Nephron 23: 276-281 (1979)
Oxygen Consumption during Maintenance Hemodialysis Alfred Blumher}’ and Guido Keller Department of Medicine. Kantonsspital, Aarau
Key Words. Anemia • Hemodialysis ■2,3-Diphosphoglycerate ■Oxygen affinity of hemoglobin • Oxygen consump tion • Cardiac index
Abbreviations Hb O2 P02 PCO>
SO2 a V
A 2,3-DPG P so su i P'jO iv
pH iic Cl
V02
hemoglobin oxygen O 2 tension CO 2 tension 0 >saturation arterial venous difference 2,3-diphosphoglycerate Pso under standard conditions P 50 in vivo intraerythrocytic pH cardiac index oxygen consumption
In patients on maintenance dialysis, nephrogenic ane mia is of importance because il lowers the oxygen-carrying capacity of blood with the consequent risk of insufficient tissue oxygenation. Although this is one of the factors responsible for the reduced working capacity of these patients, it has become clear that they usually tolerate a remarkable degree of anemia without the appearance of
incapacitating symptoms [I). Obviously they must be able to utilize some compensatory mechanism. It has been shown by us and by others that such patients exhibit a 2.3-DPG-dependent decrease in the affinity of hemoglobin for oxygen [1-4]. This facilitates oxygen delivery to tissues and is thought to represent one of the mechanisms of adap tation to anemia [5], The affinity of hemoglobin for oxygen is strongly influenced by blood pH. A rapid rise of pH in creases oxygen affinity due to the Bohr effect, and this has been thought to impair oxygen delivery to tissues. Such a rapid risein blood pH ischaracteristically induced by hemo dialysis. In several studies it has been reasoned that these changes might be potentially hazardous to the patients and that they could partly explain the dialysis disequilibrium syndrome and postdialysis fatigue [6-10]. However, these conclusions were only tentative since several important parameters such as central venous oxygen tension (Pvos) and cardiac output had not been measured directly. The purpose of this communication is a comprehensive evalu ation of the factors affecting oxygen transport in dialyzed patients, in order to find out whether the process of hemo dialysis does indeed impair tissue oxygenation.
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Abstract. The influence of hemodialysis on oxygen consumption was studied in 15 patients on maintenance dialysis. Red cell 2.3-DPG. Pr,o, an inverse measure of oxygen affinity of hemoglobin, arterial and central venous blood gases and cardiac index were measured. 2,3-DPG remained unchanged, whereas in vivo P50 fell significantly during dialysis due to a rise of pH (Bohr effect). Arterial P02 was lower after than before dialysis, but arterial and central venous oxygen satura tions did not change significantly. Cardiac index increased from 3.66 to 4.05 liter/min/m2. Oxygen consumption rose from 120.5 to 131.7 ml/min/m2 (p affinity. It was dialysis was performed twice weekly (except in patients 3 and 8 with determined tonometrically as described previously [1,6]. Normal three dialyses) using coil or parallel How dialyzers (Ultraflo II and values were obtained from 10 healthy volunteers. In 4 smokers (pa Gambro Lundia Optima 13.5 p.) with a dialysate containing acetate tients 9. 10, 13, 15) predialysis Psosui was corrected for HbCO con in a concentration of 38 mEq/l. 13 patients had arteriovenous fistulae centrations above 3% as suggested by Liclunian el al. [14], P50 under and two had saphenous vein autografts in the forearm. All medications in vivo conditions (Psoiv) was calculated from the formula [14]: were continued. Some pertinent clinical data on the patients are listed in table I. Informed consent was obtained from the patients after Psotv = antilog [log Pj Oski +0.48 (7.4 pH) + 0.0013 x base excess]. description of the procedure had been given. No correction was introduced for mean corpuscular hemoglobin After the patients had been supine for at least I h, studies were per formed immediately before and 30 min after termination of dialysis concentration (MCHC) and for 2,3-DPG content [14,15], since these which lasted from 5 to 6.5 h. Cardiac monitoring was performed during were not influenced by dialysis (MCHC 32.75 ±2.01 vs. 3 3 .I8 ± 2.19%, 2,3-DPG 48.4 7.8 vs. 47.0 9.5 ¡¿moles/lO11 erythrocytes, the entire procedure, and no serious arrhythmias were observed. respectively, mean - 1 SD, NS). A Swan-Ganz type catheter was placed into the pulmonary artery Cardiac output was measured with a COR 100A cardiac output under fluoroscopic control for dye injection and for sampling of recorder (Waters, Rochester, Minn.) using the dye dilution method. central venous blood. Arterial blood was obtained from the hemo Measurements were done in triplicate or quadruplicate and are re dialysis cannula placed close to the arteriovenous fistula, and samples ported as cardiac index. were drawn without using a tourniquet and after a delay of at least Oxygen consumption (V02 ) was calculated according to the for 10 min in order to avoid pain-induced hyperventilation. It has been mula [16]: shown that samples obtained in this way are representative of arterial blood [II). Whole blood pH, P02 and Pcoa were determined in tripli V02 —Cl x 10 x [(Hb x l.39x ASO>/l00) + (0.003l x APo.)], cate immediately after sampling with an IL model 213 blood gas where 10 = factor to convert arteriovenous O 2 content difference from analyzer. Bicarbonate was calculated from the Henderson-Hassel- ml O2/IOO ml to ml O 2/I liter blood: 1.39 = oxygen-hemoglobin balch equation and base excess from the Severinghaus blood gas equivalent (amount of O 2 capable of combining with 1 g of hemo calculator [12], Intracrythrocytic pH was measured by the freeze- globin); ASO2 = difference in O2 saturation of arterial and mixed thaw method [13]. HbOasaturations(SO 2)and HbCOconcentrations venous blood; AP02 = difference in Po> of arterial and mixed venous were measured with an IL model 182 CO-Oximeter. blood. Hemoglobin concentrations were measured spcctrophotometriThe expression cally with the cyanmethemoglobin method, hematocrit was deter 10 x (Hb x 1.39 XASO2/100)+ (0.0031 x APo>) mined in sextuplicatc by the micromethod, erythrocyte counts were done with a Coulter counter. has been termed 'Aa-v O 2 content' [16], Standard procedures were used for statistical analysis. For com Red cell 2,3-DPG was measured enzymatically as described pre parison of pre- and postdialysis values the paired t test was applied. viously [I] and was expressed in pmoles/IO" erythrocytes. Normal
Downloaded by: Karolinska Institutet, University Library 130.237.122.245 - 8/15/2018 8:03:52 PM
Methods
278
Blumberg/Keller
Table II. Red cell 2,3-DPG, plasma inorganic phosphate (Pi), pH and Oa-hemoglobin dissociation (Pso) before (B) and after (A) dialysis Patient No.
Hemoglobin g/100 ml A
B 1 2 3 4 5
6 7 8 9 10 II 12 13 14 15 Mean ± I SD
6.9 7.6 5.45 13.2 6.5 6.8 7.0 5.3 10.2 9.4 6.5 6.9 7.9 6.9 9.0 7.7 ±2.0
pH 2,3-DPG ¡¿moles/10" Ec
B
B
A
A
A
B
A
7.59 7.435 7.525 7.49 7.49 7.465 7.46 7.48 7.455 7.47 7.50 7.495 7.47 7.52 7.485
_
_
7.24 7.15 7.21 7.19 7.12 7.17 7.21 7.15 7.20 7.18 7.12 7.18 7.17 7.20
7.23 7.30 7.27 7.29 7.18 7.20 7.24 7.23 7.22 7.23 7.22 7.27 7.25 7.23
30.4 26.1 28.4 30.0 26.3 26.0 28.7 26.5 26.0 26.2 28.8 28.6 28.1 28.3 27.8
31.2 26.5 29.5 29.2 26.5 26.4 28.7 26.8 26.9 27.8 28.5 29.3 28.4 29.7 27.7
26.6 25.5 28.2 28.4 26.0 26.5 28.5 25.8 26.4 25.2 28.5 29.2 26.8 27.9 25.6
25.8 25.6 26.1 26.8 24.4 25.1 27.5 24.7 25.6 26.2 26.1 26.7 26.6 26.6 25.5
7.18 7.14-7.21
7.24 7.21-7.27
27.75 ±1.48
28.21 ±1.43
27.01 ±1.32
25.95 ±0.84
3.5 2.3 4.6 4.0 2.5 3.2 4.0 4.7 4.4 3.2 2.2 5.3 3.3 3.7 2.6
48.6 46.0 29.2 63.0 44.6 44.9 51.2 52.6 42.6 53.8 57.5 53.8 48.4 47.9 42.7
43.6 47.4 37.0 67.7 42.4 41.9 50.7 43.6 37.3 52.9 61.3 54.4 45.6 48.8 37.0
7.53 7.43 7.40 7.455 7.415 7.385 7.41 7.42 7.34 7.405 7.415 7.375 7.415 7.415 7.445
8.1 ±2.5
5.1 ±1-7
3.6 ±0.9
48.4 ±7.8
47.0 ¿.9.5
7.41 7.49 7.37-7.46 7.45-7.52
NS
Oxygen Consumption during Maintenance Hemodialysis Alfred Blumher}’ and Guido Keller Department of Medicine. Kantonsspital, Aarau
Key Words. Anemia • Hemodialysis ■2,3-Diphosphoglycerate ■Oxygen affinity of hemoglobin • Oxygen consump tion • Cardiac index
Abbreviations Hb O2 P02 PCO>
SO2 a V
A 2,3-DPG P so su i P'jO iv
pH iic Cl
V02
hemoglobin oxygen O 2 tension CO 2 tension 0 >saturation arterial venous difference 2,3-diphosphoglycerate Pso under standard conditions P 50 in vivo intraerythrocytic pH cardiac index oxygen consumption
In patients on maintenance dialysis, nephrogenic ane mia is of importance because il lowers the oxygen-carrying capacity of blood with the consequent risk of insufficient tissue oxygenation. Although this is one of the factors responsible for the reduced working capacity of these patients, it has become clear that they usually tolerate a remarkable degree of anemia without the appearance of
incapacitating symptoms [I). Obviously they must be able to utilize some compensatory mechanism. It has been shown by us and by others that such patients exhibit a 2.3-DPG-dependent decrease in the affinity of hemoglobin for oxygen [1-4]. This facilitates oxygen delivery to tissues and is thought to represent one of the mechanisms of adap tation to anemia [5], The affinity of hemoglobin for oxygen is strongly influenced by blood pH. A rapid rise of pH in creases oxygen affinity due to the Bohr effect, and this has been thought to impair oxygen delivery to tissues. Such a rapid risein blood pH ischaracteristically induced by hemo dialysis. In several studies it has been reasoned that these changes might be potentially hazardous to the patients and that they could partly explain the dialysis disequilibrium syndrome and postdialysis fatigue [6-10]. However, these conclusions were only tentative since several important parameters such as central venous oxygen tension (Pvos) and cardiac output had not been measured directly. The purpose of this communication is a comprehensive evalu ation of the factors affecting oxygen transport in dialyzed patients, in order to find out whether the process of hemo dialysis does indeed impair tissue oxygenation.
Downloaded by: Karolinska Institutet, University Library 130.237.122.245 - 8/15/2018 8:03:52 PM
Abstract. The influence of hemodialysis on oxygen consumption was studied in 15 patients on maintenance dialysis. Red cell 2.3-DPG. Pr,o, an inverse measure of oxygen affinity of hemoglobin, arterial and central venous blood gases and cardiac index were measured. 2,3-DPG remained unchanged, whereas in vivo P50 fell significantly during dialysis due to a rise of pH (Bohr effect). Arterial P02 was lower after than before dialysis, but arterial and central venous oxygen satura tions did not change significantly. Cardiac index increased from 3.66 to 4.05 liter/min/m2. Oxygen consumption rose from 120.5 to 131.7 ml/min/m2 (p affinity. It was dialysis was performed twice weekly (except in patients 3 and 8 with determined tonometrically as described previously [1,6]. Normal three dialyses) using coil or parallel How dialyzers (Ultraflo II and values were obtained from 10 healthy volunteers. In 4 smokers (pa Gambro Lundia Optima 13.5 p.) with a dialysate containing acetate tients 9. 10, 13, 15) predialysis Psosui was corrected for HbCO con in a concentration of 38 mEq/l. 13 patients had arteriovenous fistulae centrations above 3% as suggested by Liclunian el al. [14], P50 under and two had saphenous vein autografts in the forearm. All medications in vivo conditions (Psoiv) was calculated from the formula [14]: were continued. Some pertinent clinical data on the patients are listed in table I. Informed consent was obtained from the patients after Psotv = antilog [log Pj Oski +0.48 (7.4 pH) + 0.0013 x base excess]. description of the procedure had been given. No correction was introduced for mean corpuscular hemoglobin After the patients had been supine for at least I h, studies were per formed immediately before and 30 min after termination of dialysis concentration (MCHC) and for 2,3-DPG content [14,15], since these which lasted from 5 to 6.5 h. Cardiac monitoring was performed during were not influenced by dialysis (MCHC 32.75 ±2.01 vs. 3 3 .I8 ± 2.19%, 2,3-DPG 48.4 7.8 vs. 47.0 9.5 ¡¿moles/lO11 erythrocytes, the entire procedure, and no serious arrhythmias were observed. respectively, mean - 1 SD, NS). A Swan-Ganz type catheter was placed into the pulmonary artery Cardiac output was measured with a COR 100A cardiac output under fluoroscopic control for dye injection and for sampling of recorder (Waters, Rochester, Minn.) using the dye dilution method. central venous blood. Arterial blood was obtained from the hemo Measurements were done in triplicate or quadruplicate and are re dialysis cannula placed close to the arteriovenous fistula, and samples ported as cardiac index. were drawn without using a tourniquet and after a delay of at least Oxygen consumption (V02 ) was calculated according to the for 10 min in order to avoid pain-induced hyperventilation. It has been mula [16]: shown that samples obtained in this way are representative of arterial blood [II). Whole blood pH, P02 and Pcoa were determined in tripli V02 —Cl x 10 x [(Hb x l.39x ASO>/l00) + (0.003l x APo.)], cate immediately after sampling with an IL model 213 blood gas where 10 = factor to convert arteriovenous O 2 content difference from analyzer. Bicarbonate was calculated from the Henderson-Hassel- ml O2/IOO ml to ml O 2/I liter blood: 1.39 = oxygen-hemoglobin balch equation and base excess from the Severinghaus blood gas equivalent (amount of O 2 capable of combining with 1 g of hemo calculator [12], Intracrythrocytic pH was measured by the freeze- globin); ASO2 = difference in O2 saturation of arterial and mixed thaw method [13]. HbOasaturations(SO 2)and HbCOconcentrations venous blood; AP02 = difference in Po> of arterial and mixed venous were measured with an IL model 182 CO-Oximeter. blood. Hemoglobin concentrations were measured spcctrophotometriThe expression cally with the cyanmethemoglobin method, hematocrit was deter 10 x (Hb x 1.39 XASO2/100)+ (0.0031 x APo>) mined in sextuplicatc by the micromethod, erythrocyte counts were done with a Coulter counter. has been termed 'Aa-v O 2 content' [16], Standard procedures were used for statistical analysis. For com Red cell 2,3-DPG was measured enzymatically as described pre parison of pre- and postdialysis values the paired t test was applied. viously [I] and was expressed in pmoles/IO" erythrocytes. Normal
Downloaded by: Karolinska Institutet, University Library 130.237.122.245 - 8/15/2018 8:03:52 PM
Methods
278
Blumberg/Keller
Table II. Red cell 2,3-DPG, plasma inorganic phosphate (Pi), pH and Oa-hemoglobin dissociation (Pso) before (B) and after (A) dialysis Patient No.
Hemoglobin g/100 ml A
B 1 2 3 4 5
6 7 8 9 10 II 12 13 14 15 Mean ± I SD
6.9 7.6 5.45 13.2 6.5 6.8 7.0 5.3 10.2 9.4 6.5 6.9 7.9 6.9 9.0 7.7 ±2.0
pH 2,3-DPG ¡¿moles/10" Ec
B
B
A
A
A
B
A
7.59 7.435 7.525 7.49 7.49 7.465 7.46 7.48 7.455 7.47 7.50 7.495 7.47 7.52 7.485
_
_
7.24 7.15 7.21 7.19 7.12 7.17 7.21 7.15 7.20 7.18 7.12 7.18 7.17 7.20
7.23 7.30 7.27 7.29 7.18 7.20 7.24 7.23 7.22 7.23 7.22 7.27 7.25 7.23
30.4 26.1 28.4 30.0 26.3 26.0 28.7 26.5 26.0 26.2 28.8 28.6 28.1 28.3 27.8
31.2 26.5 29.5 29.2 26.5 26.4 28.7 26.8 26.9 27.8 28.5 29.3 28.4 29.7 27.7
26.6 25.5 28.2 28.4 26.0 26.5 28.5 25.8 26.4 25.2 28.5 29.2 26.8 27.9 25.6
25.8 25.6 26.1 26.8 24.4 25.1 27.5 24.7 25.6 26.2 26.1 26.7 26.6 26.6 25.5
7.18 7.14-7.21
7.24 7.21-7.27
27.75 ±1.48
28.21 ±1.43
27.01 ±1.32
25.95 ±0.84
3.5 2.3 4.6 4.0 2.5 3.2 4.0 4.7 4.4 3.2 2.2 5.3 3.3 3.7 2.6
48.6 46.0 29.2 63.0 44.6 44.9 51.2 52.6 42.6 53.8 57.5 53.8 48.4 47.9 42.7
43.6 47.4 37.0 67.7 42.4 41.9 50.7 43.6 37.3 52.9 61.3 54.4 45.6 48.8 37.0
7.53 7.43 7.40 7.455 7.415 7.385 7.41 7.42 7.34 7.405 7.415 7.375 7.415 7.415 7.445
8.1 ±2.5
5.1 ±1-7
3.6 ±0.9
48.4 ±7.8
47.0 ¿.9.5
7.41 7.49 7.37-7.46 7.45-7.52
NS
