Introduction
Materials and methods
General preparation
Neurovascular coupling measurement
Clinical chemistry
Study design
Statistics
Results
Glucose (mg/dL) | Lactate (mmol/L) | pH | pCO2 (mmHg) | Hemoglobin (mg/l) | ||||||
---|---|---|---|---|---|---|---|---|---|---|
Base | End | Base | End | Base | End | Base | End | Base | End | |
Control
| 78 ± 12 | 82 ± 8 | - | 0.7 ± 0.7 | 7.57 ± 0.06 | 7.53 ± 0.05 | 32.6 ± 4.5 | 33.5 ± 2.2 | 137 ± 7 | 135 ± 6 |
1 mg/kg
| 89 ± 18 | 55 ± 9*** | - | 2.5 ± 0.8*** | 7.53 ± 0.05 | 7.48 ± 0.04* | 34.5 ± 5.1 | 32.8 ± 2.2 | 137 ± 6 | 124 ± 15* |
5 mg/kg
| 74 ± 19 | 46 ± 15*** | - | 2.4 ± 0.7*** | 7.51 ± 0.05 | 7.46 ± 0.04*** | 35.5 ± 4.1 | 32.3 ± 1.7 | 133 ± 9 | 122 ± 15** |
1 mg/kg. + NE
| 85 ± 15 | 68 ± 14* | - | 1.4 ± 0.4*** | 7.52 ± 0.05 | 7.48 ± 0.05* | 35.4 ± 4.0 | 34.3 ± 3.1 | 139 ± 10 | 119 ± 19** |
5 mg/kg + NE
| 76 ± 14 | 70 ± 23 | - | 1.5 ± 0.6*** | 7.52 ± 0.03 | 7.46 ± 0.05** | 34.8 ± 3.2 | 32.8 ± 2.5 | 145 ± 12 | 122 ± 17** |
1 mg/kg + 1400W
| 78 ± 14 | 51 ± 7*** | - | 2.5 ± 0.6*** | 7.53 ± 0.06 | 7.46 ± 0.09** | 36.4 ± 4.8 | 35.2 ± 2.6 | 142 ± 12 | 121 ± 18** |
5 mg/kg + 1400W
| 73 ± 15 | 46 ± 8*** | - | 2.4 ± 0.4*** | 7.52 ± 0.03 | 7.46 ± 0.04*** | 34.8 ± 3.4 | 34.3 ± 1.4 | 139 ± 9 | 120 ± 15** |
Baseline | 30 min | 60 min | 120 min | 180 min | 240 min | 270 min | ||
---|---|---|---|---|---|---|---|---|
Mean BP (mmHg)
| Control | 108 ± 12 | 108 ± 9 | 101 ± 12 | 103 ± 11 | 104 ± 14 | 108 ± 18 | 107 ± 14 |
Mean BP (mmHg)
| 1 mg/kg | 110 ± 11 | 84 ± 13*** | 65 ± 8*** | 66 ± 10*** | 62 ± 12*** | 56 ± 9*** | 63 ± 10*** |
Mean BP (mmHg)
| 5 mg/kg | 115 ± 10 | 83 ± 17*** | 62 ± 7*** | 61 ± 12*** | 54 ± 14*** | 50 ± 7*** | 56 ± 11*** |
Mean BP (mmHg)
| 1 mg/kg +NE | 108 ± 12 | 84 ± 14*** | 99 ± 12 | 92 ± 11 | 97 ± 11 | 94 ± 15 | 95 ± 15 |
Mean BP (mmHg)
| 5 mg/kg +NE | 104 ± 10 | 79 ± 13*** | 93 ± 19 | 90 ± 13 | 94 ± 12 | 94 ± 16 | 92 ± 13 |
Mean BP (mmHg)
| 1 mg/kg +1400W | 106 ± 13 | 79 ± 18*** | 80 ± 7** | 83 ± 10** | 85 ± 10** | 79 ± 10*** | 82 ± 12*** |
Mean BP (mmHg)
| 5 mg/kg +1400W | 110 ± 11 | 73 ± 16*** | 77 ± 11** | 81 ± 8** | 82 ± 10** | 78 ± 13*** | 76 ± 12*** |
SEP (μV)
| Control | 21 ± 4 | 20 ± 5 | 21 ± 5 | 21 ± 5 | 20 ± 4 | 20 ± 4 | 20 ± 4 |
SEP (μV)
| 1 mg/kg | 21 ± 7 | 18 ± 6 | 15 ± 5** | 15 ± 4*** | 12 ± 3*** | 13 ± 3*** | 12 ± 4*** |
SEP (μV)
| 5 mg/kg | 20 ± 5 | 18 ± 5 | 15 ± 5** | 15 ± 5*** | 13 ± 4*** | 10 ± 3*** | 7 ± 2*** |
SEP (μV)
| 1 mg/kg +NE | 21 ± 4 | 18 ± 4 | 18 ± 3* | 17 ± 3** | 16 ± 3** | 16 ± 3** | 16 ± 3** |
SEP (μV)
| 5 mg/kg +NE | 21 ± 7 | 17 ± 4 | 15 ± 4** | 15 ± 4*** | 13 ± 2*** | 12 ± 2*** | 14 ± 3*** |
SEP (μV)
| 1 mg/kg +1400W | 22 ± 3 | 18 ± 3 | 11 ± 2*** | 11 ± 2*** | 10 ± 2*** | 9 ± 2*** | 9 ± 1*** |
SEP (μV)
| 5 mg/kg +1400W | 21 ± 3 | 17 ± 4 | 11 ± 2*** | 11 ± 2*** | 10 ± 1*** | 10 ± 2*** | 10 ± 2*** |
P1 latency (ms)
| Control | 11 ± 1 | 11 ± 1 | 11 ± 2 | 11 ± 1 | 12 ± 1 | 11 ± 1 | 12 ± 1 |
P1 latency (ms)
| 1 mg/kg | 11 ± 0.4 | 11 ± 1 | 12 ± 1* | 12 ± 1 | 12 ± 1 | 12 ± 2 | 13 ± 1 |
P1 latency (ms)
| 5 mg/kg | 11 ± 1 | 12 ± 1 | 12 ± 1* | 12 ± 2 | 12 ± 1 | 13 ± 2 | 13 ± 2 |
P1 latency (ms)
| 1 mg/kg +NE | 12 ± 0.5 | 12 ± 1 | 12 ± 1 | 12 ± 1 | 12 ± 1 | 12 ± 1 | 12 ± 1 |
P1 latency (ms)
| 5 mg/kg +NE | 11 ± 1 | 12 ± 0.4 | 12 ± 0.5* | 12 ± 2 | 12 ± 1 | 12 ± 1 | 14 ± 3 |
P1 latency (ms)
| 1 mg/kg +1400W | 12 ± 0.5 | 13 ± 1** | 14 ± 1*** | 14 ± 1*** | 15 ± 2*** | 15 ± 3*** | 15 ± 2** |
P1 latency (ms)
| 5 mg/kg +1400W | 12 ± 0.5 | 13 ± 1** | 14 ± 1*** | 14 ± 1*** | 14 ± 1*** | 14 ± 1*** | 15 ± 1* |
EFVR (%)
| Control | 20 ± 8 | 20 ± 6 | 20 ± 5 | 16 ± 6 | 17 ± 5 | 17 ± 4 | 18 ± 4 |
EFVR (%)
| 1 mg/kg | 22 ± 10 | 14 ± 7 | 10 ± 4** | 10 ± 4* | 10 ± 4** | 11 ± 5** | 10 ± 5*** |
EFVR (%)
| 5 mg/kg | 24 ± 7 | 16 ± 7 | 7 ± 2*** | 6 ± 2** | 5 ± 2*** | 6 ± 2*** | 4 ± 2*** |
EFVR (%)
| 1 mg/kg +NE | 23 ± 7 | 18 ± 6 | 16 ± 10 | 14 ± 10 | 11 ± 8** | 10 ± 7*** | 9 ± 6*** |
EFVR (%)
| 5 mg/kg +NE | 23 ± 7 | 14 ± 6 | 10 ± 7** | 5 ± 3*** | 3 ± 3*** | 4 ± 3*** | 5 ± 4*** |
EFVR (%)
| 1 mg/kg +1400W | 18 ± 5 | 16 ± 8 | 8 ± 4*** | 7 ± 3** | 6 ± 2*** | 5 ± 4*** | 5 ± 3*** |
EFVR (%)
| 5 mg/kg +1400W | 24 ± 7 | 20 ± 10 | 7 ± 4*** | 8 ± 5** | 7 ± 5*** | 6 ± 3*** | 5 ± 4*** |
Resting LDF (U)
| Control | 176 ± 49 | 166 ± 38 | 170 ± 39 | 178 ± 33 | 178 ± 35 | 183 ± 32 | 186 ± 32 |
Resting LDF (U)
| 1 mg/kg | 167 ± 60 | 180 ± 66 | 185 ± 70 | 200 ± 95 | 201 ± 94 | 203 ± 101 | 213 ± 110 |
Resting LDF (U)
| 5 mg/kg | 145 ± 25 | 149 ± 44 | 132 ± 35 | 143 ± 37 | 153 ± 50 | 166 ± 58 | 193 ± 84 |
Resting LDF (U)
| 1 mg/kg +NE | 153 ± 57 | 140 ± 38 | 187 ± 63 | 220 ± 96 | 243 ± 90* | 248 ± 92 | 258 ± 82* |
Resting LDF (U)
| 5 mg/kg +NE | 162 ± 41 | 174 ± 57 | 170 ± 51 | 208 ± 58 | 231 ± 55 | 247 ± 79 | 267 ± 81* |
Resting LDF (U)
| 1 mg/kg +1400W | 171 ± 45 | 156 ± 47 | 170 ± 90 | 176 ± 53 | 185 ± 61 | 195 ± 63 | 190 ± 85 |
Resting LDF (U)
| 5 mg/kg +1400W | 141 ± 48 | 120 ± 40* | 128 ± 39 | 140 ± 58 | 140 ± 47 | 141 ± 41 | 157 ± 47 |
NSE ng/l | S-100B ng/ml | IL 6 pg/ml | TNF-α pg/ml | IFN-γ pg/ml | |
---|---|---|---|---|---|
Control
| 0.29 ± 0.14 | 0.63 ± 0.3 | 93 ± 28 | 60 ± 22 | 32 ± 3 |
5 mg/kg LPS
| 1.8 ± 0.9 | 13 ± 8.6 | 5498 ± 1980 | 1868 ± 977 | 1600 ± 540 |
5 mg/kg LPS+1400W
| 1.6 ± 0.9 | 11 ± 9.7 | 4998 ± 1780 | 1655 ± 877 | 1800 ± 820 |
5 mg/kg LPS +NE
| 2.2 ± 0.4 | 10 ± 7.6 | 5300 ± 1654 | 1285 ± 592 | 1960 ± 660 |
General findings
Neurofunctional findings
Discussion
Conclusions
Key messages
-
Microcirculatory dysfunction occurs early in the septic brain.
-
Besides its effects on blood pressure, norepinephrine does not prevent the occurrence of sepsis-related cerebral microcirculatory failure and the effect on evoked potential amplitudes seems to be a side effect of the agent.
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Under septic conditions, 1400W stabilizes the blood pressure but shows a direct adverse effect on evoked potential amplitudes which does not appear under physiologic conditions. Due to this effect, interpretation of its effects on the neurovascular coupling is limited; however, a clear beneficial effect was lacking.