Intensive Care Med (1990) 16 [Suppl 2]:$145-S148
Intensive Care Medicine 9 Springer-Verlag1990
The relationship between oxygen demand, oxygen uptake, and oxygen supply J.-L. Vincent Department of Intensive Care, Erasmus Hospital, Free University of Brussels, Brussels, Belgium
Abstract. Results of the relationships between oxygen supply, demand, and uptake can be used to interpret cardiac output values, identify types of acute circulatory failure, guide attempts to improve cellular function, and thus prevent the development of multiple organ failure and death. Five steps in the interpretation of cardiac output values are recommended: (1) relate cardiac output to the patient's size; (2) determine the presence of anemia or hypoxemia; (3) measure mixed venous 02 saturation and (4) blood lactate levels; and (5) evaluate 02 uptake before and after a transient increase in cardiac output. Key words: Oxygen supply - Oxygen uptake - Oxygen demand - Cardiac output
The relationship between oxygen supply (DO2) and oxygen uptake (VO2) has been a subject of increasing interest in intensive care medicine. DO2 is the product of cardiac output by the arterial oxygen content. A low hemoglobin level should be corrected whenever it threatens DO2. Likewise, a low arterial oxygen pressure (PaO2) should be corrected in any critically ill patient. The interpretation of a cardiac output value is more complicated since cardiac output adapts to the 02 needs of the body. A low cardiac output should be treated only when 02 demand is normal; for example, cardiac output can be adequately low in an anesthetized, hypothermic patient. At the other extreme, since oxygen demand of the tissues is often increased in acute diseases associated with sepsis, surgery, trauma, or other inflammatory states, cardiac output must sometimes be markedly increased in these circumstances. To some extent, these conditions can be compared to exercise. When oxygen demand increases acutely, DO 2 must also increase without delay. An increase in PaO 2 to above normal levels does not increase DO 2 much because of the nearly complete oxygen saturation of the hemoglobin. Similarly, an increase in hemoglobin level cannot be achieved rapidly, and would not efficiently increase cellu-
lar 0 2 avallabifity because blood viscosity would rise simultaneously. Hence, cardiac output and, to a lesser extent, the distribution of blood flow in the organism represent the only factors that can readily and efficiently increase cellular O2 availability. Accordingly, a cardiac output value that is considered normal might still be inadequate or insufficient in the presence of an elevated O2 demand by tissues. Study of the relationship between DO2, VO2, and oxygen demand helps to interpret cardiac output values. It also allows the development of a unique concept defining all types of acute circulatory failure and can indicate therapeutic options to improve cellular function and prevent the development of multiple organ failure and death.
The DO2/VO 2 relationship in physiological conditions In normal, stable conditions, VO2 is equal to oxygen demand. In the absence of tissue hypoxia, blood lactate levels are normal at about 1 mmol/1. If DO 2 decreases for any reason, VO2 remains relatively stable over a wide range of DO2 values. Indeed, the O2 extraction, i.e., the ratio of the arteriovenous 02 difference to the arterial O2 content, or the V O z / D O 2 ratio, increases. The primary underlying mechanism lies in the microvasculature, where the capillary network dilates to provide more O2 to the cells. VO2 is therefore DOz- or supply-independent. Of course, this is true in the presence of a constant O2 demand in stable conditions. Should the 02 demand increase for any reason (during exercise, for example), the cardiac output and therefore the DO 2 would have to increase simultaneously. When DO2 falls below a critical value, O2 extraction becomes less efficient, so that the VO2 starts to fall. VO2 then becomes DO2- or supply-dependent. In the intact animal, this critical level is about 8 to 10ml/kg.min (Fig. 1) [1, 2, 3]. As shown by Cain [1] in 1965, these states are associated with tissue hypoxia, as reflected by increased blood lactate levels. In conscious lambs, Fahey and Lister [2] observed that VOz became DOz-dependent
S146
J.-L. Vincent: O z demand, uptake, and supply
VO2 < O2 Demand I VO2 = 02 Demand
a;/i
Increased
~-i Laet
I 1 IL--. . . . . . . . . . . .
~
O2 D emand
Normal
Lactate !
I
8-10 ml/kg/min
i/
O2 Supply Fig. 1. Relationship between 0 2 consumption (VO2) and O 2 supply (DO 2) at a constant 0 2 demand
when cardiac output was reduced below a critical level. Lactic acidosis appeared when this critical level of cardiac output was reached. Hence, this VO2/DO z dependency characterizes the types of circulatory shock associated with a profound reduction in cardiac output: the hypovolemic, cardiogenic, and obstructive types of shock. In pure cardiogenic or obstructive types of shock, the 02 extraction capabilities of the organism are very efficient, so that lactate levels start to rise only in extreme situations associated with high mortality.
Abnormal DO2/V02 dependency In patients with sepsis or with the adult respiratory distress syndrome (ARDS), an abnormal VO2/DO 2 dependency can be observed even when the DO 2 is normal or even high [4, 5]. These states are typically associated with a high O2 demand, so that cardiac output and DO2 are expected to be high. At the same time, O 2 extraction by the tissues is altered in septic and other inflammatory states (the "sepsis syndrome") by several factors, including the development of microthrombi, the release of various vasoactive mediators, and the alteration of the endothelial cell function [6], Cellular alterations in sepsis appear to develop later than these microvascular changes [7]. Several pieces of evidence indicate that the pathological VO2/DO2 dependency, like the physiological VO2/DO 2 dependency, is associated with tissue hypoxia and the development of anaerobic metabolism. Nelson et a!. [3] observed during graded hemorrhage in dogs that the critical DO2 level, below which the VO2/DO 2 dependency occurred, was associated with the development of increased blood lactate levels. These observations were in agreement with the results of the Cain [1] studies in which DO2 was progressively lowered by progressive anemia or hypoxemia. When a similar protocol was applied ~fter administration of endotoxin or live bacteria to the animal, the same course of events was observed, except that the critical DO 2 and oxygen extraction levels were disp!aced toward higher values [3], Hence, a reduced DO2 level that was still well tolerated in the intact animal could be associated with tissue hypoxia and lactic acido. sis after the septic challenge. The DO2/VO2 dependency in patients is usually asso. cjated wit!! lactic acidosis. In patients with sepsis and lac-
tic acidosis, Haupt et al. [8] and Gilbert et al. [9] observed an increase in VOz associated with an increase in cardiac output after fluid challenge. Such an increase was not observed in patients without lactic acidosis [8, 9]. Similar observations on the effects of fluids in patients with sepsis and lactic acidosis were made by Astiz et al. [10]. These observations were extended to the _use of blood transfusions by Gilbert et al. [9]. Fenwick et al. [i1] observed in patients with ARDS that blood traxtsfusion increased VO2 only in patients with elevated lactate levels. In contrast, Annat et al. [12] did not observe the DOz/VO 2 dependency in patients with normal blood lactate levels. We studied [13] the DO 2 and VO2 responses to the administration of a standard dose of :5 ~tg/kg.min of dobutamine in 78 critic~!y ill patients with heart failure or sepsis. An increase in VO2 was observed only in patients with increase blood lactate levels. Among ARDS patients in the septic group, VO2 was increased only when lactic acidosis was present [13]. The results of these studies demonstrate that the V O 2 / D O 2 dependency is observed only in the presence of increased blood lactate levels, indicating tissue hypoxia. Thus the increase in VO2 achieved in these conditions is probably beneficial. This is important, since another interpretation is that the increased amount of 02 being consumed is in fact utilized for non-ATP-producing systems related to the inflammatory processes. This use of 02 could contribute to the formation of free oxygen radicals and could thus be detrimental to the organism. If these mechanisms did occur, they would also be observed in the absence of tissue hypoxia and lactic acidosis. In the presence of tissue hypoxia, however, the additional O2 is preferentially used in the mitochondria, as the affinity of the extramitochondrial oxidase systems is lower than the mitochondrial O2 transport chain (r aa3). It is possible that the extramitochondrial 02 utilization takes place, but in late stages of sepsis when multiple organ failure has already occurred.
Interpretation of a cardiac output value In view of these findings, we suggest that five successive steps should be followed in the interpretation of cardiac output. The first step is to relate cardiac output to the size of the patient. Reference to the body area is made to obtain a cardiac index value. The second step is to determine the presence of anemia or hypoxemia, and, if DOE appears threatened, this should be corrected. A hemoglobin level of 10 to 11.5 g/d! (or a hematocrit of 30% to 35%) has been recommended [14]. A PaO 2 of at least 60 mmHg should be maintained to obtain a hemoglobin saturation of at least 90%. Otherwise, a false interpretation of an adequate cardiac output is easily made. For example, a cardiac index of 41/min. m z is lower than normal in the presence of a hemoglobin level of 5.5 g/dl, since for a comparable DOz that would correspond to a cardiac index of 21/min.m z in the presence of a hemoglobin level of 11 g/dl.
J.-L. Vincent: 0 2 demand, uptake, and supply
The third and fourth steps consist of a simultaneous measurement of mixed venous 02 saturation (Srr and blood lactate. S~O2 is no substitute for blood lactate and vice versa, because the two are not expected to correlate well except perhaps in the presence of isolated severe heart failure [15]. Changes in S'~O2 accompany changes in VO2/DO2: at a given VO2, a fall in cardiac output is associated with a concurrent decrease in S'~O2. The interpretation of the Sx?O2 is, however, limited by the possibility of altered 02 extraction capabilities by the tissues. The critical extraction point can be defined in precise laboratory investigations but not clinically. Lactate levels reflect the degree of anaerobic metabolism, but their interpretation can be complicated by the fact that they can also increase in other conditions, including seizures, decompensated diabetes, and in intoxication. Of more importance is that blood lactate levels are influenced not only by production but also be elimination. As lactate is predominantly metabolized by the liver, it can remain elevated when hepatic function is altered. Nevertheless, lactate levels are normal in stable patients with advanced liver insufficiency, so that normal blood lactate levels remain a strong argument to refute the presence of tissue hypoxia. Reduced lactate clearance can complicate the interpretation of its blood levels during the evolution of an episode of acute circulatory failure. Therefore, it is important to measure lactate levels serially so as to allow a dynamic interpretation of these values. In the best circumstances, associated with a good response to fluid therapy, lactate levels decrease by at least 10% during the first hour of treatment [16]. Table 1 shows how cardiac output is interpreted according to Sx302 and lactate levels. The fifth step consists of a dynamic evaluation of VO2 before and after a transient increase in cardiac output. We call this test a "VO2 challenge", and it can be accomplished with fluid administration or blood transfusion. Bihari et al. [4] showed that a dose of 5 ng/kg, min of prostacyclin could reveal the VO2/DO 2 dependency that was associated with mortality in patients with sepsis or acute respiratory failure; they called this the "02 flux test", implying that microcirculatory effects of protacyclin could play a role. We have found it particularly convenient to give 5 ~tg/kg-min of dobutamine, because at this dose dobutamine has significant effects on cardiac
Table 1. Interpretation of cardiac output data according to mixed venous 02 saturation ($902) and blood lactate levels Cardiac output
S~O 2
Blood lactate
Probable cause
High High High High Low Low Low Low
High High Low Low High High Low Low
Normal High Normal High Norm~ High Normal High
Excessive blood flow Septic shock (decreased 02 extraction) High VO 2 Septic shock (high VO2) Low V O 2 Septic shock (low V02) Low blood flow Shock with low blood flow
S147
output and thus DO 2, but minimal effects on blood pressure [13]. A larger dose of dobutamine could be associated with an increase in VO2 in all patients because of the effects of catecholamines on cellular metabolism. The VO2 challenge requires that the 02 demand of the patient remains stable during the procedure, and thus the test should not take more than 30 min and should be performed in a stable, quiet environment. Particular care must be taken to measure cardiac output accurately and to perform the Srr measurement immediately thereafter. The VO2 challenge does not require calculation of DO 2 and VO2 before and after the procedure, as this is cumbersome and requires a pocket calculator. Assuming that hemoglobin and SaO2 levels do not change during the test, the increase in cardiac output should be matched by a proportional increase in S~O2 if VO2 remains stable. In contrast, a larger increase in cardiac output than in S~r indicates an increase in VO2 associated with the increase in DO2. In this type of patient, cardiac output is probably not adequate to meet the 02 demand, so that a treatment aiming at increasing cardiac output would be rational. Because the VO2/DO 2 dependency state has been associated with increased morbidity and mortality [4, 17], its correction whenever possible has a sound rationale. This thesis is further supported by the abundant data of Shoemaker et al. [18, 19], showing that patients with higher DOE and VO2 values develop fewer complications and are more likely to survive.
References 1. Cain SM (1965) Appearance of excess lactate in anesthetized dogs during anemic and hypoxic hypoxia. Am J Physiol 209:604-608 2. Fahey JT, Lister G (1987) Postnatal changes in critical cardiac output and oxygen transport in conscious Iambs. Am J Physiol 253:HI00-HI06 3. Nelson DP, Beyer C, Samsel RW, Wood LDH, Schumacker PT (1987) Pathologic supply-dependence of O 2 uptake during bacteremia in dogs. J Appl Physiol 63:1487-I492 4. Bihari D, Smithies M, Gimson A, Tinker J (1987) The effects of vasodilatation with prostacyclin on oxygen delivery and uptake in critically ill patients. N Engl J Med 317"397-403 5. Danek SJ, Lynch JP, Weg JG, Dantzker DR (1980) The dependence of oxygen uptake on oxygen delivery in the adult respiratory distress syndrome. Am Rev Respir Dis I22:387-395 6. Rackow EC, Astiz ME, Well MH (1988) Cellular oxygen metabolism during sepsis and shock: The relationship of oxygen consumption to oxygen delivery. J Am Med Assoc 259:1989-1993 7. Geller ER, Jankouskas S, Kirkpatrick J (t9.86) Mitochondrial death in sepsis: A failed concept. J Surg Res 40:514-519 8. Haupt MT, Gilbert EM, Carlson RW (I985) Fluid loading increases oxygen consumption in septic patients with lactic acidosis. Am Rev Respir Dis 131:912-916 9. Gilbert EM, Haupt MT, Mandanas RY, Huaringa AJ, Carlson RW (1988) The effect of fluid loading, blood transfusion, and catecholamine infusion on oxygen delivery and consumption in patients with. sepsis. Am Rev Respir Dis 134:873-878 10, Astiz ME, Rackow EC, Falk JL, Kaufman BS, Well MH (1987) Oxygen delivery and consumption in patients with hyperdynamic septic si~ock. Crit Care Med 15:26-28 11. Fenwick JC, Dodek PM, Ronco J J, Phang PT, Wiggs Bi Russell JA (1990) Increased concentrations of plasma lactate predict pathologic dependence of oxygen consumption on oxygen delivery in patients with adult respiratoy distress syndt'ome. ~ Crit Care 5:81-87
S148 12. Annat G, Viale JP, Percival C, Froment M, Motin J (1986) Oxygen delivery and uptake in the adult respiratory distress syndrome: Lack of relationship when measured independently in patients with normal blood lactate concentrations. Am Rev Respir Dis 133:999-1001 13. Vincent JL, Roman A, De Backer D, Kahn RJ (1990) Oxygen uptake/supply dependency: Effects of short term dobutamine infusion. Am Rev Respir Dis 142:2-7 14. Bryan-Brown CW (1988) Blood flow to organs: Parameters for function and survival in critical illness. Crit Care Med 16:170-178 15. Weber KT, Janick J, Maskin C (1985) Pathophysiology of cardiac failure. Am J Cardiol 56:3B-6B 16. Vincent JL, Dufaye P, Berre J, Leeman M, Degaute JP, Kahn RJ (1983) Serial lactate determinations during circulatory shock. Crit Care Med 11:449- 451 17. Gutierrez G, Pohil RJ (1986) Oxygen consumption is linearly related to 0 2 supply in critically ill patients. J Crit Care 1:45-53
J.-L. Vincent: 0 2 demand, uptake, and supply 18. Shoemaker WC, Appel PL, Bland RD, Hopkins JA, Chang D (1982) Clinical trial of a algorithm for outcome prediction in acute circulatory failure. Crit Care Med 10:300-397 19. Shoemaker WC, Appel PL, Kram HB, Waxman K, Lee T (1988) Prospective trial of supranormal values of survivors as therapeutic goals in high-risk surgical patients. Chest 94:1176-1186
Dr. J.-L. Vincent D6partement de Soins Intensifs H6pital Erasme Cliniques Universitaires de Bruxelles Route de Lennik 808 B-1070 Bruxelles Belgium
Intensive Care Medicine 9 Springer-Verlag1990
The relationship between oxygen demand, oxygen uptake, and oxygen supply J.-L. Vincent Department of Intensive Care, Erasmus Hospital, Free University of Brussels, Brussels, Belgium
Abstract. Results of the relationships between oxygen supply, demand, and uptake can be used to interpret cardiac output values, identify types of acute circulatory failure, guide attempts to improve cellular function, and thus prevent the development of multiple organ failure and death. Five steps in the interpretation of cardiac output values are recommended: (1) relate cardiac output to the patient's size; (2) determine the presence of anemia or hypoxemia; (3) measure mixed venous 02 saturation and (4) blood lactate levels; and (5) evaluate 02 uptake before and after a transient increase in cardiac output. Key words: Oxygen supply - Oxygen uptake - Oxygen demand - Cardiac output
The relationship between oxygen supply (DO2) and oxygen uptake (VO2) has been a subject of increasing interest in intensive care medicine. DO2 is the product of cardiac output by the arterial oxygen content. A low hemoglobin level should be corrected whenever it threatens DO2. Likewise, a low arterial oxygen pressure (PaO2) should be corrected in any critically ill patient. The interpretation of a cardiac output value is more complicated since cardiac output adapts to the 02 needs of the body. A low cardiac output should be treated only when 02 demand is normal; for example, cardiac output can be adequately low in an anesthetized, hypothermic patient. At the other extreme, since oxygen demand of the tissues is often increased in acute diseases associated with sepsis, surgery, trauma, or other inflammatory states, cardiac output must sometimes be markedly increased in these circumstances. To some extent, these conditions can be compared to exercise. When oxygen demand increases acutely, DO 2 must also increase without delay. An increase in PaO 2 to above normal levels does not increase DO 2 much because of the nearly complete oxygen saturation of the hemoglobin. Similarly, an increase in hemoglobin level cannot be achieved rapidly, and would not efficiently increase cellu-
lar 0 2 avallabifity because blood viscosity would rise simultaneously. Hence, cardiac output and, to a lesser extent, the distribution of blood flow in the organism represent the only factors that can readily and efficiently increase cellular O2 availability. Accordingly, a cardiac output value that is considered normal might still be inadequate or insufficient in the presence of an elevated O2 demand by tissues. Study of the relationship between DO2, VO2, and oxygen demand helps to interpret cardiac output values. It also allows the development of a unique concept defining all types of acute circulatory failure and can indicate therapeutic options to improve cellular function and prevent the development of multiple organ failure and death.
The DO2/VO 2 relationship in physiological conditions In normal, stable conditions, VO2 is equal to oxygen demand. In the absence of tissue hypoxia, blood lactate levels are normal at about 1 mmol/1. If DO 2 decreases for any reason, VO2 remains relatively stable over a wide range of DO2 values. Indeed, the O2 extraction, i.e., the ratio of the arteriovenous 02 difference to the arterial O2 content, or the V O z / D O 2 ratio, increases. The primary underlying mechanism lies in the microvasculature, where the capillary network dilates to provide more O2 to the cells. VO2 is therefore DOz- or supply-independent. Of course, this is true in the presence of a constant O2 demand in stable conditions. Should the 02 demand increase for any reason (during exercise, for example), the cardiac output and therefore the DO 2 would have to increase simultaneously. When DO2 falls below a critical value, O2 extraction becomes less efficient, so that the VO2 starts to fall. VO2 then becomes DO2- or supply-dependent. In the intact animal, this critical level is about 8 to 10ml/kg.min (Fig. 1) [1, 2, 3]. As shown by Cain [1] in 1965, these states are associated with tissue hypoxia, as reflected by increased blood lactate levels. In conscious lambs, Fahey and Lister [2] observed that VOz became DOz-dependent
S146
J.-L. Vincent: O z demand, uptake, and supply
VO2 < O2 Demand I VO2 = 02 Demand
a;/i
Increased
~-i Laet
I 1 IL--. . . . . . . . . . . .
~
O2 D emand
Normal
Lactate !
I
8-10 ml/kg/min
i/
O2 Supply Fig. 1. Relationship between 0 2 consumption (VO2) and O 2 supply (DO 2) at a constant 0 2 demand
when cardiac output was reduced below a critical level. Lactic acidosis appeared when this critical level of cardiac output was reached. Hence, this VO2/DO z dependency characterizes the types of circulatory shock associated with a profound reduction in cardiac output: the hypovolemic, cardiogenic, and obstructive types of shock. In pure cardiogenic or obstructive types of shock, the 02 extraction capabilities of the organism are very efficient, so that lactate levels start to rise only in extreme situations associated with high mortality.
Abnormal DO2/V02 dependency In patients with sepsis or with the adult respiratory distress syndrome (ARDS), an abnormal VO2/DO 2 dependency can be observed even when the DO 2 is normal or even high [4, 5]. These states are typically associated with a high O2 demand, so that cardiac output and DO2 are expected to be high. At the same time, O 2 extraction by the tissues is altered in septic and other inflammatory states (the "sepsis syndrome") by several factors, including the development of microthrombi, the release of various vasoactive mediators, and the alteration of the endothelial cell function [6], Cellular alterations in sepsis appear to develop later than these microvascular changes [7]. Several pieces of evidence indicate that the pathological VO2/DO2 dependency, like the physiological VO2/DO 2 dependency, is associated with tissue hypoxia and the development of anaerobic metabolism. Nelson et a!. [3] observed during graded hemorrhage in dogs that the critical DO2 level, below which the VO2/DO 2 dependency occurred, was associated with the development of increased blood lactate levels. These observations were in agreement with the results of the Cain [1] studies in which DO2 was progressively lowered by progressive anemia or hypoxemia. When a similar protocol was applied ~fter administration of endotoxin or live bacteria to the animal, the same course of events was observed, except that the critical DO 2 and oxygen extraction levels were disp!aced toward higher values [3], Hence, a reduced DO2 level that was still well tolerated in the intact animal could be associated with tissue hypoxia and lactic acido. sis after the septic challenge. The DO2/VO2 dependency in patients is usually asso. cjated wit!! lactic acidosis. In patients with sepsis and lac-
tic acidosis, Haupt et al. [8] and Gilbert et al. [9] observed an increase in VOz associated with an increase in cardiac output after fluid challenge. Such an increase was not observed in patients without lactic acidosis [8, 9]. Similar observations on the effects of fluids in patients with sepsis and lactic acidosis were made by Astiz et al. [10]. These observations were extended to the _use of blood transfusions by Gilbert et al. [9]. Fenwick et al. [i1] observed in patients with ARDS that blood traxtsfusion increased VO2 only in patients with elevated lactate levels. In contrast, Annat et al. [12] did not observe the DOz/VO 2 dependency in patients with normal blood lactate levels. We studied [13] the DO 2 and VO2 responses to the administration of a standard dose of :5 ~tg/kg.min of dobutamine in 78 critic~!y ill patients with heart failure or sepsis. An increase in VO2 was observed only in patients with increase blood lactate levels. Among ARDS patients in the septic group, VO2 was increased only when lactic acidosis was present [13]. The results of these studies demonstrate that the V O 2 / D O 2 dependency is observed only in the presence of increased blood lactate levels, indicating tissue hypoxia. Thus the increase in VO2 achieved in these conditions is probably beneficial. This is important, since another interpretation is that the increased amount of 02 being consumed is in fact utilized for non-ATP-producing systems related to the inflammatory processes. This use of 02 could contribute to the formation of free oxygen radicals and could thus be detrimental to the organism. If these mechanisms did occur, they would also be observed in the absence of tissue hypoxia and lactic acidosis. In the presence of tissue hypoxia, however, the additional O2 is preferentially used in the mitochondria, as the affinity of the extramitochondrial oxidase systems is lower than the mitochondrial O2 transport chain (r aa3). It is possible that the extramitochondrial 02 utilization takes place, but in late stages of sepsis when multiple organ failure has already occurred.
Interpretation of a cardiac output value In view of these findings, we suggest that five successive steps should be followed in the interpretation of cardiac output. The first step is to relate cardiac output to the size of the patient. Reference to the body area is made to obtain a cardiac index value. The second step is to determine the presence of anemia or hypoxemia, and, if DOE appears threatened, this should be corrected. A hemoglobin level of 10 to 11.5 g/d! (or a hematocrit of 30% to 35%) has been recommended [14]. A PaO 2 of at least 60 mmHg should be maintained to obtain a hemoglobin saturation of at least 90%. Otherwise, a false interpretation of an adequate cardiac output is easily made. For example, a cardiac index of 41/min. m z is lower than normal in the presence of a hemoglobin level of 5.5 g/dl, since for a comparable DOz that would correspond to a cardiac index of 21/min.m z in the presence of a hemoglobin level of 11 g/dl.
J.-L. Vincent: 0 2 demand, uptake, and supply
The third and fourth steps consist of a simultaneous measurement of mixed venous 02 saturation (Srr and blood lactate. S~O2 is no substitute for blood lactate and vice versa, because the two are not expected to correlate well except perhaps in the presence of isolated severe heart failure [15]. Changes in S'~O2 accompany changes in VO2/DO2: at a given VO2, a fall in cardiac output is associated with a concurrent decrease in S'~O2. The interpretation of the Sx?O2 is, however, limited by the possibility of altered 02 extraction capabilities by the tissues. The critical extraction point can be defined in precise laboratory investigations but not clinically. Lactate levels reflect the degree of anaerobic metabolism, but their interpretation can be complicated by the fact that they can also increase in other conditions, including seizures, decompensated diabetes, and in intoxication. Of more importance is that blood lactate levels are influenced not only by production but also be elimination. As lactate is predominantly metabolized by the liver, it can remain elevated when hepatic function is altered. Nevertheless, lactate levels are normal in stable patients with advanced liver insufficiency, so that normal blood lactate levels remain a strong argument to refute the presence of tissue hypoxia. Reduced lactate clearance can complicate the interpretation of its blood levels during the evolution of an episode of acute circulatory failure. Therefore, it is important to measure lactate levels serially so as to allow a dynamic interpretation of these values. In the best circumstances, associated with a good response to fluid therapy, lactate levels decrease by at least 10% during the first hour of treatment [16]. Table 1 shows how cardiac output is interpreted according to Sx302 and lactate levels. The fifth step consists of a dynamic evaluation of VO2 before and after a transient increase in cardiac output. We call this test a "VO2 challenge", and it can be accomplished with fluid administration or blood transfusion. Bihari et al. [4] showed that a dose of 5 ng/kg, min of prostacyclin could reveal the VO2/DO 2 dependency that was associated with mortality in patients with sepsis or acute respiratory failure; they called this the "02 flux test", implying that microcirculatory effects of protacyclin could play a role. We have found it particularly convenient to give 5 ~tg/kg-min of dobutamine, because at this dose dobutamine has significant effects on cardiac
Table 1. Interpretation of cardiac output data according to mixed venous 02 saturation ($902) and blood lactate levels Cardiac output
S~O 2
Blood lactate
Probable cause
High High High High Low Low Low Low
High High Low Low High High Low Low
Normal High Normal High Norm~ High Normal High
Excessive blood flow Septic shock (decreased 02 extraction) High VO 2 Septic shock (high VO2) Low V O 2 Septic shock (low V02) Low blood flow Shock with low blood flow
S147
output and thus DO 2, but minimal effects on blood pressure [13]. A larger dose of dobutamine could be associated with an increase in VO2 in all patients because of the effects of catecholamines on cellular metabolism. The VO2 challenge requires that the 02 demand of the patient remains stable during the procedure, and thus the test should not take more than 30 min and should be performed in a stable, quiet environment. Particular care must be taken to measure cardiac output accurately and to perform the Srr measurement immediately thereafter. The VO2 challenge does not require calculation of DO 2 and VO2 before and after the procedure, as this is cumbersome and requires a pocket calculator. Assuming that hemoglobin and SaO2 levels do not change during the test, the increase in cardiac output should be matched by a proportional increase in S~O2 if VO2 remains stable. In contrast, a larger increase in cardiac output than in S~r indicates an increase in VO2 associated with the increase in DO2. In this type of patient, cardiac output is probably not adequate to meet the 02 demand, so that a treatment aiming at increasing cardiac output would be rational. Because the VO2/DO 2 dependency state has been associated with increased morbidity and mortality [4, 17], its correction whenever possible has a sound rationale. This thesis is further supported by the abundant data of Shoemaker et al. [18, 19], showing that patients with higher DOE and VO2 values develop fewer complications and are more likely to survive.
References 1. Cain SM (1965) Appearance of excess lactate in anesthetized dogs during anemic and hypoxic hypoxia. Am J Physiol 209:604-608 2. Fahey JT, Lister G (1987) Postnatal changes in critical cardiac output and oxygen transport in conscious Iambs. Am J Physiol 253:HI00-HI06 3. Nelson DP, Beyer C, Samsel RW, Wood LDH, Schumacker PT (1987) Pathologic supply-dependence of O 2 uptake during bacteremia in dogs. J Appl Physiol 63:1487-I492 4. Bihari D, Smithies M, Gimson A, Tinker J (1987) The effects of vasodilatation with prostacyclin on oxygen delivery and uptake in critically ill patients. N Engl J Med 317"397-403 5. Danek SJ, Lynch JP, Weg JG, Dantzker DR (1980) The dependence of oxygen uptake on oxygen delivery in the adult respiratory distress syndrome. Am Rev Respir Dis I22:387-395 6. Rackow EC, Astiz ME, Well MH (1988) Cellular oxygen metabolism during sepsis and shock: The relationship of oxygen consumption to oxygen delivery. J Am Med Assoc 259:1989-1993 7. Geller ER, Jankouskas S, Kirkpatrick J (t9.86) Mitochondrial death in sepsis: A failed concept. J Surg Res 40:514-519 8. Haupt MT, Gilbert EM, Carlson RW (I985) Fluid loading increases oxygen consumption in septic patients with lactic acidosis. Am Rev Respir Dis 131:912-916 9. Gilbert EM, Haupt MT, Mandanas RY, Huaringa AJ, Carlson RW (1988) The effect of fluid loading, blood transfusion, and catecholamine infusion on oxygen delivery and consumption in patients with. sepsis. Am Rev Respir Dis 134:873-878 10, Astiz ME, Rackow EC, Falk JL, Kaufman BS, Well MH (1987) Oxygen delivery and consumption in patients with hyperdynamic septic si~ock. Crit Care Med 15:26-28 11. Fenwick JC, Dodek PM, Ronco J J, Phang PT, Wiggs Bi Russell JA (1990) Increased concentrations of plasma lactate predict pathologic dependence of oxygen consumption on oxygen delivery in patients with adult respiratoy distress syndt'ome. ~ Crit Care 5:81-87
S148 12. Annat G, Viale JP, Percival C, Froment M, Motin J (1986) Oxygen delivery and uptake in the adult respiratory distress syndrome: Lack of relationship when measured independently in patients with normal blood lactate concentrations. Am Rev Respir Dis 133:999-1001 13. Vincent JL, Roman A, De Backer D, Kahn RJ (1990) Oxygen uptake/supply dependency: Effects of short term dobutamine infusion. Am Rev Respir Dis 142:2-7 14. Bryan-Brown CW (1988) Blood flow to organs: Parameters for function and survival in critical illness. Crit Care Med 16:170-178 15. Weber KT, Janick J, Maskin C (1985) Pathophysiology of cardiac failure. Am J Cardiol 56:3B-6B 16. Vincent JL, Dufaye P, Berre J, Leeman M, Degaute JP, Kahn RJ (1983) Serial lactate determinations during circulatory shock. Crit Care Med 11:449- 451 17. Gutierrez G, Pohil RJ (1986) Oxygen consumption is linearly related to 0 2 supply in critically ill patients. J Crit Care 1:45-53
J.-L. Vincent: 0 2 demand, uptake, and supply 18. Shoemaker WC, Appel PL, Bland RD, Hopkins JA, Chang D (1982) Clinical trial of a algorithm for outcome prediction in acute circulatory failure. Crit Care Med 10:300-397 19. Shoemaker WC, Appel PL, Kram HB, Waxman K, Lee T (1988) Prospective trial of supranormal values of survivors as therapeutic goals in high-risk surgical patients. Chest 94:1176-1186
Dr. J.-L. Vincent D6partement de Soins Intensifs H6pital Erasme Cliniques Universitaires de Bruxelles Route de Lennik 808 B-1070 Bruxelles Belgium
