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This article outlines the work involved in producing ESPEN’s new guidelines on parenteral nutrition and analyses the difficulties associated with such a project
Federico Bozzetti MD Istituto Nazionale per lo Studio
e la Cura dei Tumori Milan Italy Coordinator ESPEN PN Guidelines
The European Society for Clinical Nutrition and Metabolism (ESPEN) is an organisation dedicated to all issues concerning enteral (EN) and parenteral (PN) nutrition and metabolism and, among other aims, it promotes the development of clinical practice guidelines.[1]
The ESPEN clinical practice guidelines on PN reflect the current scientific knowledge in the field of clinical nutrition and summarise the evidence when PN is recommended and which outcomes can be attained in regard to the basic disease, nutritional status and quality of life. The main aim of clinical practice guidelines on PN is to guide clinicians, dieticians and nurses who are involved in the nutritional support of patients, in hospital or at home, to the correct recommendation and administration of PN.
The present clinical practice guidelines on PN are the natural continuation of the ESPEN clinical practice guidelines on EN that were published in 2006 in Clinical Nutrition[2] and they follow, whenever possible, their general structure.
They try to answer the following questions:
- What influence does the disease exert on nutritional state and energy and on substrate metabolism?
- What influence does nutritional state exert on outcome of the basic disease?
- What are the goals of PN?
- When is PN indicated?
- Is PN better than EN?
- Has PN specific contraindications or complications?
There are a few completely new sections (home PN, central venous catheter care, prevention and treatment of complications), but the majority closely mimics the frame of the EN clinical practice guidelines. Especially for some general and introductory parts, the original version of the EN clinical practice guidelines was almost integrally maintained or just updated as required.
Development and methodology
Following a formal commitment on behalf of the ESPEN Executive Committee in early 2005 the clinical practice guidelines were developed in the subsequent two years. In addition to a careful scrutiny of the literature through the usual databases (Scopus, Pubmed, Cochrane, Medline, EMBASE), the clinical practice guidelines from other scientific societies were examined, especially the two editions from the Italian Society for Parenteral and Enteral Nutrition,[3,4] those from the American Society for Parenteral and Enteral Nutrition,[5] and those from the German Society for Nutritional Medicine.[6,7] The quality and strength of the supporting literature was graded according to the criteria of SIGN[8] and the Agency for Health Care Policy and Research.[9] The grade of recommendation depended on the scientific quality of the studies as reported in Table 1.
European vs American/Canadian guidelines
In the USA the American Society for Parenteral and Enteral Nutrition has published different official documents over the years, sometimes specifically addressed to parts of the nutritional team or regarding specific problems (eg, compounding mixtures, central venous catheter care). A major difference between the American and the European guidelines is that the American deal with both enteral and intravenous nutritional support together, whereas the ESPEN clinical practice guidelines present the two approaches in separate issues of clinical nutrition.
There are also excellent guidelines published by the Canadian society.[10] However, they only relate to the nutritional support of intensive care unit patients. This limited focus allowed the authors, who worked in a national tightly connected network, the unique opportunity to elaborate ex-novo data from the literature through several systematic reviews and meta-analyses of different topics rather than to rely on already published data. They thus offer results and recommendations that are quite original.
[[HHE.C22]]
Specific problems of PN guidelines
The aim of the clinical practice guidelines is to develop recommendations that are based on good research evidence.[11,12] The majority of the recommendations in this area are based on fair research evidence or on expert consensus. This was evident also in the ASPEN Guidelines in Nutrition Support5 since only 16% of the recommendations were judged to be based on good research-based evidence (meta-analysis of RCTs or single RCTs), 29% on fair researchbased evidence (well-designed controlled or non-controlled studies without randomisation, non-experimental studies such as comparative, correlational or case studies) and finally 55% on expert opinion alone. A similar percentage also applies to the present ESPEN clinical practice guidelines. However, this should not classify the recommendations of these guidelines as poorquality statements. It simply reflects the fact that the gold standard methodology to scientifically validate a drug or a therapy (the RCT) cannot always be used to investigate the efficacy of a treatment, such as nutritional support, which is essential for survival.
As clearly stated in the ASPEN Guidelines: “a major distinction between therapeutic trials of efficacy of a drug or a procedure and the feeding of nutrients known to be essential to maintenance of human health and survival must be made. Withholding a drug or invasive procedure will not produce disease in otherwise healthy humans, whereas essential nutrients must be provided to both healthy and ill people …” [5]
Therefore, with regard to previous[13] and recent[14] claims by authoritative American colleagues that EN and PN have to be considered as a medical therapy and their proposal to replace the term “nutritional support” with “nutritional therapy”, it is apparent that such a definition can be properly applied when nutritional support is in some way “optional” and may be investigated through RCTs in clinical settings in which one arm receives an “additional” PN and the other “conventional” nutrition. However, in many clinical conditions characterised by long-term intestinal failure it is ethically impossible to randomise between nutrition and non-nutrition, because there is not “equipoise”.[15] This means that there is not a genuine uncertainty that the outcome of patients deprived of nutrition is similar to that of patients receiving a nutritional support.
The lack of appreciation that nutrition may encompass a broad area of clinical conditions that at its two extremes include a true therapy and a basic support may have worrying consequences. For instance, if PN is definitely accepted as a therapy, the medical community would expect it to be validated by RCTs, and such validation may be also required to be strongly recommended in the guidelines and to be economically covered by the public health system. Moreover, if it represents only a therapy that may be or may be not carried out, its discontinuation in incompetent patients is easier to be ethically accepted than if it is considered a simple supportive care.
This may be why scientific societies do not unanimously agree on the proper definition of artificial nutrition (especially in incompetent patients on long-term PN), and such controversy may reflect different positions of caregivers,[16] patients and the public.
Chairs of the committees of the ESPEN Guidelines
Cardiology/pneumology: SD Anker, Germany; Central venous catheters: M Pittiruti, Italy; Gastroenterology: A Van Gossum, Belgium; Geriatrics: L Sobotka, Czech Republic; Hepatology: M Plauth, Germany; Home parenteral nutrition: M Staun, Denmark; Intensive care: P Singer, Israel; Nephrology: N Cano, France; Oncology: F Bozzetti, Italy; Pancreas disease: L Gianotti, Italy; Surgery and transplantation: M Braga, Italy.
References
1. Committee to Advise the Public Health Service on Clinical Practice Guidelines, Institute of Medicine. Field MU, Lohr
KN, editors. Clinical practice guidelines: direction of a new program. Washington (DC): National Academy Press; 1990.
2. Valentini L, Schutz T, Allison S, Howard P, Pichard C, Lochs H. ESPEN Guidelines on Enteral Nutrition. Clin Nutr 2006; 25:175-360.
3. Linee Guida SINPE per la Nutrizione Artificiale nel paziente ospedalizzato. Riv Ital Nutr Parent Ent 1995;13:S 2.
4. Linee Guida SINPE per la Nutrizione Artificiale Ospedaliera. Riv Ital Nutr Parent Ent 2002;20:S1-S171.
5. ASPEN Board of Directors and Clinical Guidelines Task Force. Guidelines for the use of Parenteral and Enteral Nutrition in adult and pediatric patients. JPEN J Parenter Enter Nutr 2002;26 Suppl 1.
6. Lochs H, Lubke H, Weimann A, editors. Leitlinie Enterale Ernahrung. Aktuel Ernaehr Med 2003;28 Suppl 1:S1-S121.
7. Lochs H, Volkert D, Krys U, editors. Leitlinie Enterale Ernahrung Teil 2. Aktuel Ernaehrung Med 2004;29:187-232.
8. Scottish Intercollegiate Guidelines Network. SIGN guidelines: an introduction to SIGN methodology for the development of evidence-based clinical guidelines. SIGN Publication No. 39. Edinburgh: SIGN Secretariat, Royal
College of Physicians of Edinburgh; 1999.
9. Agency for Health Care Policy and Research. Clinical practice guideline No. 1. AHCPR Publication No. 92-0023;
1993.
10. Heyland DK, Dhalikawal R, Drower JW, et al. Canadian clinical practice guidelines for nutrition support in mechanically ventilated critically ill adult patients. JPEN J Parenter Enter Nutr 2003;27:355-73.
11. Evidence-based Medicine Working Group. Evidence-based medicine. JAMA 1992;268:2420.
12. Sackett DL, Rosenberg WMC, Haynes RB, Richardson WS. Evidencebased medicine: what it is and what it
isn’t. BMJ 1996;310:71.
13. Lipman TO. Grains or veins: is enteral nutrition really better than parenteral nutrition? A look at the evidence. JPEN J Parenter Enter Nutr 1998;22:167-82.
14. Wischmeyer PE. JPEN: state of the journal. JPEN J Parenter Enter Nutr 2008;32:101-3.
15. Freedman B. Equipoise and the ethics of clinical research. New Engl J Med 1987;317:141-5.
16. Bozzetti F. Feeding the patient with an incurable disease: a voice out of the chorus. Nutr Ther Metab 2006;
24:60-63.
