Intravenous Induction

Agents

Dr.Charulatha.R MD Fellowship in
RA
Department of Anaesthesia &
Critical care

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 11 seconds
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
Rapid onset and offset
Analgesia at subanesthetic dose
Minimal cardiorespiratory depression
No emetic effect
No excitatory and emergence phenomenon
No interaction with NM blocking agent
No pain on injection
No venous sequel

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

Drugs
BARBITURATES

PROPOFOL
KITAMINE

ETOMIDATE
BENZODIAZEPINE
OPIOIDS

BARBITURATES
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)

BARBITURATES

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

BARBITURATES

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 2030
min

This pharmacokinetic profile correlates with

clinical experiencepatients 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.

Pharmacokinetics
onset of action of i.v.injection -10 -20 sec.peak
30 -40 sec
Duration for awakening 5 -15 min
Prompt awakening after single i.v .injection is
due to rapid redistribution to lean body tissue
Volume of distribution is 2.5 l/Kg
Ultimate elimination is due to hepatic
metabolism
Effect site equilibration is rapid
Brain 30 sec Muscle 15 min Fat >30 min

BARBITURATES

Route and dose

BARBITURATES

Effects on Organ Systems

CARDIOVASCULAR
Fall in blood pressure
Elevation inheart 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 mayprotect 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 arteritis
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

Propofol
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.

Propofol
Pharmacokinetics
DISTRIBUTION

High lipid solubility

onsetof action that is almost as rapid as that of thiopental (one-armto-brain circulation time).
Awakening from a single bolus dose is also rapid due to a very short
initial distribution half-life (28 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.

Propofol
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 aninduction 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

Propofol
Use :
Induction of Anesthesia 1.5 to 2.5 mg/kg
Intravenous Sedation 25 to 100 g/kg per minute IV
Maintenance of Anesthesia 100 to 300 g/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 g/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 1015
min after intramuscular injection.

DISTRIBUTION

Ketamine is more lipid soluble and less protein bound

than thiopental
Half-life is 1015 min
Awakening is due to redistribution to peripheral
compartments.

BIOTRANSFORMATION

Liver to several metabolites (eg, norketamine)

EXCRETION

End products of biotransformation are excreted renally

KETAMINE

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.

KETAMINE
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

KETAMINE
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.

KETAMINE
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

ETOMIDATE

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

ETOMIDATE

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.

ETOMIDATE
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 stressfree anesthesia.

Benzodiaze
pine
E.g.
Midazolam
Diazepam
MECHANISM OF ACTION
Facilitating the actions of -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.

Benzodiaze
pine
Uses and Doses of Commonly Used Benzodiazepines

CVs effects of Benzodiazepenes

In preanesthetic doses they decrease BP and
increase HR
Decrease peripheral vascular resistance
Decrease LV work and cardiac output
Baroreceptor reflexes remain intact
Hypotensive effect is minimal
In patients with elevated cardiac filling pressures
,benzodiazepenes reduce preload and increase
cardiac output

Benzodiaze
pine
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.

Benzodiaze
pine
RESPIRATORY
Depress the ventilatory response to CO2
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.

Benzodiaze
pine
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

Opiatereceptor activation inhibits the presynaptic release and

postsynaptic response to excitatory neurotransmitters (eg,
acetylcholine, substance P) from nociceptive neurons.

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 H2 histamine 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 .

Case Scenario 1
A patient with intestinal obstruction having
wheezing requires an emergency
laparotomy. Which induction drug would
you use?

Ketamine
Porpofol

Case Scenario 2
A patient a history of golttis cancer has signs
of respiratory distress and marked stridor
requires a tracheostomy. Which IV induction
drug would you use?
Any difficult airway
Avoid ----IV induction drugs and muscle relaxants
(respiratory depressant properties)

It may not be possible to perform facemask ventilation

should this patient become apnoeic.
Inhalational induction with halothane or sevoflurane should
be employed.

Case Scenario 3
A patient requires a burns dressing change.
Which induction drug would you use?
Ketamine is an ideal drug to be used for minor
procedures. For burns dressing changes, a subanaesthetic dose can be used.
It will provide sedation and analgesia, preserving the
protective airway reflexes.
Propofol + ketamine
Propofol + fentanyl

Case Scenario 4
A patient with a history of heart failure and MI requires
a general anaesthetic for cholecytectomy . Which
induction drug would you choose?
Options

Etomidate due to its limited effect on the cardiovascular system.

High dose Fantanyl
Be cautious while using Propofol and thiopental
Avoid Ketamine

The important issue is that which ever

induction drug is used, the lowest possible
dose is given, it is given slowly and it is
titrated to effect. Intra-arterial blood
pressure monitoring should be considered
if available

Case Scenario 5
Which IV induction drug would be most
appropriate to use in a hypovolaemic patient.
(Blunt Trauma abdomen)
Ketamine
Etomidate
whichever drug is used, careful dose titration is
paramount.

Case Scenario 6
A patient with porphyria comes for an inguinal
hernia repair and is requesting a general
anaesthetic. Which induction drug would you
use?

Avoid ---Thiopental
Most preferred ---Propofol

Case Scenario 7
An adult patient requires sedation
on the intensive care unit. Which of
the induction drugs would be
appropriate to run as an infusion?
Preferred -- Midazolam , Propofol
Avoid
Thiopental
due to accumulation

etomidate
effect on adrenal steroid hormone synthesis

Case Scenario 8
Patient coming for Fibroadenoma excision
under GA ( Day care surgery). Drug of
choice for induction ??

Propofol

Thank You