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Intravenous Anesthetics

Intravenous anesthetics are a group of fast-acting compounds that are used to induce a state of impaired awareness or complete sedation. Commonly used intravenous anesthetics include propofol, etomidate, ketamine, and barbiturates (e.g., thiopental). Propofol is the standard drug for induction of anesthesia and etomidate is most commonly used in cases of hemodynamic instability. Ketamine plays a key role in emergency medicine because of its strong dissociative, sympathomimetic, and analgesic effects. The barbiturate thiopental reduces intracranial pressure, making it useful in patients with high intracranial pressure and/or head trauma. While the characteristics and side effects of intravenous anesthetics are highly dependent on the substance involved, they all share a strong hypnotic effect.

For more information on benzodiazepines and opioids, see the corresponding articles

Overview of intravenous anesthetics [1]
Indications Mechanism of action Adverse effects
Propofol
  • Total intravenous anesthesia (TIVA) drug of choice
  • Rapid sequence induction
  • Sedation in ICU
  • Short procedures
  • Thought to act as an agonist on sodium channels of the reticular formation, agonist on GABAA receptors, and an antagonist on NMDA receptors → ↓ intracranial pressure, global CNS depression, and hypnotic, antiemetic, and anticonvulsant effects
  • No analgesic or muscle relaxant effects
  • Dose-dependent hypotension and respiratory depression
  • Propofol infusion syndrome
Etomidate
  • IV anesthesia for patients with hemodynamic instability
  • Acts as an agonist on the GABAA receptors in the reticular formation → hypnotic and anticonvulsant effects and ↓ intracranial pressure
  • Little to no effect on the cardiovascular system [2]
  • Transient acute adrenal insufficiency
  • PONV
Ketamine
  • Ideal emergency anesthesia for polytrauma patients; ICU sedation
  • Short painful procedures (e.g., fracture reduction)
  • Treatment-resistant asthma
  • Treatment-resistant depression [3]
  • NMDA receptor antagonism → dissociative anesthesia, sympathomimetic effects, and increased cerebral blood flow
  • ↑ Intracranial pressure
  • Acute psychotomimetic effects: disorientation, hallucinations, vivid dreams, nightmares
  • Sympathomimetic effects: ↑ blood pressure, ↑ heart rate, ↑ cardiac output
Barbiturates (thiopental and methohexital)
  • IV anesthesia induction (esp., short procedures, in case of risk of raised intracranial pressure during the operation)
  • Bind to GABAA receptors → ↓ neuronal excitability in the brain → ↓ ICP, as well as sedative, hypnotic, and antiepileptic effects
  • High lipid solubility (rapid distribution into fat)
  • Hypotension, respiratory depression
  • ↓ Intracerebral blood flow
  • Cytochrome P450 induction
Opioids (e.g., fentanyl, morphine)
  • Analgesia during induction and/or maintenance anesthesia
  • Agonism at heptahelical GPCRs μ, Ī“, and/or Īŗ → ↓ synaptic transmission → analgesia, euphoria, sedation, slowed gastrointestinal transit
  • Muscle rigidity
  • Cardiovascular and respiratory depression
Benzodiazepines (e.g., midazolam)
  • IV anesthesia induction
  • Short outpatient procedures
  • Preoperative sedation
  • Endoscopy
  • Indirect GABAA receptor agonism → ↓ neuronal excitability
  • Anterograde amnesia
  • ↓ Blood pressure
  • Can cause severe respiratory depression

Mechanism of action

  • Not fully understood; propofol is thought to act as an agonist on GABAA receptors and sodium channels of the reticular formation, and as an NMDA receptor inhibitor.
  • Rapid onset and recovery

Effects

  • Hypnotic effects
  • Antiemetic
  • Antipruritic
  • Anticonvulsant
  • Bronchodilation
  • ↓ Intracranial pressure
  • No analgesic or muscle relaxant effects

Side effects

  • Hypotension (dose-dependent)
  • Respiratory depression (dose-dependent)
  • Anaphylaxis (esp. in patients with allergies to soy or egg products )
  • Pain on injection
  • Propofol infusion syndrome
    • Etiology: high doses and prolonged administration of propofol
    • Clinical features: severe metabolic acidosis, rhabdomyolysis, renal failure, and/or cardiac failure (often fatal)
    • Diagnostics: Patients undergoing prolonged propofol treatment should have triglycerides monitored at least every 3 days, as increased triglyceride levels correlate with development of propofol infusion syndrome.
    • Management: discontinue propofol immediately, symptomatic treatment

Indications

  • Standard for anesthesia induction
  • Total intravenous anesthesia (TIVA)
    • A technique for induction and maintenance of general anesthesia using IV drugs alone.
    • Propofol is the drug of choice, especially for patients with an intermediate to high risk of postoperative nausea and vomiting (PONV).

References:[4][5]

Mechanism of action

  • Enhances GABAA receptor function in the reticular formation
  • Rapid onset and recovery

Effects

  • Hypnotic effects
  • ↓ Intracranial pressure
  • Anticonvulsant effects
  • Little to no effect on the cardiovascular system [2]
  • No analgesic or muscle relaxant effect

Side effects

  • Transient acute adrenal insufficiency (due to adrenal cortex suppression → reducedcortisol production)
  • Postoperative nausea and vomiting
  • Painful injection (avoid by administering an opioid prior to injection)
  • Myoclonus

Indications

  • Anesthesia for patients with hemodynamic instability

Mechanism of action

  • NMDA receptor antagonist
  • Belongs to the arylcyclohexylamines class
  • Rapid onset

Effects

  • Dissociative anesthesia: unique anesthetic state with analgesia, intact spontaneous breathing, amnesia, and no complete loss of consciousness
  • Strong analgesia
  • Bronchodilation
  • Sympathomimetic effects: ↑ blood pressure, ↑ heart rate, ↑ cardiac output
  • Increases cerebral blood flow

Side effects

  • Nystagmus
  • ↑ Oxygen demand and ↑ pulmonary arterial pressure
  • ↑ Intracranial pressure due to increased cerebral blood flow
  • Acute psychotomimetic effects: disorientation, hallucinations, vivid dreams, nightmares, and/or abnormal EEG (concomitant administration of benzodiazepines is recommended to avoid these effects)
  • Rapid injection or high doses can lead to respiratory depression.
  • ↑ Salivation

Indications

  • Ideal emergency anesthetic for polytrauma patients and other patients with risk of hypotension (no cardiovascular depression)
  • Treatment-resistant asthma
  • Short painful procedures (e.g., fracture reduction)
  • Treatment-resistant depression [3]

Ketamine may be administered via intramuscular injection if IV access is not possible!

References:[6][7]

Agents

  • Thiopental
  • Methohexital

Mechanism of action

  • Enhanced GABA action → enhanced duration of chloride channel opening and hyperpolarization of postsynaptic neurons → ↓ neuronal excitability in the brain
  • High potency, highly-lipid soluble → rapid onset of action due to quick transfer across the blood-brain barrier → brief recovery time due to redistribution into skeletal muscles and adipose tissue

Effects

  • Hypnotic effects
  • ↓ Intracranial pressure due to reduced cerebral blood flow
  • Little to no analgesic or muscle relaxant effects

Side effects

  • Hypotension (dose-dependent)
  • Respiratory depression and/or apnea (dose-dependent)
  • Laryngospasm, bronchospasm (due to histamine release)
  • Myoclonus
  • Painful injection
  • Visual hallucinations
  • Vivid dreams
  • Bradycardia, arrhythmias
  • Cytochrome P450 induction

Indications

  • IV anesthesia induction; (esp. short procedures with minimal pain and high risk of raised intracranial pressure)
  • Reduction of intracranial pressure for brain edema following trauma or surgery
  • Sedation for electroconvulsive therapy (e.g., methohexital)
  • Convulsion during or after anesthesia

Contraindications

  • Hypersensitivity
  • Severe cardiovascular decompensation; conditions in which a decrease in blood pressure would be hazardous
  • Porphyria
  • Addison disease
  • Liver or kidney disease
  • Severe anemia
  • Thyroid disorders
  • Myasthenia gravis
  • Asthma

References:[8]