Conference: 2017 PH Professional Network Symposium
Release Date: 10.06.2017
Presentation Type: Abstracts
File Download: 2017 PHPN Abstract 1028
Download Adobe Acrobat
Abstract presented at the 2017 PH Professional Network Symposium held in Bethesda, MD on October 5-7, 2017
To determine if current empiric sildenafil dosing recommendations are appropriate for hemodynamically unstable children receiving concurrent vasoactive infusions.
Sildenafil is a first-line agent used to treat pulmonary hypertension in pediatric patients. While it is utilized in children receiving continuous infusion inotropic or vasopressor medications, it is unknown whether the administration of sildenafil worsens hemodynamic instability in this patient population. We hypothesized that hemodynamic instability occurs frequently in children receiving concurrent enteral sildenafil and vasoactive infusion administration.
This retrospective chart review included children younger than 2 years of age admitted to Riley Hospital for Children at Indiana University Health between January 1, 2010 and September 30, 2016 who received enteral sildenafil and concurrent inotropic or vasopressor medications. Patients were excluded if they received mechanical circulatory support 24 hours prior to sildenafil administration, or if they received renal replacement therapy or had suspected septic shock at any point during the study period. Data collection included demographic information, sildenafil dose and frequency, medications with known drug interactions with sildenafil, history of sildenafil exposure prior to initiation of vasoactive support, mean arterial pressures (MAP), and vasoactive infusion dosing. The primary outcome was a composite endpoint of the frequency of sildenafil discontinuation, increased vasoactive support, epinephrine intravenous push administration, or need for initiation of mechanical circulatory support within 24 hours of the first sildenafil administration with concurrent vasoactive support.
A total of 130 patients were included. The median age was 4.6 (0.3-7.7) months, and 26 (20%) had a diagnosis of Trisomy 21. The median initial sildenafil dose for all patients was 1.5 (1.0-2.5) mg/kg/day, with a median vasoactive inotrope score (VIS) of 5.0 (3.0-7.5) at the beginning of the study period. Thirty-two patients (25%) met the primary composite endpoint. Twenty-five patients (19%) required increased inotropic support and one patient required sildenafil discontinuation during the study period. Five patients (4%) required both increased inotropic support and sildenafil discontinuation. One patient required increased inotropic support and epinephrine intravenous push administration. No one required initiation of mechanical circulatory support during the study period. Patients with Trisomy 21 appeared to have a lower frequency of hemodynamic instability than patients without Trisomy 21 (15% versus 36%). Patients who met the primary composite endpoint (n=32) were younger [2.0 (0-8.0) months versus 5.0 (1.0-7.5) months], with a lower median initial sildenafil dose [1.3 (0.6-2.0) mg/kg/day versus 1.6 (1.1-2.6) mg/kg/day] and median VIS score during the study period [4.2 (3.0-7.1) versus 5.0 (3.0-7.5)].
Children receiving vasoactive infusions may be at risk for further hemodynamic instability if treated with sildenafil. Empiric sildenafil dosing recommendations may need to be decreased for this patient population. Patients with Trisomy 21 were not at increased risk of hemodynamic instability compared to those patients without Trisomy 21. Further studies are warranted to define optimal sildenafil dosing strategies for pulmonary hypertension in children receiving concomitant vasoactive infusions.