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To investigate the activity of intravenous immunoglobulin (IVIG) as a prophylactic agent against infection in trauma victims.Prospective, randomized, double-blind, placebo-controlled study.A 20-bed university intensive care unit.Thirty-nine trauma patients with injury severity scores (ISSs) of 16-50.Penicillin was given at the time of admission and continued at least until day 4. Twenty-one patients received IVIG and 18 patients received human albumin at 1 g/kg in four divided doses (days 1, 2, 3, and 6). The two groups had similarities in age, gender, Acute Physiology and Chronic Health Evaluation II score, risk of death, and Glasgow Coma Scale score, but differing ISSs (p= .02), at the time of admission. Blood was collected on days 1, 4, and 7.Clinical variables related to infection were recorded. The complement components C3c, C4 and CH50, IgG, and the fractions of IgG were measured. The serum bactericidal activity (SBA) was assessed at 37°C (98.6°F) and 40°C (104.0°F) at the time of admission and during the course of IVIG administration.Controlling for ISS, IVIG-treated patients had fewer pneumonias (p= .003) and total non-catheter-related infections (p= .04). Catheter-related infections (p= .76), length of stay in the intensive care unit, antibiotic days, and infection-related mortality did not differ between the two groups. A significantly increased trend in IgG and its subclasses was shown on days 4 and 7 in the IVIG group but not in the control group (p< .000001). No important differences were noted in complement fractions. The SBA of the groups was similar on day 1, but significantly higher on days 4 and 7 (p< .000001) in the IVIG group, remaining so controlling for complement and ISS. SBA was higher at 40°C (104.0°F) compared with 37°C (98.6°F) (p< .0001) under all three conditions. In both groups, low SBA (on days 1, 4, and 7) was associated with increased risk of pneumonia (p< .01) and non-catheter-related infections (p= .06 for day 1;p< .01 for days 4 and 7).Trauma patients receiving high doses of IVIG exhibit a reduction of septic complications and an improvement of SBA. Early SBA measurement may represent an index of susceptibility to infection.