1. For Internal use onlyFor Internal use only 11
KETAMINE
Presented by :
Dr. Poonam Mude
Guide:
Dr. Abhay Bodhey
Govt. Medical College
Department of Anesthesiology

2. For Internal use only 2
Anesthetic agents

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Anesthetic agents
 Local anesthetics
 Current inhaled general anesthetic agents
 Current intravenous anesthetic agents (non-opioid)
 Current intravenous opioid analgesic agents
 Current muscle relaxants
 Current intravenous reversal agents

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Current Intravenous Anesthetic
agents (non-opioid)
Barbiturates
Thiopental
Methohexital
Benzodiazepines
Midazolam
Lorazepam
Diazepam
Propofol
Etomidate
Ketamine

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Ketamine - Identification Data
Identifiers
CAS number: 6740-88-1
ATC code: N01AX03 N01AX14
PubChem: 3821
DrugBank: APRD00493
Chemical data
Formula: C13H16ClNO
Mol. Mass: 237.725 g/mol
Pharmacokinetic data
Half life: 2.5-3 hours.
Excretion: renal (>90%)
Arylcyclohexylamine

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Ketamine – Common Names
 K
 Ketanest
 Ketaset
 Ketalar
 Special K
 Vitamin K

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Ketamine – Introduction
 Phencyclidine derivative
 Synthesized by Stevens in 1962
 First used in humans by Domino and Corsen in 1965
 2 Stereoisomers:S-(+) and R-(-)
 S-(+)-isomer more potent with fewer side effects as it
is preservative free
 A drug with abuse potential so cautiously used

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Physical And Chemical PropertiesPhysical And Chemical Properties
 Preservative- Benzethonium chloridePreservative- Benzethonium chloride
 pH acidic (3.5-5.5)pH acidic (3.5-5.5)
 Highly lipid soluble than thiopentone and is alsoHighly lipid soluble than thiopentone and is also
water solublewater soluble
 Stored at room temp.(15 to 30 degree C)Stored at room temp.(15 to 30 degree C)
 Protected from light and heatProtected from light and heat
 Not to be mixed with barbiturate in sameNot to be mixed with barbiturate in same
syringe as precipitate may formsyringe as precipitate may form

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PharmacokineticsPharmacokinetics
 Rapid onset of action within 30 to 60 sec.Rapid onset of action within 30 to 60 sec.
 Relatively short duration of action; earlyRelatively short duration of action; early
regain of consciousness after 15 to 20regain of consciousness after 15 to 20
min.is because of redistributionmin.is because of redistribution
 Elimination half time-2-3 hrElimination half time-2-3 hr
 Volume of distribution 2.5-3.5 lit/kgVolume of distribution 2.5-3.5 lit/kg
 Clearance is 16-18ml/kg/minClearance is 16-18ml/kg/min

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PharmacokineticsPharmacokinetics
 Not significantly bound to plasma proteins.Not significantly bound to plasma proteins.
 Due to extreme lipid solubility initiallyDue to extreme lipid solubility initially
distributed to brain.distributed to brain.
 Total body clearance is approximatelyTotal body clearance is approximately
equal to liver blood flow,thus halothaneequal to liver blood flow,thus halothane
which decreases hepatic blood flowwhich decreases hepatic blood flow
decreases clearance.decreases clearance.

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MetabolismMetabolism
 Hepatic microsomalHepatic microsomal
enzymes cytochrome P450enzymes cytochrome P450
by N-demethylation toby N-demethylation to
form norketamine which isform norketamine which is
hydroxylated andhydroxylated and
conjugated to waterconjugated to water
soluble glucuronidesoluble glucuronide
derivatives and excreted inderivatives and excreted in
urine.urine.
 Norketamine is activeNorketamine is active
metabolite, contributes tometabolite, contributes to
prolonged effectsprolonged effects
(analgesia) with repeated(analgesia) with repeated
doses or a continuous i.v.doses or a continuous i.v.
infusion, may be a causeinfusion, may be a cause
of tolerance.of tolerance.

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SiteSite and Mechanism of actionand Mechanism of action
 Acts at thalamoneocortical projectionActs at thalamoneocortical projection
 Inhibits cortex(unconsciousness) and thalamusInhibits cortex(unconsciousness) and thalamus
(analgesia) and stimulates limbic system(analgesia) and stimulates limbic system
(emergence reaction and hallucinations)(emergence reaction and hallucinations)
 Blocks polysynaptic reflexes in spinal cord andBlocks polysynaptic reflexes in spinal cord and
inhibiting excitatory neurotransmitter effects ininhibiting excitatory neurotransmitter effects in
selected areas of brainselected areas of brain
 NMDA receptor (n-methyl-d-aspartate, a subtypeNMDA receptor (n-methyl-d-aspartate, a subtype
of glutamate receptor which is excitatoryof glutamate receptor which is excitatory
neurotransmitter) antagonist ,decreasesneurotransmitter) antagonist ,decreases
presynaptic release of glutamate and potentiatespresynaptic release of glutamate and potentiates
effects of inhibitory neurotransmitter gamma-effects of inhibitory neurotransmitter gamma-
amino-butyric acidamino-butyric acid

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Site and Mechanism of actionSite and Mechanism of action
 Analgesic effect is due to descending inhibitoryAnalgesic effect is due to descending inhibitory
monoaminergic pain pathways and directmonoaminergic pain pathways and direct
inhibition of cytokines in blood, also ketamineinhibition of cytokines in blood, also ketamine
suppresses neutrophil production of inflammatorysuppresses neutrophil production of inflammatory
mediators and improves blood flowmediators and improves blood flow
 Antagonist effect at muscarinic receptorsAntagonist effect at muscarinic receptors
 Interacts with voltage gated sodium channels,Interacts with voltage gated sodium channels,
sharing a binding site with local anaesthetics.sharing a binding site with local anaesthetics.

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Systemic effectsSystemic effects
CNSCNS
 ‘‘’’Dissociative anaesthesiaDissociative anaesthesia’’-’’-
A state which dissociates individual fromA state which dissociates individual from
himself and surroundings-i.e.cataleptic state-himself and surroundings-i.e.cataleptic state-
eyes open with slow nystagmic gaze, noneyes open with slow nystagmic gaze, non
communicative although awake, hypertonic andcommunicative although awake, hypertonic and
purposeful skeletal muscle movements inpurposeful skeletal muscle movements in
absence of surgical stimuli. pt.is amnesic andabsence of surgical stimuli. pt.is amnesic and
analgesia is intense.evidence on EEG ofanalgesia is intense.evidence on EEG of
dissociation between thalamocortical and limbicdissociation between thalamocortical and limbic
systems.systems.

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Systemic effectsSystemic effects
CNSCNS
 Profound analgesia-somatic more than visceral-Profound analgesia-somatic more than visceral-
due to activity in thalamic and limbic systemdue to activity in thalamic and limbic system
which are responsible for interpretation ofwhich are responsible for interpretation of
painful signals, potent cerebral vasodilator,painful signals, potent cerebral vasodilator,
causes postoperative analgesia so reducescauses postoperative analgesia so reduces
opiate requirement.opiate requirement.
 Corneal, cough, swallow reflexes may beCorneal, cough, swallow reflexes may be
present but should not be assumed to bepresent but should not be assumed to be
protectiveprotective

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Systemic effectsSystemic effects
CNS-CNS-
Increases brain OIncreases brain O22 consumption and metabolicconsumption and metabolic
rate, ICT is highly raisedrate, ICT is highly raised
 Psychedelic effects during awakening fromPsychedelic effects during awakening from
anaesthesia called emergence reactions due toanaesthesia called emergence reactions due to
depression of inferior colliculus and medialdepression of inferior colliculus and medial
geniculate nucleus.geniculate nucleus.
 Incidence-10-30%Incidence-10-30%
 Hallucinations-mainly auditory.30-40%Hallucinations-mainly auditory.30-40%
 Benzodiazepines, opioids, barbiturates given withBenzodiazepines, opioids, barbiturates given with
ketamine decreases hallucinations andketamine decreases hallucinations and
emergence reactionsemergence reactions

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Systemic effectsSystemic effects
CVSCVS
 Stimulates central sympathetic system-Stimulates central sympathetic system-
tachycardia, hypertension, increase C.O.tachycardia, hypertension, increase C.O.
 In debilitated patients catecholaminesIn debilitated patients catecholamines
depleted so direct myocardial depressantdepleted so direct myocardial depressant
effect.effect.
 Benzodiazepines and NBenzodiazepines and N22O attenuateO attenuate
responseresponse

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Respiratory SystemRespiratory System
 Potent bronchodilatorPotent bronchodilator
 Respiratory depression in child ifRespiratory depression in child if
given in bolus dosesgiven in bolus doses
 Increases salivary andIncreases salivary and
tracheobronchial secretions, sotracheobronchial secretions, so
use of atropine or glycopyrollateuse of atropine or glycopyrollate
is necessaryis necessary

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EYEEYE
Increases intraocular tension, dilates pupil, nystagmusIncreases intraocular tension, dilates pupil, nystagmus
GITGIT
Increases intragastric pressureIncreases intragastric pressure
MUSCULAR SYSTEMMUSCULAR SYSTEM
Increases muscle toneIncreases muscle tone
HEPATIC AND RENAL SYSTEMHEPATIC AND RENAL SYSTEM
No significant effectNo significant effect
PLATELETSPLATELETS
Inhibits platelet aggregationInhibits platelet aggregation
Systemic EffectsSystemic Effects

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DRUG INTERACTIONSDRUG INTERACTIONS
 Theophylline & Ketamine predisposes to seizuresTheophylline & Ketamine predisposes to seizures
 Non-depolarising neuromuscular blocking agentsNon-depolarising neuromuscular blocking agents
are potentiatedare potentiated
 Propranolol unmask direct myocardial depressantPropranolol unmask direct myocardial depressant
effect of Ketamineeffect of Ketamine
 It produces myocardial depression with volatileIt produces myocardial depression with volatile
anesthetics[VA] like halothane as VA depressesanesthetics[VA] like halothane as VA depresses
sympathetic outflow from CNSsympathetic outflow from CNS
 Lithium prolongs the duration of action of KetamineLithium prolongs the duration of action of Ketamine

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DOSESDOSES
INTRAVENOUSINTRAVENOUS
INTRAMUSCULARINTRAMUSCULAR
ORALORAL
NASALNASAL
RECTALRECTAL
EPIDURAL- Preservative – free solutionEPIDURAL- Preservative – free solution
Sedation and analgesiaSedation and analgesia
 -0.2-0.8 mg/kg i.v over 2-3 min-0.2-0.8 mg/kg i.v over 2-3 min
 2-4 mg/kg i.m.2-4 mg/kg i.m.
Preemptive/Preventive analgesiaPreemptive/Preventive analgesia
 0.15-0.25 mg/kg i.v.0.15-0.25 mg/kg i.v.
 Oral-3 to 10 mg/kgOral-3 to 10 mg/kg
 Interaction with propofol is additive, dose of each is reduced toInteraction with propofol is additive, dose of each is reduced to
halfhalf

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DOSESDOSES
Maintenance of GAMaintenance of GA
 0.5-1 mg/kg i.v.prn with 50% N0.5-1 mg/kg i.v.prn with 50% N22O in OO in O22
 15-45 microgm/kg /min i.v. with 50 to 70% N15-45 microgm/kg /min i.v. with 50 to 70% N22OO
in O2in O2
 30-90 microgm/kg/min i.v without N30-90 microgm/kg/min i.v without N2200
Induction of GAInduction of GA
 0.5 to 2 mg/kg i.v.0.5 to 2 mg/kg i.v.
 4 to 6mg/kg i.m.4 to 6mg/kg i.m.

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USESUSES
Induction and maintenance of AnaesthesiaInduction and maintenance of Anaesthesia
 Poor risk patients [ASA Class IV] with RSPoor risk patients [ASA Class IV] with RS
& CVS system disorders (excluding IHD && CVS system disorders (excluding IHD &
CAD)CAD)
 Inducing agent of choice in shockInducing agent of choice in shock
 Inducing agent of choice in AsthmaInducing agent of choice in Asthma
 Cardiac tamponade, restrictive pericarditisCardiac tamponade, restrictive pericarditis
as it preserves HR and Rt. Atrial pressureas it preserves HR and Rt. Atrial pressure
through it’s sympathetic stimulatingthrough it’s sympathetic stimulating
effects.effects.

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USESUSES
 Congential heart disease like Rt to Lt shuntsCongential heart disease like Rt to Lt shunts
[TOF] , as by causing hypertension increases[TOF] , as by causing hypertension increases
afterload and decreases shunt fraction.afterload and decreases shunt fraction.

 Malignant hyperthermia.Malignant hyperthermia.
 In known depression, improved postoperativeIn known depression, improved postoperative
depressive state.depressive state.
 As an analgesic in low doses after thoracicAs an analgesic in low doses after thoracic
surgery.surgery.

 Epidural/Caudal administration [0.5-1 mg/Kg].Epidural/Caudal administration [0.5-1 mg/Kg].

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USESUSES
SEDATIONSEDATION
 In pediatric patients for cardiac catheterization,In pediatric patients for cardiac catheterization,
radiation therapy, radiological studies, dressingradiation therapy, radiological studies, dressing
changes [Subanesthetic dose <= 1mg/Kg I.V.] ,changes [Subanesthetic dose <= 1mg/Kg I.V.] ,
dental workdental work
 Cautious use in cardiac catheterization withCautious use in cardiac catheterization with
elevated pulmonary vascular resistanceelevated pulmonary vascular resistance

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USESUSES
Other UsesOther Uses
 For Supplementation of regional anesthesiaFor Supplementation of regional anesthesia
Ketamine [0.5 mg/KG IV], combined withKetamine [0.5 mg/KG IV], combined with
diazepam [0.15 mg/KG IV]diazepam [0.15 mg/KG IV]
 Combined with Nitrous oxide and propofol forCombined with Nitrous oxide and propofol for
supplementation of local anesthesiasupplementation of local anesthesia
 In outpatients premedication with midazolam,In outpatients premedication with midazolam,
concurrent propofol and intermittent Ketamineconcurrent propofol and intermittent Ketamine
[for analgesia] in does < 3 mg/KG for[for analgesia] in does < 3 mg/KG for
debridement, skin grafting patientsdebridement, skin grafting patients
 Preferred agents for patients with full stomachPreferred agents for patients with full stomach
 Remote places and in inexperience hand as itRemote places and in inexperience hand as it
does not depress respiration and heartdoes not depress respiration and heart

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USESUSES
Other UsesOther Uses
 Reversal of Opioid toleranceReversal of Opioid tolerance
 In restless leg syndrome by inhibitingIn restless leg syndrome by inhibiting
neuroinflammation in spinal cordneuroinflammation in spinal cord
 Safe in porphyria patientsSafe in porphyria patients
 Used in veterinary medicine because of anestheticUsed in veterinary medicine because of anesthetic
and analgesic effectsand analgesic effects
 With Opioid useful for cancer painWith Opioid useful for cancer pain
 In small does [0.1 – 0.5 mg/KG/hr] as a localIn small does [0.1 – 0.5 mg/KG/hr] as a local
anesthetic for treatment of neuropathic painanesthetic for treatment of neuropathic pain

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ContraindicationsContraindications
 In raised ICT and intracranial mass lesionsIn raised ICT and intracranial mass lesions
 Patients with open eye injuryPatients with open eye injury
 Ischemic heart disease and vascular aneurysmsIschemic heart disease and vascular aneurysms
 Psychiatric disease like schizophrenia or a historyPsychiatric disease like schizophrenia or a history
of adverse reaction to ketamineof adverse reaction to ketamine
 Due to preservative chlorobutanol, which isDue to preservative chlorobutanol, which is
neurotoxic SAB route is C/Ineurotoxic SAB route is C/I
 Abruptio placentae and cord prolapse, not to beAbruptio placentae and cord prolapse, not to be
used with ergometrine as it increase uterine toneused with ergometrine as it increase uterine tone
and intrauterine pressure in both pregnant andand intrauterine pressure in both pregnant and
non pregnant uterusnon pregnant uterus
 HyperthyroidismHyperthyroidism

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Comparison between ThiopentoneComparison between Thiopentone
and Ketamineand Ketamine
 ThiopentoneThiopentone
 BarbiturateBarbiturate
 Poor analgesicPoor analgesic
 Weak muscleWeak muscle
relaxantrelaxant
 Alkaline solutionAlkaline solution
pH 10.5pH 10.5
 Powder forPowder for
reconstitutionreconstitution
 KetamineKetamine
 PhencyclidinePhencyclidine
derivativederivative
 Good analgesicGood analgesic
 Increases muscleIncreases muscle
tonetone
 Acidic solution pHAcidic solution pH
3.5 to 5.53.5 to 5.5
 Solution forSolution for
reconstitutionreconstitution

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Continued…Continued…
 Lipid solubleLipid soluble
 Highly bound toHighly bound to
plasma proteinsplasma proteins
 Depressed respirationDepressed respiration
 BronchoconstrictorBronchoconstrictor
 Metabolism affectedMetabolism affected
by hepatic enzymeby hepatic enzyme
activityactivity
 GABA A receptorGABA A receptor
inhibitorinhibitor
 Acts on RASActs on RAS
 Highly lipid solubleHighly lipid soluble
than thiopentonethan thiopentone
 Least bound to plasmaLeast bound to plasma
proteinsproteins
 Stimulates respirationStimulates respiration
 BronchodilatorBronchodilator
 Metabolism affectedMetabolism affected
by hepatic blood flowby hepatic blood flow
 NMDA receptorNMDA receptor
inhibitorinhibitor
 Acts on neocorticalActs on neocortical
projectionprojection

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Continued…Continued…
 Depresses sympatheticDepresses sympathetic
nervous systemnervous system
 Decreases BP, ICT, IOTDecreases BP, ICT, IOT
 Decreases CMRO2Decreases CMRO2
 Cerebral vasoconstrictorCerebral vasoconstrictor
 Precipitates porphyriaPrecipitates porphyria
 Induction tested by lossInduction tested by loss
of corneal and eyelidof corneal and eyelid
reflexreflex
 Used in statusUsed in status
epilepticusepilepticus
 Stimulates centralStimulates central
sympathetic systemsympathetic system
 Increases BP, ICT, IOTIncreases BP, ICT, IOT
 Increases CMRO2Increases CMRO2
 Cerebral vasodilatorCerebral vasodilator
 Safe in porphyriaSafe in porphyria
 Induction tested by pupilInduction tested by pupil
dilation, fixation anddilation, fixation and
nystagmusnystagmus
 Used in statusUsed in status
asthmaticusasthmaticus

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