Pathophysiology of Septic Shock.

Fundamental features of septic shock are vasodilation, increased permeability, hypovolemia, and ventricular dysfunction. Vasodilation owing to increased nitric oxide and prostaglandins is treated with vasopressors (norepinephrine first). Increased permeability relates to several pathways (Slit/Robo4, vascular endothelial growth factor, angiopoietin 1 and 2/Tie2 pathway, sphingosine-1-phosphate, and heparin-binding protein), some of which are targets for therapies. Hypovolemia is common and crystalloid is recommended for fluid resuscitation. Cardiomyocyte-inflammatory interactions decrease contractility and dobutamine is recommended to increase cardiac output. There is benefit in decreasing heart rate in selected patients with esmolol. Ivabradine is a novel agent for heart rate reduction without decreasing contractility.