Nutritional status and food intake in nine patients with chronic low-limb ulcers and pressure ulcers: importance of oral supplements

Nutrition 22 (2006) 82– 88 www.elsevier.com/locate/nut

Preliminary report

Nutritional status and food intake in nine patients with chronic lowlimb ulcers and pressure ulcers: importance of oral supplements Wassim Raffoul, M.D.a, Majid Shahin Far, M.D.a, Marie-Christine Cayeux, R.N.b, and Mette M. Berger, M.D., Ph.D.b,* b

a Chirurgie Plastique et Reconstructive, CHUV, Lausanne, Switzerland; Soins Intensifs de Chirurgie et Centre des brûlés, CHUV, 1011 Lausanne, Switzerland

Manuscript received December 20, 2004; accepted April 5, 2005.

Abstract

Objectives: Chronic low-limb ulcers and pressure ulcers are a serious and costly issue. Malnutrition is a risk factor. Searching for intervention strategies in elderly patients referred for surgical closure of their ulcers, the trial aimed at investigating the micronutrient status, determining the food intake of such patients, and the role of oral liquid supplements. Methods: Observational cohort study in 9 patients, starting 5 days prior to surgery until day 10 after surgery. Variables: body mass index (BMI), food intake assessed using standardized meals (energy target 25 kcal/kg/day). Oral liquid supplements were provided between meals. Laboratory: blood count, plasma proteins, antioxidant status, vitamins, Fe, Se, and Zn. Results: The patients were aged 71⫾10 y (mean⫾SD), with a BMI of 23.3⫾3.3. Baseline blood samples showed anemia and strong inflammation in 4 patients: albumin, retinol, and selenium were low; iron and zinc were very low. Food intake was largely variable and covered only about 76% (31-95%) of energy requirements. Breakfast provided 225⫾110, lunch 570⫾215, and dinner 405⫾150 kcal. Supplements were willingly consumed covering 35⫾12% of energy target. While vitamin supply was adequate, selenium and zinc requirements were not met. Conclusions: Most patients with chronic skin ulcers suffered micronutrient status alterations, and borderline malnutrition. Meals did not cover energy requirements, while oral supplements covered basic micronutrient requirements and compensated for insufficient oral energy and protein intakes, justifying their use in hospitalized elderly patients. © 2006 Elsevier Inc. All rights reserved.

Keywords:

Wound healing; hospital malnutrition; zinc; selenium; energy target; oral supplement

Introduction Chronic low-limb ulcers and pressure ulcers constitute a serious issue in hospital patients, frequently involving more women and elderly [1–3]. Ulcers are characterized by complicated and prolonged wound healing. Epidemiological data show a mean prevalence of 0.29% of leg ulcers in the general population [3] and up to 11.7% in hospitals and

Financial support: The study was partially supported by a grant from Nestec Ltd. Av Nestlé 55, 1800 Vevey, Switzerland. None of the authors has any conflict of interest, as the supplements are in use in our institution, along with other products. * Corresponding author: Tél.: ⫹41 21 31 42 095; Fax: ⫹41 21 31 43 045. E-Mail: [email protected] (M.M. Berger) 0899-9007/06/$ – see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.nut.2005.04.014

nursing homes [2]. In intensive care units, the prevalence of pressure ulcers is even higher with 29% [4]. Normal wound healing has 3 phases: 1) inflammation, 2) cellular proliferation, and 3) remodeling [5]. In chronic ulcers, phase 1 is abnormally prolonged. Frequently many surgical interventions are required, prolonging hospital stay. Nutrition directly influences the wound healing process, as malnutrition decreases anabolism and depresses immunity [6]. Substrates such as proteins, glucose, vitamins, trace elements, oxygen, and anabolic factors must all be available in adequate proportions. Depressed plasma concentrations of vitamin A and E, ␤-carotene, selenium and zinc have been shown to occur in elderly patients with chronic leg ulcers [7]. The low micronutrient concentrations are largely caused by inadequate nutritional intakes and malnutrition, which is

Nutritional status in chronic skin ulcers / Nutrition 22 (2006) 82– 88

a frequent problem in elderly [8]. In addition, hospital malnutrition is a well-recognized and widespread problem which worsens preexisting undernutrition, affecting 10-50% of the patients [9,10]. While malnutrition is one of the recognized risk factors of delayed wound healing and of altered immunity, little is know about nutrition and micronutrient status in patients with chronic skin ulcers [7]. Interventional data regarding the benefit of nutrition or pharmaconutrients on pressure ulcers are few [11]. A recent review of the literature could find no hard evidence concerning the effect of nutrition on wound healing, despite putting forward evidence of nutritional deficits in this patient group [12]. The present pilot study aimed at assessing nutritional status and wound-healing related micronutrients, to identify the nutritional risk factors of delayed wound healing. In addition we tested the feasibility of a method assessing wound healing using polytetrafluoroethylene (PTFE) implants to determine OH-proline content of the tubes and of oral liquid nutrition supplementation.

Patients and methods The trial was designed as a prospective non-comparative cohort trial lasting 15-16 days. After institutional Ethics Committee approval the study was conducted with written informed consent from each patient. Inclusion criteria were: referral for surgical treatment of deep leg or decubitus ulcers unresponsive to conservative treatment, age 55-90 years, hospitalization on a medical or surgical CHUV ward, and informed consent. Exclusion criteria were: denial of consent, infected wound, renal failure (plasma creatinine ⬎ 150 ␮mol/l, or clearance below 40 ml/min by the Cockcroft-Gault formula [13]), or active immuno-suppressing treatment. The following variables were recorded: age, weight, height, and length of stay before and after surgery. Preoperative nutritional status assessment was based on body mass index (BMI ⬍ 20, malnutrition; BMI 20 to 30, normal status). The patients were assessed clinically and blood samples were collected on day 5 before scheduled surgery (day ⫺5), on the day of surgery (day 0), and on 5th and 10th postoperative days. Nutritional support: patients were maintained on oral feeding. Energy target was set at 25 kcal/kg/day. The intervention consisted in encouraging oral food intake, and providing the patients 1-4 units of oral supplements per day (mostly as Clinutren®, Nestlé, Switzerland: 300 kcal/unit and 11.2 g proteins; others liquid supplements: 300 kcal/ unit) during the investigation period from day 5 before surgery and until D10 after surgery. Standardized meals were provided, CHUV’s food program is ISO certified: with the aim of attaining 300 kcal at breakfast, 700 kcal at lunch, and 700 kcal at dinner. All patients were supplemented with one multivitamin tablet per day (Supradyn®, Roche, Basel,

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Table 1 Micronutrient intakes resulting from mean daily consumption of oral supplements (2.4 U per patient) and from micronutrient supplements compared with the RDA [27] RDA Male/female Iron Selenium Zinc Ascorbic acid ␣-Tocopherol Retinol

10/10 mg 70/55 ␮g 15/12 mg 60/60 mg 10/8 ␮g ␣-TE 1000/800 ␮g RE

Quantity per day provided with mean supplement intake

Supradyn ⫹ Redoxon

7.9 36 7.2 72 9.6 700

3.6 0 3 680 10 3330

RDA, recommended dietary allowances; RE, retinol equivalents; TE, tocopherol equivalents.

Switzerland) and 500 mg ascorbic acid (Redoxon®, Roche, Basel, Switzerland). Feeding assessment: Oral food intake was assessed 3 times per day by the nurse-helpers: meal ingestion was evaluated using a 25% increasing consumption scale (ingestion of 0, 25, 50, 75 or 100% of the meal). In case of missing data, the entire day with partial assessment was deleted from analysis. Number of consumed oral supplements was recorded, and mean micronutrient intake resulting from their intake was calculated and compared to RDA (Table 1). Energy delivered by either food or oral supplements was then compared to the energy target and expressed as a percentage of that target. Wound healing: Wounds were assessed according to a standardized protocol, and surgery was carried out according to present state of the art after cleansing of the wound by topical disinfectants for 5 days. Percent wound healing (percentage graft take) by day 10 was recorded, with time to complete healing. Wound healing was further assessed with insertion of PTFE tubes to collect OH-proline [14]. We used sterile 8 cm long and 1.2 mm diameter tubes, with pores 90 –120␮, inserted under local or general anesthesia into the subcutaneous tissue during surgery (PTFE Impra, Advanta® Inc, Atrium Medical Corporation, Hudson, NH, USA). Tubes were kept in place for 10 days, and removed during refection of the surgical wound. Blood sampling and analysis All blood samples were collected after a 12-hours overnight fast (serum, plasma EDTA or heparin as required). Tubes were placed on ice, and centrifuged at 4000 x g for 10 min at 4°C. Plasma and erythrocytes were immediately isolated, aliquoted and stored at – 80°C until analysis. Interleukin 6 were measured by ELISA (Beckman). Peripheral leukocyte counts was determined by Coulter counter (Coulter Electronics, Hialeh, FL, USA). Hemoglobin was

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Nutritional status in chronic skin ulcers / Nutrition 22 (2006) 82– 88

analyzed by photometry (Sysmex®, Digitana, TOA Medical Electronics, Kobe, Japan). Proteins: Serum albumin and C-reactive protein (CRP) were measured by nephelometry (Behring Nephelometer, Behringwerke AG, Marburg, Germany). Serum pre-albumin was determined by immuno-nephelometry. Plasma transferrin and ferritin were measured by immunoturbidimetric and ELISA technique respectively using Dade Behring antibodies (Dade Behring S.A, Paris La Defense, France). Plasma ceruloplasmin was measured by nephelometry (Behring). Hydroxyproline content in the PTFE tubes was quantified after hydrolysis in acidic condition, HCl 6N for 24 h at 110°C, and was measured using an automatic amino acid analyzer (Beckman model 6300 High-Performance Amino Acid Analyzer, Beckman Instruments, Palo Alto, CA, USA), according to the manufacturer’s instructions. Micronutrients and antioxidant status: Plasma concentrations of ␤-carotene, lycopene, and vitamin E were quantified using HPLC [15]. Coefficients of variation were respectively 7.1%, 13.6%, and 5.1%. Total vitamin C: 400 ␮l of plasma was added to 3600 ␮l aqueous solution of metaphosphoric acid (5% w/v) and stored at – 80°C until analysis. The determination was done fluorometrically by HPLC after derivatization [16]. Coefficient of variation for vitamin C was 4.16%. Trace elements: plasma selenium level was determined by electrothermal atomic absorption spectrometry using Zeeman background correction. Plasma zinc levels were assayed by flame atomic absorption spectrometry. Seronorm Trace Element (N° 311089, Nycomed, Oslo, Norway) was used for internal quality control. Plasma iron was determined by colorimetry (ferrozine). Total antioxidant plasma capacity (TAS) was measured using a Randox kit (Randox, Montpellier Frejorgues, Mauguio cedex, France) [17]. Malondialdehyde (MDA) was determined after reaction of MDA in plasma with thiobarbituric acid at pH 6 and 100°C, the products were measured at 532 nm [18]. Urate was determined using an automated enzymatic method [19] (Hitachi 717, Roche Molecular Biochemicals, Rotkreuz, Switzerland). Total bilirubin was analyzed by enzymatic oxidation with bilirubin oxidase at pH 8.2. Glutathione peroxidase activity (GSH-Px) in plasma was evaluated by the modified Gunzler method, using terbutyl hydroperoxide (Sigma Chemical Co, Paris, France) as substrate [20]. Statistical analysis: Demographic data are presented as means⫾SD, and other variables as medians with ranges. Changes over time were analyzed using one-factor ANOVA. Linear regressions were calculated between BMI or length of hospital stay and blood variables. Significance was considered at the

level of p⬍0.05 (trends p⬍0.20). Statistical package was JMP® Version 3.1.5. (SAS Institute Inc. Cary, NC, USA).

Results Eleven patients were enrolled, but only 9 completed the trial: 2 were excluded, No. 2 because of an error in the enrollment, and No. 5 because of complete wound healing within 5 days. The patient characteristics are shown in Table 2. Median hospital stay before surgery was 9 days, with 4 patients having stayed longer (15-61 days). Nutritional status: All patients had lost 1-4 kg body weight during hospital stay. With a mean BMI of 23.3, the majority of patients were lean for age, 2 being malnourished. The borderline nutritional status was confirmed by hypoalbuminemia, low hemoglobin values in 8/9 patients, and prealbumin in the lower range combined with other micronutrient alterations. All patients took their multivitamin and vitamin C supplements. Due to iron deficiency patient no. 8 was on iron supplements before and during the trial. More than 50% of the RDAs for micronutrients was covered by the intake of oral supplements. Nutrient and food intake: Complete food intake data are available in 85 of 135 study days (10 days per patient). Oral food intake was extremely variable within and between patients: it covered 76⫾21% of the energy target (Figure 1). Mean energy intake was 225⫾110 kcal at breakfast, 570⫾215 kcal at lunch, and 405⫾150 kcal at dinner. Oral supplements were willingly consumed by majority of the patients with 2.4⫾0.8 U/d (median 3 packs), 5 patients receiving only Clinutren®, 4 taking a combination of Clinutren® and other brands. They provided 35⫾12% of the energy target (Table 2), with a mean protein intake of 27 g of per day, covering roughly 40% of protein requirements. While only hospital meals covered ⬎ 90% of energy requirement only in 2 patients, combination of oral feeding and supplements resulted in energy target (25 kcal/kg) being slightly overridden in 5 patients. Figure 1 shows the mean daily proportion of energy target covered by oral meals and by supplements. Of the 9 patients, 7 gained weight during the study without perceptible edema. Blood variables (Table 3): Hemoglobin was low and remained so throughout. Ceruloplasmin was in the upper range, in agreement with the inflammatory status of the patients. Prealbumin and albumin were in the lower range on enrollment, and remained low during the 15 days. Transferrin was low in 8 of 9 patients throughout. Mean ferritin was normal. CRP on admission was normal in only in 1 patient (i.e. ⬍10 mg/l), nearly

Table 2 Patient characteristics and details of wound healing Patient no.

Comorbities

Leg arteriopathy

4

Bilateral chronic ischemic leg ulcer Ischemic leg ulcer Pressure ulcer

6

Pressure ulcer

7

Chronic venous and autoimmune leg ulcer Chronic venous and ischemic leg ulcer Chronic venous and ischemic leg ulcer Pressure ulcer

1

3

8

9

10

11

Perineal ulcer of infectious origin Mean ⫾ SD Median

Weight change (kg)

Wound healing by day 10 (%)

Days to complete healing

Length of stay before surgery (ds)

Hospital stay after surgery (ds)

6

66

127

115

11

5

20

32

11

15

83

100

10

12

7

32

0.3

95

20

10

8

49

24.40

0.1

100

15

4

6

22

55.5

23.10

0.2

90

28

16

9

32

165

65.5

24.06

5.3

100

10

⬍3

42

72

55

173

59.5

19.88

3.1

80

20

18

39

43

71 ⫾ 10 72

164 ⫾ 10 164

62.7 ⫾ 11.0 61.5

23.3 ⫾ 3.3 24.1

79 ⫾ 32 90%

30⫾33 20

10 ⫾ 5.3 11

22⫾22 9

53⫾35 43

Bedridden

Age (y)

Height (cm)

Weight (kg)

BMI (kg/m2)

F

Y

68

155

43

17.90

0.1

80

20

Diabetes

M

N

84

152

61.5

26.62

⫺1.5

70

Multiple sclerosis Traumatic paraplegia, diabetes Rheumatoid arthritis

M

Y

75

160

67

26.17

⫺1

M

Y

72

164

73.1

27.18

0.2

M

N

59

169

57.7

20.20

M

N

80

183

81.7

F

N

79

155

Y

67

N

Leg arteriopathy

Sex

Multiple M myeloma and ICU myoneuropathy Verneuil’s M disease

0.8 ⫾ 2.1 0.2kg

0*

OH-proline on day 10 (nmol/cm)

Nutritional status in chronic skin ulcers / Nutrition 22 (2006) 82– 88

Type of ulcer

BMI, body mass index; F, female; ICU, intensive care unit; M, male; N, no; SD, standard deviation; Y, yes * Infectious complication requiring additional treatment before final closure 3 wk later.

85

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Nutritional status in chronic skin ulcers / Nutrition 22 (2006) 82– 88

deficiency and inflammatory origins). Zinc was below references (9.4⫾1.0 ␮mol/l) and increased modestly over time (p⫽0.07). Iron values were low and did not change significantly. Selenium was in the lower range (0.83⫾0.22 ␮mol/ l), being below reference in 3/9: both increases (n⫽3) and decreases (n⫽4) were observed during the 15 days. Vitamins: ␣-Tocopherol and ascorbic acid were normal, and retinol was in the lower range, being depressed in 4 of 9 patients. The ␤-carotene and lycopene concentrations were within ranges (there is no “established” range for lutein). Fig. 1. Energy intakes resulting from hospital meal ingestion and from oral supplements, expressed as proportion of individual energy target. Individual energy targets in kcal are indicated on the top of the figure.

normal in 3 patients (10-20 mg/l), and it was strongly elevated in 4 patients (⬎100 mg/l). Except in patient no. 8, CRP tended to decrease during the study (normal values only in 2 patients). IL-6 was elevated in 4 patients and decreased thereafter except in no. 8. Admission creatinine was 84 ␮mol/l (67-135 ␮mol/l) with a median calculated creatinine clearance of 60 ml/min.

Antioxidant status: Blood MDA was within normal ranges. Total antioxidant status was in the lower normal ranges. Glutathione was low throughout. Bilirubin was normal; urate was above reference ranges in 4 of 9 patients. Length of hospital stay before surgery was significantly correlated with baseline hemoglobin (r2 ⫽ 0.65, p⫽0.005) as was BMI was with baseline albumin (r2 ⫽ 0.49, p⫽0.036), hemoglobin (r2 ⫽ 0.75, p⫽0.001), and plasma iron (r2 ⫽ 0.52, p⫽ 0.02). Wound healing (Table 2):

Trace elements: Plasma iron concentration was severely depressed in 8 of 9 patients (the low to normal ferritin confirms the combined

Complete wound healing was achieved in all cases, 7 of 9 patients having straight healing. There were 2 complicated

Table 3 Blood parameters before intervention and after surgery (changes not significant)* Variable

Day ⫺5

Day 5

Day 10

Reference ranges

Hemoglobin Leukocytes CRP Albumin Prealbumin Ferritin Transferrin Ceruloplasmin Iron Selenium Zinc

111 (68–141) 8.0 (4.0–19.7) 29 (9–399) 35 (20–41) 0.21 (0.06–0.29) 196 (52–488) 2.0 (1.2–2.6) 381 (317–727) 5.5 (2.0–15.5) 0.9 (0.34–1.07) 9.4 (7.0–10)

107 (79–139) 7.6 (4.9–13.8) 41 (4–274) 32 (22–42) 0.22 (0.11–0.31) 196 (46–542) 2.0 (1.4–2.8) 358 (293–622) 7 (2.5–23.9) 0.84 (0.65–1.11) 10.4 (7.6–12.2)

107 (83–143) 8.4 (4.9–12.4) 46 (2–272) 32 (20–42) 0.24 (0.09–0.32) 135 (39–612) 2.2 (1.1–3.0) 369 (284–513) 8.4 (2.7–12.6) 0.96 (0.64–1.20) 9.4 (7.6–12.8)

Ascorbic acid ␣-Tocopherol Retinol ␤-Carotene Lutein Lycopene Glutathione Urate TAS MDA IL-6

44.5 (23.1–102.2) 27 (21.5–61.8) 1.52 (0.33–2.04) 48 (10–304) 87 (11–150) 342 (10–433) 286 (240–354) 315 (179–532) 1.13 (0.94–1.38) 2.18 (1.81–2.71) 12 (⬍10–1640)

48.4 (19.5–103.5) 31.6 (22.9–49.1) 1.55 (0.51–2.22) 54 (24–228) 91 (30–144) 250 (80–329) 264 (212–318) 348 (126–493) 1.12 (0.79–1.29) 2.24 (1.96–2.46) 13 (⬍10–1070)

46.9 (35.6–1003.5) 33.8 (22.4–58.9) 1.9 (0.66–2.84) 62 (19–202) 93 (27–113) 217 (107–381) 284 (212–363) 339 (144–427) 1.13 (0.76–1.24) 2.22 (1.66–2.62) 12 (⬍10–670)

135–175 g/L 4–10 g/L ⬍10 mg/L 35–52 g/L 0.20–0.40 mg/L 30–300 mg/L 2.5–3.5 g/L 250–450 mg/L 10.7–21.4 ␮mol/L 0.80–1.25 ␮mol/L 11.7–16.3 ␮mol/L (women), 12.7–17.3 ␮mol/L (men) 15–62 ␮mol/L 12–48 ␮mol/L 1.4–5.0 ␮mol/L 0–58 nmol/L nmol/L† 80–580 nmol/L 300–450 U/L 142–339 ␮mol/L 1.10–1.34 mmol/L 2.4–2.7 ␮mol/L ⬍ 10 ng/L

CRP, C-reactive protein; IL-6, interleukin-6; MDA, malondialdehyde; TAS, total antioxidant plasma capacity * Median (range). † No reference range.

Nutritional status in chronic skin ulcers / Nutrition 22 (2006) 82– 88

cases: a wound dehiscence of the gluteal flap (treated by a secondary closure) and a local hematoma in no. 10 (treated by local drainage) that had no significant consequences.

Discussion The main findings of this cohort study, were first, that in most of the patients the oral food intake was insufficient to cover their energy and protein requirements and hence to maintain their body mass. The patients suffered established or borderline malnutrition, being hypoalbuminemic and anemic: all had lost weight before the study. Second, oral supplements were an efficient tool to achieve energy, micronutrient and protein targets. Finally, micronutrient status was altered in the majority of patients, the strongest alterations being observed with iron and zinc. Elderly are frequently malnourished. Factors contributing to insufficient food intake include catabolic and inflammatory illness, pain, teeth and chewing problems, swallowing disorders, and drugs reducing appetite. Malnutrition is a risk factor for pressure ulcers. Variables such as impaired feeding, hypoalbuminemia, anemia, leucopenia, low body weight or BMI, and height are indeed independent, but weak predictors [1,21]. A recent survey of literature could find no hard evidence concerning the effect of nutrition on wound healing [12]. Our patients had stayed in hospital for 9 days before being referred for surgery – this time was enough for hospital feeding to impact negatively on their nutritional status [9,10]. The significant correlations observed between length of stay before surgery or BMI and either albumin, hemoglobin or iron are additional arguments in this direction. Only in 2 of 9 patients did the meals supply ⬎90% of energy targets. This low energy intake seems to be a feature of ulcer patients: lower energy (⫺185 kcal /day) and protein (⫺6.73 g/day) intakes were shown in a trial comparing patients with and without pressure ulcers [22]. Energy from oral supplements covered more than 40% of the energy target in the majority of cases, confirming that such supplements improve nutritional status in the elderly [23]. Acceptance of the oral supplements by patients with chewing problems, and the palatability and taste of the products (chocolate flavor was a favorite) were additional contributors. Low plasma micronutrient and albumin concentrations do not necessarily reflect malnutrition in the presence of inflammation. Nevertheless, in our experience with major burns, values below 20% of lowest reference range do generally reflect deficiency [24]. Micronutrient status studies in chronic ulcers are few: our data show that there is a risk of iron and zinc deficiency, complimenting the findings of Rojas et al. who showed low plasma concentrations of vitamin A and E, ␤-carotene, selenium and zinc in elderly patients with chronic leg ulcers [7]. Our patients had very low circulating zinc concentrations, which are associated with delayed wound healing [25]. But oral zinc supplements

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is not necessarily efficient in promoting leg ulcer healing [26]: only those patients with abnormally low zinc levels appeared to benefit in trials using large doses (200-440 mg Zn day). By design, no specific supplements were provided: the standard oral supplements combined with 500 mg ascorbic acid and a multi-micronutrient preparation may indeed be considered an intervention. Their aim was to provide protein and energy, but not to correct specific deficiencies. In the present trial they provided 50% of micronutrient requirements, which are impossible to guarantee with intakes less than 2000 kcal/day. Our supplements barely covered iron requirements, but not those of selenium or zinc, while vitamin allowances were largely met. Considering these findings, enrichment of oral supplements with iron, selenium, and zinc might be advocated. The study also aimed at testing the acceptance of oral supplements. Elderly patients frequently suffer malnutrition or borderline micronutrient deficiencies, and their food intakes are too small (⬍ 2000 kcal) and unpredictable to cover their requirements, hence favoring delayed wound healing. The study confirmed these observations. Wound healing can be assessed by collagen deposition (OH-proline detected in the PTFE porous tubes): larger OH-proline deposits (72.2 in supplemented and 43.1 nmol/cm in controls versus 9.1 nmol/cm presently) were observed by Williams et al. [14]. This difference is likely explained by the use of a smaller pore size (20 ␮m versus 120 ␮m), i.e. 6 times smaller. Hypothesizing that the migration of OH-proline is proportional to the pore size, or to its surface, the deposition would probably have been larger with greater pore diameter. Consequently, the method appears applicable to ulcers. Complete wound healing was achieved in all despite the difficult cases enrolled in the study: elderly patients with heavy comorbidities, referred for surgery after failure of conservative treatment, and complex etiology of the wounds. The rate of skin graft take at 10 days was more than 90%, which is an unusually favorable results specially in cases with chronic ulcers with ischemic or autoimmune origin. In case No 10 the wound was perianal with high risk of infection: the take rate was 100%. In the flap patients, 2 complications were observed, which healed completely. The nutritional intervention with oral supplements might have contributed as shown by the observed weight gain. Limitations of the study: There was by design no control group during this pilot phase, which limits our conclusions. Nevertheless creeping malnutrition and micronutrient status alterations were clearly demonstrated. Blood variables changed insignificantly over time. Compared with the supplementation trials in elderly based on 6-12 months intervention [8], 2 weeks was too short to achieve changes with a nutritional intervention. In conclusion, the present trial confirms the borderline to

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Nutritional status in chronic skin ulcers / Nutrition 22 (2006) 82– 88

deficient nutritional status of hospitalized patients suffering ulcers. It also confirms that hospital meals do not cover the nutritional requirements, and that oral supplements are an easy and well-accepted way to overcome the problem. The absence of significant changes in plasma concentration over a 15 day period can be considered an indication that actual oral supplements contain insufficient quantities of micronutrients to replete stores rapidly. Our findings need to be confirmed by a controlled trial in a larger group of patients.

Summary This pilot study in elderly hospitalized patients suffering chronic skin ulcers showed that the majority suffered underfeeding: hospital food did not cover energy nor micronutrient requirements. Liquid supplements supplied up for 40-50% of requirements. In addition the patients suffered from a deficiency of iron, selenium and zinc.

[9]

[10]

[11] [12]

[13]

[14]

[15]

[16]

Acknowledgements: [17]

The team is grateful to Mrs. Isabelle Bureau-Franz, Mr. J. Vuichoud, and Mrs C. Hager from the Nestlé Research Centre, Lausanne, Switzerland for analytical assistance, and contribution to the manuscript; to Professor Alain Favier (University of Grenoble, France) for analytical support.

[18]

[19]

References [20] [1] Allman RM, Goode PS, Patrick MM, Burst N, Bartolucci AA: Pressure ulcer risk factors among hospitalized patients with activity limitation. JAMA 1995; 273:865–70. [2] Lahmann NA, Halfens RJ, Dassen T: Prevalence of pressure ulcers in Germany. J Clin Nursing 2005; 14:165–72. [3] Nelzen O, Bergqvist D, Lindhagen A: The prevalence of chronic low-limb ulceration has been underestimated. Results of a validated population questionnaire. Br J Surg 1996; 83:255– 8. [4] Bours GJ, De Laat E, Halfens RJ, Lubbers M: Prevalence, risk factors and prevention of pressure ulcers in Dutch intensive care units. Results of a cross-sectional survey. Intensive Care Med 2001; 27: 1599 – 605. [5] Martin A: The use of antioxidants in healing. Dermatol Surg 1996; 22:156 – 60. [6] Chandra RK: Nutrition and immunity in elderly in the elderly: clinical significance. Nutrition Review 1995; 53:S80 –S3. [7] Rojas AI, Phillips TJ: Patients with chronic leg ulcers show diminished levels of vitamins A and E, carotenes, and zinc. Dermatologic Surgery 1999; 25:601– 4. [8] Girodon F, Galan P, Monget AL, et al.: Impact of trace elements and vitamin supplementation on immunity and infections in institutional-

[21] [22]

[23]

[24]

[25] [26]

[27]

ized elderly patients - A randomized controlled trial. Arch Intern Med 1999; 159:748 –54. Beck AM, Balknäs UN, Fürst P, et al.: Food and nutritional care in hospitals: how to prevent undernutrition - report and guidelines from the Council of Europe. Clin Nutr 2001; 20:455– 60. Kondrup J, Johansen N, Plum LM, et al.: Incidence of nutritional risk and causes of inadequate nutritional care in hospitals. Clin Nutr 2002; 21:461– 8. Bourdel-Marchasson I, Rondeau V: Nutritional intervention trials for preventing and treating pressure ulcer. Nutrition 2001; 17:155– 6. Heinen MM, van Achterberg T, op Reimer WS, van de Kerkhof PC, de Laat E: Venous leg ulcer patients: a review of the literature on lifestyle and pain-related interventions. J Clin Nursing 2004; 13:355– 66. Levey AS, Coresh J, Balk E, et al.: National kidney foundation practice guidelines for chronic kidney disease: Evaluation, Classification, and Stratification. Ann Intern Med 2003; 139:137– 47. Williams JZ, Abumrad N, Barbul A: Effect of a specialized amino acid mixture on human collagen deposition. Ann Surg 2002; 236: 369 –74. Steghens JP, van Kappel AL, Riboli E, Collombel C: Simultaneous measurement of seven carotenoids, retinol and a-tocopherol in serum by high performance liquid chromatography. J Chromatogr B 1997; 694:71– 81. Spears JW: Zinc methionine for ruminants: relative bioavailability of zinc in lambs and effect on growth and performance of growing heifers. J Anim Sci 1989; 67:835– 43. Miller NJ, Rice-Evans C, Davies MJ, Gopinathan V, Milner A: A novel method for measuring antioxidant capacity and its application to monitoring antioxidant status in premature neonates. Clin Sci 1993; 84:407–12. Richard MJ, Portal B, Meo J, et al.: Malondialdehyde kit evaluated for determining plasma and lipoprotein fractions that react with thiobarbituric acid. Clin Chem 1992; 38:704 –9. Thefeld W, Hoffmeister H, Busche EW, Koller PU, Vollmar J: Normalwerte der Serumharnsaure in Abhangigkeit von Alter und Geschlecht mit einem neuen enzymatischen Harnsaurefarbtest. Dtsch Med Wochenschr 1973; 98:380 – 4. Gunzler WA, Kremers H, Flohe L: An improved coupled test procedure for glutathione peroxidase (EC 1-11-1-9) in blood. Z Klin Chem Klin Biochem 1974; 12:444 – 8. Thomas DR: The role of nutrition in prevention and healing of pressure ulcers. Clin Ger Med 1997; 13:497–511. Green SM, Winterberg H, Franks PJ, et al.: Nutritional intake in community patients with pressure ulcers. J Wound Care 1999; 8:325– 30. Stratton RJ, Elia M: A critical systematic analysis of the use of oral nutritional supplements in the community. Clin Nutr 1999; 12 (Suppl 2):29 – 84. Berger MM, Spertini F, Shenkin A, et al.: Trace element supplementation modulates pulmonary infection rates after major burns: a double blind, placebo controlled trial. Am J Clin Nutr 1998; 68:365–71. Henzel JH, De Weese MS, Lichti EL: Zinc concentrations within healing wounds. Arch Surg 1970; 100:349 –57. Wilkinson EA, Hawke CI: Oral zinc for arterial and venous leg ulcers. Cochrane Database of Systematic Reviews 2000; (2): CD001273. Subcommittee on the 10th RDAs edition on Recommended Dietary Allowances, 10th ed. Washington DC: National Academy Press, 1989.