Preventing Infectious Complications With Nutrition InterventionFrom the Department of Surgery, Medical College of Georgia, Augusta, Georgia Correspondence: Robert G. Martindale, MD, PhD, Medical College of Georgia, Department of Surgery, 1120 15th Street, BI 4072, Augusta, GA 30912. Electronic mail may be sent to rmartind{at}mail.mcg.edu.
A recent focus in medical and surgical practice is the proactive management of infections, preventing their occurrence rather than relying solely upon their treatment after they have occurred. This new focus has evolved from the observation that despite "new and improved" antibiotics and advances in critical care, the incidence of infectious complications and sepsis continues to rise.1 Approximately 10% of hospitalized patients will acquire an infection after they are admitted to the hospital.2 With sepsis as the leading cause of death in noncoronary intensive care units (ICUs) and the 10th leading cause of mortality overall in the United States,3 this translates into approximately 500 deaths per day from sepsis. Even more worrisome is that the incidence of sepsis-related deaths has been increasing by 6.2% annually since 1992.1 These additional infectious and septic occurrences are estimated to increase the United States' economic burden by $17 billion annually.4 This increased cost reflects physical resources consumed in the hospital and increased resource consumption postdischarge. For example, it has been reported that patients discharged home after a hospital-related infection need professional assistance 24% of the time vs 7% of the time if no infection was experienced during the hospital stay.5 Several factors are thought to contribute to the rising infection and sepsis rates, including the broadened use of invasive devices and the increased number of immunocompromised hosts now found in acute care settings (eg, the elderly, those undergoing adjuvant chemotherapy/radiation, and HIV patients).6 Additionally, the excessive and inappropriate use of broad-spectrum antibiotics has contributed to a dramatic rise in the incidence of antibiotic-resistant organisms. Seventy percent of nosocomial infections are now resistant to at least 1 antibiotic.7 The resistant bacteria include the traditional players such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) and, more recently, even more formidable organisms such as the extended spectrum β lactamases.8 These bacteria, usually Gram-negative, are resistant to 6 or 7 classes of antibiotics. It is important to realize that bacterial resistance is not only a problem in the acute care setting but also among relatively healthy "grouped" populations; MRSA is now isolated as a source of community-acquired infections, especially in the elderly residing in nursing homes, children in daycare centers, the incarcerated, and even in healthy athletes.9 The epidemiology of postoperative nosocomial infections is changing. In the 1960s, postoperative wound infections were responsible for 46% of infections. During the 1970s and 1980s, urinary tract infections (UTI) were the most common. Currently, 43% of postoperative nosocomial infections are from pneumonia, with wound infections accounting for approximately 15%.10 This trend dramatically changes the potential morbidity of a postoperative nosocomial infection, as pneumonia carries a much higher mortality than does UTI or wound infection. In the recent PROWESS trial of 1690 patients with sepsis, the most common origin of sepsis was the lung, comprising 53.6%.11 The near-epidemic rise in resistant microbial species and greater numbers of immunocompromised patients entering into the health care setting has made prevention of infection a primary goal. This prevention strategy needs to be proactive and have clear objectives. The first objective is to optimize patient clinical outcome, second is to prevent the occurrence of resistant organisms and spread of resistant bacteria, and third is to recognize the socioeconomic impact of infections and attempt to mitigate the burden. All members of the health care team, from the senior administrators, physicians, nurses, and other key clinicians to the housekeeping services, must be aware of and adhere to the objectives of a hospital-wide infection-prevention strategy in order for the plan to be effective.
Strategies to Prevent Infections
The importance of glycemic control has come under greater scrutiny since a
landmark paper by van den Berghe et
al.13 This paper
evaluated the benefits of meticulous blood glucose control in the ICU. They
prospectively evaluated 1548 patients requiring mechanical ventilation. The
main objective was to maintain blood glucose levels between 80 and 110 mg/dL
vs 180 and 200 mg/dL. The group of euglycemic patients receiving
intensive insulin therapy had fewer episodes of acute renal failure, fewer
transfusions, less polyneuropathy, and decreased ICU length of stay. The
infectious complications were dramatically lowered, with a 46% decease in
septicemia. Meticulous glucose control also resulted in a 42% decrease in
mortality rate. Multiple mechanisms have been proposed for the benefits
observed. The adverse influence of even modest hyperglycemia on neutrophil
function has been evaluated by multiple authors over the past 15 years.
Chemotaxis, phagocytosis, oxidative burst, and bacteriocidal capacity are all
noted to be negatively
influenced.14 Other
studies have supported the growing concept that hyperglycemia produces a
proinflammatory state. Modest hyperglycemia has been shown to increase TNF
levels and activate NF- Less than optimal nutritional status in the preoperative or perioperative period has been associated with increased risk of infection.16,17 Patients undergoing major surgery for neoplastic disease commonly experience significant immunosuppression that is multifactorial in origin. Malnutrition, surgical insult, anesthesia, blood transfusions, adjuvant chemotherapy/radiation, and other metabolic changes associated with surgery all contribute to the immunosuppressed state commonly observed.18 The route, quantity, timing, and nutrient composition also have significant influence on infectious morbidity.19 Enteral nutrition, when compared with parenteral, is now well accepted as the preferred route of feeding in patients unable to volitionally consume adequate nutrients.20 This concept has been supported in more than 46 major papers in the English literature alone, the vast majority of which demonstrate enteral nutrition being far superior to parenteral when it comes to minimizing infection risk. The fact that enteral feeding maintains the gut-associated lymphoid tissue (GALT) is thought to be one of the primary reasons why this route of feeding results in significantly fewer infectious complications when compared with parenteral feeding. The GALT includes Peyer patches, intraepithelial lymphocytes, and lymphoid cells of the lamina propria. The GALT contains 70% to 80% of the body's immune cells, making it the organism's largest immune organ, modulating responses to both infectious and resident microbial flora.21 The GALT includes several classes of immune cells, including dendritic cells, lymphocytes, mast cells, macrophages, and granulocytes. The GALT has been shown to have influence on the systemic immune function in addition to the local gut influence. The naïve T and B lymphocytes, which have been sensitized in the Peyer patches, migrate under chemotactic stimuli to the mesenteric lymph nodes, where they mature and undergo proliferation. They then enter the bloodstream via the thoracic duct. Once in systemic circulation, they can enrich all epithelial surfaces, including the lung, GU, skin, and gut surfaces.21
Appropriate quantity and quality of lipids have been reported to influence
infectious outcomes. As early as the 1980s, animal studies indicated that
large volumes of IV 18 carbon
Immune-modulating enteral formulations containing nutrients such as
arginine, glutamine, Three recent meta-analyses27–29 have reported that that the use of immune-modulating formulas is associated with additional, significant reductions in infectious morbidity and hospital length of stay when compared with use of standard enteral formulas. These effects have been more uniformly seen in surgical and trauma patients than in the medical ICU populations.
Despite the advances in critical care and "new and improved" antibiotics, we as clinicians are losing the war against pathogenic organisms.30 Resistant microbes and nosocomial infections are on the rise. In addition, the patient population presented for surgery and to emergency rooms has multiple comorbid conditions that contribute to poor clinical outcomes. A multilevel team approach should be taken to combat the escalating incidence of hospital infections and the epidemic of bacterial resistance. This approach should include not only adherence to the infection control and antibiotic control policies of the hospital but also appropriate and timely nutrition intervention. Several nutrition-oriented strategies can be implemented which are focused toward prevention of infectious complication rather than treatment of infections. These include meticulous glycemic control, avoidance of excessive amounts of  -6 fatty acids, early identification and
intervention in the malnourished and critically ill patient, use of enteral
feeding in lieu of parenteral nutrition whenever possible, and consideration
of specific immune-modulating formulas for selective patient populations.
The future for nutritional modulation of the immune response looks very
promising. Data and studies continue to be published on individual nutrients
and the genotype-specific response to nutrients. The availability of
oligonucleotide arrays will allow the assessment of nutrient effects on
multiple gene expressions simultaneously. Nutritional modulation of molecular
signals in settings such as surgery and trauma has recently been shown.
Changes in NF- The optimal candidate to receive these nutrients remains controversial, and once that is determined, the optimal timing, quantity, and composition for providing these nutrients will require further exploration as well. This paper, in an overview fashion, and others in this supplement more specifically, addresses the issues of immune modulation and its role in economics of health care delivery, some of the basic science mechanisms proposed to explain the specific nutrient influences, and some suggested protocols and flow diagrams to aid in appropriate use of nutrition as a strategy of infection prevention.
This review article addresses the issues of immune modulation and its role in economics of health care delivery. It reviews basic science mechanisms proposed to explain specific nutrient effects and discusses the appropriate use of specialized nutrition as a strategy for infection protection. Received for publication August 2, 2004. Accepted for publication August 26, 2004.
Journal of Parenteral and Enteral Nutrition, Vol. 29, No. 1 suppl,
S53-S56 (2005) This article has been cited by other articles:
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B, resulting in an elevation in the systemic
inflammatory
response.
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CONCLUSIONS
CONCLUSIONS
, and FFAs to low-dose endotoxemia in humans. Am J Physiol
Endocrinol Metab. 2004;286:E766
–E772.
