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Management of Immune Dysfunction after Adult Cardiac Surgery J. Scott Rankin1, Olusola Oguntolu2, Robert S. Binford2, D. Scott Trochtenberg3, Lawrence H. Muhlbaier4, Charles W. Stratton11Vanderbilt University, Nashville, TN;2Centennial Medical Center, Nashville, TN;3Meharry Medical College, Nashville, TN;4Duke University, Durham, NC OBJECTIVES: Pulmonary dysfunction/multiorgan failure (PD/MF) due to antibiotic-refractory pulmonary infection is an important cause of mortality and morbidity after cardiac operations. Moreover, National data show that postoperative PD/MF is increasing, possibly due to emergence of antibiotic-resistant pathogens. In this study, patients with primary PD/MF after major cardiac operations were managed with immune augmentation to test the hypothesis that correction of preoperative and/or cardiopulmonary bypass-induced immune depletion would be therapeutically efficacious. METHODS: Since 2002, 44 consecutive patients who developed primary antibiotic-refractory PD/MF were treated with intravenous immunoglobulin (IVIgG) at 18-24 gms daily for 5 days (0.3 gms/kg x 5 days; 1.5 gm/kg total dose). Thirty had undergone complex valve and/or aortic surgery and 14 coronary bypass. Mean age was 66 years (range 39-90 years). Preoperatively, 94% had significant comorbidity, 73% presented acutely, 52% were hypo-albuminemic, and 39% had antecedent pulmonary derangement. Using retrospective chart review, relevant clinical variables were assessed for 3 days prior (-3) to beginning IVIgG (on Day 0) and for 5 days afterward (+5). A postoperative morbidity index (PMI) was generated as a weighted sum of: worsening lung infiltrates (I) 1=unilateral, 3=bilateral, 5=generalized; leukocytosis (L) 1 for each 2k>10k; pulmonary dysfunction (P) (sputum, work of breathing, O2 requirement, each) 1=mild, 2=moderate, 3=severe; (V) intubation=5; septic shock (S)=3; renal (R) 1 for each 0.4mg/dl creatinine elevation >1.5mg/dl; GI (G) ileus=2; hepatic dysfunction (H)=2; thrombocytopenia (T) platelet count <50k=2; and delirium (D)=2. Using each patient as his or her own control, the therapeutic effect of IVIgG was assessed with linear regression analysis of PMI over time with a spline and a knot at Day 0, coincident with beginning IVIgG (Figure). RESULTS: At Day 0, all patients were refractory to major antibiotics with morbidity of: I-100%, L-98%, P-98%, V-61%, S-24%, R-61%, G-24%, H-9%, T-36%, and D-9%. IgG levels, obtained in the last 14 patients, were consistently low. Using linear regression analysis of PMI prior to IVIgG, the patients’ clinical status was deteriorating (slope = 3.59, SE=0.41, t=8.62, p<0.0001). After beginning IVIgG at Day 0, improvement in clinical course was observed (slope = -1.98, SE=0.20, t=9.75, p<0.0001). In the spline function analysis, IVIgG administration was associated with significant improvement in clinical status (p<0.0001), as evidenced by a fall in PMI to normal over the course of immune augmentation (Figure). Despite serious baseline profiles at Day 0, 42 of 44 patients (95%) recovered uneventfully to hospital discharge. No significant complications of IVIgG therapy occurred. CONCLUSIONS: This experience suggests that management of immune dysfunction with IVIgG is safe and effective for treatment of primary PD/MF after adult cardiac surgery. In appropriately selected patients, a major therapeutic effect is evident, and the addition of immune augmentation to standard ICU management has the potential for reducing overall operative mortality for adult cardiac surgery to near-zero. Expanded treatment of patients with postoperative immune dysfunction seems indicated, together with investigation of immuno-modulatory mechanisms. 
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