AN EVALUATION OF THE HEMODYNAMIC-EFFECTS OF HA-1A HUMAN MONOCLONAL-ANTIBODY

Objectives: We sought to determine whether there might be acute change s in hemodynamics attributable to HA-1A, a monoclonal antibody to endo toxin, in patients with presumed Gramnegative sepsis. Design: Post hoc analysis of a multicenter, randomized, double-blind, placebo-controll ed study. Patients: A total of 543 patients with severe sepsis presume d to be caused by Gram-negative bacteria who were enrolled in a clinic al trial to evaluate the efficacy and safety of HA-1A human monoclonal antibody. Interventions: Patients were randomly assigned to receive e ither 100 mg of HA-1A or placebo. Measurement and Main Results: Patien ts were grouped by the study drug, HA-1A, or placebo, and the presence or absence of Gram-negative bacteremia. Hemodynamic variables were mo nitored from before, until 72 hrs after infusion of the study drug. Fo r the entire study population (n = 543), no changes over time attribut able to study drug were noted in the mean arterial pressure (p > .19), heart rate (p > .53) or the need for vasopressor administration (p > .62). One hundred ninety-seven patients underwent pulmonary artery cat heterization and had hemodynamic data available from before the infusi on of HA-1A or placebo until at least 12 hrs after infusion. Evaluatin g all 197 patients on an intent to treat basis demonstrated no signifi cant differences over time in cardiac index (p > .15), oxygen delivery index (p > .43), or left ventricular stroke work index (P > .48) betw een patients who received HA-1A and those patients receiving placebo. Grouping patients by the presence of Gram-negative bacteremia and stud y drug received also failed to demonstrate Rns significant difference attributable to HA-1A in mean arterial pressure (p > .54), heart rate (p > .84), cardiac index (P > .13), oxygen delivery index (p > .05), o r left ventricular stroke work index (p > .48) between populations. Co nclusion: There is no apparent relationship between the administration of HA-1A, the presence of Gram-negative bacteremia, and hemodynamic p rofiles over the 72-hr study period.