Parenteral Nutrition University of Colorado Department of Surgery Grand Rounds Carlos A. Rueda, M.D.
Objectives Quick Basic Nutrition Review Parenteral Nutrition vs. No Nutrition Enteral vs. Parenteral Nutrition Causes of Infections in Patients on Parenteral Nutrition
Basic Substrates VO2 (L/g) VCO2 (L/g) RQ Energy (kcal/g) Lipid 2.0 1.4 0.7 9.1 Protein 0.96 0.78 0.8 4.0 Carbohydrate 0.74 0.74 1.0 3.7 VO2 = Oxygen required; VCO2 = Carbon dioxide produced; RQ = Respiratory quotient
Daily Energy Needs Harris-Benedict: Basal energy expenditure (BEE) calculates energy needs in kcal/day. Men: 66.5 + (13.8 x wt) + (5 x ht) (6.8 x age) Women: 655 + (9.6 x wt) + (1.7 x ht) (4.7 x age) wt = ideal body weight (kg) ht = height (cm)
Daily Energy Needs Activity factors Multiply the BEE to adjust energy requirements based on patients overall status (BEE x α) Fever: α = 1.1 for each degree above 37 Mild stress (long bone fracture, mild trauma): α = 1.25 Severe stress (multi-organ trauma): = 1.6 Burns >40% TBSA: α = 2.0
Protein Requirements 1 g protein/kg/day = 0.16 N2/kg/day Hypercatabolic state Up to 2 g protein/kg/day Burns, major trauma with sepsis Goal: positive nitrogen balance Measure urinary urea nitrogen (UUN) Nitrogen balance = Nitrogen intake UUN - 4
Mix and Match NPC = non-protein calories Carbohydrates: 60-70% of total calories Primary fuel for CNS, RBC, WBC, renal medulla High RQ (1.0 vs 0.7 for lipids) Can lead to metabolic acidosis and need for increased minute ventilation Lipids: 10-25% of total calories Protein: <20% of total calories
Introduction Late 1960 s parenteral nutrition (TPN) established as a form of management. Small controlled trials suggested TPN as being harmful. Enteral nutrition became the preferred route.
Introduction Incidence of obese patients in the ICU increased. Leading to insulin resistance and hyperglycemia. Increasing the risk of infection and sepsis.
Parenteral Nutrition vs No Nutrition
Meta-Analysis 26 controlled clinical trials comparing TPN and no nutrition. 2,211 patients No reduction in mortality or incidence of major complications between groups. Malnourished patients only: significant reduction in incidence of complications. Heyland DK, et al. (1998) Total parenteral nutrition in the critically ill patient: a meta-analysis. JAMA 280: 2013-2019.
Meta-Analysis Early studies included a large number of non-obese patients and the reduction of complications was larger. More recent studies inlcuded a large number of obese patients and the reduction of complications was smaller. Obese patients received TPN and were significantly overfed. Heyland DK, et al. (1998) Total parenteral nutrition in the critically ill patient: a meta-analysis. JAMA 280: 2013-2019.
Controlled Study 395 VA surgical patients. Received either perioperative TPN or no nutritional support. Patients receiving TPN had more infections. Subgroup of malnourished patients: the incidence of infections was not increased. Non-infectious complications fell from 40% to 20%. No authors listed. (1991) Perioperative total parenteral nutrition in surgical patients. Veterans Affairs Total Parenteral Nutrition Cooperative Study Group. N Engl J Med 325: 525-532.
Controlled Study Note: Patients on TPN received 1,000 calories more than their metabolic needs. Overfeeding increases the risk of infectious complications in non-malnourished patients. No authors listed. (1991) Perioperative total parenteral nutrition in surgical patients. Veterans Affairs Total Parenteral Nutrition Cooperative Study Group. N Engl J Med 325: 525-532.
Randomized Study 124 patients undergoing hepatectomy. Average weight 50 kg, triceps skin-fold thickness only 10 mm. Randomly assigned to perioperative TPN or no nutritional support. TPN significantly reduced the incidence of complications, infections and the use of diuretics. Fan ST et al. (1994) Perioperative nutritional support in patients undergoing hepatectomy for hepatocellular carcinoma. NEJM 325: 525-532.
Meta-Analysis 7 out of 27 randomized studies. 798 malnourished patients. Compared TPN with no nutritional support. TPN significantly reduced the incidence of mortality compared to no nutrition. Trend to reduce complications and infections when compared to no nutritional support. Braunschweig CL et al. (2001) Enteral compared with parenteral nutrition: a meta-analysis. Am J Clin Nutr 74: 534-542.
Parenteral Nutrition vs No Nutrition TPN can greatly benefit patients who are malnourished when compared to no nutritional support. Excessive calorie intake via TPN given to well-nourished patients can increase the risk of infectious complications.
Parenteral Nutrition vs Enteral Nutrition
Meta-Analysis 30 controlled trials. Compared early enteral nutrition vs TPN. No difference in mortality between patients in either group. Peter JV et al. (2005) A metaanalysis of treatment outcomes of early enteral versus early parenteral nutrition in hospitalized patients. Crit Care Med 33: 213-220.
Meta-Analysis 12 controlled trials. Compared enteral nutrition vs TPN in ICU patients only. Total 748 patients in ICU. No difference in mortality between patients in either group. Heyland DK et al. (2003) Canadian clinical practice guidelines for nutrition support in mechanically ventilated critically ill adult patients. J Pareter Enteral Nutr 27: 355-373.
Intensive Care Medicine: Meta-Analysis 9 controlled trials. Compared enteral nutrition vs TPN in ICU patients. Included only studies in which 95% of patients had complete follow up. Intention to treat analysis conducted. Simpson F and Doig GS (2005) Parenteral vs enteral nutrition in the critically ill patient: a meta-analysis of trials using the intention to treat principle. Intensive Care Med 31: 12-23
Intensive Care Medicine: Meta-Analysis Patients receiving TPN had a significant reduction of mortality compared to those who received enteral nutrition started after 24 hours. Benefit lost if enteral feeds were started immediately at admission. Simpson F and Doig GS (2005) Parenteral vs enteral nutrition in the critically ill patient: a meta-analysis of trials using the intention to treat principle. Intensive Care Med 31: 12-23
Intensive Care Medicine: Meta-Analysis Benefit of reduced mortality in the group receiving TPN was robust. Persisted after the inclusion of two further studies with at least 90% completed follow up in the intention to treat analysis. Simpson F and Doig GS (2005) Parenteral vs enteral nutrition in the critically ill patient: a meta-analysis of trials using the intention to treat principle. Intensive Care Med 31: 12-23
TPN vs Enteral Meta-Analyses Incidence of infectious complications all statistically higher in patients receiving TPN. Recommendations: Enteral nutrition more favorable than TPN. Further good-quality studies are required. Infectious complications are more apparent than real because they were caused by controllable factors (hyperglycemia).
TPN vs Enteral Meta-Analyses Only 6 compared the incidence of infections. In 3 out of these 6 studies there was no difference in the incidence of infections. In the other 3 trials there was an increased incidence of infections in patients receiving TPN. Significant hyperglycemia in patients receiving TPN compared to those receiving enteral nutrition. Moore FA et al. (1989). TEN vs TPN following major abdominal trauma reduced septic mortality. J Trauma 29:916-922 Kudsk KA et al. (1992) Enteral vs parenteral feeding. Effects on septic morbidity after blunt and penetrating abdominal trauma. Ann Surg 215: 503-513 Kalfarentzos F et al. (1997) Enteral nutrition is superior to parenteral nutrition in severe acute pancreatitis: results of a randomized prospective trial. Br J Surg 84:1665-1669
TPN vs Enteral Meta-Analyses In 2 of those 3 studies: No difference between groups: Antibiotics Ventilatory support Need for dialysis Unclear if there was any clinical harm from the reported infections in the TPN groups. Kudsk KA et al. (1992) Enteral vs parenteral feeding. Effects on septic morbidity after blunt and penetrating abdominal trauma. Ann Surg 215: 503-513 Kalfarentzos F et al. (1997) Enteral nutrition is superior to parenteral nutrition in severe acute pancreatitis: results of a randomized prospective trial. Br J Surg 84:1665-1669
Parenteral Nutrition vs Enteral Nutrition TPN does not alter mortality when compared with enteral nutrition. TPN is beneficial when enteral nutrtition cannot be started within 24 hours of admission. TPN is beneficial for non- obese malnourished patients.
Parenteral Nutrition vs Enteral Nutrition TPN is associated with hyperglycemia. No differences in antibiotic use, need for ventilatory support or for dialysis among groups. Intention to treat analysis: no differences in the duration or cost of patients hospital stay.
Euglycemia Two controlled clinical trials of 2,658 medical and surgical critically ill patients. Maintenance of euglycemia has profound effect on outcome. Euglycemia reduced mortality and complications in surgical patients and reduced complications in medical patients. Van den Berghe G et al. (2001) Intensive insulin therapy in the critically ill patients. NEJM 345: 1359-1367. Van den Berghe G et al. (2006) Intensive insulin therapy in the medical ICU. NEJM 354: 449-461.
Parenteral Nutrition Special Issues
Glutamine Primary fuel for bowel mucosa: supplementation may improve integrity Conidtionally essential amino acid: rapidly mobilized during stress
Meta-Analysis World J Gastro 9 RCT with 373 surgical patients. Various abdominal surgeries. Randomized to TPN suplemented with or without glutamine. TPN with glutamine: decreased the rate of infections, reduced length of hospital stay, improved nitrogen balance. Zheng YM et al. (2006) Glutamine dipeptide for parenteral nutrition in abdominal surgery: a meta-analysis of randomized control trials. World J Gastroenterol 46:7537-7541
Omega-3 Fatty Acids Found in fish and canola oil Decreases pro-inflammatory transcription factor. Non-randomized prospective trial: 661 patients receiving TPN supplemented with fish oil. Reduced mortality, lowered antibiotic use and hospital stay. RCT are required to verify findings. Heller AR (2006). Omega-3 fatty acids improve the diagnosis-related outcome. Crit Care Med 34:1253-1255.
Causes of infections in Patients on Parenteral Nutrition
Translocation Theory Observational study in animals. Intestinal atrophy in animals receiving TPN. Intestine does not receive food enters a resting state. Atrophy promotes bacterial translocation leading to infection and sepsis. Tanaka S et al. (1992) Changes in intestinal absorption of nutrients and brush border glycoproteins after total parenteral nutrition in rats. Gut 33:484-489. Alexander JW (1990). Nutrition and translocation JPEN 14 (Suppl): 170s-174s.
Translocation Theory Author Number of Patients Nutritional Support Intestinal atrophy Guedon et al 7 NPO No atrophy after 21 days Rossi et al 7 NPO Atrophy after 9 months Pironi et al 2 TPN Atrophy after 2-3 months Sedman et al 203 TPN No atrophy after >10 days Guedon C et al (1986) Decreased brush border hydrolase activities without gross morphologic changes in human intestinal mucosa after prolonged total parenteral nutrition in adults. Gastroenterology 90: 3737-378 Rossi TIM et al ( 1993). Small intestinal mucosa changes, including epithelial cell proliferative activity, of children receiving total parenteral nutrition. Dig Dis Sci 38: 1308-1313. Pironi L et al. (1994). Morphologic and cytoproliferative patterns of duodenal mucosa in two patients after long-term total parenteral nutrition: changes with oral refeeding and relation to intestinal resection. JPEN 18:351-354. Sedman PC et al. (1995) Preoperative total parenteral nutrition is not associated with mucosal atrophy or bacterial translocation in humans. Br J Surg 82:1663-1667.
Translocation Theory Bacterial translocation: Culture bacteria from: Bowel lumen Mesenteric lymph nodes Blood
Translocation Theory 132 patients underwent laparotomy with mesenteric lymph node biopsies and blood cultures. 73% of blood cultures grew gram-positive bacteria. Only 2 patients had the same bacteria cultured from the intestine, mesenteric lymph node and blood. Moore FA et al. (1992) Postinjury shock and early bacteremia. A letal combination. Arch Surg 127:893-897.
Lipid Theory Lipids in TPN promote bacterial growth. Perhaps by altering or blocking the reticuloendothelial system.
Lipid Theory Controlled clinical trial 253 bone marrow transplant patients received 30% energy intake as TPN fat. 259 patients received 6% energy intake as TPN fat. Energy calculations were based on their resting metabolic rate. Tight glycemic control with insulin. Lenssen P et al. (1998) Intravenous lipid dose and incidence of bacteremia and fungemia in patients undergoing bone marrow transplantation. Am J Clin Nutr 67:927-933.
Lipid Theory No difference in the incidence of bacteremia or fungal infections between groups. No difference in the time to any infection over 60 days between groups. Some patients in the low fat intake group developed essential fatty acid deficiency. Lenssen P et al. (1998) Intravenous lipid dose and incidence of bacteremia and fungemia in patients undergoing bone marrow transplantation. Am J Clin Nutr 67:927-933.
Summary TPN can be life-saving for patients who cannot eat or absorb nutrients. The use of TPN does not increase mortality. TPN is likely to cause hyperglycemia in obese, insulin-resistant patients. Hyperglycemia increases the rate of infectious and non-infectious complications
Summary Enteral nutrition is safer on obese patients or those with insulin resistance. Route of nutritional support does not alter the risk of infection through either bacterial translocation or the use of IV lipids. Selection of enteral nutrition vs. TPN should depend on the availability of the GI tract.
Summary Remember that NG tubes can cause fluid aspiration and pneumonia. Avoid hyperglycemia. Avoid overfeeding obese patients. Future Focus: Metabolic effects of nutrients. Role of reduced energy intake in obese patients. Role of anti-oxidants.