HTTP 4

Ageing Research Reviews
4 (2005) 422450
www.elsevier.com/locate/arr
Review
Enteral nutritional support in prevention and

treatment of pressure ulcers: A systematic
review and meta-analysis
Rebecca J. Stratton a,*, Anna-Christina Ek b, Meike Engfer c,
Zena Moore d, Paul Rigby c, Robert Wolfe e, Marinos Elia a
a
Institute of Human Nutrition, University of Southampton, MP 113 F Level,

Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
b
University Hospital, Linkoping, Sweden
c
Royal Numico, Clinical Nutrition Division, Netherlands
d
Royal College of Surgeons in Ireland, Dublin, Ireland
e
The University of Texas, TX, USA
Received 23 December 2004; received in revised form 7 March 2005; accepted 11 March 2005
Abstract
Background: There have been few systematic reviews and no meta-analyses of the clinical benefits
of nutritional support in patients with, or at risk of developing, pressure ulcers. Therefore, this
systematic review and meta-analysis was undertaken to address the impact of enteral nutritional
support on pressure ulcer incidence and healing and a range of other clinically relevant outcome
measures in this group.
Methods: Fifteen studies (including eight randomised controlled trials (RCTs)) of oral nutritional
supplements (ONS) or enteral tube feeding (ETF), identified using electronic databases (including
Pub Med and Cochrane) and bibliography searches, were included in the systematic review.
Outcomes including pressure ulcer incidence, pressure ulcer healing, quality of life, complications,
mortality, anthropometry and dietary intake were recorded, with the aim of comparing nutritional
support versus routine care (e.g. usual diet and pressure ulcer care) and nutritional formulas of
different composition. Of these 15 studies, 5 RCTs comparing ONS (4 RCTs) and ETF (1 RCT) with
routine care could be included in a meta-analysis of pressure ulcer incidence.
Results: Meta-analysis showed that ONS (250500 kcal, 226 weeks) were associated with a
significantly lower incidence of pressure ulcer development in at-risk patients compared to routine
care (odds ratio 0.75, 95% CI 0.620.89, 4 RCTs, n = 1224, elderly, post-surgical, chronically
Abbreviations: CT, clinical trial; CCT, controlled clinical trial; ETF, enteral tube feeding; NNT, number
needed to treat; ONS, oral nutritional supplement; RCT, randomised controlled trial
* Corresponding author. Tel.: +44 23 8079 6317.
E-mail address: R.J.Stratton@soton.ac.uk (R.J. Stratton).
1568-1637/$ see front matter # 2005 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.arr.2005.03.005
R.J. Stratton et al. / Ageing Research Reviews 4 (2005) 422450
423
hospitalised patients). Similar results were obtained when a combined meta-analysis of ONS (4 RCT)
and ETF (1 RCT) trials was performed (OR 0.74, 95% CI 0.620.88, 5 RCTs, n = 1325). Individual
studies showed a trend towards improved healing of existing pressure ulcers with disease-specific
(including high protein) versus standard formulas, although robust RCTs are required to confirm this.
Although some studies indicate that total nutritional intake is improved, data on other outcome
measures (quality of life) are lacking.
Conclusions: This systematic review shows enteral nutritional support, particularly high protein
ONS, can significantly reduce the risk of developing pressure ulcers (by 25%). Although studies
suggest ONS and ETF may improve healing of PU, further research to confirm this trend is required.
# 2005 Elsevier Ireland Ltd. All rights reserved.
Keywords: Meta-analysis; Supplement; Enteral; Formula; Pressure sores; Decubitus; Wound healing;
Prevention; Nutrition
1. Introduction
The European Pressure Ulcer Advisory Panel (EPUAP) defined pressure ulcers as an
area of localised damage to the skin and underlying tissue caused by pressure, shear,
friction and/or a combination of these things (EPUAP, 2004). The severity of ulcers is
graded from I to IV (see Table 1). In-patient pressure ulcer prevalence ranges from 3 to
66%, across a range of patient groups including the elderly and those with a fractured neck
of femur (Allman et al., 1986a,b; Versluysen, 1986; Ek et al., 1991; ODea, 1995; Bours
et al., 1999; Whitfield et al., 2000; Tannen et al., 2004). Community based prevalence rates
are similar (Tannen et al., 2004), with estimates ranging from 3 to 54% across different
patient groups (Preston, 1991; Joy and Halling, 1998; Thomas et al., 1998; Bours et al.,
1999; Haalboom, 2000).
Pressure ulcers are associated with an increased risk of morbidity and mortality. There is
a four- to six-fold increase in risk of death (Allman et al., 1986). From a quality of life
perspective, pain, exudate, body image and healing are the issues of greatest concern to
patients (Fox, 2002). Furthermore, local and systemic infections are common, requiring
extended hospitalisation (Stratton et al., 2003). The economic consequences are
substantial, with the annual cost of treating pressure ulcers estimated in the region of
Table 1
Pressure ulcer staging (EPUAP, 2004)
Stage
Characteristics
Non-blanchable erythema of intact skin. Discolouration of the skin, warmth, oedema, induration or
hardness may also be used as indicators, particularly on individuals with darker skin
Partial thickness skin loss involving epidermis, dermis or both. The ulcer is superficial and
presents clinically as an abrasion or blister
Full thickness skin loss involving damage necrosis of subcutaneous tissue that may extend
down to, but not through, underlying fascia
Extensive destruction, tissue necrosis, or damage to muscle, bone or supporting structures with
or without full thickness skin loss
II
III
IV
424
750 million (s1065 million) in the UK and US$ 3 billion (s2.4 billion) in the USA
(Stratton et al., 2003).
Multivariate analyses indicate that low body mass index, low body weight, reduced
feeding activity and food intake are independent risk factors for pressure ulcer
development (Berlowitz and Wilking, 1989; Weiler et al., 1990; Ek et al., 1991; Bergstrom
and Braden, 1992; Thomas, 1997; Green et al., 1999). Furthermore, malnutrition increases
the risk of (Thomas, 2001), and impairs the healing of (Stratton et al., 2003; Harris and
Fraser, 2004), pressure ulcers, due to reduced nutrient availability for tissue maintenance
and repair, resulting in loss of the cushioning effect of fat mass, reduction of skin
resistance, physical weakness, decreased mobility and oedema (Stratton et al., 2003). The
majority of newly hospitalised patients with stage III/IV pressure ulcers (Guenter et al.,
2000), and 46% of patients with leg or foot ulcers living at home (Wissing and Unosson,
1999), are reported to be malnourished.
Several studies have examined the effect of nutritional support on the development of
pressure ulcers in at-risk patients (Delmi et al., 1990; Hartgrink et al., 1998; BourdelMarchasson et al., 2000; Houwing et al., 2002, 2003). However, there have been few
studies of the effects of nutritional support in patients with established pressure ulcers
(Myers et al., 1990; Breslow et al., 1993). The role of nutritional support using diseasespecific formulas developed specifically for patients with pressure ulcers is currently
unclear. Such formulas contain additional quantities of a number of individual nutrients
that are important in the wound healing process (including protein, arginine and Vitamin C;
Taylor et al., 1974; Barbul et al., 1990; Breslow et al., 1993; Kirk et al., 1993; Scholl and
Langkamp-Henken, 2001).
In 2003, a Cochrane review of eight randomised controlled trials (RCTs) concluded that
although there was insufficient evidence elderly people suffering from acute illness appear
to develop fewer pressure ulcers when given two daily supplement drinks (Langer et al.,
2003). The Cochrane review was based on evidence from RCTs only, did not include metaanalysis, missed some relevant information (Ek et al., 1991) within the review period (up to
September 2002) and only assessed PU incidence and time to complete healing as outcome
measures and not other clinically relevant parameters (e.g. dietary intake and quality of life).
Therefore, the aim of this systematic review was to determine the effect of enteral
nutritional support on pressure ulcer incidence, pressure ulcer healing, quality of life,
complications, mortality, nutritional status (dietary intake, body weight) and any other
clinically relevant outcome measures, specifically comparing nutritional support (oral
nutritional supplements (ONS) or enteral tube feeding (ETF)) versus routine care, enteral
formulas of different composition and ETF versus parenteral nutrition. Meta-analysis of
quantitative outcomes was also to be undertaken where possible (i.e. where consistent,
numerical measures were reported).
2. Materials and methods

The review was planned, conducted and reported following published guidelines. These
include those issued by the Cochrane Collaboration (Cochrane, 2004a,b), the UK National
Health Service Centre for Reviews and Dissemination (CRD) (CRD, 2000, 2001) and the
425
Fig. 1. Summary of methodology for the systematic review of efficacy of nutritional support for patients with, or
at risk of developing, pressure ulcers.
QUORUM guidelines (Moher et al., 1999). A flow chart (Fig. 1) illustrates the principle
stages and processes undertaken.
2.1. Identification and retrieval of studies for the systematic literature review
Potentially relevant studies were identified by searching electronic databases. These
included Pub Med (PubMed, 2004), accessed 10/08/04, Cochrane (Cochrane, 2004a),
accessed 28/07/04, Turning Research Into Practice (TRIP, 2004), accessed 12/08/04,
Clinical Evidence (Clinical evidence, 2004), accessed 12/08/04, National Electronic
Library for Health guidelines finder (NELH, 2004), accessed 12/08/04 and National
Service Frameworks (NSF, 2004), accessed 19/08/04. The search terms included:
decubitus ulcer, pressure sore*, pressure ulcer*, bed sore*, nutrition*, nutrie*, enteral*,
oral*, supplement*, sip, feed, liquid, tube, nasogastric, nasoduodenal, nasojejunal,
gastrostomy, jejunostomy, formula*, protein, nitrogen, amino acid*, arginine, zinc,
Vitamin C, ascorbic acid, Vitamin E, antioxida*. Bibliographies were checked and experts
in the field contacted for any additional studies.
426
2.2. Study selection criteria for the systematic literature review

Studies were deemed eligible for inclusion in the systematic review if they
conformed to pre-determined inclusion and exclusion criteria (Table 2). Subjects
eligible for inclusion were adults (>18 years age) with, or at risk of developing, pressure
ulcers, of any nutritional status (well-nourished and malnourished) and based in any
setting (e.g. hospital, out-patient and home). Eligible interventions were enteral
formulas, including both ONS and ETF that contained at least two macronutrients as
well as micronutrients. The intervention could provide either a portion of, or the
complete daily requirement for, energy and could be nutritionally complete or
incomplete. Studies using concurrent parenteral nutrition or dietary advice were
admissible, but those utilising only parenteral nutrition or only dietary counselling were
excluded. The primary outcome measures sought were pressure ulcer incidence and
pressure ulcer healing. Other outcomes of interest were quality of life, complications,
mortality, dietary intake and nutritional status. No other restrictions were placed on
studies with regard to type of comparator (e.g. routine care (no nutritional support),
dietary advice, parenteral nutrition), year of publication, language (providing an English
abstract was available) and source. Studies comparing two different enteral formulas,
including those specifically developed for use in the prevention and treatment of
pressure ulcers, could also be included. The priority was randomised controlled trial
evidence, although non-randomised controlled clinical trials (CCT) and beforeafter
clinical trials (CT) were admissible. Observational study designs (e.g. cohort, case
study). Although their evidence is less robust than that provided by a RCT design, non-
Table 2
Summary of inclusion and exclusion criteria applied during evaluation of studies for systematic review
Selection criterion
Inclusion criteria
Exclusion criteria
Population
All adult human studies

Nutritional status either well-nourished
or malnourished
Patients with pressure/decubitus ulcers,
or those at risk of developing them
Animal studies
Intervention
All studies using ONS and/or ETF (all

routes/methods), including those simultaneously
using or comparing with dietary counselling
and/or parenteral nutrition and/or simultaneous
standard diet
Setting in hospital or community
(e.g. out-patient, home)
Dietary counselling only

Parenteral nutrition only
Interventions with <2
macronutrients
Interventions with no
micronutrients
Main outcome
measures
Pressure ulcer incidence

Pressure ulcer healing
Quality of life
Complications
Mortality
Dietary intake
Nutritional status
427
RCT and observational studies were included in the systematic review to ensure capture
of all of the available information. All study designs (RCT, CCT, CT) were categorised
based on Pub Med definitions and study types were distinguished throughout the text.
Meta-analysis was only undertaken using RCTs.
Following the identification of potentially relevant studies based on titles and abstracts,
full papers were obtained and evaluated by one researcher; a second assessor verified
inclusion/exclusion decisions.
2.3. Data extraction and outcome measures
A pre-determined data extraction table was designed to capture study characteristics and
outcome data, and allow the assimilation of data from differing study designs. The primary
outcome measures were: pressure ulcer formation in at-risk patients (pressure ulcer
incidence) and pressure ulcer healing in those with pre-existing ulcers (e.g. ulcer surface
area and healing time). Secondary clinical outcomes were also sought, including quality of
life, mortality, complications and nutritional status (dietary intake and anthropometry).
Outcomes were recorded based on the definitions provided by the original authors of each
study.
2.4. Quality assessment
The quality of individual studies was assessed using two scales (AHCPR, 1992; Jadad
et al., 1996), this was conducted by one researcher and verified by a second assessor. The
first method was a six-point scale adapted from the Quality of evidence Quality
Assessment scale (Agency for Health Care and Policy Research) (AHCPR, 1992). The
highest grade (score 1) was given to RCTs, whilst lower grades were given to: wellcontrolled trials without randomisation (score 2); well-designed cohort or case control
analytical studies (score 3); multiple time-series or dramatic results or uncontrolled
experiments (score 4); opinions of respected authorities based on clinical evidence,
descriptive studies or reports of expert committees (score 5); evidence inadequate owing to
problems of methodology or conflicts of evidence (score 6). The second method was that
used by Jadad et al. (1996), and based on a highest score of 5, achieved only by wellconducted double blind RCTs, with adequate description of drop-outs as well as the use of
appropriate methods of randomisation and blinding.
2.5. Synthesis of data and statistical methods
Following extraction of data, where appropriate and feasible meta-analysis was
conducted for any consistent outcome measure that was represented by two or more
comparable studies and reported in the same way. Outcomes that were not consistent or
numerical were described in the text.
The main comparisons of interest were: nutritional support (ONS and ETF) versus
routine care; comparisons of different formulas given orally (ONS) or by tube (ETF); ETF
versus parenteral nutrition. Where the intention of the authors was clear, studies of
prevention and treatment of pressure ulcers were analysed separately. Separate analyses
428
were intended for studies of different duration (short-term feeding versus long-term
feeding), involving formulas containing different concentrations of specific nutrients (e.g.
high zinc versus low zinc) and according to nutritional status (malnourished versus wellnourished).
The method of Woolf (1955) was used to calculate a weighted average of the log odds
ratio of pressure ulcer incidence in each study. The odds ratios were considered statistically
significant if the 95% CI did not span the value one. Forest plots were used to present each
studys odds ratio and the meta-analysis estimate. Heterogeneity was investigated from the
Q-test of heterogeneity derived by the MantelHaenszel method (1959). Due to the small
number of studies included in the meta-analyses, it was deemed inappropriate to
investigate publication bias through the use of funnel plots (Egger et al., 1997). A fixed
effects model was used to combine the treatment estimates, which assumes no
heterogeneity between the study results. Numbers needed to treat was given by the
reciprocal of the absolute risk reduction. Meta-analysis estimate of the absolute risk
reduction was calculated as a weighted sum of the absolute relative reduction for each
study, where the weight was calculated as the reciprocal of the variance of the absolute
relative reduction for each individual study. All statistical analyses were conducted using
SAS Version 8.2 (SAS Institute Inc., Cary, NC, USA). All data are presented as
mean S.D. unless otherwise stated.
3. Results
3.1. Overall search findings
A total of 916 studies were identified by the search strategy (Fig. 1). Following
evaluation of the title/abstract, 36 papers were deemed potentially relevant and obtained
in full. Upon reading the full text of these 36 papers, 15 (Chernoff et al., 1990; Delmi
et al., 1990; Peck et al., 1990; Breslow et al., 1991, 1993; Ek et al., 1991; Henderson
et al., 1992; Bourdel-Marchasson et al., 1997, 2000; Mitchell et al., 1997; Craig et al.,
1998; Hartgrink et al., 1998; Benati et al., 2001; Houwing et al., 2003; Soriano et al.,
2004) complied with the inclusion criteria and were included in the systematic review
(Table 3). Of these, five (all RCTs) were included in the meta-analysis (Delmi et al.,
1990; Ek et al., 1991; Hartgrink et al., 1998; Bourdel-Marchasson et al., 2000; Houwing
et al., 2003).
The other 21/36 studies were rejected from the systematic review and meta-analysis
(Table 4), due to not being an original study (n = 4; Anderson and Beaton, 1974; Fulghum,
1977; Thomas, 2001; Houwing et al., 2002); using an ineligible nutritional intervention
(n = 13; Brewer et al., 1967; Abbott et al., 1968; Norris and Reynolds, 1971; Taylor et al.,
1974; Watkin and Waldron, 1981; Bildsten and Lamid, 1983; Holmes et al., 1987; Myers
et al., 1990; Welch et al., 1991; ter Riet et al., 1995; Jackobs, 1999; Houston et al., 2001;
Collins, 2004); using ineligible subjects (n = 2; Bastow et al., 1983; Larsson et al., 1990);
or because it was not possible to source the document or an English translation of it (n = 2;
Takagi et al., 1991; Barateau et al., 1998).
Table 3
Studies included in the systematic review
Citation
Study type
Bourdel-Marchasson
et al. (2000)
RCT, parallel groups, multi-centre.

Hospital wards (n = 19) stratified
by medical speciality, then wards
randomised to two treatments.
Conducted from Hospital XavierArnozan, Pessac, France
Population description
Aim of study
Proportion of
patients with
pressure ulcers
at baseline (%)
Age range 7291 years. All patients

on alternating pressure air mattress.
Activities of daily living (ADL)
scores ranged from 0 to 3.
Nutritional status not stated, but
study excluded those unlikely to
benefit from supplementation
16 cognitively impaired
elderly inpatients with
pressure ulcers, stage
not reported
Effect of
supplement on
healing of pressure
ulcers (treatment)
100
Significant differences between

experimental and control groups,
respectively, for: comorbidities
(more stroke, heart failure, dyspnea,
and fewer gait disturbances/falls,
digestive diseases, delirium, lower
limb fractures in experimental group),
Norton score (510%, n = 84 vs. 130;
1114%, n = 119 vs. 177; >14%,
n = 92 vs. 70), mean Kuntzman score
(8.2 vs. 8.4), and mean baseline serum
albumin (30.9 g/L vs. 32.5 g/L).
Similar for mean age (84 years vs.
83 years), body weight (60 kg vs. 55 kg),
CRP (54 mg/L vs. 63 mg/L). Patients unable
to move or eat alone. Control group
had higher risk of pressure ulcers
(Norton scale) were more dependent
(Kuntzmann score) and had a higher
albumin. Some of the control group
took ONS during the study
672 critically ill

elderly, at high risk
of pressure ulcers,
inpatients
Effect of
supplement
on incidence of
pressure ulcers
(prevention)
Studies of nutritional support vs.

routine care
Oral nutritional supplements (ONS)
RCTs
Benati et al. (2001)
RCT, parallel groups. Patients were
randomised into treatments.
Conducted at Morgagni-Pierantoni
Hospital, Italy
Baseline status
429
430
Table 3 (Continued )
Citation
Baseline status
Aim of study
Proportion of
patients with
pressure ulcers
at baseline (%)
Delmi et al. (1990)

randomised to two groups.
University Hospital Geneva,
Switzerland, with some patients
then transferred to a second,
convalescent hospital
Many patients underwent recent surgery.

Similar clinical and biological parameters
in experimental vs. control groups,
respectively: mean baseline serum albumin
(37.1 g/L vs. 36.3 g/L), age (80 years vs.
83 years), except 25 OHD Vitamin D status
(26 nmol/L vs. 13 nmol/L). All patients
nutritionally at riskbelow normal values
for baseline retinol binding protein
(43.9 mg/mL vs. 42.9 mg/mL), Vitamin A
(322 mg/L vs. 272 mg/L), carotene
(184 mg/L vs. 137 mg/L), triceps
skinfold (<12 mm vs. 13 mm), upper
arm circumference (<260 mm
vs. <290 mm)
59 fracture neck of
femur patients,
inpatients, elderly, at
risk for pressure ulcers
Clinical benefits of
supplement
(including
incidence of
pressure ulcers
prevention)
Ek et al. (1991)

randomised to groups. Conducted
at University Hospital, Linkoping,
Sweden
Mean age 80 years. 28.5%

malnourished at start (author
definition based on low values in
3/6 parameters: weight index,
triceps skinfold, arm muscle
circumference, pre-albumin,
albumin, delayed hypersensitivity
skin test). No further information
provided
495 elderly long-term

care, some had ulcers
on admission, pressure
ulcer stage not reported
Effect of
supplement
on development
and healing of
pressure ulcers
(treatment and
prevention)
14.1
Houwing et al. (2003)
RCT, double blind, parallel groups.

Randomised three centre study
conducted at Deventer Ziekenhuis,
Deventer, Netherlands
Mean age, baseline BMI, pressure ulcer

risk score (CBO), haemoglobin,
respectively: 82 years, 24.2 kg/m2,
11.1, 7.1 (experimental group) vs.
80.5 years, 23.7 kg/m2, 11.2, 7.1
(control group). Patients underwent
surgery
103 hip fracture patients,

elderly, at risk for
pressure ulcers
Effect of
supplement on
development of
pressure ulcers
(prevention)
CT, single group, beforeafter.

Conducted at Hospital Universitario
Gregorio Maranon, Madrid,
Spain, at 10 centres
Mean age 75 years, BMI = 22.9 kg/m 2
39 elderly inpatients
with pressure ulcers,
stage III (n = 14),
stage IV (n = 24),
unstaged (n = 1)
Effect of
supplement
on healing
pressure ulcers
(treatment)
100
Non-RCTs
Soriano et al. (2004)
Study type
Enteral tube feeding (ETF)

RCTs
Hartgrink et al. (1998)
Patients on standard hospital mattress,

underwent surgery on admission. Both groups
were comparable at admission with respect to
patient characteristics and nutritional status:
for experimental vs. control groups,
respectively, mean age (84 years vs.
83 years), baseline serum albumin
(39.7 g/L vs. 39.4 g/L), total protein
(69.6 g/L vs. 68.2 g/L), pressure ulcer
risk score (9.0 vs. 9.2)
101 hip fracture

patients, high risk
for pressure ulcers,
some had grade
I ulcers at entry1
Effect of formula
on development
and severity of
pressure ulcers
(prevention and
treatment)
15.5 (grade I only)
Prospective cohort.
Conducted at Oak
Forest Hospital, IL, USA
All the patients were long-term tube

fed, and had been on their respective
enteral diets prior to study start
(mean 24.9 months). 32.5% were in
coma/vegetative state, many had
dementia. Mean age = 64 years,
baseline serum albumin 37 g/L,
retinol binding protein 47 mg/L,
total protein 71 g/L, haemoglobin 114 g/L
40 elderly tube fed

patients. Some had
pressure ulcers at
study start, stage
not reported
Effect of formula
on nutritional
status and clinical
outcome (including
pressure ulcers
both treatment
and prevention)
65
Bourdel-Marchasson
et al. (1997)
Retrospective cohort,
parallel groups. Conducted
at Geriatric centre, Hospital
Xavier Arnozan, Pessac, France
For group A, n = 12 were <65 years

old (mean 48 years), whilst
n = 46 were older (mean 80.7 years).
For group B, n = 5 were <65 years
old (mean 54 years), whilst n = 45 were
older (mean 85 years). Kuntzmanns
score of dependence mean 9.6
(group A) vs. 9.6 (group B)
108 elderly nursing

home patients, some
had ulcers, pressure
ulcer stage not reported
Evaluation of
tolerance and
improvement
of tube feeding
practices (including
treatment and
prevention of
pressure ulcers)
65.5 (group A),

14.3 (group B)
Mitchell et al. (1997)
Prospective cohort, parallel groups.

Data obtained from database.
Multi-centre (n = 272), nursing homes.
Harvard Medical School, Boston, USA
Median age = 87 years. No

further information provided
1386 cognitively impaired

nursing home patients,
some had pressure ulcers,
stage not reported
Study of the risks of

enteral feeding (including
development of pressure
ulcersprevention)
29.6 (group A),

15.4 (group B)
Peck et al. (1990)
Retrospective cohort, parallel

groups. Jewish home and hospital
for the aged, New York, USA
Mean age, % demented patients, %

physically restrained patients, months in
nursing home, respectively: 87 years,
100%, 71%, 66 months (experimental
group) vs. 87 years, 71%, 56%,
36 months (control group)
104 elderly nursing home

patients, most of whom
were demented, some had
pressure ulcers, stage
not reported
Review of intubation
practices: nutritional
adequacy and
complications
(including pressure
ulcersprevention)
Not stated, <100
Non-RCTs
Henderson et al. (1992)
RCT, parallel groups.

Randomised
conducted at
Red Cross Hospital, The
Hague, Netherlands
431
432
Citation
Study type
Baseline status
Aim of study
Proportion of
patients with
pressure ulcers
at baseline (%)

RCTs
Craig et al. (1998)
Chernoff et al. (1990)
Non-RCTs
Breslow et al. (1993)
RCT, double blind, parallel groups.

Beth Abraham Hospital,
Parker Jewish Geriatric Institute, USA
Mean age 80 years (group A) vs.

82 years (group B), all patients had
diabetes
27 elderly patients with

type 2 diabetes mellitus,
at risk for pressure ulcers.
Not stated if any ulcers
at study start
Effect of formulas on
metabolic control and
complications of diabetes
(including pressure ulcer
developmentprevention)
Not stated, <100
RCT, parallel groups.

Randomised University
Arkansas for Medical Sciences,
Little Rock, Arizona, USA
Mean age 72 years. n = 2 in standard

formula group were in negative N
balance during study
12 institutionalised
tube fed patients
with pressure ulcers,
stage not reported
Effect of formula
on pressure ulcer
healing (treatment)
100
CCT, parallel groups.

University of Maryland, USA
Mean age 72 years both groups, baseline

BMI, albumin, respectively: 20 kg/m2,
32 g/L (group A) vs. 22 kg/m2, 33 g/L
(group B). Groups unbalanced for bed type:
ulcer management not standardised.
However, risk factors
for pressure ulcers, age, gender, diagnoses
similar. Mostly bedridden, some on
air-fluidised beds, some on alternating
pressure air mattress overlay on
standard bed. Virtually, all
urinary and faecal incontinence,
immobile, confused, lethargic.
Malnourished (serum albumin
<35 g/L or BW >10% below the
midpoint of age-specific body
weight range) or
nutritional risk (recent involuntary
weight loss (2 kg in 2 weeks) or
referral for inadequate dietary intake)
28 nursing home
residents with stage II
(n = 9), III (n = 8) and
IV (n = 16) pressure
ulcers
Effect of formula
on healing of
pressure ulcers
(treatment)
100
Studies comparing different enteral feeds, including high protein and disease-specific feeds
RCTs
Benati et al. (2001)see above
Other studies
Mean age, BMI, respectively: 70 years,

19 kg/m2 (group A) vs. 60 years,
22 kg/m2 (group B). All incontinent
(bladder and/or bowel), all immobile/
bedridden, 42% group A and 57% group
B stuporous. n = 3 in group A had
amputations. In group A, eight were
on air fluidised beds, and six on regular
beds. All of group B on regular beds
Intervention a
Studies of nutritional support vs. routine care

RCTs
Benati et al. (2001)
Disease-specific high protein supplement
(500 kcal/day, 30 En% protein + 6 g
arginine + 18 mg zinc + antioxidants)
(corrected from inaccurate published
values), n = 6
Standard high protein supplement
(500 kcal/day, 30 En% protein), n = 5
Routine care (usual hospital diet), n = 5
Bourdel-Marchasson
et al. (2000)
High protein supplement (400 kcal/day,

30 En% protein, 20 En% fat, 50 En%
carbohydrate + 3.6 mg zinc + 30 mg
Vitamin C) plus usual diet providing
1800 kcal/day and assistance during
meals, n = 295
Routine care (usual hospital diet providing
1800 kcal/day), n = 377
26 elderly nursing home

residents: group A
had at least 1 pressure
ulcer grades IIIV
(stages II and III, n = 9;
stage IV, n = 5), according
to Shea criteria. Group
B had no pressure
ulcers at entry
Relationship
between
nutritional
status and
pressure ulcer
severity
(treatment)
100 (group A),

0 (group B)
Regimen
Route
Length of
nutritional
intervention
Main outcome measures
Study
results/
findings
Supplement was prescribed as

2 200 mL aliquots/day
(total 500 kcal/day)
Oral
2 weeks
Pressure ulcer status tool
The data were provided

only graphically. The
authors concluded that
ONS, especially diseasespecific ONS, resulted
in a more rapid
improvement in
pressure ulcer healing
2 200 mL supplements/day
(total 400 kcal/day), one with
breakfast, one mid-afternoon
Oral
15 days
or until
discharge
Pressure ulcer relative risk,

dietary intake, pressure ulcer
incidence, mortality
The authors reported

significantly higher energy
and protein intakes
in the intervention
group. At day 15, the
cumulative incidence
of pressure ulcers was
40.6% in the intervention
group vs. 47.2% in
the control group
Citation
Prospective cohort, parallel groups.

University of Maryland, USA
433
434
Regimen
Route
Length of
nutritional
intervention
Study
results/
findings
Delmi et al. (1990)
Standard high protein supplement

(254 kcal/day, 32 En% protein, 21 En% fat,
46 En% carbohydrate + 525 mg Ca, 750 IU
Vitamin A, 25 IU Vitamins D, E and C, B
vitamins and minerals) n = 27
Routine care (standard hospital diet), n = 32
Started on admission.
250 mL (total = 254 kcal/day)
given at 2000 h daily for
duration of hospital stay
Oral
Mean 32 days
Pressure ulcer incidence, blood

biochemistry (albumin), length
of hospital stay, mortality,
complications (severe anaemia,
cardiac failure, infection,
gastrointestinal ulcer, other),
dietary intake, transferrin, liver
enzymes, % patients with
favourable clinical outcome
Pressure ulcer incidence at

discharge from recovery
hospital 0/9 patients in
supplemented vs. 3/15 in
control group. Clinical
outcome was significantly
better, and rate of
complications/mortality
was significantly lower in
the supplemented group.
Length of hospital
stay also significantly
shorter in supplemented
group
Ek et al. (1991)
Standard supplement (400 kcal/day,

200 mL twice daily
16 En% protein, 36 En% fat, 48 En%
(total = 400 kcal)
carbohydrate), plus usual hospital diet
from initial admission
(2200 kcal/day), assume n = 215 (not stated)
Routine care (usual hospital diet,
2200 kcal/day), assume n = 210 (not stated)
Oral
Up to
26 weeks
Pressure ulcer incidence, %

improved, % healed
9.9% (supplemented) vs.

12% (control) of patients
with no pressure ulcers
at entry1, developed them.
In supplemented group,
41.8% ulcers were healed
and 51.3% were improved,
compared to 30.3 and
43.9%, respectively,
in controls

(500 kcal/day, 32 En% protein + 6 mg
arginine, 20 mg zinc, 500 mg Vitamin C,
200 mg Vitamin E, 4 mg carotenoids), n = 51
Placebo (non-caloric water based drink
containing only sweeteners, colourings,
flavours), n = 52
Oral
4 weeks or
until discharge
Incidence of pressure ulcer,

days to onset of ulcers,
total wound size, stage of
pressure ulcer, duration
of pressure ulcer
Incidence of pressure
ulcers 27/51 (intervention)
vs. 30/52 (control), no
significant difference.
Incidence of stage II ulcers
significantly different
(18% vs. 28%). Trend
towards slower onset of
pressure ulcers in
supplemented group
Started immediately
post-operatively. Supplement
prescribed as 400 mL/day
(total = 500 kcal/day),
between meals
Intervention a
Citation
Non-RCTs
Soriano et al. (2004)
Oral
3 weeks
Anthropometry (body weight,

BMI, mid-arm muscle
circumference, triceps skinfold),
pressure ulcer incidence,
condition (e.g. necrotic,
malodour, infected, pain),
surface area, healing time
Wound area reduced

significantly by 29%. Healing
occurred at rate of 0.5 cm2/
day. Significant reduction in
amount of exudate in infected
ulcers, and in the incidence
of necrotic tissue. Changes
in anthropometry and dietary
intake were not significant
Standard formula (1500 kcal/day, 16 En%

protein, plus standard hospital diet), n = 48
Routine care (standard hospital diet), n = 53
Starting within 24 h of surgery,

1 L/day (total = 1500 kcal)
administered by nasogastric
tube by pump 21:0005:00 h
Tube
2 weeks
Pressure ulcer incidence and

grade, pressure ulcer risk score,
blood biochemistry
(total protein, albumin,
haemoglobin), dietary intake
Standard formula (3032 En% fat, no

further composition provided), n = 40
Total enteral nutrition,

intermittent gravity drip
feeding, variety of routes
(nasogastric, gastrostomy,
jejunostomy)
Tube
3 month
follow up
Pressure ulcer incidence,

mortality, dietary intake,
anthropometry (body weight,
BMI, mid-arm muscle area,
triceps skinfold), complications
(infection)
10/62 (supplemented) vs.10/67

(control) patients had stage I
ulcers at baseline. At study
end, 30/48 vs. 37/53 had ulcers
(stages IIV). Energy and
protein intakes were
significantly higher in
supplemented group
At start, 26/40
patients had ulcers; at end this
was 20/33. No change in body
weight, BMI, but arm muscle
area and triceps skinfold each
increased 7% during study
Bourdel-Marchasson
et al. (1997)
Standard formula
(no composition provided), n = 58
Routine care (usual diet), n = 50
As required, constant
infusion, 60120 mL/h
via PEG
Tube
Retrospective:
4872 weeks
Pressure ulcer incidence;

proportion of patients: healed,
improved, unchanged, worsened;
mortality; complications
(vomiting, ileus, gastrooesophageal reflux, bronchorrhea/
dyspnea, aspiration pneumonia)
During study, 6/58 (intervention)

vs. 8/50 (control) patients
developed pressure ulcers. 7/40
were healed and 13/40 improved
during the study (intervention
group) compared to 3/15 healed
in the control group
Mitchell et al. (1997)
Standard formula (composition not

provided), n = 135
Routine care (usual diet), n = 1251
Not stated
Tube
24 month
Odds ratio for feeding

tube placement, mortality
Mortality presented
graphicallyappeared to be
benefit for intervention group,
but no statistics
Peck et al. (1990)
Standard formula (15002130 kcal/day,

no further composition provided), n = 52
Routine care (usual diet providing
18002000 kcal/day), n = 52
As required. Routes included

nasogastric, gastrostomy and
jejunostomy. Usually
administered as 6 feeds/day
Tube
Retrospective:
6 months

complications (pneumonia)
21% (supplement) vs. 13%

(control) had pressure ulcers
during the follow up period

RCTs
Hartgrink et al. (1998)
Non-RCTs
Henderson et al. (1992)
435
Based on energy requirements

and food intake, 13 packages
(mean: 1.9 0.6) of supplement
prescribed per day

(1 package = 200 mL: 250 kcal, 30 En%
protein, 25 En% fat, 45 En% carbohydrate
+ 250 mg Vitamin C, 37.6 mg Vitamin E,
9 mg zinc), n = 39
436
Citation
Interventiona
Regimen
Route
Length of
nutritional
intervention
Study
results/
findings
41.2%, 17%, 58.8% (low

carbohydrate) vs. 53.3%, 13%,
73.3% (high carbohydrate)
patients had pressure ulcers,
died or had infectious
complications, respectively,
at study end
4/6 patients healed during
study in high protein group
compared to 0/6 in standard
group. Overall, 73% (high
protein) reduction in ulcer area
vs. 42% (standard)
Studies comparing different enteral feeds, including high protein and disease-specific feeds

RCTs
Craig et al. (1998)
Chernoff et al. (1990)
Non-RCTs
Standard formula low carbohydrate

(17 En% protein, 50 En% fat, 33 En%
carbohydrate), n = 14
Standard formula high carbohydrate
(17 En% protein, 30 En% fat, 53 En%
carbohydrate), n = 13
Diets were administered bolus

(via enteral access device),
continuous or intermittent, to
provide the total energy
requirement of each patient
Tube
3 months

mortality, complications
(infections), metabolic
control outcomes
(glycaemia, lipidaemia)
Standard high protein formula (25 En%

protein, no further composition provided),
n=6
Standard formula (16 En% protein,
no further composition provided), n = 6
Not stated Total

enteral nutrition?
Tube
8 weeks

ulcer area, % patients healed
Standard high protein formula

(763 kcal/day, 24 En% protein for
oral patients, volume to meet
individual requirements in tube
fed patients), n = 15
Oral supplement (n = 14 group A

Tube
vs. n = 6 group B) or total enteral
or oral
nutrition (n = 13 group A vs. n = 15
group B). Enteral: individual based on
energy requirements, route not
described, volume increased
over period of 2 weeks. Oral:
one can (240 mL) 3 daily plus
standard nursing home diet
(approximately 2000 kcal/day
and 85 g protein/day)
8 weeks
Pressure ulcer incidence

and area, dietary intake,
anthropometry (body weight,
BMI), blood biochemistry
transferrin, haemoglobin,
haematocrit, zinc), mortality,
complications (diarrhoea)
Significant
decrease in ulcer area
( 4.2 cm2) in
high protein group,
no significant change
in low protein group
( 2.1 cm2). Change
in ulcer area correlated
with protein and
energy intakes.
Energy intakes
similar, but protein
intake significantly
higher in high protein
group. No significant
changes in anthropometry
or biochemistry
RCTs
Benati et al. (2001)see above
Standard formula (720 kcal/day,

14 En% protein for oral patients,
volume to meet individual
requirements in tube fed
patients), n = 13
Other studies
As required. Gravity drip

(n = 8 in group A and n = 7
in group B) or continuous
pump (n = 6 group A and
n = 5 group B)
BMI: body mass index; En%: percentage of energy form.

a
Disease-specific high protein supplements are those formulated specifically for patients with pressure ulcers.
Tube
8 weeks?
(not stated)
Dietary intake,
blood biochemistry
transferrin, haemoglobin,
haematocrit, cholesterol,
glucose, white blood count,
lymphocytes, plasma copper
and zinc, serum urea N,
serum creatinine), pressure
ulcer incidence and area
Pressure ulcer surface

area positively correlated
with energy intake. No
baseline areas provided.
Energy intake similar,
but protein intake
slightly higher in
group A

28 En% fat, 55 En% carbohydrate),
n = 14 with pressure ulcers at baseline
28 En% fat, 55 En% carbohydrate),
n = 12 without pressure ulcers at
baseline. No control group
437
438
Table 4
Studies excluded from the systematic review, with reasons
Citation
Reason code
Reason description
Anderson and
Beaton (1974)
Fulghum (1977)

Thomas (2001)
Abbott et al. (1968)
A
A
B
Bildsten and
Lamid (1983)
Brewer et al.
(1967)
Collins (2004)
Holmes et al.
(1987)
Houston et al.
(2001)
Jackobs (1999)
Not an original study but a comment on Taylor

1974 study data
Not an original study but a review article that
cites Taylor 1974 study data
Not an original study: duplicate data of Houwing 2003
Not an original study but a review
Double blind RCT of patients with pressure sores,
oral zinc sulphate supplement. Study of pressure
sores, but the zinc supplement was provided as
discrete doses not within a multi-nutrient supplement
Case report of a single malnourished patient with brain damage
and spinal cord injury, nutritional supplementation by a variety
of means including enteral (Isocal, but only for a few days),
then oral, then food. He had a pressure sore, but this was
eventually closed by flap surgery. No pressure sore outcome
measures, but graphs of body weight and serum albumin are
provided for a period of 14 months (during which time a variety
of nutritional strategies were tried)
Double blind RCT of 14 spinal cord injured patients
with decubitus ulcers, oral zinc sulphate. Study of
pressure sores, but the zinc supplement was provided
as discrete doses not within a multi-nutrient supplement
Case report of single patient with pressure sores. Nutritional
supplements (high protein pudding, shake and cookies)
and anabolic drug Oxandrolone used. Supplement source
unclear, but author is consultant for Ross Abbott.
No pressure sore outcome data, but albumin,
pre-albumin, transferrin and lymphocyte count reported.
Results confounded by drug prescription. The case
presented in this article is a composite of
several patients
Paper describes two studies. In the first, 12/12 of the patients
had pressure sores. They were given nutritional support8/12
enterally. However, the other four were given
nutritional supplements added to their meal tray.
These two types of supplementation were not
differentiated, and it was not possible to confirm
the composition in the latter. In the second study,
0% patients had pressure sores at study start
(study of risk), but there was no nutrition
intervention for these patients
CCT of patients with pressure ulcers, zinc sulphate.
Zinc was provided as discrete doses
Study of nine patients with pressure ulcers. Nutritional
support included food, extra protein foods, house
supplement (280 kcal and 10 g protein/6 oz drink),
enteral supplements, protein powder, vitamins/minerals
No composition details. Results do not differentiate
those fed enterally vs. food, etc.
439
Citation
Reason code
Reason description
Myers et al. (1990)
Norris and
Reynolds (1971)
Taylor et al.
(1974)
ter Riet et al.

(1995)
Watkin and
Waldron (1981)
Welch et al.
(1991)
Bastow et al.
(1983)
Larsson et al.
(1990)
Barateau et al.
(1998)
Takagi et al. (1991)
Study of 80 patients with pressure sores. Prescribed

nutritional support including oral supplements, tube
feedings, parenteral nutrition, vitamins and trace
elements according to clinical condition and
nutritional assessment. No composition details.
Results are not differentiated for those fed
enterally vs. parenterally
Double blind crossover study of 14 patients with
decubitus ulcers, zinc sulphate supplement. Study
of pressure sores, but the zinc supplement was
provided as discrete doses not within a multi-nutrient
supplement
Double blind RCT of 20 surgical patients with pressure
sores, oral Vitamin C supplement. Study of pressure
sores, but the Vitamin C supplement was provided as
discrete doses not within a multi-nutrient supplement
Multi-centre blinded RCT of 88 patients with pressure
sores, 500 mg Vitamin C vs. 10 mg Vitamin C. Study
of pressure sores, but the Vitamin C supplement
was provided as discrete doses not within a
multi-nutrient supplement
A study of patients with pressure sores, oral zinc
sulphate. The zinc supplement was provided as discrete
doses not within a multi-nutrient supplement
Case study of 15 nursing home patients, some of
which had pressure sores, using nutritional supplements.
Nutritional supplements were additional food items
RCT of 122 hip fracture patients, overnight enteral feed
supplement. The patients did not have pressure ulcers
at study start. No pressure ulcer outcomes reported
RCT of 501 elderly, supplement (Biosorb drink).
The patients did not have pressure sores at study entry.
No pressure sore outcomes reported
Document could not be sourced
No English translation available
Reason codes: A, not an original study; B, ineligible nutritional intervention; C, no relevant outcomes reported; D,
document could not be sourced.
3.2. Description of studies included in the systematic literature review

The 15 studies included in the systematic review comprised RCTs (n = 8; Chernoff
et al., 1990; Delmi et al., 1990; Ek et al., 1991; Craig et al., 1998; Hartgrink et al.,
1998; Bourdel-Marchasson et al., 2000; Benati et al., 2001; Houwing et al., 2003),
CCTs (n = 1; Breslow et al., 1993), CTs (n = 1; Soriano et al., 2004) and cohort studies
(n = 5; Peck et al., 1990; Breslow et al., 1991; Henderson et al., 1992; BourdelMarchasson et al., 1997; Mitchell et al., 1997). All trials had a follow up of at least 2
440
weeks, up to a maximum of 2 years. The populations studied were mostly elderly,

including those with hip fractures, a range of critical illnesses and institutionalised
patients (Table 3).
There were six studies comparing ONS with routine care, including five RCTs (Delmi
et al., 1990; Ek et al., 1991; Bourdel-Marchasson et al., 2000; Benati et al., 2001; Houwing
et al., 2003) and one CT (Soriano et al., 2004). The aim of these studies was healing of
existing ulcers (Benati et al., 2001; Soriano et al., 2004), prevention of the development of
pressure ulcers (Bourdel-Marchasson et al., 2000; Houwing et al., 2003), both treatment
and prevention (Ek et al., 1991), or the inclusion of pressure ulcer outcomes as a secondary
aim of the study (Delmi et al., 1990) (Table 3).
There were five studies comparing ETF with routine care, including one RCT
(Hartgrink et al., 1998) and four cohort studies (Peck et al., 1990; Henderson et al.,
1992; Bourdel-Marchasson et al., 1997; Mitchell et al., 1997). The aim of these studies
was prevention of the development of pressure ulcers (Hartgrink et al., 1998), or the
inclusion of pressure ulcer outcomes as a secondary aim of the study (Peck et al., 1990;
Henderson et al., 1992; Bourdel-Marchasson et al., 1997; Mitchell et al., 1997)
(Table 3).
Four studies compared different enteral formulas, including high protein and diseasespecific feeds specifically formulated for patients with pressure ulcers. One RCT compared
the effect of an ONS specifically formulated for pressure ulcers with a standard formula
and routine care on the healing of existing pressure ulcers (Benati et al., 2001). Two studies,
one RCT of ETF (Chernoff et al., 1990) and one CCT using both ONS and ETF (Breslow
et al., 1993), compared the effect of a high protein (24% energy as protein) versus a
standard formula (14% protein). All three studies were designed to examine the effect of
the interventions on the healing of existing pressure ulcers (Table 3). One further RCT in
elderly patients with type 2 diabetes mellitus (Craig et al., 1998) investigated the impact of
a standard ETF compared to a formula specifically developed for patients with diabetes, on
pressure ulcer incidence.
A final study (Breslow et al., 1991) simply compared the intake and status of tube fed
patients with and without pressure ulcers, but this was not considered further (summarised
in Table 3). No studies were identified that compared ETF versus parenteral nutritional
support in patients with, or at risk of developing, pressure ulcers.
There were insufficient data to allow separate analysis of studies of different duration
(short-term feeding versus long-term feeding), of formulas containing different
concentrations of specific nutrients (e.g. high zinc versus low zinc) or according to the
nutritional status of patients (malnourished versus well-nourished).
3.3. Description of studies included in the meta-analysis
The only outcome measure that was meta-analysable was the incidence of pressure
ulcers. The five studies included in the meta-analysis were all RCTs (Delmi et al., 1990; Ek
et al., 1991; Hartgrink et al., 1998; Bourdel-Marchasson et al., 2000; Houwing et al., 2003).
They included four studies of ONS (Delmi et al., 1990; Ek et al., 1991; BourdelMarchasson et al., 2000; Houwing et al., 2003) and one study of ETF (Hartgrink et al.,
1998) (Table 3).
441
3.4. Quality assessment of studies included in the systematic literature review

The review included eight RCTs scoring the highest grade of 1 on the Quality of
Evidence scale (Chernoff et al., 1990; Delmi et al., 1990; Ek et al., 1991; Craig et al., 1998;
Hartgrink et al., 1998; Bourdel-Marchasson et al., 2000; Benati et al., 2001; Houwing et al.,
2003), one CCT (Breslow et al., 1993) scoring a low grade of 6 (AHCPR, 1992) due to an
unknown influence of bed type on the results, five cohort studies (Peck et al., 1990; Breslow
et al., 1991; Henderson et al., 1992; Bourdel-Marchasson et al., 1997; Mitchell et al., 1997)
scoring 3 and one CT (Soriano et al., 2004) scoring 4.
Whilst the majority of studies were RCTs, the methodology of individual RCTs was
generally judged to be poorly described or planned (with regard to methods of
randomisation, blinding and recording number of drop-outs) with only one study (Craig
et al., 1998) scoring the top grade of 5 on the Jadad scale (Jadad et al., 1996). The remaining
RCTs scored 4 (n = 1; Houwing et al., 2003), 3 (n = 1; Hartgrink et al., 1998) or 2 (n = 5;
Chernoff et al., 1990; Delmi et al., 1990; Ek et al., 1991; Bourdel-Marchasson et al., 2000;
Benati et al., 2001).
3.5. Quality assessment of studies included in the meta-analysis
All five studies included in the meta-analysis were RCTs, scoring the highest grade of 1
on the Quality of Evidence scale (Delmi et al., 1990; Ek et al., 1991; Hartgrink et al., 1998;
Bourdel-Marchasson et al., 2000; Houwing et al., 2003). However, the methodology of
individual RCTs was generally judged to be poorly described or planned (with regard to
methods of randomisation, blinding and recording number of drop-outs), with Jadad scores
of 4 (n = 1; Houwing et al., 2003), 3 (n = 1; Hartgrink et al., 1998) or 2 (n = 3; Delmi et al.,
1990; Ek et al., 1991; Bourdel-Marchasson et al., 2000).
No significant heterogeneity was found between these trials (Fig. 2).
3.6. Outcomes
3.6.1. Studies comparing nutritional support with routine care
3.6.1.1. Pressure ulcer prevention in at-risk patients. Meta-analysis of four RCTs (Delmi
et al., 1990; Ek et al., 1991; Bourdel-Marchasson et al., 2000; Houwing et al., 2003)
demonstrated that the provision of ONS (mainly high protein) in patients with no ulcers at
baseline resulted in a significantly lower incidence of pressure ulcers compared to routine
care (odds ratio 0.75, 95% CI 0.620.89, n = 1224, Fig. 2). When the RCT of ETF
(Hartgrink et al., 1998) was included in the meta-analysis the result remained similar (odds
ratio 0.74, 95% CI 0.620.88, 5 RCT, n = 1325, Fig. 2). This trial was in a mixed patient
cohort, 16% had stage I ulcers at baseline and individually this trial did not show a
significant effect on PU incidence.
Using results from all five RCTs, the number needed to treat (NNT) was calculated. This
analysis suggested that on average 19.25 patients would need to be given enteral nutritional
support in order to prevent one pressure ulcer.
442
Fig. 2. Prevention of pressure ulcers in at-risk patients following nutritional support vs. routine care: a meta-analysis (Delmi et al., 1990; Ek et al., 1991; Hartgrink et al.,
1998; Bourdel-Marchasson et al., 2000; Houwing et al., 2003).
443
Non-randomised studies of ONS and ETF were not meta-analysable, and were more
difficult to interpret since the patients were provided nutritional support prior to the study
start (Henderson et al., 1992), used groups with a significant difference in the incidence of
ulcers at baseline (Bourdel-Marchasson et al., 1997) or the authors did not present baseline
plus final incidence data (Peck et al., 1990; Mitchell et al., 1997).
3.6.1.2. Healing of existing pressure ulcers. There were insufficient comparable data to
allow meta-analysis of the effect of enteral nutritional support versus routine care on the
healing of existing pressure ulcers.
Three studies, which were not meta-analysable, presented data including two RCTs (Ek
et al., 1991; Benati et al., 2001) and one CT (Soriano et al., 2004). Although one RCT
(Benati et al., 2001) used a pressure ulcer status tool and presented the data only
graphically, the authors concluded that there was a tendency of improved wound healing
in patients fed ONS, compared to normal hospital diets. The other RCT (Ek et al., 1991)
reported that following nutritional support, 42% of ulcers were healed and 51% were
improved, compared with 30 and 41%, respectively, in those patients receiving routine care
(non-significant differences).
A similar trend towards improved healing was reported by a CT (Soriano et al., 2004),
which utilised a specifically formulated ONS in patients with grade III or IV pressure ulcers
at baseline. Compared to routine care (before supplementation), 3 weeks of nutritional
supplementation resulted in a significant reduction of wound area (median 23.619.2 cm2,
equivalent to a 29% reduction) and significant reductions in the amount of exudates in
infected ulcers, and necrotic tissue (Soriano et al., 2004). The findings of this study are
limited by the lack of a randomly selected control group (historical control subjects used).
3.6.1.3. Quality of life. None of the studies comparing enteral nutritional support with
routine care reported data on quality of life.
3.6.1.4. Complications. Three studies (one RCT and two non-RCT) of enteral nutritional
support versus routine care reported data on complications but there were insufficient
comparable data to allow meta-analysis. One RCT (Delmi et al., 1990) found no significant
difference in the rates of complications, other than pressure ulcers, including severe
anaemia, cardiac failure, infection and gastrointestinal ulcer in fractured neck of femur
patients receiving ONS compared to routine care, but not all of these patients had pressure
ulcers. A retrospective cohort of patients receiving ETF (Peck et al., 1990) suggested a
significantly greater incidence of pneumonia than during the non-tube feeding period, but
again the data were not stratified for those with and without pressure ulcers. These findings
may also reflect the tube feeding practices rather than the clinical status of the patients. One
cohort study provided no baseline data on the incidence of complications for comparison
(Henderson et al., 1992).
Nutritional support with ONS in one RCT of elderly fracture patients resulted in a
significantly reduced length of hospital stay (24 days) compared to routine care (40 days),
although again, results were not specifically presented for patients with and without
pressure ulcers (Delmi et al., 1990).
444
3.6.1.5. Mortality. There were insufficient comparable data to allow meta-analysis of the
effect of enteral nutritional support versus routine care on mortality in patients with, or at
risk of, pressure ulcers.
Two RCTs found no significant difference in the mortality rate of those receiving
nutritional support versus routine care (Delmi et al., 1990; Bourdel-Marchasson et al., 2000).
One cohort study (Henderson et al., 1992) provided no control for comparison, whilst another
(Mitchell et al., 1997) presented 24 months survival data graphically, and although there
appeared to be a benefit for ETF versus routine care, no statistical analysis was reported.
3.6.1.6. Dietary intake and nutritional status. There were insufficient comparable data to
allow meta-analysis of the effect of enteral nutritional support versus routine care on
dietary intake or nutritional status in patients with, or at risk of, pressure ulcers.
One RCT in patients with a fractured neck of femur at risk of pressure ulcers (Hartgrink
et al., 1998) demonstrated a significant increase in total energy and protein intakes
following ETF (1532 kcal and 61.7 g/day) compared to routine care (1020 kcal and 40.1 g/
day). The exact contribution from food intake and ETF was not documented. In a similar
patient group, ONS increased the intake of energy (by 23%), protein (by 62%) and calcium
(by 130%) and voluntary food intake was not suppressed (Delmi et al., 1990). However, in
both of these trials in patients with and at risk of pressure ulcers (Delmi et al., 1990;
Hartgrink et al., 1998), the intake in those who did and did not develop pressure ulcers was
not provided. In another RCT in critically ill older people at risk of pressure ulcers, patients
randomised to the ONS group had a greater total and supplement energy and protein intake
than the control group for the duration of the trial (Bourdel-Marchasson et al., 2000).
No RCTs provided data on changes in body weight or other markers of nutritional
status. Only two non-RCT studies provided relevant data and they showed no significant
changes in weight/body mass index or upper arm anthropometry following ONS (Soriano
et al., 2004) or ETF (Henderson et al., 1992). One RCT found no significant effect of ETF
versus routine care on total serum protein, albumin or haemoglobin using an intention to
treat analysis (Hartgrink et al., 1998).
3.6.2. Studies comparing different enteral formulas
3.6.2.1. Pressure ulcer prevention in at-risk patients. None of the studies comparing
different enteral formulas reported incidence data in patients at risk of developing pressure
ulcers.
3.6.2.2. Healing of existing pressure ulcers. There were insufficient comparable data to
allow meta-analysis of the effect of different enteral formulas on the healing of existing
pressure ulcers.
One RCT (Chernoff et al., 1990) reported that pressure ulcers in 4/6 patients receiving a
high protein ETF, compared to 0/6 patients receiving a standard formula, were healed. This
was associated with a 73% reduction in the surface area of pressure ulcers in the group
receiving the high protein formula compared to a 42% reduction in the control group.
However, this result was not statistically significant. Another RCT (Benati et al., 2001)
used a pressure ulcer status tool and presented the data only graphically. The authors
concluded that patients receiving an ONS specifically formulated for pressure ulcer
445
treatment demonstrated a more rapid improvement in pressure ulcer healing, compared to

standard supplements, but no statistics were reported. Although non-randomised, a CCT
(Breslow et al., 1993) conducted in patients with baseline pressure ulcers (grades IIIV)
found that compared to a standard enteral formula given orally or by tube, patients
receiving a high protein formula for 8 weeks demonstrated a significant reduction in ulcer
surface area (mean area truncal ulcers, any grade, changed from 28.6 to 24.4 cm2 for high
protein group, from 14.9 to 12.7 cm2 for standard group). This significant benefit was also
observed for the grade IV ulcers in each group (mean area truncal ulcers, grade IV, changed
from 42.6 to 35 cm2 for high protein group, from 26.6 to 23.5 cm2 for standard group).
3.6.2.3. Other clinical outcomes. None of the studies comparing different enteral formulas
reported data on quality of life or other complications in patients with or at risk of developing
pressure ulcers. One CCT reported mortality data, finding no significant differences between
patients fed a high protein versus a standard formula by tube (Breslow et al., 1993).
3.6.2.4. Dietary intake and nutritional status. There were insufficient comparable data to
allow meta-analysis of the effect of different enteral formulas on dietary intake or
nutritional status in patients with existing pressure ulcers.
One CCT (Breslow et al., 1993) reported similar energy intake and significantly
increased protein intake (0.6 g/kg body weight/day increase) in patients receiving a high
protein formula given orally or by tube compared to those receiving standard formulas.
However, this had no significant effect on body weight, body mass index, serum albumin,
serum transferrin, haemoglobin, haematocrit or plasma zinc.
3.6.3. Enteral tube feeding versus parenteral nutrition
No studies comparing ETF with parenteral administration were identified.
4. Discussion
This systematic review shows that enteral nutritional support, and in particular high
protein ONS, are associated with a significant reduction (by 25%) in pressure ulcer
development compared to routine care (e.g. usual diet and usual pressure ulcer care). ONS
and ETF may also aid pressure ulcer healing in at-risk patient groups but these trends
require confirmation with further study. Prevention of pressure ulcers is associated with
benefits for both the patient, who may be spared a common, painful and debilitating
condition, and health-care professionals, due to the reduction in work load and bed
occupancy, as well as potential cost savings (Allman et al., 1999). However, as previously
reported (Langer et al., 2003), the quality of the evidence available, including RCTs, is
generally poor, and more research is required to confirm these findings.
4.1. Prevention and possible mechanisms of prevention
Meta-analysis of four RCT of ONS (250500 kcal/day) and one RCT of ETF
(1500 kcal/day) (Delmi et al., 1990; Ek et al., 1991; Hartgrink et al., 1998; Bourdel-
446
Marchasson et al., 2000; Houwing et al., 2003) showed that development of pressure ulcers
was significantly reduced by nutritional support compared to routine care. The majority of
these studies (four out of five RCT) used ONS and were characterised by the use of high
protein feeds. These studies were typically short-term (24 weeks), involved elderly
patients (mean age > 75 years), suffering from a serious underlying condition (e.g.
fracture, critical illness, bedridden, cognitive impairment, chronic illness), and nutritional
support was provided irrespective of nutritional status (Delmi et al., 1990; Ek et al., 1991;
Hartgrink et al., 1998; Bourdel-Marchasson et al., 2000; Houwing et al., 2003). The
findings are therefore applicable to a large proportion of patients considered to be at risk for
ulcer development, both in the hospital and community care settings.
All five studies used in the analysis were RCTs, and confidence in the analysis is
supported by the results of the individual studies, all of which reported a decreased
incidence of ulcers following nutritional support. The lack of significance in the individual
studies is most likely to be due to small sample sizes (see Table 3), with the increased power
of the meta-analysis arising mostly from pooling of the data (n = 1224). Although these
individual RCT typically scored low ratings during quality assessment (Jadad et al., 1996),
this is in part to be expected since blinding of nutritional studies can be difficult (e.g. where
patients are provided supplements versus no supplements, or where one intervention
requires the insertion of a feeding tube).
The mechanisms by which nutritional support prevents the development of pressure
ulcers are not known, but are likely to include an improvement in nutritional intake and
status. The low energy intake of participants (1100 kcal (4.62 MJ)/day; Delmi et al.,
1990; Bourdel-Marchasson et al., 2000) was increased by nutritional support with liquid
ONS and ETF. Compliance with ONS was good (Houwing et al., 2003) and intervention
did not typically suppress food intake (Delmi et al., 1990). This would be especially
pertinent for malnourished patients, and from the variability in measures of nutritional
status (Delmi et al., 1990; Ek et al., 1991; Bourdel-Marchasson et al., 2000; Houwing et al.,
2003) a substantial number of patients would have had a BMI < 20 kg/m2, weight
index < 90% and a mid-upper arm circumference of <23.5 cm, indicative of chronic
protein energy malnutrition (Elia, 2003). It is not possible to tell from the current data
whether these malnourished patients benefited to a greater extent than well-nourished
individuals in each cohort.
The increased nutritional intake would be expected to improve nutritional
status (Henderson et al., 1992; Soriano et al., 2004), increasing the soft-tissue
padding over the bony prominences. This would distribute any pressure on the tissues
over a wider area, reducing the risk of occluding blood flow to tissues, which could
otherwise become ischaemic or necrotic. Skin condition may be improved, increasing its
resistance to the effects of pressure, shear and friction, whilst the enhanced arginine
content of disease-specific formulas (e.g. Houwing et al., 2003) may increase blood
flow to the skin, due to the production of the vasoactive product, nitric oxide (BodeBoger et al., 2003). It is also possible that nutritional support reduces the known adverse
effects of malnutrition on psychological function (e.g. well-being), energy levels and
voluntary activities (Keys et al., 1950). A final consideration is that the extra fluid
provided may help prevent dehydration, which predisposes to pressure ulcers (Stotts and
Hopf, 2003).
447
4.2. Healing and potential mechanisms of healing

The findings of four individual studies (one RCT (Benati et al., 2001), and one CT
(Soriano et al., 2002) of ONS one RCT (Chernoff et al., 1990) and one CCT (Breslow et al.,
1993) of ETF), which were not meta-analysable, indicate a trend towards enhanced
healing, especially with the use of high protein or disease-specific formulas. However, the
sample sizes in all studies are small (Table 1) and lack statistical power.
The mechanisms by which nutritional support may aid the healing of existing pressure
ulcers include the reversal of protein-energy and/or micronutrient deficiencies. Even in
well-nourished individuals, the supply of a range of nutrients (including protein, arginine,
Vitamins C, A and E, B vitamins, zinc, selenium) is required, and the additional nutrients
provided by ONS and ETF (e.g. Chernoff et al., 1990; Breslow et al., 1993; Benati et al.,
2001) may be used as substrates in wound and tissue repair and regeneration. The timely
provision of nutritional support could reverse or prevent, the progression of pressure ulcers
(e.g. from stages I to II). In one RCT (Ek et al., 1991), patients with a pressure ulcer
developed fewer subsequent ulcers following nutritional support (11% versus 25%).
4.3. Conclusions
In summary, enteral nutritional support using multi-nutrient feeds, particularly as high
protein ONS, can significantly reduce the development of pressure ulcers in high risk
patient groups. Studies suggest high protein/disease specific ONS and ETF may improve
the healing of PU but adequately powered, robust RCTs conducive to meta-analysis are
required to confirm these trends. Further research is also required to elucidate the specific
mechanisms, and to optimise nutritional intervention.
Acknowledgements
This study was conducted using an educational grant supplied by Numico. Thanks to
Abacus International, UK, for research support, and to Statwood, UK, for statistical
support.
References
Abbott, D.F., Exton-Smith, A.N., Millard, P.H., Temperley, J.M., 1968. Letter: zinc sulphate and bedsores. Br.
Med. J. 2 (607), 763.
AHCPR (Agency for Health Care Policy and Research), 1992. Acute Pain Management: operative or medical
procedures and trauma. Clin. Pract. Guidelines 92, 0032.
Allman, R.M., Laprade, C.A., Noel, L.B., Walker, J.M., Moorer, C.A., Dear, M.R., Smith, C.R., 1986. Pressure
sores among hospitalized patients. Ann. Int. Med. 105, 337342.
Allman, R.M., Goode, P.S., Burst, N., Bartolucci, A.A., Thomas, D.R., 1999. Pressure ulcers, hospital complications, and disease severity: impact on hospital costs and length of stay. Adv. Wound Care 12, 2230.
Anderson, T.W., Beaton, G.H., 1974. Letter: ascorbic acid in treatment of pressure-sores. Lancet 2 (7886), 957
958.
448
Barateau, M., Corompt, A., Soulan, J., Bourdel-Marchasson, I., 1998. Multicenter nursing study on the importance
of nutritional support for the prevention of bedsores in the elderly at risk. Rech. Soins. Infirm. 55, 4249.
Barbul, A., Lazarou, S.A., Efron, D.T., Wasserkrug, H.L., Efron, G., 1990. Arginine enhances wound healing and
lymphocyte immune responses in humans. Surgery 108, 331337.
Bastow, M.D., Rawlings, J., Allison, S.P., 1983. Benefits of supplementary tube feeding after fractured neck of
femur: a randomised controlled trial. Br. Med. J. 287 (6405), 15891592.
Benati, G., Delvecchio, S., Cilla, D., Pedone, V., 2001. Impact on pressure ulcer healing of an arginine-enriched
nutritional solution in patients with severe cognitive impairment. Arch. Gerontol. Geriatr. 33 (Suppl. 7), 43
47.
Bergstrom, N., Braden, B., 1992. A prospective study of pressure sore risk among institutionalised elderly. J. Am.
Geriatr. Soc. 40, 747758.
Berlowitz, D.R., Wilking, S.V., 1989. Risk factors for pressure sores: a comparison of cross sectional and cohort
derived data. J. Am. Geriatr. Soc. 37, 10431050.
Bildsten, C., Lamid, S., 1983. Nutritional management of a patient with brain damage and spinal cord injury. Arch.
Phys. Med. Rehabil. 64 (8), 382383.
Bode-Boger, S.M., Muke, J., Surdacki, A., Brabant, G., Boger, R.H., Frolich, J.C., 2003. Oral L-arginine improves
endothelial function in healthy individuals older than 70 years. Vasc. Med. 8 (2), 7781.
Bourdel-Marchasson, I., Barateau, M.R.V., Dequae-Merchadou, L., Salles-Montaudon, N., Emeriau, J.P., Manciet,
G., Dartigues, J.F., 2000. A multi-center trial of the effects of oral nutritional supplementation in critically ill
older inpatients. GAGE Group. Groupe Aquitain Geriatrique dEvaluation. Nutrition 16 (1), 15.
Bourdel-Marchasson, I., Dumas, F., Pinganaud, G., Emeriau, J.P., Decamps, A., 1997. Audit of percutaneous
endoscopic gastrostomy in long-term enteral feeding in a nursing home. Int. J. Qual. Health Care 9 (4), 297
302.
Bours, G., Halfens, R., Lubbers, M., Haalboom, J., 1999. The development of a national registration form to
measure the prevalence of pressure ulcers in the Netherlands. Ostomy Wound Manage. 45, 2840.
Breslow, R.A., Hallfrisch, J., Goldberg, A.P., 1991. Malnutrition in tubefed nursing home patients with pressure
sores. J. Parenter. Enteral Nutr. 15 (6), 663668.
Breslow, R.A., Hallfrisch, J., Guy, D.G., Crawley, B., Goldberg, A.P., 1993. The importance of dietary protein in
healing pressure ulcers. J. Am. Geriatr. Soc. 41 (4), 357362.
Brewer, R.D.J., Mihaldzic, N., Dietz, A., 1967. The effect of oral zinc sulfate on the healing of decubitus ulcers in
spinal cord injured patients. Proc. Annu. Clin. Spinal Cord Int. Conf. 16 (September (27)), 7072.
Chernoff, R.S., Milton, K.Y., Lipschitz, D.A., 1990. The effect of a very high protein liquid formula on decubitus
ulcers healing in long term tube fed institutionialised patients. J. Am. Diet Assoc. 90, A-130 (Abstract).
Clinical evidence, 2004. www.clinicalevidence.com (accessed 12/08/04).
Cochrane, 2004a. http://www.nelh.nhs.uk/cochrane.asp (accessed 28/07/04).
Cochrane, 2004b. Cochrane Reviewers Handbook 4.2.2 (updated March 2004), www.cochrane.org/resources/
handbook/hbook.htm (accessed 22/07/04).
Collins, N., 2004. The right mix: using nutritional interventions and an anabolic agent to manage a stage IV ulcer.
Adv. Skin Wound Care 17 (1), 3639.
Craig, L.D., Nicholson, S., Silverstone, F.A., Kennedy, R.D., 1998. Use of a reduced-carbohydrate, modified-fat
enteral formula for improving metabolic control and clinical outcomes in long-term care residents with type 2
diabetes: results of a pilot trial. Nutrition 14 (6), 529534.
CRD, 2000. Finding Studies for Systematic Reviews: A Basic Checklist for Researchers, www.york.ac.uk/inst/
crd/revs.htm.
CRD, 2001. Undertaking Systematic Reviews of Research on Effectiveness: CRDs Guidance for those Carrying
out or Commissioning Reviews. National Health Service Centre for Reviews and Dissemination. Report
Number 4, second ed. University of York, York, UK.
Delmi, M., Rapin, C.H., Bengoa, J.M., Delmas, P.D., Vasey, H., Bonjour, J.P., 1990. Dietary supplementation in
elderly patients with fractured neck of the femur. Lancet 335 (8696), 10131016.
Egger, M., Davey Smith, G., Schneider, M., Minder, C., 1997. Bias in meta-analysis detected by a simple,
graphical test. Br. Med. J. 315, 629634.
Ek, A.-C., Unosson, M., Larsson, J., Von Schenck, H., Bjurulf, P., 1991. The development and healing of pressure
sores related to the nutritional state. Clin. Nutr. 10, 245250.
449
Elia, M., 2003. The MUST Report. Nutritional Screening for Adults: A Multidisciplinary Responsibility.
Development and Use of the Malnutrition Universal Screening Tool (MUST) for Adults. A Report by the
Malnutrition Advisory Group of the British Association for Parenteral and Enteral Nutrition. Elia, M. (Editor
and Chairman). Report No.: ISBN 1-899467-70X.
EPUAP (European Pressure Ulcer Advisory Panel), 2004. Pressure Ulcer Treatment Guidelines, http://www.
epuap.org/gltreatment.html.
Fox, C., 2002. Living with a pressure ulcer: a descriptive study of patients experiences. Br. J. Community Nurs.
Wound Care Suppl. 10, 1214.
Fulghum, D.D., 1977. Ascorbic acid revisited. Arch. Dermatol. 113 (1), 9192.
Green, S.M., Winterberg, H., Franks, P.J., Moffatt, C.J., Eberhardie, C., McClaren, S., 1999. Dietary intake of
adults, with and without pressure sores, treated by community nursing staff. Proc. Nutr. Soc. 58, 140A.
Guenter, P., Malyszek, R., Bliss, D.Z., Steffe, T., OHara, D., LaVan, F., Monteiro, D., 2000. Survey of nutritional
status in newly hospitalized patients with stage III or stage IV pressure ulcers. Adv. Skin Wound Care 13 (4 Pt
1), 164168.
Haalboom, J., 2000. A new century without pressure ulcers? Br. J. Nurs. 9, S4S6.
Harris, C.L., Fraser, C., 2004. Malnutrition in the institutionalized elderly: the effects on wound healing. Ostomy
Wound Manage. 50 (10), 5463.
Hartgrink, H.H., Wille, J., Konig, P., Hermans, J., Breslau, P.J., 1998. Pressure sores and tube feeding in patients
with a fracture of the hip: a randomized clinical trial. Clin. Nutr. 17 (6), 287292.
Henderson, C.T., Trumbore, L.S., Mobarhan, S., Benya, R., Miles, T.P., 1992. Prolonged tube feeding in long-term
care: nutritional status and clinical outcomes. J. Am. Coll. Nutr. 11 (3), 309325.
Holmes, R., Macchiano, K., Jhangiani, S.S., Agarwal, N.R., Savino, J.A., 1987. Combating pressure sores
nutritionally. Am. J. Nurs. 10, 13011303.
Houston, S., Haggard, J., Williford, J.J., Meserve, L., Shewokis, P., 2001. Adverse effects of large-dose zinc
supplementation in an institutionalized older population with pressure ulcers. J. Am. Geriatr. Soc. 49 (8),
11301132.
Houwing, R., Rozendaal, M., Wouters-Wesseling, W., Beulens, J., Buskens, E., Haalboom, J., 2002. The effect of
nutritional supplementation on the prevention of pressure ulcers (PU) in hip-fracture patients. Clin. Nutr. 21
(Suppl. 1), 84 (Abstract P-248).
Houwing, R.H., Rozendaal, M., Wouters-Wesseling, W., Beulens, J.W., Buskens, E., Haalboom, J.R., 2003. A
randomised, double-blind assessment of the effect of nutritional supplementation on the prevention of pressure
ulcers in hip-fracture patients. Clin. Nutr. 22 (4), 401405.
Jackobs, M.K., 1999. Healing pressure ulcers. Determining the cost of medical nutrition therapy in long-term care.
Health Care Food Nutr. Focus 15 (10), 1012.
Jadad, A., Moore, R., Carroll, D., Jenkinson, C., Reynolds, D.J., Gavaghan, D.J., McQuay, H.J., 1996. Assessing
the quality of reports of randomized clinical trials: is blinding necessary? Controlled Clin. Trials Design Meth.
Anal. 17, 112.
Joy, M., Halling, J., 1998. Factors relating to the absence or presence of pressure ulcers and the degree of pressure
ulcer involvement in long term care. J. Am. Dietetic Assoc. 98, A93.
Keys, A., Brozek, J., Henschel, A., Mickelsen, O., Taylor, H.L., 1950. The Biology of Human Starvation.
University of Minnesota Press, Minneapolis, MN, pp. 81535.
Kirk, S.J., Hurson, M., Regan, M.C., Holt, D.R., Wasserkrug, H.L., Barbul, A., 1993. Arginine stimulates wound
healing and immune function in elderly human beings. Surgery 114, 155160.
Langer, G., Schloemer, G., Knerr, A., Kuss, O., Behrens, J., 2003. Nutritional interventions for preventing and
treating pressure ulcers (Cochrane review). In: The Cochrane Library, issue 4. John Wiley and Sons Ltd.,
Chichester, UK.
Larsson, J., Unosson, M., Ek, A.-C., Nilsson, L., Thorslund, S., Bjurulf, P., 1990. Effect of dietary supplement
on nutritional status and clinical outcome in 501 geriatric patients: a randomised study. Clin. Nutr. 9, 179
184.
Mantel, N., Haenszel, W., 1959. Statistical aspects of the analysis of data from retrospective studies of disease. J.
Natl. Cancer Inst. 22, 719748.
Mitchell, S.L., Kiely, D.K., Lipsitz, L.A., 1997. The risk factors and impact on survival of feeding tube placement
in nursing home residents with severe cognitive impairment. Arch. Intern. Med. 157, 327332.
450
Moher, D., Cook, D.J., Eastwood, S., Olkin, I., Rennie, D., Stroup, D.F., 1999. Improving the quality of reports of
meta-analyses of randomised controlled trials. The QUORUM statement. Quality of reporting meta-analyses.
Lancet 354, 18961900.
Myers, S.A., Takiguchi, S., Slavish, S., Rose, C.L., 1990. Consistent wound care and nutritional support in
treatment. Decubitus 3 (3), 1628.
NELH, 2004. http://rms.nelh.nhs.uk/guidelinesfinder/ (accessed 12/08/04).
Norris, J.R., Reynolds, R.E., 1971. The effect of oral zinc sulfate on decubitus ulcers. J. Am. Geriatr. Soc. 19, 793
797.
NSF, 2004. http://www.dh.gov.uk/PolicyAndGuidance/HealthAndSocialCareTopics/HealthAndSocialCareArticle/fs/en?CONTENT_ID=4070951&chk=W3ar/W (accessed 19/08/04).
ODea, K., 1995. The prevalence of pressure sores in four European countries. J. Wound Care 4, 192195.
Peck, A., Cohen, C.E., Mulvihill, M.N., 1990. Long-term enteral feeding of aged demented nursing home patients.
J. Am. Geriatr. Soc. 38 (11), 11951198.
Preston, K., 1991. Counting the cost of pressure sores. Community Outlook 9, 1924.
PubMed, 2004. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi (accessed 10/08/04).
Scholl, D., Langkamp-Henken, B., 2001. Nutrient recommendations for wound healing. J. Intravenous Nurs. 24
(2), 124132.
Soriano, L.F., Vazquez, M.A.L., Maristany, C.P.-P., Graupera, J.-M.X., Wesseling, W.W., Wagenaar, L., 2004. The
effectiveness of oral nutritional supplementation in the healing of pressure ulcers. J. Wound Care 13 (8), 319
323.
Stotts, N.A., Hopf, H.W., 2003. The link between tissue oxygen and hydration in nursing home residents with
pressure ulcers: preliminary data. J. Wound Ostomy Continence Nurs. 30 (4), 184190.
Stratton, R.J., Green, C.J., Elia, M., 2003. Consequences of disease-related malnutrition. In: Stratton, R.J., Green,
C.J., Elia, M. (Eds.), Disease-Related Malnutrition: An Evidence-Based Approach to Treatment. CABI
Publishing, Wallingford, Oxon, UK, pp. 113155.
Takagi, H., Nakatani, A., Mori, S., 1991. Intravenous and enteral nutrition in the field of dermatology (except
burn). Nippon Rinsho 49 (Suppl.), 593597.
Tannen, A., Dassen, T., Bours, G., Halfens, R., 2004. A comparison of pressure ulcer prevalence: concerted data
collection in the Netherlands and Germany. Int. J. Nurs. Stud. 41 (6), 607612.
Taylor, T.V., Rimmer, S., Day, B., Butcher, J., Dymock, I.W., 1974. Ascorbic acid supplementation in the
treatment of pressure-sores. Lancet 2 (7880), 544546.
ter Riet, G., Kessels, A.G., Knipschild, P.G., 1995. Randomized clinical trial of ascorbic acid in the treatment of
pressure ulcers. J. Clin. Epidemiol. 48 (12), 14531460.
Thomas, D.R., 1997. The role of nutrition in prevention and healing of pressure sores. Clin. Geriatr. Med. 13, 497
511.
Thomas, D.R., 2001. Improving outcome of pressure ulcers with nutritional interventions: a review of the
evidence. Nutrition 17, 121125.
Thomas, S., Bender, S., Sharkey, S., Horn, S., 1998. Preliminary nutrition findings from the long term care
pressure ulcer study. J. Am. Dietetic Assoc. 98, A93.
TRIP, 2004. www.tripdatabase.com (accessed 12/08/04).
Versluysen, M., 1986. How elderly patients with femoral fracture develop pressure sores in hospital. Br. Med. J.
(Clin. Res. Ed.) 292 (6531), 13111313.
Watkin, D.M., Waldron, W.D., 1981. A double-blind study of supplemental zinc in the management of pressure
ulcers. Fed. Proc. 40 (3), 856 (Abstract 3559).
Weiler, P.G., Franzi, C., Kecskes, D., 1990. Pressure sores in nursing home patients. Aging (Milano) 2, 267275.
Welch, P.K., Dowson, M., Endres, J.M., 1991. The effect of nutrient supplements on high risk long term care
residents receiving pureed diets. J. Nutr. Elder 10 (3), 4962.
Whitfield, M., Kaltenthaler, E., Akehurst, R., Walters, S., Paisley, S., 2000. How effective are prevention strategies
in reducing the prevalence of pressure ulcers? J. Wound Care 9, 261266.
Wissing, U., Unosson, M., 1999. The relationship between nutritional status and physical activity, ulcer history
and ulcer related problems in patients with leg and foot ulcers. Scand. J. Caring Sci. 13, 123128.
Woolf, B., 1955. On estimating the relation between blood group and disease. Ann. Hum. Genet. 19, 251253.

HTTP 4

Загружено:

Сведения о документе

Оригинальное название

Авторское право

Доступные форматы

Поделиться этим документом

Поделиться или встроить документ

Параметры публикации

Этот документ был вам полезен?

Это неприемлемый материал?

Авторское право:

Доступные форматы

HTTP 4

Загружено:

Авторское право:

Доступные форматы

Ageing Research Reviews

Enteral nutritional support in prevention and

Institute of Human Nutrition, University of Southampton, MP 113 F Level,

R.J. Stratton et al. / Ageing Research Reviews 4 (2005) 422450

R.J. Stratton et al. / Ageing Research Reviews 4 (2005) 422450

2. Materials and methods

R.J. Stratton et al. / Ageing Research Reviews 4 (2005) 422450

R.J. Stratton et al. / Ageing Research Reviews 4 (2005) 422450

2.2. Study selection criteria for the systematic literature review

All adult human studies

All studies using ONS and/or ETF (all

Dietary counselling only

Pressure ulcer incidence

R.J. Stratton et al. / Ageing Research Reviews 4 (2005) 422450

R.J. Stratton et al. / Ageing Research Reviews 4 (2005) 422450

RCT, parallel groups, multi-centre.

Age range 7291 years. All patients

Significant differences between

672 critically ill

R.J. Stratton et al. / Ageing Research Reviews 4 (2005) 422450

Studies of nutritional support vs.

Delmi et al. (1990)

RCT, parallel groups. Patients were

Many patients underwent recent surgery.

RCT, parallel groups. Patients were

Mean age 80 years. 28.5%

495 elderly long-term

Houwing et al. (2003)

RCT, double blind, parallel groups.

Mean age, baseline BMI, pressure ulcer

103 hip fracture patients,

CT, single group, beforeafter.

Mean age 75 years, BMI = 22.9 kg/m 2

R.J. Stratton et al. / Ageing Research Reviews 4 (2005) 422450

Enteral tube feeding (ETF)

Patients on standard hospital mattress,

101 hip fracture

15.5 (grade I only)

All the patients were long-term tube

40 elderly tube fed

For group A, n = 12 were <65 years

108 elderly nursing

65.5 (group A),

Mitchell et al. (1997)

Prospective cohort, parallel groups.

Median age = 87 years. No

1386 cognitively impaired

Study of the risks of

29.6 (group A),

Peck et al. (1990)

Retrospective cohort, parallel

Mean age, % demented patients, %

104 elderly nursing home

Not stated, <100

R.J. Stratton et al. / Ageing Research Reviews 4 (2005) 422450

RCT, parallel groups.

Enteral tube feeding (ETF)

Chernoff et al. (1990)

RCT, double blind, parallel groups.

Mean age 80 years (group A) vs.

27 elderly patients with

Not stated, <100

RCT, parallel groups.