Chairman’s Rounds Chairman’s Rounds October 16, 2009;October 16, 2009;
15 year old with an 15 year old with an unintentional overdoseunintentional overdose
David H. Rubin, MD, FAAPDavid H. Rubin, MD, FAAPChairman and Program Director Chairman and Program Director
Department of Pediatrics Department of Pediatrics St. Barnabas HospitalSt. Barnabas Hospital
Professor of Clinical PediatricsProfessor of Clinical PediatricsAlbert Einstein College of MedicineAlbert Einstein College of Medicine
OBJECTIVESOBJECTIVES
• Epidemiology Epidemiology • ResuscitationResuscitation• DetoxificationDetoxification• Antidotes/ToxidromesAntidotes/Toxidromes• Case report: 15 year old Case report: 15 year old
with an unintentional with an unintentional overdose overdose
EPIDEMIOLOGYEPIDEMIOLOGY(Lapus, 2007)(Lapus, 2007)
• 2004 data from American Association 2004 data from American Association of Poison Control Centersof Poison Control Centers• 2.4 million exposures2.4 million exposures
• 1.9 million secondary to ingestion1.9 million secondary to ingestion
• 93% occurred in the home93% occurred in the home• Majority of calls to poison control centers Majority of calls to poison control centers
involve children < 6 years of ageinvolve children < 6 years of age• 27 fatalities in children < 6 years of age27 fatalities in children < 6 years of age
• 20 unintentional20 unintentional• 7 intentional7 intentional• 2.3% of all fatalities (n=1,183)2.3% of all fatalities (n=1,183)
EPIDEMIOLOGYEPIDEMIOLOGY (Watson et al, 2005)(Watson et al, 2005)
Children < 6 years of age, 2004:Children < 6 years of age, 2004:• Cosmetics and personal care productsCosmetics and personal care products• Cleaning substancesCleaning substances• AnalgesicsAnalgesics• TopicalsTopicals• Foreign bodiesForeign bodies• Cough and cold preparationCough and cold preparation• PlantsPlants• PesticidesPesticides• VitaminsVitamins• AntihistaminesAntihistamines• AntimicrobialsAntimicrobials• Gastrointestinal preparationsGastrointestinal preparations• Arts/crafts/office suppliesArts/crafts/office supplies• Electrolytes/mineralElectrolytes/mineral• Hormone related preparationsHormone related preparations
AMERICAN SOCIETY OF AMERICAN SOCIETY OF POISON CONTROL CENTERS – POISON CONTROL CENTERS –
20042004(Watson et al, 2005)(Watson et al, 2005)
Age:Age: < 6 years< 6 years 13-19 years13-19 years
Number of Number of DeathsDeaths
27 27 (23% of (23% of all all
pediatric pediatric deaths)deaths)
90 90 (77% of (77% of all pediatric all pediatric
deaths)deaths)
IntentionalIntentional 7 (26%)7 (26%) 70 (78%)70 (78%)
UnintentionUnintentionalal
20 (74%) 20 (74%) 20 (22%)20 (22%)
TOP 10 CAUSES OF DEATH IN TOP 10 CAUSES OF DEATH IN CHILDREN < 6 YEARS 1995-CHILDREN < 6 YEARS 1995-
1999 1999 (Abbruzzi and Stork, 2002)(Abbruzzi and Stork, 2002)
• Carbon monoxide inhalationCarbon monoxide inhalation• Hydrocarbon aspirationHydrocarbon aspiration• Opioid ingestionOpioid ingestion• Caustic (with and without hydrofluoric acid Caustic (with and without hydrofluoric acid
ingestion)ingestion)• Iron ingestionIron ingestion• Toxic alcohol ingestionToxic alcohol ingestion• Tricyclic antidepressant ingestionTricyclic antidepressant ingestion• Calcium channel blocker or beta-agonist Calcium channel blocker or beta-agonist
sustained release ingestionsustained release ingestion• Adrenergic ingestionAdrenergic ingestion• Salicylate ingestionSalicylate ingestion
NINE COMMON AGENTS THAT NINE COMMON AGENTS THAT KILL AT LOW DOSESKILL AT LOW DOSES
(Michael, 2004)(Michael, 2004)
• Calcium channel blockersCalcium channel blockers: bradycardia : bradycardia and hypotension; 1 - 10 mg tablet of and hypotension; 1 - 10 mg tablet of nifedipinenifedipine
• CamphorCamphor: respiratory depression and : respiratory depression and seizures; 15 mL of Vicks vapo-rub (700 seizures; 15 mL of Vicks vapo-rub (700 mg of camphor)mg of camphor)
• ClonidineClonidine: severe bradycardia; 0.1 mg : severe bradycardia; 0.1 mg • Tricyclic antidepressantsTricyclic antidepressants: cardiovascular : cardiovascular
and CNS toxicity; 10-20mg/kgand CNS toxicity; 10-20mg/kg• OpioidsOpioids: CNS and respiratory : CNS and respiratory
depression; 2.5 mg of hydrocodonedepression; 2.5 mg of hydrocodone
NINE COMMON AGENTS THAT NINE COMMON AGENTS THAT KILL AT LOW DOSESKILL AT LOW DOSES
(Michael, 2004)(Michael, 2004)
• LomotilLomotil: anticholinergic overdose : anticholinergic overdose (tachycardia, seizures, coma); ½ tablet(tachycardia, seizures, coma); ½ tablet
• Salicylates:Salicylates: cerebral edema, coma; ½ cerebral edema, coma; ½ teaspoon of wintergreen fatalteaspoon of wintergreen fatal
• SulfonylureasSulfonylureas: severe hypoglycemia; 1 : severe hypoglycemia; 1 tablettablet
• Toxic alcoholsToxic alcohols: cardiac and CNS : cardiac and CNS depression; 2.9mL of 95% ethylene depression; 2.9mL of 95% ethylene glycol has been fatalglycol has been fatal
RESUSCITATION AND RESUSCITATION AND DETOXIFICATIONDETOXIFICATION
RESUSCITATION/RESUSCITATION/STABILIZATION STABILIZATION
(Osterhoudt, 2006)(Osterhoudt, 2006)• AAirwayirway
• NOT PATENT?NOT PATENT? jaw lift, jaw thrust, oropharyngeal jaw lift, jaw thrust, oropharyngeal
airway, nasaopharyngeal airway, airway, nasaopharyngeal airway, endotracheal tubeendotracheal tube
• BBreathingreathing• NONE DETECTABLE?NONE DETECTABLE?
mouth/resuscitator to mask or tracheal mouth/resuscitator to mask or tracheal tube, rescue breathingtube, rescue breathing
• CCirculationirculation• NONE DETECTABLE?NONE DETECTABLE? external compression/ventilation, volume external compression/ventilation, volume
therapy, blood studies, secure therapy, blood studies, secure intravenousintravenous line and assess perfusion line and assess perfusion
RESUSCITATION/RESUSCITATION/STABILIZATION STABILIZATION
(Osterhoudt, 2006)(Osterhoudt, 2006)
• DDisability: level of consciousness isability: level of consciousness (AVPU or GCS), pupillary size, (AVPU or GCS), pupillary size, reactivityreactivity
• DDrugsrugs• OxygenOxygen• Dextrose 0.25-1 g/kg (10 or 25% solution)Dextrose 0.25-1 g/kg (10 or 25% solution)• Naloxone (IV, IM, SC): birth-20 kg: 0.1 Naloxone (IV, IM, SC): birth-20 kg: 0.1
mg/kg/dose; > 20 kg: 2 mg/kg/dose; ETT mg/kg/dose; > 20 kg: 2 mg/kg/dose; ETT dose is 2-10 times IV dose diluted in 3-5 dose is 2-10 times IV dose diluted in 3-5 mL saline followed by positive pressuremL saline followed by positive pressure
DDECONTAMINATIONECONTAMINATION (Osterhoudt, 2006)(Osterhoudt, 2006)
• Ocular Ocular saline lavage saline lavage• Skin Skin water, then soap and water, then soap and
waterwater• GastrointestinalGastrointestinal
• NotNot recommendedrecommended::• IpecacIpecac – may delay administration of – may delay administration of
charcoal, complications (aspiration, charcoal, complications (aspiration, diaphragmatic rupture)diaphragmatic rupture)
• Gastric lavageGastric lavage – size of tube often – size of tube often smaller than pillssmaller than pills
• CatharticsCathartics – electrolyte problems, no – electrolyte problems, no benefit in RCTbenefit in RCT
ACTIVATED CHARCOALACTIVATED CHARCOAL(Lapus, 2007)(Lapus, 2007)
• 1500 BC: use of charcoal in 1500 BC: use of charcoal in medicine in Egypt; used to absorb medicine in Egypt; used to absorb odor from rotting woundsodor from rotting wounds
• 450 BC: charcoal filters used to 450 BC: charcoal filters used to purify drinking waterpurify drinking water
• 1773: absorptive powers of 1773: absorptive powers of charcoal demonstratedcharcoal demonstrated
• 1963: Holt published study 1963: Holt published study showing benefit in specific showing benefit in specific ingestionsingestions
ACTIVATED CHARCOALACTIVATED CHARCOAL
• Used in water filters, medicines that selectively remove toxins, and chemical purification processes
• How does it work? • Carbon treated with oxygen resulting in
porous charcoal• Surface area of 300-2000 m2/g allows
liquids or gases to pass through and bind with the carbon
• Interaction with carbon required for absorption
• Large organic molecules absorbed better than smaller
ACTIVATED CHARCOAL ACTIVATED CHARCOAL NOTNOT RECOMMENDED RECOMMENDED
(Lapus, 2007)(Lapus, 2007)
• PP – Pesticides, petroleum – Pesticides, petroleum distillates, distillates, unprotected airway unprotected airway
• HH – Hydrocarbons, heavy metals, – Hydrocarbons, heavy metals, > 1h delay in administration > 1h delay in administration
• AA – Acids, alkali, alcohol, altered – Acids, alkali, alcohol, altered level level of consciousness, of consciousness, aspiration riskaspiration risk
• II – Iron, ileus, intestinal obstruction – Iron, ileus, intestinal obstruction• LL – Lithium, lack of gag reflex – Lithium, lack of gag reflex• SS – Solvents, seizures – Solvents, seizures
BEZOAR CAUSING SMALL BOWEL OBSTRUCTION AFTER REPEATED
ACTIVATED CHARCOAL ADMINISTRATION
ACTIVATED CHARCOALACTIVATED CHARCOAL (Osterhoudt, 2006)(Osterhoudt, 2006)
• Single dose activated charcoalSingle dose activated charcoal• 0.5-1 gm/kg, adolescents 50-100 grams 0.5-1 gm/kg, adolescents 50-100 grams
PO; maximum dose 100 grams PO; maximum dose 100 grams • More benefit if administered within 1 More benefit if administered within 1
hour of ingestion, but still good for hour of ingestion, but still good for poison which slows gastric motility poison which slows gastric motility (anticholinergic, opiates, salicylates) (anticholinergic, opiates, salicylates)
• Strongly consider for acetaminophen Strongly consider for acetaminophen overdose > 4 hours overdose > 4 hours
• Not recommended forNot recommended for: lithium, iron, : lithium, iron, alcohols, cyanide, acid/alkali, alcohols, cyanide, acid/alkali, hydrocarbonshydrocarbons
ACTIVATED CHARCOALACTIVATED CHARCOAL (Osterhoudt, 2006)(Osterhoudt, 2006)
• Multidose activated charcoalMultidose activated charcoal• 1 gram/kg q4-6 hours1 gram/kg q4-6 hours• After absorption, drugs will re-enter After absorption, drugs will re-enter
the gut by passive diffusion if the the gut by passive diffusion if the concentration there is lower than concentration there is lower than bloodblood
• MDAC maintains a concentration MDAC maintains a concentration gradient drawing the drug into the gut gradient drawing the drug into the gut for absorptionfor absorption
• Recommended forRecommended for:: theophylline, theophylline, phenobarbital, digoxin, salicylate, phenobarbital, digoxin, salicylate, tricyclic antidepressants, tricyclic antidepressants, carbamazepine, phenytoincarbamazepine, phenytoin
ACTIVATED CHARCOALACTIVATED CHARCOAL(Lapus, 2007)(Lapus, 2007)
• If vomiting, carefully consider NG If vomiting, carefully consider NG tube tube
• ContraindicationsContraindications• Unprotected airway and Unprotected airway and level of level of
consciousness IF not intubatedconsciousness IF not intubated• Increased risk of aspiration – eg Increased risk of aspiration – eg
hydrocarbons (especially low viscosity hydrocarbons (especially low viscosity kerosene, lighter fluid, lamp oil)kerosene, lighter fluid, lamp oil)
• Potential risk of seizures: clonidine, TCA’sPotential risk of seizures: clonidine, TCA’s• Complications: Complications:
• Most common: emesisMost common: emesis• Most serious: aspirationMost serious: aspiration
WHOLE BOWEL IRRIGATIONWHOLE BOWEL IRRIGATION(Erickson, 2005)(Erickson, 2005)
• Nonabsorbable, isotonic Nonabsorbable, isotonic polyethylene glycolpolyethylene glycol
• Toxins “pushed” through GI Toxins “pushed” through GI tract; prevents absorptiontract; prevents absorption
• Concentration gradient created Concentration gradient created - allowing absorbed toxin to - allowing absorbed toxin to diffuse back into GI tractdiffuse back into GI tract
• Use where toxins Use where toxins NOTNOT absorbed absorbed by charcoal by charcoal
WHOLE BOWEL IRRIGATIONWHOLE BOWEL IRRIGATION(Erickson, 2005)(Erickson, 2005)
• Recommended forRecommended for::• Iron tabletsIron tablets• Lead paint chipsLead paint chips• TheophyllineTheophylline• Crack vials/packetsCrack vials/packets• Button batteriesButton batteries• Sustained release calcium Sustained release calcium
channel blockers channel blockers
WHOLE BOWEL IRRIGATIONWHOLE BOWEL IRRIGATION(Am Acad Clin Tox, 2004)(Am Acad Clin Tox, 2004)
• Use nasogastric tube Use nasogastric tube • No dose-response studies upon which No dose-response studies upon which
to base dosing. However, to base dosing. However, recommended dosing schedule is: recommended dosing schedule is: • Children 9 months to 6 years: 500 mL/h Children 9 months to 6 years: 500 mL/h • Children 6-12 years: 1000 mL/h Children 6-12 years: 1000 mL/h • Adolescents and adults: 1500-2000 mL/h Adolescents and adults: 1500-2000 mL/h
• Continue until rectal effluent clearContinue until rectal effluent clear• Treatment extended based on Treatment extended based on
corroborative evidence of continued corroborative evidence of continued presence of toxins in gastrointestinal presence of toxins in gastrointestinal tract (e.g., radiographs or ongoing tract (e.g., radiographs or ongoing elimination of toxins) elimination of toxins)
WHOLE BOWEL IRRIGATION - WHOLE BOWEL IRRIGATION - CONTRAINDICATIONSCONTRAINDICATIONS
(Am Acad Clin Tox, 2004)(Am Acad Clin Tox, 2004)
• Bowel Bowel perforationperforation • Bowel Bowel obstruction obstruction • Clinically significant Clinically significant
gastrointestinal hemorrhage gastrointestinal hemorrhage • Ileus Ileus • Unprotected or compromised Unprotected or compromised
airway airway • Hemodynamic instability Hemodynamic instability • Uncontrollable intractable vomiting Uncontrollable intractable vomiting
WHOLE BOWEL IRRIGATION - WHOLE BOWEL IRRIGATION - COMPLICATIONSCOMPLICATIONS(Am Acad Clin Tox, 2004)(Am Acad Clin Tox, 2004)
• Nausea, vomiting, abdominal cramps, Nausea, vomiting, abdominal cramps, and bloating when WBI used to prepare and bloating when WBI used to prepare for colonoscopy and barium enema for colonoscopy and barium enema
• Insufficient clinical data for incidence of Insufficient clinical data for incidence of complications associated with use of complications associated with use of WBI WBI
• Nausea and vomiting may complicate Nausea and vomiting may complicate use of WBI use of WBI vomiting if patient treated with ipecac or vomiting if patient treated with ipecac or
ingested agent that produces vomiting ingested agent that produces vomiting • If compromised and unprotected airway, If compromised and unprotected airway,
high risk for pulmonary aspiration high risk for pulmonary aspiration
ENHANCED EXCRETIONENHANCED EXCRETION
• Urinary alkalinization Urinary alkalinization • Salicylate, phenobarbitalSalicylate, phenobarbital
• HemodialysisHemodialysis• Lithium, ethylene glycol, Lithium, ethylene glycol,
methanol, salicylatemethanol, salicylate• Charcoal hemoperfusion Charcoal hemoperfusion
• Theophylline, phenobarbital, Theophylline, phenobarbital, carbamazepine, procainamidecarbamazepine, procainamide
• PlasmapheresisPlasmapheresis• PhenytoinPhenytoin
ANTIDOTESANTIDOTESTOXIDROMESTOXIDROMESLABORATORYLABORATORY
ANTIDOTES IANTIDOTES I• AcetaminophenAcetaminophen nn-Acetylcysteine (NAC)-Acetylcysteine (NAC)• AnticholinergicAnticholinergic PhysostigminePhysostigmine• AnticholinesteraseAnticholinesterase AtropineAtropine• OrganophosphatesOrganophosphatesAtropine/pralidoximeAtropine/pralidoxime• CarbamateCarbamate Atropine/pralidoximeAtropine/pralidoxime• BenzodiazepineBenzodiazepine FlumazenilFlumazenil• Beta adrenergic blockerBeta adrenergic blocker GlucagonGlucagon• Calcium channel blockerCalcium channel blocker Calcium chloride/calcium Calcium chloride/calcium
gluconategluconate• BotulismBotulism Botulin antitoxin trivalent Botulin antitoxin trivalent
(A,B,E)(A,B,E)• Carbon monoxideCarbon monoxide OxygenOxygen• CyanideCyanide Amyl nitrateAmyl nitrate• DigitalisDigitalis Fab. antibodiesFab. antibodies• Ethylene glycolEthylene glycol Fomepizole (4-Methylpyrazole)Fomepizole (4-Methylpyrazole)• FluorideFluoride Calcium gluconateCalcium gluconate• Heavy MetalsHeavy Metals BALBAL• ArsenicArsenic BALBAL• MercuryMercury BAL, DMSABAL, DMSA
ANTIDOTES IIANTIDOTES II• IronIron DeferoxamineDeferoxamine• IsoniazidIsoniazid PyridoxinePyridoxine• LeadLead BAL, EDTA, penicillamine. DMSABAL, EDTA, penicillamine. DMSA• MethanolMethanol Fomepizole (4-Fomepizole (4-
Methylpyrazole)Methylpyrazole)• MethemoglobinMethemoglobin Methylene blueMethylene blue• Neuroleptic syndromeNeuroleptic syndrome DantroleneDantrolene• OpioidsOpioids NaloxoneNaloxone• Phenothiazine (dystonic)Phenothiazine (dystonic) DiphenhydramineDiphenhydramine• SulfonylureaSulfonylurea OctreotideOctreotide• Tricyclic antidepressantsTricyclic antidepressants Sodium bicarbonateSodium bicarbonate• Warfarin Warfarin Vitamin KVitamin K• Snakes, spidersSnakes, spiders::• Black widowBlack widow Antivenin, Black widow spiderAntivenin, Black widow spider• CoralCoral Antivenin, coralAntivenin, coral• CrotalineCrotaline Antivenin, crotalineAntivenin, crotaline• ElapidElapid Antivenin, elapidAntivenin, elapid
DIAGNOSISDIAGNOSIS
• HistoryHistory• Substance, how much, where, whenSubstance, how much, where, when• Regular/sustained releaseRegular/sustained release• Past illnesses/hospitalizationsPast illnesses/hospitalizations• AllergiesAllergies
• Physical examinationPhysical examination• Vital signsVital signs• Neurologic examNeurologic exam
SEDATIVE/ HYPNOTIC
ExamplesExamples Benzodiazepines, Benzodiazepines, barbiturates barbiturates
Mental Mental StatusStatus
Sedations, delirium, ataxiaSedations, delirium, ataxia
PupilsPupils Blurred vision (miosis or Blurred vision (miosis or mydriasis)mydriasis)
Vital SignsVital Signs Bradycardia, hypotension, Bradycardia, hypotension, hypothermiahypothermia
Physical Physical ExamExam
Decreased bowel sounds, Decreased bowel sounds, nystagmusnystagmus
TreatmentTreatment Decontamination, Decontamination, Supportive, Flumazenil Supportive, Flumazenil
(rarely)(rarely)
SYMPATHOMIMETIC
ExamplesExamples Cocaine, amphetaminesCocaine, amphetamines
Mental Mental StatusStatus
Restless, insomnia, Restless, insomnia, hallucinationshallucinations
PupilsPupils MydriasisMydriasis
Vital SignsVital Signs Tachycardia, hypertension, Tachycardia, hypertension, hyperthermiahyperthermia
Physical Physical ExamExam
Tremor, warm skin, Tremor, warm skin, diaphoresisdiaphoresis
TreatmentTreatment Benzodiazepines, Mixed Benzodiazepines, Mixed alpha/beta blockade, Treat alpha/beta blockade, Treat
MI, CVAMI, CVA
OPIATES
ExamplesExamples Heroin, morphine, Heroin, morphine, clonidineclonidine
Mental statusMental status Sedation, confusion, Sedation, confusion, euphoria, comaeuphoria, coma
PupilsPupils MiosisMiosis
Vital signsVital signs Shallow respirations, Shallow respirations, hypotension, hypotension,
bradycardia, hypothermiabradycardia, hypothermia
Phys examPhys exam Decreased bowel sounds, Decreased bowel sounds, hyporeflexiahyporeflexia
TreatmentTreatment Decontaminate, narcanDecontaminate, narcan
CHOLINERGIC
ExamplesExamples Organophosphates, Organophosphates, muscarinic mushrooms, muscarinic mushrooms,
nerve gasesnerve gases
Mental Mental StatusStatus
Altered mental status, Altered mental status, confusion, weakness, confusion, weakness,
drowsiness, comadrowsiness, coma
PupilsPupils MiosisMiosis
Vital SignsVital Signs Bradycardia, hypothermia, Bradycardia, hypothermia, tachypneatachypnea
Physical Physical ExamExam
Salivation, lacrimation, Salivation, lacrimation, urination, defecation urination, defecation
(SLUDGE)(SLUDGE)
TreatmentTreatment Decontaminate, atropine, Decontaminate, atropine, pralidoximepralidoxime
ANTICHOLINERGIC
ExamplesExamples Atropine, TCA, antihistamineAtropine, TCA, antihistamine
Mental Mental StatusStatus
Psychosis, delirium, Psychosis, delirium, seizures, comaseizures, coma
PupilsPupils MydriasisMydriasis
Vital SignsVital Signs Tachycardia, fever, Tachycardia, fever, hypertensionhypertension
Physical Physical ExamExam
Dry as a bone, blind as a Dry as a bone, blind as a bat, etc. depressed, bat, etc. depressed,
confusedconfused
TreatmentTreatment Decontaminate, treat Decontaminate, treat seizures, fever, seizures, fever, hypertension, hypertension,
benzodiazepinesbenzodiazepines
LABORATORYLABORATORY• Electrolytes, BUN, creatinineElectrolytes, BUN, creatinine
• Anion Gap = (Na+K)-(CL+HCOAnion Gap = (Na+K)-(CL+HCO33))• 8-14 is normal8-14 is normal• Elevated seen in “MUDPILES” Elevated seen in “MUDPILES”
• MMethanol, ethanol, uuremia, remia, DDKA, KA, pparaldehyde,araldehyde, iiron/ron/iisoniazid, soniazid, llactic acidosis (cyanide), actic acidosis (cyanide), eethanol/thanol/eethylene glycol, thylene glycol, ssalicylatealicylate
• [[(Calculated osmolality) – (Serum (Calculated osmolality) – (Serum osmolality)osmolality)]] = -9 to +5 (normal range) = -9 to +5 (normal range)
• Calculated osmolality=2Na + glucose/18 + Calculated osmolality=2Na + glucose/18 + BUN/2.8+ ethanol/4.6BUN/2.8+ ethanol/4.6
• Elevated with ethanol, isopropanol, methanol, Elevated with ethanol, isopropanol, methanol, ethylene glycol intoxicationethylene glycol intoxication
LABORATORYLABORATORY• ECGECG• Arterial blood gasArterial blood gas• Pregnancy testPregnancy test• ToxicologyToxicology
• QuantitativeQuantitative: acetaminophen, : acetaminophen, carbamazepine, carboxyhemoglobin, carbamazepine, carboxyhemoglobin, digoxin, ethanol, ethylene glycol, iron, digoxin, ethanol, ethylene glycol, iron, lead, lithium, methanol, lead, lithium, methanol, methemoglobin, phenobarbital, methemoglobin, phenobarbital, phenytoin, salicylate, theophylline, phenytoin, salicylate, theophylline, valproic acidvalproic acid
LABORATORYLABORATORY
• Common urine substance Common urine substance abuse screensabuse screens
• AmphetamineAmphetamine• BarbituratesBarbiturates• BenzodiazepineBenzodiazepine• CannabinoidsCannabinoids• CocaineCocaine• OpioidsOpioids• PhencyclidinePhencyclidine
ACETAMINOPHEN (APAP) ACETAMINOPHEN (APAP) TOXICITYTOXICITY
(Amer Assoc Poison Cntl Center, 2001)(Amer Assoc Poison Cntl Center, 2001)
• Total reported exposures: 57,516 Total reported exposures: 57,516 • Reported exposures, < 19 years: 40,774 Reported exposures, < 19 years: 40,774 • Unintentional overdoses: 35,705 Unintentional overdoses: 35,705 • Intentional overdoses: 20,002 Intentional overdoses: 20,002 • Total treated for the exposure: 24,934 Total treated for the exposure: 24,934 • Impact on health from the incident: Impact on health from the incident:
none, 15,029; minor, 6,223; moderate, none, 15,029; minor, 6,223; moderate, 3,138; major, 829; fatal: 1203,138; major, 829; fatal: 120
ACETAMINOPHEN OVERDOSE IN THE ACETAMINOPHEN OVERDOSE IN THE CALGARY HEALTH REGION BY AGE AND CALGARY HEALTH REGION BY AGE AND
SUICIDAL INTENT (1997–2002)SUICIDAL INTENT (1997–2002)
ACETAMINOPHEN (APAP) ACETAMINOPHEN (APAP) TOXICITYTOXICITY
Most common drug overdose at any ageMost common drug overdose at any age Target organ: liverTarget organ: liver Principle metabolism (>90%) by sulfation Principle metabolism (>90%) by sulfation
and glucoronidation - with renal excretionand glucoronidation - with renal excretion 5% metabolized by cytochrome P-450 to 5% metabolized by cytochrome P-450 to
toxic n-acteyl-p-benzoquinoneimine toxic n-acteyl-p-benzoquinoneimine (NAPQI) (NAPQI)
Toxicity produced by saturation of Toxicity produced by saturation of metabolic pathway with excess toxic metabolic pathway with excess toxic metabolite (NAPQI)metabolite (NAPQI)
Normally glutathione detoxifies the Normally glutathione detoxifies the metabolite; with overdose, glutathione is metabolite; with overdose, glutathione is depleted causing severe hepatic injury depleted causing severe hepatic injury (centrilobular necrosis)(centrilobular necrosis)
APAP TOXICITY - CLINICAL APAP TOXICITY - CLINICAL FINDINGSFINDINGS
Stage IStage I “Gastrointestinal” (24 “Gastrointestinal” (24 hours): anorexia, nausea, vomiting, hours): anorexia, nausea, vomiting, lethargy, diaphoresis, anion gap lethargy, diaphoresis, anion gap metabolic acidosismetabolic acidosis
Stage IIStage II “Latent” (24-48 hours): “Latent” (24-48 hours): patient may feel better, subclinical patient may feel better, subclinical increase in hepatic enzymesincrease in hepatic enzymes
Stage IIIStage III (>48 hours): progressive (>48 hours): progressive hepatic encephalopathy, clinical hepatic encephalopathy, clinical hepatitis, overt comahepatitis, overt coma
Stage IVStage IV (4-14 days): recovery(4-14 days): recovery
ACETAMINOPHEN (APAP) ACETAMINOPHEN (APAP) TOXICITY/LABORATORY TOXICITY/LABORATORY
EVALUATIONEVALUATION Toxic dose: usually > 150 mg/kg or > Toxic dose: usually > 150 mg/kg or >
7.5 grams7.5 grams Try to obtain at 4 hours post ingestionTry to obtain at 4 hours post ingestion Plot on nomogram – predictor of liver Plot on nomogram – predictor of liver
toxicitytoxicity NomogramNomogram
Not accurate for chronic ingestionNot accurate for chronic ingestion Not accurate for multiple doses/overdosesNot accurate for multiple doses/overdoses If level is > potential toxic line, additional If level is > potential toxic line, additional
workup neededworkup needed
DIFFERENTIAL DIFFERENTIAL DIAGNOSISDIAGNOSIS
• Amanita mushroomsAmanita mushrooms• HydrocarbonHydrocarbon• Heavy metalsHeavy metals• IsoniazidIsoniazid• Non steroidal anti-inflammatoryNon steroidal anti-inflammatory• Erythromycin estolateErythromycin estolate• Vitamin AVitamin A• SteroidsSteroids
APAP TOXICITY APAP TOXICITY MANAGEMENTMANAGEMENT
DecontaminationDecontamination• Activated charcoal: may give up to 4 hours Activated charcoal: may give up to 4 hours
post ingestion; however need 2 hour post ingestion; however need 2 hour separation between charcoal and antidoteseparation between charcoal and antidote
Antidote: NAC (Antidote: NAC (n-acetylcysteinen-acetylcysteine))• Sulfhydryl donor to increase glutathione Sulfhydryl donor to increase glutathione
synthesis or bind with NAPQIsynthesis or bind with NAPQI• Indications: Indications: any level above nomogram any level above nomogram
lineline• Optimal use: within 8 hours of ingestion - Optimal use: within 8 hours of ingestion -
but still may be useful > 24 hrs but still may be useful > 24 hrs • Oral dose: 140 mg/kg, then 70 mg/kg q4h x Oral dose: 140 mg/kg, then 70 mg/kg q4h x
17 doses (17 doses (may dilute with cola or juice)may dilute with cola or juice)
CONSIDERATIONS FOR IV CONSIDERATIONS FOR IV NAC NAC
(Marzulo, 2005)(Marzulo, 2005)• 20 hours of 300 mg/kg (cumulative) for 10 20 hours of 300 mg/kg (cumulative) for 10
hourshours• Antihistamine therapy helpful in patients who Antihistamine therapy helpful in patients who
experience “anaphylactoid reactions” (rash, experience “anaphylactoid reactions” (rash, urticaria, pruritis) to IV NACurticaria, pruritis) to IV NAC
• Recent reports of deaths secondary to IV NAC; Recent reports of deaths secondary to IV NAC; no overwhelming support to automatically no overwhelming support to automatically choose IV over PO NAC – decide on case by choose IV over PO NAC – decide on case by case basiscase basis
• Standard IV dosing caused hyponatremia and Standard IV dosing caused hyponatremia and secondary seizures because of excess free secondary seizures because of excess free water; adjustment for pediatric patients has water; adjustment for pediatric patients has been madebeen made• Dilute 20% NAC to final concentration of 40 mg/ml Dilute 20% NAC to final concentration of 40 mg/ml
(see chart)(see chart)
UDATE ON APAP UDATE ON APAP POISONING POISONING (White, PedEmergCare, 2006)(White, PedEmergCare, 2006)
• Recent FDA revisions (2006) extended the Recent FDA revisions (2006) extended the loading dose infusion time from 15 to 60 loading dose infusion time from 15 to 60 minutes – making it a 21 hour infusionminutes – making it a 21 hour infusion
• PediatricPediatric: see revised dosing; : see revised dosing; anaphylactoid reactions usually occur anaphylactoid reactions usually occur during loading doseduring loading dose
• AdultAdult: : • 150mg/kg in 200 mL of 5% dextrose for 150mg/kg in 200 mL of 5% dextrose for
60 minutes, followed by 60 minutes, followed by • 50 mg/kg in 500 mL of 5% dextrose for 4 50 mg/kg in 500 mL of 5% dextrose for 4
hours and hours and • 100 mg/kg in 1000 mL 5% dextrose for 100 mg/kg in 1000 mL 5% dextrose for
16 hours16 hours
RECENT LITERATURERECENT LITERATURE
• James et al. Predictors of outcome after James et al. Predictors of outcome after acetaminophen poisoning in children acetaminophen poisoning in children and adolescents (2002)and adolescents (2002)• Retrospective analysis of 10 years of Retrospective analysis of 10 years of
admissions for acute acetaminophen admissions for acute acetaminophen toxicitytoxicity
• Best predictor of low risk of hepatotoxicity Best predictor of low risk of hepatotoxicity was normal values for PT, AST or ALT within was normal values for PT, AST or ALT within 48 hours of ingestion48 hours of ingestion
• Authors concluded inpatient stay of 48 Authors concluded inpatient stay of 48 hours justified post ingestion of hours justified post ingestion of acetaminophenacetaminophen
RECENT LITERATURERECENT LITERATURE• Kanter MK. Comparison of oral and IV Kanter MK. Comparison of oral and IV
acetylcysteine in the treatment of acetylcysteine in the treatment of acetaminophen poisoning (2006)acetaminophen poisoning (2006)• Consider efficacy, safety, cost; both equally Consider efficacy, safety, cost; both equally
effectiveeffective• IV prep problems: anaphylactoid reactions in IV prep problems: anaphylactoid reactions in
3-6% of patients, dosing errors, hypoNa, very 3-6% of patients, dosing errors, hypoNa, very expensiveexpensive
• Oral prep: strongly consider in those with Oral prep: strongly consider in those with history of asthma or atopyhistory of asthma or atopy
• Most important: severity of toxicity, time Most important: severity of toxicity, time interval between ingestion and treatmentinterval between ingestion and treatment
• If ingestion > 10 hours or underlying If ingestion > 10 hours or underlying reasons preventing oral use, use IV prepreasons preventing oral use, use IV prep
RECENT LITERATURERECENT LITERATURE
• Yarema et al. Comparison of the 20 hr IV Yarema et al. Comparison of the 20 hr IV and 72 hr PO protocols for treatment of and 72 hr PO protocols for treatment of acute acetaminophen toxicityacute acetaminophen toxicity• Of 4 ,048 patients analyzed, 2,086 in the 20 Of 4 ,048 patients analyzed, 2,086 in the 20
hour and 1,962 in the 72 hour groupshour and 1,962 in the 72 hour groups• No risk difference when between groups No risk difference when between groups
when treatment was started 12-18 hours when treatment was started 12-18 hours after ingestionafter ingestion
• Anaphylactoid reactions: IV 148/2,086 (7.1%); Anaphylactoid reactions: IV 148/2,086 (7.1%); • Risk of hepatotoxicity favored 20 hr protocol Risk of hepatotoxicity favored 20 hr protocol
for those presenting early and the 72 hour for those presenting early and the 72 hour protocol for those presenting lateprotocol for those presenting late
COMPETENCY ISSUESCOMPETENCY ISSUES• Medical Knowledge: treatment of poisoningMedical Knowledge: treatment of poisoning• Patient Care: careful history taking is criticalPatient Care: careful history taking is critical• System Based Practice: rapid lab turnaround System Based Practice: rapid lab turnaround
and recognition of potential for liver and recognition of potential for liver transplanttransplant
• Practice Based Learning and Improvement: Practice Based Learning and Improvement: use literature to guide treatment optionsuse literature to guide treatment options
• Interpersonal and Communication skills: Interpersonal and Communication skills: explain illness and risk to familyexplain illness and risk to family
• Professionalism: caution regarding sensitivity Professionalism: caution regarding sensitivity toward patient and family with any ingestiontoward patient and family with any ingestion
SUMMARYSUMMARY• ABC’s for unstable patient with unknown ABC’s for unstable patient with unknown
ingestioningestion• DecontaminationDecontamination• Activated charcoal, WBI when indicatedActivated charcoal, WBI when indicated
• Focused history, physical exam, can Focused history, physical exam, can someone bring in a sample?someone bring in a sample?
• ToxidromesToxidromes• AntidotesAntidotes• Follow acetaminophen levels as guideline Follow acetaminophen levels as guideline
for toxicityfor toxicity• Strongly consider PO NAC for children – Strongly consider PO NAC for children –
especially is history of asthma/atopy; if especially is history of asthma/atopy; if vomiting need to consider IV prepvomiting need to consider IV prep
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