Effects of Inhaled Anesthetics on Pulmonary Surfactant
Pulmonary surfactant decreases the work of breathing by reducing
surface tension at the fluid-gas interface. Similar to mucus, surfactant plays a
role in removing foreign particles from airways. Surfactant also enhances the bactericidal
actions of alveolar macrophages. The effects of halothane and isoflurane on cultured
alveolar type II cells, which secrete surfactant, and the metabolism of phosphatidylcholine,
the main lipid component of surfactant, have been investigated.[105]
[106]
Both agents reduced phosphatidylcholine synthesis
by alveolar cells in a dose-dependent manner during a 4-hour exposure ( Fig.
6-7
). This reduction in phosphatidylcholine production was more pronounced
with longer durations of exposure to halothane and was reversible within 2 hours
after the agent was discontinued. High concentrations of halothane also disrupted
the energy metabolism of cultured alveolar cells as indicated by reduced ATP content
and enhanced glycolytic metabolism. Halothane and isoflurane potentiated the hydrogen
peroxide-mediated reduction of phosphatidylcholine in alveolar type II cells.[105]
[107]
Pretreatment with an inhibitor of H2
O2
-induced
oxidation (i.e., nicotinamide) did not attenuate the adverse effects of halothane
on alveolar cells. These data suggested a mechanism, possibly related to halothane-specific
effects on cell energetics, by which inflammatory lung disease may be worsened during
administration of a volatile anesthetic. Clinically relevant concentrations of halothane
increase surfactant-associated protein C mRNA in vitro but exert the converse effect
in mechanically ventilated rats.[108]
Whether effects
of halothane on surfactant protein C mRNA are related to similar actions on the actual
protein has yet to be established.
Figure 6-6
Mucociliary clearance measured as tantalum clearance
in patients undergoing surgery with general or local anesthesia (i.e., awake). Notice
the decrease in mucociliary clearance in the peripheral and central airways during
halothane and thiopental anesthesia. (Adapted from Forbes AR, Gamsu G:
Mucociliary clearance in the canine lung during and after general anesthesia. Anesthesiology
50:26, 1979.)
