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Background: Corticosteroids suppress the inflammatory response to cardiopulmonary bypass in children undergoing cardiac surgery. What is less clear is the impact of corticosteroids on the postoperative course., Methods: A systematic review and meta-analysis was made of prospective randomized blinded placebo-controlled trials of pediatric patients who received corticosteroids or saline placebo before surgery was performed. Ten studies met inclusion criteria for a total of 768 patients. In a prespecified subgroup analysis, studies that either were limited to The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery congenital heart surgery mortality categories 1 and 2 or excluded neonates were eliminated and a secondary analysis was conducted, which consisted of seven studies and 555 patients., Results: Corticosteroids were associated with a significant improvement in fluid balance at 24 and 36 hours after surgery, with a mean difference of -15.2 mL/kg (95% confidence interval, 25.3 to -5.1 mL/kg; P < .01) and -5.7 mL/kg (95% confidence interval, -9.8 to -1.6 mL/kg; P < .01), respectively. Corticosteroids had no impact on the incidence of infection or mortality. With the secondary analysis, corticosteroids were associated with a trend toward significance in shortening the duration of mechanical ventilation (mean difference -0.7 days; 95% confidence interval, -1.7 to 0.1; P = .08)., Conclusions: Corticosteroids were found to have a favorable impact on postoperative fluid balance and may be associated with shortening the duration of mechanical ventilation. Although corticosteroids had no impact on mortality, they may be beneficial particularly for neonates and patients undergoing highly complex surgery., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Thyroid hormone modifies metabolic, immune and cardiovascular functions and has been administered perioperatively to treat a relative reduction of thyroid function in children following cardiopulmonary bypass (CPB) for correction of congenital heart disease. However, it remains unclear whether its use is associated with improved outcomes. We performed a meta-analysis of studies that evaluated the impact of thyroid hormone supplementation on clinical outcomes in children undergoing repair of congenital heart disease using CPB. A systematic review of published trials was conducted to identify studies of children randomized to thyroid hormone supplementation or placebo undergoing congenital heart surgery. A meta-analysis was then conducted to determine the clinical impact of thyroid hormone replacement on cardiac function and postoperative characteristics. The following outcomes were included for the study: duration of mechanical ventilation, duration of intensive care unit (ICU) stay, duration of postoperative hospital stay, inotrope score, cardiac index at 24 hours postoperatively, and inpatient mortality. A total of 9 studies with 711 patients were included in the analyses. All included studies were prospective and patients were randomized to either thyroid hormone or placebo. There was wide variation in thyroid hormone dosing, ranging from 0.4 μg/kg up to 5 μg/kg over a 24-hour period, and duration of therapy, ranging from a single dose after cessation of CPB to continued thyroid hormone for the duration of the ICU stay. There was a significant difference in the mean inotrope score between the 2 groups of -1.249 (95% confidence interval -1.570 to -0.929, P < 0.001), with the inotrope score being significantly lower in the thyroid group. There was no difference in duration of mechanical ventilation, duration of ICU stay, duration of hospital stay, cardiac index, and mortality between groups. In this meta-analysis, routine thyroid hormone replacement with approximately 1-5 μg/kg administered over 24 hours does not significantly alter the postoperative course in children following CPB. However, given a clinically small but significant difference in respect to lower inotrope score and shorter duration of ICU and hospital stays with higher thyroid replacement additional studies are warranted., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A surge in cortisol levels is seen after surgery with cardiopulmonary bypass (CPB). Based on evidence of attenuation of the cortisol response to repeated stress in other settings, we hypothesized that the magnitude of cortisol increase in children after a second exposure to CPB would be reduced. Serial cortisol levels were measured at three time points after each CPB: immediately (day 0), on the first morning (day 1), and second morning (day 2). Forty-six children underwent two surgeries with CPB during the study period. The mean age (standard deviation) at first and second surgery was 3.5 (6.3) months and 10.4 (9.9) months, respectively. Cortisol levels at the first surgery were 109 (105) µg/dl, 29 (62) µg/dl, and 17 (12) µg/dl on day 0, 1, and 2, respectively; similarly at second surgery, it was 61 (57) µg/dl on day 0 to 20 (16) µg/dl and 11 (10) µg/dl on day 1 and 2, respectively. After log-transformation and adjusting for time interval between surgeries, cortisol levels at the second surgery were lower by 42% on day 0 (p = 0.02), and 46% lower on day 2 (p = 0.02). A second exposure to CPB in children with congenital heart disease is associated with an attenuated cortisol release.

Introduction Maternal obesity is associated with an increased risk for adverse perinatal outcomes. Obesity is also associated with a chronic inflammatory state and metabolic derangements that affect the newborn. The additional use of cardiopulmonary bypass during the neonatal period could impact the systemic inflammatory response in the immediate postoperative period that manifests as cardiac depression and multi-organ dysfunction. This study aimed to determine the association of maternal obesity and excessive weight gain during pregnancy with the immediate postoperative morbidity of neonatal patients undergoing cardiopulmonary bypass., Methods: A retrospective review of neonates who underwent cardiopulmonary bypass within the first 30 days of life at our institution between 2011 and 2013 was conducted. Postoperative variables investigated included the duration of length of mechanical ventilation, length of stay in the ICU, peak vasoactive inotrope scores, and peak lactate level. Maternal obesity was defined as 1st trimester body mass index ⩾30 kg/m2. Excessive weight gain was defined as ⩾12 kg gained during pregnancy. In order to determine the association between maternal obesity or excessive weight gain and postoperative variables, we used multiple linear regression, adjusting for birth weight and risk adjustment for congenital heart surgery score., Results: Records from 58 mother-baby dyads were examined. After controlling for birth weight and risk adjustment for congenital heart surgery score, there were no significant associations between maternal obesity and excessive weight gain during pregnancy versus all postoperative outcomes measured., Conclusion: Despite the known negative impact of maternal obesity on perinatal outcomes, we were unable to find associations between maternal obesity and excessive weight gain during pregnancy versus postoperative outcomes.

Objective: Cardiac surgery requiring cardiopulmonary bypass and cardioplegic arrest leads to myocardial ischemic and reperfusion injury. Gaseous nitric oxide has been demonstrated to have a myocardial protective effect following ischemia-reperfusion. We hypothesized that gaseous nitric oxide administered during cardiopulmonary bypass would have similar beneficial effects., Methods: In a prospective, randomized, blinded, placebo-controlled study, children undergoing repair of tetralogy of Fallot received either 20 ppm of gaseous nitric oxide or placebo delivered to the membrane oxygenator during cardiopulmonary bypass., Results: A total of 16 children were randomized into 2 equal groups once their parents or guardians had given written informed consent. No differences were found in age, crossclamp time, cardiopulmonary bypass time, or methemoglobin between the 2 groups. The group receiving gaseous nitric oxide had a significantly shortened duration of mechanical ventilation (8.4 ± 7.6 vs 16.3 ± 6.5 hours; P < .05) and intensive care unit length of stay (53.8 ± 19.7 vs 79.4 ± 37.7 hours; P < .05) compared with the placebo group. The patients had significantly lower troponin levels at 12, 24, and 48 hours (P < .05) and lower B-type natriuretic peptide levels at 12 and 24 hours (P < .05). A trend was found toward a less positive fluid balance, with significantly less diuretic usage. The study patients had a greater mean hemoglobin at 48 hours, despite the absence of differences in chest tube output, packed red blood cell transfusion, platelet counts or transfusion requirements, fresh frozen plasma transfusion, or prothrombin time/partial thromboplastin time in the first 48 hours., Conclusions: The delivery of gaseous nitric oxide to the cardiopulmonary bypass circuit for children undergoing cardiac surgery results in myocardial protection, improved fluid balance, and an improved postoperative intensive care unit course., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Objectives: We sought to determine the effect of cardiopulmonary bypass and surgical intervention on the natriuretic hormone system in children and to assess whether such changes are associated with morbidity., Methods: At 6 perioperative time points in 25 patients, plasma levels of atrial natriuretic peptide, brain natriuretic peptide, and guanosine 3', 5'-monophosphate were measured, and the biologic activity of the natriuretic hormone system was quantified. Relationships were sought between changes in brain natriuretic peptide levels, biologic activity, and a number of morbidity indicators., Results: There was a significant change in atrial natriuretic peptide levels (P = .037), brain natriuretic peptide levels (P = .001), and biologic activity of the natriuretic hormone system (P = .009) over the first 4 time points in the study. Atrial natriuretic peptide levels transiently decreased from baseline to 12 hours after surgical intervention. Compared with baseline values, brain natriuretic peptide levels were increased at 12 hours after surgical intervention and on postoperative day 1. The increase in brain natriuretic peptide levels from baseline to 12 hours after surgical intervention was associated with cardiopulmonary bypass time (r(s) = 0.4, P = .047). The biologic activity transiently decreased from baseline to intensive care unit admission but was not associated with any morbidity indicators., Conclusions: Increased postoperative brain natriuretic peptide levels are associated with longer bypass times. The biologic activity of the natriuretic hormone system is transiently impaired. Larger studies should investigate brain natriuretic peptide as a predictor of postoperative morbidity and the potential for natriuretic hormone infusions to improve postoperative hemodynamics and urine output.

Objective: Steroid administration before pediatric cardiac operations using cardiopulmonary bypass has been shown to modulate the inflammatory response and reduce myocardial injury. We hypothesized that current steroid administration practices among pediatric cardiac surgical centers are highly variable., Design: Questionnaire survey., Setting: Pediatric intensive care units., Subjects: All members of the Pediatric Cardiac Intensive Care Society., Interventions: A self-administered survey was sent to >130 members and 70 institutions participating in the Pediatric Cardiac Intensive Care Society., Measurements and Main Results: Thirty-six questionnaires were returned: 14 international and 22 domestic centers. Cumulatively, these centers treat >11,000 pediatric cardiac patients per year. Ninety-seven percent (35 of 36) of these centers report the use of steroids before cardiopulmonary bypass, yet only 40% (14 of 35) administer steroids with every case. Of the 21 centers that selectively use steroids, 12 do so only for neonates, five administer steroids based on surgeon preference, and four administer steroids for cases anticipated to involve bypass time >2 hrs or deep hypothermic circulatory arrest. Of the 35 centers using steroids, 11 deliver a single dose in the circuit prime, 18 administer a single dose to the patient, and six give multiple doses. The timing of the steroid dose to the patient is variable; 12 centers administer a dose on induction of anesthesia; six centers administer the dose 2-12 hrs before operation. Regimens in the six centers using multiple doses of steroids before cardiopulmonary bypass are as follows: administration at induction and in the prime (two centers); 12 hrs preoperatively and at induction (one center); prime, induction, and 6 hrs preoperatively (one center); prime and midnight preoperatively (one center); and prime plus 2 and 8 hrs preoperatively (one center). Eight centers continue steroid administration following bypass., Conclusion: Although nearly all centers surveyed administer steroids before cardiopulmonary bypass, the type, dosing, route, and timing of administration are highly variable. The inconsistencies in these data and the pediatric literature would support the undertaking of a large, multiple-center clinical trial to evaluate the risks and benefits of steroid administration before pediatric cardiopulmonary bypass.

This study examined changes in the natriuretic hormone system in five infants with congestive heart failure (CHF) due to intracardiac left-to-right shunting who were exposed to cardiopulmonary bypass (CPB) during surgical repair. Plasma concentrations of three hormones [atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and dendroaspis natriuretic peptide (DNP)] and their secondary messenger, guanosine 3',5'-monophosphate (cGMP), were measured, and the biological activity of the system was quantified. At baseline, BNP and DNP concentrations were normal in our patients, a finding that is strikingly different from that of adult CHF patients, whereas ANP concentrations were elevated. Following CPB, ANP concentrations decreased (median, 175 vs 44 pg/ml; p = 0.043) and BNP concentrations increased (median, 25 vs 66 pg/ ml; p = 0.043), whereas DNP concentrations did not change. Following modified ultrafiltration, BNP concentrations increased (p = 0.043), but other natriuretic peptide concentrations did not change. The calculated biological activity of the natriuretic hormone system decreased following CPB [molar ratio, cGMP / (ANP + BNP + DNP); median, 213 vs 127; p = 0.043)]. Additional studies are needed to expand on these findings and identify patients with other types of congenital heart disease who have perioperative disturbances in the natriuretic hormone system and thus might benefit from pharmacologic intervention.

Objective: We previously demonstrated that dexamethasone treatment before cardiopulmonary bypass in children reduces the postoperative systemic inflammatory response. The purpose of this study was to test the hypothesis that dexamethasone administration before cardiopulmonary bypass in children correlates with a lesser degree of myocardial injury as measured by a decrease in cardiac troponin I release., Design: A prospective, randomized, double-blind study., Setting: The cardiac surgery operating room and intensive care unit of a pediatric referral hospital., Subjects: Twenty-eight patients who underwent open-heart surgery for congenital heart defects., Interventions: Patients received either placebo (group I, n = 13) or dexamethasone, 1 mg/kg iv (group II, n = 15), 1 hr before initiation of cardiopulmonary bypass. Plasma cardiac troponin I samples were obtained at three time points: immediately before study agent (sample 1), 10 mins after protamine sulfate administration after cardiopulmonary bypass (sample 2), and 24 hrs postoperatively (sample 3)., Measurements and Main Results: Mean cardiac troponin I levels (+/-sd) were significantly lower at sample time 3 in group II (dexamethasone; 33.4 +/- 20.0 ng/mL) vs. group I (control; 86.9 +/- 81.1) (p =.04)., Conclusion: Dexamethasone administration before cardiopulmonary bypass in children resulted in a significant decrease in cardiac troponin I levels at 24 hrs postoperatively. We postulate that this may represent a decrease in myocardial injury, and, thus, a possible cardioprotective effect produced by dexamethasone.