Anaesthesia iv induction drugs information

1. IV INDUCTION AGENTS
BY SUBASHINI (JR1)
DEPARTMENT OF ANESTHESIA

2. SYNOPSIS
• INDRODUCTION
• PROPOFOL
• ETOMIDATE
• KETAMINE
• THIOPENTONE

3. Introduction
Classification of IV induction agent
Rapid onset Slow onset
• Propofol
• Etomidate
• Ketamine
• Thiopentone
• Benzodiazepines
• Opioids

5. Propofol

6. PROPOFOL
• Structure
• Composition
• Dosage
• Mechanism of action
• Pharmacodynamics
• Clinical uses – anesthesia uses and non-anesthesia uses
• Effect of organ systems
• Side effects
• Propofol in ICU

7. Structure

8. Composition
s.no components Percentage Uses
1 soyabean oil 10% (aqueous solution ) Medium that can stabilize and
hold propofol for dispersion
2 Glycerol 2.25% Maintain tonicity with blood
3 Purified egg phosphatide 1.2% (lecithin) Emulsifier to stabilize small
propofol droplets
4 Sodium hydroxide residual Maintains pH between 6 to 8.5
5 Preservative 1.Disodium edetate ( 0.005%)
2. Sodium metabisulfite (0.25 mg/dl)
1.Added to sodium hydroxide to
maintain pH (6 to 8.5)
2.Added for maintaining lower pH
(4.5 – 6.5) but not used nowadays
as it causes bronchoconstriction

9. Dosage (Adult)
S.
No
Requirements Dosage
1. Induction (IV) 1- 2.5 mg/kg
2. Maintenance infusion (IV) 50 – 200mcg/kg/min
3. Sedation infusion (IV) 25 – 100 mcg/kg/min

11. Mechanism of action

12. Pharmacodynamics

13. Pharmacodynamics
S.n
o
Parameters Dosage
1. Elimination half time (hour) 0.5 – 1.5
2. Volume of distribution
(L/kg)
3.5-4.5
3. Clearance (ml/kg/min) 30-60
4. Systemic BP Decreased
5. Heart rate Decreased

14. Clinical uses (as IV induction agent)
s.no parameters Comments
1. Induction dose 1.5 – 2.5 mg/kg
2. Levels in blood to produce
unconsciousness
2 – 6 µg/ml (depends of age of patient and
associated comorbities)
3. Children Require larger doses due to higher central volume of
distribution and high clearance rate
4. Elders Requires smaller doses (25% to 50% decrease) as a
result of lesser central volume of distribution and
higher clearance rate
5. Awakening 1.0 - 1.5 µg/ml (doesn’t cause residual CNS effects)
6. Rapid sequence induction Full bolus dose given

15. Clinical uses (as IV induction agent)
S.No Parameters Comment
7. Not a rapid sequence induction Induction dose can be given in divided doses , first
divided dose can be followed after 1-2min
(treating first dose as test dose)
8. Loss of consciousness 30 seconds
9. Clinical end point of induction dosage Loss of verbal communication
10. Advantages of induction with propofol Ease of administration, clear minded recovery,
better pharyngeal relaxation, decreased chances of
post op nausea and vomiting, better airway
resistance profile, antipruritic property,
HYPOTENSIVE AGENT, prevents tachycardia,
anti-arrhythmic agents.

16. Clinical uses (As intravenous sedation )
s.no Parameters Comment
1. Dose 25-100 µg/kg/minute
2. Advantages • Short half life
• Short effect-site equilibrium
• Prompt recovery without any residual effects
3. Used in • GI endoscopy
• Colonoscopy
• Sedative during mechanical ventilation (ICU)
4. Controlled analgesia delivery system
(alternative to IV sedation)
0.7 mg/kg doses with 3 minute lookout period

17. Clinical uses (other uses)
s.no Uses Doses Mechanism of action Uses
1. Antiemetic 10-15mg/kg (
subhypnotic doses)
IV
Inhibition of
dopaminergic activity
Chemotherapy induced
nausea and vomiting
2. Antipruritic 10mg IV can depress spinal cord
activity
Pruritis induced by
neuraxial opioids or
cholestasis
3. Anticonvulsant Doses greater than
1mg/kg decreases
seizure duration in
35% to 45% of
patients
GABA mediated pre
and post synaptic
inhibition of chloride
ion channels
Electroconvulsive
therapy

18. Effect of organ systems

19. Side effects
• Pain on injection
• Allergic reactions
• Propofol infusion syndrome (PRIS)
• Abuse potential

20. Pain on injection

21. Pain on injection

22. Propofol infusion syndrome (PRIS)

24. Propofol in ICU

25. Etomidate

26. Etomidate
• Structure
• Mechanism of action
• Pharmacokinetics
• Clinical uses
• Effect on organ systems
• Side effects

27. Structure

28. Mechanism of action

30. Clinical uses (as IV induction agent)
S.No Parameter Dosage Comment
1. Standard induction dose 0.2 – 0.4 mg/kg IV Preferred in patients with cardiac
instability
2. Loss of unconsciousness One arm brain circulation
time
Rapid onset of action
3. Myoclonus activity during
induction
Can be reduced by prior
administration of opioid
Due to excitatory and inhibitory
effect on thalamocortical tract
4. Awakening At 0.1 – 0.3 mg/kg levels in
blood
5 to 15 minutes of administration
5 To decrease duration of
seizures
0.15 to 0.3 mg/kg IV Minimal effect but can be an
option in electroconvulsive
therapy

31. Effect on organ systems
S.No Organ systems Effects
1. CNS • Potent cerebral vasoconstrictor
• Decreases cerebral blood flow and CMRO2 by 35% to 45%
• Burst pattern in EEG seen which is more significant than
propofol
(hence used with caution with patient with history of seizures)2
2. CVS • CARIOVASCULAR STABILITY
• Induction agent of choice for patients with low or no cardiac
reserve
• Significant hypotension caused intra-op can be treated by beta
adrenergic agonist
3. Other systems • Hepatic and renal functions are unaltered .
• Intraocular pressure is decreased
• RVS – transient decrease in tidal volume

32. Side effects
• Pain on injection ( can be eliminated using lipid emulsion as
aqueous formulation uses propylene glycol of 35% as pH is
6.5)
• Myoclonus ( can be eliminated by injecting opioids )
• Allergic reactions
• Adrenocortical suppression

33. Adrenocortical suppression

34. Adrenocortical suppression
• This effect maybe desirable for stress free anaesthesia
• This enzyme inhibition can last for 4-6 hours
• The inhibition is dose dependent
• However due to this effect, etomidate cannot be used
as an agent of induction for sepsis, septic shock,
haemorrhagic shock where patient’s cortisol
production is needed intact.

35. Ketamine

36. Ketamine
• Structure
• Mechanism of action
• Pharmacokinetics
• Metabolism
• Clinical uses
• Effect on organ systems
• Side effects

37. Structure
S (+) ketamine R (-)ketamine
• Phencyclidine derivative
• More intensive analgesia
• More rapid metabolism and recovery
• Lower incidence of emergence reaction
• Four times more potent than R-ketamine
• Used in Europe
• Also phencyclidine derivative
• Usually used in USA

38. Mechanism of action
S NO Receptor Action
1. NMDA receptor • Ligand gated glutamate based receptors
• Inhibits the activation of receptor by non-competitive antagonism
• This decreases presynaptic release of glutamate
• S(+) isomer for affinity to this receptor
2. Opioid receptor • Directly interacts with µ , δ and κ- opioid receptor
• Agonist at κ receptor
• Antagonist at µ receptor
3. Monoaminergic receptors • Activates descending inhibitory monoaminergic pain pathways
4. Muscarinic receptors • Ketamine anesthesia is partially antagonized by anticholinesterase drugs
• Hence patients experiences emergence delirium , bronchodilation,
sympathomimetic action
5. Sodium channels • Interaction with sodium voltage gated channels gives mild local anesthetic
effect

39. Pharmacokinetics
S.NO Parameter Comment
1. Peak plasma concentration Achieved within one minute of IV administration and
within five minutes after IM administration
2. Plasma binding not significantly bound to plasma, hence distributes to
highly perfused tissues
3. Hepatic clearance 1L/ minute
4. Volume of distribution 3L/kg
5. Elimination half-time 2-3 hours

40. Metabolism

41. Clinical uses ( as analgesic )
S.NO Parameters Comment
1. Dose • 0.2 - 0.5 mg/kg IV
• For post –op analgesia and sedation – 1 to 2 mg/kg/hr infusions can
be made
2. Site of action Thalamic and limbic pathways ( antagonistic action on NMDA
receptors on these pathways inhibits pain)
3. Metabolites action • Hydroxyketamine increases analgesic effect without motor
incoordination .
• Norketamine produces more somatic pain than visceral pain relief
4. Neuraxial analgesia • Due to action of spinal opioid receptors and sodium voltage gated
receptors
• Epidurally when combined with other drugs (opioids , local
anesthetics ) produces better analgesic effect
• Intrathecal administration ( 5-50mg in 3ml of saline) with or
without epinephrine produces brief and variable analgesia

42. Clinical uses ( for induction )
1. Dose 1 – 2mg/kg IV or 4-8mg/kg IM ( does not produce pain
on IV injection or venous irritation)
2. Loss of consciousness • Within 30 – 60 seconds after IV administration or 2
to 4 minutes if IM administration
• Consciousness loss is associated with maintenance
of normal or slightly reduced airway reflexes
3. Return of
consciousness
• 10 – 20 minutes but coming back to full orientation
requires at least 60 – 90 minutes
• No retrograde amnesia seen

43. Clinical uses (for IV induction )
Ketamine is preferred for Ketamine is not preferred for
• Induction in pediatric age group ( due to
rapid onset of action )
• Mentally challenged patients ( due to
rapid onset of action )
• Burn dressing, debridement , skin
grafting (for its intense analgesic action)
• Hypovolemic / shock patients ( due to
sympathetic action)
• Patients with bronchial asthma ( as it can
cause bronchodilation)
• Patients planned for vascular procedures
( as it can increase the oxygen
consumption of myocardium)
• Ocular procedures ( due to nystagmus)
• Patients with increased intracranial
procedures
• Patients with systemic or pulmonary
hypertension

44. Effect on organ systems
S.No Organ systems effects
1. CNS • Increase in ICP is seen
• The antagonistic role on NMDA receptors have neuroprotective role
• EEG may show myoclonic and seizure like activity but this is normal and it may have
anti-convulsant property
2. CVS • Posses sympathetic action
• Systemic BP, heart rate, cardiac output, myocardial oxygen consumption all are
increased with ketamine
• Ketamine maintains systemic BP by vasoconstriction thereby decreasing blood flow to
periphery
3. RS • Bronchodilation with preservation of upper airway reflexes and muscle tone
• Increase in tracheobronchial and salivary gland secretions are present and hence ant
sialagogue is added in premedication
4. Others • Can cause allergic reactions
• Can cause platelet aggregation ( can be used in patients with bleeding disorders)

45. Emergence delirium
S.NO Effects Causes
1. Mechanism Secondary to ketamine induced depression of inferior colliculus and
medial geniculate nucleus leading to misinterpretation of auditory and
visual stimuli
2. Incidence • Age older than 15 years
• Female gender
• Doses of ketamine greater than 2mg/kg IV
• A history of personality problems or frequent dreaming
3. Manifestation • Transient cortical blindness
• Vivid dreaming and hallucinations (can be there up to 24 hours)
• Sensation of floating
4. Prevention • Administration of benzodiazepines IV preferably 5 minutes before
induction with ketamine
• Midazolam is considered more effective than diazepam

46. Thiopentone

47. Thiopentone
• Structure
• Preparation
• Dose
• Handling
• Mechanism of action
• Pharmacokinetics
• Pharmacodynamics
• Indications
• Contraindications
• Side effects

48. Structure

52. Handling

55. Pharmacokinetics

56. Pharmacokinetics

58. Pharmacodynamics

59. Pharmacodynamics

60. Pharmacodynamics

64. Intra-arterial injection of Thiopentone

65. Intra-arterial injection of Thiopentone
symptoms

67. Corrective measures

68. SUMMARY
• Propofol is used as induction agent of choice for
majority of cases
• Etomidate is used in patients with cardiac instability
• Ketamine is used in pediatric inductions and for
patients in shock and patients with asthma
• Thiopentone is very selectively used in patients who
require neuroprotection

70. Thankyou