Intravenous Anaesthetic Agents,induction agents

Induction Agents

1. INTRAVENOUS INTRAVENOUS
INDUCTION AGENTSINDUCTION AGENTS
Monnaf AliMonnaf Ali
Msc in OTATMsc in OTAT
BDIPS, Charusat UniversityBDIPS, Charusat University

2. CLASSIFICATIONCLASSIFICATION
•True induction agents produce loss of consciousness within True induction agents produce loss of consciousness within
one arm-brain circulation timeone arm-brain circulation time
•Approximately 30 secondsApproximately 30 seconds

3. CLASSIFICATIONCLASSIFICATION
Rapidly –Acting
“true induction
agents”
Slower-acting
•Thiopentone
•Etomidate
•Propofol
•Ketamine
•Benzodiazepines
•Neuroleptic-
anaesthetics
•Opioids

4. ADVANTAGES OF IV INDUCTIONADVANTAGES OF IV INDUCTION
•Rapid onset of actionRapid onset of action
•More pleasant & acceptable for the patientMore pleasant & acceptable for the patient
•Pollution freePollution free
•Low incidence of side-effectsLow incidence of side-effects
•Smooth induction with rapid transfer through stage 2Smooth induction with rapid transfer through stage 2

5. DISADVANTAGESDISADVANTAGES
•Need IV accessNeed IV access
•It is easy to give too much .... Side-effectsIt is easy to give too much .... Side-effects
•No removal of drug via the lungs as with inhalationalsNo removal of drug via the lungs as with inhalationals
•Recovery requiresRecovery requires
•RedistributionRedistribution
•MetabolismMetabolism
•Excretion Excretion
•Sudden loss of normal protective reflexesSudden loss of normal protective reflexes

6. MECHANISM OF ACTIONMECHANISM OF ACTION
•MostMost sedative hypnotics exert their effect via the sedative hypnotics exert their effect via the inhibitory inhibitory
GABAGABA
AA receptors receptors
•GABA – GABA – γγ (gamma)-(gamma)-aminobutyric acidaminobutyric acid
•Increased chloride conductance hyperpolarisation neuronal
→ →
Increased chloride conductance hyperpolarisation neuronal
→ →
inhibitioninhibition
•Some Some inhibit the release of glutamateinhibit the release of glutamate, an excitatory amino , an excitatory amino
acid, in brainacid, in brain
•Not clearly understoodNot clearly understood

7. PHARMACOKINETICSPHARMACOKINETICS
•The The onset of action onset of action depends on the drug reaching the effect site (the depends on the drug reaching the effect site (the
brain) by crossing the BBBbrain) by crossing the BBB
•Arm-brain circulation time Arm-brain circulation time is determined byis determined by
Speed of injectionSpeed of injection
Lipid solubilityLipid solubility
Protein bindingProtein binding
Blood flow to brainBlood flow to brain
•RecoveryRecovery is determined by is determined by
•RedistributionRedistribution from vessel-rich to vessel-poor organs (brain muscle etc)
→
from vessel-rich to vessel-poor organs (brain muscle etc)
→
•Metabolism and excretionMetabolism and excretion

8. REDISTRIBUTIONREDISTRIBUTION
•Following IV Induction, the patient will wake up after a few Following IV Induction, the patient will wake up after a few
minutes due to REDISTRIBUTION of the drug from brain to minutes due to REDISTRIBUTION of the drug from brain to
other tissues that are less well perfusedother tissues that are less well perfused
•Rapid awakening is not due to metabolism or excretionRapid awakening is not due to metabolism or excretion
•Low concentrations of the drug will remain in the brainLow concentrations of the drug will remain in the brain
•This impairs concentration and higher functioningThis impairs concentration and higher functioning
•Recommended not to drive or make important decisions for 48-Recommended not to drive or make important decisions for 48-
72 hours post anaesthesia72 hours post anaesthesia

9. CHARACTERISTICS OF AN IDEAL CHARACTERISTICS OF AN IDEAL
IV INDUCTION AGENTIV INDUCTION AGENT
•Smooth and rapid onsetSmooth and rapid onset
•Rapid recoveryRapid recovery
•No pain on injectionNo pain on injection
•Minimal side-effectsMinimal side-effects
•No toxicityNo toxicity

10. PROPOFOLPROPOFOL

11. PROPOFOLPROPOFOL
Physical propertiesPhysical properties
•2,6 di-isopropylphenol2,6 di-isopropylphenol
•Preparation:Preparation:
•10% soya bean oil10% soya bean oil
•1.2% egg phosphatitide1.2% egg phosphatitide
•From egg lecithin (yolk)From egg lecithin (yolk)
•2.25% glycerol2.25% glycerol
•Fat emulsionFat emulsion
•Culture mediumCulture medium
•Use within 6 hours of openingUse within 6 hours of opening
•Multiple amp sizesMultiple amp sizes
•20ml20ml, 50ml or 100ml, 50ml or 100ml
•1%1% or 2% or 2%
•1% = 10mg/ml1% = 10mg/ml
PharmacokineticsPharmacokinetics
•Extra-hepatic metabolismExtra-hepatic metabolism
•++ lipid-soluble++ lipid-soluble
•Rapid plasma clearanceRapid plasma clearance
•Unique, therefore versatileUnique, therefore versatile
UsesUses
•InductionInduction
•Maintenance (TIVA)Maintenance (TIVA)
•SedationSedation

12. PHARMACODYNAMICS OF PHARMACODYNAMICS OF
PROPOFOLPROPOFOL
DosesDoses
•Induction: Induction:
•Adults: 2 – 2.5 mg/kgAdults: 2 – 2.5 mg/kg
•Elderly: 1 – 1.5 mg/kgElderly: 1 – 1.5 mg/kg
•Children: 2.5 – 3 mg/kgChildren: 2.5 – 3 mg/kg
Organ EffectsOrgan Effects
•CNSCNS
•CVSCVS
•RespiratoryRespiratory
•GITGIT
•MetabolicMetabolic

13. •CNSCNS
•rapid LOC + recoveryrapid LOC + recovery
•Less hangover effect than Less hangover effect than
other induction agents or other induction agents or
gasesgases
•No real excitatory effectsNo real excitatory effects
•No antalgesia, infact very No antalgesia, infact very
slight analgesic effectslight analgesic effect
•AntipruriticAntipruritic
•Pain on injection!!Pain on injection!!
•CVSCVS
•Dose-related CVS Dose-related CVS
depressiondepression
•↓↓ed SVRed SVR
•↓↓ed BPed BP
•Slight HR
↑
Slight HR
↑
•RespiratoryRespiratory
•Dose-dependent Dose-dependent
depressiondepression
•Apnoea on induction close Apnoea on induction close
to 100%to 100%
•IInhibits laryngeal nhibits laryngeal
reflexesreflexes
•No histamine releaseNo histamine release
•GITGIT
•Anti-emeticAnti-emetic
•MetabolicMetabolic
•Propofol infusion Propofol infusion
syndrome (PRIS) syndrome (PRIS)
LipaemiaLipaemia
Metabolic acidosisMetabolic acidosis
Cardiomyopathy and shockCardiomyopathy and shock
Skeletal myopathySkeletal myopathy
deathdeath

14. PROPOFOLPROPOFOL
•Most commonly usedMost commonly used
•Ideal for these specific Ideal for these specific
scenariosscenarios
TIVATIVA
Conscious sedationConscious sedation
AsthmaAsthma
PorphyriaPorphyria
History of PONVHistory of PONV
History of Malignant History of Malignant
HyperthermiaHyperthermia
•Use with caution !!Use with caution !!
•ElderlyElderly
•Cardiac failureCardiac failure
•HypovolaemiaHypovolaemia
•Fixed cardiac outputFixed cardiac output
•Aortic / Mitral stenosisAortic / Mitral stenosis
•HOCMHOCM

15. THIOPENTONETHIOPENTONE

16. THIOPENTONETHIOPENTONE
Physical propertiesPhysical properties
•Yellow powderYellow powder
•Mix with HMix with H
22O or N/SalO or N/Sal
•pH 10.5pH 10.5
•precipitatesprecipitates
•Strength 2.5% (25mg/ml)Strength 2.5% (25mg/ml)
•Solution stable for 24-48 Solution stable for 24-48
hourshours
DoseDose
•Induction:Induction:
•Adults: 3 – 5mg/kgAdults: 3 – 5mg/kg
•Children: 5-6mg/kgChildren: 5-6mg/kg
•Caution in elderlyCaution in elderly

17. ORGAN EFFECTS OF ORGAN EFFECTS OF
THIOPENTONETHIOPENTONE
•CNSCNS
•LOC in 30secLOC in 30sec
•Classically described Classically described
for RSIfor RSI
•Smooth, no reflex Smooth, no reflex
movements or coughingmovements or coughing
•AntalgesiaAntalgesia
•Anti-convulsantAnti-convulsant
•Used in treatment of Used in treatment of
STATUS EPILEPTICUSSTATUS EPILEPTICUS
•NeuroprotectiveNeuroprotective
•↓↓CMRO2 CMRO2
•
↓

↓
ICP\ICP\
•No pain on injectionNo pain on injection
•CVSCVS
•
↓

↓
C.O. (10 – 20%)C.O. (10 – 20%)
•VasodilatationVasodilatation
•negative inotropynegative inotropy
•
↓

↓
central central
catecholaminescatecholamines
•Compensatory HR
↑
Compensatory HR
↑
•Exaggerated response Exaggerated response
withwith
•ElderlyElderly
•Cardiac failureCardiac failure
•Fixed cardiac outputFixed cardiac output
•HypovolaemiaHypovolaemia
•ACIDOSISACIDOSIS

18. •RespiratoryRespiratory
•Dose-dependent apnoeaDose-dependent apnoea
•No depression of laryngeal No depression of laryngeal
reflexesreflexes
•Histamine releaseHistamine release
•Renal, Hepatic, Renal, Hepatic,
GITGIT
•No real issuesNo real issues
•Local EffectsLocal Effects
•Irritant to tissuesIrritant to tissues
•Venous thrombosis with 5% Venous thrombosis with 5%
solutionssolutions
•Intra-arterial injection is a Intra-arterial injection is a
disasterdisaster
•Precipitation of solid Precipitation of solid
crystals of thiopentone in crystals of thiopentone in
arteries due to blood pH of arteries due to blood pH of
7.47.4
•Acute ischaemia of limbAcute ischaemia of limb

19. CONTRA-INDICATIONS FOR CONTRA-INDICATIONS FOR
THIOPENTONETHIOPENTONE
•Absolute:Absolute:
•PorphyriaPorphyria
•Known allergy (rare)Known allergy (rare)
•Relative:Relative:
•Asthma (Theoretical - It has been used in many asthmatics Asthma (Theoretical - It has been used in many asthmatics
without problems)without problems)
•Cardiovascular instabilityCardiovascular instability

20. ETOMIDATEETOMIDATE

21. ETOMIDATEETOMIDATE
Physical PropertiesPhysical Properties
•10 ml ampoules (2mg/ml)10 ml ampoules (2mg/ml)
DoseDose
•0.2-0.3mg/kg0.2-0.3mg/kg
PharmacokineticsPharmacokinetics
•Rapid recoveryRapid recovery
•Repeated doses are not cumulativeRepeated doses are not cumulative
•But not used for infusions because But not used for infusions because
of adrenocortical suppressionof adrenocortical suppression

22. ORGAN EFFECTS OF ETOMIDATEORGAN EFFECTS OF ETOMIDATE
•CNSCNS
•Rapid LOCRapid LOC
•Myoclonus and involuntary Myoclonus and involuntary
movementsmovements
•Reduced by concurrent Reduced by concurrent
opiate and benzodiazepine opiate and benzodiazepine
useuse
•Pain on injectionPain on injection
•CVSCVS
•Most stable Most stable
•Little change in BP or HRLittle change in BP or HR
•RespiratoryRespiratory
–Minimal respiratory Minimal respiratory
depressiondepression
–No histamine release No histamine release
•Least likely to cause Least likely to cause
analphylaxisanalphylaxis
•GITGIT
–Severe Severe PONV!PONV!
–““VOMIDATE”VOMIDATE”
•EndocrineEndocrine
–Inhibition of steroid Inhibition of steroid
synthesissynthesis

23. KETAMINEKETAMINE

24. KETAMINEKETAMINE
Physical PropertiesPhysical Properties
•Solutions Solutions
•1% (10mg/ml)1% (10mg/ml)
•5% (50mg/ml)5% (50mg/ml)
•10% (100mg/ml)10% (100mg/ml)
•Long-shelf half lifeLong-shelf half life
•No pain on injectionNo pain on injection
DosesDoses
•iv, im or oraliv, im or oral
•Induction:Induction:
•1-2mg/kg iv 1-2mg/kg iv
•onset 30-60sonset 30-60s
•Lasts 5-15 minLasts 5-15 min
•5-10mg/kg im5-10mg/kg im
•Onset 3-8minOnset 3-8min
•Lasts 10-30minLasts 10-30min
•Analgesia:Analgesia:
•0.2-0.4mg/kg iv0.2-0.4mg/kg iv

25. ORGAN EFFECTS OF KETAMINEORGAN EFFECTS OF KETAMINE
•CNSCNS
–DissociativeDissociative anaesthetic anaesthetic
–Complete analgesia Complete analgesia with with
superficial sleepsuperficial sleep
–↑↑ed ICP and IOPed ICP and IOP
–Psychic reactions: Psychic reactions:
•Hallucinations and Hallucinations and
emergence deliriumemergence delirium
•Less in kids, males, elderly, Less in kids, males, elderly,
long procedures and long procedures and
repeated administrationrepeated administration
•Worse if pt stimulated on Worse if pt stimulated on
awakeningawakening
•CVSCVS
–Sympathetic stimulant Sympathetic stimulant
centrallycentrally
•
↑

↑
HRHR
•
↑

↑
BPBP
•
↑

↑
C.O.C.O.
•
↑

↑
SVRSVR
–But...But...
•Direct myocardial Direct myocardial
depressantdepressant
–Not arrhythmogenicNot arrhythmogenic

26. •RespiratoryRespiratory
–Minimal or no respiratory Minimal or no respiratory
depressiondepression
–Preserved pharyngeal Preserved pharyngeal
reflexesreflexes
–Maintains airwayMaintains airway
•Do not need to intubate or Do not need to intubate or
insert LMAinsert LMA
–BronchodilatorBronchodilator
•Sympathetic stimulationSympathetic stimulation
•Safe in asthma (no histamine Safe in asthma (no histamine
release)release)
•Last line treatment of status Last line treatment of status
asthmaticusasthmaticus
–Increased salivation and Increased salivation and
bronchial secretionsbronchial secretions
•Use anti-sialogogue Use anti-sialogogue
(anticholinergic like (anticholinergic like
atropine or atropine or
glycopyrrolate)glycopyrrolate)
•GITGIT
–PONVPONV
•UterusUterus
–Uterine contractions in 1Uterine contractions in 1
stst

trimester trimester

27. KETAMINEKETAMINE
IndicationsIndications
•Sick and unstable adults and childrenSick and unstable adults and children
•Burns surgeryBurns surgery
•DebridementDebridement
•Change of dressingsChange of dressings
•Short diagnostic proceduresShort diagnostic procedures
•AnalgesiaAnalgesia
•Field anaesthesiaField anaesthesia
•Status asthmaticusStatus asthmaticus
Contra-indicationsContra-indications
•CVS diseasesCVS diseases
•IHD, hypertension, AAA, CCFIHD, hypertension, AAA, CCF
•↑↑ed ICPed ICP
•↑↑ed IOP and “open eye”ed IOP and “open eye”
•Psychiatric patientsPsychiatric patients
•EpilepticsEpileptics
•ThyrotoxicosisThyrotoxicosis
•Full stomachFull stomach
•Early pregnancyEarly pregnancy

28. BENZODIAZEPINESBENZODIAZEPINES
•SedativesSedatives
•Also act on the GABA receptorsAlso act on the GABA receptors
•Used mainly as premedication and intra-operative sedation in Used mainly as premedication and intra-operative sedation in
anaesthesiaanaesthesia
•Rarely used as induction agentsRarely used as induction agents
•Premeds:Premeds:
•Lorazepam, temazepam, diazepam, midazolamLorazepam, temazepam, diazepam, midazolam
•Sedation:Sedation:
•midazolammidazolam

29. MIDAZOLAMMIDAZOLAM

30. MIDAZOLAMMIDAZOLAM
Physical PropertiesPhysical Properties
•preparationspreparations
•5 mg ampoules (1mg/ml)5 mg ampoules (1mg/ml)
•15mg ampoules (5mg/ml)15mg ampoules (5mg/ml)
•Look identical so be Look identical so be
careful when checkingcareful when checking
•Tablets availableTablets available
PharmacokinetcsPharmacokinetcs
•Short duration of actionShort duration of action
DoseDose
•Premed:Premed: 0.5mg/kg 0.5mg/kg
–Adults 7.5-15mg orallyAdults 7.5-15mg orally
–Works within 30 minWorks within 30 min
–Kids – amx 7.5mg/kgKids – amx 7.5mg/kg
•Induction:Induction: 0.1-0.3mg/kg 0.1-0.3mg/kg
•Sedation:Sedation: 0.1mg/kg0.1mg/kg
–Less with elderlyLess with elderly

31. ORGAN EFFECTS OF ORGAN EFFECTS OF
MIDAZOLAMMIDAZOLAM
•CNSCNS
–Induction does not occur Induction does not occur
within 1 arm-rain circulation within 1 arm-rain circulation
timetime
•Takes 55-140secTakes 55-140sec
–Anterograde amnesiaAnterograde amnesia
–AnxiolysisAnxiolysis
–SedationSedation
–Prolonged recoveryProlonged recovery
•CVSCVS
–StableStable
–Often used in cardiac surgeryOften used in cardiac surgery
•RespiratoryRespiratory
–Little effectLittle effect
•GITGIT
–Low incidence PONVLow incidence PONV
•UterusUterus
–Crosses placenta and cause Crosses placenta and cause
floppy neonatefloppy neonate

32. DIAZEPAMDIAZEPAM
•Drug name: Diazepam (Valium)
•Drug Class: Benzodiazepine
•MOA: Enhances GABA activity, leading
to sedative, anxiolytic, muscle relaxant,and
anticonvulsant effects.

33. PHARMACOKINETICSPHARMACOKINETICS
•AbsorptionAbsorption:: Rapidly absorbed after oral administration Rapidly absorbed after oral administration
•DistributionDistribution:: Highly lipophilic, widely distributed, crosses Highly lipophilic, widely distributed, crosses
blood-brain barrierblood-brain barrier
•MetabolismMetabolism:: Hepatic metabolism via CYP450 (CYP2C19, Hepatic metabolism via CYP450 (CYP2C19,
CYP3A4) into active metabolites (desmethyldiazepam, CYP3A4) into active metabolites (desmethyldiazepam,
oxazepam)oxazepam)
•Elimination:Elimination:
•Half-life: 20–50 hours (active metabolite can extend effect)Half-life: 20–50 hours (active metabolite can extend effect)
•Excreted primarily via urineExcreted primarily via urine

34. •Indications:
•Anxiety disorders
•Muscle spasms
•Seizures (status epilepticus)
•Alcohol withdrawal
•Preoperative sedation
•Side Effects:
•Common: Drowsiness, dizziness,
fatigue, muscle weakness
•Serious: Respiratory depression,
dependence, withdrawal symptoms

35. LORAZEPAMLORAZEPAM
•Drug Class: Benzodiazepines
•MOA: Enhance GABAergic activity, leading
to sedative, anxiolytic, muscle relaxant, and
anticonvulsant effects.
•Main Differences:
•Diazepam (Valium): Longer half-life, highly lipophilic.
•Lorazepam (Ativan): Shorter half-life, less lipophilic, more potent.

36. PHARMACOKINETICSPHARMACOKINETICS
Parameter Diazepam Lorazepam
Absorption
Rapid, oral
bioavailability ~90%
Rapid, oral bioavailability ~85%
Distribution
Highly lipophilic,
crosses BBB easily
Less lipophilic, slower CNS
penetration
Metabolism
Hepatic (CYP2C19,
CYP3A4), active
metabolites
Hepatic (glucuronidation), inactive
metabolites
Half-life
20–50 hours (active
metabolite extends
effect)
10–20 hours
Elimination
Renal excretion
(urine)
Renal excretion (urine)

37. •IndicationsIndications::
•Anxiety disordersAnxiety disorders
•Status epilepticusStatus epilepticus
•Preoperative sedationPreoperative sedation
•Insomnia (short-term use)Insomnia (short-term use)
•Side EffectsSide Effects::
•Common: Drowsiness, Common: Drowsiness,
dizziness, fatigue, confusiondizziness, fatigue, confusion
•Serious: Respiratory Serious: Respiratory
depression, dependence, depression, dependence,
withdrawal symptomswithdrawal symptoms

38. TIVATIVA
•TIVA = Total Intravenous TIVA = Total Intravenous
AnaesthesiaAnaesthesia
–Ideal: PROPOFOLIdeal: PROPOFOL
–Ketamine Ketamine
•IndicationsIndications
–Risk of malignant Risk of malignant
hyperthermiahyperthermia
–Severe PONV in prior caseSevere PONV in prior case
–Day-case surgeryDay-case surgery
–Cheaper than gasesCheaper than gases
•BenefitsBenefits
•Rapid wake-upRapid wake-up
•No PONVNo PONV
•RequirementsRequirements
•Infusion pumpsInfusion pumps

39. PRACTICAL POINTS ON IV PRACTICAL POINTS ON IV
INDUCTIONINDUCTION
•Reduce pain on injectionReduce pain on injection
–Iv lignocaine 10-20mg in syringeIv lignocaine 10-20mg in syringe
–New big dripNew big drip
•Titrate to effectTitrate to effect..... You can always give more..... You can always give more
•Less in elderly .... More in childrenLess in elderly .... More in children

40. THANK YOUTHANK YOU