Abstract
IntroductionTo investigate the effects of G-CSF or GM-CSF therapy in non-neutropenic patients with sepsis.MethodsA systematic literature search of Medline, Embase and Cochrane Central Register of Controlled Trials was conducted using specific search terms. A manual review of references was also performed. Eligible studies were randomized control trials (RCTs) that compared granulocyte-colony stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factor (GM-CSF) therapy with placebo for the treatment of sepsis in adults. Main outcome measures were all-cause mortality at 14 days and 28 days after initiation of G-CSF or GM-CSF therapy, in-hospital mortality, reversal rate from infection, and adverse events.ResultsTwelve RCTs with 2,380 patients were identified. In regard to 14-day mortality, a total of 9 death events occurred among 71 patients (12.7%) in the treatment group compared with 13 events among 67 patients (19.4%) in the placebo groups. Meta-analysis showed there was no significant difference in 28-day mortality when G-CSF or GM-CSF were compared with placebo (relative risks (RR) = 0.93, 95% confidence interval (CI): 0.79 to 1.11, P = 0.44; P for heterogeneity = 0.31, I2 = 15%). Compared with placebo, G-CSF or GM-CSF therapy did not significantly reduce in-hospital mortality (RR = 0.97, 95% CI: 0.69 to 1.36, P = 0.86; P for heterogeneity = 0.80, I2 = 0%). However, G-CSF or GM-CSF therapy significantly increased the reversal rate from infection (RR = 1.34, 95% CI: 1.11 to 1.62, P = 0.002; P for heterogeneity = 0.47, I2 = 0%). No significant difference was observed in adverse events between groups (RR = 0.93, 95% CI: 0.70 to 1.23, P = 0.62; P for heterogeneity = 0.03, I2 = 58%). Sensitivity analysis by excluding one trial did not significantly change the results of adverse events (RR = 1.05, 95% CI: 0.84 to 1.32, P = 0.44; P for heterogeneity = 0.17, I2 = 36%).ConclusionsThere is no current evidence supporting the routine use of G-CSF or GM-CSF in patients with sepsis. Large prospective multicenter clinical trials investigating monocytic HLA-DR (mHLA-DR)-guided G-CSF or GM-CSF therapy in patients with sepsis-associated immunosuppression are warranted.
Highlights
To investigate the effects of granulocyte colony stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factor (GM-CSF) therapy in non-neutropenic patients with sepsis
Seven trials of the included 12 trials presented the information of trial sample calculation of various clinical outcome indices based on statistical principle (14-day mortality: 1 trial [43]; 28-day mortality: 2 trials [42,46]; in-hospital mortality: 1 trial [47]; reverse rate from infection: 2 trials [37,38]; others: 1 trial [48])
In the present meta-analysis, we found no significant differences in all-cause mortality at 14 days or 28 days, inhospital mortality, or adverse events between the G-CSF or GM-CSF group and placebo group in adult patients with sepsis
Summary
To investigate the effects of G-CSF or GM-CSF therapy in non-neutropenic patients with sepsis. The effects of these approaches on patient. One approach is the use of granulocyte colony stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factor (GM-CSF), to augment myeloid cell functions in patients with sepsis. G-CSF, widely used in reducing the duration of febrile neutropenia following cytotoxic chemotherapy, has been shown to stimulate the production of neutrophils and modulate the function and activity of developing and mature neutrophils [24]. Compared to G-CSF, GM-CSF exhibits broader effects and induces proliferation and differentiation of neutrophils, monocytes, macrophages, and myeloid-derived dendritic cells. GM-CSF has been demonstrated to increase monocytic HLA-DR (mHLA-DR) expression and endotoxininduced proinflammatory cytokine production in ex vivo whole blood cultures of patients with severe sepsis [25,26]
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