Barbaro RP, Paden ML, Guner YS, Raman L, Ryerson LM, Alexander P, et al. Pediatric extracorporeal life support organization registry international report 2016. ASAIO J. 2017;63(4):456–63.

Article  Google Scholar 

Barbaro RP, Boonstra PS, Paden ML, Roberts LA, Annich GM, Bartlett RH, et al. Development and validation of the pediatric risk estimate score for children using extracorporeal respiratory support (Ped-RESCUERS). Intensive Care Med. 2016;42(5):879–88.

Article  Google Scholar 

Bembea MM, Felling R, Anton B, Salorio CF, Johnston MV. Neuromonitoring during extracorporeal membrane oxygenation: a systematic review of the literature. Pediatr Crit Care Med. 2015;16(6):558–64.

Article  Google Scholar 

Dalton HJ, Reeder R, Garcia-Filion P, Holubkov R, Berg RA, Zuppa A, et al. Factors associated with bleeding and thrombosis in children receiving extracorporeal membrane oxygenation. Am J Respir Crit Care Med. 2017;196(6):762–71.

Article  CAS  Google Scholar 

Kaddoura R, Omar AS, Ibrahim MIM, Alkhulaifi A, Lorusso R, Elsherbini H, et al. The effectiveness of levosimendan on veno-arterial extracorporeal membrane oxygenation management and outcome: a systematic review and meta-analysis. J Cardiothorac Vasc Anesth. 2021;35(8):2483–95.

Article  CAS  Google Scholar 

Silvetti S, Belletti A, Bianzina S, Momeni M. Effect of levosimendan treatment in pediatric patients with cardiac dysfunction: an update of a systematic review and meta-analysis of randomized controlled trials. J Cardiothorac Vasc Anesth. 2022;36(3):657–64.

Article  CAS  Google Scholar 

Wang A, Cui C, Fan Y, Zi J, Zhang J, Wang G, et al. Prophylactic use of levosimendan in pediatric patients undergoing cardiac surgery: a prospective randomized controlled trial. Crit Care. 2019;23(1):428.

Article  Google Scholar 

Figgitt DP, Gillies PS, Goa KL. Levosimendan. Drugs. 2001;61(5):613–27.

Article  CAS  Google Scholar 

Wilson ID, Nicholson JK. Gut microbiome interactions with drug metabolism, efficacy, and toxicity. Transl Res. 2017;179:204–22.

Article  CAS  Google Scholar 

Antila S, Sundberg S, Lehtonen LA. Clinical pharmacology of levosimendan. Clin Pharmacokinet. 2007;46(7):535–52.

Article  CAS  Google Scholar 

Antila S, Kivikko M, Lehtonen L, Eha J, Heikkila A, Pohjanjousi P, et al. Pharmacokinetics of levosimendan and its circulating metabolites in patients with heart failure after an extended continuous infusion of levosimendan. Br J Clin Pharmacol. 2004;57(4):412–5.

Article  CAS  Google Scholar 

Antila S, Pesonen U, Lehtonen L, Tapanainen P, Nikkanen H, Vaahtera K, et al. Pharmacokinetics of levosimendan and its active metabolite OR-1896 in rapid and slow acetylators. Eur J Pharm Sci. 2004;23(3):213–22.

Article  CAS  Google Scholar 

Kaddoura R, Mohamed Ibrahim MI, Omar A. Levosimendan for VA-ECMO weaning: the silver lining. ESC Heart Fail. 2022;9(1):236–40.

Article  Google Scholar 

Fang M, Cao H, Wang Z. Levosimendan in patients with cardiogenic shock complicating myocardial infarction: a meta-analysis. Med Intensiva (Engl Ed). 2018;42(7):409–15.

Article  CAS  Google Scholar 

Wang H, Luo Q, Li Y, Zhang L, Wu X, Yan F. Effect of prophylactic levosimendan on all-cause mortality in pediatric patients undergoing cardiac surgery-an updated systematic review and meta-analysis. Front Pediatr. 2020;8:456.

Article  Google Scholar 

Grześk G, Wołowiec Ł, Rogowicz D, Gilewski W, Kowalkowska M, Banach J, et al. The importance of pharmacokinetics, pharmacodynamic and repetitive use of levosimendan. Biomed Pharmacother. 2022;153: 113391.

Article  Google Scholar 

Tukacs M. Pharmacokinetics and extracorporeal membrane oxygenation in adults: a literature review. AACN Adv Crit Care. 2018;29(3):246–58.

Article  Google Scholar 

Thakkar N, Salerno S, Hornik CP, Gonzalez D. Clinical pharmacology studies in critically ill children. Pharm Res. 2017;34(1):7–24.

Article  CAS  Google Scholar 

ICH guideline M10 on bioanalytical method validation and study sample analysis. Step 5 [cited 4 Nov 2022]. Available at: https://www.ema.europa.eu/en/documents/scientific-guideline/ich-guideline-m10-bioanalytical-method-validation-step-5_en.pdf

Traynard P, Ayral G, Twarogowska M, Chauvin J. Efficient pharmacokinetic modeling workflow with the monolixsuite: a case study of remifentanil. CPT Pharmacometrics Syst Pharmacol. 2020;9(4):198–210.

Article  CAS  Google Scholar 

Mould D, Upton R. Basic concepts in population modeling, simulation, and model-based drug development. Pharmacometr Syst Pharmacol. 2012;1(9):6.

Article  Google Scholar 

Delattre M, Lavielle M, Poursat MA. A note on BIC in mixed-effects models. Electron J Stat. 2014;8(1):456–75.

Article  Google Scholar 

Zhou H. Pharmacokinetic strategies in deciphering atypical drug absorption profiles. J Clin Pharmacol. 2003;43(3):211–27.

Article  CAS  Google Scholar 

Savic RM, Jonker DM, Kerbusch T, Karlsson MO. Implementation of a transit compartment model for describing drug absorption in pharmacokinetic studies. J Pharmacokinet Pharmacodyn. 2007;34(5):711–26.

Article  CAS  Google Scholar 

Roberts JA, Lipman J. Pharmacokinetic issues for antibiotics in the critically ill patient. Crit Care Med. 2009;37(3):840–51.

Article  CAS  Google Scholar 

Pellicer A, Riera J, Lopez-Ortego P, Bravo MC, Madero R, Perez-Rodriguez J, et al. Phase 1 study of two inodilators in neonates undergoing cardiovascular surgery. Pediatr Res. 2013;73(1):95–103.

Article  CAS  Google Scholar 

Wildschut ED, Ahsman MJ, Allegaert K, Mathot RAA, Tibboel D. Determinants of drug absorption in different ECMO circuits. Intensive Care Med. 2010;36(12):2109–16.

Article  CAS  Google Scholar 

Shekar K, Roberts JA, Barnett AG, Diab S, Wallis SC, Fung YL, et al. Can physicochemical properties of antimicrobials be used to predict their pharmacokinetics during extracorporeal membrane oxygenation? Illustrative data from ovine models. Crit Care. 2015;19(1):437.

Article  Google Scholar 

Shekar K, Roberts JA, Mcdonald CI, Ghassabian S, Anstey C, Wallis SC, et al. Protein-bound drugs are prone to sequestration in the extracorporeal membrane oxygenation circuit: results from an ex vivo study. Crit Care. 2015;19:164.

Article  Google Scholar 

Raffaeli G, Pokorna P, Allegaert K, Mosca F, Cavallaro G, Wildschut ED, et al. Drug disposition and pharmacotherapy in neonatal ECMO: from fragmented data to integrated knowledge. Front Pediatr. 2019;7:360.

Article  Google Scholar 

Papp Z, Csapó K, Pollesello P, Haikala H, Édes I. Pharmacological mechanisms contributing to the clinical efficacy of levosimendan. Cardiovasc Drug Rev. 2005;23(1):71–98.

Article  CAS  Google Scholar 

Szilágyi S, Pollesello P, Levijoki J, Kaheinen P, Haikala H, Édes I, et al. The effects of levosimendan and OR-1896 on isolated hearts, myocyte-sized preparations and phosphodiesterase enzymes of the guinea pig. Eur J Pharmacol. 2004;486(1):67–74.

Article  Google Scholar 

Puttonen J, Laine T, Ramela M, Häkkinen S, Zhang W, Pradhan R, et al. Pharmacokinetics and excretion balance of OR-1896, a pharmacologically active metabolite of levosimendan, in healthy men. Eur J Pharm Sci. 2007;32(4–5):271–7.

Article  CAS  Google Scholar 

Chan CC, Lee KT, Ho WJ, Chan YH, Chu PH. Levosimendan use in patients with acute heart failure and reduced ejection fraction with or without severe renal dysfunction in critical cardiac care units: a multi-institution database study. Ann Intensive Care. 2021;11(1):27.

Article  CAS  Google Scholar 

Tholén M, Ricksten SE, Lannemyr L. Effects of levosimendan on renal blood flow and glomerular filtration in patients with acute kidney injury after cardiac surgery: a double blind, randomized placebo-controlled study. Crit Care. 2021;25(1):207.

Article  Google Scholar 

Cui X, Wang Z, Dong X, Cheng Z, Zhang L, Mu Y, et al. Comparative effectiveness and safety of milrinone and levosimendan as initial inotrope therapy in patients with acute heart failure with renal dysfunction. J Cardiovasc Pharmacol. 2022;79(6):781–90.

Article  CAS  Google Scholar 

Puttonen J, Kantele S, Ruck A, Ramela M, Häkkinen S, Kivikko M, et al. Pharmacokinetics of intravenous levosimendan and its metabolites in subjects with hepatic impairment. J Clin Pharmacol. 2008;48(4):445–54.

Article  CAS  Google Scholar 

Jonsson EN, Antila S, McFadyen L, Lehtonen L, Karlsson MO. Population pharmacokinetics of levosimendan in patients with congestive heart failure. Br J Clin Pharmacol. 2003;55(6):544–51.

Article  CAS  Google Scholar 

Lunghetti S, Palmerini E, Urselli R, Maffei S, Guarino E, Focardi M, et al. Effects of levosimendan without loading dose on systolic and diastolic function in patients with end-stage heart failure. Cardiol J. 2011;18(5):532–7.

Article  Google Scholar 

Kabbani TA, Pallav K, Dowd SE, Villafuerte-Galvez J, Vanga RR, Castillo NE, et al. Prospective randomized controlled study on the effects of Saccharomyces boulardii CNCM I-745 and amoxicillin-clavulanate or the combination on the gut microbiota of healthy volunteers. Gut Microbes. 2017;8(1):17–32.

Article  CAS  Google Scholar 

Ellouze O, Soudry Faure A, Radhouani M, Abou-Arab O, Besnier E, Moussa M, et al. Levosimendan in venoarterial ECMO weaning. Rational and design of a randomized double blind multicentre trial. ESC Heart Fail. 2021;8(4):3339–47.

Article  Google Scholar 

Assistance Publique - Hôpitaux de Paris. LEVOSIMENDAN to Facilitate Weaning From ECMO in Severe Cardiogenic Shock Patients. ClinicalTrials.gov; 2021 Oct. Report No.: NCT04728932 [cited 9 Sep 2022]. Available at: https://clinicaltrials.gov/ct2/show/NCT04728932

Vally S, Ferdynus C, Persichini R, Bouchet B, Braunberger E, Lo Pinto H, et al. Impact of levosimendan on weaning from peripheral venoarterial extracorporeal membrane oxygenation in intensive care unit. Ann Intensive Care. 2019;9(1):24.

Article  Google Scholar