Induction Agents - Propofol, Sodium Thiopental, Ketamine,

Intravenous Anaesthetics are a group of fast-acting
compounds that are used to induce a state of impaired
awareness of complete sedation.
These are drugs that, when given intravenously in an
appropriate dose, cause a rapid loss of consciousness.

1. Induction Agents
Mr. Harshad Khade
MSc. Medical Technology (OTA)
Symbiosis International University, Pune.

2. Introduction
Intravenous Anaesthetics are a group of fast-acting
compounds that are used to induce a state of impaired
awareness of complete sedation.
These are drugs that, when given intravenously in an
appropriate dose, cause a rapid loss of consciousness.

3. They are used:
To induce anaesthesia prior to other drugs being given
to maintain anaesthesia.
As the sole drug for short procedures.
To maintain anaesthesia for longer procedures by
intravenous infusion.
To provide sedation

4. Ideal IV InductionDrug
Physical properties
•Water soluble & stable in solution
•Stable on exposure to light
•Long shelf life
•No pain on intravenous injection
•Cheap
Pharmacokinetic properties
•Rapid onset in one arm-brain
circulation time
•Rapid redistribution to vessel
rich tissue
•Rapid clearance and metabolism

5. Drugs
Propofol Sodium Thiopental
OpioidsBenzodiazepineEtomediate
Ketamine
Intra-venous Anesthetic Agents

6. Propofol
Class
Alkylphenolintravenous anesthetic agent.
Uses
1. for the induction and maintenance of general anaesthesia
2. for sedation during intensive care and regional anaesthesia, and has
been used
3. in the treatment of refractory nausea and vomiting in patients receiving
chemotherapy and
4. in the treatment of status epilepticus.
Main action Hypnotic

7. Mode ofaction
•The mode of action is unclear. It potentiates the inhibitory transmitters
glycine and GABA (via different mechanisms to those of Thio-barbiturates
and benzodiazepines) and may reduce Na+ channel opening times.
Presentation
•Being highly lipid-soluble, as a white oil-in-water emulsion containing
•1% or 2% w/v of Propofol in soybean oil (100 mg/ml),
•egg lecithin (purified egg phosphatide) (12 mg/ml),
•benzyl alcohol (1 mg/ml) (to retard the growth of accidental
microorganism inoculation),
•glycerol (22.5 mg/ml), and
•sodium hydroxide to adjust pH (7–8.5).

8. Routes ofadministration/doses
•Propofol is administered intravenously in a bolus dose of 1.5–2.5 mg/kg
for induction and as an infusion of 4–12 mg/kg/hour for maintenance of
Anaesthesia in adults.
•Children require a bolus dose increase of 50% and an increase of
maintenance infusion by 25–50%.
•Patients who are elderly or unstable require dose reductions accordingly
(induction 1–1.5 mg/kg, maintenance 3–6 mg/kg/ hour).
•Co-induction of an opioid and/or benzodiazepine, or administration as
premedication, will lower the required dose of propofol further.
•Plasma concentrations of 2–6 micrograms/ml and 0.5–1.5 micrograms/ml
are associated with hypnosis and sedation, respectively.

9. Onset
•Within one arm-brain circulation time (approximately 20 seconds).
Duration
•Approximately 5-8 minutes after single induction dose. Offset of effect is
more prolonged
Elimination
•Rapid redistribution away from central nervous system (CNS) into lean
body compartment accounts for prompt awakening.
•Metabolized by liver and extrahepatic sites then excreted by kidney.
•when administered as a continuous infusion.

10. Effects
•CNS
•Profound CNS depressant, potentiating the depressant effects of opioids,
sedatives and volatile anesthetics.
•Decreases cerebral metabolic rate and intracranial pressure.
•Occasionally excitement, tonic-clonicmovements or opisthotonusis seen
on induction with Propofol.
•CVS
•Causes direct myocardial depression and vasodilation leading to
hypotension.
•Propofol must be used with caution in patients with poor left ventricular
function or critical coronary artery insufficiency or in those who are
seriously ill or debilitated

11. •Respiratory
•Depression of respiratory center leads to brief apnea.
•Propofol effectively blunts the airway’s response to manipulation thus
hiccoughing and bronchospasm are rarely seen.
•Misc.
•Pain on injection seen in up to 20%.
•Mild anti-emetic properties.
•Patients often experience pleasant dreams under anesthesia followed by
a smooth, clear-headed emergence.
•Strict aseptic technique must be used when handling propofol as the
vehicle is capable of supporting rapid growth of micro-organisms.
Contraindications
•Allergies to egg, egg products, soybeans or soy products

12. Sodium Thiopental
Class
•Short-acting barbiturate.
Main actions
•Hypnotic and anticonvulsant.
Mechanism of action
•Decreases the rate of dissociation of the inhibitory neurotransmitter GABA
from its receptors resulting in depression of the reticular activating system

13. Uses
1. Induction of anaesthesia.
2. In the management of status epilepticus and has been used
3. It is also useful as an anticonvulsant or for the rapid reduction of elevated
intracranial pressure.
4. An anesthetic induction agent but has largely been replaced by propofol.
Presentation
•As a hygroscopic yellow powder, containing thiopental sodium and 6%
sodium carbonate, stored under an atmosphere of nitrogen.
•The drug is reconstituted in water prior to use to yield a 2.5% solution with
a pH of 10.8 and pKaof 7.6, which is stable in solution for 24–48 hours.

14. Routes ofadministration/doses
•The dose by the intravenous route is 2–7 mg/kg;
•3-5 mg/kg IV for healthy adults
•5-6 mg/kg IV for children
•7-8 mg/kg IV for infants
•following bolus administration,
•Thiopental acts in one arm–brain circulation time and lasts for 5–15
minutes; it is cumulative with repeated administration.
Onset
•Within one arm-brain circulation time (approximately 20 seconds).
Duration
•Approximately 5-10 minutes after single induction dose

15. Effects
•CNS
•Profound CNS depressant.
•Decreases cerebral metabolic rate and intracranial pressure.
•May cause hyper tonus, twitching and tremors during induction.
•May contribute to post-operative confusion and delirium.
•Potentiates the depressant effects of opioids, sedatives, alcohol and volatile
anesthetics.
•CVS
•Depression of myocardial contractility and vasodilation leads to decreased
cardiac output and blood pressure with a mild compensatory tachycardia.
•Must be used with caution in patients with poor left ventricular function or
critical coronary artery insufficiency or in those who are seriously ill or
debilitated

16. •Respiratory
•Depresses the rate and depth of breathing leading to brief period of
apnea.
•Does not blunt the airway’s response to manipulation therefore coughing,
hiccoughing, laryngospasm and bronchospasm may be seen at light
planes of anesthesia.
•GINausea and vomiting
•Misc.
•Incompatible with drugs with acidic pH.For example, if given in the IV
line with vecuronium (a NDMR no longer in use), precipitation would
occur.
•Arterial or extravascular injection produces necrosis.
ContraindicationsPorphyria

17. Ketamine
Class
•Phencyclidine derivative.
Uses
1. For the induction of anaesthesia, especially in poor-risk patients with
hypotension or asthma
2. As a sole agent for short procedures such as change of burns dressings
3. For pre-hospital care and mass casualties
4. For analgesia both post-operatively and in patients receiving intensive care
5. For pain relief in patients with chronic pain, and
6. For the reversal of severe unresponsive asthma.

18. Main actions
•Dissociative anaesthesia(a combination of profound analgesia with
superficial sleep.
Presentation
•Ketamine has a molecular weight of 238 and is presented as a colorless
solution containing 10/50/100 mg/ml of racemic ketamine hydrochloride.
•It has a pH of between 3.5 and 5.5, with a pKaof 7.5.
•The racemic mixture contains in equal proportions two enantiomers due
to its chiral center of the cyclo-hexanonering ([S-(+)-ketamine] and [R-
(−)-ketamine]).
•All preparations now contain 0.1 mg/ml of benzethoniumchloride as a
preservative.
•S-(+)-ketamine is available in 5 and 25 mg/ ml concentrations.

19. Mode ofaction
•Ketamine is a non-competitive antagonist of the NMDA receptor Ca2+ channel
pore and also inhibits NMDA receptor activity by interaction with the
phencyclidine binding site.
•Inhibition of glutamate-gated NMDA receptors by ketamine provides a
mechanism of a predominant analgesic profile.
•It reduces the pre-synaptic release of glutamate, in addition to complex
interactions with opioid receptors.
•There is some evidence suggesting that ketamine acts as an antagonist at
monoaminergic, muscarinic, and nicotinic receptors.
•Ketamine has local anaestheticactivity at high doses which may be the result of
sodium channel inhibition.
•S-(+)-ketamine has four times greater affinity for the NMDA receptor than R-(−)-
ketamine.
•It is twice as potent as the racemic mixture and three times as potent as the R(−)
form.

20. Routes ofadministration/doses
•The intramuscular dose for induction of anaesthesiais 4–10 mg/kg; the onset of action is
2–8 minutes, and the duration of action is 10–20 minutes.
•The corresponding intravenous dose is 0.5–2 mg/kg, administered over a period of 60
seconds; the onset of action occurs within 30 seconds, and the duration of action is 5–10
minutes.
•Ketamine may be used for the maintenance of anaesthesia,
•using an intravenous infusion at a rate of between 10 and 50 micrograms/ kg/min.
•For sedation and analgesia, an intramuscular dose of 2–4 mg/kg or an intravenous dose of
0.2–0.75 mg/kg may be used, followed by an infusion of 5–20 micrograms/kg/min.
•Ketamine may also be administered orally, rectally, nasally, intrathecally, or extradurally.
•When used neuroaxially, the preservative-free solution must be used
•Tolerance develops with repeated drug exposure.

21. Dose
•Induction of anesthesia: 2 mg/kg IV
•Induction of anesthesia: 5 mg/kg IM
Onset
•Within one arm-brain circulation time (approximately 20 seconds).
Duration
•Approximately 10-15 minutes after single induction dose, with full
orientation occurring after 15-30 minutes.
Elimination
•Redistribution from central nervous system (CNS) to inactive tissue sites
accounts for termination of unconsciousness. Ultimate clearance is via
hepatic metabolism and renal excretion.

22. Effects
•CNS:
•Produces “dissociative anesthesia” with patient in a cataleptic state.
•Ketamine provides a state of unconsciousness and intense analgesia however the
patient’s eyes may remain open and roving, and their limbs may move
purposelessly.
•Cerebral metabolic rate and intracranial pressure are increased.
•CVS
•Ketamine increases sympathetic outflow from the CNS leading to increased heart
rate, blood pressure and cardiac output.
•Because of this effect, ketamine plays an important role in the management of
patients with hypovolemic shock or cardiac tamponade.
•However, ketamine does possess direct myocardial depressant effects which may
lead to worsened hypotension in patients in a prolonged shock state

23. •Respiratory
•Some degree of airway protection is maintained.
•The patient may cough or swallow.
•Airway secretions increase.
•Bronchodilatoryeffect is secondary to increased sympathetic tone.
•Apnea is rare as respiratory drive is maintained.
•Misc.
•Undesirable psychological reactions are common on emergence: vivid,
unpleasant dreams, excitement, confusion, fear.
•They tend to occur in the first hour of emergence and abate within one to several
hours.
•Pretreatmentwith benzodiazepines may help minimize this effect.
Contraindications
•Raised intracranial pressure, coronary ischemia, psychiatric disease, eye surgery.

24. Etomidate
Class
•Short-acting hypnotic; anesthetic induction agent. Useful in hemodynamically-
compromiseedpatients.
Uses
1. for the intravenous induction of general anaesthesia
2. in treatment prior to surgery for Cushing’s syndrome
Main actionHypnotic
Presentation
•As a clear, colourlesssolution for injection containing 2mg/ml of etomidatein an
aqueous vehicle of 35% propylene glycol andwater.
•Etomidate is a weak base with a pKaof 4.2. The pH of the aqueous solution is 8.1.

25. Mode ofaction
•Etomidate appears to act upon GABA type Areceptors to modulate fast
inhibitory synaptic transmission within the CNS.
•In animal models, the beta-3 subunit of the GABAA receptor appears to
have a role in etomidate-induced anaesthesia.
•It has a chiral centreresulting in enantiomers.
•The R(+) isomer of etomidateis ten times more potent than its S(−) isomer
at potentiating GABAA receptor activity.
Routes ofadministration/dose
•Etomidate is administered intravenously in a dose of 0.3 mg/kg; the drug
acts in 10–65 seconds, with a duration of action of 6–10 minutes.
•In elderly patients, the dose should be reduced to 0.15–0.2 mg/kg.
•Etomidate is non-cumulative with repeated administration

26. Dose
•Induction: 0.2-0.6 mg/kg IV
Onset
•Within one arm-brain circulation time (approximately 20 seconds).
Duration
•Approximately 5-10 minutes after single induction dose.
Elimination
•Rapid redistribution from central nervous system (CNS) to lean body
tissue accounts for brief duration of action.
•Ultimately metabolized by hepatic and plasma esterasesto inactive
products

27. Effects
•CNS
•CNS depressant, potentiating the depressant effects of opioids, sedatives
and volatile anesthetics.
•Decreases cerebral metabolic rate and intracranial pressure.
•The cerebroprotectiveeffects of etomidatemake it useful in the
management of the head-injured patient. Can cause seizure-like activity.
•CVS
•Etomidate is notable for the lack of significant cardiovascular depression
that it causes.
•Therefore it is commonly chosen to facilitate intubation in the trauma
patient, patients with hypovolemic shock or other unstable patients.

28. •Respiratory
•Etomidate causes a brief period of apnea.
•GI
•Nausea and vomiting
•Misc.
•Etomidate suppresses corticosteroid synthesis in the adrenal cortex and
can lead to primary adrenal suppression.
•For this reason, its use in patients with sepsis is controversial.
•Etomidate can result in trismusif administered too quickly

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