A critical evaluation of new agents for the treatment of sepsis
R. C. Bone
Department of Internal Medicine, Rush-Presbyterian-St Luke's Medical Center, Chicago, Ill 60612.
OBJECTIVE - To evaluate new treatments directed against endotoxin, tumor
necrosis factor alpha, and interleukin 1 for use in sepsis and related
disorders (sepsis syndrome and septic shock). DATA SOURCES - Investigations
of these treatments in animal models, healthy human volunteers, and
patients with sepsis and related disorders. STUDY SELECTION - Particular
attention was paid to studies of patients with sepsis and related
disorders, especially randomized, double-blind, controlled trials. DATA
EXTRACTION - Animal studies and investigations with human volunteers were
judged by how closely the experimental model replicated the clinical
disorder (sepsis). Patient trials were assessed by sample size and design.
Results of all studies were used to evaluate the likelihood that a given
treatment would reduce mortality. DATA SYNTHESIS - Direct comparison of E5
and HA-1A antibody studies is difficult because of differences in their
design, definitions of shock, and methods of subgroup analysis. However,
both antibodies improve outcome in some subgroups: E5 benefits patients
with gram-negative infection (bacteremic or focal) who do not have
refractory shock, and HA-1A benefits those with gram-negative bacteremia
(regardless of whether shock is present) but not those with focal
gram-negative infection. Two agents that may be beneficial in gram-positive
and gram-negative infection are monoclonal antibodies to tumor necrosis
factor alpha and receptor antagonists to interleukin 1. Preliminary results
with both are reviewed. CONCLUSIONS - All three types of treatment may
improve outcome in sepsis. The best results will probably be obtained with
combination therapy that interrupts multiple points of the inflammatory
cascade underlying sepsis.
