title: An evaluation of the hemodynamic effects of HA-1A human monoclonal antibody.
abstract: OBJECTIVE
  We sought to determine whether there might be acute changes in hemodynamics attributable to HA-1A, a monoclonal antibody to endotoxin, in patients with presumed Gram-negative sepsis.
  
  
  METHODS
  Post hoc analysis of a multicenter, randomized, double-blind, placebo-controlled study.
  
  
  METHODS
  A total of 543 patients with severe sepsis presumed to be caused by Gram-negative bacteria who were enrolled in a clinical trial to evaluate the efficacy and safety of HA-1A human monoclonal antibody.
  
  
  METHODS
  Patients were randomly assigned to receive either 100 mg of HA-1A or placebo.
  
  
  RESULTS
  Patients were grouped by the study drug, HA-1A, or placebo, and the presence or absence of Gram-negative bacteremia. Hemodynamic variables were monitored from before, until 72 hrs after infusion of the study drug. For the entire study population (n = 543), no changes over time attributable 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 catheterization and had hemodynamic data available from before the infusion of HA-1A or placebo until at least 12 hrs after infusion. Evaluating all 197 patients on an intent to treat basis demonstrated no significant differences over time in cardiac index (p > .15), oxygen delivery index (p > .43), or left ventricular stroke work index (p > .48) between patients who received HA-1A and those patients receiving placebo. Grouping patients by the presence of Gram-negative bacteremia and study drug received also failed to demonstrate any 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), or left ventricular stroke work index (p > .48) between populations.
  
  
  CONCLUSIONS
  There is no apparent relationship between the administration of HA-1A, the presence of Gram-negative bacteremia, and hemodynamic profiles over the 72-hr study period.
authors.affiliation: Section of Critical Care Medicine, Miami Veterans Affairs Medical Center, FL.
authors.forename: D H
authors.initials: DH
authors.lastname: Kett
authors.forename: A A
authors.initials: AA
authors.lastname: Quartin
authors.forename: C L
authors.initials: CL
authors.lastname: Sprung
authors.forename: C J
authors.initials: CJ
authors.lastname: Fisher
authors.forename: M A
authors.initials: MA
authors.lastname: Peña
authors.forename: S O
authors.initials: SO
authors.lastname: Heard
authors.forename: J L
authors.initials: JL
authors.lastname: Zimmerman
authors.forename: T E
authors.initials: TE
authors.lastname: Albertson
authors.forename: E A
authors.initials: EA
authors.lastname: Panacek
authors.forename: L A
authors.initials: LA
authors.lastname: Eidelman
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D016470:Bacteremia / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology*; D002407:Catheterization, Swan-Ganz; D004311:Double-Blind Method; D004731:Endotoxins / Q000276:immunology*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology*; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects; D012044:Regression Analysis; D012720:Severity of Illness Index; D015996:Survival Rate; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004731:Endotoxins; D014662:Vasoconstrictor Agents; C068069:nebacumab