Do critically ill surgical neonates have increased energy expenditure?

BACKGROUND/PURPOSE: Adult metabolic studies suggest that critically ill patients have increased energy expenditures and thus require higher caloric allotments. To assess whether this is true in surgical neonates the authors utilized a validated, gas leak-independent, nonradioactive, isotopic technique to measure the energy expenditures of a stable postoperative group and a severely stressed cohort. METHODS: Eight (3.46+/-1.0 kg), hemodynamically stable, total parenteral nutrition (TPN)-fed, nonventilated, surgical neonates (5 with gastroschisis, 2 with intestinal atresia, and 1 with intestinal volvulus) were studied on postoperative day 15.5+/-11.9. These were compared with 10 (BW = 3.20+/-0.2 kg), TPN-fed, extracorporeal life support (ECLS)-dependent neonates, studied on day of life 7.0+/- 2.8. Energy expenditure was obtained using a primed, 3-hour infusion of NaH(13)CO(3'), breath (13)CO(2) enrichment determination by isotope ratio mass spectroscopy, and the application of a standard regression equation. Interleukin (IL)-6 levels and C-reactive protein (CRP) concentrations were measured to assess metabolic stress. Comparisons between groups were made using 2 sample Student's t tests. RESULTS: The mean energy expenditure was 53+/-5.1 kcal/kg/d (range, 45.6 to 59.8 kcal/kg/d) for the stable cohort and 55+/-20 kcal/kg/d (range, 32 to 79 kcal/kg/d) for the ECLS group (not significant, P =.83). The IL-6 and CRP levels were significantly higher in the ECLS group (29 +/-11.5 v 0.7+/-0.6 pg/mL [P<.001], and 31+/-22 v 0.6+/-1.3 mg/L [P<.001], respectively). Mortality rate was 0% for the stable postoperative patients and 30% for the ECLS group. CONCLUSIONS: Severely stressed surgical neonates, compared with controls, generally do not show increased energy expenditures as assessed by isotopic dilution methods. These data suggest that the routine administration of excess calories may not be warranted in critically ill surgical neonates and support the hypothesis that neonates obligately redirect energy, normally used for growth, to fuel the stress response. This is a US government work. There are no restrictions on its use.

Ligation of a patent ductus arteriosus under fentanyl anesthesia improves protein metabolism in premature neonates.

BACKGROUND/PURPOSE: Although surgical ligation effectively reverses the cardiopulmonary failure associated with patent ductus arteriosus (PDA), previous findings have suggested that such surgery itself elicits a catabolic response in premature neonates. Therefore, the authors sought to quantitatively assess whether PDA ligation under fentanyl anesthesia aggravated or improved the protein metabolism of premature neonates. METHODS: Seven ventilated, premature neonates (birth weight 815 +/- 69 g) underwent PDA ligation with standardized fentanyl anesthesia (15 microg/kg) on day-of-life 8.4 +/- 1.2 and were studied immediately pre- and 16 to 24 hours postoperatively while receiving continuous total parenteral nutrition (TPN). Whole-body protein kinetics were calculated using intravenous 1-[13C]leucine, and skeletal muscle protein breakdown was measured from the urinary 3-methylhistidine to creatinine ratio (MH:Cr). RESULTS: Whole-body protein breakdown (10.9 +/- 1.2 v8.9 +/- 0.8 g/kg/d, P < .05), turnover (17.4 +/- 1.2 v 15.4 +/- 0.8 g/kg/d, P< .05), and MH:Cr (1.95 +/- 0.20 v 1.71 +/- 0.16 micromol:mg, P< .05) decreased significantly after operation. This resulted in a 60% improvement in protein balance (1.6 +/- 0.8 v 2.6 +/- 0.6 g/kg/d, P = 0.08) postoperatively. CONCLUSIONS: Because of decreased whole-body protein breakdown, whole-body protein turnover, skeletal muscle protein breakdown, and increased protein accrual, surgical PDA ligation under fentanyl anesthesia promptly improves the protein metabolism of premature neonates enduring the stress of a PDA.

Validation of a [13C]bicarbonate tracer technique to measure neonatal energy expenditure.

The use of a stable isotope-labeled [13C]bicarbonate infusion to measure energy expenditure is advantageous, as a complete collection of expired air is not required. This technique allows for facile measurements of energy expenditure in intubated neonates. The aim of the present study was to determine the accuracy of energy expenditure estimates in postsurgical neonates by using the [13C]bicarbonate method compared with the current standard, indirect calorimetry. Eight neonates who were receiving total parenteral nutrition [98 +/- 21 (SD) kcal x kg(-1) x d(-1); 3.1 +/- 0.7 (SD) protein g x kg(-1) x d(-1)] were studied on postoperative d 15.5 +/- 11.9. A primed continuous 3-h intravenous infusion of NaH13CO3 and indirect calorimetry were performed simultaneously. Energy expenditure was calculated separately from the Weir equation and from the dilution of 13CO2 in the breath in combination with the individual energy equivalents of CO2 from the diet. The rate of CO2 appearance and energy expenditure calculated from the bicarbonate method (0.725 +/- 0.021 mol x kg(-1) x d(-1); 89.5 +/- 2.5 kcal x kg(-1) x d(-1)) highly correlated (r = 0.94 and 0.98, respectively) with the CO2 excretion and energy expenditure determined by indirect calorimetry (0.489 +/- 0.016 mol x kg(-1) x d(-1); 60.2 +/- 2.0 kcal x kg(-1) x d(-1)) when analyzed nonproportionately to weight. Bland-Altman analysis demonstrated the 95% confidence interval to be +/- 8.2 kcal x kg(-1) x d(-1). Linear regression analysis revealed a highly statistically significant equation relating the two energy expenditures: Indircal (kcal/d) = -9.341 + [0.705 x Bicarb (dcal/d)]; p < 0.001, r2 = 96.4%. We conclude that energy expenditure in neonates can be accurately determined using the [13C]bicarbonate method and a regression equation. Therefore, the bicarbonate method may be useful for determining energy expenditure in neonates not readily accessible to indirect calorimetry, such as those being mechanically ventilated or on extracorporeal life support.

The determinants of protein catabolism in neonates on extracorporeal membrane oxygenation.

BACKGROUND/PURPOSE: Protein catabolism appears to be markedly elevated among neonates on extracorporeal membrane oxygenation (ECMO). The aim of this study was to determine the effect of dietary caloric intake on protein catabolism in neonates on ECMO to help construct therapies that may promote anabolism. METHODS: Twelve total parenteral nutrition (TPN)-fed (88.1 +/- 5.0 [SE] kcal/kg/d; range, 60 to 113 kcal/kg/d; 2.3 +/- 0.2 g/kg/d protein) neonates were studied on ECMO at day of life 7.2 +/- 0.8 d. Protein kinetics were determined using infusions of NaH13CO3 and 1-[13C]leucine. RESULTS: As expected, C-reactive protein levels were significantly elevated compared with normal controls (44.0 +/- 7.6 mg/L v 1.9 +/- 1.1 mg/L; P < .001). Negative protein balance (-2.3 +/- 0.6 g/kg/d; range, 1 to -6.4 g/kg/d) highly correlated (r = -0.88, P < .001) with total protein turnover. Increased dietary caloric intake correlated with increased amino acid oxidation (r = 0.85, P < .001), increased total protein turnover (r = 0.73, P < .01), continued negative protein balance (r = 0.72, P < .01), increased whole-body protein breakdown (r = 0.66, P < .05), and increased CO2 production rate (r = 0.73, P < .01). CONCLUSIONS: A surplus of dietary caloric intake does not improve protein catabolism and merely increases CO2 production in these highly stressed neonates. Thus, judicious caloric supplementation is warranted.

Stable isotopic quantitation of protein metabolism and energy expenditure in neonates on- and post-extracorporeal life support.

It is generally assumed that extracorporeal life support (ECLS) provides a metabolic "rest state" by replacing approximately 80% of cardiopulmonary work. The aim of this study was to precisely quantify neonatal energy expenditure (EE) and whole-body protein metabolism on (during) and post (after) venoarterial ECLS using stable isotope tracer techniques. Nine parenterally fed neonates on-ECLS were studied at 7.8 +/- 1.0 days of life (mean +/- SE), five of which were studied post-ECLS on 27.0 +/- 5.4 days of life. EE and whole-body protein metabolism were quantified using a primed, continuous infusion of L-[1-(13)C]leucine and NaH13CO3. The neonates studied on- and post-ECLS had similar rates of endogenous leucine flux (370 +/- 46 micromol/kg/h v 339 +/- 76 micromol/kg/h), leucine oxidation (161 +/- 22 micromol/kg/h v 121 +/- 25 micromol/kg/h), nonoxidative disposal rates of leucine (313 +/- 37 micromol/kg/h v 331 +/- 75 micromol/kg/h), net protein balance (-2.31 +/- 0.8 g/kg/d v -0.33 +/- 1.1 g/kg/d), and EE (88.6 +/- 7.7 kcal/kg/d v 84.3 +/- 9.2 kcal/kg/d). These results demonstrate that neonates on-ECLS are in hypermetabolic and protein catabolic states that continue in the post-ECLS phase. The authors conclude that ECLS does not provide a metabolic "rest state."

Does extracorporeal membrane oxygenation benefit neonates with congenital diaphragmatic hernia? Application of a predictive equation.

The overall survival of neonates with congenital diaphragmatic hernia (CDH) remains poor despite the advent of extracorporeal membrane oxygenation (ECMO). Attempts at accurately predicting survival have been largely unsuccessful. The purpose of this study was twofold: (1) to identify independent predictors of survival from a cohort of CDH neonates treated at the authors' institution when ECMO was not available and combine them to form a predictive equation, and (2) to apply the equation prospectively in a cohort of CDH neonates, treated at the same institution when ECMO was available, to determine whether ECMO improves outcome. From the clinical data of 62 CDH neonates treated at the authors' center by the same team of university neonatologists and pediatric surgeons between 1983 and 1993 (before ECMO availability), 15 preoperative and seven operative variables were selected as potential independent predictors. When subjected to multivariate, stepwise logistic regression analysis, four variables were identified as statistically significant (P < .05), independent predictors of survival: (1) ventilatory index (VI), (2) best preoperative PaCO2, (3) birth weight (BW), and (4) Apgar score at 5 minutes. When combined via logistic regression analysis, the following predictive equation was formulated: P (probability of survival to discharge) = [1 + e(x)]-1 where x = 4.9 - 0.68 (Apgar) - 0.0032 (BW) + 0.0063 (VI) + 0.063 (PaCO2). Applying a standard cut-off rate of survival at less than 20%, the equation yielded a sensitivity of 94% and a specificity of 82% in identifying the correct outcome of patients treated with conventional ventilatory management. The overall survival rate was 66%. Since the availability of ECMO at the center, 32 CDH neonates were treated using the same conventional ventilatory treatment and surgical repair by the same university staff. The overall survival rate was 69%. The predictive equation was applied prospectively to all neonates to determine predicted outcome, but was not used to decide the treatment method. Eighteen neonates received conventional therapy alone; 16 of 18 survived (89%). Fifteen of the 16 patients who survived had their outcomes predicted correctly (94%). Fourteen neonates did not respond to conventional therapy and required ECMO; 6 of 14 survived (43%). Six of the eight patients predicted to survive, lived (75%). All six patients predicted to die, died despite the addition of ECMO therapy (100%). The mean hospital cost, per ECMO patient who died, was $277,264.75 +/- $59,500.71 (SE). An odds ratio analysis, using the four independent predictors to standardize for degree of illness, was performed to assess the risk associated with adding ECMO therapy. The result was 1.25 (P = 0.75). Although the cohort was not large enough to eliminate significant beta error, the data strongly suggested no advantage of ECMO. At this center, absolute survival rates for neonates with CDH have not been significantly altered since ECMO has become available (66% v 69%). The authors conclude that the predictive equation remains an accurate measurement of survival at their center even when ECMO is used as a salvage therapy. The method of creating a predictive equation may be applied at any institution to determine the potential outcome of CDH neonates and assess the effect of ECMO, or other salvage therapies, on survival rates.

Compartmentation of endogenously synthesized amino acids in neonates.

The conversion of D-[U-13C]glucose to proline (Pro), aspartate (Asp), and cysteine (Cys) is limited in premature neonates, implying that these amino acids (AA) are conditionally essential. This study was performed to determine whether these findings resulted from an insufficient precursor dose or intracellular compartmentation of newly synthesized amino acids, rather than inadequate synthesis. In the first phase of this study, seven total parenteral nutrition-fed, premature neonates received IV D-[U-13C]glucose at 5 mg/kg/min for 4 hr. In the second phase, a separate cohort of eight patients received an identical infusion. Blood was obtained before and at the end of the infusion. Isotopic enrichments of the free plasma AA and glucose were measured using gas chromatography/mass spectrometry in both studies. In phase 2, the isotopic enrichments of the AA bound to the hepatically synthesized proteins, fibrinogen and VLDL-apolipoprotein B-100 (apo B-100), were measured. In phase 1, despite a glucose precursor enrichment greater than 66%, Pro, Asp, and Cys remained the least enriched of all amino acids studied (P < 0.05). Asp, but not Pro, demonstrated very high enrichments in apo B-100 (P < 0.001), reflecting distinct intracellular compartmentation. We conclude that the limited conversion Of D-[U-13C]glucose to Pro, Asp, and Cys did not result from low precursor glucose enrichment and that there is evidence of Asp compartmentation (intracellular) in premature neonates. However, the low Pro enrichment in the free plasma AA pool and the absence of intracellular Pro compartmentation suggest that Pro may be a conditionally essential AA for premature neonates.

Clinical and pathological features of pediatric dermatofibrosarcoma protuberans.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon malignant mesenchymal tumor characterized by local invasion and recurrence. Fewer than 50 cases have been reported in the pediatric population. We reviewed our experience in the treatment of children with DFSP to define clinical and pathological characteristics. Seven pediatric patients were included in the study (mean age, 11.7 yr). Clinically, the tumors were described as firm nodules fixed to the skin but mobile over the deep fascia, with slow, progressive growth. Diagnosis was made by excisional biopsy in 6 patients and punch biopsy in 1 patient. Six of 7 patients had positive margins after the diagnostic procedure. Pathologically, diagnosis was based on histology, with confirmation by CD34 staining. Definitive surgical therapy consisted of wide local excision (1-3 cm margins) in 5 patients and Moh's micrographic resection in 2 patients. There have been no local recurrences or distant metastases, with a mean follow-up of 15.1 months. Pathological and clinical diagnostic criteria for the pediatric population are reviewed, and treatment options are discussed.