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Review Article


Intradialytic Parenteral Nutrition (IDPN): An Evidence Based Review

Tze Chin Tan MD, MRCP1, Roy Debajyoti MD, FRCP2

Senior Resident, Advanced Internal Medicine, Singhealth1

Senior Consultant, Division of Nephrology,Changi General Hospital,Singapore2


Key words: IDPN, malnutrition, nutritional status, dialysis


Introduction

It is estimated that 40-50% of patients on dialysis are malnourished and 10% of these patients are severely malnourished1. Protein-energy malnutrition (PEM) is one of the strongest predictors of mortality and morbidity2.

The causes of PEM in end-stage renal disease (ESRD) patients on regular thrice weekly chronic dialysis are numerous: inadequate food intake; catabolic response to intercurrent illnesses; dialysis procedure; chronic inflammation with hyper catabolism and anorexia; blood loss; endocrine disorders of uremia; socioeconomic factors, and mobility limitations.

Uremia contributes to decreased appetite and nausea; chronic kidney disease and other co-morbidities such as diabetes mellitus affects the ultilsation of nutrients4. Dietary restrictions imposed by a renal diet limits absorption of nutrients. Socioeconomic factors and mobility limitations can affect procurement of food. Apart from inadequate intake of food, the dialysis process can cause nutrient losses. Up to 10-12 g of protein can be lost during each hemodialysis session, and 5-15g protein per day in patients undergoing peritoneal dialysis4.

The National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (KDOQI) made a recommendation that the dietary protein intake for clinically stable ESRD patients should be 1.2grams/kg/day3.


Dietary Supplementation And Nutritional Assessment

Intensive nutritional counseling is aimed to increase the nutrient density of dietary intake; by encouraging consistent intake over a period of minimum three to four months4. However, increasing protein intake will invariably lead to increase in phosphorus and acid production. Thus NKF/ KDOQI guidelines recommend that every ESRD patient should receive intensive nutritional counseling at least every 3 months3. The aim of nutritional counseling serves to draw up an individualized care plan consisting of monitoring

of laboratory values, dietician input and, in some cases modification of dialysis prescription.

Subjective Global Assessment (SGA) is a tool recommended by NKF/KDOQI for use in nutritional assessment in adult dialysis patients3. The original SGA comprises five components of a medical history (i.e. weight change, dietary intake, gastrointestinal symptoms, functional capacity, disease and its relation to nutritional requirements) and three components of a brief physical examination (i.e. signs of fat and muscle wasting, nutrition-associated alternations in fluid balance). The patient’s nutritional status is then scored as A (well nourished), B (mild to moderately nourished) and C (severely malnourished)8. The tool has been expanded to a 7-point scale for patients with chronic kidney disease: 6 or 7 (very mild nutrition risk to well nourished), 3,4, or 5 (mild to moderately malnourished), and 1 or 2 (severely malnourished)3.

Many dialysis patients consume less than 80% of the recommended intake of 1.2g/kg/day protein in spite of intensive counseling9. Nutritional status should be assessed using a global assessment strategy and then look for reversible causes of poor nutrition.Patients should be closely monitored to assess if the normalized protein equivalent of total nitrogen appearance (nPNA) is on an increasing trend. If the above measures fail, nutritional support should be considered


Enteral Nutritional Support

Enteral nutritional support requires a functional gastrointestinal tract. In patients who are able to tolerate oral diet, the use of enteral nutritional supplements is recommended. Patients who have swallowing impairment can be given nutritional supplements via enteral feeding tube. Enteral feeding is able to provide a patient’s total nutritional needs on a daily basis; in a smaller fluid volume compared to parenteral nutrition. Moreover, the risk of infection is lower compared to parenteral nutrition and is cost-effective.

In a meta-analysis10 of 18 studies (five of which were randomized controlled trials; total of 541 patients) looking at effects of oral nutritional supplements and tube feeding in dialysis patients, total energy and protein intakes can be increased by 20-50% with enteral nutritional support. An equivalent of approximately 19grams of protein, 425 calories per eight fluid ounces (such as Nepro © feeds) was given to patients daily or on dialysis days. Patients who received enteral nutritional support had significantly higher serum albumin concentration (0.227 g/dL; 95% confidence interval,

0.037 to 0.418 g/dL). No adverse effects on electrolytes or volume status were reported. However there was insufficient data to assess mortality, morbidity, change in quality of life and complications relating to infection, cardiovascular outcomes.

However, in some circumstances, oral or enteral nutritional supplements are not tolerated well. Patients may refuse oral nutritional supplements due to palatability problems or poor appetite. In some, fluid management poses a challenge; which could be overcome by changes in dialysis prescription. Patients with severe disability limiting oral feeding, oral nutritional supplements are unable to provide the shortfall in nutritional needs. Lastly, in patients who have a malfunctioning gastrointestinal tract (massive bowel resection, short gut syndrome, complete intestinal obstruction not amenable to surgery, or severe enteritis requiring prolonged bowel rest), oral nutritional supplements are inappropriate2. In such circumstances, intradialytic parenteral nutrition (IDPN) may be an option.


Intradialytic Parenteral Nutrition

IDPN is the provision of nutrients through the venous drip chamber while the patient is undergoing hemodialysis. This circumvents the problem of limitations in oral intake; it is able to provide a larger amount of supplementation in a short period of time. IDPN is not designed to provide a dialysis patient all his caloric or nutrient needs as it is only given thrice weekly during dialysis. It is a support to oral or tube feeding when nutritional targets cannot be achieved. It is also not by design a long term nutritional therapy but an interim measure to break the vicious cycle of protein energy wasting (PEW).3

When should IDPN be considered? The criteria for initiation and exclusion are outlined in Table 111.

The components of IDPN formulations generally include dextrose and amino acids with or without lipids. Vitamins and trace elements are not routinely added to IDPN because the additives can be lost in the dialysate. However, vitamins can be added in the last 30 minutes of the IDPN cycle for patients who do not tolerate oral multivitamin preparations12. IDPN can provide 500-100 kcal and 100g protein in a volume of less than one litre12,13,14.Both essential and nonessential amino acids are included in an IDPN formulation.

The presence of dextrose in IDPN formulations poses a concern with glycemic control. Serum glucose levels have been reported to increase by 20-100 mg/dL15 one hour into

the IDPN infusion in patients without diabetes; and another study of non-diabetic patients reported a highest glucose level of 214± 38 mg/dL, which decreased to <120mg/dL two hours post-dialysis16. Hence diabetic patients may require insulin in the IDPN infusion as well as subcutaneous insulin sliding scale injections. Capillary blood glucose levels should be checked before starting IDPN and at least once during the infusion4, although ideal glycemic levels for patients on IDPN are unknown. The conventional guideline for adding insulin to parenteral nutrition for diabetic patients is 0.1 unit of insulin per gram of dextrose17. However in light of prolonged action of insulin in ESRD patients, the addition of 5-8 units of insulin per liter of IDPN infusion when serum glucose concentrations approach 300 mg/dL has been suggested13,14. It is also important to observe for potential hypoglycemia after the discontinuation of IDPN with insulin. A 15-g carbohydrate snack during last half hour of IDPN has been proposed12. Table 2 provides examples of IDPN formulations.

Lipids are contraindicated in patients with soy or egg allergy, and are associated with thrombocytopenia and hepatic abnormalities, prompting caution with use in the dialysis population14. Lipid intolerance include nausea, vomiting, headache, dizziness, fever, flushing, drowsiness, chest and back pain, and erythema at the infusion site13. Nephrologists may choose to defer addition of lipids in IDPN for the first week of therapy to remove the confounding factor of lipid intolerance. Serum triglyceride levels should be monitored


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Table 1. Inclusion and Exclusion Criteria for IntradialyticParenteral Nutrition4

Criteria for Initiation:

Table 2. Examples of Intradialytic Parenteral Nutrition formulations (adapted from 2)


Amino Acids, Initial Concentration, % (Volume, ml)

Dextrose, Initial Concentration, % (Volume, mL) [Absolute value, g]

Kcal/ Protein, g


Volume, mL

Low protein/low dextrose

10 (500)

50 (150) [75]

455/50

750

Moderate protein/moderate dextrose

15 (500)

50 (250) [125]

725/75

750

High protein/ high dextrose

20 (500)

70 (250) [175]

995/100

750

High protein/ low dextrose

20 (500)

70 (100) [70]

638/100

600

High protein/ very low dextrose

20 (500)

70 (65) [45]

553/100

565

20% lipid emulsion can be added to any of the solutions to increase total kcal and final volume



Table 3. Protocol for IDPN administration21


Administering IDPN

Smofkabiven 8 EF chamber bags are mixed, attached to IV infusion pump and administered via venous return chamber.

Volume per hour

Total IDPN volume

1st IDPN session

125ml/hr

500ml

2nd IDPN session

200ml/hr

800ml

3rd IDPN session & thereafter

240ml/hr

960ml

Monitoring IDPN

Monitoring during IDPN Infusion

Parameter

Schedule

Capillary blood glucose

Pre-infusion, every hour on dialysis & 30 min post infusion

Laboratory tests

Urea, Creatinine, Sodium, Potassium, Calcium, Phosphate, Albumin

Liver function test Triglycerides levels

Initial session & thereafter weekly Initial session & thereafter monthly


prior to the first infusion and 6-24 hours after first infusion to determine adequacy of lipid clearance. A serum triglyceride level > 250mg/dL 6 hours after infusion or >400 mg/dL during infusion indicates poor lipid clearance17.

Our hospital protocol of IDPN is demonstrated in Table 3; correct mixing of Smofkabiven 8 EF chamber bags are vital for safe administration. IDPN is to be attached to an IV infusion pump and administered via venous return chamber; and infused at a constant rate during a typical four hour dialysis session given three times weekly. IDPN delivery is to be progressively built up18 over the first three sessions as outlined in Table 3. Capillary blood glucose is to be monitored prior, during and after IDPN infusion. Other parameters such as urea, creatinine, electrolytes, albumin, liver function, triglycerides levels should also be monitored weekly to monthly.


Effectiveness Of Idpn

In a study of eight patients comparing oral supplementation, IDPN and no supplementation (control), net whole body

net protein balance was significantly increased for both oral and IDPN group.15The effect of supplementation persisted in patients with oral supplementation after intradialytic nutrition therapy, but was lost in the IDPN group. This study was not carried out prospectively over time to test compliance and tolerance of the oral supplementation, however. Furthermore, the oral nutritional supplement and IDPN were not identical in nutrient distribution.

Chertow et al. carried out a retrospective, intent-to-treat study looking at effects of IDPN on morbidity of 1679 IDPN- treated patients with 22517 non-treated patients19 over a one-year period. Most IDPN patients received 15 kcal/kg and

1.2 g/kg of protein at each dialysis session. Dialysis patients with serum albumin <3.4 g/dL who were treated with IDPN had significant increases in albumin and creatinine (marker of muscle mass). Patients with serum albumin <3.4 g/dL and IDPN treated had lower odds ratio of death compared to those not treated. Serum levels of albumin 3 g/dL and creatinine 8 mg/dL resulted in odds ratio (OR) of 0.63 in the IDPN treated group. On the other hand, providing IDPN

to patients with normal serum albumin levels was associated with an increased risk of mortality (IDPN group with albumin 4 g/dL, creatinine > 8 mg/dL; Or 2.6, confidence interval (CI) 1.24 – 5.04, p<0.005; control group: CI 1.0). The survival disadvantage with IDPN in patients with normal serum albumin level could be related to risks outweigh benefits when the nutritional status is adequate. As this study was uncontrolled for, the association between IDPN and decreased mortality cannot be validated. The treatment effect for patients with serum albumin <3.4 g/dL could be due to positive effects of energy and protein provided for by IDPN, and at the same time, selection bias (very ill patients who were expected to die were not offered IDPN).

The first prospective, randomized, controlled trial evaluating effects of IDPN on mortality outcomes was published in 2007 by Cano et al20. 186 patients were randomized into oral supplement alone (500kcal/day and 25g/day protein) to oral supplement plus IDPN over one year. Consumption of oral supplementation were not limited to dialysis days, IDPN was not standardized among patients. Outcomes were monitored for total two years. These patients had at least two markers of malnutrition: BMI <20 kg/m2, body weight loss within six months >10%, serum albumin <3.5 g/dL, and serum prealbumin <30 mg/dL. The primary outcome was 2-year mortality and was similar between two groups (43% in


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References

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    IDPN group vs 39% in control group). Both groups showed improved BMI, albumin, prealbumin, decreased number of hospitalizations. Thus IDPN did not show additional benefit compared to oral nutritional supplementation. Compliance to oral nutritional supplements ranged from 61% to 75%. This suggests that consistent oral nutritional supplement will improve nutrition and decrease mortality; and IDPN should be reserved for those who are unable to tolerate oral nutritional supplementation or have contraindications against oral supplementation.


    Conclusion

    The use of IDPN has been shown to bring about improved serum albumin values in ESRD patients however the impact on long term patient survival is unclear. Studies to date are limited to short term parameters such as laboratory values. IDPN may be beneficial in patients who are malnourished and unable to consume adequate energy and protein, unable to tolerate oral supplementation, and who are able to meet nutritional needs via combination of oral diet plus IDPN3. Hence IDPN should be limited to those with profound malnourishment, serum albumin <3.4 g/dL, and who have failed attempts at enteral supplementation. More well- designed, prospective, randomized studies are needed to evaluate mortality differences among the different nutritional therapies.


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