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. 1989 Dec;419:509–517. doi: 10.1113/jphysiol.1989.sp017883

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

D L Bourke 1, A Warley 1
PMCID: PMC1190018  PMID: 2516128

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berkenbosch A., Bovill J. G., Dahan A., DeGoede J., Olievier I. C. The ventilatory CO2 sensitivities from Read's rebreathing method and the steady-state method are not equal in man. J Physiol. 1989 Apr;411:367–377. doi: 10.1113/jphysiol.1989.sp017578. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berkenbosch A., DeGoede J., Olievier C. N., Schuitmaker J. J. A pseudo-rebreathing technique for assessing the ventilatory response to carbon dioxide in cats. J Physiol. 1986 Dec;381:483–495. doi: 10.1113/jphysiol.1986.sp016340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bourke D. L., Malit L. A., Smith T. C. Respiratory interactions of ketamine and morphine. Anesthesiology. 1987 Feb;66(2):153–156. doi: 10.1097/00000542-198702000-00008. [DOI] [PubMed] [Google Scholar]
  4. Carlsson C., Smith D. S., Keykhah M. M., Englebach I., Harp J. R. The effects of high-dose fentanyl on cerebral circulation and metabolism in rats. Anesthesiology. 1982 Nov;57(5):375–380. doi: 10.1097/00000542-198211000-00005. [DOI] [PubMed] [Google Scholar]
  5. Dempsey J. A. CO2 response: stimulus definition and limitations. Chest. 1976 Jul;70(1 Suppl):114–118. doi: 10.1378/chest.70.1.114. [DOI] [PubMed] [Google Scholar]
  6. Finck A. D., Ngai S. H. Opiate receptor mediation of ketamine analgesia. Anesthesiology. 1982 Apr;56(4):291–297. doi: 10.1097/00000542-198204000-00011. [DOI] [PubMed] [Google Scholar]
  7. Goodman N. W., Curnow J. S. The ventilatory response to carbon dioxide. An analysis of data obtained by the rebreathing method. Br J Anaesth. 1985 Mar;57(3):311–318. doi: 10.1093/bja/57.3.311. [DOI] [PubMed] [Google Scholar]
  8. Irsigler G. B. Carbon dioxide response lines in young adults: the limits of the normal response. Am Rev Respir Dis. 1976 Sep;114(3):529–536. doi: 10.1164/arrd.1976.114.3.529. [DOI] [PubMed] [Google Scholar]
  9. Jennett S., Barker J. G., Forrest J. B. A double-blind controlled study of the effects on respiration of pentazocine, phenoperidine and morphine in normal man. Br J Anaesth. 1968 Nov;40(11):864–875. doi: 10.1093/bja/40.11.864. [DOI] [PubMed] [Google Scholar]
  10. Jordan C. Assessment of the effects of drugs on respiration. Br J Anaesth. 1982 Jul;54(7):763–782. doi: 10.1093/bja/54.7.763. [DOI] [PubMed] [Google Scholar]
  11. LOESCHCKE H. H., SWEEL A., KOUGH R. H., LAMBERTSEN C. J. The effect of morphine and of meperidine (dolantin, demerol) upon the respiratory response of normal men to low concentrations of inspired carbon dioxide. J Pharmacol Exp Ther. 1953 Jul;108(3):376–383. [PubMed] [Google Scholar]
  12. Linton R. A., Poole-Wilson P. A., Davies R. J., Cameron I. R. A comparison of the ventilatory response to carbon dioxide by steady-state and rebreathing methods during metabolic acidosis and alkalosis. Clin Sci Mol Med. 1973 Aug;45(2):239–249. doi: 10.1042/cs0450239. [DOI] [PubMed] [Google Scholar]
  13. Read D. J. A clinical method for assessing the ventilatory response to carbon dioxide. Australas Ann Med. 1967 Feb;16(1):20–32. doi: 10.1111/imj.1967.16.1.20. [DOI] [PubMed] [Google Scholar]
  14. Read D. J., Leigh J. Blood-brain tissue Pco2 relationships and ventilation during rebreathing. J Appl Physiol. 1967 Jul;23(1):53–70. doi: 10.1152/jappl.1967.23.1.53. [DOI] [PubMed] [Google Scholar]
  15. Rebuck A. S. Measurement of ventilatory response to CO2 by rebreathing. Chest. 1976 Jul;70(1 Suppl):118–121. doi: 10.1378/chest.70.1_supplement.118. [DOI] [PubMed] [Google Scholar]
  16. Rigg J. R. Ventilatory effects and plasma concentration of morphine in man. Br J Anaesth. 1978 Aug;50(8):759–765. doi: 10.1093/bja/50.8.759. [DOI] [PubMed] [Google Scholar]
  17. Sahn S. A., Zwillich C. W., Dick N., McCullough R. E., Lakshminarayan S., Weil J. V. Variability of ventilatory responses to hypoxia and hypercapnia. J Appl Physiol Respir Environ Exerc Physiol. 1977 Dec;43(6):1019–1025. doi: 10.1152/jappl.1977.43.6.1019. [DOI] [PubMed] [Google Scholar]
  18. Smith D. J., Pekoe G. M., Martin L. L., Coalgate B. The interaction of ketamine with the opiate receptor. Life Sci. 1980 Mar 10;26(10):789–795. doi: 10.1016/0024-3205(80)90285-4. [DOI] [PubMed] [Google Scholar]
  19. Strachova Z., Plum F. Reproducibility of the rebreathing carbon dioxide response test using an improved method. Am Rev Respir Dis. 1973 May;107(5):864–869. doi: 10.1164/arrd.1973.107.5.864. [DOI] [PubMed] [Google Scholar]
  20. Takeshita H., Michenfelder J. D., Theye R. A. The effects of morphine and N-allylnormorphine on canine cerebral metabolism and circulation. Anesthesiology. 1972 Dec;37(6):605–612. doi: 10.1097/00000542-197212000-00007. [DOI] [PubMed] [Google Scholar]
  21. Vernhiet J., Renou A. M., Orgogozo J. M., Constant P., Caille J. M. Effects of a diazepam-fentanyl mixture on cerebral blood flow and oxygen consumption in man. Br J Anaesth. 1978 Feb;50(2):165–169. doi: 10.1093/bja/50.2.165. [DOI] [PubMed] [Google Scholar]

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