Table 2. Results of the main analysis and sub-group analyses performed.
| Analysis | Number of trials | Treatment mortality | Controls mortality | RR | 95% CI | P for effect | P for heterogeneity | I 2 |
|---|---|---|---|---|---|---|---|---|
| Overall | 20 | 34.3% (278/810) | 38.7% (309/798) | 0.88 | 0.79 to 0.98 | 0.02 | 0.88 | 0 |
| SETTING | ||||||||
| Sepsis | 10 | 44.5% (240/539) | 51.1% (262/513) | 0.87 | 0.77 to 0.98 | 0.02 | 0.98 | 0 |
| Vasopressin / Terlipressin | 8 | 44.9% (231/514) | 51.4% (251/488) | 0.87 | 0.77 to 0.98 | 0.03 | 0.96 | 0 |
| Methylene blue | 2 | 36% (9/25) | 44% (11/25) | 0.78 | 0.42 to 1.47 | 0.45 | 0.64 | 0 |
| Cardiac surgery | 7 | 0% (0/199) | 5.7% (12/213) | 0.16 | 0.04 to 0.69 | 0.01 | 0.93 | 0 |
| Vasopressin / Terlipressin | 4 | 0% (0/106) | 3.4% (4/120) | 0.21 | 0.02 to 1.74 | 0.15 | 0.72 | 0 |
| Methylene blue | 3 | 0% (0/93) | 8.6% (8/93) | 0.12 | 0.02 to 0.95 | 0.04 | 0.65 | 0 |
| DRUGS | ||||||||
| Vasopressin | 11 | 36.7% (226/616) | 40.1% (248/617) | 0.90 | 0.80 to 1.02 | 0.11 | 0.81 | 0 |
| Terlipressin | 5 | 56.7% (43/76) | 66.7% (52/78) | 0.85 | 0.69 to 1.05 | 0.13 | 0.92 | 0 |
| Vasopressin / Terlipressin | 15* | 38.9% (269/692) | 42.6% (290/680) | 0.89 | 0.80 to 0.99 | 0.04 | 0.94 | 0 |
| Methylene blue | 5 | 7.6% (9/118) | 16.1% (19/118) | 0.65 | 0.33 to 1.29 | 0.22 | 0.34 | 10 |
| FOLLOW-UP | ||||||||
| Hospital stay | 7 | 5.6% (9/160) | 11.4% (20/176) | 0.65 | 0.29 to 1.47 | 0.30 | 9.30 | 17% |
| Vasopressin / Terlipressin | 4 | 7.5% (5/67) | 9.6% (8/83) | 0.75 | 0.23 to 2.49 | 0.64 | 0.30 | 17% |
| Methylene blue | 3 | 4.3% (4/93) | 12.9% (12/93) | 0.39 | 0.08 to 1.98 | 0.26 | 0.20 | 38% |
| 28/30-days | 6 | 33.6% (179/533) | 37.3% (196/525) | 0.88 | 0.76 to 1.02 | 0.09 | 0.60 | 0 |
| Vasopressin / Terlipressin | 5 | 33.3% (174/523) | 36.7% (189/515) | 0.88 | 0.76 to 1.04 | 0.13 | 0.49 | 0 |
| Methylene blue | 1 | 50% (5/10) | 70% (7/10) | 0.71 | 0.34 to 1.50 | 0.37 | N/A | N/A |
| ADDITIONAL SENSITIVITY ANALYSES | ||||||||
| Established shock | 11 | 46.8% (261/558) | 53.2% (282/530) | 0.88 | 0.79 to 0.98 | 0.02 | 0.98 | 0 |
| Vasopressin / Terlipressin | 10 | 46.7% (256/548) | 52.9% (275/520) | 0.89 | 0.79 to 0.99 | 0.03 | 0.98 | 0 |
| Methylene blue | 1 | 50% (5/10) | 70% (7/10) | 0.71 | 0.34 to 1.50 | 0.37 | N/A | N/A |
| Prophylactic administration | 5 | 0% (0/122) | 4.34% (6/138) | 0.20 | 0.04 to 1.16 | 0.07 | 0.94 | 0 |
| Vasopressin / Terlipressin | 3 | 0% (0/57) | 5.5% (4/73) | 0.21 | 0.02 to 1.74 | 0.15 | 0.72 | 0 |
| Methylene blue | 2 | 0% (0/65) | 3.1% (2/65) | 0.20 | 0.01 to 4.06 | 0.29 | N/A | N/A |
| Low risk of bias | 6 | 40.1% (197/491) | 43% (214/497) | 0.90 | 0.78 to 1.04 | 0.15 | 0.72 | 0 |
| Vasopressin / Terlipressin | 5 | 40.5% (193/476) | 43.6% (210/482) | 0.90 | 0.78 to 1.04 | 0.15 | 0.56 | 0 |
| Methylene blue | 1 | 26.7% (4/15) | 26.7% (4/15) | 1.00 | 0.31 to 3.28 | 1.00 | N/A | N/A |
| Versus placebo | 10 | 10.2% (22/217) | 14.7% (34/233) | 0.76 | 0.45 to 1.30 | 0.32 | 0.31 | 16 |
| Vasopressin / Terlipressin | 6 | 8.8% (13/149) | 10.4% (17/165) | 0.65 | 0.22 to 1.95 | 0.94 | 0.27 | 23 |
| Methylene blue | 4 | 13.2% (9/68) | 25% (17/68) | 0.67 | 0.30 to 1.52 | 0.34 | 0.26 | 26% |
| Versus catecholamines | 5 | 43.7% (207/474) | 49.1% (219/446) | 0.88 | 0.77 to 1.01 | 0.08 | 0.92 | 0% |
| Influence analysis | ||||||||
| Removing Russell JA 2008 [10] | 19 | 25.1% (101/405) | 28.7% (115/403) | 0.88 | 0.75 to 1.02 | 0.09 | 0.84 | 0 |
| Removing all other trials | All 95% CIs of RR<1 and p<0.05 | |||||||
One study randomized patients to three treatment groups: terlipressin, vasopressin, and norepinephrine. CI: confidence interval; I2: I-squared; RR: risk ratio.