Application of the optimized carbon monoxide rebreathing method for the measurement of total haemoglobin mass in chronic liver disease

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

Hemoglobin concentration, total hemoglobin mass and plasma volume in patients: implications for anemia

In practice, clinicians generally consider anemia (circulating hemoglobin concentration < 120 g.l-1 in non-pregnant females and < 130 g.l-1 in males) as due to impaired hemoglobin synthesis or increased erythrocyte loss or destruction. Rarely is a rise in plasma volume relative to circulating total hemoglobin mass considered as a cause. But does this matter? We explored this issue in patients, using the optimized carbon-monoxide rebreathing method to measure hemoglobin concentration and thereby calculate plasma volume in healthy volunteers, surgical patients, and those with inflammatory bowel disease, chronic liver disease or heart failure. We studied 109 participants. Hemoglobin mass correlated well with its concentration in the healthy, surgical and inflammatory bowel disease groups (r= 0.687-0.871, p< 0.001). However, they were poorly related in liver disease (r= 0.410, p= 0.11) and heart failure patients (r= 0.312, p= 0.16). Here, hemoglobin mass explained little of the variance in its concentration (adjusted R2= 0.109 and 0.052; p= 0.11 and 0.16), whilst plasma volume did (R2 change 0.724 and 0.805 in heart and liver disease respectively, p<0.0001). Exemplar patients with identical (normal or raised) total hemoglobin masses were diagnosed as profoundly anemic (or not) depending on differences in plasma volume that had not been measured or even considered as a cause. The traditional inference that anemia generally reflects hemoglobin deficiency may be misleading, potentially resulting in inappropriate tests and therapeutic interventions to address 'hemoglobin deficiency not plasma volume excess. Measurement of total hemoglobin mass and plasma volume is now simple, cheap and safe, and its more routine use advocated

A carbon monoxide ‘single breath’ method to measure total haemoglobin mass: a feasibility study

NEW FINDINGS: What is the central question of this study? Is it possible to modify the CO-rebreathing method to acquire reliable measurements of haemoglobin mass in ventilated patients? What is the main finding and its importance? A 'single breath' of carbon monoxide with a subsequent 30 sec breath hold provides almost as exact a measure of haemoglobin mass as the established optimized CO-rebreathing method when applied to healthy subjects. The modified method has now to be checked in ventilated patients before it can be used to quantify the contributions of blood loss and of dilution to the severity of anaemia. ABSTRACT: Anaemia is defined by the concentration of haemoglobin ([Hb]). However, this value is dependent upon both the total circulating haemoglobin mass (tHb-mass) and the plasma volume (PV) - neither of which are routinely measured. Carbon monoxide- (CO) rebreathing methods have been successfully used to determine both PV and tHb-mass in various populations. However, these methods are not yet suitable for ventilated patients. This study aimed to modify the CO-rebreathing procedure such that a single inhalation of a CO bolus would enable its use in ventilated patients. Eleven healthy volunteers performed four CO-rebreathing tests in a randomized order, inhaling an identical CO-volume. In two tests, CO was rebreathed for 2min (oCOR), and in the other two tests, a single inhalation of a CO bolus was conducted with a subsequent breath hold of 15sec (Procnew 15sec) or 30sec (Procnew 30sec). Subsequently, the CO volume in the exhaled air was continuously determined for 20 min. The amount of CO exhaled after 7min (after 20min) for oCOR was 3.1 ±0.3ml (5.9 ±1.1ml); for Procnew 15sec, 8.7 ±3.6ml (12.0 ±4.4ml); and for Procnew 30sec, 5.1 ±2.0ml (8.4 ±2.6ml)). tHb-mass determined by oCOR was 843 ±293g, from Procnew 15sec 821 ±288g (difference: p <0.05), and from Procnew 30sec 849 ±311g. Bland-Altman plots demonstrated slightly lower tHb-mass values for Procnew 15sec compared with oCOR (-21.8 ±15.3g) and similar values for Procnew 30sec. In healthy volunteers, a single inhalation of a CO bolus, preferably followed by a 30 sec breath hold, can be used to determine tHb-mass. These results must now be validated for ventilated patients. This article is protected by copyright. All rights reserved

Total haemoglobin mass, but not haemoglobin concentration, is associated with preoperative cardiopulmonary exercise testing (CPET) derived oxygen consumption variables

BACKGROUND: Cardiopulmonary exercise testing (CPET) measures peak exertional oxygen consumption ( V˙O2peakV˙O2peak ) and that at the anaerobic threshold ( V˙O2V˙O2 at AT, i.e. the point at which anaerobic metabolism contributes substantially to overall metabolism). Lower values are associated with excess postoperative morbidity and mortality. A reduced haemoglobin concentration ([Hb]) results from a reduction in total haemoglobin mass (tHb-mass) or an increase in plasma volume. Thus, tHb-mass might be a more useful measure of oxygen-carrying capacity and might correlate better with CPET-derived fitness measures in preoperative patients than does circulating [Hb]. METHODS: Before major elective surgery, CPET was performed, and both tHb-mass (optimized carbon monoxide rebreathing method) and circulating [Hb] were determined. RESULTS: In 42 patients (83% male), [Hb] was unrelated to V˙O2V˙O2 at AT and V˙O2peakV˙O2peak (r=0.02, P=0.89 and r=0.04, P=0.80, respectively) and explained none of the variance in either measure. In contrast, tHb-mass was related to both (r=0.661, P<0.0001 and r=0.483, P=0.001 for V˙O2V˙O2 at AT and V˙O2peakV˙O2peak , respectively). The tHb-mass explained 44% of variance in V˙O2V˙O2 at AT (P<0.0001) and 23% in V˙O2peakV˙O2peak (P=0.001). CONCLUSIONS: In contrast to [Hb], tHb-mass is an important determinant of physical fitness before major elective surgery. Further studies should determine whether low tHb-mass is predictive of poor outcome and whether targeted increases in tHb-mass might thus improve outcome