Ventilatory Responses to Hypoxemia
Volatile anesthetics and nitrous oxide attenuate the ventilatory
response to hypoxia in experimental animals and humans in a dose-dependent manner.
[320]
[321]
[322]
[323]
[324]
The
peripheral chemoreceptors appear to be the major site of this inhibitory action.
[325]
Evidence supporting this hypothesis is indicated
by the rapid inhibition (30 seconds) of the hypoxic response[326]
and the reduction of carotid sinus nerve discharge when the peripheral chemoreceptors
are stimulated by a variety of methods during administration of halothane (0.5 to
1.0%) to decerebrate cats.[327]
Alternatively,
Stuth and colleagues[328]
demonstrated that the
phrenic nerve response to hypoxia is attenuated but not abolished by halothane in
vagotomized dogs. These results also did not indicate a relatively selective depression
of peripheral compared with central effects of chemoreflexes in this phenomenon.
The cause for these differences may be attributed to the profound degree of hypoxia
(arterial oxygen tension <40 mm Hg) conducted in experimental animals, compared
with those in human investigations (i.e., PaO2
50 mm Hg). A significant depression of hypoxia-induced ventilatory responsiveness
was observed at 1 MAC of halothane, and the usual synergistic effect of hypoxia and
hypercarbia on ventilation was profoundly attenuated. The ventilatory response to
hypoxia also depends on the degree to which carbon dioxide exceeds the peripheral
chemoreflex threshold rather than its elevation above resting partial pressure[329]
and the presence of NO (and presumably, a fully functional pulmonary arterial endothelium).
[330]
This latter role of NO may be more complicated,
because NO is released in the ventrolateral medulla after activation of peripheral
chemoreceptors during hypoxia in response to sympathoexcitation.[331]
Humans have a biphasic response to hypoxia. Adults and neonates
display a similar initial hypoxia-induced increase in ventilation, but neonates exhibit
a more pronounced ventilatory decline in response to prehypoxic oxygen concentration
compared with adults. This reaction may represent a balance between active inhibition
of brainstem neuronal activities and augmentation of peripheral chemoreceptor function.
[332]
Halothane also produces a biphasic ventilatory
response (similar to that observed in the newborn) in kittens that have previously
attained an adult-like hyperventilatory hypoxic response.[325]
Whether the cause of this altered response during halothane anesthesia is mediated
by peripheral chemoreceptors is unknown, but it is unlikely that activity at the
level of the brainstem is solely responsible for this phenomenon.[333]
The ventilatory decline occurring during sustained hypoxia is not attenuated by
low concentrations of enflurane.[334]
Gender-based
differences, known to exist within the peripheral but not the central chemoreflex
loop in morphine-induced ventilatory depression,[335]
do not appear to play a role during sevoflurane-induced reduction in hypoxic drive.
[336]
Knill and Gelb[321]
demonstrated
that peripheral chemoreceptor function was more sensitive to the effects of volatile
anesthetics in humans than in dogs. Significant attenuation of the peripheral chemoreceptor
response occurred at concentrations of halothane as low as 0.1 MAC. The hypoxic
ventilatory response was also proposed to be more sensitive to the effects of inhaled
anesthetics than was the response to hypercapnia,[320]
[321]
[337]
but
considerable
controversy about the influence of subanesthetic concentrations of volatile agents
on hypoxic ventilatory drive has arisen. Several groups have shown that 0.1 MAC
of sevoflurane[338]
or isoflurane does not affect
hypoxic drive in humans[339]
[340]
or animals,[341]
but Dahan and coworkers[310]
[311]
[342]
and
others
[334]
[343]
confirmed
the original findings of Knill and Gelb ( Fig.
6-22
). As was observed in studies examining the effects of volatile anesthetics
on hypercapnia-induced ventilatory responses, the reasons for these disparate findings
may be related to differences in techniques and study conditions. Most notably,
differences in the state of arousal achieved during each study and the wide variability
that may occur by studying subjects on different experimental days might have played
important roles.[340]
Subanesthetic concentrations
of most volatile anesthetics, with the exception of desflurane, depress the ventilatory
response to hypoxia in normocapnic resting subjects ( Fig.
6-23
). However, subanesthetic concentrations of desflurane decrease hypoxic
sensitivity during concomitant hypercapnia, suggesting an effect at the peripheral
chemoreceptors.[313]
Diffusion hypoxia is a well-known effect and may occur during
recovery from nitrous anesthesia. Rapid elimination of nitrous oxide from blood
to the alveoli combined with slower nitrogen diffusion reduces alveolar oxygen concentration.
However, diffusion hypoxia may not occur during xenon anesthesia, as the blood-gas
partition coefficient of xenon (0.12) is similar to that of nitrogen.[84]
