Table 2.
Main results. Subgroup and sensitivity analyses were conducted in regard to our primary outcome
| Outcome or subgroup | Studies | Participants | Statistical method | Effect estimate | Heterogeneity |
|---|---|---|---|---|---|
| Mortality (subgroup analysis on bias risk) | 29 | 3882 | Risk ratio (M–H, fixed, 95 % CI) | 0.95 (0.88 to 1.03) | I 2 = 0 % |
| Trials with low bias risk | 9 | 2915 | Risk ratio (M–H, fixed, 95 % CI) | 0.96 (0.88 to 1.04) | I 2 = 0 % |
| Trials with high bias risk | 20 | 967 | Risk ratio (M–H, fixed, 95 % CI) | 0.94 (0.77 to 1.14) | I 2 = 0 % |
| Overall mortality (subgroup analysis on median follow-up) | 28 | 3848 | Risk ratio (M–H, fixed, 95 % CI) | 0.95 (0.88 to 1.03) | I 2 = 0 % |
| Mortality in trials with follow-up less than median of all trials | 18 | 1024 | Risk ratio (M–H, fixed, 95 % CI) | 0.93 (0.77 to 1.13) | I 2 = 0 % |
| Mortality in trials with follow-up longer than median of all trials | 10 | 2824 | Risk ratio (M–H, fixed, 95 % CI) | 0.96 (0.88 to 1.04) | I 2 = 0 % |
| Overall mortality (subgroup analysis on duration of intervention) | 28 | 3848 | Risk ratio (M–H, fixed, 95 % CI) | 0.95 (0.88 to 1.03) | I 2 = 0 % |
| Median duration of AT III intervention equal to or less than 1 week | 25 | 3640 | Risk ratio (M–H, fixed, 95 % CI) | 0.95 (0.88, 1.03) | I 2 = 0 % |
| Median duration of AT III intervention longer than 1 week | 3 | 208 | Risk ratio (M–H, fixed, 95 % CI) | 0.89 (0.59 to 1.34) | I 2 = 0 % |
| Overall mortality (trauma) | 2 | 68 | Risk ratio (M–H, fixed, 95 % CI) | 2.15 (0.81 to 5.72) | I 2 = 0 % |
| Trials with high bias risk | 1 | 28 | Risk ratio (M–H, fixed, 95 % CI) | 3.43 (0.15 to 77.58) | Not applicable |
| Trials with low bias risk | 1 | 40 | Risk ratio (M–H, fixed, 95 % CI) | 2.00 (0.72 to 5.59) | Not applicable |
| Overall mortality (obstetrics) | 2 | 332 | Risk ratio (M–H, fixed, 95 % CI) | 1.03 (0.33 to 3.21) | I 2 = 0 % |
| Overall maternal mortality, trials with low bias risk | 2 | 174 | Risk ratio (M–H, fixed, 95 % CI) | Not estimable | Not applicable |
| Overall fetal and neonatal mortality, trials with low bias risk | 2 | 158 | Risk ratio (M–H, fixed, 95 % CI) | 1.03 (0.33 to 3.21) | I 2 = 0 % |
| Overall mortality (paediatrics) | 4 | 365 | Risk ratio (M–H, fixed, 95 % CI) | 1.44 (0.73 to 2.83) | I 2 = 0 % |
| Trials with low bias risk | 2 | 182 | Risk ratio (M–H, fixed, 95 % CI) | 1.60 (0.54 to 4.72) | I 2 = 21 % |
| Trials with high bias risk | 2 | 183 | Risk ratio (M–H, fixed, 95 % CI) | 1.32 (0.56 to 3.15) | Not applicable |
| Overall mortality (heparin, Warren et al. as a trial with adjuvant heparin therapy) | 26 | 3779 | Risk ratio (M–H, fixed, 95 % CI) | 0.95 (0.88 to 1.03) | I 2 = 0 % |
| Trials with complete or partially adjuvant heparin therapy | 16 | 3121 | Risk ratio (M–H, fixed, 95 % CI) | 0.96 (0.88 to 1.04) | I 2 = 0 % |
| Trials without adjuvant heparin | 10 | 658 | Risk ratio (M–H, fixed, 95 % CI) | 0.93 (0.71 to 1.23) | I 2 = 0 % |
| Overall mortality (heparin, Warren et al. as a trial without adjuvant heparin therapy) | 26 | 3779 | Risk ratio (M–H, fixed, 95 % CI) | 0.95 (0.88 to 1.03) | I 2 = 0 % |
| Trials with complete or partially adjuvant heparin therapy | 15 | 807 | Risk ratio (M–H, fixed, 95 % CI) | 0.96 (0.79 to 1.17) | I 2 = 0 % |
| Trials without adjuvant heparin | 11 | 2972 | Risk ratio (M–H, fixed, 95 % CI) | 0.95 (0.88 to 1.03) | I 2 = 0 % |
| Overall mortality (heparin, Warren et al. data split based on heparin administration) | 26 | 3779 | Risk ratio (M–H, random, 95 % CI) | 0.95 (0.88 to 1.02) | I 2 = 0 % |
| Trials with complete or partially adjuvant heparin therapy | 16 | 2423 | Risk ratio (M–H, random, 95 % CI) | 0.98 (0.90 to 1.08) | I 2 = 0 % |
| Trials without adjuvant heparin | 11 | 1356 | Risk ratio (M–H, random, 95 % CI) | 0.89 (0.78 to 1.01) | I 2 = 0 % |
| Overall mortality among patients with severe sepsis and DIC | 12 | 2858 | Risk ratio (M–H, fixed, 95 % CI) | 0.95 (0.88 to 1.03) | I 2 = 0 % |
| Trials with low bias risk | 4 | 2529 | Risk ratio (M–H, fixed, 95 % CI) | 0.95 (0.88 to 1.04) | I 2 = 0 % |
| Trials with high bias risk | 8 | 329 | Risk ratio (M–H, fixed, 95 % CI) | 0.87 (0.64 to 1.20) | I 2 = 0 % |
| Complications during the in-patient stay specific to the trial intervention | 3 | 2454 | Risk ratio (M–H, random, 95 % CI) | 1.26 (0.83 to 1.92) | I 2 = 9 % |
| Trials with low bias risk | 2 | 2429 | Risk ratio (M–H, random, 95 % CI) | 1.62 (0.96 to 2.73) | I 2 = 0 % |
| Trials with high bias risk | 1 | 25 | Risk ratio (M–H, random, 95 % CI) | 0.92 (0.51 to 1.66) | Not applicable |
| Complications during the in-patient stay not specific to the trial intervention | 2 | 65 | Risk ratio (M–H, random, 95 % CI) | 0.71 (0.08 to 6.11) | I 2 = 28 % |
| Trials with low bias risk | 1 | 40 | Risk ratio (M–H, random, 95 % CI) | 3.00 (0.13 to 69.52) | Not applicable |
| Trials with high bias risk | 1 | 25 | Risk ratio (M–H, random, 95 % CI) | 0.31 (0.04 to 2.57) | Not applicable |
| Complication specific to the trial intervention other than bleeding | 3 | 187 | Risk ratio (M–H, fixed, 95 % CI) | 0.72 (0.42 to 1.25) | I 2 = 0 % |
| Trials with low bias risk | 1 | 60 | Risk ratio (M–H, fixed, 95 % CI) | 0.75 (0.18 to 3.07) | Not applicable |
| Trials with high bias risk | 2 | 127 | Risk ratio (M–H, fixed, 95 % CI) | 0.72 (0.40 to 1.30) | I 2 = 0 % |
| Bleeding events | 11 | 3019 | Risk ratio (M–H, fixed, 95 % CI) | 1.58 (1.35 to 1.84) | I 2 = 0 % |
| Trials with low bias risk | 6 | 2791 | Risk ratio (M–H, fixed, 95 % CI) | 1.58 (1.35 to 1.85) | I 2 = 37 % |
| Trials with high bias risk | 5 | 228 | Risk ratio (M–H, fixed, 95 % CI) | 1.57 (0.71 to 3.49) | I 2 = 0 % |
| Amount of red blood cells administered | 4 | 137 | Mean difference (IV, random, 95 % CI) | 138.49 (−391.35 to 668.34) | I 2 = 88 % |
| Trials with low bias risk | 1 | 35 | Mean difference (IV, random, 95 % CI) | −600.00 (−899.18 to −300.82) | Not applicable |
| Trials with high bias risk | 3 | 102 | Mean difference (IV, random, 95 % CI) | 595.10 (−287.14 to 1477.34) | I 2 = 82 % |
| Incidence of surgical intervention | 3 | 103 | Risk ratio (M–H, fixed, 95 % CI) | 1.04 (0.85 to 1.27) | I 2 = 0 % |
| Trials with low bias risk | 3 | 103 | Risk ratio (M–H, fixed, 95 % CI) | 1.04 (0.85 to 1.27) | I 2 = 0 % |
| Severity of sepsis I | 3 | 156 | Mean difference (IV, random, 95 % CI) | −1.24 (−2.18 to −0.29) | I 2 = 48 % |
| Final MOF score among survivors, trials with low bias risk | 1 | 88 | Mean difference (IV, random, 95 % CI) | −0.70 (−1.22, to −0.18) | Not applicable |
| Final MOF score among survivors, trials with high bias risk | 2 | 68 | Mean difference (IV, Random, 95 % CI) | −1.92 (−3.05, to −0.78) | I 2 = 0 % |
| Severity of sepsis II | 3 | 102 | Mean difference (IV, fixed, 95 % CI) | −2.18 (−4.36 to −0.00) | I 2 = 0 % |
| Final APACHE I and II scores among survivors, trials with high bias risk | 3 | 102 | Mean difference (IV, fixed, 95 % CI) | −2.18 (−4.36 to −0.00) | I 2 = 0 % |
| Incidence of respiratory failure not present at admission | 6 | 2591 | Risk ratio (M–H, random, 95 % CI) | 0.93 (0.76 to 1.14) | I 2 = 32 % |
| Trials with low bias risk | 5 | 2564 | Risk ratio (M–H, random, 95 % CI) | 0.97 (0.77 to 1.22) | I 2 = 40 % |
| Trials with high bias risk | 1 | 27 | Risk ratio (M–H, random, 95 % CI) | 0.73 (0.45 to 1.18) | Not applicable |
| Duration of mechanical ventilation | 3 | 190 | Mean difference (IV, fixed, 95 % CI) | 2.20 (−1.21 to 5.60) | I 2 = 0 % |
| Trials with low bias risk | 2 | 162 | Mean difference (IV, fixed, 95 % CI) | 2.26 (−1.69 to 6.22) | I 2 = 0 % |
| Trials with high bias risk | 1 | 28 | Mean difference (IV, fixed, 95 % CI) | 2.00 (−4.68 to 8.68) | Not applicable |
| Length of stay in hospital | 4 | 202 | Mean difference (IV, random, 95 % CI) | 1.10 (−7.16 to 9.36) | I 2 = 74 % |
| Trials with low bias risk | 2 | 89 | Mean difference (IV, random, 95 % CI) | −5.67 (−16.24 to 4.90) | I 2 = 53 % |
| Trials with high bias risk | 2 | 113 | Mean difference (IV, random, 95 % CI) | 7.17 (2.75 to 11.59) | I 2 = 0 % |
| Mean length of stay in ICU | 7 | 376 | Mean difference (IV, fixed, 95 % CI) | 0.24 (−1.34 to 1.83) | I 2 = 0 % |
| Trials with low bias risk | 3 | 195 | Mean difference (IV, fixed, 95 % CI) | −0.73 (−3.41 to 1.95) | I 2 = 3 % |
| Trials with high bias risk | 4 | 181 | Mean difference (IV, fixed, 95 % CI) | 0.77 (−1.20 to 2.74) | I 2 = 0 % |
APACHE acute physiology and chronic health evaluation, CI confidence interval, ICU intensive care unit, M–H Mantel–Haenszel, MOFS multiorgan failure score