The influence of endotoxemia on the electroencephalographic and antinociceptive effects of isoflurane in a swine model.
BACKGROUND
We have previously reported that hemorrhagic shock decreases the minimum alveolar anesthetic concentration (MAC) of isoflurane but minimally alters the electroencephalographic (EEG) effect. In this study, we investigated the influence of endotoxemia on the EEG effect and the MAC of isoflurane.


METHODS
Eighteen swine (25.7 +/- 2.3 kg) were anesthetized by inhalation of isoflurane. The inhaled concentration was decreased to 0.5% and maintained for 20 min, before being returned to 2% and maintained for a further 20 min. End-tidal isoflurane concentrations and spectral edge frequencies were recorded. Analysis of the pharmacodynamics was performed using a sigmoidal inhibitory maximal effect model for spectral edge frequencies versus effect-site concentration. After measurement of the EEG effect, MAC was determined using the dewclaw clamp technique in which movement in response to clamping is recorded. After completion of control measurements, infusion of lipopolysaccharide (LPS, 1 microg x kg(-1) x h(-1)) was started after a 100-microg bolus administration. After 1 h, the inhaled concentration of isoflurane was varied as in the control period, and the MAC was assessed again (LPS1h). The same procedures were also performed after 3 h of LPS infusion (LPS3h).


RESULTS
Endotoxemia decreased the effect-site concentration that produced 50% of the maximal effect from 1.31% +/- 0.22% to 1.13% +/- 0.14% (LPS1h) and 1.03% +/- 0.22% (LPS3h) and decreased the MAC from 2.05% +/- 0.20% to 1.51% +/- 0.30% (LPS1h) and 1.21% +/- 0.29% (LPS3h).


CONCLUSIONS
Endotoxemia increases both the hypnotic and antinociceptive effects of isoflurane, in contrast to hemorrhagic shock, and the extent of these alterations increases with progression of endotoxemia.
Kurita
Tadayoshi
T
Department of Anesthesiology and Intensive Care, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan. tadkur@hama-med.ac.jp
Takata
Kotaro
K
Morita
Koji
K
Uraoka
Masahiro
M
Sato
Shigehito
S
D000700:Analgesics / Q000494:pharmacology*; D000769:Anesthesia, Inhalation; D018685:Anesthetics, Inhalation / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D004569:Electroencephalography / Q000187:drug effects*; D019446:Endotoxemia / Q000503:physiopathology*; D007530:Isoflurane / Q000493:pharmacokinetics / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity; D010147:Pain Measurement / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism; D013552:Swine; D014693:Ventricular Fibrillation / Q000503:physiopathology
D000700:Analgesics; D018685:Anesthetics, Inhalation; D008070:Lipopolysaccharides; D007530:Isoflurane