Does a reduced glucose intake prevent hyperglycemia in children early after cardiac surgery? a randomized controlled crossover study.

INTRODUCTION: Hyperglycemia in children after cardiac surgery can be treated with intensive insulin therapy, but hypoglycemia is a potential serious side effect. The aim of this study was to investigate the effects of reducing glucose intake below standard intakes to prevent hyperglycemia, on blood glucose concentrations, glucose kinetics and protein catabolism in children after cardiac surgery with cardiopulmonary bypass (CPB). METHODS: Subjects received a 4-hour low glucose (LG; 2.5 mg/kg per minute) and a 4-hour standard glucose (SG; 5.0 mg/kg per minute) infusion in a randomized blinded crossover setting. Simultaneously, an 8-hour stable isotope tracer protocol was conducted to determine glucose and leucine kinetics. Data are presented as mean ± SD or median (IQR); comparison was made by paired samples t test. RESULTS: Eleven subjects (age 5.1 (20.2) months) were studied 9.5 ± 1.9 hours post-cardiac surgery. Blood glucose concentrations were lower during LG than SG (LG 7.3 ± 0.7 vs. SG 9.3 ± 1.8 mmol/L; P < 0.01), although the glycemic target (4.0-6.0 mmol/L) was not achieved. No hypoglycemic events occurred. Endogenous glucose production was higher during LG than SG (LG 2.9 ± 0.8 vs. SG 1.5 ± 1.1 mg/kg per minute; P = 0.02), due to increased glycogenolysis (LG 1.0 ± 0.6 vs. SG 0.0 ± 1.0 mg/kg per minute; P < 0.05). Leucine balance, indicating protein balance, was negative but not affected by glucose intake (LG -54.8 ± 14.6 vs. SG -58.8 ± 16.7 µmol/kg per hour; P = 0.57). CONCLUSIONS: Currently recommended glucose intakes aggravated hyperglycemia in children early after cardiac surgery with CPB. Reduced glucose intake decreased blood glucose concentrations without causing hypoglycemia or affecting protein catabolism, but increased glycogenolysis. TRIAL REGISTRATION: Dutch trial register NTR2079.

Implementing an enhanced recovery after thoracic surgery programme in the Netherlands: a qualitative study investigating facilitators and barriers for implementation.

OBJECTIVES: This study aims to elucidate determinants for succesful implementation of the Enhanced Recovery After Thoracic Surgery (ERATS) protocol for perioperative care for surgical lung cancer patients in the Netherlands. SETTING: Lung cancer operations are performed in both academic and regional hospitals, either by cardiothoracic or general thoracic surgeons. Limiting the impact of these operations by optimising and standardising perioperative care with the ERATS protocol is thought to enable reduction in length of stay, complications and costs. PARTICIPANTS: A broad spectrum of stakeholders in perioperative care for patients with lung resection participated in this study, ranging from patient representatives, healthcare professionals to an insurance company representative. INTERVENTIONS: Semistructured interviews (N=14) were conducted with the stakeholders (N=18). The interviews were conducted one on one by telephone and two times, face to face, in small groups. Verbatim transcriptions of these interviews were coded for the purpose of thematic analysis. OUTCOME MEASURES: Determinants for successful implementation of the ERATS protocol in the Netherlands. RESULTS: Several determinants correspond with previous publications: having a multidisciplinary team, leadership from a senior clinician and support from an ERAS-coordinator as facilitators; lack of feedback on performance and absence of management support as barriers. Our study underscores the potential detrimental effect of inconsistent communication, the lack of support in the transition from hospital to home and the barrier posed by lack of accessible audit data. CONCLUSIONS: Based on a structured problem analysis among a wide selection of stakeholders, this study provides a solid basis for choosing adequate implementation strategies to introduce the ERATS protocol in the Netherlands. Emphasis on consistent and sufficient communication, support in the transition from hospital to home and adequate audit and feedback data, in addition to established implementation strategies for ERAS-type programmes, will enable a tailored approach to implementation of ERATS in the Dutch context.

Wide Variation in Perioperative Care in Anatomical Lung Resections in the Netherlands: A National Survey.

This study aimed to describe perioperative care after anatomical lung resection in the Netherlands, before publication of Enhanced Recovery After Surgery/European Society of Thoracic Surgeons (ERAS/ESTS) guidelines in 2019. An online survey was sent to all 43 Dutch lung surgical centers in December 2017, addressing topics in the 4 phases of perioperative care (preoperative, admission, perioperative, postoperative). Respondents were requested to report care that would be delivered to a standardized patient without perioperative complications. To compare current care with ERAS/ESTS guidelines, we assigned an ERAS/ESTS score per hospital, weighted for evidence level per recommendation. Higher scores indicate higher application of recommendations. Response rate of centers was 100%, median response rate per question was 98% (interquartile range 94-100). Some perioperative recommendations are commonly applied (>85%), such as minimally invasive surgery and regional anesthesia; others, such as admission carbohydrate drinks, are not (<35%). Wide variation was observed regarding patient counselling, pre- and postoperative admission logistics, anemia correction, fluid management, pain management, and chest drain management. Median 62% (interquartile range 53%-72%) of the maximum ERAS/ESTS score was achieved. Large variation in ERAS/ESTS score between hospitals were found in all phases (preoperative: 6.0 [6.5-10.5] points, admission: 5.0 [1.0-6.0] points, perioperative: 21.5.0 [16.0-22.5] points, postoperative: 8.0 [5.0-8.5] points). Large variation exists in perioperative care after anatomical lung resection in the Netherlands. Given previously published data linking variation in perioperative care to variation in outcomes, standardization of perioperative care in lung surgery, preferably based on the ERAS/ESTS guidelines, may be warranted but requires further study.

24-Hour protein, arginine and citrulline metabolism in fed critically ill children - A stable isotope tracer study.

BACKGROUND & AIMS: The reference method to study protein and arginine metabolism in critically ill children is measuring plasma amino acid appearances with stable isotopes during a short (4-8 h) time period and extrapolate results to 24-h. However, 24-h measurements may be variable due to critical illness related factors and a circadian rhythm could be present. Since only short duration stable isotope studies in critically ill children have been conducted before, the aim of this study was to investigate 24-h appearance of specific amino acids representing protein and arginine metabolism, with stable isotope techniques in continuously fed critically ill children. METHODS: In eight critically ill children, admitted to the pediatric (n = 4) or cardiovascular (n = 4) intensive care unit, aged 0-10 years, receiving continuous (par)enteral nutrition with protein intake 1.0-3.7 g/kg/day, a 24-h stable isotope tracer protocol was carried out. L-[ring-2H5]-phenylalanine, L-[3,3-2H2]-tyrosine, L-[5,5,5-2H3]-leucine, L-[guanido-15N2]-arginine and L-[5-13C-3,3,4,4-2H4]-citrulline were infused intravenously and L-[15N]-phenylalanine and L-[1-13C]leucine enterally. Arterial blood was sampled every hour. RESULTS: Coefficients of variation, representing intra-individual variability, of the amino acid appearances of phenylalanine, tyrosine, leucine, arginine and citrulline were high, on average 14-19% for intravenous tracers and 23-26% for enteral tracers. No evident circadian rhythm was present. The pattern and overall 24-h level of whole body protein balance differed per individual. CONCLUSIONS: In continuously fed stable critically ill children, the amino acid appearances of phenylalanine, tyrosine, leucine, arginine and citrulline show high variability. This should be kept in mind when performing stable isotope studies in this population. There was no apparent circadian rhythm. CLINICAL TRIAL REGISTER: NCT01511354 on clinicaltrials.gov.

Changes in arginine metabolism during sepsis and critical illness in children.

Arginine is an important amino acid during disease and healing because of functions in the immune system and as precursor of nitric oxide (NO). In critically ill adults and children, plasma arginine and citrulline concentrations are substantially decreased, indicating an arginine-deficient state. Arginine availability is reduced because of increased arginine disposal in combination with reduced de novo arginine synthesis. The latter is most likely caused by reduced citrulline availability. As a result, NO synthesis may be impaired, which might compromise microcirculation. These metabolic changes seem to be dependent on the severity of inflammation. Arginine or citrulline supplementation in severe inflammation might therefore be beneficial. Possibly, the use of protein-energy-enriched formulas may be a first step to improve arginine availability and NO synthesis. In critically ill children, arginine metabolism and supplementation is however a virtually unexplored field. Since pediatric sepsis is a significant health problem, which differs in epidemiology and pathophysiology from sepsis in adults, and because of the scarcity of data in this population, studies focused on pathophysiological mechanisms and possible interventions in arginine metabolism in pediatric critical illness are warranted.

Arginine appearance and nitric oxide synthesis in critically ill infants can be increased with a protein-energy-enriched enteral formula.

BACKGROUND: Arginine is considered an essential amino acid during critical illness in children, and supplementation of arginine has been proposed to improve arginine availability to facilitate nitric oxide (NO) synthesis. Protein-energy-enriched enteral formulas (PE-formulas) can improve nutrient intake and promote anabolism in critically ill infants. However, the effect of increased protein and energy intake on arginine metabolism is not known. OBJECTIVE: We investigated the effect of a PE-formula compared with that of a standard infant formula (S-formula) on arginine kinetics in critically ill infants. DESIGN: A 2-h stable-isotope tracer protocol was conducted in 2 groups of critically ill infants with respiratory failure because of viral bronchiolitis, who received either a PE-formula (n = 8) or S-formula (n = 10) in a randomized, blinded, controlled setting. Data were reported as means ± SDs. RESULTS: The intake of a PE-formula in critically ill infants (aged 0.23 ± 0.14 y) resulted in an increased arginine appearance (PE-formula: 248 ± 114 µmol · kg(-1) · h(-1); S-formula: 130 ± 53 µmol · kg(-1) · h(-1); P = 0.012) and NO synthesis (PE-formula: 1.92 ± 0.99 µmol · kg(-1) · h(-1); S-formula: 0.84 ± 0.36 µmol · kg(-1) · h(-1); P = 0.003), whereas citrulline production and plasma arginine concentrations were unaffected. CONCLUSION: In critically ill infants with respiratory failure because of viral bronchiolitis, the intake of a PE-formula increases arginine availability by increasing arginine appearance, which leads to increased NO synthesis, independent of plasma arginine concentrations. This trial was registered at www.trialregister.nl as NTR515.

Reducing glucose infusion safely prevents hyperglycemia in post-surgical children.

BACKGROUND & AIMS: To investigate the effects of two different glucose infusions on glucose homeostasis and amino acid metabolism in post-surgical children. METHODS: This randomized crossover study evaluated glucose and amino acid metabolism in eight children (age 9.8 ± 1.9 months, weight 9.5 ± 1.1 kg) admitted to a pediatric intensive care unit in a tertiary university hospital after surgical correction for non-syndromal craniosynostosis. Patients were randomized to receive low (LG; 2.5 mg kg(-1) min(-1)) and standard (SG; 5.0 mg kg(-1) min(-1)) glucose infusion in a crossover setting. After a bolus (4 g kg(-1)) of deuterium oxide, we conducted a primed, constant, 8 h tracer infusion with [6,6-²H2]Glucose, [1-¹³C]Leucine, [ring-²H5]Phenylalanine and [3,3-²H2]Tyrosine. RESULTS: SG resulted in hyperglycemia (defined as > 6.1 mmol L(-1)), while during LG plasma glucose levels were normoglycemic (5.9 ± 0.6 vs. 7.5 ± 1.7 mmol L(-1); LG vs. SG respectively, p = 0.02). Hypoglycemia did not occur during LG infusion. Endogenous glucose production was not fully suppressed during the hyperglycemic state under SG and increased with reduced glucose infusion (2.6 ± 1.5 vs. 1.1 ± 1.4 mg kg(-1) min(-1); LG vs. SG; p = 0.05). Whole body protein balance derived from leucine and phenylalanine kinetics was slightly negative but not further affected with a decrease in glucose infusion. CONCLUSIONS: The current recommended glucose infusion induces hyperglycemia in post-surgical children. A reduced glucose infusion safely reduced high glucose levels, while children were capable to sustain normoglycemia with increased endogenous glucose production. The reduced glucose infusion did not exacerbate the mild catabolic state in which the patients were.