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J Thorac Cardiovasc Surg 2007;133:441-448
© 2007 The American Association for Thoracic Surgery
Surgery for Congenital Heart Disease |
Cardiac Program, the Hospital for Sick Children, Toronto, Ontario, Canada.
Received for publication May 5, 2006; revisions received August 11, 2006; accepted for publication September 6, 2006. * Address for reprints: Glen S. Van Arsdell, MD, Division of Cardiovascular Surgery, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada M5G 1X8 (Email: glen.vanarsdell{at}sickkids.ca).
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Abstract |
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 Top Abstract IntroductionMaterials and MethodsResultsDiscussionLimitationsInferences and ConclusionsReferences |
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METHODS: Fourteen neonates had continuous respiratory mass spectrometry to measure oxygen consumption (VO2). Arterial, superior vena caval, and pulmonary venous saturations were measured at 2- to 4-hour intervals for 72 hours postoperatively. Systemic (Qs) and pulmonary (Qp) blood flows, systemic vascular resistance (SVR) and pulmonary vascular resistance inclusive of the Blalock–Taussig shunt (BT-PVR), systemic oxygen delivery (DO2), and the oxygen extraction ratio (ERO2) were calculated.
RESULTS: Qs and DO2 were low during the first 12 hours (1.8 ± 0.6 L · min–1 · m–2 and 281 ± 86 mL · min–1 · m–2 at the 12th hour, respectively) and increased over the study period (P < .05 for both). VO2 decreased markedly during the first 24 hours (101 ± 26 to 86 ± 16 mL · min–1 · m–2, P < .0001). Consequently, ERO2 decreased significantly over the study, most rapidly during the first 24 hours (0.44 ± 0.11 to 0.28 ± 0.09, P < .0001). There was a close correlation of DO2 to SVR and to Qs (P < .0001 for both). There was no correlation of DO2 to BT-PVR (P = .14) or to Qp (P = .67). DO2 was closely correlated with hemoglobin value (P < .0001), weakly correlated with PaO 2 (P = .0002), and not correlated with arterial oxygen saturation (P = .32).
CONCLUSIONS: There is wide variability of hemodynamics and oxygen transport after the Norwood procedure. The decrease in VO2 during the first 24 hours is the main contributor to improving the balance of oxygen transport. DO2 is most closely correlated to SVR and hemoglobin and weakly correlated to PaO 2. It is not correlated to Qp. Postoperative management strategies to decrease VO2 and maintain a high hemoglobin level and a low SVR appear to be rational.
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Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionLimitationsInferences and ConclusionsReferences |
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Despite advances in surgical and postoperative management, these infants have little hemodynamic reserve. Instability after repair is inherent to the single ventricle supplying parallel pulmonary and systemic circulations and is compounded by the variable effects of cardiopulmonary bypass (CPB) and ischemia and reperfusion injury. As a result, the marginal systemic oxygen delivery (DO2) is dependent on a balance between pulmonary blood flow (Qp) and systemic blood flow (Qs). A number of theoretic studies,3,4 clinical studies,5 and experimental models6 have been reported analyzing the effect of manipulation of Qp or Qs and its relationship to DO2. Previous human studies have used 2 key assumptions: constant pulmonary venous O2 saturation and unchanged systemic oxygen consumption (VO2).7-11 There is little theoretic or clinical evidence for the validity of such assumptions, and therefore our understanding of postoperative hemodynamics in these patients is incomplete.
In human studies arterial and superior vena caval O2 saturations and their derivations are most commonly used as surrogates of DO2.5,7-11 In a study using measured VO2 and pulmonary venous saturation, we reported that superior vena caval O2 saturation, arteriovenous O2 saturation difference, and Omega all very highly correlated with the oxygen extraction ratio (ERO2) but at best moderately correlated with DO2. This finding is due to the fact that a single measurement cannot discriminate between the relative contribution of the 2 variables DO2 and VO2.12 Derived values of Qp, Qs, or Qp/Qs ratio have been made but are based on assuming a pulmonary venous O2 saturation of greater than 95% and a fixed VO2 value of 160 or 180 mL · min–1
· m–2.7,8,10 Significant pulmonary venous O2 desaturation might occur after the Norwood procedure, thereby confounding Qp/Qs ratio assessments.13 We have previously shown that postoperative VO2 has wide interpatient and intrapatient variability in children.12,14,15 Thus significant errors might be introduced in the calculation of hemodynamic indices incorporating these variables.
In this study we used direct continuous measurement of VO2 and intermittent measurement of arterial, pulmonary venous, and superior vena caval O2 saturations to accurately profile hemodynamics and oxygen transport after the Norwood procedure.12,16 Changes and interrelationships of these variables were examined to determine factors that might contribute to hemodynamic instability in a group of neonates during the first 72 hours after the Norwood procedure. The patients studied in this report had a modified Blalock-Taussig shunt as the source of Qp.
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Materials and Methods |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionLimitationsInferences and ConclusionsReferences |
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The clinical characteristics of the patients are shown in Table E1
. Patients excluded from this study were those having an alternative strategy for palliation of hypoplastic left heart syndrome. During this time frame, 3 patients undergoing a conventional Norwood procedure were not offered the study because of reasons pertaining to equipment or technical support availability.
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All patients had a 3.5-mm right modified Blalock-Taussig shunt, with the distal anastomosis placed centrally on the intramediastinal pulmonary artery. CPB was maintained for 66 to 172 minutes (median, 133 minutes), and an aortic crossclamp was maintained for 38 to 126 minutes (median, 62 minutes). Circulatory arrest was performed for 1 to 46 minutes (median, 12 minutes), and selected cerebral perfusion was performed in 13 of 14 patients for 20 to 70 minutes (median, 53 minutes) at 30 to 35 mL · min–1
· kg–1 (Table E1). Phenoxybenzamine, 0.25 mg/kg, was given in the heart-lung machine circuit after initiation of CPB. A bolus of 50,000 KIU of aprotinin was administered, followed by 100,000 KIU per 100 mL of prime. Before termination of CPB, milrinone (100 µg/kg) was administered, and dopamine (5 µg · kg–1
· min–1) was initiated. A pulmonary venous line was inserted into the orifice of the right upper pulmonary vein. A direct oximetric line (Abbott Critical Care Systems, Abbott Laboratories, Chicago, Ill) was inserted in the superior vena cava.
Critical Care
Infants received time-cycled volume ventilation with pressure support. Sedation was obtained with a continuous intravenous infusion of morphine (20-40 µg · h–1
· kg–1) and intermittent injections of a muscle relaxant (pancuronium, 0.1 mg/kg) and lorazepam (0.1 mg/kg). Pancuronium was discontinued when the patient achieved satisfactory hemodynamic stability.
The central temperature was maintained at 36°C to 37°C. Inotropic and vasoactive agents (milrinone, dopamine, phenoxybenzamine, and vasopressin) and ventilatory settings (the minute ventilation volume/rate) were adjusted according to our standard protocol, with an inspiratory oxygen fraction at or close to 0.21 (mean arterial blood pressure of 40-45 mm Hg with systolic pressure in the range of 55-65 mm Hg, arterial oxygen saturation of 70%-80%, and superior vena caval saturation of 44%-55%).18 Inspired oxygen was titrated upward for saturation of less than 70%. Volume infusions (5% albumin or blood) were given to maintain filling pressures of 7 to 10 mm Hg. Transfusions were given for a hemoglobin (Hb) value of less than 14 mg/dL, and the Hb value was generally maintained between 14 and 16 mg/dL.
Methods of Measurement
Patient monitoring
All patients had continuous invasive monitoring of systemic, superior vena caval, and pulmonary venous pressures. Continuous monitoring of superior vena caval O2 saturation was used, as was heart rate and central body temperature (esophageal).
VO2
VO2 was measured continuously by using an AMIS2000 mass spectrometer (Innovision A/S, Odense, Denmark). This is a sensitive and accurate method for continuous gas analysis that allows simultaneous measurements of multiple gas fractions.19
Calculations of hemodynamics and oxygen transport
Blood samples were taken from the arterial superior vena cava, and pulmonary venous lines for the measurements of blood gases. Qp and Qs were then calculated by using the direct Fick method. Total cardiac output (CO), DO2, systemic vascular resistance (SVR), pulmonary vascular resistance inclusive of the Blalock-Taussig shunt (BT-PVR), and ERO2 were calculated by using standard equations (Table E2
).
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Data Analysis
Data are expressed as means ± standard deviation. Simple linear regression was used to determine correlations between preoperative (age, weight, and body surface area) and intraoperative demographics (duration of CPB, aortic crossclamp time, total circulatory arrest, or partial circulatory arrest with regional cerebral perfusion) and the first postoperative hemodynamic and oxygen transport measures. The comparison of intraindividual variations between 2 data sets was performed by using the Hartley F-max method. Mixed linear regression analysis for repeated measures was used to determine the nature of any time trend of the measures over the 72-hour study period. For some measures, various transformations of time (logarithmic and polynomial) were tested regarding the best fit for the time course. Interrelationships among the measures were sought by using mixed linear regression analysis for repeated measures without regard to time. Logarithmic transformation of both variables being compared was used when necessary to model nonlinear relationships. The extent of change and correlation was indicated by the intercept and parametric estimate. All data analysis was performed with SAS statistical software version 8 (SAS Institute, Inc, Cary, NC).
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionLimitationsInferences and ConclusionsReferences |
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Profiles of Hemodynamics and Oxygen Transport
Table E3
shows the results for the trends of central body temperature, hemodynamics, oxygen transport, arterial oxygenation, and Hb value.
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None of the initial oxygen transport and hemodynamic values were correlated with age, body weight, and body surface area (P < .05 for all). None of the operative variables (duration of CPB, aortic crossclamping, circulatory arrest, or regional cerebral perfusion time) correlated with the initial measured postoperative characteristics (P > .05 for all).
Oxygen transport changes during the study period
All the studied hemodynamic and oxygen transport measures showed substantial interindividual variations over the study period. The time course and the extent of changes in hemodynamic and oxygen transport measures also varied greatly (Table E3 and Figure 1).
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longitudinal trends in temperature of VO2 AND DO2
Central temperature did not change significantly during the study period (P > .05), except for the initial significant increase during the first 2 hours after arrival in the ICU (P = .005). VO2 was significantly related to time after logarithmic transformation and showed a rapid decrease in the first 24 hours (P < .0001). There were wide interindividual and intraindividual fluctuations. Total VO2 range was from 45 to 152 mL · min–1
· m–2. DO2 was significantly related to time in a complex polynomial function, with an early increase peaking around 28 to 36 hours (P < .0001), followed by a slow decrease (P < .0001). Wide variations were noted within individuals.
Ero2. ero2
was significantly related to time in a complex polynomial function, with an initial rapid decrease in the first 24 hours, followed by a slow decrease (P < .0001) and a subsequent small but significant increase at 48 hours (P < .0001).
arterial serum lactate
Lactate levels were significantly related to time after logarithmic transformation and showed an initial rapid decrease in the first 6 hours, followed by a slower steady decrease (P < .0001).
longitudinal trends in contributors to arterial O2 CONTENT
There was a small but significant increase in pulmonary venous O2 saturation over time (P < .0001). Both PaO
2 and arterial oxygen saturation (SaO
2) were significantly related to time after logarithmic transformation, with a fast increase in the first 24 hours, followed by a slow increase (P < .0001 for both). Hb value showed a small significant linear decrease over time (P < .0001). Arterial O2 content was related to time in a complex polynomial function, with an early increase in the first 10 hours (P = .004), followed by a slow decrease (P = .0009). Of note, pulmonary venous O2 saturation was less than 95% in 40% of the total sample times (140/350).
Interrelationships Among the Variables
The statistical results of the interrelationships among the variables using mixed linear regressions are seen in Table E4
and Figure 2
. The extent of the correlation is indicated by the intercept and coefficient values.
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BT-PVR
BT-PVR was significantly negatively and linearly correlated with Qp/Qs ratio (P = .002) and CO (P < .0001) and nonlinearly with Qp (after logarithmic transformation, P < .0001). The influence of BT-PVR on Qp/Qs ratio, Qs, and CO was not as strong as that seen with SVR, as demonstrated by the difference in the intercept and parameter estimates in Table E4. There was a weak correlation of BT-PVR with Qs (P = .008) but not DO2 (P = .14).
Qp/Qs ratio
The Qp/Qs ratio was significantly (P < .001) affected by both Qs and Qp; however, Qs showed a stronger correlation, as seen by the difference in the intercept and coefficient in Table E4.
DO2
There was a close linear correlation of DO2 with Qs (P < .0001) but not with Qp (P = .67). DO2 was significantly and nonlinearly negatively correlated with Qp/Qs ratio (after logarithmic transformation, P < .0001).
Arterial O2 content and DO2
Qp had a weak positive correlation with SaO
2 and PaO
2 (P < .0001 for both). PaO
2 had a weak positive correlation with DO2 (P = .0002). There was no correlation of SaO
2 with DO2 (P = .32). Inclusion of SaO
2, PaO
2, Hb value, and Qs showed that SaO
2 and PaO
2 were positively but weakly correlated with DO2 (P < .0001 for SaO
2 and P = .002 for PaO
2). Hb value had a high positive correlation with DO2 (P < .0001).
ERO2
ERO2 had a close positive correlation with VO2 and a negative correlation with DO2 (P < .0001 for both).
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionLimitationsInferences and ConclusionsReferences |
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Those assumptions are much higher than what was observed in our patients (range, 45-152 mL · min–1
· m–2; mean at arrival in the ICU, 101 mL · min–1
· m–2). Overestimation of VO2 leads to a direct proportional change in the estimation for the calculated variables. For example, an assumed VO2 of 170 mL · min–1
· m–2 compared with the measured mean VO2 on arrival to the ICU of 101 mL · min–1
· m–2 would lead to a 68% overestimation of total CO, Qp, and Qs and a 68% underestimation of PVR and SVR. Taeed and colleagues13 previously noted the occurrence of pulmonary venous O2 desaturation after the Norwood procedure. We found pulmonary venous desaturation (defined as <95% saturation) in 40% of the pulmonary venous samples taken. The effect of a falsely high assumption of pulmonary venous saturation can be seen in the following example from one of our observed patients: measured pulmonary venous saturation was 90%, and an assumed pulmonary venous saturation of 96% would have lead to an underestimation of Qp by 35% and therefore the Qp/Qs ratio by 35% as well. The data demonstrate that continuous VO2 and measured pulmonary venous O2 saturation have a significant effect on the calculated variables and therefore potential for having an effect on management strategy.
Cardiac Output and Characteristics of Qp and Qs
The single ventricle is subject to considerable demand for total CO. There is great variation both individually and within the cohort (total range, 1.9-8.3 L · min–1
· m–2; mean range, 3.7-4.9 L · min–1
· m–2). On an individual basis, the Qp/Qs ratio was highly variable (0.35-2.8) but on a mean basis, it was less varied for 0.9 to 1.5. On analysis, SVR was tightly correlated with the Qp/Qs ratio and negatively correlated with Qs, CO, and DO2. BT-PVR was negatively correlated with the Qp/Qs ratio, CO, and Qp, but this was a weaker correlation than with SVR. In other words, SVR was far more important in determining the balance of the Qp/Qs ratio than was BT-PVR. SVR was also significantly more variable than BT-PVR, despite the use of 
blockade and phosphodiesterase inhibitors. These findings are important because, historically, the postoperative management strategy of patients undergoing the Norwood procedure was directed at diminishing Qp by increasing PVR.5,20,21 More recently, some, including us, have advocated aggressive reduction of SVR as a primary management strategy. This has resulted in improved outcomes for those who have reported the strategy.10,18,22 In the presence of aggressive afterload reduction, it has been thought that PVR was relatively fixed.10,11 The findings of this study indicate that both the systemic and pulmonary vascular compartments have variable resistance, but the systemic circulation has a more profound effect on the balance of the Qp/Qs ratio. SVR also has an effect on Qs and total CO. Although the study does not address the ability of ventilation and oxygenation strategy to alter BT-PVR, a rational clinical approach would appear to be a combined approach of ventilation strategies to increase BT-PVR (additional inspired CO2) plus effective afterload reduction. Both would promote an improved Qp/Qs ratio and increased Qs and therefore improved DO2. Interestingly, increasing PaO
2 had only a weak positive correlation with Qp, implying that relative hypoxia yields little benefit to the balance of the Qp/Qs ratio.
Contribution of VO2 to the Balance of Oxygen Transport
Matching DO2 to VO2 is one of the tenets of care in critically ill patients.15,19,23,24 The first 24-hour improvement seen in this group of patients in ERO2 and arterial lactate levels occurred when CO, Qs, and DO2 were most decreased. The data demonstrate that the main early contributor to the improved ERO2 was decreasing VO2.
VO2 can be increased after CPB as a consequence of rewarming15,19,25 and the systemic inflammatory response.15,26 After arrival in the ICU, there was a continuous but biphasic decrease in VO2 in the presence of normothermia. A more rapid decrease occurred for 24 hours, followed by a slower decrease for the following 48 hours. After 24 hours, DO2 became the primary contributor to the balance of DO2 and VO2.
Another important issue with respect to VO2 is the potential effect of vasoactive and inotropic agents. In a neonatal lamb model the use of ß-sympathomimetic drugs was associated with a rapid and substantial increase in VO2, offsetting the benefits of increased DO2.24 Our routine is to terminate CPB on 5 µg · min–1
· kg–1 dopamine but to subsequently discontinue its use in the ICU to try to decrease myocardial oxygen demand. Cessation of dopamine might have contributed to the decrease in VO2 in the first 24 hours in the ICU.16 The introduction of blockade might also be important in this regard. Animal data suggest that inhibition of stimulation in brown fat tissue might reduce the metabolic rate.27 Further studies might be warranted to directly quantitatively assess the effects of inotropes and vasoactive drugs on VO2 and DO2 in these patients, while controlling for other variables that might affect VO2.
Optimizing Oxygen Delivery
Systemic DO2 mean values were 281 ± 86 mL · min–1
· m–2 at the 12th hour after the Norwood procedure. Although there were significant interindividual and intraindividual variations throughout the study, these values are low in comparison with our studies of complete repair for congenital heart defects in older children (281 ± 86 vs 368 ± 94 mL · min–1
· m–2).15 DO2 is limited by the effects of common mixing and low Qs (1.8 ± 0.6 L · min–1
· m–2).28,29 The variables for potentially improving DO2 include increasing SaO
2, PaO
2, and Hb value; altering the Qp/Qs ratio; and absolutely increasing total CO. Our analysis demonstrated that within the ranges of SaO
2 and PaO
2 observed, there was only weak correlation with DO2. There was, however, a tight correlation between DO2 and Hb value. Our data therefore support the common practice of maintaining the postoperative hematocrit value at greater than 40%.
With respect to the Qp/Qs ratio, Barnea and associates4 theorized that maximal DO2 occurs at a Qp/Qs ratio of less than 1 over a wide range of COs. Our data show that DO2 was closely, negatively, and logarithmically correlated with the Qp/Qs ratio within the wide range (0.35-2.8) for our patients. Mean DO2 (for a similar Hb value) was highest (460 ± 152 mL · min–1
· m–2) when the Qp/Qs ratio was less than 0.7 and lower (260 ± 69 mL · min–1
· m–2) when the Qp/Qs ratio was 1.0 or greater. The data suggest that a direct increase in Qs would result in a lower Qp/Qs ratio and therefore a higher DO2. Therefore maintaining a high Hb value and decreasing the SVR to most effectively optimize the Qp/Qs ratio would be most effective in improving DO2.
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Limitations |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionLimitationsInferences and ConclusionsReferences |
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Pulmonary venous saturations were obtained from only 1 pulmonary vein. This would not account for regional lung perfusion and ventilation differences in pulmonary vein saturation. PVR in this study is actually a measure of resistance across the Blalock-Taussig shunt and the pulmonary vasculature. An indwelling pulmonary arterial catheter would be required to directly measure pulmonary arterial pressure to differentiate actual PVR from that including the Blalock-Taussig shunt.
Finally, the hemodynamic and oxygen transport measurements were derived by using the common variables of VO2, blood gases, and pressures. Some were calculated from one another; for example, DO2 and SVR were calculated from Qs. This might induce mathematic coupling and therefore affect correlation analysis.32 This study does not address oxygen transport for hypoplastic left heart syndrome palliation by using the Sano modification (right ventricle–pulmonary artery conduit).
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Inferences and Conclusions |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionLimitationsInferences and ConclusionsReferences |
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Footnotes |
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionLimitationsInferences and ConclusionsReferences |
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