epoprostenol (Caripul)

Short-term physical compatibility of milrinone and epoprostenol for inhalation in cardiac surgery.

Denis-Mdawar Elianne E, Audet Sylvia S, Friciu Mihaela M, Denault André A et al.

Hypotensive Events Associated With PDE-5 Inhibitors in Pulmonary Arterial Hypertension: Assessment of the USFDA Adverse Event Reporting System Using Disproportionality and Interaction Analysis.

Sridharan Kannan K, Sivaramakrishnan Gowri G

Phosphodiesterase-5 inhibitors (PDE-5is) are fundamental in pulmonary arterial hypertension (PAH) treatment, often used in combination with other therapeutic agents. However, hypotension signals associated with these combinations remain inadequately characterized. We analyzed the United States Food and Drug Administration Adverse Event Reporting System (FAERS) to evaluate disproportionate signals of hypotension associated with PDE-5is alone and in combination therapy. We conducted a pharmacovigilance analysis of FAERS data from 2004 to 2024, employing both frequentist (reporting odds ratio, proportional reporting ratio) and Bayesian (information component, empirical Bayes geometric mean) approaches. Interaction signal scores (INTSS) were calculated to assess potential drug interactions between PDE-5is and other PAH therapies. Clinical outcomes were evaluated for both monotherapy and combination regimens. Among 29 163 222 reports analyzed, 704 cases of PDE-5i-associated hypotension were identified (533 monotherapy, 171 combination therapy). While PDE-5i monotherapy showed no significant hypotension signals, combinations with endothelin antagonists (particularly bosentan) and prostacyclin analogs (notably epoprostenol) generated strong safety signals. Significant INTSS were detected for sildenafil and tadalafil with endothelin antagonists. Paradoxically, despite fewer hypotension reports, PDE-5i monotherapy was associated with higher rates of death and life-threatening events compared to combination therapy (P = .02). This analysis reveals significant hypotension signals with specific PDE-5i combinations in PAH treatment, particularly with endothelin antagonists and prostacyclin analogs. While combination therapy showed a higher frequency of hypotensive events, these episodes appeared more manageable than those occurring with monotherapy. These findings emphasize the need for careful monitoring and individualized risk assessment in PAH patients receiving PDE-5i-based therapy.

Novel use of the Nuwellis® dual extended length catheter (dELC) as umbilical venous access for neonatal kidney replacement therapy: case series.

Short Kara K, Umberger Alyssa A, Mathis Meggie M, Walker Mallory M et al.

Neonates with congenital kidney failure or acute kidney injury often require continuous kidney replacement therapy (CKRT). Historically, venous access for CKRT in this population has relied on non-approved adult catheters, commonly via the internal jugular (IJ) vein. Limited international reports describe using the umbilical vein for CKRT, but this practice is not widespread in the USA. The Nuwellis® dual lumen extended length catheter (dELC), originally created for adult ultrafiltration, may support alternative access for neonatal CKRT. This case series describes the clinical course of four neonates requiring CKRT using a 6 French Nuwellis® dELC placed in the umbilical vein at University of Iowa Stead Family Children's Hospital and Children's of Alabama. Patient demographics, CKRT prescriptions, access characteristics, and complications were reviewed. All four neonates underwent successful umbilical vein placement of the 6 Fr dELC. Weight at initiation ranged from 2.23 to 4.1 kg, with blood flow rates 20-40 mL/min. Epoprostenol anticoagulation was used in three patients. Half of the cohort later transitioned to a tunneled catheter, and one transitioned to an IJ catheter following fluid removal. One catheter developed hub cracks likely related to lumen caps, and one patient experienced flow limitations attributed to positioning rather than catheter function. Two patients had no catheter-related complications. Umbilical venous access using the 6Fr dELC may represent a viable alternative for neonatal CKRT. Coil reinforcement within the catheter may support patency and better functionality. Additional studies are needed to assess safety and broader applicability.

Descriptive study of the effects of treprostinil and/or epoprostenol in newborn infants with inhaled NO refractory persistent pulmonary hypertension of the newborn (PPHN).

Mazepa Charlotte C, Mur Sébastien S, Gascoin Géraldine G, Storme Laurent L et al.

Epoprostenol and treprostinil, prostacyclin analogues, are used in some neonatal intensive care units (NICU) in the treatment of persistent pulmonary hypertension of the newborn (PPHN) refractory to inhaled nitric oxide (iNO). The aim of this retrospective multicentric descriptive study was to assess the profile and evolution of these newborns. Inclusion of neonates born ≥ 34 weeks of gestational age (WGA) and aged ≤ 28 days of life, presenting clinical signs of PPHN (respiratory and/or hemodynamic lability), and at least one echocardiographic sign of pulmonary hypertension. We collected data on the use of prostacyclin analogues, their tolerance, and their efficacy, by collecting clinical, biological, and echocardiographic data of these newborns. Seventy patients were included from 4 French NICU. It appears that there may be an improvement in pulmonary hypertension (PH) at the initiation of prostacyclin analogues, showing by an increase in post-ductal SpO2, a decrease in FiO2 and an improvement in PH'level on echocardiography. Only four patients needed a treatment discontinuation due to poor hemodynamic tolerance. Our study highlighted the safety of the use of epoprostenol and treprostinil in neonates suffering from iNO refractory PPHN, without significant adverse effect. It appears to be necessary to carry out further study to establish recommendations for the management of PPHN, and also to define more precisely the place of treprostinil and epoprostenol in this pathology.