**5.2 VO2 and its contribution to the balance of oxygen transport**

Previous studies used assumptions for VO2 of 160 or 180 mL/min/m2 to calculate hemodynamics (Charpie, Dekeon et al. 2001; Hoffman, Ghanayem et al. 2000; Maher, Pizarro et al. 2003; Tweddell, Hoffman et al. 1999)**.** Those values are much higher than the directly measured VO2 in our patients, which ranged from 45 to 152 mL/min/m2 (Figure 8).

Fig. 8. The changes in oxygen consumption (VO2), oxygen delivery (DO2) and oxygen extraction ration (ERO2) in neonates in the first 72 hours after the Norwood procedure. Dotted lines indicate individual patients; solid line indicates the mean.

Accurate Measurement of Systemic

Oxygen Consumption in Ventilated Children with Congenital Heart Disease 309

transport and tissue oxygenation. Some reports indicate favorable responses to catecholamine treatment in adults and older children after cardiac surgery (Kawamura, Minamikawa et al. 1980; Merin, Bitran et al. 1977; Rosenblum and Frieden 1972). In neonates, however, catecholamines have additional thermogenic actions through their effects on brown adipose tissue, resulting in an exaggerated increase in VO2 (Maxwell, Crompton et al. 1985; Penny, Sano et al. 2001; Sell, Deshaies et al. 2004). Furthermore, neonatal hearts are known to have limited reserves to increase cardiac contractility. The reserves might become marginal in a Norwood circulation, with the injured single right ventricle providing parallel pulmonary and systemic circulations. In these patients, efforts to improve DO2 by catecholamines are more likely to be associated with predominately adverse effects. As we have reported, terminating a moderate dose of dopamine (5 g/kg/min) was not associated with any significant changes in CO or DO2, but with a significant decrease in heart rate and rate-pressure product, an indirect indicator of myocardial oxygen consumption (Li, Zhang et al. 2006). VO2 also decreased by 16±14 mL/min/m2, representing a change of 20±11%. Terminating dopamine resulted overall in an improvement of the balance of oxygen transport, as indicated by the significant decrease in ERO2 (Figure 10). Therefore, a moderate dose of dopamine induces predominantly an increase in VO2, adversely affecting the VO2–DO2 relationship. Figure 11 shows examples of

Fig. 9. Correlations between oxygen delivery (DO2) and systemic vascular resistance (SVR), systemic blood flow (Qs), total pulmonary vascular resistance including the B-T shunt (BT-

PVR), and pulmonary blood flow ( Qp).

on-line VO2 monitoring before and after dopamine termination.

An overestimation of VO2 leads to a direct proportional change in the estimates for the calculated variables. For example, an assumed VO2 of 170 mL/min/m2, compared with the measured mean VO2 on arrival in ICU of 101 mL/min/m2, leads to a 68% overestimation of total CO, Qp, and Qs, and a 68% underestimation of PVR and SVR. Even more important, VO2 is highly variable both between and within individual patients over time. Using a single assumed VO2 makes no provision for the highly dynamic patient milieu that is inherent in the Norwood physiology.

VO2 increases immediately after the Norwood procedure, mainly due to the systemic inflammatory response (Li, Hoschtitzky et al. 2004; Oudemans-van Straaten, Jansen et al. 1996), re-warming from hypothermic CPB and fever (Li, Hoschtitzky et al. 2004; Li, Schulze-Neick et al. 2000), and the use of inotropes (Li, Zhang et al. 2006). After arrival of the patient in the ICU, VO2 decreases rapidly in the first 24 hours, followed by a slower decrease over the following 48 hours. In the first 24 hours, CO, Qs, and DO2 are the variables most decreased. However, during the critical first 24-hour period, the balance of VO2 and DO2 improves significantly, as indicated by the rapid decrease in ERO2 (Figure 8). The observed improvement in balance results primarily from a decrease in VO2, rather than DO2 as previously reported. After 24 hours, DO2 became the primary contributor to the balance of oxygen transport.

#### **5.3 Optimizing oxygen delivery**

Historically, the postoperative management strategy for patients after the Norwood procedure was directed at diminishing Qp by increasing PVR, in order to increase Qs and DO2. Analysis of our data reveals that SVR is far more important in determining Qs and DO2 than is PVR. This indicates that both the systemic and pulmonary vascular compartments have variable resistance, but the systemic circulation has a more profound effect on DO2, whereas the pulmonary compartment is relatively fixed with the mechanical limitation of the shunt. Interestingly, increases in SaO2 and PaO2 have only a weak positive correlation with Qp, implying that relative hypoxia to increase PVR and reduce Qp yields little benefit to DO2. Our data also show that hemoglobin is an important contributor to DO2, with a tight correlation between DO2 and hemoglobin values. Therefore, treatment strategies should be designed to improve DO2 and its balance with VO2. Specifically, management strategies to maintain a high hemoglobin value, a low VO2, and a relatively low and stable SVR appear to be rational.

#### **5.4 Factors that affect the balance of oxygen transport**

Direct measurements of VO2 have allowed us to study the complex effects of some routine treatments on oxygen transport. Some routine treatments used in an effort to improve the balance of oxygen transport in fact have adverse effects.

#### **5.4.1 Catecholamines**

Catecholamines, such as dopamine, epinephrine, and norepiphrine, are commonly used in patients after CPB to augment cardiac contractility and DO2 (Kawamura, Minamikawa et al. 1980; Merin, Bitran et al. 1977; Rosenblum and Frieden 1972). Catecholamines also stimulate VO2 through their effects on myocardial work and metabolic rate (Cori and Buchwald 1930; Ensinger, Weichel et al. 1993; Maxwell, Crompton et al. 1985). If the increase in DO2 is greater than the increase in VO2, catecholamines will improve the overall balance of oxygen

An overestimation of VO2 leads to a direct proportional change in the estimates for the calculated variables. For example, an assumed VO2 of 170 mL/min/m2, compared with the measured mean VO2 on arrival in ICU of 101 mL/min/m2, leads to a 68% overestimation of total CO, Qp, and Qs, and a 68% underestimation of PVR and SVR. Even more important, VO2 is highly variable both between and within individual patients over time. Using a single assumed VO2 makes no provision for the highly dynamic patient milieu that is

VO2 increases immediately after the Norwood procedure, mainly due to the systemic inflammatory response (Li, Hoschtitzky et al. 2004; Oudemans-van Straaten, Jansen et al. 1996), re-warming from hypothermic CPB and fever (Li, Hoschtitzky et al. 2004; Li, Schulze-Neick et al. 2000), and the use of inotropes (Li, Zhang et al. 2006). After arrival of the patient in the ICU, VO2 decreases rapidly in the first 24 hours, followed by a slower decrease over the following 48 hours. In the first 24 hours, CO, Qs, and DO2 are the variables most decreased. However, during the critical first 24-hour period, the balance of VO2 and DO2 improves significantly, as indicated by the rapid decrease in ERO2 (Figure 8). The observed improvement in balance results primarily from a decrease in VO2, rather than DO2 as previously reported. After 24 hours, DO2 became the primary contributor to the balance of

Historically, the postoperative management strategy for patients after the Norwood procedure was directed at diminishing Qp by increasing PVR, in order to increase Qs and DO2. Analysis of our data reveals that SVR is far more important in determining Qs and DO2 than is PVR. This indicates that both the systemic and pulmonary vascular compartments have variable resistance, but the systemic circulation has a more profound effect on DO2, whereas the pulmonary compartment is relatively fixed with the mechanical limitation of the shunt. Interestingly, increases in SaO2 and PaO2 have only a weak positive correlation with Qp, implying that relative hypoxia to increase PVR and reduce Qp yields little benefit to DO2. Our data also show that hemoglobin is an important contributor to DO2, with a tight correlation between DO2 and hemoglobin values. Therefore, treatment strategies should be designed to improve DO2 and its balance with VO2. Specifically, management strategies to maintain a high hemoglobin value, a low VO2, and a relatively

Direct measurements of VO2 have allowed us to study the complex effects of some routine treatments on oxygen transport. Some routine treatments used in an effort to improve the

Catecholamines, such as dopamine, epinephrine, and norepiphrine, are commonly used in patients after CPB to augment cardiac contractility and DO2 (Kawamura, Minamikawa et al. 1980; Merin, Bitran et al. 1977; Rosenblum and Frieden 1972). Catecholamines also stimulate VO2 through their effects on myocardial work and metabolic rate (Cori and Buchwald 1930; Ensinger, Weichel et al. 1993; Maxwell, Crompton et al. 1985). If the increase in DO2 is greater than the increase in VO2, catecholamines will improve the overall balance of oxygen

inherent in the Norwood physiology.

oxygen transport.

**5.3 Optimizing oxygen delivery** 

low and stable SVR appear to be rational.

**5.4.1 Catecholamines** 

**5.4 Factors that affect the balance of oxygen transport** 

balance of oxygen transport in fact have adverse effects.

transport and tissue oxygenation. Some reports indicate favorable responses to catecholamine treatment in adults and older children after cardiac surgery (Kawamura, Minamikawa et al. 1980; Merin, Bitran et al. 1977; Rosenblum and Frieden 1972). In neonates, however, catecholamines have additional thermogenic actions through their effects on brown adipose tissue, resulting in an exaggerated increase in VO2 (Maxwell, Crompton et al. 1985; Penny, Sano et al. 2001; Sell, Deshaies et al. 2004). Furthermore, neonatal hearts are known to have limited reserves to increase cardiac contractility. The reserves might become marginal in a Norwood circulation, with the injured single right ventricle providing parallel pulmonary and systemic circulations. In these patients, efforts to improve DO2 by catecholamines are more likely to be associated with predominately adverse effects. As we have reported, terminating a moderate dose of dopamine (5 g/kg/min) was not associated with any significant changes in CO or DO2, but with a significant decrease in heart rate and rate-pressure product, an indirect indicator of myocardial oxygen consumption (Li, Zhang et al. 2006). VO2 also decreased by 16±14 mL/min/m2, representing a change of 20±11%. Terminating dopamine resulted overall in an improvement of the balance of oxygen transport, as indicated by the significant decrease in ERO2 (Figure 10). Therefore, a moderate dose of dopamine induces predominantly an increase in VO2, adversely affecting the VO2–DO2 relationship. Figure 11 shows examples of on-line VO2 monitoring before and after dopamine termination.

Fig. 9. Correlations between oxygen delivery (DO2) and systemic vascular resistance (SVR), systemic blood flow (Qs), total pulmonary vascular resistance including the B-T shunt (BT-PVR), and pulmonary blood flow ( Qp).

Accurate Measurement of Systemic

improve oxygen delivery.

**5.4.3 Hyperglycemia** 

**5.4.2 CO2** 

Oxygen Consumption in Ventilated Children with Congenital Heart Disease 311

CO2 has been suggested as a factor increasing DO2 in neonates both before and after the Norwood procedure (Bradley, Simsic et al. 2001; Mora, Pizarro et al. 1994). Consequently, it is a common practice to maintain a relatively high arterial CO2 tension (PaCO2), primarily by hypoventilation. The potent pulmonary vasoconstrictive effect of CO2 was believed to decrease pulmonary blood flow (Qp), thereby increasing Qs (Mora, Pizarro et al. 1994). We studied the effect of stepwise increases in PaCO2 from 40 to 50 to 60 mmHg, and found complex effects of CO2 on systemic and regional oxygen transport (Li, Zhang et al. 2008). Moderate hypercapnia increases Qs as a result of its effect on SVR, rather than via PVR as previously proposed. The increase in systemic blood flow is primarily a consequence of increased cerebral blood flow that compromises splanchnic circulation. Moderate hypercapnia also decreases VO2 and stimulates the release of catecholamines. The decrease in VO2 improves the balance of oxygen transport, but the increase in catecholamines may be undesirable (Figures 12). Clinically, CO2 should be used with caution when the aim is to

Fig. 12. During stepwise increases in PaCO2 from 40 to 50 to 60 mmHg and after termination of CO2, changes in systemic and total pulmonary vascular resistances (SVR and PVR), systemic and pulmonary blood flow (Qp and Qs), oxygen consumption and delivery (VO2 and DO2), oxygen extraction ration (ERO2), and lactate, cerebral and splanchnic oxygen

Hyperglycemia has been identified as a risk factor for adverse outcomes in critically ill patients, including those after CPB. Tight glucose control with insulin therapy has been shown to improve outcomes, but is not common practice for children following CPB. In our

saturations (ScO2 and SsO2) and in epinephrine and norepinephrine.

Fig. 10. The individual (thin line) and mean (bold line) changes in systemic hemodynamics and oxygen transport before and after termination of dopamine following the Norwood procedure.

Fig. 11. Examples of the on-line measurement of oxygen consumption (VO2) in three patients showing rapid and (A) small, (B) moderate, and (C) large decreases in VO2 after terminating dopamine.
