Permissive Underfeeding With Parenteral Nutrition
Guest Editors:
Karen C. McCowen, MD and Bruce R. Bistrian,MD, PhD
Beth Israel Deaconess Medical Center, Harvard Medical School,
Boston, Massachusetts
Parenteral nutrition (PN) therapy has been often confused with hyperalimentation, which describes early, conscious overfeeding to minimize catabolism and hasten nutritional recovery. However, the literature is replete with studies demonstrating that feeding above energy expenditure can be associated with many deleterious sequelae, notably hyperglycemia, hepatic steatosis, and difficulty with ventilator weaning. Hypocaloric PN, in contrast, has been shown to provide clinical benefits in patients in whom enteral feeding is contraindicated, and is especially useful when volume restriction limits PN administration.
A widely quoted but seriously flawed clinical trial published in 1991 has been used as evidence that PN can be harmful.1 Patients who required laparotomy or noncardiac thoracotomy were allowed ad libitum food and randomized to perioperative PN. Infectious complications were significantly increased in the TPN group. Unfortunately, energy intake in the PN group was ~46 kcal/kg, whereas controls ate 20 kcal/kg; this substantial overfeeding led to marked hyperglycemia (and consequent infections) in the PN group. A subsequent landmark clinical trial stressed the importance of tight glycemic control in an intensive care unit (ICU) population being fed close to energy balance.2 Fifteen hundred forty eight patients were randomized to usual glucose management or intensive insulin therapy. The latter treatment emphasized maintenance of normoglycemia (80-110 mg/dL). Nutrition support was used in all patients, both enteral and parenteral, with mean intakes of approximately 20 kcal/kg in each group. Normal glucose homeostasis significantly lowered mortality, mostly by reduction of sepsis from bacteremia and multi-organ failure.
Analysis of these 2 studies leads to the conclusion that avoiding overfeeding and preventing hyperglycemia are critical components of good nutritional care in the ICU. Even aggressive use of nutrition support fails to prevent lean tissue catabolism in sepsis.3 Keeping dextrose infusions below 4 mg/kg/min reduces the incidence of serum glucose concentrations exceeding 200 mg/dL.4 Carbohydrate feeding in critically ill patients fails to suppress endogenous glucose production as it does in noncritically ill patients, but permits de novo lipogenesis, with potential deleterious consequences. 5 In one large survey of a predominantly surgical ICU, 73% of patients with glucose infusion rates above this threshold had a respiratory quotient (RQ) >1.6 In this group, oxygen consumption and energy expenditure were significantly greater than the group with RQ<1. A highly significant correlation existed between glucose infusion rate and RQ. In patients with acute renal failure receiving continuous venovenous hemodialysis, once protein provision exceeded 1.5 g/kg/day, nitrogen catabolism was minimized in patients receiving a low-energy PN, compared with those being fed > 25-35 kcal/kg/day.7 Hypocaloric PN might be defined as permissive reduction in dextrose calories in PN while providing generous protein (up to 1.5-2 g/kg/day using dry weight or ideal weight in the obese) and the usual vitamins and minerals.
The clearest indication for use of permissive underfeeding is in obesity. One study examined the effects of a 50% decrease in dextrose and lipid energy provided in PN to patients >130% of ideal body weight (IBW) with postoperative complications.8Wound healing and fistula closure were not impeded, and nitrogen balance was zero or positive, using 2 g protein/kg IBW/day. Similarly, a study in morbid obesity showed that hypocaloric feeding presents no disadvantage, with potential benefits. Thirty patients with an average body mass index (BMI) >35 kg/m2 were randomized to receive either hypocaloric or standard PN. All were fed 2 g protein/kg IBW/day for an average of 10 days.9 Nitrogen balance was the same for the 2 groups, as was the clinical outcome. The number of days on which insulin therapy was needed was lower in the hypocaloric group.
Another study investigated whether reaching energy needs affected nitrogen balance in critically ill catabolic patients.10 Trauma patients requiring mechanical ventilation were randomly assigned to 1 of 3 PN regimens: (1) nonprotein calorie group—dextrose and lipid intake equal to measured energy expenditure (MEE); (2) total calorie group—dextrose, lipid, and protein intake equal to MEE; and (3) hypocaloric group—dextrose and lipid intake equal to 50% MEE. All groups received 1.7 g/kg protein. The protocol started 48 hours after injury and was completed in 4 days. Nitrogen loss, nitrogen balance, and catabolic rate were similar in all groups, yet energy balance differed significantly. Catabolic rate was associated with energy expenditure. Loss of nitrogen correlated positively with energy expenditure percentage met by nonprotein calorie intake. Therefore, reaching energy balance did not acutely lower catabolic rate or nitrogen loss.
In a more heterogeneous group of patients, hypocaloric PN (1 L containing 70 g protein and 1000 kcal) was compared in randomized fashion with weight-based feeding (1.5 g/kg protein with energy at 25 kcal/kg) in 40 patients for >=5 days.11 The primary goal was to compare infectious complications and glycemic control. No differences were seen. Secondary outcomes showed a trend toward greater insulin requirements in the control group, and more negative nitrogen balance in the hypocaloric group, presumably due to suboptimal protein intake. Length of stay, clinical outcome and mortality rates were identical between the groups.
To sum up these randomized trials, hypocaloric PN is an adequate treatment for many critically ill patients. Patients most likely to benefit include those with severe or morbid obesity and those at risk of hyperglycemia. Hypocaloric PN is particularly advantageous in patients in whom fluid restriction is important, since 1 L of maximally concentrated PN had no major clinical sequelae. One caveat with this therapy is the suggestion from a retrospective study that elderly patients develop more negative nitrogen balance than younger patients.12In this study of an obese, hospitalized population, energy requirements were calculated using the Harris-Benedict equation. Patients were given 1.5 g/kg/day protein, 75% of energy requirements when body weight was >120% and <150% IBW, and 60% energy requirements when body weight was >150% IBW. Negative nitrogen balance occurred in only 1 of the 18 patients who were less than 60 years old, but occurred in 5 of 12 patients in the over age 60 group. Furthermore, there are theoretic concerns about the use of hypocaloric PN in severely malnourished patients where endogenous fat stores are limited. In general, we make no specific recommendations about use of lipid as a component of hypocaloric TPN, since fat is generally less protein sparing than dextrose under reduced energy intake conditions.13,14 These considerations suggest that randomized trials should be performed in older patients and in severely malnourished patients, comparing hypocaloric with eucaloric PN, and looking at length of stay or other important end-points, before a blanket recommendation may be given for use of this therapy.
In summary, feeding to energy balance—and not to excess, in the absence of hyperglycemia, volume overload, or severe obesity—is highly recommended. However, presence of any of these potential complicating factors should prompt consideration of hypocaloric PN, without fear of deleterious consequences for at least 10 days of therapy. For practical purposes, this might consist of 1 liter containing 70 g protein and ~1000 kcal initially, maximally concentrated (when using 10% amino acids [700 mL] and 70% dextrose [300 mL] as stock solutions), along with the usual vitamins and minerals, providing up to 1500 kcals and 1.5 g protein/kg as optimal when volume allowances and glycemia permit.
References
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8. Dickerson RN, Rosato EF, Mullen JL. Net protein anabolism with hypocaloric parenteral nutrition in obese stressed patients. Am J Clin Nutr. 1986;44:747-755.
9. Choban PS, Burge JC, Scales D, Flancbaum L. Hypoenergetic nutrition support in hospitalized obese patients: A simplified method for clinical application. Am J Clin Nutr. 1997;66:546-550.
10. Frankenfield DC, Smith JS, Cooney RN. Accelerated nitrogen loss after traumatic injury is not attenuated by achievement of energy balance. J Parenter Enteral Nutr. 1997;21:324-329.
11. McCowen KC, Friel C, Sternberg J, et al. Hypocaloric total parenteral nutrition: effectiveness in prevention of hyperglycemia and infectious complications—a randomized clinical trial. Crit Care Med. 2000;28:3606-3611.
12. Liu KJM, Cho MJA, Atten MJ, et al. Hypocaloric parenteral nutrition support in elderly obese patients. Am Surg. 2003;66:394-399.
13. Vazquez JA, Paul HS, Adibi SA. Regulation of leucine catabolism by caloric sources. Role of glucose and lipid in nitrogen sparing during nitrogen deprivation. Clin Invest. 1988;82:1606-1613.
14. Hart DW, Wolf SE, Zhang XJ, et al. Efficacy of a high-carbohydrate diet in catabolic illness. Crit Care Med. 2001;29:1318-1324.
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