Open AccessProstanoids in pediatric pulmonary hypertension: clinical response, time‐to‐effect, and dose–response
Author(s) -
Tella Joseph B.,
Kulik Thomas J.,
McSweeney Julia E.,
Sleeper Lynn A.,
Lu Minmin,
Mullen Mary P.
Publication year - 2020
Publication title -
pulmonary circulation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.791
H-Index - 40
ISSN - 2045-8940
DOI - 10.1177/2045894020944858
Subject(s) - medicine , treprostinil , pulmonary hypertension , adverse effect , hemodynamics , cardiac index , vascular resistance , prostanoid , anesthesia , prostacyclin , iloprost , cardiology , cardiac output , receptor
For pediatric pulmonary arterial hypertension (PAH) patients treated with parenteral prostanoids, response predictors, and the dose–effect relationship are ill defined. We determined the following: (1) which pulmonary vascular hemodynamic variable, after initiating prostanoids, best correlates with a significant clinical response; (2) the time interval after treatment when if no pulmonary hemodynamic improvement has occurred, none is ever likely to; and (3) the relationship between the prostanoid dose and its hemodynamic effects. This is a retrospective cohort study of 31 pediatric patients with Group 1 PAH treated with parenteral prostanoids. We found the following: (1) A fall in mean pulmonary arterial pressure (mPAP) of ≥25% predicted freedom from adverse clinical events with 80.7% accuracy and was also associated with improved functional class. (2) Thirty‐three percent of patients who avoided an adverse clinical event demonstrated a ≥25% reduction in mPAP after 1 year of treatment, and 65% by 2 years. (3) Lower mPAP was seldom seen with doses of epoprostenol >60 ng/kg/min (100 ng/kg/min for treprostinil). Cardiac index was positively correlated with the dose of epoprostenol but not treprostinil; cardiac index >4 l/min/m 2 was seen at modest as well as high doses. We conclude that a ≥25% fall in mPAP on prostanoids indicates a positive clinical response which, if validated in other studies, may be useful for patient management or clinical trials. Some patients take more than 2 years for this change. Exceptionally high doses were generally not more effective than lower, although we could not determine whether lower doses would have been as effective.