Table 3. Primary, Secondary, and Exploratory Outcomes.
| Outcomes | Hydroxyethyl Starch 130/0.4 (n = 389) | 0.9% Saline (n = 386) | Absolute Difference (95% CI) | Relative Risk (95% CI)a | P Valueb |
|---|---|---|---|---|---|
| Primary Outcome | |||||
| Primary composite outcome at day 14, No. (%) | 139 (36) | 125 (32) | 3.3 (−3.3 to 10.0) | 1.10 (0.91-1.34) | .33 |
| Components of primary outcome, No. (%)c | |||||
| Death | 12 (3) | 6 (2) | 1.5 (−0.6 to 3.6) | 1.98 (0.75-5.23) | .85 |
| Acute kidney injury stage ≥1 | 85 (22) | 63 (16) | 5.5 (0.1 to 11.1) | 1.34 (1.00-1.80) | .30 |
| Acute respiratory failure | 32 (8) | 31 (8) | 0.2 (−3.7 to 4.0) | 1.02 (0.64-1.64) | .92 |
| Acute heart failure | 7 (2) | 4 (1) | 0.8 (−0.9 to 2.4) | 1.74 (0.51-5.88) | .92 |
| Major sepsis complications | 61 (16) | 65 (17) | −1.2 (−6.4 to 4.0) | 0.93 (0.68-1.28) | .92 |
| Sepsis | 49 (13) | 56 (15) | −1.9 (−6.7 to 2.9) | 0.87 (0.61-1.24) | .70 |
| Severe sepsis or septic shock | 15 (4) | 17 (4) | −0.5 (−3.4 to 2.3) | 0.88 (0.34-2.26) | .70 |
| Unplanned reoperation | 39 (10) | 48 (12) | −2.4 (−6.9 to 2.0) | 0.81 (0.54-1.20) | .92 |
| Secondary Outcomes | |||||
| Day 2 scores, median (IQR) | |||||
| SOFAd | 1 (0-2) | 1 (0-2) | −0.02 (−0.31 to 0.26) | NA | .34 |
| SIRSe | 2 (2-3) | 2 (2-3) | 0.05 (−0.08 to 0.18) | NA | .51 |
| Kidney dysfunction up to day 14, No. (%)f | 85 (22) | 63 (16) | 5.5 (0.1 to 11.1) | 1.34 (1.00-1.80) | .05 |
| Pulmonary complications up to day 14, No. (%)g | 62 (16) | 66 (17) | −1.1 (−6.4 to 4.1) | 0.93 (0.68-1.28) | .66 |
| Infectious complications up to day 14, No. (%)h | 78 (20) | 86 (22) | −2.2 (−8.0 to 3.5) | 0.90 (0.69-1.18) | .45 |
| Surgical complications up to day 14, No. (%)i | 60 (15) | 67 (17) | −1.9 (−7.1 to 3.3) | 0.89 (0.65-1.22) | .47 |
| Major adverse cardiovascular events up to day 14, No. (%)j | 40 (10) | 44 (11) | −1.1 (−5.5 to 3.3) | 0.90 (0.60-1.35) | .62 |
| Unplanned admission to ICU up to day 28, No. (%) | 39 (10) | 45 (12) | −1.6 (−6.0 to 2.7) | 0.86 (0.57-1.29) | .47 |
| Length of stay, median (IQR), d | |||||
| HDU or ICU | 4 (2-8) | 4 (2-7) | −0.2 (−1.4 to 0.9) | NA | 68 |
| Hospital | 10 (7-17) | 11 (7-17) | −0.4 (−1.5 to 0.7) | NA | .49 |
| Mortality, No. (%) | |||||
| At day 28 | 16 (4) | 9 (2) | 1.8 (−0.7 to 4.3) | 1.76 (0.79-3.94) | .17 |
| At day 90 | 26 (7) | 18 (5) | 2.0 (−1.2 to 5.3) | 1.43 (0.80-2.57) | .23 |
| Prespecified Exploratory Outcomesk | |||||
| Acute kidney injury KDIGO stage, No. (%) | |||||
| Stage 1 | 59 (15) | 39 (10) | 5.5 (0.5 to 10.4) | 1.61 (1.04-2.48) | .03 |
| Stage 2 | 14 (4) | 11 (3) | 0.8 (−1.8 to 3.3) | 1.35 (0.60-3.02) | .46 |
| Stage 3 | 12 (3) | 13 (3) | −0.3 (−2.8 to 2.2) | 0.98 (0.44-2.18) | .96 |
| Need for renal replacement therapy, No. (%) | 6 (2) | 10 (3) | −1.1 (−3.1 to 1.0) | 0.60 (0.22-1.62) | .31 |
| Pulmonary complications, No. (%) | |||||
| Hypoxemia | 55 (14) | 52 (13) | 0.07 (−4.2 to 5.6) | 1.05 (0.74-1.49) | .79 |
| Pneumonia | 15 (4) | 19 (5) | −1.1 (−4.0 to 1.8) | 0.78 (0.40-1.52) | .47 |
| Acute respiratory distress syndrome | 3 (1) | 4 (1) | −0.3 (−1.6 to 1.1) | 0.74 (0.17-3.30) | .70 |
| Surgical site infection up to day 14, No. (%) | 30 (8) | 40 (10) | −2.7 (−6.7 to 1.4) | 0.74 (0.47-1.17) | .20 |
| Anastomotic leak, No./total (%)l | 25/250 (10) | 33/240 (14) | −3.8 (−9.5 to 2.0) | 0.73 (0.45-1.19) | .20 |
| Major adverse cardiovascular events, No. (%) | |||||
| Cardiac arrhythmia | 27 (7) | 31 (8) | −1.1 (−4.8 to 2.6) | 0.90 (0.60-1.35) | .62 |
| Myocardial infarction | 1 (1) | 1 (1) | 0.0 (−0.7 to 0.7) | 0.99 (0.06-15.8) | .99 |
| Pulmonary embolism | 9 (2) | 9 (2) | 0.0 (−2.1 to 2.1) | 0.99 (0.40-2.47) | .99 |
| Post Hoc Outcomes | |||||
| Death or major postoperative complications up to day 28, No. (%)m | 159 (41) | 148 (38) | 2.5 (−4.4 to 9.4) | 1.07 (0.90-1.27) | .47 |
| Acute kidney injury up to day 28, No. (%)n | 88 (23) | 64 (17) | 6.0 (0.5 to 11.6) | 1.36 (1.02-1.82) | .04 |
| Acute respiratory failure up to day 28, No. (%) | 35 (9) | 36 (9) | −0.3 (−4.4 to 3.7) | 0.96 (0.62-1.50) | .87 |
| Sepsis up to day 28, No. (%) | 76 (20) | 83 (22) | −2.0 (−7.7 to 3.7) | 0.91 (0.69-1.20) | .50 |
| Acute heart failure up to day 28, No. (%) | 45 (12) | 45 (12) | 0 (−4.6 to 4.4) | 0.99 (0.67-1.46) | .97 |
| Unplanned reoperation up to day 28, No. (%) | 62 (16) | 63 (16) | −0.4 (−5.6 to 4.8) | 0.98 (0.71-1.35) | .89 |
| Day 1 fluid balance, median (IQR)o | 3200 (2450-4200) | 3800 (2650-5100) | 575 (304 to 846) | NA | <.001 |
| Need for blood transfusion, No. (%) | 75 (19) | 45 (12) | 7.6 (2.6 to 12.7) | 1.65 (1.18-2.33) | .003 |
| Need for vasoactive medication, No. (%) | NA | ||||
| Norepinephrine | 104 (27) | 117 (30) | −3.6 (−9.9 to 2.8) | ||
| Phenylephrine | 64 (16) | 79 (20) | −4.0 (−9.5 to 1.4) | ||
| Ephedrine | 242 (62) | 240 (62) | 0.0 (−6.8 to 6.9) | ||
| Epinephrine | 0 | 3 (1) | −0.8 (−1.7 to 0.0) | ||
Abbreviations: HDU, high dependency unit; ICU, intensive care unit; IQR, interquartile range; KDIGO, Kidney Disease: Improving Global Outcomes; NA, not applicable.
Unadjusted relative risk. For adjusted analysis, see eTable 3 in Supplement 2.
Calculated using the χ2 test or Fisher exact test, as appropriate, for categorical data and the unpaired t test or Mann-Whitney U test for continuous data.
All components of the composite primary outcome were assessed at 14 days after surgery. The Hochberg procedure was used to correct for multiple testing of the components of the composite primary outcome.
Scores on the Sequential Organ Failure Assessment (SOFA) scale range from 0 to 4 for each organ system, with higher scores indicating more severe organ dysfunction.
The systemic inflammatory response syndrome (SIRS) score (range, 0 [best] to 4 [worst]) assigns 1 point for each of the following variables: temperature >38°C or <36°C, white blood cell count >12 000/μL or <4000/μL, heart rate >90/min and respiratory rate >20/min, and Paco2 <32 mm Hg.
Defined as any kidney injury assessed using the 3-category KDIGO classification system.
Defined as hypoxemia (Pao2 <60 mm Hg or peripheral oxygen saturation as measured by pulse oximetry <90% when breathing room air, Pao2 <80 mm Hg when breathing 15 L/min of supplemental oxygen, or Pao2/fraction of inspired oxygen ratio <300 mm Hg within 14 days after surgery), pneumonia, acute respiratory distress syndrome, or acute respiratory failure requiring invasive or noninvasive mechanical ventilation.
Defined as sepsis, severe sepsis, septic shock, or surgical site infection.
Defined as reoperation and anastomotic leak.
Defined as acute heart failure, cardiac arrhythmia, myocardial infarction, or pulmonary embolism.
All prespecified exploratory analyses (individual components of the secondary analyses) were measured up to postoperative day 14.
Anastomotic leak data are expressed as No./total (%) patients who had an operation in which an anastomosis was performed.
Major postoperative complications were KDIGO stage ≥1 acute kidney injury, acute respiratory failure requiring invasive or noninvasive mechanical ventilation, acute heart failure, major sepsis complications, and unplanned reoperation.
Defined as KDIGO stage ≥1 acute kidney injury.
Fluid balance was calculated by subtracting the total fluid output from the total fluid intake. Fluid intake was the sum of all intravenous fluids, and fluid output was the sum of the volumes of urine output and blood loss. Insensible fluid losses were not included. Fluid balance was calculated as the median for all patients.