Am. J. Respir. Crit. Care Med.,
Volume 160, Number 3, September 1999, 852-857
Impact of Immunomodulating Therapy on
Morbidity in Patients with Severe Sepsis
DIDIER
PITTET,
STEPHAN
HARBARTH,
PETER M.
SUTER,
KONRAD
REINHART,
ANTON
LEIGHTON,
CHRISTOPHER
BARKER,
FRANCES
MACDONALD,
EDWARD
ABRAHAM,
and
the Ro 45-2081 Study Group
Infection Control Program and Division of Surgical Intensive Care, Geneva University Hospitals, Geneva, Switzerland; Department of
Anesthesia and Intensive Care, University Hospital of Jena, Germany; F. Hoffmann-La Roche Ltd., Basel, Switzerland; and Division
of Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado
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.
