Fever control in septic shock: beneficial or harmful?

The beneficial effects of interventions to control fever in sepsis are controversial. We investigated whether the use of acetaminophen and external cooling is beneficial to control fever in septic shock. We studied 24 fasted, anesthetized, invasively monitored, mechanically ventilated female sheep (27.0 +/- 4.6 kg) that received 0.5 g/kg body weight of feces into the abdominal cavity to induce sepsis. Ringer's lactate (RL) was titrated to maintain pulmonary artery occlusion pressure (PAOP) at baseline levels throughout the experimental period. During the 2 h after the surgical operation, animals were placed in the hypothermia group if their temperature fell below 36.0 degrees C; the other animals were randomized to three groups: high fever (T > 39.0 degrees C), mild fever (37.5 degrees C < T < 38.5 degrees C), and normothermia (36.0 degrees C < T < 37.0 degrees C). The administration of 25 mg/kg acetaminophen every 4 to 6 h combined with external cooling (ice pad) was used to control core temperature in these three groups. The PaO2/FiO2 ratio was higher and blood lactate concentration was lower in the high fever than in the other groups (P < 0.01 and 0.05, respectively). Survival time was longer in the high fever group (25.2 +/- 3.0 h) than in the mild fever (17.7 +/- 3.5 h), normothermia (16.0 +/- 1.9 h), and hypothermia (18.5 +/- 2.5 h) groups (P < 0.05 for all). Plasma heat shock protein (HSP) 70 levels were higher in the two fever groups than in the other groups (P < 0.05). In this clinically relevant septic shock model, the febrile response thus resulted in better respiratory function, lower blood lactate concentration, and prolonged survival time. Antipyretic interventions including acetaminophen and external cooling were associated with lower circulating HSP70 levels. These data challenge the temperature control practices often used routinely in acutely ill patients.

Use of low tidal volume in septic shock may decrease severity of subsequent acute lung injury.

Recent studies have indicated that protective lung strategies may improve outcomes in acute lung injury. We hypothesized that the use of a lower tidal volume early during septic shock may protect against the subsequent development of acute lung injury. Fourteen fasted, anesthetized, invasively monitored, mechanically ventilated, female sheep (26.4 +/- 4.5 kg) underwent cecal ligation and perforation to induce sepsis. Sheep were then randomized to ventilation with low (6 mL/kg) or high (12 mL/kg) tidal volumes. A positive end-expiratory pressure of 10 cm H(2)O was applied in each case. Ringer's lactate was titrated to maintain pulmonary artery occlusion pressure at baseline levels. No vasoactive agents or antibiotics were used. Survival time was longer in the low- than in the high-tidal-volume group (21.8 +/- 2.4 vs. 17.6 +/- 4.1 h, respectively, P < 0.05). The times to develop hypotension and anuria were longer in the low-tidal-volume group (18.1 +/- 3.1 vs. 12.0 +/- 2.8 h, P < 0.05, and 17.6 +/- 1.6 vs. 14.1 +/- 3.8 h, P < 0.05). Although the Pao2/Fio2 tended to be lower in the low- than in the high-tidal-volume group (P = 0.06), postmortem examination showed a lower lung tissue wet/dry ratio in the low- than in the high-tidal-volume group (7.1 +/- 0.5 vs. 9.1 +/- 0.7, P < 0.05). A low-tidal-volume ventilation strategy applied early during septic shock may be beneficial in terms of reducing the amount of lung edema and prolonging survival time.