Introduction
Materials and methods
Results
Identification of eligible trials
Study | Year | Country of origin | Randomization | Conventional therapy | PMX-F | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|
N
| Percentage of males | APACHE II score | Predicted mortality (percentage) |
N
| Percentage of males | APACHE II score | Predicted mortality (percentage) | ||||
Tani et al. [21] (a)a | 1998 | Japan | No | 33 | 69.7 | SSS 39.1 | N/A | 37 | 78.4 | SSS 46.2 | N/A |
Nakamura et al. [10] | 1999 | Japan | Yes | 20 | 60.0 | NS | N/A | 30 | 60.0 | 24.8 | 52.6 |
Nemoto et al. [14] | 2001 | Japan | Yes | 44 | 61.4 | 23 | 46.0 | 54 | 64.7 | 22 | 42.4 |
Nakamura et al. [11] (a) | 2002 | Japan | Yes | 9 | 66.7 | 27.5 | 62.2 | 9 | 66.7 | 28.5 | 65.6 |
Suzuki et al. [15] | 2002 | Japan | Yes | 24 | 70.8 | 25 | 53.3 | 24 | 75.0 | 25 | 53.3 |
Tsushima et al. [33] | 2002 | Japan | No | 10 | 80.0 | NS | N/A | 24 | 70.8 | 22.4 | 43.9 |
Tsugawa et al. [31] | 2002 | Japan | No | 51 | 43.1 | NS | N/A | 31 | 45.2 | NS | N/A |
Nakamura et al. [8] (b) | 2003 | Japan | Yes | 10 | 60.0 | 27 | 60.5 | 10 | 60.0 | 27.6 | 62.5 |
Nakamura et al. [12] (c) | 2003 | Japan | Yes | 25 | 64.0 | 23 | 46.4 | 35 | 68.6 | 24.2 | 50.4 |
Nakamura et al. [29] (d) | 2003 | Japan | No | 108 | 62.0 | 24 | 49.7 | 206 | 64.1 | 24.6 | 51.9 |
Nakamura et al. [13] (e) | 2004 | Japan | Yes | 10 | 60.0 | 28 | 63.9 | 15 | 60.0 | 28.4 | 65.2 |
Nakamura et al. [9] (f) | 2004 | Japan | Yes | 50 | 64.0 | 24.8 | 52.6 | 70 | 61.4 | 25.4 | 54.8 |
Ono et al. [30] | 2004 | Japan | No | 13 | 61.5 | 8.8 | 9.7 | 10 | 60.0 | 19.6 | 34.2 |
Tsujimoto et al. [32] | 2004 | Japan | No | 10 | 20.0 | 10.6 | 12.2 | 7 | 85.7 | 19.4 | 33.5 |
Nakamura et al. [19] (g) | 2005 | Japan | No | 12 | 58.3 | 25 | 53.3 | 14 | 64.3 | 25.5 | 55.1 |
Vincent et al. [28] | 2005 | Belgium, UK, Germany, Netherlands, Spain | Yes | 18 | 47.4 | 18.7 | 31.3 | 17 | 76.5 | 16.7 | 25.4 |
Total | 447 | 593 |
Study | Year | Country of origin |
N
| Percentage of males | APACHE II score | Predicted mortality (percentage) |
---|---|---|---|---|---|---|
Nakamura et al. [16] (h) | 1998 | Japan | 24 | 58.3 | 26.8 | 59.8 |
Nakamura et al. [17] (i) | 1998 | Japan | 17 | 58.8 | 23.1 | 46.4 |
Shimada et al. [20] | 2000 | Japan | 40 | NS | NS | N/A |
Tani et al. [36] (b) | 2001 | Japan | 88 | 71.6 | 24.2 | 50.4 |
Uriu et al. [24] | 2002 | Japan | 24 | 66.7 | NS | N/A |
Ikeda et al. [34] | 2004 | Japan | 66 | NS | 26.2 | 57.6 |
Nakamura et al. [18] (j) | 2004 | Japan | 12 | 66.7 | 24.5 | 51.5 |
Tojimbara et al. [22] | 2004 | Japan | 24 | 45.8 | 21.4 | 40.3 |
Kushi et al. [35] | 2005 | Japan | 36 | 58.3 | 24 | 49.7 |
Ueno et al. [23]a | 2005 | Japan | 16 | 31.3 | SSS 32 | N/A |
Kojika et al. [37] | 2006 | Japan | 24 | 62.5 | 14.2 | 19.1 |
Casella et al. [38] | 2006 | Italy | 14 | 57.1 | 26.5 | 58.7 |
Total | 385 |
Methodological quality of included studies
Characteristics of patients and interventions
Effects on MAP and dose of vasoactive agents
No. of studies | No. of patients | Effect size | 95% CI | Overall effect (P value) | Heterogeneity (P value) | |
---|---|---|---|---|---|---|
Change in MAP | (mm Hg) | |||||
All | 12 | 275 | 19 | (15, 22) | < 0.001 | < 0.001 |
n > 20 | 5 | 175 | 18 | (13, 22) | < 0.001 | < 0.001 |
Pre-PMX MAP < 70 | 3 | 41 | 26 | (22, 30) | < 0.001 | 0.85 |
Pre-PMX MAP ≥ 70 | 9 | 234 | 16 | (13, 18) | < 0.001 | 0.07 |
Center duplication | 11 | 268 | 18 | (15, 21) | < 0.001 | < 0.001 |
Change in dopamine/dobutamine dose | (μg/kg per minute) | |||||
Alla | 4 | 96 | -1.8 | (-3.3, -0.4) | 0.01 | < 0.001 |
Pre-PMX MAP <70 | 1 | 24 | -5.0 | (-6.6, -3.4) | < 0.001 | N/A |
Pre-PMX MAP ≥ 70 | 3 | 72 | -0.8 | (-1.2, -0.4) | < 0.001 | 0.33 |
Change in PaO2/FiO2 ratio | (Units) | |||||
Alla | 7 | 151 | 32 | (23, 41) | < 0.001 | 0.87 |
Pre-PMX PaO2/FiO2 ratio < 200 | 2 | 36 | 30 | (19, 40) | < 0.001 | 0.62 |
Pre-PMX PaO2/FiO2 ratio ≥200 | 5 | 115 | 40 | (20, 60) | < 0.001 | 0.84 |
Change in endotoxin level | (pg/ml) | |||||
All | 17 | 455 | -21.2 | (-24.9, -17.5) | < 0.001 | < 0.001 |
Excluding MRSA | 15 | 410 | -24.1 | (-28.0, -20.2) | < 0.001 | < 0.001 |
Pre-PMX endotoxin <30 pg/ml | 5 | 97 | -9.8 | (-12.1, -7.5) | < 0.001 | 0.007 |
Pre-PMX endotoxin ≥30 pg/ml | 12 | 358 | -28.2 | (-32.3, -24.1) | < 0.001 | < 0.001 |
Pre-PMX endotoxin <40 pg/ml | 10 | 283 | -14.9 | (-18.7, -11.1) | < 0.001 | < 0.001 |
Pre-PMX endotoxin ≥40 pg/ml | 7 | 172 | -37.4 | (-41.9, -32.8) | < 0.001 | 0.25 |
Center duplication | 6 | 225 | -16.4 | (-24.0, -8.9) | < 0.001 | < 0.001 |
Mortality | Risk ratio | |||||
All | 15 | 920 | 0.53 | (0.43, 0.65) | < 0.001 | 0.07 |
RCT | 8 | 354 | 0.50 | (0.37, 0.68) | < 0.001 | 0.12 |
Parallel non-RCT | 7 | 566 | 0.55 | (0.38, 0.81) | 0.002 | 0.07 |
Excluding MRSA | 13 | 840 | 0.55 | (0.44, 0.69) | < 0.001 | 0.08 |
RCT excluding MRSA | 6 | 274 | 0.55 | (0.40, 0.76) | < 0.001 | 0.2 |
n > 20 | 7 | 722 | 0.56 | (0.46, 0.68) | < 0.001 | 0.17 |
APACHE II score < 25 | 9 | 713 | 0.56 | (0.43, 0.73) | < 0.001 | 0.06 |
APACHE II score ≥ 25 | 6 | 207 | 0.45 | (0.30, 0.68) | < 0.001 | 0.25 |
28- to 30-day mortality only | 9 | 704 | 0.54 | (0.43, 0.68) | < 0.001 | 0.12 |
Center duplication | 8 | 673 | 0.61 | (0.46, 0.82) | 0.001 | 0.03 |
Effects on PaO2/FiO2 ratio
Effects on mortality
Effects on endotoxin levels
Adverse events
Discussion
Conclusion
Key messages
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Polymyxin B binds endotoxin, one of the principal biological substances that cause gram-negative septic shock, but has adverse nephrotoxic and neurotoxic effects.
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DHP-PMX would theoretically allow removal of circulating endotoxin without systemic side effects.
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Based on published literature, DHP-PMX appears to effectively reduce endotoxin levels and have some positive effects on blood pressure, use of vasoactive agents, gas exchange, and mortality.
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These putative benefits have to be confirmed in adequately powered prospective trials.