Sepsis: Evidence-based pathogenesis and treatment

Figure 3 Sepsis and intervening variables: Hydrogen peroxide is an intervening variable between a critical illness (exposure), which triggers a systemic hypermetabolic response, and sepsis (effect). Hypermetabolism, characterized by the systemic inflammatory response syndrome, is the clinical manifestation of supraphysiological cellular H₂O₂ production. This will eventually lead to reductive depletion and sepsis (H₂O₂ toxicity, bioenergetic organ failure) if allowed to persist. Prolonged critical illness (hypermetabolism) and dietary restriction severely limit the body’s ability to re-establish and maintain redox homeostasis. Under these circumstances, direct acting reducing equivalents must be supplied to the patient to aid in neutralizing excess H₂O₂. A hypermetabolic response to critical illness or injury may continue for years after hospital discharge and contribute to increased inpatient and post-discharge morbidity and mortality (chronic critical illness and post sepsis syndrome respectively)[52-55].