then 1-10

mg/hmg/h milrinone/pressors, pacing, IABPmilrinone/pressors, pacing, IABP

Cardiac drugs - treatmentCardiac drugs - treatment

Digoxin – Digoxin immune Fab (Digibind)Digoxin – Digoxin immune Fab (Digibind) Indications for Digibind Indications for Digibind

Ventricular dysrhythmiaVentricular dysrhythmia Progressive/refractory hemodynamic instabilityProgressive/refractory hemodynamic instability K > 5 with acute toxicityK > 5 with acute toxicity Acute ingestion > 10 mgAcute ingestion > 10 mg

Dosing of DigibindDosing of Digibind Empiric tx acute toxicity– 10 vialsEmpiric tx acute toxicity– 10 vials Empiric tx chronic toxicity – 4-6 vialsEmpiric tx chronic toxicity – 4-6 vials Known dose: (dose in mg x 0.8)/0.5 = # vialsKnown dose: (dose in mg x 0.8)/0.5 = # vials Steady state Vd at 6hrs: (serum dig level x wt)/100 = # vialsSteady state Vd at 6hrs: (serum dig level x wt)/100 = # vials

Tricyclic antidepressantsTricyclic antidepressants Rapidly absorbed, large Vd, variable protein Rapidly absorbed, large Vd, variable protein

binding, lipophilicbinding, lipophilic Mechanism of action Mechanism of action

Voltage dependent Na channel blockade –Voltage dependent Na channel blockade –prolonged QRSprolonged QRS Inward rectifier K channel blockade –Inward rectifier K channel blockade –prolonged QTcprolonged QTc HH11 and H and H22 receptor blockade – receptor blockade – mixed effectsmixed effects Muscarinic receptor blockade - Muscarinic receptor blockade - anticholinergicanticholinergic αα-adrenergic receptor blockade - -adrenergic receptor blockade - hypotensionhypotension Blocks reuptake DA, NE – Blocks reuptake DA, NE – altered mental statusaltered mental status GABA receptor blockade - GABA receptor blockade - seizuresseizures

Tricyclic antidepressantsTricyclic antidepressants

Drug levels do not correlate with toxicityDrug levels do not correlate with toxicity ECG can be diagnostic of Na channel ECG can be diagnostic of Na channel

blockade:blockade: QRS > 100 msec - 30% risk seizuresQRS > 100 msec - 30% risk seizures QRS > 160 msec – 50% risk arrhythmiasQRS > 160 msec – 50% risk arrhythmias Right axis deviation of terminal 40 msec of Right axis deviation of terminal 40 msec of

QRS – look in aVRQRS – look in aVR Prolonged QTProlonged QT Sinus tachycardiaSinus tachycardia

Tricyclic antidepressants – Tricyclic antidepressants – ECG ECG

Tricyclic antidepressants - Tricyclic antidepressants - treatmenttreatment

Gastric lavage and AC if indicatedGastric lavage and AC if indicated Beware rapid decrease in LOCBeware rapid decrease in LOC

Avoid acidosis (Sz, Avoid acidosis (Sz, ↓BP)↓BP) Serum alkalinization (hyperventilation, bicarb)Serum alkalinization (hyperventilation, bicarb)

Uncouples TCA from Na channelUncouples TCA from Na channel Increases Na gradient (mass effect)Increases Na gradient (mass effect) Increased pH decreases tissue penetration of TCAIncreased pH decreases tissue penetration of TCA

Indications for alkalinizationIndications for alkalinization QRS > 100 msecQRS > 100 msec VT/Cardiac arrestVT/Cardiac arrest Seizures or hypotensionSeizures or hypotension

Toxic AlcoholsToxic Alcohols MethanolMethanol

Present in windshield washer fluid, solvents, Present in windshield washer fluid, solvents, formaldehyde – bitter tastingformaldehyde – bitter tasting

Metabolized by alcohol DH, then aldehyde DH to Metabolized by alcohol DH, then aldehyde DH to formaldehyde, then formic acidformaldehyde, then formic acid

Formic acid – inhibits oxidative phosphorylation and Formic acid – inhibits oxidative phosphorylation and toxic to eyes and CNStoxic to eyes and CNS

Clinical PresentationClinical Presentation Early (0-6h)– inebriation, gastritis, altered LOCEarly (0-6h)– inebriation, gastritis, altered LOC Late (6-72h)– visual changes “snowstorm blindness”, Late (6-72h)– visual changes “snowstorm blindness”,

metabolic acidosis, seizures, metabolic acidosis, seizures, ↓LOC↓LOC

Toxic alcoholsToxic alcohols Ethylene glycolEthylene glycol

Found in antifreeze, coolants – sweet tastingFound in antifreeze, coolants – sweet tasting Metabolized by alcohol dehydrogenase to Metabolized by alcohol dehydrogenase to

glycoaldehyde, glycolic acid and oxalic acidglycoaldehyde, glycolic acid and oxalic acid Inhibit oxidative phosphorylation, and are toxic to Inhibit oxidative phosphorylation, and are toxic to

CNS, lung and kidneyCNS, lung and kidney Clinical PresentationClinical Presentation

Acute neurologic stage (30min-12hrs)Acute neurologic stage (30min-12hrs) Cardiopulmonary stage (12-24hrs)Cardiopulmonary stage (12-24hrs) Renal stage (24-72hrs)Renal stage (24-72hrs) Delayed neurologic stage (6-12d)Delayed neurologic stage (6-12d)

Toxic alcohols - treatmentToxic alcohols - treatment Correct acidemiaCorrect acidemia

bicarbonate, allow hyperventilationbicarbonate, allow hyperventilation Prevents diffusion of toxic metabolites into Prevents diffusion of toxic metabolites into

tissuestissues Inhibit alcohol dehydrogenaseInhibit alcohol dehydrogenase

EtOH – aim for level 22-33mmol/LEtOH – aim for level 22-33mmol/L Fomepizole – easier administration, safer, longer Fomepizole – easier administration, safer, longer

t1/2, but significantly more expensivet1/2, but significantly more expensive Treat if EG>3mmol/L, MeOH >6mmol/LTreat if EG>3mmol/L, MeOH >6mmol/L Documented or suspected ingestion and OG>10Documented or suspected ingestion and OG>10

Toxic alcohols - treatmentToxic alcohols - treatment Enhance elimination by hemodialysisEnhance elimination by hemodialysis

Serum EG > 8 or MeOH > 15Serum EG > 8 or MeOH > 15 Metabolic acidosis (pH < 7.25)Metabolic acidosis (pH < 7.25) End organ symptoms (i.e. visual changes)End organ symptoms (i.e. visual changes) Renal impairment, electrolyte abnormalitiesRenal impairment, electrolyte abnormalities Deteriorating vital signsDeteriorating vital signs Continue dialysis until EG < 3 or MeOH <6Continue dialysis until EG < 3 or MeOH <6

Adjunctive treatmentsAdjunctive treatments Thiamine 100mg IV/IM q6H, pyridoxine 50mg Thiamine 100mg IV/IM q6H, pyridoxine 50mg

IV/IM q6h (glyoxalateIV/IM q6h (glyoxalateglycine, other non-toxic)glycine, other non-toxic) Folate 50 mg IV/IM q6h (FormateFolate 50 mg IV/IM q6h (FormateC0C022 +H +H220)0)

SummarySummary

ABC’sABC’s Supportive therapy sufficient for Supportive therapy sufficient for

most overdosesmost overdoses Decontamination/enhancing Decontamination/enhancing

eliminationelimination Antidotes/specific treatment Antidotes/specific treatment

indicated for certain overdosesindicated for certain overdoses

QuestionsQuestions

PupilsPupilsMiosisMiosis CCholinergics/clonidineholinergics/clonidine OOpiates/piates/

organophosphatesorganophosphates PPhenothiazines, henothiazines,

pilocarpine, pontine pilocarpine, pontine bleedbleed

SSedative hypnoticsedative hypnotics

MydriasisMydriasis AAntihistaminesntihistamines AAntidepressantsntidepressants AAnticholinergicsnticholinergics SSympathomimeticsympathomimetics

OdorsOdors

Bitter almondsBitter almonds – cyanide – cyanide FruityFruity – DKA, isopropanol – DKA, isopropanol Minty Minty – methyl salicylates– methyl salicylates Rotten eggsRotten eggs – sulfur dioxide, – sulfur dioxide,

hydrogen sulfidehydrogen sulfide PearsPears – chloral hydrate – chloral hydrate GarlicGarlic – organophosphates, arsenic – organophosphates, arsenic MothballsMothballs - camphor - camphor

Drugs that don’t adsorb to ADrugs that don’t adsorb to ACC PHAILSPHAILS

PPesticidesesticides HHydrocarbonsydrocarbons AAcids/alkaliscids/alkalis IIronron LLithiumithium SSolventsolvents

Radiodense substances that mRadiodense substances that may be visible on AXRay be visible on AXR CHIPESCHIPES

CChloral hydratehloral hydrate HHeavy metalseavy metals IIronron PPhenothiazineshenothiazines EEnteric coated prepsnteric coated preps SSustained release prepsustained release preps

Drug PacketsDrug Packets