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Anaesthesiology
Intravenous Anesthetics
Built from Barash Clinical Anesthesia, 9th Edition
What’s inside
11 sections · 186 slides
Overview
- Scope of this topic
- Key messages of the chapter
- Further key messages
Pharmacokinetics of Intravenous Anesthetics
- From induction-only drugs to routine infusions
- Properties of the ideal intravenous anesthetic
- Properties of the ideal intravenous anesthetic agent
- Properties of the ideal intravenous anesthetic agent (continued)
- Propofol as the current gold standard
- Limitations of propofol
- Onset and offset after a single bolus
- Why infusion rates fall over time
- Three phases of plasma concentration after a bolus
- Fate of a bolus of intravenous anesthetic
- Three-compartment model of drug disposition
- Consequences of a prolonged infusion
- Elimination half-time versus context-sensitive half-time
- Context-sensitive half-time of intravenous anesthetics
- Remifentanil and infusion-independent offset
- Target-controlled infusion devices
- Regulatory position on target-controlled infusion
Propofol
- Chemical structure of propofol
- Range of uses for propofol
- Development of the propofol formulation
- Physical properties of the emulsion
- Propofol: key pharmacology and clinical uses
- Metabolism and excretion of propofol
- Extrahepatic metabolism of propofol
- Compartment models applied to propofol
- Mechanism of propofol-induced unconsciousness
- Additional receptor targets of propofol
- Dose-related progression of propofol effect
- Electroencephalogram changes with propofol
- Burst suppression with propofol
- Neuroprotective effects of propofol
- Anti-inflammatory and anticonvulsant actions
- Propofol and electroconvulsive therapy
- Propofol abuse and diversion
- Scheduling status and partial reversal
- Cardiovascular effects of propofol
- Loss of the baroreceptor reflex
- Respiratory effects of propofol
- Induction dosing of propofol
- Patient factors that change propofol induction dose
- Maintenance of anesthesia with propofol
- Situations that favour a propofol infusion
- Sedation with propofol
- Pain on injection with propofol
- Less successful measures for injection pain
- Propofol infusion syndrome
- Mechanism and dosing limits in propofol infusion syndrome
- Green urine after prolonged propofol infusion
Etomidate
- Chemical structure of etomidate
- Etomidate: key pharmacology and clinical uses
- Formulation and handling of etomidate
- Pharmacokinetics of etomidate
- Etomidate pharmacokinetic values
- Central nervous system actions of etomidate
- Epileptogenic activity with etomidate
- Etomidate and evoked potentials
- Cardiovascular profile of etomidate
- Respiratory effects and sedation use
- Adrenocortical suppression by etomidate
- Managing the adrenal risk of etomidate
Ketamine
- Chemical structure and origin of ketamine
- Historical limits and modern revival of ketamine
- Ketamine: key pharmacology and clinical uses
- Enantiomers and routes of ketamine
- Onset, dose and duration of ketamine
- Elimination and metabolism of ketamine
- Mechanism of action of ketamine
- Blocking wind-up at the NMDA channel
- Imaging evidence for ketamine analgesia
- Non-NMDA receptor actions of ketamine
- Features of dissociative anesthesia
- Ketamine for induction of anesthesia
- When ketamine is unsuitable for induction
- Ketamine for procedural sedation
- Ketamine for acute postoperative pain
- Ketamine in chronic pain
- Intranasal ketamine
- Ketamine in major depression
- Central nervous system side effects of ketamine
- Cardiovascular side effects of ketamine
- Respiratory and intracranial effects of ketamine
Dexmedetomidine
- Chemical structure and introduction of dexmedetomidine
- Dexmedetomidine: key pharmacology and clinical uses
- Distribution and elimination of dexmedetomidine
- Metabolism and organ impairment
- Mechanism of action of dexmedetomidine
- Clinical picture and cardiovascular effects
- Dexmedetomidine for intensive care sedation
- Dexmedetomidine for procedural sedation
- Dexmedetomidine compared with propofol for sedation
- Dexmedetomidine in children
- Dexmedetomidine in spine surgery and emergence delirium
- Dexmedetomidine as a regional anesthesia adjuvant
- Bradycardia with dexmedetomidine
- Hypotension and overdose reports
Benzodiazepines
- Clinical effects of benzodiazepines
- Chemical structure and clinical role of midazolam
- Oral midazolam premedication in children
- Midazolam versus propofol infusion in intensive care
- Benzodiazepines: key pharmacology and clinical uses
- Protein binding and lipophilicity of benzodiazepines
- Metabolism of benzodiazepines
- Pharmacokinetic values for midazolam
- Accumulation during continuous midazolam infusion
- Benzodiazepine metabolism and clearance
- Benzodiazepine pharmacokinetic values
- Formulation differences between benzodiazepines
- How benzodiazepines act at the GABA-A receptor
- The ceiling effect of benzodiazepines
- Central nervous system effects of benzodiazepines
- Anticonvulsant and muscle relaxant roles
- Respiratory and cardiovascular effects of benzodiazepines
- Midazolam dosing by clinical use
- Side effects of benzodiazepines
Barbiturates
- Historical position of thiopental
- Chemical classes of the clinical barbiturates
- Solution chemistry and storage of barbiturates
- Barbiturates: key pharmacology and clinical uses
- Metabolism and clearance of barbiturates
- Barbiturate kinetics after bolus and after infusion
- Mechanism of action of barbiturates
- Electroencephalogram changes with barbiturates
- Methohexital and electroconvulsive therapy
- Cerebral metabolic effects of barbiturates
- Mechanisms of barbiturate neuroprotection
- The reverse steal effect
- Clinical evidence for barbiturate brain protection
- Cardiovascular effects of thiopental
- Patient factors and methohexital haemodynamics
- Respiratory effects of barbiturates
- Induction dosing with thiopental
- Patient factors that change thiopental dose requirement
- Methohexital dosing
- Barbiturates as maintenance infusions
- Barbiturate coma for raised intracranial pressure
- Injection-related side effects of barbiturates
- Barbiturates and acute intermittent porphyria
New Intravenous Anesthetics
- Design goals for new intravenous anesthetics
- Drawbacks of the propofol lipid emulsion
- Approaches to reformulating propofol
- The problem with reformulating propofol
- Fospropofol
- Why fospropofol has not entered US practice
- Remimazolam compared with midazolam
- Development targets for remimazolam
- Trial evidence for remimazolam
- Cyclopropyl-methoxycarbonyl metomidate
- CPMM versus propofol
- THRX-918661 / AZD-3043
- Sedasys: computer-assisted sedation
- Concerns raised about Sedasys
- Why Sedasys failed
Summary
- Primary receptor target of each agent
- Choosing an agent by haemodynamic need
- Choosing an agent by respiratory need
- Which agents suit a continuous infusion
- Signature adverse effects to remember
- Practical take-home messages
References
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- Barash, Cullen, and Stoelting's Clinical Anesthesia, 9th Edition