definitions and nomenclature workshop...report of the toxic chemical syndrome definitions and...

Report on the Toxic Chemical Syndrome Definitions and Nomenclature Workshop May 8-9 2012

Under contract to the U.S. Department of Homeland Security (DHS), American College of Medical Toxicology (ACMT) Subject Matter Experts (SMEs) reviewed this report and accompanying comments which were submitted by the 2012 Workshop participants provided in follow-up to the meeting. Following an iterative discussion of the nature, scope, and specific content of the participant stakeholder comments, the original 2012 DRAFT workshop document was edited to incorporate these subsequent comments and discussions. These edits were reviewed and approved by DHS Office of Health Affairs’ Chemical Defense Program, and have been incorporated into this updated workshop report. The 23 pages of this report represent updated Sections 1 and 2 of the 2012 Draft document. These edits involved:

1) Consolidating the initial 12 toxidromes from the Workshop’s breakout activities into a final total of 9; with the 3 routes of exposure (inhalation, ingestion, dermal) described within the single “Irritant/Corrosive” toxidrome; 2) Combining the “Cyanide-like” and “Knockdown Agents” into a single toxidrome: “Knockdown” and; 3) Expanded narrative to the toxidrome descriptions.

A detailed memo about specific changes is available from the CHEMM project team.

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Report of the Toxic Chemical Syndrome Definitions and Nomenclature Workshop, May 2012

Report of the Toxic Chemical Syndrome Definitions and Nomenclature Workshop, May 2012 Page 1

Report of the Toxic Chemical Syndrome Definitions and Nomenclature Workshop

May 8-9, 2012

Submitted to: National Library of Medicine and Department of Homeland Security

Submitted by: Toxicology Excellence for Risk Assessment


FederalPointsofContactCAPTJoselitoIgnacio,MA,MPH,CIH,CSP,REHSActingDirector,ChemicalDefenseProgramDepartmentofHomelandSecurityOfficeofHealthAffairsJoselito.ignacio@hq.dhs.gov

Pertti(Bert)Hakkinen,PhDActingHead,OfficeofClinicalToxicologySpecializedInformationServicesNationalLibraryofMedicineNationalInstitutesofHealthPertti.hakkinen@nih.gov


ContentsContents.........................................................................................................................................................3

ListofFiguresandTables ............................................................................................................................... 4

ListofAcronyms............................................................................................................................................. 5

1. Introduction ...............................................................................................................................................8

1.1 WorkshopOrganizingCommittee ...................................................................................................….8

1.2 Background.........................................................................................................................................9

1.3 IntendedUseoftheResultsoftheWorkshop..................................................................................10

1.4 OrganizationofthisReport ..............................................................................................................11

2. ToxicChemicalSyndromeDefinitionsandNomenclatureWorkshop ....................................................11

2.1 BreakoutGroups ..............................................................................................................................13

2.1.1 BreakoutGroupInstructions .....................................................................................................13

2.1.2 BreakoutGroupResults.............................................................................................................13

2.1.3 RecommendedToxidromes.......................................................................................................14

2.1.4 ToxidromeNaming ....................................................................................................................15

2.1.5 ParticipantBallots......................................................................................................................16

2.2 Discussion ........................................................................................................................................ .17

2.3 Conclusions.......................................................................................................................................19

2.4 ReferencesandSources ...................................................................................................................20


ListofFiguresandTablesFigure1IntersectionofToxidromeUserGroups .......................................................................................10Table1BreakoutGroupAssignments ........................................................................................................13Table2.BreakoutGroupRecommendationsforToxidromeNamesandDescriptions ..............................14


ListofAcronyms

AHLS–AdvancedHazmatLifeSupportprogram

ALS–Advancedlifesupport

BLS–BasiclifesupportCHEMM–ChemicalHazardsEmergencyMedicalManagement

CHEMM-IST–ChemicalHazardsEmergencyMedicalManagementIntelligentSyndromesTool

CNS–Centralnervoussystem

CSAC–ChemicalSecurityAnalysisCenter

CTRA–ChemicalTerrorismRiskAssessment

CWAs–Chemicalwarfareagents

DHS–DepartmentofHomelandSecurity

EMTs–Emergencymedicaltechnicians

F&ES–FireandEmergencyServices

GI–GastrointestinalHazmat–Hazardousmaterials

HHS–U.S.DepartmentofHumanandHealthServices

HPV–HighProductionVolume

HSDB–HazardousSubstancesDataBank

NICC–NationalInteragencyCoordinationCentersNIOSH–NationalInstituteforOccupationalSafetyandHealth

NLM–NationalLibraryofMedicine

NOC–NationalOperationsCenter

OHA–OfficeofHealthAffairs

PNS–Peripheralnervoussystem


SAS–Solvents,Anesthetics,orSedatives

SLTT–State,Local,TribalandTerritorial

SME–Subjectmatterexpert

SOCs–SupportandOperationsCentersTERA–ToxicologyExcellenceforRiskAssessment

TICS–Toxicindustrialchemicals

TIMS–ToxicindustrialmaterialsWISER–WirelessInformationSystemforEmergencyResponders


1. IntroductionTheDepartmentofHomelandSecurity(DHS)OfficeofHealthAffairs(OHA),withtheNationalLibraryofMedicine(NLM),sponsoredatechnicalworkshoponMay8-9,2012todiscussanddevelopaconsistent

lexicontodescribetoxicchemicalsyndromes,ortoxidromes1.Theworkshopgoalwastoreachconsensusonalistofsyndromes,theirdefinitions,anddesignatedsyndromenamestoestablishacommonlanguageforchemicaldefenseplanners,policymakers,firstresponders,firstreceivers,andhazardousmaterials(Hazmat)stakeholders.Thesyndromelistaimstoprovidethiscommonlexicontoassistkeystakeholdercommunitiesinquicklyandaccuratelyidentifyingthebroadchemicalagentcategory(ifnotthespecificchemicalagent)bywhichapatientwasexposedinordertorapidlydetermineappropriateemergencytreatment.Comprehensiveness,accuracy,andclearunderstandingofthelexiconservedastheprimarycriteriaindevelopingthislexicon.

Overfortypeopleparticipatedintheworkshop,includingfirstresponders,firstreceivers,medicaldirectors,trainers,andsubjectmatterexperts(SMEs)inemergencymedicine,emergencyresponse,andmedicaltoxicology.Participantswerefromcivilianandmilitaryagencies,universities,hospitals,and

emergencyresponseentities.

Aworkshoporganizingcommitteeconductedextensiveliteraturereviewsofcurrenttoxicsyndromesanddevelopedproposedcriteriaandsyndromestoserveasastartingpointfortheworkshop

discussionsandconsensusbuilding.Workshopparticipantsreviewedthesematerialsandprovidedwrittencommentspriortotheworkshop.TheWorkshopOrganizingCommitteesharedcommentswithparticipantsandusedthevaluableinputtostructuretheworkshopdiscussionsandprocess.

Theworkshopwashighlyinteractivetofullyutilizetheexperienceandknowledgeoftheparticipatingsubjectmatterexperts.Thefirstdayfocusedondiscussingandagreeinguponkeycomponentsand

issuesrelatedtotoxicsyndromedefinitionsandnomenclature.Theparticipantsthendividedintothreebreakoutgroupstodiscussandreachagreementonspecificsyndromedefinitionsandnomenclature.Thebreakoutgroupsreportedbacktothelargergrouponthesecondafternoonwithproposed

syndromesanddefinitions.ThisreportprovidesanaccuraterecordfortheworkshopparticipantsandwillserveasareferenceforthenextphasesofToxidromeLexicondevelopment.

1.1 WorkshopOrganizingCommitteeAcommitteecomprisedofDHS/OfficeofHealthAffairs(OHA),NLMandToxicologyExcellenceforRisk

Assessment(TERA)scientistsorganizedtheworkshop.Membersincluded:

· Dr.MarkKirk,DivisionofMedicalToxicology,DepartmentofEmergencyMedicine,UniversityofVirginia

· Capt.JoselitoIgnacio,DepartmentofHomelandSecurity 1Workshopattendeesagreedthatthetermstoxicsyndromeandtoxidromecanbeusedinterchangeablyastoxidromeisacontractionof“toxicsyndrome.”SeeDiscussionforfurtherexplanation.


· JenPakiam,NationalInstitutesofHealth,NationalLibraryofMedicine · HillarySadoff,BestValueTechnologyInc.,contractsupporttotheDepartmentofHomeland

Security · MichaelCarringer,BestValueTechnologyInc.,contractsupporttotheDepartmentofHomeland

Security

· Dr.DavidSiegel,NationalInstitutesofHealth,NationalInstituteofChildHealth&HumanDevelopment

· Dr.Pertti(Bert)Hakkinen,NationalInstitutesofHealth,NationalLibraryofMedicine · FlorenceChang,NationalInstitutesofHealth,NationalLibraryofMedicine · StaceyArnesen,NationalInstitutesofHealth,NationalLibraryofMedicine · Dr.AndrewMaier,ToxicologyExcellenceforRiskAssessment · JacquelinePatterson,ToxicologyExcellenceforRiskAssessment · Dr.SueRoss,ToxicologyExcellenceforRiskAssessment(Fellow) · OliverKroner,ToxicologyExcellenceforRiskAssessment

1.2 BackgroundTensofthousandsofchemicalsareharmfultohumansandknowingthespecifictoxiceffectsofevenaportionofthepossiblechemicalagentswouldbeanimpossibletask.Toxicchemicalscanoftenbe

groupedintoclasses,wherebyallthechemicalsinagivenclasscausesimilartypesofadversehealtheffects.Theseconstellationsoftoxiceffectsorsyndromescompriseasetofclinical‘‘fingerprints’’forgroupsoftoxicants.Moreover,allthetoxicchemicalsassociatedwithagiventoxicsyndromeare

treatedsimilarly.Hence,duringtheearlyphasesofatoxicchemicalemergency,whentheexactchemicalisoftenunknown,identificationofthetoxicsyndromesthatarepresentcanbeausefuldecisionmakingtoolthatcanovercomemanyoftheproblemsassociatedwiththelackofinformation

onchemicalidentity.

Toxicsyndromesareeasilyidentifiedwithonlyafewobservations,suchas:

· Vitalsigns · Mentalstatus · Pupilsize · Mucousmembraneirritation · Lungexamforwheezesorcrackles · Skinforburns,moisture,andcolor

Toxicsyndromerecognitionisimportantbecauseitprovidesatoolforrapiddetectionofthesuspectedcauseandcanfocusthedifferentialdiagnosistoonlyafewchemicalswithsimilartoxiceffects.By

focusingoncertainchemicals,specificdiagnostictestingandtreatmentcanberenderedbasedonobjectiveclinicalevidence.Specifically,duringamassexposure,recognitioncanprovideatriagetoolforidentifyingtoxiceffectsandalsoprovideacommon‘‘language’’sothatallpersonnel,fromemergency

respondersonthescenetothehospitalemergencydepartment,canclearlycommunicateaclinicalmessage(Figure1).Withtheextraordinarynumberofchemicalsinuse,thistooldoesnotapplyto


everychemicalbuttomostofthecommonlyencounteredchemicalsreportedinhazmatincidents,includingchemicalsthatarenotspecificallynamedbutthatmayconceivablybeusedinintentionalterroristreleases(i.e.,agentsofopportunityorchemicalwarfareagents).Theuseoftoxicsyndromesasadiagnostictoolisfundamentaltoaneffective,timelymedicalresponse.

Figure1IntersectionofToxidromeUserGroups.

Thescopeoftheworkshopwasprimarilyfocusedonon-sceneandhospitalresponsesintheearlyphasesofalarge-scalechemicalrelease.Theexposuresinthisscenarioarelikelytobeinhalationandpossiblydermal.Ingestionislesslikely.Thereforechemicalsthatwouldcausefood/waterborneoutbreaksorcovert/delayedpoisoningswerenotconsideredinthisworkshop.Thisworkshopfocused

ondevelopingadecision-makingtoolthatwillbeusedintheearlypartofaresponsewheninformationislimited.Delayedeffectswerelessemphasizedandtheclinicalcourseinitsentirety–hourstodayswasnotthefocus.Thisreportprovidesanaccuraterecordfortheworkshopparticipantsanda

referenceforthenextphasesofLexicondevelopment.

1.3 IntendedUseoftheResultsoftheWorkshopTheNLMandDHSareworkingtogetheronthisprojecttoimprovecommunicationthatassuresacoordinatedandeffectiveresponsetomassexposureincidentsinvolvingtoxicindustrialchemicals

(TICS),toxicindustrialmaterials(TIMS),orchemicalwarfareagents(CWAs).JointlywiththeU.S.DepartmentofHealthandHumanServices(HHS),DHS/OHAintendstopublishproductsfromthis


workshoptolaythefoundationforaconsistentlexicondescribingtoxicsyndromesamongState,Local,Tribal,andTerritorial(SLTT),aswellasfederalfirstrespondersandfirstreceivers.Communicationinacrisisrequiresaccurateandsuccincttermswhichconveythehealthconditionsofpatients.Asdescribed,theDHSrecognizesthemyriadoftoxicsyndrometermsused,particularlybetweentheDepartmentof

Defenseandthecivilianmedicalandemergencyresponsecommunities.Bridgingthisgap,throughthisworkshopandtheproductsproducedthereafter,providesaframeworktobeginusingaconsistentsetoftermsanddefinitions.

TheNLMintendstousetheresultsofthisprojectinitsCHEMM(ChemicalHazardsEmergencyMedicalManagement)program.CHEMM(http://chemm.nlm.nih.gov/)enablesfirstresponders,firstreceivers,otherhealthcareproviders,andplannerstoplanfor,respondto,recoverfrom,andmitigatetheeffects

ofmass-casualtyincidentsinvolvingchemicals.CHEMMprovidesacomprehensive,user-friendly,web-basedresourcethatisalsodownloadableinadvance,sothatitwouldbeavailableduringaneventifthe

internetisnotaccessible.CHEMMwasproducedbytheHHS,OfficeoftheAssistantSecretaryforPreparednessandResponse,OfficeofPlanningandEmergencyOperations,incooperationwiththeNLM’sDivisionofSpecializedInformationServices,andmanymedical,emergencyresponse,toxicology,

andotherrelevantexperts.ResultsoftheworkshopmaybeusedtoexpandtheCHEMMIntelligentSyndromesTool(CHEMM-IST).CHEMM-ISTisaprototypedecisionsupporttooldevelopedbyexpertsinmedicineandemergencyresponseasanaidforidentifyingthechemicalsinamasscasualtyincidentand

providingguidelinesfortreatment.SinceCHEMM-ISTiscurrentlyintheprototypephaseofdevelopment,itshouldnotbeusedforpatientcare.Thistoolisintendedforusebybasiclifesupport(BLS)andadvancedlifesupport(ALS)providersaswellashospitalfirstreceivers.Moreinformation

aboutCHEMM-ISTisavailableathttp://chemm.nlm.nih.gov/chemmist.htm.

1.4 OrganizationofthisReportThepurposeofthisreportistocapturethekeyinformationfromtheworkshopandserveasreferencematerialforfurtherdevelopmentoftheToxidromeLexicon.

· Section1providesanintroductionandbackgroundontheneedfortoxicsyndromesandacommonlexicon.

· Section2summarizestheworkshopandresults.

2. ToxicChemicalSyndromeDefinitionsandNomenclatureWorkshopTheworkshopagendawasdesignedtobehighlyinteractivetotakeadvantageoftheexperienceandknowledgeoftheparticipants.Theworkshoporganizingcommitteemetbyteleconferencenumerous


timespriortotheworkshopandhadextensivediscussionstodefinethescopeoftheprojectandidentifykeyindividualsandorganizationstoinviteandinvolveintheproject.Researchwasconductedtoidentifyotherorganization’slexiconsanddefinitions,andthesewereevaluatedforapplicabilitytothisproject.Acrosswalkcomparingandcontrastingtoxicsyndromesystemsfromover20organizations

wasdeveloped,alongwithaproposedlistofsyndromesanddefinitionsfortheworkshop’sinitialconsideration.Thecommitteesentapackagewiththesematerialstotheinviteespriortotheworkshopandsolicitedinputonkeyquestionsfromtheinvitees.Inviteesprovidedtheirinitialthoughtsand

commentsregardingthekeyquestionstothecommitteepriortotheworkshop.Thecommitteereviewedtheresponsesandmodifiedtheworkshopsessionstomakebestuseoftheworkshoptimeandreachtheobjectiveofdevelopingaconsensuslistoftoxicsyndromes,definitions,and

nomenclature.

OpeningremarkswereprovidedbyDr.JamesPolkandCapt.JoselitoIgnaciooftheDHS.Theydescribed

theneedtopreparecommunitieswhoarepotentiallyinharm’swayfromindustrialchemicalexposuresaswellaspotentialterroristattack.TheDHShaspartneredwiththeNLMtodevelopacommonvocabularyforchemicalsyndromesthatwillbereadilyunderstoodbybothcivilianandmilitaryfirst

responderandfirstreceivercommunities,therebyimprovingcommunicationandultimatelythepublichealthresponse.Dr.PerttiHakkinenwelcomedparticipantsonbehalfoftheNLMandbrieflydescribedhowtheworkshopresultsareintendedtobeincorporatedintotheNLM’ssuiteofdecisionsupporttools

(e.g.,CHEMM).

Thefirstday’sagendafocusedonsharinginformationonkeycomponentsandissuesrelatedtotoxicsyndromedefinitionsandnomenclature.Twoplenaryspeakersprovidedbackgroundonissuesand

currentefforts.Dr.MarkKirk,currentlyattheUniversityofVirginia,andpreviouslytheDirectoroftheChemicalDefenseProgramattheDHS,explainedwhytoxicsyndromerecognitionandtrainingisvitalandproposedatieredapproachtosyndromerecognitionandresponse.Ms.JessicaCoxoftheDHS

ChemicalSecurityAnalysisCenterdescribedworkonChemicalTerrorismRiskAssessment(CTRA).Shepresentedinformationontoxidromesthatweredevelopedforthatprogram.

Followingtheplenaryspeakers,Dr.AndyMaierofTERAledthegroupthroughdiscussionsanddecisions

onkeyaspectsfortheworkshop,includingtheidealnumberofsyndromes,guidanceforsyndromenames,andelementsofsyndromedefinitions.Thegroupthendividedintothreebreakoutgroupstodiscussandreachagreementonspecificsyndromedefinitionsandnomenclature.Thebreakoutgroups

reportedbacktothelargergrouponthesecondafternoonwithalistofsyndromesandtheirdefinitions.Thelargergroupdiscussedthebreakoutgrouprecommendationsandkeyissues,andidentifiedresearchneeds.


2.1 BreakoutGroups2.1.1 BreakoutGroupInstructionsTheworkshopattendeesdividedintothreebreakoutgroupstodiscussandreachagreementonalistofsyndromesanddefinitions.

Table1BreakoutGroupAssignments

Group TypesofChemicalsandEndpoints

Group1 UpperandLowerPulmonary,Vesicants,Irritants,Corrosives

Group2 BloodAgents,Hemolytic,Metabolic,Anticoagulants,Asphyxiants

Group3 Convulsants,CholinergicCWA,Cholinergicpesticide,Opioids,Anxiety

Thebreakoutgroupswerechargedwithdiscussingandreportingontwelveelementsforeach

recommendedsyndrome.

1. Clinicallyrelevantroutesofexposureandtypesofsources2. Organsystemsgenerallyaffected3. Initialsignsandsymptoms4. Progressionofsignsandsymptoms5. Underlyingpathology,biologicalprocesses,ormodesofaction6. Industrialchemicalusesandchemicalwarfare/terrorismexamples7. Commontreatmentprotocols,specificantidotes,andkeysupportivemeasures8. Recommendationforasyndromenamethatwouldmeettheagreeduponcriteria9. Aclearandconcisesyndromedefinitionthatwillbereadilyunderstoodbythetargetaudiences10. Anyissuesorconcernsaboutthesyndrome11. Identifydatagapsorresearchthatcouldbedonetosignificantlyaidintherapididentificationof

atoxicsyndromebyfirstrespondersandreceivers12. Rationaleorreasoningfortoxidromegroupingandnamingdecisions

Rapporteursfromeachbreakoutgroupreportedbacktotheworkshopontheirgroup’sdiscussionsand

recommendations.

2.1.2 BreakoutGroupResultsThethreebreakoutgroupsdiscussedpossibletoxidromes.Eachgroupdevelopedanumberofsyndromes,definitions,andrationales.Section2.1.3containsasummaryofthenineindividualtoxidromesthatthebreakoutgroupsrecommended,withconsolidationof“Cyanide-like”and“Knockdown/Asphyxiants”agentsintoone“Knockdown”toxidromeandgroupingof

“irritants/corrosives”intoasingletoxidromeirrespectiveofrouteofexposure.


2.1.3 RecommendedToxidromesTable2.ToxidromeNamesandDescriptions:ConsolidatedBreakoutGroupRecommendations

AnticholinergicToxidrome

Understimulationofcholinergicreceptorsleadingtodilatedpupils(mydriasis),decreasedsweating,elevatedtemperature,andmentalstatuschanges,includingcharacteristichallucinations.

AnticoagulantsToxidromeAlterationofbloodcoagulationthatresultsinabnormalbleedingindicatedbyexcessivebruising,andbleedingfrommucousmembranes,thestomach,intestines,urinarybladder,andwounds,aswellasotherinternal(e.g.intracranial,retroperitoneal)bleeding.

Acuteexposuretosolvents,anesthetics,orsedatives(SAS)ToxidromeCentralnervoussystemdepressionleadingtoadecreasedlevelofconsciousness(progressingtocomainsomecases),depressedrespirations,andinsomecasesataxia(difficultybalancingandwalking).

CholinergicToxidromeOverstimulationofcholinergicreceptorsleadingtofirstactivation,andthenfatigueoftargetorgans,leadingtopinpointpupils(miosis),seizing,wheezing,twitching,andexcessiveoutputfromallsecretorycells/organs(“leakingallover”–bronchialsecretions,sweat,tears,saliva,vomiting,incontinence).

ConvulsantToxidromeCentralnervoussystemexcitation(GABAantagonismand/orglutamateagonismand/orglycineantagonism)leadingtogeneralizedconvulsions.

Irritant/CorrosiveImmediateeffectsrangefromminorirritationofexposedskin,mucousmembranes,pulmonary,andgastrointestinal(GI)tracttocoughing,wheezing,respiratorydistressandmoresevereGIsymptomsthatmayprogressrapidlytosystemictoxicity.

KnockdownToxidromeDisruptedcellularoxygendeliverytotissuesmaybecausedbysimpleasphyxiaduetooxygendisplacementbyinertgases,hemoglobinopathies(e.g.carbonmonoxide,methemoglobininducers)impairingoxygentransportbytheredbloodcell,and/orimpairmentofthecell’sabilitytouseoxygen(e.g.mitochondrialinhibitorssuchascyanide).Allofthesesituationsleadtoalteredstatesofconsciousness,progressingfromfatigueandlightheadednesstoseizuresand/orcoma,withcardiacsignsandsymptoms,includingthepossibilityofcardiacarrest.

OpioidToxidromeOpioidagonismleadingtopinpointpupils(miosis),andcentralnervoussystemandrespiratorydepression.

Stress-Response/SympathomimeticStress-ortoxicant-inducedcatecholamineexcessorcentralnervoussystemexcitationleadingtoconfusion,panic,andincreasedpulse,respiration,andbloodpressure.


2.1.4 ToxidromeNamingThebreakoutgroupsdiscussedtheirreasoningbehindgroupingchemicalsintothetoxidromesandthenamingofthetoxidromes.Notethattheinitialtwelvebreakoutgrouptoxidromeslistedbelowhavebeenreducedtonine(Table2).Theroutesofexposurefor“Irritant/Corrosive”wereconsolidatedinto

asingletoxidrome,andthe“Knockdown/Asphyxiants”and“Cellularasphyxia(cyanide-like)”toxidromeswerecombined,inordertosimplifytrainingandrecall.

Acuteexposuretosolvents,anesthetics,orsedatives(SAS)Toxidrome

Thebasisforcreatingandnamingthistoxidromeistheexistenceofasimilarclinicalpresentationin

casualtiesexposedtoanyofthemembersofthesegroups(solvents,inhalationalanesthetics,andsedative-hypnoticcompounds)followingacuteexposure.Thedelayedeffectsofsolventexposuredo

notformpartofthistoxidrome.

AnticholinergicToxidrome

Exposuretoananticholinergicchemicalmayresultinunderstimulationofcholinergicreceptorsleadingtosymptomsandsignssuchasdilatedpupils(mydriasis),decreasedsweating,elevatedtemperature,rapidheartrate,andmentalstatuschanges,andcharacteristichallucinations.

AnticoagulantsToxidromeThistoxidromeisbasedontheclearlydefinedunderlyingtoxicmodeofactionofalterationofbloodcoagulation.

CholinergicToxidrome

Thistoxidromenamewaschosenbaseduponclinicalrelevanceandaccuracyaswellaseaseofrecall.Examplesofnamesinitiallyconsideredincluded:SLUDGE,DUMBBEL[L]S,BBB,MTWHF,CCC,

organophosphate-like,acetylcholinesterase,pinpointpupils,wetallover,twitching,andseizing*(*threeseizingtoxidromes).

ConvulsantToxidrome

Thistoxidromenamewaschosenbaseduponclinicalrelevanceandaccuracyaswellaseaseofrecall.Examplesofnamesinitiallyconsideredincluded:Generalconvulsanttoxidrome,Convulsants,convulsions,andseizuresnothingelse*(threeseizingtoxidromes).

Knockdown/AsphyxiantsToxidromeThereisaunifyingpathophysiologicalbasis(i.e.,disruptedcellularoxygendeliveryand/oruse)forall

agentsinthistoxidromefortheinitialpresentation;however,someagentshavespecifictreatmentsorantidotesthatareaccommodatedinthesecondtierofthistoxidrome.

Cellularasphyxia(cyanide-like)ToxidromeThistoxidromenamewaschosenbaseduponclinicalrelevanceandaccuracyaswellaseaseofrecall.Examplesofnamesinitiallyconsideredincludethefollowing:Cellularasphyxiatoxidrome,Cellularasphyxiants,Cyanide,Cyanide-like,cherry-red,notwetallover,severearrhythmiaearly,dilatedpupils,

andseizing*(threeseizingtoxidromes).


OpioidToxidromeThistoxidromenamewaschosenbaseduponclinicalrelevanceandaccuracyaswellaseaseofrecall.

Examplesofnamesinitiallyconsideredincludethefollowing:Opioids,Sedative,Solvent,andchanged

mentalstatusunresponsivewithorwithoutseizures.

Stress-response/sympathomimeticToxidrome

Thistoxidromenamewaschosenbaseduponclinicalrelevanceandaccuracyaswellaseaseofrecall.

Examplesofnamesinitiallyconsideredincludethefollowing:Anxiety,psychological/stressresponse,fight-flight-or-freezeresponse,andsympathomimetic.

Irritant/CorrosiveToxidromesSubstanceswithsignificantirritantandcorrosivepropertiesweredividedintothreetoxidromesbasedontherouteofexposureasitcorrespondstotheorgansystemand/ortissuedamaged.

Irritant/CorrosiveInhalationToxidrome

Fortheinhalationtoxidrome,thespectrumofinjurypresentationsuggeststhatacombinationofupperandlowerpulmonaryinjuriesintoonetoxidromeisappropriateforusebyfirstresponders.

Theinitialassessmentwillfocusongeneralrespiratorycomplaints,whichwillnotdifferentiatebetweenupperandlowerpulmonaryinjuryandtheinitialtreatmentswillbesimilarforbothupperandlowerpulmonary.

Irritant/CorrosiveIngestionToxidrome

Theeffectsofthistoxidromeareimmediate,withinitialtreatmentbeingsimilar(i.e.,

supportivecare).Additionalinformation(e.g.,epidemiologicalreview)willberequiredgiventhetargetednatureofaningestionpoisoning.

Irritant/CorrosiveTopicalToxidrome

Chemicalburns,vesicants,andotherskinirritants/corrosivesarelumpedtogetherunderthis

syndromeforthefollowingreasons:treatment(initialemergencymedicalresponse)issimilar,regardlessofthedegreeofskinoreyeeffects;differentiationbetweencorrosivesandchemical

burnscouldnotbedistinguishedsignificantlyfromadiagnosticandemergencymedicaltreatmentperspective;and,irritantsandcorrosivespresentinaprogressivespectrumofinjurytotheskinandeyes.

2.1.5 ParticipantBallotsWithineachbreakoutgroup,theparticipantswereaskedtocompleteballotsindicatingtheiragreement/disagreementwiththeirbreakoutgroup’stoxidromesandanyadditionalcomments.

Seventeenworkshopparticipantscompletedandreturnedballotstorecordtheir“votes”andcommentsonthebreakoutgrouprecommendations(Group1:n=4;Group2:n=7;Group3:n=6).

Areviewoftheballotsdeterminedthatallbreakoutgroupparticipantsagreedwiththeirgroup’s

recommendationsaspresentedtothelargerworkshop,withoneexception.OneparticipantinGroup3questionedtheinclusionoftheAnticholinergicToxidrome“becausethereisalowlikelihoodthatanyofthesechemicalswouldbeencounteredbyfirstresponders.”


2.2 DiscussionAnumberofgeneralandspecificissueswerediscussedbytheworkshopparticipantsduringtheplenarysessions.Thesearebrieflydescribedbelow.

Useofterm“Toxidrome”versus“ToxicSyndrome.”Thegroupnotedthatthesetermscanappropriatelybeusedinterchangeably.ManySMEsfavored“toxidrome”–primarilyforeaseofuseinthefieldand

training.Thereisvalueindocumentingtheconnectionbetweentheterm“toxidrome”anditslongerform“ToxicSyndrome.”Toxidrome,asusedforthecurrentapplication,alsoavoidsconfusionwithothertermsandvariantsinthemedicalliteraturesuchas“ToxicChemicalSyndrome”or“ToxicShock

Syndrome”whichwouldnotbeequivalenttoa“toxidrome.”

Toxidromenameandshortdefinition.TheSMEsagreedonguidingprinciplesfortoxidromenamingandtheneedforandkeycomponentsofaconcisename.Atoxidromenamemustbememorable(appliedin

thefield)andmeaningful(toguideatreatmentaction).Theconcisedefinitionshouldbeonetotwosentences,capturingaconstellationofthekeyobservableelementsoftheclinicalpresentationaswellaskeytreatmentsoractions.Formatissufficientlyflexibletoincludeotherinformationthatfacilitates

recognition.TheSMEsindicatedthattheuseofthetoxidromeconceptwouldnecessarilyentailsomemisclassificationofpatientsasthereisatrade-offbetweenusabilityinthefieldanddiagnosticaccuracy.Theallowanceformisdiagnosisshouldtypicallyerronthesideofover-treatment,basedonthenature

oftheconsequencesoftreatment.

ToxidromePackaging,OutreachandCommunication:TheSMEsdiscussedtheneedforpackagingofthetoxidromestofacilitatefielduse.Thegoalofidentifyingandactingonaconstellationof

undifferentiatedfindingswasnotedasaneedinpackagingthetoxidromes(andsymptomconstellations)inameaningfulwaytousers.Suggestionsfordoingthisincludedasimplifiedsignsandsymptomsassessmentapproach(e.g.,speech,sight,skin,seizures)andamatrixconceptthatallowsa

processforlinkingtoxidromesandmakingadjustmentintreatment.Othergroupingstrategieswerementioned.

Learning,Heuristics,CognitiveBiases,andLevelsofExpertise:Asystemthatrecognizesthedifferentusersofthetoxidromesandtheirvaryingmethodsforidentifyingtoxidromes,aswellasdifferinglevelsofexpertise,willbeneeded.Thelevelofunderstandingofthetoxidromesusedbyfirstresponders,fire

andemergencyservices,lawenforcement,emergencymedicaltechnicians,willbedifferentandwillincorporatecognitivebiasesthatmustbeunderstood.Thisinformationmightbeincludedaspartofthelearningpackagedevelopedforthetoxidromes.Firstreceiversattheemergencydepartment,primary

carephysicians,andmedicalschools/studentsneedadeeperunderstandingofthetoxidromesandabilitytoconsiderbroaderdifferentialdiagnoses.PoisonControlCentersneedamoredetailedlevelofguidanceplusdirectreachbacktoMedicalToxicologists.MedicalToxicologistsmustserveasthefinal

backstopfordefinitivediagnosis,aswellashavetheabilitytoprovidespecificfollow-uporcriticalinformationrequestsandrecommendationsforrefiningtreatmentandresponse.


CommunicationsandKnowledgeManagement:Thecompletepackageshoulddrawupontheknowledgemanagement/communicationsystemsavailable.Knowledgemanagementmustincludetwo-waycommunications,leveragecurrentsystems(e.g.,StateFusionCenters,PoisonControlCenters,NLM

toolssuchasCHEMM-IST,Federalreachbackcenters/SupportandOperationsCenters[SOCs])andintegratewithlocalemergencyoperationscenters.Participantssuggestedresourcessuchas“PowertotheEdge”byDavidAlbertsandconceptssuchasprinciplesof“NetcentricOperations”and“postand

smartpull”(whereallinformationispostedtothenetworkwhichallowsforpullingorpushingofrelevantinformationtopeoplewhoneedit).Inaddition,Dr.Canevadescribedaconcept,the“TrinityofKnowledge,”whichencompassesthreedimensionsofhowpeopleacquireanddevelopknowledge:

learning,knowledgemanagement,andsense-making.Understandingtheseconceptscanaidindevelopingthetoxidromesandfortrainingusers.

ResearchNeeds:Avarietyofideasforresearchneedswerehighlightedasstartingpointsforfutureefforts.Researchaimedatevaluatingtheeffectivenessoftoxidromesinthefieldasatoolforguiding

treatmentwasviewedasaresearchneed.NoneoftheSMEswereawareofsignificantresearchinthisarea.Suggestionsformovingforwardincludeddevelopingaclinicaltrial-likeapproachorevaluatingdatafrompastincidentswithdataanalytics.Researchthatprovidesinformationoftherelationship

betweenfieldapplicabilityanddiagnosticaccuracywasalsonotedasausefuloutcomeoffutureanalyses.Participantsnotedthatsomedata(andexperience)oneffectivenessoftrainingonfieldretentionoftoxidromeshasbeendone.

Thecurrenteffortfocusesonmasscasualty(exposure)incidentsfollowingprincipallyacuteexposurestochemicalagents(withfocusonCWA,TICs,andTIMs).Addingscenariosformass-scaleexposurestocommercialpharmaceuticalsviaingestionmayaddadditionalcomplicationsthatwillneedtobe

exploredasthismightbroadenthearrayofspecifictoxidromesneeded(e.g.,theideaofcardiotoxicants).

Severaladditionaltopicswereraisedbutnotdiscussedin-depth.Thesetopicsincludeduseof

“informationmining”strategiesortoolsandhowtoadapttofutureandchangingneedstoensuretheproductofthisworkshopisanevergreenresource(i.e.,updatedandimprovedtoreflectnewinformationandknowledge).

Aftertheworkshop,severalattendeesprovidedadditionalmaterialsandsuggestionsforconsideration.AnarticlebyPaulWaxandcolleagues(Wax,BeckerandCurry,2003)reviewswhatisknownabout

incapacitatingagentssuchasfentanylderivatives,theiraerosolization,andtherationalefortheiruse

asincapacitatingagents.ApaperbyBurklow,Yu,andMadsen(2003)reviewsindustrialchemicalsand

theiruseaschemicalweaponsorforterroristattacks,focusingonchlorineandphosgene.Thepaperdiscusseslarge-airways(TypeI)damage,damagetosmallairwaysandalveolarsepta(TypeIIdamage),

andboth.Italsoaddressesriskstochildrenfromthesetypesofchemicals.Athirdsuggestedpaperwas

onthetopicofacuteorganophosphatepoisoningandmedicalmanagement(Eddlestonetal.,2008).


2.3 ConclusionsAcommonlanguagetodescribeandrecognizetoxicchemicalexposuresisessentialforemergencyrespondersandfirstreceiverstobepreparedtoproviderapidandappropriateresponsestoindustrialchemicalmassexposures,aswellaspotentialterroristattacks.Thecurrenteffortandthisworkshop

focusedonmassexposureincidentsfollowingacuteexposurestochemicalagents(withafocusonCWA,TICs,andTIMs).Thescopeoftheworkshopwasprimarilyfocusedonthesceneandhospitalresponseintheearlyphasesofalarge-scalechemicalrelease,withexposureslikelytobeinhalationandpossibly

dermal.Thisworkshopfocusedondevelopingadecision-makingtoolthatwillbeusedintheearlypartofaresponsewheninformationislimited.Delayedeffectswerelessemphasizedandtheclinicalcourseinitsentirety–hourstodayswasnotthefocus.

TheToxicChemicalSyndromeDefinitionsandNomenclatureWorkshopwasheldonMay8-9,2012attheDepartmentofHomelandSecurityofficesinWashington,DC.Morethanfortyparticipants

discussedtheessentialelementsoftoxicchemicalsyndromesortoxidromesthatwouldbeusefultotrainfirstreceiversandrespondersincasesofterroristattackorindustrialaccidents.Theworkshopattendeeswereadiversegroupandincludedfirstresponders,firstreceivers,medicaldirectorsof

poisoncontrolcenters,andsubjectmatterexperts(SMEs)inemergencymedicine,emergencyresponse,medicaltoxicology,andtrainers.Theycamefromcivilianandmilitaryagencies,universities,hospitals,andemergencyresponseentities.Thediversityoftheparticipantsprovidedtheneeded

breadthofexpertiseandbackgroundstodevelopaconsensuslexiconthatwillbeofmostvaluetotheintendedusers.

Workshopparticipantsagreedthattheterms“toxidrome”and“toxicsyndrome”canbeused

interchangeably,andthat“toxidrome”hasanumberofadvantagesthatmakeiteasiertouseinthefield.Theyagreeduponguidingprinciplesforthenamingoftoxidromesandforatoxidromedescription(i.e.,aconcisedefinitionofonetotwosentencesthatcapturesaconstellationofthekeyobservable

elementsoftheclinicalpresentationaswellaskeytreatmentsoractions).Theexpertsrecognizedthattheuseofthetoxidromeconceptwouldnecessarilyentailsomemisclassificationofpatientsasthereisatrade-offbetweenusabilityinthefieldanddiagnosticaccuracy.Theallowanceformisdiagnosisshould

typicallyerronthesideofover-treatment,basedonthenatureoftheconsequencesoftreatment.

Theexpertworkshopinitiallyrecommendedtwelvetoxidromestoestablishacommonlanguageforchemicaldefenseplanners,policymakers,firstresponders,firstreceivers,andhazardousmaterials

(hazmat)stakeholders.Thesetwelvetoxidromesweresubsequentlyconsolidatedtotheninelisted

inTable2inordertoprovideacommonlexicontoassistkeystakeholdercommunitiestoquickly

andaccuratelyidentifythebroadchemicalagentcategory(ifnotthespecificchemicalagent)towhichapatientwasexposedandtotherebyrapidlydetermineappropriateemergencytreatment.

Theninetoxidromeswerebuiltaroundclinicalpresentations,ratherthanchemicalgroupingor

treatmentoptions.Theexpertsfocusedondescribingtoxidromeswithsignsandsymptomsthatfirst

respondersandfirstreceiverswouldbeabletoobserveinthepatients.Thefocuswasonacute

exposures.Theworkshopexpertssoughttodevelopnamesforthetoxidromesthatwerebasedonclinicalrelevanceandaccuracy,aswellaseaseofrecall.


Workshopparticipantsbrieflydiscussedhowtheinformationontoxidromescouldbepackagedfor

trainingandcommunicationtotheintendedusersandfielduseandofferedseveralsuggestionsincludinggroupingstrategiesoralgorithmsforeaseofremembrance.Inaddition,theydiscussedthatdifferenttypesofuserswillhavedifferingrequirementsforlevelsandtypesofinformationthatwill

needtobeaccommodated.Thecompletetoxidromepackageshouldincorporateavailableknowledgemanagementandcommunicationsystemsandincludeprovisionsforfeedbackandrevision.

Theworkshopexpertsidentifiedavarietyofideasforresearchneedsandfuturework.Theseincludeddevelopingaclinicaltrial-likeapproachorevaluatingdatafrompastincidentswithdataanalyticsand

exploringadditionalscenarios(andrelevanttoxidromes)formass-scaleexposurestocommercial

pharmaceuticalsviaingestion.

Thisreportisintendedtoprovideanaccuraterecordofworkshoppreparations,discussions,and

conclusionstoserveasaresourceforparticipantsandothersinthenextphasesofLexicondevelopment.

2.4 ReferencesandSourcesAlberts,D.S.andR.E.Hayes.2003.PowertotheEdge:Command...Control...intheInformationAge.DepartmentofDefense,CommandandControlResearchProgram(CCRP)PublicationSeries,Washington,DC.

Burklow,T.,C.Yu,andJ.Madsen.2003.Industrialchemicals:Terroristweaponsofopportunity.

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[email protected].

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CHEMM-IST.CHEMMIntelligentSyndromesTool.http://chemm.nlm.nih.gov/chemmist.htm

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DepartmentofHomelandSecurity(DHS).ChemicalSecurityAnalysisCenter(CSAC).2011.ChemicalSegregationbyToxidromeforChemicalTerrorismRiskAssessment.PowerPoint

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pesticidepoisoning.Lancet,371:597–607.

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Report of the Toxic Chemical Syndrome Definitions and Nomenclature Workshop, May 2012


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