Table 2.
Clinical Outcomes
| Outcome* | n | Balanced (n=7942) |
Saline (n=7860) |
Adjusted OR (95% CI)† |
Adjusted P Value† |
|---|---|---|---|---|---|
| Primary Outcome | |||||
| Major Adverse Kidney Event within 30 days – no. (%)‡ | 15802 | 1139 (14.3) | 1211 (15.4) | 0.90 (0.82–0.99) | 0.04 |
| Components of the Primary Outcome | |||||
| In-hospital mortality before 30 days | 15802 | 818 (10.3) | 875 (11.1) | 0.90 (0.80–1.01) | 0.06 |
| Receipt of new renal replacement therapy – no. (%)§ | 15016 | 189 (2.5) | 220 (2.9) | 0.84 (0.68–1.02) | 0.08 |
| Among survivors | 13444 | 106 (1.6) | 117 (1.8) | ||
| Final creatinine ≥ 200% baseline – no. (%)§ | 15016 | 487 (6.4) | 494 (6.6) | 0.96 (0.84–1.11) | 0.60 |
| Among survivors | 13444 | 259 (3.8) | 273 (4.1) | ||
| Among survivors without new RRT | 13221 | 215 (3.2) | 219 (3.3) | ||
| Secondary Clinical Outcomes | |||||
| In-hospital mortality – no. (%) | 15802 | ||||
| Before intensive care unit discharge | 528 (6.6) | 572 (7.3) | 0.89 (0.78–1.02) | 0.08 | |
| Before 60 days | 928 (11.7) | 975 (12.4) | 0.92 (0.83–1.02) | 0.13 | |
| Intensive care unit-free days¶ | 15802 | 25.3 [22.1–26.6] | 25.3 [22.2–26.6] | 1.00 (0.89–1.13) | 0.94 |
| Mean ± SD | 21.8 ± 8.3 | 21.7 ± 8.6 | |||
| Ventilator-free days¶ | 15802 | 28.0 [26.0–28.0] | 28.0 [26.0–28.0] | 1.06 (0.97–1.16) | 0.22 |
| Mean ± SD | 24.2 ± 8.6 | 23.9 ± 8.9 | |||
| Vasopressor-free days¶ | 15802 | 28.0 [27.0–28.0] | 28.0 [27.0–28.0] | 1.05 (0.97–1.14) | 0.26 |
| Mean ± SD | 24.7 ± 8.5 | 24.4 ± 8.8 | |||
| Renal replacement therapy-free days¶ | 15802 | 28.0 [28.0–28.0] | 28.0 [28.0–28.0] | 1.11 (1.02–1.20) | 0.01 |
| Mean ± SD | 25.0 ± 8.6 | 24.8 ± 8.9 | |||
| Secondary Renal Outcomes§ | |||||
| Stage II or greater AKI developing after enrollment – no. (%)ǁ | 15016 | 807 (10.7) | 858 (11.5) | 0.91 (0.82–1.01) | 0.09 |
| Creatinine**, mg/dL | 14155 | ||||
| Highest before discharge or day 30 | 0.99 [0.78–1.53] | 0.99 [0.78–1.52] | 1.01 (0.97–1.05) | 0.58 | |
| Change from baseline to highest value | 0.04 [−0.08–0.31] | 0.04 [−0.08–0.32] | 0.98 (0.94–1.02) | 0.35 | |
| Final value before discharge or 30 days | 0.83 [0.70–1.11] | 0.83 [0.70–1.11] | 1.02 (0.97–1.06) | 0.51 |
Continuous data are presented as median [25th percentile – 75th percentile] unless otherwise noted. Categorical data are presented as number (no.) and percentage (%).
The adjusted odds ratio is for the balanced crystalloid group compared with the saline group. Categorical outcomes are compared between study groups using a generalized linear mixed-effects model adjusting for intensive care unit as a random effect and pre-specified covariates as fixed effects.13 Continuous outcomes are compared between groups using a proportional odds model adjusting for the same variables.
Major Adverse Kidney Events within 30 days (MAKE30) is the composite of death, receipt of new renal replacement therapy, or final creatinine ≥ 200% baseline, all censored at the first of hospital discharge or 30 days after intensive care unit admission. The effect of study group on MAKE30 shown in the table is the conditional effect. The marginal effect was odds ratio, 0.91; 95% confidence interval, 0.84 – 0.99.
Receipt of new renal replacement therapy, Final creatinine ≥ 200% baseline, and Secondary Renal Outcomes are among the 15,016 patients not known to have received RRT prior to ICU admission.
Intensive care unit-, ventilator-, vasopressor-, and renal replacement therapy-free days refer to the number of days alive and free from the specified therapy in the first 28 days after enrollment. Odds ratios ≥ 1.0 indicate a better outcome (i.e., more days alive and free from the specified therapy) with balanced crystalloids compared with saline.
Stage II or greater acute kidney injury (AKI) developing after enrollment is defined using the Kidney Disease Improving Global Outcomes (KDIGO) creatinine criteria22 as any creatinine value between enrollment and discharge or 30 days that is (1) increased at least 0.3 mg/dL from a preceding post-enrollment value and (2) at least 200% of the baseline value, at least 200% of a preceding post-enrollment value, or at least 4.0 mg/dL; or new receipt of renal replacement therapy.
Among patients who had not received prior renal replacement therapy, plasma creatinine was measured a mean of 8.0 times between enrollment and the first of discharge or 30 days in each group; plasma creatinine was not measured between enrollment and the first of discharge or 30 days for 418 patients (5.5%) in the balanced crystalloid group and 443 patients (5.9%) in the saline group.