LinkedIn emplea cookies para mejorar la funcionalidad y el rendimiento de nuestro sitio web, así como para ofrecer publicidad relevante. Si continúas navegando por ese sitio web, aceptas el uso de cookies. Consulta nuestras Condiciones de uso y nuestra Política de privacidad para más información.
LinkedIn emplea cookies para mejorar la funcionalidad y el rendimiento de nuestro sitio web, así como para ofrecer publicidad relevante. Si continúas navegando por ese sitio web, aceptas el uso de cookies. Consulta nuestra Política de privacidad y nuestras Condiciones de uso para más información.
Substitution at the number 5 carbon (C5) determines hypnotic potency and anticonvulsant activity. For example, a long-branched chain conveys more potency than does a short straight chain. Likewise, the phenyl group in phenobarbital is anticonvulsive, whereas the methyl group in methohexital is not. Replacing the oxygen at C2 (oxybarbiturates) with a sulfur atom (thiobarbiturates) increases lipid solubility. As a result, thiopental and thiamylal have a greater potency, more rapid onset of action, and shorter durations of action than pentobarbital and secobarbital. The short duration of action of methohexital is related to the methyl substitution at N1. The sodium salts of the barbiturates are water soluble but markedly alkaline (pH of 2.5% thiopental &gt; 10) and relatively unstable (2-week shelf-life for 2.5% thiopental solution). Concentrations higher than recommended cause an unacceptable incidence of both pain on injection and venous thrombosis.
Propofol and thiopental probably provide a similar degree of cerebral protection during focal ischemia
Intense analgesia can be achieved with subanesthetic doses of ketamine, 0.2 to 0.5 mg/kg IV. Analgesia is thought to be greater for somatic than for visceral pain Intravenous injection of ketamine does not produce pain or venous irritation. Consciousness is lost in 30 to 60 seconds after an intravenous administration and in 2 to 4 minutes after an intramuscular injection. Unconsciousness is associated with the maintenance of normal or only slightly depressed pharyngeal and laryngeal reflexes. The return of consciousness usually occurs in 10 to 20 minutes after an injected induction dose of ketamine, but return to full orientation may require an additional 60 to 90 minutes. Amnesia persists for about 60 to 90 minutes after recovery of consciousness, but ketamine does not produce retrograde amnesia. Because of its rapid onset of action, ketamine has been used as an intramuscular induction drug in children and difficult-to-manage mentally retarded patients regardless of age.
Compared with thiopental, induction with benzodiazepines is associated with a slower loss of consciousness and a longer recovery. Benzodiazepines have no direct analgesic properties.
Intravenous induction agents
Dr.Indubala Maurya MD,DNB
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
• They are used:
•To induce anaesthesia prior to other drugs being given to maintain
•As the sole drug for short procedures.
•To maintain anaesthesia for longer procedures by intravenous infusion.
•To provide sedation
Ideal IV induction drug
•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
• Rapid onset in one arm-brain circulation time
• Rapid redistribution to vessel rich tissue
•Rapid clearance and metabolism
•No active metabolites
• 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
Mechanisms of Action
• Depress the reticular activating
• Suppress transmission of excitatory neurotransmitters
• Enhance transmission of inhibitory neurotransmitters
• 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
• 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.
• Hepatic oxidation to inactive water-soluble metabolites.
• Renal excretion
• Important for less protein-bound and less lipid-soluble agents such as
• Water-soluble end products of hepatic biotransformation.
Effects on Organ Systems
• Fall in blood pressure
• Elevation in heart rate
• Ventilatory response to hypercapnia and hypoxia ---Decreases
• Tidal volume --- decreased
• Respiratory rate --- decreased
• Bronchospasm in asthmatic patients or laryngospasm in lightly anesthetized
• Barbiturates do not completely depress noxious airway reflexes
• Release of histamine
• Cerebral blood flow --- Decrease
• Intracranial pressure---Decrease
• Cerebral perfusion pressure--- Increased
• (CPP equals cerebral artery pressure minus cerebral venous pressure or
• 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.
• Reduce renal blood flow and glomerular filtration rate in proportion
to the fall in blood pressure.
• Hepatic blood flow is decreased.
• Induction of hepatic enzymes increases the rate of metabolism of
• 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.
• Sulfur-containing thiobarbiturates evoke mast cell histamine release
in vitro, whereas oxybarbiturates do not.
Specific complication :
• 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.
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.
• 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 (2,6-diisopropylphenol)
• Propofol is not water soluble
• 1% solution (10 mg/mL) --- an oil-in-water emulsion
• soybean oil
• egg lecithin
•Mechanisms of Action
• Facilitation of inhibitory neurotransmission mediated by
• High lipid solubility
• onset of action that is almost as rapid as that of thiopental (one-arm-to-brain
• 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.
• Hepatic and extra hepatic metabolism
• Primarily excreted in the urine
• chronic renal failure does not affect clearance of the parent drug.
Effects on organ
• Blood pressure ---decrease due to a
• Fall in systemic vascular resistance
• Hypotension is more pronounced than with thiopental.
• HR: No change /Bradycardia
• Profound respiratory depressant following an induction dose---apnea
• Inhibits hypoxic ventilatory drive and depresses the normal response to
• Depression of upper airway reflexes
• Helpful during intubation or laryngeal mask placement in the absence of
• Lower incidence of wheezing
• Safe in asthmatic patients.
• 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
• 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
• Lactic Acidosis or propofol infusion syndrome
• Prolonged high-dose infusions of propofol (>75 µg/kg per minute) for
longer than 24 hours.
• Mechanism –
• Cytopathic hypoxia of the electron transport chain and impaired
oxidation of long-chain fatty acids
• Unexpected tachycardia
• Arterial blood gases and serum lactate concentrations
• Metabolic acidosis in its early stages is reversible with
discontinuation of propofol administration.
• 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.
• 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.
Mechanisms of Action
• N-methyl-D-aspartate receptor antagonist.
• Produce dissociative Anaesthesia
• structural analogue of phencyclidine
• Intravenously or intramuscularly
• Peak plasma levels are usually achieved within 10–15 min after
• Ketamine is more lipid soluble and less protein bound than
• Half-life is 10–15 min
• Awakening is due to redistribution to peripheral compartments.
• Liver to several metabolites (eg, norketamine)
• End products of biotransformation are excreted renally
• Induction of Anesthesia
• Intravenous ketamine, 1 to 2 mg/kg
• Intramuscular administration of 4 to 8 mg/kg.
• Subanesthetic doses of ketamine, 0.2 to 0.5 mg/kg IV.
• Neuraxial Analgesia
• Limited value.
Effects on organ system
Central Nervous System
• cerebral blood flow --- Increase
• Intracranial Pressure--- Increase
• Sympathetic nervous system stimulation
• Systemic and pulmonary arterial blood pressure---- increased
• Heart rate ---- increased
• Cardiac output---- increased
• Myocardial oxygen requirements ---- increased
• 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
• Use antisialagogue before ketamine
• Bronchodilatory effects
• Drug of choice for induction patients with asthma
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.
• 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
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
• 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 (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
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 stability (minimal changes in heart rate, stroke volume,
• Preferred for Induction of anesthesia in patients with little or no
• 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”
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.
Uses and Doses of Commonly Used Benzodiazepines
Effects on Organ Systems
•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.
•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.
• Cerebral oxygen consumption, cerebral blood flow, and
• 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
Mechanisms of Action
• Opioids bind to specific receptors located throughout the central
nervous system and other tissues.
• Four major types of opioid receptor
• Opiate–receptor activation inhibits the presynaptic release and postsynaptic
response to excitatory neurotransmitters (eg, acetylcholine, substance P) from
Effects on Organ Systems
•Do not seriously impair cardiovascular function.
•Cardiac contractility--- do not depress (except meperidine)
• Increase ----Meperidine
• Decrease ---High doses of morphine, fentanyl, sufentanil.
•Blood pressure --- Decreased
• As a result of bradycardia, venodilation, and decreased sympathetic
• Meperidine and morphine --- can lead to profound drops in systemic
vascular resistance and arterial blood pressure due to histamine
• 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.
• Respiratory rate– decrease
• Apneic threshold( the highest PaCO2 at which a patient remains apneic)
• 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
• 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
• Management of perioperative shivering ---Intravenous meperidine
• slow gastric emptying time by reducing peristalsis.
• Biliary colic may result from opioid-induced contraction of the
sphincter of Oddi.
• 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?
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
• It may not be possible to perform facemask ventilation should this
patient become apnoeic.
• Inhalational induction with halothane or sevoflurane should be
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 sub-anaesthetic dose can be used.
• It will provide sedation and analgesia, preserving the protective airway
• Propofol + ketamine
• Propofol + fentanyl
A patient with a history of heart failure and MI requires a
general anaesthetic for cholecytectomy . Which induction
drug would you choose?
• 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
Case sCenario 4
Case sCenario 5
Which IV induction drug would be most appropriate to use
in a hypovolaemic patient. (Blunt Trauma abdomen)
• 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
• due to accumulation
• effect on adrenal steroid hormone synthesis
Case sCenario 8
• Patient coming for Fibroadenoma excision under GA ( Day
care surgery). Drug of choice for induction ??