Immunotherapy for refractory pulmonary infection after adult cardiac surgery: immune dysregulation syndrome

Abstract

Background and aim of the study: Pulmonary dysfunction/multiorgan failure (PD/MF), usually due to refractory pulmonary infection, is an important cause of mortality and morbidity after cardiac operations. Moreover, the incidence of PD/MF may be increasing due to the emergence of antibiotic-resistant pathogens.

Methods: Fifteen consecutive patients (median age 69 years) who were developing antibiotic-refractory PD/MF were administered 24 g per day intravenous immunoglobulin (IV-IgG; Carimune) for five days. Ten patients had undergone complex valve surgery, and five coronary bypass. Preoperatively, 93% of patients had significant comorbidity, 73% presented acutely, 53% were hypoalbuminemic and 47% had antecedent acute pulmonary derangement. Clinical variables were assessed by retrospective chart review for three days prior to (-3) the start of IV-IgG (day 0) and for five days afterwards (+5). A postoperative morbidity index (PMI) was generated as a weighted sum of: worsening lung infiltrates (I); leukocytosis (L); pulmonary dysfunction (P); ventilator requirement (V); septic shock (S); renal (R), gastrointestinal (G), or hepatic (H) dysfunction; thrombocytopenia (T); and delirium (D).

Results: At day 0, all patients were refractory to major antibiotics, with morbidities of: 1-100%, L-93%, P-93%, V-60%, S-27%, R-67%, G-40%, H-13%, T-27%, and D-20%. Using regression analysis, IV-IgG administration was associated with a statistically significant fall in white blood count and improvement in PMI (p <0.006). Fourteen patients (93%) recovered uneventfully, and one patient (7%) died from progressive sepsis. No complications of IV-IgG therapy occurred.

Conclusion: Given the high predicted mortality of PD/MF patients, these data suggest that IV-IgG is a safe and efficacious adjunct to antibiotics in this setting. Further studies, including a randomized trial and investigation of immunomodulatory mechanisms, seem indicated.