http://repub.eur.nl/res/aut/12982/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/33716/ 2011-02-01T00:00:00Z This study aimed to evaluate the time course of perioperative blood glucose levels of children undergoing cardiac surgery for congenital heart disease in relation to endogenous stress hormones, inflammatory mediators, and exogenous factors such as caloric intake and glucocorticoid use. The study prospectively included 49 children undergoing cardiac surgery. Blood glucose levels, hormonal alterations, and inflammatory responses were investigated before and at the end of surgery, then 12 and 24 h afterward. In general, blood glucose levels were highest at the end of surgery. Hyperglycemia, defined as a glucose level higher than 8.3 mmol/l (>150 mg/dl) was present in 52% of the children at the end of surgery. Spontaneous normalization of blood glucose occurred in 94% of the children within 24 h. During surgery, glucocorticoids were administered to 65% of the children, and this was the main factor associated with hyperglycemia at the end of surgery (determined by univariate analysis of variance). Hyperglycemia disappeared spontaneously without insulin therapy after 12-24 h for the majority of the children. Postoperative morbidity was low in the study group, so the presumed positive effects of glucocorticoids seemed to outweigh the adverse effects of iatrogenic hyperglycemia. http://repub.eur.nl/res/pub/29755/ 2008-01-01T00:00:00Z Objective: To investigate the effect of one single bolus of etomidate used for intubation on adrenal function in children with meningococcal sepsis. Design: Retrospective study conducted between 1997 and 2004. Setting: University-affiliated paediatric intensive care unit (PICU). Patients and participants: Sixty children admitted to the PICU with meningococcal sepsis, not treated with steroids. Interventions: Adrenal hormone concentrations were determined as soon as possible after PICU admission, and after 12 h and 24 h. To assess disease severity, PRISM score and selected laboratory parameters were determined. Measurements and main results: On admission, before blood was drawn, 23 children had been intubated with etomidate, 8 without etomidate and 29 were not intubated. Children who were intubated had significantly higher disease severity parameters than those not intubated, whereas none of these parameters significantly differed between children intubated with or without etomidate. Children who received etomidate had significantly lower cortisol, higher ACTH and higher 11-deoxycortisol levels than those who did not receive etomidate. Arterial glucose levels were significantly lower in children who were intubated with etomidate than in non-intubated children. When children were intubated with etomidate, cortisol levels were 3.2 times lower for comparable 11-deoxycortisol levels. Eight children died, seven of whom had received etomidate. Within 24 h cortisol/ACTH and cortisol/11-deoxycortisol ratios increased significantly in children who received etomidate, but not in children who did not, resulting in comparable cortisol/ACTH ratios with still significantly lowered cortisol/11-deoxycortisol ratios 24 h after admission. Conclusions: Our data imply that even one single bolus of etomidate negatively influences adrenal function for at least 24 h. It might therefore increase risk of death. http://repub.eur.nl/res/pub/7990/ 2006-02-08T00:00:00Z The understanding of the endocrine changes in critically ill children is important, as it provides insights in the pathophysiology of the acute stress in children and its differences compared with adults. Furthermore, it delineates prognostic factors for survival and supports the rational use of present and future pharmaceutical interventions. Much more than in critically ill adults, the acute phase of critical illness comes into prominence in critically ill children, as they show a very rapid and fierce course of disease, followed by a quick recovery if they survive. This chapter presents a comprehensive summary of the results of various studies undertaken to evaluate endocrine changes seen during the acute stress response in critically ill children suffering from sepsis or septic shock with purpura (Chapters 2 to 6) or undergoing open-heart surgery (Chapter 7). These studies evaluated three hypothalamic-pituitary-end-organ axes: I. Hypothalamic-pituitary-adrenal axis (Chapter 2 and Chapter 3) II. Hypothalamic-pituitary-thyroid axis (Chapter 4 and Chapter 5) III. Growth hormone / insulin-like growth factor axis (Chapter 6 and Chapter 7) Chapter 1 provides a general overview of these hormonal axes and the current knowledge on the changes during the acute phase of critical illness in children and adults. http://repub.eur.nl/res/pub/13881/ 2005-10-01T00:00:00Z CONTEXT AND OBJECTIVES: The objective of this study was to elucidate the influence of disease severity, deiodination, sulfation, thyroid hormone binding, and dopamine use on thyroid function in euthyroid sick syndrome. SETTING: The study was performed at a university-affiliated pediatric intensive care unit (PICU). DESIGN: This was an observational cohort study. PATIENTS: Sixty-nine children with meningococcal sepsis were studied. MAIN OUTCOME MEASURES: Differences in thyroid function among nonsurvivors, shock survivors, and sepsis survivors on PICU admission were the main outcome measures. RESULTS: The main study group consisted of 45 non-dopamine-treated children. All children had decreased total T3 (TT3)/rT3 ratios without elevated TSH. T4 sulfate levels were decreased in 88%. Nonsurvivors had paradoxically higher TT3/rT3 ratios than shock survivors (0.71 vs. 0.30); this ratio also correlated with shorter duration of disease (r = -0.43). TT4 and T4-binding globulin (TBG) levels declined with increasing disease severity. TBG levels correlated inversely with elastase levels (r = -0.46). Only TSH levels were significantly lower in 24 dopamine-treated children compared with non-dopamine-treated children (0.65 vs. 0.84), whereas other thyroid hormones did not significantly differ. Both higher TT3/rT3 ratios and lower TT4 levels were predictive for mortality, but this disappeared when IL-6 was entered into the regression model. CONCLUSIONS: All children with meningococcal sepsis showed signs of euthyroid sick syndrome. Alterations in peripheral thyroid hormone metabolism related inversely to the duration of disease and seemed to be enacted by profound induction of type 3 deiodinase rather than by down-regulation of type 1. Lower TT4 levels were related to increased turnover of TBG by elastase. Dopamine was found to suppress only TSH secretion, not other thyroid hormone levels, on PICU admission. Both the TT3/rT3 ratio and TT4 levels were predictive for mortality, but were not superior to IL-6. http://repub.eur.nl/res/pub/13842/ 2005-09-01T00:00:00Z CONTEXT: Adequate adrenal function is pivotal to survive meningococcal sepsis. OBJECTIVES: The objective of the study was to evaluate adrenocortical function in meningococcal disease. DESIGN: This was an observational cohort study. SETTING: The study was conducted at a university-affiliated pediatric intensive care unit. PATIENTS: Sixty children with meningococcal sepsis or septic shock participated in the study. MAIN OUTCOME MEASURES: The differences in adrenal function between nonsurvivors (n = 8), shock survivors (n = 43), and sepsis survivors (n = 9) on pediatric intensive care unit admission were measured. RESULTS: Nonsurvivors had significantly lower median cortisol to ACTH ratio than shock survivors and sepsis survivors. Because cortisol binding globulin and albumin levels did not significantly differ among the groups, bioavailable cortisol levels were also significantly lower in nonsurvivors than sepsis survivors. Nonsurvivors had significantly lower cortisol to 11-deoxycortisol ratios but not lower 11-deoxycortisol to 17-hydroxyprogesterone ratios than survivors. Using multiple regression analysis, decreased cortisol to ACTH ratio was significantly related to higher IL-6 levels and intubation with etomidate (one single bolus), whereas decreased cortisol to 11-deoxycortisol ratio was significantly related only to intubation with etomidate. Aldosterone levels tended to be higher in nonsurvivors than shock survivors, whereas plasma renin activity did not significantly differ. CONCLUSIONS: Our study shows that the most severely ill children with septic shock had signs of adrenal insufficiency. Bioavailable cortisol levels were not more informative on adrenal function than total cortisol levels. Besides disease severity, one single bolus of etomidate during intubation was related to decreased adrenal function and 11beta-hydroxylase activity. Decreased adrenal function was not related to decreased 21-hydroxylase activity. Based on our results, it seems of vital importance to take considerable caution using etomidate and consider combining its administration with glucocorticoids during intubation of children with septic shock.