High-sensitive troponinT, interleukin-8, and interleukin-6 link with post-surgery risk in infant heart surgery.

BACKGROUND: This study focuses on biomarkers in infants after open heart surgery, and examines the association of high-sensitive troponin T (hs-cTnT), interleukin-6 (IL-6), and interleukin-8 (IL-8) with postoperative acute kidney injury (AKI), ventilatory support time and need of vasoactive drugs. METHODS: Secondary exploratory study from a double-blinded clinical randomized trial (Mile-1) on 70 infants undergoing open heart surgery with cardiopulmonary bypass (CPB). In this sub-study, the entire study population was examined without considering the study drugs. The biomarkers' peak concentration (highest concentration at 2 or 6 h post-CPB) were used for statistical analyses. RESULTS: Peak IL-8, hs-cTnT, and IL-6 occurred at 2 h post-CPB for 96%, 79%, and 63% of the patients, respectively. The odds ratio of developing AKI2-3 for IL-6 > 293 pg/mL was 23.4 (95% CI 5.3;104.0), for IL-8 > 100 pg/mL it was 11.5 (3.0;44.2), and for hs-cTnT >5597 pg/mL it was 6.1 (1.5; 24.5). In more than two third of the patients with the highest peak concentrations of IL-8, IL-6, and hs-cTnT, there was a need for ventilatory support for >24 h and use of vasoactive drugs at 24 h post-CPB, while in less than one third of the patients with the lowest peak concentrations of IL-8 and hs-cTnT such requirements were observed. CONCLUSIONS: The peak biomarker concentrations and CPB-time strongly predicted AKI2-3, with IL-6 and IL-8 emerging as strongest predictors. Furthermore, our findings suggest that measuring hs-cTnT and IL-8 just 2 h post-CPB-weaning may assist in identifying infants suitable for early extubation and highlight those at risk of prolonged ventilation.

Levosimendan Versus Milrinone and Release of Myocardial Biomarkers After Pediatric Cardiac Surgery: Post Hoc Analysis of Clinical Trial Data.

OBJECTIVES: We compared the effect of two inodilators, levosimendan and milrinone, on the plasma levels of myocardial injury biomarkers, that is, high-sensitivity troponin T and heart-type fatty acid binding protein, and on N-terminal prohormone of brain natriuretic peptide as a biomarker of ventricular function. We hypothesized that levosimendan could attenuate the degree of myocardial injury when compared with milrinone. DESIGN: A post hoc, nonprespecified exploratory secondary analysis of the Milrinone versus Levosimendan-1 trial (ClinicalTrials.gov Identifier: NCT02232399). SETTING: Two pediatric tertiary university hospitals. PATIENTS: Infants 1-12 months old, diagnosed with ventricular septal defect, complete atrioventricular septal defect, or Tetralogy of Fallot undergoing corrective surgery with cardiopulmonary bypass. INTERVENTIONS: Seventy patients received a loading dose of either levosimendan or milrinone at the start of cardiopulmonary bypass followed by an infusion of the respective drug, which continued for 26 hours. MEASUREMENTS AND MAIN RESULTS: Plasma levels of the three cardiac biomarkers were measured prior to the initiation of cardiopulmonary bypass and 2, 6, and 24 hours after weaning from cardiopulmonary bypass. In both groups, the levels of high-sensitivity troponin T and heart-type fatty acid binding protein were highest at 2 hours post cardiopulmonary bypass, whereas the highest level of N-terminal prohormone of brain natriuretic peptide occurred at 24 hours post cardiopulmonary bypass. There was no significant difference in the biomarkers' plasma levels between the study groups over time. Neither was there a significant difference in the postoperative peak plasma levels of the cardiac biomarkers. CONCLUSIONS: In this post hoc analysis of the MiLe-1 trial, there was no demonstrable difference in the postoperative cardiac biomarker profile of myocardial injury and ventricular function when comparing infants managed in the perioperative period with levosimendan versus milrinone.

Levosimendan Versus Milrinone for Inotropic Support in Pediatric Cardiac Surgery: Results From a Randomized Trial.

OBJECTIVE: The present study aimed to determine the differential effects of intraoperative administration of milrinone versus levosimendan on myocardial function after pediatric cardiac surgery. Transthoracic echocardiography was used for myocardial function evaluation using biventricular longitudinal strain with 2-dimensional speckle tracking echocardiography in addition to conventional echocardiographic variables. DESIGN: A secondary analysis of a randomized, prospective, double-blinded clinical drug trial. SETTING: Two pediatric tertiary university hospitals. PARTICIPANTS: Infants between 1 and 12 months old diagnosed with ventricular septal defect, complete atrioventricular septal defect, or tetralogy of Fallot who were scheduled for corrective surgery with cardiopulmonary bypass. INTERVENTIONS: The patients were randomly assigned to receive an infusion of milrinone or levosimendan at the start of cardiopulmonary bypass and for 26 consecutive hours. MEASUREMENTS AND MAIN RESULTS: Biventricular longitudinal strain and conventional echocardiographic variables were measured preoperatively, on the first postoperative morning, and before hospital discharge. The association between perioperative parameters and postoperative myocardial function also was investigated. Images were analyzed for left ventricular (n = 67) and right ventricular (n = 44) function. The day after surgery, left ventricular longitudinal strain deteriorated in both the milrinone and levosimendan groups (33% and 39%, respectively). The difference was not significant. The corresponding deterioration in right ventricular longitudinal strain was 42% and 50% (nonsignificant difference). For both groups, biventricular longitudinal strain approached preoperative values at hospital discharge. Preoperative N-terminal pro-brain natriuretic peptide could predict the left ventricular strain on postoperative day 1 (p = 0.014). CONCLUSIONS: Levosimendan was comparable with milrinone for left and right ventricular inotropic support in pediatric cardiac surgery.

The Effect of Levosimendan Versus Milrinone on the Occurrence Rate of Acute Kidney Injury Following Congenital Heart Surgery in Infants: A Randomized Clinical Trial.

OBJECTIVES: It has been shown that, in contrast to other inotropic agents, levosimendan improves glomerular filtration rate after adult cardiac surgery. The aim of this study was to investigate the efficacy of levosimendan, compared with milrinone, in preventing acute kidney dysfunction in infants after open-heart surgery with cardiopulmonary bypass. DESIGN: Two-center, double-blinded, prospective, randomized clinical trial. SETTING: The study was performed in two tertiary pediatric centers, one in Sweden (Gothenburg) and one in Finland (Helsinki). PATIENTS: Infants between 1 and 12 months old, diagnosed with Tetralogy of Fallot, complete atrioventricular septal defect or nonrestrictive ventricular septal defect, undergoing total corrective cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Seventy-two infants were randomized to receive a perioperative infusion of levosimendan (0.1 µg/kg/min) or milrinone (0.4 µg/kg/min). The infusion was initiated at the start of cardiopulmonary bypass and continued for 26 hours. MEASUREMENTS AND MAIN RESULTS: The primary outcome variable was the absolute value of serum creatinine data on postoperative day 1. Secondary outcomes included the following: 1) acute kidney injury according to the serum creatinine criteria of the Kidney Diseases: Improving Global Outcomes; 2) acute kidney injury with serum creatinine corrected for fluid balance; 3) plasma neutrophil gelatinase-associated lipocalin; 4) cystatin C; 5) urea; 6) lactate; 7) hemodynamic variables; 8) use of diuretics in the PICU; 9) need of dialysis; 10) length of ventilator therapy; and 11) length of PICU stays. There was no significant difference in postoperative serum creatinine between the treatment groups over time (p = 0.65). The occurrence rate of acute kidney injury within 48 hours was 46.9% in the levosimendan group and 39.5% in the milrinone group (p = 0.70). There were no significant differences in other secondary outcome variables between the groups. CONCLUSIONS: Levosimendan compared with milrinone did not reduce the occurrence rate of acute kidney injury in infants after total corrective heart surgery for atrioventricular septal defect, ventricular septal defect, or Tetralogy of Fallot.