Intravenous Induction

Agents

Moderator – Dr Lalit Gupta

Presenter – Dr. Mansimrat Singh
What are IV induction drugs

• These are drugs that, when given intravenously in an appropriate

dose, cause a rapid loss of consciousness.
• One arm-brain circulation time

• 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
Ideal IV induction drug

Physical properties

•Water soluble & stable in solution

• Stable on exposure to light
• Long shelf life
• No pain on intravenous injection
•Non-irritant when injected subcutaneously
• Low incidence of thrombophlebitis
• Cheap
Pharmacokinetic properties
• Rapid onset in one arm-brain circulation time
• Rapid redistribution to vessel rich tissue
•Rapid clearance and metabolism
•No active metabolites

Pharmacodynamics properties
• High therapeutic ratio
•Minimal cardiovascular and respiratory effects
•No histamine release/hypersensitivity reactions
• No emetic effects
• No involuntary movements
•No emergence nightmares
•No hang over effect
•No adrenocortical suppression
• Safe to use in porphyria
Drug
s
BARBITURATES

PROPOFOL
KETAMINE

ETOMIDATE

BENZODIAZEPINE

OPIOIDS
 BARBITURAT
ES
e.g.
• Thiopental
• Thiamylal
• Pentobarbital
• Secobarbital
• Methohexital

Mechanisms of Action
• Depress the reticular activating
• Suppress transmission of excitatory neurotransmitters
(acetylcholine)
• Enhance transmission of inhibitory neurotransmitters
(GABA)
 BARBITURAT
ES

Structure

• Barbiturates are barbituric acid derivatives

• Pale yellow colored powder
• Kept in environment of nitrogen
• The sodium salts of the barbiturates are water soluble
• pH of 2.5% thiopental 10 .5
• Self life : 2 wk 2.5% thiopental solution
 BARBITURAT
ES

Pharmacokinetics

• Highly protein bound (80%)

• The duration of action of is determined by redistribution, not
metabolism or elimination
• Maximal brain uptake within 30 s
• Subsequent redistribution to the peripheral lowers plasma and brain
concentration to 10% of peak levels within 20–30 min
• This pharmacokinetic profile correlates with clinical
experience—patients typically lose consciousness within 30 s
and awaken within 20 min.
 BARBITURATES

• BIOTRANSFORMATION
• Hepatic oxidation to inactive water-soluble metabolites.

• EXCRETION
• Renal excretion
• Important for less protein-bound and less lipid-soluble agents such as
phenobarbital,
• Water-soluble end products of hepatic biotransformation.
 BARBITURATES

Route and dose

 BARBITURAT
ES
Effects on Organ Systems
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
• Barbiturates do not completely depress noxious airway reflexes
• Release of histamine
 BARBITURATES

• Cerebral
• Cerebral blood flow --- Decrease
• Intracranial pressure---Decrease
• Cerebral perfusion pressure--- Increased
• (CPP equals cerebral artery pressure minus cerebral venous pressure or
intracranial pressure.)
• Cerebral oxygen consumption --- Decrease

• 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).

• To have an antianalgesic effect by lowering the pain threshold

• Do not produce muscle relaxation.
 BARBITURATES

• RENAL
• Reduce renal blood flow and glomerular filtration rate in proportion
to the fall in blood pressure.
• HEPATIC
• Hepatic blood flow is decreased.
• Induction of hepatic enzymes increases the rate of metabolism of
some drugs
• The induction of aminolevulinic acid synthetase stimulates the formation of
porphyrin (an intermediary in heme synthesis), which may precipitate acute
intermittent porphyria or variegate porphyria in susceptible individuals.

• IMMUNOLOGICAL
• Sulfur-containing thiobarbiturates evoke mast cell histamine release
in vitro, whereas oxybarbiturates do not.
 BARBITURATES

 Specific complication :

 Intra-arterial Injection
• Immediate, intense vasoconstriction and excruciating pain that radiates
along the distribution of the artery.
• Severe Vasoconstriction may obscure distal arterial pulses.
• Gangrene and permanent nerve damage may occur.
 BARBITURATES

Mechanism of Damage
• Due to be the precipitation of thiopental crystals inflammatory
response and arteriti s microembolization that follows, eventually
results in occlusion of the distal circulation.
Treatment
• Immediate attempts to dilute the drug --- injection of saline
• Prevention of arterial spasm & sustain adequate blood flow—
• lidocaine, papaverine, or phenoxybenzamine
• stellate ganglion block or brachial plexus block
 Propofo
l
• Structure
• Propofol (2,6-diisopropylphenol)
• Propofol is not water soluble
• 1% solution (10 mg/mL) --- an oil-in-water emulsion
Containing
• soybean oil
• glycerol
• egg lecithin
• Mechanisms of Action
• Facilitation of inhibitory neurotransmission mediated by
GABA.
 Propof
ol
Pharmacokinetics
• DISTRIBUTION
• High lipid solubility
• onset of action that is almost as rapid as that of thiopental (one-arm-to-brain
circulation time).
• Awakening from a single bolus dose is also rapid due to a very short initial
distribution half-life (2–8 min).
• Recovery --- rapid
• Hangover --- less
• This makes it a good agent for outpatient anesthesia.

• BIOTRANSFORMATION
• Hepatic and extra hepatic metabolism
• EXCRETION
• Primarily excreted in the urine
• chronic renal failure does not affect clearance of the parent
drug.
 Propof
ol
Effects on organ
CARDIOVASCULAR
• Blood pressure ---decrease due to a
• Fall in systemic vascular resistance
• Hypotension is more pronounced than with thiopental.
• HR: No change /Bradycardia

RESPIRATORY
• Profound respiratory depressant following an induction dose---apnea
• Inhibits hypoxic ventilatory drive and depresses the normal response to
hypercarbia.
• Depression of upper airway reflexes
• Helpful during intubation or laryngeal mask placement in the absence of
paralysis.
• Lower incidence of wheezing
• Safe in asthmatic patients.
 Propofol

CEREBRAL
• Cerebral blood flow---- decreases
• Intracranial pressure---- decreases.

• Antiemetic effects
• preferred drug for outpatient anesthesia.
• Anticonvulsant properties (ie burst suppression)
• used to terminate status epilepticus.
• Safely administered to epileptic patients.
• Intraocular pressure----Decreases
 Propof
ol

Use :
• Induction of Anesthesia 1.5 to 2.5 mg/kg
• Intravenous Sedation 25 to 100 µg/kg per minute IV
• Maintenance of Anesthesia 100 to 300 µg/kg per minute IV
• Nonhypnotic Therapeutic Applications
• Antiemetic Effects
• Mech –unknown
• 10 to 15 mg IV
• Anticonvulsant Activity
• Attenuation of Bronchoconstriction
 Propofol
Specific complication

• Lactic Acidosis or propofol infusion syndrome

• Prolonged high-dose infusions of propofol (>75 µg/kg per minute) for
longer than 24 hours.
• Mechanism –
• Unclear
• Cytopathic hypoxia of the electron transport chain and impaired
oxidation of long-chain fatty acids
• C/F
• Unexpected tachycardia
• Diagnosis
• Arterial blood gases and serum lactate concentrations
• Treatment
• Metabolic acidosis in its early stages is reversible with
discontinuation of propofol administration.
 Propofol
• Pain on Injection
• Most common
• Reduced by
• 1% lidocaine
• Potent short-acting opioid eg Fentanyl

• Bacterial Growth
• Supports the growth of Escherichia coli and Pseudomonas aeruginosa.
• Recommendation:
• An aseptic technique be used in handling propofol, as reflected by disinfecting
the ampule neck surface or vial rubber stopper with 70% isopropyl alcohol.
• The contents of the ampule containing propofol should be withdrawn into a
sterile syringe immediately after opening and administered promptly.
• The contents of an opened ampule must be discarded if they are not used within
6 hours. In the ICU, the tubing and any unused portion of propofol must be
discarded after 12 hours.
 KETAMINE

Mechanisms of Action
• N-methyl-D-aspartate receptor antagonist.
• Produce dissociative Anaesthesia

Structure :
• structural analogue of phencyclidine
 KETAMINE

Pharmacokinetics
• ABSORPTION
• Intravenously or intramuscularly
• Peak plasma levels are usually achieved within 10–15 min after
intramuscular injection.
• DISTRIBUTION
• Ketamine is more lipid soluble and less protein bound than
thiopental
• Half-life is 10–15 min
• Awakening is due to redistribution to peripheral
compartments.
• BIOTRANSFORMATION
• Liver to several metabolites (eg, norketamine)
• EXCRETION
• End products of biotransformation are excreted renally
 KETAMIN
E

Uses
• Induction of Anesthesia
• Intravenous ketamine, 1 to 2 mg/kg
• Intramuscular administration of 4 to 8 mg/kg.
• Analgesia
• Subanesthetic doses of ketamine, 0.2 to 0.5 mg/kg IV.
• Neuraxial Analgesia
• Limited value.
 KETAMIN
E
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
 KETAMIN
E
• But in Critically ill patients
• Unexpected decreases in systemic blood pressure and cardiac output, which
may reflect a depletion of endogenous catecholamine stores and exhaustion
of sympathetic nervous system compensatory mechanisms.
• Unmasking of ketamine's direct myocardial depressant effects.
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 are
increased
• Use antisialagogue before ketamine
• Bronchodilatory effects
• Drug of choice for induction patients with asthma
 KETAMINE

Specific Complications
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
administration of 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.
 KETAMIN
E

• The loss of skin and musculoskeletal sensations results in a decreased

ability to perceive gravity producing a sensation of bodily detachment or
floating in space

• 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)
• Prospective discussion with patient about side effects of
ketamine
 ETOMIDAT
E

• Structure
• Carboxylated imidazole-containing compound

• Commercial Preparation
• Etomidate is prepared as a fat emulsion, and pain on injection and venous
irritation is unlikely.

• Mechanism of Action
• GABA receptors
 ETOMIDAT
E

Uses
• Etomidate (0.2 to 0.4 mg/kg IV)
• As an alternative to propofol or barbiturates for the induction of
anesthesia, especially in the presence of an unstable cardiovascular
system.
 ETOMIDATE

Effects on organ system

•Central Nervous System
• Potent direct cerebral vasoconstrictor that decreases cerebral blood
flow and CMRO2
• Activate seizure foci
• Caution in patients with focal epilepsy
• Facilitate the localization of seizure foci in patients undergoing the cortical
resection of epileptogenic tissue.
•Cardiovascular System
• Cardiovascular stability (minimal changes in heart rate, stroke volume,
cardiac output)
• Preferred for Induction of anesthesia in patients with little
or no cardiac reserve.
 ETOMIDAT
E
• Ventilation
• Depressant effects on ventilation
• Pain on Injection
• Pain on injection and venous irritation has been virtually eliminated
with use of etomidate preparations utilizing a lipid emulsion vehicle
rather than propylene glycol
• Myoclonus (spontaneous movements)
• Caution in the use of this drug for the induction of anesthesia in patients with
a history of seizure activity.
• Adrenocortical Suppression
• lasts 4 to 8 hours after an intravenous induction dose of etomidate.
• Be considered desirable from the standpoint of “stress-free”
anesthesia.
 Benzodiazepi
ne
• E.g.
• Midazolam
• Diazepam

MECHANISM OF ACTION
• Facilitating the actions of γ-aminobutyric acid (GABA), the
principal inhibitory neurotransmitter in the CNS

• Benzodiazepines do not activate GABAA receptors but

rather enhance the affinity of the receptors for GABA.
 Benzodiazepine
Uses and Doses of Commonly Used Benzodiazepines
 Benzodiazepi
ne
Effects on Organ Systems
CARDIOVASCULAR
•Minimal cardiovascular depressant effects even at induction doses.
•Arterial blood pressure
•Cardiac output decline slightly
•Peripheral vascular resistance

•Heart rate ---- slight rise

•Midazolam tends to reduce blood pressure and peripheral vascular

resistance more than diazepam.
 Benzodiazepi
ne

RESPIRATORY
•Depress the ventilatory response to CO
2

•Apnea may be less common after benzodiazepine induction

than after barbiturate induction.
•Ventilation must be monitored in all patients receiving
intravenous benzodiazepines, and resuscitation equipment
must be immediately available.
 Benzodiazepi
ne

CEREBRAL

• Cerebral oxygen consumption, cerebral blood flow, and

intracranial pressure----Reduce
• Anti seizures properties
• Antegrade amnesia------premedication
• Mild muscle-relaxant property --- mediated at the
spinal cord level, not at the neuromuscular junction.
• Slower loss of consciousness and a longer recover
 OPIOIDS
• E.g.
• Morphine
• Fentanyl
• Sufentanyl
• Meperidine

Mechanisms of Action
• Opioids bind to specific receptors located throughout the central
nervous system and other tissues.
• Four major types of opioid receptor
•µ
•Κ
•σ
•δ

• Opiate–receptor activation inhibits the presynaptic release and postsynaptic

response to excitatory neurotransmitters (eg, acetylcholine, substance P) from
 OPIOIDS
Uses and Doses of Common Opioids
 OPIOIDS
Effects on Organ Systems
CARDIOVASCULAR
•Do not seriously impair cardiovascular function.
•Cardiac contractility--- do not depress (except meperidine)
•Heart rate
• Increase ----Meperidine
• Decrease ---High doses of morphine, fentanyl, sufentanil.
•Blood pressure --- Decreased
• As a result of bradycardia, venodilation, and decreased sympathetic
reflexes
• Meperidine and morphine --- can lead to profound drops in systemic
vascular resistance and arterial blood pressure due to histamine
release
• The effects of histamine release can be minimized in susceptible
patients by slow opioid infusion, adequate intravascular volume, or
pretreatment with H1 and H2histamine antagonists.
 OPIOIDS
Respiratory
• Respiratory rate– decrease
• Apneic threshold( the highest PaCO2 at which a patient remains apneic)
--- elevated
• Hypoxic drive -- decreased.
• Histamine-induced bronchospasm --- Morphine and meperidine
• Chest wall rigidity ( fentanyl, sufentanil, and alfentanil)
• Enough to prevent adequate ventilation.
• Centrally mediated muscle contraction
• After large drug boluses
• Effectively treated with neuromuscular blocking agents.
• Blunt airway reflex
 OPIOIDS

CEREBRAL

• Effects on cerebral perfusion and intracranial pressure ---variable

• Cerebral oxygen consumption, cerebral blood flow, and intracranial
pressure--- slight reduction.
• Stimulation of the medullary chemoreceptor trigger zone is ----high
incidence of nausea and vomiting.
• Physical dependence

• Use of opioids in epidural and subdural spaces has revolutionized

pain management.
• Management of perioperative shivering ---Intravenous
meperidine
 OPIOIDS

• GASTROINTESTINAL
• slow gastric emptying time by reducing peristalsis.
• Biliary colic may result from opioid-induced contraction of the
sphincter of Oddi.

• ENDOCRINE
• Stress response to surgical stimulation ---decresed
• Ischemic heart disease patients may benefit from attenuation of the
stress response .
Thank You