Feeding May Modulate the Relationship Between Systemic Inflammation, Insulin Resistance, and Poor Outcome Following Cardiopulmonary Bypass for Pediatric Cardiac Surgery.

BACKGROUND: Hyperglycemia is common following cardiopulmonary bypass (CPB) surgery and is associated with poor outcomes, often attributed to hyperinsulinemia and an acquired state of insulin resistance. This study examined the underpinnings of hyperglycemia and the effects of nutrition on the association with inflammation and clinical outcomes. METHODS: This prospective, observational cohort study enrolled consecutive children (<18 years) undergoing CPB. Serial measurements of inflammatory cytokines, glucose, insulin, and nutrition delivery were obtained. Glucose-insulin ratio (G:I) was calculated for each time point as a measure of insulin resistance (lower G:I reflects higher resistance). Clinical outcomes were recorded using a composite morbidity score. RESULTS: The 200 subjects studied were predominantly females (58%) undergoing biventricular repair (85%) at a median (interquartile range) age of 0.58 years (0.28, 3.4) and weight of 7.0 kg (3.1, 59.5). Hyperglycemia was common (49% of patients), coinciding with peak cytokine concentrations. Insulin levels were highest and G:I lowest immediately following separation from CPB but had no consistent relationship with cytokines. The morbidity outcome was reached by 23% of patients, with increased odds associated with higher interleukin (IL)6 and IL8 levels but not by glucose, insulin, or G:I. Providing higher feeding volumes attenuated this association between inflammation and morbidity. Higher feeds were not associated with G:I but appeared to decrease the strength of the relationship between cytokines and glycemic indices. CONCLUSION: Postoperative morbidity is independently associated with increased inflammation but not with hyperglycemia or markers of insulin resistance. Higher feeding volume may modify these relationships and have a protective role.

Can Vco2-Based Estimates of Resting Energy Expenditure Replace the Need for Indirect Calorimetry in Critically Ill Children?

BACKGROUND: Optimal energy provision, guided by measured resting energy expenditure (REE), is fundamental in the care of critically ill children. REE should be determined by indirect calorimetry (IC), which has limited availability. Recently, a novel equation was developed for estimating REE derived from carbon dioxide production (Vco2). The aim of this study was to validate the accuracy of this equation in a population of critically ill children following cardiopulmonary bypass (CPB). METHODS: This is an ancillary study to a larger trial of children undergoing CPB. Respiratory mass spectrometry was used measure oxygen consumption (Vo2) and Vco2. REE was then calculated according to the established Weir equation (REEW) and the modified, Vco2-based equation (REECO2). The agreement between the 2 measurements was assessed using Bland-Altman plots and mixed-model regressions accounting for repeated measures. RESULTS: Data from 104 patients, which included 575 paired measurements, were included. The agreement between REEW and REECO2 was biased during the 72-hour observation period post CPB, with a mean percentage error between measurements of 11% (±7%). The most important determinant of the bias with the Vco2-based equation was the respiratory quotient (RQ). The percentage error between REEW and REECO2 dropped to 4.4% (±2.4%) in those with an RQ between 0.8 and 1. The within-subject variability for RQ in this cohort was wide (11%). CONCLUSIONS: IC remains the most accurate method to determine the REE of critically ill patients. Widespread availability of Vco2 data renders Vco2-based approaches to measurement of REE attractive; however, further research is needed to ensure that REE is estimated accurately.

Systemic inflammation increases energy expenditure following pediatric cardiopulmonary bypass.

OBJECTIVES: To examine the association between cardiopulmonary bypass-related systemic inflammation and resting energy expenditure in pediatric subjects following cardiac surgery. DESIGN: Single-center, prospective cohort study. SETTING: Pediatric cardiac critical care unit in Toronto, Canada. PATIENTS: Children with congenital heart disease undergoing cardiopulmonary bypass surgery. INTERVENTIONS: Resting energy expenditure was determined by indirect calorimetry and the modified Weir equation, using VO2 and VCO2 measured by in-line respiratory mass spectrometry. Measurements were taken at baseline and 6-hour intervals from separation from cardiopulmonary bypass for a maximum of 72 hours. Plasma interleukin-6, glucose delivery, feeding status, and cardiac output (calculated by Fick equation) were monitored at each resting energy expenditure measurement. MEASUREMENTS AND MAIN RESULTS: We studied 111 subjects at a median (interquartile range) age of 5.3 months (0.8-10.5 mo), weighing 5.7 kg (3.9-8.1 kg), of whom 88% underwent biventricular repair. Resting energy expenditure decreased from 51 kcal/kg/d to 45 kcal/kg/d during the study period. Resting energy expenditure was positively associated with increased plasma interleukin-6 (estimate variable, 1.76; p = 0.001) and inversely associated with preoperative methylprednisolone use (estimate variable, -6.7; p = 0.003) even after accounting for other predictors. Increase in cardiac output was also associated (estimate variable, 13.7; p < 0.0001) with higher resting energy expenditure. CONCLUSIONS: Resting energy expenditure ranges between 40 and 60 kcal/kg/d and decreases progressively in children following cardiopulmonary bypass surgery. It is directly associated with increased inflammation and higher cardiac output and inversely associated with anti-inflammatory strategies. Further studies are required to predict the appropriate caloric delivery in this cohort.

Validation of a new method based on ultrasound velocity dilution to measure cardiac output in paediatric patients.

PURPOSE: To validate a novel method of ultrasound dilution (COstatus(®); Transonic Systems, Ithaca, NY) for measuring cardiac output in paediatric patients after biventricular repair of congenital heart disease. METHODS: Children undergoing biventricular repair of congenital heart disease were prospectively identified. Patients with significant intracardiac shunts were excluded. Postoperative cardiac output was measured by ultrasound dilution (COud) and concurrently calculated by the Fick equation (COrms) using measured oxygen consumption by respiratory mass spectrometry. RESULTS: Thirty-five patients were studied generating 66 individual data sets. Subjects had a median (interquartile range) age of 147 days (11, 216), weight of 4.98 kg (3.78, 6.90) and body surface area of 0.28 m(2) (0.22, 0.34). Of the patients, 66% had peripheral arterial catheters and 34% had femoral cannulation; peripheral arterial lines accounted for 6/8 of unsuccessful studies due to inability to generate sufficient flow. The site of the central venous cannula did not impact the feasibility of completing the study. A mean bias of 0.00 L/min [2 standard deviation (SD) ± 0.76 L/min] between COud and COrms was found with a percentage error of 97%. When comparing cardiac index, bias increased to 0.13 L/min/m(2) (2SD ± 2.16 L/min/m(2)). CONCLUSIONS: Cardiac output by ultrasound dilution showed low bias with wide limits of agreement when compared to measurement derived by the Fick equation. Although measurements through central and peripheral arterial lines were completed with minimal difficulties in the majority of patients, the application of COstatus(®) in neonates with low body surface area may be limited.

Determinants and clinical significance of flow via the fenestration in the Fontan pathway: a multimodality study.

BACKGROUND: The use of a fenestration in the Fontan pathway remains controversial, partly because its hemodynamic effects and clinical consequences are insufficiently understood. The objective of this study was to quantify the magnitude of fenestration flow and to characterize its hemodynamic consequences after an intermediate interval after surgery. METHODS: Twenty three patients with a fenestrated extracardiac conduit prospectively underwent investigation by cardiac magnetic resonance (CMR), echocardiography, and invasive manometry under the same general anesthetic 12 ± 4 months after Fontan surgery. Fenestration flow was determined using phase contrast CMR by subtracting flow in the Fontan pathway above the fenestration from Fontan flow below the fenestration. RESULTS: Fenestration flow constituted a mean of 31 ± 12% (range 8-50%) of ventricular preload. It was associated with a lower Qp/Qs (r = -0.64, p=0.001) and oxygen saturation (r = -0.74, p<0.0001). Fenestration flow volume was correlated with pulmonary vascular resistance (r = 0.45, p = 0.04) and markers of ventricular diastolic function (early diastolic strain rate r = 0.57, p = 0.008 and ventricular untwist rate r = 0.54, p = 0.02). In 14 patients (61%) all of the net inferior vena cava flow and part of the superior vena cava flow were diverted into the systemic atrium and did not reach the lungs. CONCLUSIONS: Fenestration flow can be measured accurately with CMR. In two-thirds of the patients not only all of the inferior vena cava flow, but also some of the superior vena cava flow is diverted through the fenestration. Fenestration flow is driven by a balance between pulmonary vascular resistance and early diastolic ventricular function.

Aortopulmonary collateral flow volume affects early postoperative outcome after Fontan completion: a multimodality study.

OBJECTIVE: Aortopulmonary collaterals are a frequent phenomenon in patients after bidirectional cavopulmonary connection. The aortopulmonary collateral flow volume can be quantified using cardiac magnetic resonance imaging. However, the significance of aortopulmonary collateral flow for the postoperative outcome after total cavopulmonary connection is unclear and was sought to be determined. METHODS: The data from 33 patients were prospectively studied with cardiac magnetic resonance, echocardiography, and cardiac catheterization before the total cavopulmonary connection operation. The early postoperative outcomes after total cavopulmonary connection completion were recorded. RESULTS: Aortopulmonary collateral flow was 1.59 L/min/m(2) ± 0.65 L/min/m(2) (range, 0.54 L/min/m(2)-3.34 L/min/m(2)), constituting 43% ± 13% (range, 12-87%) of pulmonary blood flow and 35% ± 12% (range, 11-62%) of the cardiac index, resulting in a pulmonary blood flow/systemic blood flow ratio of 1.06 ± 0.17 (range, 0.79-1.55). The aortopulmonary collateral flow correlated with pulmonary blood flow/systemic blood flow ratio (r = 0.69, P < .0001), oxygen saturation (r = 0.42, P = .018), and cardiac index (r = 0.53, P = .002). Of the 36 patients, 24 underwent fenestrated total cavopulmonary connection during the study period. The aortopulmonary collateral flow, relative to the cardiac index, correlated with the duration of hospital stay (r = 0.48, P = .02) and pleural drainage (r = 0.45, P = .03). Patients whose pleural drainage lasted 1 week or less had less aortopulmonary collateral flow before the Fontan operation than those with a longer period until chest tube removal (1.23 L/min/m(2) ± 0.38 L/min/m(2) vs 1.73 L/min/m(2) ± 0.76 L/min/m(2); P = .03). Compared with a contemporary group of total cavopulmonary connection patients with fenestration in their extracardiac conduit who were studied prospectively, with a similar protocol, the bidirectional cavopulmonary connection had a greater amount of aortopulmonary collateral flow (1.59 L/min/m(2) ± 0.65 L/min/m(2) vs 1.30 L/min/m(2) ± 0.57 L/min/m(2), P = .04). CONCLUSIONS: Patients after bidirectional cavopulmonary connection routinely acquire a large amount of aortopulmonary collateral flow. The hemodynamic consequences of aortopulmonary collateral flow translate into adverse outcomes early after total cavopulmonary connection completion.

Airway pressure release ventilation improves pulmonary blood flow in infants after cardiac surgery.

OBJECTIVE: We hypothesized that spontaneous inspiratory effort transmitted to the pleural space during airway pressure release ventilation would result in increased lung perfusion after surgery for tetralogy of Fallot or following a cavopulmonary shunt as a consequence of transient decreases in intrapleural pressure. DESIGN: Prospective crossover cohort study. SETTING: A tertiary care cardiac pediatric intensive care unit. PATIENTS: Children after tetralogy of Fallot repair, cavopulmonary shunt, or Fontan operation. INTERVENTIONS: Lung perfusion and cardiac output were measured during airway pressure release ventilation and pressure control ventilation with pressure support, both with and without spontaneous ventilation. Oxygen consumption was measured (mass spectrometer) and lung perfusion/cardiac output calculated (Fick equation). Constant levels of CO2 and mean airway pressure were targeted in all study phases. MEASUREMENTS AND MAIN RESULTS: Twenty patients were enrolled in the study, nine after repair of tetralogy of Fallot and 11 after a cavopulmonary shunt. In the absence of spontaneous ventilation, there were no differences in lung perfusion or any of the measured gas exchange or hemodynamic parameters. In the presence of spontaneous ventilation for all patients, mean pulmonary blood flow increased from 2.4 to 2.9 L·min⁻¹M⁻² (p = .02). Oxygen delivery increased from 594 to 774 mL/min/m² (p = .05) in the patients with tetralogy of Fallot patients and from 473 to 518 L·min⁻¹M⁻² (p = .07) in the cavopulmonary shunt group. CONCLUSION: Ventilation with airway pressure release ventilation (at comparable mean airway pressure) improves lung perfusion compared with pressure control ventilation in children after tetralogy of Fallot repair and cavopulmonary shunt operations. Although this study focused on tetralogy of Fallot and cavopulmonary shunt operations, the improved cardiopulmonary interactions may be beneficial in other situations in which hemodynamics are impaired by positive pressure ventilation.

A comparison of cardiac output by thoracic impedance and direct fick in children with congenital heart disease undergoing diagnostic cardiac catheterization.

OBJECTIVE(S): To evaluate the measurement of cardiac output (CO) using continuous electrical bioimpedance cardiography (Physioflow; Neumedx, Philadelphia, PA) (CO(PF)) with a simultaneous direct Fick measurement (CO(FICK)) in children with congenital heart disease. DESIGN: A prospective cohort study comparing 2 methods of measurement of CO. SETTING: A quaternary university-affiliated pediatric hospital. PARTICIPANTS: Children undergoing cardiac catheterization for clinical care. INTERVENTIONS: The Physioflow measured continuous real time CO in 15-second epochs and simultaneous measurement of cardiac output by direct Fick (with mass spectrometry to assess VO(2)) were acquired. MEASUREMENTS AND MAIN RESULTS: Sixty-five patients were recruited, and data from 56 (25 males) were adequate for analysis. The median age at study was 3.5 years (range, 0.4-16.6 years), and the median body surface area was 0.62 m(2) (range, 0.31-1.71). There were 25 of 56 (45%) with univentricular physiology. A total of 19,228 Physioflow data points were available for the analysis of which 14,569 (76%) were valid; 96% of the invalid measurements were identified as artifacts by the device. The average cardiac index of valid measurements was 3.09 ± 0.72 L/min/m(2). Compared with the Fick CO, the mean bias was -0.09 L/min, but the 95% limits of agreement were -3.20 to +3.01 L/min/m(2). Consequently, only 20 of 56 (36%) of measurements were within 20%, and 31 of 56 (55%) of measurements were within 30% of each other. CONCLUSIONS: Compared with measurements made by direct Fick, CO measured using the Physioflow device was unreliable in anesthetized children with congenital heart disease.

Control of cardiac myofilament activation and PKC-betaII signaling through the actin capping protein, CapZ.

Actin capping protein (CapZ) anchors the barbed ends of sarcomeric actin to the Z-disc. Myofilaments from transgenic mice (TG-CapZ) expressing a reduced amount of CapZ demonstrate altered function and protein kinase C (PKC) signaling [Pyle WG, Hart MC, Cooper JA, Sumandea MP, de Tombe PP, and Solaro RJ., Circ. Res. 90 (2002) 1299-306]. The aims of the current study were to determine the direct effects of CapZ on myofilament function and on PKC signaling to the myofilaments. Our studies compared mechanical properties of single myocytes from TG-CapZ mouse hearts to wild-type myocytes from which CapZ was extracted using PIP(2). We found that myofilaments from CapZ-deficient transgenic myocardium exhibited increased Ca(2+) sensitivity and maximum isometric tension. The extraction of CapZ from wild-type myofilaments replicated the increase in maximum isometric tension, but had no effect on myofilament Ca(2+) sensitivity. Immunoblot analysis revealed that the extraction of CapZ was associated with a reduction in myofilament-associated PKC-beta(II) and that CapZ-deficient transgenic myofilaments also lacked PKC-beta(II). Treatment of wild-type myofilaments with recombinant PKC-beta(II) reduced myofilament Ca(2+) sensitivity, whereas this effect was attenuated in myofilaments from TG-CapZ mice. Our results indicate that cardiac CapZ directly controls maximum isometric tension generation, and establish CapZ as an important component in anchoring PKC-beta(II) at the myofilaments, and for mediating the effects of PKC-beta(II) on myofilament function.