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* Department of Surgery, Peking Union Medical College Hospital, Beijing 100730, China.
After injury, extensive chemotherapy, infection and other severe illness, both protein and fat are lost from the body. Although minor alterations in body composition are probably of little clinical importance, a 10% or greater loss of body protein will contribute to morbidity and debility. The accelerated net breakdown of body protein can be slowed down by adequate parenteral nutrition. It has therefore been assumed that parenteral nutrition prevents the loss of body protein. However, serial measurements of body composition and substrate-flux studies indicate that it is extremely difficult to maintain or replenish body protein during critical illness (STREAT, BEDDOE and HILL, 1987; WILMORE, 1991).
Parenteral nutrition also has some side effects. Water retention, for example, is characteristic of critical illnesses in patients supported by long-term parenteral nutrition. SCHELTINGA et al. (1991) recently reported that glutamine-enriched intravenous feeding attenuated extracellular fluid expansion after the stress of radiation and chemotherapy.
Although glutamine may be a conditionally essential nutrient during catabolic states, intravenous nutrition solutions usually do not contain this amino acid. In addition, glutamine-supplemented parenteral nutrition might enhance cellularity of the gastrointestinal mucosa and modify the capillary permeability during critical periods of chemotherapy, irradiation, trauma or severe infection.
In Scheltinga's study, two groups of patients were studied. Figure 1 shows that subjects who received the standard TPN solution (without glutamine) retained more than 3 L of extracellular water (ECW) (p=0.012), which was associated with a tendency to increase total body water (TBW) (P=0.075). In contrast, patients who received glutamine-enriched parenteral nutrition showed stable ECW and TBW values.
Figure 2 shows the relationship between ECW expansion and infection. A clinical infection (pneumonia, bacteremia or soft-tissue infection) was present in half of the patients who received the standard parenteral nutrition; the average ECW expansion in these patients with infection was 5.0 ± 1.4 L. In contrast, infection was absent in patients receiving the glutamine-enriched solutions in whom ECW volumes were stable (0.4 ± 0.5 L).
Figure 1. Body water changes with standard and glutamine-enriched parenteral nutrition.
This indicates that glutamine-enriched parenteral nutrition (0.5 g/kg/d) can attenuate fluid retention in stressed patients. In recent cooperative research between Boston and Beijing, we found that the glutamine dipeptide had metabolic effects similar to free glutamine which has recently been used in the United States. Since glutamine dipeptide solutions can be heat-sterilized, glutamine dipeptide-enriched parenteral nutrition support may become clinically useful in Asia and Europe where cold-sterilization is not allowed.
The conventional fat emulsion (long-chain triglyceride, LCT) is widely used in China at the present time. But the newer fat emulsions, such as the medium-chain triglyceride (MCT) emulsion, may be more effective and without the problems that arise with conventional parenteral fat emulsion. We conducted a cooperative study on the utilization of MCT emulsions in Chinese volunteers and perioperative patients (JIANC et al., unpublished). There has been no previous report of the use of MCT emulsion in Asian people.
Figure 3 shows results of a clearance test in Chinese volunteers expressed in venous samples. The results show that the MCT emulsion was cleared from the bloodstream faster than conventional emulsions.
Figure 4. Clearance of long- vs medium-chain triglycerides in healthy Chinese volunteers.
When areas under the clearance curves were compared, we could find statistically significant differences between MCT and LCT groups (Figure 4).
Figure 5 shows the results of patients' MCT/LCT clearance test in venous samples. MCT emulsions were cleared from the bloodstream faster than conventional emulsions. The rate of clearance was even faster during the post-operative period.
Figure 6 shows that the blood ketone body level was higher with the MCT emulsion than with the conventional fat emulsion.
Figure 7 shows that nitrogen balance was improved in the MCT emulsion infusion group.
Improved nitrogen balance might be due to the higher ketone body level in the MCT study group (Figure 8), or it may be related to an insulin stimulation mechanism. Data are forthcoming on these issues.
Enteral feeding is safer, less expensive and results in a quicker return of intestinal barrier function, with diminished inflammatory response. But enteral feeding cannot be tolerated in many critically ill patients, for example in patients with acute stage gastrointestinal skin fistulae, acute necrotizing pancreatitis or those undergoing high-dose chemoradiotherapy.
We studied two groups of patients who underwent major abdominal operations with parenteral nutrition based on isonitrogenous and isocaloric intake (JIANG et al., 1989). The study was designed to reduce the caloric intake to 20 kcal/kg/d (about 1200 kcal per day in an adult patient), while keeping the protein intake at a regular amount (1 g/kg/d) and providing low-dose recombinant human growth hormone of 0.015 m/kg/d (about 4 mg per day). Therefore the protein/energy (P/E) ratio of this modified parenteral nutrition was changed from approximately 1/35 to 1/20. These results show that growth hormone does attenuate the protein-catabolic response.
Figure 9 shows the results of nitrogen and potassium balance of patients treated with growth hormone and controls. The upper line represents the quantity of the substances infused. The black area shows negative balance and the shaded area shows positive balance. We can see that the group treated with growth hormone has much better nitrogen balance than the control group.
Figure 10 shows cumulative nitrogen balance in both groups. Here we can see the differences more clearly.
Figure 11 shows the body composition study results expressing the components of weight loss in control and growth hormone-treated patients following operation. The controls lost 490 g fat, 2 L water and 800 g hydrated protein. In contrast, the growth hormone-treated group only lost 950 g fat.
These approaches, whether used alone or in combination, will reduce the loss of body protein, which should accelerate recovery, shorten the length of hospitalization, and reduce convalescence.
Figure 9. Nitrogen and potassium balance in patients treated with growth hormone and controls.
Figure 10. Cumulative nitrogen balance in patients treated with growth hormones and controls.
11. Body composition changes in patients treated with growth
hormone and controls.
JIANG Z.M., YANG N.F., WILMORE D.W. et al., Low-dose growth hormone and hypocaloric nutrition attenuate the protein-catabolic response major to operation. Ann. Surg., 210, 514-525 (1989).
JIANG, Z.M., ZHANG, S.Y., WILMORE, D.W. et al., The metabolic effect of medium chain triglyceride (MCT) emulsion on parenteral nutrition in Chinese surgical illnesses (unpublished).
SCHELTINGA, M.R., SCHLOERB, P.R., WILMORE, D.W. et al., Glutamine-enriched intravenous feeding attenuates extracellular fluid expansion after a standard stress. Ann. Surg., 214, 385-395 (1991).
STREAT, S.J., BEDDOE, A.H., HILL, G.L.: Aggressive nutritional support does not prevent protein loss despite fat gain in septic intensive care patients. J. Trauma, 27, 262-266 (1987).
WILMORE, D.W.: Catabolic illness - Strategies for enhancing recovery. N. Engl. J. Med., 325, 695-702 (1991).
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