Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep

Pulmonary hypertension of the newborn (PHN) constitutes a critical condition with severe cardiovascular and neurological consequences. One of its main causes is hypoxia during gestation, and thus, it is a public health concern in populations living above 2500 m. Although some mechanisms are recognized, the pathophysiological facts that lead to PHN are not fully understood, which explains the lack of an effective treatment. Oxidative stress is one of the proposed mechanisms inducing pulmonary vascular dysfunction and PHN. Therefore, we assessed whether melatonin, a potent antioxidant, improves pulmonary vascular function. Twelve newborn sheep were gestated, born, and raised at 3600 meters. At 3 days old, lambs were catheterized and daily cardiovascular measurements were recorded. Lambs were divided into two groups, one received daily vehicle as control and another received daily melatonin (1 mg/kg/d), for 8 days. At 11 days old, lung tissue and small pulmonary arteries (SPA) were collected. Melatonin decreased pulmonary pressure and resistance for the first 3 days of treatment. Further, melatonin significantly improved the vasodilator function of SPA, enhancing the endothelial‐ and muscular‐dependent pathways. This was associated with an enhanced nitric oxide‐dependent and nitric oxide independent vasodilator components and with increased nitric oxide bioavailability in lung tissue. Further, melatonin reduced the pulmonary oxidative stress markers and increased enzymatic and nonenzymatic antioxidant capacity. Finally, these effects were associated with an increase of lumen diameter and a mild decrease in the wall of the pulmonary arteries. These outcomes support the use of melatonin as an adjuvant in the treatment for PHN.     

Impact of medication therapy management on pharmacotherapy safety in an intensive care unit

Background Drug-related problems are mostly preventable or predictable circumstances that may impact on health outcomes. Clinical pharmacy activities such as medication therapy management can identify and solve these problems, with potential to improve medication safety and effectiveness. Objective To evaluate ability of medication therapy management service to detect drug-related problems and prevent adverse drug events. This study also aimed to assess the risk factors for drugrelated problem occurrence. Setting Medical intensive care unit of a public tertiary hospital in Brazil. Methods Patients were evaluated by a clinical pharmacist, who provided medication therapy management service. Detected drug-related problems were categorized according to the Pharmaceutical Care Network Europe methodology and analyzed in multinomial regression to identify risk factors. Main outcome measure Potential risk factors for drug-related problem occurrence. Results The proposed medication therapy management service allowed detection of 170 drug-related problems that had potential to reach patients causing harm and other 50 unavoidable adverse events. Drug-related problems identified were more often associated with antibacterial use, caused by improper combinations or inadequate drug dosage. These problems required interventions that were accepted by the multidisciplinary team, resulting in more than 85% adherence and total problem solving. Main risk factors identified were previous diagnosis of kidney injury (OR?=?8.38), use of midazolam (OR?=?7.96), furosemide (OR?=?5.87) and vancomycin (OR?=?4.82). Conclusion Medication therapy management proved to be an effective method not only for drug-related problem detection, but also for adverse drug event prevention, contributing to improve patient safety.