An evaluation of the hemodynamic effects of HA-1A human monoclonal antibody.
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.
Kett
D H
DH
Section of Critical Care Medicine, Miami Veterans Affairs Medical Center, FL.
Quartin
A A
AA
Sprung
C L
CL
Fisher
C J
CJ
Peña
M A
MA
Heard
S O
SO
Zimmerman
J L
JL
Albertson
T E
TE
Panacek
E A
EA
Eidelman
L A
LA
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
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D004731:Endotoxins; D014662:Vasoconstrictor Agents; C068069:nebacumab