|Disturbance of glucose homeostasis after pediatric cardiac surgery.|
|Jump to Full Text|
|PMID: 21082177 Owner: NLM Status: MEDLINE|
|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.|
|Jennifer J Verhoeven; Anita C S Hokken-Koelega; Marieke den Brinker; Wim C J Hop; Robert J van Thiel; Ad J J C Bogers; Wim A Helbing; Koen F M Joosten|
Related Documents :
|7760217 - Social competence of siblings of children with sickle cell anemia.
21339277 - Implementation of goal-directed therapy for children with suspected sepsis in the emerg...
11824177 - Externalizing behaviors and television viewing in children of low-income minority parents.
11227987 - Utility of the pediatric symptom checklist for behavioral screening of disadvantaged ch...
21034927 - Rectocele in children: a case report.
1473507 - Epilepsy and retarded growth in a hyperendemic focus of onchocerciasis in rural western...
|Type: Journal Article Date: 2010-11-17|
|Title: Pediatric cardiology Volume: 32 ISSN: 1432-1971 ISO Abbreviation: Pediatr Cardiol Publication Date: 2011 Feb|
|Created Date: 2011-02-04 Completed Date: 2011-06-17 Revised Date: 2011-07-26|
Medline Journal Info:
|Nlm Unique ID: 8003849 Medline TA: Pediatr Cardiol Country: United States|
|Languages: eng Pagination: 131-8 Citation Subset: IM|
|Intensive Care, Erasmus MC-Sophia Children's Hospital, P.O. Box 2060, 3000 CB, Rotterdam, The Netherlands. email@example.com|
|APA/MLA Format Download EndNote Download BibTex|
Analysis of Variance
Cardiac Surgical Procedures / adverse effects*
Cytokines / blood
Enzyme-Linked Immunosorbent Assay
Glucocorticoids / therapeutic use
Health Status Indicators
Heart Defects, Congenital / surgery*
Hyperglycemia / chemically induced*
Hypoglycemic Agents / therapeutic use
Inflammation / prevention & control
Insulin / therapeutic use
|0/Blood Glucose; 0/Cytokines; 0/Glucocorticoids; 0/Hypoglycemic Agents; 0/Interleukin-6; 11061-68-0/Insulin; 130068-27-8/Interleukin-10|
Journal ID (nlm-ta): Pediatr Cardiol
Publisher: Springer-Verlag, New York
© The Author(s) 2010
Received Day: 15 Month: 8 Year: 2010
Accepted Day: 25 Month: 10 Year: 2010
Electronic publication date: Day: 17 Month: 11 Year: 2010
pmc-release publication date: Day: 17 Month: 11 Year: 2010
Print publication date: Month: 2 Year: 2011
Volume: 32 Issue: 2
First Page: 131 Last Page: 138
PubMed Id: 21082177
Publisher Id: 9829
|Disturbance of Glucose Homeostasis After Pediatric Cardiac Surgery|
|Jennifer J. Verhoeven12||
Address: +31-10-7040704 +31-10-7036288 firstname.lastname@example.org
|Anita C. S. Hokken-Koelega3|
|Marieke den Brinker14|
|Wim C. J. Hop5|
|Robert J. van Thiel6|
|Ad J. J. C. Bogers6|
|Wim A. Helbing7|
|Koen F. M. Joosten1|
1Intensive Care, Erasmus MC-Sophia Children’s Hospital, P.O. Box 2060, 3000 CB Rotterdam, The Netherlands
2Department of Pediatrics, Maasstad Hospital, Rotterdam, The Netherlands
3Department of Pediatrics, Division of Pediatric Endocrinology, Erasmus MC, Sophia Children’s Hospital, Rotterdam, The Netherlands
4Department of Pediatrics, Ghent University Hospital, Ghent, Belgium
5Department of Epidemiology and Biostatistics, Erasmus MC, Rotterdam, The Netherlands
6Department of Cardiothoracic Surgery, Erasmus MC, Rotterdam, The Netherlands
7Department of Pediatrics, Division of Pediatric Cardiology, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands
Hyperglycemia is a regular phenomenon in critically ill children after surgical repair or palliation of congenital heart defects. Some recent studies have shown an association of hyperglycemia with increased postoperative morbidity and mortality in these children [7, 18, 35].
The adult literature contains a debate on the usefulness of intensive insulin therapy for glucose control to improve morbidity and mortality rates for cardiac surgical patients [8, 13]. The only randomized controlled study of critically ill children showed improved short-term outcome after treatment with intensive insulin therapy targeting blood glucose levels to age-adjusted normal fasting concentrations , but debate exists on the harm of insulin-induced hypoglycemic events .
For glucose control protocols to be most efficient, they should be based on pathophysiologic mechanisms . Several studies have addressed this topic for critically ill adults [15, 16, 26], but such studies of critically ill children are lacking.
Hyperglycemia in critically ill children is caused by multiple factors, among which endogenous stress hormones , inflammatory mediators, oxidative stress, and therapeutic interventions such as glucose and drug administration are the main causative factors.
Children undergoing cardiopulmonary bypass (CPB) surgery often receive perioperative glucocorticoids to attenuate the systematic inflammatory response, but to date, no clinical benefit has been shown . However, hyperglycemia is a well-known side effect of glucocorticoid use. We hypothesized that in some settings, the adverse effects of steroid-induced hyperglycemia could outweigh the anticipated benefits.
The current study aimed to evaluate blood glucose levels in children undergoing open heart surgery relative to stress-induced endogenous hormonal production, inflammatory mediators, and exogenous factors such as caloric intake and glucocorticoid use.
Eligible subjects were consecutive children with congenital heart disease who had undergone open-heart surgery in the Erasmus MC during a 2-year period. Children were not eligible for the study if they had endocrine or chromosomal abnormalities or had received radiation or chemotherapy within the previous 6 months. The Erasmus MC Medical Ethics Review Board approved the study (196.429/2000/222), and written informed consent was obtained from the parents or legal representatives of each child and of all children older than 12 years.
Anthropometric measurements were taken the day before cardiac surgery. The children were fasted before and during surgery and received glucose intravenously (4–6 mg/kg/min) after surgery according to protocol. Enteral nutrition was initiated on the first postoperative day if clinically possible.
Severity of illness was assessed by Risk Adjustment for Congenital Heart Surgery (RACHS) , the pediatric risk of mortality (PRISM) score , the pediatric logistic organ dysfunction (PELOD) score , and levels of established biomarkers such as interleukin-6 (IL-6), IL-10, and arterial lactate.
Congestive heart failure was defined by the criteria of Van der Kuip et al.  adjusted for age. The presence of cyanotic heart disease, the duration of CPB, and the aorta cross-clamp time were recorded.
During cardiac surgery, most of the children received mild hypothermia (median, 31°C), and one child (age, 16.6 years) received deep hypothermia (22.5°C). All the children received standardized analgesia during and after surgery. Glucocorticoids were administered at the discretion of the attending anesthetist. The decision to administer glucocorticoids was made before the start of surgery and independently of the operative course. Standardized protocols were used for administration of inotropes and weaning from the ventilator. The weighted inotropic (WI) score based on maximum inotropic support during surgery and intensive care unit (ICU) stay was calculated . Duration of mechanical ventilation, presence of wound infections, length of ICU and hospital stays, and survival were recorded.
Arterial blood samples were obtained at the start of surgery after induction of anesthesia, at the end of surgery after sternal closure, and then 12 and 24 h afterward. All laboratory parameters except cytokines were determined immediately. Serum and plasma were stored at −80°C until assayed.
Glucose and lactate were determined on an ABL 725 blood gas analyser (Radiometer; Copenhagen, Denmark) in a certified clinical chemistry laboratory (ISO 17025 and 9001). Hypoglycemia was defined as a blood glucose level of 2.2 mmol/l (≤40 mg/dl) or lower and hyperglycemia as a blood glucose level of 8.3 mmol/l (>150 mg/dl) or higher . The normal value for lactate was less than 2.0 mmol/l.
Serum insulin concentrations were determined with an immunoradiometric assay on an Immulite 2000 (Diagnostic Product Corporation, Los Angeles, CA, USA) with a minimum detection level of 35 pmol/l . In our laboratory, the maximum fasting reference value for insulin is 180 pmol/l. The insulin/glucose ratio was calculated to assess insulin sensitivity. To date, no strict reference values exist for the (non)-fasting glucose-to-insulin ratio. In our study, the maximum reference value for the insulin–glucose ratio was defined as 18 pmol/mmol. We derived this value from current literature data, taking into account the differences between insulin assays and units of analysis [5, 28, 32].
Serum cortisol concentrations were determined using an Immulite 2000 competitive luminescence immunoassay (DPC) with detection limits of 3–1,380 nmol/l. The normal level of cortisol during stress was defined as a cortisol level higher than 496 nmol/l . Plasma adrenocorticotrope hormone (ACTH) concentrations were determined by an immunoradiometric assay (Bio International, Gif sur Yvette, France). The within- and between-assay variation coefficients for the assays of cortisol and ACTH were less than 7%.
Plasma cytokine levels were analyzed with an enzyme-linked immunosorbent assay (Sanquin, Amsterdam, The Netherlands). The detection limit of IL-6 (lowest positive standard) was 10 pg/ml, and that of IL-10 was 25 pg/ml.
Data were analyzed with SPSS 16.0 (SPSS inc., Chicago, IL, USA). The results are expressed as median (interquartile range) unless specified otherwise. The Mann–Whitney U test, the chi-square test, and Fisher’s exact test were used for group comparison. Univariate analysis of variance (ANOVA) was used to assess relationships between glucose, steroid use, and disease severity as expressed by WI score and CPB time. Data were log-transformed when necessary. Two-tailed p values less than 0.05 were considered statistically significant.
The study group consisted of 49 children (24 boys) ages 2 months to 18 years. The children had surgery for left–right shunt patch closure of ventricular septal defect (n = 13, including 6 children with combined closure of atrial septal defect and 1 child with additional repair of the tricuspid valve), closure of atrial septal defect (n = 7), patch closure of the aortopulmonary window together with reimplantation of anomalous left coronary artery from the pulmonary artery (n = 1); corrective surgery for tetralogy of Fallot (n = 9), univentricular heart (partial cavopulmonary connection, n = 4; total cavopulmonary connection, n = 2), left ventricular outflow tract obstruction (enucleation, n = 4; pulmonary autograft, n = 2; allograft aortic root replacement, n = 2), right ventricular outflow tract obstruction (infundibulectomy, n = 2; pulmonary allograft, n = 1), and mitral valve insufficiency (mitral valve annuloplasty, n = 2).
All the children underwent elective cardiac surgery upon CPB support, and 45 of the children underwent cardioplegic arrest. All survived.
At the end of surgery, 30 of the children were receiving inotropic support, with 16 receiving dopamine, 6 receiving dobutamine, 7 receiving both dopamine and dobutamine, and 1 receiving noradrenalin.
During cardiac surgery, 32 (65%) of the children received one bolus of glucocorticoids. The bolus was received by 12 children after induction of anesthesia before surgical incision, 8 children at the start of heparinization before CPB, and 12 children at aortic cross-clamping. All except two of the children received methylprednisolone (30 mg/kg), with one child receiving dexamethasone (1 mg/kg) and one child receiving hydrocortisone (2 mg/kg).
For the purpose of this study, we created two groups: those treated with glucocorticoids (n = 32) and those treated without glucocorticoids (n =17). No wound infections occurred. None of the patients received insulin during surgery or ICU stay. The clinical parameters are depicted in Table 1.
Table 2 shows the laboratory results at the start of surgery, at the end of surgery, and at 12 and 24 h after surgery for the group as a whole.
Table 2 shows the blood glucose levels from the start of surgery up to 24 h after surgery. Hypoglycemia (≤2.2 mmol/l [≤40 mg/dl]) did not occur. In general, blood glucose levels were highest at the end of surgery.
At start of surgery, hyperglycemia (>8.3 mmol/l [>150 mg/dl]) was present in one patient. At the end of surgery, hyperglycemia was present in 52% (25/48) of the children, decreasing to 11% (5/47) after 12 h and to 6% (3/47) after 24 h. Thus, almost all the children were normoglycemic after 24 h. Hyperglycemia was not associated with ventilation days nor with the length of the ICU or hospital stays.
Table 2 shows the endogenous plasma insulin levels and the insulin–glucose ratios from the start of surgery to 24 h after surgery. At the start of surgery, the plasma levels of insulin in all the children were below the maximum fasting reference level. In all but one of the children (98%), the insulin–glucose ratios were below the maximum reference value.
At the end of surgery, the plasma levels of insulin in 6% (3/48) of the children were above the maximum reference level. The insulin–glucose ratio was increased more than 18 pmol/mmol in 9% (4/47) of the children. They had blood glucose levels varying between 7.4 and 10.8 mmol/l. Of the remaining children, with an insulin–glucose ratio of 18 pmol/mmol or less, 53% (23/43) had hyperglycemia.
At 12 h after surgery, none of the children had plasma insulin levels or an insulin–glucose ratio above the maximum reference value. The insulin levels and insulin–glucose ratios were highest 24 h after surgery. The plasma insulin levels in 9% (4/46) of the children were above the maximum reference level. The insulin–glucose ratio was increased more than 18 pmol/mmol in 20% (9/46) of the children, but only three of them were hyperglycemic. In the remaining children, with an insulin–glucose ratio less than 18 pmol/mmol, hyperglycemia did not occur.
During surgery, 65% (32/49) of the children were treated with glucocorticoids. The clinical parameters before surgery did not differ between the children with and those without glucocorticoid treatment except for the prevalence of cyanotic heart disease and the WI score, both of which were significantly higher in the children with steroid treatment (Table 1). The laboratory results at the various time points are shown in Table 2 and Fig. 1.
The blood glucose levels at the start of surgery, before glucocorticoid treatment, did not differ between the groups (Fig. 1a). At the end of surgery, the blood glucose levels in the children treated with glucocorticoids were significantly higher than in those without glucocorticoid treatment. Hyperglycemia occurred significantly more often in the group that had glucocorticoid treatment (p = 0.001).
The effect of glucocorticoid treatment on the blood glucose levels at the end of surgery was independent of other parameters such as glucose intake, presence of cyanotic heart disease, WI score, and CPB time. At 12 and 24 h after surgery, the median blood glucose levels did not differ between the groups. The insulin levels and insulin–glucose ratios did not differ between the groups at any time point (Fig. 1b, c).
The maximum peak cortisol levels were found at the end of surgery, with significantly higher cortisol levels and cortisol–ACTH ratios in the children treated with glucocoricoids (Fig. 1d). At 12 and 24 h after surgery, the cortisol levels and cortisol–ACTH ratios of the children with glucocorticoid treatment had spontaneously decreased to the levels in the children without glucocorticoid treatment. In both groups, however, the cortisol levels still were higher than the levels at the start of surgery. The IL-6 level 12 and 24 h after surgery was significantly lower in the children treated with glucocorticoids. The IL-10 level at the end of surgery and 12 h after surgery was significantly higher in the children treated with glucocorticoids. There were no other differences in laboratory parameters between the two groups.
Our study showed that treatment with glucocorticoids during surgery was the main factor associated with the occurrence of hyperglycemia at the end of CPB surgery for congenital heart defects. Hyperglycemia frequently occurred with the highest blood glucose levels at the end of surgery and disappeared spontaneously (without insulin therapy) within 12–24 h in the majority of the children without significant postoperative morbidity.
The occurrence of hyperglycemia was not associated with increased morbidity, as shown by duration of ventilation, ICU stay, or hospital stay. Moreover, the overall morbidity in our population was low. The median duration of mechanical ventilation was 9 h, whereas the ICU say was 2 days and the hospital stay was 7 days. Renal dialysis and extracorporeal life support did not occur, and all the patients survived.
Hyperglycemia in critically ill children is caused by multiple proposed mechanisms including counterregulatory hormone-mediated upregulation of gluconeogenesis and glycogenolysis and downregulation of glucose transporters with decreased peripheral use of glucose by tissues such as skeletal muscle and liver .
In the current study, we evaluated how many hyperglycemic patients showed signs of insulin resistance because this is described as the main factor causing hyperglycemia in critically ill adults [23, 26, 36]. In only four children (9%) was an increased insulin–glucose ratio (>18 pmol/mmol) seen at the end of surgery. The remaining hyperglycemic children showed a normal or (relatively) decreased insulin–glucose ratio. The plasma insulin levels increased 24 h after surgery, which might have been due to the fact that most patients were detubated and already receiving enteral nutrition. The increase in insulin levels can be interpreted as a recovery response to the administered enteral feeding.
The decreased insulin response after surgery might be due to the fact that critically ill children seem to be more vulnerable than adults to beta-cell dysfunction. Preissig and Rigby  hypothesized that beta cells, known to be exquisitely sensitive to rapid physiologic changes, may become dysfunctional if these changes occur acutely above a certain threshold. These changes may be induced by multiple factors such as hypothermia, vasopressors, elevations of proinflammatory cytokines, and use of glucocorticoids [1, 9, 12, 20].
In the study by Preissig and Rigby , the vasopressor score of critically ill children with respiratory and cardiovascular failure was inversely correlated with the C-peptide level, indicating beta-cell dysfunction due to the suppressing effect of exogeneous catecholamines. In our study, the use of vasopressors was low, with only one patient receiving noradrenalin. This may explain the relatively normal plasma insulin levels at the end of surgery.
Another explanation for the less pronounced hypoinsulinemic response in our study might be the mild effect of cardiac surgery on the inflammatory response, as shown by the low levels of Il-6 and the mildly increased IL-10 at the end of surgery in the patients without glucocorticoid treatment. Perioperative administration of glucocorticoids was associated with decreased IL-6 and increased IL-10 levels after CPB. This accords with adult studies showing that glucocorticoids may decrease the inflammatory response during the CPB procedure . However, for pediatric patients with congenital heart disease undergoing CPB surgery, the clinical benefit of this suppressed cytokine response remains unclear.
Debate exists about the positive effects of steroid use during CPB in pediatric patients and whether the potential positive effects of corticosteroid treatment during CPB surgery outweigh the potential adverse effects, such as hyperglycemia [4, 22]. High blood glucose levels at the end of CPB surgery for congenital heart defects also were found in previous studies [1, 7, 21, 24]. We found a spontaneous normalization of blood glucose levels within 24 h postoperatively, which is in line with the finding of one other study . However, a few other studies show a more gradual decrease in blood glucose levels over 3 days [18, 35]. This could be related to our relatively low postoperative morbidity compared with other studies and comparable preoperative illness severity as expressed by RACHS.
Other authors  have reported an increase in ICU stay (median, 3–6 days), mechanical ventilation (4.4 days), dialysis (1.1–4%), extracorporeal life support (3–8%), and mortality (4–11%). Vlasselaers et al.  reported their results from a prospective randomized controlled trial of treatment for critically ill children (75% were patients after cardiac surgery for congenital heart defects). Intensive insulin therapy for hyperglycemia improved morbidity and reduced mortality, but the harm of insulin-induced hypoglycemic events is debated . It is important to realize that not only hyperglycemia but also hypoglycemia is associated with an adverse outcome [7, 25, 34, 35].
In general, important differences exist between centers in terms of morbidity and mortality after pediatric cardiac surgery. In our study, none of the patients were treated with insulin for hyperglycemia, and overall morbidity was low, so the standard use intensive insulin therapy is not needed for tight glycemic control.
A limitation of this study was that glucocorticoids were administered at the discretion of the attending anesthetist. Although treatment was not randomized, glucocorticoids were administered before aortic clamping and thus were independent of the operative course. Moreover, there were no differences in age, clinical course, or duration of CPB time between the patients with and those without glucocorticoid treatment. Furthermore, although the patients with cyanotic heart disease were more likely to receive glucocorticoids and although the median WI score was higher for the glucocorticoid-treated patients, univariate analysis of variance showed that preoperatively administered glucocorticoids were independently associated with increased blood glucose levels at the end of surgery.
In summary, our study showed that the development of hyperglycemia at the end of cardiac surgery for congenital heart disease was associated with glucocorticoid administration during surgery. Postoperative hyperglycemia was frequent, but in almost all cases (94%), blood glucose levels spontaneously normalized within 24 h without the use of insulin administration and without significant morbidity or mortality. The standard use of intensive insulin therapy for tight glycemic control is not needed in this patient group. In contrast to our hypothesis, we conclude that because postoperative morbidity was low in the study group, the presumed positive effects of glucocorticoids seemed to outweigh the adverse effects of iatrogenic hyperglycemia.
Future research should focus on the value of glucocorticoid therapy during pediatric cardiac surgery, weighing both the pros and cons of either hyperglycemia or glucocorticoid therapy.
The authors acknowledge research nurse M. Maliepaard for her assistance in data collection and K. Hagoort for his careful editing. They also are grateful to Dr. D. Tibboel for critically reviewing the manuscript.
Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
|1..||Benzing G III,Francis PD,Kaplan S,Helmsworth JA,Sperling MA. Glucose and insulin changes in infants and children undergoing hypothermic open heart surgeryAm J CardiolYear: 19835213313610.1016/0002-9149(83)90083-86344608|
|2..||Bouwmeester NJ,Anand KJ,Dijk M,Hop WC,Boomsma F,Tibboel D. Hormonal and metabolic stress responses after major surgery in children aged 0–3 years: a double-blind, randomized trial comparing the effects of continuous versus intermittent morphineBr J AnaesthYear: 20018739039910.1093/bja/87.3.39011517122|
|3..||Celik JB,Gormus N,Okesli S,Gormus ZI,Solak H. Methylprednisolone prevents inflammatory reaction occurring during cardiopulmonary bypass: effects on TNF-alpha, IL-6, IL-8, IL-10PerfusionYear: 20041918519110.1191/0267659104pf733oa15298427|
|4..||Chaney MA. Corticosteroids and cardiopulmonary bypass: a review of clinical investigationsChestYear: 200212192193110.1378/chest.121.3.92111888978|
|5..||Conwell LS,Trost SG,Brown WJ,Batch JA. Indexes of insulin resistance and secretion in obese children and adolescents: a validation studyDiabetes CareYear: 20042731431910.2337/diacare.27.2.31414747206|
|6..||Brinker M,Joosten KF,Liem O,Jong FH,Hop WC,Hazelzet JA,Dijk M,Hokken-Koelega AC. Adrenal insufficiency in meningococcal sepsis: bioavailable cortisol levels and impact of interleukin-6 levels and intubation with etomidate on adrenal function and mortalityJ Clin Endocrinol MetabYear: 2005905110511710.1210/jc.2005-110715985474|
|7..||Falcao G,Ulate K,Kouzekanani K,Bielefeld MR,Morales JM,Rotta AT. Impact of postoperative hyperglycemia following surgical repair of congenital cardiac defectsPediatr CardiolYear: 20082962863610.1007/s00246-007-9178-818176772|
|8..||Furnary AP. Clinical benefits of tight glycaemic control: focus on the perioperative settingBest Pract Res Clin AnaesthesiolYear: 20092341142010.1016/j.bpa.2009.10.00120108580|
|9..||Gesina E,Tronche F,Herrera P,Duchene B,Tales W,Czernichow P,Breant B. Dissecting the role of glucocorticoids on pancreas developmentDiabetesYear: 2004532322232910.2337/diabetes.53.9.232215331541|
|10..||Jenkins KJ,Gauvreau K,Newburger JW,Spray TL,Moller JH,Iezzoni LI. Consensus-based method for risk adjustment for surgery for congenital heart diseaseJ Thorac Cardiovasc SurgYear: 200212311011810.1067/mtc.2002.11906411782764|
|11..||Joosten K, Verbruggen SC, Verhoeven JJ (2009) Glycaemic control in paediatric critical care. Lancet 373:1423–1424 (author reply 1424)|
|12..||Lambillotte C,Gilon P,Henquin JC. Direct glucocorticoid inhibition of insulin secretion: an in vitro study of dexamethasone effects in mouse isletsJ Clin InvestYear: 19979941442310.1172/JCI1191759022074|
|13..||Lazar HL,McDonnell M,Chipkin SR,Furnary AP,Engelman RM,Sadhu AR,Bridges CR,Haan CK,Svedjeholm R,Taegtmeyer H,Shemin RJ. The Society of Thoracic Surgeons practice guideline series: blood glucose management during adult cardiac surgeryAnn Thorac SurgYear: 20098766366910.1016/j.athoracsur.2008.11.01119161815|
|14..||Leteurtre S,Martinot A,Duhamel A,Proulx F,Grandbastien B,Cotting J,Gottesman R,Joffe A,Pfenninger J,Hubert P,Lacroix J,Leclerc F. Validation of the paediatric logistic organ dysfunction (PELOD) score: prospective, observational, multicentre studyLancetYear: 200336219219710.1016/S0140-6736(03)13908-612885479|
|15..||Marik PE,Raghavan M. Stress hyperglycemia, insulin and immunomodulation in sepsisIntensive Care MedYear: 20043074875610.1007/s00134-004-2167-y14991101|
|16..||Mizock BA. Alterations in fuel metabolism in critical illness: hyperglycaemiaBest Pract Res Clin Endocrinol MetabYear: 20011553355110.1053/beem.2001.016811800522|
|17..||Parker MM,Hazelzet JA,Carcillo JA. Pediatric considerationsCrit Care MedYear: 200432S591S59410.1097/01.CCM.0000145904.97821.0D15542968|
|18..||Polito A,Thiagarajan RR,Laussen PC,Gauvreau K,Agus MS,Scheurer MA,Pigula FA,Costello JM. Association between intraoperative and early postoperative glucose levels and adverse outcomes after complex congenital heart surgeryCirculationYear: 20081182235224210.1161/CIRCULATIONAHA.108.80428619001022|
|19..||Pollack MM,Ruttimann UE,Getson PR. Pediatric risk of mortality (PRISM) scoreCrit Care MedYear: 1988161110111610.1097/00003246-198811000-000063048900|
|20..||Preissig CM,Rigby MR. Hyperglycaemia results from beta-cell dysfunction in critically ill children with respiratory and cardiovascular failure: a prospective observational studyCrit CareYear: 200913R2710.1186/cc773219245691|
|21..||Preissig CM,Rigby MR,Maher KO. Glycemic control for postoperative pediatric cardiac patientsPediatr CardiolYear: 2009301098110410.1007/s00246-009-9512-419705188|
|22..||Robertson-Malt S, Afrane B, El Barbary M (2007) Prophylactic steroids for pediatric open heart surgery. Cochrane Database Syst Rev CD005550|
|23..||Robinson LE,Soeren MH. Insulin resistance and hyperglycemia in critical illness: role of insulin in glycemic controlAACN Clin IssuesYear: 200415456210.1097/00044067-200401000-0000414767364|
|24..||Rossano JW,Taylor MD,Smith EO,Fraser CD Jr,McKenzie ED,Price JF,Dickerson HA,Nelson DP,Mott AR. Glycemic profile in infants who have undergone the arterial switch operation: hyperglycemia is not associated with adverse eventsJ Thorac Cardiovasc SurgYear: 200813573974510.1016/j.jtcvs.2007.11.03018374750|
|25..||Srinivasan G,Jain R,Pildes RS,Kannan CR. Glucose homeostasis during anesthesia and surgery in infantsJ Pediatr SurgYear: 19862171872110.1016/S0022-3468(86)80395-53528450|
|26..||Berghe G. How does blood glucose control with insulin save lives in intensive care?J Clin InvestYear: 20041141187119515520847|
|27..||Kuip M,Hoos MB,Forget PP,Westerterp KR,Gemke RJ,Meer K. Energy expenditure in infants with congenital heart disease, including a meta-analysisActa PaediatrYear: 20039292192710.1111/j.1651-2227.2003.tb00625.x12948067|
|28..||Waardenburg DA,Jansen TC,Vos GD,Buurman WA. Hyperglycemia in children with meningococcal sepsis and septic shock: the relation between plasma levels of insulin and inflammatory mediatorsJ Clin Endocrinol MetabYear: 2006913916392110.1210/jc.2006-052516735484|
|29..||Vanhorebeek I,Langouche L,Berghe G. Glycemic and nonglycemic effects of insulin: how do they contribute to a better outcome of critical illness?Curr Opin Crit CareYear: 20051130431110.1097/01.ccx.0000170506.61281.9416015107|
|30..||Verbruggen SC,Joosten KF,Castillo L,Goudoever JB. Insulin therapy in the pediatric intensive care unitClin NutrYear: 20072667769010.1016/j.clnu.2007.08.01217950500|
|31..||Vlasselaers D,Milants I,Desmet L,Wouters PJ,Vanhorebeek I,Heuvel I,Mesotten D,Casaer MP,Meyfroidt G,Ingels C,Muller J,Cromphaut S,Schetz M,Berghe G. Intensive insulin therapy for patients in paediatric intensive care: a prospective, randomised controlled studyLancetYear: 200937354755610.1016/S0140-6736(09)60044-119176240|
|32..||Vuguin P,Saenger P,Dimartino-Nardi J. Fasting glucose insulin ratio: a useful measure of insulin resistance in girls with premature adrenarcheJ Clin Endocrinol MetabYear: 2001864618462110.1210/jc.86.10.461811600513|
|33..||Wernovsky G,Wypij D,Jonas RA,Mayer JE Jr,Hanley FL,Hickey PR,Walsh AZ,Chang AC,Castaneda AR,Newburger JW,et al. Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants: a comparison of low-flow cardiopulmonary bypass and circulatory arrestCirculationYear: 199592222622357554206|
|34..||Wintergerst KA,Buckingham B,Gandrud L,Wong BJ,Kache S,Wilson DM. Association of hypoglycemia, hyperglycemia, and glucose variability with morbidity and death in the pediatric intensive care unitPediatricsYear: 200611817317910.1542/peds.2005-181916818563|
|35..||Yates AR,Dyke PC II,Taeed R,Hoffman TM,Hayes J,Feltes TF,Cua CL. Hyperglycemia is a marker for poor outcome in the postoperative pediatric cardiac patientPediatr Crit Care MedYear: 2006735135510.1097/01.PCC.0000227755.96700.9816738506|
|36..||Zauner A,Nimmerrichter P,Anderwald C,Bischof M,Schiefermeier M,Ratheiser K,Schneeweiss B,Zauner C. Severity of insulin resistance in critically ill medical patientsMetabolismYear: 2007561510.1016/j.metabol.2006.08.01417161218|
|Variable||Glucocorticoids (n = 32)||No glucocorticoids (n = 17)||All patients (n = 49)|
|Age: years (range)||1.4 (0.5–6.2)||3.2 (0.6–13.3)||1.7 (0.5–8.7)|
|Weight: kg (range)||8.7 (6.6–18.2)||13.0 (6.3–42.0)||12.3 (6.6–24.4)|
|Body mass index: kg/m2 (range)||14.8 (13.6–15.9)||15.1 (14.3–17.5)||14.9 (14.1–16.3)|
|Congestive heart failure: n (%)||11/32 (34)||3/17 (18)||14/49 (29)|
|Cyanotic heart disease: n (%)||10/32 (31)a||1/17 (6)||11/49 (22)|
|RACHS score (range)||3 (2–3)||2 (1–3)||3 (2–3)|
|PRISM score (range)||14 (11–17)||13 (11–17)||13 (11–17)|
|PELOD score (range)||11(1–11)||6 (1–11)||11 (1–11)|
|WI score: n (range)||38 (22–54)a||3 (0–28)||30 (0–45)|
|CPB time: min (range)||78 (55–126)||64 (44–117)||73 (50–120)|
|Aortic crossclamp time: min (range)||50 (37–90)||39 (25–83)||45 (34–86)|
|Hypothermia: °C (range)||30.0 (28.7–31.7)||32.4 (29.8–34.1)||31.0 (28.8–33.0)|
|Glucose intake: mg/kg/min (range)b||3.5 (1.8–7.4)||3.3 (1.0–6.2)||3.4 (1.8–6.5)|
|Ventilation duration: h (range)||11 (7–25)||7 (6–11)||9 (6–17)|
|Inotropes: n (%)||24 (75)||6 (35)||30 (61)|
|Length of ICU stay: days (range)||2 (2–2)||2 (2–2)||2 (2–2)|
|Length of hospital stay: days (range||7 (7–9)||7 (7–8)||7 (7–8)|
Data are expressed as median (interquartile range) or numbers (percentage)
RACHS risk adjustment for congenital heart surgery, PRISM score pediatric risk of mortality score, PELOD score pediatric logistic organ dysfunction score, WI score weighted inotropic score based on maximum inotropic support during surgery and ICU stay, CPB cardiopulmonary bypass, ICU intensive care unit
aDenotes significant difference between patients treated with and without glucocorticoids, P < 0.05
bGlucose intake started at ICU admission
Time course of laboratory parameters for patients with and those without glucocorticoid treatmenta
|Variable||Glucocorticoids||No glucocorticoids||All patients|
|Start||End||12 h||24 h||Start||End||12 h||24 h||Start||End||12 h||24 h|
|Glucose (mmol/l)||4.8 (4.1–5.1)||9.5a (7.6–10.8)||6.8 (4.9–7.5)||6.2 (5.4–7.2)||4.6 (4.2–4.9)||7.4a (5.9–8.2)||5.5 (4.5–7.1)||6.6 (5.2–7.4)||4.7 (4.1–5.0)||8.5 (6.7–10.4)||6.3 (4.9–7.4)||6.2 (5.4–7.2)|
|Insulin (pmol/l)||15 (14–20)||59 (39–76)||36 (14–71)||63 (29–94)||17 (14–34)||41 (27–57)||33 (14–60)||75 (22–140)||15 (14–21)||54 (28–74)||34 (14–64)||66 (29–101)|
|Insulin/glucose (pmol/mmol)||3 (3–4)||6 (4–8)||5 (3–9)||10 (5–15)||4 (3–6)||5 (4–10)||7 (3–12)||10 (4–19)||4 (3–5)||6 (4–9)||5 (3–9)||10 (5–15)|
|Cortisol (nmol/l)||213 (165–308)||6972b (5,409–8,327)||1185 (549–1,729)||352 (170–1,077)||156 (109–274)||250b (111–516)||1037 (581–1497)||627 (447–917)||203 (130–302)||5455 (340–7280)||1158 (549–1713)||590 (222–943)|
|ACTH (pmol/l)||2.2 (2.1–2.8)||3.6 (1.5–10.7)||2.1b (1.0–2.2)||2.1 (1.0–2.2)||2.2 (2.1–2.6)||2.6 (2.1–7.1)||3.6 b (2.4–7.9)||2.2 (1.2–2.5)||2.2 (2.1–2.8)||3.3 (1.9–8.3)||2.2 (1.4–3.6)||2.1 (1.0–2.2.)|
|Cortisol/ACTH (kmol/mol)||90a (66–135)||1485b (522–3,126)||590b (309–1184)||239 (109–547)||58a (43–104)||61b (36–96)||263b (91–489)||293 (169–463)||80 (56–115)||557 (79–2197)||489 (228–823)||276 (116–504)|
|Lactate (mmol/l)||0.9 (0.7–1.1)||1.7 (1.3–2.6)||1.3 (1.0–1.8)||1.3 (0.9–1.5)||0.9 (0.8–1.1)||1.6 (1.1–1.9)||1.3 (1.1–1.6)||1.3 (1.0–1.6)||0.9 (0.7–1.1)||1.6 (1.3–2.4)||1.3 (1.0–1.8)||1.3 (1.3–1.5)|
|IL-6 (pg/ml)||10||21 (10–35)||27b (15–44)||18a (10–26)||10||26 (10–43)||56b (40–90)||41a (21–48)||<10||22 (10–40)||38 (20–55)||19 (10–40)|
|IL-10 (pg/ml)||25||274b (101–363)||25 (25–37)||25 (25–25)||25||61b (27–82)||25 (25–25)||25 (25–25)||25 (25–25)||157 (69–294)||25 (25–28)||25 (25–25)|
ACTH adrenocorticotrope hormone, IL interleucine
Laboratory parameters at start of surgery, end of surgery, and 12 and 24 h after surgery of patients treated with and without glucocorticoids. Data are expressed as median (interquartile range)
aSignificant difference between patients treated with and without glucocorticoids (p < 0.05)
bSignificant difference between patients treated with and without glucocorticoids (p < 0.001)
Keywords: Keywords Cardiac surgery, Child, Critical illness, Glucocorticoids, Hyperglycemia, Insulin.
Previous Document: Early Echocardiographic Findings in ?-Thalassemia Intermedia Patients Using Standard and Tissue Dopp...
Next Document: A 2-year assessment of the main environmental factors driving the free-living bacterial community st...