Effect of treatment delay on disease severity and need for resuscitation in porcine fecal peritonitis.

OBJECTIVE: Early treatment in sepsis may improve outcome. The aim of this study was to evaluate how the delay in starting resuscitation influences the severity of sepsis and the treatment needed to achieve hemodynamic stability.\n\nDESIGN: Prospective, randomized, controlled experimental study.\n\nSETTING: Experimental laboratory in a university hospital.\n\nSUBJECTS: Thirty-two anesthetized and mechanically ventilated pigs.\n\nINTERVENTIONS: Pigs were randomly assigned (n=8 per group) to a nonseptic control group or one of three groups in which fecal peritonitis (peritoneal instillation of 2 g/kg autologous feces) was induced, and a 48-hr period of protocolized resuscitation started 6 (ΔT-6 hrs), 12 (ΔT-12 hrs), or 24 (ΔT-24 hrs) hrs later. The aim of this study was to evaluate the impact of delays in resuscitation on disease severity, need for resuscitation, and the development of sepsis-associated organ and mitochondrial dysfunction.\n\nMEASUREMENTS AND MAIN RESULTS: Any delay in starting resuscitation was associated with progressive signs of hypovolemia and increased plasma levels of interleukin-6 and tumor necrosis factor-α prior to resuscitation. Delaying resuscitation increased cumulative net fluid balances (2.1±0.5 mL/kg/hr, 2.8±0.7 mL/kg/hr, and 3.2±1.5 mL/kg/hr, respectively, for groups ΔT-6 hrs, ΔT-12 hrs, and ΔT-24 hrs; p