Replicating measurements of total hemoglobin mass (tHb-mass) within a single day: precision of measurement; feasibility and safety of using oxygen to expedite carbon monoxide clearance

Abstract

Hemoglobin concentration ([Hb]) is a function of total hemoglobin mass (tHb-mass) and plasma volume. [Hb] may fall by dilution due to plasma volume expansion and changes in the perioperative period may therefore correlate poorly with blood loss. A simple, reliable, repeatable way to measure plasma volume and tHb-mass would have substantial clinical utility. The "optimized carbon monoxide re-breathing method" (oCOR) meets these criteria. However, it is recommended that a minimum of 12 h (when breathing room air) is left between repeat measurements. Twenty-four subjects underwent 3 days of testing. Two oCOR tests were performed (T1 and T2), 3 h apart, with a different CO clearance method employed between tests aiming to keep the carboxyhemoglobin level below 10%. The primary aim was to ascertain whether tHb-mass testing could be safely repeated within 3 h if carboxyhemoglobin levels were actively reduced by breathing supplemental oxygen (PROC_A ). Secondary aims were to compare two other clearance methods; moderate exercise (PROC_B ), or a combination of the two (PROC_C ). Finally, the reliability of the oCOR method was assessed. Mean (SD) tHb-mass was 807.9 ± (189.7 g) (for T1 on day 1). PROC_A lowered the carboxyhemoglobin level from the end of T1 (mean 6.64%) to the start of T2 (mean 2.95%) by a mean absolute value of 3.69%. For PROC_B and PROC_C the mean absolute decreases in carboxyhemoglobin were 4.00% and 4.31%, respectively. The fall in carboxyhemoglobin between T1 and T2 was greatest in PROC_C ; this was statistically significantly lower than that of PROC_A (P = 0.0039) and PROC_B (P = 0.0289). The test-retest reliability for the measurement of total hemoglobin mass was good with a mean typical error (TE) of 2.0%. The oCOR method is safe and can be repeated within 3 h when carbon monoxide is suitably cleared between tests. Using oxygen therapy alone adequately achieves this.

Keywords: Blood volume; optimized carbon monoxide re-breathing; plasma volume; red cell volume; total hemoglobin mass (tHb-mass).

Figure 1

Schematic to describe the experimental sequence.

Figure 2

Comparing the fall in carboxyhemoglobin (COHb%) between test 1 and test 2 of each procedure (T1 and T2). Median with interquartile range shown for each procedure. *Denotes the significant difference between PROC _C and PROC _A (after multiple comparison correction using the Bonferroni method). COHb, carboxyhemoglobin; PROC _A/B/C procedures A/B/C.

Figure 3

Bland‐Altman plots comparing tHb‐mass measurements between T1 and T2 for each procedure.

Figure 4

Change is serum carboxyhemoglobin (%) over test 1 and 2 (T1 and T2) of each procedure. Results are presented as median and range. Safety of duplicating the oCOR method is dependent on ensuring that the clearance procedure removes enough COHb after T1 to avoid excess COHb (>10%, red dotted line) during T2. Seven‐minute values are calculated and not measured values but are included as they are used to calculate COHb. COHb: carboxyhemoglobin; oCOR, optimized carbon monoxide rebreathing technique; PROC _A/B/C, Procedure A/B/C, T1: test 1 or first measurement of the day, T2: test 2 or second measurement of the day.