Background
Methods
Cohort 1
Experimental protocol
Blood gas analyses
Mitochondrial function and skeletal muscle adenosine triphosphate content
Cohort 2
Surgical preparation
Experimental protocol
Blood measurements
Calculations
Statistical analysis
Results
Cohort 1
Mortality
Administered treatments
Parameters | Lac ≥10% | Lac <10% |
p value |
---|---|---|---|
Propofol, mg/kg/h | 5.7 (5.1–6.2) | 5.5 (4.9–5.9) | 0.459a
|
Fentanylb, μg/kg/h | 4.9 (4.5–5.7) | 5.2 (5.0–8.1) | 0.072a
|
Midazolam, mg/kg/h | 0.05 (0.04–0.06) | 0.06 (0.05–00.7) | 0.331a
|
Fluid bolusc,d, ml/kg/h | 0.80 (0.53–1.24) | 1.68 (0.50–2.82) | 0.186a
|
Ringer’s lactate | 0.45 (0.30–0.65) | 0.84 (0.28–1.75) | 0.186a
|
HES | 0.39 (0.23–0.58 | 0.84 (0.21–1.07) | 0.150a
|
Norepinephrine | |||
n/Total n, % | 7/13 (53.8) | 8/11 (72.7) | 0.423e
|
Dose, μg/kg/minute | 0.02 (0.01–0.07) | 0.10 (0.06–0.22) | 0.054a
|
Dobutamine | |||
n/Total n, % | 2/13 (15.4) | 5/11 (45.5) | 0.182e
|
Dose, μg/kg/minute | 1.89 (0.65–3.13) | 0.44 (0.33–0.58) | 0.190a
|
Total volume receivedf, ml/kg/h | 3.61 (3.49–4.11) | 4.12 (3.43–5.39) | 0.303a
|
Urine output, ml/kg/h | 1.00 (0.96–1.15) | 1.21 (0.99–1.36) | 0.134a
|
Gastric tube output, ml/kg/h | 0.22 (0.05–0.30) | 0.42 (0.22–0.71) | 0.036a
|
Final balanceg, ml/kg/h | 2.48 (2.15–2.75) | 2.45 (1.93–4.13) | 1.000a
|
Hemodynamics and respiratory and acid-base parameters
Parameters | Group | BL | BR | RP 6 h | End |
p Value |
---|---|---|---|---|---|---|
Heart rate, beats/minute | Lac ≥10% | 94 ± 20 | 160 ± 40 | 165 ± 26 | 132 ± 34 | 0.369a
|
Lac <10% | 97 ± 17 | 166 ± 30 | 161 ± 34 | 154 ± 33 | ||
MAP, mmHg | Lac ≥10% | 85 ± 12 | 75 ± 11 | 82 ± 13 | 65 ± 10 | 0.113a
|
Lac <10% | 88 ± 13 | 77 ± 19 | 71 ± 12 | 56 ± 20 | ||
MPAP, mmHg | Lac ≥10% | 14 ± 3 | 17 ± 3 | 17 ± 3 | 21 ± 5 | 0.594a
|
Lac <10% | 15 ± 6 | 17 ± 5 | 20 ± 6 | 22 ± 4 | ||
CVP, mmHg | Lac ≥10% | 4 ± 1 | 3 ± 2 | 3 ± 2 | 7 ± 2 | 0.632a
|
Lac <10% | 5 ± 3 | 2 ± 2 | 3 ± 2 | 8 ± 4 | ||
Cardiac output, ml/kg/minute | Lac ≥10% | 131 ± 14 | 106 ± 16 | 120 ± 20 | 151 ± 32 | 0.618a
|
Lac <10% | 132 ± 22 | 119 ± 33 | 122 ± 24 | 144 ± 46 | ||
SVRI, mmHg, L/kg/minute | Lac ≥10% | 629 ± 112 | 696 ± 146 | 677 ± 154 | 393 ± 92 | 0.322a
|
Lac <10% | 654 ± 171 | 652 ± 164 | 575 ± 164 | 326 ± 73 | ||
SvO2, % | Lac ≥10% | 55 ± 8 | 59 ± 11 | 64 ± 9 | 63 ± 12 | 0.264a
|
Lac <10% | 53 ± 9 | 57 ± 6 | 60 ± 6 | 52 ± 18 | ||
DO2, ml/minute | Lac ≥10% | 625 ± 99 | 684 ± 116 | 739 ± 76 | 653 ± 151 | 0.796a
|
Lac <10% | 610 ± 148 | 702 ± 133 | 697 ± 156 | 609 ± 197 | ||
VO2, ml/minute | Lac ≥10% | 273 ± 63 | 270 ± 86 | 249 ± 79 | 220 ± 81 | 0.987a
|
Lac <10% | 275 ± 61 | 281 ± 48 | 256 ± 60 | 234 ± 59 | ||
O2ER | Lac ≥10% | 0.44 ± 0.08 | 0.40 ± 0.11 | 0.34 ± 0.10 | 0.34 ± 0.13 | 0.511a
|
Lac <10% | 0.46 ± 0.09 | 0.41 ± 0.05 | 0.37 ± 0.06 | 0.43 ± 0.18 | ||
Fractional carotid artery blood flow, % | Lac ≥10% | 5.8 ± 1.9 | 4.7 ± 1.8 | 4.6 ± 1.5 | 4.4 ± 1.5 | 0.340a
|
Lac <10% | 5.8 ± 1.2 | 5.4 ± 1.3 | 5.6 ± 1.3 | 5.0 ± 2.0 | ||
Fractional femoral artery blood flow, % | Lac ≥10% | 3.3 ± 1.1 | 2.0 ± 0.5 | 1.7 ± 0.5 | 1.9 ± 0.5 | 0.499a
|
Lac <10% | 3.3 ± 0.8 | 2.1 ± 0.7 | 2.2 ± 0.9 | 2.1 ± 0.8 | ||
Arterial Lac, mmol/L | Lac ≥10% | 0.8 ± 0.1 | 1.4 ± 0.7 | 1.1 ± 0.6 | 1.1 ± 0.7 | 0.124a
|
Lac <10% | 0.9 ± 0.3 | 1.6 ± 1.2 | 1.9 ± 1.4 | 2.3 ± 2.5 |
Inflammatory markers and skeletal muscle ATP
Parameters | Group | BL | BR | End |
p Value |
---|---|---|---|---|---|
IL-6, pg/ml | Lac ≥10% | 0 (0–0) | 854 (481–990) | 45 (37–204) | 0.003a
|
Lac <10% | 16 (0–180) | 873 (531–1983) | 166 (128–310) | <0.001a
| |
0.047b
| |||||
CRP, pg/ml | Lac ≥10% | 1.6 (0.6–2.9) | 10.7 (5.6–12.8) | 19.2 (9.9–39.8) | 0.139c
|
Lac <10% | 3.2 (1.8–5.7) | 16.7 (4.9–31.1) | 16.7 (13.5–33.3) | ||
TNF-α, pg/ml | Lac ≥10% | 53 (38–55) | 119 (94–169) | 72 (47–88) | 0.579c
|
Lac <10% | 47 (37–67) | 178 (120–219) | 92 (57–144) | ||
ATP content, μmol/g wet tissue weight | Lac ≥10% | 2.1 (1.2–2.3) | 2.3 (1.8–3.1) | 0.6 (0.4–0.9) | 0.081c
|
Lac <10% | 2.8 (1.8–4.5) | 3.3 (1.5–4.8) | 0.6 (0.3–0.7) |
Mitochondrial respiration
Cohort 2
Mortality
Hemodynamics
Regional blood flow and Lac exchange
Parameters | Group | BL | 3 h | 6 h | 12 h | End |
p value | Time × group p valuea
| Time p valuea
| Group p valuea
|
---|---|---|---|---|---|---|---|---|---|---|
Carotid artery | Lac ≥10% | 4.2 ± 0.9 | 3.8 ± 1.1 | 3.6 ± 0.5 | 3.2 ± 0.7 | 5.7 ± 2.6 | 0.030b
| 0.077 | 0.458 | 0.078 |
Lac <10% | 3.9 ± 0.9 | 4.1 ± 1.3 | 4.1 ± 1.4 | 5.0 ± 2.0 | 4.9 ± 1.6 | 0.457c
| ||||
0.028c
| ||||||||||
Superior mesenteric artery | Lac ≥10% | 18.4 ± 8.0 | 17.7 ± 9.8 | 17.5 ± 6.6 | 18.8 ± 9.6 | 26.6 ± 11.0 | 0.010b
| 0.858 | 0.179 | 0.807 |
Lac <10% | 13.7 ± 2.9 | 15.7 ± 3.1 | 16.6 ± 3.4 | 18.2 ± 4.1 | 15.3 ± 7.6 | 0.028c
| ||||
Celiac trunk | Lac ≥10% | 9.2 ± 4.6 | 10.8 ± 3.4 | 9.8 ± 4.4 | 12.5 ± 3.9 | 11.8 ± 5.9 | 0.191b
| 0.067 | 0.221 | 0.067 |
Lac <10% | 8.8 ± 3.7 | 9.2 ± 4.1 | 9.9 ± 4.2 | 9.3 ± 5.0 | 7.0 ± 2.1 | |||||
Hepatic artery | Lac ≥10% | 4.2 ± 3.7 | 5.2 ± 2.9 | 5.0 ± 3.0 | 6.3 ± 3.6 | 5.5 ± 2.6 | 0.232b
| 0.100 | 0.149 | 0.142 |
Lac <10% | 3.7 ± 1.8 | 3.0 ± 1.6 | 3.7 ± 1.8 | 3.6 ± 2.3 | 2.5 ± 0.9 | |||||
Portal vein | Lac ≥10% | 20.5 ± 7.0 | 20.5 ± 11.5 | 19.2 ± 6.7 | 20.5 ± 8.4 | 27.4 ± 11.6 | 0.006b
| 0.717 | 0.408 | 0.488 |
Lac <10% | 19.3 ± 5.4 | 22.3 ± 5.6 | 21.8 ± 4.3 | 22.3 ± 6.0 | 17.3 ± 10.0 | 0.083c
| ||||
Total hepaticd
| Lac ≥10% | 24.8 ± 8.2 | 25.7 ± 12.1 | 24.2 ± 8.0 | 26.8 ± 9.4 | 32.8 ± 13.0 | 0.006b
| 0.371 | 0.224 | 0.965 |
Lac <10% | 23.0 ± 5.4 | 25.3 ± 6.1 | 25.4 ± 4.7 | 25.9 ± 7.8 | 19.8 ± 10.1 | 0.040c
| ||||
Spleen artery | Lac ≥10% | 1.1 ± 0.4 | 1.1 ± 1.1 | 1.0 ± 0.8 | 1.2 ± 1.0 | 1.2 ± 1.2 | 0.049b
| 0.115 | 0.341 | 0.766 |
Lac <10% | 1.1 ± 0.3 | 1.5 ± 1.2 | 1.3 ± 0.8 | 1.2 ± 1.0 | 0.5 ± 0.2 | 0.167c
| ||||
Renal artery | Lac ≥10% | 5.2 ± 1.9 | 5.1 ± 1.4 | 4.4 ± 1.0 | 5.0 ± 1.0 | 3.9 ± 1.3 | 0.036b
| 0.059 | 0.409 | 0.782 |
Lac <10% | 5.8 ± 2.0 | 5.4 ± 2.1 | 5.7 ± 2.9 | 4.3 ± 2.7 | 2.1 ± 1.4 | 0.018c
|
Parameters | Group | BL | 3 h | 6 h | 12 h | End |
p value | Time × group p valuea
| Time p valuea
| Group p valuea
|
---|---|---|---|---|---|---|---|---|---|---|
Hepatic Lac uptake | Lac ≥10% | 10.3 (7.0 to 14.8) | 7.8 (5.5 to 15.7) | 10.6 (2.3 to 11.4) | 15.4 (8.0 to 17.3) | 23.0 (8.9 to 26.3) | 0.066b
| 0.389 | 0.221 | 0.754 |
Lac <10% | 12.1 (11.9 to 19.5) | 15.0 (10.2 to 22.5) | 11.4 (9.3 to 12.7) | 7.0 (3.5 to 22.3) | 7.5 (6.6 to 11.2) | |||||
Hepatic Lac influx | Lac ≥10% | 24.8 (19.0 to 30.2) | 30.8 (18.8 to 57.8) | 23.9 (19.0 to 49.4) | 39.4 (13.6 to 47.1) | 32.6 (29.0 to 59.6) | 0.066c
| |||
Lac <10% | 27.1 (19.3 to 45.0) | 35.2 (16.5 to 56.5) | 25.5 (18.3 to 33.7) | 32.5 (17.5 to 45.2) | 20.3 (10.1 to 32.5) | 0.321c
| ||||
Hepatic Lac efflux | Lac ≥10% | 12.7 (8.1 to 26.3) | 15.0 (5.5 to 52.4) | 21.3 (7.7 to 35.9) | 26.0 (6.8 to 27.1) | 22.1 (10.1 to 30.3) | 0.645b
| 0.576 | 0.036 | 0.560 |
Lac <10% | 12.4 (9.1 to 23.7) | 14.7 (4.7 to 38.8) | 15.4 (8.1 to 20.9) | 19.9 (14.0 to 32.3) | 14.3 (3.5 to 21.6) | |||||
Gut Lac uptake | Lac ≥10% | −2.6 (−2.9 to 0.3) | −2.2 (−2.8 to −2.1) | −1.7 (−3.9 to 0.3) | −2.4 (−6.8 to 0.5) | −3.8 (−9.9 to −0.6) | 0.942b
| 0.440 | 0.779 | 0.299 |
Lac <10% | −1.4 (−3.7 to 5.2) | −3.3 (−10.7 to 1.3) | −2.9 (−4.0 to −0.9) | −4.7 (−11.6 to −1.8) | −2.1 (−3.8 to −0.4) | |||||
Spleen Lac uptake | Lac ≥10% | −0.2 (−0.7 to −0.2) | −0.2 (−0.6 to −0.1) | −0.2 (−1.1 to −0.1) | −0.1 (−0.9 to −0.1) | 0.0 (−0.4 to 0.2) | 0.185b
| 0.465 | 0.347 | 0.911 |
Lac <10% | −0.1 (−0.3 to 0.1) | −0.1 (−0.3 to 0.1) | −0.3 (−1.6 to −0.1) | −0.1 (−0.7 to 0.0) | −0.1 (−0.2 to 0.0) | |||||
Kidney Lac uptake | Lac ≥10% | −0.4 (−1.0 to 0.0) | −1.0 (−1.9 to −0.7) | −0.4 (−2.3 to 0.2) | −0.5 (−2.5 to 1.1) | 0.3 (0.1 to 0.9) | 0.110b
| 0.743 | 0.546 | 0.921 |
Lac <10% | −0.1 (−0.8 to 2.5) | 0.4 (−2.0 to 1.7) | −0.6 (−2.1 to 0.2) | −0.2 (−0.7 to 0.4) | −0.4 (−1.0 to 0.3) | |||||
Lung Lac uptake | Lac ≥10% | −2.0 (−8.3 to 5.4) | −1.1 (−5.9 to 1.6) | −4.4 (−19.8 to 2.7) | −5.4 (−11.9 to 4.3) | 0.0 (−5.4 to 108.3) | 0.622c
| |||
Lac <10% | 4.8 (−3.0 to 7.2) | −4.1 (−18.3 to 25.7) | −0.1 (−6.5 to 5.4) | −6.5 (−17.8 to 3.2) | −5.6 (−32.2 to 5.3) | 0.525c
| ||||
Whole-body venous Lac efflux | Lac ≥10% | 76.9 (61.6 to 116.3) | 84.0 (57.1 to 174.6) | 105.4 (93.8 to 162.8) | 119.7 (47.6 to 123.6) | 104.3 (79.7 to 131.9) | 0.635b
| 0.144 | 0.253 | 0.692 |
Lac <10% | 98.3 (59.2 to 38.6) | 107.3 (61.7 to 215.6) | 90.2 (76.1 to 109.1) | 104.3 (84.3 to 188.1) | 110.5 (69.4 to 327.1) | |||||
Extrahepatic organ Lac efflux | Lac ≥10% | 69.6 (56.5 to 90.0) | 59.1 (39.1 to 137.2) | 97.0 (72.5 to 117.6) | 91.4 (40.2 to 102.4) | 82.0 (71.0 to 101.6) | 0.346b
| 0.077 | 0.883 | 0.397 |
Lac <10% | 66.3 (50.0 to 123.5) | 92.6 (53.3 to 176.8) | 74.8 (61.5 to 94.8) | 87.9 (66.8 to 154.6) | 102.9 (63.9 to 191.1) |