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Application of the optimized carbon monoxide rebreathing method for the measurement of total haemoglobin mass in chronic liver disease.
Physiol Rep. 2020 03; 8(6):e14402.PR

Abstract

BACKGROUND

Anemia is common in liver cirrhosis. This generally infers a fall in total hemoglobin mass (tHb-mass). However, hemoglobin concentration ([Hb]) may fall due to an expansion in plasma volume (PV). The "optimized carbon monoxide rebreathing method" (oCOR) measures tHb-mass directly and PV (indirectly using hematocrit). It relies upon carboxyhemoglobin (COHb) distribution throughout the entire circulation. In healthy subjects, such distribution is complete within 6-8 min. Given the altered circulatory dynamics in cirrhosis, we sought in this pilot study, to assess whether this was true in cirrhosis. The primary aim was to ascertain if the standard timings for the oCOR were applicable to patients with chronic liver disease and cirrhosis. The secondary aim was to explore the applicability of standard CO dosing methodologies to this patient population.

METHODS

Sixteen patients with chronic liver parenchymal disease were studied. However, tHb-mass was determined using the standard oCOR technique before elective paracentesis. Three subjects had an inadequate COHb% rise. In the remaining 13 (11 male), mean ± standard deviation (SD) age was 52 ± 13.8 years, body mass 79.1 ± 11.4 kg, height 175 ± 6.8 cm. To these, mean ± SD dose of carbon monoxide (CO) gas administered was 0.73 ± 0.13 ml/kg COHb values at baseline, 6 and 8 min (and "7-min value") were compared to those at 10, 12, 15 and 20 min after CO rebreathing.

RESULTS

The "7-min value" for median COHb% (IQR) of 6.30% (6.21%-7.47%) did not differ significantly from those at subsequent time points (8 min: 6.30% (6.21%-7.47%), 10 min: 6.33% (6.00%-7.50%), 12 min: 6.33% (5.90%-7.40%), 15 min: 6.37% (5.80%-7.33%), 20 min: 6.27% (5.70%-7.20%)). Mean difference in calculated tHb-mass between minute 7 and minute 20 was only 4.1 g, or 0.6%, p = .68. No subjects reported any adverse effects.

CONCLUSIONS

The oCOR method can be safely used to measure tHb-mass in patients with chronic liver disease and ascites, without adjustment of blood sample timings. Further work might refine and validate appropriate dosing regimens.

Links

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Authors+Show Affiliations

Plumb JOM
Respiratory and Critical Care Research Area, NIHR Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust / University of Southampton, Southampton, UK. Centre for Human Integrative Physiology, Faculty of Medicine, University of Southampton, Southampton, UK. Anaesthesia, Perioperative Medicine and Critical Care Research Unit, University Hospital Southampton NHSFT, Southampton, UK. Shackleton Department of Anaesthesia, University Hospital Southampton NHSFT, Southampton, UK.
Otto JM
Respiratory and Critical Care Research Area, NIHR Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust / University of Southampton, Southampton, UK. Centre for Human Integrative Physiology, Faculty of Medicine, University of Southampton, Southampton, UK. Anaesthesia, Perioperative Medicine and Critical Care Research Unit, University Hospital Southampton NHSFT, Southampton, UK. Shackleton Department of Anaesthesia, University Hospital Southampton NHSFT, Southampton, UK. University of Southampton Medical School, Southampton, UK.
Kumar SB
Centre for Human Integrative Physiology, Faculty of Medicine, University of Southampton, Southampton, UK. University of Southampton Medical School, Southampton, UK.
Wright M
Department of Hepatology, University Hospital Southampton, Southampton, UK.
Schmidt W
Department of Sports Medicine/Sports Physiology, University of Bayreuth, Bayreuth, Germany.
Grocott MPW
Respiratory and Critical Care Research Area, NIHR Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust / University of Southampton, Southampton, UK. Centre for Human Integrative Physiology, Faculty of Medicine, University of Southampton, Southampton, UK. Anaesthesia, Perioperative Medicine and Critical Care Research Unit, University Hospital Southampton NHSFT, Southampton, UK. Shackleton Department of Anaesthesia, University Hospital Southampton NHSFT, Southampton, UK. Department of Anesthesiology, Duke University School of Medicine, Durham, NC, USA.
Montgomery HE
Centre for Human Health and Performance/ Institute of Sport, Exercise and Health, University College London, and NIHR University College London Hospitals Biomedical Research Centre, London, UK.

MeSH

Carbon MonoxideCarboxyhemoglobinFemaleFibrosisHemoglobinsHumansLiver DiseasesMaleMiddle AgedPilot Projects

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32207243

Citation

Plumb, James O M., et al. "Application of the Optimized Carbon Monoxide Rebreathing Method for the Measurement of Total Haemoglobin Mass in Chronic Liver Disease." Physiological Reports, vol. 8, no. 6, 2020, pp. e14402.
Plumb JOM, Otto JM, Kumar SB, et al. Application of the optimized carbon monoxide rebreathing method for the measurement of total haemoglobin mass in chronic liver disease. Physiol Rep. 2020;8(6):e14402.
Plumb, J. O. M., Otto, J. M., Kumar, S. B., Wright, M., Schmidt, W., Grocott, M. P. W., & Montgomery, H. E. (2020). Application of the optimized carbon monoxide rebreathing method for the measurement of total haemoglobin mass in chronic liver disease. Physiological Reports, 8(6), e14402. https://doi.org/10.14814/phy2.14402
Plumb JOM, et al. Application of the Optimized Carbon Monoxide Rebreathing Method for the Measurement of Total Haemoglobin Mass in Chronic Liver Disease. Physiol Rep. 2020;8(6):e14402. PubMed PMID: 32207243.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Application of the optimized carbon monoxide rebreathing method for the measurement of total haemoglobin mass in chronic liver disease. AU - Plumb,James O M, AU - Otto,James M, AU - Kumar,Shriya B, AU - Wright,Mark, AU - Schmidt,Walter, AU - Grocott,Michael P W, AU - Montgomery,Hugh E, PY - 2020/01/09/received PY - 2020/02/20/revised PY - 2020/02/23/accepted PY - 2020/3/25/entrez PY - 2020/3/25/pubmed PY - 2021/3/19/medline KW - anemia KW - chronic liver disease KW - optimized carbon monoxide rebreathing method (oCOR) KW - total hemoglobin mass (tHb-mass) SP - e14402 EP - e14402 JF - Physiological reports JO - Physiol Rep VL - 8 IS - 6 N2 - BACKGROUND: Anemia is common in liver cirrhosis. This generally infers a fall in total hemoglobin mass (tHb-mass). However, hemoglobin concentration ([Hb]) may fall due to an expansion in plasma volume (PV). The "optimized carbon monoxide rebreathing method" (oCOR) measures tHb-mass directly and PV (indirectly using hematocrit). It relies upon carboxyhemoglobin (COHb) distribution throughout the entire circulation. In healthy subjects, such distribution is complete within 6-8 min. Given the altered circulatory dynamics in cirrhosis, we sought in this pilot study, to assess whether this was true in cirrhosis. The primary aim was to ascertain if the standard timings for the oCOR were applicable to patients with chronic liver disease and cirrhosis. The secondary aim was to explore the applicability of standard CO dosing methodologies to this patient population. METHODS: Sixteen patients with chronic liver parenchymal disease were studied. However, tHb-mass was determined using the standard oCOR technique before elective paracentesis. Three subjects had an inadequate COHb% rise. In the remaining 13 (11 male), mean ± standard deviation (SD) age was 52 ± 13.8 years, body mass 79.1 ± 11.4 kg, height 175 ± 6.8 cm. To these, mean ± SD dose of carbon monoxide (CO) gas administered was 0.73 ± 0.13 ml/kg COHb values at baseline, 6 and 8 min (and "7-min value") were compared to those at 10, 12, 15 and 20 min after CO rebreathing. RESULTS: The "7-min value" for median COHb% (IQR) of 6.30% (6.21%-7.47%) did not differ significantly from those at subsequent time points (8 min: 6.30% (6.21%-7.47%), 10 min: 6.33% (6.00%-7.50%), 12 min: 6.33% (5.90%-7.40%), 15 min: 6.37% (5.80%-7.33%), 20 min: 6.27% (5.70%-7.20%)). Mean difference in calculated tHb-mass between minute 7 and minute 20 was only 4.1 g, or 0.6%, p = .68. No subjects reported any adverse effects. CONCLUSIONS: The oCOR method can be safely used to measure tHb-mass in patients with chronic liver disease and ascites, without adjustment of blood sample timings. Further work might refine and validate appropriate dosing regimens. SN - 2051-817X UR - https://www.unboundmedicine.com/medline/citation/32207243/Application_of_the_optimized_carbon_monoxide_rebreathing_method_for_the_measurement_of_total_haemoglobin_mass_in_chronic_liver_disease_ DB - PRIME DP - Unbound Medicine ER -