ABSTRACT
PURPOSE: To evaluate the physical and chemical compatibilities of treprostinil sodium and dopamine hydrochloride. METHODS: Treprostinil sodium (4,000, 76,000, and 500,000 ng/mL) were mixed with dopamine hydrochloride (0.6, 3.2, 6, and 40 mg/mL). Samples were obtained at hours 0, 1, 2, and 4 for physical compatibility and chemical stability testing. Physical compatibility was assessed by visual examination and measurements of turbidity and pH. Drug concentrations were assessed using stability-indicating liquid chromatography mass spectrophotometry (LCMS) for treprostinil sodium and stability-indicating high-performance liquid chromatography (HPLC) for dopamine hydrochloride. RESULTS: Treprostinil sodium 4,000 and 76,000 ng/mL, when mixed with dopamine hydrochloride 0.6, 3.2, 6, and 40 mg/mL, were stable for 4 hours. Treprostinil sodium 500,000 ng/mL was stable when mixed with dopamine hydrochloride 0.6 mg/mL for 4 hours, but when mixed with dopamine hydrochloride 3.2, 6, and 40 mg/mL, significant precipitation was seen. CONCLUSION: Treprostinil sodium 4,000 and 76,000 ng/mL were stable for 4 hours during simulated Y-site coadministration with dopamine hydrochloride 0.6, 3.2, 6, and 40 mg/mL. Treprostinil sodium 500,000 ng/mL is stable when mixed with dopamine hydrochloride 0.6 mg/mL.
Subject(s)
Antihypertensive Agents/chemistry , Dopamine Agents/chemistry , Dopamine/chemistry , Drug Incompatibility , Epoprostenol/analogs & derivatives , Administration, Intravenous , Epoprostenol/chemistry , Hydrogen-Ion Concentration , Time FactorsABSTRACT
OBJECTIVE: To evaluate the effect of continuous treprostinil in infants with severe pulmonary hypertension associated with congenital diaphragmatic hernia (CDH) on specific markers of pulmonary hypertension severity and to report the safety and tolerability of treprostinil. STUDY DESIGN: We conducted a retrospective cohort study of infants with CDH-associated pulmonary hypertension treated with treprostinil from January 2011 to September 2016. Severity of pulmonary hypertension was assessed by echocardiogram and serum B-type natriuretic peptide (BNP) by using time points before initiation and 24 hours, 1 week, and 1 month after treprostinil initiation. Fisher exact tests, Wilcoxon-rank sum tests, and mixed-effects models were used for analysis. RESULTS: Seventeen patients were treated with treprostinil for a median of 54.5 days (IQR 44.3-110 days). Compared with the concurrent CDH population (n = 147), infants treated with treprostinil were more likely to require extracorporeal support (76.5% vs 25.2%, P < .0001), to have a longer hospital stay (144 vs 60 days, P < .0001), and to need longer mechanical ventilator support (76.5 vs 30.9 days, P < .0001). Following treprostinil initiation, there was a significant reduction in BNP at 1 week (1439 vs 393 pg/mL, P < .01) and 1 month (1439 vs 242 pg/mL, P = .01). Severity of pulmonary hypertension by echocardiogram improved at 1 month (OR 0.14, CI 95% 0.04-0.48, P = .002). Despite these improvements, overall mortality remained high (35%). There were no adverse events related to treprostinil, including no hypotension, hypoxia, or thrombocytopenia. CONCLUSIONS: In this cohort, treprostinil use was associated with improved severity of pulmonary hypertension assessed by echocardiogram and decreased BNP, with no significant side effects.
Subject(s)
Epoprostenol/analogs & derivatives , Hernias, Diaphragmatic, Congenital/complications , Hypertension, Pulmonary/drug therapy , Pulmonary Wedge Pressure/drug effects , Registries , Antihypertensive Agents/administration & dosage , Dose-Response Relationship, Drug , Epoprostenol/administration & dosage , Female , Follow-Up Studies , Humans , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/physiopathology , Infant , Infant, Newborn , Male , Retrospective Studies , Treatment OutcomeSubject(s)
Heart Ventricles/physiopathology , Hernias, Diaphragmatic, Congenital/complications , Hypertension, Pulmonary/etiology , Ventricular Dysfunction, Left/etiology , Echocardiography , Fetus , Hernias, Diaphragmatic, Congenital/therapy , Humans , Hypertension, Pulmonary/therapy , Infant, Newborn , Ventricular Dysfunction, Left/therapySubject(s)
Bronchopulmonary Dysplasia/diagnosis , Bronchopulmonary Dysplasia/therapy , Disease Management , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/therapy , Infant, Very Low Birth Weight , Bronchopulmonary Dysplasia/epidemiology , Child, Preschool , Combined Modality Therapy , Disease Progression , Female , Humans , Hypertension, Pulmonary/epidemiology , Infant , Infant, Newborn , Male , Practice Guidelines as Topic , Prognosis , Risk Assessment , Severity of Illness Index , Survival RateABSTRACT
Pulmonary hypertension (PH) does not refer to a specific disease but rather a clinical manifestation emanating from a decrease in functional pulmonary vasculature resulting in progressively elevated right ventricle pressure and ultimately right heart failure. It is an uncommon disease process, but because of advancements in treatment, improved survival, and increasing prevalence, there is a greater likelihood that the emergency clinician will have to care for a child with PH. This review article, intended for emergency medical providers for children, is aimed at familiarizing clinicians with pediatric PH including the pathophysiology, clinical presentation and initial diagnostic strategies, basic chronic management, and management of a pulmonary hypertensive crisis.