Targeted Treatment of Microvascular Dysfunction

Nearly all critically ill patients requiring advanced life support exhibit systemic inflammation. Septic shock, the most common disorder in the critically ill, results from the direct adverse consequences of infection combined with a maladaptive response resulting in fulminant systemic inflammation. This powerful interaction results in a mortality rate of up to 50 % for victims of this disease [1–4]. While septic shock is most often described as ‘warm’ hypotension (particularly lowering diastolic blood pressure) despite initial resuscitation, the patient often exhibits circulatory failure demonstrated by mottled extremities and low mixed or central venous oxygen saturation as a result of inadequate oxygen delivery. A key component of the shock due to severe sepsis, cardiac impairment, can be demonstrated in 50–100 % of patients diagnosed with septic shock [5–9]. While diagnosed at the macrovascular level, cardiac pump failure is itself due to microcirculatory dysfunction and impaired oxygen extraction in the heart [10]. A daily clinical challenge faced by those caring for the critically ill is that while the patient presents with circulatory failure, advanced studies such as echocardiography and measurement of central venous oxygen tension (ScvO2) actually demonstrate normal or even supra-normal cardiac output. This picture is often accompanied by an increasing lactate level and progressive organ dysfunction. It is now believed that this failure to adequately perfuse vital organs despite an ostensibly normal macrocirculation is due to dysfunction of the microcirculation.