Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Standard intravenous immune globulin but not core-lipopolysaccharide immunoglobulin reduced postsurgical infection in high-risk patients

ACP J Club. 1992 Nov-Dec;117:72. doi:10.7326/ACPJC-1992-117-3-072


Source Citation

The Intravenous Immunoglobulin Collaborative Study Group. Prophylactic intravenous administration of standard immune globulin as compared with core-lipopolysaccharide immune globulin in patients at high risk of postsurgical infection. N Engl J Med. 1992 Jul 23;327:234-40.


Abstract

Objective

To evaluate the effectiveness of standard intravenous immune globulin and core-lipopolysaccharide (LPS) intravenous immune globulin in preventing infection in high-risk surgical patients.

Design

Randomized, double-blind, placebo-controlled, multicenter trial.

Setting

7 hospitals in Europe and the United States.

Patients

352 patients who had esophageal surgery for cancer, contaminated or second-look abdominal operations, surgery for severe gastrointestinal hemorrhage, peritoneal lavage for severe pancreatitis, surgery for ruptured aortic aneurysms or aneurysms requiring transfusion of > 20 units of blood, or surgery for severe abdominal or retroperitoneal trauma requiring > 10 units of blood and tracheal intubation for > 24 hours. Exclusion criteria were systemic infection, bacteremia, shock, likelihood of death within 48 hours, pregnancy, and receipt of immune globulin in the last 3 months. 329 patients (93%) completed the study.

Intervention

Patients received the standard immune globulin, 400 mg/kg body weight to a maximum of 30 g per infusion (n = 109), core-LPS globulin, 400 mg/kg to a maximum of 30 g per infusion (n = 108), or placebo (n = 112). Infusions were given every 7 days until intensive care unit (ICU) discharge, for a maximum of 4 infusions.

Main outcome measures

Occurrence of acquired focal infection, systemic infection, septic shock, or death; and length of stay in the ICU and in the hospital.

Main results

36 patients (33%) developed focal infection in the standard immune globulin group compared with 53 patients (47%) receiving placebo (P = 0.03). {This absolute risk reduction (ARR) of 14% means that 7 patients would need to be treated (NNT) with standard immunoglobulin (compared with placebo) to prevent 1 addtional focal infection, 95% CI 4 to 73; the relative risk reduction (RRR) was 30%, CI 3% to 50%.}* 15 patients (14%) developed pneumonia in the standard immune globulin group compared with 30 patients (27%) receiving placebo (P = 0.04): {ARR 13%; NNT 8, CI 4 to 41; RRR 49% CI 11% to 71%}*. This effect was mainly caused by a reduction in the incidence of gram-negative pneumonia (5 [5%] vs 16[14%], P = 0.02): {ARR 9%; NNT 10, CI 6 to 47; RRR 68%, CI 19% to 87%}.* The length of stay in the ICU was shorter in the standard immune therapy group compared with placebo (4 vs 6 d, P = 0.02). Core-LPS immune globulin had no prophylactic effect on focal or systemic infections or on septic shock.

Conclusions

Intravenous immune globulin given prophylactically reduced the incidence of infections in high-risk postsurgical patients. Core-lipopolysaccharide hyperimmune globulin was not effective in preventing gram-negative infections or their systemic complications.

Sources of funding: Baxter Healthcare Corporation; American Red Cross; Swiss National Science Foundation.

For article reprint: Dr. A. Cometta, Department of Medicine, Centre Hospitalier Universitaire Vaudois, 1011-Lausanne, Switzerland.

*Numbers calculated from data in article.


Commentary

Nosocomial infection is a major source of preventable morbidity, mortality, and increased hospital cost among critically ill patients. Approximately 25% of all nosocomial infections, including 40% of nosocomial bacteremias and pneumonias, are acquired in the ICU. Advances in molecular biology and immunology have brought us to the threshold of preventing nosocomial infections by enhancing immune mechanisms in sick but otherwise immunologically normal patients.

In the Intravenous Immunoglobulin Collaborative Study the inability of core-LPS hyperimmune globulin to be at least as protective as standard immune globulin is unexplained. Both preparations were made by the same method, but core-LPS hyperimmune globulin was derived from a much smaller pool of donors and was stored frozen before final processing. Binding studies and functional assays, however, detected no difference between this preparation and the standard immune globulin. The results suggest that screening donors on the basis of antibodies to core-LPS did not select for the protective antibodies that were present in standard immune globulin. Further, this study did not identify which antibodies in standard immune globulin were associated with benefit. Given the variability among immune globulin lots and preparations, it is not clear that any product will show consistent benefit in preventing nosocomial infections (1). Finally, in this study, neither immune globulin preparation altered the incidence of systemic infection, shock, or death.

Careful clinical studies are important to critically evaluate the new immunologic tools that are rapidly being developed. We need to learn more before routine prophylactic use of immune globulin in critically ill surgical patients can be recommended. These results need to be confirmed in additional well-controlled trials, and the antibody characteristics that predict protection need to be determined.

Robert L. Danner, MD
National Institutes of HealthBethesda, Maryland, USA

Robert L. Danner, MD
National Institutes of Health
Bethesda, Maryland, USA


Reference

1. Siber GR. Immune globulin to prevent nosocomial infections [Editorial]. N Engl J Med. 1992;327:269-71.