Reduced Red Cell 2,3-Diphosphoglycerate Concentrations in Critical Illness without Decreased in Vivo P50

Abstract

We investigated whether red cell 2,3-diphosphoglycerate (2,3-DPG) concentrations are reduced in critical illness, whether acidaemia, hypophosphataemia or anaemia influence 2,3-DPG, and whether there is any net effect on in vivo P50. Twenty healthy, non-smoking, male volunteers were compared with 20 male intensive care patients with APACHE 2 scores >20 on the preceding day. Those transfused in this time were excluded. Venous red cell 2,3-DPG concentrations were measured in both groups. In the patient group, routine multichannel biochemical profile and arterial blood gas analysis were also performed and in vivo P50 calculated. The mean 2,3-DPG concentration was significantly lower in the patient group than in the controls (4.2±1.3 mmol/l vs 4.9±0.5 mmol/l, P=0.016). The patients were well oxygenated (lowest arterial PO 2 =75 mm Hg) and showed a tendency to acidaemia (median pH 7.37, range 7.06 to 7.48) and anaemia (median haemoglobin concentration 113 g/l, range 89 to 154 g/l). By linear regression of patient data, pH had a significant effect on 2,3-DPG concentrations (r=0.6, P=0.011). Haemoglobin and phosphate concentrations did not, but there were few abnormal phosphate values. There was no correlation between 2,3-DPG concentrations and in vivo P50 (r 2 ≤ 0.08). We conclude that 2,3-DPG concentrations were reduced in a broad group of critically ill patients. Although this would normally reduce the P50, the reduction was primarily linked with acidaemia, which increases the P50. Overall, there was no net effect on the P50 and thus no affinity-related decrease in tissue oxygenation.

A left shift in the oxyhaemoglobin dissociation curve in patients with severe coronavirus disease 2019 (COVID‐19)

“…A slower mechanism is a decrease in 2,3‐diphosphoglycerate (DPG) or other organic phosphates 17 . Reduced 2,3‐DPG levels were observed in critically ill normoxaemic patients; however, the effect on p 50 was diminished potentially due to acidaemia in this cohort 20 …”

The Effect of Sepsis on the Erythrocyte

“…However, in critically ill and septic patients, acidemia, hypophosphatemia and transfusion of 2,3-BPG depleted blood are all factors that can shift the ODC to the left, decrease the P 50 [ 62 ], increase Hb affinity for oxygen and decrease oxygen release. Numerous experimental and clinical studies have reported decreased levels of RBC 2,3-BPG and reduced P 50 including in endotoxemic baboons [ 68 ], and critically ill and sepsis patients [ 61 , 67 , 69 ], respectively.…”

“…The primary mechanism in critically ill patients appears to be associated with acidemia [ 70 ], and several studies have reported that RBC 2,3-BPG (or P 50 ) is correlated with pH [ 64 , 65 , 69 , 71 ]. This was supported by Chillar et al [ 71 ] who reported that 2,3-DPG correlated with arterial pH over a range of 6.9 to 7.6 in septic shock patients.…”

Decreased 2,3‐Diphosphoglycerate Concentration in Low Cardiac Output Patients and Its Influence on the Determination of In Vivo P50

“…They also reported a discrepancy between standard P 50 and in vivo P 50 . Differences in measured and estimated 2,3‐DPG may result in errors in calculating P 50 in patients with abnormal concentrations of 2,3‐DPG (10). We found that in vivo P 50 calculated by the oxygen status algorithm was greater than in vivo P 50 calculated as proposed by Bellingham and coworkers (5) by about 8 mm Hg.…”