CAM 80144

Intradialytic Parenteral Nutrition

Category:Therapy   Last Reviewed:September 2019
Department(s):Medical Affairs   Next Review:September 2020
Original Date:December 2003    

Description:
Intradialytic parenteral nutrition is the infusion of an intravenous hyperalimentation formula, such as amino acids, glucose, and lipids, during dialysis, to treat protein calorie malnutrition in an effort to decrease the morbidity and mortality experienced in patients with renal failure.

For individuals who are undergoing hemodialysis who receive intradialytic parenteral nutrition, the evidence includes multiple randomized controlled trials, observational studies, and systematic reviews of these studies. The relevant outcomes are overall survival, change in disease status, morbid events, health status measures, quality of life, treatment-related mortality and morbidity.Published systematic reviews, which includedrandomized controlled trials but could not pool data, haveconcluded that the current evidence does not demonstrate benefits in patient outcomes with the use of intradialytic parenteral nutrition for those who would not otherwise qualify for total parenteral nutrition. The evidence is insufficient to determine the effects of the technology on health outcomes. 

Background
PROTEIN CALORIE MALNUTRITION
Protein calorie malnutrition occurs in an estimated 25% to 40% of patients undergoing dialysis. The cause of malnutrition in patients on dialysis is often multifactorial and may include underdialysis, chronic inflammation, protein loss in the dialysate solution (particularly in peritoneal dialysis), untreated metabolic acidosis, and decreased oral intake.

Diagnosis
The clinical evaluation of malnutrition is multifactorial but typically includes measurement of serum albumin. Serum albumin levels correlate with nutritional status but are imperfect measures of nutrition because they can be affected by other disease states. Protein calorie malnutrition is associated with increased morbidity and mortality. For example, the risk of death is increased more than 10-fold in those whose serum albumin levels are less than 2.5 g/dL, and those with a serum albumin near the normal range (i.e., 3.5-3.9 g/dL) have a mortality rate twice as high as those with an albumin level greater than 4.0 g/dL.

Treatment
In patients receiving chronic dialysis, the National Kidney Foundation currently recommends a daily protein intake of 1.2 g/kg or more in patients undergoing hemodialysis and 1.3 g/kg or more in patients undergoing peritoneal dialysis.1 When malnutrition is present, a stepwise approach to treatment is generally used, beginning with dietary counseling and diet modifications, followed by oral nutrition supplements, and then by enteral nutrition supplements or parenteral nutrition supplements if needed. 

Intradialytic parenteral nutrition (IDPN), which refers to the infusion of hyperalimentation fluids at the time of hemodialysis or peritoneal dialysis, has been investigated as a technique to treat protein calorie malnutrition in an effort to decrease associated morbidity and mortality. IDPN solutions are similar to those used for total parenteral nutrition (TPN). A typical solution contains 10% amino acids, 40% to 50% glucose, 10% to 20% lipids, or a mixture of carbohydrate or lipids, depending on patient needs. In hemodialysis, the IDPN infusion is administered through the venous port of the dialysis tubing, typically, 30 minutes after dialysis has begun, and continued throughout the dialysis session.

Regulatory Status
TPN solutions are compounded by an individual pharmacy from individual ingredients (e.g., dextrose, amino acids, trace elements) into a finished medication based on a prescription and are not required to have approval from the U.S. Food and Drug Administration (FDA) through a new drug application process. Compounding pharmacies have historically been subject to regulation by state pharmacy boards, although FDA has increased its regulatory oversight with the Drug Quality and Security Act of 2013.

Peritoneal dialysis solutions are regulated as drugs by FDA. One amino acid-based peritoneal dialysate, Nutrineal PD4, 1.1% Amino Acid Peritoneal Dialysis Solution (Baxter Corp.) is available commercially outside of the United States, but has not been FDA approved.

Policy:

  • Intradialytic parenteral nutrition may be considered MEDICALLY NECESSARY when it is offered as an alternative to a regularly scheduled regimen of total parenteral nutrition only in those patients who would be considered candidates for total parenteral nutrition (TPN), i.e., a severe pathology of the alimentary tract that does not allow absorption of sufficient nutrients to maintain weight and strength commensurate with the patient’s general condition.
  • Intradialytic parenteral nutrition is considered NOT MEDICALLY NECESSARY in those patients who would be considered a candidate for TPN, but for whom the intradialytic parenteral nutrition is not offered as an alternative to TPN, but in addition to regularly scheduled infusions of TPN.
  • Intradialytic parenteral nutrition is considered INVESTIGATIONAL in those patients who would not otherwise be considered candidates for TPN.

Policy Guidelines
Patients who are considered candidates for TPN are those who have a severe pathology of the alimentary tract that does not allow absorption of sufficient nutrients to maintain weight and strength commensurate with the patient’s general condition.

This policy only addresses intravenous parenteral nutrition as an adjunct to hemodialysis (not peritoneal dialysis).

Benefit Application
BlueCard®/National Account Issues

As discussed further in the Rationale section, Medicare coverage for intradialytic parenteral nutrition is considered contractually excluded for those who would not otherwise qualify for total parenteral nutrition (TPN). For those who do qualify, claims may be reviewed for medical necessity to determine whether the intradialytic parenteral nutrition is offered in lieu of scheduled infusions of TPN (considered medically necessary), or offered in addition to regularly scheduled infusions of TPN (potentially not medically necessary)

Rationale
This evidence review was created in December 2003 and has been updated regularly with searches of the MEDLINE database. The most recent literature update was performed through March 6, 2019. 

Evidence reviews assess the clinical evidence to determine whether the use of technology improves the net health outcome. Broadly defined, health outcomes are the length of life, quality of life (QOL), and ability to function -- including benefits and harms. Every clinical condition has specific outcomes that are important to patients and managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms. 

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of technology, two domains are examined: the relevance, and quality and credibility. To be relevant, studies must represent one or more intended clinical uses of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. RCTs are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice. 

For patients who qualify for total parenteral nutrition and are concomitantly receiving hemodialysis, it is reasonable to administer intradialytic parenteral nutrition (IDPN) solution, which is similar to a total parenteral nutrition solution. IDPN is administered via the existing venous port of the dialysis tubing rather than through an alternative intravenous site. This evidence review focuses on studies evaluating whether IDPN as an adjunct to hemodialysis improves outcomes for individuals who may be at risk for malnutrition but who would not otherwise receive parenteral nutrition. 

Intradialytic Parenteral Nutrition 
Clinical Context and Therapy Purpose
The purpose of IDPN in patients who are undergoing hemodialysis is to provide a treatment option that is an alternative to or an improvement on existing therapies.
The question addressed in this evidence review is: Does IDPN improve the net health outcome in patients who are undergoing hemodialysis? 

The following PICOs were used to select literature to inform this review. 

Patients 
The relevant population of interest areis patients who are undergoing hemodialysis. 

The cause of malnutrition in patients on dialysis is often multifactorial and may include underdialysis, chronic inflammation, protein loss in the dialysate solution (particularly in peritoneal dialysis), untreated metabolic acidosis, and decreased oral intake. 

Interventions 
The therapy being considered is IDPN. IDPN is the infusion of an intravenous hyperalimentation formula, such as amino acids, glucose, and lipids, during dialysis, to treat protein calorie malnutrition. 

Comparators 
The following practices are currently being used to make decisions about IDPN. 

Relevant comparators are standard of care. When malnutrition is present, a stepwise approach to treatment is generally used, beginning with dietary counseling and diet modifications, followed by oral nutrition supplements, and then by enteral nutrition supplements or parenteral nutrition supplements if needed. 

Outcomes 
The general outcomes of interest are overall survival, change in disease status, morbid events, health status measures, QOLquality of life, treatment-related mortality, and treatment-related morbidity. 

Systematic Reviews
A systematic review conducted for the U.S. Department of Veterans Affairs Evidence Synthesis Program was published in 2018 (Table 1).2, The review addressed the effectiveness and adverse effects of IDPN for the treatment of malnutrition in hemodialysis patients (Table 1). The reviewers included five RCTs and six comparative observational studies (four prospective and tworetrospective). The reviewers also identified three systematic reviews but because they did not include a formal quality assessment of individual studies or did not include any relevant primary studies, these were used only to identify additional primary studies. Outcomes included clinically relevant improvements in individual indicators of nutrition status, global nutrition status, mortality, morbidity, hospitalization, and QOL. Included primary studies compared IDPN to oral suppements, dietary counseling, or usual care. Usual care was not well-defined in the studies and could include dietary counseling or oral supplements based on patient condition and physician recommendation. The study sample sizes were small (range 12 to 196), with the exception of one large retrospective cohort study (n=24196). The critiera for malnutrition varied across the studies, with most using serum albumin of < 3.5 g/dL or < 4.0 g/dL along with at least one other predictor of malnutrition (weight loss, BMI, nutritional score or assessment). No studies compared IDPN to enteral nutrition.

Table 1. Systematic Review  Characteristics  

Study

Dates

Studies

Participants

N (Range)

Design

Duration

Anderson et al (2018)2,

2009-2017

5 RCTs, 4 prospective cohort, 2 retrospective cohort

Mean age 65 years (37 to 80)

Mean 50% male

At least 6 months on dialysis prior to inclusion in study

Mean serum albumin 3.77 g/dL (range 3.02 to 3.8 g/dL)

BMI range 19.2 to 23.4 kg/m2

602 (12 to 196), excluding one large retrospective cohort study (N=24,196)

RCTs and observational studies

12 weeks to 2 years

 

 

RCT: randomized controlled trial; BMI: body mass index.

Compared to oral supplements and dietary counseling, IDPN did not improve the patient health outcomes mortality, hospitalization, or QOL (See Table 2). Observational studies found mixed results for IDPN compared to usual care for mortality, with results differing based on baseline serum albumin levels. The effect of IDPN on nutritional indicators also varied across comparisons and studies.

Table 2. Systematic Review Results

Study

IDPN vs Oral Supplements: Mortality

IDPN vs Oral Supplements: Hospitalization IDPN vs Oral Supplements: Quality of life IDPN vs Oral Supplements: Nutritional Indicators IDPN vs Dietary Counseling: Mortality IDPN vs Dietary Counseling: Hospitalization IDPN vs Dietary Counseling: Quality of life IDPN vs Dietary Counseling: Nutritional Indicators IDPN vs Ususal Care: Mortality IDPN vs Usual Care: Quality of life IDPN vs Usual Care: Nutritional indicators

Anderson et al (2018)

                     
Evidence 1 RCT3, 1 RCT3, 1 RCT3, 2 RCTs,3,4, 1 cohort study5, 1 RCT6, 1 RCT6, 1 RCT6, 1 RCT6, 3 cohort studies5,7, 1 RCT8,

2 RCTs,3,8, 3 cohort studies5,7,9,

                       

Total N (range)

186 (NA)

186 (NA) 186 (NA)

238 (20 to 186)

107 (NA) 107 (NA) 107 (NA) 107 (NA)

24,305 (28 to 24,196)

40 (NA) 347 (12 to 186)

Effect

43% vs 39%; P = NS

# days hospitalized/days followup: 0.008 vs 0.06 (P = NS) No difference in Karnofsky score (data NR)

Mean change: SA (g/dl): 0.18 (P =.048) vs 0.28 (P =.17)

Mean change: BMI: -0.10 (P = 0.87) vs -0.10 (P =.69) MAC: -1 (P =.09) vs 0.47 (P =.35) TSF: -0.43 (P = 0.5) vs 0.42 (P =.66)

26.4% (14/53) vs 12.9% (7/54) (P-value NR) 59.0% vs 43.2%, P =.1509 (SF-12) score change from baseline at 16 wks. -2.74 vs 0.34, P =.1175

Positive response to IDPN (≥ 30mg/L increase in PA) 48.7% vs 31.8% at week 16 (P =.1164) Patients achieving > 15% increase from baseline at week 4, PA (mg/L): 41% vs 20.5%, P =.0415

Improved SGA score by one grade: 20.5% vs 13.6%, P =.4037

Survival: RR = 1.34, P <.01 (Cox) Time to death (mo) for nonsurvivors: 16.9 vs 7.5, P <.01

OR death: (SA ≥ 4.0 g/dL & CRE > 8.0 mg/dL) = 2.6 (95% CI 1.34 - 5.04) SA ≤ 3.3 =0.72* (P <.01) SA ≤ 3.0 g/dL = 0.57 (95% CI 0.44 - 0.77)

Mortality: 0% vs 27.8%, (P <.02)

No improvement in functional capacity (data NR)

No difference in change in SA or PA (data NR)

No difference in change in BMI (data NR)

Mean change: SA (g/dL) 0.93 (P =.001) vs - 0.14 (P = 0.316)

Mean change: BMI 2.8 (P =.001) vs 0.03 (P =.981)

Mean change: MIS -8.75 (P =.001) vs 0.25 (P =.716)

 

 

                   

Summary

No improvement

No improvement No improvement Variable effect with no improvement  except serum albumin in a single study No improvement No improvement No improvement Variable effects on serum prealbumin No improvement in serum albumin or subjective global assessment Variable effect on mortality; effect differs by baseline serum albumin level No improvement Variable effect, with improvement in at least one nutritional indicator

IDPN: intradialytic parenteral nutrition; RCT: randomized controlled trial; N: sample size; NA: not applicable; NS: nonsignificant; NR: not reported; SA: serum albumin; BMI: body mass index; OR: odds ratio; PA: serum prealbumin; SGA: subjective global assessment; RR: relative risk; CI: confidence interval; SF-12: 12-Item Short-Form Health Survey; TSF: tricep skin fold; MAC: mid-arm circumference.  

The reviewers concluded that "IDPN does not appear to improve patient health or clinically important nutritional outcomes compared to the standard and recommended treatments of oral supplementation or dietary counseling." They further concluded, "Although IDPN has not been explicitly studied in hemodialysis patients who have failed adequate trials of or are unable to receive dietary counseling, oral, and/or enteral tube feeding due to malfunctioning GI tract or other issues, since evidence ‒ albeit limited ‒ has not raised concerns about IDPN safety, we agree with existing guidelines that it appears reasonable to consider use of IDPN in this population."2, 

Randomized Controlled Trials
Five RCTs on IDPN were included in the systematic review conducted by Anderson et al(2018) and are discussed above.  

Summary of Evidence
For individuals who are undergoing hemodialysis who receive IDPN, the evidence includes multiple RCTs, observational studies, and systematic reviews of these studies. The relevant outcomes are overall survival, change in disease status, morbid events, health status measures, QOL, treatment-related mortality and morbidity. Published systematic reviews, which included RCTs but could not pool data, haveconcluded that the current evidence does not demonstrate benefits in patient outcomes with the use of IDPN for those who would not otherwise qualify for total parenteral nutrition. The evidence is insufficient to determine the effects of the technology on health outcomes.

Practice Guidelines and Position Statements
National Kidney Foundation
National Kidney Foundation (2001) clinical guidelines established target daily protein requirements in patients undergoing chronic dialysis.1,The Foundation (2008) updated its pediatric nutrition guidelines to recommend a trial of intradialytic parenteral nutrition (IDPN) to augment inadequate nutritional intake for malnourished children (body mass index for height and age <5th percentile) receiving maintenance hemodialysis who are unable to meet their nutritional requirements through oral and tube feeding.3,

American Society for Parenteral and Enteral Nutrition
TheASPEN (2010) issued guidelines on nutritional support in adults in acute and chronic renal failure. The ASPEN assigned a level C recommendation (supported by at least one level II investigation) that IDPN should not be used as a nutritional supplement in malnourished chronic kidney disease-V hemodialysis patients. The basis for the recommendation was a large randomized controlled trial that found mortality rates did not differ between malnourished patients receiving IDPN and malnourished patients receiving oral supplements without IDPN. An additional concern was that IDPN "is limited by the need to complete the entire nutrient infusion during the hemodialysis" treatment, which may cause adverse events because of the rapid infusion of glucose and lipids. ASPEN further recommended larger randomized controlled trials "in malnourished patients are needed to ensure that a clinical benefit of IDPN does not exist."10,

U.S. Preventive Services Task Force Recommendations
Not applicable.

Ongoing and Unpublished Clinical Trials
A search of ClinicalTrials.gov in April 2019 did not identify any ongoing or unpublished trials that would likely influence this review.

References:

  1. Kopple JD. The National Kidney Foundation K/DOQI clinical practice guidelines for dietary protein intake for chronic dialysis patients. Am J Kidney Dis. Oct 2001;38(4 Suppl 1):S68-73. PMID 11576926.
  2. Anderson J, Peterson K, Bourne D, Boundy E. Evidence Brief: Use of Intradialytic Parenteral Nutrition (IDPN) to Treat Malnutrition in Hemodialysis Patients. VA ESP Project #09-199; 2018; https://www.ncbi.nlm.nih.gov/books/NBK518608/. Accessed April 2, 2019.
  3. KDOQI Clinical Practice Guideline for Nutrition in Children with CKD: 2008 update. Executive summary. Am J Kidney Dis. Mar 2009;53(3 Suppl 2):S11-104. PMID 19231749.
  4. Liu, YY, Xiao, XX, Qin, DD, Tan, RR, Zhong, XX, Zhou, DD, Liu, YY, Xiong, XX, Zheng, YY. Comparison of Intradialytic Parenteral Nutrition with Glucose or Amino Acid Mixtures in Maintenance Hemodialysis Patients. Nutrients, 2016 Jun 9;8(6). PMID 27271658.
  5. OÄŸuz, YY, Bulucu, FF, Vural, AA. Oral and parenteral essential amino acid therapy in malnourished hemodialysis patients. Nephron, 2001 Sep 11;89(2). PMID 11549907.
  6. Capelli JP, Kushner H, Camiscioli TC, et al. Effect of intradialytic parenteral nutrition on mortality rates in end- stage renal disease care. Am J Kidney Dis. Jun 1994;23(6):808-816. PMID 8203363.
  7. Hiroshige, KK, Iwamoto, MM, Kabashima, NN, Mutoh, YY, Yuu, KK, Ohtani, AA. Prolonged use of intradialysis parenteral nutrition in elderly malnourished chronic haemodialysis patients. Nephrol. Dial. Transplant., 1998 Aug 27;13(8). PMID 9719170.
  8. Thabet, AA, Moeen, SS, Labiqe, MM, Saleh, MM. Could intradialytic nutrition improve refractory anaemia in patients undergoing haemodialysis?. J Ren Care, 2017 Jun 22;43(3). PMID 28636166.
  9. Joannidis, MM, Rauchenzauner, MM, Leiner, BB, Rosenkranz, AA, Ebenbichler, CC, Laimer, MM, Tatarczyk, TT, Meusburger, EE, Mayer, GG. Effect of intradialytic parenteral nutrition in patients with malnutrition-inflammation complex syndrome on body weight, inflammation, serum lipids and adipocytokines: results from a pilot study. Eur J Clin Nutr, 2007 May 25;62(6). PMID 17522619.
  10. Brown RO, Compher C, American Society for Parenteral Enteral Nutrition Board of Directors. A.S.P.E.N. clinical guidelines: nutrition support in adult acute and chronic renal failure. JPEN J Parenter Enteral Nutr. Jul-Aug 2010;34(4):366-377. PMID 20631382.
  11. Kopple JD, Foulks CJ, Piraino B, et al. Proposed Health Care Financing Administration guidelines for reimbursement of enteral and parenteral nutrition. Am J Kidney Dis. Dec 1995;26(6):995-997. PMID 7503076.
  12. Department of Health and Human Services, Health Care Financing Administration. HCFA Rulings. Ruling No. 96-3. 1996; https://www.cms.gov/Regulations-and-Guidance/Guidance/Rulings/downloads//hcfar963.pdf. Accessed April 9, 2018.

Coding Section

Codes

Number

Description

CPT  90935-90940 

Hemodialysis, code range 

  90945-90947

Peritoneal dialysis, code range 

  90951-90970

End-stage renal disease services, code range 

HCPCS  B4164-B5200 

Parenteral nutrition, code range 

ICD-9 Diagnosis  585.1-585.9  Chronic kidney disease, code range 
  586  Renal failure, unspecified 
ICD-10-CM (effective 10/01/15)  N18.1-N18.9  Chronic kidney disease, code range 
  N19  Unspecified kidney failure 
ICD-10-PCS (effective 10/01/15)    ICD-10-PCS codes are only used for inpatient services. There is no specific ICD-10-PCS code for this procedure. 
  3E0336Z, 3E0436Z, 3E0536Z, 3E0636Z  Introduction, physiological systems and anatomical regions, percutaneous, nutritional substance, code by body part (peripheral vein, central vein, peripheral artery , central artery) 
  5A1D00Z, 5A1D60Z  Extracorporeal assistance and performance, performance, urinary, code by duration (single filtration or multiple filtration) 
  3E1M39Z  Irrigation, peritoneal cavity percutaneous dialysate 
Type of Service     
Place of Service    

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each Policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross and Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

"Current Procedural Terminology© American Medical Association.  All Rights Reserved" 

History From 2014 Forward     

09/03/2019 

Annual review, no change to policy intent. Updating description, rationale and references. 

09/04/2018 

Annual review, no change to policy intent. Updating rationale and references. 

09/19/2017 

Annual review, no change to policy intent. Updating background, description, rationale and references. 

09/01/2016 

Annual review, no change to policy intent. 

09/01/2015 

Annual review, no change to policy intent. Updating background, description, rationale, references and coding. Added guidelines and regulatory status. 

09/17/2014

Annual review. Updated description/background, rationale and references. No change to policy intent. 


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