IN THE NAME OF GOD. AN APPROACH TO A POISONED PATIENT DR. FAZEL GOUDARZI;TRAUMATO PATHOLOGIST AND...

IN THE NAME OF GODIN THE NAME OF GOD

AN APPROACH TO A AN APPROACH TO A POISONED PATIENTPOISONED PATIENT

DR. FAZEL GOUDARZI;TRAUMATO DR. FAZEL GOUDARZI;TRAUMATO PATHOLOGIST AND CLINICAL PATHOLOGIST AND CLINICAL

TOXICOLOGISTTOXICOLOGIST

SHIRAZ UNIVERCITY OF MEDICAL SHIRAZ UNIVERCITY OF MEDICAL SCIENCESSCIENCES

IntroductionIntroduction

What is a poison?

In common usage - poisons are In common usage - poisons are chemicals or chemical products chemicals or chemical products that are distinctly harmful to that are distinctly harmful to humanhuman

More precisely - a poison is a More precisely - a poison is a foreign chemical (xenobiotic) foreign chemical (xenobiotic) that is capable of producing a that is capable of producing a harmful effect on a biologic harmful effect on a biologic systemsystem

Other terminologyOther terminology

What is a toxin?

It originally referred to a It originally referred to a poison of animal or plant poison of animal or plant originorigin

Toxicant is the currently Toxicant is the currently preferred scientific term preferred scientific term for all poisons. for all poisons.

EpidemiologyEpidemiology

Ingestion of a potentially poisonous Ingestion of a potentially poisonous substance by a young child is common.substance by a young child is common.

American Association of Poison Control American Association of Poison Control Centers reported 1.2 million ingestions Centers reported 1.2 million ingestions in children < 6 years of age in 2001. in children < 6 years of age in 2001.

Death is uncommon in this age group.Death is uncommon in this age group. Decline in death rate from 500 Decline in death rate from 500

mortalities per year in the 1940s mortalities per year in the 1940s to 25 mortalities in 1997to 25 mortalities in 1997

EpidemiologyEpidemiology

Decline in mortality attributed to:Decline in mortality attributed to: child resistant containerschild resistant containers safer medicationssafer medications anticipatory guidanceanticipatory guidance public educationpublic education legislationlegislation establishment of poison control centersestablishment of poison control centers sophisticated medical caresophisticated medical care antidotes antidotes

Clinical assessment

Approach to the Poisoned Approach to the Poisoned PatientPatient

HistoryHistory

Time of ingestionTime of ingestion Medications in the householdMedications in the household Amount ingestedAmount ingested Onset of symptomsOnset of symptoms IntentionalityIntentionality Underlying medical conditionsUnderlying medical conditions


Physical ExaminationPhysical Examination

Vital SignsVital Signs Pupillary exam (miosis, mydriasis)Pupillary exam (miosis, mydriasis) Skin (dry, cyanotic)Skin (dry, cyanotic) Lungs (crackles, wheezing)Lungs (crackles, wheezing) Cardiac (tachycardia, bradycardia)Cardiac (tachycardia, bradycardia) Abdomen (decreased bowel sounds, Abdomen (decreased bowel sounds,

tenderness)tenderness) Neurologic (altered mental status, Neurologic (altered mental status,

seizure)seizure)

Approach to the Poisoned Approach to the Poisoned Patient Patient Initial ManagementInitial Management

AirwayAirwayBreathingBreathingCirculationCirculationDisabilityDisabilityExposureExposure

Clinical assessmentClinical assessment Airway - ensure clear airway, clear

secretions, check for cough/gag

Breathing - check oxygenation, supplemental O2, breathing pattern & adequacy

Circulation - heart rate, rhythm, blood pressure

Clinical assessmentClinical assessment Neurologic - GCS, seizures, agitation,

spasms, pupils, autonomic dysfunction

Miscellaneous - odour, temperature, pallor, cyanosis, jaundice

Abdomen - rigidity, bleeding, urine output

Laboratory and imaging(paraclinical)

assessment


Diagnostic EvaluationDiagnostic Evaluation

CBCDCBCDElectrolytesElectrolytesABGABGLFTsLFTsCXRCXRECGECG

AXRAXRSerum ToxSerum ToxUrine ToxUrine ToxASA levelASA levelTylenol levelTylenol levelSerum OSMSerum OSMCholinstraseCholinstrase

Laboratory assessmentLaboratory assessment Electrolytes

Hypokalemia– Oduvanthalai poisoning (Clistanthis collinis)– Diuretics, Methyl xanthine, Toluene

Hyperkalemia– Digoxin– Beta-blocker

Liver function tests– Acetaminophen, Ethanol, Carbon tetrachloride

Renal function tests– Ethylene glycol, NSAIDS

Anion Gap (AG)Anion Gap (AG)

Anion Gap = NaAnion Gap = Na+ + - [Cl- [Cl- - + + HCOHCO3 3

--]]

Normal AG: 8-16Normal AG: 8-16

Toxins Toxins associatedassociated with with increased AGincreased AG

MethanolMethanol ParaldehydeParaldehyde INHINH FeFe Ethylene glycolEthylene glycol SalicylatesSalicylates COCO CyanideCyanide

Hydrogen SulfideHydrogen Sulfide ETOH (ketones)ETOH (ketones) MetforminMetformin PhenforminPhenformin SulfurSulfur TheophyllineTheophylline TolueneToluene

Toxins associated with decreased AGToxins associated with decreased AG

LithiumLithiumBromideBromide

Osmolal Gap Osmolal Gap (OG)(OG)

Serum OSM: 2[Na] + Serum OSM: 2[Na] + [[Glc]/18 + Glc]/18 + [BUN]/2.6[BUN]/2.6

OG: Measured OSM-Calculated OSMOG: Measured OSM-Calculated OSM

Normal OG: -3 to 10 mOSM/kg H2ONormal OG: -3 to 10 mOSM/kg H2O

Toxins Toxins associatedassociated with increased with increased OGOG

MethanolMethanolEthanolEthanolEthylene glycolEthylene glycolAcetoneAcetone IsopropanolIsopropanol

Useful Toxin LevelsUseful Toxin Levels

AcetaminophenAcetaminophen Carbon MonoxideCarbon Monoxide EthanolEthanol Ethylene glycolEthylene glycol Heavy metalsHeavy metals IronIron MethanolMethanol MethemoglobinMethemoglobin

SalicylatesSalicylates CarbamazepineCarbamazepine DigoxinDigoxin lithiumlithium PhenobarbitalPhenobarbital PhenytoinPhenytoin TheophyllineTheophylline ValproateValproate

Set time point Serial levels

ECG and Imaging AssessmentECG and Imaging Assessment ECG

Digoxin toxicity

TCA overdose - sinus tachycardia, QT prolongation, increased QRS

Beta-blockers - conduction abnormalities

Imaging Chest x-ray Abdominal x-ray Cervical x-ray (lateral) C.T scan or MRI in decrease L.O.C.

Radiopaque drugsRadiopaque drugs Bezoars/BagsBezoars/Bags Calcium carbonateCalcium carbonate Chloral hydrateChloral hydrate Enteric-coated tabletsEnteric-coated tablets Heavy metalsHeavy metals IodineIodine Fe Fe PhenothiazinesPhenothiazines Potassium compoundsPotassium compounds

Other terminologyOther terminology

What is a toxidrome?(TOXICOLOGIC SYNDROME)?

It is the association of several clinically It is the association of several clinically recognizable features, signs, symptoms, recognizable features, signs, symptoms, phenomena or characteristics which often phenomena or characteristics which often occuroccur togethertogether, so that the presence of , so that the presence of one feature alerts the physician to the one feature alerts the physician to the presence of the others. presence of the others.

Common toxidromesCommon toxidromes

Opiate toxidromeOpiate toxidrome

Toxidromes Toxidromes OpiatesOpiates

MiosisMiosis Respiratory depressionRespiratory depression Cns depressionCns depression HypotensionHypotension SedationSedation Decreased GI motilityDecreased GI motility Urinary retentionUrinary retention

ToxidromesToxidromesOpiatesOpiates

Seizures-Meperidine; occur Seizures-Meperidine; occur secondary to the metabolite secondary to the metabolite normeperidinenormeperidine

Dysrhythmias-Propoxyphene; Dysrhythmias-Propoxyphene; occur from the metabolite occur from the metabolite norpropoxyphenenorpropoxyphene

Rigid Chest-FentanylRigid Chest-Fentanyl

The cholinergic toxidromeThe cholinergic toxidrome

ToxidromesToxidromesCholinergics-Muscarinic Cholinergics-Muscarinic EffectsEffects

SSalivationalivation LLacrimationacrimation UUrination rination DDefecationefecation GGastrointestinal Distressastrointestinal Distress EEmesismesis

TOXIDROMETOXIDROMECHOLINERGIC CNS EFFECTCHOLINERGIC CNS EFFECT

RESTLESSNESSRESTLESSNESS AGITATIONAGITATION CONFUSIONCONFUSION CONVULSIONCONVULSION COMACOMA DEATHDEATH

ToxidromesToxidromesCholinergics-Nicotinic EffectsCholinergics-Nicotinic Effects

Muscle FasciculationsMuscle FasciculationsWeaknessWeaknessParalysisParalysisSympathomimetic effectSympathomimetic effect

What toxidrome?What toxidrome?

The anticholinergic The anticholinergic toxidrometoxidrome

Hot as a hare

Dry as a bone

Red as a beet

Mad as a hatter

Blind as a bat

ToxidromesToxidromesAnticholinergicsAnticholinergics

““Red as a beet”- Flushed skinRed as a beet”- Flushed skin ““Hot as a hare”-HyperthermiaHot as a hare”-Hyperthermia ““Mad as a hatter”-PsychosisMad as a hatter”-Psychosis ““Dry as a bone”-Dry skin, Dry as a bone”-Dry skin,

urinary retentionurinary retention TachycardiaTachycardia MydriasisMydriasis

What toxidrome?What toxidrome?

disorientation Amphetamine

hallucinations Cocaine

Hallucinogenic hyperactive bowel Pseudoephedrine

panic PhencyclidineBenzodiazepenes

seizure Ephedrine

Toxidrome Hypertension

Tachycardia

Tachypnea

HallucinogenicHallucinogenicSympathomimetic Sympathomimetic toxidrometoxidrome



Hallucinogenic and

stimulants hyperactive bowel Pseudoephedrine


seizure Ephedrine


Tachycardia

Tachypnea



Hallucinogenic hyperactive bowel Pseudoephedrine


seizure Ephedrine


Tachycardia

Tachypnea

HallucinogenicHallucinogenicSympathomimetic Sympathomimetic toxidrometoxidrome

Sedative/hypnotic toxidromeSedative/hypnotic toxidrome

Sedative/hypnotic Sedative/hypnotic toxidrometoxidrome

Serotonergic syndromeSerotonergic syndrome

ToxidromesToxidromesSympathomimeticsSympathomimetics

HypertensionHypertension TachycardiaTachycardia Psychomotor AgitationPsychomotor Agitation HyperthermiaHyperthermia DiaphoresisDiaphoresis MydriasisMydriasis

Recognition of poisoningRecognition of poisoning

May be difficult because of non-specific symptoms

High index of suspicion - especially occult poisoning

history may be unreliable look for corroborative history - missing pills, empty

container

Course that a poison runs (toxidromes) ! - may help

Toxicology screening - helpful only in a few

Clinical manifestationsClinical manifestations

Very diverse and varied - depends on the poison

Clinical examination should be focused on the possible manifestations of common poisons in the geographical area

Clinical manifestationsClinical manifestations

Skin and mucosal damage

Neurotoxic manifestations

Cardiovascular manifestations

Metabolic consequences

Eye manifestations

Hepatic dysfunction

When do you consider When do you consider ICU?ICU?

Respiratory

Airway protection

Respiratory failure

Cardiovascular

Hypotension despite fluid challenge

Heart block, arrhythmias, QTc prolongation as in TCA

When do you consider When do you consider ICU?ICU?

Neurologic GCS < 8 (grade 3 and4) Seizures

Metabolic Hypoglycaemia Significant electrolyte abnormalities metabolic acidosis Hepatic failure Coagulopathy with bleeding

Goals of treatment

Goals of treatmentGoals of treatment

Reduce absorption of the toxin (xenobiotic)

Enhance elimination

Neutralise toxin

Reduce absorption of the toxin

Reduce absorptionReduce absorption

Removal from surface skin & eye Emesis induction Gastric lavage Activated charcoal administration & cathartics Dilution - milk/other drinks for corrosives Whole bowel irrigation Endoscopic or surgical removal of ingested

chemical


Skin decontamination Skin decontamination

– Important aspect – not to be Important aspect – not to be neglectedneglected

– Remove contaminated clothingRemove contaminated clothing

– Wash with soap and water (soaps Wash with soap and water (soaps containing 30% ethanol advocated)containing 30% ethanol advocated)

– However, no evidence for benefit However, no evidence for benefit even in OP poisoningeven in OP poisoning

Decontamination

Gastric decontaminationGastric decontamination

– Forced emesis if patient is awake by Forced emesis if patient is awake by gag stimulation or by ipecac(?)gag stimulation or by ipecac(?)

– Gastric lavageGastric lavage– Activated charcoal 1g/kg and MDAC Activated charcoal 1g/kg and MDAC

in some casesin some cases– Sorbitol as catharticSorbitol as cathartic– Whole bowel irrigationWhole bowel irrigation

IpecacIpecac

NO!!!!NO!!!! Had been previously been Had been previously been

recommended for administration at recommended for administration at home immediately following ingestionhome immediately following ingestion

No longer recommended in the AAP No longer recommended in the AAP policy statement - policy statement - Poison Treatment in Poison Treatment in the Homethe Home ( (PediatricsPediatrics Vol. 112 No. 5, Vol. 112 No. 5, November 2003)November 2003)

Why Not Ipecac?Why Not Ipecac? Variable percentage of removal of toxic Variable percentage of removal of toxic

medication medication In adult volunteers:In adult volunteers:51-83% removal (5 minutes after ingestion) 51-83% removal (5 minutes after ingestion) 2-59% removal (30 minutes after ingestion)2-59% removal (30 minutes after ingestion)

May cause persistent vomiting, lethargy, and May cause persistent vomiting, lethargy, and diarrheadiarrhea

Vomiting may preclude later administration of Vomiting may preclude later administration of oral antidotesoral antidotes

Why Not Ipecac?Why Not Ipecac?

Lethargy and vomiting together Lethargy and vomiting together increase risk of aspirationincrease risk of aspiration

Inappropriate use-following Inappropriate use-following ingestion of acid or lyeingestion of acid or lye

Misuse-children with eating Misuse-children with eating disordersdisorders

Misuse-Munchausen by proxy Misuse-Munchausen by proxy

Gastric LavageGastric Lavage

Early following ingestionEarly following ingestion Airway must be protectedAirway must be protected Use the largest available tube Use the largest available tube

(40 French) (40 French) Contraindicated in caustic Contraindicated in caustic

ingestions, hydrocarbons, ingestions, hydrocarbons, previous vomitingprevious vomiting

Reduce absorptionReduce absorption Gastric lavage

Gastric lavage decreases absorption by 42% if done 20 min and by 16% if performed at 60 min

Performed by first aspirating the stomach and then repetitively instilling & aspirating fluid

Left lateral position better - delays spont. absorption

No evidence that larger tube better Simplest, quickest & least expensive way - funnel Choice of fluid is tap water - 5-10 ml/kg Choice of fluid is NL SALIN for children


Gastric lavage

Preferrably done on awake patients Presence of an ET tube does not preclude

aspiration, though preferred if GCS is low

Activated CharcoalActivated CharcoalSingle DoseSingle Dose

Toxic ingestions that adhere to Toxic ingestions that adhere to charcoalcharcoal

Dose is 1 g/kg PO or NGTDose is 1 g/kg PO or NGT Administered with SorbitolAdministered with Sorbitol Airway must be protectedAirway must be protected Contraindicated in caustics, Contraindicated in caustics,

hydrocarbon, foreign body, ileus or hydrocarbon, foreign body, ileus or gastric perforationgastric perforation

Activated CharcoalActivated CharcoalMultiple DosesMultiple Doses

Large ingestionsLarge ingestions Drugs that undergo Drugs that undergo

enterohepatic circulationenterohepatic circulation Drugs with low VDrugs with low Vdd

Drugs with low protein bindingDrugs with low protein binding Drugs with long tDrugs with long t1/21/2

Activated CharcoalActivated CharcoalMultiple DosesMultiple Doses

Only the FIRST dose should be Only the FIRST dose should be administered with Sorbitoladministered with Sorbitol

Dose 1 g/kg PO or NGT Q6 x 24 Dose 1 g/kg PO or NGT Q6 x 24 hours or until charcoal is hours or until charcoal is passed in the stoolpassed in the stool

Which drugs do not adsorb to charcoal?Which drugs do not adsorb to charcoal?

LithiumLithium IronIron AlcoholsAlcohols AcidsAcids AlkalisAlkalis CyanideCyanide HydrocarbonsHydrocarbons

Whole Bowel IrrigationWhole Bowel Irrigation

Life threatening ingestionLife threatening ingestion Sustained-release toxinSustained-release toxin Prolonged absorption time of the toxinProlonged absorption time of the toxin Must protect the airwayMust protect the airway Contraindicated in caustic, hydrocarbon, Contraindicated in caustic, hydrocarbon,

foreign body, ileus, gastric perforationforeign body, ileus, gastric perforation

Whole Bowel IrrigationWhole Bowel IrrigationPolyethylene GlycolPolyethylene Glycol

Dose: up to 500 ml/hDose: up to 500 ml/h Continue until stool is clearContinue until stool is clear Patient may get bloated and Patient may get bloated and

vomitvomit Antiemetics (metoclopramide or Antiemetics (metoclopramide or

ondansetron) may be helpfulondansetron) may be helpful Monitor electrolytes closelyMonitor electrolytes closely

Toxins and their AntidotesToxins and their Antidotes

AcetaminophenAcetaminophen N-acetylcysteineN-acetylcysteine

Physostigmine

AtropineAtropine(muscarinic effects)(muscarinic effects)

PralidoximePralidoxime(nicotinic effects)(nicotinic effects)-controversial in -controversial in carbamate carbamate ingestionsingestions

AnticholinergicsAnticholinergics

Anticholinesterases/Anticholinesterases/ CholinergicsCholinergics


BenzodiazepinesBenzodiazepines

BotulismBotulism

Beta-blockersBeta-blockers

Calcium channel blockersCalcium channel blockers

Carbon monoxideCarbon monoxide

Cyanide, NitritesCyanide, Nitrites

FlumazenilFlumazenil

Botulinum antitoxinBotulinum antitoxin

GlucagonGlucagon

CalciumCalcium

Hyperbaric OHyperbaric O22, O, O22

Amil nitrit;Na Amil nitrit;Na nitrit(300mg/10ml); ;Sodium Na nitrit(300mg/10ml); ;Sodium Na thiosulfate(12.5g/50ml)thiosulfate(12.5g/50ml)


DigoxinDigoxin

Ethylene GlycolEthylene Glycol

HeparinHeparin

IronIron

IsoniazidIsoniazid

Digibind aka Digoxin Fab antibodiesDigibind aka Digoxin Fab antibodies

EthanolEthanol

ProtamineProtamine

DeferoxamineDeferoxamine

PyridoxinePyridoxine


LeadLead EDTA, BAL, DMSAEDTA, BAL, DMSA

EthanolEthanol

Methylene blueMethylene blue

NaloxoneNaloxone

NaHCO3NaHCO3

Vitamin KVitamin K

MethanolMethanol

MethemoglobinMethemoglobin

OpioidsOpioids

Tricyclic antidepressantsTricyclic antidepressants

Warfarin (Superwarfarins)Warfarin (Superwarfarins)

Enhance elimination

Enhance eliminationEnhance elimination

Increased elimination is possible only if

the drug is distributed predominantly in the ECF

has a low protein binding the induced rate of elimination is faster than

the normal rate hazards of having a longer time of exposure

to the drug are potentially fatal

Enhance eliminationEnhance elimination Methods

Keep a good urine output 150-200 ml/hr Alkalinisation of urine - clinical efficacy

accepted for salicylate & phenobarbital poisoning

Extracorporeal removal– Hemodialysis - Barbiturates, Salicylates,

Acetaminophen, Valproate, Alcohols, Glycols

– Hemoperfusion - theophylline, digitalis, lipid soluble drugs

Enhance EliminationEnhance EliminationMethodsMethods

Alkalinization and Urinary ion Alkalinization and Urinary ion trappingtrapping

HemodialysisHemodialysis

Charcoal hemoperfusionCharcoal hemoperfusion

Alkalinization/Urinary Ion Alkalinization/Urinary Ion TrappingTrapping

Effective for drugs that are excreted Effective for drugs that are excreted renallyrenally

The drugs must be either weak acids The drugs must be either weak acids or weak bases e.g. ASA and or weak bases e.g. ASA and PhenobarbitalPhenobarbital

HA HA H H++ +A +A--

pKa

At a Urine pH < pKa Non-ionized form*Not excreted in urine

At a Urine pH > pKa Ionized form*Excreted in urine

HemodialysisHemodialysis Low volume of distribution less than Low volume of distribution less than

1L/Kg1L/Kg Low protein bindingLow protein binding Low molecular weight less than 500 DAL. Low molecular weight less than 500 DAL. Also helpful in managing acidosis, Also helpful in managing acidosis,

electrolyte abnormalitieselectrolyte abnormalities Low fat solubilityLow fat solubility High Water Solubility High Water Solubility

Which drugs are high Which drugs are high dialyzable?dialyzable?

SalicylatesSalicylates Methanol and ethanolMethanol and ethanol LithiumLithium Ethylene glycolEthylene glycol AmphetaminesAmphetamines TheophyllineTheophylline VancomycinVancomycin

0

1

2

3

4

5

6Pt #1Pt #2

Hours

Li

mEq/ L

CVVHD following HD for Lithium poisoningHD started

CVVHD started CT-190 (HD)Multiflo-60both patientsBFR-pt #1 200 ml/minHD & CVVHD -pt # 2 325 ml/minHD & 200 ml/min

CVVHDPO4 Based dialysate at

2L/1.73m2/hr

Li Therapeutic range0.5-1.5 mEq/L

(p. brophy)

HemoperfusionHemoperfusion Blood is passed through a cartridge Blood is passed through a cartridge

containing charcoal or carboncontaining charcoal or carbon Drugs with low VdDrugs with low Vd Toxins can be larger than those Toxins can be larger than those

removed by hemodialysisremoved by hemodialysis Can be more protein bound than Can be more protein bound than

those cleared by hemodialysisthose cleared by hemodialysis Toxin must bind well to charcoalToxin must bind well to charcoal

Which drugs can be removed by Which drugs can be removed by hemoperfusion?hemoperfusion?

TheophyllineTheophylline PhenobarbitalPhenobarbital CarbamazepineCarbamazepine PhenytoinPhenytoin SalicylatesSalicylates ParaquateParaquate

Complications of Complications of HemoperfusionHemoperfusion

ThrombocytopeniaThrombocytopenia HypocalcemiaHypocalcemia LeukopeniaLeukopenia RigorsRigors

HEMOFILTRATIONHEMOFILTRATION optimal drug characteristics for optimal drug characteristics for

removal:removal: relative molecular mass less than the cut-relative molecular mass less than the cut-

off of the filter fibres (usually < 40,000)off of the filter fibres (usually < 40,000) small Vd (< 1 L/Kg)small Vd (< 1 L/Kg) single compartment kineticssingle compartment kinetics low endogenous clearance (< 4ml/Kg/min)low endogenous clearance (< 4ml/Kg/min)

(Pond, SM - Med J Australia 1991; 154: 617-(Pond, SM - Med J Australia 1991; 154: 617-622)622)

(p. brophy)

Continuous Detoxification methodsContinuous Detoxification methods CAVHF, CAVHD, CAVHP, CVVHF, CAVHF, CAVHD, CAVHP, CVVHF,

CVVHD, CVVHPCVVHD, CVVHP Indicated in cases where removal of Indicated in cases where removal of

plasma toxin is then replaced by plasma toxin is then replaced by redistributed toxin from tissueredistributed toxin from tissue

Can be combined with acute high Can be combined with acute high flux HDflux HD

(p. brophy)

Intoxicants amenable to Intoxicants amenable to HemofiltrationHemofiltration vancomycinvancomycin methanolmethanol procainamideprocainamide hirudinhirudin thalliumthallium lithiumlithium methotrexatemethotrexate

(p. brophy)

Plasmapheresis / Exchange Blood Plasmapheresis / Exchange Blood TransfusionsTransfusions Plasmapheresis Plasmapheresis (Seyffart G. Trans Am Soc Artif Intern (Seyffart G. Trans Am Soc Artif Intern

Organs 1982; 28:673)Organs 1982; 28:673)

role in intoxication not clearly establishedrole in intoxication not clearly established most useful for highly protein bound agentsmost useful for highly protein bound agents

Exchange Blood TransfusionsExchange Blood Transfusions Pediatric experience > than adultPediatric experience > than adult MethemoglobinemiaMethemoglobinemia overall very limited role in poisoningoverall very limited role in poisoning

(p. brophy)

SummarySummary Poisoning a common problem in our country

A high index of suspicion required to diagnose

Know common toxidrome

Don’t panic and follow a plan of action Decreasing absorption Enhancing elimination Neutralising toxins

Avoid potentially harmful Rxs - risk vs benefit

Thank you

Case Presentation 1

A 15 year old girl presents to the ED four A 15 year old girl presents to the ED four hours after taking 20 extra-strength (500 hours after taking 20 extra-strength (500 mg/tablet) Tylenol tablets. The ingestion mg/tablet) Tylenol tablets. The ingestion was prompted by a fight with her boyfriend was prompted by a fight with her boyfriend earlier that day. She has a history of an earlier that day. She has a history of an attempted suicide in the past. She is attempted suicide in the past. She is awake and alert with stable vital signs. awake and alert with stable vital signs. She complains of nausea and has had one She complains of nausea and has had one episode of vomiting. Physical exam is episode of vomiting. Physical exam is normal. Baseline labs show normal normal. Baseline labs show normal electrolytes, with normal LFTs, normal electrolytes, with normal LFTs, normal coags and a Tylenol level of 120 coags and a Tylenol level of 120 microgram/ml. microgram/ml.

What would you do?What would you do? A. Call psychiatry to evaluate the patient. A. Call psychiatry to evaluate the patient.

No No medical intervention is required.medical intervention is required. B. Administer 1g/kg of activated charcoal B. Administer 1g/kg of activated charcoal

with sorbitol every 6 hours and 17 with sorbitol every 6 hours and 17 doses of doses of oral N-acetylcysteine.oral N-acetylcysteine.

C. Administer one dose of activated C. Administer one dose of activated charcoal charcoal with sorbitol followed by with sorbitol followed by intravenous intravenous N-acetylcysteine for 21 N-acetylcysteine for 21 hours.hours.

D. Gastric lavage in an attempt to recover D. Gastric lavage in an attempt to recover pill pill fragments.fragments.

Acetaminophen PoisoningAcetaminophen Poisoning

Toxic dose: 150 mg/kg or a Toxic dose: 150 mg/kg or a total total dose of 7.5 g dose of 7.5 g

Toxic level: 150 microgram/ml Toxic level: 150 microgram/ml at 4 hoursat 4 hours

Antidote: N-acetylcysteineAntidote: N-acetylcysteine

Acetaminophen Acetaminophen MetabolismMetabolism

90% undergoes glucuronidation and 90% undergoes glucuronidation and sulfate conjugation in the liver to sulfate conjugation in the liver to harmless metabolites excreted in the harmless metabolites excreted in the kidneykidney

< 5%, together with some insignificant < 5%, together with some insignificant metabolites are excreted in the kidney metabolites are excreted in the kidney unchangedunchanged

Remainder undergoes oxidation by Remainder undergoes oxidation by the cyt-p450 system to N-acetyl-p-the cyt-p450 system to N-acetyl-p-benzoquinoneimine (NAPQI)benzoquinoneimine (NAPQI)

NAPQINAPQI

ElectrophileElectrophile

Covalently binds to hepatocytes Covalently binds to hepatocytes

Results in cell deathResults in cell death

Half life is about Half life is about

POTENTIAL TOXICITYPOTENTIAL TOXICITY

Acute: 7g (10g)Acute: 7g (10g)

Chronic: 4g per day (7g)Chronic: 4g per day (7g)

Susceptible patients Susceptible patients (alcoholics, ACs, INH)(alcoholics, ACs, INH) Similar risk for acute ingestionSimilar risk for acute ingestion Potential higher risk in chronic Potential higher risk in chronic

ingestions (4g)ingestions (4g)

Phases of ToxicityPhases of Toxicity I: (½-24 h):nausea, vomiting, diaphoresisI: (½-24 h):nausea, vomiting, diaphoresis

May be normalMay be normal II: (24-72 h): less nausea, vomiting; RUQ II: (24-72 h): less nausea, vomiting; RUQ

pain; LFTs and coags begin to risepain; LFTs and coags begin to rise III: (72-96 h): Coagulation abnormalities, III: (72-96 h): Coagulation abnormalities,

renal failure, encephalopathy, death renal failure, encephalopathy, death related to hepatic failurerelated to hepatic failure

IV: (4 d-2 wk):If stage III damage is IV: (4 d-2 wk):If stage III damage is reversible, resolution of hepatic reversible, resolution of hepatic dysfunctiondysfunction

N-ACETYLCYSTEINEN-ACETYLCYSTEINE Very effective – 100% within 8 hoursVery effective – 100% within 8 hours

Oral in U.S. – IV in EuropeOral in U.S. – IV in Europe

Dose: 140mg/kg load, 70mg/kg Q Dose: 140mg/kg load, 70mg/kg Q 4hrs4hrs Traditional – 72 hoursTraditional – 72 hours Short course – reassess at 20 hoursShort course – reassess at 20 hours

INTRAVENOUS NACINTRAVENOUS NAC

Oral preparation vs AcetadoteOral preparation vs Acetadote®®

Concern is anaphylacConcern is anaphylactoidtoid reactions reactions

Indications:Indications: Can’t tolerate oral NACCan’t tolerate oral NAC Contraindication to oral therapyContraindication to oral therapy Ongoing GI decon (coingestant)Ongoing GI decon (coingestant) Fulminant hepatic failure?Fulminant hepatic failure? Pregnant patient?Pregnant patient?

N-acetylcysteine (NAC) N-acetylcysteine (NAC) mechanismmechanism

Prevents binding of NAPQI to Prevents binding of NAPQI to hepatocyteshepatocytes

Reduces NAPQIReduces NAPQI Conjugates NAPQIConjugates NAPQI Increases sulfation Increases sulfation

metabolism***metabolism***

NACNAC

Must be administered within 8 hours Must be administered within 8 hours IV dose: 150 mg/kg infused over 60 IV dose: 150 mg/kg infused over 60

minutes; followed by a 4-hour infusion of minutes; followed by a 4-hour infusion of 50 mg/kg; followed by a 16-hour infusion 50 mg/kg; followed by a 16-hour infusion of 100 mg/kg; equivalent to a total dose of 100 mg/kg; equivalent to a total dose of 300 mg/kg infused over 21 hoursof 300 mg/kg infused over 21 hours

Oral dose: 140 mg/kg x 1 followed by Oral dose: 140 mg/kg x 1 followed by 70 mg/kg x 17 doses70 mg/kg x 17 doses

NACNAC

Smells like rotten eggsSmells like rotten eggs Oral formulation may need to be Oral formulation may need to be

given via NGTgiven via NGT Dilute with juiceDilute with juice Use metoclopramide or ondansetron Use metoclopramide or ondansetron

if not tolerated due to vomitingif not tolerated due to vomiting Use hydrocortisoe and antihistamin Use hydrocortisoe and antihistamin

in sensitvity casesin sensitvity cases

Review of case

A 15 year old girl presents to the ED four A 15 year old girl presents to the ED four hours after taking 20 extra-strength (500 hours after taking 20 extra-strength (500 mg/tablet) Tylenol tablets. The ingestion mg/tablet) Tylenol tablets. The ingestion was prompted by a fight with her boyfriend was prompted by a fight with her boyfriend earlier that day. She has a history of an earlier that day. She has a history of an attempted suicide in the past. She is attempted suicide in the past. She is awake and alert with stable vital signs. awake and alert with stable vital signs. She complains of nausea and has had one She complains of nausea and has had one episode of vomiting. Physical exam is episode of vomiting. Physical exam is normal. Baseline labs show normal normal. Baseline labs show normal electrolytes, with normal LFTs, normal electrolytes, with normal LFTs, normal coags and a Tylenol level of 120 coags and a Tylenol level of 120 microgram/ml. microgram/ml.

What would you do for our What would you do for our patient?patient? A. Call psychiatry to evaluate the patient. No A. Call psychiatry to evaluate the patient. No

medical intervention is required.medical intervention is required. B. Administer 1g/kg of activated charcoal B. Administer 1g/kg of activated charcoal with with

sorbitol every 6 hours and 17 doses of sorbitol every 6 hours and 17 doses of oral N-oral N-acetylcysteine.acetylcysteine.

C. Administer one dose of activated charcoal C. Administer one dose of activated charcoal with sorbitol followed by with sorbitol followed by intravenous intravenous N-N-acetylcysteine for 21 hours.acetylcysteine for 21 hours.

D. Gastric lavage in an attempt to recover pill D. Gastric lavage in an attempt to recover pill fragments.fragments.

The correct answer is:The correct answer is:

C. C. Administer one dose of Administer one dose of activated activated charcoal with charcoal with sorbitol followed sorbitol followed by by intravenous N-acetylcysteine intravenous N-acetylcysteine for 21 hours.for 21 hours.

Key PointsKey Points Despite the fact that our patient’s Tylenol Despite the fact that our patient’s Tylenol

level was only 120 microgram/ml at four level was only 120 microgram/ml at four hours and falls below the toxic level on the hours and falls below the toxic level on the nomogram, she must be treated with NAC. nomogram, she must be treated with NAC. She ingested a total of 10 g (20 tablets x She ingested a total of 10 g (20 tablets x 500 mg) which is > 7.5 g and toxic.500 mg) which is > 7.5 g and toxic.

NAC may be given orally or IV. NAC may be given orally or IV. IV NAC has only recently been approved IV NAC has only recently been approved

for use in the US.for use in the US.

Key PointsKey Points The administration of activated charcoal in The administration of activated charcoal in

Tylenol ingestion has been controversial as Tylenol ingestion has been controversial as it may interfere with it may interfere with oraloral NAC. NAC.

Some studies have shown decreased Some studies have shown decreased absorption of Tylenol when activated absorption of Tylenol when activated charcoal is given in a timely fashion.charcoal is given in a timely fashion.

Activated charcoal will not interfere with Activated charcoal will not interfere with administration of IV NAC and therefore administration of IV NAC and therefore may be given.may be given.

Key PointsKey Points

If activated charcoal is administered, If activated charcoal is administered, only one dose should be given.only one dose should be given.

For ingestions requiring administration For ingestions requiring administration of multiple doses of charcoal, only the of multiple doses of charcoal, only the first should be given with sorbitol. first should be given with sorbitol.

Gastric lavage is not likely to be Gastric lavage is not likely to be efficacious four hours following efficacious four hours following ingestion.ingestion.

IN THE NAME OF GOD. AN APPROACH TO A POISONED PATIENT DR. FAZEL GOUDARZI;TRAUMATO PATHOLOGIST AND...

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Transcript of IN THE NAME OF GOD. AN APPROACH TO A POISONED PATIENT DR. FAZEL GOUDARZI;TRAUMATO PATHOLOGIST AND...