Introduction
Materials and methods
Animal preparation and experimental setting
Experimental protocol
Statistical analysis
Results
Fluid balance
Mortality
Systemic hemodynamics, oxygen transport and lactate concentrations
Variable | Group | N | Intra-operative | Baseline | 3 hours | 6 hours | 12 hours | End | Interactions |
P
|
---|---|---|---|---|---|---|---|---|---|---|
Cardiac index (ml/kg/min) | Time × model effect: |
0.02
| ||||||||
C 10 ml/kg | 8 | n. a. | 89 ± 14 | 88 ± 21 | 93 ± 22 | 100 ± 32 | 103 ± 24 | |||
C 20 ml/kg | 8 | n. a. | 73 ± 24 | 88 ± 10 | 92 ± 11 | 96 ± 22 | 99 ± 14 | |||
E 10 ml/kg | 7 | n. a. | 75 ± 17 | 69 ± 21 | 84 ± 25 | 98 ± 29 | 113 ± 32 | |||
E 20 ml/kg | 8 | n. a. | 87 ± 19 | 83 ± 24 | 106 ± 33 | 130 ± 37 | 117 ± 38 | ANOVArm E: |
0.002
| |
P 10 ml/kg | 8 | n. a. | 86 ± 17 | 92 ± 28 | 105 ± 26 | 87 ± 26 | 94 ± 13 | |||
P 20 ml/kg | 8 | n. a. | 82 ± 12 | 113 ± 31 | 103 ± 21 | 108 ± 24 | 133 ± 73 | ANOVArm P: |
0.04
| |
Heart rate (beats/min) | Time × model effect: |
0.001
| ||||||||
C 10 ml/kg | 8 | 116 ± 19 | 114 ± 38* | 129 ± 40 | 138 ± 45 | 147 ± 42 | 138 ± 27 | ANOVArm C: |
0.04
| |
C 20 ml/kg | 8 | 126 ± 24 | 112 ± 25* | 107 ± 18 | 124 ± 33 | 125 ± 29 | 135 ± 37 | |||
E 10 ml/kg | 7 | 119 ± 20 | 99 ± 12* | 114 ± 28 | 130 ± 28 | 153 ± 27 | 166 ± 20 | ANOVArm E: |
0.002
| |
E 20 ml/kg | 8 | 122 ± 16 | 111 ± 22* | 99 ± 15 | 117 ± 25 | 137 ± 36 | 136 ± 33 | |||
P 10 ml/kg | 8 | 115 ± 19 | 114 ± 12* | 164 ± 24 | 186 ± 27 | 165 ± 37 | 148 ± 36 | ANOVArm P: |
0.001
| |
P 20 ml/kg | 8 | 117 ± 13 | 99 ± 11* | 158 ± 37 | 175 ± 20 | 154 ± 35 | 156 ± 47 | |||
Stroke volume index (ml/kg/beat) | Time × volume effect: |
0.03
| ||||||||
C 10 ml/kg | 8 | n. a. | 0.8 ± 0.2 | 0.7 ± 0.3 | 0.7 ± 0.3 | 0.7 ± 0.2 | 0.8 ± 0.3 | ANOVArm moderate-volume: |
0.018
| |
C 20 ml/kg | 8 | n. a. | 0.7 ± 0.3 | 0.8 ± 0.1 | 0.8 ± 0.2 | 0.8 ± 0.2 | 0.8 ± 0.2 | |||
E 10 ml/kg | 7 | n. a. | 0.8 ± 0.1 | 0.6 ± 0.2 | 0.7 ± 0.2 | 0.7 ± 0.3 | 0.7 ± 0.2 | |||
E 20 ml/kg | 8 | n. a. | 0.8 ± 0.2 | 0.9 ± 0.3 | 0.9 ± 0.3 | 1.0 ± 0.4 | 1.0 ± 0.5 | |||
P 10 ml/kg | 8 | n. a. | 0.8 ± 0.1 | 0.6 ± 0.2 | 0.6 ± 0.1 | 0.6 ± 0.3 | 0.7 ± 0.2 | |||
P 20 ml/kg | 8 | n. a. | 0.8 ± 0.1 | 0.8 ± 0.3 | 0.6 ± 0.2 | 0.7 ± 0.2 | 0.9 ± 0.5 | |||
Mean arterial pressure (mmHg) | Time × model effect: Time × volume effect: |
0.001
0.03
| ||||||||
C 10 ml/kg | 8 | 91 ± 13 | 71 ± 7# | 69 ± 14 | 72 ± 12 | 75 ± 5 | 72 ± 14 | |||
C 20 ml/kg | 8 | 92 ± 5 | 69 ± 11# | 75 ± 15 | 77 ± 15 | 83 ± 15 | 76 ± 24 | ANOVArm high-volume: |
0.001
| |
E 10 ml/kg | 7 | 97 ± 8 | 69 ± 8# | 86 ± 12 | 76 ± 14 | 78 ± 11 | 80 ± 11 | |||
E 20 ml/kg | 8 | 99 ± 19 | 70 ± 13# | 105 ± 8 | 102 ± 16 | 86 ± 18 | 74 ± 23 | ANOVArm E: |
0.001
| |
P 10 ml/kg | 8 | 87 ± 13 | 69 ± 10# | 75 ± 14 | 64 ± 10 | 66 ± 15 | 49 ± 20 | |||
P 20 ml/kg | 8 | 86 ± 16 | 74 ± 26# | 86 ± 23 | 83 ± 23 | 76 ± 27 | 61 ± 25 | ANOVArm P: |
0.002
| |
Mean pulmonary artery pressure (mmHg) | Time × model effect: Time × volume effect: |
0.003
0.01
| ||||||||
C 10 ml/kg | 8 | n. a. | 17 ± 4 | 19 ± 6 | 18 ± 3 | 20 ± 4 | 25 ± 3 | ANOVArm moderate-volume: |
0.001
| |
C 20 ml/kg | 8 | n. a. | 18 ± 4 | 20 ± 5 | 19 ± 5 | 23 ± 7 | 29 ± 6 | ANOVArm C: |
0.001
| |
E 10 ml/kg | 7 | n. a. | 17 ± 2 | 27 ± 7 | 25 ± 6 | 22 ± 5 | 26 ± 5 | ANOVArm E: |
0.001
| |
E 20 ml/kg | 7 | n. a. | 17 ± 3 | 33 ± 12 | 27 ± 6 | 29 ± 13 | 34 ± 11 | |||
P 10 ml/kg | 8 | n. a. | 16 ± 3 | 23 ± 6 | 20 ± 3 | 21 ± 4 | 24 ± 3 | ANOVArm P: |
0.001
| |
P 20 ml/kg | 7 | n. a. | 18 ± 3 | 25 ± 5 | 25 ± 4 | 29 ± 6 | 36 ± 6 | ANOVArm high-volume: |
0.001
|
Variable | Group | N | Baseline | 3 hours | 6 hours | 12 hours | End | Interactions |
P
|
---|---|---|---|---|---|---|---|---|---|
Central venous pressure (mmHg) | |||||||||
C 10 ml/kg | 8 | 4 ± 2 | 4 ± 2 | 5 ± 2 | 5 ± 1 | 7 ± 2 | ANOVArm moderate-volume: |
0.001
| |
C 20 ml/kg | 8 | 4 ± 2 | 6 ± 2 | 5 ± 2 | 7 ± 4 | 10 ± 5 | ANOVArm C: |
0.001
| |
E 10 ml/kg | 7 | 4 ± 2 | 4 ± 2 | 5 ± 2 | 5 ± 2 | 6 ± 3 | ANOVArm E: |
0.001
| |
E 20 ml/kg | 8 | 3 ± 2 | 6 ± 3 | 7 ± 3 | 7 ± 2 | 9 ± 1 | |||
P 10 ml/kg | 8 | 3 ± 2 | 3 ± 1 | 4 ± 1 | 6 ± 2 | 7 ± 2 | ANOVArm P: |
0.001
| |
P 20 ml/kg | 8 | 5 ± 3 | 6 ± 3 | 8 ± 4 | 10 ± 3 | 14 ± 3 | ANOVArm high-volume: |
0.001
| |
Pulmonary artery occlusion pressure (mmHg) | |||||||||
C 10 ml/kg | 8 | 4 ± 2 | 5 ± 2 | 5 ± 2 | 5 ± 2 | 8 ± 2 | ANOVArm: |
0.001
| |
C 20 ml/kg | 8 | 5 ± 3 | 6 ± 3 | 6 ± 2 | 7 ± 4 | 10 ± 5 | ANOVArm: |
0.013
| |
E 10 ml/kg | 7 | 5 ± 1 | 5 ± 2 | 5 ± 2 | 5 ± 2 | 7 ± 4 | ANOVArm: |
0.10
| |
E 20 ml/kg | 7 | 5 ± 3 | 9 ± 5 | 7 ± 4 | 8 ± 5 | 10 ± 3 | ANOVArm: |
0.018
| |
P 10 ml/kg | 8 | 4 ± 1 | 4 ± 1 | 5 ± 2 | 6 ± 2 | 8 ± 2 | ANOVArm: |
0.001
| |
P 20 ml/kg | 7 | 7 ± 2 | 7 ± 2 | 8 ± 3 | 10 ± 2 | 17 ± 8 | ANOVArm: |
0.008
| |
Mixed venous saturation (%) | Time × model effect: |
0.009
| |||||||
C 10 ml/kg | 8 | 55 ± 6 | 54 ± 11 | 55 ± 1 | 55 ± 8 | 57 ± 7 | |||
C 20 ml/kg | 8 | 49 ± 7 | 59 ± 5 | 59 ± 4 | 60 ± 1 | 55 ± 18 | |||
E 10 ml/kg | 7 | 49 ± 6 | 51 ± 5 | 55 ± 6 | 57 ± 3 | 55 ± 8 | ANOVArm E: |
0.013
| |
E 20 ml/kg | 7 | 49 ± 5 | 49 ± 11 | 60 ± 8 | 66 ± 2 | 56 ± 11 | |||
P 10 ml/kg | 8 | 53 ± 7 | 59 ± 4 | 58 ± 7 | 55 ± 6 | 47 ± 13 | ANOVArm P: |
0.008
| |
P 20 ml/kg | 7 | 46 ± 1 | 57 ± 12 | 56 ± 14 | 57 ± 9 | 43 ± 24 | |||
Arterial lactate (mmol/l) | Time × model effect: |
0.046
| |||||||
C 10 ml/kg | 8 | 0.6 ± 0.2 | 0.5 ± 0.2 | 0.7 ± 0.5 | 0.6 ± 0.1 | 0.7 ± 0.2 | |||
C 20 ml/kg | 8 | 0.6 ± 0.1 | 0.6 ± 0.2 | 0.6 ± 0.1 | 0.6 ± 0.1 | 1.0 ± 1.0 | |||
E 10 ml/kg | 7 | 0.7 ± 0.1 | 1.2 ± 0.7 | 0.9 ± 0.4 | 0.8 ± 0.3 | 0.9 ± 0.5 | ANOVArm E: |
0.04
| |
E 20 ml/kg | 8 | 0.7 ± 0.1 | 1.0 ± 0.3 | 0.9 ± 0.3 | 1.0 ± 0.2 | 1.0 ± 0.3 | |||
P 10 ml/kg | 8 | 0.6 ± 0.2 | 1.4 ± 0.6 | 1.5 ± 0.6 | 1.1 ± 0.4 | 1.5 ± 0.6 | ANOVArm P: |
0.001
| |
P 20 ml/kg | 8 | 0.8 ± 0.6 | 1.1 ± 0.6 | 1.1 ± 0.6 | 1.1 ± 0.3 | 1.4 ± 0.6 |
Mitochondrial function
Lungs
Variable | Group | N | Baseline | 3 hours | 6 hours | 12 hours | End | Interactions |
P
|
---|---|---|---|---|---|---|---|---|---|
Dynamic compliance | Time effect: |
0.001
| |||||||
C 10 ml/kg | 8 | 28 ± 6 | 25 ± 8 | 26 ± 7 | 25 ± 8 | 17 ± 5 | |||
C 20 ml/kg | 8 | 30 ± 7 | 25 ± 8 | 26 ± 6 | 21 ± 5 | 14 ± 5 | |||
E 10 ml/kg | 7 | 31 ± 7 | 27 ± 5 | 28 ± 6 | 24 ± 5 | 18 ± 4 | |||
E 20 ml/kg | 8 | 32 ± 3 | 25 ± 3 | 24 ± 3 | 22 ± 5 | 22 ± 5 | |||
P 10 ml/kg | 8 | 28 ± 2 | 24 ± 6 | 20 ± 3 | 20 ± 2 | 15 ± 2 | |||
P 20 ml/kg | 8 | 32 ± 8 | 25 ± 6 | 21 ± 3 | 18 ± 2 | 14 ± 6 | |||
Plateau pressure (cmH2O) | Time × volume effect: |
0.043
| |||||||
C 10 ml/kg | 8 | 18 ± 2 | 19 ± 2 | 20 ± 3 | 19 ± 4 | 24 ± 4 | |||
C 20 ml/kg | 8 | 18 ± 2 | 20 ± 2 | 20 ± 2 | 22 ± 4 | 28 ± 8 | |||
E 10 ml/kg | 7 | 16 ± 3 | 18 ± 4 | 18 ± 4 | 17 ± 4 | 22 ± 6 | ANOVArm moderate-volume: |
0.001
| |
E 20 ml/kg | 7 | 15 ± 5 | 19 ± 7 | 21 ± 6 | 18 ± 6 | 21 ± 7 | |||
P 10 ml/kg | 8 | 17 ± 3 | 19 ± 3 | 20 ± 4 | 22 ± 2 | 24 ± 5 | |||
P 20 ml/kg | 7 | 16 ± 4 | 19 ± 6 | 22 ± 5 | 22 ± 6 | 28 ± 6 | ANOVArm high-volume: |
0.001
| |
Oxygenation index (mmHg/%) | Time × model effect: |
0.026
| |||||||
C 10 ml/kg | 8 | 434 ± 67 | 394 ± 92 | 384 ± 97 | 346 ± 67 | 212 ± 97 | ANOVArm C: |
0.001
| |
C 20 ml/kg | 8 | 456 ± 48 | 412 ± 80 | 424 ± 48 | 347 ± 106 | 236 ± 122 | |||
E 10 ml/kg | 7 | 477 ± 33 | 418 ± 44 | 401 ± 57 | 352 ± 101 | 208 ± 116 | ANOVArm E: |
0.001
| |
E 20 ml/kg | 7 | 447 ± 44 | 313 ± 88 | 291 ± 102 | 252 ± 110 | 170 ± 139 | |||
P 10 ml/kg | 8 | 449 ± 29 | 356 ± 54 | 300 ± 69 | 317 ± 99 | 217 ± 106 | ANOVArm P: |
0.001
| |
P 20 ml/kg | 8 | 412 ± 61 | 292 ± 104 | 247 ± 74 | 193 ± 112 | 63 ± 12 |
Kidney
Variable | Group | N | Baseline | End | Interactions |
P
|
---|---|---|---|---|---|---|
Creatinine kinase - MB (U/L) | Time × volume effect: |
0.006
| ||||
Control 10 ml/kg | 8 | 0.9 ± 0.1 | 1.0 ± 0.2 | |||
Control 20 ml/kg | 8 | 0.9 ± 0.1 | 1.2 ± 0.2 | ANOVArm high-volume: |
0.001
| |
Endotoxin 10 ml/kg | 8 | 1.0 ± 0.2 | 1.0 ± 0.2 | |||
Endotoxin 20 ml/kg | 7 | 1.0 ± 0.2 | 1.1 ± 0.3 | |||
Peritonitis 10 ml/kg | 8 | 1.1 ± 0.2 | 1.1 ± 0.3 | |||
Peritonitis 20 ml/kg | 8 | 0.8 ± 0.3 | 1.3 ± 0.2 | |||
Creatinine (μmol/L) | Time × model effect: Time × volume effect: |
0.014
0.029
| ||||
Control 10 ml/kg | 8 | 87 ± 18 | 78 ± 17 | ANOVArm Control: |
0.007
| |
Control 20 ml/kg | 8 | 99 ± 13 | 74 ± 24 | ANOVArm high-volume: |
0.04
| |
Endotoxin 10 ml/kg | 8 | 86 ± 21 | 79 ± 16 | |||
Endotoxin 20 ml/kg | 7 | 85 ± 15 | 74 ± 10 | |||
Peritonitis 10 ml/kg | 8 | 81 ± 10 | 114 ± 31 | |||
Peritonitis 20 ml/kg | 8 | 82 ± 17 | 76 ± 36 | |||
ALAT (U/L) | Time × volume effect: |
0.001
| ||||
Control 10 ml/kg | 8 | 18.1 ± 4.3 | 14.8 ± 4.5 | |||
Control 20 ml/kg | 8 | 20.5 ± 10.5 | 11.3 ± 10.6 | ANOVArm high-volume: |
0.001
| |
Endotoxin 10 ml/kg | 8 | 17 ± 5.2 | 15.1 ± 4.3 | |||
Endotoxin 20 ml/kg | 7 | 19 ± 5.7 | 11.4 ± 2.4 | |||
Peritonitis 10 ml/kg | 8 | 16.9 ± 6.4 | 16.7 ± 11.2 | |||
Peritonitis 20 ml/kg | 8 | 19.5 ± 9.2 | 11.3 ± 5 | |||
ASAT (U/L) | ||||||
Control 10 ml/kg | 8 | 84 ± 31 | 60 ± 27 | |||
Control 20 ml/kg | 8 | 114 ± 57 | 76 ± 23 | |||
Endotoxin 10 ml/kg | 8 | 96 ± 23 | 86 ± 44 | |||
Endotoxin 20 ml/kg | 7 | 136 ± 84 | 117 ± 23 | |||
Peritonitis 10 ml/kg | 8 | 104 ± 43 | 129 ± 88 | |||
Peritonitis 20 ml/kg | 8 | 101 ± 50 | 100 ± 55 |
Liver
Heart
Discussion
Conclusions
Key messages
-
Aggressive volume resuscitation increases mortality in experimental sepsis.
-
Mitochondrial complex I- or II-dependent muscle and hepatic respiration is maintained after 24 hours of endotoxemia and fecal peritonitis.