|Year : 2017 | Volume
| Issue : 1 | Page : 68-75
Comparative study between enteral and intradialytic parenteral nutrition in hemodialysis patients
Ahmed M El demerdash, Sherif G Anis, Heba Abd Elazim Labib, Sherif Farouk Ibrahim, Alaa El-din Abd Elwahab Koraa
Department of Anesthesia, Intensive Care, and Pain Management, Ain Shams University, Cairo, Egypt
|Date of Web Publication||3-Aug-2018|
Sherif G Anis
Department of Anesthesia, Intensive Care, and Pain Management, Ain Shams University, Cairo, 11165
Source of Support: None, Conflict of Interest: None
Background Protein–energy malnutrition is very common among patients with end-stage renal disease undergoing maintenance hemodialysis therapy.
Aim The aim of this prospective randomized study was to compare the effect of enteral nutrition (EN) and intradialytic parenteral nutrition (IDPN) on malnourished hemodialysis patients receiving nutritional support admitted in the intensive care unit.
Patients and methods A total of 135 patients between 18 and 60 years of age admitted in Ain shams University Hospitals’ intensive care units and on regular hemodialysis were randomly allocated to three groups of 45 each. Group A received enteral and IDPN (250 ml dextrose 25%, 250 ml intralipid 10%, 250 nephrosteril 7%, and trace elements and vitamins). Group B received enteral and IDPN (250 ml dextrose 25%, 250 ml intralipid 10%, 250 aminosteril N-Hepa 8%, and trace elements and vitamins). Group C received only EN.
The following evaluations were carried out: biochemical evaluation, which included serum albumin, prealbumin, transferrin, and urinary urea nitrogen evaluation every 20, 4, 8, and 0 days, respectively, and after 6 weeks at the end of the study, and anthropometric parameter measurement, which included BMI, mid-arm circumference, and dialysis malnutrition score (DMS).
Results Serum albumin, prealbumin, BMI, and DMS significantly increased (P≤0.001) at the end in all groups. Serum transferrin increased only in groups A and B (P≤0.001), and there was a nonsignificant increase in group C (P≤0.05). No significant difference was found at the end between group A and group B as regards serum albumin (P=0.056), serum prealbumin (0.062), serum transferrin (0.0942), BMI (0.455), and DMS (P=0.840). Serum albumin, prealbumin, transferrin, and BMI showed a significant difference (P≤0.001) in group C at the end of the study in comparison with groups A and B with lower SD.
Conclusion IDPN, either aromatic or branched amino acid, in addition to EN showed the same and greater improvement compared with patients who received only EN.
Keywords: chronic kidney disease, enteral, hemodialysis, nutrition, parenteral
|How to cite this article:|
El demerdash AM, Anis SG, Labib HA, Ibrahim SF, Koraa AE. Comparative study between enteral and intradialytic parenteral nutrition in hemodialysis patients. Ain-Shams J Anaesthesiol 2017;10:68-75
|How to cite this URL:|
El demerdash AM, Anis SG, Labib HA, Ibrahim SF, Koraa AE. Comparative study between enteral and intradialytic parenteral nutrition in hemodialysis patients. Ain-Shams J Anaesthesiol [serial online] 2017 [cited 2019 Jun 20];10:68-75. Available from: http://www.asja.eg.net/text.asp?2017/10/1/68/238455
| Introduction|| |
Protein–energy malnutrition (PEM) is very common among patients with end-stage renal disease (ESRD) undergoing maintenance hemodialysis therapy. Its prevalence in the ESRD population varies between 18 and 70% (severe PEM can occur in 10% of the patients) and it is one of the strongest predictors of mortality and morbidity in this population, and thus has been a target of intense interest for clinicians .
Typically, most studies of PEM and its link to outcomes have focused on traditional markers of poor nutritional status, including albumin, serum prealbumin, and BMI. PEM in ESRD patients has many causes such as inadequate food intake, catabolic response to superimposed illness, dialysis procedure, chronic inflammation with hypercatabolism and anorexia, blood loss during dialysis, the accumulation of uremic toxins, and mobility limitation .
For some malnourished patients in whom standard enteral nutrition (EN) has been unsuccessful, intradialytic parenteral nutrition (IDPN) is a feasible option; it provides substantial calories and protein to augment oral intake . In acutely ill patients with chronic kidney disease (CKD) on dialysis, the goal of PN is to reduce protein catabolism and nutritional depletion-associated morbidity and mortality. In chronically malnourished HD patients, IDPN aims to prevent the decrease in plasma amino acid concentration encountered in hemodialysis session and the subsequent decrease in protein synthesis and then improve the quality of life to reduce PEM-related complications, hospitalization rate, and mortality .
Proteins are the primary structural and functional polymers in living systems. They have a broad range of activities, including catalysis of metabolic reactions and transport of vitamins, minerals, oxygen, and fuels . Tyrosine, a semiessential aromatic amino acid, can only be synthesized by the hydroxylation of an essential aromatic amino acid phenylalanine. Renal phenylalanine hydroxylation accounts for 50% of whole-body phenylalanine hydroxylation. Chronic renal failure patients have low arterial tyrosine concentrations. This can be attributed to net protein catabolism and muscle wasting in these individuals . Metabolic acidosis in CKD and hemodialysis patients increases protein catabolism and branched-chain amino acid degradation. Low plasma valine, frequently together with depleted leucine and isoleucine extracellular pools, has been described as a typical branched-chain amino acid pattern for chronic uremia .
This prospective randomized study was designed to compare the effect of EN and IDPN on malnourished hemodialysis patients receiving nutritional support admitted in the ICU.
Patients and methods
This study was conducted in the ICU of Ain Shams university Hospitals from 2012 to 2014, after obtaining approval from the medical ethical committee in Ain Shams University and after informed consent taken from all patients; 135 patients were included in the study. Patients of both sexes between 18 and 60 years of age on regular hemodialysis three times per week with duration of dialysis of at least 3 h/session, albumin level of less than 3.4 g/dl, prealbumin level of less than 15 mg/dl, and BMI of less than 18.5 were included in this study. Exclusion criteria included known hypersensitivity to any used drugs, cardiac disease, liver cell failure, chemotherapy or radiotherapy, cancer disease, pregnancy and lactation, and patient refusal.
Full medical history was taken from them, including history of weight loss in the last 6 months, comorbidity, and nutritional habits as regards protein, carbohydrate, and fat intakes. The severity of illness of these patients was evaluated using the Acute Physiology and Chronic Health Evaluation II score.
A thorough cardiorespiratory, abdominal, and neurologic examination was performed for all patients. Patients were also examined for the presence of lower limb edema. Nutritional status was assessed within 24 h of admission. Patient’s nutritional status was determined from anthropometric parameters, biochemical measurements, and medical status . Biochemical evaluation included the following: serum albumin (3.4–5.4 g/dl) measured every 20 days from the beginning of the study and after 6 weeks at the end of the study; serum prealbumin (15.7–29.6 mg/dl) measured every 4 days from the beginning of the study and after 6 weeks at the end of the study; serum transferrin (204–360 mg/dl) measured every 8 days from the beginning of the study and after 6 weeks at the end of the study; and urinary urea nitrogen (UUN) (10–12 g/day) measured at the beginning of the study and after 6 weeks at the end of the study. Nitrogen balance=[total protein intake (g/day)/6.25 g protein/g nitrogen] − [UUN+4 g]; the factor 4 represents the daily nitrogen loss (g) other than UUN .
In addition, the following parameters were assessed on routine basis: total proteins (6.3–8 g/dl), blood urea nitrogen (10–20 mg/dl), serum creatinine (1–2 mg/dl), lipid profile (cholesterol, triglyceride, and LDL), fasting blood sugar, complete blood picture, liver function tests (alanine transaminase and aspartate transaminase), serum sodium, serum potassium, serum magnesium, serum phosphate, serum calcium, and ionized calcium. Anthropometric parameters were assessed to evaluate body composition, which included height, body weight, BMI, and skin fold thickness that was measured with a Holten skin fold caliper over the triceps, biceps, and iliac crest area. Mid-arm muscle circumference (MAC) (represents the muscle protein) was calculated using mid-arm circumference and triceps skin thickness . As fluid retention and edema frequently occur in critically ill patients, pre-ICU admission body weights were calculated; the BMI was calculated using weight (kg)/height2 (m), (normal range from 18 to 25 kg/m2), and mid-MAC was calculated as follows: MAC (cm) − [triceps skin fold (cm)×3.14].
The history used in the dialysis malnutrition score (DMS) focused on seven features: weight loss in the previous 6 months (mild, 5%; moderate, 5–10%; and severe, 10%), dietary intake (normal or abnormal as judged by change in intake), gastrointestinal symptoms (anorexia, nausea, vomiting, diarrhea, and abdominal pain), functional capacity (bedridden, suboptimally active, or full capacity), comorbidity, subcutaneous fat loss, and signs of muscle wasting (in the triceps region and the midaxillary line at the level of the lower ribs, the temporal areas, and in the deltoids and quadriceps). Each component has a score from 1 (normal) to 5 (very severe). Thus, the DMS (sum of all seven components) is a number between 7 (normal) and 35 (severely malnourished) .
Patients receiving parenteral and EN received their caloric requirements according to the formula of daily basal energy expenditure (BEE) . For men, BEE (Kcal/24 h)=66+(13.7×wt.)+(5.0×ht.)−(6.7×age), and, for women, BEE (Kcal/24 h)=655+(9.6×wt.)+(1.8×ht.) − (4.7×age) (wt.=weight in kilograms, ht.=height in inches).
Patients were divided using computer-generated random numbers into three equal groups of 45 patients each.
Group A (n=45) included patients who received IDPN in the form of more aromatic amino acids in addition to EN: 250 ml of dextrose 25% will supply 62.5 g (212.5 Kcal) of carbohydrates; 250 ml of intralipid 10% will supply 25 g (225 Kcal) of lipids; 250 ml of nephrosteril 7% will supply 17.5 g of proteins with more aromatic amino acids (l-tryptophan, l-phenylalanine, and l-serine)and Addamel N will supply the daily requirements of chromic chloride (Cr), copper chloride (Cu), ferric chloride (Fe), manganese chloride (Mn), potassium iodide (I), sodium fluoride (F), sodium molybdate (Mo), sodium selenite anhydrous (Se), and zinc chloride (Zn).
Vitamins: Becozyme will supply the daily requirements of vitamin B1, biotin, vitamin B2, folic acid, nictoinamide, vitamin B12, vitamin B6, glycine, pantothenic acid, sodium edetate, vitamin C, and methy1 parahydroxybenzoate. EN: milk (320 Kcal), yoghurt (240 Kcal), juice (banana 274 Kcal and orange 198 Kcal), chicken (298 Kcal), jam (165 Kcal), jelly (177 Kcal), cheese (58 Kcal), and vegetable soup (200 Kcal).
Group B (n=45) included patients who received IDPN in the form of more branched-chain amino acids in addition to EN: 250 ml of dextrose 25% will supply 62.5 g (212.5 Kcal) of carbohydrates; 250 ml of intralipid 10% will supply 25 g (225 Kcal) of lipids; 250 ml of aminosteril N-Hepa 8% will supply 20 g of proteins with more branched-chain amino acids; and trace elements, vitamins, and EN were given as in group A
Group C (n=45) included patients who received EN similar to that in groups A and B and did not receive intradialytic parenteral nutrition.
For dialysis interruption longer than 10 min, IDPN was discontinued. Once dialysis was reinitiated, infusing solution was recommenced at the previous rate. The remainder of the solution upon discontinuation of dialysis was discarded. In case of antibiotic infusion, the IDPN solution was switched to the arterial chamber and the antibiotic infusion was given through the venous chambers. Iron products were infused through the arterial chamber with the IDPN solution continuing in the venous chamber; blood or blood products may be given concurrently with IDPN infusion during dialysis but infused through the same chamber. Gastrointestinal complications were reported; a single episode of emesis was not an indication to discontinue EN. Repeated emesis or emesis not in association with stimulation was assessed with description of metoclopramide. Diarrhea (the presence of 3–5 liquid stools or more than 300–500 ml over a 24 h period) is often multifactorial. When diarrhea occurred, the EN formula was not diluted, the rate was not reduced or EN not discontinued except in severe cases in which the patient had more than 10 loose, watery stools in 24 h. Constipation when occurred was reported. Narcotic agents, immobility, and dehydration, all contribute to constipation. It may result in fecal impaction and/or mega colon. Narcotic agents were to be minimized, adequate water was provided, and regular bowel care was encouraged.
Before the study, a power analysis was performed to determine the minimal acceptable number of patients in each group. The minimal number for each group sufficient to detect an 0.6 g/dl change in serum albumin level with a SD of 1.39 was 42 patients, with type I α error of 0.05 and type II β error of 0.8 and the power of the test at 90%; hence, we set the group number at 45 to compensate for possible dropouts.
The data were coded, entered, and processed on computer using SPSS (version 15, IBM, Corp, USA, 2012). The level P less than 0.05 was considered the cutoff value for significance, and the level P less than 0.0001 for highly significant difference. Analysis of variance evaluates the equality of several group means; it was used to test the difference between mean values of some parameters among multiple groups (post-hoc test: Bonferroni), and the paired test was used to compare related samples. The χ2-test was used for comparison of qualitative data. Continuous parametric data were presented as mean±SD, nonparametric data as median (interquartile range), and categorical data were presented as number of patients.
| Results|| |
There was no significant difference in both age and sex distribution among groups (P for sex 0.158 and P for age 0.431) ([Table 1]).
Serum albumin significantly increased at the end of the study in all groups in comparison with the beginning and the middle of the study (P<0.001). The increase from the beginning to the middle and from the middle to the end of the study was gradual in manner. Patients in group A and group B showed an increase in serum albumin level at the end of study, with no significant difference between the two (P=0.056) and nearly the same SD (0.36). Serum albumin level at the end of study for patients in group C showed a significant difference (P<0.001) compared with results of groups A and B, with a lower SD (0.26) ([Table 2]). Serum prealbumin significantly increased at the end of the study in all groups in comparison with the beginning and the middle of the study (P<0.001). The increase from the beginning to the middle of the study was at a higher rate compared with the increase from the middle to the end of the study. Patients in group A and group B showed an increase in serum prealbumin level at the end of study, with no significant difference between the two groups (P=0.062) and nearly the same SD (SD for group A=0.96 and that for group B=0.93). Serum prealbumin level at the end of study for patients in group C showed a significant difference (P<0.001) compared with results of groups A and B, with a lower SD (0.71) ([Figure 1]).
|Figure 1 Serum prealbumin level at the beginning, the middle, and the end of the study for each group. Data are presented as mean (SD). *P<0.001 at the end of the study compared with the beginning and the middle of the study. **P<0.001 at the end of study compared with groups A and B.|
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Serum transferrin significantly increased at the end of the study in comparison with the beginning and the middle of the study for groups A and B (P<0.001), which was nonsignificant in group C (P<0.632). The increase from the middle to the end of the study for both groups A and B was at a higher rate compared with the increase from the beginning to the middle of the study. Patients in group A and group B showed an increase in serum transferrin level at the end of study, with no significant difference between the two (P=0.942) and nearly the same SD (SD for group A=9.93 and for group B=9.91). Serum transferrin level at the end of study for patients in group C showed a significant difference compared with results of groups A and B (P=0.012 and 0.030, respectively) with a lower SD (7.9) ([Table 3]). BMI significantly increased at the end of the study in all groups in comparison with the beginning of the study (P<0.001). Patients in group A and group B showed an increase in BMI at the end of study, with no significant difference between the two groups (P=0.455) and nearly the same SD (0.89). BMI at the end of the study for patients in group C showed a significant difference (P<0.001) compared with results of groups A and B with a lower SD (0.78) ([Table 4]).
DMS significantly improved at the end of the study in all groups in comparison with the beginning of the study (P<0.001). Patients in group A and group B showed an improvement in DMS at the end of study, with no significant difference between the two groups (P=0.840) and nearly the same SD (SD for group A=2.21 and that for group B=2.23). DMS at the end of study for patients in group C showed a significant difference compared with results of groups A and B (P<0.001 and 0.003, respectively) with a higher SD (2.35), which indicates little improvement compared with groups A and B ([Table 5]).
Nitrogen balance significantly improved at the end of the study in all groups in comparison with the beginning of the study (P<0.001).
There was no significant difference in the end results for the three groups (P=0.260). Forty patients in group A showed a change from negative to positive nitrogen balance at the end of study (88.9%). Forty-one patients in group B showed a change from negative to positive nitrogen balance at the end of study (91.1%). Thirty-six patients from group C showed a change from negative to positive nitrogen balance at the end of study (80%) ([Table 6]).
|Table 6 Nitrogen balance at the beginning and the end of the study for each group|
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| Discussion|| |
The purposes of nutrition therapy in dialysis patients are to promote the nutrition to correct patients’ appetite, as well as systemic complications composed by the loss of nephrons in progress, and to reduce protein catabolism to the lowest level. Nutrition therapy to prevent an increase in fluid and electrolyte disorders reduces uremic symptoms such as itching, nausea, vomiting, and loss of appetite and prevents renal osteodystrophy keeping the consumption of calcium and phosphorus under control . This study was designed to compare the effect of EN and IDPN on malnourished hemodialysis patients. Assessment of the state of nutrition or more accurately the level of nutritional deficit of a patient is clearly the first step in deciding the degree of nutritional support required. An isolated parameter does not characterize the general nutritional condition of an individual; it is therefore necessary to use a combination of various nutritional state indicators to increase the diagnostic precision. This study was designed to measure serum albumin (g/dl), serum prealbumin (mg/dl), serum transferrin (mg/dl), BMI (kg/m2), DMS, and nitrogen balance within 6 weeks.
Serum albumin showed a significant increase at the end of the study in all groups in comparison with the beginning and the middle of the study. This is in agreement with the findings of Arques et al. , who stated that serum albumin is the best predictor of malnutrition in every age group. Moreover, Panichi et al.  added that hypoalbuminemia in hemodialysis patients is a strong indicator for mortality and morbidity. Serum albumin level was on average below normal, normal, or low normal for all patients throughout the study. This might be due to the long half-life of albumin that limits its usefulness in following rapid nutritional changes, thus making it a poor indicator of nutritional status. In addition, critical illness decreases the synthesis of albumin, causes a shift in the distribution of albumin from the vascular space to the interstitial space, and releases hormones that increase the metabolic destruction of albumin. Plasma albumin level will not increase in metabolically stressed patients until the cause of the stress is removed . Serum prealbumin showed a significant increase at the end of the study in all groups in comparison with the beginning and the middle of the study. This result is in agreement with the finding of Parrish , who stated that serum prealbumin changes more rapidly with changes in nutrient intake (shorter half-life 4 days). Sathishbabu and Suresh  confirmed that serum prealbumin correlates positively and significantly with other nutritional markers in ESRD patients on hemodialysis. Serum transferrin showed an increase at the end of the study in all groups in comparison with the beginning and the middle of the study. This is in agreement with the findings of Kung and Lui . However, Huang et al.  and Parrish  stated that the level of serum transferrin (half-life 8 days) is influenced by iron status (iron deficiency causes an increase in transferrin level due to increased iron absorption and is often used as an indirect method of determining total iron binding capacity). BMI showed a significant increase at the end of the study in all groups in comparison with the beginning of the study, especially for patients who received intradialytic parenteral nutrition in addition to EN (groups A and B) compared with those who received only EN (group C). However, Higgins et al.  stated that body weight is not a good marker for nutritional status, as edema and fluid retention occur frequently due to hypoalbuminemia, and accurate weighting is often not possible. Current body weight could only be used as a reference but not as a good indicator when evaluating nutritional status. In this study, DMS showed an improvement at the end of the study in all groups in comparison with the beginning of the study. Mutsert et al.  demonstrated that the DMS is a quick, valid, and reliable nutrition assessment tool.
Nitrogen balance showed an improvement at the end of the study in all groups in comparison with the beginning of the study. This is in agreement with the findings of Bortano , who stated that decreased protein intake depletes the body’s nitrogen reserve, which is manifested as a negative nitrogen balance. In this study, patients who received IDPN using same amount of proteins in the form of more aromatic amino acids in addition to EN (group A) showed an elevation in nutritional markers and anthropometric measurements within the period of the study. This was explained by Bohé and Rennie , who stated that net protein degradation and negative nitrogen balance occur during hemodialysis and added that net release of free tyrosine and phenylalanine from the muscles increased ∼100% in hemodialysis patients. The increased release of aromatic amino acids suggests that dialysis enhanced catabolism of muscle proteins. Therefore, supplementation of intradialytic parenteral nutrition enriched with tyrosine and phenylalanine would improve the amino acid pool of hemodialysis patients, which reflected on nutritional markers, especially albumin and prealbumin. Kopple  noted that, in humans with CKD, plasma, erythrocyte, and skeletal muscle tyrosine concentrations are often decreased and plasma and red cell phenylalanine is normal to slightly increased. These findings suggested that there may be impairment in the conversion of phenylalanine to tyrosine by phenylalanine hydroxylase. Activity for this enzyme has been found in the liver, kidney, and pancreatic cells.
Branched-chain amino acids, such as valine, leucine, and isoleucine, are essential amino acids used for protein synthesis. With other amino acids in a balanced formula, they have been shown to promote nitrogen retention and reduce urea production compared with standard amino acid formulations; metabolic acidosis in CKD and hemodialysis patients increases protein catabolism and branched-chain amino acid degradation. Low plasma valine, frequently together with depleted leucine and isoleucine extracellular pools, has been described as a typical branched-chain amino acid pattern for chronic uremia . Furthermore, Kadiri and colleagues added that, in CKD patients, nutritional indices such as BMI, DMS, and serum prealbumin are correlated with plasma leucine, isoleucine, and particularly valine. Conversely, nutritional supplementation with IDPN is reported to induce an improvement in nutritional status together with an increase in plasma leucine. However, Holecek  stated that branched-chain amino acid supplementation in high concentrations for a long time may lead to enhanced ammonia production from glutamine breakdown in the intestine and the kidneys; 70% of all ammonia generated in this reaction will be released into the renal vein to be converted to urea in the liver (urea cycle), and thus exert harmful effects on the prognosis of CKD.
Patients who received only EN (group C) showed an elevation in nutritional markers and anthropometric measurements within the period of the study. This was explained by Moller , who stated that, in people with CKD, there was net uptake of amino acids by the gastrointestinal tract. After ingestion of a meal, there was a release of amino acids from the splanchnic bed into the circulation, which was significantly greater in CKD patients compared with the normal individuals. The elevation in nutritional markers and anthropometric measurements in patients from group C was mild, and this is in agreement with the findings of Cano et al. , who found that, after a 2-year study, there was no significant difference between supplementation of IDPN and EN as regards nutritional markers, anthropometric measurements, hospitalization, and mortality rate. This may indicate that EN needs more time to reach notable improvement in nutritional parameters.
| Conclusion|| |
Malnourished hemodialysis patients need supplementation of adequate nutritional regimen for improvement of their nutritional status. The improvement with the intradialytic parenteral nutrition, either for patients who received same amount of proteins in the form of more aromatic amino acids in addition to EN or patients who received same amount of proteins in the form of more branched-chain amino acid, in addition to EN, was nearly the same or greater when compared with patients who received only EN, whose improvement was mild. Serum albumin, serum prealbumin, serum transferrin, BMI, and DMS were helpful in the evaluation of the nutritional status of malnourished hemodialysis patients.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]