INDUCTION AGENTS
Don Daniels, M.D.
DON DANIELS COL MC
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Thiopental
• Standard 2.5% has pH >9 • Arterial injection causes vasoconstriction, thrombosis, and necrosis • Rx art injection: immediate admin papaverine and lidocaine, sympathetic blockade & heparinization
DON DANIELS COL MC
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Thiopental
• Metabolized by liver, metabolites have nil CNS activity • High doses are desulfurated to pentobarbital which has long lasting CNS effects • low elimination clearance contributes to long elimination half life
DON DANIELS COL MC
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Thiopental
• Induction 3-5 mg/kg adults
– 5-6 mg/kg in children – 6-8 mg/kg in infants
• Reduced dose in premed patients • Geriatrics reduce 30-40%
DON DANIELS COL MC
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Thiopental
• Produce proportional decrease in CMRO2 & CBF which lowers ICP • Isoelectric EEG can be maintained at infusion of 4-6 mg/kg/hr • Ideal for neuroprotection?
DON DANIELS COL MC
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Thiopental
• Causes dose dependent respiratory depression • Bronchospasm or laryngospasm at induction is due to lightly anesthetized pts • Decreases cardiac output, systemic arterial pressure and peripheral vascular resistance
DON DANIELS COL MC
6
Methohexital
• • • • • Metabolized by the liver & short half life Induction dose 1.5 mg/kg Reduce dose in geriatrics Decreases CMRO2, CBF & ICP Freq causes myoclonic like muscle tremors & hiccups • Less BP decrease than STP
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Propofol
• A egg lecithin emulsion formulation (10% Soya bean oil, 2.25% glycerol and 1.2% egg phosphatide) • Small vein irritation
DON DANIELS COL MC
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Propofol
• Induction 1.5 - 2.5 mg/kg healthy adults • Maintenance
– 100 - 200 mcg/kg/min for hypnosis – 25 - 75 mcg/kg/min for sedation
DON DANIELS COL MC
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Propofol
• • • • • Decreases CMRO2, CBF and ICP Large doses decrease CPP Cerebral autoregulation is not affected + neuroprotective effect Anticonvulsant
DON DANIELS COL MC
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Propofol
• Dose dependent respiratory depression • Can produce bronchodilation • does not inhibit hypoxic pulmonary vasoconstriction
DON DANIELS COL MC
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Propofol
• • • • Can cause profound myocardial depression Causes arterial and veno dilation Alters baroreceptors Increased age enhances these effects
DON DANIELS COL MC
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Propofol
• • • • Antiemetic Antipruitic Does not trigger Malignant hyperthermia Sedation infusions associated with pediatric ICU deaths • Does not inhibit cortisol synthesis • Inhibits phagocytosis • Anaphylactoid reactions
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Etomidate
• Carboxylated imidazole • D isomer possesses anesthetic activity • Aqueous solution is unstable @ physiologic pH, therefore is formulated in a 0.2% solution w 35% propylene glycol
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Etomidate
• • • • • Induction dose 0.2 - 0.4 mg/kg Involuntary myoclonic movements common Emergence time after induction is short PONV is high Adrenal suppression last 5-8 hrs
DON DANIELS COL MC
15
Etomidate
• Decreases CMRO2, CBF & ICP • CPP is maintained through hemodynamic preservation • Anticonvulsant
DON DANIELS COL MC
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Etomidate
• Causes minimal cardiovascular depression • Does not cause histamine release • Does not effectively blunt laryngotracheal response
DON DANIELS COL MC
17
Ketamine
• A Arylcyclohexylamine • S(+) isomer is clinically active, but only racemic is available • Metabolized by hepatic microsomal cytochrome P-450 • Metabolites excreted by kidney • Short distribution & redistribution 1/2 life
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Ketamine
• Dissociative anesthesia • Profound analgesia & anesthesia even with consciousness • Analgesia due to interaction @ thalamic & limbic systems
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Ketamine
• Parenteral route most common
– 6 mg/kg
• Induction dose
– – – – 1 - 2 mg/kg IV 4 - 8 mg/kg IM Anesthesia duration 10 - 20 min Full recovery 60 - 90 min
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Ketamine
• High incidence psychomimetic reactions
– incidence lowered w benzodiazepines, barbiturates or propofol
• Increases CMRO2, CBF & ICP
– Contraindicated in pts with high ICP or reduced cerebral compliance
DON DANIELS COL MC
21
Ketamine
• Has bronchodilatory activity • Protective airway reflexes are preserved
– Does not prevent aspiration in pt w full stomach
• Minimal respiratory depression • Increases oral secretions
– larygospasm in lightly anesthetized pts
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Ketamine
• • • • Cardiovascular stimulator Increases myocardial oxygen consumption Increases cardiac work ** Has intrinsic myocardial depressant effects in pts with limited or depleted cardiac reserves ** • May also increase pulmonary artery pressure
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General Pharmacology of Induction Agents
• Barbiturates, Propofol & etomidate, benzodiazepines act via modulation of the GABA system. • Ketamine produces dissociation between thalamocortical & limbic systems. CNS effects related to antagonistic activity @ NMDA receptor
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General Pharmacology of Induction Agents
• Primary cause of short action is redistribution
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