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

Abstract

SUMMARY1. We examined the quantitative and qualitative differences between the steadystate and rebreathing methods of determining C02-response curves before and after each of two doses of intravenous morphine (0 07 and 0-14 mg kg-') in four healthy male humans.2. During each study session steady-state and rebreathing C02-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-' 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 C02-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 C02-response curve. We suggest that the parallel shift of the steadystate C02-response curve is specific to drugs acting on opioid receptors.

Fatty Acid Amide Hydrolase–morphine Interaction Influences Ventilatory Response to Hypercapnia and Postoperative Opioid Outcomes in Children

“…The negative association of MV with increasing morphine concentrations is in accordance with our premise that morphine causes a nonspecific decrease in the slope of rebreathing CO 2 -MV response slope [9]. Although increased MV response in females compared with males, in the presence of morphine, was an unexpected finding, female rats have been found to have a greater HCVR than male rats [54], and morphine-induced changes in central sensitivity, were found to be sex-independent [55,56].…”

“…This takes less time than the steady-state method and although less specific for opioid effects [9], it is the most suitable method realistically possible in a pre-and postsurgical clinical pediatric setting [7,10]. It is known that in analgesic doses, morphine causes a reduction in HCVR slope [9,11]; this method has been previously used to discern genetic effects on opioid-induced RD [12]. In this study, we evaluate the effect of FAAH variants on morphine-induced depression of HCVR and morphine-associated adverse clinical outcomes, in an adolescent population undergoing invasive surgery (spine fusion) and requiring prolonged opioids via patient-controlled analgesia (PCA).…”

“…A quantifiable objective indicator of sensitivity to opioidinduced RD is the hypercapnic ventilatory response (HCVR), measured by the rebreathing method [7,8]. This takes less time than the steady-state method and although less specific for opioid effects [9], it is the most suitable method realistically possible in a pre-and postsurgical clinical pediatric setting [7,10]. It is known that in analgesic doses, morphine causes a reduction in HCVR slope [9,11]; this method has been previously used to discern genetic effects on opioid-induced RD [12].…”

On a pseudo‐rebreathing technique to assess the ventilatory sensitivity to carbon dioxide in man.

“…Indeed, we found that the CO2 sensitivity from rebreathing experiments exceeded the steady-state CO2 sensitivity by roughly a factor of 2. This was recently confirmed by others (Jacobi, Patil & Saunders, 1989;Bourke & Warley, 1989). These results are at variance with those of Read (1967) who found good agreement between the CO2 sensitivities obtained with both methods.…”

“…This has been demonstrated by Linton, Poole-Wilson, Davies & Cameron (1973) in a study on the effect on ventilation of chronic acid-base disturbances in man, and more recently by Bourke & Warley (1989) in a study on the effects of morphine on ventilation.…”