The Rationale for Vasodilator Therapy in Sepsis

  • M. Siegemund
  • I. Racovitza
  • C. Ince

Abstract

In 1969, Joly and Weil showed a direct correlation between toe skin temperature, cardiac output and survival [1]. Since that time many hemodynamic studies in sepsis and septic shock have evaluated therapeutic strategies to increase cardiac output, blood pressure and organ blood flow. Their effect on the skin and other micro-circulatory areas has been neglected for the most part, probably because no monitoring techniques were available. Initial studies showed improved survival after the optimization of oxygen delivery (DO2) [2, 3]. However, controlled clinical trials establishing normal or even supra-normal DO2 values failed to show any survival benefits [4, 5]. A therapeutic increase in blood pressure did not significantly affect surrogate markers of microcirculatory tissue perfusion and function [6]. In addition, the non-selective inhibition of the endothelial vasodilator nitric oxide (NO), acting primarily in the microcirculation, by L-NG-methylarginine increased mortality in patients with septic shock [7]. One possible cause of this increased mortality is that unselective blockade of NO synthase (NOS) further harms the microcirculatory blood flow and aggravates the already existing impaired tissue oxygenation [8]. This tissue dysoxia, a primary feature of endotoxemia and sepsis, may result from disturbed tissue DO2 and/or a defect in cellular oxygen utilization resulting in a cellular oxygen extraction deficit [9, 10]. This extraction deficit could be causally related to a shut down of vulnerable microcirculatory units in organ beds promoting shunt flow of oxygen from the microcirculation to the venous system [10]. This effect could be aggravated in sepsis where normally available autoregulatory mechanisms are disturbed leaving these weak microcirculatory units dysoxic [11–15]. In the present chapter, we will address pathophysiologic changes in the microcirculation in sepsis regarding a possible role of vasodilator drugs or selective inducible NOS (iNOS) blocking drugs to improve microcirculatory blood flow and oxygenation.

Keywords

Nitric Oxide Endotoxic Shock Vasodilator Therapy Microvascular Blood Flow Microcirculatory Blood Flow 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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© Springer Science+Business Media New York 2002

Authors and Affiliations

  • M. Siegemund
  • I. Racovitza
  • C. Ince

There are no affiliations available

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