The steady‐state and rebreathing methods compared during morphine administration in humans.

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Abstract
1. We examined the quantitative and qualitative differences between the steady‐state and rebreathing methods of determining CO2‐response curves before and after each of two doses of intravenous morphine (0.07 and 0.14 mg kg‐1) in four healthy male humans. 2. During each study session steady‐state and rebreathing CO2‐response curves were determined as an ordered pair (separated by 15 min). Carbon dioxide‐response curves were determined for control, after 0.07 mg kg‐1 morphine, and after a total of 0.21 mg kg‐1 morphine. Each subject was studied on a second occasion when the order of the CO2‐response pairing was reversed. 3. The results are discussed and related to a model that may account for the differences based on the step increase in CO2 at the onset of rebreathing, the rate of rise of CO2 during rebreathing and the time constant for the central chemoreflex. 4. Our empirical conclusion is that morphine causes a parallel right shift of the steady‐state CO2‐response curve and causes a non‐specific decrease in the slope of the rebreathing CO2‐response curve. We suggest that the parallel shift of the steady‐state CO2‐response curve is specific to drugs acting on opioid receptors.