RESUMEN
Pulmonary arterial hypertension (PAH) remains a progressive disease without a cure, despite the development of several treatment options over the past several decades. Its management strategy consists of the endothelin receptor antagonists (ambrisentan, bosentan, macitentan), phosphodiesterase-5 inhibitors (sildenafil, tadalafil, vardenafil), and prostacyclin analogs (epoprostenol, treprostinil, iloprost). Treprostinil, a stable prostacyclin analog, displays vasodilatory effects in the pulmonary vasculature, as well as antiplatelet aggregation properties. Clinical practice guidelines recommend oral endothelin receptor antagonist or phosphodiesterase inhibitor therapy in mild to moderate PAH. Epoprostenol is specifically suggested as first-line therapy in moderate to severe PAH patients (ie, World Health Organization/New York Heart Association functional class III-IV). However, treprostinil may be an alternative option in these severe PAH patients. The longer half-life and stability at room temperature with treprostinil may be associated with lower risk of pulmonary hemodynamic worsening as a result of abrupt infusion discontinuation and less frequent drug preparation. These characteristics make treprostinil an attractive alternative to continuous infusion of epoprostenol, due to convenience and patient safety. The purpose of this review is to evaluate the safety and efficacy of continuous infusion of treprostinil as well as the inhaled and oral routes of administration in PAH.
RESUMEN
OBJECTIVE: To review the literature evaluating the clinical safety and efficacy of conivaptan in the management of hyponatremia in a neurologic and neuro-surgical adult patient population. DATA SOURCES: A literature search was conducted using MEDLINE, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials (1966-May 2013). Search limits were English, human, and adult using the terms vasopressin receptor antagonist, conivaptan, tolvaptan, lixivaptan, neurology, neurological disorder, neurosurgery, neurointensive care, and neurocritical care. STUDY SELECTION AND DATA EXTRACTION: All case reports, case series, and clinical trials investigating the use of conivaptan in neurosurgical patients were included. DATA SYNTHESIS: Seven reports were identified using conivaptan as monotherapy or adjunctive treatment for hyponatremia in a neurosurgical patient population. One study was a prospective, randomized, controlled trial, while 6 reports were case reports or case series. The prospective randomized trial found a significant increase in serum sodium concentration over baseline with a conivaptan 20-mg intravenous bolus dose followed by a 20-mg/day continuous infusion for 24 hours compared to "usual care" at 6 hours (7.0 ± 1.7 vs -0.6 ± 2.1 mEq/L, respectively; p = 0.008) and 36 hours (8.0 ± 5.6 vs -1.7 ± 2.1 mEq/L, respectively; p = 0.05) after treatment. One case series found that the mean serum sodium remained significantly increased from baseline up to 72 hours (5.12 ± 4.0 mEq/L; p < 0.001) after a single conivaptan 20-mg intravenous bolus dose. All reports demonstrated clinical effectiveness of conivaptan in significantly increasing serum sodium concentrations following administration compared to baseline. However, the clinical significance of this finding remains debatable since some of these patients remained hyponatremic. CONCLUSIONS: Overall, conivaptan is a promising and well-tolerated agent for the management of hyponatremia in neurologic and neurosurgical patients. However, its use should be limited to patients in whom conventional therapies fail or as adjunctive therapy.