Immunoglobulin G treatment of postcardiac surgery patients with score-identified severe systemic inflammatory response syndrome--the ESSICS study.
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.


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


METHODS
Intensive care units of 11 cardiothoracic centers.


METHODS
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).


METHODS
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).


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.
Werdan
Karl
K
Department of Medicine III, Martin-Luther-University Halle-Wittenberg, Germany. karl.werdan@medizin.uni-halle.de
Pilz
Günter
G
Müller-Werdan
Ursula
U
Maas  Enriquez
Monika
M
Schmitt
Dierk V
DV
Mohr
Friedrich-Wilhelm
FW
Neeser
Gertraud
G
Schöndube
Friedrich
F
Schäfers
Hans-Joachim
HJ
Haverich
Axel
A
Fraunberger
Peter
P
Andersson
Jan
J
Kreuzer
Eckart
E
Thijs
Lambert G
LG
D018806:APACHE; D000368:Aged; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D008297:Male; D012720:Severity of Illness Index; D018746:Systemic Inflammatory Response Syndrome / Q000188:drug therapy* / Q000209:etiology*
D007074:Immunoglobulin G