Exploratory Assessment of Levosimendan in Infants With Congenital Diaphragmatic Hernia

Schroeder, Lukas; Gries, Kristina; Ebach, Fabian; Müeller, Andreas; Kipfmueller, Florian

doi:10.1097/pcc.0000000000002665

Cited by 17 publications

(16 citation statements)

References 28 publications

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“…2). As levosimendan is known to improve PH severity in both, infants and adults [6,21], levosimendan can have a positive impact on the oxygenation impairment in critically-ill patients. Furthermore, research data show that levosimendan can also improve cerebral oxygenation and peripheral tissue oxygenation in newborns [1].…”

Section: Discussionmentioning

confidence: 99%

“…Inclusion criteria: documented use of levosimendan, echocardiographic diagnosis of AHF or PH at baseline and available echocardiographic data at baseline and 24 h after onset of levosimendan administration. Exclusion criteria: congenital heart defect with need for operative correction, severe syndromic disorder or chromosomal anomalies, palliative care after birth, and infants with a congenital diaphragmatic hernia (CDH), as levosimendan treatment was already evaluated recently in a subgroup of preterm and term infants with CDH [21].…”

Section: Study Population and Ethical Approvalmentioning

confidence: 99%

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Evaluation of levosimendan as treatment option in preterm infants with cardiac dysfunction and pulmonary hypertension

Schroeder

Holcher

Leyens

et al. 2023

Preprint

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Objectives Levosimendan as a calcium-sensitizer is a promising innovative therapeutical option for the treatment of severe cardiac dysfunction (CD) and pulmonary hypertension (PH) in preterm infants, but no data are available analyzing levosimendan in cohorts of preterm infants. Design/ Setting Retrospective single-center cohort study. Patients and Methods Retrospective single-center cohort study. Data of all preterm infants (gestational age (GA) <37 weeks) with levosimendan treatment and CD and/or PH in the echocardiographic assessment between 01/2018 and 06/2021 were screened for analysis. Main outcome measures The primary clinical endpoint was defined as echocardiographic response to levosimendan. Results 105 preterm infants were finally enrolled for further analysis. 48% of the preterm infants were classified as extremely low for GA newborns (ELGANs, <28 weeks of GA) and 73% as extremely low birth weight infants (<1500g, ELBW). The primary endpoint was reached in 71%, without difference regarding GA or BW. The incidence of moderate or severe PH decreased from baseline to follow-up (24h) in about 30%, with a significant decrease in the Responder-group (p<0.001). The incidence of left-ventricular dysfunction and bi-ventricular dysfunction decreased significantly from baseline to follow-up (24h) in the Responder-group (p=0.007, and p<0.001, respectively). The arterial lactate level decreased significantly from baseline (4.7 mmol/l) to 12h (3.6 mmol/l, p<0.05), and 24h (3.1 mmol/l, p<0.01). Conclusion Levosimendan treatment is associated with an improvement of both CD and PH in preterm infants, with a stabilization of the MAP during the treatment and a significant decrease of arterial lactate levels. Future prospective trials are highly warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Study Population and Ethical Approvalmentioning

confidence: 99%

Evaluation of levosimendan as treatment option in preterm infants with cardiac dysfunction and pulmonary hypertension

Schroeder

Holcher

Leyens

et al. 2023

Preprint

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“…The use of pulmonary vasodilators did not differ between groups at the time of the first echocardiography study and was also similar on DOL 2 and DOL 5–7 in ECMO patients, regardless of survival or non-survival. Our treatment approach incorporates the early initiation of pulmonary vasodilators, such as iNO, intravenous sildenafil, milrinone and levosimendan [ 29 , 30 ]. However, this study was not designed to investigate a direct effect of these agents on PAP and PH, and it remains uncertain whether improving PAAT:ET values in surviving patients result from the use of this medication or reflect a physiological decline in the PVR over time.…”

Section: Discussionmentioning

confidence: 99%

Echocardiographic Assessment of Pulmonary Hypertension in Neonates with Congenital Diaphragmatic Hernia Using Pulmonary Artery Flow Characteristics

Kipfmueller

Akkas

Pugnaloni

et al. 2022

JCM

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Background: Assessment of pulmonary hypertension (PH) is essential in neonates with congenital diaphragmatic hernia (CDH). Echocardiography is widely established to quantify PH severity, but currently used parameters have inherent limitations. The aim of our study was to investigate the prognostic utility of the index of the pulmonary artery acceleration time to the right ventricular ejection time (PAAT:ET) in CDH neonates assessed using echocardiography. Methods: PAAT:ET values were prospectively measured in CDH neonates on admission, on day of life (DOL) 2 and DOL 5–7. Optimal cut-off values to predict mortality and need for ECMO were calculated and PAAT:ET values were compared between non-ECMO survivors, ECMO-survivors, and ECMO-non-survivors. Results: 87 CDH neonates were enrolled and 39 patients required ECMO therapy. At baseline, PAAT:ET values were significantly lower in ECMO patients compared to non-ECMO patients (p < 0.001). ECMO survivors and ECMO non-survivors had similar values at baseline (p = 0.967) and DOL 2 (p = 0.124) but significantly higher values at DOL 5–7 (p = 0.003). Optimal PAAT:ET cut-off for predicting ECMO was 0.290 at baseline and 0.310 for predicting non-survival in patients on ECMO at DOL 5–7. Conclusion: PAAT:ET is a feasible parameter for early risk assessment in CDH neonates.

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“…In addition to a vasodilatory effect, levosimendan, a calcium sensitiser and a selective PDE-3 inhibitor, has cardiac inotropic and lusitropic effects. In neonatal patients with CDH-PH on iNO and intravenous sildenafil, addition of levosimendan improved pulmonary hypertension, RV and LV dysfunction, prompting further investigation in RCTs 31…”

Section: Neonatal Therapymentioning

confidence: 98%

Neonatal and fetal therapy of congenital diaphragmatic hernia-related pulmonary hypertension

Bie

Avitabile

Joyeux

et al. 2021

Arch Dis Child Fetal Neonatal Ed

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Congenital diaphragmatic hernia (CDH) is a complex malformation characterised by a triad of pulmonary hypoplasia, pulmonary hypertension (PH) and cardiac ventricular dysfunction. Much of the mortality and morbidity in CDH is largely accounted for by PH, especially when persistent beyond the neonatal period and refractory to available treatment. Gentle ventilation, haemodynamic optimisation and pulmonary vasodilation constitute the foundations of neonatal treatment of CDH-related PH (CDH-PH). Moreover, early prenatal diagnosis, the ability to assess severity and the developmental nature of the condition generate the perfect rationale for fetal therapy. Shortcomings of currently available clinical therapies in combination with increased understanding of CDH pathophysiology have spurred experimental drug trials, exploring new therapeutic mechanisms to tackle CDH-PH. We herein discuss clinically available neonatal and fetal therapies specifically targeting CDH-PH and review the most promising experimental treatments and future research avenues.

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Exploratory Assessment of Levosimendan in Infants With Congenital Diaphragmatic Hernia

Cited by 17 publications

References 28 publications

Evaluation of levosimendan as treatment option in preterm infants with cardiac dysfunction and pulmonary hypertension

Evaluation of levosimendan as treatment option in preterm infants with cardiac dysfunction and pulmonary hypertension

Echocardiographic Assessment of Pulmonary Hypertension in Neonates with Congenital Diaphragmatic Hernia Using Pulmonary Artery Flow Characteristics

Neonatal and fetal therapy of congenital diaphragmatic hernia-related pulmonary hypertension

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