WhyWhy Ketamine?Ketamine?
JenniferJennifer Davis,Davis, M.D.M.D. HospiceHospice andand PalliativePalliative CareCare CenterCenter MayMay 13,13, 20112011 ObjectivesObjectives
BeBe familiarfamiliar withwith thethe pharmacology,pharmacology, dosing,dosing, andand administrationadministration ofof KetamineKetamine
UnderstandUnderstand thethe indications,indications, contraindications,contraindications, benefits,benefits, andand sideside effectseffects ofof KetamineKetamine
KnowKnow thethe variousvarious usesuses ofof KetamineKetamine andand itsits abuseabuse potentialpotential HistoryHistory
DevelopedDeveloped inin earlyearly 1960s1960s andand FDAFDA approvedapproved inin 19701970
FirstFirst usedused inin soldierssoldiers inin VietnamVietnam WarWar forfor warfarewarfare surgicalsurgical proceduresprocedures
ClassifiedClassified asas scheduleschedule IIIIII drugdrug AugustAugust 19991999
OutlawedOutlawed inin UnitedUnited KingdomKingdom JanuaryJanuary 20062006 HistoryHistory
AccordingAccording toto DEA,DEA, 80%80% seizedseized isis fromfrom MexicoMexico
MostMost commonlycommonly usedused inin clubsclubs atat ravesraves
20022002 statistic,statistic, almostalmost 3%3% ofof 1212th gradegrade studentsstudents admittedadmitted toto usingusing ketamineketamine inin thethe lastlast yearyear Rave?Rave? HistoryHistory
TheThe ScientistScientist byby JohnJohn LillyLilly
JourneysJourneys intointo thethe BrightBright WorldWorld byby MarciaMarcia MooreMoore andand HowardHoward AlltounianAlltounian
TheThe EssentialEssential PsychedelicPsychedelic GuideGuide byby D.M.D.M. TurnerTurner PharmacologyPharmacology
DissociativeDissociative anestheticanesthetic andand analgesicanalgesic thatthat bindsbinds thethe phencyclidinephencyclidine (PCP)(PCP) sitesite
NoncompetitivelyNoncompetitively blocksblocks thethe excitatoryexcitatory NMDANMDA-- glutamateglutamate receptor,receptor, aa calciumcalcium channelchannel inin thethe transmissiontransmission ofof painpain signalssignals viavia dorsaldorsal hornhorn
NMDANMDA receptorreceptor playsplays aa rolerole inin opioidopioid tolerancetolerance
PharmacologyPharmacology
AlsoAlso interactsinteracts withwith otherother calciumcalcium andand sodiumsodium channels,channels, dopaminedopamine receptors,receptors, cholinergiccholinergic transmission,transmission, noradrenergicnoradrenergic andand serotoninergicserotoninergic reuptake,reuptake, mu/delta/kappamu/delta/kappa opioidopioid receptors,receptors, monoaminergicmonoaminergic andand muscarinicmuscarinic receptors,receptors, andand possiblypossibly GABAGABA receptorsreceptors
== DIRTYDIRTY DRUGDRUG PharmacologyPharmacology
CentralCentral sensitization:sensitization: persistentpersistent noxiousnoxious stimulistimuli leadlead toto progressivelyprogressively higherhigher painpain intensityintensity viavia NMDANMDA receptorreceptor hyperexcitationhyperexcitation
WindWind upup phenomenon:phenomenon: repeatedrepeated transmissiontransmission ofof nociceptivenociceptive stimulistimuli resultingresulting inin summationsummation ofof thethe stimulistimuli withwith coco--releaserelease ofof excitatoryexcitatory aminoamino acidacid andand slowslow lastinglasting potentialspotentials leadingleading toto hyperhyper--responsiveresponsive spinalspinal neuronsneurons andand decreaseddecreased opioidopioid responsivenessresponsiveness
PharmacologyPharmacology
Hyperalgesia:Hyperalgesia: anan exaggerateexaggerate painpain responseresponse toto mildlymildly noxiousnoxious stimulistimuli
SecondarySecondary hyperalgesia:hyperalgesia: perceptionperception ofof painpain outsideoutside thethe areaarea initiallyinitially injuredinjured
Allodynia:Allodynia: painpain elicitedelicited byby nonnon--noxiousnoxious stimulistimuli
PharmacologyPharmacology
MostlyMostly aa racemicracemic mixturemixture ofof twotwo stereoisomers:stereoisomers: R(R(--)) andand S(+)S(+)
SS enantiomerenantiomer isis 44 timestimes moremore potentpotent thanthan RR enantiomerenantiomer andand twicetwice asas potentpotent asas mixturemixture
S(+)S(+) producesproduces longerlonger hypnosis,hypnosis, greatergreater BPBP andand HR,HR, lessless locomotorlocomotor activity,activity, shortershorter recoveryrecovery timetime
PharmacologyPharmacology
Metabolism:Metabolism: 80%80% firstfirst passpass hepatichepatic metabolismmetabolism
Metabolite:Metabolite: norketaminenorketamine isis 1/31/3 asas potentpotent asas parenteralparenteral formform asas anestheticanesthetic butbut equipotentequipotent asas anan analgesicanalgesic
Bioavailability:Bioavailability: rangesranges fromfrom 93%93% IMIM toto 16%16% POPO
Excretion:Excretion: inin thethe urineurine primarilyprimarily PharmacologyPharmacology
OnsetOnset ofof action:action: IV=30sec,IV=30sec, IM=3IM=3--5min,5min, SC=15SC=15--30min,30min, PO=30minPO=30min
DurationDuration ofof action:action: IV=5IV=5--10min,10min, IM=12minIM=12min--2hr,2hr, PO=4PO=4--6hr6hr
HalfHalf life:life: 33 hourshours
SteadySteady state:state: 1212--1515 minmin PharmacologyPharmacology
NoNo adjustmentadjustment neededneeded forfor renalrenal impairment,impairment, andand insufficientinsufficient datadata forfor liverliver impairmentimpairment
BindingBinding isis lessless inin elderly,elderly, soso dosedose reductionreduction wouldwould bebe reasonablereasonable
AvoidAvoid inin pregnancypregnancy andand breastfeeding,breastfeeding, nono datadata PharmacologyPharmacology
AdverseAdverse drugdrug reactions:reactions: clonidine,clonidine, anticholinergics,anticholinergics, benzodiazepines,benzodiazepines, barbiturates,barbiturates, risperidone,risperidone, opioids,opioids, anesthetics,anesthetics, alcoholalcohol
GenericGeneric ketamineketamine 50mg/ml50mg/ml inin 10ml10ml vialvial ($17.70)($17.70) vs.vs. KetalarKetalar ($33)($33)
100ml100ml ofof 50mg/5ml50mg/5ml solutionsolution forfor IV:IV: 2x10ml2x10ml ketamineketamine vialsvials (50mg/ml)(50mg/ml) ++ 80ml80ml purifiedpurified waterwater IndicationsIndications
InductionInduction andand maintenancemaintenance anesthesiaanesthesia PainPain unresponsiveunresponsive toto standardstandard treatmenttreatment FailureFailure ofof opioidopioid rotationrotation SevereSevere neuropathicneuropathic painpain OpioidOpioid tolerancetolerance basedbased onon rapidrapid escalationescalation BronchospasmBronchospasm inin asthmaasthma andand COPDCOPD DepressionDepression inin bipolarbipolar disorderdisorder MinorMinor proceduresprocedures MigraineMigraine headachesheadaches ContraindicationsContraindications
IncreasedIncreased bloodblood pressurepressure IncreasedIncreased intracranialintracranial pressurepressure AcuteAcute intermittentintermittent porphyriaporphyria (induces(induces ALAALA syn)syn) CurrentCurrent oror historyhistory ofof psychiatricpsychiatric disorder,disorder, seizures,seizures, glaucoma,glaucoma, heartheart failure,failure, ischemicischemic heartheart disease,disease, CVA,CVA, severesevere hepatichepatic impairment,impairment, severesevere neurologicneurologic impairmentimpairment WHOWHO LadderLadder
IsIs therethere aa placeplace forfor Ketamine?Ketamine? ProsPros
CanCan bebe givengiven PO,PO, IV,IV, IM,IM, SL,SL, SC,SC, PR,PR, intranasal,intranasal, transdermal,transdermal, topical,topical, andand epidural,epidural, intrathecalintrathecal
CanCan bebe appliedapplied directlydirectly toto thethe skinskin asas anan aerosolaerosol sprayspray toto woundswounds
CanCan bebe usedused asas anan oraloral rinserinse forfor mucositismucositis ProsPros
OpioidOpioid sparingsparing effecteffect leadsleads toto reducedreduced opioidopioid requirementrequirement andand opioidopioid associatedassociated sideside effectseffects
MayMay preventprevent opioidopioid tolerancetolerance andand reducereduce centralcentral sensitizationsensitization andand hyperalgesiahyperalgesia
MayMay havehave antianti--inflammatoryinflammatory effectseffects ProsPros
ExcellentExcellent analgesiaanalgesia withwith limitedlimited respiratoryrespiratory depressiondepression
PatientPatient cancan remainremain awakeawake andand breathebreathe unassistedunassisted butbut notnot awareaware
UsedUsed inin ICUICU forfor prolongedprolonged statusstatus epilepticusepilepticus ProsPros
RecentRecent useuse inin treatmenttreatment ofof alcoholism,alcoholism, heroinheroin addiction,addiction, andand depressiondepression
RapidRapid onsetonset andand minimalminimal sideside effectseffects atat subanestheticsubanesthetic dosesdoses
SmallSmall dosedose ketamineketamine hashas beenbeen shownshown usefuluseful andand safesafe asas additiveadditive toto standardstandard opioidopioid therapytherapy inin 54%54% ofof studiesstudies (A&A(A&A 2004)2004) ConsCons
ThereThere areare notnot sufficientsufficient DBRCTDBRCT studiesstudies showingshowing efficacyefficacy asas anan analgesic,analgesic, butbut numerousnumerous casecase reportsreports andand smallsmall trialstrials
ConcernConcern forfor withdrawwithdraw andand associatedassociated hyperalgesiahyperalgesia andand allodyniaallodynia uponupon suddensudden cessationcessation
SignificantSignificant numbernumber ofof clinicalclinical trialstrials 45%45% demonstratdemonstrateded nono benefitbenefit toto addingadding ketamineketamine toto opioidsopioids explainedexplained bbyy thethe naturenature ofof thethe procedure,procedure, degreedegree ofof postpost--opop pain,pain, andand methodmethod ofof administrationadministration ConsCons
ShouldShould requirerequire informedinformed consentconsent
RequiresRequires closeclose monitoringmonitoring
IrritationIrritation toto SCSC sitesite
CrossesCrosses thethe bloodblood brainbrain barrierbarrier
BitterBitter tastetaste
ConcernConcern forfor sideside effectseffects ConsCons
StudiesStudies havehave shownshown nono benefitbenefit whenwhen addedadded toto opioidopioid PCAPCA afterafter majormajor abdominalabdominal surgerysurgery
IneffectiveIneffective inin intrathecalintrathecal route,route, peripheralperipheral regionaregionall use,use, locallocal anesthesia,anesthesia, intraintra--articular,articular, nervenerve block,block, andand wouldwould infiltrationinfiltration
PreemptivePreemptive andand postoperativepostoperative benefitsbenefits havehave beenbeen difficultdifficult toto determinedetermine withwith conflictingconflicting resultsresults andand manymany differentdifferent kindskinds ofof surgeriessurgeries HOLIDAYSHOLIDAYS PainPain
PostPost spinalspinal cordcord injuryinjury chronicchronic painpain
SickleSickle cellcell vasovaso--occlusiveocclusive painpain
ChronicChronic postpost surgicalsurgical painpain
MajorMajor surgerysurgery withwith highhigh opioidopioid requirementrequirement PainPain
PrePre andand postpost incisionalincisional
ChronicChronic regionalregional painpain syndromesyndrome II
FractureFracture reductionsreductions
CalciphylaxisCalciphylaxis PainPain
IncidentIncident painpain fromfrom movementmovement
OpioidOpioid refractoryrefractory painpain
NeuropathicNeuropathic pain:pain: postpost--herpeticherpetic neuralgia,neuralgia, trigeminaltrigeminal neuralgia,neuralgia, spinalspinal cordcord injury,injury, phantomphantom limblimb pain,pain, lilimbmb ischemia,ischemia, fibromyalgia,fibromyalgia, multiplemultiple sclerosis,sclerosis, GuillainGuillain-- BarreBarre syndromesyndrome
ChronicChronic abdominalabdominal painpain suchsuch asas pancreatitispancreatitis andand angianginana PainPain
ChronicChronic neck,neck, back,back, andand legleg painpain
MigraineMigraine headachesheadaches
CancerCancer relatedrelated painpain inin childrenchildren andand adultsadults
PainfulPainful dressingdressing changeschanges suchsuch asas burnsburns HowHow muchmuch dodo wewe give?give?
LetLet’’ss looklook atat thethe evidenceevidence ...... TrialsTrials andand CaseCase SeriesSeries
FineFine JPSMJPSM 19991999 (2(2 casecase reports):reports): KetamineKetamine bolusbolus 0.10.1--0.2mg/kg0.2mg/kg IVIV oror 0.5mg/kg0.5mg/kg SCSC oror IMIM AfterAfter 1515 minutesminutes ifif nono reliefrelief doubledouble dosedose ContinueContinue toto reassessreassess andand increaseincrease dosedose untiluntil painpain reliefrelief oror undesirableundesirable sideside effectseffects occuroccur ConvertConvert toto constantconstant IVIV infusioninfusion DecreaseDecrease opioidopioid byby 50%50% everyevery 66--1212 hourshours asas toleratedtolerated RebolusRebolus andand increaseincrease infusioninfusion asas neededneeded TrialsTrials andand CaseCase SeriesSeries
MercadanteMercadante JPSMJPSM 20002000 (DBRCT):(DBRCT): OnOn 33 separateseparate days,days, 22 daysdays apart,apart, 1010 patientspatients givengiven slowslow bolusbolus ofof eithereither 0.25mg/kg0.25mg/kg vs.vs. 0.50mg/kg0.50mg/kg vs.vs. normalnormal salinesaline Ketamine,Ketamine, butbut notnot saline,saline, significantlysignificantly reducedreduced painpain inin almostalmost allall patientspatients atat bothboth dosesdoses
BergerBerger AJHPCAJHPC 20002000 (small(small trial):trial): IVIV KK--FF--MM 2mg/ml2mg/ml -- 5ug/ml5ug/ml -- 0.1mg/ml0.1mg/ml atat raterate rangerange ofof 22--12ml/hr12ml/hr AllAll 99 patientspatients showedshowed improvementimprovement TrialsTrials andand CaseCase SeriesSeries
ReevesReeves A&AA&A 20012001 (DBRCT):(DBRCT): 7171 patientspatients eithereither receivedreceived morphinemorphine 1mg/ml1mg/ml oror morphinemorphine 1mg/ml1mg/ml ++ ketamineketamine 1mg/ml1mg/ml viavia PCAPCA PostPost--op,op, therethere waswas nono differencedifference exceptexcept worseworse cognitivecognitive testingtesting inin thethe MKMK groupgroup
JacksonJackson JPSMJPSM 20012001 (unblinded(unblinded trial):trial): 3939 patientspatients receivedreceived 33--55 dayday ketamineketamine infusioninfusion atat 100mg/24h100mg/24h forfor 33 daysdays oror increasedincreased toto 300mg/24h300mg/24h forfor 33 daysdays oror increasedincreased toto 500mg/24h500mg/24h forfor 33 daysdays OverallOverall responseresponse raterate ofof 67%67% TrialsTrials andand CaseCase SeriesSeries
KannanKannan JPSMJPSM 20022002 (small(small trial)trial) :: 0.5mg/kg0.5mg/kg threethree timestimes dailydaily POPO asas adjuvantadjuvant 7/97/9 patientspatients showedshowed improvementimprovement
MitchellMitchell PainPain 20022002 (DBRCT):(DBRCT): 3535 patientspatients receivedreceived eithereither OpioidsOpioids ++ ketamineketamine infusinfusionion (0.6mg/kg)(0.6mg/kg) vs.vs. opioidsopioids ++ placeboplacebo overover 44 hourshours OKOK groupgroup (16/28)(16/28) showedshowed statisticallystatistically significantsignificant differencedifference inin painpain improvementimprovement TrialsTrials andand CaseCase SeriesSeries
Fitzgibbon JPM 2005 (retrospective audit): Ketamine was effective in 11/16 patients with range of use from 1-120 days Starting dose of 40-90mg/24h increased by 50-100mg/24h every 24 hours with stable dose of 50-768mg/24h
Lossignol SCC 2005 (small trial): 12 patients received a test dose of 5mg and if tolertoleratedated were given starting dose of 1.5mg/kg/24h Final doses ranged from 195-1000mg/24h with duration of treatment ranging from 7-350 days Pain control remained acceptable in 11/12 patients TrialsTrials andand CaseCase SeriesSeries
PolizzottoPolizzotto JPSMJPSM 20062006 (case(case series):series): CalciphylaxisCalciphylaxis patientspatients receivedreceived dosesdoses rangingranging fromfrom bolusesboluses ofof SCSC ketamineketamine 50mg50mg forfor dressingdressing changeschanges andand continuouscontinuous infusionsinfusions ofof 300300--500mg/24hr500mg/24hr
FinkelFinkel JPJP 20072007 (small(small trial):trial): 8/118/11 childrenchildren onon adjuvantadjuvant ketamineketamine infusioninfusion hadhad opioidopioid sparingsparing effects,effects, improvementimprovement ofof pain,pain, andand mormoree familyfamily interactioninteraction DosesDoses rangedranged fromfrom 0.10.1--1mg/kg/hr1mg/kg/hr andand durationduration rangedranged fromfrom 11--7575 daysdays TrialsTrials andand CaseCase SeriesSeries
MercadanteMercadante CJPCJP 20092009 (2(2 casecase reports):reports): OpioidOpioid switchingswitching fromfrom morphinemorphine toto methadonemethadone andand burstburst ketamineketamine inin incidentincident painpain 22 dayday infusioninfusion ofof ketamineketamine 100mg/d100mg/d thenthen stopped,stopped, continuedcontinued onon methadone,methadone, andand D/CD/C
SchwartzmanSchwartzman PainPain 20092009 (DBRCT):(DBRCT): 1919 CRPSCRPS patientspatients infusedinfused withwith salinesaline withwith oror withoutwithout ketamineketamine (50mg/h)(50mg/h) 44 hours/dayhours/day forfor 55 daysdays on,on, 22 daysdays off,off, 55 daysdays onon KetamineKetamine groupgroup hadhad statisticallystatistically significantsignificant reductireductionon inin manymany painpain parametersparameters TrialsTrials andand CaseCase SeriesSeries
Zempsky CJP 2010 (retrospective case review): 5 children received ketamine infusion for Sickle CelCelll pain (4 with opioids and 1 in place of) 2 patients has significant pain control and 1 patienpatientt had significant opioid reduction Dose ranged from 0.06-0.2 mg/kg/h and duration ranged from 19-90 hours
Amr Pain Physician 2010 (DBRCT): 40 patients randomized to ketamine + gabapentin and placebo + gabapentin Ketamine dose 80mg IV over 5hours daily for 7 days KG group showed significant improvement over PG grougroupp during infusion and 2 weeks after TrialsTrials andand CaseCase SeriesSeries
IrwinIrwin JPMJPM 20102010 (case(case series):series): 22 casescases ofof anxietyanxiety andand depressiondepression treatedtreated withwith ketamineketamine 0.5mg/kg0.5mg/kg POPO singlesingle dosedose PORTRAITSPORTRAITS DosingDosing
InitialInitial testtest dosedose givengiven toto assessassess tolerabilitytolerability andand efficacyefficacy SomeSome givegive prophylacticprophylactic concurrentconcurrent benzodiazepinebenzodiazepine oror antipsychoticantipsychotic OftenOften mixedmixed withwith otherother drugsdrugs suchsuch asas opioidsopioids OpioidOpioid dosedose shouldshould bebe reducedreduced byby 2525--50%50% withwith parenteralparenteral ketamineketamine Conversion:Conversion: afterafter fewfew daysdays CSCI=PO,CSCI=PO, afterafter weeksweeks toto monthsmonths 2525--50%CSCI=PO50%CSCI=PO DosingDosing
PO:PO: 1010--25mg25mg TIDTID--QIDQID andand prnprn,, increaseincrease byby 1010-- 25mg25mg incrementsincrements upup toto 200mg200mg QIDQID OrOr weightweight basedbased 0.250.25--0.5mg/kg0.5mg/kg TIDTID GiveGive smallersmaller moremore frequentfrequent dosesdoses ifif sideside effectseffects occuroccur DirectDirect fromfrom vialvial oror diluteddiluted mixedmixed inin tastytasty liquidliquid DosingDosing
SL:SL: 1010--25mg,25mg, dodo notnot swallowswallow forfor 22 minutesminutes UseUse higherhigher concentrationsconcentrations toto minimizeminimize volumevolume SC:SC: 1010--25mg25mg prnprn IncreaseIncrease inin incrementsincrements ofof 2525--33%33% IV:IV: 0.50.5--1mg/kg1mg/kg GiveGive overover 11--22 minutesminutes precededpreceded byby benzodiazepinebenzodiazepine DosingDosing
CSCI:CSCI: DiluteDilute inin largelarge volumevolume toto avoidavoid sitesite irritationirritation 11--2.5mg/kg/24h2.5mg/kg/24h IncreaseIncrease byby 5050--100mg/24h,100mg/24h, maxmax dosedose 3.6g/24h3.6g/24h SomeSome useuse loadingloading dosedose 0.5mg/kg0.5mg/kg overover 3030 min,min, followedfollowed byby continuouscontinuous 2mg/h2mg/h SomeSome justjust startstart withwith 100mg/24h,100mg/24h, ““burstburst”” IncreaseIncrease toto 300mg/24h,300mg/24h, thenthen 500mg/24h500mg/24h andand stopstop 33 daysdays afterafter lastlast incrementincrement DosingDosing
CIVI:CIVI: 5050--200microgram/kg/h200microgram/kg/h andand titratetitrate SingleSingle burstburst 600micrograms/kg600micrograms/kg upup toto 6mg/4h6mg/4h IncreaseIncrease nextnext dosedose byby 30%30% ifif nono responseresponse RepeatRepeat dailydaily forfor upup toto 55 daysdays VariousVarious titrationtitration techniquestechniques reportedreported SomeSome startstart withwith 0.1mg/kg0.1mg/kg andand doubledouble Q15minQ15min OthersOthers startstart atat 10mg/h10mg/h andand titratetitrate upup fromfrom therethere
SideSide EffectsEffects euphoria,euphoria, dysphasia,dysphasia, bluntedblunted affect,affect, psychomotorpsychomotor retardation,retardation, vividvivid dreams,dreams, nightmares,nightmares, impairedimpaired attention,attention, memorymemory problems,problems, impairedimpaired judgment,judgment, illusions,illusions, hallucinations,hallucinations, alteredaltered bodybody image,image, delirium,delirium, dizziness,dizziness, diplopia,diplopia, blurredblurred vision,vision, nystagmus,nystagmus, alteredaltered hearing,hearing, hypertension,hypertension, tachycardia,tachycardia, hypersalivation,hypersalivation, nausea,nausea, vomiting,vomiting, erythema,erythema, painpain atat injectioninjection site,site, fatigue,fatigue, increasedincreased musclemuscle tone,tone, increasedincreased pulmonarypulmonary arteryartery pressurepressure SideSide EffectsEffects slurredslurred speech,speech, confusion,confusion, disorientation,disorientation, hypotension,hypotension, bradycardia,bradycardia, respiratoryrespiratory depression,depression, apnea,apnea, malignantmalignant hyperthermia,hyperthermia, agitation,agitation, coma,coma, seizure,seizure, laryngospasm,laryngospasm, bronchorrhea,bronchorrhea, arrhythmia,arrhythmia, increasedincreased intracranialintracranial pressure,pressure, morbilliformmorbilliform rash,rash, anorexia,anorexia, anaphylaxis,anaphylaxis, outout--ofof--bodybody experience,experience, sedation,sedation, euphoria,euphoria, sensesense ofof calmcalm andand serenity,serenity, increasedincreased energy,energy, openopen andand closedclosed eyeeye visuals,visuals, meaningfulmeaningful spiritualspiritual experiences,experiences, ataxiaataxia SideSide EffectsEffects
ForFor analgesicanalgesic doses,doses, impairedimpaired attention,attention, memory,memory, andand judgmentjudgment
OccurOccur lessless withwith subanestheticsubanesthetic dosedose givengiven POPO oror CSCICSCI andand seemseem toto bebe dosedose relatedrelated
CanCan bebe controlledcontrolled withwith concurrentconcurrent benzodiazepinebenzodiazepine oror haloperidolhaloperidol SideSide EffectsEffects
CanCan bebe reducedreduced byby slowingslowing dosedose titrationtitration andand providingproviding medicationsmedications forfor sideside effectseffects
OccurOccur moremore oftenoften inin thethe elderly,elderly, inin women,women, andand patientspatients withwith anxietyanxiety disordersdisorders
ChronicChronic useuse leadsleads toto cognitivecognitive impairmentimpairment UrinaryUrinary SideSide EffectsEffects UrinaryUrinary ToxicityToxicity
Frequency,Frequency, urgency,urgency, dysuria,dysuria, hematuriahematuria
SuprapubicSuprapubic pain,pain, ““KK--painspains”” andand ““KetamineKetamine CrampsCramps”” usuallyusually withwith greatergreater thanthan 1gm/day1gm/day
InterstitialInterstitial cystitis,cystitis, detrusordetrusor overactivity,overactivity, decreadecreasedsed bladderbladder capacitycapacity
VesicoVesico--uretericureteric reflux,reflux, hydronephrosis,hydronephrosis, papillarypapillary necrosis,necrosis, renalrenal impairment,impairment, renalrenal failurefailure UrinaryUrinary ToxicityToxicity
UrinalysisUrinalysis negativenegative forfor bacteriabacteria oror sterilesterile pyuriapyuria
2020--30%30% ofof frequentfrequent usersusers ofof highhigh quantitiesquantities reportreport bladderbladder symptomssymptoms
AppearsAppears toto bebe aa temporaltemporal linklink wherewhere severityseverity ofof damagedamage isis determineddetermined byby chronicitychronicity ofof abuseabuse UrinaryUrinary ToxicityToxicity
Cystoscopy:Cystoscopy: epithelialepithelial inflammation,inflammation, ulceration,ulceration, petechialpetechial hemorrhage,hemorrhage, neovascularization,neovascularization, contactcontact bleedingbleeding
Histology:Histology: denudeddenuded bladderbladder epithelium,epithelium, eosinophiliceosinophilic infiltrationinfiltration
Urography:Urography: shrunkenshrunken bladder,bladder, decreaseddecreased bladderbladder compliance,compliance, detrusordetrusor overactivity,overactivity, papillarypapillary necrosinecrosis,s, hydronephrosishydronephrosis UrinaryUrinary ToxicityToxicity
WithdrawalWithdrawal ofof ketamineketamine resultsresults inin somesome degreedegree ofof resolutionresolution ofof symptomssymptoms dependingdepending onon severityseverity
OtherOther treatments:treatments: NSAIDs,NSAIDs, steroids,steroids, anticholinergics,anticholinergics, cystodistension,cystodistension, intravesicalintravesical instillationinstillation ofof hyaluranichyaluranic acid,acid, oraloral pentosanpentosan polysulfphate,polysulfphate, andand tyrosinetyrosine
NicknamesNicknames K Super K Vitamin K Special K Mean green Rockmesc Ket Kitties K2 Jet Super acid Green Cat valium KitKat CombinationsCombinations
Strawberry:Strawberry: ketamineketamine ++ ephedrineephedrine ++ selegilineselegiline
SittingSitting Duck:Duck: ketamineketamine ++ ecstasyecstasy
CK1:CK1: ketamineketamine ++ cocainecocaine KetamineKetamine AbuseAbuse AbuseAbuse
SimilarSimilar toto PCPPCP butbut withwith lessless violent,violent, confusedconfused behaviorbehavior whenwhen comingcoming offoff SevereSevere impairmentimpairment ofof working,working, episodic,episodic, andand semanticsemantic memorymemory IncreasedIncreased schizotypalschizotypal andand dissociativedissociative symptomssymptoms ““KK holehole””:: atat thethe brinkbrink ofof beingbeing fullyfully sedated,sedated, outout--ofof--bodybody oror nearnear--deathdeath experienceexperience DesiredDesired depersonalizationdepersonalization andand derealizationderealization AbuseAbuse
MortalityMortality isis lowlow ConsequencesConsequences areare relatedrelated toto dangerousdangerous behaviorsbehaviors andand accidentsaccidents UsedUsed asas aa datedate raperape drugdrug LongLong termterm adverseadverse effects:effects: flashbacks,flashbacks, attentionalattentional dysfunction,dysfunction, memorymemory impairment,impairment, tolerance,tolerance, highhigh dependencydependency potentialpotential AbuseAbuse
RapidRapid onsetonset andand durationduration meansmeans quickquick recoveryrecovery OnlyOnly 4%4% ofof dosedose recoveredrecovered inin urineurine NotNot includedincluded inin standardstandard urineurine toxicologytoxicology screensscreens BloodBlood levels:levels: therapeutictherapeutic use:use: 0.50.5--5mg/L,5mg/L, arrestarrest forfor impairment:impairment: 11--2mg/L,2mg/L, fatalfatal overdose:overdose: 33-- 20mg/L20mg/L AbuseAbuse
PowderPowder cancan bebe insufflated,insufflated, injectedinjected oror oraloral InjectionInjection bypassesbypasses liverliver metabolismmetabolism providingproviding moremore efficient,efficient, smoothersmoother highhigh upup toto 22 hourshours OralOral routeroute requiresrequires moremore drugdrug butbut longerlonger triptrip withoutwithout dissociativedissociative statestate OnsetOnset forfor injection:injection: 11--5min,5min, snorted:snorted: 55--15min,15min, oral:oral: 55--30min30min WhatWhat havehave wewe learned?learned?
AA littlelittle HistoryHistory andand AA LOTLOT ofof PharmacologyPharmacology
AboutAbout UseUse andand AbuseAbuse ofof thisthis mysticmystic drugdrug
RecentRecent SupportiveSupportive EvidenceEvidence inin PalliationPalliation
DosingDosing andand AdministrationAdministration andand SideSide EffectsEffects
WhoWho isis readyready toto givegive somesome KetamineKetamine ?????? TALENTSTALENTS ReferencesReferences
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