Other effects of inhalational anaesthetic agents

[SH4:p72]

Skeletal muscle effects

• Nitrous oxide does NOT relax skeletal muscles
  --> Cause muscle rigidity at >1 MAC
  * Does not potentiate muscle relaxants
• Halogenated ethers (enflurane, isoflurane, desflurane, isoflurane) produce more muscle relaxation than halothane
  * Also cause dose-dependent enhancement of neuromuscular-blocking drugs

Malignant hyperthermia

• Volatile agents and succinylcholine are triggers for malignant hyperthermia
• Halothane is most potent
• Nitrous oxide is a weak trigger

Obstetric effects

• All inhalational anaesthetic agentss (except N2O) produce similar and dose-dependent decreases in:
  * Uterine smooth muscle contractility
  * Uterine blood flow
  * Modest at 0.5 MAC, and substantial at >1MAC
  * Contribute to blood loss due to uterine atony
• N2O does NOT alter uterine contractility
• Inhaled anaesthetics rapidly cross placenta to foetus
  * But also exhaled rapidly

NB:

• GTN and salbutamol also relax uterine muscles

Immune system effects

All inhalational anaesthetic agents (especially N2O) produce

• Dose-dependent inhibition of polymorphonuclear leukocyte
• Inhibition of chemotaxis

Phagocytic actions are unaffected

• Decreased resistance to bacterial infection seems unlikely

Genetic effects

• Increased incidence of spontaneous abortions in operating room personnel
  --> Possible teratogenic effect from chronic exposure to traces of inhalational anaesthetic agents, especially N2O
• N2O irreversibly oxidise vitamin B12-dependent enzymes
  * Methionine synthetase - formation of myelin
  * Thymidylate synthetase - conversion of DNA to thymidine and formation of DNA
• Other inhalational anaesthetic agents does not alter activity of B12-dependent enzymes

Bone marrow effects

• N2O interferes with DNA synthesis
  * Inhibition of methionine synthetase is rapid
  * Recovery is slow
  * Possible culmulative effect when repeated exposure at intervals < 3days
• Exposure of N2O for 24hr
  --> Megaloblastic changes in bone marrow
• Exposure of N2O for 4 days
  --> Agranulocytosis

However,

• N2O does not influence bone marrow viability in bone marrow transplantation

NB:

• N2O oxidises the cobalt in vitamin B12
  --> Unable to be used as the cofactor for methionine synthase
  * This is in addition to the direct inhibitory action on methionine synthase
  * [PHW2:p109]

Peripheral neuropathy

• Chronic exposure (up to 15 days) of 15% N2O in animals
  --> Ataxia and spinal cord and peripheral nerve degeneration
• Chronic exposure in human
  --> Sensorimotor polyneuropathy, plus signs of posterior lateral spinal cord degeneration
  * Resembling pernicious anaemia

Total body O2 requirement

• Total body oxygen requirement decreases by inhalational anaesthetic agentss
  * Reflecting depressed metabolism and decreased functional needs
• Requirement for heart decrease more than for other organs
  * Reflecting the reduced cardiac work requirement