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Effects of Hypercaloric Feeding on Nutrition Status and Carbon Dioxide Production in Patients With Long-Term Mechanical Ventilation

Posted on: Sunday, 4 September 2005, 03:01 CDT

ABSTRACT. Background: To clarify clinical arguments regarding nutrition support in patients with long-term mechanical ventilation, we investigated the effects of hypercaloric feeding on nutrition status and carbon dioxide production. Methods: Twenty-eight mechanically ventilated, clinically stable patients with nasogastric tube feeding were recruited and randomly divided into the control and hypercaloric groups, which were provided with 1.2- and 1.8-fold of resting energy expenditure (REE), respectively. The arterial and venous blood samples were collected, the anthropometric measurements were determined, the serum concentrations of nutrition-related proteins were measured, and the parameters on the ventilator and indirect calorimeter were recorded on weeks 0, 2, and 4. Results: There were no significant changes in anthropometric measurements, blood gas tensions, and REE between the control and hypercaloric groups during the experimental period (mixed model with repeated measures analysis, p < .05). After adjusted for values on week 0 and time, patients with hypercaloric feeding had significantly increased levels in white blood cells, hemoglobin, and hematocrit. However, the control group had significantly decreased and the hypercaloric group had significantly increased serum concentrations of prealbumin and transferrin, rate of carbon dioxide production, and respiratory quotient (RQ) from week 0 to week 4. Conclusion: Our results suggest that 4 weeks of hypercaloric feeding may significantly increase the production of carbon dioxide but may not significantly alter the clinical outcomes in patients with long-term mechanical ventilation. The adverse effects of hypercaloric feeding may easily be overlooked, and the appropriateness of nutrition support should be carefully monitored in patients with mechanical ventilation. (Journal of Parenteral and Enteral Nutrition 29:380-387, 2005)

Nutrition support is essential for mechanically ventilated patients to meet their energy requirement and to maintain or even to enhance their muscle strength for facilitating ventilator weaning.1 However, problems with inappropriate feeding occur frequently in these patients because of the wide individual variation in energy expenditure resulting from the variety of diseases and the different degree of stress.2-5 Indirect calorimetry (IC), a useful and accurate instrument to determine patients' energy requirement, has been used to monitor the adequacy and appropriateness of current nutrition support.3-6

It has been reported that the complications of overfeeding, such as hyperlipidemia, hyperglycemia, hepatic dysfunction, impaired cardiopulmonary function, and the inability to wean from the ventilator, can be identified from patients fed with energy more than 2-fold of their requirement.2,7-10 In order to increase lean body mass and to enhance respiratory muscle strength, most patients with mechanical ventilation were still fed with more nutrients than they required, as long as there were no significant clinical symptoms of overfeeding. Our previous study showed that about 80% of patients with long-term mechanical ventilation were fed with energy as 1.2- to 2-fold of resting energy expenditure (REE) in the chronic respiratory care unit.11 However, there was little information regarding the beneficial or adverse effects of moderate hypercaloric feeding, that is, <2-fold of REE, in mechanically ventilated patients, especially for those who have stable clinical condition. Therefore, divergent opinions exist between physicians and dieticians in dealing with the nutrition support of these patients.

Our objective was to investigate whether moderate hypercaloric feeding (1.8-fold of REE) might result in a physiologic burden to interfere with nutrition status and ventilator weaning in mechanically ventilated patients, as assessed by the anthropometries, nutrition-related serum proteins, and parameters of indirect calorimetry. In this study, mechanically ventilated patients with stable hemodynamic status and controlled energy intake via nasogastric tube feeding were recruited. We expect to clarify the clinical arguments regarding the effects of moderate hypercaloric feeding and to evaluate the importance of IC in the management of nutrition support in patients with long-term mechanical ventilation.

FIGURE 1. The experimental scheme. = Represents 24-hour urine collection; * represents blood drawing and anthropometric measurement; and [arrow down] represents IC measurement.

SUBJECTS AND METHODS

Subjects

Twenty-eight patients (16 male patients and 12 female patients) from the chronic respiratory care unit, who had stable clinical condition, were supported by mechanical ventilator for more than 2 months, and cannulated with nasogastric tube feeding were recruited into this study. Ethical approval to carry out this study was obtained from the institutional review board of Changhua Christian Hospital. Informed consents signed by patients or patients' families were also obtained before conducting the study. Exclusion criteria were defined as those patients who had parenteral nutrition infusion or unstable hemodynamic status during the experimental period. In addition, patients with clinical conditions such as a fraction of inspired oxygen (FiO^sub 2^) over 0.6, positive end-expiratory pressure (PEEP) over 5 cm H2O, seizure, incompetent endotracheal or tracheotomy tube cuff, or chest tube insertion were excluded.

Experimental Protocol

Once recruited, patients were provided with energy as 30 kcal per kg of body weight via continuous nasogastric tube feeding as suggested by dieticians. The gender, age, APACHE II score, total hospital length of stay (LOS), and total days on ventilator (LOV) were recorded. When the experiment was started on week 0, all of the patients received at least 3 days of continuous tube feeding (d0 to d3). On d2-d3, urine samples were collected for 24 hours through urinary bladder catheters. On d3, body height, body weight, and midarm circumference (MAC) were measured and body mass index (BMI) was calculated. Triceps skinfold thickness (TSF) was obtained by a Holtain skinfold caliper at the left midtriceps. In the meanwhile, arterial and venous blood samples were obtained at 10 AM, and then indirect calorimeter was used to measure REE. Subsequently, patients were randomly divided into the control (CON, n = 14) and hypercaloric (HIGH, n = 14) feeding groups, which were provided with energy as 1.2- and 1.8-fold of measured REE, respectively.

Two weeks later (week 2), the procedures performed on week 0 were repeated, such as the collection of urine and blood samples, the measurements of anthropometry, and the documentation of IC and ventilator parameters (Figure 1). After the IC measurement, patients in the CON and HIGH groups were provided with energy as 1.2- and 1.8- fold of measured REE on week 2, respectively. On week 4, same procedures were repeated. The experimental scheme is shown in Figure 1. In order to avoid the interferences resulting from the respiratory status, all of the patients were under maximal pulmonary support for 24 hours per day and were not weaned from the mechanical ventilators during the experimental period.

Energy Intake

During the experimental period, nasogastric tube feeding was the main source of nutrients for patients, and no patient had problems in finishing the assigned amount of formula. The liquid formula for tube feeding was prepared from a commercial powdered formula (Osmolite HN, Abbott Laboratories Service Corp, Taiwan), which contained 54.3%, 29%, and 16.7% of total calories from carbohydrate, lipid, and protein, respectively. The energy was provided as 30 kcal per kg of body weight before the REE was measured on d3. After the IC measurement on weeks 0 and 2, the feeding regimen was readjusted to provide 1.2- or 1.8-fold of measured REE. The caloric density of the liquid formula was 1 kcal/mL. The daily energy intake was recorded by nurses.

Biochemical Data

Urine samples were collected for 24 hours, and the volume was recorded on d3, d17, and d31 (Figure 1). The concentrations of creatinine and urea nitrogen were analyzed and the creatinine clearance (C^sub CR^) was calculated. Nitrogen balance was calculated as the following formula: nitrogen balance = (protein intake/6.25) - (urinary urea nitrogen 1.25 + 4).

For the blood samples, complete blood counts, including white blood cells (WBC), red blood cells (RBC), hemoglobin, hematocrit, and platelets, were measured using a hematology analyzer (GEN'S, Coulter Inc, FL). Serum concentrations of glucose, albumin, glutamate oxaloacetate transaminase (GOT), glutamate pyruvic transaminase (GPT), and blood urea nitrogen (BUN) were measured using an automatic analyzer (Hitachi 747, Tokyo, Japan). Serum concentrations of prealbumin, transferrin and C-reactive protein (CRP) were measured using the immunonephelometric method. Serum concentration of retinol-binding protein (RBP) was determined by a sandwich enzyme-linked immunosorbent assay (ELISA) as described by Topping et al.12 Serum concentrations of thyroid-stimulating hormone (TSH) and free thyroxin (T^sub 4^) were determined by commercial ELISA kits (Bayer Diagnostics, Tarrytown\, NY).

Arterial Blood Gas Tensions and Ventilator Parameters

The arterial blood gas tensions, such as pH value, arterial carbon dioxide partial pressure (PaCO^sub 2^), arterial oxygen partial pressure (PaO^sub 2^), bicarbonate (HCO^sub 3^^sup -^), and base excess (BE), were measured by a blood gas analyzer (AVL OMNI 4, AVL medical Instrument AG, Bad Homburg, Germany). The parameters on ventilators including tidal volume, respiratory rate, minute ventilation (MV), PEEP, and FiO^sub 2^ were recorded by qualified respiratory therapists.

IC

Oxygen consumption (V^sub O^sub 2^^), carbon dioxide production (V^sub CO^sub 2^^), respiratory quotient (RQ), and REE were measured by a computerized open-circuit indirect calorimeter (Deltatrac II MBM-200 metabolic monitor, Datex-Engstrom Co, Finland) for 1 hour with at least 20 continuous minutes of steady state in each patient. The device was warmed up for over 30 minutes, standardized for temperature, barometric pressure, and humidity, and calibrated with a reference gas mixture (contained 95% O2 and 5% CO2) just before each measurement. The initial 5 minutes of measurements were deleted. In addition, patients were not administered with analgesia or stimulation and did not undergo any changes in ventilator settings for at least 2 hours before and during the measurement.13,14 Steady state is defined as minute-to-minute variations of V^sub O^sub 2^^, V^sub CO^sub 2^^, and RQ <5%. One certain technician was charged to conduct the indirect calorimeter in this study, under the supervision of qualified respiratory therapists.

Statistical Analysis

Values are expressed as means SD. Student's t test was used to investigate the baseline difference of each parameter between the CON and HIGH groups on week 0. To investigate group effect, time effect, and the interactions between group and time, we analyzed the data from weeks 0, 2, and 4 by the mixed model with repeated- measures analysis. Statistical significance was assumed at p < .05.

RESULTS

Patients' Characteristics

The clinical characteristics of mechanically ventilated patients are listed in Table I. The final numbers of patients in the CON and HIGH groups were 11 (6 men and 5 women) and 14 (9 men and 5 women), respectively. Two patients were excluded during the experimental period for the unstable clinical conditions, such as fever and urinary tract infection, and 1 patient was excluded for refusal of continuation. All of these excluded patients were in the CON group. There were no significant differences in age, APACHE II score, LOS, LOV, and body height between the CON and HIGH groups. All of the patients were diagnosed as respiratory failure with other diseases, such as diabetes mellitus, hypertension, hypoxic cncophalopathy, stroke, and so on (Table I).

TABLE I

The clinical characteristics of ventilator-dependent patients

Energy Intake

On week 0, energy intake was not significantly different between the CON and HIGH groups (1873 283 and 1917 317 kcal/d, respectively). In the first 2 weeks (d4 to d17), patients in the HIGH group were fed with 2142 287 kcal/d (ie, 1.8-fold of measured REE on week 0), and those in the CON group were fed with 1562 256 kcal/d (ie, 1.2-fold of measured REE on week 0). Similarly, on the third and fourth weeks (d18 to d31), patients in the HIGH group were fed with 2251 298 kcal/d and those in the CON group were fed with 1548 274 kcal/d, which were 1.8- and 1.2-fold of measured REE on week 2.

Anthropometric Measurements

There were no significant differences in body weight, BMI, MAC, and TSF between the CON and HIGH groups on week 0. The results of mixed model with repeated measures analysis indicated that there were no significant group effect, time effect, and interactions between group and time on body weight, BMI (Table II), and MAC (data not shown). However, there was a significant time effect on TSF (p < .001) as shown in the increased TSF on week 4 in the CON and HIGH groups (23.4 8.0 and 21.1 7.1 mm on week O, 23.8 7.7 and 23.9 7.5 mm on week 2, and 29.5 11.3 and 26.1 7.9 mm on week 4, respectively).

TABLE II

The anthropometries and complete blood cell counts of ventilator- dependent patients

Complete Blood Cell Counts

The levels of WBC (Table II), RBC, and platelets (data not shown) were not significantly different between the CON and HIGH groups on week 0. However, patients with hypercaloric feeding had significantly lower levels of hemoglobin and hematocrit on week 0 (Table II). After adjusting for the levels on week 0 and time, the levels of WBC, hemoglobin, and hematocrit were significantly increased in the HIGH group compared with the CON group, as shown in the significant group effect. In addition, there was a significant time effect (p = .045) on the concentration of platelets.

Biochemical Data

There were no significant differences in serum concentrations of glucose, RBP, GOT, GPT, BUN, Free T^sub 4^, TSH, and C^sub CR^ (data not shown) and in serum concentrations of albumin, prealbumin, transferrin, CRP, and nitrogen balance (Table III) between the CON and HIGH groups on week 0. The results of mixed model with repeated measures analysis indicated that there was a significant group effect on nitrogen balance (p = .006), a significant time effect on serum albumin concentration (p = .016), and significant interactions between group and time on serum concentrations of prealbumin (p = .048), transferrin (p = .005), and BUN (p = .003). For instance, serum albumin concentration was significantly increased in both groups from week 0 to week 4. Nitrogen balance was significantly decreased in the CON group compared with the HIGH group during the experimental period. In addition, serum concentrations of prealbumin, transferrin, and BUN were increased in the HIGH group during the experimental period. There were no significant group effect, time effect, and the interactions between group and time on serum concentrations of glucose, RBP, GOT, GPT, free T^sub 4^, TSH, and C^sub CR^.

TABLE III

Biochemical data of ventilator-dependent patients

Arterial Blood Gas Tensions and Ventilator Parameters

The data of arterial blood gas tensions including the levels of pH, PaCO^sub 2^, PaO^sub 2^, HCO^sub 3^^sup -^, and BE are listed in Table IV. There were no significant differences in the values of blood pH, PaO^sub 2^, PaCO^sub 2^, HCO^sub 3^^sup -^, and BE between the CON and HIGH groups on week 0. The analysis of mixed model with repeated measures analysis indicated that there were no significant group effect and interactions between group and time on the levels of blood pH, PaCO^sub 2^, PaO^sub 2^, HCO^sub 3^^sup -^, and BE during the experimental period. However, there were significant time effects on blood levels of PaCO^sub 2^, PaO^sub 2^, HCO^sub 3^^sup - ^, and BE. For instance, the CON and HIGH groups had significantly decreased levels in PaCO^sub 2^, HCO^sub 3^^sup -^, and BE had significantly increased level in PaO^sub 2^ on weeks 2 and 4 compared with those on week 0.

TABLE IV

The blood gas tensions of ventilator-dependent patients

Values on mechanical ventilators, such as tidal volume, respiratory rate, MV, PEEP, and FiO^sub 2^, were not significantly different between the CON and HIGH groups on week 0 (data not shown). In addition, there were no significant group effect, time effect, and interactions between group and time in tidal volume, respiratory rate, MV, PEEP, and FiO^sub 2^ during the experimental period.

FIGURE 2. The rate of carbon dioxide production (V^sub CO^sub 2^^ ), resting energy expenditure (REE), respiratory quotient (RQ), and nonprotein respiratory quotient (npRQ) in mechanically ventilated patients on weeks O, 2, and 4. Values for mixed model with repeated measures analysis (in the box) are p values for group effect, time effect, and the interactions between group and time.

IC

Values of V^sub CO^sub 2^^, REE, RQ, and npRQ measured by indirect calorimeter are shown in Figure 2. V^sub O^sub 2^^ (data not shown), V^sub CO^sub 2^^ , REE, RQ, and npRQ were not significantly different between the CON and HIGH groups on week O. There were no significant group effect, time effect, and interactions between group and time on V^sub O^sub 2^^ and REE. However, there was a significant interaction between group and time in V^sub CO^sub 2^^, as it was decreased in the CON group and increased in the HIGH group on weeks 2 and 4 compared with week 0. In addition, there were significant group effects on RQ and npRQ, as they were increased in the HIGH group and decreased in the CON group on weeks 2 and 4 compared with week 0.

DISCUSSION

Extensive evidence indicates that malnutrition commonly occurred in patients with long-term mechanical ventilation, which may lead to increased nosocomial infections, poor wound healing, respiratory muscle dysfunction, and respiratory failure.15 On the other hand, the adverse effects of overfeeding, for example, hyperglycemia, hyperlipidemia, and elevated CO2 production that fails the efforts of weaning from ventilator, are usually neglected in patients fed with energy more than 2-fold of their energy expenditure during clinical care. Our previous study showed that about 80% of patients with long-term mechanical ventilation were fed with energy as 1.2- to 2-fold of REE in the chronic respiratory care unit.11 However, there was little information regarding the beneficial and adverse effects of moderate hyper caloric feeding (<2-fold of REE) in patients with long-term mechanical ventilation. Using IC, we measured the energy requirement of mechanically ventilated, clinically stable patients with nasogastric tube feeding. Thereafter, we investigated whether moderate hypercaloric feeding might result in physiologic burden to interfere with nutrition status and ventilator weaning in mechanically ventilated patients via the anthropometries, nutrition-related serum proteins, and parameters of indirect ca\lorimetry.

It has been demonstrated that the value of REE measured by IC is 0%-30% below total energy expenditure. 13-15 According to this information, we provided energy as 1.2-fold of measured REE to mechanically ventilated patients to fulfill their energy requirement. Patients in the hypercaloric group consumed energy as 1.8-fold of measured REE and were provided with 50% more energy than they required. Several clinical studies showed that healthy volunteers with high-energy diet had significantly increased whole- body fat, carbohydrate balance, and hepatic de novo lipogenesis.16- 18 However, we observed that ventilator-dependent patients with moderate hypercaloric feeding (ie, 1.8-fold of REE) for 4 weeks did not have significant impacts on body weight, BMI, MAC, and TSF. These unaltered anthropometries may lead physicians to further increase the energy support to improve the nutrition status of these patients.

Additionally, patients in the hypercaloric group had a significantly higher nitrogen balance than those in the control group, with a difference of about 2 g of nitrogen per day on week 4. Joosten et al6 indicated that the ratio of energy intake to measured REE was significantly higher in ventilator-dependent children with a positive nitrogen balance when compared with those with a negative nitrogen balance. These results suggest that the patients with hypercaloric feeding may preserve more body protein as the goal of nutrition support. The body protein preservation induced by hypercaloric feeding was commonly observed during clinical care, which is another reason for clinicians to increase the energy intake of patients with mechanical ventilation. However, how much of the nutrients should be provided to avoid the adverse effects of overfeeding was still uncertain.

During the nutrition care, obscure sources of nutrition intake were easily overlooked, such as dextrose in the peritoneal dialysis solution and regular dextrose IV solution.2 This unintentional feeding is usually the reason for overfeeding and causes an increased risk of nutrition complications in patients. Hyperglycemia is one of the complications associated with overfeeding.19 In the present study, we found that patients with hypercaloric feeding tended to have increased serum glucose concentration compared with those with normal feeding (p = .062 in the interaction between group and time). The reason that patients with hypercaloric feeding did not show the symptoms of hyperglycemia is partly due to the use of hypoglycemie agents to control their blood glucose level. Therefore, hyperglycemia may not always be found in patients with overfeeding, especially when they had intensive clinical care.

We tried to use serum concentrations of nutrition-related proteins, such as albumin, prealbumin, transferrin, and RBP, to monitor the nutrition status in patients with mechanical ventilation. However, only serum concentrations of prealbumin and transferrin were significantly altered during the experimental period. Even though serum concentrations of prealbumin and transferrin were increased in the HIGH group from week O to week 4, those were not significantly different from the CON group. According to the low albumin concentrations (at 30-34 g/L), we suspected that these patients were mildly undernourished, although they had maintained body weight and BMI during the experimental period. Therefore, in this study, only nitrogen balance and serum concentrations of prealbumin and transferrin could sensitively reflect the effects of moderate hypercaloric feeding in patients with long-term mechanical ventilation.

The impact of hypercaloric feeding on blood cells was found in the present study. Patients with hypercaloric feeding had significantly increased WBC, hemoglobin, and hematocrit compared with those with control feeding. The increases in hemoglobin and hematocrit may be explained by the catch-up response induced by hypercaloric feeding because these levels were significantly lower in the HIGH group compared with the CON group on week 0. However, the increased levels of WBC revealed that hypercaloric feeding may be stressful for mechanically ventilated patients. In addition, when concerned about the high CRP concentrations in the HIGH group on week 0, we could not exclude the possibility that the metabolic disadvantages of overfeeding may be presumably more prominent when the criticalness of illness is greater.

From the clinical point of view, it should be noted that hypercaloric feeding increases the work of breathing for the elevated production in carbon dioxide, which is particularly important in patients with mechanical ventilation, van den Berg and Stam10 provided ventilator-dependent patients with energy equal to 1.5- or 2.0-fold of REE and found that carbon dioxide production was increased by the high-energy feeding, which resulted in a rise in arterial carbon dioxide tension and respiratory distress. We confirmed that patients with energy as 1.8-fold of REE had significantly increased carbon dioxide production (Figure 2). However, the blood gas tensions were not significantly different between the control and hypercaloric groups. It is noticed that the signs of inappropriate feeding may be masked by adjustment in clinical care,5 such as ventilator setting and medical treatment. Because all of our patients were under maximal pulmonary support and the parameters we collected were not intrinsic measures of lung function, we could not exclude the adverse effects of hypercaloric feeding on respiratory status.

IC has a distinct role in identifying individual energy requirement by measuring carbon dioxide production and oxygen consumption.20-24 Even though several studies indicated that hypercaloric feeding may increase the REE in patients with mechanical ventilation,25,26 our results showed that patients fed with energy as 1.8-fold of REE did not have significantly altered REE, which was the same as the results of the Malone24 study. According to the ratio of CO2 production to O2 consumption, RQ can be calculated. Traditionally, RQ has been used as an indirect measure of substrate use.27 Recently, RQ is merely used to confirm test validity with the physiologic range of 0.67-1.3 13,27,28 After feeding for 2 or 4 weeks, all of the patients had RQ between 0.81 and 1.04. These data demonstrate that the use of IC is valid in this study. The results of mixed model with repeated measure analysis showed that patients with hypercaloric feeding had significantly increased RQ and npRQ compared with those with controlled feeding. In addition, over 50% of patients with hypercaloric feeding had npRQ >1. Additional studies will be needed to clarify whether patients with hypercaloric feeding had increased carbohydrate oxidation and decreased fat oxidation.

In summary, our results suggest that 4 weeks of moderate hypercaloric feeding (1.8-fold of REE) has no serious adverse effects and may be beneficial in improving nutrition repletion; however, it may significantly increase the production of carbon dioxide in patients with long-term mechanical ventilation. In addition, the unaltered results in clinical examinations, such as anthropometric measurements, nutrition-related serum proteins, and blood gas tensions, may lead the physicians to overlook the signs of overfeeding. Therefore, the adverse effects of long-term hypercaloric feeding should still be considered. We expect that the information provided by this study may help clinicians to be aware of the potential problems of hypercaloric feedings and to understand the importance of IC in managing nutrition support for patients with long-term mechanical ventilation, especially for those with stable hemodynamic status. Further studies are needed to investigate the effects of moderate hypercaloric feeding on clinical respiratory status via the measurements of the intrinsic lung function and to clarify the optimal nutrition support for mechanically ventilated patients with weaning attempts.

ACKNOWLEDGMENTS

Hui-Chen Lo and Ching-Hsiung Lin contributed equally. We thank Dr Wen-Miin Liang and Dr Sing-Kai Lo for their statistical advice, the nurses, dietitians, and respiratory therapists in the respiratory care unit for their clinical assistance, and Bo-Chin Chiou, Fu-Ann Tsai and Su-Chen Lin for their laboratory assistance. This work was supported by a fund CCH4604 from the Changhua Christian Hospital.

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Hui-Chen Lo, PhD*[dagger], Ching-Hsiung Lin, MD[double dagger]; and Ling-Jang Tsai, MS

From the * Department of Bioscience Technology, Chang-Jung Christian University, Tainan, Taiwan, ROC; and the [dagger] Department of Medical Education and Research, [double dagger] Division of Chest Medicine, Department of Internal Medicine, and Department of Nutrition and Dietetics, Changhua Christian Hospital, Changhua, Taiwan, ROC

Received for publication November 29, 2004.

Accepted for publication May 11, 2005.

Correspondence: Ching-Hsiung Lin, MD, Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, 135 Nanhsiao Street, Changhua, 500, Taiwan, ROC. Electronic mail may be sent to 66161@cch.org.tw.

Copyright American Society for Parenteral and Enteral Nutrition Sep/ Oct 2005

Source: JPEN, Journal of Parenteral and Enteral Nutrition

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