Immunoglobulin G treatment of postcardiac surgery patients with score-identified severe systemic inflammatory response syndrome--the ESSICS study
Werdan K, Pilz G, Müller-Werdan U, Maas Enrique M, Schmitt DV, Mohr FW, Neeser G, Schöndube F, Schäfers HJ, Haverich A, et al
Critical Care Medicine. 2008;36((3):):716-23.
OBJECTIVE A minority of patients develop severe systemic inflammatory response syndrome (SIRS) with high mortality following cardiopulmonary bypass-assisted cardiac surgery. We assessed whether intravenous immunoglobulin G (ivIgG) improves postoperative short-term (5-day) morbidity and reduces 28-day mortality in these patients. DESIGN Randomized, double-blind, placebo-controlled, multicenter trial. SETTING Intensive care units of 11 cardiothoracic centers. PATIENTS AND INTERVENTIONS Of 6,984 patients screened, we identified 244 with severe SIRS (Acute Physiology and Chronic Health Evaluation II score > or = 28 on the first postoperative day). INTERVENTIONS The 244 patients with severe SIRS were randomly assigned to receive an intravenous infusion of either albumin 0. 1% (placebo group, 6 mL [6 mg]/kg of body weight on day 1 and 3 mL [3 mg]/kg of body weight on day 2) or immunoglobulin G 10% (ivIgG group, 6 mL [600 mg]/kg of body weight on day 1 and 3 mL [300 mg]/kg of body weight on day 2). MEASUREMENTS AND MAIN RESULTS The prospectively defined primary end points were improvement in morbidity on day 5 and death from any cause assessed on day 28. A total of 218 patients received both doses of the study drug (placebo n = 108, ivIgG n = 110). Acute Physiology and Chronic Health Evaluation II scores in the placebo group decreased from 31. 8 +/- 4. 0 (day 1) to 25. 8 +/- 9. 3 (day 5) and in the ivIgG group from 31. 8 +/- 3. 4 (day 1) to 25. 9 +/- 10. 3 (day 5), with no significant difference between the groups (p = . 56). The 28-day mortality rate was not significantly different between the groups (per protocol population, placebo group 31. 5%, ivIgG group 39. 1%; intent-to-treat population, placebo group 37. 2%, ivIgG group: 44. 7%). No effect of ivIgG on plasma levels of interleukin-6, tumor necrosis factor, and tumor necrosis factor receptor I/II was observed. Drug-related adverse events were rare in both groups. CONCLUSIONS Patients undergoing cardiac surgery (involving cardiopulmonary bypass) who develop severe SIRS derive no improvement in short-term morbidity or 28-day mortality from ivIgG.
Reduced incidence of postoperative infection after intravenous administration of an immunoglobulin A- and immunoglobulin M-enriched preparation in anergic patients undergoing cardiac surgery
Kress HG, Scheidewig C, Schmidt H, Silber R
Critical Care Medicine. 1999;27((7):):1281-7.
OBJECTIVE To evaluate the efficacy of a commercial immunoglobulin (Ig) A- and IgM-enriched immunoglobulin preparation containing high antibody titers against various human pathogens in the prevention of postoperative infections in anergic patients undergoing cardiac surgery. DESIGN A single-center, prospective, double-blind, randomized study comparing the effect of a polyvalent intravenous human immunoglobulin (IVIG) preparation vs. placebo. LOCATION OF THE STUDY Institute of Anesthesiology and Department of Thoracic and Cardiovascular Surgery, University Hospital, Wurzburg, Germany. PATIENTS A total of 515 patients awaiting elective open-heart surgery with the aid of cardiopulmonary bypass were tested for their in vivo immune response to intradermally administered recall antigens. Forty patients who were preoperatively shown to be anergic in this skin test, and therefore at high risk of developing serious postoperative infections, were selected from this group. Twenty patients with normal immune responses, and thus having a normal risk of infection, were randomly selected from the same patient group to serve as an immunoreactive control group. INTERVENTIONS After obtaining approval from the local institutional review board and informed consent from patients, the 40 anergic patients were randomized and assigned either to the IVIG group (n = 19), to receive a commercially available human IgA- and IgM-enriched immunoglobulin preparation (dose, 20 g), or to the placebo group (n = 21), to receive physiologic saline. These treatments were started 4 hrs after surgery as a 400-mL continuous infusion over a period of 53 hrs. Patients were observed for the development of postoperative infection for the next 2 wks. Group comparisons were made using repeated-measures analysis of variance and Fisher's exact test. A p value < .05 was considered statistically significant MEASUREMENTS AND MAIN RESULTS Postoperative infections were detected in nine of 21 patients (43%) in the placebo group but in only one of 19 patients (5%) in the IVIG-treated group (p = .007; Fisher's exact test). Three of the 20 patients (15%) with normal immune response who received standard postoperative treatment developed postoperative infections. CONCLUSIONS A commercially available IgA- and IgM-enriched intravenous immunoglobulin preparation administered immediately after cardiac surgery significantly reduced the incidence of postoperative infections in preoperatively anergic patients.