The ESPEN clinical practice guidelines on Parenteral Nutrition: Present status and
perspectives for future research
Federico Bozzettia,c, Alastair Forbesb,d
aDepartment of Surgery, Hospital of Prato, Piazza dell’Ospedale 5, 59100 Prato, Italy
bDepartment of Gastroenterology & Clinical Nutrition, University College London, Windeyer Institute, Cleveland Street, London W1, UK
a r t i c l e i n f o
Received 11 May 2009
Accepted 11 May 2009
s u m m a r y
The ESPEN Guidelines on Parenteral Nutrition (PN) reflect current scientific knowledge in the field of
clinical nutrition in adults. They summarize the indications for PN and its anticipated outcomes in
respect of the underlying disease, nutritional status and quality of life. They are companion documents to
the ESPEN Guidelines on Enteral Nutrition and follow the same general format. They address the
influence of the underlying disease on the patient’s nutritional status, and that of malnutrition on the
outcome of the disease. Contraindications to and complications of PN are considered, together with
comparative analyses of the roles of the parenteral and enteral routes in different illness states.
The quality and strength of the supporting literature has been graded according to the criteria of the
Scottish Intercollegiate Guidelines Network (SIGN) and the Agency for Health Care Policy and Research.
Hence, meta-analysis of randomised clinical trials (level of evidence Ia) or at least one randomised
clinical trial (level of evidence Ib) translate to a Grade A recommendation. Levels of evidence IIa, IIb and
III are attributed respectively to: at least one well-designed controlled trial without randomisation; at
least one other type of well-designed, quasi-experimental study; or well-designed non-experimental
descriptive studies such as comparative studies, correlation studies, case-control studies; each of these
sustains a Grade B recommendation. Grade C recommendations reflect expert opinion and/or the clinical
experience of respected authorities (level of evidence IV).
Each of the 11 sets of PN Guidelines was devised by an international working group, the total faculty
comprising no fewer than 87 experts from 16 European/Mediterranean countries, each group’s contri-
butions being co-ordinated by a designated chairman. Once each guideline had been approved by all the
members of the relevant working group, this version was reviewed by at least two independent external
reviewers (one selected from ESPEN’s Education and Clinical Practice Committee, and at least one from
outside the ESPEN committee structure). Following this review each guideline was hosted in draft form
on the public pages of the ESPEN website for at least one month to permit the receipt of comments or
suggestions from any interested party. At this point the Guidelines were reviewed and revised again by
the original working group chairman and submitted to the Clinical Nutrition editorial process. At least 3
further reviewers were selected by the Journal’s editorial office for each guideline, in line with the
normal selection process. Final revisions were performed by the Chairmen of the working groups, and by
ourselves as commissioning editors of the whole project.
More than 300 evidence-based recommendations are now presented. Fewer than one sixth of the
recommendations are Grade A, and disappointingly, but unsurprisingly, more than 50% are Grade C. The
need for more and better controlled trials in the field remains apparent.
? 2009 European Society for Clinical Nutrition and Metabolism. All rights reserved.
‘‘Knowledge is the enemy of disease’’
1. Definitions and aims of the guidelines
The past decade has seen a dramatic increase in the number of
guidelines produced worldwide, with literally hundreds of Clinical
Practice Guidelines (CPGs) having been issued by different medical
organisations. The stimulus for such proliferation has been attrib-
uted in part to the unexplained variety in medical practices in
E-mail addresses: email@example.com (F. Bozzetti), firstname.lastname@example.org, espenjournals@
espen.org (A. Forbes).
cTel.: þ39 02 26410267, 329 7655385.
dTel.: þ44 8451 555 000x9011.
Contents lists available at ScienceDirect
journal homepage: http://www.elsevier.com/locate/clnu
0261-5614/$ – see front matter ? 2009 European Society for Clinical Nutrition and Metabolism. All rights reserved.
Clinical Nutrition 28 (2009) 359–364
different countries, and concerns about inappropriate use (over-,
under- and mis-use) of interventions, and the use of interventions
in the absence of established effectiveness.1The expansion has also
been driven by evidence-based medicine and the increasing need
for health care purchasers to base spending on proven effective
measures. CPGs aim to improve consistency of care and cost-
effectiveness. When there has been variation in practice, explicit
guidelines may improve clinical practice.2The European Society for
Clinical Nutrition and Metabolism (ESPEN), as an international
organisation dedicated to all issues concerning enteral (EN) and
parenteral (PN) nutrition and metabolism, therefore, among its
aims, promotes the development of CPGs.
CPGs are commonly defined as ‘‘systematically developed
statements to assist practitioner and patient decisions about
appropriate health care for specific clinical circumstances’’.3The
ESPEN CPGs on PN are mainly intended for physicians, but, since
correct practical administration plays a fundamental role in terms
of safety and efficiency, some parts are addressed more specifically
to nurses and other health care workers.
These CPGs do not address the autonomy, choices and respon-
sibilities of health professionals, since the complexity and vari-
ability of institutions, health organisations, pathologies and
patients is too great to be neatly encapsulated. However, they are
intended to present safe-guards for the user, by virtue of supplying
guidance so as to improve the well-being of the patient and to
minimise the chance of exposing the patient to hazardous or futile
health interventions. The CPGs should be used flexibly with adap-
tation to specific situations and circumstances taking into account
availability of resources, the specific medical condition to be
addressed, and the characteristics (medical, social, administrative)
of the clinical setting.
The present CPGs on PN reflect current scientific knowledge in
clinical nutrition, and summarize the evidence for indications for
PN, and the outcomes which can be attained in respect of the
underlying disease, and the patient’s nutritional status and
quality of life. Their main aim is to guide clinicians, dieticians,
nurses and other caregivers involved in the nutritional support of
patients in hospital or at home, to the optimal use of PN. Theyare
intended to be complementary to the ESPEN CPGs on enteral
nutrition,4and accordingly, whenever possible, follow their general
The CPGs on PN aim to answer the following questions:
- What influence does the disease exert on nutritional state and
energy and substrate metabolism?
- What influence does nutritional state exert on the outcome of
the underlying disease?
- What are the goals of PN?
- When is PN indicated?
- Is PN better than EN?
- Does PN have specific contraindications or complications?
Depending on the topic concerned, there is variable availability
of evidence-based literature. Consequently the proportion of
practical evidence-based recommendations, compared to those
based only on considerations of pathophysiology or on conflicting
results from literature varies substantially. In general, the larger the
number of recommendations from the evidence-based literature,
the lower the requirement for explanation in the comments. As the
percentage of Grade A recommendations lies between 7% and 30%
for different topics it is clear that each chapter should be read and
In drafting the CPGs for PN the authors had the opportunity to
consider the ESPEN EN guidelines4as a model with regard to the
methodology of scrutinizing the scientific literature, determining
rationale and recommendations, scoring their strength, and in
presenting the document.
of PN as it so often becomes necessaryonly whenpatients requiring
nutritional support cannot be fed orally or enterally. There are very
the enteral one. The time-honoured dogma that the ‘‘bowel rest’’
achieved through exclusive PN was safe and useful in gastrointes-
tinal disease has been progressively eroded, to be replaced by the
recognition that enteral disuse contributes to mucosal atrophy,
disturbances in gut permeability, disruption of enteric hormone
function, and to potentially damaging alteration of the gut flora and
the immune response. In only a few conditions does PN retain
aprivilegedrole over ENin the presence of a functioninggut.6–8The
new guidelines also contain technique-specific sections on home
PN, and on central venous catheters used in nutritional support.
2. Development and methodology
The present guidelines were commissioned by the Executive
Committee of ESPEN in 2005, to the then current standards for
guideline construction, and are now formally adopted by ESPEN.
The published literature was scrutinized carefully using such
search terms as ‘‘parenteral’’, ‘‘TPN’’, ‘‘nutritional support’’, ‘‘intra-
venous’’, ‘‘HPN’’, together with terms for the disease, organ or
pathological process determined by the chapter concerned.
Searches were performed on general electronic databases (Scopus,
PubMed, Cochrane Library, Medline, EMBASE). Existing topic-
specific ESPEN CPGs and guidelines from other scientific societies
were also examined, including: those of the Italian Society for
Parenteral and Enteral Nutrition9,10; the Italian guidelines on Home
Artificial Nutrition11,12; those from the German Society for Nutri-
tional Medicine13,14; those from the Scottish Home Parenteral
Nutrition Managed Clinical Network Protocols15; those from the
Australasian Society of Parenteral and Enteral Nutrition16; the
several publications of the American Society for Parenteral and
Enteral Nutrition17–21; the joint recommendations of the American
Society for Parenteral and Enteral Nutrition and the American
Society for Clinical Nutrition22; and the guidelines from the UK
National Institute for Health & Clinical Excellence (NICE) on
Nutrition Support in Adults.23There was no systematic attempt to
search for ‘‘grey literature’’ such as abstracts, theses, conference
reports, and unpublished literature. The search strategy was
restricted toadult patients given the recent comprehensive reviews
of parenteral and enteral nutrition in pediatrics.24–26
The quality and strength of the supporting literature was graded
according to the Scottish Intercollegiate Guidelines Network (SIGN)
criteria27and those of the Agency for Health Care Policy and
Research.28The grade of recommendation depends on the scientific
quality of the studies reported (Table 1).
Grades of recommendation and levels of evidence.
Meta-analysis of randomised controlled trials
At least one randomised controlled trial
At least one well-designed controlled trial without
At least one other type of well-designed, quasi
Well-designed non-experimental descriptive studies
such as comparative studies, correlation studies, case-
Expert opinions and/or clinical experience of respected
F. Bozzetti, A. Forbes / Clinical Nutrition 28 (2009) 359–364 360
Prospective randomised controlled trials (RCTs) minimise bias in
the selection and grouping of patients, the practical conduct of the
protocol, and in the final interpretation and presentation of results,
while systematic reviews and meta-analyses provide ‘‘an efficient
scientific technique to identify and summarize evidence on the effec-
tiveness of interventions and to allow the generalizability and
consistency of research findings to be assessed and data inconsis-
tencies to be explored’’.29On the contrary, the flaws and pitfalls of
non-RCTs have been widely recognized and reported.30RCTs are
therefore considered as the gold standard for the determination of
the overall efficacy of clinical therapies, and their use underpins the
assignation of a Grade A recommendation, either from a single
strong and relevant study (level Ib evidence) or through meta-
analysis of multiple RCTs (level Ia evidence). Levels of evidence IIa,
IIb and III are attributed to: at least one well-designed controlled
trial without randomisation; at least one other type of well-
designed, quasi-experimental study; or well-designed non-exper-
imental descriptive studies such as comparative studies, correlation
studies, or case-control studies, respectively, and support a grade of
recommendation B. Grade C recommendations reflect expert
opinion and/or clinical experience of respected authorities (level of
evidence IV). The differentiation of Grade A recommendations from
the others is generally simple, but it may sometimes appear almost
arbitrary whether a conclusion is graded B or C. A practice
considered widely accepted and diffuse across the world clearly
rests on more than the opinion of few experts, but in the absence of
scientifically-structured reports in the literature this practice
warrants only a designation of Grade C. Where there was a general
lack of data, a lack of rationale, or where there was controversy or
unresolved discrepancy between existing publications we have
allocated the less dogmatic designation.
The PN CPG programme involved 11 international committees,
each co-ordinated by a chairman (Table 2), comprising 87 experts
from 16 European-Mediterranean countries. The committees were
multidisciplinary, including experts in clinical nutrition from
different fields of medicine, nursing and dietetics, and they were
responsible for the literature research, the preparation, discussion
and revisions of draft guidelines. Once each guideline had been
approved by all the members of the relevant working group, this
draft was reviewed byat least two independent external reviewers.
In each case one of these reviewers was a member of ESPEN’s
Education and Clinical Practice Committee who had not previously
been involved in that guideline’s creation, and at least one reviewer
came from outside the ESPEN committee structure (often also from
outside Europe). Following this review and amendments being
made each guideline was hosted in draft form on the public pages
of the ESPEN website for at least one month to permit the receipt of
comments or suggestions from any interested party. Comments
received from representatives of the nutrition industry were
addressed on their scientific merit on the same basis as those from
clinical and academic colleagues. At this point the guidelines were
reviewed and revised again by the original working group
chairman and submitted into the Clinical Nutrition editorial
process. At least 3 further reviewers were selected by the Journal’s
editorial office for each guideline, in line with the normal selection
process. Final revisions were performed by the chairmen of the
working groups, and by ourselves as commissioning editors of the
whole project, which now presents more than 300 evidence-based
recommendations in 11 areas of clinical practice (Table 2).
3. European and non-European clinical practice guidelines
Other publications aiming to guide nutritional practice exist
elsewhere and it may be helpful to consider where there is over-lap
and where these ESPEN guidelines present distinctive features. The
American Society for Parenteral and Enteral Nutrition (ASPEN) has
published several guidelines,17–21and also a range of documents
defining standards of practice in nutrition support,31–38which
address themselves to particular members of the nutrition team
(pharmacist, nurse, dietician) or to a specific patient population.
The most similar to the ESPEN CPGs, in being focussed on the
medical community, are the 2002 ASPEN guidelines,21which differ
most obviouslyin considering
approaches in the same document. The Canadian Society of Clinical
Nutrition has published the results of their meticulous work on the
nutritional support of the Intensive Care Unit patient.39This more
limited focus has allowed the authors, who work in a tightly con-
nected national network, the unique opportunity to elaborate ex
novo data from the literature thus creating systematic reviews and
meta-analyses which are not entirely reliant on already published
the enteraland parenteral
3.1. Nutritional therapy versus nutritional support. Does the
The aim of CPGs is to develop recommendations which are
based on good research. The term ‘‘evidence-based medicine’’
originated at McMaster Medical School during the 1980s40where it
was defined as ‘‘the conscientious, explicit, and judicious use of
current best evidence in making decisions about the care of individual
patients’’.41Despite more than 20 years of best intentions the
majority of the recommendations in nutritional care remain based
on low-grade research evidence or on expert consensus. This was
evident in the 1993 ASPEN guidelines, in which only 16% of the
recommendations were judged to be based on good research-based
evidence (meta-analysis of RCTs or single RCTs), and 29% on fair
research-based evidence (essentially level II and III evidence) with
55% of guidance based on expert opinion alone.19Sadly little
progress appears to have been made as we find similar percentages
in the present CPGs (Grade A, 15.8%; Grade B, 28.2%; and Grade C,
56.0%). Nonetheless we should not conclude that these guidelines
are of poor-quality. A large part of the problem distinguishing
nutritional studies from those of a pharmacological agent is the
frequent impossibility of performing studies to gold standard
methodology. It is rarely ethically justifiable or clinically feasible to
perform a placebo controlled trial in which some patients will
deliberately be denied nutritional support, and in the particular
context of PN it is applied now mainly as a ‘‘substitutive’’ treatment
for a vital function when the normal enteral route is unavailable.
The ASPEN Guidelines21summarize this as follows: ‘‘A major
distinction between therapeutic trials of efficacy of a drug or a proce-
dure and the feeding of nutrients known to be essential to mainte-
nance 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’’.
Chairmen of the Committees of the ESPEN Parenteral Nutrition Guidelines.
Central venous catheters
Home Parenteral Nutrition
Surgery & Transplantation
SD Anker, Germany
M Pittiruti, Italy
A Van Gossum, Belgium
L Sobotka, Czech Republic
M Plauth, Germany
M Staun, Denmark
P Singer, Israel
N Cano, France
F Bozzetti, Italy
L Gianotti, Italy
M Braga, Italy
F. Bozzetti, A. Forbes / Clinical Nutrition 28 (2009) 359–364361
In many clinical conditions (exemplified by long-term intestinal
failure), it is ethically unjustifiable to randomise between nutrition
and non-nutrition,42given the lack of ‘‘equipoise’’.43Controlled
trials should always rest on a genuine uncertainty that the outcome
from one intervention (or the lack of it) is better or worse than the
alternative. Despite these constraints the effects of PN can be
investigated in a structured, randomised fashion under certain
- when the planned duration of PN is so short that a non-
nutrition arm is ethically acceptable (eg in the immediate
postoperative state; it is understandable that one third of our
Grade A recommendations are in this area).
- when in one arm of the study, the investigator adds one or
more special substrates (eg BCAA, n-3 emulsions, etc.) to the
conventional (control) nutritional regimen.
- when the investigator compares different nutritional regimens
(eg glucose-based versus lipid-based PN, etc.), or different
routes of administration (eg PN versus tube feeding etc.) or
different times of administration (eg early versus delayed,
continuous versus intermittent, etc.).
Even in these circumstances it can prove very difficult or
impossible to construct blinded studies in order to minimise bias.
The assertion44,45that EN and PN, as medical interventions,
should thus be termed ‘‘nutritional therapies’’ rather than ‘‘nutri-
tional support’’, raises some interesting questions on the legitimacy
and potential consequences of this attribution. PN is clearly
a medical intervention that surpasses ‘‘ordinarycare’’, but to equate
it (as a therapy) to a drug, could lead to the assumption that the use
of PN should be limited to conditions where it can be evaluated
according to the pharmacological gold standard of the randomised
controlled trial (RCT). An excessive emphasis on PN as ‘‘medical
therapy’’ might paradoxically imply that in conditions in which its
efficacy cannot be tested by RCT, it could only be considered as
a simple ‘‘supportive’’ measure, even though it may then be an
essential and life-saving treatment substituting for the failing gut.
Nutritional intervention in fact encompasses a broad spread of
clinical indications which include but go beyond the narrow defi-
nitions of ‘‘true therapy’’. By way of illustration Table 3 identifies
some of the dichotomies in the perception of PN and how this
might influence clinical actions, while at the same time indicating
how often elements from the therapy and support columns co-
exist. Challenges are posed in at least three domains: the scientific
validation of the use of PN; its financing; and the ethical implica-
tions of withholding/withdrawing PN.
Some of the problems associated with scientific validation have
already been addressed, and it will be noted that the most
malnourished patients and those with a non-functional gut - those
who would appear most likely to benefit - cannot normally be
randomised to a no-feeding group and are therefore excluded from
evaluation. Only patients who are marginal candidates for PN will
satisfy the requirement for equipoise so as to be included in the
study, which potentially masks any benefit of the intervention. A
technical review of PN in cancer based on a meta-analysis of 26
RCTs (w1000 patients), concluded that PN was associated with
increases in total and infectious complication rates.47This study
formed the basis for an official statement from the American
Gastroenterological Association to the effect that PN caused net
harm in cancer patients.48However patients with severe malnu-
trition or hypophagia were excluded and the scientific credibility
for PN in these patients was thus (unintentionally) diminished. The
Veterans Affairs Perioperative PN Study49met with similar prob-
lems: of 459 patients who would accept randomisation, 97 (17%)
were excluded because PN was judged to be clinically essential,
such that randomisation to an unfed group would be unethical. The
study showed that, overall, PN led to an increase in infectious
complications. However, in the subgroup of 50 severely malnour-
ished patients, the frequency of infectious complications was
similar in the two arms, and non-infectious complications were
more than 8 times more frequent in the controls than in those on
PN (43% versus 5%). Similar results came from the Maastricht
study.50It can be concluded that controlled studies of patients with
marginal degrees of malnutrition will generally demonstrate the
morbidity of PN, but potential benefits tothose most in need will be
obscured by the absence of major benefit to the majority. Restric-
tion of trial entry to those with weight loss permitted a more
persuasive positive result in perioperative patients51PN proving
able to reduce both morbidity and mortality.
The absence of placebo-controlled trials and the uncertainties
that have arisen from studies that appear to show harm from PN
have added to the difficulties in funding PN research and its clinical
application. In most countries now the health care system requires
a clear demonstration of treatment efficacy in order for its expense
to be covered, which sometimes seems to stem from a contention
that treatments are guilty until proven innocent52! If PN is
considered exclusively as a therapy, both the medical community
and public health authorities will expect it to be validated by RCTs
before its endorsement for public funding.
Most cultures allow for the final decision on accepting or
refusing therapy to be taken by the patient. The ethical issue
admittedly becomes more complicated when the caregiver has to
decidewhether tostartordiscontinue treatment in an incompetent
patient, but most clinicians will feel comfortable declining the
provision of a treatment sought by the patient which is considered
ill-advised.53The ethical issues surrounding the provision of basic/
essential care may however require a different approach, including
the proposition that the decisional autonomy of the individual
about any such element - including nutrition - must always be
respected. Ultimately this controversy reflects the differences
between two general beliefs which dominate modern medicine: on
the one hand evidence-based medicine, which follows a positiv-
istic, biomedical perspective that is disease-oriented and doctor-
oriented, and which considers therapy from the cognitive-rational
perspective; and on the other hand patient-centred holistic medi-
cine in which the focus is humanistic and biopsychosocial
combining the ethical values of the ‘‘ideal physician’’ with the
individual perspectives and belief systems of the patient.
With respect to parenteral nutrition, the few Grade A recom-
mendations available reflects the paucity of level I studies and
might suggest that PN has been introduced in a way that we would
consider suboptimal compared to other therapeutic interventions.
Compelling PN to conform to methods of analysis devised for drug
Potential implications of the dual conception of parenteral nutrition as therapy or
PN as a therapyPN as support
Any chemical agent which affects
living processes is a drug46
‘‘Natural’’ nutrition affects living processes
(and all humans received intrauterine PN)
Physicians prescribe PN Patients and relatives may call for PN
Physicians and medical societies
consider PN as a therapy
Nourishment is viewed by relatives as an act of
love and care
PN is a medical therapy for
Nutrition is essential to both the ill and the
As a therapy PN should be
validated by RCT
It is ethically impossible to have a no nutrition
(no PN) arm and hence a Grade A
recommendation is precluded
F. Bozzetti, A. Forbes / Clinical Nutrition 28 (2009) 359–364 362
treatments is however inappropriate, as it can be seen that these
methodologies will condemn it to remain poorly-proven. We will
never be able to justify withholding this intervention in a patient
who cannot otherwise be nourished. However to avoid the charge
that PN is nonetheless a poor-quality intervention we should
perform randomised trials where feasible and actively seek other
approaches to validate its use in clinical settings which preclude
Van Way54suggests that in such conditions a hierarchy of
benefit versus risk might be the best way to discriminate whether
or not a therapeutic intervention should be undertaken. With this
in mind the American Preventive Services Task Force has proposed
a specimen classification which permits the clinician to advise
semi-objectively in favour of or against an intervention even when
the data are weak (Table 4).55The Commission for the Study of
Ethical Problems in Medicine and Biomedical and Behavioral
Research reached similar conclusions as long ago as 1983.56PN will
continue to occupy a middle ground between high-tech medical
treatment, and as natural a means as possible to secure continued
provision of essential nourishment in the patient with intestinal
failure. In our decisions we can do well to recall the words of
Sackett – one of the fathers of evidence based medicine – who
urged the integration of ‘‘individual clinical expertise with the best
available external clinical evidence from systematic research’’.41
3.2. The future
Scientifically validated guidelines are developed to produce
specific health gains, and must be effectively disseminated and
implemented if these gains are to be achieved. Evidence suggests
that they are effective in changing practice and improving
outcomes, including improved patient selection, quality of life, and
minimization of complications.2However, little will be accom-
plished if target users are unaware or unfamiliar with a guideline, if
professional scepticism is notovercome, and whenphysicians resist
their adoption because they feel that guidelines are eroding their
role in decision making.57
It should be understood that while guidelines are carefully
considered recommendations, they are not mandatory require-
ments to be applied uncritically. It may be the case that CPGs are
‘‘the best advice about the most effective intervention in a particular
clinical situation’’,58but the clinical situation under consideration
may not correspond precisely to that in the guidelines, or the rec-
ommended intervention may be unavailable or inappropriate.
Nonetheless, when a strong guideline exists it should increasingly
be considered to be the default from which deviations should be
justifiable and documented. Hence, sponsors and endorsers of CPGs
have a responsibility to disseminate them through appropriate
channels to potential users, and also to try to encourage their
uptake and implementation. Experience in Switzerland59and
Canada60demonstrates the magnitude of the additional effort
needed to achieve concordance with nutritional guidelines.
The responsibility of the originators of CPGs extends to the
regular revision of the guidelines themselves, taking into account
new scientific knowledge, but also review of the consequences of
their inclusion in regular practice. ESPEN intends to take both these
roles seriously. Despite their foundation on systematic, structured
reviews of the literature, guidelines retain elements of controversy
and disagreement, as is almost inevitable with the nature of
pathology and human intervention. If unequivocal factual analyses
existed we would have little need for guidelines. The high
proportion of Grade C recommendations in the PN guidelines
indicates to what degree our guidance is dependent on experience
and expert opinion. The guidelines can therefore be considered to
be hypothesis-generating, and to act as a specific stimulus for tar-
geted future research. Now the work ‘‘on the guidelines’’ is over, the
true work ‘‘of the guidelines’’ has to begin.
The creation of the ESPEN PN guidelines has been dependent on
the contributions of many of our colleagues to whom we are most
grateful. We acknowledge also the support and assistance of the
editorial team at Clinical Nutrition. We confirm that there has been
no financial involvement of the nutrition industry in the develop-
ment of the guidelines.
Conflict of interest
Conflict of interest on file at ESPEN (email@example.com).
1. Tunis SR, Hayward RSA, Wilson MC, et al. Internists’ attitudes about clinical
practice guidelines. Ann Intern Med 1994;120:956–63.
2. Grimshaw JM, Russell IT. Effect of clinical guidelines on medical practice. A
systematic review of rigorous evaluations. Lancet 1993;342:1317–22.
3. Committee to Advise the Public Health Service on Clinical Practice Guidelines,
Institute of Medicine. In: Field MU, Lohr KN, editors. Clinical practice guidelines:
direction of a new program. Washington, DC: National Academy Press; 1990.
4. Valentini L, Schutz T, Allison S, et al. ESPEN guidelines on enteral nutrition. Clin
5. Schutz T, Herbst B, Koller M. Methodology for the development of the ESPEN
guidelines on enteral nutrition. Clin Nutr 2006;25:203–9.
6. Bozzetti F. HPN in radiation enteropathy. In: Bozzetti F, Staun M, Van Gossum A,
editors. Home parenteral nutrition. CAB International; 2006. p. 93–102.
7. Smoke A, Delegge H. Chyle leaks: consensus on management? Nutr Clin Pract
8. Sheng-Zhang L, Hong-Fei T, Zhong-Lin N, et al. Treatment and prevention of
lymphorrhea. J Cancer Res Clin Oncol; 2008 Oct 10. epub.
9. Linee Guida SINPE per la Nutrizione Artificiale nel paziente ospedalizzato. Riv
Ital Nutr Parent Ent 1995;13:S2.
10. Linee Guida SINPE per la Nutrizione Artificiale Ospedaliera. Riv Ital Nutr Parent
11. Development Committee, Agenzia per i Servizi Sanitari Regionali (ASSR). Home
artificial nutrition: nationalguidelines
12. Silvestri N, Mazzuoli N, Regano N, et al. The practical utility of guidelines in
medicine and artificial nutrition. Nutr Ther Metab 2008;26:59–64.
13. Lochs H, Lubke H, Weimann A, editors. Leitlinie enterale ernahrung. Aktuel
Ernaehr Med 2003;28(Suppl. 1):S1–121.
14. Lochs H, Volkert D, Krys U, editors. Leitlinie enterale ernahrung Teil 2. Aktuel
Ernaehrung Med 2004;29:187–232.
15. Baxter JP, McKee RF. Organization of managed clinical networking for home
parenteral nutrition. Curr Opin Nutr Metab Care 2006;9:270–5.
16. Gillanders L, Andstmann K, Ball P, et al. AuSPEN clinical practice guidelines for
home parenteral nutrition patients in Australia and New Zealand. Nutrition
of reference. NutrTher Metab
Classification proposed by the American Preventive Services Task Force to guide
clinicians in contexts of varying robustness of evidence.55
- Level A: good scientific evidence suggests that benefits of the clinical service
substantially outweigh the potential risks. Clinicians should discuss the service
with eligible patients.
- Level B: at least fair scientific evidence suggests that the benefits of the clinical
service outweigh the potential risks. Clinicians should discuss the service with
- Level C: at least fair scientific evidence suggests that there are benefits
provided by the clinical service, but the balance between benefits and risks are
too close to make general recommendations. Clinicians need not offer it unless
there are individual considerations.
- Level D: at least fair scientific evidence suggests that the risks of the clinical
service outweigh potential benefits. Clinicians should not routinely offer the
service to asymptomatic patients.
- Level E: scientific evidence is lacking, of poor quality, or conflicting, such that
the risk:benefit balance cannot be assessed. Clinicians should help patients
understand the uncertainty surrounding the clinical service.
F. Bozzetti, A. Forbes / Clinical Nutrition 28 (2009) 359–364 363
17. ASPEN Board of Directors. Guidelines for Total Parenteral Nutrition in the Download full-text
hospitalized adult patient. J Parenter Enteral Nutr 1986;10:441–5.
18. ASPEN Board of Directors. Guidelines for use of home total parenteral nutrition.
J Parenter Enteral Nutr 1987;11:342–4.
19. ASPEN Board of Directors. Guidelines for the use of parenteral and enteral nutri-
tion in adult and pediatric patients. Parenter Enteral Nutr 1993;17(Suppl.):
20. ASPEN. Nutrition support in clinical practice :review of published data and
recommendations for future research directions. J Parenter Enteral Nutr
21. ASPEN Board of Directors and Clinical Guidelines Task Force. Guidelines for the
use of parenteral and enteral nutrition in adult and pediatric patients. J Parenter
Enteral Nutr 2002;26(Suppl. 1).
22. Klein S, Kinney J, Jeejeebhoy K, et al. Nutrition support in clinical practice:
review of published data and recommendations for future research directions.
J Parenter Enteral Nutr 1997;21:133–56.
23. National Collaborating Centre for Acute Care. Nutrition support in adults: oral
nutrition support, enteral tube feeding and parenteral nutrition. Available at:
24. Parenteral Nutrition Guidelines Working Group. Guidelines on paediatric
parenteral nutrition. J Pediatr Gastroenterol Nutr 2005;41(Suppl. 2):s1–87.
25. Koletzko B, Baker S, Cleghorn C, et al. Global standard for composition of infant
formula: recommendations of an ESPGHAN coordinated international expert
group. J Pediatr Gastroenterol Nutr 2005;41:584–99.
26. Koletzko B, Lien C, Agostoni C, et al. The role of long-chain polyunsaturated
fatty acids in pregnancy, lactation and infancy: review of current knowledge
and consensus recommendations. J Perinat Med 2008;36:5–14.
27. Scottish Intercollegiate Guidelines Network. SIGN guidelines – an introduction to
SIGN methodology for the development of evidence-based clinical guidelines.
Edinburgh: SIGN Publication No.39, SIGN Secretariat, Royal College of Physi-
cians of Edinburgh; 1999.
28. Agency for Health Care Policy and Research. Clinical practice guideline N0.1
AHCPR Publication No. 1 AHCPR Publication No. 92-0023; 1993.
29. Woolf S. Practice guidelines-a new reality in medicine. II. Methods of devel-
oping guidelines. Arch Intern Med 1992;152:946–52.
30. Wen SW, Hernandez R, Naylor CD. Pitfalls in nonrandomised outcome studies:
the case of incidental appendectomy with open cholecystectomy. J Am Med
31. ASPEN. Standards of practice, nutrition support pharmacist. Nutr Clin Pract
32. ASPEN Standard of Practice. Nutrition support nurse. Nutr Clin Pract 1988;
33. ASPEN Standard of Practice. Nutrition support physician. Nutr Clin Pract
34. ASPEN. Standard of practice, nutrition support dietitian. Nutr Clin Pract 5:
35. ASPEN Standard for Nutrition Support. Hospitalized patients. Nutr Clin Pract
36. ASPEN Standard for Nutrition Support. Home patients. Nutr Clin Pract 1998;
37. ASPEN Standard for Nutrition Support. Hospitalized pediatric patients. Nutr Clin
38. ASPEN Standard for nutrition support for resident of long-term care facilities.
Nutr Clin Pract 1989;4:148–53.
39. Heyland DK, Dhalikawal R, Drower JW, et al. Canadian clinical practice guide-
lines for nutrition support in mechanically ventilated critically ill adult
patients. J Parenter Enteral Nutr 2003;27:355–73.
40. Evidence-based medicine Working Group. Evidence-based medicine. J Am Med
41. Sackett DL, Rosenberg WMC, Haynes RB, et al. Evidence-based medicine: what
it is and what it isn’t. BMJ 1996;310:71.
42. Wolfe B, Mathiesen HA. Clinical practice guidelines in nutrition support: can
they be based on randomised clinical trials? J Parenter Enteral Nutr
43. Freedman B. Equipoise and the ethics of clinical research. N Engl J Med
44. Lipman TO. Grains or veins: is enteral nutrition really better than parenteral
nutrition? A look at the evidence. J Parenter Enteral Nutr 1998;22:167–82.
45. Wischmeyer PE.JPEN:state of
46. Goodman LS, Gilman A. The pharmacological basis of therapeutics. Toronto: The
MacMillan Company; 1940.
47. Koretz RL, Lipman TO, Klein S. AGA technical review on parenteral nutrition.
48. American Gastroenterological Association Medical Position Statement: Paren-
teral nutrition. Gastroenterology 2001;121:966–9.
49. The Veterans Affairs Total Parenteral Nutrition Cooperative Study Group.
Perioperative total parenteral nutrition in surgical patients. N Engl J Med
50. Von Meyenfeldt MF, Mejerink WJHJ, Rouflart MMJ, et al. Perioperative nutri-
tional support: arandomised clinical trial. Clin Nutr 1992;11:180–6.
51. Bozzetti F, Gavazzi C, Miceli R, et al. Perioperative parenteral nutrition in
malnourished gastrointestinal cancer patients: a randomised clinical trial.
J Parenter Enteral Nutr 2000;24:7–14.
52. Eddy DM. Health system reform: will controlling costs require rationing
services? J Am Med Assoc 1994;272:324–8.
53. Bozzetti F. Feeding the patient with an incurable disease: a voice out of the
chorus. Nutr Ther Metab 2006;24:60–3.
54. Van Way CW. If we’re doing so much good, why can’t we prove it? J Parenter
Enteral Nutr 2007;31:341–2.
55. US preventive Services Task Force. Available at: http://www.ahrq.gov/clinic/
56. President’s Commission for the Study of Ethical Problems in Medicine and
Biomedical Behavioral Research. Deciding to forego life-sustaining treatment.
Washington, DC: Author; 1983. Available from: U.S. Superintendent of Docu-
ments, Washington, DC.
57. Lubbe AS. Risks and misconceptions in medicine and palliative medicine in
particular. Prog Palliat Care 2002;10:273–9.
58. Keeley PW. Clinical guidelines. Palliat Med 2003;17:368–74.
59. Marin Caro MM, Darmon P, Jacqueline-Ravel N, et al. Routine nutritional care in
an oncology support care program: comparison with the ESPEN oncology
guidelines. Clin Nutr 2008;(Suppl. 1):106.
60. Miller CA, Grossman S, Hindley E, et al. Are enterally fed ICU patients meeting
clinical practice guidelines? Nutr Clin Pract 2008;23:642–50.
the journal.J ParenterEnteral Nutr
F. Bozzetti, A. Forbes / Clinical Nutrition 28 (2009) 359–364 364