**1. Introduction**

292 Congenital Heart Disease – Selected Aspects

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Measuring systemic oxygen consumption (VO2) is a fundamental part of hemodynamic and oxygen transport assessment when using the Fick principle. This measure is pivotal for children with congenital heart disease, at cardiac catheterization and in the Intensive Care Unit (ICU) after cardiopulmonary bypass surgery (CPB). According to the direct Fick principle (Fick, 1870), VO2 may be combined with the difference between arterial and venous oxygen content, and the pressure gradient, to allow the calculation of each parameter of systemic hemodynamics and oxygen transport. Parameters that may be calculated include systemic and pulmonary blood flows (Qs and Qp) and resistances (SVR and PVR), systemic oxygen delivery (DO2), and oxygen extraction ratio (ERO2). Importantly, these parameters can be derived in a variety of simple or complex circulations in congenital heart defects before and after surgical repair or palliation, including *1)* biventricular circulation with or without left to right or right to left shunt (Li, Hoschtitzky et al. 2004; Li, Schulze-Neick et al. 2000; Schulze-Neick, Li et al. 2001; Schulze-Neick, Li et al. 2002), *2)* functionally single ventricular circulation such as hypoplastic left heart syndrome before and after the Norwood procedure (Li, Zhang et al. 2006; Li, Zhang et al. 2006; Li, Zhang et al. 2007; Li, Zhang et al. 2007; Li, Zhang et al. 2008), and *3)* one-and-a-half ventricular circulation such as after the bidirectional cavopulmonary shunt operation (Hoskote, Li et al. 2004; Li, Hoskote et al. 2005).

If VO2 needs to be measured, then accuracy of the measurement cannot be overemphasized (Kendrick, West et al. 1988; Laitinen and Rasanen 1998; Shanahan, Wilson et al. 2003). Any error in VO2 measurement will translate directly into an equivalent magnitude of underestimation or over-estimation of hemodynamics and oxygen transport parameters, which may misdirect surgical and clinical treatment strategies. Prognostic cardiac catheterization is often used for evaluation of systemic and pulmonary blood flows and vascular resistances, particularly pulmonary vascular resistance, in patients with primary or secondary pulmonary hypertension, and in patients with functionally single ventricular abnormalities undergoing staged surgical palliations. In this latter group, elevated pulmonary vascular resistance is a risk factor for poor outcome (Gentles, Gauvreau et al. 1997; Gentles, Mayer et al. 1997; Mair, Hagler et al. 1990), emphasizing the need for accurate hemodynamic assessment before staged palliations.

Accurate Measurement of Systemic

disease before and after CPB.

et al. 2008).

1973; Westenskow, Jordan et al. 1978)

Oxygen Consumption in Ventilated Children with Congenital Heart Disease 295

measurement of VO2 in both clinical care and research in children with congenital heart

Although techniques for metabolic monitoring using indirect calorimetry or respiratory mass spectrometry are available for the direct measurement of VO2, it is still common practice to estimate VO2 values from tables or published predictive equations (LaFarge and Miettinen 1970; Lindahl 1989; Lundell, Casas et al. 1996; Wessel, Rorem et al. 1969). Despite attempts to improve the accuracy of estimated VO2 values, large discrepancies are still observed between measured and estimated values (Laitinen and Rasanen 1998; Shanahan, Wilson et al. 2003; Wolf, Pollman et al. 1998). Such discrepancies present challenges in the clinical application of predictive equations e.g., in the catheterization laboratory setting, because subsequent hemodynamic calculations will be impaired. In ICU patients during the early postoperative period after CPB, estimation of VO2 is even further exposed to inaccuracies due to significant variability of VO2 between and within patients over time (Li, Zhang et al. 2006; Li, Zhang et al. 2006; Li, Zhang et al. 2007; Li, Zhang et al. 2008). Furthermore, estimating VO2 by predictive equations gives a single value for a given patient and makes no provision for the dynamic patient milieu that is inevitable in the early postoperative period (Li, Zhang et al. 2006; Li, Zhang et al. 2006; Li, Zhang et al. 2007; Li, Zhang

We have compared results from four commonly used equations for estimating VO2 (LaFarge and Miettinen 1970; Lindahl 1989; Lundell, Casas et al. 1996; Wessel, Rorem et al. 1969) against VO2 measured directly by respiratory mass spectrometry. Both the equations and the direct measurements were applied to children with congenital heart defects, during cardiac catherization and in the ICU after CPB. We found poor agreement between the direct measurements and all estimated values, especially in children younger than 3 years of

In patients undergoing cardiac catheterization, there is a general *over-estimation* of VO2 introduced by the equations (Figure 1) (Li, Bush et al. 2003). The conditions of conscious sedation with spontaneous ventilation were used to generate the predictive equations decades ago. In contrast in current practice, general anesthesia and mechanical ventilation are used in most children undergoing cardiac catheterization. General anesthesia and muscle relaxants with mechanical ventilation may decrease the cardiopulmonary work and metabolic rate, resulting in a reduction in VO2 of up to 20 to 30%.(Nisbet, Dobbinson et al.

In the ICU patients, a general *under-estimation* of VO2 is introduced by the equations, with very poor agreement to actual measurements, as the equations were generated in preoperative patients undergoing cardiac catheterization (Li, Bush et al. 2003). After CPB, VO2 is significantly increased and highly variable between patients and within each patient (Figure 2) (Li, Zhang et al. 2006; Li, Zhang et al. 2007; Li, Zhang et al. 2008). Thus, the direct measurement of VO2 is essential for these patients; continuous or repeated measurements are also essential to reflect the dynamic changes in these patients that occur over time.

age and in the ICU patients (Li, Bush et al. 2003; Rutledge, Bush et al. 2010).

**2.1.1 VO2 values during cardiac catheterization versus in the ICU after CPB** 

**2. The inaccurate techniques for measurement of VO2**

**2.1 The inaccuracies of predictive equations** 

In ICU patients, the importance of the accurate measurement of VO2 has been increasingly realized in the past decade or two. Significant alterations in systemic oxygen transport and the contribution of VO2 in the impaired balance of oxygen transport during the early postoperative period after CPB are now better understood (Chiara, Giomarelli et al. 1987; Li, Hoschtitzky et al. 2004; Li, Schulze-Neick et al. 2000; Li, Zhang et al. 2007; Li, Zhang et al. 2007; Oudemans-van Straaten, Jansen et al. 1996). VO2 has its own meaning in the balance of oxygen transport, which has been largely ignored. A hypermetabolic response with increased VO2 occurs in patients after CPB, due mainly to *1)* a systemic inflammatory response (Li, Hoschtitzky et al. 2004; Oudemans-van Straaten, Jansen et al. 1996), *2)* rewarming from hypothermic CPB and fever (Li, Hoschtitzky et al. 2004; Li, Schulze-Neick et al. 2000), and *3)* the use of inotropes (Li, Zhang et al. 2006). The increase in VO2 is an important contributor to the imbalance of oxygen transport in the early postoperative period, when cardiac function and oxygen delivery are depressed due to myocardial injury by surgery and ischemia-reperfusion (Li, Zhang et al. 2006; Li, Zhang et al. 2007; Wernovsky, Wypij et al. 1995). VO2 varies greatly between patients and within individual patients over time. Variation in VO2 results from varied circulatory, metabolic, and hormonal responses to CPB (Li, Hoschtitzky et al. 2004; Oudemans-van Straaten, Jansen et al. 1996), from patient body temperature (Li, Hoschtitzky et al. 2004; Li, Schulze-Neick et al. 2000;), and from pharmacological (Li, Zhang et al. 2006) and ventilator manipulations (Li, Hoskote et al. 2005; Li, Zhang et al. 2008) (please see section 4 for details). In this dynamic milieu, continuous or repeated monitoring of VO2 is necessary to reflect changes over time.

Accurate measurement of VO2 allows precise assessment of systemic hemodynamics and oxygen transport parameters in varied circulations after complete repair or palliations (Li, Hoschtitzky et al. 2004; Li, Hoskote et al. 2005; Li, Schulze-Neick et al. 2000; Li, Zhang et al. 2006; Li, Zhang et al. 2006; Li, Zhang et al. 2007; Li, Zhang et al. 2007; Li, Zhang et al. 2008; Schulze-Neick, Li et al. 2001; Schulze-Neick, Li et al. 2002). Actual measurements are superior to the indirect indicators, such as blood pressure and arterial and venous oxygen saturations that are most commonly used in postoperative management. Superiority of actual measurements is seen particularly clearly after the Norwood procedure, when profound hemodynamic instability and oxygen transport imbalance occurs. Furthermore, actual measurements of hemodynamics and oxygen transport parameters are fundamental to bedside physiological research on factors affecting the imbalance of oxygen transport, research aimed at improving the management of critically ill children. With direct and continuous measurement of VO2 using state-of-the-art technique respiratory mass spectrometry, we have conducted extensive studies in neonates after the Norwood procedure (Li, Zhang et al. 2006; Li, Zhang et al. 2006; Li, Zhang et al. 2007; Li, Zhang et al. 2007; Li, Zhang et al. 2008; Li, Zhang et al. 2008; Li, Zhang et al. 2008; Li, Zhang et al. 2008). We use the Norwood circulation and physiology in this Chapter as a model to understand oxygen transport and the factors affecting oxygen kinetics in children after CPB.

The objectives of this chapter are two-fold. 1) To review the currently available techniques of VO2 measurement, including published predictive equations and indirect Fick principle using themodilution, their advantages and disadvantages, with special emphasis on respiratory mass spectrometry to assess VO2 in children undergoing cardiac cauterization and after CPB in the ICU. 2) Using the Norwood physiology as the model to introduce the concept of oxygen transport and further emphasize the importance of direct and continuous measurement of VO2 in both clinical care and research in children with congenital heart disease before and after CPB.
