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Current drug treatment of sepsis

By Robert Shulman

Sepsis is defined as the systemic inflammatory response to infection. This response results from the action of endogenous mediators producing generalised inflammatory reactions in organs remote from the initial focus, leading to varying degrees of end-organ dysfunction. Sepsis is the most common cause of death in the intensive care unit (ICU). Patients with sepsis are not all equally ill. Sepsis is a continuum of injury response ranging from sepsis to septic shock to multiple organ dysfunction syndrome (MODS).

In 1991, a consensus conference produced definitions of sepsis and its adverse sequelae.1 The term systemic inflammatory response syndrome (SIRS) defines the clinical manifestations of the widespread inflammation that results from a variety of insults, including infection, pancreatitis, trauma and burns. Sepsis was defined as the systemic inflammatory response to a documented infection. Severe sepsis is associated with organ dysfunction, hypoperfusion or hypotension (after excluding other causes of hypotension). Septic shock refers to those patients who remain hypotensive despite adequate fluid resuscitation (fluid replacement) and who display perfusion abnormalities such as lactic acidosis, oliguria and acute alteration in mental state. MODS describes the presence of altered organ function such that haemostasis cannot be maintained without intervention.

The incidence of mortality varies with the severity of the disease. One study of 153 septic patients found that 51 per cent died before they were discharged from hospital. By one month after discharge, 56.2 per cent of patients had died, which increased to 68 per cent after six months. At one year after admission, the mortality was greater than 71 per cent.2

Standard treatment

Routine management of the septic patient includes use of suitable antibiotics, taking into account any positive microbiological culture results, the likely source of infection and likely tissue uptake of the antibiotic.3

In septic shock, there is an imbalance between oxygen supply and demand, resulting in cellular and organ dysfunction.4 Fluid resuscitation attempts to reverse hypotension, which generally refers to a mean arterial pressure below 65–70mmHg.

The choice of fluid is hotly debated: Europeans traditionally favour colloids, whereas North Americans prefer crystalloids. In the presence of a dilated, high output circulation, vasopressors, such as noradrenaline, are started if fluids fail to restore adequate arterial pressure and organ perfusion.

Download the attached PDF to read the full article.

Citation: Hospital Pharmacist URI: 10975341

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