Lucinactant for the treatment of respiratory distress syndrome in neonates.

Respiratory distress syndrome (RDS) is a leading cause of morbidity and mortality in premature neonates. This syndrome is caused by a lack of endogenous surfactant production in the lungs. Surfactant replacement was established as a safe and effective treatment in the 1990s and has become the standard of care for these infants. Surfactant products are either protein-free synthetic phospholipid compounds or animal-derived lung preparations. Currently, about 90,000 infants a year receive treatment with one of the commercially available animal-derived surfactants. Lucinactant (Surfaxin®) is a new synthetic surfactant with a pulmonary surfactant-associated protein B mimic that recently received FDA approval. The clinical trials that have been performed, although underpowered, may indicate that lucinactant is superior to phospholipid synthetic surfactant preparations and at least as effective as animal-derived surfactants in reducing morbidity and mortality from RDS. This review summarizes the current clinical knowledge about lucinactant.

Sugammadex, the first selective relaxant binding agent for neuromuscular block reversal.

Neuromuscular blocking agents (NMBAs) are widely used to provide muscle relaxation for endotracheal intubation, certain modes of mechanical ventilation and surgical procedures. Full and rapid reversal of this muscle relaxation is needed to prevent residual muscle paralysis and respiratory compromise. The novel selective reversal binding agent, sugammadex, rapidly reverses muscle paralysis from steroidal NMBAs. Sugammadex encapsulates steroidal NMBAs in the plasma and renders them unavailable to the neuromuscular junction receptors. Unlike other reversal agents, sugammadex has the ability to provide fast and thorough reversal of neuromuscular paralysis regardless of the level of blockade. Sugammadex has shown limited adverse effects and avoids the cardiovascular and autonomic effects commonly seen with the conventional reversal of NMBAs (anticholinesterase plus anticholinergic). This review summarizes the current knowledge about sugammadex, its pharmacology and safety profile, dosing recommendations, potential clinical applications and economic impact.

Regional pulmonary inflammation in an endotoxemic ovine acute lung injury model.

The regional distribution of inflammation during acute lung injury (ALI) is not well known. In an ovine ALI model we studied regional alveolar inflammation, surfactant composition, and CT-derived regional specific volume change (sVol) and specific compliance (sC). 18 ventilated adult sheep received IV lipopolysaccharide (LPS) until severe ALI was achieved. Blood and bronchoalveolar lavage (BAL) samples from apical and basal lung regions were obtained at baseline and injury time points, for analysis of cytokines (IL-6, IL-1ß), BAL protein and surfactant composition. Whole lung CT images were obtained in 4 additional sheep. BAL protein and IL-1ß were significantly higher in injured apical vs. basal regions. No significant regional surfactant composition changes were observed. Baseline sVol and sC were lower in apex vs. base; ALI enhanced this cranio-caudal difference, reaching statistical significance only for sC. This study suggests that apical lung regions show greater inflammation than basal ones during IV LPS-induced ALI which may relate to differences in regional mechanical events.

Disseminated intravascular coagulopathy in aortic aneurysms.

Aneurysm-induced disseminated intravascular coagulopathy (DIC) constitutes a rare presentation form of aortic aneurysms. The majority of DIC cases are asymptomatic and this condition is usually diagnosed during the perioperative workup; yet, in a minority of cases, DIC leads to the diagnosis of the vascular abnormality. The management of aneurysm-induced DIC is based both on the treatment of the underlying disorder and on an active scrutiny of the hemodynamic and blood support requirements. Blood replacement therapy should be individualized, guided by the clinical situation of the patient (especially considering the bleeding risk or the presence of hemorrhages), and accompanied by a close monitoring of the coagulation status. Fresh frozen plasma is usually the preferred initial option to replace coagulation factors, but fibrinogen, cryoprecipitates, and platelet concentrates are adequate options in certain contexts. Heparins, both non-fractionated and low-weight molecular types, are the most widely accepted agents for achieving adequate control of the coagulation activation and consumption. Other antithrombotic drugs are under study, including antithrombin III and activated protein C, although only the latter has demonstrated a benefit in terms of survival in a comparative, randomized context. Antifibrinolytic agents such as gabexate mesilate, tranexamic acid, and epsilon-aminocaproic acid (EACA) have been used with conflicting results. These agents may have a role for patients with catastrophic bleeding resistant to other therapeutical options, but their relevance as a first line of treatment is, at present, undefined. An assessment of the multitude of therapeutic approaches available would seem to indicate that there is a lack of standardization in the management of these patients. Multi-center, randomized clinical trials are needed to elucidate the most adequate therapy in this context.