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Characterization of the Glucocorticoid Receptor in Children Undergoing Cardiac Surgery.

ABSTRACT: OBJECTIVES:Postoperative administration of corticosteroids is common practice for managing catecholamine refractory low cardiac output syndrome. Since corticosteroid activity is dependent on the glucocorticoid receptor, we sought to characterize glucocorticoid receptor levels in children undergoing cardiac surgery and examined the association between glucocorticoid receptor levels and cardiovascular dysfunction. DESIGN:Prospective observational cohort study. SETTING:Large, tertiary pediatric cardiac center. SUBJECTS:Children undergoing corrective or palliative cardiac surgery. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:A prospective observational cohort study was conducted in 83 children with congenital heart disease. Total glucocorticoid receptor levels were measured in the peripheral WBCs using flow cytometry. In addition, blood samples were collected for total cortisol levels. The primary outcome studied was the time to being inotrope free. An increase in glucocorticoid receptor level from postoperative day 1 to postoperative day 3 was associated with a longer time to being inotrope free (hazard ratio, 0.49 [0.29-0.81]; p = 0.01) in the univariate analysis. This association remained significant after adjusting for age, weight, cardiopulmonary bypass time, cross clamp time, Risk Adjustment for Congenital Heart Surgery-1 score, and postoperative steroid use (hazard ratio, 0.53 [0.29-0.99]; p = 0.05). Postoperative day 3 glucocorticoid receptor level showed a trend to have longer time to being inotrope free (hazard ratio, 0.66 [0.42-1.02]; p = 0.0.06). The cortisol levels minimally increased during the study duration and did not correlate with glucocorticoid receptor levels. CONCLUSIONS:Increasing glucocorticoid receptor levels in peripheral WBCs of children undergoing cardiac surgery are associated with a longer time to being inotrope free. Cortisol levels minimally increased during the study duration. These results suggest that exposure to high-dose perioperative corticosteroids may suppress the hypothalamic-pituitary-adrenal axis leading to increase in glucocorticoid receptor levels in response to a low cortisol environment. Further studies are required to better delineate the interplay between glucocorticoid receptor levels, cortisol levels, corticosteroid exposure, and postoperative inotropic requirements.

SUBMITTER: Flores S

PROVIDER: S-EPMC6086750 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Characterization of the Glucocorticoid Receptor in Children Undergoing Cardiac Surgery.

Flores Saul S Cooper David S DS Opoka Amy M AM Iliopoulos Ilias I Pluckebaum Sarah S Alder Matthew N MN Krallman Kelli A KA Sahay Rashmi D RD Fei Lin L Wong Hector R HR

Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies 20180801 8

<h4>Objectives</h4>Postoperative administration of corticosteroids is common practice for managing catecholamine refractory low cardiac output syndrome. Since corticosteroid activity is dependent on the glucocorticoid receptor, we sought to characterize glucocorticoid receptor levels in children undergoing cardiac surgery and examined the association between glucocorticoid receptor levels and cardiovascular dysfunction.<h4>Design</h4>Prospective observational cohort study.<h4>Setting</h4>Large, ...[more]

PMID: 29677033

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Project description:BackgroundLevosimendan has pharmacologic and hemodynamic advantages over conventional intravenous inotropic agents. It has been used mainly as a rescue drug in the pediatric intensive care unit or in the operating room. We present the largest single-center experience of levosimendan in children.MethodsRetrospective analysis of all children who received levosimendan infusions between July 5, 2001 and July 4, 2010 in a pediatric intensive care unit. The results of a questionnaire for physicians (anesthesiologist/intensivists, cardiologists and cardiac surgeons) concerning their clinical perceptions of levosimendan are evaluatedResultsDuring the study period a total of 484 infusions were delivered to 293 patients 53% of whom were male. The median age of the patients was 0.4 years (4 hours-21.1 years) at the time of levosimendan administration. A majority of levosimendan infusions were administered to children who were undergoing cardiac surgery (72%), 14% to children with cardiomyopathy and 14% to children with cardiac failure. Eighty-nine out of the 293 patients (30.4%) received repeated doses of levosimendan (up to 11 infusions). The most common indication for the use of levosimendan (94%) was when the other inotropic agents were insufficient to maintain stable hemodynamics. Levosimendan was especially used in children with cardiomyopathy (100%) or with low cardiac output syndrome (94%). A majority (89%) of the respondents believed that levosimendan administration postponed the need for mechanical assist devices in some children with cardiomyopathy. Moreover, 44% of respondents thought that the mechanical support was totally avoided in some patients undergoing cardiac surgery after receiving levosimendan.ConclusionLevosimendan is widely used in our institution and many physicians believe that its use could decrease the need for mechanical support in children undergoing cardiac surgery or in children with decompensated heart failure. However, there is a lack of good empirical evidence in children to support this perception.

Project description:Background: The benefit-risk profile of perioperative corticosteroids in pediatric patients undergoing cardiac surgery remains controversial. Objective: To investigate the influence of perioperative corticosteroids on the postoperative mortality and clinical outcomes in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass. Methods: We conducted a systematic search using MEDLINE, EMBASE, and Cochrane Database through August 31, 2019. We included randomized controlled trials comparing perioperative corticosteroids with other clinical interventions, placebo, or no treatment in children between 0 and 18 years of age undergoing cardiac surgery. The primary outcome of interest was all-cause in-hospital mortality. The secondary outcomes were length of intensive care unit stay (LOIS), duration of mechanical ventilation (DMV), postoperative insulin therapy, postoperative low cardiac output syndrome (LCOS), postoperative infection, maximal temperature (T max) in the first 24 h postoperatively, urine output (UO) in the first 24 h postoperatively, serum lactate at postoperative day (POD) 1, blood glucose at POD 1, vasoactive inotrope score (VIS) at POD 1, and postoperative acute kidney injury (AKI). Study quality was assessed using the Cochrane Risk of Bias Assessment Tool. Results: Our analysis included 17 studies and 848 pediatric patients. The data demonstrated that children receiving corticosteroids showed no significant difference on the all-cause in-hospital mortality with a fixed-effect model (RR = 0.59, 95% CI = 0.28-1.25, P = 0.55) compared with controls. For the secondary outcomes, corticosteroids had a statistically significant reduction on the VIS at POD1 (MD = -2.04, 95% CI = -3.96 -0.12, P = 0.04), while it might be significantly associated with an increased blood glucose at POD1 (MD = 1.38, 95% CI = 0.68-2.09, P = 0.0001) and a 2.69-fold higher risk of postoperative insulin therapy (RR = 2.69, 95% CI = 1.37-5.27, P = 0.004). No statistical significance was shown in other secondary outcomes. Conclusion: Perioperative corticosteroids might not significantly improve clinical outcomes identified as mortality, LOIS, DMV, AKI, and LCOS other than VIS at POD1. However, it might increase the blood glucose and episodes of insulin therapy. Perioperative corticosteroids to attenuate the inflammatory response are not supported by available evidence from our study. Further results from ongoing randomized controlled trials with a larger sample size are required.

Project description:IntroductionCardiac surgery (CS) in pediatric patients induces an overt oxidative stress (OS) response. Children are particularly vulnerable to OS related injury. The immaturity of their organs and antioxidant systems as well as the induction of OS in cardio-pulmonary bypass (CPB) surgery may have an important impact on outcomes. The purpose of this study was to describe the OS response, measured by urinary free 8-iso-PGF2α, in infants undergoing CS and to evaluate the relationship between OS response and post-operative clinical outcomes.MethodsInfants with congenital heart disease undergoing CS with or without CPB were eligible for enrollment. Children were classified as neonates (<30 days) or infants (30 days-6 months) based on the age at surgery. Perioperative continuous non-invasive neuromonitoring included amplitude-integrated electroencephalogram and cerebral regional oxygen saturation measured with near-infrared spectroscopy. Urine 8-iso-PGF2α levels were measured before, immediately post-, and 24-hours post-surgery, and the 8-iso-PGF2 clearance was calculated.ResultsSixty-two patients (60% neonates) were included. Urine 8-iso-PGF2α levels 24 hours after surgery (8.04 [6.4-10.3] ng/mg Cr) were higher than pre-operative levels (5.7 [4.65-7.58] ng/mg Cr) (p<0.001). Those patients with a severe degree of cyanosis caused by Transposition of the Great Arteries (TGA) had the highest post-operative 8-iso-PGF2α levels. Patients with intra-operative seizures had higher post-operative 8-iso-PGF2α levels. 8-iso-PGF2α clearance at 24 hours post-surgery was different between newborns and infant patients, and it was inversely correlated with days of mechanical ventilation (p = 0.05), ICU LOS (p = 0.05) and VIS score at 24 hours (p = 0.036).ConclusionsChildren undergoing CS, particularly neonatal patients, experience a significant post-operative OS response that might play an important role in postoperative morbidity. TGA patients undergoing arterial switch operations demonstrate the highest post-operative OS response. Rapid clearance of isoprostanes, which occurs more frequently in older patients with more mature antioxidant systems, might be associated with better clinical outcomes.

Project description:BackgroundLow cardiac output syndrome (LCOS) is an important complication of cardiac surgery. It is associated with increased morbidity and mortality. The incidence of LCOS after surgery is high in patients with congenital heart disease (CHD). Therefore, determining the risk factors of LCOS has clinical significance for the management of CHD. This study aimed to analyze the risk factors of LCOS.MethodsWe conducted a retrospective analysis of children with CHD who underwent cardiac surgery at Shanghai Children's Medical Center between January 1, 2014, and December 31, 2017. Demographic characteristics and baseline data were extracted from the health data resource center of the hospital, which integrates clinical routine data including medical records, diagnoses, orders, surgeries, laboratory tests, imaging, nursing, and other subsystems. Logistic regressions were performed to analyze the risk factors of LCOS.ResultsOverall, 8660 infants with CHD were included, and 864 (9.98%) had LCOS after surgery. The multivariate regression analysis identified that age (OR 0.992, 95% CI: 0.988-0.997, p = 0.001), tricuspid regurgitation (1.192, 1.072-1.326, p = 0.001), Risk Adjustment in Congenital Heart Surgery-1 risk grade (1.166, 1.011-1.345, p = 0.035), aortic shunt (left-to-right: 1.37, 1.005-1.867, p = 0.046; bi-directional: 1.716, 1.138-2.587, p = 0.01), atrial shunt (left-to-right: 1.407, 1.097-1.805, p = 0.007; right-to-left: 3.168, 1.944-5.163, p < 0.001; bi-directional: 1.87, 1.389-2.519, p < 0.001), ventricular level shunt (left-to-right: 0.676, 0.486-0.94, p = 0.02; bi-directional: 2.09, 1.611-2.712, p < 0.001), residual shunt (3.489, 1.502-8.105, p = 0.004), left ventricular outflow tract obstruction (3.934, 1.673-9.254, p = 0.002), right ventricular outflow tract obstruction (3.638, 1.225-10.798, p = 0.02), circulating temperature (mild hypothermia: 1.526, 95% CI: 1.205-1.934, p < 0.001; middle and low temperature: 1.738, 1.236-2.443, p = 0.001), duration of cardiopulmonary bypass (1.009, 1.006-1.012, p < 0.001), myocardial preservation using histidine-tryptophan-ketoglutarate (1.677, 1.298-2.167, p < 0.001), and mitral insufficiency (1.714, 1.239-2.37, p < 0.001) were independent risk predictors of LCOS.ConclusionsThe incidence of postoperative LCOS in CHD children remains high. Circulation temperature, myocardial preservation using histidine-tryptophan-ketoglutarate, and usage of residual shunt after surgery were independent risk predictors for LCOS.

Dataset Information

Characterization of the Glucocorticoid Receptor in Children Undergoing Cardiac Surgery.

Publications

Characterization of the Glucocorticoid Receptor in Children Undergoing Cardiac Surgery.

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