Inhaled Anesthetics

Snapshot

• A 25-year-old woman is on the operative table for an elective laparoscopic cholecystectomy. After administration of isoflurane and succinylcholine, the patient developed hypercarbia that is resistant to increasing the patient’s minute ventilation. She also developed massester and generalized muscle rigidity. The patient is immediately treated with dantrolene and a malignant hyperthermia protocol is initiated. (Malignant hyperthermia)

Introduction

• General anesthesia
  • is a central nervous system (CNS) depressive state that is reversible and provides
    • analgesia
    • sedation and decreased anxiety
    • amnesia and impaired consciousness
    • relaxation of skeletal muscle
    • prevention of reflexes
  • can be divided into
    • intravenous anesthesia 
    • inhaled anesthesia
• Inhaled anesthesia
  • primarily used for maintenance of anesthesia
    • leads to increased cerebral blood flow, decreased blood pressure, and decreased respiratory rate 
  • potency
    • the index of potency is the inverse of the Minimum Alveolar Concentration (potency = 1/MAC) 
      • MAC is the concentration of inhaled anesthetic needed to prevent movement in 50% of patients in response to a noxious stimuli (e.g., surgical incision)
      • for example, a high potency inhaled anesthetic has a low MAC
        • the more lipid soluble the inhaled anesthetic is, the more potent it is; thus, the lower the MAC 
  • the goal of inhalation anesthesia is to maintain an optimal brain partial pressure (Pbr)
    • the movement of the anesthetic from one body compartment to the next is based on the drug partial pressure gradient
      • the inhaled anesthetic drug would move
        • from the alveolar partial pressure (Palv) → arterial partial pressure (Pa) → Pbr
          • eventually this steady state is achieved so that
            • Palv = Pa = Pbr
              • the speed of achieving this steady state is determined by a number of factors, such as
                • blood solubility  
                • alveolar wash-in
• replacing normal lung gases with the inhaled anesthetic
  • cardiac output
    • tissue type’s effect on the anesthetic
    • blood solubility 
      • this is determined by the blood/gas partition coefficient
        • this is the concentration ratio of the inhaled anesthetic in the blood phase to the gas phase when equilibrium is achieved 
          • anesthetics with low blood solubility
• equilibrium is achieved rapidly
• quickly saturates the blood
• results in a rapid induction and recovery
• Examples
  • nitrous oxide
    • low blood solubility → low blood/gas partition coefficient → rapid induction/recovery 
    • low lipid solubility → low potency → high MAC
  • halothane and -fluranes 
    • high blood solubility → high blood/gas partition coefficient → slow induction/recovery
• high lipid solubility → high potency → low MAC

Medications

• Medications
  • desflurane, enflurane, halothane, isoflurane, methoxyflurane, sevoflurane, and nitrous oxide
• Mechanism of action
  • unknown
• Side effects
  • myocardial depression (halogenated hydrocarbons are vagomimetic)
  • respiratory depression
  • ↑ cerebral blood flow, which in turn
    • ↓ cerebral metabolic demand
• Adverse effects
  • cardiac arrhythmias
  • concentration-dependent hypotension
  • malignant hyperthermia 
    • clinical presentation
      • fever and severe muscle contractions after
        • administration of a volatile anesthetic or succinylcholine
    • pathogenesis
      • autosomal dominant with variable penetrance
      • mutation in the ryanodine receptor which
        • increases calcium release from the sarcoplasm reticulum
    • treatment
      • dantrolene 
  • hepatotoxicity (halothane) 
  • nephrothoxicity (methoxyflurane)
  • increased risk of seizure (enflurane)
  • expansion of trapped gas within a body cavity (nitrous oxide)