Levosimendan vs. Milrinone: Early Renal and Hemodynamic Outcomes after lnfant Cardiac Surgery
Background: Myocardial and renal dysfunction are common after cardiac surgery in young children, which increases risk of complications and delayed recovery. Inodilators, such as milrinone and levosimendan, are frequently used to reduce the risk of low cardiac output syndrome in infants after cardiac surgery. Levosimendan has been demonstrated to increase renal blood flow and glomerular filtration rate in adult cardiac surgery, however there is a lack of infant studies. In the present thesis, the ability of levosimendan compared to milrinone in reducing renal and myocardial injuries after cardiac surgery in infants was investigated. Methods: Two Nordic pediatric heart centers, Gothenburg and Helsinki, performed a double-blinded, randomized clinical trial (MiLe-1). Seventy infants, scheduled for total corrective cardiac surgery with cardiopulmonary bypass (CPB), received either levosimendan or milrinone. We performed the following comparisons between the two study groups: 1) the incidence of postoperative acute kidney injury (AKI), 2) the myocardial function with echocardiography, 3) changes in the plasma concentrations of myocardial biomarkers over time, and 4) in the whole study population, the associations between biomarkers of inflammation, renal and myocardial dysfunction, with early clinical outcome after cardiac surgery. Results: The postoperative incidence of AKI was 39.5% in the milrinone group and 46.9% in the levosimendan group. The difference was not statistically significant. Neither was there a significant difference between the study groups regarding hemodynamic parameters, echocardiographic measurements, or the cardiac biomarkers. The peak plasma concentrations of the cardiac injury and inflammatory biomarkers were strong predictors of the development of severe AKI. In the patients with the lowest and highest quartile of the cardiac injury biomarker hs-cTnT and the proinflammatory biomarker IL-8 (measured at 2 hours post-CPB), we observed a strong association with the postoperative duration of ventilatory support, and the need of vasopressors. Conclusion: We could not detect any significant differences in the incidence of AKI, myocardial function, or in the myocardial biomarkers after cardiac surgery in infants who received either levosimendan or milrinone. Plasma hs-cTnT and IL-8, measured 2 hours post-CPB, may have clinical value in infants after cardiac surgery, including early weaning of ventilatory support.
Parts of work
I. Thorlacius EM, Suominen PK, Wahlander H, et al. The effect of levosimendan versus milrinone on the occurrence rate of acute kidney injury following congenital heart surgery in infants: A randomized clinical trial. Pediatr Crit Care Med 2019;20:947–56. ::doi::10.1097/pcc.0000000000002017II. Thorlacius EM, Wåhlander H, Ojala T, et al: Levosimendan versus milrinone for inotropic support in pediatric cardiac surgery: Results from a randomized trial. J Cardiothorac Vasc Anesth 2020; 34:2072–2080 ::doi::10.1053/j.jvca.2020.02.027III. Thorlacius EM, Vistnes M, Ojala T, et al. Levosimendan Versus Milrinone and Release of Myocardial Biomarkers After Pediatric Cardiac Surgery: Post Hoc Analysis of Clinical Trial Data. Ped. Crit. Care Med. 2021;22(7):e402-e409 ::doi::10.1097/PCC.0000000000002712IV. Thorlacius EM, Keski-Nisula J, Vistnes M, et al: High-sensitive troponin T and interleukin-8 may serve as postoperative risk differentiators in infants undergoing congenital heart surgery. Manuscript.
Doctor of Philosophy (Medicine)
University of Gothenburg. Sahlgrenska Academy
Institute of Clinical Sciences. Department of Anesthesiology & Intensive Care Medicine
Onsdagen den 16 november 2022, kl 13.00, Hörsal Tallen, Drottning Silvias barnsjukhus, Behandlingsvägen 7, Göteborg
Date of defence
Thorlacius, Elin M
congenital heart lesions
acute kidney injury