Despite widespread advances in intensive care practices, and more pote
nt and effective antimicrobials, septic shock continues to have a mort
ality rate of greater than 40%. Although antimicrobials can treat the
etiologic organism, they do not alter the host response. It is becomin
g clear that invading organisms and other insults induce the release o
f cytokines and secondary mediators by the host. These mediators produ
ce alterations in cellular, metabolic and physiologic functions produc
ing the clinical picture of septic shock. Recent advances in cellular
and molecular biology have permitted the identification of some of the
mediators involved in this inflammatory cascade. Potential therapies
are being developed which block or interrupt their activity. Treatment
populations must be meticulously defined if we are to extract useful
information concerning the efficacy of these new treatment modalities.
In the following, proposed definitions for clinical patterns seen in
patients with sepsis, and their inherent problems when applied to pedi
atrics are discussed. The pathophysiology of sepsis is discussed, and
specific therapies designed to interrupt the inflammatory cascade are
examined.