Hypogammaglobulinemia after cardiopulmonary bypass in infants

Abstract

Background Hypogammaglobulinemia has been reported after cardiac surgery and may be associated with adverse outcomes. We sought to define baseline immunoglobulin (Ig) concentration in neonates and infants with congenital heart disease, determine its course following cardiopulmonary bypass (CPB), and determine if post-CPB hypogammaglobulinemia was associated with increased morbidity. Methods Single center, retrospective analysis of infants who underwent cardiac surgery with CPB between June 2010 and December 2011. Ig concentration obtained from banked plasma of 47 patients from a prior study (pre-CPB, immediately post-CPB, and 24- and 48-hours post-CPB). Additionally, any Ig levels drawn for clinical purposes after CPB were included. Ig levels were excluded if drawn after chylothorax diagnosis or intravenous immunoglobulin G administration. Results Median age was 7 days. Preoperative Ig concentration was similar to that described in healthy children. IgG level fell to less than 50% of preoperative concentration by 24-hr post-CPB and failed to recover by 7 days. 25/47 (53%) patients had low IgG after CPB (<248 mg/dl). Despite no difference in demographics or risk factors between patients with low and normal IgG, low IgG patients had more positive fluid balance at 24-hours, increased pro-inflammatory plasma cytokine levels, duration of mechanical ventilation, and CICU length of stay. Additionally, low IgG patients had increased incidence of post-operative infections (40% vs. 14%, p=0.056). Conclusions Hypogammaglobulinemia occurs in half of infants after CPB. Its association with fluid overload and increased inflammatory cytokines suggests it may result from capillary leak. Postoperative hypogammaglobulinemia is associated with increased morbidity, including more secondary infections.

A Prospective Observational Study of Hypogammaglobulinemia in the First Year After Lung Transplantation

“…We hypothesize that the high prevalence of severe HGG immediately after transplant could be related to a lower pretransplant IgG level, baseline patient’s inflammatory condition, the use of an induction agent, mechanical losses, and third spacing with a capillary leak syndrome that can be seen in CPB surgery. 7 - 10 However, in our study, we did not find an association between severe HGG and CPB/ECMO use. After the initial posttransplant measurement, severe HGG improved and remained below 10% at all subsequent time points.…”

Pediatric Cardiac Intensive Care Society 2014 Consensus Statement

“…The inflammatory cascade induced by CPB promotes interstitial edema by altering Starling forces. Resultant changes include increased capillary hydrostatic pressure, decreased plasma oncotic pressure, increased tissue osmotic pressure, increased capillary permeability or filtration surface area, and decreased lymphatic drainage (20)(21)(22). Hypogammaglobulinemia occurs in 50% of infants following CPB and is associated with increased proinflammatory cytokines and a positive 24-hour fluid balance (20).…”

“…Resultant changes include increased capillary hydrostatic pressure, decreased plasma oncotic pressure, increased tissue osmotic pressure, increased capillary permeability or filtration surface area, and decreased lymphatic drainage (20)(21)(22). Hypogammaglobulinemia occurs in 50% of infants following CPB and is associated with increased proinflammatory cytokines and a positive 24-hour fluid balance (20). Independent of inflammatory effects, the use of hypothermia during CPB is associated with a four-fold increase in net fluid extravasation (23,24).…”

Hypogammaglobulinemia as a Predictive Factor of Postoperative Complications in Pediatric Cardiac Surgery

“…Hypogammaglobulinemia, developed as a result of cardiac surgery accompanied by cardiopulmonary bypass (CPB), may be caused by hemodilution, destruction of immunoglobulin, extravasation into the interstitial space related to systemic inflammation, and capillary leak syndrome [1,2]. Normally, neonatal serum immunoglobulin G (IgG) levels could be equal to or slightly higher than maternal serum IgG levels, gradually falling by three months of age and progressively increasing as IgG synthesis becomes established [3].…”