Post on 30-Jul-2018
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
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