Echocardiographic assessment of cardiovascular physiology of preterm miniature piglets supported with a pumped artificial placenta system.

OBJECTIVES: We evaluated fetal cardiovascular physiology and mode of cardiac failure in premature miniature piglets on a pumped artificial placenta (AP) circuit. METHODS: Fetal pigs were cannulated via the umbilical vessels and transitioned to an AP circuit composed of a centrifugal pump and neonatal oxygenator and maintained in a fluid-filled biobag. Echocardiographic studies were conducted to measure ventricular function, umbilical blood flow, and fluid status. In utero scans were used as control data. RESULTS: AP fetuses (n = 13; 102±4d gestational age [term 115d]; 616 ± 139 g [g]; survival 46.4 ± 46.8 h) were tachycardic and hypertensive with initially supraphysiologic circuit flows. Increased myocardial wall thickness was observed. Signs of fetal hydrops were present in all piglets. Global longitudinal strain (GLS) measurements increased in the left ventricle (LV) after transition to the circuit. Right ventricle (RV) and LV strain rate decreased early during AP support compared with in utero measurements but recovered toward the end of the experiment. Fetuses supported for >24 h had similar RV GLS to in utero controls and significantly higher GLS compared to piglets surviving only up to 24 h. CONCLUSIONS: Fetuses on a pump-supported AP circuit experienced an increase in afterload, and redistribution of blood flow between the AP and systemic circulations, associated with elevated end-diastolic filling pressures. This resulted in heart failure and hydrops. These preterm fetuses were unable to tolerate the hemodynamic changes associated with connection to the current AP circuit. To better mimic the physiology of the native placenta and preserve normal fetal cardiovascular physiology, further optimization of the circuit will be required.

Epinephrine Dosing Use During Extracorporeal Cardiopulmonary Resuscitation: Single-Center Retrospective Cohort.

OBJECTIVES: During pediatric cardiac arrest, contemporary guidelines recommend dosing epinephrine at regular intervals, including in patients requiring extracorporeal membrane oxygenation (ECMO). The impact of epinephrine-induced vasoconstriction on systemic afterload and venoarterial ECMO support is not well-defined. DESIGN: Nested retrospective observational study within a single center. The primary exposure was time from last dose of epinephrine to initiation of ECMO flow; secondary exposures included cumulative epinephrine dose and arrest time. Systemic afterload was assessed by mean arterial pressure and use of systemic vasodilator therapy; ECMO pump flow and Vasoactive-Inotrope Score (VIS) were used as measures of ECMO support. Clearance of lactate was followed post-cannulation as a marker of systemic perfusion. SETTING: PICU and cardiac ICU in a quaternary-care center. PATIENTS: Patients 0-18 years old who required ECMO cannulation during resuscitation over the 6 years, 2014-2020. Patients were excluded if ECMO was initiated before cardiac arrest or if the resuscitation record was incomplete. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 92 events in 87 patients, with 69 events having complete data for analysis. The median (interquartile range) of total epinephrine dosing was 65 mcg/kg (37-101 mcg/kg), with the last dose given 6 minutes (2-16 min) before the initiation of ECMO flows. Shorter interval between last epinephrine dose and ECMO initiation was associated with increased use of vasodilators within 6 hours of ECMO ( p = 0.05), but not with mean arterial pressure after 1 hour of support (estimate, -0.34; p = 0.06). No other associations were identified between epinephrine delivery and mean arterial blood pressure, vasodilator use, pump speed, VIS, or lactate clearance. CONCLUSIONS: There is limited evidence to support the idea that regular dosing of epinephrine during cardiac arrest is associated with increased in afterload after ECMO cannulation. Additional studies are needed to validate findings against ECMO flows and clinically relevant outcomes.

Reintervention Before Bidirectional Cavopulmonary Shunt and Intermediate Outcomes in Children with Single Ventricle Who Underwent Main Pulmonary Artery Banding.

Unplanned reinterventions following pulmonary artery banding (PAB) in single ventricle patients are common before stage 2 palliation (S2P) but associated risk factors are unknown. We hypothesized that reintervention is more common when PAB is placed at younger age and with a looser band, reflected by lower PAB pressure gradient. Retrospective single center study of single ventricle patients undergoing PAB between Jan 2000 and Dec 2020. The association with reintervention and successful S2P was modeled using exploratory cause-specific hazard regression. A multivariable model was developed adjusting for clinical and statistically relevant predictors. The cumulative proportion of patients undergoing reintervention were summarized using a competing risk model. 77 patients underwent PAB at median (IQR) 47 (24-66) days and 3.73 (3.2-4.5) kg. Within18 months of PAB, 60 (78%) reached S2P, 9 (12%) died, 1 (1%) transplanted and 7 (9%) were alive without S2P. Within 18 months of PAB 10 (13%) patients underwent reintervention related to pulmonary blood flow modification: PAB adjustment (n = 6) and conversion to Damus-Kaye-Stansel/Blalock-Taussig-Thomas shunt (n = 4). 6/10 (60%) reached S2P following reintervention. A trend toward higher intervention in patients with a genetic syndrome (p-0.06) and weight < 3 kg (p-0.057) at time of PAB was noted. Only genetic syndrome was a risk factor associated with poor outcome (p-0.025). PAB has a reasonable outcome in SV patients with unobstructed systemic and pulmonary blood flow, but with a high reintervention rate. Only a quarter of patients with genetic syndromes reach S2P and further study is required to explore the benefits from an alternative palliative strategy.

Comparison between Del Nido and conventional blood cardioplegia in pediatric open-heart surgery.

BACKGROUND: Del Nido cardioplegia (DNc) was designed for superior myocardial protection during cardiopulmonary bypass (CPB). We conducted a retrospective review to explore if DNc was associated with increase in systemic ventricle dysfunction (sVD) following pediatric CPB. METHODS AND RESULTS: This single-center, retrospective study included 1534 patients undergoing CPB between 2013 and 2016, 997 prior to center-wide conversion to DNc and 537 following. The primary outcome was new postoperative ≥moderate sVD by echocardiogram. Secondary outcomes included sVD of any severity and right ventricular dysfunction. Data was evaluated by interrupted time-series analysis. Groups had similar cardiac diagnoses and surgical complexity. Del Nido cardioplegia was associated with longer median (IQR) CPB [117 (84-158) vs 108 (81-154), p = 0.04], and aortic cross-clamp [83 (55-119) vs 76 (53-106), p = 0.03], and fewer cardioplegia doses [2 (1-2) vs 3 (2-4), p < 0.0001]. Mortality was similar in both groups. Frequency of sVD was unchanged following DNc, including predetermine subgroups (neonates, infants, and prolonged cross-clamp). Logistic regression showed a significant rise in right ventricular dysfunction (OR 5.886 [95% CI: 0.588, 11.185], p = 0.03) but similar slope. CONCLUSIONS: Use of DNc was not associated with increased in reported sVD, and provided similar myocardical protection to the systemic ventricle compared to conventional cardioplegia but may possibly impact right ventricular function. Studies evaluating quantitative systolic and diastolic function are needed.

Impact of the Addition of a Centrifugal Pump in a Preterm Miniature Pig Model of the Artificial Placenta.

The recent demonstration of normal development of preterm sheep in an artificial extrauterine environment has renewed interest in artificial placenta (AP) systems as a potential treatment strategy for extremely preterm human infants. However, the feasibility of translating this technology to the human preterm infant remains unknown. Here we report the support of 13 preterm fetal pigs delivered at 102 ± 4 days (d) gestation, weighing 616 ± 139 g with a circuit consisting of an oxygenator and a centrifugal pump, comparing these results with our previously reported pumpless circuit (n = 12; 98 ± 4 days; 743 ± 350 g). The umbilical vessels were cannulated, and fetuses were supported for 46.4 ± 46.8 h using the pumped AP versus 11 ± 13 h on the pumpless AP circuit. Upon initiation of AP support on the pumped system, we observed supraphysiologic circuit flows, tachycardia, and hypertension, while animals maintained on a pumpless AP circuit exhibited subphysiologic flows. On the pumped AP circuit, there was a progressive decline in umbilical vein (UV) flow and oxygen delivery. We conclude that the addition of a centrifugal pump to the AP circuit improves survival of preterm pigs by augmenting UV flow through the reduction of right ventricular afterload. However, we continued to observe the development of heart failure within a matter of days.

Rapid Advancement in Enteral Nutrition Does Not Affect Systemic Inflammation and Insulin Homeostasis Following Pediatric Cardiopulmonary Bypass Surgery.

OBJECTIVES: To determine impact of enteral nutrition delivery on the relationship among inflammation, insulin resistance, and outcomes following pediatric cardiopulmonary bypass surgery. DESIGN: Pilot, randomized study analyzed according to intention-to-treat analysis. SETTING: Pediatric cardiac ICU. PATIENTS: Infants (≤ 6 mo) undergoing cardiopulmonary bypass. INTERVENTIONS: Patients randomly assigned to receive rapid escalation to enteral nutrition reaching goal feeds by 27 hours or standard feeding practice reaching goal feeds by 63 hours. Feeds were initiated on the first postoperative day. MEASUREMENTS AND MAIN RESULTS: Fifty patients were randomized equally to study arms. Patients were a median (interquartile range) of 16 days old (7-110 d old), undergoing biventricular surgery (88%) with a median cardiopulmonary bypass time of 125 minutes (105-159 min). Serial blood samples were drawn before and after cardiopulmonary bypass, cardiac ICU admission, and every 12 hours (up to 96 hr) for glucose, insulin, and cytokines (interleukin-1α, interleukin-6, interleukin-8, interleukin-10, and tumor necrosis factor-α) levels. Glucose-insulin ratio was calculated to quantify insulin resistance. Patient characteristics, time to enteral nutrition initiation, enteral nutrition interruptions, and insulin administration were similar across intervention arms. FF reached goal feeds at similar intervals as standard feeding (39 hr [30-60 hr] vs 60 hr [21-78 hr]; p = 0.75). No difference in cytokine, insulin, or glucose-insulin ratio was noted between groups. Higher inflammation was associated with increased glucose-insulin ratio and higher risk of adverse events. In multivariable models of interleukin-8, FF was associated with increased glucose-insulin ratio (estimate of effect [95% CI], 0.152 [0.033-0.272]; p = 0.013). Although higher interleukin-8 was associated with an elevated risk of adverse event, this relationship was possibly mitigated by FF (odds ratio [95% CI], 0.086 [0.002-1.638]; p = 0.13). CONCLUSIONS: A FF strategy was not associated with changes to early enteral nutrition delivery. Inflammation, insulin resistance, and morbidity were similar, but FF may modify the relationship between inflammation and adverse event. Multicenter nutrition studies are possible and necessary in this vulnerable population.

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.

Priorities for Nutrition Research in Pediatric Critical Care.

BACKGROUND: Widespread variation exists in pediatric critical care nutrition practices, largely because of the scarcity of evidence to guide best practice recommendations. OBJECTIVE: The objective of this paper was to develop a list of topics to be prioritized for nutrition research in pediatric critical care in the next 10 years. METHODS: A modified 3-round Delphi process was undertaken by a newly established multidisciplinary group comprising 11 international researchers in the field of pediatric critical care nutrition. Items were ranked on a 5-point Likert scale. RESULTS: Forty-five research topics (with a mean priority score >3(0-5) were identified within the following 10 domains: the pathophysiology and impact of malnutrition in critical illness; nutrition assessment: nutrition risk assessment and biomarkers; accurate assessment of energy requirements in all phases of critical illness; the role of protein intake; the role of pharmaco-nutrition; effective and safe delivery of enteral nutrition; enteral feeding intolerance: assessment and management; the role of parenteral nutrition; the impact of nutrition status and nutrition therapies on long-term patient outcomes; and nutrition therapies for specific populations. Ten top research topics (that received a mean score >4(0-5) were identified as the highest priority for research. CONCLUSIONS: This paper has identified important consensus-derived priorities for clinical research in pediatric critical care nutrition. Future studies should determine topics that are a priority for patients and parents. Research funding should target these priority areas and promote an international collaborative approach to research in this field, with a focus on improving relevant patient outcomes.

Indirect Calorimetry: History, Technology, and Application.

Measurement of energy expenditure is important in order to determine basal metabolic rate and inform energy prescription provided. Indirect calorimetry is the reference standard and clinically recommended means to measure energy expenditure. This article reviews the historical development, technical, and logistic challenges of indirect calorimetry measurement, and provides case examples for practicing clinicians. Formulae to estimate energy expenditure are highly inaccurate and reinforce the role of the indirect calorimetry and the importance of understanding the strength and limitation of the method and its application.

Retrospective Application of New Pediatric Ventilator-Associated Pneumonia Criteria Identifies a High-Risk Population.

OBJECTIVES: To promote standardization, the Centers for Disease Control and Prevention introduced a new ventilator-associated pneumonia classification, which was modified for pediatrics (pediatric ventilator-associated pneumonia according to proposed criteria [PVAP]). We evaluated the frequency of PVAP in a cohort of children diagnosed with ventilator-associated pneumonia according to traditional criteria and compared their strength of association with clinically relevant outcomes. DESIGN: Retrospective cohort study. SETTING: Tertiary care pediatric hospital. PATIENTS: Critically ill children (0-18 yr) diagnosed with ventilator-associated pneumonia between January 2006 and December 2015 were identified from an infection control database. Patients were excluded if on high frequency ventilation, extracorporeal membrane oxygenation, or reintubated 24 hours following extubation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were assessed for PVAP diagnosis. Primary outcome was the proportion of subjects diagnosed with PVAP. Secondary outcomes included association with intervals of care. Two hundred seventy-seven children who had been diagnosed with ventilator-associated pneumonia were eligible for review; 46 were excluded for being ventilated under 48 hours (n = 16), on high frequency ventilation (n = 12), on extracorporeal membrane oxygenation (n = 8), ineligible bacteria isolated from culture (n = 8), and other causes (n = 4). ICU admission diagnoses included congenital heart disease (47%), neurological (16%), trauma (7%), respiratory (7%), posttransplant (4%), neuromuscular (3%), and cardiomyopathy (3%). Only 16% of subjects (n = 45) met the new PVAP definition, with 18% (n = 49) having any ventilator-associated condition. Failure to fulfill new definitions was based on inadequate increase in mean airway pressure in 90% or FIO2 in 92%. PVAP was associated with prolonged ventilation (median [interquartile range], 29 d [13-51 d] vs 16 d [8-34.5 d]; p = 0.002), ICU (median [interquartile range], 40 d [20-100 d] vs 25 d [14-61 d]; p = 0.004) and hospital length of stay (median [interquartile range], 81 d [40-182 d] vs 54 d [31-108 d]; p = 0.04), and death (33% vs 16%; p = 0.008). CONCLUSIONS: Few children with ventilator-associated pneumonia diagnosis met the proposed PVAP criteria. PVAP was associated with increased morbidity and mortality. This work suggests that additional study is required before new definitions for ventilator-associated pneumonia are introduced for children.

The advantage of early plication in children diagnosed with diaphragm paresis.

BACKGROUND: In this single-center study, we sought to determine the frequency of phrenic nerve injury leading to diaphragm paresis (DP) in children following open cardiac surgery over the last 10 years, and to identify possible variables that predict the need for plication and associated clinical outcomes. METHODS: Patients diagnosed with DP were identified from departmental databases and a review of clinical diaphragm ultrasound images. A cohort was analyzed for predictors of diaphragm plication and associations with clinical outcomes. Cumulative proportion graphs modeled the association between plication and length of stay. RESULTS: DP was diagnosed in 161 of 6448 patients (2.5%) seen between January 2002 and December 2012. All diagnoses but 1 were confirmed by ultrasound. Plication of the diaphragm was performed in 30 patients (19%); compared with patients who did not undergo plication, these patients were younger (median age, 10 days vs 138 days; P < .001), more likely to have undergone deep hypothermic circulatory arrest (47% vs 18%; P = .005), had a longer duration of positive pressure ventilation (median, 15 days vs 7 days; P < .001), and had longer lengths of stay in both the intensive care unit (median, 23 days vs 8 days; P < .0001) and the hospital (median, 37 days vs 15 days; P < .0001). Early plication was associated with reduction in all intervals of care. CONCLUSIONS: Early plication should be considered for patients with diaphragm paresis requiring prolonged respiratory support after cardiac bypass surgery. Longer follow-up evaluation is required to better define the long-term implications of plication.

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.

Assessment of Growth 6 Years after the Norwood Procedure.

At 6 years of age, patients with hypoplastic left heart syndrome had mean age-adjusted z-scores for weight and height below the normative population, and body mass index was similar to the normative population. Males had the greatest increase in z-scores for body mass index. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00115934.

Nutrition and Mesenteric Issues in Pediatric Cardiac Critical Care.

OBJECTIVES: The objectives of this review are to discuss the challenges of delivering adequate nutrition to children with congenital heart disease, including pre- and postoperative factors and the role of enteral and parenteral nutrition, as well as the evidence supporting current practices. DATA SOURCE: MEDLINE and PubMed. CONCLUSION: Providing adequate nutritional support is paramount for critically ill infants with congenital heart disease, a population at particular risk for malnutrition. Improved nutritional support has been associated with increased survival and reduction in overall morbidity. Further gains can be achieved by creating a clinical culture that emphasizes optimal perioperative nutritional support. Additional research is required to identify the specific nutrient composition, optimal mode, and timing of delivery to maximize clinical benefit.

Outcomes in Patients with Persistent Ventricular Dysfunction After Stage I Palliation for Hypoplastic Left Heart Syndrome.

We sought to describe the clinical course for patients with hypoplastic left heart syndrome and persistent ventricular dysfunction and identify risk factors for death or transplantation before stage II palliation. 138 children undergoing stage I palliation from 2004 to 2011 were reviewed. Twenty-two (16 %) patients (seven Hybrid, 15 Norwood) with two consecutive echocardiograms reporting at least moderate dysfunction were included and compared to case-matched controls. Eleven of the 22 patients with dysfunction (50 %) underwent stage II, seven (32 %) were transplanted, and four (18 %) died prior to stage II. Of the patients who survived to hospital discharge (n = 17) following stage 1, 14 (82 %) required readmission for heart failure (HF) compared to only two (10 %) for controls (p < 0.001). Among patients with ventricular dysfunction, there was an increased use of ACE inhibitors or beta-blockers (82 vs. 25 %; p = 0.001), inotropes (71 vs. 15 %; p = 0.001), ventilation (58 vs. 10 %; p = 0.001), and ECMO (29 vs. 0 %; p = 0.014) for HF management post-discharge when compared to controls. There was a lower heart transplant-free survival at 7 months in patients with dysfunction compared to controls (50.6 vs. 90.9 %; p = 0.040). ECMO support (p = 0.001) and duration of inotropic support (p = 0.04) were significantly associated with death or transplantation before stage II palliation. Patients with ventricular dysfunction received more HF management and related admissions. Longer inotropic support should prompt discussion regarding alternative treatment strategies given its association with death or transplant.

Pharmacological Manipulation of Peripheral Vascular Resistance in Single Ventricle Patients (Stages I, II, and III of Palliation).

Pharmacological manipulation of afterload is often used in the management of single ventricle patients, both in the acute post-operative setting and more chronically. After the first stage of palliation the pulmonary and systemic circulations are in parallel and afterload reduction is often used to increase total cardiac output and systemic oxygen delivery. The effectiveness of this approach is likely to be dependent on the intrinsic contractile state of the myocardium as well as the post-operative vascular tone. A variety of clinical studies and theoretical models support this approach. The use of afterload reduction in this context must be balanced with the need to maintain a critical systemic blood pressure for organ perfusion and to promote pulmonary blood flow. After the second and third stages of palliation the use of acute afterload reduction is less complex and primarily directed at promoting cardiac output when it is low and/or controlling high blood pressure. Second stage palliation is particularly unique in that the cerebral and pulmonary circulations are in series and respond differently to many manipulations designed to control vascular resistance. The incidence of long-term circulatory failure in single ventricle patients has led to frequent use of afterload reducing agents in this population but data to suggest that this improves overall outcomes is lacking. Newer studies suggest there may be a role for drugs that reduce pulmonary vascular resistance. This chapter will discuss the principles of manipulation of systemic vascular resistance, or afterload, following each of the three stages of single ventricle reconstruction. This article addresses the seventh of eight topics comprising the special issue entitled "Pharmacologic strategies with afterload reduction in low cardiac output syndrome after pediatric cardiac surgery".

Insulin resistance and inflammation are a cause of hyperglycemia after pediatric cardiopulmonary bypass surgery.

OBJECTIVES: Hyperglycemia is common after pediatric cardiopulmonary bypass (CPB) surgery and is attributed to a state of insulin resistance. We examined the role of CPB-induced inflammation on postoperative plasma glucose, insulin, and the glucose-to-insulin ratio, which was used as a marker of insulin resistance; a decrease in the ratio reflects increased resistance. METHODS: We conducted an ancillary study on a previously published randomized trial of children undergoing CPB surgery. Serial blood glucose, insulin, and cytokines were drawn after CPB and at selected intervals for up to 48 hours after surgery. The primary outcome was plasma insulin levels and glucose-to-insulin ratio. Glucose delivery and feeding status were monitored for potential modifying effects. RESULTS: The 299 children studied were predominantly male (55%) with a median age of 2.7 (interquartile range [IQR]: 0.5-6.5) years, and weight of 12.6 (IQR: 6.4-10.8) kg. Operations had a median Society of Thoracic Surgery-European Association for Cardio-Thoracic Surgery complexity score of 1 (IQR: 1-2) and CPB time of 82 (IQR: 58-122) minutes. Hyperglycemia occurred in 85% of subjects; odds of hyperglycemia peaked at 6 hours after CPB. Plasma glucose was associated with increased insulin and a lower glucose-to-insulin ratio. Increased interleukin (IL)-6 concentrations were associated with increased glucose (estimate [EST]: 0.55 (±0.13) mmol/L; P < .001) and insulin (EST: 1.14 (±0.12) µmol/L; P < .001) in linear regression adjusted for repeated measures. Paradoxically, increased cytokines were associated with an increased glucose-to-insulin ratio (EST: 0.21 (±0.03) mmol/µmol; P < .001). CONCLUSIONS: Hyperglycemia after pediatric CPB surgery is associated with hyperinsulinemia, which may reflect insulin resistance in some patients. Inflammation induced by CPB may play a causative role in insulin resistance.

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.