European Journal of Applied Physiology

, Volume 95, Issue 5–6, pp 486–495 | Cite as

The optimised CO-rebreathing method: a new tool to determine total haemoglobin mass routinely

  • Walter SchmidtEmail author
  • Nicole Prommer
Original Article


A routine method to determine total haemoglobin mass (tHb) in clinical practice and sports medicine is non-existent. Radioactive tracers or other dilution procedures like the common CO-rebreathing method (Proccom) are impractical, the latter in particular because of the relatively long time of respiration. According to the multicompartment model of Bruce and Bruce (J Appl Physiol 95:1235–1247, 2003) the respiration time can be considerably reduced by inhaling a CO-bolus instead of the commonly used gas mixture. The aim of this study was to evaluate this theoretical concept in practice. The kinetics of the HbCO formation were compared in arterialised blood sampled from an hyperaemic earlobe after inhaling a CO-bolus (Procnew) for 2 min and a CO–O2 mixture (Proccom) for ∼10 min. The reliability of Procnew was checked in three consecutive tests, and phlebotomy was used to determine the validity. VO2max was determined with and without previous application of Procnew and the half-time of HbCO was registered also in arterialised blood after resting quietly and after the VO2max test. Procnew yielded virtual identical tHb values compared to Proccom when HbCO determined 5 min after starting CO-rebreathing was used for calculation. The typical error of Procnew was 1.7%, corresponding to a limit of agreement (95%) of 3.3%. The loss of 95 g (19) haemoglobin was detected with an accuracy of 9 g (12). After application of Procnew VO2max was reduced by 3.0% (3.7) (P=0.022) and half-time was lowered from 132 min (77) to 89 min (23) after the VO2max test. Inhaling a CO-bolus markedly simplifies the CO-rebreathing method without reducing validity and reliability and can be used for routine determination of tHb for various indications.


Carbonmonoxide Carboxyhaemoglobin Mixing time Myoglobin HbCO half-time 



The project was supported by the German Federal Institute of Sports Sciences (BISp,# VF 0407/03/42). The authors wish to thank Mrs. H. Gaisser, Mr. A. Beller, Mr. A. Schmeiduch and Mr. M. Gebert for their excellent technical assistance.


  1. Arnold HR, Carrier EB, Smith HP, Whipple GH (1921) Blood volume studies. Am J Physiol 56:313–327Google Scholar
  2. Ashenden MJ, Gore CJ, Dobson GP, Hahn AG (1999) Live high, train low does not change the total haemoglobin mass of male endurance athletes sleeping at a simulated altitude of 3000 m for 23 nights. Eur J Appl Physiol 80:479–484CrossRefGoogle Scholar
  3. Barker SJ (1998) Blood volume measurement. Anesthesiology 89:1310–1312PubMedCrossRefGoogle Scholar
  4. Barnett K, Wilson JF (1998) Quantitation of carboxyhaemoglobin in blood: external quality assessment of techniques. Br J Biomed Sci 55:123–126PubMedGoogle Scholar
  5. Bland JM, Altman DG (1986) Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 8476:307–310Google Scholar
  6. Böning D, Rojas J, Serrato M, Ulloa C, Coy L, Mora M, Hütler M (2001) Haemoglobin mass and peak oxygen uptake in untrained and trained residents of moderate altitude. Int J Sports Med 22:1–7CrossRefGoogle Scholar
  7. Bruce EN, Bruce MC (2003) A multicompartment model of carboxyhaemoglobin and carboxymyoglobin responses to inhalation of carbon monoxide. J Appl Physiol 95:1235–1247PubMedGoogle Scholar
  8. Burge CM, Skinner SL (1995) Determination of haemoglobin mass and blood volume with CO: evaluation and application of a method. J Appl Physiol 79:623–631PubMedGoogle Scholar
  9. Douglas CG, Haldane JS, Haldane JBS (1912) The laws of combination of haemoglobin with carbon monoxide and oxygen. J Physiol 44:275–304PubMedGoogle Scholar
  10. Drabkin DL (1951) Metabolism of the hemin chromoproteins. Physiol Rev 31:345–431PubMedGoogle Scholar
  11. Ekblom B, Huot R (1972) Response to submaximal and maximal exercise at different levels of carboxyhaemoglobin. Acta Physiol Scand 86:474–482PubMedGoogle Scholar
  12. Fogh-Andersen N, Thomsen JK, Foldager N, Siggaard-Andersen O (1990) pH effect on the COHb absorption spectrum: importance for calibration of the OSM3 and measurement of circulating haemoglobin and blood volume. Scand J Clin Lab Invest 50:247–252CrossRefGoogle Scholar
  13. Friedmann B, Jost J, Rating T, Weller E, Werle E, Eckhardt K-U, Bärtsch P, Mairläurl H (1999) Effects of iron supplement on total body haemoglobin during endurance training at moderate altitude. Int J Sports Med 20:78–85PubMedCrossRefGoogle Scholar
  14. Gibson JG, Evans WA Jr (1937) Clinical studies of the blood volume. I. Clinical application of a method employing the azo dye “Evans Blue” and the spectrophotometer. J Clin Invest 16:301–316PubMedCrossRefGoogle Scholar
  15. Godin G, Shephard RJ (1972) On the course of carbon monoxide uptake and release. Respiration 29:317–329PubMedGoogle Scholar
  16. Gore CJ, Hahn AG, Burge CM, Telford RD (1997) VO2max and haemoglobin mass of trained athletes during high intensity training. Int J Sports Med 18:477–482PubMedCrossRefGoogle Scholar
  17. Gorelov V (2004) Theoretical value of Hüfner’s count. Anesthesia 59:97CrossRefGoogle Scholar
  18. Hauck H (1989) Parameters influencing carbon monoxide kinetics. Exp Pathol 37:170–176PubMedGoogle Scholar
  19. He Y-L, Tanigami H, Ueyama H, Mashimo T, Yoshiya I (1998) Measurment of blood volume using indocyanine green measured with pulse-spectrophotometry: its reproducibility and reliability. Crit Care Med 26:1446–1451PubMedCrossRefGoogle Scholar
  20. Heinicke K, Wolfahrt B, Winchenbach P, Biermann B, Schmid A, Huber G, Friedmann B, Schmidt W (2001) Blood volume and haemoglobin mass in elite athletes of different disciplines. Int J Sports Med 22:504–512PubMedCrossRefGoogle Scholar
  21. Hirsch GL, Sue DY, Wasserman K, Robinson TE, Hansen JE (1985) Immediate effects of cigarette smoking on cardiorespiratory responses to exercise. J Appl Physiol 58:1975–1981PubMedGoogle Scholar
  22. Hogan MC, Bebout DE, Gray AT, Wagner PD, West JB, Haab PE (1990) Muscle maximal O2 uptake at constant O2 delivery with and without CO in the blood. J Appl Physiol 69:830–836PubMedGoogle Scholar
  23. Hopkins WG (2000) Measures of reliability in sports medicine and science. Sports Med 30:1–15PubMedCrossRefGoogle Scholar
  24. Horvath SM, Raven PB, Dahms TE, Gray DJ (1975) Maximal aerobic capacity at different levels of caboxyhaemoglobin. J Appl Physiol 38:300–303PubMedGoogle Scholar
  25. Hütler M, Beneke R, Böning D (2000) Determination of circulating haemoglobin mass and related quantities by using capillary blood. Med Sci Sports Exerc 32:1024–1027PubMedCrossRefGoogle Scholar
  26. International Committee for Standardization in Haematology (1980) Recommended methods for measurement of red-cell and plasma volume: International Committee for Standardization in Haematology. J Nucl Med 21:793–800Google Scholar
  27. Joels N, Pugh LGCE (1958) The carbon monoxide dissociation curve of human blood. J Physiol 142:63–77PubMedGoogle Scholar
  28. Kisch H, Leucht S, Lichtwarck-Schoff M, Pfeiffer UJ (1995) Accuracy and reproducibility of the measurement of actively circulating blood volume with an integrated fiberoptic monitoring system. Crit Care Med 23:885–893PubMedCrossRefGoogle Scholar
  29. Klausen K, Andersen C, Nandrup S (1983) Acute effects of cigarette smoking and inhalation of carbon monoxide during maximal excercise. Eur J Appl Physiol 51:371–379CrossRefGoogle Scholar
  30. Lee RC, Wang Z, Heo M, Ross R, Janssen I, Heymsfield SB (2000) Total-body skeletal muscle mass: development and cross-validation of anthropometric prediction models. Am J Clin Nutr 72:796–803PubMedGoogle Scholar
  31. Möller P, Sylvén C (1981) Myoglobin in human skeletal muscle. Scand J Clin Lab Invest 41:479–482PubMedCrossRefGoogle Scholar
  32. Mollison PL (1967) Blood volume. In: Mollison PL (ed) Blood transfusion in clinical medicine. Blackwell, Oxford, pp 115–150Google Scholar
  33. Peterson JE, Stewart RD (1970) Absorption and elimination of carbon monoxide by inactive young men. Arch Environ Health 21:165–171PubMedGoogle Scholar
  34. Pirnay F, Dujardin J, Deroann R, Petit JM (1971) Muscular exercise during intoxication by carbon monoxide. J Appl Physiol 31:573–575PubMedGoogle Scholar
  35. Remington JW, Baker CH (1961) Evaluation of blood volume measurment techniques. Circ Res 9:60–68PubMedGoogle Scholar
  36. Richardson RS, Noyszewski EA, Saltin B, Gonzáles-Alonso J (2002) Effect of mild carboxy-haemoglobin on exercising skeletal muscle: intravascular and intracellular evidence. Am J Physiol Regul Integr Comp Physiol 283:1131–1139Google Scholar
  37. Sawka MN, Convertino VA, Eichner ER, Schnieder SM, Young AJ (2000) Blood volume: importance and adaptions to exercise training, environmental stresses, and trauma /sickness. Med Sci Sports Exerc 32:332–348PubMedCrossRefGoogle Scholar
  38. Shimazu T, Ikeuchi H, Sugomoto H, Goodwin CW, Mason AD, Pruitt BA (2000) Half-life of blood carboxyhaemoglobin after short-term and long-term exposure to carbon monoxide. J Trauma Inj Infect Crit Care 49:126–131CrossRefGoogle Scholar
  39. Thomsen JK, Fogh-Andersen N, Bülow K, Devantier A (1991) Blood and plasma volumes determined by carbon monoxide gas, 99mTc-labelled erythrocytes, 125 I-albumin and the T 1824 technique. Scand J Clin Lab Invest 51:185–190PubMedCrossRefGoogle Scholar
  40. Tikuisis P, Buick F, Kane DM (1987) Percent carboxyhaemoglobin in resting humans exposed repeatedly to 1,500 and 7,500 ppm CO. J Appl Physiol 63:820–827PubMedGoogle Scholar
  41. Togores B, Bosch M, Agustí AGN (2000) The measurement of exhaled carbon monoxide is influenced by airflow obstruction. Eur Respir J 15:177–180PubMedCrossRefGoogle Scholar
  42. Tschaikowsky K, Meisner M, Durst R, Rügheimer E (1997) Blood volume determination using hydroxyethyl starch: a rapid and a simple intravenous injection method. Crit Care Med 25:599–606PubMedCrossRefGoogle Scholar
  43. Vogel JA, Gleser MA (1972) Effect of carbon monoxide on oxygen transport during exercise. J Appl Phys 32:234–239Google Scholar
  44. Weaver LK, Howe S, Hopkins R, Chan KJ (2001) Carboxyhaemoglobin half-life in carbon monoxide-poisoned patients treated with 100% oxygen at atmospheric pressure. Chest 117:801–808CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Department of Sports Medicine and Sports PhysiologyUniversity of BayreuthBayreuthGermany

Personalised recommendations