Measuring Mitochondrial Oxygen Tension during Red Blood Cell Transfusion in Chronic Anemia Patients: A Pilot Study

Abstract

In light of the associated risks, the question has been raised whether the decision to give a blood transfusion should solely be based on the hemoglobin level. As mitochondria are the final destination of oxygen transport, mitochondrial parameters are suggested to be of added value. The aims of this pilot study were to investigate the effect of a red blood cell transfusion on mitochondrial oxygenation as measured by the COMET device in chronic anemia patients and to explore the clinical usability of the COMET monitor in blood transfusion treatments, especially the feasibility of performing measurements in an outpatient setting. To correct the effect of volume load on mitochondrial oxygenation, a red blood cell transfusion and a saline infusion were given in random order. In total, 21 patients were included, and this resulted in 31 observations. If patients participated twice, the order of infusion was reversed. In both the measurements wherein a blood transfusion was given first and wherein 500 mL of 0.9% saline was given first, the median mitochondrial oxygen tension decreased after red blood cell transfusion. The results of this study have strengthened the need for further research into the effect of blood transfusion tissue oxygenation and the potential role of mitochondrial parameters herein.

Keywords: chronic anemia; mitochondrial oxygen tension; mitochondrial oxygenation; red blood cell transfusion.

Figure 1

Jablonski diagram representing the states and transitions of porphyrins and oxygen, with S₀, S₁, S₂, and S₃ representing the ground state and three excited states of porphyrin. T₁ equals the first excited triplet state of porphyrin, and 1 O₂ and 3 O₂ represent the excited singlet oxygen state and the triplet ground state of oxygen. I represents absorption, II is fluorescence, III are radiationless transmissions, IV phosphorescence, V energy transfer, VI represents internal conversion, and VII represents intersystem crossing.

Figure 2

Clinical COMET system and skin sensor placed on the sternum of a volunteer. On the right side of the screen, mitoPO₂ (mmHg), temperature (°C), and signal quality are displayed in numbers. On the left, a graph depicts mitoPO₂ (mmHg) on the y-axis and time (min) on the x-axis.

Figure 3

Flowcharts of patient enrollment (A) and study protocol (B). FC: fluid challenge, RBCT: red blood cell transfusion.

Figure 4

An example of mitochondrial oxygen tension (mitoPO₂) measurements as measured using the COMET monitor (interval in min). The red dots represent the values during RBCT, and the blue triangles the values during a subsequent FC. The first five green squares are baseline measurements.

Figure 5

The mitochondrial oxygen tension (mitoPO₂) in kPa for each group. The boxplot shows the median in the middle with hinges depicting the first and third quartiles (25 and 75% percentiles). Whiskers are the min–max values within 1.5 × interquartile range (IQR). The lines represent one data sequence per patient. # Paired t-test with Bonferroni correction, ** ANOVA repeated measures test, and blue diamond is the mean value.

Figure 6

Correlation between mitochondrial oxygen tension (mitoPO₂) and baseline hemoglobin level. (A) Linear regression model (blue line) of the relationship between baseline mitoPO₂ (dots) and baseline hemoglobin level. (B) Delta mitoPO₂ was calculated as the change in mitoPO₂ value between baselines and after RBCT or the last part of both the saline infusion and RBCT, depending on the order in which the fluids were administered. The gray area is the standard error around the linear model.

Figure 7

Correlation between change in mitochondrial oxygen tension (mitoPO₂) red blood cell unit age. Linear regression model (blue line) of the relationship between delta mitoPO₂ (dots) and age of the administered erythrocytes. Delta mitoPO₂ was calculated as the change in mitoPO₂ value between either baseline and after RBCT or the last part of both the FC and RBCT, depending on the order in which the fluids were administered. Gray area is the standard error around the linear model.

Figure 8

Change in skin temperature after red blood cell transfusion and fluid challenge. (A) Median skin temperature during the first sequence (RBCT followed by FC). (B) Median skin temperature during the second sequence (FC followed by RBCT). In panels (C,D), the individual start and end temperatures are presented using lines during the first (panel (C)) and second sequence (panel (D)). Within the boxplot, the median is represented in the middle with the hinges depicting the first and third quartiles (25 and 75% percentiles). The whiskers are the min–max values within 1.5 × IQR.