Matt Harmon

100 Chapter five Abstract Background Induced normothermia as a treatment for sepsis is controversial. In this study, we aimed to investigate the effect of induced normothermia on the host physiological parameters and the immune response during lipopolysaccharide (LPS)-induced endotoxemia in healthy human volunteers. Methods A total of 12 volunteers received an LPS-infusion of 2ng/kg. Subjects were assigned to either the induced normothermia group or the fever group. In the induced normothermia group, normothermia consisted of external surface cooling, cooled intravenous fluids (4°C) and medication to reduce shivering (buspirone, clonidine and magnesium sulphate). Blood samples were taken prior to- and at 1, 3, 6, and 8 hours after LPS-infusion. We measured plasma cytokine levels of tumor necrosis factor alpha (TNFa), interleukin (iL)-6 and iL-10. A mixed effects model was used to compare variables between groups over time. An area under the curve (AUC) was calculated for cytokine levels and compared using a Wilcoxon signed rank test. Results Induced normothermia significantly reduced peak core body temperature compared to the control group (37.2°C (±0.3) vs. 38.7°C (±0.3); p < 0.0001). LPS resulted in an increased heart rate (59 ± 6 beats per minute (BPM) at baseline to 93 ± 11 BPM at t=3 hours, p = 0.002). Induced normothermia resulted in a significantly lower heart rate compared to controls (p < 0.0001) while mean arterial pressure (p = 0.7) and lactate levels were unchanged (p=0.06). Normothermia also lowered iL-10 levels (p = 0.04) but did not lower C-reactive protein (CRP) (p = 0.08) or plasma cytokine levels of iL-6 or TNFa (p = 0.4 and p = 0.5 respectively). Induced normothermia with external surface cooling was well tolerated in the awake subjects. Conclusions In conclusion, induced normothermia with external cooling and pharmacological adjuncts in awake subjects after LPS infusion was feasible. Induced normothermia lowered heart rate while maintaining perfusion compared to febrile controls. Induced normothermia decreased iL-10 levels, but did not lower pro-inflammatory cytokine levels or CRP.