Comparison of the effects of sub-hypnotic concentrations of propofol and halothane on the acute ventilatory response to hypoxia.
To compare the effects of sub-anaesthetic concentrations of propofol and halothane on the respiratory control system, we have studied the acute ventilatory response to isocapnic hypoxia (AHVR) in 12 adults with and without three different concentrations of propofol and halothane. Target doses for propofol were 0, 0.05, 0.1 and 0.2 of the effective plasma concentration (EC50 = 8.1 micrograms ml-1). Target doses for halothane were 0, 0.05, 0.1 and 0.2 minimum alveolar concentration (MAC = 0.77%). The doses achieved experimentally were 0.01, 0.06, 0.13 and 0.26 of the EC50 for propofol and 0, 0.05, 0.11 and 0.20 MAC for halothane. During the experiment subjects breathed via a mouthpiece from an end-tidal forcing system. End-tidal PO2 (PE'O2) was held at 13.3 kPa for 5 min, and then at 6.7 kPa for 5 min. End-tidal PCO2 (PE'CO2) was held constant at 0.13-0.27 kPa greater than the subject's natural level throughout. The mean values for AHVR with propofol were: 12.8 (SEM 2.4) litre min-1 (0.01 EC50), 10.0 (1.9) litre min-1 (0.06 EC50), 9.8 (2.3) litre min-1 (0.13 EC50) and 4.9 (1.2) litre min-1 (0.26 EC50). The values for AHVR with halothane were: 11.9 (2.4) litre min-1 (0 MAC), 7.8 (1.6) litre min-1 (0.05 MAC), 5.9 (1.2) litre min-1 (0.11 MAC) and 3.2 (1.6) litre min-1 (0.2 MAC). The decline in AHVR with increasing dose for both drugs was statistically significant (ANOVA, P < 0.001); there was no significant difference between the two drugs with respect to this decline. Normoxic ventilation with propofol declined from 13.2 (1.6) litre min-1 (0.01 EC50) to 8.3 (0.9 litre min-1 (0.26 EC50), and with halothane declined from 13.5 (2.0) litre min-1 (0 MAC) to 11.8 (1.6) litre min-1 (0.2 MAC). This was significant for both drugs (ANOVA, P < 0.001).
Nagyova
B
B
University Laboratory of Physiology, Oxford.
Dorrington
K L
KL
Gill
E W
EW
Robbins
P A
PA
D000293:Adolescent; D000328:Adult; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006221:Halothane / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D010100:Oxygen / Q000502:physiology; D010313:Partial Pressure; D015742:Propofol / Q000008:administration & dosage / Q000494:pharmacology*; D012119:Respiration / Q000187:drug effects*
D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D002245:Carbon Dioxide; D010100:Oxygen; D006221:Halothane; D015742:Propofol