Inhaled Anesthetics
Volatile anesthetics are potent bronchodilators. In a retrospective
study, Schnider and Papper[2]
demonstrated halothane
was superior to ether, cyclopropane, and ethylene in decreasing wheezing in 49 patients
with symptoms of bronchospasm before anesthesia. Colgan[18]
observed an increase in "bronchial distensibility" in dogs anesthetized with halothane,
ether, or methoxyflurane. Halothane had the most pronounced effect. Increasing
concentrations of halothane also caused a dose-dependent decrease in resting airway
resistance in spontaneously breathing dogs.[19]
Nevertheless, bronchodilation resulting from hypercarbia associated with deeper
planes of anesthesia may have affected the results of these studies. Halothane and
diethyl ether caused relaxation of resting tone in isolated guinea pig tracheal strips.
[20]
These anesthetics also attenuated tracheal
muscle constriction produced by acetylcholine, but only halothane accomplished this
in clinically relevant doses.
Hickey and colleagues[21]
demonstrated
the importance of controlled levels of arterial carbon dioxide tension (PaCO2
)
during the evaluation of the effects of drugs on bronchial smooth muscle tone. Halothane
and cyclopropane did not alter the resistance of the resting, unstimulated airway
in anesthetized, mechanically ventilated, normocapnic dogs. However, 1.5 minimum
alveolar concentration (MAC) of halothane produced significant bronchodilation compared
with cyclopropane during histamine- or vagal stimulation-induced bronchoconstriction.
Halothane and, to a lesser degree, enflurane and methoxyflurane reversed hypocapnia-induced
bronchoconstriction in the isolated canine left lower lobe.[22]
Halothane also attenuated the bronchoconstricting effects of hypocarbia without
affecting the resistive work of breathing (described more fully in "Ventilatory Mechanics")
in the unstimulated state in humans under-going cardiopulmonary bypass.[23]
Hypercapnia-induced bronchodilation and hypocapnia-induced bronchoconstriction were
shown to be attenuated by isoflurane.[24]
A bronchospasm model developed by Hirshman and Bergman[25]
using dogs sensitized to aerosolized Ascaris antigen
has greatly contributed to our understanding of the effect of anesthetics on airway
smooth muscle. Halothane and enflurane (1 MAC) similarly attenuate antigen-induced
bronchospasm. Unlike an asthmatic attack during anesthesia, the stimulus to incite
bronchospasm in this model is not maintained during experimentation. Isoflurane
and halothane (1.5 MAC) produced a similar reduction in airway resistance in this
canine model.[26]
Similar results were obtained
with volatile agents during methacholine-induced airway constriction. Taken together,
these data suggest that isoflurane and halothane produce direct bronchodilation and
depress airway reflexes. Although isoflurane appears to share significant bronchodilating
properties with halothane and enflurane, halothane increased dynamic
compliance (a measure of small airway resistance) to a greater extent than did isoflurane.
This finding is made more interesting in light of data demonstrating that isoflurane
preferentially relaxes the bronchiole rather than the bronchus in vitro.[27]
The structure of the respiratory epithelium changes from pseudostratified columnar
cells of the large airways to thinner, cuboidal cells of the bronchioles, and it
is not surprising that topographic heterogeneity exists between these regions. Park
and colleagues[28]
demonstrated that isoflurane
and halothane dilate fourth-order bronchi at equivalent MAC values. The ability
of halothane, isoflurane, sevoflurane, and desflurane to attenuate methacholine-induced
bronchoconstriction in open-chest, pentobarbital-anesthetized rats was assessed.
[29]
These volatile anesthetics produced similar
reductions in airway resistance, but they did not cause further effects at concentrations
greater than 1 MAC.
Ascaris antigen-induced asthma
was associated with increased plasma histamine levels that were not prevented by
administration of halothane.[30]
Halothane and
topical atropine decreased bronchoconstriction during histamine-induced bronchospasm,
but these effects were not additive or synergistic.[31]
Using computed tomography (CT), Brown and colleagues[32]
showed that halothane causes greater bronchodilation than does isoflurane at low
concentrations ( Fig. 6-1
).
Halothane also had a more pronounced relaxing
Figure 6-1
High-resolution computed tomography scans from one dog:
control (upper left), during 0.5% halothane (upper
right), during 1.0% halothane (lower left),
and during 1.5% halothane (lower right). Notice
the progressive dilation of the airways as indicated by the arrow.
(Adapted from Brown RH, Mitzner W, Zerhouni E, et al: Direct in vivo visualization
of bronchodilation induced by inhalational anesthesia using high-resolution computed
tomography. Anesthesiology 78:295, 1993.)
effect than did isoflurane at a similar MAC in intact airway smooth muscle as measured
by high-resolution CT.[33]
All volatile agents,
including sevoflurane[34]
[35]
and desflurane,[36]
relax airway smooth muscle.
Sevoflurane (1 MAC) reduced respiratory system resistance (determined using the
isovolume technique) by 15% in patients undergoing elective surgery. In contrast,
desflurane did not alter resistance (+5%).[37]
Halothane, desflurane, and isoflurane appear to relax distal airways (i.e., bronchioles)
to a greater extent than proximal airways (i.e., bronchi).[38]
Similarly, isoflurane and sevoflurane had greater inhibitory effects on bronchial
than tracheal smooth contraction.[39]
Administration of 1 or 2 MAC of halothane, enflurane, sevoflurane,
and isoflurane did not alter baseline pulmonary resistance and dynamic pulmonary
compliance. However, these agents significantly attenuated increases in pulmonary
resistance and decreases in dynamic pulmonary compliance in response to intravenous
histamine. Halothane was most effective in altering indices of bronchodilation,
whereas responses to isoflurane, enflurane, and sevoflurane were nearly identical.
[35]
In contrast, halothane, enflurane, and sevoflurane
were found to be equivalent at dilating third- or fourth-generation bronchi as measured
directly with a fiberoptic bronchoscope in vivo.[40]
