At risk patients undergoing cardiac surgery with
cardiopulmonary bypass have increased rates of postoperative infectious morbidity. Postoperatively, after cardiac surgery, an immunosuppression in the form of a polarization of T helper (Th) cells with a decreased Th1 response (IL-2 and IFN-gamma) and an increased Th2 response (IL-4 and IL-10) is recognized. Therapeutic strategies to modulate the immunological response include special key nutrients such as the
amino acid glutamine favoring the Th2 response. There is no information available concerning its effect in patients undergoing cardiac surgery. The aim of this clinical study was to evaluate the effects of a perioperative infusion of
glutamine on the polarized lymphocyte T cell
cytokine expression and on infectious morbidity in cardiac surgery patients at risk of
infection. Seventy-eight patients were included in the study undergoing elective cardiac surgery with a
lymphopenia less than 1.2 giga/l. One or more of the following criteria had to be met: age older than 70 years, ejection fraction less than 40%, or mitral valve replacement. We randomly assigned patients to receive infusions of either high-dose L-alanyl-
L-glutamine dipeptide [0.5 g/(kg day)
glutamine] dissolved in an
amino acid solution or an isonitrogeneous, isocaloric, isovolemic nutritional
solution. An additional group with
normal saline served as control to eliminate any nonspecific nutritional effect. We started the infusion after induction of
anesthesia with 1,000 ml/24 h and continued it for 3 days. The primary endpoint was intracellular T cell
cytokine expression (including the description in tertiles) on the first postoperative day (pod 1). Secondary endpoints were postoperative
infection rate, mortality rate, cardiovascular circulation ventilation time, and renal function. A high-dose perioperative
glutamine application leading to mean plasma levels of 1,177 microM had only a minor influence on the polarized intracellular T cell
cytokine expression. On pod 1 there was a polarization of T cells, i.e., an augmented Th2 response with an increased number of
IL-6 and
IL-10 producing cells. On the other side the Th1 response with
IL-2 and
TNF-alpha declined on pods 1 and 2. Only the intracellular
IL-2 response in the lower tertile of
IL-2 production was improved with
glutamine indicating a small influence. We did not observe any effects on the numbers of postoperative
infections; on mortality rate; on cardiovascular circulation; on ventilation time or on renal function. The elevation of
glutamine plasma levels by a perioperative
intravenous infusion of L-alanyl-
L-glutamine influenced the intracellular expression of
IL-2 in the lower tertile only slightly. However, mean
glutamine values in the other groups remained above or close 500 microM, thus suggesting that
glutamine supply to the immune cells was still adequate in most patients, and that
glutamine deficiency, if it occurred, was marginal. In the event of a severe
glutamine deficiency the observed effect on
cytokine production could be more pronounced. Furthermore, we could not observe any obvious clinical advantage in this at risk cardiac surgical patient population. A
glutamine supplementation for patients undergoing cardiac surgery without a clear
glutamine deficiency is not recommended.