The Impact of Preoperative Oral Glutamine Intake on the Immunocompetence and Outcomes of Malnourished Patients Undergoing Major Abdominal Surgery Due to Malignancies

Background

Malnutrition occurs in up to 50% of patients requiring elective surgery for neoplastic diseases. It exerts a detrimental influence on outcome of surgery, because it can suppress immune function, exaggerate stress response and cause organ system dysfunction. Increased susceptibility to infection, protracted wound healing, impaired blood clotting and vessel wall fragility have been shown to be the leading causes of postoperative morbidity and mortality in malnourished patients undergoing major surgical resections.

Immuno- or pharmaconutrition, defined as enteral or parenteral nutritional therapy based on a variety of products, such as omega-3-fatty acids, glutamine, arginine, sulfur-containing amino acids, nucleotides and anti-oxidants, is thought to have beneficial effects on postoperative recovery in a wide variety of surgical patients. Studies have shown its clinical effectiveness in terms of reduced postoperative complications, shortening the hospital stay and reduced hospitalization costs. Torosian et al. showed that severely malnourished patients benefit from preoperative nutrition, which reduce postoperative complications by 20%.

Although there is clinical evidence for the administration of immunonutrition to patients in the perioperative period, our understanding of the optimal type and time of immunonutrition, the characteristics of patients that benefit most, as well as the immunological mechanisms responsible for its beneficial effect is limited.

Objective

To assess in malnourished cancer patients the effect of 30g oral glutamine/day (3 sachets KABI® glutamine, Fresenius Kabi/day) for a preoperative course of 5 days on:

• Postoperative morbidity (surgical site infections, pneumonia, sepsis, incidence of wound and fascial dehiscence, incisional hernia, anastomotic break down)
• Nutritional status of the patients
• Postoperative cell damage and inflammatory response
• Perioperative immunocompetence

Methods

Seven days before surgery, the patients will receive a tetanus booster shot and will be randomly enrolled in either the 'glutamine group' or into the 'placebo group'. The patients as well as the responsible surgeons will be blinded.

• Patients in the 'glutamine group' will receive 30g oral glutamine / day for 5 days before surgery.
• Patients in the 'control group' will receive 30g oral maltodextrin / day for 5 days before surgery.

Inclusion criteria

• Histologically confirmed and surgically resectable carcinomas
• Candidates for elective surgery with an estimated surgical stress score
• A Nutritional Risk Screening 2002 (NRS-200232) score ≥3
• Age ≥ 18 years
• Completed primary immunization with tetanus toxoid
• Last tetanus booster ≥10 years back
• Informed consent

Exclusion criteria

• Refusal to participate
• Clinically relevant alterations of the pulmonary renal of hepatic function
• Insulin-dependent diabetes mellitus
• Pre-existing autoimmune diseases and immune-deficiencies
• Neutropenia
• Pregnancy
• Age <18 years
• Last tetanus booster <10 years back
• Ongoing infection
• Intestinal obstruction at the time of entry into the study