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The relationship between colloid osmotic pressure and plasma proteins during and after cardiopulmonary bypass
The relationship between colloid osmotic pressure and plasma proteins during and after cardiopulmonary bypass C. E. Webber and E. S. Garnett, Hamilton, Ontario, Canada
o
pen-heart surgery is complicated during the early postoperative period by a decrease in the circulating blood volume and an increase in the extracellular fluid volume.' It has been suggested that this situation is analogous to that found in the nephrotic syndrome in which hypoproteinemia and the consequent reduction in colloid osmotic pressure disturb the normal distribution of fluid between the intra- and extravascular compartments. English and colleagues 2 have measured plasma protein concentration and colloid osmotic pressure during and immediately after open-heart surgery. They found that changes in the plasma protein concentration were not paralleled by changes in the colloid osmotic pressure during the period of the operation. This is a surprising result which suggests that the familiar relationship between colloid osmotic pressure and plasma protein concentration does not hold during cardiopulmonary bypass. To investigate this phenomenon, we have restudied the relationship between the measured colloid osmotic pressure and the concentration of the plasma protein fractions during bypass. From the McMaster University Medical Centre, Hamilton, Ontario, Canada. Received for publication June 26, 1972.
234
Patients Patients were studied during cardiopulmonary bypass, in which a Travenol bubble oxygenator was used, and for up to 7 days after operation. The pump oxygenator was primed with a blood-dextrose-saline mixture that had a hematocrit value of 20 per cent and a glucose concentration in excess of 2 Gm. per 100 mt. Additional fluid was given if required during a pump run. The colloid osmotic pressure of this fluid was always less than 13.0 cm. H 20. Methods Colloid osmotic pressure was measured by means of the Tybjaerg Hansen- osmometer with an Amicon V-I0 membrane. The osmometer responded linearly with changes of hydrostatic pressure across the membrane. The within-batch reproducibility and the between-batch reproducibility of the measurements of normal plasma colloid osmotic pressure were ± 0.3 and ± 0.7 em. H 2 0 , respectively. No pressure could be recorded by the osmometer from either an ultrafiltrate of plasma or from the supernatant of ultracentrifuged plasma. Increasing the plasma glucose concentration up to 5 Gm. per 100 ml. did not influence the accuracy or the within-batch reproducibility, although the time required for the system
Volume 65
Study of colloid osmotic pressure and plasma proteins
Number 2 Februory, 1973
20
35 COLLOID OSMOTIC PRESSURE (CmH201
COLLOID 18 OSMOTIC PRESSURE (C.. H 16 20)
14·
ALBUMIN
2.81 2.•
(e/100.-11 2.0
GAMMA GLOBULIN
(e/100 .. 11
t-
O'.j 0.2
L
0
-f---}
r
0.2
ALPHA I 0.2] GLOBULIN
le/100 .. 11
-}---I
-
0 .•] FIBRINOGEN
le/100.. 11
H--1
o
i
i
10
~
20
i i i :
30
.0
50
ALBUMIN (s/100ml)
30
Fig. 1.
to come into equilibrium was prolonged. The total protein concentration in plasma was measured by a refractometer method and checked by the biuret method. The protein fractions were separated by a standard electrophoretic technique. Results Twenty-four hours before operation. The mean total protein concentration in plasma was 7.2 Gm. per 100 mi. The mean albumin, alpha-I, alpha-2, beta, and gamma globulin concentrations were 4.45, 0.26, 0.62, 0.85, and 1.06 Gm. per 100 mI., respectively. The mean colloid osmotic pressure was 33.8 em, H~O and ranged from 28.3 to 39.7 em. H 2 0 . Priming solution. The mean total protein concentration of the priming solution was 2.4 Gm. per 100 mI., the albumin concentration was ~.5 Gm. per 100 mI., and the colloid osmotic pressure was 11.0 em. H 2 0 . During operation. The patterns of change in the concentrations of albumin, alpha-I globulin, gamma globulin, and fibrinogen
1
25
4.4j 3.6
2.8 GAMMA l.0j GLOBULIN
(sIlOOml)
0.6
ALPHA I 0.6] GLOBULIN
(sIlOOml)
0.2
ALPHA 2 GLOBULIN
1.0~
(sllOOmll 0.6
60
MINS. ON CARDIOPULMONARY BYPASS
235
BETA GLOBULIN
(sIlOOml)
t
f-,yt-H
1.t:~i-+-+-1
0.6
1ft
i i i
1
PRE.BYPASS
3
5
i
7
DAYS AFTER BYPASS
Fig. 2.
were similar in all of the patients and are summarized in Fig. 1. The patterns of change of colloid osmotic pressure were also similar in each patient (Fig. 1). The concentrations of alpha-2 and beta globulin during the operation could not be measured electrophoretically due to a rising concentration of plasma hemoglobin. After operation. The patterns of change of concentration of albumin, alpha-I, alpha2, beta, and gamma globulin, and colloid osmotic pressure were again similar in each patient and are summarized in Fig. 2. Discussion In the present series, the colloid osmotic pressure before operation was lower than that reported by English's group- but was the same as that found by Ladegaard-Pedersen' and Zweifach and Intaglietta" in normal plasma. This difference may be due to dif-
The Journal of
236
Webber and Garnett
Thoracic and Cardiovascular Surgery
Table I. Changes in colloid osmotic pressure and total protein concentration during cardiopulmonary bypass 60
Series English et al. Colloid osmotic pressure (em. H 2 0 ) Total protein (Gm./IOO ml.)
40.0
24.5
25.8
24.9
25.5
25.7
7.5
2.8
4.8
4.9
5.0
5.1
Present series Colloid osmotic pressure (em. H 20 ) Total protein (Gm./100 ml.)
33.0
11.0
15.4
17.1
18.4
7.1
2.4
3.6
3.9
4.1
2
ferent patient postures at the time the samples were taken. The colloid osmotic pressure of the priming fluid was 11 em. H 20 compared with 24.5 em. H 20 found by English's group." This difference cannot be explained on the basis of different protein concentrations (Table I) or on the basis of different glucose concentrations in the perfusates, since we have shown that the measured colloid osmotic pressure is not affected by increasing the glucose concentration up to 5 Gm. per 100 ml. During the operation, the colloid osmotic pressure in our patients rose at a rate of approximately 30 per cent per 100 minutes. No further measurements were made until 24 hours after operation because of widely varying postoperative intravenous therapies. These results contrast with those of English and co-workers,2 who did not find any change in pressure during bypass. This constant pressure was maintained in the face of a rising total protein concentration. Interestingly, English's group'> noticed a return toward preoperative levels in the immediate postoperative period. In view of the differences in the results of the measurements of colloid osmotic pressure between the two groups, it is surprising to find such similar patterns in the total protein concentration (Table I). In each group, the total protein concentration rose during bypass. Colloid osmotic pressure is derived al-
most entirely from the plasma proteins and is a measure of particle concentration. Albumin and gamma globulin together account for a major fraction of the plasma colloid osmotic pressure because of their relatively high concentrations and low molecular weights. Fig. 1 shows that the colloid osmotic pressure follows the albumin concentration during bypass, whereas there is relatively little change in the gamma globulin concentration. Fig. 2 shows that, after bypass, the colloid osmotic pressure is reduced and remains relatively constant while the albumin concentration falls. This result can be explained by concomitant changes in the concentration of the other protein fractions. The colloid osmotic pressure, calculated from measurements of albumin and globulin concentrations, follows the measured pressure very closely. Therefore, our results show that the usual relationship between colloid osmotic pressure and protein concentration holds during and after bypass. Although the pattern of change of concentration of the plasma protein fractions has not previously been measured during openheart surgery, our results in the period from 1 to 7 days after operation agree well with those obtained by Wallace and associates.7 Furthermore, these patterns do not differ, except in magnitude, from those seen after a variety of noncardiac operations. 8 The system used by English and coworkers- to measure colloid osmotic pres-
Volume 65 Number 2
Study of colloid osmotic pressure and plasma proteins
237
Februory, 1973
sure was originally designed as a rapidresponse flow-through osmometer and is identical to the one used in this series apart from a modification in the shape of the sample chamber." We have shown that, in the presence of glucose at concentrations similar to those found during bypass, the equilibrium time of the system is prolonged. This suggests that the system used by English's group may not have reached equilibrium for the samples taken during the operation. This would tend to make the results of colloid osmotic pressure obtained in the early stages of bypass falsely high and would also explain the return to consistency between colloid osmotic pressure and protein concentration after bypass, when the blood sugar would be decreasing rapidly. Summary
1. Colloid osmotic pressure and the concentrations of the plasma protein fractions were measured before, during, and for 7 days after open-heart surgery. 2. Colloid osmotic pressure, albumin, and gamma globulin concentrations fell precipitously as soon as cardiopulmonary bypass was begun. 3. During the period of bypass, the colloid osmotic pressure increased 30 per cent every 100 minutes. This rate of rise of colloid osmotic pressure could be accounted for by the changes in albumin and gamma globulin concentrations.
4. During the week following operation, the colloid osmotic pressure and the albumin concentration remained at 80 per cent of the preoperative level. REFERENCES
2
3
4 5 6
7
8
Beattie, H. W., Evans, G., Garnett, E. S., and Webber, C. E.: Sustained Hypovolemia and Extracellular Fluid Volume Expansion Following Cardiopulmonary Bypass, Surgery 71: 891, 1972. English, T. A. H., Digerness, S., and Kirklin, J. W.: Changes in Colloid Osmotic Pressure During and Shortly After Open Intracardiac Operation, J. THoRAc. CARDIOVASC. SURG. 61: 338, 1971. Hansen, A. T.: A Self-Recording Electronic Osmometer for Quick, Direct Measurement of Colloid Osmotic Pressure in Small Samples, Acta PhysioI. Scand. 53: 197, 1961. Ladegaard-Pedersen, H. J.: Measurement of the Colloid Osmotic Pressure in Patients, Scand. J. Clin. Lab. Invest. 20: 79, 1967. Zweifach, B. W., and Intaglietta, M.: Measurement of Blood Plasma CoIloid Osmotic Pressure, Microvasc. Rec. 3: 83, 1971. Prather, J. W., Gaar, K. A., and Guyton, A. C.: Direct Continuous Recording of Plasma CoIloid Osmotic Pressure of Whole Blood, J. AppI. PhysioI. 24: 602, 1968. Wallace, H. W., Arai, K., and Blakemore, W. S.: Plasma Protein Alterations Accompanying Cardiac and General Surgical Procedures, Surg, Gynecol, Obstet. 131: 268, 1970. Werner, M., and Cohnen, G.: Changes in Serum Proteins in the Immediate Postoperative Period, Clin. Sci. 36: 173, 1969.
o
pen-heart surgery is complicated during the early postoperative period by a decrease in the circulating blood volume and an increase in the extracellular fluid volume.' It has been suggested that this situation is analogous to that found in the nephrotic syndrome in which hypoproteinemia and the consequent reduction in colloid osmotic pressure disturb the normal distribution of fluid between the intra- and extravascular compartments. English and colleagues 2 have measured plasma protein concentration and colloid osmotic pressure during and immediately after open-heart surgery. They found that changes in the plasma protein concentration were not paralleled by changes in the colloid osmotic pressure during the period of the operation. This is a surprising result which suggests that the familiar relationship between colloid osmotic pressure and plasma protein concentration does not hold during cardiopulmonary bypass. To investigate this phenomenon, we have restudied the relationship between the measured colloid osmotic pressure and the concentration of the plasma protein fractions during bypass. From the McMaster University Medical Centre, Hamilton, Ontario, Canada. Received for publication June 26, 1972.
234
Patients Patients were studied during cardiopulmonary bypass, in which a Travenol bubble oxygenator was used, and for up to 7 days after operation. The pump oxygenator was primed with a blood-dextrose-saline mixture that had a hematocrit value of 20 per cent and a glucose concentration in excess of 2 Gm. per 100 mt. Additional fluid was given if required during a pump run. The colloid osmotic pressure of this fluid was always less than 13.0 cm. H 20. Methods Colloid osmotic pressure was measured by means of the Tybjaerg Hansen- osmometer with an Amicon V-I0 membrane. The osmometer responded linearly with changes of hydrostatic pressure across the membrane. The within-batch reproducibility and the between-batch reproducibility of the measurements of normal plasma colloid osmotic pressure were ± 0.3 and ± 0.7 em. H 2 0 , respectively. No pressure could be recorded by the osmometer from either an ultrafiltrate of plasma or from the supernatant of ultracentrifuged plasma. Increasing the plasma glucose concentration up to 5 Gm. per 100 ml. did not influence the accuracy or the within-batch reproducibility, although the time required for the system
Volume 65
Study of colloid osmotic pressure and plasma proteins
Number 2 Februory, 1973
20
35 COLLOID OSMOTIC PRESSURE (CmH201
COLLOID 18 OSMOTIC PRESSURE (C.. H 16 20)
14·
ALBUMIN
2.81 2.•
(e/100.-11 2.0
GAMMA GLOBULIN
(e/100 .. 11
t-
O'.j 0.2
L
0
-f---}
r
0.2
ALPHA I 0.2] GLOBULIN
le/100 .. 11
-}---I
-
0 .•] FIBRINOGEN
le/100.. 11
H--1
o
i
i
10
~
20
i i i :
30
.0
50
ALBUMIN (s/100ml)
30
Fig. 1.
to come into equilibrium was prolonged. The total protein concentration in plasma was measured by a refractometer method and checked by the biuret method. The protein fractions were separated by a standard electrophoretic technique. Results Twenty-four hours before operation. The mean total protein concentration in plasma was 7.2 Gm. per 100 mi. The mean albumin, alpha-I, alpha-2, beta, and gamma globulin concentrations were 4.45, 0.26, 0.62, 0.85, and 1.06 Gm. per 100 mI., respectively. The mean colloid osmotic pressure was 33.8 em, H~O and ranged from 28.3 to 39.7 em. H 2 0 . Priming solution. The mean total protein concentration of the priming solution was 2.4 Gm. per 100 mI., the albumin concentration was ~.5 Gm. per 100 mI., and the colloid osmotic pressure was 11.0 em. H 2 0 . During operation. The patterns of change in the concentrations of albumin, alpha-I globulin, gamma globulin, and fibrinogen
1
25
4.4j 3.6
2.8 GAMMA l.0j GLOBULIN
(sIlOOml)
0.6
ALPHA I 0.6] GLOBULIN
(sIlOOml)
0.2
ALPHA 2 GLOBULIN
1.0~
(sllOOmll 0.6
60
MINS. ON CARDIOPULMONARY BYPASS
235
BETA GLOBULIN
(sIlOOml)
t
f-,yt-H
1.t:~i-+-+-1
0.6
1ft
i i i
1
PRE.BYPASS
3
5
i
7
DAYS AFTER BYPASS
Fig. 2.
were similar in all of the patients and are summarized in Fig. 1. The patterns of change of colloid osmotic pressure were also similar in each patient (Fig. 1). The concentrations of alpha-2 and beta globulin during the operation could not be measured electrophoretically due to a rising concentration of plasma hemoglobin. After operation. The patterns of change of concentration of albumin, alpha-I, alpha2, beta, and gamma globulin, and colloid osmotic pressure were again similar in each patient and are summarized in Fig. 2. Discussion In the present series, the colloid osmotic pressure before operation was lower than that reported by English's group- but was the same as that found by Ladegaard-Pedersen' and Zweifach and Intaglietta" in normal plasma. This difference may be due to dif-
The Journal of
236
Webber and Garnett
Thoracic and Cardiovascular Surgery
Table I. Changes in colloid osmotic pressure and total protein concentration during cardiopulmonary bypass 60
Series English et al. Colloid osmotic pressure (em. H 2 0 ) Total protein (Gm./IOO ml.)
40.0
24.5
25.8
24.9
25.5
25.7
7.5
2.8
4.8
4.9
5.0
5.1
Present series Colloid osmotic pressure (em. H 20 ) Total protein (Gm./100 ml.)
33.0
11.0
15.4
17.1
18.4
7.1
2.4
3.6
3.9
4.1
2
ferent patient postures at the time the samples were taken. The colloid osmotic pressure of the priming fluid was 11 em. H 20 compared with 24.5 em. H 20 found by English's group." This difference cannot be explained on the basis of different protein concentrations (Table I) or on the basis of different glucose concentrations in the perfusates, since we have shown that the measured colloid osmotic pressure is not affected by increasing the glucose concentration up to 5 Gm. per 100 ml. During the operation, the colloid osmotic pressure in our patients rose at a rate of approximately 30 per cent per 100 minutes. No further measurements were made until 24 hours after operation because of widely varying postoperative intravenous therapies. These results contrast with those of English and co-workers,2 who did not find any change in pressure during bypass. This constant pressure was maintained in the face of a rising total protein concentration. Interestingly, English's group'> noticed a return toward preoperative levels in the immediate postoperative period. In view of the differences in the results of the measurements of colloid osmotic pressure between the two groups, it is surprising to find such similar patterns in the total protein concentration (Table I). In each group, the total protein concentration rose during bypass. Colloid osmotic pressure is derived al-
most entirely from the plasma proteins and is a measure of particle concentration. Albumin and gamma globulin together account for a major fraction of the plasma colloid osmotic pressure because of their relatively high concentrations and low molecular weights. Fig. 1 shows that the colloid osmotic pressure follows the albumin concentration during bypass, whereas there is relatively little change in the gamma globulin concentration. Fig. 2 shows that, after bypass, the colloid osmotic pressure is reduced and remains relatively constant while the albumin concentration falls. This result can be explained by concomitant changes in the concentration of the other protein fractions. The colloid osmotic pressure, calculated from measurements of albumin and globulin concentrations, follows the measured pressure very closely. Therefore, our results show that the usual relationship between colloid osmotic pressure and protein concentration holds during and after bypass. Although the pattern of change of concentration of the plasma protein fractions has not previously been measured during openheart surgery, our results in the period from 1 to 7 days after operation agree well with those obtained by Wallace and associates.7 Furthermore, these patterns do not differ, except in magnitude, from those seen after a variety of noncardiac operations. 8 The system used by English and coworkers- to measure colloid osmotic pres-
Volume 65 Number 2
Study of colloid osmotic pressure and plasma proteins
237
Februory, 1973
sure was originally designed as a rapidresponse flow-through osmometer and is identical to the one used in this series apart from a modification in the shape of the sample chamber." We have shown that, in the presence of glucose at concentrations similar to those found during bypass, the equilibrium time of the system is prolonged. This suggests that the system used by English's group may not have reached equilibrium for the samples taken during the operation. This would tend to make the results of colloid osmotic pressure obtained in the early stages of bypass falsely high and would also explain the return to consistency between colloid osmotic pressure and protein concentration after bypass, when the blood sugar would be decreasing rapidly. Summary
1. Colloid osmotic pressure and the concentrations of the plasma protein fractions were measured before, during, and for 7 days after open-heart surgery. 2. Colloid osmotic pressure, albumin, and gamma globulin concentrations fell precipitously as soon as cardiopulmonary bypass was begun. 3. During the period of bypass, the colloid osmotic pressure increased 30 per cent every 100 minutes. This rate of rise of colloid osmotic pressure could be accounted for by the changes in albumin and gamma globulin concentrations.
4. During the week following operation, the colloid osmotic pressure and the albumin concentration remained at 80 per cent of the preoperative level. REFERENCES
2
3
4 5 6
7
8
Beattie, H. W., Evans, G., Garnett, E. S., and Webber, C. E.: Sustained Hypovolemia and Extracellular Fluid Volume Expansion Following Cardiopulmonary Bypass, Surgery 71: 891, 1972. English, T. A. H., Digerness, S., and Kirklin, J. W.: Changes in Colloid Osmotic Pressure During and Shortly After Open Intracardiac Operation, J. THoRAc. CARDIOVASC. SURG. 61: 338, 1971. Hansen, A. T.: A Self-Recording Electronic Osmometer for Quick, Direct Measurement of Colloid Osmotic Pressure in Small Samples, Acta PhysioI. Scand. 53: 197, 1961. Ladegaard-Pedersen, H. J.: Measurement of the Colloid Osmotic Pressure in Patients, Scand. J. Clin. Lab. Invest. 20: 79, 1967. Zweifach, B. W., and Intaglietta, M.: Measurement of Blood Plasma CoIloid Osmotic Pressure, Microvasc. Rec. 3: 83, 1971. Prather, J. W., Gaar, K. A., and Guyton, A. C.: Direct Continuous Recording of Plasma CoIloid Osmotic Pressure of Whole Blood, J. AppI. PhysioI. 24: 602, 1968. Wallace, H. W., Arai, K., and Blakemore, W. S.: Plasma Protein Alterations Accompanying Cardiac and General Surgical Procedures, Surg, Gynecol, Obstet. 131: 268, 1970. Werner, M., and Cohnen, G.: Changes in Serum Proteins in the Immediate Postoperative Period, Clin. Sci. 36: 173, 1969.