Elsevier

The Lancet

Volume 358, Issue 9283, 1 September 2001, Pages 696-701
The Lancet

Articles
Effect of preoperative oral immune-enhancing nutritional supplement on patients at high risk of infection after cardiac surgery: a randomised placebo-controlled trial

https://doi.org/10.1016/S0140-6736(01)05836-6Get rights and content

Summary

Background

Elderly patients and those with poor ventricular function have increased morbidity and mortality rates when undergoing surgery. We aimed to ascertain whether an oral immune-enhancing nutritional supplement could improve preoperative host defence, and subsequently lower postoperative infections and organ dysfunction in patients undergoing elective cardiac surgery who are at high risk of infection.

Methods

In this prospective, randomised, double-blind, placebo-controlled study, we randomly assigned 50 patients who were scheduled to undergo coronary artery bypass to receive either an oral immune-enhancing nutritional supplement containing L-arginine, ω3 polyunsaturated fatty acids, and yeast RNA (n=25), or a control (n=25) for a minimum of 5 days. Patients were included if they were aged 70 years or older, or had an ejection fraction of less than 0·4, or were scheduled to undergo mitral valve replacement. The main outcome was preoperative host defence (delayed-type hypersensitivity response to recall antigens, expression of HLA-DR epitopes on monocytes, and concentration of interleukin 6 in plasma). Analysis was per protocol.

Findings

Five patients (two in the treatment group) were excluded because they did not take the minimum dose. Preoperative expression of HLA-DR epitopes on monocytes was significantly higher in patients given the study treatment (109% [95% CI 92–128]) than those given the control (69% [58–82]) compared with baseline (100%) (p=0·02, repeated measures ANOVA). However, concentration of interleukin 6 was significantly lower in the treatment group (0·90 pg/L [0·69–1·18]) than in the control group (1·94 pg/L [1·45–2·59]) (p=0·032, repeated measures ANOVA). Additionally, delayed-type hypersensitivity response to recall antigens improved preoperatively and remained better until hospital discharge.

Interpretation

Intake of an oral immune-enhancing nutritional supplement for a minimum of 5 days before surgery can improve outlook in high-risk patients who are undergoing elective cardiac surgery.

Introduction

Elderly patients and patients with poor ventricular function who are undergoing cardiac operations with hypothermic cardiopulmonary bypass have increased postoperative morbidity and mortality rates.1 Host defence can be diminished by nutritional deficiencies, hypoperfusion, anaesthesia, and operative trauma. Immune function is also depressed by use of cardiopulmonary bypass and hypothermia.2 Results of studies have suggested that L-arginine can improve postoperative outcome in patients having cardiac surgery, and ω3 polyunsaturated fatty acids can restrict the postoperative generalised inflammatory response.3

Experimental studies have shown that the use of nutritional supplements containing L-arginine, ω3 polyunsaturated fatty acids, and nucleotides boost immune responsiveness after surgery or trauma.3 L-arginine is a semi-essential aminoacid and a precursor of nitric oxide, the most important endothelial vasodilator. In experimental studies,4, 5, 6 L-arginine improved wound healing, restored postoperative depressed macrophage function and lymphocyte responsiveness, and augmented resistance to infections. Arginine protected against ischaemia-reperfusion injury by increasing oxygen delivery upon reflow, thereby improving cardiac function. Intake of additional ω3 polyunsaturated fatty acids alters cell-membrane phospholipid content and prostaglandin synthesis.3, 7 This alteration might be an important factor in suppression of the generalised inflammatory response and subsequent immunosuppression and capillary leakage after major surgery.3, 8, 9 Purines and pyrimidines are semi-essential nutrients for rapidly dividing cells.10 Administration of nucleotides in the form of yeast RNA has improved the host immune response to infections.10, 11

These three immunonutrients have been combined into a single enteral feed. For trauma patients, critically ill patients, and those who are undergoing surgery for cancer, use of this immune-enhancing formula after surgery has improved immunocompetence, reduced infections, and shortened length of stay in hospital.12 The effect of postoperative immune-enhancing nutrition starts after 3 days and seems to be dose dependent.13 For this reason, an oral immune enhancing nutritional supplement before surgery might be beneficial. L-arginine, ω3 polyunsaturated fatty acids, and yeast RNA have been combined into a single oral immune-enhancing nutritional supplement. We aimed to ascertain whether this oral immune-enhancing nutritional supplement taken for at least 5 days before an operation in high-risk patients undergoing cardiac surgery improves preoperative host defence and subsequently reduces postoperative infections and organ dysfunction.

Section snippets

Patients

We selected 50 patients who were scheduled to undergo cardiac surgery and met one or more of the following criteria: age 70 years or older, ejection fraction less than 0·40, or replacement of mitral valve. All patients gave written informed consent. Patients were excluded if they were younger than 21 years, were pregnant, had insulin-dependent diabetes mellitus, had severe renal or liver failure or both, had a known malignancy, used immunosuppressive medication, or used non-steroidal

Discussion

In this study, we investigated the effect of an oral immune-enhancing nutritional supplement on preoperative host defence, incidence of infections, and postoperative organ function. We recorded a significant increase in preoperative serum arginine concentration, indicating good substrate bioavailability and good compliance of patients to their supplemental diet. This increase in serum arginine concentration was close to concentrations previously reported.22 Our results show that intake of an

References (30)

  • CS Rinder et al.

    Lymphocyte and monocyte subset changes during cardiopulmonary bypass: effects of aging and gender

    J Lab Clin Med

    (1997)
  • WG Cheadle et al.

    HLA-DR antigen expression on peripheral blood monocytes correlates with surgical infection

    Am J Surg

    (1991)
  • DT Efron et al.

    Arginine and nutrition in renal disease

    J Ren Nutr

    (1999)
  • TL Higgins et al.

    Stratification of morbidity and mortality outcome by preoperative risk factors in coronary artery bypass patients: a clinical severity score

    JAMA

    (1992)
  • HG Kress et al.

    Reduced incidence of postoperative infection after intravenous administration of an immunoglobulin A- and immunoglobulin M-enriched preparation in anergic patients undergoing cardiac surgery

    Crit Care Med

    (1999)
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