Impact of immunomodulating therapy on morbidity in patients with severe sepsis.
We assessed the impact, over a 28-d period, of therapy with the tumor necrosis factor (TNF) neutralizing receptor fusion protein (p55-IgG) on the incidence of end-organ failures in patients with severe sepsis or early septic shock in a subgroup of 165 patients recruited into a randomized, multicenter clinical trial to receive placebo (n = 78) or a single infusion of p55-IgG, 0.083 mg/kg (n = 87). At study entry, distribution of organ dysfunctions and other baseline characteristics were similar for the two study groups. Treatment with p55-IgG was associated with a trend toward reduced 28-d mortality (p = 0.07), a decreased incidence of new organ dysfunctions (relative risk [RR], 0.57; 95% confidence interval [95% CI] 0.29 to 1.10, p = 0.10), and a decreased overall incidence-density of organ failures (RR 0.65; 95% CI 0.60 to 0.71, p = 0.0001). Patients treated with p55-IgG had more organ failure-free days after study entry than those who received placebo. Average intensive care unit (ICU) stay was 2.6 d shorter (95% CI 0.2 to 5.0) for patients who received p55-IgG than for those who received placebo. For those patients who survived, this difference was 4.1 d (95% CI 1.6 to 6.6). Duration of ventilatory support was 3.2 d shorter (95% CI 0.1 to 6.3) among 28-d survivors who received p55-IgG, compared with placebo. In conclusion, in the population of septic patients studied, treatment with p55-IgG was associated with a trend toward shorter need for mechanical ventilatory support, a decreased length of stay (LOS), and a decreased incidence and duration of organ failure.
Pittet
D
D
Infection Control Program and Division of Surgical Intensive Care, Geneva University Hospitals, Geneva, Switzerland. didier.pittet@hcuge.ch
Harbarth
S
S
Suter
P M
PM
Reinhart
K
K
Leighton
A
A
Barker
C
C
Macdonald
F
F
Abraham
E
E
D018806:APACHE; D000328:Adult; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007143:Immunoglobulin Heavy Chains; D007142:Immunoglobulin gamma-Chains; D007902:Length of Stay / Q000706:statistics & numerical data; D008297:Male; D009102:Multiple Organ Failure; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use; D018805:Sepsis / Q000188:drug therapy* / Q000503:physiopathology; D012772:Shock, Septic / Q000188:drug therapy / Q000503:physiopathology; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007142:Immunoglobulin gamma-Chains; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; C099374:Ro 45-2081