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

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.

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

“…We thus explored whether it is possible to reliably measure tHb-mass using a single-breath inhalation (with a 15 or 30 s breath hold) of CO gas and showed for the first time that it is feasible Modifications to the CO rebreathing technique for the measurement of tHb-mass have therefore been made many times since the technique was revived by Fogh-Andersen et al (1990), notably in 1995 when Burge and Skinner achieved improved precision of the measurement (Burge & Skinner, 1995). The current technique described by Schmidt and Prommer reduced the rebreathing period to only 2 min to improve convenience for participants (Otto et al, 2017a,b;Plumb et al, 2020;Schmidt & Prommer, 2005). The finding that a bolus of CO gas inhaled with a single breath and only rebreathed for 2 min led to valid and reliable results characterized by a typical error between 1% and 2% allowed the method to be used in a variety of different settings.…”

“…We hypothesize that this method might be used to diagnose and provide more information on the origin of anaemia in intensive care (Magee & Zbrozek, 2013) and the amount of blood loss during surgery (Shoemaker et al., 1996), as well as for distinguishing between dilutional anaemia and genuine anaemia in patients with heart failure (Miller & Mullan, 2015) and liver failure (Plumb et al., 2020). Here, it is of critical importance that the modified method has sufficient accuracy to reveal clinically relevant changes in tHb‐mass and their contribution to changes in [Hb].…”

“…We hypothesize that this method might be used to diagnose and provide more information on the origin of anaemia in intensive care (Magee & Zbrozek, 2013) and the amount of blood loss during surgery (Shoemaker et al, 1996), as well as for distinguishing between dilutional anaemia and genuine anaemia in patients with heart failure (Miller & Mullan, 2015) and liver failure (Plumb et al, 2020 (Wachsmuth et al, 2015), the accuracy of the method should be sufficient to distinguish anaemia due to reduced tHb-mass from that due to dilution. This contention is supported by Otto et al (2017a) who describe two patients with liver disease who had identical tHb-mass (9.2 g/kg body mass), but with a normal [Hb] (16.1 g/dl) in one and dilutional anaemia ([Hb] 10.7 g/dl) in the other.…”

Blood volume and hemoglobin mass in long-term heart transplant recipients with and without Anemia

“…As CO rebreathing allowed a detection of the withdrawal of small quantities of blood it can be considered as precise [ 17 , 31 ] and less time consuming compared to radiolabeling techniques [ 26 , 32 ]. Its application was safely possible in several groups of patients with anemia [ 26 ], coronary artery disease [ 27 ], chronic heart failure [ 11 , 28 ], liver disease [ 33 ] as well as in the preoperative setting [ 34 ].…”

Letter to the editor: “Comment on: Application of the optimized carbon monoxide rebreathing method for the measurement of total haemoglobin mass in chronic liver disease”

“…With great interest, we have read the article "Application of the optimized carbon monoxide rebreathing method for the measurement of total hemoglobin mass in chronic liver disease" by Plumb et al (2020) and agree that CO-rebreathing is a promising method to determine vascular volumes in clinical patients. However, we would like to point out that special attention should be paid to the distribution of the vascular volumes in patients with liver cirrhosis.…”