This document provides an overview of several intravenous anaesthetic agents including propofol, etomidate, ketamine, thiopental, midazolam, and dexmedetomidine. It describes the mechanism of action, pharmacokinetics, clinical uses, and effects on organ systems for each agent. The ideal properties of intravenous anaesthetics are discussed. Propofol, etomidate, ketamine and thiopental are described as rapid-acting induction agents while midazolam and dexmedetomidine provide sedation with minimal respiratory depression.

1. IV Anaesthetic Agents
Dr. Priyanka Mahanta
Senior Resident
Dept. of Anaesthesiology

2.  Drugs when given intravenously in an appropriate dose, cause a rapid loss of
consciousness.
 Occurs within ‘one arm-brain circulation time’.

4. Uses
 Induction of anaesthesia
 Maintenance of anaesthesia
 Sedation
 As the sole anaesthetic agent for a small procedure

5. Properties of an ideal IV anaesthetic agent
 Water soluble and stable in solution
 Long shelf life
 No pain on injection
 Rapid and smooth onset of action
 Rapid metabolism to pharmacologically inactive metabolites
 Rapid and smooth recovery
 Absence of post op. nausea vomiting

6. Propofol
 2,6 di-iso propylphenol
 Available in 1% concentration
 Contains soyabean oil, egg lecithin, disodium edetate or sodium metabisulfite
(preservative)
 Supports bacterial growth
 Pain on injection
 Low lipid emulsions- Ampofol
 Non lipid formulation- Aquavan
 Should not be mixed with other drugs

7. 1% emulsion available as 10/20 ml vials/ampoules & 50 and 100
ml vials

8. Mechanism of Action
 Acts at GABAA receptor
 Activates GABAA receptor facilitation of inhibitory neurotransmission mediated by
GABA receptor binding.
 It increases binding affinity of GABA for GABAA receptor.
 Activation of receptor increase in transmembrane chloride conductance
hyperpolarisation of postsynaptic cell membrane functional inhibition
of postsynaptic neuron

9. Pharmacokinetics
 Rapid onset of action
 Rapid clearance- both hepatic as well as extrahepatic
 Oxidized and conjugated in liver and then excreted by kidneys
 After single bolus dose levels decrease rapidly due to redistribution and elimination
with initial distribution half-life 2-8min
 Context sensitive half-time 10 minutes for infusions up to 3 hours and 40 minutes
for 3-8hours
 Clearance not hampered by cirrhosis or renal dysfunction

10. Clinical Uses
 Induction of anaethesia -1.5 to 2.5 mg/kg IV
 Sedation- 25 to 100 mcg/kg/min
 Maintenance of anaesthesia- 100 to 300 mcg/kg/min
 Total intravenous anaesthesia (TIVA)
 Other uses- antiemetic effect- 10 to 20 mg IV
antipruritic effect- 10 mg IV
anticonvulsant effect- >1mg/kg
relieves bronchospasm

11. Effects on organ system
-CNS
 Decrease CMRO2
 Decrease CBF
 Decreae ICP
 Large dose systemic BP cerebral perfusion pressure

12. CVS
 Decrease systemic blood pressure
 Decease cardiac output
 Decrease peripheral vascular resistance

13. Respiratory system
 Depression of ventilation- dose dependent
Propofol infusion syndrome
 Development of lactic acidosis in prolonged high dose propofol infusion (>75mcg
/kg/min for >24 hrs)

14. Etomidate
 Carboxylated imidazole containing
compound
 Avilable as a fat emulsion (2 mg/ml)
 Less irritant and less painful on IV
injection

15. Mechanism of action
 Acts at GABAA receptors
 Increases affinity of the inhibitory neurotransmitter to GABA receptors
Activation of receptor
increase in transmembrane chloride conductance
hyperpolarisation of postsynaptic cell membrane
functional inhibition of postsynaptic neuron

16.  Used as IV induction agent in patients with cardiovascular instability
 Dose - 0.2 to 0.4 mg/kg
 Large volume of distribution
 Highly bound to albumin (76%)
 Prompt recovery due to redistribution as well as metabolism
 Metabolism by hydrolysis by hepatic microsomal enzymes and plasma esterase
 Excreted in urine and bile
 Elimination half time 2-5 hrs

17. Effects on organ system
 CNS – decrease cerebral blood flow
Activates seizure foci
 CVS – minimal effect in heart rate, stroke volume, cardiac output
preferred in patients with poor cardiac reserve
 RS – depresses ventilation
 Myoclonus – use cautiously in patients with seizure disorder
 Adrenocortical suppression –inhibits 11-B-hydroxylase, an enzyme important in
adrenal steroid production
lasts for 4-8 hrs after administration

18. Ketamine
 Phencyclidine derivative
 Produces dissociative anesthesia –
dissociation between thalamocortical
and limbic system
 Intense analgesic effect
 Produces emergence delirium
 Abuse potential

19. Mechanism of action
Acts on multiple CNS receptors
 NMDA receptors- Inhibits NMDA rec activation by Glutamate.
Reduces presynaptic release of Glutamate.
 Opioid receptors- directly interacts with mu, kappa and delta receptors
 Monoaminergic receptors- activates descending inhibitory monoaminergic pain
pathway
 Muscarinic- antagonistic effect
 Sodium channel- interacts with voltage gated sodium channel- mild LA like effects
 Nicotinic acetylcholine receptors- may have a role in analgesic property

20.  Rapid onset of action
 Short duration of action
 High lipid solubility
 Metabolised by hepatic microsomal enzymes to norketamine
 Excreted in urine and stool
 Elimination half time 2-3 hrs

21. Uses
 Induction of anaesthesia- 1-2 mg/ml IV or 4-8mg/kg IM
 Analgesia- subanaesthetic dose of 0.2 -0.5 mg/kg
 Adjuvant in epidural anesthesia

22. Effects on organ system
 Central Nervous System
• cerebral blood flow --- Increase
• CMRO2---Increase
• Intracranial Pressure--- Increase
 Cardiovascular System
• Sympathetic nervous system stimulation
• Systemic and pulmonary arterial blood pressure---- increased
• Heart rate ---- increased • Cardiac output---- increased
• Myocardial oxygen requirements ---- increased

23.  Ventilation and Airway
• Depression of ventilation: not significant
• Upper airway skeletal muscle tone :maintained,
• Upper airway reflexes : intact
• Salivary and tracheobronchial mucous gland: Increased secretions
• Use antisialagogue before ketamine
• Bronchodilatory effects

24.  Emergence Delirium (Psychedelic Effects)
•In postoperative period visual, auditory, proprioceptive, and confusional
illusions, which may progress to delirium.
•Dreams and hallucinations can occur up to 24 hours after the
ketamine.
•Mechanisms - Emergence delirium probably occurs secondary to ketamine
induced depression of the inferior colliculus and medial geniculate nucleus, thus
leading to the misinterpretation of auditory and visual stimuli.
• The loss of skin and musculoskeletal sensations results in a decreased
perceive gravity producing a sensation of bodily detachment or floating in space

25. FACTORS ASSOCIATED WITH AN INCREASED INCIDENCE
• Age greater than 15 years
• Female gender
• Dose greater than 2 mg/kg IV
• History of frequent dreaming
PREVENTION OF KETAMINE-INDUCED EMERGENCE DELIRIUM
• Midazolam (administer IV about 5 minutes before induction of
anesthesia with ketamine)
• use of thiopentone or inhaled anaesthetic

26. Thiopental
 Barbituric acid derivative
 Commercially available as dry
amorphous pale yellow coloured
powder
 Reconstituted with sterile water
 Dose 4-5 mg/kg IV

27. Mechanism of Action
 Potentiate GABA activity in CNS.
 Increases affinity of neurotransmitter GABA for its binding site
 Prolongs duration of GABA activated chloride channel
 At higher doses, mimics the action of GABA
 Also acts on Glutamate, Adenosine and neuronal Nicotinic Acetylcholine receptors

28. Pharmacokinetics
 Rapid onset and rapid awakening after single IV injection
 Rapid redistribution from brain to inactive tissues
 Highly protein bound
 Prolonged context sensitive half time
 Metabolised in liver and excreted in urine

29. Effects on organ system
 CARDIOVASCULAR
• Fall in blood pressure
• Elevation in heart rate
 RESPIRATORY
• Ventilatory response to hypercapnia and hypoxia ---Decreases
• Tidal volume --- decreased
• Respiratory rate --- decreased
• Bronchospasm in asthmatic patients or laryngospasm in lightly
anesthetized patients
• Release of histamine

30.  CNS
• Cerebral blood flow --- Decreased
• Intracranial pressure---Decreased
• Cerebral perfusion pressure--- Increased (CPP equals cerebral artery pressure
minus cerebral venous pressure or intracranial pressure.)
• Cerebral oxygen consumption --- Decreased
• This effect of barbiturates may protect the brain from transient episodes of
focal ischemia (eg, cerebral embolism) but probably not from global ischemia (eg,
cardiac arrest).

31.  Liver-
• hepatic microsomal enzyme induction
• Precipitates porphyria

32. Benzodiazepine- Midazolam
 Anxiolytic
 Sedative
 Anticonvulsant
 Spinal cord mediated skeletal muscle relaxant
 Anterograde amnesia

33. Mechanism of action
 Facilitates the action of GABA at its receptor site
 Dose- 0.07- 0.12 mg/kg IM for premedication
0.01- 0.1 mg/kg IV for sedation
0.1- 0.4 mg/kg IV for induction

34.  Metabolised by hepatic and intestinal cytochrome P450 enzyme
 Metabolite 1hydroxymedazolam has half of its activity
 Conjugated with glucuronide in liver
 Excreted by kidney

35. Effects on Organ Systems
CARDIOVASCULAR
 Minimal cardiovascular depressant effects even at induction doses.
 Arterial blood pressure ,Cardiac output, Peripheral vascular resistance -
decline slightly
 Heart rate ---- slight rise
 Midazolam tends to reduce blood pressure and peripheral vascular resistance more
than diazepam.

36. RESPIRATORY
 Dose dependent respiratory depression
 Depresses swallowing reflexes and upper airway reflex activity

37. CNS
 Cerebral oxygen consumption, cerebral blood flow, and intracranial pressure----
Reduce
 Anti convulsant properties
 Anterograde amnesia
 Mild muscle-relaxant property --- mediated at the spinal cord level, not at the
neuromuscular junction
 Slower loss of consciousness and a longer recovery

38. Dexmedetomidine
 Alpha 2 adrenergic agonist
 Provide analgesia, sedation, anxiolysis, hypnosis and sympatholysis
 Acts on 2 receptors in locus ceruleus – sedative-hypnotic effect
 At spinal level – analgesia
 Produce conscious sedation with minimal respiratory depression

39. Effects on organ system
 CVS – decrease heart rate, SVR, myocardial contractility, CO, SBP
effects more pronounced with the loading dose
 Respiratory system – reduction in minute ventilation but ventilatory response to
hypercarbia is retained.
 CNS – decrease intracerebral catecholamine outflow, modulation of proapoptotic
and aniapoptotic proteins - neuroprotection

40.  Metabolised in liver- methyl and glucuronide conjugation
 Excreted by kidney

41. Uses
 Premedication- 0.33-0.67 mcg/kg IV
 Blunts tracheal intubation reflex
 Intra and post operative sedation – loading dose 1 mcg/kg over 10 mins followed
by 0.2-0.7 mcg/kg/hr IV infusion

42. Which drug to use?
 Type of the surgical procedure
 Pathophysiological condition of the patient
 pharmacokinetic and pharmacodynamics properties of the drugs
 Cost and availability

43. Thank you