• Clinical science

Inhalational anesthetics (Volatile anesthetics)


Inhalational anesthetics are used for the induction and maintenance of general anesthesia as well as sedation. The exact mechanisms by which they act are still unknown. The most common inhalational anesthetics are sevoflurane, desflurane, and nitrous oxide. Of these, sevoflurane is the most common because of its rapid onset of action and the fact that patients recover quickly from it. Inhalational anesthetics cause respiratory depression, a decrease in arterial blood pressure and cerebral metabolic demand, and an increase in cerebral blood flow. While side effects differ based on the substance (e.g., halothane can cause hepatotoxicity), the most common side effect is nausea.


  • Inhalational anesthetics provide both analgesia and narcosis and can be used for induction and maintenance of general anesthesia.
  • The most widely used inhalational anesthetics are:


Pharmacokinetics and pharmacodynamics

Pharmacokinetic principles

  • Uptake into the blood: Inhalational anesthetics are taken up passively via diffusion, which depends on
    • Blood solubility of the anesthetic
    • Lung ventilation, volumes, and perfusion
  • Distribution and uptake into the brain: Transport to and uptake into the brain depend on cerebral perfusion and the fat solubility of the inhalational anesthetic.
    • Brain-blood partition coefficient: the ratio of anesthetic concentrations between blood and brain tissue when partial pressures are equal The higher the brain-blood partition coefficient, the higher the solubility of that substance in brain tissue.
  • Onset of effect: : The lower the blood-gas partition coefficient of an inhalational anesthetic, the faster the substance takes effect (less induction time)
  • Elimination
    • Inhalational anesthetics are eliminated by the lungs
    • Inhalational anesthetics are metabolized only to a small degree
    • With prolonged duration of anesthesia in obese patients, inhalational anesthetics with a high fat solubility can accumulate in adipose tissue and slow down recovery from anesthesia (increased context-sensitive half-life).

Pharmacodynamic principles

  • Measure of potency of inhalational anesthetics: minimal alveolar concentration (MAC)
    • MAC is the fraction of volume of the anesthetic present in the inspired air that provides sufficient analgesia in 50% of patients.
    • MAC is, therefore, a measure of anesthetic potency ; and represents the ED50 value.
    • The lower the MAC value, the more fat soluble the anesthetic.

Pharmacokinetics and pharmacodynamics of common inhalational anesthetics

Blood-gas partition coefficient Brain-blood partition coefficient Minimal alveolar concentration (MAC)
Nitrous oxide
  • 0.47
  • 1.1
  • > 104%
  • 0.42
  • 1.3
  • 6–7%
  • 0.69
  • 1.7
  • 2%
  • 1.40
  • 2.6
  • 1.4%
  • 1.80
  • 1.4
  • 1.7%
  • 2.30
  • 2.9
  • 0.75%



General effects

  • Anesthesia
  • Sedation/narcosis
  • ↓ Respiration
  • ↓ Arterial blood pressure
  • ↓ Cerebral metabolic demand
  • ↑ Cerebral blood flow

Specific characteristics of common inhalational anesthetics

Specific characteristics
Nitrous oxide
  • Usually insufficient if used alone → often combined with a more potent inhalational anesthetic to achieve the “second gas effect”
  • Rapid onset and recovery
  • Very rapid onset and recovery
  • Pungent odor; irritates airways → not suitable for induction of anesthesia
  • Most commonly used inhalational anesthetic
  • Rapid onset and recovery
  • Non-pungent → suitable for induction of anesthesia
  • Most potent of the fluranes
  • Relatively slow onset and recovery
  • Pungent odor → not suitable for induction of anesthesia
  • Medium speed of onset and recovery
  • Medium speed of onset and recovery


Side effects

  • General side effects
    • Nausea/vomiting → inhalational anesthetics are contraindicated in patients who are not sober (see rapid sequence induction)
    • Risk of malignant hyperthermia
    • Postoperative shivering
  • Side effects of specific substances
    • Nitrous oxide:
      • Can diffuse into gas-filled body compartments and cause expansion of the gas present there → potential damage to organs/tissues → should not be used in patients with conditions such as pneumothorax
      • Causes mild myocardial depression and increases pulmonary vessel resistance → should not be used in patients with conditions such as pulmonary hypertension
    • Desflurane: sympatho-adrenergic reaction → ↑ blood pressure and heart rate
    • Sevoflurane: interacts with soda lime nephrotoxic breakdown products (known as compounds A–E)
    • Enflurane: proconvulsive
    • Halothane: hepatotoxic halothane hepatitis [5]
      • Pathophysiology: underlying mechanism not fully understood
      • Clinical features
        • Occurs 2 days to 3 weeks after halothane exposure
        • Signs of acute hepatitis
        • Rash, arthralgias
      • Diagnostics: diagnosis of exclusion
      • Treatment: depending on the severity of liver damage, ranges from supportive treatment to liver transplantation [6]


We list the most important adverse effects. The selection is not exhaustive.

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  • 5. Drug record - Halothane. https://livertox.nih.gov/Halothane.htm. Accessed October 6, 2017.
  • 6. Peralta, Poterack, Talavera, Manning, Grier. Halothane Hepatotoxicity. http://emedicine.medscape.com/article/166232-overview. Updated October 17, 2016. Accessed October 12, 2017.
  • 7. ASA. Practice guidelines for preoperative fasting and the use of pharmacologic agents to reduce the risk of pulmonary aspiration: Application to healthy patients undergoing elective procedures. Anesthesiology. 2011; 114(3): pp. 495–511. doi: 10.1097/aln.0b013e3181fcbfd9.
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last updated 06/16/2019
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