in the name of god. an approach to a poisoned patient dr. fazel goudarzi;traumato pathologist and...
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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
Approach to the Poisoned Approach to the Poisoned PatientPatient
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
Approach to the Poisoned Approach to the Poisoned PatientPatient
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
Opiate toxidromeOpiate toxidrome
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
Common toxidromesCommon toxidromes
The cholinergic toxidromeThe cholinergic toxidrome
The cholinergic toxidromeThe cholinergic toxidrome
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
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
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
disorientation Amphetamine
hallucinations Cocaine
Hallucinogenic and
stimulants hyperactive bowel Pseudoephedrine
panic PhencyclidineBenzodiazepenes
seizure Ephedrine
Toxidrome Hypertension
Tachycardia
Tachypnea
disorientation Amphetamine
hallucinations Cocaine
Hallucinogenic hyperactive bowel Pseudoephedrine
panic PhencyclidineBenzodiazepenes
seizure Ephedrine
Toxidrome Hypertension
Tachycardia
Tachypnea
HallucinogenicHallucinogenicSympathomimetic Sympathomimetic toxidrometoxidrome
disorientation Amphetamine
hallucinations Cocaine
Hallucinogenic hyperactive bowel Pseudoephedrine
panic PhencyclidineBenzodiazepenes
seizure Ephedrine
Toxidrome Hypertension
Tachycardia
Tachypnea
HallucinogenicHallucinogenicSympathomimetic Sympathomimetic toxidrometoxidrome
disorientation Amphetamine
hallucinations Cocaine
Hallucinogenic hyperactive bowel Pseudoephedrine
panic PhencyclidineBenzodiazepenes
seizure Ephedrine
Toxidrome Hypertension
Tachycardia
Tachypnea
HallucinogenicHallucinogenicSympathomimetic Sympathomimetic toxidrometoxidrome
Common toxidromesCommon toxidromes
Sedative/hypnotic toxidromeSedative/hypnotic toxidrome
Sedative/hypnotic toxidromeSedative/hypnotic toxidrome
Sedative/hypnotic Sedative/hypnotic toxidrometoxidrome
Common toxidromesCommon toxidromes
Serotonergic syndromeSerotonergic syndrome
Serotonergic syndromeSerotonergic syndrome
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
Reduce absorptionReduce absorption
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
Reduce absorptionReduce absorption
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
Toxins and their AntidotesToxins and their Antidotes
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)
Toxins and their AntidotesToxins and their Antidotes
DigoxinDigoxin
Ethylene GlycolEthylene Glycol
HeparinHeparin
IronIron
IsoniazidIsoniazid
Digibind aka Digoxin Fab antibodiesDigibind aka Digoxin Fab antibodies
EthanolEthanol
ProtamineProtamine
DeferoxamineDeferoxamine
PyridoxinePyridoxine
Toxins and their AntidotesToxins and their Antidotes
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.