Nutrition 26 (2010) 867872

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Nutrition
journal homepage: www.nutritionjrnl.com

Applied nutritional investigation

Specic nutritional support accelerates pressure ulcer healing and reduces

wound care intensity in non-malnourished patients
R.D. van Anholt Ph.D. a, *, L. Sobotka Ph.D. b, E.P. Meijer Ph.D. a, H. Heyman R.N. c, H.W. Groen M.D. d,
E. Topinkova Ph.D. e, M. van Leen M.D. f, J.M.G.A. Schols Ph.D. g
a
Nutricia Advanced Medical Nutrition, Danone Research, Centre for Specialised Nutrition, Wageningen, The Netherlands
b
Department of Gerontology and Metabolic Care, Charles University, Hradec Kralove, Czech Republic
c
Openbare Centra voor Maatschappelijk Welzijn (OCMW), Antwerp, Belgium
d
ZINN, Groningen, The Netherlands
e
Department of Geriatrics, First Faculty of Medicine, Charles University and General Faculty Hospital, Prague, Czech Republic
f
Avoord Zorg & Wonen, Etten-Leur, The Netherlands
g
CAPHRI/Department General Practice (Nursing Home Medicine), Maastricht University, Maastricht, The Netherlands

a r t i c l e i n f o a b s t r a c t

Article history: Objective: We investigated the potential of a high-protein, arginine- and micronutrient-enriched
Received 5 February 2010 oral nutritional supplement (ONS) to improve healing of pressure ulcers in non-malnourished
Accepted 19 May 2010 patients who would usually not be considered for extra nutritional support.
Methods: Forty-three non-malnourished subjects with stage III or IV pressure ulcers were included
Keywords: in a multicountry, randomized, controlled, double-blind, parallel group trial. They were offered 200
Pressure ulcers
mL of the specic ONS or a non-caloric control product three times per day, in addition to their
Oral nutritional supplement
regular diet and standard wound care, for a maximum of 8 wk. Results were compared with
Non-malnourished
Protein repeated-measures mixed models (RMMM), analysis of variance, or Fishers exact tests for cate-
Arginine gorical parameters.
Zinc Results: Supplementation with the specic ONS accelerated pressure ulcer healing, indicated by
Vitamins a signicantly different decrease in ulcer size compared with the control, over the period of 8 wk
(P  0.016, RMMM). The decrease in severity score (Pressure Ulcer Scale for Healing) in the
supplemented group differed signicantly (P  0.033, RMMM) from the control. Moreover,
signicantly fewer dressings were required per week in the ONS group compared with the control
(P  0.045, RMMM) and less time was spent per week on changing the dressings (P  0.022,
RMMM). At the end of the study, blood vitamin C levels had signicantly increased in the ONS
group compared with the control (P 0.015, analysis of variance).
Conclusion: Specic nutritional supplementation accelerated healing of pressure ulcers and
decreased wound care intensity in non-malnourished patients, which is likely to decrease overall
costs of pressure ulcer treatment.
2010 Elsevier Inc. All rights reserved.

Introduction
Pressure ulcers occur in individuals with limited mobility due
to pressure, or pressure in combination with shear, which
decreases circulation and causes tissue damage [1]. Prevalence
The study was sponsored by Nutricia Advanced Medical Nutrition. R. D. van
Anholt and E. P. Meijer are employees of Nutricia Advanced Medical Nutrition,
which is part of Danone Research. J. M. G. A. Schols has received several
(unrestricted) research grants from Nutricia.
* Corresponding author. Tel.: 31-317-467800; fax: 31-317-466500.
E-mail address: rogier.vananholt@nutricia.com (R. D. van Anholt).
rates in health care facilities generally vary from a few percent to
around 30% of patients, although large differences occur
between countries [25]. Elderly patients are particularly at risk,
as are patients with specic predisposing conditions such as hip
fractures, of whom as many as 66% have been reported to
develop pressure ulcers [6,7]. Besides affecting the quality of life
of the patients [8], pressure ulcers pose a high cost burden on
health care systems worldwide. For instance, the annual costs of
pressure ulcer care were estimated to be around 4% of the total
expenditure of the National Health Service in the United
Kingdom (1.42.1 billion GBP) and 1.2% to 6.6% of the total health
care costs in The Netherlands [9,10].

0899-9007/$ - see front matter 2010 Elsevier Inc. All rights reserved.
doi:10.1016/j.nut.2010.05.009
868 R. D. van Anholt et al. / Nutrition 26 (2010) 867872
A patients individual risk to develop a pressure ulcer appears
to be two- to three-fold higher when malnourished or under-
weight, after controlling for other demographic variables and
several risk factors (odds ratios 1.8 [11], 2.29 [12], 2.6 [13]).
Nevertheless, the increased individual risk does not imply that
non-malnourished patients are therefore protected from devel-
oping such lesions. For instance, when 484 geriatric patients
were screened for pressure ulcers and their nutritional status
was assessed, only 39.5% of the 81 patients with an ulcer were
identied as malnourished [14]. Another survey of 3214 elderly
patients admitted to hospital showed similar results; although
the prevalence of pressure ulcers was greatest in the under-
weight patients, only 22% of the 378 patients with an ulcer were
actually classied as underweight [11].
Improving the nutritional status of patients with oral nutri-
tional supplements (ONS) has been associated with a lower
incidence of pressure ulcer development and patients who
received specic energy- and protein-enriched supplements,
containing elevated amounts of arginine, zinc, and antioxidants,
tended to heal better [7]. However, from the studies that have
been previously performed with ONS, it cannot be derived
whether (specic) nutritional support can be benecial in
patients who are not malnourished and/or underweight. For
example, some of these studies did not include control groups
[15,16], selection criteria were not disclosed [17], nutritional
status differed between groups at baseline [18], or patients
requiring tube feeding were included [19].
In the present multicenter, multicountry, randomized,
controlled, double-blind, parallel group trial, we assessed the
potential of a specic ONS to improve the healing of pressure
ulcers and decrease the intensity of wound care in patients who
were not malnourished. The supplement used is rich in protein,
arginine, and micronutrients, ingredients that can promote
neoangiogenesis, stimulate collagen synthesis, and have a posi-
tive effect on wound healing [2022].
Materials and methods
Patients
Patients were recruited from eight health care centers, hospitals, and long-
term care facilities in four countries (Czech Republic, Belgium, The
Netherlands, and Curacao). Inclusion criteria were 1) age 18 to 90 y, 2) at least one
stage III to IV pressure ulcer according to the revised European Pressure Ulcer
Advisory Panel classication system [23], and 3) receiving standard care and
a standard (institutional) diet without nutritional supplements for at least 2 wk
before the study. Malnourished patients, as indicated by a body mass index (BMI)
below 18.5 kg/m2 for patients 18 to 70 y old or a BMI below 21 kg/m2 for those
older than 70 y, were excluded. Other exclusion criteria were severe medical
conditions, nonpressure-related ulcers (e.g., diabetic ulcers), life expectancy
shorter than 6 mo, receiving palliative care, use of corticosteroids, and/or dietary
restrictions, i.e., a protein-restricted diet. Standard nutritional diets and wound
care were maintained according to the locally used protocols.
Nutritional intervention
Patients were randomly allocated to receive a specic ONS, which was a high-
energy supplement enriched with arginine, antioxidants, and other micronutrients
(Cubitan, Nutricia N.V., Zoetermeer, The Netherlands), or a non-caloric, avored
placebo (similar in taste and appearance) for a maximum of 8 wk. All participants
were prescribed three coded servings (three times 200 mL) per day between meals to
be consumed preferably within 1 h. The ONS provides per 200-mL serving, among
other nutrients, 250 kcal, 28.4 g of carbohydrates (45% energy), 20 g of protein (30%
energy) including 3 g of arginine, 7 g of fat (25% energy), 238 mg of vitamin A, 250
mg of vitamin C, 38 mg of vitamin E (a-tocopherol equivalents), 1.5 mg of carot-
enoids, 9 mg of zinc, 64 mg of selenium, 1.35 mg of copper, and 200 mg of folic acid.
Primary endpoint: Ulcer size
The primary endpoint was pressure ulcer healing, as assessed by the change
in pressure ulcer surface area over 8 wk. Starting at baseline, the pressure ulcer
was assessed weekly by measuring the maximum length and width of the ulcer
with a ruler. The surface area of the ulcer was assumed to have an ellipse form,
which was calculated with the formula: length/2  width/2  3.14 [15,24]. In case
a patient had multiple pressure ulcers, the local investigator selected one
representative ulcer to be assessed throughout the study.
Secondary endpoint: Pressure Ulcer Scale for Healing tool
As a secondary parameter the change in the Pressure Ulcer Scale for Healing
(PUSH tool 3.0) was assessed over the period of 8 wk: at weekly intervals cate-
gorical subscores for the surface area (length by width), the amount of exudates
(drainage), and the type of wound tissue were determined and combined to
obtain a total score from 0 (completely healed) to 17 (greatest severity),
according to the National Pressure Ulcer Advisory Panel (NPUAP) [25].
Other parameters
Length, weight, BMI, Malnutrition Universal Screening Tool scores, and blood
parameters were assessed at baseline and at the end of study participation. Blood
measurements included vitamin C, zinc, alanine aminotransferase, g-glutamyl
transpeptidase, creatinine, blood cell and platelet counts, hemoglobin, troponin I,
transthyretin, and C-reactive protein.
Of each serving offered, the volume consumed was estimated (0, , , G, 1)
and recorded in a diary. Product compliance was calculated for the days on which
the patients participated. Each week (gastrointestinal) tolerance was assessed by
standardized questionnaires on the following symptoms: headache, nausea,
vomiting, abdominal distention, burping, atulence, diarrhea (more than two 2
liquid stools per day), and constipation (>72 h with no bowel movement).
The total number of dressings applied during the preceding week was
recorded at weekly intervals. In addition, at three time points (week 1, week 4,
and week 8) the time spent on (re)applying the dressings was recorded. The
recorded time spent per dressing was multiplied by the total number of dressing
changes during the preceding week. Mobility and activity levels were recorded at
baseline, week 4, and at the end of study participation using validated ques-
tionnaires based on the Braden Scale for predicting pressure sore risk [26].
Activity levels were categorized as bedfast, chairfast, walks occasionally, or walks
frequently. The level of mobility was categorized as completely immobile, very
limited, slightly limited, or no limitation. See Bergstrom et al. [26] for a descrip-
tion of these categories.
Statistical analyses
Analyses were performed on the intention-to-treat (ITT) group according to
a predened statistical plan. In case data did not meet the assumption of normal
distribution, they were (log-)transformed to enhance normality before statistical
analysis (i.e., pressure ulcer size, number of dressings per week, some blood
parameters). In case the ulcer was diagnosed as healed before the end of the
8-wk period, data for ulcer size were xed and PUSH (sub)scores were set to
0 cm2, closed, and no exudate for the remaining time points. In case of
dropouts the parameters of the remaining time-points were set at missing.
Repeated-measures mixed models (RMMM) were used to compare the changes
in time between treatments; treatment and center were treated as categor-
ical variables. Second-order polynomial functions (y constant time time2)
tted best with the results. Data were adjusted for center and baseline by
including these factors as covariates in all analyses. Baseline measurements and
blood parameters were analyzed by analysis of variance (ANOVA). Fishers exact
tests were used for the categorical variables. Statistical signicance was accepted
at P  0.05 and all statistical analyses were performed in SPSS 15.0 for Windows
(SPSS, Inc., Chicago, IL, USA). Only data of the ITT population are shown in the
RESULTS.
Ethical conduct
The study was conducted in compliance with the principles of the World
Medical Association Declaration of Helsinki, according Internal Conference on
Harmonisation (ICH) guidelines for Good Clinical Practice, as appropriate to
nutritional products and in agreement with the local laws and regulations of the
relevant countries. The protocol was approved by the ethics committees for all
centers, registered in the Dutch Trial Register (NTR1154), and written informed
consent was obtained from all patients before inclusion in the study.
Results
Forty-seven patients were randomized from August 2007 to
October 2008, after which the inclusion was stopped early; due
to limited availability of patients who fullled the criteria in the
 R. D. van Anholt et al. / Nutrition 26 (2010) 867872 869

participating centers, the original objective of 100 subjects was

not reached. Forty-three subjects were included in the ITT
analysis: 22 in the ONS group and 21 in the control group.
Four patients were not included in the ITT analysis due to death
(n 1), hospitalization (n 1), exceeding the inclusion criteria
for BMI (n 1), or withdrawal of informed consent (n 1) before
consuming a single serving of the (control) product. Dropouts
consisted of ve patients in the ONS group and six patients in the
control group. Reasons for early termination were withdrawn
consent (n 1), exclusion criterion (n 1), diarrhea and/or
dyspepsia (n 2), ischemic heart disease (n 1), lost to follow-
up/discharge (n 3), stroke recurrence (n 2), and taste of the
(control) product (n 1).
No statistically signicant differences were detected between
groups for any of the demographic, nutritional, and biochemical
parameters at baseline (ANOVA, Fishers exact test; Table 1).
Moreover, there were no signicant differences in the pressure
ulcer characteristics between the ONS and control groups at the
start of the study (ANOVA, Fishers exact test). Fig. 1. Mean pressure ulcer size (square centimeters) in time in the group receiving
The decline in pressure ulcer size in the ONS group differed specic oral nutritional supplement (closed symbols) and in the control group
signicantly from the control group over the period of 8 wk (P (open symbols). Ulcers of patients in the oral nutritional supplement group healed
signicantly faster than those of patients in the control group (P 0.006, treatment
0.006, treatment by time; P 0.016, treatment by time2, RMMM;
by time; P 0.016, treatment by time2, repeated-measures mixed models). Data,
Fig. 1). Post hoc analysis of the within-group changes in ulcer size adjusted for center, represent mean  SEM.
from baseline showed that the ulcers in the ONS group were

signicantly smaller compared with baseline from week 3 (P

0.019, ANOVA) and onward (P  0.012, ANOVA); in the control
Table 1
Baseline characteristics*
group the ulcers were signicantly smaller compared with
baseline in week 5 (P 0.019, ANOVA) and all subsequent time
Variable ONS (n 22) Control (n 21) points (P  0.008, ANOVA).
Men/women 8/14 11/10 Similarly, PUSH scores improved signicantly in the ONS
Age (y) 76.2  3.2 73.0  3.3
group compared with the control group (P 0.011, treatment by
Body weight (kg) 66.3  4.5 75.6  5.3
Body mass index (kg/m2) 23.7  1.0 25.8  1.1 time; P 0.033, treatment by time2, RMMM; Fig. 2). The distri-
MUST score bution of the categorical subscores of tissue types differed
Low risk 15 18 signicantly between treatments after 4 wk, with fewer ulcers
Medium risk 3 2 scored as granulated or necrotic and more ulcers scored as
High risk 4 1
Activity
closed or epithelial in the ONS group than in the control
Bedfast 7 11 group (P 0.037, Fishers exact test; Table 2). Neither the
Chairfast 10 6 distribution of the categorical subscores of pressure ulcer size
Walks occasionally 3 2
Walks frequently 2 2
Mobility
Completely immobile 2 3
Very limited 12 10
Slightly limited 7 6
No limitation 1 2
Ulcer location
Heel 8 8
Ischium 2 0
Sacrum 8 8
Trochanter 4 5
Ulcer size (cm2) 10.5  2.3 11.5  2.5
5.0 (0.642.4) 5.2 (0.838.4)
Ulcer stage
Stage III 17 14
Stage IV 5 7
PUSH tool (total score) 11.5  0.7 11.4  0.7
Time spent on dressings 65.5  7.0 54.6  7.3
(min/wk)
Dressings/wk 5.6  0.5 4.9  0.5
7 (17) 7 (114)

MUST, Malnutrition Universal Screening Tool; ONS, oral nutritional supplement;

PUSH, Pressure Ulcer Scale for Healing
* Subjects were randomized to receive a specic ONS or a non-caloric control
product in addition to their regular (institutional) diets. There were no statically
signicant differences between the groups at baseline (analysis of variance,
Fishers exact test). Data, adjusted for center, represent numbers or mean  SEM.
Median values (minimummaximum) are provided for data that are not nor-
mally distributed.
Fig. 2. Mean PUSH scores. The group receiving the specic oral nutritional
supplement is represented by closed symbols and the control group by open
symbols. PUSH scores improved signicantly in the oral nutritional supplement
group compared with the control group (P 0.011, treatment by time; P 0.033,
treatment by time2, repeated-measures mixed models). Data, adjusted for center,
represent mean  SEM. PUSH, Pressure Ulcer Scale for Healing.
870 R. D. van Anholt et al. / Nutrition 26 (2010) 867872

Table 2
Categorical subscores for tissue types according to the Pressure Ulcer Scale for
Healing for the group receiving a specic ONS or a placebo (control)*

Tissue type Baseline Week 4 Week 8

ONS Closed 0 2 6
Epithelial 0 4 2
Granulated 8 6 7
Slough 7 5 2
Necrotic 7 0 0
Control Closed 0 0 5
Epithelial 0 2 3
Granulated 8 13 8
Slough 9 1 0
Necrotic 4 2 0
Py 0.683 0.037 0.714

ONS, oral nutritional supplement

* For simplicity, only the results at baseline, week 4, and week 8 are listed. See
text for information on the subscores for ulcer size and amount of exudate.
y
Treatments were compared with Fishers exact tests.

nor the subscores of the amount of exudate differed signicantly
between groups at any time point (ANOVA).
The average numbers of dressings required per week are
represented in Figure 3. The decrease in the number of dressings
in the ONS group differed signicantly from the change in the
control group over the study period of 8 wk (P 0.003, treat-
ment by time; P 0.045, treatment by time2, RMMM, post hoc).
Separate analyses per time point showed that signicantly fewer
dressings were required in the ONS group during weeks 3, 5, 6,
and 7 compared with the control group (P 0.030, 0.037, 0.032,
and 0.009, respectively, ANOVA).
In Figure 4 the average time spent per week on dressing the
ulcer is represented for both groups. The change over time in
the ONS group was signicantly different from the change in the
control group (P 0.006, treatment by time; P 0.022, treatment
by time2, RMMM, post hoc). Comparison per time point showed
that signicantly less time was spent in the ONS group compared
with the control group during week 4 (P 0.010, ANOVA).
The daily records showed that 75.8  3.7% (mean  standard
error of the mean) of the ONS offered was consumed by the
patients during the study, whereas signicantly more, 86.5 
Fig. 3. The average number of dressings required per week. Over the period of 8 wk
signicantly fewer dressings were required in the oral nutritional supplement
group (closed symbols) than in the control group (open symbols; P 0.003,
treatment by time; P 0.045, treatment by time2, repeated-measures mixed
models). Data, adjusted for center, represent mean  SEM. Baseline measurement
(week 0) concerns the week before supplementation.
Fig. 4. Total time spent on changing ulcer dressings per week (in minutes) for the
oral nutritional supplement group (closed symbols) and the control group (open
symbols). Over the period of 8 wk signicantly less time was required to change the
dressings in the oral nutritional supplement group than in the control group (P
0.006, treatment by time; P 0.022, treatment by time2, repeated-measures mixed
models). Data are adjusted for center and represent mean  SEM.
2.3%, was consumed of the control product (P 0.042, ANOVA).
No signicant differences were observed in the patients activity
levels or mobility levels between treatments or in time (Fishers
exact test, ANOVA). Blood parameters showed no statistically
signicant differences between treatments or time points with
the exception of vitamin C: blood vitamin C levels had increased
signicantly in the ONS group at the end of study participation
(60.2  7.4 mmol/L) compared with the control group (26.6  11.2
mmol/L; P 0.015, ANOVA; Table 3). The BMI (kilograms per
square meter) of patients receiving ONS did not differ signicantly
between time points or between treatments (ANOVA; Table 4).
The number of complaints about (gastrointestinal) tolerance
varied from zero to four per time point during the study. No
signicant differences were observed in the incidence of
(gastrointestinal) tolerance parameters, with the exception
reported constipation: constipation was reported by four
subjects in the ONS group compared with no subjects in the
control group at week 4 (baseline four and three subjects,
respectively; P 0.029, Fishers exact test).
In total 41 adverse events (AEs) were reported for 16 subjects
in the ONS group and 35 AEs were reported for 13 subjects in the
control group; the majority was of mild or moderate intensity
(88%). In the control group four AEs were interpreted as related
to the product (diarrhea two times, nausea once, vomiting once).
Of the AEs in the ONS group nine were interpreted as related to
the product (diarrhea six times, constipation once, dyspepsia
once, nausea once). Two subjects in the ONS group discontinued
due to diarrhea or the combination of diarrhea and dyspepsia,
which the investigators judged to be related to the study
product. Furthermore, in the control group two subjects dis-
continued due to serious (non-related) AEs (death due to cere-
bral vascular accident, stroke recurrence). None of the
differences were signicant (Fishers exact test).
Discussion
To our knowledge this is the rst prospective randomized
controlled trial that explicitly addressed the effect of a specic
 R. D. van Anholt et al. / Nutrition 26 (2010) 867872 871

Table 3 previously in an open-label cohort study, in which 245 malnour-

Main (nutritional) blood parameters of the group receiving a specic ONS and the ished and non-malnourished patients received the same specic
control group*
ONS for a period of 9 wk [16]. In that cohort, the average healing
Baseline End of study rate over the rst 3 wk was 0.23 cm2/d, which then decreased to an
ONS average of 0.13 cm2/d during 9 wk of treatment. Another
C-reactive protein (mg/L) 18.5 (3.0220.9) 13.8 (0.5240.8) open-label intervention with the same specic ONS resulted in an
Total leukocytes (109/L) 9.2  0.5 8.9  0.9
average healing rate of 0.34 cm2/d of stage III/IV ulcers in 3 wk [15],
Total erythrocytes (1012/L) 4.0  0.1 4.3  0.1
Thrombocytes (109/L) 398.4  34.6 304.2  27.6 which was higher than the healing rates in the rst 4 wk in the
Hemoglobin (mmol/L) 7.3  0.2 7.8  0.2 present study and in the open-label study described by Heyman
Transthyretin (mg/L) 178  16 199  22 et al. [16]. This higher healing rate in the open-label intervention
Zinc (mmol/L) 11.2  1.2 10.6  0.8 by Frias Soriano et al. [15] might be due to the combination of the
Vitamin C (mmol/L) 23.0  5.3 60.2  7.4a
Control
inclusion of patients with a reasonable nutritional status and
C-reactive protein (mg/L) 20.1 (2.012.0) 8.3 (0.6325.5) larger ulcers at baseline (23.6 cm2); in the study described by
Total leukocytes (109/L) 8.1  0.5 6.7  0.9 Cereda et al. [19], the ulcers were comparable in size at baseline
Total erythrocytes (1012/L) 4.1  0.1 4.2  0.1 (20.7/21.5 cm2), whereas the healing rates were much lower.
Thrombocytes (109/L) 353.8  37.0 316.7  30.3
In line with the accelerated ulcer healing, the patients
Hemoglobin (mmol/L) 7.5  0.2 7.6  0.2
Transthyretin (mg/L) 180  16 180  33 receiving the nutritional supplement in the present study
Zinc (mmol/L) 11.6  1.2 11.1  0.9 required fewer dressing changes from 3 wk and onward, and less
Vitamin C (mmol/L) 19.8  6.2 26.6  11.2b time was required to change the dressings after 4 wk compared
ONS, oral nutritional supplement with the control group: 22 min was saved per patient per week
* Blood samples were collected before consumption of the test products after 4 wk of supplementation compared with the control group
(baseline) and at the end of study participation. With the exception of vitamin C after that same period. The time spent on wound dressings only
levels, there were no signicant differences between time points or between
reects part of the wound care, which may increase to 18 to
treatments. Data, adjusted for center, represent mean  SEM or median
(minimummaximum) if data are not normally distributed. 68 min per patient per day for a stage III to IV ulcer, respectively,
a,b
The changes in vitamin C levels (from baseline to the end of study) differed if cleaning and debridement of the wounds and maintaining
signicantly between the ONS group and the control group (P 0.015, analysis of optimum skin health are taken into account [30]. As pointed out
variance). by Bennett et al. [10], the costs of treatment are largely deter-
mined by the costs of nursing time in the stage I and II ulcers
ONS in non-malnourished patients with pressure ulcers.
(96%), and the costs increase in the most severe stage III and IV
Assessments of BMI, the Malnutrition Universal Screening Tool,
ulcers with complications attributing to 30% of the costs. We did
and plasma transthyretin levels at baseline indicated that most
not follow patients on discharge, so it remains to be determined
patients in the trial were not nutritionally at risk and would
whether the accelerated healing shortened hospital length of
normally not be considered for nutritional support [27].
stay. Nevertheless, the time saved with the ONS during admis-
The high-protein, arginine- and micronutrient-enriched ONS
sion will not only decrease the costs per patient but also leave
accelerated the healing of the pressure ulcers, as indicated by the
time available that can be spent by nurses to attend to other
signicant differences in the reduction of the ulcers and the
needs and/or patients.
difference in PUSH tool scores between the treatments. This effect
The effectiveness of combinations of macro- and/or specic
was most pronounced in the rst weeks: the average healing rate
micronutrients to prevent or improve healing of pressure ulcers
in the ONS group was 0.26 cm2/d over the rst 3 wk, leveling off to
has been tested with variable success in clinical settings (see
0.16 cm2/d after 8 wk, whereas the average healing rates in the
reviews [7,31,32]). In particular protein, arginine, vitamin A,
control group remained consistently lower (3- and 8-wk healing
vitamin C, and zinc have been linked to improved healing of
rates 0.14 and 0.15 cm2/d, respectively). Cereda et al. [19] recently
wounds [20,21,33]. Providing additional calories alone has
reported improved healing of pressure ulcers in 28 elderly patients
previously been shown to be ineffective in improving wound
supplemented with the same ONS or a similar arginine- and
healing [34] and more recent studies have shown that the energy
micronutrient-enriched tube feed. The average healing rate in the
requirements of elderly patients with ulcers are not likely to be
supplemented group was 0.14 cm2/d during the rst 4 wk
elevated [35]. According to the most recent guidelines of the
compared with 0.12 cm2/d in the control group (standard tube feed
European Pressure Ulcer Advisory Panel/NPUAP [23] the recom-
or hospital diet). Toward the end of the 12-wk study period the
mended energy intake for elderly patients (under stress) with
average healing rate had increased to an average of 0.17 cm2/d in
a pressure ulcer is similar to that for elderly patients in general
the supplemented group, whereas the healing rate had decreased
[36]. Moreover, the improvement in the healing rate in the
to 0.10 cm2/d in the control group. It is possible that the overall
present trial was considerably higher than what was achieved in
lower healing rates in the supplemented and control groups in the
a trial in which the protein content of nutritional supplements
study by Cereda et al. [19] are related to the poor nutritional status
was increased from 14% to 24% energy of patients with stage III
of the included patients, which is known to delay wound healing
and IV pressure ulcers; the 8-wk healing rates were 0.04 and 0.08
[28,29]. Our ndings are more in line with those obtained
cm2/d, despite the larger ulcers at baseline [10]. A recent review
Table 4 by Ellinger and Stehle [37] supports the additional role of vitamins
BMI of subjects randomized to receive a specic ONS or a non-caloric control and micronutrients in the treatment of pressure ulcers; they
product (control)* concluded that evidence for the effectiveness of single supple-
BMI (kg/m2) Baseline End of study mentation with high doses of vitamin C (13 g/d) was lacking, in
ONS 23.7  1.0 24.2  0.3 contrast to the combination of vitamin C, zinc, and arginine.
Control 25.8  1.1 24.1  0.3 In conclusion, the present study shows that pressure ulcer
BMI, body mass index; ONS, oral nutritional supplement
healing can be accelerated in non-malnourished patients by
* Data, adjusted for center, represent mean  SEM. No signicant differences providing a specic ONS enriched in arginine, zinc, and antioxi-
were found between time points or treatments (analysis of variance). dants, suggesting that the benets of this supplement reach
872 R. D. van Anholt et al. / Nutrition 26 (2010) 867872
beyond restoring caloric and protein deciencies. Supplementa-
tion is also likely to improve the quality of life of the patients and
save costs by decreasing wound care, in particular nursing time.
The incentive to prescribe (oral) nutritional supplements is in
most cases based on a poor nutritional status of the patient or an
expected risk of failing nutritional intake. Specic nutritional
supplementation should also be considered when treating non-
malnourished patients with pressure ulcers, especially because
nutritional support is usually not contemplated for these patients.
Acknowledgments
The following investigators are acknowledged for their contri-
bution to the study: J. Neyens (De Riethorst Stromenland, The
Netherlands), F. van Eijndhoven (Betesda, Curacao), A. Jiroudkova
(Regional Hospital Liberec, Czech Republic), A. Matejkova
(Regional Hospital Pardubice, Czech Republic), M. Vandewoude
(ZNA Sint-Elisabeth Antwerp, Belgium), J. Melchior (Prof Hopital
Raymond Poincare, Garches, France), E. Alix (Le Centre Hospi-
talier du Mans, Le Mans, France). Statistical analyses were per-
formed by H. Balder and S. Swinkels (Danone Research, Centre
for Specialised Nutrition, Wageningen, The Netherlands).
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