Intensive Care Medicine

, Volume 31, Issue 10, pp 1394–1400 | Cite as

Glucose-lipid ratio is a determinant of nitrogen balance during total parenteral nutrition in critically ill patients: a prospective, randomized, multicenter blind trial with an intention-to-treat analysis

  • P. Boulétreau
  • D. Chassard
  • B. Allaouchiche
  • J. C. Dumont
  • C. Auboyer
  • M. Bertin-Maghit
  • H. Bricard
  • R. Ecochard
  • J. Rangaraj
  • C. Chambrier
  • C. Schneid
  • L. Cynober
Original

Abstract

Objective

Protein sparing, the major goal of nutritional support, may be affected by the glucose/lipid ratio. This study in critically ill patients compared the efficacy and tolerance of two isocaloric isonitrogenous total parenteral nutritions (TPN) having different glucose/lipid ratios.

Design

Multicentric prospective randomized study.

Patients

47 patients with SAPS I score higher than 8 and requiring exclusive TPN.

Interventions

Patients received glucose/lipid ratios of 50/50 or 80/20. For 7 days all patients received 32 glucidolipidic kcal/kg and 0.27 g/kg nitrogen daily. All-in-one bags were prepared using industrial mixtures and a fat emulsion.

Measurements and results

We determined TPN efficacy by nitrogen balance, urinary 3-methylhistidine/creatinine ratio, transthyretin and tolerance by glycemia, and liver enzymes. After controlling for five variables with significant effects, patients receiving the 50/50 ratio during TPN had significantly higher nitrogen balance than those receiving the 80/20 ratio. The daily difference in mean nitrogen sparing effect in favor of the latter group was 1.367 g (95% CI 0.0686–2.048). Glycemia on day 4 and γ-glutamyltranspeptidase on day 8 were higher in group receiving the the 80/20 ratio.

Conclusions

In critically ill patients TPN at a glucose/lipid ratio of 80/20 ratio induces a small nitrogen sparing effect compared to the ratio of 50/50, at the expense of poorer glycemic control. The clinical significance is unclear.

Keywords

Critically ill patients Glucose-lipid ratio Glycemic control Nitrogen balance Protein sparing 

Introduction

Injury-associated protein wasting is responsible for increased morbidity in ICU patients. Protein sparing is therefore one of the major goals of nutritional support in critically ill patients. In addition to the importance of protein intake, classic studies have reported that nitrogen balance depends on concomitant energy intake. This issue is complicated by the fact that the energy sources (i.e., carbohydrates vs. lipids and their ratio) may modulate nitrogen balance differently. Whenever nitrogen and energy supply are adequate in moderately ill patients, the protein-sparing effect of glucose or lipids appears to be similar [1, 2, 3, 4]. On the other hand, in more severely ill patients a prevalent glucose system (≥80%) appears to be the most efficient to optimize protein metabolism [5]. However, this opinion is supported by only a few studies [5, 6, 7, 8, 9] comparing extreme glucose to lipid (G/L) ratios (varying from 20/80 to 90/10); between these studies there are also wide differences in protocols, patients, and interventions. However, the possible adverse effects of a high-lipid or high-glucose load must be considered; lipid overload induces impaired lung function, immune suppression, and hyperglycemia which can be particularly deleterious in critically ill patients [10, 11, 12, 13].

The aim of this study was to compare the nitrogen-sparing effect and tolerance of two isocaloric isonitrogenous total parenteral nutrition (TPN) formulas with different (G/L) ratios in critically ill patients.

Patients and methods

The study was conducted as a prospective, single-blind, randomized, multicenter phase IV trial between January 1996 and December 1999 in seven French university hospitals Lyon, Saint Etienne, Caen, and Marseille. The study was approved by the local ethics committee in Lyon in accordance with the European Community principles of good clinical practice and with the Declaration of Helsinki. Written informed consent was obtained from each patient directly or by a family member in agreement with the French law.

Patients

Fifty patients were selected in an attempt to study a rather homogeneous group of patients according to the following inclusion criteria: adult, hospitalized in an intensive care unit for thermal injury, multiple trauma, sepsis, pancreatitis or complicated digestive surgery, Simplified Acute Physiology Score I (SAPS I) equal to or greater than 8, and requiring an exclusive TPN for at least 7 days. Exclusion criteria were life expectancy less than 7 days, body mass index below 18.5 or above 30, heart failure (by NYHA classification), epilepsy, stroke (occurring within 6 months previously), immune suppression (B or C class AIDS, neutrophil count <1000 mm3), hypertriglyceridemia (more than twice the normal value), persistent acidosis, diabetes or other endocrinopathy, previous liver dysfunction, kidney dysfunction (creatinine clearance <0.5 ml/s), unstable hemodynamic condition (blood pressure still unstable after a 24-h specific treatment), heavily transfused (≥ one body blood volume), and administration or continuous high-dose corticotherapy (≥ 1 mg/kg per day).

Three patients did not participate in the trial until day 7: one dropped out on day 5 because of no further need for TPN, and two others stopped on days 5 and 6 because of adverse events or the occurrence of an exclusion criterion. There were thus 47 evaluable patients in the study (35 men, 12 women; Table 1). These included 35 admitted to an ICU following digestive surgery or for postoperative sepsis, 10 for multiple traumas, and 2 after severe burn injury. The Glasgow Coma Scale (GCS) score on admission ( n =44) was 8 or less in 14 patients and 10 or more in 30; 23 patients had the maximum of 15. On the Simplified Severity Index I (SSI I) 31 patients scored 12 or more, with a median score of 11 and mean of 11.47±2.7.
Table 1

Patients’ demographic and clinical characteristics: median values (parentheses interquartile range)

Group A (50/50) (n=26)

Group B (80/20) (n=21)

p

Gender: M/F

22/4

14/6

Reason for total parenteral nutrition

Multiple trauma

6

4

Gastrointestinal surgery

19

16

Burns

1

1

Age (years)

63 (25)*

64 (38)

NS

Body mass index

24.3 (5.1)

23.1 (4.3)

NS

Glasgow Coma Scale score at admission

13 (10)

15 (8)

NS

SAPS I

12 (4)

10 (4)

NS

CRP (mg)

  Day −1 (n=42)

159 (129)

84.5 (95)

0.09

  Day 4 (n=38)

94.5 (115)

69 (81)

NS

  Day 8 (n=38)

69 (93)

33 (48)

0.02

Total parenteral nutrition

The patients were randomized in each center by prelabeled envelopes to receive parenteral mixtures with G/L ratios of either 50/50 (group A) or 80/20 (group B) for at least 7 days. The mixtures were prepared for each patient in the hospital pharmacies using commercially available products (Aminomix 1, Aminomix 2, and Lipoven, Fresenius). Aminomix 1 and Aminomix 2 have a double-pouch structure with two different solutions: one containing amino acid and one containing glucose enriched with a polyionic solution. The two solutions are mixed just before use by breaking an obturator. After reconstitution Aminomix 1 and Aminomix 2 contain equal amounts of electrolytes and amino acids (50 g/l), but Aminomix 1 contains more glucose than Aminomix 2 (200 vs. 120 g/l). Lipoven is a 20% soja oil emulsion. Aminomix 1 and Aminomix 2 were prepared and mixed at the pharmacy facilities with Lipoven so that daily glucidolipidic energy and nitrogen supplies were the same for all patients: 32 kcal/kg and 0.27 g/kg, respectively. The only difference was the G/L ratio, 50/50 in group A and 80/20 in group B.

These preparations were the only parenteral nutrition solutions administered. When necessary, additional electrolytes were administered either directly through the pouches after obturator rupture or using a Y-shaped connection. All other glucose-containing mixtures were forbidden. The parenteral preparations were infused regularly and continuously 24 h/24 h for 7 days. No other nutrients were allowed, except water by mouth. Insulin was provided subcutaneously or intravenously to maintain glycemia lower than 12 mmol/l. During the 24 h preceding inclusion substrate supplies were limited to hydroelectrolytic fluids or 5% glucose. In patients who had previously received parenteral nutrition, this period was considered as a washout period. The two groups of subjects were comparable at inclusion regarding age, sex, body mass index, body surface, clinical indications for TPN, severity of clinical condition (GCS, SSI I), and biological parameters (Table 2).
Table 2

Total parenteral nutrition

Group A (50/50)

Group B (80/20)

Commercially available solutions

Aminomix I

Aminomix II

Glucose 200 g/l

Glucose 120 g/l

AA 50 g/l

AA 50 g/l

Lipoven 20%

Lipoven 20%

LCT 200 g/l

LCT 200 g/l

Patients’ caloric and nitrogen supply

Glucidolip 32 kcal/kg per day

Glucidolip 32 kcal/kg per day

N=0.27 g/kg per day

N=0.27 g/kg per day

G/L ratio 50/50

G/L ratio 80/20

Example: actual constituents of the daily feed for a standard 70 kg patient

Glucidic kcal=1140, lipidic kcal=1140

Glucidic kcal=1792, lipidic kcal=448

N=18.9 g

N=18.9 g

Methods

Before inclusion all patients underwent a complete physical examination during which essential vital signs, current medications, and history of surgery and medical treatments were recorded. Other clinical, biological, and nutritional assessments were carried out from days 1 to 8. Tolerance to the TPN was assessed on adverse event data as well on examination of biological criteria: plasma and urine glucose (each day), serum urea, creatinine, proteins, triglycerides, cholesterol, liver enzymes and blood cell counts (on days −1, 4, and 8). These parameters were routinely measured in each center, and results presented in absolute values.

Analysis of TPN efficacy was based on serum transthyretin (formerly called prealbumin) dosage, urinary 3 methylhistidine (3MH)/creatinine ratio, and nitrogen balance (difference between nitrogen supplies and quantifiable losses, calculated by total nitrogen in urine and other loss). Expressing 3MH as a ratio to creatinine takes muscle mass into account; therefore the 3MH/creatinine ratio is independent of sex and age variations. Serum transthyretin was measured on days −1 (day before the first infusion), 4, and 8. From day 1 to day 8 the 24-h urine was carefully collected every day. Nitrogen, 3MH, and creatinine were measured daily in urine throughout the study. All serum and urine samples were immediately frozen after sampling and measurements were made within 3 months in a single laboratory to limit analytical variability [14].

Transthyretin and C-reactive protein (CRP) were measured by nephelmetry using an Array Apparatus (Beckman, Palo Alto, Calif., USA). 3MH was measured by an ion-exchange chromatography with ninhydrin postcolumn derivatization (using a Hitachi analyzer, Tokyo, Japan). Creatinine was routinely measured (Jaffé reaction), and nitrogen was measured by chimioluminescence using an Antek apparatus (Houston, Tex., USA). On all these measurements the variability in between-run reproducibility was less than 5%.

Statistical analysis

The main dependent variable was nitrogen balance. In the absence of relevant data in the literature, the number of patients under study was chosen using a pragmatic approach (i.e., feasible on a reasonable period of time) Variance over time were studied using multilevel model regression to account for the dependence of repeated measurements in the same patient. The analysis controlled for several factors that could explain any differences in nitrogen balance between the two groups: gender, age, weight, height, body mass index, GCS, and SSI I scores on admission, initial nitrogen balance, G/L ratio axial, day of TPN. The final model retained only variables with significant effects. Quantitative variables were compared using the Wilcoxon rank sum test and covariance analysis for repeated measurements. Qualitative variables were analyzed using Pearson’s χ2 test or Fisher’s exact test. Statistical tests were carried using SAS programs (Cary Institute, Cary, N.C., USA). Multilevel analysis used MlwiN (Institute of Education, University of London, UK). Results are presented as median and interquartile ranges. In all analyses significance was defined as p =0.05.

Results

Tolerance to TPN

No clinically adverse event was observed. The serum levels of urea, creatinine, cholesterol, triglycerides, bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and blood cell counts did not differ between the two groups on days 1, 4, or 8. However, glycemia was significantly higher on day 4 and γ- glutamyltranspeptidase (γGT) were significantly higher on day 8 in group B (Table 3).
Table 3

Couse of glycemia, γ- glutamyltranspeptidase (γGT), triglycerides, and cholesterol. Normal values: glycemia 4.8–6.0 mmol/l, γGT 5–45 UI/l, triglycerides 0.50–2.0 mmol/l, cholesterol 3.50–6.50 mmol/l

Group A (50/50)

Group B (80/20)

p

n

Median

IQR

n

Median

IQR

Glycemia (mmol/l)

  Day −1

26

7.9

3.7

21

8.3

2.3

NS

  Day 4

26

7. 25

3.5

20

8.9

5.9

0.02

  Day 8

24

7.35

1.9

19

8.0

5.6

NS

γGT

  Day −1

26

19

148

21

29

76

NS

  Day 4

25

116

204

20

148

185

NS

  Day 8

24

162

184

18

241

200

0.02

Triglycerides

  Day −1

25

1.20

0.70

18

1.0

0.62

NS

  Day 4

24

1.76

1.13

18

1.80

2.0

NS

  Day 8

22

1.65

1.42

16

1.60

1.10

NS

Cholesterol

  Day −1

26

2.40

1.65

21

2.20

2.05

NS

  Day 4

25

3.0

1.95

18

2.80

1.70

NS

  Day 8

23

3.50

1.40

17

3.20

1.80

NS

Efficacy of TPN

The course of serum levels of transthyretin, daily nitrogen balance, and 3MH/creatinine ratios are presented in Table 4. Nitrogen balance was significantly higher and 3MH/creatinine ratio significantly lower in group B on day 4 (Table 4). Figure 1 shows the variations in nitrogen balance during the TPN period controlling for five variables with significant effects: GCS and SSI I scores on admission, initial nitrogen balance, TPN formula, and day of TPN. Analysis of the model underlying this representation revealed the following. Firstly, group B patients had significantly higher values than group A patients during the TPN period ( p =0.045). The mean daily nitrogen sparing effect difference in favor of group B was 1.367 g (95% CI 0.0686–2.048). Secondly, nitrogen balance values decreased steadily over time under TPN. The absolute slope was steeper for group A than for group B, but the difference statistically significant. On day 8 CRP levels were significantly lower in group B. However, there was no correlation between changes in CRP and those in nitrogen balance (parametric regression).
Table 4

Serum transthyretin, nitrogen balance, and 3-methylistidine (3MH)/creatinine ratio throughout the study

Group A (50/50)

Group B (80/20)

pa

n

Median

IQR

n

Median

IQR

Serum transthyretin (mg/l)

  Day −1

24

101

56

18

103

47

NS

  Day 4

23

119

89

16

127

74

NS

  Day 8

23

179

96

15

200

153

NS

Daily nitrogen balance (g)

  Day 1

24

2.97

5.99

21

4.8

2.08

NS

  Day 2

24

2.62

4.82

21

3.44

2.87

NS

  Day 3

26

2.26

3.81

20

1.76

2.26

NS

  Day 4

25

−0.89

4.78

19

1.71

3.61

0.05

  Day 5

25

0.12

4.60

18

0.02

4.30

NS

  Day 6

27

−1.70

8.31

18

0.71

3.15

NS

  Day 7

21

−2.71

5.54

17

−1.06

5.31

NS

Urinary 3 MH/creatinine ratio

  Day −1

25

30.7

19

21

32.1

19.8

NS

  Day 1

24

37.0

13

20

35.0

27.3

NS

  Day 2

26

30.1

14

20

31.0

20.0

NS

  Day 3

25

29.3

17

19

25.8

14.8

NS

  Day 4

25

27.7

12

17

19.8

11.7

0.04

  Day 5

22

26.7

23

19

24.0

11.0

NS

  Day 6

24

26.8

15

18

25.0

14.2

NS

  Day 7

23

26.6

18

16

23.7

25.0

NS

  Day 8

24

25.6

13

15

24.0

15.5

NS

aWilcoxon rank sum test

Fig. 1

Variations in of nitrogen balance during the TPN period

Discussion

This study evaluated the nitrogen sparing effect of two isocaloric isonitrogenous parenteral nutrition formulas with different G/L ratios and observed a greater nitrogen sparing effect with the 80/20 ratio than with the 50/50 ratio; the clinical significance of this issue was not assessed in this study. Our results show a constant nitrogen loss in both groups in spite of theoretically adequate caloric and nitrogen supplies. These findings are consistent with those from other studies performed in severely catabolic patients [15, 16, 17, 18, 19] and suggest that provision of parenteral nutrition attenuates but does not prevent negative nitrogen balance. In these patients factors other than nutrition are important determinants of protein catabolism and nitrogen loss (e.g., hormonal milieu, inflammatory cytokines, and bed rest).

Nevertheless, multivariate analysis demonstrated that a better nitrogen balance in group B (i.e., glucose system). As the catabolic state, assessed by clinical severity scores and by 3MH/creatinine ratio (which is a marker of myofibril proteins) did not differ between groups on inclusion, the same caloric and nitrogenous intake had a higher protein sparing effect when the G/L ratio was 80/20 rather than 50/50. The clinical significance of this effect is of course questionable and is in any case difficult to assess in critically ill patients.

Some limitations must be noted. In spite of the mixed population including postoperative, critically ill, and burned patients the interpretation of the results may be valid, as the main clinical and biological characteristics of the two groups were the same upon entering the study. On the other hand, CRP levels were lower in group B; the difference was not significant on day −1 but was significant on day 8; this suggest a lower inflammatory state during the course in group B patients, which could in part explain their better nitrogen balance. The reason for this difference in CRP is not clear; possible explanations include spontaneous difference in patient course and the role of the greater amount of soja oil infused in group A, providing a high amount of n-6 polyunsaturated fatty acids, precursors of proinflammatory eicosanoids and cytokines. However, the absence of correlation between CRP levels and nitrogen balance over time suggests that this lower inflammatory state was not responsible for the better nitrogen balance.

The relative effects of glucose and lipids on nitrogen balance have been addressed in several reports with conflicting results. However, to our knowledge, only few randomized prospective studies have compared two levels of G/L ratio in a homogeneous group of severely catabolic patients. Some studies have found glucose to achieve better nitrogen retention than lipids [8, 20, 21], but usually there is no benefit of one fuel source over the other [9, 22, 23, 24, 25, 26]. A recent study by Hart et al. [7] reported that muscle protein catabolism was markedly decreased in pediatric burn patients with a high carbohydrate diet (82% vs. 42% carbohydrates). Unfortunately, several pitfalls limit the conclusions that can drawn from these studies: the groups are often small, patients are frequently mildly catabolic, and G/L ratios vary from 100/0 to 25/75. In a review of the literature that attempted to take into account the potential confounding factors, Iapichino et al. [5] compared the effects of glucose alone vs. glucose fat mixed system on protein metabolism. In 40 groups of catabolic patients a satisfactory result on protein balance (positive, near equilibrium, or marginally negative) was more frequently observed with a glucose system (17 of 19 studies) than with a mixed system (12 of 21 studies).

In severely stressed patients changes in insulin sensitivity are constant for carbohydrate and lipid metabolism [27]. However, numerous clinical and experimental studies suggest that the protein sparing effect of insulin persists in burn or septic patients if high levels of insulin and glucose are provided [7, 26, 28, 29, 30, 31]. This nitrogen sparing effect is usually considered as a consequence of insulin-induced reduction in protein breakdown studied by leucine kinetics and oxidation or arteriovenous differences [7, 29, 32, 33]. In the same way the reduction in basal insulin secretion by somatostatin infusion results in a significant increase in the rate of leucine oxidation in septic patients [34]. In other studies the protein-sparing effects of high doses of insulin are more the consequence of a promotion of muscle protein synthesis [31]. All of these findings are in agreement with our data which show a better nitrogen sparing effect of glucose-rich parenteral solutions, even when total caloric intake is near the estimated resting energy expenditure.

The role of insulin could not be assessed in our study. Despite the higher amount of infused glucose the amounts of exogenous infused insulin varied substantially from one patient to another, although not differing between groups (100±137 U in group A vs. 102±209 U in group B, for 7 days). The plasma levels of insulin were not measured, precluding any definitive conclusion. An important question is the tolerance of such glucose-rich parenteral solutions since hyperglycemia and liver steatosis are well known complications of glucose infusion, especially in stressed patients. The very high levels of glucose and insulin infusion reported in several studies are harmful [35] and obviously cannot be recommended under usual clinical conditions. The amount of glucose infused in our group B patients was lower (4.4 mg/kg per minute). In all patients a hyperglycemia was observed due to stress. As would be expected, glucose levels were higher in group B (significant difference only on day 4) but thanks to insulin therapy did not exceed the levels of glycemia usually tolerated in these patients. In addition, we cannot say how many patients in the two groups had blood sugar under 6.16 mmol/l, as in the Van den Berghe et al. [13] study, or whether better results would have been obtained with better control of glycemia.

Abnormalities of serum liver enzymes, especially alkaline phosphatase and γGT, are frequent in patients on TPN even for a short period [36, 37] and usually well correlated with the amount of glucose perfused [38, 39]. In our study all patients exhibited high levels of γGT, even before beginning TPN, probably due to stress. These serum levels rose during the TPN period and the higher elevation in group B on day 8 was probably related to the higher amount of glucose provided and the greater glycemia, although these were transient. For a short period of TPN these biological abnormalities are usually transient and reversible after the discontinuation of TPN [37]. However, they should limit the possibility of safe continuation of this infusion for a longer period. A more intensive insulin therapy, maintaining blood glucose at or below 6.16 mmol/l, could provide better hepatic tolerance [13].

In conclusion, in severely stressed patients receiving adequate nitrogen and caloric supplies the G/L ratio in TPN fuels has an effect on nitrogen balance: a ratio of 80/20 has a better nitrogen sparing effect than one of 50/50. However, because of an insufficient glycemic control in this study the higher provision of glucose induced greater glycemia, and the clinical relevance of these results has not been assessed. Further studies using more intensive insulin therapy could be of interest.

References

  1. 1.
    Brennan MF, Fitzpatrick GF, Cohen KH, Moore FD (1975) Glycerol: major contributor to the short-term protein sparing effect of fat emulsions in normal mal. Ann Surg 182:386–394PubMedGoogle Scholar
  2. 2.
    Jeejeebhoy KN, Andersson GH, Nakooda AF, Greenberg GR, Sanderson I, Marliss EB (1976) Metabolic studies in total parenteral nutrition with lipid in man. Comparison with glucose. J Clin Lab Invest 57:25–136Google Scholar
  3. 3.
    Van Itallie TB, Moore FD, Geyer RP (1954) Will fat emulsions given intravenously promote protein synthesis? Metabolic studies on normal subjects and surgical patients. Surgery 36:720–731PubMedGoogle Scholar
  4. 4.
    Wilmore DW, Moylan JA, Helmkamp GM, Pruitt BA (1973) Clinical evaluation of a 10% intravenous fat emulsion for parenteral nutrition in thermally injury patients. Ann Surg 178:503–513PubMedGoogle Scholar
  5. 5.
    Iapichino G, Radrizzani D, Solca M, Pesenti A, Gattinoni L, Ferro A, Leoni L, Langar M, Vesconi S, Damia G (1994) The main determinants of nitrogen balance during parenteral nutrition in critically ill injured patients. Intensive Care Med 10:251–254Google Scholar
  6. 6.
    Battistella FD, Wildergren JT, Anderson JT, Siepler JK, Weber JC, MacColl K (1997) A prospective, randomized trial of intravenous fat emulsion administration in trauma victims requiring total parenteral nutrition. J Trauma 43:52–58PubMedGoogle Scholar
  7. 7.
    Hart DW, Wolf SE, Zhang XJ, Chinkes DL, Buffalo MC, Matin SI, DebRoy MA, Wolfe RR, Herndon DN (2001) Efficacy of a high-carbohydrate diet in catabolic illness. Crit Care Med 29:318–1324Google Scholar
  8. 8.
    Tappy L, Schwarz JM, Schneitez P, Cayeux C, Revelly JP, Fagerquist CK, Jequier E, Chiolero R (1998) Effects of isoenergetic glucose-based or lipid-based parenteral nutrition on glucose metabolism, de novo lipogenesis, and respiratory gas exchanges in critically ill patients. Crit Care Med 26:860–867CrossRefPubMedGoogle Scholar
  9. 9.
    Garrel DR, Razi M, Larivière F, Jobin N, Naman N, Emptoz-Bonneton A, Pugeat MM (1995) Improved clinical status and length of ware with low-fat nutrition support in burn patients. JPEN J Parenter Enteral Nutr 19 482–491Google Scholar
  10. 10.
    Gogos CA, Kalfarentzos FE, Zoumbos NC (1990) Effect of different types of total parenteral nutrition on T-lymphocyte subpopulations and NK cells 1:2. Am J Clin Nutr 51:119–122PubMedGoogle Scholar
  11. 11.
    Gore DC, Chinkes DL, Hart DW, Wolf SE, Herndon DN, Sanford AP (2002) Hyperglycemia exacerbates muscle protein catabolism in burn-injured patients. Crit Care Med 30:2438–2442CrossRefPubMedGoogle Scholar
  12. 12.
    Jensen GL, Mascioli EA, Seidner DL, Istfan NW, Donitch AM, Selleck K, Babayan VK, Blackburn GL, Bistrian BR (1990) Parenteral nutrition of long- and medium-chain triglycerides and reticuloendothelial system function in man. JPEN J Parenter Enteral Nutr 14:467–471PubMedGoogle Scholar
  13. 13.
    Van Den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R (2001) Intensive insulin therapy in critically ill patients. N Engl J Med 345:1359–1367PubMedGoogle Scholar
  14. 14.
    Cardenas D, Blonde-Cynober F, Ziegler F, Cano N, Cynober L (2001) Should a single centre for the assay of biochemical markers of nutritional status be mandatory in multicentric trial? Clin Nutr 20:553–558CrossRefPubMedGoogle Scholar
  15. 15.
    Cerra F, Blackburn G, Hirsch J (1987) The effect of stress level, amino acid formula and nitrogen dose on nitrogen retention in traumatic and septic stress. Ann Surg 205:282–287PubMedGoogle Scholar
  16. 16.
    Cerra FB (1987) Hypermetabolism, organ failure and metabolic support. Surgery 101:1–14PubMedGoogle Scholar
  17. 17.
    Clowes GHA, Heideman M, Lindberg B, Randall HD, Hirsch HF, Cha CJ, Martin H (1980) Effect of parenteral alimentation on amino acid metabolism in septic patient. Surgery 88:531–543PubMedGoogle Scholar
  18. 18.
    Frankenfield DC, Smith JS, Cooney RN (1997) Accelerated nitrogen loss after traumatic injury is not attenuated by achievement of energy balance. JPEN J Parenter Enteral Nutr 21:324–329PubMedGoogle Scholar
  19. 19.
    Greig PD, Elwyn DH, Askanazi J, Kinney JM (1987) Parenteral nutrition in septic patients: effects of increasing nitrogen intake. Am J Clin Nutr 46:1040–1047PubMedGoogle Scholar
  20. 20.
    Long JM III, Wilmore DW, Mason AD Jr, Pruitt BA Jr (1977) Effect of carbohydrate and fat intake on nitrogen excretion during total intravenous feeding. Ann Surg 185:417–422PubMedGoogle Scholar
  21. 21.
    Woolfson AM, Heatley RV, Allison SP (1979) Insulin to inhibit protein catabolism after injury. N Engl J Med 300:14–17PubMedGoogle Scholar
  22. 22.
    Baker JP, Detsky AS, Stewart S, Whitwell J, Marlisss EB, Jeejeebhoy KN (1984) Randomized trial of total parenteral nutrition in critically ill patients: metabolic effects of varying glucose-lipid ratios as the energy source. Gastroenterology 87:53–59PubMedGoogle Scholar
  23. 23.
    De Chalain TM, Michell WL, O’Keefe SJ, Ogden JM (1992) The effect of fuel source on amino acid metabolism in critically ill patients. J Surg Res 52:167–176CrossRefPubMedGoogle Scholar
  24. 24.
    Nordenstrom J, Askanazi J, Elwyn DH, Martin P, Carpentier YA, Robin AP, Kinney JM (1983) Nitrogen balance during total parenteral nutrition: glucose vs. fat. Ann Surg 197:27–33PubMedGoogle Scholar
  25. 25.
    Paluzzi M, Meguid MM (1987) A prospective randomized study of the optimal source of nonprotein calories in total parenteral nutrition. Surgery 102:711–717PubMedGoogle Scholar
  26. 26.
    Shaw JH, Holdaway CM (1988) Protein-sparing effect of substrate infusion in surgical patients is governed by the clinical state, and not by the individual substrate infused. JPEN J Parenter Enteral Nutr 12:433–440PubMedGoogle Scholar
  27. 27.
    Chambrier C, Laville M, Rhzioul Berrada K, Odeon M, Boulétreau P, Beylot M (2000) Insulin sensitivity of glucose and fat metabolism in severe sepsis. Clin Sci (Lond) 99:321–328Google Scholar
  28. 28.
    Pierre EJ, Barrow RE, Harvkins HK, Nguyen TT, Sajurai Y, Desai M, Wolfe RR, Herdon DN (1998) Effects of insulin on wound healing. J Trauma 44:342-PubMedGoogle Scholar
  29. 29.
    Ferrando AA, Chinkes DL, Wolf SE, Matin S, Herndon DN, Wolfe RR (1999) A submaximal dose of insulin promotes net skeletal muscle protein synthesis in patients with severe burns. Ann Surg 229:11–18CrossRefPubMedGoogle Scholar
  30. 30.
    Hinton P, Allison SP, Littlejohn S, Lloyd J (1971) Insulin and glucose to reduce catabolic response to injury in burned patients. Lancet 1:767–769CrossRefPubMedGoogle Scholar
  31. 31.
    Sakurai Y, Aarsland A, Herndon DN, Chinkes DL, Pierre E, Nguyen TT, Patterson BW, Wolfe RR (1995) Stimulation of muscle protein synthesis by long-term insulin infusion in severely burned patients. Ann Surg 222:283–297PubMedGoogle Scholar
  32. 32.
    Gelfand RA, Barrett EJ (1987) Effect of physiologic hyperinsulinemia on skeletal muscle protein synthesis and breakdown in man. J Clin Invest 80:1–6PubMedGoogle Scholar
  33. 33.
    Jahoor F, Shangraw RE, Miyoshi H, Wallfish H, Herndon DN, Wolfe RR (1989) Role of insulin and glucose oxidation in mediating protein catabolism of burns and sepsis. Am J Physiol 275:E323–E331Google Scholar
  34. 34.
    Zang XJ, Kunkel KR, Jahoor F, Wolfe RR (1991) Role of basal insulin in the regulation of protein kinetics and energy metabolism in septic patients. JPEN J Parenter Enteral Nutr 15:394–349PubMedGoogle Scholar
  35. 35.
    Burke JF, Wolfe RR, Mullany CJ, Mathews DE, Bier DM (1980) Glucose requirements folowing burn injury. Ann Surg 190:274–285Google Scholar
  36. 36.
    Clarke PJ, Ball MJ, Kettlewell (1991) Liver function tests in patients receiving parenteral nutrition. JPEN J Parenter Enteral Nutr 15:54–59PubMedGoogle Scholar
  37. 37.
    Quigley EMM, Marsh MN, Shaffer JL, Markin RS (1993) Hepatobiliary complications of total parenteral nutrition. Gastroenterology 104:286–301PubMedGoogle Scholar
  38. 38.
    Buchmiller CE, Kleiman Wexler RL, Ephgrave KS, Booth B, Hensley II CE (1993) Liver dysfunction and energy source: results of a randomized clinical trial. JPEN J Parenter Enteral Nutr 17:301–306PubMedGoogle Scholar
  39. 39.
    Messing B, Bitoun A, Galian A, Mary JY, Goll A, Bernier JJ (1977) La stéatose hépatique au cours de la nutrition parentérale dépend-elle de l’apport calorique glucidique? Gastroenterol Clin Biol 1:1015–1025PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • P. Boulétreau
    • 1
  • D. Chassard
    • 1
  • B. Allaouchiche
    • 1
  • J. C. Dumont
    • 2
  • C. Auboyer
    • 3
  • M. Bertin-Maghit
    • 1
  • H. Bricard
    • 4
  • R. Ecochard
    • 5
  • J. Rangaraj
    • 6
  • C. Chambrier
    • 1
  • C. Schneid
    • 7
  • L. Cynober
    • 7
  1. 1.Department of Anesthesiology and NutritionCHU, Hôpital E HerriotLyon Cedex 03France
  2. 2.Department of AnesthesiologyCHUMarseilleFrance
  3. 3.Department of AnesthesiologyCHUSt. EtienneFrance
  4. 4.Department of AnesthesiologyCHUCaenFrance
  5. 5.Department of BiostatisticsCHULyonFrance
  6. 6.Lab FreseniusSèvresFrance
  7. 7.Laboratory of Biological NutritionParis 5 University and Hotel-Dieu, AP-HPParisFrance

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