Background
Methods
Design
Selection criteria
Exposure
Outcomes
Statistical analyses
Sensitivity analyses
Results
Patient population and characteristics
N (%) | Overall cohort | Lower | Intermediate | Higher | P value |
---|---|---|---|---|---|
N = 650 | 215 (100.0) | 220 (100.0) | 215 (100.0) | ||
Demographic characteristics | |||||
Gender, male, N (%) | 467 (71.8) | 145 (67.8) | 160 (72.7) | 161 (74.9) | 0.243 |
Age, years | 66.00 [58.00, 73.00] | 65.00 [57.00, 71.00] | 66.50 [58.75, 72.25] | 66.00 [59.00, 73.00] | 0.289 |
Weight, kg | 86.00 [78.00, 96.00] | 85.00 [75.00, 94.60] | 86.00 [79.00, 96.00] | 88.40 [80.00, 98.30] | 0.023 |
Height, cm | 175.00 [169.00, 182.00] | 175.00 [168.00, 180.00] | 175.00 [169.00, 182.00] | 176.00 [170.00, 182.50] | 0.341 |
Body mass index, kg/m2 | 27.78 [25.72, 30.86] | 27.44 [25.06, 30.48] | 27.99 [25.71, 30.47] | 28.34 [26.02, 31.62] | 0.081 |
Comorbid conditions (%) | |||||
Comorbid. None | 156 (24) | 42 (19.6) | 55 (25.0) | 59 (27.4) | 0.153 |
Hypertension | 209 (32.2) | 83 (38.8) | 58 (26.4) | 67 (31.2) | 0.02 |
Heart failure | 29 (4.5) | 11 (5.1) | 7 (3.2) | 11 (5.1) | 0.524 |
Diabetes mellitus | 141 (21.7) | 54 (25.2) | 34 (15.5) | 53 (24.7) | 0.021 |
Chronic kidney disease | 25 (3.8) | 10 (4.7) | 5 (2.3) | 10 (4.7) | 0.326 |
Liver cirrhosis | 2 (0.3) | 0 (0.0) | 1 (0.5) | 1 (0.5) | 0.61 |
COPD | 50 (7.7) | 15 (7.0) | 18 (8.2) | 17 (7.9) | 0.892 |
Hematological malignancy | 10 (1.5) | 3 (1.4) | 4 (1.8) | 3 (1.4) | 0.919 |
Solid tumor malignancy | 18 (2.8) | 7 (3.3) | 8 (3.6) | 3 (1.4) | 0.314 |
Neuromuscular disease | 4 (0.6) | 1 (0.5) | 1 (0.5) | 2 (0.9) | 0.772 |
Immunosuppression use | 10 (3.1) | 7 (3.3) | 6 (2.7) | 7 (3.3) | 0.932 |
Other comorbidities | 315 (48.5) | 108 (50.5) | 108 (49.1) | 99 (46.0) | 0.644 |
Unknown comorbidities | 2 (0.3) | 1 (0.5) | 1 (0.5) | 0 (0.0) | 0.608 |
Creatinine (µmol/L) | 76.00 [61.00, 95.00] | 74.00 [61.00, 93.00] | 73.00 [57.50, 93.50] | 79.00 [64.00, 103.25] | 0.079 |
N (%) | Overall cohort | Lower | Intermediate | Higher | P value |
---|---|---|---|---|---|
N = 650 | 215 (100.0) | 220 (100.0) | 215 (100.0) | ||
Day 0 variables (median [interquartile range]) | |||||
Tidal volume (set) | 410.50 [400.00, 480.00] | 450.00 [400.00, 485.00] | 400.00 [400.00, 420.00] | 400.00 [380.00, 440.00] | 0.271 |
Tidal volume (expired) | 438.00 [387.00, 491.00] | 434.50 [389.50, 476.25] | 425.50 [379.25, 477.50] | 450.00 [400.00, 508.00] | 0.007 |
PEEP | 12.00 [10.00, 15.00] | 12.00 [10.00, 15.00] | 12.00 [10.00, 14.00] | 12.00 [10.00, 15.00] | 0.125 |
Peak pressures | 27.00 [24.00, 30.00] | 28.00 [24.00, 31.00] | 26.00 [24.00, 30.00] | 27.00 [24.00, 30.00] | 0.019 |
FiO2 | 0.70 [0.60, 0.85] | 0.70 [0.60, 0.90] | 0.65 [0.58, 0.80] | 0.70 [0.60, 0.80] | 0.105 |
pH | 7.36 [7.30, 7.42] | 7.36 [7.31, 7.41] | 7.37 [7.31, 7.43] | 7.36 [7.29, 7.41] | 0.428 |
PaO2 | 10.88 [9.40, 13.00] | 10.80 [9.50, 12.66] | 10.80 [9.00, 13.15] | 10.90 [9.50, 13.50] | 0.682 |
PaO2/FiO2 ratio | 123.00 [94.69, 165.66] | 120.00 [96.59,153.92] | 121.88 [92.78, 176.87] | 130.03 [93.33, 171.25] | 0.126 |
Dynamic compliance (Cdyn) | 30.16 [24.16, 37.23] | 28.62 [22.79, 34.62] | 30.36 [23.79, 37.51] | 31.38 [26.10, 40.77] | < 0.001 |
Lactate | 1.20 [0.90, 1.50] | 1.2 [0.97, 1.50] | 1.20 [0.90, 1.50] | 1.10 [0.90, 1.40] | 0.084 |
SAPS | 34.50 [28.75, 43.00] | 32.00 [27.00, 38.00] | 32.00 [26.50, 39.50] | 38.00 [32.00, 45.50] | 0.001 |
APACHE II | 17.00 [12.00, 22.00] | 16.00 [12.00, 22.00] | 17.00 [11.50, 22.00] | 16.00 [13.25, 19.75] | 0.979 |
APACHE IV | 56.95 [45.00, 69.00] | 51.00 [43.00, 65.25] | 56.50 [44.00, 65.00] | 59.00 [46.00, 72.50] | 0.083 |
SOFA | 7.00 [6.00, 10.00] | 7.00 [6.00, 10.00] | 7.00 [6.00, 9.00] | 8.00 [6.00, 9.00] | 0.489 |
Creatinine (µmol/L) | 73.00 [58.00, 93.00] | 70.00 [57.00, 87.00] | 73.00 [57.50, 93.50] | 75.00 [63.00, 99.50] | 0.055 |
Daily administered fluid (ml) | 923.64 [298.50, 1744.25] | 1131.50 [345.60, 1944.25] | 784.05 [250.00, 1594.50] | 875.00 [290.50, 1733.50] | 0.034 |
Urine (ml) | 780.00 [417.50, 1200.00] | 780.00 [450.00, 1220.00] | 825.00 [460.00, 1240.00] | 725.00 [398.75, 1130.00] | 0.152 |
Urine (ml/kg) | 8.57 [4.71, 14.00] | 9.07 [4.88, 14.67] | 8.96 [5.11, 14.40] | 7.76 [4.45, 12.69] | 0.043 |
Ventilator-free days | 3.00 [0.00, 11.00] | 3.00 [0.00, 9.00] | 4.00 [0.00, 11.25] | 0.00 [0.00, 12.00] | 0.286 |
Cumulative fluid balance day 0 (ml) | 661.50 [91.33, 1496.00] | 698.00 [− 34.00, 1598.00] | 556.00 [37.50, 1283.10] | 826.00 [212.00, 1762.00] | 0.016 |
Number of patients on norepinephrine | 649 (99.8) | 213 (99.5) | 220 (100) | 215 (100) | 0.361 |
Norepinephrine dose, mg | 0.45 [0.01, 3.37] | 0.04 [0.01, 2.17] | 0.78 [0.01, 3.40] | 0.89 [0.01, 4.14] | 0.005 |
Day 1 variables | |||||
SOFA | 7.00 [6.00, 9.00] | 7.00 [6.00, 9.00] | 7.00 [5.25, 9.00] | 7.00 [6.00, 9.00] | 0.373 |
Creatinine (µmol/L) | 84.00 [66.00, 118.00] | 83.00 [66.00, 123.00] | 80.00 [63.00, 111.00] | 86.00 [68.00, 121.75] | 0.171 |
Daily administered fluid (ml) | 1670.50 [743.70, 2577.50] | 1758.50 [848.05, 2588.50] | 1435.50 [644.58, 2299.25] | 1725.00 [750.00, 2851.35] | 0.152 |
Urine (ml) | 780.00 [417.50, 1200.00] | 1125.00 [778.75, 1588.25] | 1062.50 [805.00, 1446.25] | 1202.02(697.48) | 0.759 |
Urine (ml/kg) | 8.57 [4.71, 14.00] | 13.50 [8.92, 19.07] | 12.62 [8.76, 17.38] | 11.88 [8.40, 17.58] | 0.043 |
Cumulative fluid balance (ml) day 1 | 1621.00 [871.42, 2382.25] | 1460.90 [649.70, 21,621.00] | 1507.50 [824.12, 2116.50] | 1918.00 [1173.35, 2867.45] | < 0.001 |
Number of patients on norepinephrine | 576 (88.6) | 186 (86.9) | 189 (85.9) | 200 (93) | 0.042 |
Norepinephrine, mg/24-h | 11.20 [4.44, 49.96] | 11.98 [3.60, 9216.00] | 8.99 [3.46, 21.56] | 12.21 [6.00, 41.40] | 0.021 |
Day 2 variables | |||||
SOFA | 7.00 [6.00, 10.00] | 7.00 [6.00, 11.00] | 7.00 [5.00, 9.00] | 7.00 [6.00, 9.00] | 0.232 |
Creatinine (µmol/L) | 85.00 [66.00, 133.00] | 86.00 [64.00, 131.00] | 83.00 [63.75, 124.25] | 87.00 [70.00, 143.00] | 0.215 |
Daily administered fluid (ml) | 1243.15 [460.90, 1997.75] | 1288.50 [476.28, 1936.75] | 1169.00 [411.67, 1822.57] | 1230.00 [511.00, 2252.40] | 0.191 |
Urine (ml) | 1075.00 [774.00, 1503.25] | 1407.50 [990.00, 2071.25] | 1095.00 [833.75, 1437.75] | 1121.19 (696.37) | < 0.001 |
Urine (ml/kg) | 12.56 [8.74, 17.75] | 17.19 [11.00, 24.66] | 12.96 [8.97, 17.48] | 11.00 [8.39, 16.16] | < 0.001 |
Cumulative fluid balance (ml) day 2 | 1241.95 [548.75, 1979.75] | 773.50 [0.25, 1398.75] | 1157.00 [615.00, 1807.25] | 1782.00 [1219.50, 2530.00] | < 0.001 |
Number of patients on norepinephrine | 551 (84.8) | 167 (78) | 187 (85) | 196 (91.2) | 0.001 |
Norepinephrine, mg/24-h | 10.70 [4.12, 86.25] | 12.40 [3.74, 9216.00] | 7.92 [3.33, 26.64] | 14.65 [5.11, 41.00] | 0.017 |
Day 3 variables | |||||
SOFA | 7.00 [6.00, 10.00] | 7.00 [6.00, 11.00] | 7.00 [5.00, 9.00] | 7.00 [6.00, 9.00] | 0.56 |
Creatinine (µmol/L) | 84.00 [63.00, 140.00] | 85.00 [62.00, 129.00] | 79.50 [61.00, 127.50] | 86.00 [68.00, 171.00] | 0.07 |
Daily administered fluid (ml) | 956.40 [276.75, 1719.25] | 977.98 [252.50, 1555.75] | 650.70 [238.00, 1607.60] | 1189.90 [504.00, 2160.00] | < 0.001 |
Urine (ml) | 1155.00 [830.00, 1640.00] | 2112.50 [1511.25, 2735.00] | 1280.00 [867.50, 1722.50] | 1030.17 (641.13) | < 0.001 |
Urine (ml/kg) | 13.33 [9.23, 19.22] | 24.04 [17.82, 32.83] | 15.05 [10.43, 20.24] | 11.23 [7.93, 14.72] | < 0.001 |
Cumulative fluid balance (ml) day 3 | 780.00 [7.47, 1623.25] | − 344.75 [− 751.55, 1.72] | 780.00 [499.72, 1013.75] | 1988.00 [1638.30, 2397.00] | < 0.001 |
Number of patients on norepinephrine | 499 (76.8) | 144 (67.3) | 168 (76.4) | 186 (86.5) | < 0.001 |
Norepinephrine, mg/24-h | 9.90 [3.30, 91.78] | 8.75 [2.70, 9216.00] | 6.90 [2.45, 19.74] | 13.75 [5.18, 58.13] | 0.003 |
Cumulative fluid balance distribution
Association of cumulative fluid balance with outcomes
Secondary outcomes and sensitivity analysis
Lower | Intermediate | Higher | P value | |
---|---|---|---|---|
Overall cohort, N = 650, N (%) | 215 (100.0) | 220 (100.0) | 215 (100.0) | |
Acute kidney injury | 110 (52.1) | 102 (46.6) | 122 (56.7) | 0.105 |
Requiring RRT | 63 (29.4) | 58 (26.4) | 67 (31.2) | 0.535 |
CVVH/CVVHDF | 46 (21.5) | 43 (19.5) | 55 (25.6) | 0.304 |
Hemodialysis | 3 (1.4) | 7 (3.2) | 7 (3.3) | 0.395 |
Peritoneal dialysis | 0 (0.0) | 0(0.0) | 1 (0.5) | 0.364 |
28-day mortality | 62 (29.0) | 61 (27.7) | 78 (36.3) | 0.116 |
Duration of intubation at 28 days | 8.00 [4.00, 16.00] | 11.00 [5.00, 21.00] | 11.00 [4.00, 21.00] | 0.019 |
Survivors | 8.00 [4.00, 18.25] | 12.00 [6.00, 26.00] | 14.00 [7.00, 28.00] | < 0.001 |
Non-survivors | 6.50 [3.00, 13.75] | 10.00 [2.00, 14.00] | 5.50 [2.00, 11.00] | 0.228 |
Tracheostomy incidence in ICU | 36 (16.9%) | 31 (14.1%) | 43 (20%) | 0.260 |
Intensive care unit length of stay | 14.00 [9.00, 22.75] | 18.00 [11.00, 28.00] | 17.00 [9.50, 29.00] | 0.019 |
Survivors | 15.00 [9.75, 27.25] | 20.00 [13.00, 34.00] | 23.00 [14.00, 37.00] | < 0.001 |
Non-survivors | 10.50 [7.00, 17.75] | 14.00 [6.00, 18.00] | 9.50 [6.00, 15.00] | 0.249 |
Hospital length of stay | 20.00 [13.00, 32.00] | 24.00 [15.00, 38.00] | 22.00 [12.00, 39.00] | 0.076 |
Survivors | 25.00 [16.00, 38.00] | 30.00 [20.00, 44.00] | 34.00 [21.50, 47.50] | 0.001 |
Non-survivors | 10.50 [7.00, 17.75] | 15.00 [6.00, 18.00] | 9.50 [6.00, 15.00] | 0.192 |