Triiodothyronine Supplementation in Infants Undergoing Cardiopulmonary Bypass: A Randomized Controlled Trial.

Cardiopulmonary bypass (CPB) profoundly suppresses circulating thyroid hormone levels in infants. We performed a multicenter randomized placebo controlled trial to determine if triiodothyronine (T3) supplementation improves reduces time to extubation (TTE) in infants after CPB. Infants (n = 220) undergoing cardiac surgery with CPB and stratified into 2 age cohorts: ≤30 days and >30 days to <152 days were randomization to receive either intravenous triiodothyronine or placebo bolus followed by study drug infusion until extubated or at 48 hours, whichever preceded. T3 did not significantly alter the primary endpoint, TTE (hazard ratio for chance of extubation (1.08, 95% CI: 0.82-1.43, P = 0.575) in the entire randomized population with censoring at 21 days. T3 showed no significant effect on TTE (HR 0.82, 95% CI:0.55-1.23, P = 0.341) in the younger subgroup or in the older (HR 1.38, 95% CI:0.95-2.2, P = 0.095). T3 also did not significantly impact TTE during the first 48 hours while T3 levels were maintained (HR 1.371, 95% CI:0.942-1.95, P = 0.099) No significant differences occurred for arrhythmias or other sentinel adverse events in the entire cohort or in the subgroups. This trial showed no significant benefit on TTE in the entire cohort. T3 supplementation appears safe as it did not cause an increase in adverse events. The study implementation and analysis were complicated by marked variability in surgical risk, although risk categories were balanced between treatment groups.

Congenital heart disease in low-birth-weight infants: effects of small for gestational age (SGA) status and maturity on postoperative outcomes.

Few studies have examined the role that small for gestational age (SGA) status plays in postoperative outcomes for low-birth-weight (LBW) infants with congenital heart disease (CHD). This study aimed to examine the effect of SGA status, gestational and chronologic age, and weight on differences in morbidities and mortalities during the immediate postoperative hospitalization period. The charts of infants with CHD weighing less than 2.5 kg who underwent operative repair during the neonatal period between 2004 and 2011 were reviewed. Infants with an isolated patent ductus arteriosus were excluded from the study. Data on hospital morbidities and mortality before discharge were collected. The study identified 136 LBW infants with a diagnosis of CHD. Among the 74 infants who underwent surgery and had complete chart records, the SGA infants had a higher gestational age at birth (36.8 vs. 32.3 weeks; p < 0.0001). The SGA and non-SGA infants did not differ in terms of survival to discharge or immediate postoperative outcomes. A lower weight at surgery was significantly associated with an increased risk of postoperative infection. In contradistinction, an older postnatal age at surgery was associated with an increased risk of preoperative infection (p < 0.0001). Additionally, lower gestational age at birth was associated with home oxygen use, higher tracheostomy rates, and discharge with a gastrostomy tube. Small for gestational age status played no protective role in the outcome for LBW infants after primary surgery for CHD. A weight of 2.4 kg or greater at the time of surgery was associated with lower rates of postoperative infections. Greater duration of time between birth and surgery was associated with a greater risk of preoperative infection. A gestational age of 32 weeks or more at birth was associated with decreased morbidities, which could influence obstetric management.

Impaired c-src activation and motility defects in PEA3-null fibroblasts.

Null mutations in the pea3 allele compromise the capacity of mammary tumors to metastasize in MMTV-Neu/ErbB2/HER2 transgenic mice, indicating a motility defect in PEA3-null cells. Cellular and biochemical analyses of established PEA3-null fibroblasts show impaired motility and aberrant localization of adhesion proteins in spreading cells. Our results show that PEA3-/- cells express normal levels of key adhesion components, but that spreading PEA3-null cells fail to activate c-src and to downregulate phospho-FAK(Y397), suggesting that focal adhesion signaling is impaired. Supporting this, biochemical analysis revealed that adhesion complex-associated proteins such as p130Cas failed to undergo tyrosine phosphorylation and dissociated from the adhesion complex with delayed kinetics. Overall our data show that the motility defects observed in PEA3-null cells are due to altered adhesion signaling.

Triiodothyronine Supplementation in Infants and Children Undergoing Cardiopulmonary Bypass (TRICC): a multicenter placebo-controlled randomized trial: age analysis.

BACKGROUND: Triiodothyronine levels decrease in infants and children after cardiopulmonary bypass. We tested the primary hypothesis that triiodothyronine (T3) repletion is safe in this population and produces improvements in postoperative clinical outcome. METHODS AND RESULTS: The TRICC study was a prospective, multicenter, double-blind, randomized, placebo-controlled trial in children younger than 2 years old undergoing heart surgery with cardiopulmonary bypass. Enrollment was stratified by surgical diagnosis. Time to extubation (TTE) was the primary outcome. Patients received intravenous T3 as Triostat (n=98) or placebo (n=95), and data were analyzed using Cox proportional hazards. Overall, TTE was similar between groups. There were no differences in adverse event rates, including arrhythmia. Prespecified analyses showed a significant interaction between age and treatment (P=0.0012). For patients younger than 5 months, the hazard ratio (chance of extubation) for Triostat was 1.72. (P=0.0216). Placebo median TTE was 98 hours with 95% confidence interval (CI) of 71 to 142 compared to Triostat TTE at 55 hours with CI of 44 to 92. TTE shortening corresponded to a reduction in inotropic agent use and improvement in cardiac function. For children 5 months of age, or older, Triostat produced a significant delay in median TTE: 16 hours (CI, 7-22) for placebo and 20 hours (CI, 16-45) for Triostat and (hazard ratio, 0.60; P=0.0220). CONCLUSIONS: T3 supplementation is safe. Analyses using age stratification indicate that T3 supplementation provides clinical advantages in patients younger than 5 months and no benefit for those older than 5 months. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00027417.

Cardiac medications are not associated with clinically important preoperative electrolyte disturbances in children presenting for cardiac surgery.

BACKGROUND: Preoperative laboratory examination of patients undergoing elective surgical procedures has been routinely performed for decades. Although there is a large body of literature concerning the appropriate preoperative assessment of adult patients, corresponding literature for the pediatric population is not as well defined. Children and young adults with cardiac disease are a particularly vulnerable subset of patients who often undergo an extensive battery of preoperative laboratory testing. We examined the serum chemistry profiles for children with cardiac disease presenting for outpatient surgery. The investigation aims to define the effectiveness of preoperative electrolyte determination in this population of children and young adults. METHODS: A retrospective chart review of all children presenting as outpatients to a tertiary care, freestanding children's hospital for elective cardiac surgery between January 1, 2000 and January 31, 2003 was performed. All patient charts in which the admission date matched the cardiac surgical date were examined. Patients were excluded if the preoperative laboratory evaluation was performed outside of our facility, preoperative laboratory investigation was not performed, or the patient was transported by medical transport to our hospital. Patients were grouped according to three methods: the number of cardiac medications (none to four), and cardiac medications, noncardiac medications, and no medications. The presence of electrolyte abnormalities was also examined in the context of cardiac medications with various pharmacologic effects. The primary outcome measure was the incidence of abnormal laboratory values for children taking various cardiac medications. RESULTS: Of the 933 initial entries found, 774 met the investigational criteria and were included in the analysis. Although statistically significant differences in preoperative electrolytes were associated with the use of cardiac and noncardiac medication, there was no clinical value to this correlation. The data demonstrate a very low incidence of hypokalemia and hypomagnesemia in the entire study population. CONCLUSION: Preoperative electrolyte disturbances in children and young adults presenting for cardiac surgery are uncommon. The concern of hypokalemia or hypomagnesemia important in the adult population taking cardiac medications was not identified in the pediatric population. These data do not support the need for routine preoperative electrolyte evaluation in children taking cardiac medications.