PrehospitalPharmacologyReview

February7

This document is a pharmacological review of medications carried by PRPS Advanced Care Paramedics.  It includes applications as per the ALS PCS Medical Directives and other applications for medications as per the ACP scope of practice not included in a Medical Directive.  Paramedics are required to PATCH to a BHP to receive a verbal order to treat patients with medications when a ‘PROVICNCIAL PATCH POINT’ exists, or when there is no Medical Directive for a specific injury / illness where the paramedic feels the patient may benefit from pharmacological treatment. 

Trauma2013

DrugName:Midazolam/Versed

Classification:Benzodiazepine,shortacting

DrugProfile:

MidazolamisaCNSdepressantwhichiswater‐soluble,availableasanintranasalspray,intravenous,intramuscularinjectionandbuccaladministration.

Midazolamisawhitetolightyellowcrystallinecompound,insolubleinwater.Itisapotentsedativeagentthatrequiresslowadministrationandindividualizationofdosage.Clinicalexperiencehasshownmidazolamtobe3to4timesaspotentpermgasdiazepam.Becauseseriousandlife‐threateningcardiorespiratoryadverseeventshavebeenreported,provisionsformonitoring/detectionandpreventingthesereactionsmustbemadeforeachpatienttowhommidazolamhasbeenadministered,regardlessofageorhealthstatus.

Actions/Pharmacokinetics:

MidazolamisafastactingdrugthateasilypenetratesthebloodbrainbarrierandaffectsdirectlyonGABA(gammaamino‐butyricacid)receptorsintheRASandthusinducessedationandmusclerelaxation.

IVadministrationofmidazolamwillaffectthepatientalmostimmediately(+/‐30sec)andwilllastforapproximately10to15minutes.Duetomidazolamproducinganamnesticsideeffect,it’swidelyusedintheemergencysettingforshortandpainfulproceduressuchascardioversionandexternalpacing.Althoughmidazolamisusedforpainfulprocedures,ithasalmostnoanalgesiceffectandpaincontrolistobetakenunderconsiderationforsuchtreatments.

Midazolam’shalf‐lifeisbetween2‐6hoursdependingontheadministrationroute,metabolicstatusandliverfunction.Midazolamismetabolizedintheliverandclearedbythekidneys.

TherapeuticUses(Common):

Midazolamisusedasatreatmentof

Seizuredisorders

Musclespasms (Asahypnoticandshortactingsedative)(Cardioversion) Alcoholwithdrawal(DT’s) Pre–postintubationsedation

Overdose/AdverseEffects:Seriousandsometimelife‐threateningconditionscanbeseenwithpatientsreceivingmidazolam.Suchadverseeffectsare:

1. Oversedation2. Headache3. Blurredvision4. Paradoxicalcombativeness(morecommoninpediatrics)5. Hypotension6. Bradycardia7. Nauseaandvomiting8. Respiratorydepression/apnea9. Tendernessatinjectionsite

GeneralPrecautions/Contraindications:

Midazolamadministrationshouldbeavoidedinthefollowingsituations:

1. Hypersensitivityorallergytothedrug2. PatientsufferingfromAcutenarrowangledglaucoma3. Shock4. Coma5. Alcoholintoxication6. Depressedvitalsigns7. AnyTCA/MAOI/sedativeoverdose

PrehospitalApplicationsaspertheALSPCSMedicalDirectives:

IntheprehospitalsettingmidazolamisutilizedinthefollowingMedicalDirectives.

ProceduralSedationMedicalDirective CombativePatientMedicalDirective(afterrulingoutreversiblecauses)

nodifferenceinIVandIMdose SeizureMedicalDirective

a. 0.1mg/kgIVb. 0.2mg/kgIN,IMandBuccalroutes

PleasenotethatthemostcommonmidazolamvarianceidentifiedthroughtheBHauditsystemisanunder‐doseofMidazolamforseizureswhenadministeringviatheIM/INorbuccalroutes.ParamedicsconsistentlyadministertheIVdose.RemembertodoublethedoseifutilizingIN,IMorbuccalroute.

PrehospitalusesrequiringaBHPpatchorder:

Duetoitspotentialeffectonthepatient’shemodynamicstatus,midazolamshouldnotbegiventopatientssufferinghypotensionorshockofanykind.

Inaddition,someMedicalDirectiveshavebuiltin“mandatorypatch”pointswhichrequireparamedicstoconsultaBHPtoobtainaverbalorderinordertoadministermidazolam.

Combativepatient,whentheparamedicisunabletoassessthepatientforreversiblecauses(hypoxia,hypotensionandhypoglycemia).

Paramedicsmayencounterothermedicalemergencieswheremidazolamwouldbebeneficialtouseinthemanagementofaclinicalsituation.Insituationswhereaparamedicfeelsthatmidazolamadministrationisindicatedtotreatapatientandnomedicaldirectiveexists,paramedicisrequiredtoconsultaBHPandobtainanordertoutilizemidazolam.AnexampleofasituationinwhichmidazolammaybebeneficialinthemanagementofapatientwherethereisnoMedicalDirectivefor,wouldbeapatientwhoisin

trismusandrequiresventilation/airwaycontrolandnasalintubationisunsuccessfulorcontraindicated.

DrugName:Diazepam

Classification:Benzodiazepine,Anxiolytic

DrugProfile:

DiazepamactsonGABAreceptorsthatarelocatedintheCNS.GABAisaninhibitoryneurotransmitterthatactsonpresynapticterminalnervefibrils.Thiscausesanincreaseintheinfluxofnegativechlorideions.Thisincreaseinnegativeionsactstocanceloutmuchoftheexcitatoryeffectofthepositivelychargedsodiumionsthatenterasaresultofthearrivingactionpotential.Theactionpotentialisthereforereduced,whichinturnreducesthedegreeofexcitationonthepostsynapticneuronaswell.Theoveralleffectsarereducedneuronalexcitability.Thisoveralleffectisbeneficialforthetreatmentofseizures,musclespasms,andanxietyrelateddisorders.

TherapeuticUses:(Common)Diazepamisusedasatreatmentof

Anxietyrelateddisorders(oral) Seizuredisorders Musclespasms (Asahypnoticandsedative)(Cardioversion) Alcoholwithdrawal(DT’s)

Overdose/AdverseEffects:

Purebenzodiazepineoverdoses(oral)arenotusuallyfatal.Themoreseriouscasesoftoxicityareseenwhenbenzodiazepinesaremixedwithotherdrugsoralcohol.Thenewershortactingbenzodiazepinederivatives(Triazolam,Alprazolam,andTemazepam)havebeenrelatedinfataloverdoses.

Rapidlargedoses(IV)cancauseseriouscardiorespiratoryeffectssuchashypotension,bradycardiaandcardiovascularcollapse.Patientsthathavetakenalcoholareatgreaterriskofadversereactions.Themusclerelaxanteffectsofdiazepamcancausethepatienttohaveprolongedperiodsofapnea.CNSsideeffectsincludedrowsiness,dizziness,slurredspeech,ataxia,andconfusion.DiazepamcancausephlebitisandaburningsensationintheveinwhengivenIV.

NotesonAdministration/SpecialPreHospitalConcerns:

Theelderlyareparticularlysensitivetosomeoftheabovementionedadversesideeffectsthatareassociatedwithdiazepam.Intheseizingpatientdiazepamadministrationshouldbestoppeduponabatementoftheseizure.WhenusingDiazepamforsedationsmallincrementaldosescanbetitratedtoeffect.

Respiratorydepressionduetothemusclerelaxanteffectsofdiazepamcannotbeoverstressedandconstantmonitoringofthepatient’sairwayandbreathingstatusiscrucial.

Diazepamisincompatiblewithmostdrugsandthereforeshouldneverbemixedordilutedwithotherdrugsorsolutions.ItshouldbeadministeredascloseaspossibletotheIVcathetersiteasdiazepamcanprecipitateorbindwiththeIVtubing.

Ifhighdosesofdiazepamaregiveninordertoarrestseizeractivity,paramedicsmustbepreparedtoprovidedairwayandventilatorysupportifneeded.

Whenadministeringpediatricdoses,diazepamshouldbedrawnupina1ccsyringeinordertoaccuratelyadministerthedrug.

RectalroutecanbeusedwhenanIVcannotbeestablished;thisismoreeffectiveinthepediatricpopulation.

Prehospitalapplicationsaccordingtothemedicaldirectives:

Inthepast,diazepamhasbeenwidelyusedforshorttermsedationinquickorongoingpainfulprocedures.

InthemostrecentreleaseoftheALSPCSMedicalDirectives,midazolamwasintroducedastheprimarybenzodiazepineandreplaceddiazepaminallrelevantMedicalDirectives.Assuch,thelatestMOHEquipmentStandardsdoesnotlistdiazepamasarequiredmedicationforEMSservicestocarryandinmostEMSservices,diazepamisnolongeravailable.

AlthoughthereisnospecificMedicalDirectiveforDiazepam,thisdrugstillmaybeusedforthesameconditionsasmidazolambutrequiresapatchtoBHPforanordertoadminister.

Somecommonconditionsthatdiazepammaybeconsideredforinclude:

AnyMedicalDirectivethatutilizesmidazolamandwhereapatientcannotreceivemidazolambutwherenocontraindicationsexistfordiazepam.Also,intheeventmidazolamisunavailableforanyreason.

PatchRequired

Combativepatient,whentheparamedicisunabletoassessthepatientforreversiblecauses(hypoxia,hypotensionandhypoglycemia).

ProceduralSedationMedicalDirective CombativePatientMedicalDirective(afterrulingoutreversiblecauses)

nodifferenceinIVandIMdose SeizureMedicalDirective

Typicaldosingfordiazepam:>5y/o=5mgIVor(10mgrectally)1‐5y/o=1.0mgIV/IOperyearofageor(2mgperyearofagerectally)<1y/o=0.5mgIV/IOor(1mgrectally)

OthersituationsaparamedicmayconsiderconsultingaBHPfordiazepamadministrationmayinclude:

TreatmentofsevereDT’s SympathomimeticODsuchasCocaine

Specialconsiderations/Patchingrequirements:

Whenpatchingfordiazepam,theparamedicshouldcarefullygatherallrelevantinformationwithregardtopatient’sconditionandthespecificreasonwhyhewouldliketoadministerdiazepamandnotmidazolam.

Duetoitspotentialeffectonthepatient’shemodynamicstatus,diazepamshouldnotbegiventopatientssufferinghypotensionorshockofanykind.

DrugName:MorphineSulfate

Classification:Opioid,Narcoticanalgesic

DrugProfile:

Derivedfromthepoppyseedsoftheopiumplantandhasbeenusedforover2000yearsasapainmedicationandcardiovascularalteringdrug.Itsjuicewasknowntocontainanagentthatrelievedpain(=analgesic)andcausesleepordrowsiness(somniferum=sleep).TheGreekwordnarcosisdesignatesthesleepstatehencethewordnarcotic.MostoftheopiateanalgesicsandsyntheticsubstitutesfallundertheNarcoticControlActinCanada,whichiswhymedicsandnursesalikemustaccountforthesedrugsatthebeginningandendofeachshift.Additionally,onlyACP’sareallowedtocontrolandcarrynarcoticsunderthisAct.

Morphineandrelateddrugs(MeperidineandFentanylCitrate)exactanumberofeffects,bothcentrallyandperipherally.Somearedirectlyrelatedtotheanalgesiceffectwhileothereffectsarenot.Eachdrugseemstohaveaspecificaffinityordegreeofbindingtoeachofthedifferentreceptorsscatteredthroughoutthebody.

Opioidsexerttheiractiononbyinteractingwithopioidreceptorsatthespinalcordlevel(painmodulation)whichleadstoadecreaseinimpulsetransmission.Dependingontheaffinityofthedrugforthereceptorandthe

locationofthereceptor,thedrugsvaryfromoneanotherintheireffectandoverallefficacy(effectiveness).

Actions/Pharmacokinetics:

Neuronal:

Theresultofthebindingofopioidstotheirrespectivereceptorsoncellmembranesisthree‐fold.

1. Hyperpolarizationofnervecells2. Inhibitionofnervefiring3. Presynapticinhibitionofneurotransmitterrelease.

Analgesia:Opioidnarcoticsrelievepainbyraisingthepainthresholdwithinthespinalcordlevelandbyalteringthebrainsperceptionofthepain.Morphineiseffectiveagainstalltypesofpain,visceral,somaticandcutaneous.

Orderofpotency:Meperidine<Morphine<Fentanyl

RespiratoryDepression:Morphinereducesthesensitivityoftheneuronsintherespiratorycentertocarbondioxide.Thiscanoccurwithnormaldosesofmorphinesoitisimperativetomonitorthesepatientscloselyandbepreparedtointervenewithairwaymaneuvers.ThisdiminishingofsensitivitytoCO2isimportanttorememberwhendealingwithcertainpatienttypessuchasCOPDer’swhoareverysensitivetocarbondioxidelevels.Themostfrequentunwantedsideeffectfrommorphineadministrationisrespiratorydepression.

AnothersideeffectofmorphineisthatitcausescerebralCO2torise,inadvertentlycausingcerebralvasodilatationandasubsequentriseinICP.Thereforebecautiousofmorphineuseintheacuteclosedheadinjuredpatient,especiallywithoutproperAWcontrol/ventilatorysupport/monitoring.

Morphine'srespiratorydepressanteffectismuchmoreseverewhenotherdrugsareonboardsuchasbarbiturates,alcoholandotherCNSdepressants(synergisticaffect)

Euphoria/Sedation;

Partoftheanalgesiceffectisafoggy,dreamy,pleasant“unreal"feelingwhichisthereasonthatmorphineandothernarcoticsareactivelysoughtafterstreetdrugs.Theseeffectsareusuallyatlowdosesofmorphineorfentanyl.Notallopiatesproduceeuphoriainallsubjects.

MorphineproducesasedativeeffectontheCNSinmanypatientsbutthedegreeofsedationvariesbasedonmanyotherphysiologicalfactors.

Cardiovascular/HistamineRelease;Morphinecausesasmallamountofhistaminereleasefrommastcellsinthebodywhichmaycauseurticaria(hives),sweatingandmostimportantlyfromacardiovascularpointofview,vasodilatation.Thisisduetoperipheralarteriolarandvenousdilatation.Thisleadstosystemicvascularresistancedecreasesatthispoint,anddecreasedpreloadandthemyocardialoxygendemandisalsodiminished.Forthisreasonandtheanalgesicpropertiesofmorphine,itisthemostfrequentlyusednarcoticforthetreatmentofischemicchestpain.

Morphineshouldbeusedwithextremecautioninthevolumedepletedpatientduetoitspotentialforproducinghypotension.Forthisreason,fentanylisthemedicationofchoiceintraumapatientsduetothefactthatitdoesnotcauseaclinicallysignificanthistaminereleaselikemorphinecan(aswellitisshorteracting).

Duetothepotentialforbronchoconstriction,itshouldbeusedwithcautioninasthmatics.

OtherCNSEffect:Occasionallysomepatientswhoreceivemorphineorotheropioidnarcoticsexperienceunexpectedextremeexcitationorrestlessnessafterveryloworhighdosesofthedrug.

OtherOpioidEffects:Miosis‐isseeninmosthumansaftermorphineadministrationandisprobablyduetotheremovalofcorticalinhibitiononthethirdcranialnerve.

NauseaandVomiting:Afrequentsideeffectofmorphineadministration,andthereasonthatmanypractitionersgiveananti‐emeticwiththeopioid.Thissideeffectismorefrequentwhenadministeringmorphinerapidly(IV)andinhigherdoses.

CoughSuppression:Unrelatedtorespiratorydepressionbutadirectinhibitionofthecoughcenter.Codeineisoftenprescribedforapersistentcoughinpatientswhocannottakeothercoughsuppressants.

TemperatureRegulation:Opioidsinhibitthethermoregulatorycenterandtheabilitytomaintainabodytemperatureisinhibited.Thisisseenmostprominentlyinlongtermopioidusepatientssuchasthosewithcancerrelatedpaincontrol.

TherapeuticUses:(Common)

Morphineiswidelyusedformanythingsinthepre‐hospitalandinter‐hospitalsetting.DuringtheWorldWarsitwasthemostfrequentlyadministereddrug.Itisgivenfor:

Ischemicchestpain Preloadreductionforotherpurposes Acutepainmanagementintraumaandlongtermtreatmentof

chronicpain(cancerpatients) Sedationinconjunctionwithbenzodiazepines(Versed)

(Antidote)

Naloxone(Narcan)‐narcoticantagonist

Overdose/AdverseEffects:

Sedation Constipation Nauseaandvomiting UrinaryRetention Hypotension Potentialforaddiction(longtermtherapy) Flushing,Sweating Respiratorydepression

PrehospitalApplicationsaspertheALSPCSMedicalDirectives:

PleaserefertotheALSPCSMedicalDirectivesforaccuratedoses

CardiacIschemiaMedicalDirectivea. Considermorphineafterthe3rddoseofNTGifthepatientisstill

experiencingpainorifNTGiscontraindicated

PainMedicalDirective:a. FentanylisthepreferredmedicationtobeusedforthePain

MedicalDirectiveoftheALSPCSinEMSserviceswhocarryitinadditiontomorphine.

b. ParamedicscannotswitchfromfentanyltomorphineorviceversawhiletreatingapatientforpainwithoutconsultingaBHP.

Usually,thereisnopatchingrequiredpriortoadministrationofmorphineforthetreatmentofpainassociatedwithcardiacischemiaorpain.ParamedicsarerequiredtopatchanytimetheyfeelthepatientmaybenefitfrompaincontrolbutdoesnotmeettheMedicalDirective.

DrugName:Naloxone(Narcan)

Classification:Narcoticantagonist

DrugProfile:ActsbybindingtovariousopioidreceptorsintheCNSandperipheralNSandthusquicklyreversingtheeffectsofopioidnarcoticsuchasmorphine,heroinorfentanyl.Naloxonehasaveryhigh(uptox10)affinitytoopioidreceptorsanditreversestheOpioideffectbycompetitively"bumping"outanopioidforthesamereceptor.Thisbindingofnaloxonedoesnotactivatethereceptorandtherefore,reversestheopioidnarcoticeffects.

Naloxoneworksveryquickly,approximately30secondsafterintravenousinjectiontherespiratorydepressionandcomacharacteristicsofaheroinoverdosebegintoreverse.Itshalf‐lifeisabout60‐100minuteswhichmaybeshorterorlongerthanthehalf‐lifeofthedrugsitantagonizes.Therefore,closeobservationandmonitoringofthepatientiswarrantedandsubsequentdosesmayberequired.

Therouteofadministrationwillalsoimpactthedurationofeffect.IMandSCadministrationhasasloweronsetbutlongereffectthantheIVroute.ThisiswhythenewALSPCSMedicalDirectiveslisttheorderofpreferenceasSCthenIMthenINthenIVasroutesforadministration.

Naloxonealsoworksonthenaturallyoccurringpainmediatorsofthebody,theenkephalinsandwillreversethemaswell.Carefuladministrationofnaloxoneisrequiredtoachievethedesiredeffectwithoutcausingcompletereversalofanalgesia.

Examplesofsomedrugsreversedbynaloxone

morphine,fentanyl,Percodan,heroin,codeine,Talwin,Darvon,hydromorphone(Dilaudid)Methadone

TherapeuticUses:(Common)

DiagnosticorTherapeuticUse

SometimesusedasadiagnosticaidinpatientpresentingwithsignsandsymptomsofanarcoticOD,butnohistoryof.

Reversalofunwantedrespiratorydepression/sedationinaknownnarcoticoverdosewhenpatientcannotprotectairway/ventilation.

Inadvertentnarcoticoverdose.

(AsAntidote)

Isanantidotefornarcoticoverdose.

Overdose/AdverseEffects:

Abruptreversalofnarcoticdepressionmayresultin–nausea/vomiting,sweating,tachycardia,increasedbloodpressure,tremulousness,seizuresandcardiacarrest(rare).

Inpatientsreceivingongoingnarcoticpaincontrol,largedosesofnaloxonecancausesignificantreversalofanalgesia

PrehospitalApplicationsaspertheALSPCSMedicalDirectives:

Ingeneral,naloxoneshouldbeusedonlytoimprovepatient’srespirations.Naloxoneshouldnotbeusedtocompletelyreverseallopioideffects.

OpioidToxicityMedicalDirective:

AlteredLOAandrespiratorydepressionandsuspectedopioidoverdose

Paramedicsarerequiredbythe“MandatoryProvincialPatchPoint”tocontactaBHPforauthorizationtoproceedwiththemedicaldirective.

Thingstoremember:

1. TheMedicalDirectiveiswritteninorderofpreferencefortherouteofadministration.SC,IM,INthenIV.

2. IftheIVrouteistobeused,ensurethesiteissecuredproperlytoavoidinadvertentremoval.

3. Naloxoneshouldbeadministeredslowlyandwithcaution.Especiallyinpatientswhoarebeingtreatedforseverepain(cancer)orwhoareaddictedtonarcotics.Watchforsignsofpainandorwithdrawalsuchastachycardia,hypertensionanddysrhythmias.

4. Naloxoneshouldbetitratedtoeffectinsmallincrements.

5. Alwaysexercisecautionwithheroinorotherillicitnarcoticdrugoverdoses.Applyrestraintspriortoadministeringnaloxone.Propertitrationtoreverserespiratorydepressionshouldavoidanyinadvertentcompletereversalcausingaggressivebehaviour.

Specialconsiderations/Patchingrequirements

Naloxoneiscontraindicatedinpatientswithuncontrolledhypoglycemiaandsensitivitytothedrug.

AmandatorypatchpointisrequiredpriortoadministrationofNaloxonetoallpatients.

DrugName:Fentanyl

Classification:SyntheticNarcoticDrugProfile:

Fentanyl,alsoknownasSublimaze,Durogesic,Fentora,Onsolis,Instanyl,Abstral,Lazandaandothers,isapotentsyntheticnarcoticanalgesicwitharapidonsetandshortdurationofaction.Itisastrongagonisttotheμ‐opioidreceptors.

Historically,ithasbeenusedtotreatacuteandseverepainandiscommonlyusedinproceduresasapainrelieveraswellasananestheticincombinationwithbenzodiazepines.

Fentanylisapproximately100timesmorepotentthanmorphine,with100mcgoffentanylapproximatelyequivalentto10mgofmorphine.

Inthemid‐1990s,fentanylwasfirstintroducedforwidespreadpalliativeusewiththeclinicalintroductionoftheDuragesicpatch.Inthefollowingdecade,introductionofthefirstquick‐actingprescriptionformulationsoffentanylforpersonalusewasintroduced,theActiqlollipopandFentorabuccaltablets.Throughthedeliverymethodoftransdermalpatches,asof2012fentanylwasthemostwidelyusedsyntheticopioidinclinicalpractice.Withseveralnewdeliverymethodscurrentlyindevelopment,includingasublingualsprayforcancerpatients,paramedicswillcontinuetoseemorepatientsutilizingfentanylathome.

Fentanylandderivativesarenowwidelyusedasrecreationaldrugs;assuch,theyhavecausedfatalities.ParamedicsaremoreandmorerespondingtopatientswhohaveoverdosedonFentanylfornon‐medicinalusage.

Actions/Pharmacokinetics:

Theprecisemechanismofactionoffentanylisnotknown,althoughitrelatestothestimulationofopiatereceptorsinpresynapticandpostsynapticstereospecificCNSandothertissues.Opioidsmimictheactionofendorphinsbybindingtoopioidµreceptorsresultingininhibitionofadenylatecyclaseactivity.Thisismanifestedbyhyperpolarizationoftheneuronresultinginsuppressionofspontaneousdischargeandevokedresponsesrelatedtomodulation.

Fentanylmayalsointerferewiththetransportofcalciumionsandactinthepresynapticmembraneinterferingwiththereleaseofneurotransmitters.

ThefirsteffectsoffentanylaremanifestedintheCNSandorganscontainingsmoothmuscle.Fentanylproducesanalgesia,euphoria,sedation,decreasestheabilitytoconcentrate,feelingofheatinthebody,heavinessofthelimbs,anddrymouth.

Fentanylproducesdose‐dependentventilatorydepressionprimarilybyadirecteffectontherespiratorycenterintheCNS.Thisischaracterizedbya

decreaseinthecarbondioxideresponsemanifestinganincreaseinPaCO2andidledisplacementoftheresponsecurveofCO2totheright.Fentanylmayalsocauseskeletalmusclerigidity,particularlyinthethoracicandabdominalmuscles,inlargeparenteraldosesandadministeredquickly.Fentanylcancausebiliarytractspasmandincreasethecommonbileductpressure;thismaybeassociatedwithepigastricdistressorbiliarycolic.

FentanylcansometimescausenauseaandvomitingbydirectstimulationoftheCTZ(chemoreceptortriggerzone)inthefloorofthefourthventricle,andincreasedgastrointestinalsecretions.However,itappearstohavelessemeticactivitythanmorphine.

Fentanyl,unlikemorphine,doesnotcauseclinicallysignificanthistaminereleaseevenathighdoses.Therefore,thesecondaryhypotensionbyvasodilationisunlikely.Fentanyladministeredtoinfantscanproduceamarkeddepressionofheartrate.Thebradycardiaismorepronouncedwithfentanylcomparedwiththatofmorphineandcanleadtolowerbloodpressureandcardiacoutput.

Comparedwithmorphine,fentanylisapproximately100timesmorepotent,morerapidonsetofaction(lessthan30sec),andashorterdurationofaction.Fentanylhasahigherlipidsolubilitycomparedwiththatofmorphineandresultsinaneasierpassagethroughthebloodbrainbarriercausingahigherpowerandafasteronsetofaction.Rapidredistributionbytissueproducesashorterdurationofaction.

Fentanylismetabolizedbydealkylation,hydroxylation,andamidehydrolysistoinactivemetabolitesthatareexcretedinthebileandurine.Theeliminationhalf‐lifeoffentanylisapproximately3.5hours,reflectingthelargevolumeofdistribution.

Therapeuticuses:

Fentanyliswidelyusedintheprehospitalandinter‐hospitalsetting.Itisoneofthemostfrequentlyadministereddrugs.

Commonusesforfentanylare:

Ischemicchestpain Severemusculoskeletalpainintraumaandlongtermtreatmentof

chronicpain Sedationinconjunctionwithbenzodiazepines

Antidote:Naloxone(Narcan)‐narcoticantagonistOverdose/AdverseEffects:

Deepsedation Respiratorydepression‐apnea Musclerigidity

PrehospitalApplicationsaspertheALSPCSMedicalDirectives:

TheMedicalDirectivesorderofpreferencefornarcoticsforpainisfentanyl.ThisisduetofentanylhavinglessofanimpactonBPandshorteractingtimethanmorphine.

Underallcircumstances,theparamedicshouldpaycarefulattentiontothepatient’srespiratoryconditionafteradministrationoffentanyl.Intheeventofrespiratorycompromisesecondarytonarcoticadministration,paramedicsshouldpatchfornaloxoneandprovidedappropriateAWmanagementandrespiratorysupport.

DrugName:SodiumBi‐carbonate(NaHCO3)

Classification:Alkalinizingagent,electrolytesolution,buffersolution

DrugProfile:

Formanyyearssodiumbi‐carb(NaHCO3)wasusedroutinelyincardiacarrestsaspartofthedrugregiment.Studiesdevelopedlessthan10yearsagoshowedthatroutineuseofNaHCO3mightbeactuallydetrimentaltopatientoutcomeasthesepatientswouldhavealkalosisdevelopasaresultofthe

NaHCO3administrationwhichwasmoredifficultforthemyocardiumtodealwiththantheacidosisthatresultsfrominadequateventricularoutput.

RemembertheformulathebodyusestobalancepH:

H2O+CO2H2Co3HCO3+H+

*Theenzymeusedtocatalyzethisreactioniscarbonicanhydrase

Thisformulaandtheseelectrolytesinsolutionarewhatthebodyusestodealwithexcessacidsorexcessbasethatareproducedthroughmetabolism,takeninthroughingestionetc.orbyproductsoftoxins.

Thebodydealswithacidsprimarily/initiallythroughthebuffersystem,thenthroughtherespiratorysystem,therenalsystemandproteins.Whenapatientcreatesacids,thebodymustbeabletoexcretethemorturnthemintootherproductsbecausethebodiespHisverysensitivetoanarrowrange7.35‐7.45.Metabolicacidosisresultsfromeitheranaccumulationofafixedacidorlossofextracellularbuffer.

Therearemanycausesoflacticacidosissuchasanoxia,respiratoryfailure,anemia,increasedmetabolicdemand,alcohol,diabetesandmore.Incardiacarrestitisusuallyduetoacutecardiorespiratoryfailure.CO2isproducedbyaerobicmetabolisminischemictissueduringthefirstfewminutesaftercardiacarresthasoccurred(remember–thecellsarestillalive).Assuch,CO2isnotclearedlocallyfromtissuesandventilationisobviouslyimpaired.

NaHCO3actsbyreversingtheaboveequationand"tying"upexcesshydrogenionstodecreasearterialbloodH+levels.

UndernormalconditionstheCO2producedbythetissuesistransportedtothelungsbyNaHCO3(aspartoftheoverallbuffermechanism)andisclearedviabreathingoutH2OandCO2.However,incardiacarrestsituations,thisdoesnotoccurandCO2buildsuplocallyandcausesaparadoxicaltissueandhypercarbicacidosis(notreflectedinbloodgasanalysis).Intheheartthiscanresultindecreasemyocardialfunction.TheproductionofCO2bytheadministrationofNaHCO3decreasesthestimulationoftheperipheralchemoreceptors(respondtoH+)butdoesnotaffectcentralchemoreceptors.

Therefore,withoutcirculationandventilation,anincreaseinmetabolicacidosiswilloccur.

SomestudieshaveshownthataccumulatedCO2willgetclearedviathelungsoncecardiacoutputisrestored.NolongerisroutineadministrationofNaHCO3recommendedforpatientsincardiacarrest,unlessthearrestisprolongedoroccurredduetoseveremetabolicacidosisandthepatientisintubated.

TherapeuticUses:

Knownmetabolicacidosis TCAoverdose Crushinjuries:

a. Alkalinizingtheurine(excretionofmyoglobinprecipitatedinthekidneyssecondarytoRhabdomyolysis)

b. Hyperkalemia–intheabsenceofABG’s,thedegreeofhyperkalemiacanbeestimatedbyECGchanges(crudeestimate)

PeakedTwaves WideningofQRSwithdecreaseorlossofPwaveamplitude Lifethreateningventriculararrhythmias;furtherwideningof

theQRSwhicheventuallyformsasinewave Hyperkalemia(alongwithVentoliniforderedbytheBHPtodrive

potassiumintothecell) Phenobarbitaloverdose(alkalizingdiuresistoenhanceurinary

eliminationofthedrug).Alkalizingdiuresis,ifperformedshouldbeaccompaniedbyIVfluidbolus.

Supportrespiration’saspatientwillproducemoreCO2andblowitoff.Makesuretogiveitslowly.

Overdose/AdverseEffects:

IfNaHCO3istoorapidlyinjected,thenthebicarbonate‐bloodmixture"fizzles"asitpassesthelungsandchangestheintra‐alveolarpCO2andarterialpCO2,whichreachesthecerebralbloodflowandcausestransientcerebralvasodilatation.Patientsmaycomplainofdizzinessorevensyncope.

NotesonAdministration/SpecialPreHospitalConcerns Administerslowly LargeveinorIO(pediatric) Hypernatremiacanoccurwithadministration

Don'tmixwithotherdrugs(especiallyDopamine!),getprecipitation

Dosing:

Adults:1mEg/kgIVof8.4%slowIVbolus

Pediatric:IV/IO1mEq/kgof8.4%slowIVbolus

Infant<30days:(4.2%)1mEg/kgslowIVbolus

Referencesandacknowledgments

1. Farquhar,Steve:CMEpharmacology,1999.Updated–2013

2. TintinalliJ,Gabork,StapczynskiJ:EmergencyMedicine,6thedition.McGraw‐Hill2004

3. SamsonR,HazinskiM,SchexanyderS:2010EmergencyCardiovascularcareforHealthcareProviders.AmericanHeartAssociationGuidelinesCPRECC2012

4. HarveyR,ChampeP:Pharmacology2ndEdition:Lippincott’sIllustratedReviews