Poisoning and Drug Overdose - Olson1 PDF

Poisoning&DrugOverdose,6e>
Chapter1.EmergencyEvaluationand
Treatment
KentR.Olson,MD
EmergencyEvaluationandTreatment
Eventhoughtheymaynotappeartobeacutelyill,allpoisonedpatientsshouldbetreatedasifthey
haveapotentiallylifethreateningintoxication.FigureI1providesachecklistofemergency
evaluationandtreatmentprocedures.Moredetailedinformationonthediagnosisandtreatmentfor
eachemergencystepisreferencedbypageandpresentedimmediatelyafterthechecklist.
FigureI1.
Checklistofemergencyevaluationandtreatmentprocedures.
Whentreatingsuspectedpoisoningcases,quicklyreviewthechecklisttodeterminethescopeof
appropriateinterventionsandbeginneededlifesavingtreatment.Iffurtherinformationisrequired
foranystep,turntothecitedpagesforadetaileddiscussionofeachtopic.Althoughthechecklistis
presentedinasequentialformat,manystepsmaybeperformedsimultaneously(eg,airway
management,naloxoneanddextroseadministration,andgastriclavage).
Airway
I.Assessment.Themostcommonfactorcontributingtodeathfromdrugoverdoseorpoisoningis
lossofairwayprotectivereflexeswithsubsequentairwayobstructioncausedbytheflaccid
tongue,pulmonaryaspirationofgastriccontents,orrespiratoryarrest.Allpoisonedpatients
shouldbesuspectedofhavingapotentiallycompromisedairway.
A.Patientswhoareawakeandtalkingarelikelytohaveintactairwayreflexesbutshouldbe
monitoredcloselybecauseworseningintoxicationcanresultinrapidlossofairwaycontrol.
B.Inalethargicorobtundedpatient,theresponsetostimulationofthenasopharynx(eg,
doesthepatientreacttoplacementofanasalairway?)orthepresenceofaspontaneous
coughreflexmayprovideanindirectindicationofthepatient'sabilitytoprotecttheairway.
Ifthereisanydoubt,itisbesttoperformendotrachealintubation(seebelow).
II.Treatment.Optimizetheairwaypositionandperformendotrachealintubationifnecessary.Early
useofnaloxone(SeeNaloxoneandNalmefene)orflumazenil(SeeFlumazenil)mayawakena
patientintoxicatedwithopioidsorbenzodiazepines,respectively,andobviatetheneedfor
endotrachealintubation.(Note:Flumazenilisnotrecommendedexceptinveryselect
circumstances,asitsusemayprecipitateseizures.)
A.Positionthepatientandcleartheairway.
1.Optimizetheairwaypositiontoforcetheflaccidtongueforwardandmaximizethe
airwayopening.Thefollowingtechniquesareuseful.Caution:Donotperformneck
manipulationifyoususpectaneckinjury.
a.Placetheneckandheadinthesniffingposition,withtheneckflexed
forwardandtheheadextended.
b.Applythejawthrustmaneuvertocreateforwardmovementofthetongue
withoutflexingorextendingtheneck.Pullthejawforwardbyplacingthefingers
ofeachhandontheangleofthemandiblejustbelowtheears.(Thismotion
alsocausesapainfulstimulustotheangleofthejaw,theresponsetowhich
reflectsthepatient'sdepthofcoma.)
c.Placethepatientinaheaddown,leftsidedpositionthatallowsthetongueto
fallforwardandsecretionsorvomitustodrainoutofthemouth.
2.Iftheairwayisstillnotpatent,examinetheoropharynxandremoveanyobstruction
orsecretionsbysuction,byasweepwiththefinger,orwithMagillforceps.
3.Theairwaycanalsobemaintainedwithartificialoropharyngealor
nasopharyngealairwaydevices.Thesedevicesareplacedinthemouthornoseto
liftthetongueandpushitforward.Theyareonlytemporarymeasures.Apatientwho
cantolerateanartificialairwaywithoutcomplaintprobablyneedsanendotracheal
tube.
B.Performendotrachealintubationifpersonneltrainedintheprocedureareavailable.
Intubationofthetracheaprovidesthemostreliableprotectionoftheairway,preventing
obstructionandreducingtheriskforpulmonaryaspirationofgastriccontents,aswellas
allowingmechanicallyassistedventilation.However,itisnotasimpleprocedureand
shouldbeattemptedonlybythosewithtrainingandexperience.Complicationsinclude
vomitingwithpulmonaryaspirationlocaltraumatotheoropharynx,nasopharynx,and
larynxinadvertentintubationoftheesophagusoramainstembronchusandfailureto
intubatethepatientafterrespiratoryarresthasbeeninducedbyaneuromuscularblocker.
Therearetworoutesforendotrachealintubation:nasotrachealandorotracheal.
1.Nasotrachealintubation.Innasotrachealintubation,asoft,flexibletubeispassed
throughthenoseandintothetracheabyusingablindtechnique(FigureI2A).
FigureI2.
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Tworoutesforendotrachealintubation.A:Nasotrachealintubation.B:Orotracheal
intubation.
a.Advantages
1.Itmaybeperformedinaconsciousorsemiconsciouspatientwithoutthe
needforneuromuscularparalysis.
2.Onceplaced,itisusuallybettertoleratedthananorotrachealtube.
b.Disadvantages
1.Perforationofthenasalmucosawithepistaxis.
2.Stimulationofvomitinginanobtundedpatient.
3.Patientmustbebreathingspontaneously.
4.Anatomicallymoredifficultininfantsbecauseoftheiranteriorepiglottis.
2.Orotrachealintubation.Inorotrachealintubation,thetubeispassedthroughthe
patient'smouthintothetracheaunderdirectvision(FigureI2B)orwiththeaidofa
bougie.
a.Technique
b.Advantages
1.Performedunderdirectvision,makingaccidentalesophagealintubation
lesslikely.
2.Insignificantriskforbleeding.
3.Patientneednotbebreathingspontaneously.
4.Highersuccessratethanthatachievedviathenasotrachealroute.
c.Disadvantages
1.Frequentlyrequiresneuromuscularparalysis,creatingariskforfatal
respiratoryarrestifintubationisunsuccessful.
2.Requiresneckmanipulation,whichmaycausespinalcordinjuryifthe
patienthasalsohadnecktrauma.
C.Extraglotticairwaydevices.Theroleofneweradvancedairwayequipment,suchasthe
laryngealmaskairway(LMA),inpatientswithpoisoningordrugoverdoseisnotknown
althoughthesedevicesareeasiertoinsertthanendotrachealtubes,especiallyinsome
patientswithdifficultairways,theydonotprovideadequateprotectionagainstpulmonary
aspirationofgastriccontents,andtheycannotbeusedinpatientswithlaryngealedemaor
laryngospasm.
FigureI2.
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Tworoutesforendotrachealintubation.A:Nasotrachealintubation.B:Orotrachealintubation.
Breathing
Alongwithairwayproblems,breathingdifficultiesarethemajorcauseofmorbidityanddeathin
patientswithpoisoningordrugoverdose.Patientsmayhaveoneormoreofthefollowing
complications:ventilatoryfailure,hypoxia,andbronchospasm.
I.Ventilatoryfailure
A.Assessment.Ventilatoryfailurehasmultiplecauses,includingfailureoftheventilatory
muscles,centraldepressionofrespiratorydrive,andseverepneumoniaorpulmonary
edema.Examplesofdrugsandtoxinsthatcauseventilatoryfailureandthecausative
mechanismsarelistedinTableI1.
TableI1SelectedDrugsandToxinsCausingVentilatoryFailurea
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Paralysisofventilatorymuscles Depressionofcentralrespiratorydrive
Botulinumtoxin(botulism) Antihistamines
Neuromuscularblockers Barbiturates
Nicotine Clonidineandothersympatholyticagents
Organophosphatesandcarbamates Ethanolandalcohols
Saxitoxin(redtide) Gammahydroxybutyrate(GHB)
Snakebite Opioids
Strychnineandtetanus(musclerigidity) Phenothiazinesandantipsychoticdrugs
Tetrodotoxin Sedativehypnotics
Warfarenervegases Tricyclicantidepressants
aAdaptedinpart,withpermission,fromOlsonKR,PentelPR,KellyMT:Physical
assessmentanddifferentialdiagnosisofthepoisonedpatient.MedToxicol19872:52.
B.Complications.Ventilatoryfailureisthemostcommoncauseofdeathinpoisoned
patients.
1.Hypoxiamayresultinbraindamage,cardiacdysrhythmias,andcardiacarrest.
2.Hypercarbiaresultsinacidosis,whichmaycontributetodysrhythmias,especiallyin
patientswithsalicylateortricyclicantidepressantoverdoses.
C.Differentialdiagnosis.Ruleoutthefollowing:
1.Bacterialorviralpneumonia.
2.Viralencephalitisormyelitis(eg,polio).
3.Traumaticorischemicspinalcordorcentralnervoussystem(CNS)injury.
4.Tetanus,causingrigidityofchestwallmuscles.
5.Pneumothorax.
D.Treatment.Obtainmeasurementsofthearterialbloodgases.Quicklyestimatethe
adequacyofventilationfromthePco2levelobtundationwithanelevatedorrisingPco2
(eg,>60mmHg)indicatesaneedforassistedventilation.Donotwaituntilthepatientis
apneicoruntilthePco2isabove60mmtobeginassistedventilation.
1.Assistbreathingmanuallywithabagvalvemaskdeviceorbagvalveendotracheal
tubedeviceuntilthemechanicalventilatorisreadyforuse.
2.Ifnotalreadyaccomplished,performendotrachealintubation.
3.Programtheventilatorfortidalvolume(usually15mL/kg),rate(usually1215
breaths/min),andoxygenconcentration(usually3035%tostart).Monitorthe
patient'sresponsetotheventilatorsettingsfrequentlybyobtainingarterialbloodgas
values.Note:Insalicylatepoisonedpatientswithsevereacidosisandmarked
compensatorytachypnea,theventilatorshouldbeprogrammedtomatchthe
patient'shighminuteventilation.Otherwise,anyriseinthepatient'sPco2and
consequentfallinbloodpHcandramaticallyincreasetissuelevelsofsalicylate,with
disastrousconsequences.
a.Ifthepatienthassomespontaneousventilation,themachinecanbesetto
allowthepatienttobreathespontaneouslywithonlyintermittentmandatory
ventilation(usually1012breaths/min).
b.Iftheendotrachealtubehasbeenplacedonlyforairwayprotection,thepatient
canbelefttobreatheentirelyspontaneouslywithblowbyoxygenmist(T
piece).
II.Hypoxia
A.Assessment.ExamplesofdrugsortoxinscausinghypoxiaarelistedinTableI2.Hypoxia
canbecausedbythefollowingconditions:
TableI2SelectedCausesofHypoxiaa
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Pneumoniaornoncardiogenicpulmonary
Inertgases
edema
Carbondioxide Aspirationofgastriccontents
Methaneandpropane Aspirationofhydrocarbons
Nitrogen Chlorineandotherirritantgases
Cardiogenicpulmonaryedema Cocaine
Betareceptorantagonists Ethchlorvynol(IVandoral)
Quinidine,procainamide,and
Ethyleneglycol
disopyramide
Tricyclicantidepressants Mercuryvapor
Verapamil Metalfumes(metalfumesfever)
Cellularhypoxia Nitrogendioxide
Carbonmonoxide Opioids
Cyanide Paraquat
Hydrogensulfide Phosgene
Methemoglobinemia Salicylates
Sulfhemoglobinemia Sedativehypnoticdrugs
Smokeinhalation
aSeealsoTableI1.
1.Insufficientoxygeninambientair(eg,displacementofoxygenbyinertgases).
2.Disruptionofoxygenabsorptionbythelung(eg,resultingfrompneumoniaor
pulmonaryedema).
a.Pneumonia.Themostcommoncauseofpneumoniainoverdosedpatientsis
pulmonaryaspirationofgastriccontents.Pneumoniamayalsobecausedby
theIVinjectionofforeignmaterialorbacteria,aspirationofpetroleum
distillates,orinhalationofirritantgases.
b.Pulmonaryedema.Allagentsthatcancausechemicalpneumonia(eg,irritant
gasesandhydrocarbons)canalsocausepulmonaryedema.Thisusually
involvesanalterationofpermeabilityinpulmonarycapillaries,resultingin
noncardiogenicpulmonaryedema(acuterespiratorydistresssyndrome
[ARDS]).Innoncardiogenicpulmonaryedema,thepulmonarycapillarywedge
pressure(reflectingfillingpressureintheleftventricle)isusuallynormalorlow.
Incontrast,cardiogenicpulmonaryedemacausedbycardiacdepressant
drugsischaracterizedbylowcardiacoutputwithelevatedpulmonarywedge
pressure.
3.Cellularhypoxia,whichmaybepresentdespiteanormalarterialbloodgasvalue.
a.Carbonmonoxidepoisoning(SeeCarbonmonoxide)and
methemoglobinemia(SeeMethemoglobinemia)mayseverelylimitoxygen
bindingtohemoglobin(andthereforetheoxygencarryingcapacityofblood)
withoutalteringthePo2becauseroutinebloodgasdeterminationmeasures
dissolvedoxygenintheplasmabutdoesnotmeasureactualoxygencontent.
Insuchcases,onlythedirectmeasurementofoxygensaturationwithaco
oximeter(notitscalculationfromthePo2)willrevealdecreasedoxyhemoglobin
saturation.Note:Conventionalpulseoximetrygivesfalselynormalor
inaccurateresultsandisnotreliable.Anewerpulseoximetrydevice(the
Masimopulsecooximeter)canestimatecarboxyhemoglobinand
methemoglobinconcentrations,butitsaccuracyandsensitivityareuncertain.
b.Cyanidepoisoning(SeeCyanide)andhydrogensulfidepoisoning(See
HydrogenSulfide)interferewithcellularoxygenutilization,resultingin
decreasedoxygenuptakebythetissues,andmaycauseabnormallyhigh
venousoxygensaturation.
B.Complications.Significantorsustainedhypoxiamayresultinbraindamageandcardiac
dysrhythmias.
1.Erroneoussampling(eg,inadvertentlymeasuringvenousbloodgasesratherthan
arterialbloodgases).
2.Bacterialorviralpneumonia.
3.Pulmonarycontusioncausedbytrauma.
4.Acutemyocardialinfarctionwithpumpfailure.
D.Treatment
1.Correcthypoxia.Administersupplementaloxygenasindicated,basedonarterial
Po2.Intubationandassistedventilationmayberequired.
a.Ifcarbonmonoxidepoisoningissuspected,give100%oxygenandconsider
hyperbaricoxygen(SeeOxygenandHyperbaricOxygen).
b.Seealsotreatmentguidesforcyanide(SeeCyanide),hydrogensulfide(See
HydrogenSulfide),andmethemoglobinemia(SeeMethemoglobinemia).
2.Treatpneumonia.Obtainsputumsamplesandinitiateappropriateantibiotictherapy
whenthereisevidenceofinfection.
3.Treatpulmonaryedema.
a.Avoidexcessivefluidadministration.Assessmentofvolumestatusby
ultrasoundorpulmonaryarterycannulationandwedgepressure
measurementsmaybenecessarytoguidefluidtherapy.
b.AdministersupplementaloxygentomaintainaPo2ofatleast6070mmHg.
Endotrachealintubationandtheuseofpositiveendexpiratorypressure
(PEEP)ventilationmaybenecessarytomaintainadequateoxygenation.
III.Bronchospasm
A.Assessment.ExamplesofdrugsandtoxinsthatcausebronchospasmarelistedinTable
I3.Bronchospasmmayresultfromthefollowing:
TableI3SelectedDrugsandToxinsCausingBronchospasm
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Betareceptorantagonists Isocyanates
Brevetoxin Organophosphatesandotheranticholinesterases
Chlorineandotherirritantgases Particulatedusts
Drugscausingallergicreactions Smokeinhalation
Hydrocarbonaspiration Sulfites(eg,infoods)
1.Directirritantinjuryfromtheinhalationofgasesorpulmonaryaspirationof
petroleumdistillatesorstomachcontents.
2.Pharmacologiceffectsoftoxins(eg,organophosphateorcarbamateinsecticidesor
betaadrenergicantagonists).
3.Hypersensitivityorallergicreactions.
B.Complications.Severebronchospasmmayresultinhypoxiaandventilatoryfailure.
Exposuretohighconcentrationsofirritantgasescanleadtoasthma(reactiveairway
dysfunctionsyndrome[RADS]).
1.Asthmaorotherpreexistingbronchospasticdisorders.
2.Stridorcausedbyupperairwayinjuryandedema(progressiveairwayedemamay
resultinacuteairwayobstruction).
3.Airwayobstructionbyaforeignbody.
D.Treatment
1.Administersupplementaloxygen.Assistventilationandperformendotracheal
intubationifneeded.
2.Removethepatientfromthesourceofexposuretoanyirritantgasorotheroffending
agent.
3.Immediatelydiscontinueanybetaadrenergicantagonisttreatment.
4.Administerbronchodilators:
a.Aerosolizedbeta2receptorstimulant(eg,albuterol[2.55mg]innebulizer).
Repeatasneededorgive515mgasacontinuousnebulizertreatmentover1
hour(children:0.30.5mg/kg/h).
b.Aerosolizedipratropiumbromide,0.5mgevery46hours,especiallyif
excessivecholinergicstimulationissuspected.
c.Forreactiveairways,considerinhaledororalsteroids.
5.Forpatientswithbronchospasmandbronchorrheacausedbyorganophosphate,
carbamate,orothercholinesteraseinhibitorpoisoning,giveatropine(SeeAtropine
andGlycopyrrolate)IV.Ipratropiumbromide(seeItem4.babove)mayalsobe
helpful.
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Paralysisofventilatorymuscles Depressionofcentralrespiratorydrive
Botulinumtoxin(botulism) Antihistamines
Neuromuscularblockers Barbiturates
Nicotine Clonidineandothersympatholyticagents
Organophosphatesandcarbamates Ethanolandalcohols
Saxitoxin(redtide) Gammahydroxybutyrate(GHB)
Snakebite Opioids
Strychnineandtetanus(musclerigidity) Phenothiazinesandantipsychoticdrugs
Tetrodotoxin Sedativehypnotics
Warfarenervegases Tricyclicantidepressants
aAdaptedinpart,withpermission,fromOlsonKR,PentelPR,KellyMT:Physicalassessmentand
differentialdiagnosisofthepoisonedpatient.MedToxicol19872:52.
ViewLarge|
Inertgases Pneumoniaornoncardiogenicpulmonaryedema
Carbondioxide Aspirationofgastriccontents
Methaneandpropane Aspirationofhydrocarbons
Nitrogen Chlorineandotherirritantgases
Cardiogenicpulmonaryedema Cocaine
Betareceptorantagonists Ethchlorvynol(IVandoral)
Quinidine,procainamide,anddisopyramide Ethyleneglycol
Tricyclicantidepressants Mercuryvapor
Verapamil Metalfumes(metalfumesfever)
Cellularhypoxia Nitrogendioxide
Carbonmonoxide Opioids
Cyanide Paraquat
Hydrogensulfide Phosgene
Methemoglobinemia Salicylates
Sulfhemoglobinemia Sedativehypnoticdrugs
Smokeinhalation
aSeealsoTableI1.
ViewLarge|
Betareceptorantagonists Isocyanates
Brevetoxin Organophosphatesandotheranticholinesterases
Chlorineandotherirritantgases Particulatedusts
Drugscausingallergicreactions Smokeinhalation
Hydrocarbonaspiration Sulfites(eg,infoods)
Circulation
I.Generalassessmentandinitialtreatment
A.Checkbloodpressureandpulserateandrhythm.Performcardiopulmonary
resuscitation(CPR)ifthereisnopulseandperformadvancedcardiaclifesupport(ACLS)
fordysrhythmiasandshock.Note:SomeACLSdrugsmaybeineffectiveordangerousin
patientswithdrugorpoisoninducedcardiacdisorders.Forexample,procainamideand
othertypeIaantiarrhythmicdrugsarecontraindicatedinpatientswithtricyclic
antidepressantorothersodiumchannelblockeroverdose,andatropineandisoproterenol
areineffectiveinpatientswithbetareceptorantagonistpoisoning.
B.Begincontinuouselectrocardiographic(ECG)monitoring.Dysrhythmiasmay
complicateavarietyofdrugoverdoses,andallpatientswithpotentiallycardiotoxicdrug
poisoningshouldbemonitoredintheemergencydepartmentoranintensivecareunitfor
atleast6hoursaftertheingestion.
C.Securevenousaccess.Antecubitalorforearmveinsareusuallyeasytocannulate.
Alternativesitesincludefemoral,subclavian,internaljugular,andothercentralveins.
Accesstocentralveinsistechnicallymoredifficultbutallowsmeasurementofthecentral
venouspressureandplacementofapacemakerorpulmonaryarterylines.Intraosseous
(IO)accessmayalsobeusedinurgentsituations.
D.Drawbloodforroutinestudies(SeeDiagnosisofPoisoning).
E.BeginIVinfusionofnormalsaline(NS),5%dextroseinNS(D5NS),5%dextroseinhalf
NS(D5W0.45%sodiumchloride),or5%dextroseinwater(D5W)atakeepopenratefor
children,use5%dextroseinquarterNS(D5W0.25%sodiumchloride).Ifthepatientis
hypotensive(SeeHypotension),NSoranotherisotoniccrystalloidsolutionispreferred.
F.Inseriouslyillpatients(eg,thosewhoarehypotensive,obtunded,convulsing,or
comatose),placeaFoleycatheterinthebladder,obtainurineforroutineandtoxicologic
testing,andmeasurehourlyurineoutput.
II.Bradycardiaandatrioventricular(AV)block
A.Assessment.ExamplesofdrugsandtoxinscausingbradycardiaorAVblockandtheir
mechanismsarelistedinTableI4.
TableI4SelectedDrugsandToxinsCausingBradycardiaorAtrioventricularBlocka
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Cholinergicorvagotonicagents Sympatholyticagents
Digitalisglycosides Betareceptorantagonists
Organophosphatesandcarbamates Clonidine
Physostigmine,neostigmine Opioids
Membranedepressantdrugs Other
Propranolol Calciumantagonists
Encainideandflecainide Carbamazepine
Lithium
disopyramide
Phenylpropanolamineandotheralphaadrenergic
Tricyclicantidepressants
agonists
Propoxyphene
aAdaptedinpart,withpermission,fromOlsonKRetal:MedToxicol19872:71.
1.BradycardiaandAVblockarecommonfeaturesofintoxicationwithcalcium
antagonists(SeeCalciumChannelAntagonists)anddrugsthatdepresssympathetic
toneorincreaseparasympathetictone(eg,digoxin).Theseconditionsmayalso
resultfromsevereintoxicationwithmembranedepressant(sodiumchannel
blocking)drugs(eg,tricyclicantidepressants,quinidine,andothertypesIaandIc
antiarrhythmicagents).
2.BradycardiaorAVblockmayalsobeareflexresponse(baroreceptorreflex)to
hypertensioninducedbyalphaadrenergicagentssuchasphenylpropanolamineand
phenylephrine.
3.Inchildren,bradycardiaiscommonlycausedbyrespiratorycompromiseandusually
respondstoventilationandoxygenation.
B.Complications.BradycardiaandAVblockfrequentlycausehypotension,whichmay
progresstoasystoliccardiacarrest.
1.Hypothermia.
2.Myocardialischemiaorinfarction.
3.Electrolyteabnormality(eg,hyperkalemia).
4.Metabolicdisturbance(eg,hypothyroidism).
5.Physiologicorigin,resultingfromabaroreceptorresponsetohypertension,an
intrinsicallyslowpulserate(commoninathletes),oranacutevasovagalreaction.
6.Cushingreflex(causedbysevereintracranialhypertension).
D.Treatment.DonottreatbradycardiaorAVblockunlessthepatientissymptomatic(eg,
exhibitssignsofsyncopeorhypotension).Note:BradycardiaorevenAVblockmaybea
protectivebaroreceptorreflextolowerthebloodpressureinapatientwithsevere
hypertension(seeItemVIIbelow).
1.Maintainanopenairwayandassistventilation(SeeAirway)ifnecessary.Administer
supplementaloxygen.
2.Rewarmhypothermicpatients.Asinusbradycardiaof4050beats/miniscommon
whenthebodytemperatureis3235C(9095F)andwillusuallyreturntonormal
withwarming.
3.Administeratropine,0.010.03mg/kgIV(SeeAtropineandGlycopyrrolate).Ifthisis
notsuccessful,useisoproterenol,110mcg/minIV(SeeIsoproterenol),titratedto
thedesiredrate,oruseanemergencytranscutaneousortransvenouspacemaker.
4.Usethefollowingspecificantidotesifappropriate:
a.Forbetareceptorantagonistoverdose,giveglucagon(SeeGlucagon).
b.Fordigoxin,digitalis,orothercardiacglycosideintoxication,useFabantibody
fragments(SeeDigoxinSpecificAntibodies).
c.Fortricyclicantidepressantormembranedepressantdrugoverdose,
administersodiumbicarbonate(SeeBicarbonate,Sodium).
d.Forcalciumantagonistoverdose,givecalcium(SeeCalcium),hyperinsulin
euglycemiatherapy(SeeInsulin),orintralipidrescue(SeeLipidEmulsion).
III.QRSintervalprolongation
A.Assessment.ExamplesofdrugsandtoxinscausingQRSintervalprolongationarelisted
inTableI5.
TableI5SelectedDrugsandToxinsCausingQRSIntervalProlongationa
ViewLarge|
Bupropion Lamotrigine
Chloroquineandrelatedagents Phenothiazines(thioridazine)
Cocaine(highdose) Propoxyphene
Digitalisglycosides(completeheartblock) Propranolol
Diphenhydramine(highdose) Quinidine,procainamide,anddisopyramide
Encainideandflecainide Tricyclicantidepressants
Hyperkalemia Venlafaxine
1.QRSintervalprolongationofgreaterthan0.12secondinthelimbleads(FigureI3)
stronglyindicatesseriouspoisoningbytricyclicantidepressants(See
Antidepressants,Tricyclic)orothermembranedepressantdrugs(eg,quinidine(See
QuinidineandOtherTypeIAAntiarrhythmicDrugs),flecainide[SeeAntiarrhythmic
Drugs],chloroquine[SeeChloroquineandOtherAminoquinolines],andpropranolol
[SeeBetaAdrenergicBlockers]).Rightwardaxisdeviationoftheterminal40
millisecondsoftheECG,whichiseasilyrecognizedasalateRwaveintheaVR
lead,mayprecedeQRSwideninginpatientswithtricyclicantidepressantintoxication
(FigureI4).
FigureI3.
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WidenedQRSintervalcausedbytricyclicantidepressantoverdose.A:Delayed
intraventricularconductionresultsinprolongedQRSinterval(0.18s).BandC:
SupraventriculartachycardiawithprogressivewideningofQRScomplexesmimics
ventriculartachycardia.(Modifiedandreproduced,withpermission,fromBenowitz
NL,GoldschlagerN:Cardiacdisturbancesinthetoxicologicpatient.In:HaddadLM,
WinchesterJF[editors]:ClinicalManagementofPoisoningandDrugOverdose,p
71.WBSaunders,1983.)
FigureI4.
ViewFullSize|
Rightaxisdeviationoftheterminal40milliseconds,easilyrecognizedasalateR
waveinaVR.
2.QRSintervalprolongationmayalsoresultfromaventricularescaperhythmina
patientwithcompleteheartblock(eg,fromdigitalis,calciumantagonistpoisoning,or
intrinsiccardiacdisease).
B.Complications.QRSintervalprolongationinpatientswithtricyclicantidepressantor
similardrugpoisoningisoftenaccompaniedbyhypotension,AVblock,andseizures.
1.Intrinsicconductionsystemdisease(bundlebranchblockorcompleteheartblock)
causedbycoronaryarterydisease.CheckanoldECGifavailable.
2.Brugadasyndrome.
3.Hyperkalemiawithcriticalcardiactoxicitymayappearasasinewavepatternwith
markedlywideQRScomplexes.TheseareusuallyprecededbypeakedTwaves
(FigureI5).
FigureI5.
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Electrocardiogramofapatientwithhyperkalemia.(Modifiedandreproduced,with
permission,fromGoldschlagerN,GoldmanMJ:Effectofdrugsandelectrolyteson
theelectrocardiogram.In:GoldschlagerN,GoldmanMJ[editors]:
Electrocardiography:EssentialsofInterpretation,p199.Appleton&Lange,1984.)
4.Hypothermiawithacoretemperatureoflessthan32C(90F)oftencausesan
extraterminalQRSdeflection(JwaveorOsbornewave),resultinginawidenedQRS
appearance(FigureI6).
FigureI6.
ViewFullSize|
Electrocardiogramofapatientwithhypothermia,showingprominentJwaves.(Modified
andreproduced,withpermission,fromGoldschlagerN,GoldmanMJ:Miscellaneous
abnormalelectrocardiogrampatterns.In:GoldschlagerN,GoldmanMJ[editors]:
Electrocardiography:EssentialsofInterpretation,p227.Appleton&Lange,1984.)
D.Treatment
1.Maintaintheairwayandassistventilationifnecessary(SeeAirway).Administer
supplementaloxygen.
2.Treathyperkalemia(SeeDiagnosisofPoisoning)andhypothermia(SeeAltered
MentalStatus)iftheyoccur.
3.TreatAVblockwithatropine(SeeAtropineandGlycopyrrolate),isoproterenol(See
Isoproterenol),andapacemakerifnecessary.
4.Fortricyclicantidepressantorothersodiumchannelblockingdrugoverdose,give
sodiumbicarbonate,1to2mEq/kgIVbolus(SeeBicarbonate,Sodium)repeatas
needed.
IV.Tachycardia
A.Assessment.Examplesofdrugsandtoxinscausingtachycardiaandtheirmechanisms
arelistedinTableI6.
TableI6SelectedDrugsandToxinsCausingTachycardiaa
ViewLarge|
Sympathomimeticagents Anticholinergicagents
Amphetaminesandderivatives Amanitamuscariamushrooms
Caffeine Antihistamines
Cocaine Atropineandotheranticholinergics
Ephedrineandpseudoephedrine Phenothiazines
Phencyclidine(PCP) Plants(many[SeePlants])
Theophylline Tricyclicantidepressants
Agentscausingcellularhypoxia Other
Carbonmonoxide Ethanolorsedativehypnoticdrugwithdrawal
Cyanide Vasodilators(reflextachycardia)
Hydrogensulfide Thyroidhormone
Oxidizingagents(methemoglobinemia)
aAdapted,withpermission,fromOlsonKRetal:MedToxicol19872:71.
1.Sinustachycardiaandsupraventriculartachycardiaareoftencausedbyexcessive
sympatheticstimulationorinhibitionofparasympathetictone.Sinustachycardiamay
alsobeareflexresponsetohypotensionorhypoxia.
2.SinustachycardiaandsupraventriculartachycardiaaccompaniedbyQRSinterval
prolongation(eg,withtricyclicantidepressantpoisoning)mayhavetheappearance
ofventriculartachycardia(seeFigureI3).
B.Complications.Simplesinustachycardia(heartrate<140beats/min)israrelyof
hemodynamicconsequencechildrenandhealthyadultseasilytolerateratesofupto160
180beats/min.However,sustainedrapidratesmayresultinhypotension,chestpain,
myocardialischemia,orsyncope.
1.Occultbloodloss(eg,fromgastrointestinalbleedingortrauma).
2.Fluidloss(eg,fromgastritisorgastroenteritis).
3.Hypoxia.
4.Feverandinfection.
5.Myocardialinfarction.
6.Anxiety.
7.Intrinsicconductionsystemdisease(eg,WolffParkinsonWhitesyndrome).
D.Treatment.Iftachycardiaisnotassociatedwithhypotensionorchestpain,observation
andsedation(especiallyforstimulantintoxication)areusuallyadequate.
1.Forsympathomimeticinducedtachycardia,giveesmolol,0.0250.1mg/kg/minIV
(SeeEsmolol).Note:Iftachycardiaisaccompaniedbyhypertension,adda
vasodilator(seeSectionVII.D.2below).
2.Anticholinergicinducedtachycardiamayrespondtophysostigmine(See
PhysostigmineandNeostigmine)orneostigmine,buttachycardiaaloneisrarelyan
indicationforuseofthesedrugs.Moreover,inpatientswithtricyclicantidepressant
overdose,additivedepressionofconductionbythesedrugsmayresultinsevere
bradycardia,heartblock,orasystole.
V.Ventriculardysrhythmias
A.Assessment.Examplesofdrugsandtoxinscausingventriculardysrhythmiasarelistedin
TableI7.
TableI7SelectedDrugsandToxinsCausingVentricularArrhythmiasa
ViewLarge|
Ventriculartachycardiaorfibrillation
Amphetaminesandothersympathomimeticagents Digitalisglycosides
Aromatichydrocarbonsolvents Fluoride
Caffeine Phenothiazines
Chloralhydrate Theophylline
Chlorinatedorfluorinatedhydrocarbonsolvents Tricyclicantidepressants
Cocaine
QTprolongationwithwelldocumentedriskfortorsadedepointesb
Amiodarone Ibutilide
Arsenictrioxide Levomethadyl
Astemizole Mesoridazine
Bepridil Methadone
Chloroquine Pentamidine
Chlorpromazine Pimozide
Cisapride Probucol
Clarithromycin Procainamide
Disopyramide Organophosphateinsecticides
Dofetilide Quinidine
Domperidone Sotalol
Droperidol Sparfloxacin
Erythromycin Terfenadine
Halofantrine Thallium
Haloperidol Thioridazine
aReferences:OlsonKRetal:MedToxicol19872:71andArizonaCenterforEducation
andResearchonTherapeutics:DrugsWithRiskofTorsadesdePointes.
http://www.torsades.org.AccessedMarch3,2010.
bTorsadedepointescandeteriorateintoventricularfibrillationandcardiacarrest.
1.Ventricularirritabilityiscommonlyassociatedwithexcessivesympatheticstimulation
(eg,fromcocaineoramphetamines).Patientsintoxicatedbychlorinated,fluorinated,
orotherhydrocarbonsmayhaveheightenedmyocardialsensitivitytothe
arrhythmogeniceffectsofcatecholamines.
2.Ventriculartachycardiamayalsobeamanifestationofintoxicationbyatricyclic
antidepressantoranothersodiumchannelblockingdrug,althoughwiththesedrugs
trueventriculartachycardiamaybedifficulttodistinguishfromsinusor
supraventriculartachycardiaaccompaniedbyQRSintervalprolongation(seeFigure
I3).
3.AgentsthatcauseQTintervalprolongation(QTc>0.43secondsinmen,>0.45
secondsinwomen)mayproduceatypicalventriculartachycardia(torsadede
pointes).Torsadedepointesisapolymorphousventriculartachycardiainwhichthe
axisappearstorotatecontinuously(FigureI7).Torsadedepointesmayalsobe
causedbyhypokalemia,hypocalcemia,orhypomagnesemia.
FigureI7.
ViewFullSize|
Polymorphicventriculartachycardia(torsadedepointes).(Modifiedandreproduced,with
permission,fromGoldschlagerN,GoldmanMJ:Effectofdrugsandelectrolytesonthe
electrocardiogram.In:GoldschlagerN,GoldmanMJ[editors]:Electrocardiography:
EssentialsofInterpretation,p197.Appleton&Lange,1984.)
B.Complications.Ventriculartachycardiainpatientswithapulsemaybeassociatedwith
hypotensionormaydeteriorateintopulselessventriculartachycardiaorventricular
fibrillation.
C.Differentialdiagnosis.Ruleoutthefollowingpossiblecausesofventricularpremature
beats,ventriculartachycardia,orventricularfibrillation:
1.Hypoxemia.
2.Hypokalemia.
3.Metabolicacidosis.
4.Myocardialischemiaorinfarction.
5.Electrolytedisturbances(eg,hypocalcemiaorhypomagnesemia)orcongenital
disordersthatmaycauseQTprolongationandtorsadedepointes.
6.Brugadasyndrome.
D.Treatment.PerformCPRifnecessaryandfollowstandardACLSguidelinesforthe
managementofdysrhythmias,withtheexceptionthattypeIaantiarrhythmicdrugsshould
notbeused,especiallyiftricyclicantidepressantorsodiumchannelblockingdrug
overdoseissuspected.
1.Maintainanopenairwayandassistventilationifnecessary(SeeAirway).Administer
supplementaloxygen.
2.Correctacidbaseandelectrolytedisturbances.
3.Forventricularfibrillation,immediatelyapplydirectcurrentcountershockat35
J/kg.Repeattwiceifnoresponse.ContinueCPRifthepatientisstillwithoutapulse
andadministerepinephrine,repeatedcountershocks,amiodarone,and/orlidocaine
asrecommendedinadvancedcardiaclifesupport(ACLS)guidelines.
4.Forventriculartachycardiainpatientswithoutapulse,immediatelygivea
precordialthumporapplysynchronizeddirectcurrentcountershockat13J/kg.If
thisisnotsuccessful,beginCPRandapplycountershockat35J/kgadminister
amiodaroneand/orlidocaineandrepeatedcountershocksasrecommendedinACLS
guidelines.
5.Forventriculartachycardiainpatientswithapulse,uselidocaine,13mg/kgIV
(SeeLidocaine),oramiodarone,300mgIVor5mg/kginchildren.Donotuse
procainamideorothertypeIaantiarrhythmicagents.Forsuspectedmyocardial
sensitivitycausedbychloralhydrateorhalogenatedoraromatichydrocarbons,use
esmolol,0.0250.1mg/kg/minIV(SeeEsmolol),orpropranolol,0.53mgIV(See
Propranolol).
6.Fortricyclicantidepressantorothersodiumchannelblockingdrugoverdose,
administersodiumbicarbonate,12mEq/kgIV(SeeBicarbonate,Sodium)in
repeatedbolusesuntiltheQRSintervalnarrowsortheserumpHexceeds7.7.
7.Foratypicalorpolymorphicventriculartachycardia(torsadedepointes),do
thefollowing:
a.AdministerIVmagnesiumsulfate,12ginadults,over2030minutes(See
Magnesium).
b.Useoverdrivepacingorisoproterenol,110mcg/minIV(SeeIsoproterenol),to
increasetheheartrate(thismakesrepolarizationmorehomogeneousand
abolishesthedysrhythmia).
VI.Hypotension
A.Assessment.Examplesofdrugsandtoxinscausinghypotensionandtheirmechanisms
arelistedinTableI8.
TableI8SelectedDrugsandToxinsCausingHypotensiona
ViewLarge|
HYPOTENSIONWITHRELATIVEBRADYCARDIA
Sympatholyticagents
Betareceptorantagonists
Bretylium
Clonidineandmethyldopa
Hypothermia
Opioids
Reserpine
Tetrahydrozolineandoxymetazoline
Membranedepressantdrugs
Encainideandflecainide
Quinidine,procainamide,anddisopyramide
Propoxyphene
Propranolol
Others
Barbiturates
Calciumantagonists(verapamil,diltiazem)
Fluoride
Organophosphatesandcarbamates
Sedativehypnoticagents
Tilmicosin
HYPOTENSIONWITHTACHYCARDIA
Fluidlossorthirdspacing
Amatoxincontainingmushrooms
Arsenic
Colchicine
Coppersulfate
Hyperthermia
Iron
Rattlesnakeenvenomation
Peripheralvenousorarteriolardilation
Alphaantagonists(doxazosin,prazosin,terazosin)
Beta2receptoragonists(eg,albuterol)
Caffeine
Calciumantagonists(nifedipine,amlodipine,nicardipine)
Hydralazine
Hyperthermia
Minoxidil
Nitrites
Sodiumnitroprusside
Phenothiazines
Quetiapine
Theophylline
1.Physiologicderangementsresultinginhypotensionincludevolumelossbecauseof
vomiting,diarrhea,orbleedingapparentvolumedepletioncausedbyvenodilation,
arteriolardilation,depressionofcardiaccontractility,anddysrhythmiasthatinterfere
withcardiacoutputandhypothermia.
2.Volumeloss,venodilation,andarteriolardilationarelikelytoresultinhypotension
withreflextachycardia.Incontrast,hypotensionaccompaniedbybradycardiashould
suggestintoxicationbysympatholyticagents,membranedepressantdrugs,calcium
antagonists,orcardiacglycosides,orthepresenceofhypothermia.
B.Complications.Severeorprolongedhypotensioncancauseacuterenaltubularnecrosis,
braindamage,andcardiacischemia.Metabolicacidosisisacommonfinding.
1.Hypothermia,whichresultsinadecreasedmetabolicrateandloweredblood
pressuredemands.
2.Hyperthermia,whichcausesarteriolardilationandvenodilationanddirectmyocardial
depression.
3.Fluidlosscausedbygastroenteritis.
4.Bloodloss(eg,fromtraumaorgastrointestinalbleeding).
5.Myocardialinfarction.
6.Sepsis.
7.Spinalcordinjury.
D.Treatment.Fortunately,hypotensionusuallyrespondsreadilytoempirictherapywithIV
fluidsandlowdosesofvasoactivedrugs(eg,dopamine,norepinephrine).When
hypotensiondoesnotresolveaftersimplemeasures,asystematicapproachshouldbe
followedtodeterminethecauseofhypotensionandselecttheappropriatetreatment.
supplementaloxygen.
2.Treatcardiacdysrhythmiasthatmaycontributetohypotension(heartrate<4050
beats/minor>180200beats/min[SeeCirculation]).
3.Hypotensionassociatedwithhypothermiaoftenwillnotberelievedwithroutinefluid
therapy,butthepressurewillnormalizerapidlyonrewarmingofthepatient.A
systolicbloodpressureof8090mmHgisexpectedwhenthebodytemperatureis
32C(90F).
4.GiveanIVfluidchallengewithNS,1020mL/kg,oranothercrystalloidsolution.
5.Administerdopamine,515mcg/kg/min(SeeDopamine).Notethatdopaminemay
beineffectiveinsomepatientswithdepletedneuronalstoresofcatecholamines(eg,
fromdisulfiram[SeeDisulfiram],reserpine,ortricyclicantidepressant[See
Antidepressants,Tricyclic]overdose)orinpatientsinwhomalphaadrenergic
receptorsmaybeblocked(tricyclicantidepressants,phenothiazines).Insuchcases,
norepinephrine,0.1mcg/kg/minIV(SeeNorepinephrine),orphenylephrine(See
Phenylephrine)maybemoreeffective.
6.Considerspecificantidotes:
a.Sodiumbicarbonate(SeeBicarbonate,Sodium)fortricyclicantidepressantor
othersodiumchannelblockingdrugoverdose.
b.Glucagon(SeeGlucagon)forbetareceptorantagonistoverdose.
c.Calcium(SeeCalcium)forcalciumantagonistoverdose.
d.Propranolol(SeePropranolol)oresmolol(SeeEsmolol)fortheophylline,
caffeine,ormetaproterenolorotherbetaagonistoverdose.
7.Othertreatments:
a.Severehypotensionduetocalciumantagonistorbetablockerpoisoningmay
respondtohyperinsulineuglycemiatherapy(SeeInsulin).
b.Intralipidrescue(SeeLipidEmulsion)maybeusefulforseverecardiotoxicity
duetolipidsolubledrugs(eg,bupivacaine,verapamil,bupropion).
c.Ifadrenalinsufficiencyissuspected,administercorticosteroids(eg,
hydrocortisone,100mgIVevery8hours).
8.Ifempiricmeasurestorestorethebloodpressureareunsuccessful,assessvolume
statusandcardiaccontractilitywithbedsideultrasound,orinsertacentralvenous
pressure(CVP)monitororpulmonaryarterycathetertodeterminewhetherfurtherIV
fluidsareneededandtomeasurethecardiacoutput(CO)andcalculatethesystemic
vascularresistance(SVR):
Selectfurthertherapyonthebasisofthefollowing:
a.Ifthecentralvenouspressureorpulmonaryarterywedgepressureremains
low,givemoreIVfluids.
b.Ifthecardiacoutputislow,givemoredopamineordobutamine.
c.Ifthesystemicvascularresistanceislow,administernorepinephrine,48
mcg/min(SeeNorepinephrine),orphenylephrine(SeePhenylephrine).
VII.Hypertension
A.Assessment.Hypertensionisfrequentlyoverlookedindrugintoxicatedpatientsandoften
goesuntreated.Manyyoungpeoplehavenormalbloodpressuresintherangeof90/60to
100/70mmHginsuchaperson,anabruptelevationto170/100mmHgismuchmore
significant(andpotentiallycatastrophic)thanthesamebloodpressureelevationinan
olderpersonwithchronichypertension.Examplesofdrugsandtoxinscausing
hypertensionarelistedinTableI9.Hypertensionmaybecausedbyavarietyof
mechanisms:
TableI9SelectedDrugsandToxinsCausingHypertensiona
ViewLarge|
HYPERTENSIONWITHTACHYCARDIA
Generalizedsympathomimeticagents Anticholinergicagentsb
Amphetaminesandderivatives Antihistamines
Ephedrineandpseudoephedrine Tricyclicantidepressants
Epinephrine Others
Ethanolandsedativehypnoticdrug
Levodopa
withdrawal
LSD(lysergicaciddiethylamide) Nicotine(earlystage)
Marijuana Organophosphates(earlystage)
Monoamineoxidaseinhibitors
HYPERTENSIONWITHBRADYCARDIAORATRIOVENTRICULARBLOCK
Clonidine,tetrahydrozoline,and
Norepinephrine
oxymetazolinec
Ergotderivatives Phenylephrine
Methoxamine Phenylpropanolamine
bHypertensionisusuallymildandassociatedwiththerapeuticorslightlysupratherapeutic
levels.Overdosemaycausehypotension,especiallywithtricyclics.
cHypertensionisoftentransientandfollowedbyhypotension.
1.Amphetaminesandotherrelateddrugscausehypertensionandtachycardiathrough
generalizedsympatheticstimulation.
2.Selectivealphaadrenergicagentscausehypertensionwithreflex(baroreceptor
mediated)bradycardiaorevenAVblock.
3.Anticholinergicagentscausemildhypertensionwithtachycardia.
4.Substancesthatstimulatenicotiniccholinergicreceptors(eg,organophosphates)
mayinitiallycausetachycardiaandhypertension,followedlaterbybradycardiaand
hypotension.
5.Withdrawalfromsedativehypnoticdrugs,ethanol,opioids,orclonidinecancause
hypertensionandtachycardia.
B.Complications.Severehypertensioncanresultinintracranialhemorrhage,aortic
dissection,myocardialinfarction,andcongestiveheartfailure.
1.Idiopathichypertension(whichiscommoninthegeneralpopulation).However,
withoutapriorhistoryofhypertension,itshouldnotbeinitiallyassumedtobethe
causeoftheelevatedbloodpressure.
2.Pheochromocytomaorotherparaganglionictumorsthatsecreteepinephrine,
norepinephrine,orbotharerarebutpotentiallylethal.Theytypicallycause
paroxysmalattacksofhypertension,headache,perspiration,andpalpitations.
3.Increasedintracranialpressurecausedbyspontaneoushemorrhage,trauma,or
othercauses.Thismayresultinhypertensionwithreflexbradycardia(Cushing
reflex).
D.Treatment.Rapidloweringofthebloodpressureisdesirableaslongasitdoesnotresult
inhypotension,whichcanpotentiallycauseanischemiccerebralinfarctioninolder
patientswithcerebrovasculardisease.Forapatientwithchronichypertension,lowering
thediastolicpressureto100mmHgisacceptable.However,forayoungpersonwhose
normaldiastolicbloodpressureis60mmHg,thediastolicpressureshouldbeloweredto
80mmHg.
1.Forhypertensionwithlittleornotachycardia,usephentolamine,0.020.1mg/kg
IV(SeePhentolamine),ornitroprusside,210mcg/kg/minIV(SeeNitroprusside).
2.Forhypertensionwithtachycardia,addtothetreatmentinItem1above
propranolol,0.020.1mg/kgIV(SeePropranolol),oresmolol,0.0250.1mg/kg/min
IV(SeeEsmolol),orlabetalol,0.20.3mg/kgIV(SeeHydroxocobalamin).Caution:
Donotusepropranololoresmololwithoutavasodilatortotreathypertensivecrisis
betareceptorantagonistsmayparadoxicallyworsenhypertensionbecauseany
alphamediatedvasoconstrictionisunopposedwhenbeta2mediatedvasodilationis
blocked.
3.Ifhypertensionisaccompaniedbyafocallyabnormalneurologicexamination
(eg,hemiparesis),performcomputedtomography(CT)asquicklyaspossible.Ina
patientwithacerebrovascularaccident,hypertensionshouldgenerallynotbetreated
unlessspecificcomplicationsoftheelevatedpressure(eg,heartfailureorcardiac
ischemia)arepresent.Consultaneurologistorneurosurgeon.
ViewLarge|
Cholinergicorvagotonicagents Sympatholyticagents
Digitalisglycosides Betareceptorantagonists
Organophosphatesandcarbamates Clonidine
Physostigmine,neostigmine Opioids
Membranedepressantdrugs Other
Propranolol Calciumantagonists
Encainideandflecainide Carbamazepine
Lithium
disopyramide
Phenylpropanolamineandotheralphaadrenergic
agonists
Propoxyphene
ViewLarge|
Bupropion Lamotrigine
Chloroquineandrelatedagents Phenothiazines(thioridazine)
Cocaine(highdose) Propoxyphene
Digitalisglycosides(completeheartblock) Propranolol
Diphenhydramine(highdose) Quinidine,procainamide,anddisopyramide
Encainideandflecainide Tricyclicantidepressants
Hyperkalemia Venlafaxine
FigureI3.
ViewFullSize|
WidenedQRSintervalcausedbytricyclicantidepressantoverdose.A:Delayedintraventricular
conductionresultsinprolongedQRSinterval(0.18s).BandC:Supraventriculartachycardiawith
progressivewideningofQRScomplexesmimicsventriculartachycardia.(Modifiedandreproduced,
withpermission,fromBenowitzNL,GoldschlagerN:Cardiacdisturbancesinthetoxicologicpatient.
In:HaddadLM,WinchesterJF[editors]:ClinicalManagementofPoisoningandDrugOverdose,p71.
WBSaunders,1983.)
FigureI4.
ViewFullSize|
Rightaxisdeviationoftheterminal40milliseconds,easilyrecognizedasalateRwaveinaVR.
FigureI5.
ViewFullSize|
Electrocardiogramofapatientwithhyperkalemia.(Modifiedandreproduced,withpermission,from
GoldschlagerN,GoldmanMJ:Effectofdrugsandelectrolytesontheelectrocardiogram.In:
GoldschlagerN,GoldmanMJ[editors]:Electrocardiography:EssentialsofInterpretation,p199.
Appleton&Lange,1984.)
FigureI6.
ViewFullSize|
Electrocardiogramofapatientwithhypothermia,showingprominentJwaves.(Modifiedand
reproduced,withpermission,fromGoldschlagerN,GoldmanMJ:Miscellaneousabnormal
electrocardiogrampatterns.In:GoldschlagerN,GoldmanMJ[editors]:Electrocardiography:
ViewLarge|
Sympathomimeticagents Anticholinergicagents
Amphetaminesandderivatives Amanitamuscariamushrooms
Caffeine Antihistamines
Ephedrineandpseudoephedrine Phenothiazines
Phencyclidine(PCP) Plants(many[SeePlants])
Theophylline Tricyclicantidepressants
Agentscausingcellularhypoxia Other
Carbonmonoxide Ethanolorsedativehypnoticdrugwithdrawal
Cyanide Vasodilators(reflextachycardia)
Hydrogensulfide Thyroidhormone
Oxidizingagents(methemoglobinemia)
ViewLarge|
Ventriculartachycardiaorfibrillation
Amphetaminesandothersympathomimeticagents Digitalisglycosides
Aromatichydrocarbonsolvents Fluoride
Caffeine Phenothiazines
Chloralhydrate Theophylline
Chlorinatedorfluorinatedhydrocarbonsolvents Tricyclicantidepressants
Cocaine
QTprolongationwithwelldocumentedriskfortorsadedepointesb
Amiodarone Ibutilide
Arsenictrioxide Levomethadyl
Astemizole Mesoridazine
Bepridil Methadone
Chloroquine Pentamidine
Chlorpromazine Pimozide
Cisapride Probucol
Clarithromycin Procainamide
Disopyramide Organophosphateinsecticides
Dofetilide Quinidine
Domperidone Sotalol
Droperidol Sparfloxacin
Erythromycin Terfenadine
Halofantrine Thallium
Haloperidol Thioridazine
aReferences:OlsonKRetal:MedToxicol19872:71andArizonaCenterforEducationand
ResearchonTherapeutics:DrugsWithRiskofTorsadesdePointes.http://www.torsades.org.
AccessedMarch3,2010.
bTorsadedepointescandeteriorateintoventricularfibrillationandcardiacarrest.
FigureI7.
ViewFullSize|
Polymorphicventriculartachycardia(torsadedepointes).(Modifiedandreproduced,withpermission,
fromGoldschlagerN,GoldmanMJ:Effectofdrugsandelectrolytesontheelectrocardiogram.In:
ViewLarge|
HYPOTENSIONWITHRELATIVEBRADYCARDIA
Sympatholyticagents
Betareceptorantagonists
Bretylium
Clonidineandmethyldopa
Hypothermia
Opioids
Reserpine
Tetrahydrozolineandoxymetazoline
Membranedepressantdrugs
Encainideandflecainide
Quinidine,procainamide,anddisopyramide
Propoxyphene
Propranolol
Others
Barbiturates
Calciumantagonists(verapamil,diltiazem)
Fluoride
Organophosphatesandcarbamates
Tilmicosin
HYPOTENSIONWITHTACHYCARDIA
Fluidlossorthirdspacing
Amatoxincontainingmushrooms
Arsenic
Colchicine
Coppersulfate
Hyperthermia
Iron
Rattlesnakeenvenomation
Peripheralvenousorarteriolardilation
Alphaantagonists(doxazosin,prazosin,terazosin)
Beta2receptoragonists(eg,albuterol)
Caffeine
Calciumantagonists(nifedipine,amlodipine,nicardipine)
Hydralazine
Hyperthermia
Minoxidil
Nitrites
Sodiumnitroprusside
Phenothiazines
Quetiapine
Theophylline
ViewLarge|
HYPERTENSIONWITHTACHYCARDIA
Generalizedsympathomimeticagents Anticholinergicagentsb
Amphetaminesandderivatives Antihistamines
Ephedrineandpseudoephedrine Tricyclicantidepressants
Epinephrine Others
Levodopa Ethanolandsedativehypnoticdrugwithdrawal
LSD(lysergicaciddiethylamide) Nicotine(earlystage)
Marijuana Organophosphates(earlystage)
HYPERTENSIONWITHBRADYCARDIAORATRIOVENTRICULARBLOCK
Clonidine,tetrahydrozoline,andoxymetazolinec Norepinephrine
Ergotderivatives Phenylephrine
Methoxamine Phenylpropanolamine
bHypertensionisusuallymildandassociatedwiththerapeuticorslightlysupratherapeuticlevels.
Overdosemaycausehypotension,especiallywithtricyclics.
cHypertensionisoftentransientandfollowedbyhypotension.
AlteredMentalStatus
I.Comaandstupor
A.Assessment.Adecreasedlevelofconsciousnessisthemostcommonserious
complicationofdrugoverdoseorpoisoning.Examplesofdrugsandtoxinsthatcause
comaarelistedinTableI10.
TableI10SelectedDrugsandToxinsCausingComaorStupora
ViewLarge|
Generalcentralnervoussystem
Cellularhypoxia
depressants
Anticholinergics Carbonmonoxide
Antihistamines Cyanide
Barbiturates Hydrogensulfide
Benzodiazepines Methemoglobinemia
Carbamazepine Sodiumazide
Ethanolandotheralcohols Otherorunknownmechanisms
GHB(gammahydroxybutyrate) Bromide
Phenothiazines Diquat
Sedativehypnoticagents Disulfiram
Tricyclicantidepressants Hypoglycemicagents
Valproicacid Lithium
Nonsteroidalantiinflammatorydrugs
Sympatholyticagents
(NSAIDs)
Clonidine,tetrahydrozoline,and
Phencyclidine(PCP)
oxymetazoline
Methyldopa Salicylates
Opioids
1.Comaismostoftenaresultofglobaldepressionofthebrain'sreticularactivating
system,causedbyanticholinergicagents,sympatholyticdrugs,generalizedCNS
depressants,ortoxinsthatresultincellularhypoxia.
2.Comasometimesrepresentsapostictalphenomenonafteradrugortoxininduced
seizure.
3.Comamayalsobecausedbybraininjuryassociatedwithinfarctionorintracranial
bleeding.Braininjuryissuggestedbythepresenceoffocalneurologicdeficitsandis
confirmedbyCT.
B.Complications.Comafrequentlyisaccompaniedbyrespiratorydepression,whichisa
majorcauseofdeath.Otherconditionsthatmayaccompanyorcomplicatecomainclude
hypotension(SeeHypotension),hypothermia(SeeHypothermia),hyperthermia(See
Hyperthermia),andrhabdomyolysis(SeeRhabdomyolysis).
1.Headtraumaorothercausesofintracranialbleeding.
2.Abnormallevelsofbloodglucose,sodium,orotherelectrolytes.Hypoglycemiaisa
commoncauseofalteredmentalstatus.
3.Hypoxia.
4.Hypothyroidism.
5.Liverorrenalfailure.
6.Environmentalhyperthermiaorhypothermia.
7.Seriousinfectionssuchasencephalitisandmeningitis.
D.Treatment
supplementaloxygen.
2.Consideradministrationofdextrose,thiamine,naloxone,andpossiblyflumazenil.
a.Dextrose.Allpatientswithdepressedconsciousnessshouldreceive
concentrateddextroseunlesshypoglycemiaisruledoutwithanimmediate
bedsideglucosedetermination.Useasecureveinandavoidextravasation
concentrateddextroseishighlyirritatingtotissues.Initialdosesincludethe
following:
1.Adults:50%dextrose,50mL(25g)IV.
2.Children:25%dextrose,2mL/kgIV.
b.Thiamine.ThiamineisgiventopreventortreatWernickesyndromeresulting
fromthiaminedeficiencyinalcoholicpatientsandotherswithsuspectedvitamin
deficiencies.Itisnotgivenroutinelytochildren.Givethiamine,100mg,inthe
IVsolutionorIM(SeeThiamine(Thiamin,VitaminB1)).
c.Naloxone.Allpatientswithrespiratorydepressionshouldreceivenaloxone
(SeeNaloxoneandNalmefene)ifapatientisalreadyintubatedandisbeing
artificiallyventilated,naloxoneisnotimmediatelynecessaryandcanbe
consideredadiagnosticratherthanatherapeuticdrug.Caution:Although
naloxonehasnoCNSdepressantactivityofitsownandnormallycanbegiven
safelyinlargedoses,itmayprecipitateabruptopioidwithdrawal.Ifan
amphetamineorcocainehasbeeninjectedorconsumedalongwithheroin,
reversaloftheopioidinducedsedationmayunmaskstimulantmediated
hypertension,tachycardia,orpsychosis.Inaddition,acutepulmonaryedemais
sometimestemporallyassociatedwithabruptnaloxonereversalofopioid
intoxication.
1.Givenaloxone,0.20.4mgIV(mayalsobegivenIMorthroughan
intraosseousline).
2.Ifthereisnoresponsewithin12minutes,givenaloxone,2mgIV.
3.Ifthereisstillnoresponseandopioidoverdoseishighlysuspectedbythe
historyorclinicalpresentation(pinpointpupils,apnea,orhypotension),
givenaloxone,upto1020mgIV.
d.Considerflumazenilifbenzodiazepinesaretheonlysuspectedcauseofcoma
andtherearenocontraindications(SeeFlumazenil).Caution:Theuseof
flumazenilcanprecipitateseizuresinpatientswhoaredependenton
benzodiazepinesorwhohavecoingestedaconvulsantdrugorpoison.
3.Normalizethebodytemperature(seeHypothermiaandHyperthermia).
4.IfthereisanyquestionofCNStraumaorcerebrovascularaccident,performaCT
scanofthehead.
5.Ifmeningitisorencephalitisissuspected,performalumbarpunctureandtreatwith
appropriateantibiotics.
II.Hypothermia
A.Assessment.Hypothermiamaymimicorcomplicatedrugoverdoseandshouldbe
suspectedineverycomatosepatient.Examplesofdrugsandtoxinsthatcause
hypothermiaarelistedinTableI11.
TableI11SelectedDrugsandToxinsAssociatedwithHypothermiaa
ViewLarge|
Barbiturates Phenothiazines
Ethanolandotheralcohols Sedativehypnoticagents
Hypoglycemicagents Tricyclicantidepressants
Opioids Vasodilators
1.Hypothermiaisusuallycausedbyexposuretolowambienttemperaturesinapatient
withbluntedthermoregulatoryresponsemechanisms.Drugsandtoxinsmayinduce
hypothermiabycausingvasodilation,inhibitingtheshiveringresponse,decreasing
metabolicactivity,orcausinglossofconsciousnessinacoldenvironment.
2.Apatientwhosetemperatureislowerthan30C(86F)mayappeartobedead,with
abarelydetectablepulseorbloodpressureandwithoutreflexes.TheECGmay
revealanabnormalterminaldeflection(JwaveorOsbornewave[seeFigureI6]).
B.Complications.Becausethereisageneralizedreductionofmetabolicactivityandless
demandforbloodflow,hypothermiaiscommonlyaccompaniedbyhypotensionand
bradycardia.
1.Mildhypotension(systolicbloodpressureof7090mmHg)inapatientwith
hypothermiashouldnotbetreatedaggressivelyexcessiveIVfluidsmaycausefluid
overloadandfurtherloweringofthetemperature.
2.Severehypothermia(temperature<2830C)maycauseintractableventricular
fibrillationandcardiacarrest.Thismayoccurabruptly,suchaswhenthepatientis
movedorrewarmedtooquicklyorwhenCPRisperformed.
1.Sepsis.
2.Hypoglycemia.
3.Hypothyroidism.
4.Adrenalinsufficiency.
5.Thiaminedeficiency.
D.Treatment
supplementaloxygen.
2.Becausethepulseratemaybeprofoundlyslowandweak,performcarefulcardiac
evaluationbeforeassumingthatthepatientisincardiacarrest.Donottreat
bradycardiaitwillresolvewithrewarming.
3.Unlessthepatientisincardiacarrest(asystoleorventricularfibrillation),rewarm
slowly(withblankets,warmedIVfluids,andinhalationofwarmedmist)toprevent
rewarmingdysrhythmias.
4.Forpatientsincardiacarrest,usualantiarrhythmicagentsanddirectcurrent
countershockarefrequentlyineffectiveuntilthecoretemperatureisabove3032C
(8690F).PerformCPRandinitiateactiveinternalrewarming(eg,pleural,gastricor
peritoneallavagewithwarmedfluidsextracorporealbypass).Forrefractory
ventricularfibrillation,bretylium,510mg/kgIV,wasrecommendedinthepast,but
thedrugisnolongeravailableintheUnitedStates.
5.Opencardiacmassage,withdirectwarmirrigationoftheventricle,orapartial
cardiopulmonarybypassmaybenecessaryinhypothermicpatientsincardiacarrest
whoareunresponsivetotheabovetreatment.
6.Ifthepatientishypoglycemic,givedextroseandthiamine(SeeAlteredMental
Status).
7.Ifadrenalinsufficiencyissuspected,drawbloodforaserumcortisolleveland
administer100mgofhydrocortisoneIV.
III.Hyperthermia
A.Assessment.Hyperthermia(temperature>40Cor104F)maybeacatastrophic
complicationofintoxicationbyavarietyofdrugsandtoxins(TableI12).Itcanbecaused
byexcessiveheatgenerationresultingfromsustainedseizures,rigidity,orothermuscular
hyperactivityanincreasedmetabolicrateimpaireddissipationofheatsecondaryto
impairedsweating(eg,anticholinergicagents)orhypothalamicdisorders.
TableI12SelectedDrugsandToxinsAssociatedwithHyperthermiaa
ViewLarge|
Excessivemuscularhyperactivity, Impairedheatdissipationordisrupted
rigidity,orseizures thermoregulation
Amoxapine Amoxapine
Amphetaminesandderivatives(including
Anticholinergicagents
MDMA)
Cocaine Antihistamines
Phenothiazinesandotherantipsychotic
Lithium
agents
LSD(lysergicaciddiethylamide) Tricyclicantidepressants
Maprotiline Other
Monoamineoxidaseinhibitors Exertionalheatstroke
Phencyclidine(PCP) Malignanthyperthermia
Tricyclicantidepressants Metalfumefever
Increasedmetabolicrate Neurolepticmalignantsyndrome(NMS)
Dinitrophenolandpentachlorophenol Serotoninsyndrome
Withdrawalfromethanolorsedativehypnotic
Salicylates
drugs
Thyroidhormone
1.Neurolepticmalignantsyndrome(NMS)isahyperthermicdisorderseeninsome
patientstakingantipsychoticagentsandischaracterizedbyhyperthermia,muscle
rigidity(oftensosevereastobecalledleadpiperigidity),metabolicacidosis,and
confusion.
2.Malignanthyperthermiaisaninheriteddisorderthatcausesseverehyperthermia,
metabolicacidosis,andrigidityaftertheadministrationofcertainanestheticagents
(mostcommonlysuccinylcholineandinhaledanesthetics).
3.Serotoninsyndromeoccursprimarilyinpatientstakingmonoamineoxidase(MAO)
inhibitors(SeeMonoamineOxidaseInhibitors)whoalsotakeserotoninenhancing
drugssuchasmeperidine,fluoxetine,orotherselectiveserotoninreuptakeinhibitors
(SSRIsseeAntidepressants)andischaracterizedbyirritability,musclerigidityand
myoclonus(especiallyofthelowerextremities),diaphoresis,autonomicinstability,
andhyperthermia.Itmayalsooccurinpeoplewhohavetakenanoverdoseora
combinationofSSRIs,evenwithouttheconcurrentuseofMAOinhibitors.
B.Complications.Untreated,severehyperthermiaislikelytoresultinhypotension,
rhabdomyolysis,coagulopathy,cardiacandrenalfailure,braininjury,anddeath.Survivors
oftenhavepermanentneurologicsequelae.
1.Sedativehypnoticdrugorethanolwithdrawal(deliriumtremens).
2.Exertionalorenvironmentalheatstroke.
3.Thyrotoxicosis.
4.Meningitisorencephalitis.
5.Otherseriousinfections.
D.Treatment.Immediaterapidcoolingisessentialtopreventdeathorseriousbrain
damage.
supplementaloxygen.
2.AdministerglucosecontainingIVfluidsandgiveaconcentratedglucosebolus(See
Glucose)ifthepatientishypoglycemic.
3.Rapidlygaincontrolofseizures(seebelow),agitation(SeeAgitation,delirium,or
psychosis),ormuscularrigidity(SeeOtherComplications).
4.Beginexternalcoolingwithtepid(lukewarm)spongingandfanning.Thisevaporative
methodisthemostefficientmethodofcooling.
5.Shiveringoftenoccurswithrapidexternalcooling,anditmaygenerateevenmore
heat.Somephysiciansrecommendchlorpromazinetoabolishshivering,butthis
agentcanlowertheseizurethreshold,inhibitsweating,andcausehypotension.Itis
preferabletouseabenzodiazepinesuchasdiazepam,0.10.2mg/kgIV,or
lorazepam,0.050.1mg/kgIV,ormidazolam,0.050.1mg/kgIVorIM(See
Benzodiazepines(Diazepam,Lorazepam,andMidazolam)),ortouseneuromuscular
paralysis(seebelow).
6.Themostrapidlyeffectiveandreliablemeansofloweringthetemperatureis
neuromuscularparalysis.Administeranondepolarizingagent(SeeNeuromuscular
Blockers)suchasvecuronium,0.1mg/kgIV.Caution:Thepatientwillstop
breathingbepreparedtoventilateandintubateendotracheally.
7.Malignanthyperthermia.Ifmusclerigiditypersistsdespiteadministrationof
neuromuscularblockers,adefectatthemusclecelllevel(ie,malignant
hyperthermia)shouldbesuspected.Givedantrolene,110mg/kgIV(See
Cyproheptadine).
8.Neurolepticmalignantsyndrome(NMS).Considerbromocriptine(See
Bromocriptine).
9.Serotoninsyndrome.Anecdotalcasereportssuggestbenefitwithcyproheptadine
(Periactin),12mgorally(PO)initially,followedby4mgeveryhourfor34doses
(SeeCyproheptadine).Chlorpromazine,2550mgIV,hasalsobeenused.
IV.Seizures
A.Assessment.Seizuresareamajorcauseofmorbidityandmortalityfromdrugoverdoseor
poisoning.Seizuresmaybesingleandbrieformultipleandsustainedandmayresultfrom
avarietyofmechanisms(TableI13).
TableI13SelectedDrugsandToxinsCausingSeizuresa
ViewLarge|
Adrenergicsympathomimeticagents
Amphetaminesandderivatives(includingMDMA)
Caffeine
Cocaine
Ephedrine
Phencyclidine(PCP)
Phenylpropanolamine
Theophylline
Others
Antihistamines(diphenhydramine,hydroxyzine)
Betareceptorantagonists(primarilypropranololnotreportedforatenolol,metoprolol,
pindolol,orpractolol)
Boricacid
Camphor
Carbamazepine
Cellularhypoxia(eg,carbonmonoxide,cyanide,hydrogensulfide)
Chlorinatedhydrocarbons
Cholinergicagents(carbamates,nicotine,organophosphates)
Cicutoxin(waterhemlock)andotherplanttoxins
Citrate
DEET(diethyltoluamide)(rare)
Ethyleneglycol
Fipronil
Fluoride
Foscarnet
GHB(gammahydroxybutyrate)
Isoniazid(INH)
Lamotrigine
Leadandotherheavymetals
Lidocaineandotherlocalanesthetics
Lithium
Mefenamicacid
Meperidine(normeperidinemetabolite)
Metaldehyde
Methanol
Methylbromide
Phenols
Phenylbutazone
Piroxicam
Salicylates
Strychnine(opisthotonusandrigidity)
Tiagabine
Tramadol
Withdrawalfromethanolorsedativehypnoticdrugs
Antidepressantsandantipsychotics
Amoxapine
Bupropion
Haloperidolandbutyrophenones
Loxapine,clozapine,andolanzapine
Phenothiazines
Venlafaxineotherserotoninreuptakeinhibitors
1.Generalizedseizuresusuallyresultinlossofconsciousness,oftenaccompaniedby
tonguebitingandfecalandurinaryincontinence.
2.Othercausesofmuscularhyperactivityorrigidity(SeeOtherComplications)maybe
mistakenforseizures,especiallyifthepatientisalsounconscious.
B.Complications
1.Anyseizurecancauseairwaycompromise,resultinginapneaorpulmonary
aspiration.
2.Multipleorprolongedseizuresmaycauseseveremetabolicacidosis,hyperthermia,
rhabdomyolysis,andbraindamage.
1.Anyseriousmetabolicdisturbance(eg,hypoglycemia,hyponatremia,hypocalcemia,
orhypoxia).
2.Headtraumawithintracranialinjury.
3.Idiopathicepilepsy.
4.Withdrawalfromalcoholorasedativehypnoticdrug.
5.Exertionalorenvironmentalhyperthermia.
6.CNSinfectionsuchasmeningitisorencephalitis.
7.Febrileseizuresinchildren.
D.Treatment
supplementaloxygen.
2.Administernaloxone(SeeNaloxoneandNalmefene)ifseizuresarethoughttobe
causedbyhypoxiaresultingfromopioidassociatedrespiratorydepression.
3.Checkforhypoglycemiaandadministerdextroseandthiamineasforcoma(See
AlteredMentalStatus).
4.Useoneormoreofthefollowinganticonvulsants.Caution:Anticonvulsantscan
causehypotension,cardiacarrest,orrespiratoryarrestifadministeredtoorapidly.
a.Diazepam,0.10.2mg/kgIV(SeeBenzodiazepines(Diazepam,Lorazepam,
andMidazolam)).
b.Lorazepam,0.050.1mg/kgIV(SeeBenzodiazepines(Diazepam,Lorazepam,
andMidazolam)).
c.Midazolam,0.10.2mg/kgIM(usefulwhenIVaccessisdifficult)or0.050.1
mg/kgIV(SeeBenzodiazepines(Diazepam,Lorazepam,andMidazolam)).
d.Phenobarbital,1015mg/kgIVslowinfusionover1520minutes(See
Phenobarbital).
e.Pentobarbital,56mg/kgIVslowinfusionover810minutes,thencontinuous
infusionat0.53mg/kg/htitratedtoeffect(SeePentobarbital).
f.Propofol,22.5mg/kgIV(children:2.53.5mg/kg),infusedinincrements(40
mgatatimeinadults)IVevery1020secondsuntildesiredeffect(See
Propofol).
g.Phenytoin,1520mg/kgIVslowinfusionover2530minutes(SeePhenytoin
andFosphenyton).Note:Phenytoinisineffectiveforconvulsionscausedby
theophyllineandisconsideredtheanticonvulsantoflastchoiceformostdrug
inducedseizures.
5.Immediatelychecktherectalortympanictemperatureandcoolthepatientrapidly
(SeeSeizures)ifthetemperatureisabove40C(104F).Themostrapidandreliably
effectivemethodoftemperaturecontrolisneuromuscularparalysiswithvecuronium,
0.1mg/kgIV(SeeNeuromuscularBlockers)oranothernondepolarizing
neuromuscularblocker.Caution:Ifparalysisisused,thepatientmustbeintubated
andventilatedinaddition,monitortheelectroencephalogramforcontinuedbrain
seizureactivitybecauseperipheralmuscularconvulsionsarenolongervisible.
6.Usethefollowingspecificantidotesifavailable:
a.Pyridoxine(SeePyridoxine(VitaminB6))forisoniazid(INHSeeIsoniazid
(INH)).
b.Pralidoxime(2PAMSeePralidoximeandOtherOximes)oratropine(See
AtropineandGlycopyrrolate)orbothfororganophosphateorcarbamate
insecticides(SeeOrganophosphorusandCarbamateInsecticides).
V.Agitation,delirium,orpsychosis
A.Assessment.Agitation,delirium,orpsychosismaybecausedbyavarietyofdrugsand
toxins(TableI14).Inaddition,suchsymptomsmayresultfromafunctionalthought
disorderormetabolicencephalopathycausedbymedicalillness.
TableI14SelectedDrugsandToxinsCausingAgitation,Delirium,orConfusiona
ViewLarge|
Predominantagitationor
Predominantconfusionordelirium
psychosis
Amantadine Amphetaminesandderivatives
Anticholinergicagents Caffeine
Antihistamines Cocaine
Bromide Cycloserine
Carbonmonoxide Dextromethorphan
Cimetidine LSD(lysergicaciddiethylamide)
Disulfiram Marijuana
Leadandotherheavymetals Mercury
Levodopa Phencyclidine(PCP)
Lidocaineandotherlocalanesthetics Procaine
Lithium Serotoninreuptakeinhibitors(SSRIs)
Salicylates Steroids(eg,prednisone)
Theophylline
drugs
1.Functionalpsychosisorstimulantinducedagitationandpsychosisareusually
associatedwithanintactsensorium,andhallucinationsarepredominantlyauditory.
2.Withmetabolicencephalopathyordruginduceddelirium,thereisusuallyalterationof
thesensorium(manifestedbyconfusionordisorientation).Hallucinations,whenthey
occur,arepredominantlyvisual.Anticholinergicdeliriumisoftenaccompaniedby
tachycardia,dilatedpupils,flushing,dryskinandmucousmembranes,decreased
peristalsis,andurinaryretention.
B.Complications.Agitation,especiallyifaccompaniedbyhyperkineticbehaviorand
struggling,mayresultinhyperthermia(SeeHyperthermia)andrhabdomyolysis(See
Rhabdomyolysis).
1.Seriousmetabolicdisturbance(hypoxia,hypoglycemia,orhyponatremia).
2.Alcoholorsedativehypnoticdrugwithdrawal.
3.Thyrotoxicosis.
4.CNSinfectionsuchasmeningitisorencephalitis.
5.Exertioninducedorenvironmentalhyperthermia.
D.Treatment.Sometimes,thepatientcanbecalmedwithreassuringwordsandreductionof
noise,light,andphysicalstimulation.Ifthisisnotquicklyeffective,rapidlygaincontrolof
thepatienttodeterminetherectalortympanictemperatureandbeginrapidcoolingand
othertreatmentifneeded.
supplementaloxygen.
2.Treathypoglycemia(SeeHypernatremiaandhyponatremia),hypoxia(SeeHypoxia),
orothermetabolicdisturbances.
3.Administeroneofthefollowingbenzodiazepines:
a.Midazolam,0.050.1mg/kgIVover1minute,or0.10.2mg/kgIM(See
Benzodiazepines(Diazepam,Lorazepam,andMidazolam)).
b.Lorazepam,0.050.1mg/kgIVover1minute(SeeBenzodiazepines
(Diazepam,Lorazepam,andMidazolam)).
c.Diazepam,0.10.2mg/kgIVover1minute(SeeBenzodiazepines(Diazepam,
Lorazepam,andMidazolam)).
4.Consideruseofanantipsychoticagent:
a.Ziprasidone,1020mgIM,orolanzapine,510mgIM(SeeAntipsychotic
Drugs(Haloperidol,Droperidol,Olanzapine,andZiprasidone)).
b.Olderantipsychoticagentsthatareoftenusedforagitationincludedroperidol,
2.55mgIV,orhaloperidol,0.10.2mg/kgIMorIVover1minute(See
AntipsychoticDrugs(Haloperidol,Droperidol,Olanzapine,andZiprasidone)).
Note:Donotgivehaloperidoldecanoatesaltintravenously.Caution:Both
droperidolandhaloperidolhavecausedprolongationoftheQTintervaland
polymorphicventriculartachycardia(torsadedepointes)andshouldbeavoided
orusedwithgreatcautioninpatientswithpreexistingQTprolongationorwith
toxicityfromagentsknowntoprolongtheQTinterval.
5.Foranticholinergicinducedagitateddelirium,consideruseofphysostigmine,0.51
mgIV(SeePhysostigmineandNeostigmine).Caution:Donotuseinpatientswith
tricyclicantidepressantorothersodiumchannelblockeroverdoseifthereisevidence
ofacardiacconductiondisturbance(eg,prolongedQRSinterval).
6.Ifhyperthermiaoccursasaresultofexcessivemuscularhyperactivity,skeletal
muscleparalysisisindicated.Usevecuronium,0.1mg/kgIV(SeeNeuromuscular
Blockers),oranothernondepolarizingneuromuscularblocker.Caution:Beprepared
toventilateandendotracheallyintubatethepatientaftermuscleparalysis.
ViewLarge|
Generalcentralnervoussystemdepressants Cellularhypoxia
Anticholinergics Carbonmonoxide
Antihistamines Cyanide
Barbiturates Hydrogensulfide
Benzodiazepines Methemoglobinemia
Carbamazepine Sodiumazide
Ethanolandotheralcohols Otherorunknownmechanisms
GHB(gammahydroxybutyrate) Bromide
Phenothiazines Diquat
Sedativehypnoticagents Disulfiram
Tricyclicantidepressants Hypoglycemicagents
Valproicacid Lithium
Sympatholyticagents Nonsteroidalantiinflammatorydrugs(NSAIDs)
Clonidine,tetrahydrozoline,andoxymetazoline Phencyclidine(PCP)
Methyldopa Salicylates
Opioids
ViewLarge|
Barbiturates Phenothiazines
Ethanolandotheralcohols Sedativehypnoticagents
Hypoglycemicagents Tricyclicantidepressants
Opioids Vasodilators
ViewLarge|
Excessivemuscularhyperactivity,rigidity,or Impairedheatdissipationordisrupted
seizures thermoregulation
Amoxapine Amoxapine
Amphetaminesandderivatives(including
Anticholinergicagents
MDMA)
Cocaine Antihistamines
Lithium Phenothiazinesandotherantipsychoticagents
LSD(lysergicaciddiethylamide) Tricyclicantidepressants
Maprotiline Other
Monoamineoxidaseinhibitors Exertionalheatstroke
Phencyclidine(PCP) Malignanthyperthermia
Tricyclicantidepressants Metalfumefever
Increasedmetabolicrate Neurolepticmalignantsyndrome(NMS)
Dinitrophenolandpentachlorophenol Serotoninsyndrome
Salicylates
drugs
Thyroidhormone
ViewLarge|
Adrenergicsympathomimeticagents
Amphetaminesandderivatives(includingMDMA)
Caffeine
Cocaine
Ephedrine
Phencyclidine(PCP)
Phenylpropanolamine
Theophylline
Others
Antihistamines(diphenhydramine,hydroxyzine)
Betareceptorantagonists(primarilypropranololnotreportedforatenolol,metoprolol,pindolol,or
practolol)
Boricacid
Camphor
Carbamazepine
Cellularhypoxia(eg,carbonmonoxide,cyanide,hydrogensulfide)
Cholinergicagents(carbamates,nicotine,organophosphates)
Cicutoxin(waterhemlock)andotherplanttoxins
Citrate
DEET(diethyltoluamide)(rare)
Ethyleneglycol
Fipronil
Fluoride
Foscarnet
GHB(gammahydroxybutyrate)
Isoniazid(INH)
Lamotrigine
Leadandotherheavymetals
Lidocaineandotherlocalanesthetics
Lithium
Mefenamicacid
Meperidine(normeperidinemetabolite)
Metaldehyde
Methanol
Methylbromide
Phenols
Phenylbutazone
Piroxicam
Salicylates
Strychnine(opisthotonusandrigidity)
Tiagabine
Tramadol
Withdrawalfromethanolorsedativehypnoticdrugs
Antidepressantsandantipsychotics
Amoxapine
Bupropion
Haloperidolandbutyrophenones
Loxapine,clozapine,andolanzapine
Phenothiazines
Venlafaxineotherserotoninreuptakeinhibitors
ViewLarge|
Predominantconfusionordelirium Predominantagitationorpsychosis
Amantadine Amphetaminesandderivatives
Anticholinergicagents Caffeine
Antihistamines Cocaine
Bromide Cycloserine
Carbonmonoxide Dextromethorphan
Cimetidine LSD(lysergicaciddiethylamide)
Disulfiram Marijuana
Leadandotherheavymetals Mercury
Levodopa Phencyclidine(PCP)
Lidocaineandotherlocalanesthetics Procaine
Lithium Serotoninreuptakeinhibitors(SSRIs)
Salicylates Steroids(eg,prednisone)
Withdrawalfromethanolorsedativehypnoticdrugs Theophylline
OtherComplications
I.Dystonia,dyskinesia,andrigidity
A.Assessment.Examplesofdrugsandtoxinscausingabnormalmovementsorrigidityare
listedinTableI15.
TableI15SelectedDrugsandToxinsCausingDystonias,Dyskinesias,andRigiditya
ViewLarge|
Dystonia Dyskinesias
Haloperidolandbutyrophenones Amphetamines
Metoclopramide Anticholinergicagents
Phenothiazines(prochlorperazine) Antihistamines
Ziprasidoneandotheratypicalantipsychoticagents Caffeine
Rigidity Carbamazepine
Blackwidowspiderbite Carisoprodol
Lithium Cocaine
Malignanthyperthermia GHB(gammahydroxybutyrate)
Methaqualone Ketamine
Monoamineoxidaseinhibitors Levodopa
Neurolepticmalignantsyndrome Lithium
Phencyclidine(PCP) Phencyclidine(PCP)
Strychnine Serotoninreuptakeinhibitors(SSRIs)
Tetanus Tricyclicantidepressants
1.Dystonicreactionsarecommonwiththerapeuticortoxicdosesofmany
antipsychoticagentsandwithsomeantiemetics.Themechanismtriggeringthese
reactionsisthoughttoberelatedtocentraldopamineblockade.Dystoniasusually
consistofforced,involuntary,andoftenpainfulneckrotation(torticollis),tongue
protrusion,jawextension,ortrismus.Otherextrapyramidalorparkinsonian
movementdisorders(eg,pillrolling,bradykinesia,andmaskedfacies)mayalsobe
seenwiththeseagents.
2.Incontrast,dyskinesiasareusuallyrapid,repetitivebodymovementsthatmay
involvesmall,localizedmusclegroups(eg,tonguedarting,focalmyoclonus)ormay
consistofgeneralizedhyperkineticactivity.Thecauseisnotdopamineblockadebut,
morecommonly,increasedcentraldopamineactivityorblockadeofcentral
cholinergiceffects.
3.RigiditymayalsobeseenwithanumberoftoxinsandmaybecausedbyCNS
effectsorspinalcordstimulation.Neurolepticmalignantsyndromeandserotonin
syndrome(SeeHyperthermia)arecharacterizedbyrigidity,hyperthermia,metabolic
acidosis,andanalteredmentalstatus.Rigidityseenwithmalignanthyperthermia
(SeeHyperthermia)iscausedbyadefectatthemusclecelllevelandmaynot
reversewithneuromuscularblockade.
B.Complications.Sustainedmuscularrigidityorhyperactivitymayresultinrhabdomyolysis
(SeeRhabdomyolysis),hyperthermia(SeeHyperthermia),ventilatoryfailure(See
Breathing),ormetabolicacidosis(SeeAniongapmetabolicacidosis).
1.Catatonicrigiditycausedbyfunctionalthoughtdisorder.
2.Tetanus.
3.Cerebrovascularaccident.
4.Postanoxicencephalopathy.
5.Idiopathicparkinsonism.
D.Treatment
supplementaloxygen.
2.Checktherectalortympanictemperatureandtreathyperthermia(SeeHyperthermia)
rapidlyifthetemperatureisabove40C(102.2F).
3.Dystonia.Administerananticholinergicagentsuchasdiphenhydramine(See
Diphenhydramine),0.51mg/kgIMorIV,orbenztropine(SeeBenztropine),14mg
IM,inadults.Followthistreatmentwithoraltherapyfor23days.
4.Dyskinesia.Donottreatwithanticholinergicagents.Instead,administerasedative
suchasdiazepam,0.10.2mg/kgIV(SeeBenzodiazepines(Diazepam,Lorazepam,
andMidazolam)),orlorazepam,0.050.1mgIVorIM,ormidazolam,0.050.1
mg/kgIVor0.10.2mg/kgIM(SeeBenzodiazepines(Diazepam,Lorazepam,and
Midazolam)).
5.Rigidity.Donottreatwithanticholinergicagents.Instead,administerasedative(see
Item4directlyabove)orprovidespecificpharmacologictherapyasfollows:
a.Dantrolene(SeeCyproheptadine)formalignanthyperthermia(See
Hyperthermia).
b.Bromocriptine(SeeBromocriptine)forneurolepticmalignantsyndrome(See
Hyperthermia).
c.BenzodiazepinesorLatrodectusantivenom(SeeAntivenom,Latrodectus
Mactans(BlackWidowSpider))forablackwidowspiderbite(SeeSpiders).
II.Rhabdomyolysis
A.Assessment.Musclecellnecrosisisacommoncomplicationofpoisoning.Examplesof
drugsandtoxinsthatcauserhabdomyolysisarelistedinTableI16.
TableI16SelectedDrugsandToxinsAssociatedwithRhabdomyolysis
ViewLarge|
Excessivemuscularhyperactivity,rigidity,orseizures
Amphetaminesandderivatives
Clozapineandolanzapine
Cocaine
Lithium
Phencyclidine(PCP)
Seizurescausedbyavarietyofagents
Strychnine
Tetanus
Otherorunknownmechanisms
Carbonmonoxide
Chlorophenoxyherbicides
Colchicine
Ethanol
Ethyleneglycol
Gemfibrozil
Haffdisease(unknowntoxinfoundinBalticfish,buffalofish)
Hemlock
Hyperthermiacausedbyavarietyofagents
Hypokalemia
Mushrooms(someAmanita,Russula,Tricholomaspecies)
Prolongedimmobility(eg,comaduetocentralnervoussystemdepressantdrug
overdose)
Statincholesteroldrugs(eg,cerivastatin)
Trauma
1.Causesofrhabdomyolysisincludeprolongedimmobilizationonahardsurface,
excessiveseizuresormuscularhyperactivity,hyperthermia,anddirectcytotoxic
effectsofthedrugortoxin(eg,carbonmonoxide,colchicine,Tricholomaand
Russulamushrooms,andsomesnakevenoms).
2.ThediagnosisismadebyfindingHematestpositiveurinewithfewornointactred
bloodcellsoranelevatedserumcreatinekinase(CK)level.
B.Complications.Myoglobinreleasedbydamagedmusclecellsmayprecipitateinthe
kidneys,causingacutetubularnecrosisandrenalfailure.Thisismorelikelywhenthe
serumCKlevelexceedsseveralthousandIU/Landifthepatientisdehydrated.With
severerhabdomyolysis,hyperkalemia,hyperphosphatemia,hyperuricemia,and
hypocalcemiamayalsooccur.
C.Differentialdiagnosis.HemolysisleadingtohemoglobinuriamayalsoproduceHematest
positiveurine.
D.Treatment
1.Aggressivelyrestorevolumeindehydratedpatients.Thenestablishasteadyurine
flowrate(35mL/kg/h)withIVfluids.Formassiverhabdomyolysisaccompaniedby
oliguria,alsoconsiderabolusofmannitol,0.5g/kgIV(SeeMannitol).
2.Somecliniciansalkalinizetheurinebyadding100mEqofsodiumbicarbonateto
eachliterof5%dextrose.(Acidicurinemaypromotethedepositionofmyoglobinin
thetubules.)
3.Provideintensivesupportivecare,includinghemodialysisifneeded,foracuterenal
failure.Kidneyfunctionisusuallyregainedin23weeks.
III.Anaphylacticandanaphylactoidreactions
A.Assessment.Examplesofdrugsandtoxinsthatcauseanaphylacticoranaphylactoid
reactionsarelistedinTableI17.Thesereactionsarecharacterizedbybronchospasmand
increasedvascularpermeabilitythatmayleadtolaryngealedema,skinrash,and
hypotension.
TableI17ExamplesofDrugsandToxinsCausingAnaphylacticorAnaphylactoid
Reactions
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TableI17ExamplesofDrugsandToxinsCausingAnaphylacticorAnaphylactoid
Reactions
Anaphylacticreactions(IgEmediated) Anaphylactoidreactions(notIgEmediated)
Antisera(antivenins) Acetylcysteine(whengivenIV)
Foods(nuts,fish,shellfish) Bloodproducts
Hymenopteraandotherinsectstings Iodinatedcontrastmedia
Immunotherapyallergenextracts Opioids(eg,morphine)
Penicillinsandotherantibiotics Scombroid
Vaccines Tubocurarine
Otherorunclassified
Exercise
Sulfites
Tartrazinedye
1.AnaphylaxisoccurswhenapatientwithantigenspecificimmunoglobulinE(IgE)
boundtothesurfaceofmastcellsandbasophilsisexposedtotheantigen,triggering
thereleaseofhistamineandvariousothervasoactivecompounds.
2.Anaphylactoidreactionsarealsocausedbyreleaseofactivecompoundsfrom
mastcellsbutdonotinvolvepriorsensitizationormediationthroughIgE.
B.Complications.Severeanaphylacticoranaphylactoidreactionscanresultinlaryngeal
obstruction,respiratoryarrest,hypotension,anddeath.
1.Anxietywithvasodepressorsyncopeorhyperventilation.
2.Pharmacologiceffectsofthedrugortoxin(eg,procainereactionwithprocaine
penicillin).
3.Bronchospasmorlaryngealedemafromirritantgasexposure.
D.Treatment
1.Maintaintheairwayandassistventilationifnecessary(SeeAirway).Endotracheal
intubationmaybeneedediflaryngealswellingissevere.Administersupplemental
oxygen.
2.TreathypotensionwithIVcrystalloidfluids(eg,normalsaline)andplacethepatient
inasupineposition.
3.Administerepinephrine(SeeEpinephrine)asfollows:
a.Formildtomoderatereactions,administer0.30.5mgsubcutaneously(SC
children:0.01mg/kgtoamaximumof0.5mg).
b.Forseverereactions,administera0.05to0.1mgIVbolusevery5minutes,or
giveaninfusionstartingatarateof14mcg/minandtitratingupwardas
needed.
4.Administerdiphenhydramine(SeeDiphenhydramine),0.51mg/kgIVover1minute.
Followwithoraltherapyfor23days.Ahistamine2(H2)blockersuchasranitidine
(SeeCimetidineandOtherH2Blockers),150mgIVevery12hours,isalsohelpful.
5.Administeracorticosteroidsuchashydrocortisone,200300mgIV,or
methylprednisolone,4080mgIV.
ViewLarge|
Dystonia Dyskinesias
Haloperidolandbutyrophenones Amphetamines
Metoclopramide Anticholinergicagents
Phenothiazines(prochlorperazine) Antihistamines
Ziprasidoneandotheratypicalantipsychoticagents Caffeine
Rigidity Carbamazepine
Blackwidowspiderbite Carisoprodol
Lithium Cocaine
Malignanthyperthermia GHB(gammahydroxybutyrate)
Methaqualone Ketamine
Monoamineoxidaseinhibitors Levodopa
Neurolepticmalignantsyndrome Lithium
Phencyclidine(PCP) Phencyclidine(PCP)
Strychnine Serotoninreuptakeinhibitors(SSRIs)
Tetanus Tricyclicantidepressants
ViewLarge|
Excessivemuscularhyperactivity,rigidity,orseizures
Amphetaminesandderivatives
Clozapineandolanzapine
Cocaine
Lithium
Phencyclidine(PCP)
Seizurescausedbyavarietyofagents
Strychnine
Tetanus
Otherorunknownmechanisms
Carbonmonoxide
Chlorophenoxyherbicides
Colchicine
Ethanol
Ethyleneglycol
Gemfibrozil
Haffdisease(unknowntoxinfoundinBalticfish,buffalofish)
Hemlock
Hyperthermiacausedbyavarietyofagents
Hypokalemia
Mushrooms(someAmanita,Russula,Tricholomaspecies)
Prolongedimmobility(eg,comaduetocentralnervoussystemdepressantdrugoverdose)
Statincholesteroldrugs(eg,cerivastatin)
Trauma
TableI17ExamplesofDrugsandToxinsCausingAnaphylacticorAnaphylactoidReactions
ViewLarge|
TableI17ExamplesofDrugsandToxinsCausingAnaphylacticorAnaphylactoidReactions
Anaphylacticreactions(IgEmediated) Anaphylactoidreactions(notIgEmediated)
Antisera(antivenins) Acetylcysteine(whengivenIV)
Foods(nuts,fish,shellfish) Bloodproducts
Hymenopteraandotherinsectstings Iodinatedcontrastmedia
Immunotherapyallergenextracts Opioids(eg,morphine)
Penicillinsandotherantibiotics Scombroid
Vaccines Tubocurarine
Otherorunclassified
Exercise
Sulfites
Tartrazinedye
DiagnosisofPoisoning
Thediagnosisandtreatmentofpoisoningoftenmustproceedrapidlywithouttheresultsofextensive
toxicologicscreening.Fortunately,inmostcasesthecorrectdiagnosiscanbemadebyusingcarefully
collecteddatafromthehistory,adirectedphysicalexamination,andcommonlyavailablelaboratory
tests.
I.History.Althoughfrequentlyunreliableorincomplete,thehistoryofingestionmaybeveryuseful
ifcarefullyobtained.
A.Askthepatientaboutalldrugstaken,includingnonprescriptiondrugs,herbalmedicines,
andvitamins.
B.Askfamilymembers,friends,andparamedicalpersonnelaboutanyprescriptionsorover
thecountermedicationsknowntobeusedbythepatientorothersinthehouse.
C.Obtainanyavailabledrugsordrugparaphernaliaforlatertesting,buthandlethemvery
carefullytoavoidpoisoningbyskincontactoraninadvertentneedlestickwithpotentialfor
hepatitisBorhumanimmunodeficiencyvirus(HIV)transmission.
D.Checkwiththepharmacyonthelabelofanymedicationsfoundwiththepatientto
determinewhetherotherprescriptiondrugshavebeenobtainedthere.
II.Physicalexamination
A.Generalfindings.Performacarefullydirectedexamination,emphasizingkeyphysical
findingsthatmayuncoveroneofthecommonautonomicsyndromes.Importantvariables
intheautonomicphysicalexaminationincludebloodpressure,pulserate,pupilsize,
sweating,andperistalticactivity.TheautonomicsyndromesaresummarizedinTableI18.
TableI18AutonomicSyndromesa,b
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Blood Pulse Pupil
Sweating Peristalsis
Pressure Rate Size
Alphaadrenergic + + +
Betaadrenergic +
Mixedadrenergic + + + +
Sympatholytic
Nicotinic + + + +
Muscarinic + +
Mixedcholinergic + +
Anticholinergic
+ +
(antimuscarinic)
aKeytosymbols:+=increased++=markedlyincreased=decreased=markedly
decreased=mixedeffect,noeffect,orunpredictable.
bAdapted,withpermission,fromOlsonKRetal:MedToxicol19872:54.
1.Alphaadrenergicsyndrome.Hypertensionwithreflexbradycardiaischaracteristic
ofalphaadrenergicsyndrome.Thepupilsareusuallydilated.(Examples:
phenylpropanolamineandphenylephrine.)
2.Betaadrenergicsyndrome.Beta2mediatedvasodilationmaycausehypotension.
Tachycardiaiscommon.(Examples:albuterol,metaproterenol,theophylline,and
caffeine.)
3.Mixedalphaandbetaadrenergicsyndrome.Hypertensionisaccompaniedby
tachycardia.Thepupilsaredilated.Theskinissweaty,althoughmucousmembranes
aredry.(Examples:cocaineandamphetamines.)
4.Sympatholyticsyndrome.Bloodpressureandpulseratearebothdecreased.
(Exceptions:Peripheralalphareceptorantagonistsmaycausehypotensionwith
reflextachycardiaalpha2agonistsmaycauseperipheralvasoconstrictionwith
transienthypertension.)Thepupilsaresmall,oftenofpinpointsize.Peristalsisis
oftendecreased.(Examples:centrallyactingalpha2agonists[clonidineand
methyldopa],opioids,andphenothiazines.)
5.Nicotiniccholinergicsyndrome.Stimulationofnicotinicreceptorsatautonomic
gangliaactivatesbothparasympatheticandsympatheticsystems,withunpredictable
results.Excessivestimulationfrequentlyleadstodepolarizationblockade.Thus,
initialtachycardiamaybefollowedbybradycardia,andmusclefasciculationsmaybe
followedbyparalysis.(Examples:nicotineandthedepolarizingneuromuscular
blockersuccinylcholine,whichactonnicotinicreceptorsinskeletalmuscle.)
6.Muscariniccholinergicsyndrome.Muscarinicreceptorsarelocatedateffector
organsoftheparasympatheticsystem.Stimulationcausesbradycardia,miosis,
sweating,hyperperistalsis,bronchorrhea,wheezing,excessivesalivation,andurinary
incontinence.(Example:bethanechol.)
7.Mixedcholinergicsyndrome.Becausebothnicotinicandmuscarinicreceptorsare
stimulated,mixedeffectsmaybeseen.Thepupilsareusuallymiotic(ofpinpoint
size).Theskinissweaty,andperistalticactivityisincreased.Fasciculationsarea
manifestationofnicotinicstimulationoftheneuromuscularjunctionandmayprogress
tomuscleweaknessorparalysis.(Examples:organophosphateandcarbamate
insecticidesandphysostigmine.)
8.Anticholinergic(antimuscarinic)syndrome.Tachycardiawithmildhypertensionis
common.Thepupilsarewidelydilated.Theskinisflushed,hot,anddry.Peristalsis
isdecreased,andurinaryretentioniscommon.Patientsmayhavemyoclonicjerking
orchoreoathetoidmovements.Agitateddeliriumiscommon,andhyperthermiamay
occur.(Examples:atropine,scopolamine,benztropine,antihistamines,and
antidepressantsallofthesedrugsareprimarilyantimuscarinic.)
B.Eyefindings
1.Pupilsizeisaffectedbyanumberofdrugsthatactontheautonomicnervous
system.TableI19listscommoncausesofmiosisandmydriasis.
TableI19SelectedCausesofPupilSizeChangesa
ViewLarge|
CONSTRICTEDPUPILS(MIOSIS) DILATEDPUPILS(MYDRIASIS)
Sympatholyticagents Sympathomimeticagents
Clonidine Amphetaminesandderivatives
Opioids Cocaine
Phenothiazines Dopamine
Tetrahydrozolineandoxymetazoline LSD(lysergicaciddiethylamide)
Valproicacid Monoamineoxidaseinhibitors
Cholinergicagents Nicotineb
Carbamateinsecticides Anticholinergicagents
Nicotineb Antihistamines
Organophosphates Atropineandotheranticholinergics
Physostigmine Carbamazepine
Pilocarpine Glutethimide
Others Tricyclicantidepressants
Heatstroke
Pontineinfarct
Subarachnoidhemorrhage
bNicotinecancausethepupilstobedilated(rare)orconstricted(common).
2.Horizontalgazenystagmusiscommonwithavarietyofdrugsandtoxins,including
barbiturates,ethanol,carbamazepine,phenytoin,andscorpionenvenomation.
Phencyclidine(PCP)maycausehorizontal,vertical,andevenrotatorynystagmus.
C.Neuropathy.Avarietyofdrugsandpoisonscancausesensoryormotorneuropathy,
usuallyafterchronicrepeatedexposure(TableI20).Someagents(eg,arsenicand
thallium)cancauseneuropathyafterasinglelargeexposure.
TableI20SelectedCausesofNeuropathy
ViewLarge|
Cause Comments
Acrylamide Sensoryandmotordistalaxonalneuropathy
Vincristinemoststronglyassociated(SeeAntineoplastic
Antineoplasticagents
Agents)
Nucleosidereversetranscriptaseinhibitors(SeeAntiviraland
Antiretroviralagents
AntiretroviralAgents)
Arsenic Sensorypredominantmixedaxonalneuropathy(SeeArsenic)
Buckthorn(K
Livestockandhumandemyelinatingneuropathy(SeePlants)
humboldtiana)
Sensoryandmotordistalaxonalneuropathy(SeeCarbon
Carbondisulfide
Disulfide)
Dimethylaminopropionitrile Urogenitalanddistalsensoryneuropathy
Disulfiram Sensoryandmotordistalaxonalneuropathy(SeeDisulfiram)
Ethanol Sensoryandmotordistalaxonalneuropathy(SeeEthanol)
nHexane Sensoryandmotordistalaxonalneuropathy(SeeTableIV4)
Preventablewithcoadministrationofpyridoxine(SeeIsoniazid
Isoniazid(INH)
(INH))
Lead Motorpredominantmixedaxonalneuropathy(SeeLead)
Mercury Organicmercurycompounds(SeeMercury)
Methylnbutylketone Actslikenhexanevia2,5hexanedionemetabolite
Nitrofurantoin Sensoryandmotordistalaxonalneuropathy
Sensoryaxonalneuropathywithlossofproprioception(See
Nitrousoxide
NitrousOxide)
Organophosphate
Specificagentsonly(eg,triorthocresylphosphate)
insecticides
Sensoryneuropathywithchronicexcessivedosing(See
Pyridoxine(vitaminB6)
Pyridoxine(VitaminB6))
Selenium Polyneuritis(SeeSelenium)
Thallium Sensoryandmotordistalaxonalneuropathy(SeeThallium)
Tickparalysis Ascendingflaccidparalysisafterbitesbyseveraltickspecies
D.Abdominalfindings.Peristalticactivityiscommonlyaffectedbydrugsandtoxins(see
TableI18).
1.Ileusmayalsobecausedbymechanicalfactorssuchasinjurytothe
gastrointestinaltractwithperforationandperitonitisormechanicalobstructionbya
swallowedforeignbody.
2.Abdominaldistensionandileusmayalsobeamanifestationofacutebowel
infarction,ararebutcatastrophiccomplicationthatresultsfromprolonged
hypotensionormesentericarteryvasospasm(caused,forexample,byergotor
amphetamines).RadiographsorCTscansmayrevealairintheintestinalwall,biliary
tree,orhepaticvein.Theserumphosphorusandalkalinephosphataselevelsare
oftenelevated.
3.Vomiting,especiallywithhematemesis,mayindicatetheingestionofacorrosive
substance.
E.Skinfindings
1.Sweatingortheabsenceofsweatingmayprovideacluetooneoftheautonomic
syndromes(seeTableI18).
2.Flushedredskinmaybecausedbycarbonmonoxidepoisoning,boricacidtoxicity,
chemicalburnsfromcorrosivesorhydrocarbons,oranticholinergicagents.Itmay
alsoresultfromvasodilation(eg,phenothiazinesordisulfiramethanolinteraction).
3.Palecolorationwithdiaphoresisisfrequentlycausedbysympathomimeticagents.
Severelocalizedpallorshouldsuggestpossiblearterialvasospasm,suchasthat
causedbyergot(SeeErgotDerivatives)orsomeamphetamines[See
Amphetamines].
4.Cyanosismayindicatehypoxia,sulfhemoglobinemia,ormethemoglobinemia(See
Methemoglobinemia).
F.Odors.Anumberoftoxinsmayhavecharacteristicodors(TableI21).However,theodor
maybesubtleandmaybeobscuredbythesmellofvomitorbyotherambientodors.In
addition,theabilitytosmellanodormayvaryforexample,onlyabout50%ofthegeneral
populationcansmellthebitteralmondodorofcyanide.Thus,theabsenceofanodor
doesnotguaranteetheabsenceofthetoxin.
TableI21SomeCommonOdorsCausedbyToxinsandDrugsa
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Odor DrugorToxin
Acetone Acetone,isopropylalcohol
Acridorpearlike Chloralhydrate,paraldehyde
Bitteralmonds Cyanide
Carrots Cicutoxin(waterhemlock)
Garlic Arsenic(arsine),organophosphates,selenium,thallium
Mothballs Naphthalene,paradichlorobenzene
Pungentaromatic Ethchlorvynol
Rotteneggs Hydrogensulfide,stibine,mercaptans,oldsulfadrugs
Wintergreen Methylsalicylate
III.Essentialclinicallaboratorytests.Simple,readilyavailableclinicallaboratorytestsmay
provideimportantcluestothediagnosisofpoisoningandmayguidetheinvestigationtoward
specifictoxicologytesting.
A.Routinetests.Thefollowingtestsarerecommendedforroutinescreeningoftheoverdose
patient:
1.Measuredserumosmolalityandcalculationoftheosmolegap.
2.Electrolytesfordeterminationofthesodium,potassium,andaniongap.
3.Serumglucose.
4.Bloodureanitrogen(BUN)andcreatinineforevaluationofrenalfunction.
5.Hepaticaminotransferases(AST,ALT)andhepaticfunctiontests.
6.Completebloodcellcountorhemogram.
7.Urinalysistocheckforcrystalluria,hemoglobinuria,ormyoglobinuria.
8.ECG.
9.Statserumacetaminophenlevelandethanollevel.
10.Pregnancytest(femalesofchildbearingage).
B.Serumosmolalityandosmolegap.Serumosmolalitymaybemeasuredinthelaboratory
withthefreezingpointdepressionosmometerortheheatofvaporizationosmometer.
Undernormalcircumstances,themeasuredserumosmolalityisapproximately290
mOsm/Landcanbecalculatedfromtheresultsofthesodium,glucose,andbloodurea
nitrogen(BUN)tests.Thedifferencebetweenthecalculatedosmolalityandtheosmolality
measuredinthelaboratoryistheosmolegap(TableI22).Note:Clinicalstudiessuggest
thatthenormalosmolegapmayvaryfrom14to+10mOsm/L.Thus,smallosmolegaps
maybedifficulttointerpret.
TableI22CausesofElevatedOsmoleGapa
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Acetone Mannitol
Dimethylsulfoxide(DMSO) Metaldehyde
Ethanol Methanol
Ethylether Osmoticcontrastdyes
Ethyleneglycolandotherlow
Propyleneglycol
molecularweightglycols
Isopropylalcohol Renalfailurewithoutdialysis
Severealcoholicketoacidosis,diabetic
Magnesium
ketoacidosis,orlacticacidosis
aOsmolegap=measuredcalculatedosmolality.Normal=0510.Calculated
osmolality=2[Na]+[glucose]/18+[BUN]/2.8.Na(serumsodium)inmEq/Lglucoseand
BUN(bloodureanitrogen)inmg/dL.
Note:Theosmolalitymaybemeasuredasfalselynormalifavaporizationpoint
osmometerisusedinsteadofthefreezingpointdevicebecausevolatilealcoholswillbe
boiledoff.
1.Causesofanelevatedosmolegap(seeTableI22)
a.Theosmolegapmaybeincreasedinthepresenceoflowmolecularweight
substancessuchasethanol,otheralcohols,andglycols,anyofwhichcan
contributetothemeasuredbutnotthecalculatedosmolality.TableI23
describeshowtoestimatealcoholandglycollevelsbyusingtheosmolegap.
TableI23EstimationofAlcoholandGlycolLevelsfromtheOsmoleGapa
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AlcoholorGlycol MolecularWeight(mg/mmol) ConversionFactorb
Acetone 58 5.8
Ethanol 46 4.6c
Ethyleneglycol 62 6.2
Isopropylalcohol 60 6
Methanol 32 3.2
Propyleneglycol 76 7.6
aAdapted,withpermission,fromHoMT,SaundersCE(editors):Current
EmergencyDiagnosis&Treatment,3rded.Appleton&Lange,1990.
bToobtainestimatedserumlevel(inmg/dL),multiplyosmolegapby
conversionfactor.
cOneclinicalstudy(PurssellRAetal:AnnEmergMed200138:653)found
thataconversionfactorof3.7wasmoreaccurateforestimatingthe
contributionofethanoltotheosmolegap.
b.Anosmolegapaccompaniedbyaniongapacidosisshouldimmediately
suggestpoisoningbymethanolorethyleneglycol.Note:Afalselynormal
osmolegapdespitethepresenceofvolatilealcoholsmayresultfromusinga
heatofvaporizationmethodtomeasureosmolalitybecausethealcoholswill
boiloffbeforetheserumboilingpointisreached.
2.Differentialdiagnosis
a.Combinedosmoleandaniongapelevationmayalsobeseenwithsevere
alcoholicketoacidosisordiabeticketoacidosis,owingtotheaccumulationof
unmeasuredanions(betahydroxybutyrate)andosmoticallyactivesubstances
(acetone,glycerol,andaminoacids).
b.Patientswithchronicrenalfailurewhoarenotundergoinghemodialysismay
haveanelevatedosmolegapowingtotheaccumulationoflowmolecular
weightsolutes.
c.Falseelevationoftheosmolegapmaybecausedbytheuseofan
inappropriatesampletube(lavendertop,ethylenediaminetetraaceticacid
[EDTA]graytop,fluorideoxalatebluetop,citrateseeTableI33).
d.Afalselyelevatedgapmayoccurinpatientswithseverehyperlipidemia.
3.Treatmentdependsonthecause.Ifethyleneglycol(SeeEthyleneGlycolandOther
Glycols)ormethanol(SeeMethanol)poisoningissuspected,basedonanelevated
osmolegapnotaccountedforbyethanolorotheralcoholsandonthepresenceof
metabolicacidosis,antidotaltherapy(eg,fomepizole[SeeFomepizole(4
Methylpyrazole,4Mp)]orethanol[SeeEthanol])andhemodialysismaybeindicated.
C.Aniongapmetabolicacidosis.Thenormalaniongapof812mEq/Laccountsfor
unmeasuredanions(eg,phosphate,sulfate,andanionicproteins)intheplasma.Metabolic
acidosisisusuallyassociatedwithanelevatedaniongap.
1.Causesofelevatedaniongap(TableI24)
TableI24SelectedDrugsandToxinsCausingElevatedAnionGapAcidosisa,b
ViewLarge|
Lacticacidosis Otherthanlacticacidosis
Acetaminophen(levels>600mg/L) Alcoholicketoacidosis(betahydroxybutyrate)
Antiretroviraldrugs Benzylalcohol
Betaadrenergicreceptoragonists Diabeticketoacidosis
Caffeine Ethyleneglycol(glycolicandotheracids)
Carbonmonoxide Exogenousorganicandmineralacids
Cyanide Formaldehyde(formicacid)
Hydrogensulfide Ibuprofen(propionicacid)
Iron Metaldehyde
Isoniazid(INH) Methanol(formicacid)
Metforminandphenformin 5Oxoprolinuriaandotherorganicacidurias
Propofol(highdose,children) Salicylates(salicylicacid)
Salicylates Valproicacid
Seizures,shock,orhypoxia
Sodiumazide
Theophylline
aAniongap=[Na][Cl][HCO ]=812mEq/L.
3
bAdaptedinpart,withpermission,fromOlsonKRetal:MedToxicol19872:73.
a.Anelevatedaniongapacidosisisusuallycausedbyanaccumulationoflactic
acidbutmayalsobecausedbyotherunmeasuredacidanions,suchas
formate(eg,methanolpoisoning),glycolateoroxalate(eg,ethyleneglycol
poisoning),andbetahydroxybutyrate(inpatientswithketoacidosis).
b.Inanypatientwithanelevatedaniongap,alsochecktheosmolegapa
combinationofelevatedanionandosmolegapssuggestspoisoningby
methanolorethyleneglycol.Note:Combinedosmoleandaniongapelevation
mayalsobeseenwithseverealcoholicketoacidosisandevendiabetic
ketoacidosis.
c.Anarrowaniongapmayoccurwithanoverdosebybromideornitrate,bothof
whichcanincreasetheserumchloridelevelmeasuredbysomelaboratory
instruments.Also,highconcentrationsoflithium,calcium,ormagnesiumwill
narrowtheaniongapowingtorelativeloweringoftheserumsodium
concentrationorthepresenceoftheirsalts(chloride,carbonate).
2.Differentialdiagnosis.Ruleoutthefollowing:
a.Commoncausesoflacticacidosissuchashypoxiaandischemia.
b.FalsedepressionoftheserumbicarbonateandPco2measurements,whichcan
occurfromincompletefillingoftheredtoppedVacutainerbloodcollectiontube.
c.FalsedepressionofthePco2andcalculatedbicarbonatemeasurements,which
canresultfromexcessheparinwhenarterialbloodgasesareobtained(0.25
mLofheparinin2mLofbloodfalselylowersthePco2byabout8mmHgand
bicarbonatebyabout5mEq/L).
d.Falseelevationoftheserumlactateowingtoanaerobicglycolysisintheblood
sampletubebeforeseparationandtesting.
3.Treatment
a.Treattheunderlyingcauseoftheacidosis.
1.Treatseizures(SeeSeizures)withanticonvulsantsorneuromuscular
paralysis.
2.Treathypoxia(SeeHypoxia)andhypotension(SeeHypotension)ifthey
occur.
3.Treatmethanol(SeeMethanol)orethyleneglycol(SeeEthyleneGlycol
andOtherGlycols)poisoningwithfomepizole(orethanol)and
hemodialysis.
4.Treatsalicylateintoxication(SeeSalicylates)withalkalinediuresisand
hemodialysis.
b.TreatmentoftheacidemiaitselfisnotgenerallynecessaryunlessthepHis
lessthan77.1.Infact,mildacidosismaybebeneficialbypromotingoxygen
releasetotissues.However,acidemiamaybeharmfulinpoisoningby
salicylatesortricyclicantidepressants.
1.Insalicylateintoxication(SeeSalicylates),acidemiaenhancessalicylate
entryintothebrainandmustbeprevented.Alkalinizationoftheurine
promotessalicylateelimination.
2.Inatricyclicantidepressantoverdose(SeeAntidepressants,Tricyclic),
acidemiaenhancescardiotoxicity.MaintaintheserumpHat7.457.5with
bolusesofsodiumbicarbonate.
D.Hyperglycemiaandhypoglycemia.Avarietyofdrugsanddiseasestatescancause
alterationsintheserumglucoselevel(TableI25).Apatient'sbloodglucoselevelcanbe
alteredbythenutritionalstate,endogenousinsulinlevels,andendocrineandliverfunction
andbythepresenceofvariousdrugsortoxins.Ifinsulinadministrationissuspectedasthe
causeofthehypoglycemia,obtainserumlevelsofinsulinandCpeptidealowCpeptide
levelinthepresenceofahighinsulinlevelsuggestsanexogenoussource.
TableI25SelectedCausesofAlterationsinSerumGlucose
ViewLarge|
Hyperglycemia
Beta2adrenergicreceptoragonists
Caffeineintoxication
Corticosteroids
Dextroseadministration
Diabetesmellitus
Diazoxide
Excessivecirculatingepinephrine
Glucagon
Ironpoisoning
Theophyllineintoxication
Thiazidediuretics
Vacor
Hypoglycemia
Akeefruit(unripe)
Endocrinedisorders(hypopituitarism,Addisondisease,myxedema)
Ethanolintoxication(especiallypediatric)
Fasting
Hepaticfailure
Insulin
Oralsulfonylureahypoglycemicagents
Pentamidine
Propranololintoxication
Renalfailure
Salicylateintoxication
Streptozocin
Valproicacidintoxication
1.Hyperglycemia,especiallyifsevere(>500mg/dL[28mmol/L])orsustained,may
resultindehydrationandelectrolyteimbalancecausedbytheosmoticeffectof
excessglucoseintheurineinaddition,theshiftingofwaterfromthebraininto
plasmamayresultinhyperosmolarcoma.Morecommonly,hyperglycemiain
poisoningordrugoverdosecasesismildandtransient.Significantorsustained
hyperglycemiashouldbetreatedifitisnotresolvingspontaneouslyorifthepatientis
symptomatic.
a.Ifthepatienthasalteredmentalstatus,maintainanopenairway,assist
ventilationifnecessary,andadministersupplementaloxygen(SeeAirway).
b.ReplacefluiddeficitswithIVnormalsalineoranotherisotoniccrystalloid
solution.Monitorserumpotassiumlevels,whichmayfallsharplyastheblood
glucoseiscorrected,andgivesupplementalpotassiumasneeded.
c.Correctacidbaseandelectrolytedisturbances.
d.Administerregularinsulin,510UIVinitially,followedbyinfusionof510U/h,
whilemonitoringtheeffectsontheserumglucoselevel(children:administer
0.1U/kginitiallyand0.1U/kg/h[SeeInsulin)]).
2.Hypoglycemia,ifsevere(serumglucose<40mg/dL[2.2mmol/L])andsustained,
canrapidlycausepermanentbraininjury.Forthisreason,wheneverhypoglycemiais
suspectedasacauseofseizures,coma,oralteredmentalstatus,immediateempiric
treatmentwithdextroseisindicated.
a.Ifthepatienthasalteredmentalstatus,maintainanopenairway,assist
ventilationifnecessary,andadministersupplementaloxygen(SeeAirway).
b.Ifavailable,performrapidbedsidebloodglucosetesting(nowpossibleinmost
emergencydepartments).
c.Ifthebloodglucoseislow(<6070mg/dL[3.33.9mmol/L])orifbedside
testingisnotavailable,administerconcentrated50%dextrose,50mLIV(25g).
Inchildren,give25%dextrose,2mL/kg(SeeGlucose).Insmallinfants,some
cliniciansuse10%dextrose.
d.Inmalnourishedoralcoholicpatients,alsogivethiamine,100mgIMorIV,to
treatorpreventacuteWernickesyndrome.
e.Forhypoglycemiacausedbyoralsulfonylureadrugoverdose(SeeAntidiabetic
Agents),considerantidotaltherapywithoctreotide(SeeOctreotide)or,if
octreotideisnotavailable,diazoxide(SeeDiazoxide).
E.Hypernatremiaandhyponatremia.Sodiumdisordersoccurinfrequentlyinpoisoned
patients(seeTableI26).Morecommonlytheyareassociatedwithunderlyingdisease
states.Antidiuretichormone(ADH)isresponsibleforconcentratingtheurineand
preventingexcesswaterloss.
TableI26SelectedDrugsandToxinsAssociatedwithAlteredSerumSodium
ViewLarge|
Hypernatremia Hyponatremia
Catharticabuse Beerpotomania
Cerebralsaltwastingsyndrome(eg,after
Lactulosetherapy
trauma)
Lithiumtherapy(nephrogenicdiabetes
Diuretics
insipidus)
Mannitol Iatrogenic(IVfluidtherapy)
Severegastroenteritis(manypoisons) SyndromeofinappropriateADH(SIADH):
Sodiumorsaltoverdose Amitriptyline
Valproicacid(divalproexsodium) Chlorpropamide
Clofibrate
MDMA(ecstasy)
Oxytocin
Phenothiazines
1.Hypernatremia(serumsodium>145mEq/L)maybecausedbyexcessivesodium
intake,excessivefreewaterloss,orimpairedrenalconcentratingability.
a.Dehydrationwithnormalkidneyfunction.Excessivesweating,
hyperventilation,diarrhea,orosmoticdiuresis(eg,hyperglycemiaormannitol
administration)maycausedisproportionalwaterloss.Theurineosmolalityis
usuallygreaterthan400mOsm/kg,andtheantidiuretichormone(ADH)
functionisnormal.
b.Impairedrenalconcentratingability.Excessfreewaterislostintheurine,
andurineosmolalityisusuallylessthan250mOsm/L.Thismaybecausedby
hypothalamicdysfunctionwithreducedADHproduction(diabetesinsipidus
[DI])orimpairedkidneyresponsetoADH(nephrogenicDI).NephrogenicDI
hasbeenassociatedwithlongtermlithiumtherapyaswellasacuteoverdose.
2.Treatmentofhypernatremia.Treatmentdependsonthecause,butinmostcases,
thepatientishypovolemicandneedsfluids.Caution:Donotreducetheserum
sodiumleveltooquicklybecauseosmoticimbalancemaycauseexcessivefluidshift
intobraincells,resultingincerebraledema.Thecorrectionshouldtakeplaceover
2436hourstheserumsodiumshouldbeloweredabout1mEq/L/h.
a.Hypovolemia.AdministerNS(0.9%sodiumchloride)torestorevolume,then
switchtohalfNSindextrose(D5W0.45%sodiumchloride).
b.Volumeoverload.Treatwithacombinationofsodiumfreeorlowsodiumfluid
(eg,5%dextroseorD5W0.25%sodiumchloride)andaloopdiureticsuchas
furosemide,0.51mg/kgIV.
c.LithiuminducednephrogenicDI.Administerfluids(seeItem2.aabove).
Discontinuelithiumtherapy.Partialimprovementmaybeseenwithoral
administrationofindomethacin,50mg3timesaday,andhydrochlorothiazide,
50100mg/d.(Note:However,thiazidesmayalsoimpairrenallithium
clearance.)
3.Hyponatremia(serumsodium<130mEq/L)isacommonelectrolyteabnormality
andmayresultfromavarietyofmechanisms.Severehyponatremia(serumsodium
<110120mEq/L)canresultinseizuresandalteredmentalstatus.
a.Pseudohyponatremiamayresultfromashiftofwaterfromtheextracellular
space(eg,hyperglycemia).Plasmasodiumfallsbyabout1.6mEq/Lforeach
100mg/dL(5.6mmol/L)riseinglucose.Reducedrelativebloodwatervolume
(eg,hyperlipidemiaorhyperproteinemia)mayalsoproduce
pseudohyponatremiaifolder(flameemission)devicesareused,butthisis
unlikelywithcurrentdirectmeasurementelectrodes.
b.Hyponatremiawithhypovolemiamaybecausedbyexcessivevolumeloss
(sodiumandwater)thatispartiallyreplacedbyfreewater.Tomaintain
intravascularvolume,thebodysecretesADH,whichcauseswaterretention.A
urinesodiumleveloflessthan10mEq/Lsuggeststhatthekidneyis
appropriatelyattemptingtocompensateforvolumelosses.Anelevatedurine
sodiumlevel(>20mEq/L)impliesrenalsaltwasting,whichcanbecausedby
diuretics,adrenalinsufficiency,ornephropathy.Asyndromeofsaltwastinghas
beenreportedinsomepatientswithheadtrauma(cerebralsaltwasting
syndrome).
c.Hyponatremiawithvolumeoverloadoccursinconditionssuchascongestive
heartfailureandcirrhosis.Althoughthetotalbodysodiumisincreased,
baroreceptorssenseaninadequatecirculatingvolumeandstimulatethe
releaseofADH.Theurinesodiumlevelisnormallylessthan10mEq/Lunless
thepatienthasbeenondiuretics.
d.Hyponatremiawithnormalvolumeoccursinavarietyofsituations.
Measurementofserumandurineosmolalitiesmayhelpdeterminethe
diagnosis.
1.SyndromeofinappropriateADHsecretion(SIADH).ADHissecreted
independentlyofvolumeorosmolality.Causesincludemalignancies,
pulmonarydisease,severeheadinjury,andsomedrugs(seeTableI26).
Theserumosmolalityislow,buttheurineosmolalityisinappropriately
increased(>300mOsm/L).TheserumBUNisusuallylow(<10mg/dL
[3.6mmol/L]).
2.Psychogenicpolydipsia,orcompulsivewaterdrinking(generally>10
L/d),causesreducedserumsodiumbecauseoftheexcessivefreewater
intakeandbecausethekidneyexcretessodiumtomaintaineuvolemia.
Theurinesodiumlevelmaybeelevated,buturineosmolalityis
appropriatelylowbecausethekidneyisattemptingtoexcretetheexcess
waterandADHsecretionissuppressed.
3.Beerpotomaniamayresultfromchronicdailyexcessivebeerdrinking
(>4L/d).Itusuallyoccursinpatientswithcirrhosiswhoalreadyhave
elevatedADHlevels.
4.Othercausesofeuvolemichyponatremiaincludehypothyroidism,
postoperativestate,andidiosyncraticreactionstodiuretics(generally
thiazides).
4.Treatmentofhyponatremia.Treatmentdependsonthecause,thepatient'svolume
status,and,mostimportantly,thepatient'sclinicalcondition.Caution:Avoidoverly
rapidcorrectionofthesodiumbecausebraindamage(centralpontinemyelinolysis)
mayoccurifthesodiumisincreasedbymorethan25mEq/Linthefirst24hours.
Obtainfrequentmeasurementsoftheserumandurinesodiumlevelsandadjustthe
rateofinfusionasneededtoincreasetheserumsodiumbynomorethan11.5
mEq/h.Arrangeconsultationwithanephrologistassoonaspossible.Forpatients
withprofoundhyponatremia(serumsodium<110mEq/L)accompaniedbycoma
orseizures,administerhypertonic(3%sodiumchloride)saline,100200mL.
a.Hyponatremiawithhypovolemia.ReplacelostvolumewithNS(0.9%sodium
chloride).Ifadrenalinsufficiencyissuspected,givehydrocortisone,100mg
every68hours.Hypertonicsaline(3%sodiumchloride)israrelyindicated.
b.Hyponatremiawithvolumeoverload.Restrictwater(0.51L/d)andtreatthe
underlyingcondition(eg,congestiveheartfailure).Ifdiureticsaregiven,donot
allowexcessivefreewaterintake.Hypertonicsalineisdangerousinthese
patientsifitisused,alsoadministerfurosemide,0.51mg/kgIV.Consider
hemodialysistoreducevolumeandrestorethesodiumlevel.
c.Hyponatremiawithnormalvolume.Asymptomaticpatientsmaybetreated
conservativelywithwaterrestriction(0.51L/d).Psychogeniccompulsivewater
drinkersmayhavetoberestrainedorseparatedfromallsourcesofwater,
includingwashbasinsandtoilets.Demeclocycline(atetracyclineantibioticthat
canproducenephrogenicDI),300600mgtwiceaday,canbeusedtotreat
mildchronicSIADHtheonsetofactionmayrequireaweek.Forpatientswith
comaorseizures,givehypertonic(3%)saline,100200mL,alongwith
furosemide,0.51mg/kg.
F.Hyperkalemiaandhypokalemia.Avarietyofdrugsandtoxinscancauseserious
alterationsintheserumpotassiumlevel(TableI27).Potassiumlevelsaredependenton
potassiumintakeandrelease(eg,frommuscles),diureticuse,properfunctioningofthe
ATPasepump,serumpH,andbetaadrenergicactivity.Changesinserumpotassium
levelsdonotalwaysreflectoverallbodygainorlossbutmaybecausedbyintracellular
shifts(eg,acidosisdrivespotassiumoutofcells,butbetaadrenergicstimulationdrivesit
intocells).
TableI27SelectedDrugsandToxinsandOtherCausesofAlteredSerumPotassiuma
ViewLarge|
Hyperkalemia Hypokalemia
Acidosis Alkalosis
Angiotensinconvertingenzyme(ACE)inhibitors Barium
Betareceptorantagonists Betaadrenergicdrugs
Digitalisglycosides Caffeine
Fluoride Cesium
Lithium Diuretics(chronic)
Potassium Epinephrine
Renalfailure Theophylline
Rhabdomyolysis Toluene(chronic)
1.Hyperkalemia(serumpotassium>5mEq/L)producesmuscleweaknessand
interfereswithnormalcardiacconduction.PeakedTwavesandprolongedPR
intervalsaretheearliestsignsofcardiotoxicity.Criticalhyperkalemiaproduces
widenedQRSintervals,AVblock,ventricularfibrillation,andcardiacarrest(see
FigureI5).
a.Hyperkalemiacausedbyfluorideintoxication(SeeFluoride)isusually
accompaniedbyhypocalcemia.
b.Digoxinorothercardiacglycosideintoxicationassociatedwith
hyperkalemiaisanindicationforadministrationofdigoxinspecificFab
antibodies(SeeDigoxinSpecificAntibodies).
2.Treatmentofhyperkalemia.Apotassiumlevelhigherthan6mEq/Lisamedical
emergencyalevelhigherthan7mEq/Liscritical.
a.MonitortheECG.QRSprolongationindicatescriticalcardiacpoisoning.
b.Administer10%calciumchloride,510mL,or10%calciumgluconate,1020
mL(SeeCalcium),iftherearesignsofcriticalcardiactoxicitysuchaswide
QRScomplexes,absentPwaves,andbradycardia.
c.Sodiumbicarbonate,12mEq/kgIV(SeeBicarbonate,Sodium),rapidlydrives
potassiumintocellsandlowerstheserumlevel.
d.Glucoseplusinsulinalsopromotesintracellularmovementofpotassium.Give
50%dextrose,50mL(25%dextrose,2mL/kginchildren),plusregularinsulin,
0.1U/kgIV.
e.Inhaledbeta2adrenergicagonistssuchasalbuterolalsoenhancepotassium
entryintocellsandcanprovidearapidsupplementalmethodofloweringserum
potassiumlevels.
f.Sodiumpolystyrenesulfonate(SPSKayexalate),0.30.6g/kgorallyin2mLof
70%sorbitolperkilogram,iseffectiveatremovingpotassiumfromthebodybut
takesseveralhours.
g.Hemodialysisrapidlylowersserumpotassiumlevels.
3.Hypokalemia(serumpotassium<3.5mEq/L)maycausemuscleweakness,
hyporeflexia,andileus.Rhabdomyolysismayoccur.TheECGshowsflattenedT
wavesandprominentUwaves.Inseverehypokalemia,AVblock,ventricular
dysrhythmias,andcardiacarrestmayoccur.
a.Withtheophylline,caffeine,orbeta2agonistintoxication,anintracellular
shiftofpotassiummayproduceaverylowserumpotassiumlevelwithnormal
totalbodystores.PatientsusuallydonothaveserioussymptomsorECGsigns
ofhypokalemia,andaggressivepotassiumtherapyisnotrequired.
b.Withbariumpoisoning(SeeBarium),profoundhypokalemiamayleadto
respiratorymuscleweaknessandcardiacandrespiratoryarresttherefore,
intensivepotassiumtherapyisnecessary.Upto420mEqhasbeengivenin24
hours.
c.Hypokalemiaresultingfromdiuretictherapymaycontributetoventricular
dysrhythmias,especiallythoseassociatedwithchronicdigitalisglycoside
poisoning.
4.Treatmentofhypokalemia.Mildhypokalemia(potassium,33.5mEq/L)isusually
notassociatedwithserioussymptoms.
a.AdministerpotassiumchlorideorallyorIV.SeePotassiumforrecommended
dosesandinfusionrates.
b.MonitorserumpotassiumandtheECGforsignsofhyperkalemiafrom
excessivepotassiumtherapy.
c.Ifhypokalemiaiscausedbydiuretictherapyorgastrointestinalfluidlosses,
measureandreplaceotherions,suchasmagnesium,sodium,andchloride.
G.Renalfailure.ExamplesofdrugsandtoxinsthatcauserenalfailurearelistedinTableI
28.Renalfailuremaybecausedbyadirectnephrotoxicactionofthepoisonoracute
massivetubularprecipitationofmyoglobin(rhabdomyolysis),hemoglobin(hemolysis),or
calciumoxalatecrystals(ethyleneglycol),oritmaybesecondarytoshockcausedby
bloodorfluidlossorcardiovascularcollapse.
TableI28ExamplesofDrugsandToxinsandOtherCausesofAcuteRenalFailure
ViewLarge|
Directnephrotoxiceffect
Acetaminophen
Acyclovir(chronic,highdosetreatment)
Amanitaphalloidesmushrooms
Amanitasmithianamushrooms
Analgesics(eg,ibuprofen,phenacetin)
Antibiotics(eg,aminoglycosides)
Bromates
Chlorates
Cortinariusspeciesmushrooms
Cyclosporine
Ethylenediaminetetraaceticacid(EDTA)
Ethyleneglycol(glycolate,oxalate)
Foscarnet
Heavymetals(eg,mercury)salts
Indinavir
Hemolysis
Arsine
Naphthalene
Oxidizingagents(especiallyinpatientswithglucose6phosphatedehydrogenase[G6PD]
deficiency)
Rhabdomyolysis(seealsoTABLEI16)
Amphetaminesandcocaine
Comawithprolongedimmobility
Hyperthermia
Phencyclidine(PCP)
Statusepilepticus
Strychnine
1.Assessment.Renalfailureischaracterizedbyaprogressiveriseintheserum
creatinineandbloodureanitrogen(BUN)levels,usuallyaccompaniedbyoliguriaor
anuria.
a.Theserumcreatinineconcentrationusuallyrisesabout11.5mg/dL/d(88132
mcmol/L/d)aftertotalanuricrenalfailure.
b.Amoreabruptriseshouldsuggestrapidmusclebreakdown(rhabdomyolysis),
whichincreasesthecreatineloadandalsoresultsinelevatedserumCKlevels
thatmayinterferewithadeterminationoftheserumcreatininelevel.
c.Oliguriamaybeseenbeforerenalfailureoccurs,especiallywithhypovolemia,
hypotension,orheartfailure.Inthiscase,theBUNlevelisusuallyelevatedout
ofproportiontotheserumcreatininelevel.
d.Falseelevationofthecreatininelevelcanbecausedbynitromethane,
isopropylalcohol,andketoacidosisowingtointerferencewiththeusual
colorimetriclaboratorymethod.TheBUNremainsnormal,whichmayhelpto
distinguishfalsefromrealelevationofthecreatinine.
2.Complications.Theearliestcomplicationofacuterenalfailureishyperkalemia(See
DiagnosisofPoisoning)thismaybemorepronouncedifthecauseoftherenal
failureisrhabdomyolysisorhemolysis,bothofwhichreleaselargeamountsof
intracellularpotassiumintothecirculation.Latercomplicationsincludemetabolic
acidosis,delirium,andcoma.
3.Treatment
a.Preventrenalfailure,ifpossible,byadministeringspecifictreatment(eg,
acetylcysteineforacetaminophenoverdose[althoughofuncertainbenefitfor
thiscomplication],BritishantiLewisite[BALdimercaprol]chelationformercury
poisoning,andIVfluidsforrhabdomyolysisorshock).
b.Monitortheserumpotassiumlevelfrequentlyandtreathyperkalemia(See
DiagnosisofPoisoning)ifitoccurs.
c.Donotgivesupplementalpotassium,andavoidcatharticsorothermedications
containingmagnesium,phosphate,orsodium.
d.Performhemodialysisasneeded.
H.Hepaticfailure.Avarietyofdrugsandtoxinsmaycausehepaticinjury(TableI29).
Mechanismsoftoxicityincludedirecthepatocellulardamage(eg,Amanitaphalloidesand
relatedmushrooms[SeeMushrooms,AmatoxinType]),metaboliccreationofa
hepatotoxicintermediate(eg,acetaminophen[SeeAcetaminophen]orcarbontetrachloride
[SeeCarbonTetrachlorideandChloroform]),andhepaticvenoocclusivedisease(eg,
pyrrolizidinealkaloidsseePlants).
TableI29ExamplesofDrugsandToxinsCausingHepaticDamage
ViewLarge|
Acetaminophen
Amanitaphalloidesandsimilarmushrooms
Arsenic
Carbontetrachlorideandotherchlorinatedhydrocarbons
Copper
Dimethylformamide
Ethanol
Gyrometramushrooms
Halothane
Iron
Kava
Niacin(sustainedreleaseformulation)
2Nitropropane
Pennyroyaloil
Phenol
Phosphorus
Polychlorinatedbiphenyls(PCBs)
Pyrrolizidinealkaloids(seePlants)
Thallium
Troglitazone
Valproicacid
1.Assessment.Laboratoryandclinicalevidenceofhepatitisoftendoesnotbecome
apparentuntil2436hoursafterexposuretothepoison.Thenaminotransferase
(AST,ALT)levelsrisesharplyandmayfalltonormaloverthenext35days.If
hepaticdamageissevere,measurementsofhepaticfunction(eg,bilirubinand
prothrombintime)willcontinuetoworsenafter23days,evenasaminotransferase
levelsarereturningtonormal.Metabolicacidosisandhypoglycemiausuallyindicate
apoorprognosis.
2.Complications
a.Abnormalhepaticfunctionmayresultinexcessivebleedingowingto
insufficientproductionofvitaminKdependentcoagulationfactors.
b.Hepaticencephalopathymayleadtocomaanddeath,usuallywithin57days,
frommassivehepaticfailure.
3.Treatment
a.Preventhepaticinjuryifpossiblebyadministeringspecifictreatment(eg,
acetylcysteineforacetaminophenoverdose).
b.Obtainbaselineanddailyaminotransferase,bilirubin,andglucoselevelsand
prothrombintime.
c.Provideintensivesupportivecareforhepaticfailureandencephalopathy(eg,
glucoseforhypoglycemia,freshfrozenplasmaorclottingfactorconcentrates
forcoagulopathy,orlactuloseforencephalopathy).
d.Livertransplantmaybetheonlyeffectivetreatmentoncemassivehepatic
necrosishasresultedinsevereencephalopathy.
IV.Toxicologyscreening.*Tomaximizetheutilityofthetoxicologylaboratory,itisnecessaryto
understandwhatthelaboratorycanandcannotdoandhowknowledgeoftheresultswillaffect
thepatient.Comprehensivebloodandurinescreeningisoflittlepracticalvalueintheinitialcare
ofthepoisonedpatient,mainlybecauseofthelongtimeneededobtainresults.However,
specifictoxicologicanalysesandquantitativelevelsofcertaindrugsmaybeextremelyhelpful.
Beforeorderinganytests,alwaysaskthesetwoquestions:(1)Howwilltheresultofthetest
altertheapproachtotreatment?and(2)Cantheresultofthetestbereturnedintimetoaffect
therapypositively?
A.Limitationsoftoxicologyscreens.Owingtolongturnaroundtime(15days),lackof
availability,reliabilityfactors,andthelowriskforseriousmorbiditywithsupportiveclinical
management,toxicologyscreeningisestimatedtoaffectmanagementinfewerthan15%
ofallcasesofpoisoningordrugoverdose.
1.Althoughimmunoassaysforurinedrugtestingarewidelyavailableandinexpensive,
andhavefastturnaroundtimes,someassayssufferfrompoorsensitivitytosome
membersofadrugclass,whereasotherassaysproducefalsepositiveresultsto
structuralanalogsanddrugsthatarethemselvesnotpartofatargeteddrugclass.In
manyothercases,therearenoimmunoassaysavailableatall.
2.Comprehensivetoxicologyscreensorpanelsmaylookspecificallyforonly40100
drugsamongmorethan10,000possibledrugsortoxins(or6millionchemicals).
However,these4050drugs(TablesI30andI31)accountformorethan80%of
overdoses.
TableI30DrugsCommonlyIncludedinaComprehensiveUrineScreena
ViewLarge|
Alcohols Sedativehypnoticdrugs
Acetone Barbituratesc
Ethanol Benzodiazepinesc
Isopropylalcohol Carisoprodol
Methanol Chloralhydrate
Analgesics Ethchlorvynol
Acetaminophen Glutethimide
Salicylates Meprobamate
Anticonvulsants Methaqualone
Carbamazepine Stimulants
Phenobarbital Amphetaminesc
Phenytoin Caffeine
Primidone Cocaineandbenzoylecgonine
Antihistamines Phencyclidine(PCP)
Benztropine Strychnine
Chlorpheniramine Tricyclicantidepressants
Diphenhydramine Amitriptyline
Pyrilamine Desipramine
Trihexyphenidyl Doxepin
Opioids Imipramine
Codeine Nortriptyline
Dextromethorphan Protriptyline
Hydrocodone Cardiacdrugs
Meperidine Diltiazem
Methadone Lidocaine
Morphine Procainamide
Oxycodoneb Propranolol
Pentazocine Quinidineandquinine
Propoxyphene Verapamil
Phenothiazines
Chlorpromazine
Prochlorperazine
Promethazine
Thioridazine
Trifluoperazine
aNewerdrugsinanycategorymaynotbeincludedinscreening.
bDependsontheorderoftesting.
cNotalldrugsinthisclassaredetected.
TableI31DrugsCommonlyIncludedinaHospitalDrugsofAbusePanela
ViewLarge|
DetectionTime
Windowfor
Drug Comments
Recreational
Doses
OftenmissesMDAorMDMA.Manyfalse
Amphetamines 2days
positives(seeTableI33).
Lessthan2days
formostdrugs,up
Barbiturates
to1weekfor
phenobarbital
27days(varies
withspecificdrug Maynotdetecttriazolam,lorazepam,
Benzodiazepines
anddurationof alprazolam,othernewerdrugs.
use)
Cocaine 2days Detectsmetabolitebenzoylecgonine.
Ethanol Lessthan1day
Marijuana 25daysafter
(tetrahydrocannabinol singleuse(longer
[THC]) forchronicuse)
Syntheticopioids(meperidine,methadone,
propoxyphene,oxycodone)areoftennot
Opioids 23days
detected.Separatetestingformethadone
issometimesoffered.
Phencyclidine(PCP) Upto7days SeeTableI33.
aLaboratoriesoftenperformonlysomeofthesetests,dependingonwhattheir
emergencydepartmentrequestsandlocalpatternsofdruguseinthecommunity.
Also,positiveresultsareusuallynotconfirmedwithasecond,morespecifictest
thus,falsepositivesmaybereported.
3.Todetectmanydifferentdrugs,comprehensivescreensusuallyincludemultiple
methodswithbroadspecificity,andsensitivitymaybepoorforsomedrugs(resulting
inanalyticfalsenegativeresults).However,somedrugspresentintherapeutic
amountsmaybedetectedonthescreeneventhoughtheyarecausingnoclinical
symptoms(clinicalfalsepositives).
4.Becausemanyagentsareneithersoughtnordetectedduringatoxicologyscreening
(TableI32),anegativeresultdoesnotalwaysruleoutpoisoningthenegative
predictivevalueofthescreenisonlyabout70%.Incontrast,apositiveresulthasa
predictivevalueofabout90%.
TableI32DrugsandToxinsNotCommonlyIncludedinEmergencyToxicologic
ScreeningPanelsa
ViewLarge|
TableI32DrugsandToxinsNotCommonlyIncludedinEmergencyToxicologic
ScreeningPanelsa
Anestheticgases Ethyleneglycol
Antiarrhythmicagents Fentanylandotheropiatederivatives
Antibiotics Fluoride
Formate(formicacid,frommethanol
Antidepressants(newer)
poisoning)
Antihypertensives Hypoglycemicagents
Antipsychoticagents(newer) Isoniazid(INH)
Benzodiazepines(newer) Lithium
Betareceptorantagonistsotherthan
LSD(lysergicaciddiethylamide)
propranolol
Borate MAOinhibitors
Bromide Noxiousgases
Calciumantagonists(newer) Plant,fungal,andmicrobiologictoxins
Colchicine Pressors(eg,dopamine)
Cyanide Solventsandhydrocarbons
Digitalisglycosides Theophylline
Diuretics Valproicacid
Ergotalkaloids Vasodilators
aManyoftheseareavailableasseparatespecifictests.
5.Thespecificityoftoxicologictestsisdependentonthemethodandthelaboratory.
Thepresenceofotherdrugs,drugmetabolites,diseasestates,orincorrectsampling
maycauseerroneousresults(TableI33).
TableI33InterferencesinToxicologicBloodorUrineTests
ViewLarge|
DrugorToxin Methoda CausesofFalselyIncreasedLevel
Salicylate,salicylamide,methylsalicylate(eachwill
increaseacetaminophenlevelby10%oftheirlevelin
Acetaminophen SCb mg/L)bilirubinphenolsrenalfailure(each1mg/dL
increaseincreatininecanincreaseacetaminophenlevel
by30mg/L).
GC,IA Phenacetin.
HPLCb Cephalosporins,sulfonamides.
HPLC,
Amitriptyline Cyclobenzaprine.
GC
Othervolatilestimulantamines(misidentified).GCmass
Amphetamines
(urine) GCc spectrometrypoorlydistinguishesdmethamphetamine
fromlmethamphetamine(foundinVicksinhaler).
Allassaysarereactivetomethamphetamineand
amphetamine,aswellasdrugsthataremetabolizedto
amphetamines(benzphetamine,clobenzorex,
famprofazone,fenproporex,selegiline).Thepolyclonal
assayissensitivetocrossreactingsympathomimetic
amines(ephedrine,fenfluramine,isometheptene,MDA,
MDMA,phentermine,phenmetrazine,
IAc phenylpropanolamine,pseudoephedrine,andother
amphetamineanalogs)crossreactingnonstimulant
drugs(bupropion,chlorpromazine,labetalol,ranitidine,
sertraline,trazodone,trimethobenzamide).The
monoclonalassayisreactivetodamphetamineandd
methamphetamineinaddition,manyhavesome
reactivitytowardsMDAandMDMA.
Oxaprozin.Notethatmanybenzodiazepineassaysgive
falsenegativeresultsfordrugsthatdonotmetabolizeto
Benzodiazepines IA
oxazepamornordiazepam(eg,lorazepam,alprazolam,
others).
Chloride SC,EC Bromide(variableinterference).
Ketoacidosis(mayincreasecreatinineupto23mg/dLin
nonratemethods)isopropylalcohol(acetone)
Creatinine SCb nitromethane(upto100foldincreaseinmeasured
creatininewithuseofJaffereaction)cephalosporins
creatine(eg,withrhabdomyolysis).
Creatine,lidocainemetabolite,5fluorouracil,
EZ
nitromethanefuel
Cyanide SC Thiosulfate
Endogenousdigoxinlikenatriureticsubstancesin
newbornsandinpatientswithhypervolemicstates
(cirrhosis,heartfailure,uremia,pregnancy)andrenal
failure(upto0.5ng/mL)plantoranimalglycosides
Digoxin IA
(bufotoxinsChanSuoleander)afterdigoxinantibody
(Fab)administration(withteststhatmeasuretotalserum
digoxin)presenceofheterophileorhumanantimouse
antibodies(upto45.6ng/mLreportedinonecase).
Falselyloweredserumdigoxinconcentrationsduring
MEIA
therapywithspironolactone,canrenone.
Ethanol SCb Otheralcohols,ketones(byoxidationmethods).
EZ IsopropylalcoholpatientswithelevatedlactateandLDH.
Ethyleneglycol EZ Otherglycols,elevatedtriglycerides.
Propyleneglycol(mayalsodecreasetheethyleneglycol
GC
level).
Glucoselevelmayfallbyupto30mg/dL/hwhen
Any
Glucose transporttolaboratoryisdelayed.(Thisdoesnotoccurif
method
specimeniscollectedingraytoptube.)
Deferoxaminecauses15%loweringoftotalironbinding
Iron SC capacity(TIBC).LavendertopVacutainertubecontains
EDTA,whichlowerstotaliron.
Skindisinfectantcontainingisopropylalcoholusedbefore
Isopropanol GC venipuncture(highlyvariable,usuallytrivial,butupto40
mg/dL).
Acetylcysteine,valproicacid,captopril,levodopa.Note:
Acetestmethodisprimarilysensitivetoacetoaceticacid,
whichmaybelowinpatientswithalcoholicketoacidosis.
Ketones SC
Anassayspecificforbetahydroxybutyricacidisamore
reliablemarkerforearlyevaluationofacidosisand
ketosis.
GreentopVacutainerspecimentube(maycontainlithium
Lithium FE,SC
heparin)cancausemarkedelevation(upto68mEq/L).
SC Procainamide,quinidinecanproduce515%elevation.
Methadone(urine) IA Diphenhydramine,verapamil,disopyramide.
Sulfhemoglobin(crosspositive10%bycooximeter)
methyleneblue(2mg/kgdosegivestransientlyfalse
Methemoglobin SC positive15%methemoglobinlevel)hyperlipidemia
(triglyceridelevelof6000mg/dLmaygivefalse
methemoglobinof28.6%).
Falselydecreasedlevelwithinvitrospontaneous
reductiontohemoglobininVacutainertube(10%/h).
Analyzewithin1hour.
Crossreactingopioids:hydrocodone,hydromorphone,
monoacetylmorphine,morphinefrompoppyseed
ingestion.Alsorifampinandofloxacinandother
Morphine/codeine
(urine) IAc quinolonesindifferentIAs.Note:Methadone,oxycodone,
andmanyotheropioidsareoftennotdetectedbyroutine
opiatescreen,mayrequireseparatespecific
immunoassays.
Lavendertop(EDTA)Vacutainerspecimentube(15
mOsm/L)graytop(fluorideoxalate)tube(150mOsm/L)
Osmolality Osm
bluetop(citrate)tube(10mOsm/L)greentop(lithium
heparin)tube(theoretically,upto68mOsm/L).
Falselynormalifvaporpressuremethodused(alcohols
arevolatilized).
Manyfalsepositivesreported:chlorpromazine,
dextromethorphan,diphenhydramine,doxylamine,
Phencyclidine(urine) IAc
ibuprofen,imipramine,ketamine,meperidine,methadone,
thioridazine,tramadol,venlafaxine.
Phenothiazines(urine),diflunisal,ketosis,csalicylamide,
Salicylate SC accumulatedsalicylatemetabolitesinpatientswithrenal
failure(10%increase).
EZ Acetaminophen(slightsalicylateelevation).
IA,SC Diflunisal.
Decreasedoralteredsalicylatelevel:bilirubin,
SC
phenylketones.
Pantoprazole,efavirenz,riboflavin,promethazine,
Tetrahydrocannabinol
IA nonsteroidalantiinflammatorydrugs(dependingonthe
(THC,marijuana)
immunoassay).
Caffeineoverdoseaccumulatedtheophyllinemetabolites
Theophylline IA
inrenalfailure.
Tricyclic
IA Carbamazepine,quetiapine.
antidepressants
aEC=electrochemicalEZ=enzymaticFE=flameemissionGC=gaschromatography
(interferencesprimarilywitholdermethods)HPLC=highpressureliquid
chromatographyIA=immunoassayMEIA=microparticleenzymaticimmunoassaySC=
spectrochemicalTLC=thinlayerchromatography.
bUncommonmethodology,nolongerperformedinmostclinicallaboratories.
cMorecommonwithurinetest.Confirmationbyasecondtestisrequired.Note:Urine
testingissometimesaffectedbyintentionaladulterationtoavoiddrugdetection.
B.Adulterationofurinemaybeattemptedbypersonsundergoingenforceddrugtestingto
evadedrugdetection.Methodsusedincludedilution(ingestedoraddedwater)and
additionofacids,bakingsoda,bleach,metalsalts,nitritesalts,glutaraldehyde,or
pyridiniumchlorochromate.Theintentistoinactivate,eitherchemicallyorbiologically,the
initialscreeningimmunoassaytoproduceanegativetest.Adulterationisvariably
successfuldependingontheagentusedandthetypeofimmunoassay.Laboratoriesthat
routinelyperformurinetestingfordrugsurveillanceprogramsoftenhavemethodstotest
forsomeoftheadulterantsaswellassayindicatorsthatsuggestpossibleadulterations.
C.Usesfortoxicologyscreens
1.Comprehensivescreeningofurineandbloodshouldbecarriedoutwheneverthe
diagnosisofbraindeathisbeingconsideredtoruleoutthepresenceofcommon
depressantdrugsthatmightresultinatemporarylossofbrainactivityandmimic
braindeath.Toxicologyscreensmaybeusedtoconfirmclinicalimpressionsduring
hospitalizationandcanbeinsertedinthepermanentmedicolegalrecord.Thismay
beimportantifhomicide,assault,orchildabuseissuspected.
2.Selectivescreens(eg,fordrugsofabuse)withrapidturnaroundtimesareoften
usedtoconfirmclinicalimpressionsandmayaidindispositionofthepatient.Positive
resultsmayneedtobeverifiedbyconfirmatorytestingwithasecondmethod,
dependingonthecircumstances.
D.Approachtotoxicologytesting
1.Communicateclinicalsuspicionstothelaboratory.
2.Obtainbloodandurinespecimensonadmissioninunusualcasesandhavethe
laboratorystorethemtemporarily.Ifthepatientrecoversrapidly,theycanbe
discarded.
3.Urineisusuallythebestsampleforbroadqualitativescreening.Bloodsamples
shouldbesavedforpossiblequantitativetesting,butbloodisnotagoodspecimen
forscreeningformanycommondrugs,includingpsychotropicagents,opioids,and
stimulants.
4.Decideifaspecificquantitativebloodlevelmayassistinmanagementdecisions(eg,
useofanantidoteordialysisTableI34).Quantitativelevelsarehelpfulonlyifthere
isapredictablecorrelationbetweentheserumlevelandtoxiceffects.
TableI34SpecificQuantitativeLevelsandPotentialInterventionsa
ViewLarge|
DrugorToxin PotentialIntervention
Acetaminophen Acetylcysteine
Carbamazepine Repeatdosecharcoal,hemoperfusion
Carboxyhemoglobin 100%oxygen
Digoxin Digoxinspecificantibodies
Ethanol Lowlevelindicatessearchforothertoxins
Ethyleneglycol Ethanolorfomepizoletherapy,hemodialysis
Iron Deferoxaminechelation
Lithium Hemodialysis
Methanol Ethanolorfomepizoletherapy,hemodialysis
Methemoglobin Methyleneblue
Salicylate Alkalinization,hemodialysis
Theophylline Repeatdosecharcoal,hemoperfusion
Valproicacid Hemodialysis,repeatdosecharcoal
aForspecificguidance,seeindividualchaptersinSectionII.
5.Aregionalpoisoncontrolcenter(18002221222)ortoxicologyconsultantmay
provideassistanceinconsideringcertaindrugetiologiesandinselectingspecific
tests.
V.Abdominalradiographsmayrevealradiopaquetablets,drugfilledcondoms,orothertoxic
material.
A.Theradiographisusefulonlyifpositiverecentstudiessuggestthatfewtypesoftablets
arepredictablyvisible(TableI35).
TableI35RadiopaqueDrugsandPoisonsa
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Usuallyvisible
Bismuthsubsalicylate(PeptoBismol)
Calciumcarbonate(Tums)
Irontablets
Leadandleadcontainingpaint
Metallicforeignbodies
Potassiumtablets
Sometimes/weaklyvisible
Acetazolamide
Arsenic
Brompheniramineanddexbrompheniramine
Busulfan
Chloralhydrate
Entericcoatedorsustainedreleasepreparations(highlyvariable)
Meclizine
Perphenazinewithamitriptyline
Phosphorus
Prochlorperazine
Sodiumchloride
Thiamine
Tranylcypromine
Trifluoperazine
Trimeprazine
Zincsulfate
aReference:SavittDL,HawkinsHH,RobertsJR:Theradiopacityofingestedmedications.
AnnEmergMed198716:331.
B.Donotattempttodeterminetheradiopacityofatabletbyplacingitdirectlyonthexray
plate.Thisoftenproducesafalsepositiveresultbecauseofanaircontrasteffect.
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BloodPressure PulseRate PupilSize Sweating Peristalsis
Alphaadrenergic + + +
Betaadrenergic +
Mixedadrenergic + + + +
Sympatholytic
Nicotinic + + + +
Muscarinic + +
Mixedcholinergic + +
Anticholinergic(antimuscarinic) + +
aKeytosymbols:+=increased++=markedlyincreased=decreased=markedlydecreased
=mixedeffect,noeffect,orunpredictable.
bAdapted,withpermission,fromOlsonKRetal:MedToxicol19872:54.
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CONSTRICTEDPUPILS(MIOSIS) DILATEDPUPILS(MYDRIASIS)
Sympatholyticagents Sympathomimeticagents
Clonidine Amphetaminesandderivatives
Opioids Cocaine
Phenothiazines Dopamine
Tetrahydrozolineandoxymetazoline LSD(lysergicaciddiethylamide)
Valproicacid Monoamineoxidaseinhibitors
Cholinergicagents Nicotineb
Carbamateinsecticides Anticholinergicagents
Nicotineb Antihistamines
Organophosphates Atropineandotheranticholinergics
Physostigmine Carbamazepine
Pilocarpine Glutethimide
Others Tricyclicantidepressants
Heatstroke
Pontineinfarct
Subarachnoidhemorrhage
bNicotinecancausethepupilstobedilated(rare)orconstricted(common).
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Cause Comments
Acrylamide Sensoryandmotordistalaxonalneuropathy
Antineoplasticagents Vincristinemoststronglyassociated(SeeAntineoplasticAgents)
Nucleosidereversetranscriptaseinhibitors(SeeAntiviraland
Antiretroviralagents
AntiretroviralAgents)
Arsenic Sensorypredominantmixedaxonalneuropathy(SeeArsenic)
Buckthorn(K
Livestockandhumandemyelinatingneuropathy(SeePlants)
humboldtiana)
Carbondisulfide Sensoryandmotordistalaxonalneuropathy(SeeCarbonDisulfide)
Dimethylaminopropionitrile Urogenitalanddistalsensoryneuropathy
Disulfiram Sensoryandmotordistalaxonalneuropathy(SeeDisulfiram)
Ethanol Sensoryandmotordistalaxonalneuropathy(SeeEthanol)
nHexane Sensoryandmotordistalaxonalneuropathy(SeeTableIV4)
Isoniazid(INH) Preventablewithcoadministrationofpyridoxine(SeeIsoniazid(INH))
Lead Motorpredominantmixedaxonalneuropathy(SeeLead)
Mercury Organicmercurycompounds(SeeMercury)
Methylnbutylketone Actslikenhexanevia2,5hexanedionemetabolite
Nitrofurantoin Sensoryandmotordistalaxonalneuropathy
Sensoryaxonalneuropathywithlossofproprioception(SeeNitrous
Nitrousoxide
Oxide)
Organophosphate
Specificagentsonly(eg,triorthocresylphosphate)
insecticides
Sensoryneuropathywithchronicexcessivedosing(SeePyridoxine
Pyridoxine(vitaminB6)
(VitaminB6))
Selenium Polyneuritis(SeeSelenium)
Thallium Sensoryandmotordistalaxonalneuropathy(SeeThallium)
Tickparalysis Ascendingflaccidparalysisafterbitesbyseveraltickspecies
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Odor DrugorToxin
Acetone Acetone,isopropylalcohol
Acridorpearlike Chloralhydrate,paraldehyde
Bitteralmonds Cyanide
Carrots Cicutoxin(waterhemlock)
Garlic Arsenic(arsine),organophosphates,selenium,thallium
Mothballs Naphthalene,paradichlorobenzene
Pungentaromatic Ethchlorvynol
Rotteneggs Hydrogensulfide,stibine,mercaptans,oldsulfadrugs
Wintergreen Methylsalicylate
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Acetone Mannitol
Dimethylsulfoxide(DMSO) Metaldehyde
Ethanol Methanol
Ethylether Osmoticcontrastdyes
Ethyleneglycolandotherlowmolecular
Propyleneglycol
weightglycols
Isopropylalcohol Renalfailurewithoutdialysis
Severealcoholicketoacidosis,diabeticketoacidosis,or
Magnesium
lacticacidosis
aOsmolegap=measuredcalculatedosmolality.Normal=0510.Calculatedosmolality=2[Na]
+[glucose]/18+[BUN]/2.8.Na(serumsodium)inmEq/LglucoseandBUN(bloodureanitrogen)in
mg/dL.
Note:Theosmolalitymaybemeasuredasfalselynormalifavaporizationpointosmometerisused
insteadofthefreezingpointdevicebecausevolatilealcoholswillbeboiledoff.
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AlcoholorGlycol MolecularWeight(mg/mmol) ConversionFactorb
Acetone 58 5.8
Ethanol 46 4.6c
Ethyleneglycol 62 6.2
Isopropylalcohol 60 6
Methanol 32 3.2
Propyleneglycol 76 7.6
aAdapted,withpermission,fromHoMT,SaundersCE(editors):CurrentEmergencyDiagnosis&
Treatment,3rded.Appleton&Lange,1990.
bToobtainestimatedserumlevel(inmg/dL),multiplyosmolegapbyconversionfactor.
cOneclinicalstudy(PurssellRAetal:AnnEmergMed200138:653)foundthataconversionfactorof
3.7wasmoreaccurateforestimatingthecontributionofethanoltotheosmolegap.
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Lacticacidosis Otherthanlacticacidosis
Acetaminophen(levels>600mg/L) Alcoholicketoacidosis(betahydroxybutyrate)
Antiretroviraldrugs Benzylalcohol
Betaadrenergicreceptoragonists Diabeticketoacidosis
Caffeine Ethyleneglycol(glycolicandotheracids)
Carbonmonoxide Exogenousorganicandmineralacids
Cyanide Formaldehyde(formicacid)
Hydrogensulfide Ibuprofen(propionicacid)
Iron Metaldehyde
Isoniazid(INH) Methanol(formicacid)
Metforminandphenformin 5Oxoprolinuriaandotherorganicacidurias
Propofol(highdose,children) Salicylates(salicylicacid)
Salicylates Valproicacid
Seizures,shock,orhypoxia
Sodiumazide
Theophylline
aAniongap=[Na][Cl][HCO ]=812mEq/L.
3
bAdaptedinpart,withpermission,fromOlsonKRetal:MedToxicol19872:73.
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Hyperglycemia
Beta2adrenergicreceptoragonists
Caffeineintoxication
Corticosteroids
Dextroseadministration
Diabetesmellitus
Diazoxide
Excessivecirculatingepinephrine
Glucagon
Ironpoisoning
Theophyllineintoxication
Thiazidediuretics
Vacor
Hypoglycemia
Akeefruit(unripe)
Endocrinedisorders(hypopituitarism,Addisondisease,myxedema)
Ethanolintoxication(especiallypediatric)
Fasting
Hepaticfailure
Insulin
Oralsulfonylureahypoglycemicagents
Pentamidine
Propranololintoxication
Renalfailure
Salicylateintoxication
Streptozocin
Valproicacidintoxication
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Hypernatremia Hyponatremia
Catharticabuse Beerpotomania
Lactulosetherapy Cerebralsaltwastingsyndrome(eg,aftertrauma)
Lithiumtherapy(nephrogenicdiabetesinsipidus) Diuretics
Mannitol Iatrogenic(IVfluidtherapy)
Severegastroenteritis(manypoisons) SyndromeofinappropriateADH(SIADH):
Sodiumorsaltoverdose Amitriptyline
Valproicacid(divalproexsodium) Chlorpropamide
Clofibrate
MDMA(ecstasy)
Oxytocin
Phenothiazines
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Hyperkalemia Hypokalemia
Acidosis Alkalosis
Angiotensinconvertingenzyme(ACE)inhibitors Barium
Betareceptorantagonists Betaadrenergicdrugs
Digitalisglycosides Caffeine
Fluoride Cesium
Lithium Diuretics(chronic)
Potassium Epinephrine
Renalfailure Theophylline
Rhabdomyolysis Toluene(chronic)
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Directnephrotoxiceffect
Acetaminophen
Acyclovir(chronic,highdosetreatment)
Amanitaphalloidesmushrooms
Amanitasmithianamushrooms
Analgesics(eg,ibuprofen,phenacetin)
Antibiotics(eg,aminoglycosides)
Bromates
Chlorates
Cortinariusspeciesmushrooms
Cyclosporine
Ethylenediaminetetraaceticacid(EDTA)
Ethyleneglycol(glycolate,oxalate)
Foscarnet
Heavymetals(eg,mercury)salts
Indinavir
Hemolysis
Arsine
Naphthalene
Oxidizingagents(especiallyinpatientswithglucose6phosphatedehydrogenase[G6PD]deficiency)
Rhabdomyolysis(seealsoTABLEI16)
Amphetaminesandcocaine
Comawithprolongedimmobility
Hyperthermia
Phencyclidine(PCP)
Statusepilepticus
Strychnine
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Acetaminophen
Amanitaphalloidesandsimilarmushrooms
Arsenic
Carbontetrachlorideandotherchlorinatedhydrocarbons
Copper
Dimethylformamide
Ethanol
Gyrometramushrooms
Halothane
Iron
Kava
Niacin(sustainedreleaseformulation)
2Nitropropane
Pennyroyaloil
Phenol
Phosphorus
Polychlorinatedbiphenyls(PCBs)
Pyrrolizidinealkaloids(seePlants)
Thallium
Troglitazone
Valproicacid
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Alcohols Sedativehypnoticdrugs
Acetone Barbituratesc
Ethanol Benzodiazepinesc
Isopropylalcohol Carisoprodol
Methanol Chloralhydrate
Analgesics Ethchlorvynol
Acetaminophen Glutethimide
Salicylates Meprobamate
Anticonvulsants Methaqualone
Carbamazepine Stimulants
Phenobarbital Amphetaminesc
Phenytoin Caffeine
Primidone Cocaineandbenzoylecgonine
Antihistamines Phencyclidine(PCP)
Benztropine Strychnine
Chlorpheniramine Tricyclicantidepressants
Diphenhydramine Amitriptyline
Pyrilamine Desipramine
Trihexyphenidyl Doxepin
Opioids Imipramine
Codeine Nortriptyline
Dextromethorphan Protriptyline
Hydrocodone Cardiacdrugs
Meperidine Diltiazem
Methadone Lidocaine
Morphine Procainamide
Oxycodoneb Propranolol
Pentazocine Quinidineandquinine
Propoxyphene Verapamil
Phenothiazines
Chlorpromazine
Prochlorperazine
Promethazine
Thioridazine
Trifluoperazine
aNewerdrugsinanycategorymaynotbeincludedinscreening.
bDependsontheorderoftesting.
cNotalldrugsinthisclassaredetected.
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DetectionTime
Drug Windowfor Comments
RecreationalDoses
OftenmissesMDAorMDMA.Manyfalsepositives
Amphetamines 2days
(seeTableI33).
Lessthan2daysfor
Barbiturates mostdrugs,upto1
weekforphenobarbital
27days(varieswith
Maynotdetecttriazolam,lorazepam,alprazolam,
Benzodiazepines specificdrugand
othernewerdrugs.
durationofuse)
Cocaine 2days Detectsmetabolitebenzoylecgonine.
Ethanol Lessthan1day
Marijuana 25daysaftersingle
(tetrahydrocannabinol use(longerforchronic
[THC]) use)
Syntheticopioids(meperidine,methadone,
Opioids 23days propoxyphene,oxycodone)areoftennotdetected.
Separatetestingformethadoneissometimesoffered.
Phencyclidine(PCP) Upto7days SeeTableI33.
aLaboratoriesoftenperformonlysomeofthesetests,dependingonwhattheiremergency
departmentrequestsandlocalpatternsofdruguseinthecommunity.Also,positiveresultsare
usuallynotconfirmedwithasecond,morespecifictestthus,falsepositivesmaybereported.
TableI32DrugsandToxinsNotCommonlyIncludedinEmergencyToxicologicScreeningPanelsa
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TableI32DrugsandToxinsNotCommonlyIncludedinEmergencyToxicologicScreeningPanelsa
Anestheticgases Ethyleneglycol
Antiarrhythmicagents Fentanylandotheropiatederivatives
Antibiotics Fluoride
Antidepressants(newer) Formate(formicacid,frommethanolpoisoning)
Antihypertensives Hypoglycemicagents
Antipsychoticagents(newer) Isoniazid(INH)
Benzodiazepines(newer) Lithium
Betareceptorantagonistsotherthanpropranolol LSD(lysergicaciddiethylamide)
Borate MAOinhibitors
Bromide Noxiousgases
Calciumantagonists(newer) Plant,fungal,andmicrobiologictoxins
Colchicine Pressors(eg,dopamine)
Cyanide Solventsandhydrocarbons
Digitalisglycosides Theophylline
Diuretics Valproicacid
Ergotalkaloids Vasodilators
aManyoftheseareavailableasseparatespecifictests.
ViewLarge|
Salicylate,salicylamide,methylsalicylate(eachwillincrease
acetaminophenlevelby10%oftheirlevelinmg/L)bilirubin
Acetaminophen SCb phenolsrenalfailure(each1mg/dLincreaseincreatininecan
increaseacetaminophenlevelby30mg/L).
GC,IA Phenacetin.
HPLCb Cephalosporins,sulfonamides.
HPLC,
Amitriptyline Cyclobenzaprine.
GC
Othervolatilestimulantamines(misidentified).GCmass
Amphetamines
(urine) GCc spectrometrypoorlydistinguishesdmethamphetaminefroml
methamphetamine(foundinVicksinhaler).
Allassaysarereactivetomethamphetamineandamphetamine,as
wellasdrugsthataremetabolizedtoamphetamines
(benzphetamine,clobenzorex,famprofazone,fenproporex,
selegiline).Thepolyclonalassayissensitivetocrossreacting
sympathomimeticamines(ephedrine,fenfluramine,isometheptene,
IAc MDA,MDMA,phentermine,phenmetrazine,phenylpropanolamine,
pseudoephedrine,andotheramphetamineanalogs)crossreacting
nonstimulantdrugs(bupropion,chlorpromazine,labetalol,ranitidine,
sertraline,trazodone,trimethobenzamide).Themonoclonalassay
isreactivetodamphetamineanddmethamphetamineinaddition,
manyhavesomereactivitytowardsMDAandMDMA.
Oxaprozin.Notethatmanybenzodiazepineassaysgivefalse
Benzodiazepines IA negativeresultsfordrugsthatdonotmetabolizetooxazepamor
nordiazepam(eg,lorazepam,alprazolam,others).
Chloride SC,EC Bromide(variableinterference).
Ketoacidosis(mayincreasecreatinineupto23mg/dLinnonrate
methods)isopropylalcohol(acetone)nitromethane(upto100fold
Creatinine SCb increaseinmeasuredcreatininewithuseofJaffereaction)
cephalosporinscreatine(eg,withrhabdomyolysis).
EZ Creatine,lidocainemetabolite,5fluorouracil,nitromethanefuel
Cyanide SC Thiosulfate
Endogenousdigoxinlikenatriureticsubstancesinnewbornsandin
patientswithhypervolemicstates(cirrhosis,heartfailure,uremia,
pregnancy)andrenalfailure(upto0.5ng/mL)plantoranimal
Digoxin IA glycosides(bufotoxinsChanSuoleander)afterdigoxinantibody
(Fab)administration(withteststhatmeasuretotalserumdigoxin)
presenceofheterophileorhumanantimouseantibodies(upto45.6
ng/mLreportedinonecase).
Falselyloweredserumdigoxinconcentrationsduringtherapywith
MEIA
spironolactone,canrenone.
Ethanol SCb Otheralcohols,ketones(byoxidationmethods).
EZ IsopropylalcoholpatientswithelevatedlactateandLDH.
Ethyleneglycol EZ Otherglycols,elevatedtriglycerides.
GC Propyleneglycol(mayalsodecreasetheethyleneglycollevel).
Glucoselevelmayfallbyupto30mg/dL/hwhentransportto
Any
Glucose laboratoryisdelayed.(Thisdoesnotoccurifspecimeniscollectedin
method
graytoptube.)
Deferoxaminecauses15%loweringoftotalironbindingcapacity
Iron SC (TIBC).LavendertopVacutainertubecontainsEDTA,whichlowers
totaliron.
Skindisinfectantcontainingisopropylalcoholusedbefore
Isopropanol GC
venipuncture(highlyvariable,usuallytrivial,butupto40mg/dL).
Acetylcysteine,valproicacid,captopril,levodopa.Note:Acetest
methodisprimarilysensitivetoacetoaceticacid,whichmaybelowin
Ketones SC patientswithalcoholicketoacidosis.Anassayspecificforbeta
hydroxybutyricacidisamorereliablemarkerforearlyevaluationof
acidosisandketosis.
GreentopVacutainerspecimentube(maycontainlithiumheparin)
Lithium FE,SC
cancausemarkedelevation(upto68mEq/L).
SC Procainamide,quinidinecanproduce515%elevation.
Methadone(urine) IA Diphenhydramine,verapamil,disopyramide.
Sulfhemoglobin(crosspositive10%bycooximeter)methylene
blue(2mg/kgdosegivestransientlyfalsepositive15%
Methemoglobin SC
methemoglobinlevel)hyperlipidemia(triglyceridelevelof6000
mg/dLmaygivefalsemethemoglobinof28.6%).
Falselydecreasedlevelwithinvitrospontaneousreductionto
hemoglobininVacutainertube(10%/h).Analyzewithin1hour.
Crossreactingopioids:hydrocodone,hydromorphone,
monoacetylmorphine,morphinefrompoppyseedingestion.Also
Morphine/codeine rifampinandofloxacinandotherquinolonesindifferentIAs.Note:
(urine) IAc Methadone,oxycodone,andmanyotheropioidsareoftennot
detectedbyroutineopiatescreen,mayrequireseparatespecific
immunoassays.
Lavendertop(EDTA)Vacutainerspecimentube(15mOsm/L)gray
top(fluorideoxalate)tube(150mOsm/L)bluetop(citrate)tube(10
Osmolality Osm
mOsm/L)greentop(lithiumheparin)tube(theoretically,upto68
mOsm/L).
Falselynormalifvaporpressuremethodused(alcoholsare
volatilized).
Manyfalsepositivesreported:chlorpromazine,dextromethorphan,
Phencyclidine(urine) IAc diphenhydramine,doxylamine,ibuprofen,imipramine,ketamine,
meperidine,methadone,thioridazine,tramadol,venlafaxine.
Phenothiazines(urine),diflunisal,ketosis,csalicylamide,
Salicylate SC accumulatedsalicylatemetabolitesinpatientswithrenalfailure
(10%increase).
EZ Acetaminophen(slightsalicylateelevation).
IA,SC Diflunisal.
SC Decreasedoralteredsalicylatelevel:bilirubin,phenylketones.
Tetrahydrocannabinol Pantoprazole,efavirenz,riboflavin,promethazine,nonsteroidalanti
IA
(THC,marijuana) inflammatorydrugs(dependingontheimmunoassay).
Caffeineoverdoseaccumulatedtheophyllinemetabolitesinrenal
Theophylline IA
failure.
Tricyclic
IA Carbamazepine,quetiapine.
antidepressants
aEC=electrochemicalEZ=enzymaticFE=flameemissionGC=gaschromatography
(interferencesprimarilywitholdermethods)HPLC=highpressureliquidchromatographyIA=
immunoassayMEIA=microparticleenzymaticimmunoassaySC=spectrochemicalTLC=thin
layerchromatography.
bUncommonmethodology,nolongerperformedinmostclinicallaboratories.
cMorecommonwithurinetest.Confirmationbyasecondtestisrequired.Note:Urinetestingis
sometimesaffectedbyintentionaladulterationtoavoiddrugdetection.
ViewLarge|
DrugorToxin PotentialIntervention
Acetaminophen Acetylcysteine
Carbamazepine Repeatdosecharcoal,hemoperfusion
Carboxyhemoglobin 100%oxygen
Digoxin Digoxinspecificantibodies
Ethanol Lowlevelindicatessearchforothertoxins
Ethyleneglycol Ethanolorfomepizoletherapy,hemodialysis
Iron Deferoxaminechelation
Lithium Hemodialysis
Methanol Ethanolorfomepizoletherapy,hemodialysis
Methemoglobin Methyleneblue
Salicylate Alkalinization,hemodialysis
Theophylline Repeatdosecharcoal,hemoperfusion
Valproicacid Hemodialysis,repeatdosecharcoal
aForspecificguidance,seeindividualchaptersinSectionII.
ViewLarge|
Usuallyvisible
Bismuthsubsalicylate(PeptoBismol)
Calciumcarbonate(Tums)
Irontablets
Leadandleadcontainingpaint
Metallicforeignbodies
Potassiumtablets
Sometimes/weaklyvisible
Acetazolamide
Arsenic
Brompheniramineanddexbrompheniramine
Busulfan
Chloralhydrate
Entericcoatedorsustainedreleasepreparations(highlyvariable)
Meclizine
Perphenazinewithamitriptyline
Phosphorus
Prochlorperazine
Sodiumchloride
Thiamine
Tranylcypromine
Trifluoperazine
Trimeprazine
Zincsulfate
aReference:SavittDL,HawkinsHH,RobertsJR:Theradiopacityofingestedmedications.Ann
EmergMed198716:331.
*ByAlanWu,PhD.
Decontamination
I.Surfacedecontamination
A.Skin.Corrosiveagentsrapidlyinjuretheskinandmustberemovedimmediately.In
addition,manytoxinsarereadilyabsorbedthroughtheskin,andsystemicabsorptioncan
bepreventedonlybyrapidaction.TableII20listsseveralcorrosivechemicalagentsthat
canhavesystemictoxicity,andmanyofthemarereadilyabsorbedthroughtheskin.
1.Becarefulnottoexposeyourselforothercareproviderstopotentiallycontaminating
substances.Wearprotectivegear(gloves,gown,andgoggles)andwashexposed
areaspromptly.Contactaregionalpoisoncontrolcenterforinformationaboutthe
hazardsofthechemicalsinvolvedinthemajorityofcases,healthcareprovidersare
notatsignificantpersonalriskforsecondarycontamination,andsimplemeasures
suchasemergencydepartmentgownsandplainexaminationglovesprovide
sufficientprotection.Forradiationandotherhazardousmaterialsincidents,seealso
SectionIV.
2.Removecontaminatedclothingandflushexposedareaswithcopiousquantitiesof
tepid(lukewarm)waterorsaline.Washcarefullybehindears,undernails,andinskin
folds.Usesoapandshampooforoilysubstances.
3.Thereisrarelyaneedforchemicalneutralizationofasubstancespilledontheskin.
Infact,theheatgeneratedbychemicalneutralizationcanpotentiallycreateworse
injury.SomeofthefewexceptionstothisrulearelistedinTableI36.
TableI36SomeTopicalAgentsforChemicalExposurestotheSkina
ViewLarge|
ChemicalCorrosive
TopicalTreatment
Agent
Hydrofluoricacid Calciumsoaks
Oxalicacid Calciumsoaks
Phenol Mineraloilorotheroilisopropylalcohol
Coppersulfate1%(colorsembeddedgranulesblue,facilitates
Phosphorus(white)
mechanicalremoval)
aReference:EdelmanPA:Chemicalandelectricalburns.In:AchauerBM(editor):
ManagementoftheBurnedPatient,pp183202.Appleton&Lange,1987.
B.Eyes.Thecorneaisespeciallysensitivetocorrosiveagentsandhydrocarbonsolventsthat
mayrapidlydamagethecornealsurfaceandleadtopermanentscarring.
1.Actquicklytopreventseriousdamage.Flushexposedeyeswithcopiousquantities
oftepidtapwaterorsaline.Ifavailable,instilllocalanestheticdropsintheeyefirstto
facilitateirrigation.Removethevictim'scontactlensesiftheyarebeingworn.
2.PlacethevictiminasupinepositionunderataporuseIVtubingtodirectastreamof
wateracrossthenasalbridgeintothemedialaspectoftheeye.Useatleast1Lto
irrigateeacheye.
3.Iftheoffendingsubstanceisanacidorabase,checkthepHofthevictim'stears
afterirrigationandcontinueirrigationifthepHremainsabnormal.
4.DonotinstillneutralizingsolutioninanattempttonormalizethepHthereisno
evidencethatsuchtreatmentworks,anditmayfurtherdamagetheeye.
5.Afterirrigationiscomplete,checktheconjunctivalandcornealsurfacescarefullyfor
evidenceoffullthicknessinjury.Performafluoresceinexaminationoftheeyeby
usingfluoresceindyeandaWood'slamptorevealcornealinjury.
6.Patientswithseriousconjunctivalorcornealinjuryshouldbereferredtoan
ophthalmologistimmediately.
C.Inhalation.Agentsthatinjurethepulmonarysystemmaybeacutelyirritatinggasesor
fumesandmayhavegoodorpoorwarningproperties(SeeGases,Irritant).
1.Becarefulnottoexposeyourselforothercareproviderstotoxicgasesorfumes
withoutadequaterespiratoryprotection(SeePersonalprotectiveequipment).
2.Removethevictimfromexposureandgivesupplementalhumidifiedoxygen,if
available.Assistventilationifnecessary(SeeAirway).
3.Observecloselyforevidenceofupperrespiratorytractedema,whichisheraldedby
ahoarsevoiceandstridorandmayprogressrapidlytocompleteairwayobstruction.
Endotracheallyintubatepatientswhoshowevidenceofprogressiveairway
compromise.
4.Alsoobserveforlateonsetnoncardiogenicpulmonaryedemaresultingfrommore
slowlyactingtoxins(eg,nitrogenoxide,phosgene),whichmaytakeseveralhoursto
appear.Earlysignsandsymptomsincludedyspnea,hypoxemia,andtachypnea(See
Gases,Irritant).
II.Gastrointestinaldecontamination.Thereremainscontroversyabouttheroleofgastric
emptyingandactivatedcharcoaltodecontaminatethegastrointestinaltractinthemanagement
ofingestedpoisons.Thereislittlesupportinthemedicalliteratureforgutemptyingprocedures,
andstudieshaveshownthatafteradelayof60minutesormore,onlyasmallproportionofthe
ingesteddoseisremovedbyinducedemesisorgastriclavage.Moreover,studiessuggestthat
inthetypicaloverdosedpatient,simpleoraladministrationofactivatedcharcoalwithoutpriorgut
emptyingisprobablyjustaseffectiveasthetraditionalsequenceofgutemptyingfollowedby
charcoal.Formanyoverdosepatientswhohaveingestedasmalldose,arelativelynontoxic
substance,oradrugthatisrapidlyabsorbed,itisevenquestionablewhetheractivatedcharcoal
makesadifferenceinoutcome.
However,therearesomecircumstancesinwhichaggressivegutdecontaminationmay
potentiallybelifesavingandisadvised,evenaftermorethan12hours.Examplesinclude
ingestionofhighlytoxicdrugs(eg,calciumantagonists,colchicine),ingestionofdrugsnot
adsorbedtocharcoal(eg,iron,lithium),ingestionofmassiveamountsofadrug(eg,150200
aspirintablets),andingestionofsustainedreleaseorentericcoatedproducts.
A.Emesis.Syrupofipecacinducedemesisisnolongerthetreatmentofchoiceforany
ingestions.Itmaybeemployedinraresituationswhenmedicalcareisexpectedtobe
delayedmorethan60minutes,whenthepatientisawake,andiftheipecaccanbegiven
withinafewminutesoftheingestion.Ipecacisnolongerusedinemergencydepartments
becauseofthereadyavailabilityofactivatedcharcoal.Aftersyrupofipecacadministration,
vomitingusuallyoccurswithin2030minutes.Iftheingestionoccurredmorethan3060
minutesbeforeipecacadministration,emesisisnotveryeffective.Moreover,persistent
vomitingafteripecacuseislikelytodelaytheadministrationofactivatedcharcoal(see
ItemCbelow).
1.Indications
a.Earlyprehospitalmanagementofselected(seeContraindicationsbelow)
potentiallyseriousoralpoisonings,particularlyinthehomeimmediatelyafter
ingestion,whenothermeasures(eg,activatedcharcoal)arenotavailableand
transporttimetoamedicalfacilitymaybeprolonged(eg,>1hour).
b.Possiblyusefultoremoveingestedagentsnotadsorbedbyactivatedcharcoal
(eg,iron,lithium,potassium).However,mostofthesecasesarepreferably
managedwithwholebowelirrigation(seebelow).
2.Contraindications
a.Obtunded,comatose,orconvulsingpatient.
b.IngestionofasubstancelikelytocauseonsetofCNSdepressionorseizures
withinashortclinicaltimeframe(eg,opioids,sedativehypnoticagents,tricyclic
antidepressants,camphor,cocaine,isoniazid,orstrychnine).
c.Ingestionofacorrosiveagent(eg,acids,alkali,orstrongoxidizingagents).
d.Ingestionofasimplealiphatichydrocarbon(SeeHydrocarbons).These
hydrocarbonsarelikelytocausepneumonitisifaspiratedbutusuallydonot
causesystemicpoisoningoncetheyenterthestomach.
3.Adverseeffects
a.Persistentvomitingmaydelayadministrationofactivatedcharcoalororal
antidotes(eg,acetylcysteine).
b.ProtractedforcefulvomitingmayresultinhemorrhagicgastritisoraMallory
Weisstear.
c.Vomitingmaypromotepassageoftoxicmaterialintothesmallintestine,
enhancingabsorption.
d.Drowsinessoccursinabout20%anddiarrheain25%ofchildren.
e.Repeateddailyuse(eg,bybulimicpatients)mayresultinelectrolyte
disturbancesaswellascardiacdysrhythmiasandcardiomyopathyowingto
accumulationofcardiotoxicalkaloids.
4.Technique.Useonlysyrupofipecac,notthefluidextract(whichcontainsmuch
higherconcentrationsofemeticandcardiotoxicalkaloids).
a.Administer30mLofsyrupofipecacorally(15mLforchildrenyoungerthan5
years,10mLforchildrenyoungerthan1yearnotrecommendedforchildren
youngerthan6months).After1015minutes,give23glassesofwater(there
isnoconsensusonthequantityofwaterorthetimingofadministration).
b.Ifemesishasnotoccurredafter20minutes,aseconddoseofipecacmaybe
given.Havethepatientsitupormovearoundbecausethissometimes
stimulatesvomiting.
c.Asoapywatersolutionmaybeusedasanalternativeemetic.Useonly
standardhandwashingliquidsoap,twotablespoonsinaglassofwater.Donot
usepowderedlaundryordishwasherdetergentorliquiddishwashing
concentratetheseproductsarecorrosive.Thereisnootheracceptable
alternativetosyrupofipecac.Manualdigitalstimulation,coppersulfate,salt
water,mustardwater,apomorphine,andotheremeticsareunsafeandshould
notbeused.
B.Gastriclavage.Gastriclavageisonlyoccasionallyusedinhospitalemergency
departments.Althoughthereislittleclinicalevidencetosupportitsuse,gastriclavageis
probablyslightlymoreeffectivethanipecac,especiallyforrecentlyingestedliquid
substances.However,itdoesnotreliablyremoveundissolvedpillsorpillfragments
(especiallysustainedreleaseorentericcoatedproducts).Inaddition,theproceduremay
delaytheadministrationofactivatedcharcoalandmayhastenthemovementofdrugsand
poisonsintothesmallintestine,especiallyifthepatientissupineorintherightdecubitus
position.Gastriclavageisnotnecessaryforsmalltomoderateingestionsofmost
substancesifactivatedcharcoalcanbegivenpromptly.
1.Indications
a.Toremoveingestedliquidandsoliddrugsandpoisonswhenthepatienthas
takenamassiveoverdoseorhasingestedaparticularlytoxicsubstance.
Lavageismorelikelytobeeffectiveifinitiatedwithin3060minutesofthe
ingestion,althoughitmaystillbeusefulseveralhoursafteringestionofagents
thatslowgastricemptying(eg,salicylates,opioids,oranticholinergicdrugs).
b.Toadministeractivatedcharcoalandwholebowelirrigationtopatientsunwilling
orunabletoswallowthem.
c.Todiluteandremovecorrosiveliquidsfromthestomachandtoemptythe
stomachinpreparationforendoscopy.
2.Contraindications
a.Obtunded,comatose,orconvulsingpatients.Becauseitmaydisturbthenormal
physiologyoftheesophagusandairwayprotectivemechanisms,gastriclavage
mustbeusedwithcautioninobtundedpatientswhoseairwayreflexesare
dulled.Insuchcases,endotrachealintubationwithacuffedendotrachealtube
shouldbeperformedfirsttoprotecttheairway.
b.Ingestionofsustainedreleaseorentericcoatedtablets.(Owingtothesizeof
mosttablets,lavageisunlikelytoreturnintacttablets,eventhrougha40F
orogastrichose.)Insuchcases,wholebowelirrigation(seebelow)is
preferable.
c.Useofgastriclavageafteringestionofacorrosivesubstanceiscontroversial
somegastroenterologistsrecommendthatinsertionofagastrictubeand
aspirationofgastriccontentsbeperformedassoonaspossibleafterliquid
causticingestiontoremovecorrosivematerialfromthestomachandtoprepare
forendoscopy.
3.Adverseeffects
a.Perforationoftheesophagusorstomach.
b.Nosebleedfromnasaltraumaduringpassageofthetube.
c.Inadvertenttrachealintubation.
d.Vomitingresultinginpulmonaryaspirationofgastriccontentsinanobtunded
patientwithoutairwayprotection.
4.Technique
a.Ifthepatientisdeeplyobtunded,protecttheairwaybyintubatingthetrachea
withacuffedendotrachealtube.
b.Placethepatientintheleftlateraldecubitusposition.Thishelpsprevent
ingestedmaterialfrombeingpushedintotheduodenumduringlavage.
c.Insertalargegastrictubethroughthemouthornoseandintothestomach(36
40F[cathetersize]inadultsasmallertubewillsufficeforremovalofliquid
poisonsorifsimpleadministrationofcharcoalisallthatisintended).Check
tubepositionwithairinsufflationwhilelisteningwithastethoscopepositioned
onthepatient'sstomach.
d.Withdrawasmuchofthestomachcontentsaspossible.Iftheingestedpoison
isatoxicchemicalthatmaycontaminatehospitalpersonnel(eg,cyanide,
organophosphateinsecticide),takestepstoisolateitimmediately(eg,usea
selfcontainedwallsuctionunit).
e.Administeractivatedcharcoal,60100g(1g/kgseeItemCbelow),downthe
tubebeforestartinglavagetobeginadsorptionofmaterialthatmayenterthe
intestineduringthelavageprocedure.
f.Instilltepid(lukewarm)waterorsaline,200to300mLaliquots,andremoveby
gravityoractivesuction.Userepeatedaliquotsforatotalof2Loruntilthe
returnisfreeofpillsortoxicmaterial.Caution:Useofexcessivevolumesof
lavagefluidorplaintapwatercanresultinhypothermiaorelectrolyte
imbalanceininfantsandsmallchildren.
C.Activatedcharcoalisahighlyadsorbentpowderedmaterialmadefromadistillationof
woodpulp.Owingtoitsverylargesurfacearea,itishighlyeffectiveinadsorbingmost
toxinswhengiveninaratioofapproximately10:1(charcoaltotoxin).Onlyafewtoxinsare
poorlyadsorbedtocharcoal(TableI37),andinsomecasesthisrequiresahigherratio
(eg,forcyanidearatioofabout100:1isnecessary).Studiesinvolunteerstakingnontoxic
dosesofvarioussubstancessuggestthatactivatedcharcoalgivenalonewithoutprior
gastricemptyingisaseffectiveasorevenmoreeffectivethanemesisandlavage
proceduresinreducingdrugabsorption.However,therearenowelldesignedprospective
randomizedclinicalstudiesdemonstratingitseffectivenessinpoisonedpatients.Asa
result,sometoxicologistsadviseagainstitsroutineuse.
TableI37DrugsandToxinsPoorlyAdsorbedbyActivatedCharcoala
ViewLarge|
Alkali Inorganicsalts(variable)
Cyanideb Iron
Ethanolandotheralcohols Lithium
Ethyleneglycol Mineralacids
Fluoride Potassium
Heavymetals(variable)
aFewstudieshavebeenperformedtodeterminetheinvivoadsorptionoftheseandother
toxinstoactivatedcharcoal.Adsorptionmayalsodependonthespecifictypeand
concentrationofcharcoal.
bCharcoalshouldstillbegivenbecauseusualdosesofcharcoal(60100g)willadsorb
usuallethalingesteddosesofcyanide(200300mg).
1.Indications
a.Usedafteringestiontolimitdrugabsorptionfromthegastrointestinaltractifit
canbegivensafelyandinareasonabletimeperiodaftertheingestion.
b.Charcoalisoftengiveneveniftheoffendingsubstancemaynotbewell
adsorbedtocharcoalincaseothersubstanceshavebeencoingested.
c.Repeatedoraldosesofactivatedcharcoalmayenhancetheeliminationof
somedrugsfromthebloodstream(SeeRepeatdoseactivatedcharcoal).
2.Contraindications.Ileuswithoutdistensionisnotacontraindicationtoasingledose
ofcharcoal,butfurtherdosesshouldbewithheld.Charcoalshouldnotbegiventoa
drowsypatientunlesstheairwayisadequatelyprotected.
3.Adverseeffects
a.Constipationorintestinalimpactionandcharcoalbezoararepotential
complications,especiallyifmultipledosesofcharcoalaregiven.
b.Distensionofthestomachwithapotentialriskforpulmonaryaspiration,
especiallyinadrowsypatient.
c.Manycommerciallyavailablecharcoalproductscontaincharcoalandthe
catharticsorbitolinapremixedsuspension.Evensingledosesofsorbitoloften
causestomachcrampsandvomiting,andrepeateddosesmaycauseserious
fluidshiftstotheintestine,diarrhea,dehydration,andhypernatremia,especially
inyoungchildrenandelderlypersons.
d.Maybindcoadministeredacetylcysteine(notclinicallysignificant).
4.Technique.(SeeTableI38forguidelinesonprehospitalandhospitaluse.)
TableI38GuidelinesforAdministrationofActivatedCharcoal
ViewLarge|
General
Theriskofthepoisoningjustifiestheriskofcharcoaladministration.
Activatedcharcoalcanbeadministeredwithin60minutesoftheingestion.a
Prehospital
Thepatientisalertandcooperative.
Activatedcharcoalwithoutsorbitolisreadilyavailable.
Administrationofcharcoalwillnotdelaytransporttoahealthcarefacility.
Hospital
Thepatientisalertandcooperative,ortheactivatedcharcoalwillbegivenvia
gastrictube(assumingtheairwayisintactorprotected).
aThetimeafteringestionduringwhichcharcoalremainsaneffective
decontaminationmodalityhasnotbeenestablishedwithcertaintyinclinicaltrials.
Fordrugswithsloworerraticintestinalabsorption,orforthosewithanticholinergic
oropioideffectsorotherpharmacologiceffectsthatmaydelaygastricemptyinginto
thesmallintestine,orfordrugsinamodifiedreleaseformulation,oraftermassive
ingestionsthatmayproduceatabletmassorbezoar,itisappropriatetoadminister
charcoalmorethan60minutesafteringestion,orevenseveralhoursafteringestion.
a.Giveactivatedcharcoalaqueoussuspension(withoutsorbitol),60100g(1
g/kg),orallyorbygastrictube.
b.Oneortwoadditionaldosesofactivatedcharcoalmaybegivenat1or2hour
intervalstoensureadequategutdecontamination,particularlyafterlarge
ingestions.Inrarecases,asmanyas8or10repeateddosesmaybeneeded
toachievethedesired10:1ratioofcharcoaltopoison(eg,afteraningestionof
200aspirintablets)insuchcircumstances,thedosesshouldbegivenovera
periodofseveralhours.
D.Cathartics.Controversyremainsovertheuseofcatharticstohasteneliminationoftoxins
fromthegastrointestinaltract.Sometoxicologistsstillusecatharticsroutinelywhengiving
activatedcharcoal,eventhoughfewdataexisttosupporttheirefficacy.
1.Indications
a.Toenhancegastrointestinaltransitofthecharcoaltoxincomplex,decreasing
thelikelihoodofdesorptionoftoxinorthedevelopmentofacharcoalbezoar.
b.Tohastenthepassageofirontabletsandotheringestionsnotadsorbedby
charcoal.
2.Contraindications
a.Ileusorintestinalobstruction.
b.Sodiumormagnesiumcontainingcatharticsshouldnotbeusedinpatients
withfluidoverloadorrenalinsufficiency,respectively.
c.Thereisnoroleforoilbasedcathartics(previouslyrecommendedfor
hydrocarbonpoisoning).
3.Adverseeffects
a.Severefluidloss,hypernatremia,andhyperosmolaritymayresultfromoveruse
orrepeateddosesofcathartics.
b.Hypermagnesemiamayoccurinpatientswithrenalinsufficiencywhoaregiven
magnesiumbasedcathartics.
c.Abdominalcrampingandvomitingmayoccur,especiallywithsorbitol.
4.Technique
a.Administerthecatharticofchoice(10%magnesiumcitrate,34mL/kg,or70%
sorbitol,1mL/kg)alongwithactivatedcharcoalormixedtogetherasaslurry.
Avoidusingcommerciallyavailablecombinationproductscontainingcharcoal
plussorbitolbecausetheyhavealargerthandesirableamountofsorbitol(eg,
96gofsorbitol/50gofcharcoal).
b.Repeatwithonehalftheoriginaldoseifthereisnocharcoalstoolafter68
hours.
E.Wholebowelirrigation.Wholebowelirrigationhasbecomeanacceptedmethodforthe
eliminationofsomedrugsandpoisonsfromthegut.Thetechniquemakesuseofa
surgicalbowelcleansingsolutioncontaininganonabsorbablepolyethyleneglycolina
balancedelectrolytesolutionthatisformulatedtopassthroughtheintestinaltractwithout
beingabsorbed.Thissolutionisgivenathighflowratestowashintestinalcontentsoutby
sheervolume.
1.Indications
a.Largeingestionsofiron,lithium,orotherdrugspoorlyadsorbedtoactivated
charcoal.
b.Largeingestionsofsustainedreleaseorentericcoatedtabletscontaining
valproicacid(eg,Depakote),theophylline(eg,TheoDur),aspirin(eg,Ecotrin),
verapamil(eg,CalanSR),diltiazem(eg,CardizemCD),orotherdangerous
drugs.
c.Ingestionofforeignbodiesordrugfilledpacketsorcondoms.Although
controversypersistsabouttheoptimalgutdecontaminationforbodystuffers
(personswhohastilyingestdrugcontainingpacketstohideincriminating
evidence),prudentmanagementinvolvesseveralhoursofwholebowel
irrigationaccompaniedbyactivatedcharcoal.Followupimagingstudiesmay
beindicatedtosearchforretainedpacketsiftheamountofdrugorits
packagingisofconcern.
2.Contraindications
a.Ileusorintestinalobstruction.
b.Obtunded,comatose,orconvulsingpatientunlesstheairwayisprotected.
3.Adverseeffects
a.Nauseaandbloating.
b.Regurgitationandpulmonaryaspiration.
c.Activatedcharcoalmaynotbeaseffectivewhengivenwithwholebowel
irrigation.
4.Technique
a.Administerbowelpreparationsolution(eg,CoLyteorGoLytely),2L/hbygastric
tube(children:500mL/hor35mL/kg/h),untilrectaleffluentisclear.
b.Sometoxicologistsrecommendtheadministrationofactivatedcharcoal2550
gevery23hourswhilewholebowelirrigationisproceeding,iftheingested
drugisadsorbedbycharcoal.
c.Bepreparedforalargevolumestoolwithin12hours.Passarectaltubeor,
preferably,havethepatientsitonacommode.
d.Stopadministrationafter810L(children:150200mL/kg)ifnorectaleffluent
hasappeared.
F.Otheroralbindingagents.Otherbindingagentsmaybegivenincertaincircumstances
totraptoxinsinthegut,althoughactivatedcharcoalisthemostwidelyusedeffective
adsorbent.TableI39listssomealternativebindingagentsandthetoxin(s)forwhichthey
maybeuseful.
TableI39SelectedOralBindingAgents
ViewLarge|
DrugorToxin BindingAgent(s)
Calcium Cellulosesodiumphosphate
Chlorinatedhydrocarbons Cholestyramineresin
Digitoxina Cholestyramineresin
Heavymetals(arsenic,mercury) Demulcents(eggwhite,milk)
Iron Sodiumbicarbonate
Lithium Sodiumpolystyrenesulfonate(Kayexalate)
Paraquata Fuller'searth,Bentonite
Potassium Sodiumpolystyrenesulfonate(Kayexalate)
Thallium Prussianblue
aActivatedcharcoalisalsoveryeffective.
G.Surgicalremoval.Occasionally,drugfilledpacketsorcondoms,intacttablets,ortablet
concretionspersistdespiteaggressivegastriclavageorwholegutlavage,andsurgical
removalmaybenecessary.Consultaregionalpoisoncontrolcenteroramedical
toxicologistforadvice.
ViewLarge|
ChemicalCorrosive
TopicalTreatment
Agent
Hydrofluoricacid Calciumsoaks
Oxalicacid Calciumsoaks
Phenol Mineraloilorotheroilisopropylalcohol
Coppersulfate1%(colorsembeddedgranulesblue,facilitatesmechanical
Phosphorus(white)
removal)
aReference:EdelmanPA:Chemicalandelectricalburns.In:AchauerBM(editor):Managementof
theBurnedPatient,pp183202.Appleton&Lange,1987.
ViewLarge|
Alkali Inorganicsalts(variable)
Cyanideb Iron
Ethanolandotheralcohols Lithium
Ethyleneglycol Mineralacids
Fluoride Potassium
Heavymetals(variable)
aFewstudieshavebeenperformedtodeterminetheinvivoadsorptionoftheseandothertoxinsto
activatedcharcoal.Adsorptionmayalsodependonthespecifictypeandconcentrationofcharcoal.
bCharcoalshouldstillbegivenbecauseusualdosesofcharcoal(60100g)willadsorbusuallethal
ingesteddosesofcyanide(200300mg).
ViewLarge|
General
Theriskofthepoisoningjustifiestheriskofcharcoaladministration.
Activatedcharcoalcanbeadministeredwithin60minutesoftheingestion.a
Prehospital
Thepatientisalertandcooperative.
Activatedcharcoalwithoutsorbitolisreadilyavailable.
Administrationofcharcoalwillnotdelaytransporttoahealthcarefacility.
Hospital
Thepatientisalertandcooperative,ortheactivatedcharcoalwillbegivenviagastrictube(assuming
theairwayisintactorprotected).
aThetimeafteringestionduringwhichcharcoalremainsaneffectivedecontaminationmodalityhas
notbeenestablishedwithcertaintyinclinicaltrials.Fordrugswithsloworerraticintestinalabsorption,
orforthosewithanticholinergicoropioideffectsorotherpharmacologiceffectsthatmaydelaygastric
emptyingintothesmallintestine,orfordrugsinamodifiedreleaseformulation,oraftermassive
ingestionsthatmayproduceatabletmassorbezoar,itisappropriatetoadministercharcoalmore
than60minutesafteringestion,orevenseveralhoursafteringestion.
ViewLarge|
DrugorToxin BindingAgent(s)
Calcium Cellulosesodiumphosphate
Chlorinatedhydrocarbons Cholestyramineresin
Digitoxina Cholestyramineresin
Heavymetals(arsenic,mercury) Demulcents(eggwhite,milk)
Iron Sodiumbicarbonate
Lithium Sodiumpolystyrenesulfonate(Kayexalate)
Paraquata Fuller'searth,Bentonite
Potassium Sodiumpolystyrenesulfonate(Kayexalate)
Thallium Prussianblue
aActivatedcharcoalisalsoveryeffective.
EnhancedElimination
Measurestoenhanceeliminationofdrugsandtoxinshavebeenoveremphasizedinthepast.
Althoughadesirablegoal,rapideliminationofmostdrugsandtoxinsisfrequentlynotpracticaland
maybeunsafe.Alogicalunderstandingofpharmacokineticsasitappliestotoxicology(toxicokinetics)
isnecessaryfortheappropriateuseofenhancedremovalprocedures.
I.Assessment.Threecriticalquestionsmustbeanswered:
A.Doesthepatientneedenhancedremoval?Askthefollowingquestions:Howisthe
patientdoing?Willsupportivecareenablethepatienttorecoverfully?Isthereanantidote
oranotherspecificdrugthatmightbeused?Importantindicationsforenhanceddrug
removalincludethefollowing:
1.Obviouslysevereorcriticalintoxicationwithadeterioratingconditiondespite
maximalsupportivecare(eg,phenobarbitaloverdosewithintractablehypotension).
2.Thenormalorusualrouteofeliminationisimpaired(eg,lithiumoverdoseinapatient
withrenalfailure).
3.Thepatienthasingestedaknownlethaldoseorhasalethalbloodlevel(eg,
theophyllineormethanol).
4.Thepatienthasunderlyingmedicalproblemsthatcouldincreasethehazardsof
prolongedcomaorothercomplications(eg,severechronicobstructivepulmonary
diseaseorcongestiveheartfailure).
B.Isthedrugortoxinaccessibletotheremovalprocedure?Foradrugtobeaccessible
toremovalbyextracorporealprocedures,itshouldbelocatedprimarilywithinthe
bloodstreamorintheextracellularfluid.Ifitisextensivelydistributedtotissues,itisnot
likelytobeeasilyremoved.
1.Thevolumeofdistribution(Vd)isanumericconceptthatprovidesanindicationof
theaccessibilityofthedrug:
AdrugwithaverylargeVdhasaverylowplasmaconcentration.Incontrast,adrug
withasmallVdispotentiallyquiteaccessiblebyextracorporealremovalprocedures.
TableI40listssomecommonvolumesofdistribution.
TableI40VolumeofDistributionofSomeDrugsandPoisons
ViewLarge|
LargeVd(>510L/kg) SmallVd(<1L/kg)
Antidepressants Alcohols
Digoxin Carbamazepine
Lindane Lithium
Opioids Phenobarbital
Phencyclidine(PCP) Salicylate
Phenothiazines Theophylline
2.Proteinbinding.Highlyproteinbounddrugshavelowfreedrugconcentrationsand
aredifficulttoremovebydialysis.
C.Willthemethodwork?Doestheremovalprocedureefficientlyextractthetoxinfromthe
blood?
1.Theclearance(CL)istherateatwhichagivenvolumeoffluidcanbeclearedof
thesubstance.
a.TheCLmaybecalculatedfromtheextractionratioacrossthedialysismachine
orhemoperfusioncolumn,multipliedbythebloodflowratethroughthe
followingsystem:
b.AcrudeurinaryCLmeasurementmaybeusefulforestimatingthe
effectivenessoffluidtherapyforenhancingrenaleliminationofsubstancesnot
secretedorabsorbedbytherenaltubule(eg,lithium):
Note:Theunitsofclearancearemillilitersperminute.Clearanceisnotthe
sameaseliminationrate(milligramsperminute).Ifthebloodconcentrationis
small,theactualamountofdrugremovedisalsosmall.
2.TotalCListhesumofallsourcesofclearance(eg,renalexcretionplushepatic
metabolismplusrespiratoryandskinexcretionplusdialysis).Ifthecontributionof
dialysisissmallcomparedwiththetotalclearancerate,theprocedurewillcontribute
littletotheoveralleliminationrate(TableI41).
TableI41EliminationofSelectedDrugsandToxinsa
ViewLarge|
ReportedClearanceby:
Volumeof UsualBody
Dialysis Hemoperfusionb
DrugorToxin Distribution Clearance
(mL/min) (mL/min)
(L/kg) (mL/min)
Acetaminophen 0.81 400 120150 125300
Amitriptyline 610 500800 NHDc 240d
Bromide 0.7 5 100 N/Ac
Carbamazepine 1.43 6090 59100e 80130
Digitoxin 1.5 4 1026 N/Ac
Digoxin 510 150200 NHDc 90140
Ethanol 0.7 100300 100200 NHPc
Ethchlorvynol 24 120140 2080 150300d
Ethyleneglycol 0.60.8 200 100200 NHPc
Glutethimide 2.7 200 70 300d
Isopropylalcohol 0.7 30 100200 NHPc
Lithium 0.71.4 2530 50150 NHPc
Meprobamate 0.75 60 60 85150
Metformin 80Lf 491652g 68170 56h
Methanol 0.7 4060 100200 NHPc
Formicacid
(methanol 198248
metabolite)
Methaqualone 2.46.4 130175 23 150270
Methotrexate 0.51 50100 N/Ac 54
Nadolol 2 135 46102 N/Ac
Nortriptyline 1527 5001000 2434 216d
Paraquat 2.8 30200 10 50155
Pentobarbital 0.651 2736 2355 200300
Phenobarbital 0.51 215 144188i 100300
Phenytoin 0.50.8 1530 NHD 76189
Procainamide 1.52.5 650 70 75
N
acetylprocainamide 1.4 220 48 75
(NAPA)
Salicylate 0.10.3 30 3580 57116
Theophylline 0.5 80120 3050 60225
Thiocyanate
(cyanide 83102
metabolite)
Volumeof UsualBody
Dialysis Hemoperfusionb
DrugorToxin Distribution Clearance
(mL/min) (mL/min)
(L/kg) (mL/min)
Trichloroethanol
0.61.6 25 68162 119200
(chloralhydrate)
Valproicacid 0.10.5 10 23 55
aAdaptedinpartfromPondSM:Diuresis,dialysis,andhemoperfusion:indications
andbenefits.EmergMedClinNorthAm19842:29andCutlerREetal:
Extracorporealremovalofdrugsandpoisonsbyhemodialysisandhemoperfusion.
AnnRevPharmacolToxicol198727:169.
bHemoperfusiondataaremainlyforcharcoalhemoperfusion.
cAbbreviations:N/A=notavailableNHD=nothemodialyzableNHP=not
hemoperfusable.
dDataareforXAD4resinhemoperfusion.
eLowerclearances(1459mL/min)reportedwitholderdialysisequipmentnewer
highfluxdialysismayproduceclearancesof59mL/minuptoestimated100mL/min
(basedoncasereports).
fLiteraturereportsofmetforminVdvarywidely.
gMetforminclearanceismarkedlyreducedinpatientswithrenalinsufficiency(108
130mL/min).
hClearancebycontinuousvenovenoushemofiltration(CVVH).
iLowerclearancesof6075mL/minreportedwitholderdialysisequipmentnewer
highfluxdialysismayproduceclearancesof144188mL/min(PalmerBF:AmJKid
Dis200036:640).
3.Thehalflife(T)dependsonthevolumeofdistributionandtheclearance:
wheretheunitofmeasurementofVdisliters(L)andthatofCLislitersperhour
(L/h).
II.Methodsavailableforenhancedelimination
A.Urinarymanipulation.Thesemethodsrequirethatthekidneybeasignificantcontributor
tototalclearance.
1.Forceddiuresismayincreasetheglomerularfiltrationrate,andiontrappingby
urinarypHmanipulationmayenhancetheeliminationofpolardrugs.
2.Alkalinizationiscommonlyusedforsalicylateoverdose,butforceddiuresis
(producingurinevolumesofupto1L/h)isgenerallynotusedbecauseoftheriskfor
fluidoverload.
B.Hemodialysis.Bloodistakenfromalargevein(usuallyafemoralvein)withadouble
lumencatheterandpumpedthroughthehemodialysissystem.Thepatientmustbegiven
anticoagulantmedicationtopreventclottingofbloodinthedialyzer.Drugsandtoxinsflow
passivelyacrossthesemipermeablemembranedownaconcentrationgradientintoa
dialysate(electrolyteandbuffer)solution.Fluidandelectrolyteabnormalitiescanbe
correctedconcurrently.
1.Flowratesofupto300500mL/mincanbeachieved,andclearanceratesmay
reach200300mL/minormore.Removalofdrugisdependentontheflowrate
insufficientflow(ie,duetoclotting)willreduceclearanceproportionately.
2.Characteristicsofthedrugortoxinthatenhanceitsextractabilityincludesmallsize
(molecularweight<500daltons),watersolubility,andlowproteinbinding.
3.Note:Smaller,portabledialysisunitsthatusearesincolumnorfiltertorecyclea
smallervolumeofdialysate(minidialysis)donotefficientlyremovedrugsor
poisonsandshouldnotbeused.
C.Hemoperfusion.Withtheuseofequipmentandvascularaccesssimilartothatfor
hemodialysis,thebloodispumpeddirectlythroughacolumncontaininganadsorbent
material(eithercharcoalorAmberliteresin).Becausethedrugortoxinisindirectcontact
withtheadsorbentmaterial,drugsize,watersolubility,andproteinbindingareless
importantlimitingfactors.Systemicanticoagulationisrequired,ofteninhigherdosesthan
areusedforhemodialysis,andthrombocytopeniaisacommoncomplication.Atthe
presenttime,fewdialysiscentershavetheequipmentforhemoperfusion,andthe
procedureisrarelycarriedout.
D.Peritonealdialysis.Dialysatefluidisinfusedintotheperitonealcavitythrougha
transcutaneouscatheteranddrainedoff,andtheprocedureisrepeatedwithfresh
dialysate.Thegutwallandperitonealliningserveasthesemipermeablemembrane.
1.Peritonealdialysisiseasiertoperformthanhemodialysisorhemoperfusionanddoes
notrequireanticoagulation,butitisonlyabout1015%aseffectiveowingtopoor
extractionratiosandslowerflowrates(clearancerates,1015mL/min).
2.However,peritonealdialysiscanbeperformedcontinuously,24hoursadaya24
hourperitonealdialysiswithdialysateexchangeevery12hoursisapproximately
equalto4hoursofhemodialysis.
E.Continuousrenalreplacementtherapy(eg,continuousarteriovenoushemofiltration
[CAVH],continuousvenovenoushemofiltration[CVVH],continuousarteriovenous
hemodiafiltration[CAVHDF],orcontinuousvenovenoushemodiafiltration[CVVHDF])has
beensuggestedasanalternativetoconventionalhemodialysiswhentheneedforrapid
removalofthedrugislessurgent.Likeperitonealdialysis,theseproceduresare
associatedwithlowerclearanceratesbuthavetheadvantageofbeingminimallyinvasive,
withnosignificantimpactonhemodynamics,andcanbecarriedoutcontinuouslyfor
manyhours.However,theirroleinthemanagementofacutepoisoningremainsuncertain.
F.Repeatdoseactivatedcharcoal.Repeateddosesofactivatedcharcoal(2030gor0.5
1g/kgevery23hours)aregivenorallyorviagastrictube.Thepresenceofaslurryof
activatedcharcoalthroughoutseveralmetersoftheintestinallumenreducesblood
concentrationsbyinterruptingenterohepaticorenteroentericrecirculationofthedrugor
toxin,amodeofactionquitedistinctfromthesimpleadsorptionofingestedbut
unabsorbedtablets.Thistechniqueiseasyandnoninvasiveandhasbeenshownto
shortenthehalflifeofphenobarbital,theophylline,andseveralotherdrugs(TableI42).
However,ithasnotbeenproveninclinicaltrialstoalterpatientoutcome.Caution:
Repeatdosecharcoalmaycauseseriousfluidandelectrolytedisturbancesecondaryto
largevolumediarrhea,especiallyifpremixedcharcoalsorbitolsuspensionsareused.
Also,itshouldnotbeusedinpatientswithileusorobstruction.
TableI42SomeDrugsRemovedbyRepeatDoseActivatedCharcoala
ViewLarge|
Caffeine Phenobarbital
Carbamazepine Phenylbutazone
Chlordecone Phenytoin
Dapsone Salicylate
Digitoxin Theophylline
Nadolol
aNote:Basedonvolunteerstudies.Therearefewdataonclinicalbenefitindrugoverdose.
ViewLarge|
LargeVd(>510L/kg) SmallVd(<1L/kg)
Antidepressants Alcohols
Digoxin Carbamazepine
Lindane Lithium
Opioids Phenobarbital
Phencyclidine(PCP) Salicylate
Phenothiazines Theophylline
ViewLarge|
DrugorToxin
Volumeof UsualBody Dialysis Hemoperfusionb
Distribution(L/kg) Clearance(mL/min) (mL/min) (mL/min)
Acetaminophen 0.81 400 120150 125300
Amitriptyline 610 500800 NHDc 240d
Bromide 0.7 5 100 N/Ac
Carbamazepine 1.43 6090 59100e 80130
Digitoxin 1.5 4 1026 N/Ac
Digoxin 510 150200 NHDc 90140
Ethanol 0.7 100300 100200 NHPc
Ethchlorvynol 24 120140 2080 150300d
Ethyleneglycol 0.60.8 200 100200 NHPc
Glutethimide 2.7 200 70 300d
Isopropylalcohol 0.7 30 100200 NHPc
Lithium 0.71.4 2530 50150 NHPc
Meprobamate 0.75 60 60 85150
Metformin 80Lf 491652g 68170 56h
Methanol 0.7 4060 100200 NHPc
Formicacid(methanol
198248
metabolite)
Methaqualone 2.46.4 130175 23 150270
Methotrexate 0.51 50100 N/Ac 54
Nadolol 2 135 46102 N/Ac
Nortriptyline 1527 5001000 2434 216d
Paraquat 2.8 30200 10 50155
Pentobarbital 0.651 2736 2355 200300
Phenobarbital 0.51 215 144188i 100300
Phenytoin 0.50.8 1530 NHD 76189
Procainamide 1.52.5 650 70 75
Nacetylprocainamide
1.4 220 48 75
(NAPA)
Salicylate 0.10.3 30 3580 57116
Theophylline 0.5 80120 3050 60225
Thiocyanate(cyanide
83102
metabolite)
Trichloroethanol
0.61.6 25 68162 119200
(chloralhydrate)
Valproicacid 0.10.5 10 23 55
aAdaptedinpartfromPondSM:Diuresis,dialysis,andhemoperfusion:indicationsandbenefits.
EmergMedClinNorthAm19842:29andCutlerREetal:Extracorporealremovalofdrugsand
poisonsbyhemodialysisandhemoperfusion.AnnRevPharmacolToxicol198727:169.
bHemoperfusiondataaremainlyforcharcoalhemoperfusion.
cAbbreviations:N/A=notavailableNHD=nothemodialyzableNHP=nothemoperfusable.
dDataareforXAD4resinhemoperfusion.
eLowerclearances(1459mL/min)reportedwitholderdialysisequipmentnewerhighfluxdialysis
mayproduceclearancesof59mL/minuptoestimated100mL/min(basedoncasereports).
fLiteraturereportsofmetforminVdvarywidely.
gMetforminclearanceismarkedlyreducedinpatientswithrenalinsufficiency(108130mL/min).
hClearancebycontinuousvenovenoushemofiltration(CVVH).
iLowerclearancesof6075mL/minreportedwitholderdialysisequipmentnewerhighfluxdialysis
mayproduceclearancesof144188mL/min(PalmerBF:AmJKidDis200036:640).
ViewLarge|
Caffeine Phenobarbital
Carbamazepine Phenylbutazone
Chlordecone Phenytoin
Dapsone Salicylate
Digitoxin Theophylline
Nadolol
aNote:Basedonvolunteerstudies.Therearefewdataonclinicalbenefitindrugoverdose.
DispositionofthePatient
I.Emergencydepartmentdischargeorintensivecareunitadmission?
A.Allpatientswithpotentiallyseriousoverdoseshouldbeobservedforatleast68hours
beforedischargeortransfertoanonmedical(eg,psychiatric)facility.Ifsignsorsymptoms
ofintoxicationdevelopduringthistime,admissionforfurtherobservationandtreatmentis
required.Caution:Bewareofdelayedcomplicationsfromtheslowabsorptionof
medications(eg,fromatabletconcretionorbezoarorsustainedreleaseorentericcoated
preparations).Inthesecircumstances,alongerperiodofobservationiswarranted.If
specificdruglevelsaredetermined,obtainrepeatedserumlevelstobecertainthatthey
aredecreasingasexpected.
B.Mostpatientsadmittedforpoisoningordrugoverdosewillneedobservationinan
intensivecareunit,althoughthisdependsonthepotentialforseriouscardiorespiratory
complications.Anypatientwithsuicidalintentmustbekeptundercloseobservation.
II.Regionalpoisoncontrolcenterconsultation:18002221222.Consultwitharegionalpoison
controlcentertodeterminetheneedforfurtherobservationoradmission,administrationof
antidotesortherapeuticdrugs,selectionofappropriatelaboratorytests,ordecisionsabout
extracorporealremoval.Anexperiencedclinicaltoxicologistisusuallyavailableforimmediate
consultation.Asingletollfreenumberisineffectnationwideandwillautomaticallyconnectthe
callertotheregionalpoisoncontrolcenter.
III.Psychosocialevaluation
A.Psychiatricconsultationforsuiciderisk.Allpatientswithintentionalpoisoningordrug
overdoseshouldundergoapsychiatricevaluationforsuicidalintent.
1.Itisnotappropriatetodischargeapotentiallysuicidalpatientfromtheemergency
departmentwithoutacarefulpsychiatricevaluation.Moststateshaveprovisionsfor
thephysiciantoplaceanemergencypsychiatrichold,forcinginvoluntarypatientsto
remainunderpsychiatricobservationforupto72hours.
2.Patientscallingfromhomeafteranintentionalingestionshouldalwaysbereferredto
anemergencydepartmentformedicalandpsychiatricevaluation.
B.Childabuse(seealsobelow)orsexualabuse
1.Childrenshouldbeevaluatedforthepossibilitythattheingestionwasnotaccidental.
Sometimesparentsorotheradultsintentionallygivechildrensedativesor
tranquilizerstocontroltheirbehavior.
2.Accidentalpoisoningsmayalsowarrantsocialservicesreferral.Occasionally,
childrengetintostimulantsorotherabuseddrugsthatareleftaroundthehome.
Repeatedingestionssuggestoverlycasualornegligentparentalbehavior.
3.Intentionaloverdoseinachildoradolescentshouldraisethepossibilityofphysicalor
sexualabuse.Teenagegirlsmayhaveoverdosedbecauseofunwantedpregnancy.
IV.Overdoseinthepregnantpatient
A.Ingeneral,itisprudenttocheckforpregnancyinanyyoungwomanwithdrugoverdoseor
poisoning.Unwantedpregnancymaybeacauseforintentionaloverdose,orspecial
concernsmayberaisedabouttreatmentofthepregnantpatient.
B.Inducingemesiswithsyrupofipecacisprobablysafeinearlypregnancy,butprotracted
vomitingisunwelcome,especiallyinthethirdtrimester.Gastriclavageororalactivated
charcoalispreferableinalltrimesters.
C.Sometoxinsareknowntobeteratogenicormutagenic(seeSpecialConsiderationsin
PediatricPatientsandTableI45).However,adverseeffectsonthefetusaregenerally
associatedwithchronic,repeateduseasopposedtoacute,singleexposure.
Copyright2017McGrawHillEducation.Allrightsreserved.
Checklistofemergencyevaluationandtreatmentprocedures.
Tworoutesforendotrachealintubation.A:Nasotrachealintubation.B:Orotrachealintubation.
WidenedQRSintervalcausedbytricyclicantidepressantoverdose.A:Delayedintraventricular
conductionresultsinprolongedQRSinterval(0.18s).BandC:Supraventriculartachycardiawith
progressivewideningofQRScomplexesmimicsventriculartachycardia.(Modifiedandreproduced,
withpermission,fromBenowitzNL,GoldschlagerN:Cardiacdisturbancesinthetoxicologicpatient.
In:HaddadLM,WinchesterJF[editors]:ClinicalManagementofPoisoningandDrugOverdose,p71.
WBSaunders,1983.)
Rightaxisdeviationoftheterminal40milliseconds,easilyrecognizedasalateRwaveinaVR.
Electrocardiogramofapatientwithhyperkalemia.(Modifiedandreproduced,withpermission,from
GoldschlagerN,GoldmanMJ:Effectofdrugsandelectrolytesontheelectrocardiogram.In:
Electrocardiogramofapatientwithhypothermia,showingprominentJwaves.(Modifiedand
reproduced,withpermission,fromGoldschlagerN,GoldmanMJ:Miscellaneousabnormal
electrocardiogrampatterns.In:GoldschlagerN,GoldmanMJ[editors]:Electrocardiography:
Polymorphicventriculartachycardia(torsadedepointes).(Modifiedandreproduced,withpermission,
fromGoldschlagerN,GoldmanMJ:Effectofdrugsandelectrolytesontheelectrocardiogram.In:

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