Matt Harmon

104 Chapter five as median (25-75th percentile). Results from the linear mixed models were presented as Beta-coefficient (b) and 95% confidence interval (95% CI). A p-value below 0.05 was considered statistically significant. Results The impact of induced normothermia on the physiologic response to LPS-infusion There were no baseline differences in heart rate, mean arterial pressure (MAP) and lab values between groups (data not shown). Subjects in both groups received similar amounts of fluids during the study period. The normothermia group received a total of 7.8g (±1.1g) magnesium and 321mg (±63mg) clonidine. In the fever group, LPS induced shivering, resulting in fever with a peak temperature of 38.7°C (±0.3) at T=3 hours after LPS infusion (figure 1A). In the normothermia group, body temperature was significantly lower compared to the fever group (figure 1A, p<0.0001). The mean peak body temperature was 37.2°C (±0.3) in the normothermia group, at T=3 hours. Supplemental figure 1 shows the individual temperature plots for each volunteer. LPS resulted in an increased heart rate (figure 1B; 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 volunteers with fever (p < 0.0001). MAP values did not differ between groups over time (figure 1C; p = 0.08). At T=3 hours after admission of LPS, Systemic inflammatory response syndrome (SIRS) scores peaked at 2 [2-2] (figure 1D). In the normothermia group, SIRS score was lower compared to the fever group (p = 0.001). LPS increased pH (from 7.42 ± 0.01 at baseline to 7.47 ± 0.05 at t=3 hours, p=0.02) and decreased PCO2 levels (from 5.19 ± 0.19 kPa at baseline to 4.28 ± 0.81 kPa at t=3 hours, p= 0.04), likely due to hyperventilation (figure 2D & E respectively). Induced normothermia lowered pH (p = 0.01) and PCO2 p = (0.05) during the study period compared to the fever group. Lactate levels increased after LPS infusion, but not significantly (figure 2F; from 1.26 ± 0.29 mmol/L at baseline to 1.56 ± 0.50 mmol/L at T=1-hour, p=0.26). Lactate levels were consistently lower in the normothermia group compared to the fever but were not significantly different (p = 0.06). Shivering was largely prevented in the normothermia group (figure 3A). One hour after LPS infusion, volunteers in both groups reported cold discomfort. In the fever group, this gradually changed to heat discomfort at T=4 hours. The normothermia group reported cold discomfort at T=1 hour gradually returned to neutral at T=4 hours (figure 3B).