Research from JAMA — Effect of Heart Rate Control With Esmolol on Hemodynamic and Clinical Outcomes in Patients With Septic Shock — A Randomized Clinical Trial

The molecular background of the Ca(2+)-sensitizing effect of levosimendan relates to its specific interaction with the Ca(2+)-sensor troponin C molecule in the cardiac myofilaments. Over the years, significant preclinical and clinical evidence has accumulated and revealed a variety of beneficial pleiotropic effects of levosimendan and of its long-lived metabolite, OR-1896. First of all, activation of ATP-sensitive sarcolemmal K(+) channels of smooth muscle cells appears as a powerful vasodilator mechanism. Additionally, activation of ATP-sensitive K(+) channels in the mitochondria potentially extends the range of cellular actions towards the modulation of mitochondrial ATP production and implicates a pharmacological mechanism for cardioprotection. Finally, it has become evident, that levosimendan possesses an isoform-selective phosphodiesterase-inhibitory effect. Interpretation of the complex mechanism of levosimendan action requires that all potential pharmacological interactions are analyzed carefully in the framework of the currently available evidence. These data indicate that the cardiovascular effects of levosimendan are exerted via more than an isolated drug-receptor interaction, and involve favorable energetic and neurohormonal changes that are unique in comparison to other types of inodilators.

Non-invasive ventilation (NIV) has become a common treatment for acute and chronic respiratory failure. In comparison with conventional invasive mechanical ventilation, NIV has the advantages of reducing patient discomfort, procedural complications, and mortality. However, NIV is associated with frequent uncomfortable or even life-threatening adverse effects, and patients should be thoroughly screened beforehand to reduce potential severe complications. We performed a detailed review of the relevant medical literature for NIV complications. All major NIV complications are potentially life-threatening and can occur in any patient, but are strongly correlated with the degree of pulmonary and cardiovascular involvement. Minor complications can be related to specific structural features of NIV interfaces or to variable airflow patterns. This extensive review of the literature shows that careful selection of patients and interfaces, proper setting of ventilator modalities, and close monitoring of patients from the start can greatly reduce NIV complications.