Ea. Stuth et al., DOSE-DEPENDENT EFFECTS OF HALOTHANE ON THE PHRENIC-NERVE RESPONSES TOACUTE-HYPOXIA IN VAGOTOMIZED DOGS, Anesthesiology, 87(6), 1997, pp. 1428-1439
Background: Previous studies in dogs and humans suggest that the carot
id body chemoreceptor response to hypoxia is selectively impaired by h
alothane. The present studies in an open-loop canine preparation were
performed to better delineate the effects of anesthetic concentrations
of halothane an the carotid body chemoreceptor-mediated phrenic nerve
response to an acute hypoxic stimulus. Methods: Three protocols were
performed to study the effects of halothane anesthesia on the phrenic
nerve response to 1 min of isocapnic hypoxia (partial pressure of oxyg
en [Pa-O2] at peak hypoxia, 35-38 mmHg) in unpremedicated, anesthetize
d, paralyzed, vagotomized dogs during constant mechanical ventilation.
In protocol 1, the dose-dependent effects of halothane from 0.5-2.0 m
inimum alveolar concentration (MAC) on the hypoxic response during mod
erate hypercapnia (partial pressure of carbon dioxide [Pa-CO2], 60-65
mmHg) were studied in 10 animals. In protocol 2, the hypoxic responses
at 1 MAC halothane near normocapnia (Pa-CO2, 40-45 mmHg) and during m
oderate hypercapnia were compared in an additional four animals. In pr
otocol 3, the hypoxic response of 4 of 10 dogs from protocol 1 was als
o studied under sodium thiopental (STP) anesthesia after they complete
d protocol 1. Results: Protocol 1: Peak phrenic nerve activity (PPA) i
ncreased significantly during the hypoxic runs compared with the isoca
pnic hyperoxic controls at all halothane doses. The phrenic nerve resp
onse to the hypoxic stimulus was present even at the 3 MAC dose. Proto
col 2: The net hypoxic responses for the two carbon dioxide background
levels at 1 MAC were not significantly different. Protocol 3: The net
hypoxic response of PPA. for the STP anesthetic was not significantly
different from the 1 MAC halothane dose, Bilateral carotid sinus dene
rvation abolished the PPA response to hypoxia. Conclusions: The phreni
c nerve response to an acute, moderately severe isocapnic hypoxic stim
ulus is dose-dependently depressed but not abolished by surgical doses
of halothane, This analysis does not suggest a selective depression o
f the carotid body chemoreceptor response by halothane. The observed h
ypoxic phrenic response was mediated hy the carotid body chemoreceptor
s in vagotomized dogs because bilateral carotid sinus denervation abol
ished all increases in PPA.