Respiratory sites of action of propofol: absence of depression of peripheral chemoreflex loop by low-dose propofol.
BACKGROUND
Propofol has a depressant effect on metabolic ventilatory control, causing depression of the ventilatory response to acute isocapnic hypoxia, a response mediated via the peripheral chemoreflex loop. In this study, the authors examined the effect of sedative concentrations of propofol on the dynamic ventilatory response to carbon dioxide to obtain information about the respiratory sites of action of propofol.


METHODS
In 10 healthy volunteers, the end-tidal carbon dioxide concentration was varied according to a multifrequency binary sequence that involved 13 steps into and 13 steps out of hypercapnia (total duration, 1,408 s). In each subject, two control studies, two studies at a plasma target propofol concentration of 0.75 microg/ml (P(low)), and two studies at a target propofol concentration of 1.5 microg/ml (P(high)) were performed. The ventilatory responses were separated into a fast peripheral component and a slow central component, characterized by a time constant, carbon dioxide sensitivity, and apneic threshold. Values are mean +/- SD.


RESULTS
Plasma propofol concentrations were approximately 0.5 microg/ml for P(low) and approximately 1.3 mg/ml for P(high), Propofol reduced the central carbon dioxide sensitivity from 1.5 +/- 0.4 to 1.2 +/- 0.3 (P(low); P < 0.01 vs. control) and 0.9 +/- 0.1 l x min(-1) x mmHg(-1) (P(high); P < 0.001 vs. control). The peripheral carbon dioxide sensitivity remained unaffected by propofol (control, 0.5 +/- 0.3; P(low), 0.5 +/- 0.2; P(high), 0.5 +/- 0.2 l x min(-1) x mmHg(-1)). The apneic threshold was reduced from 36.3 +/- 2.7 (control) to 35.0 +/- 2.1 (P(low); P < 0.01 vs. control) and to 34.6 +/- 1.9 mmHg (P(high); P < 0.01 vs. control).


CONCLUSIONS
Sedative concentrations of propofol have an important effect on the control of breathing, showing depression of the ventilatory response to hypercapnia. The depression is attributed to an exclusive effect within the central chemoreflex loop at the central chemoreceptors. In contrast to low-dose inhalational anesthetics, the peripheral chemoreflex loop, when stimulated with carbon dioxide, remains unaffected by propofol.
Nieuwenhuijs
D
D
Department of Anesthesiology, Leiden University Medical Center, The Netherlands.
Sarton
E
E
Teppema
L J
LJ
Kruyt
E
E
Olievier
I
I
van Kleef
J
J
Dahan
A
A
D000293:Adolescent; D000328:Adult; D000465:Algorithms; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D001049:Apnea / Q000097:blood; D002245:Carbon Dioxide / Q000097:blood; D002628:Chemoreceptor Cells / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D010100:Oxygen / Q000097:blood; D017933:Peripheral Nervous System / Q000187:drug effects; D015742:Propofol / Q000008:administration & dosage / Q000494:pharmacology*; D012018:Reflex / Q000187:drug effects*; D012137:Respiratory System / Q000187:drug effects*
D018686:Anesthetics, Intravenous; D002245:Carbon Dioxide; D010100:Oxygen; D015742:Propofol