Intravenous treprostinil via an implantable pump in pediatric pulmonary arterial hypertension

Abstract

Intravenous prostacyclin-based therapy improves survival in children with pulmonary arterial hypertension (PAH), but is typically administered via an external infusion pump, which places a considerable burden on the patient. Implanted pumps may overcome some of the limitations of external pumps. We describe the first long-term use of an implanted pump for intravenous treprostinil delivery in a pediatric patient with PAH. Our patient was experiencing marked dyspnea on exertion despite triple combination therapy with bosentan, sildenafil, and inhaled iloprost. Parenteral prostacyclin-based therapy was discussed and the patient rejected options involving external pumps; she finally chose intravenous treprostinil delivery via an implanted pump (LENUS Pro®; fixed flow rate; 20 ml reservoir). The patient underwent pump implantation in July 2012 (aged 14 years) under general anesthesia with no peri- or postoperative complications. She showed marked improvements in fatigue and dyspnea over the subsequent weeks, and her inhaled iloprost regimen was slowly decreased and stopped after six months. During follow-up, the pump showed an unexpected, progressive increase in flow rate that allowed a treprostinil dose of 170 ng/kg/min to be achieved, but at the cost of shortened intervals between refills. The pump was therefore replaced in August 2017 with a newer model with an adjustable flow rate (Siromedes®). A catheter dislocation was corrected under local anesthesia one week after the replacement surgery. The patient is currently receiving treprostinil 170 ng/kg/min with percutaneous refills every 12-13 days. Thus, implantable pumps might be a valuable alternative to external pumps for treprostinil infusion in pediatric PAH.

Flow rate variance of a fully implantable pump for the delivery of intravenous treprostinil in pulmonary arterial hypertension

“…Reports of flow rate variance with the LENUS Pro® pump have been published previously. 3,5,8 The constant flow rate is regulated by a glass capillary, and it was speculated that chemical substances within the intravenous treprostinil sodium formulation slowly cause alterations within the glass capillary over a long period of time; 3 this is consistent with the results of the current study in which relevant flow rate variances only occurred in the third year after pump implantation. In the recently published long-term safety study of the LENUS Pro® pump, variances of the non-adjustable flow rate were classified as pump defects.…”

Implantable LENUS pro pump for treprostinil infusion in three pediatric patients

“…After our experience, we can conclude that the intravenous administration of treprostinil through the implantable 40 mL Lenus pro pump is a feasible alternative for pediatric patients who do not tolerate subcutaneous administration of treprostinil 10 . Nevertheless, the need for surgery and general anesthesia makes this alternative risky in patients with advanced functional class and deteriorated right ventricular function, as in case 1.…”

“…In a mean follow‐up of 14 months (maximum of 21 months), we did not observe any pump dysfunction. Considering the reported experience by Desole et al 10 and Richter et al, 9 we should bear in mind that the lifetime of the pump might be shorter than expected and the patients might require, in the follow‐up, replacement of the pump, undergoing a new general anesthesia and surgery.…”

“…To date, there has been only one report of a pediatric patient who received a Lenus pump of 20 mL, which was replaced after 5 years due to a progressive increase in the pump infusion rate 10 . This was attributed to a possible interaction between treprostinil and the glass capillary of the pump, causing an increase in the cross‐section of the capillary canal and therefore an augmentation of flow by 10%.…”

“…To date, there is mainly experience with the Lenus pro pump for treprostinil administration in adults with PAH, 7–9 and there is only one pediatric case, using the 20 mL pump, that has been reported 10 …”