CE ARTICLE
Nutritional treatment of pressure ulcers: What is the evidence? Loretta A. Sernekos, PhD, MSN, ANP-BC (Lecturer B)1,2 1 2
University of Pennsylvania School of Nursing, Philadelphia, Pennsylvania Advocare Gigliotti Family Medicine, Berlin, New Jersey
Keywords Geriatric; long-term care (LTC); nutrition; wound care. Correspondence Loretta A. Sernekos, PhD, MSN, ANP-BC, University of Pennsylvania School of Nursing, Claire M. Fagin Hall, 418 Curie Boulevard, Philadelphia, PA 19104-4217. Tel: 856-694-0377; E-mail: [email protected] Received: July 2012; accepted: January 2013 doi: 10.1002/2327-6924.12025 To obtain CE credit for this activity, go to www.aanp.org and click on the ce Center. Locate the listing for this article and complete the post-test. Follow the instructions to print your CE certificate. Disclosures The author reports no competing interests.
Abstract Purpose: To review the literature on the nutritional treatment of pressure ulcers, with an emphasis on long-term care issues. The focus is on studies that have used high energy or high protein diets, supplementation with vitamin C, zinc, or arginine, or some combination of those four approaches. The goal of this review is to clarify the evidence (if any) supporting each nutritional treatment. Data sources: A search of the literature was conducted including PubMed, CINAHL, and MEDLINE. Search terms included “pressure ulcers,” in combination with “treatment,” “nutrition,” “supplements,” “Vitamin C,” “zinc,” and “arginine.” Conclusions: Studies of high energy and high protein intake provide some evidence that those may be useful interventions, but the evidence is not strong. Although we have basic science providing evidence of the role of vitamin C, zinc, and arginine in wound healing processes, data on those nutrients related to pressure ulcer healing is equivocal. Implications for practice: Nurse practitioners should assess the nutritional status of patients with pressure ulcers and treat deficiencies within current guidelines. At this time, there is not strong evidence to support the use of specific nutritional supplements.
Pressure ulcers remain a vexing and distressingly common problem in older adults who are residents of longterm care (LTC) facilities, and nurse practitioners (NPs) practicing in those settings are likely to have reason to treat them. They cause significant pain and reduction in the quality of life, as well as increased mortality (Horn et al., 2004). Additionally, they are costly to treat: total cost of treating pressure ulcers in the United States is estimated to be over $11 billion annually (White-Chu, Flock, Struck, & Aronson, 2011). Recent pressure ulcer prevalence estimates range from 11% to 14.4% of all nursing home residents (Park-Lee & Caffrey, 2009; VanGilder, MacFarlane, & Meyer, 2008). The incidence rate in a 2004 study of 95 LTC facilities was 29% (Horn et al., 2004). Risk factors for developing a pressure ulcer include: being bedfast or chairfast, comorbidities including stroke and renal failure, significant weight loss, eating difficulties, incontinence, and use of positioning devices (Horn et al., 2004; Kwong, Pang, Aboo, & Law, 2009; Park-Lee & Caffrey, 2009). Risk for a pressure ulcer increases with age, with one large 2005
survey of multiple institution types finding that 27.2% of persons over 70 and 33.8% of persons over 80 had a pressure ulcer (VanGilder et al., 2008). Healing a pressure ulcer is a complex cellular, molecular, and biochemical process that requires a multipronged approach to care. The most recent European Pressure Ulcer Advisory Panel (EPUAP) and American National Pressure Ulcer Advisory Panel (NPUAP) treatment guidelines address: assessment and monitoring, nutrition, support surfaces, cleansing, debridement, dressing choice, assessment and treatment of infection, biophysical agents (e.g., ultraviolet light, ultrasound, etc.), and surgery (EPUAP & NPUAP, 2009). Although this article focuses on nutritional approaches to pressure ulcer treatment, it should be viewed in the larger context of malnutrition and weight loss as indicators of underlying pathologies, evaluation, and treatment of which may ameliorate concomitant nutritional deficiencies. Some possible causes of malnutrition and weight loss include: chronic obstructive pulmonary disease, cancer, malabsorption syndromes, peptic ulcer
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disease, atrophic gastritis, oral disease, dysphagia, renal failure, cardiac failure, Parkinson’s disease, thyroid dysfunction, chronic pain, alcoholism, dementia, and depression (Chapman, 2007; Visvanathan & Chapman, 2009). Medications may also contribute to anorexia, weight loss, and malnutrition and consideration should be given to strategies for overcoming age-related changes, including reduced smell and taste sensation and early satiety (Alibhai, Greenwood, & Payette, 2005).
Nutritional considerations in pressure ulcer healing Increased energy and protein requirements The phases of wound healing place great demands on the body’s energy resources. Cell proliferation, protein synthesis, and the activities of enzymes consume energy (i.e., kilocalories) and protein reserves. A 2011 systematic review and meta-analysis of studies of energy balance in patients with pressure ulcers demonstrated that patients with pressure ulcers have a significantly higher resting energy expenditure than patients without pressure ulcers (Cereda, Klersy, Rondanelli, & Caccialanza, 2011). Dietary protein is of special concern in older adults, because sarcopenia may be accelerated under the stress of disease and the demands of wound healing (Dorner, Posthauer, Thomas, & NPUAP, 2009). For these reasons, the EPUAP and NPUAP guidelines recommend providing 30–35 kcal/kg body weight per day and 1.25–1.5 g protein/kg body weight for patients with a pressure ulcer. In patients with renal disease, appropriateness of increasing protein intake must be considered (Dorner et al., 2009; EPUAP & NPUAP, 2009).
Weight loss and malnutrition concerns in the LTC setting Estimates of unintended weight loss and malnutrition in the LTC setting vary widely and range up to 85% of resident populations (Ahmed & Haboubi, 2010; Dorner et al., 2009). Research on the relationship between weight loss, malnutrition, and pressure ulcers has tended to focus on the influence of malnutrition on development, as opposed to healing, of pressure ulcers (Harris & Fraser, 2004). Horn et al. (2004) found that significant weight loss was associated with a greater likelihood of developing a pressure ulcer. A 2005 study of one Veterans Administration nursing home found that 13 of 23 (56.5%) older male residents (mean age 79 ± 1 years) with pressure ulcers who were screened with the Mini Nutritional Assessment (MNA ) Screening Form were malnourished and an additional seven (30.4%) were at risk for malnutrition (Langkamp-Henken, Hud R
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gens, Stechmiller, & Herrlinger-Garcia, 2005). Shahin et al. (2010) found that of 290 residents with pressure ulcers in German nursing homes (mean age 82.3 years) and hospitals (mean age 65.2 years), 14% had had an undesired weight loss of 5%–10% in 6 months or less and 3.7% had had an undesired weight loss of greater than 10%. Sixteen percent had a body mass index of less than 18.5 kg/m2 . There is a paucity of data on the influence of malnutrition or weight loss on pressure ulcer healing. But because malnutrition is likely to complicate pressure ulcer healing, EPUAP and NPUAP guidelines recommend performing a nutritional assessment on admission for persons with a pressure ulcer, with any condition change and/or when pressure ulcer healing is not progressing. Anyone with a pressure ulcer should be referred to a registered dietician immediately. Additionally, weight status, weight loss, ability to eat independently, and adequacy of total nutrient intake should be assessed (EPUAP & NPUAP, 2009).
Relevant studies Only one study has examined the effect of increased caloric intake alone on pressure ulcer healing, and it is confounded by the fact that the supplement administered had additional vitamins and trace elements. Ohura, Nakajo, Okada, Omura, and Adachi (2011) conducted an open randomized trial of 60 Japanese tube-fed bedbound older adults (mean age 81.4 ± 8.13 years) with Stage III or IV pressure ulcers. The control group (N = 30) received the same daily calories as before the study. The treatment group (N = 30) received an individualized additional caloric supplement based on basal energy expenditure multiplied by two factors that take the stress of wound healing and being bedbound into account. The primary outcome was reduction in the size of the pressure ulcer surface and the depth of the ulcer. In both cases, patients who received greater calories had statistically significant greater reductions in wound surface size and depth. Few studies have examined increased protein supplementation in isolation as it relates to pressure ulcer healing. In a pilot study, Chernoff, Milton, and Lipschitz (1990) randomized 12 tube-fed patients (mean age 71.5 years) with pressure ulcers to either a high protein (16% of calories) or very high protein (25% of calories) dietary formula. The outcome measure was the reduction in mean surface area of the ulcer after 8 weeks. Patients in the very high protein cohort had a 73% reduction in mean surface area, compared to 42% in the high protein group. The difference was statistically significant, but the small sample size limits generalizability.
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Breslow, Hallfrisch, Guy, Crawley, and Goldberg (1993) studied 28 malnourished tube-fed and orally fed nursing home residents (mean age 72 ± 18 years) with truncal pressure ulcers (Stages II through IV); participants were nonrandomized. Fifteen residents received a 24% protein oral supplement and 13 received a 14% protein oral supplement. There was a statistically significant decrease in the total pressure ulcer surface area of the residents taking the 24% protein supplement, as compared to the 14% protein supplement cohort. Lee, Posthauer, Dorner, Redovian, and Maloney (2006) randomized 89 residents of LTC facilities with Stage II, III, or IV pressure ulcers to receive a commercial concentrated, fortified, collagen protein hydrolysate supplement or placebo; the study was double-blinded. Seventy-one residents completed the study. Wound healing was measured using the Pressure Ulcer Scale for Healing (PUSH) validated tool (Stotts et al., 2001), which scores pressure ulcers on a scale ranging from 0 (complete healing) to 17 (greatest severity). At the end of 8 weeks the statistically significant change in PUSH scores in the treatment group was 3.55 ± 4.66 vs. 3.22 ± 4.11 in the control group. The treatment group also had a significantly higher rate of healing at 2, 6, and 8 weeks.
The role of vitamin C Vitamin C, in the form of ascorbic acid, is needed for the hydroxylation of proline and lysine in the synthesis, cross-linking, and structural stabilization of collagen. Vitamin C also is required for immune response, cell mitosis, and monocyte migration into wound tissue, in addition to its role as an antioxidant (Collins, 2004; Wild, Rahbarnia, Kellner, Sobotka, & Eberlein, 2010). Vitamin C deficiency is known as scurvy and can result in fatigue, weakness, swollen gums, and capillaries that rupture easily. Its role in maintaining the integrity of skin has been known since at least the 1930s and was suspected long before (Magiorkinis, Beloukas, & Diamantis, 2011). The National Academy of Sciences (2011a, 2011b) has set the required dietary allowance (RDA) for vitamin C at 75 mg/day for women over age 70 and 90 mg/day for men over age 70. The Tolerable Upper Limit (TUL) for both sexes is 2000 mg/day (Collins, 2004). Vitamin C deficiency can be expensive to diagnose via assay, but the supplement is generally well tolerated and is frequently prescribed as part of a wound care regimen (Doley, 2010). At doses of 10 times the RDA or higher, nausea, diarrhea, and abdominal cramps may occur. It should be used cautiously in patients who tend to get kidney stones or who have iron overload (Collins, 2004). EPUAP and NPUAP (2009) guidelines do not recommend routine prescribing of vitamin C for
pressure ulcer management, unless there is a known or suspected deficiency.
Relevant studies There have been only two studies of vitamin C’s effect on pressure ulcer healing. Both studies are older and came to contradictory conclusions. Taylor, Rimmer, Day, Butcher, and Dymock (1974) carried out a double-blind, randomized controlled trial with 20 postsurgery patients (mean age 74.5 years) with pressure ulcers. Half the patients received 500 mg ascorbic acid twice daily for 4 weeks, while the other half received a placebo. At the end of 4 weeks, patients in the treatment group had a statistically significant mean reduction in the surface area of their pressure ulcers of 84%; the placebo group had a 42.7% reduction. In contrast, ter Riet, Kessels, and Knipschild (1995) conducted a blinded, randomized controlled trial with 88 patients (from 11 nursing homes and one hospital) with pressure ulcers. Patients in the treatment group received 500 mg ascorbic acid twice daily for 12 weeks. Patients in the control group received 10 mg ascorbic acid twice daily. There were no statistically significant differences between the groups in wound surface area, volume, relative healing rates, healing velocities, or overall improvement (as judged by a panel viewing slides of the wounds).
The role of zinc Zinc, a trace element, is a cofactor for many reactions involved in the synthesis of RNA and DNA and thus, proteins (Wild et al., 2010). It is needed for the formation of granulation tissue and epithelial tissue; it also has anti-inflammatory and antimicrobial effects (Doley, 2010). Zinc deficiency can result in hair loss, diarrhea, poor appetite, decreased taste sensation, skin lesions, and erectile dysfunction (Gray, 2003). The National Academy of Sciences (2011a, 2011b) has set the RDA for elemental zinc at 8 mg/day for women over age 70 and 11 mg/day for men over age 70. The TUL for both sexes is 40 mg/day. Commercially available zinc sulfate is made in doses of 110 and 220 mg, which contain 25 and 50 mg of elemental zinc, respectively. Assays of zinc can be unreliable, but plasma zinc levels of less than 60 µg/dL are generally considered indicative of deficiency (Jamshed & Schneider, 2010). Excessive zinc intake can result in copper deficiency, immunosuppression, and gastrointestinal distress (Jamshed & Schneider, 2010). One brief 2001 report of the use of a 100 mg elemental zinc supplement in 25 older adults with pressure ulcers (Stages II through IV) 283
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compared them to 43 observational controls who also had pressure ulcers. The participants taking the zinc supplement were 12.5 times more likely to have nausea and vomiting and, paradoxically, were 7.8 times more likely to acquire an infection requiring an antibiotic (Houston, Haggard, Williford, Meserve, & Shewokis, 2001). EPUAP and NPUAP (2009) guidelines do not recommend routine prescribing of zinc for pressure ulcer management, unless there is a known or suspected deficiency.
Relevant studies There is very little data available regarding zinc’s effect on pressure ulcer healing. Norris and Reynolds (1971) conducted a randomized, double-blind, crossover study with 14 hospitalized patients (mean age 59.3 years) with pressure ulcers. Participants received 200 mg zinc sulfate three times a day or placebo for 24 weeks. Crossover occurred after 12 weeks. Pressure ulcer volume was measured by filling the ulcers with a rapid-setting alginate hydrocolloid. Although a statistically significant difference in the net pressure ulcer volume is reported, only three patients completed the full crossover study, making it impossible to draw any clinically relevant conclusions. There have been two other brief reports published as abstracts or letters. Watkin and Waldron (1981) randomized 29 male Veterans Administration hospital patients with pressure ulcers to receive 220 mg zinc sulfate daily and an additional 28 patients to receive placebo. After 10 weeks, healing was assessed by measuring changes in the area of the pressure ulcers, evaluated both by serial photographs and ulcer border tracings. There were no statistically significant differences in each group’s result. As previously described, Houston et al. (2001) compared 25 older adults with pressure ulcers who took 100 mg elemental zinc daily to 43 adults with pressure adults who did not take zinc. There were no statistically significant differences in wound healing between the two groups.
The role of arginine Arginine is a semiessential (also known as conditionally essential) amino acid. This means that the human body can make its own arginine, but that during times of physiological stress, the amount made may be insufficient and arginine must be supplied through the diet (Collins, 2001; Crowe & Brockbank, 2009). Arginine has several functions that are important to wound repair:
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It is nitrogen rich and contributes to a positive nitrogen balance;
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it is a precursor of proline, which is converted to hydroxyproline and then collagen; it is also a precursor of polyamines, the “building blocks” of proteins; and it is the only substrate for nitric oxide (NO) synthesis. NO is crucial to wound healing because it is toxic to bacteria, contributes to angiogenesis, and acts as a vasodilator, immune response mediator, and neurotransmitter (Collins, 2001; Crowe & Brockbank, 2009; Doley, 2010). There is a strong relationship between the availability of NO and the quality of collagen deposited in a wound (Curran, Winter, & Bouchier-Hayes, 2006).
Average dietary intake of arginine is 5–6 g/day, but older adults living in nursing homes have been reported to have much lower arginine intakes, in the range of 2.4– 3.3 g/day (Crowe & Brockbank, 2009). Arginine is available as a powdered drink supplement from multiple manufacturers. Maximum safe dosages of arginine have not been established and the EPUAP and NPUAP guidelines state that additional research is needed before arginine alone or in combination can be recommended to treat pressure ulcers (Dorner et al., 2009; EPUAP & NPUAP, 2009).
Relevant studies There have been no studies of the effect of arginine in isolation on pressure ulcer healing. Commercial preparations such as Cubitan , Argiment , and Arginaid contain arginine in combination with additional protein, various vitamins, minerals, and other nutrients, and these are the types of preparations that have been studied (trade names and/or manufacturers are usually, but not always, identified in published studies). Frias Soriano et al. (2004) conducted an open intervention study of 39 patients in Spanish hospitals (mean age 74.7 ± 12.9 years) with Stage III or IV pressure ulcers. They were given an oral supplement that contained 20 g of protein, of which 3 g were arginine. The supplement also included vitamin C, vitamin E, zinc, and other unnamed “essential micronutrients” (p. 320). Patients were given a variable amount of supplement, based on their calculated energy needs; average intake was 1.9 ± 0.5 packages per day. Primary outcome was a reduction in surface wound area at 3 weeks compared to baseline; the statistically significant median reduction was 29%. Desneves, Todorovic, Cassar, and Crowe (2005) randomized 16 patients from spinal cord and geriatric hospital units in Australia with Stage II through IV pressure ulcers to one of three diets: (a) standard hospital diet (mean age 63.0 ± 9.9 years); (b) standard hospital diet plus two R
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daily high calorie, high protein supplements containing vitamin C and zinc (mean age 75.6 ± 5.9 years); or (c) standard hospital diet plus two daily supplements containing the same contents as the second diet, but containing an additional 9 g of arginine (mean age 83.2 ± 1.1 years). Pressure ulcers were evaluated using the PUSH tool for 3 weeks. Patients receiving the arginine supplement had statistically significant improvement in pressure ulcer healing versus the other two groups. The small number of patients in each group limits generalizability. Heyman, Van De Looverbosch, Meijer, and Schols (2008) conducted an open study in which they enrolled 245 residents (mean age 82.2 ± 10.1 years) of LTC facilities in Belgium and Luxembourg; all had Stage II, III, or IV pressure ulcers. All received their normal diet or enteral feeding plus three servings of a 200 mL supplement containing 20 g total protein, 3 g arginine, 250 mg vitamin C, 38 mg vitamin E, and 9 mg zinc, plus “other micronutrients” (p. 477). Primary outcome was a reduction in mean pressure ulcer surface area. There was a significant reduction in surface area after 9 weeks. Cereda, Gini, Pedrolli, and Vanotti (2009) conducted a study of 28 residents of LTC facilities in Italy (mean age 82.1 ± 9.6 years); both tube-fed and nontube-fed residents were eligible. The treatment group (N = 13) received, if orally fed, a standard hospital diet plus 400 mL of an oral supplement that contained 34 g total protein, 6 g of arginine, 500 mg vitamin C, and 18 mg zinc. If tubefed, residents received 1000 mL of a supplement containing 55 g total protein, 8.5 g of arginine, 320 mg vitamin C, and 20 mg zinc. The control group (N = 15) received a standard hospital oral- or tube-fed diet. The primary outcomes were pressure ulcer healing, measured with the PUSH tool and reduction of ulcer surface area. The PUSH score was significantly lower, and the reduction in surface area was significantly higher in the treatment group. Van Anholt et al. (2010) randomized 43 European hospital and LTC facility patients (mean age 76.2 ± 3.2 years) with Stage III or IV pressure ulcers to one of two groups: the treatment group (N = 22) received a 200 mL supplement containing 20 g total protein, 3 g arginine, 238 mg vitamin A, 250 mg vitamin C, 38 mg vitamin E, 9 mg of zinc, plus carotenoids, selenium, copper, and folic acid. Supplementation was three times a day. The control group (N = 21) received a noncaloric flavored placebo. The primary endpoint was a reduction in pressure ulcer surface area over 8 weeks; a secondary endpoint was the change in the PUSH score. Pressure ulcer surface area and PUSH scores both declined significantly in the treatment group versus the controls. Leigh et al. (2012) randomized 23 Australian hospital and rehabilitation patients with Stage II through IV
ulcers to receive either of (a) a supplement containing 4.5 g arginine, 155 mg vitamin C, and 40.5 mg vitamin E or (b) a supplement containing 9 g arginine, but also twice as much vitamins C and E. The average age of Group (a) (N = 12) was 69.8 ± 5.2 years; Group (b) (N = 11) was 67.5 ± 4.9 years old. Primary outcome was pressure ulcer healing, measured via PUSH scores. After 3 weeks, both groups had statistically significant reductions in PUSH scores compared to baseline, but there was no statistically significant difference in the rates of healing of both groups. The authors concluded that a lower dose arginine supplement was as effective as a higher dose supplement.
Strengths and weaknesses of literature reviewed Strengths Studies included in this review had several strengths that will be of value to NPs who treat patients with pressure ulcers. All of the studies evaluated a nutritional intervention with specific reference to treatment of pressure ulcers and not to wounds more broadly defined. Generally speaking, the studies focused on older adults, although not all studies gave the demographics of participants. Many of the studies included or focused on residents of LTC facilities, where NPs are likely to encounter residents with pressure ulcers. The arginine combination supplement studies employed commercially available supplements, making it possible for NPs to investigate using these supplements clinically. However, no study gave cost data, which is an important consideration.
Weaknesses A number of weaknesses of the literature reviewed are evident. Some studies, such as Norris and Reynolds (1971), Taylor et al. (1974), and Desneves et al. (2005) had very small numbers of participants. This weakens the generalizability of the studies and makes it difficult to draw meaningful conclusions about their clinical relevance. Few studies were fully randomized, blinded, and placebo-controlled, which raises issues of nonrandom bias. Measurement of healing of pressure ulcers varied among studies, making cross-study comparisons difficult. The two most common methods of evaluating pressure ulcer healing were the measurement of surface area and the PUSH validated tool. Further, some studies had participants with Stage II, III, and IV pressure ulcers (now referred to as Category II, III, and IV pressure ulcers;
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EPUAP & NPUAP, 2009). There is a significant difference between a Category II and Category III or IV pressure ulcer, and a single approach to treating them may be less than optimal. An additional weakness of the literature on arginine supplementation is that the studies used commercial preparations that included other vitamins and minerals, including vitamin C and zinc. As noted above, there is very little evidence to support the use of vitamin C and zinc in pressure ulcer treatment. The addition of vitamin A, vitamin E, and other nutrients confounds the data, as we do not know their effect on pressure ulcer healing. Many studies did not detail the participants’ baseline nutrition status. In view of the fact that malnutrition is known to contribute to pressure ulcer development (Horn et al., 2004) and the fact that malnourished patients would likely require additional nutrition beyond the needs of well-nourished patients, this is a major oversight. As detailed above, malnutrition is a very common problem in LTC facilities. Some studies (Cereda et al., 2009; Heyman et al., 2008) mixed oral-fed and tube-fed participants, without giving details about those participants’ mobility status; both feeding route and mobility status would affect their energy requirements. Finally, other pressure ulcer treatment was nonstandardized across these studies, introducing another confounding variable. For example, ter Riet et al. (1995) noted that they used enzymatic or surgical debridement on some wounds during their vitamin C study. Some studies refer to patients receiving “standard” pressure ulcer care, without outlining the details of that care (Heyman et al., 2008; van Anholt et al., 2010). While recognizing that pressure ulcer treatment is a multimodal undertaking, details on the type of care would help the reader make decisions about the clinical applicability of the nutritional intervention.
Conclusion and implications for practice Adequate nutritional intake is an important part of pressure ulcer treatment, and current guidelines recommend assessing patients’ nutritional status and insuring their energy and protein intake meets certain minimum standards (EPUAP & NPUAP, 2009). Studies of high energy and high protein intake provide some evidence that those may be useful interventions, but the evidence is not strong, given the small number of studies and their overall methodological weakness. Although we have basic science providing evidence of the role of certain nutrients in wound healing in general, data on those nutrients related to pressure ulcer healing is more equivocal. In the case of vitamin C, we have only
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two older studies drawing opposite conclusions. Data on zinc are so sparse (and not peer reviewed) that it is impossible to make generalizations about the utility of zinc in pressure ulcer healing. It is for these reasons that the EPUAP and NPUAP (2009) guidelines do not recommend use of vitamin C or zinc unless there is a deficiency. Further research is needed in this area before any recommendations regarding their use can be made. The evidence for arginine supplementation is generally favorable, but it is confounded by the addition of other nutrients in commercially available preparations. There may be a degree of synergy occurring among all the ingredients of the supplements. We do not know if arginine, in isolation, is beneficial for pressure ulcer healing. NPs, in collaboration with a registered dietician, should assess the nutritional status of patients with pressure ulcers and develop nutritional plans to treat deficiencies within current guidelines. Several validated tools are available for screening and assessing nutritional status of geriatric patients and are also appropriate for use in LTC facilities. Screening tools include the Malnutrition Screening Tool (MST), Malnutrition Universal Screening Tool (MUST), Mini Nutritional AssessmentShort Form (MNA -SF), and Simplified Nutritional Assessment Questionnaire (SNAQ). Two widely used and validated tools for assessing nutritional status are the Subjective Global Assessment (SGA) and MNA (Isenring, Banks, Ferguson, & Bauer, 2012). The MNA in particular is recommended for LTC residents, as it has been the extensively studied in geriatric populations and in the LTC setting (Thomas, 2008); it also provides data to support a diagnosis of malnutrition on the Minimum Data Set (MDS) 3.0 active diagnoses list (Skates & Anthony, 2012). The MNA and MNA -SF, as well as user guides for their implementation, are available for download (www.mna-elderly.com). A finding of malnutrition or high risk for malnutrition resulting from any of these screening tools should prompt a comprehensive nutritional assessment by a registered dietician or other qualified nutrition expert (Skates & Anthony, 2012). At this time, there is not strong evidence to support the use of specific nutritional supplements in the treatment of pressure ulcers. More scientifically rigorous studies with larger participant populations and standardized interventions are needed to create an evidence-based model of nutritional interventions in the treatment of pressure ulcers. R
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Acknowledgments The author wishes to thank Susan Renz, DNP, CRNP, and Melissa Taylor, MSN, CRNP, for their mentoring
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and comments on an earlier version of this manuscript. Many thanks also go to the anonymous reviewers and the Editor.
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Heyman, H., Van De Looverbosch, D. E., Meijer, E. P., & Schols, J. M. (2008). Benefits of an oral nutritional supplement on pressure ulcer healing in long-term care residents. Journal of Wound Care, 17, 476–478, 480. Horn, S. D., Bender, S. A., Ferguson, M. L., Smout, R. J., Bergstrom, N., Taler, G., . . . Voss, A. C. (2004). The national pressure ulcer long-term care study: Pressure ulcer development in long-term care residents. Journal of the American Geriatrics Society, 52, 359–367. Houston, S., Haggard, J., Williford, J., Jr, Meserve, L., & Shewokis, P. (2001). Adverse effects of large-dose zinc supplementation in an institutionalized older population with pressure ulcers. Journal of the American Geriatrics Society, 49, 1130–1131. Isenring, E. A., Banks, M., Ferguson, M., & Bauer, J. D. (2012). Beyond malnutrition screening: Appropriate methods to guide nutrition care for aged care residents. Journal of the Academy of Nutrition and Dietetics, 112, 376–381. doi:10.1016/j.jada.2011.09.038 Jamshed, N., & Schneider, E. L. (2010). Is the use of supplemental vitamin C and zinc for the prevention and treatment of pressure ulcers evidence-based? Annals of Long-Term Care, 18, 28–32. Kwong, E. W., Pang, S. M., Aboo, G. H., & Law, S. S. (2009). Pressure ulcer development in older residents in nursing homes: Influencing factors. Journal of Advanced Nursing, 65, 2608–2620. doi:10.1111/j.1365–2648.2009.05117.x Langkamp-Henken, B., Hudgens, J., Stechmiller, J. K., & Herrlinger-Garcia, K. A. (2005). Mini nutritional assessment and screening scores are associated with nutritional indicators in elderly people with pressure ulcers. Journal of the American Dietetic Association, 105, 1590–1596. doi:10.1016/j.jada.2005.07.005 Lee, S. K., Posthauer, M. E., Dorner, B., Redovian, V., & Maloney, M. J. (2006). Pressure ulcer healing with a concentrated, fortified, collagen protein hydrolysate supplement: A randomized controlled trial. Advances in Skin & Wound Care, 19(2), 92–96. Leigh, B., Desneves, K., Rafferty, J., Pearce, L., King, S., Woodward, M. C., . . . Crowe, T. C. (2012). The effect of different doses of an arginine-containing supplement on the healing of pressure ulcers. Journal of Wound Care, 21, 150–156. Magiorkinis, E., Beloukas, A., & Diamantis, A. (2011). Scurvy: Past, present and future. European Journal of Internal Medicine, 22, 147–152. doi:10.1016/j.ejim.2010.10.006 National Academy of Science, Institute of Medicine, Food and Nutrition Board. (2011a). Dietary reference intakes (DRIs): Recommended dietary allowances and adequate intakes, vitamins and elements. Retrieved from http://iom.edu/ Activities/Nutrition/SummaryDRIs/∼/media/Files/Activity%20Files/ Nutrition/DRIs/RDA%20and%20AIs Vitamin%20and%20Elements.pdf National Academy of Science, Institute of Medicine, Food and Nutrition Board. (2011b). Dietary reference intakes (DRIs): Tolerable upper intake levels, vitamins and elements. Retrieved from http://iom.edu/Activities/Nutrition/ SummaryDRIs/∼/media/Files/Activity%20Files/Nutrition/DRIs/ULs% 20for%20Vitamins%20and%20Elements.pdf Norris, J. R., & Reynolds, R. E. (1971). The effect of oral zinc sulfate therapy on decubitus ulcers. Journal of the American Geriatrics Society, 19, 793–797. Ohura, T., Nakajo, T., Okada, S., Omura, K., & Adachi, K. (2011). Evaluation of effects of nutrition intervention on healing of pressure ulcers and nutritional states (randomized controlled trial). Wound Repair and Regeneration, 19, 330–336. doi:10.1111/j.1524–475X.2011.00691.x; 10.1111/j.1524–475X.2011.00691.x Park-Lee, E., & Caffrey, C. (2009). Pressure ulcers among nursing home residents: United States, 2004. NCHS Data Brief, 14, 1–8. Shahin, E. S., Meijers, J. M., Schols, J. M., Tannen, A., Halfens, R. J., & Dassen, T. (2010). The relationship between malnutrition parameters and pressure ulcers in hospitals and nursing homes. Nutrition, 26, 886–889. doi:10.1016/j.nut.2010.01.016 Skates, J. J., & Anthony, P. S. (2012). Identifying geriatric malnutrition in nursing practice: The Mini Nutritional Assessment (MNA )—An evidence-based screening tool. Journal of Gerontological Nursing, 38, 18–27; quiz 28–29. doi:10.3928/00989134–20120207–02 R
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Stotts, N. A., Rodeheaver, G. T., Thomas, D. R., Frantz, R. A., Bartolucci, A. A., Sussman, C., . . . Maklebust, J. (2001). An instrument to measure healing in pressure ulcers: Development and validation of the Pressure Ulcer Scale for Healing (PUSH). Journals of Gerontology, Series A, Biological Sciences and Medical Sciences, 56, M795–M799. 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), 544–546. ter Riet, G., Kessels, A. G., & Knipschild, P. G. (1995). Randomized clinical trial of ascorbic acid in the treatment of pressure ulcers. Journal of Clinical Epidemiology, 48, 1453–1460. Thomas, D. R. (2008). Nutrition assessment in long-term care. Nutrition in Clinical Practice, 23, 383–387. doi:10.1177/0884533608321129 van Anholt, R. D., Sobotka, L., Meijer, E. P., Heyman, H., Groen, H. W., Topinkova, E., . . . Schols, J. M. (2010). Specific nutritional support accelerates pressure ulcer healing and reduces wound care intensity in
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non-malnourished patients. Nutrition, 26, 867–872. doi:10.1016/j.nut.2010.05.009 VanGilder, C., MacFarlane, G. D., & Meyer, S. (2008). Results of nine International Pressure Ulcer Prevalence Surveys: 1989 to 2005. Ostomy/Wound Management, 54(2), 40–54. Visvanathan, R., & Chapman, I. M. (2009). Undernutrition and anorexia in the older person. Gastroenterology Clinics of North America, 38, 393–409. doi:10.1016/j.gtc.2009.06.009 Watkin, D. M., & Waldron, W. D. (1981). A double-blind study of supplemental zinc in the management of pressure ulcers. Federation Proceedings, 40, 856. White-Chu, E. F., Flock, P., Struck, B., & Aronson, L. (2011). Pressure ulcers in long-term care. Clinics in Geriatric Medicine, 27, 241–258. doi:10.1016/j.cger.2011.02.001 Wild, T., Rahbarnia, A., Kellner, M., Sobotka, L., & Eberlein, T. (2010). Basics in nutrition and wound healing. Nutrition, 26, 862–866. doi:10.1016/j.nut.2010.05.008
Nutritional treatment of pressure ulcers: What is the evidence? Loretta A. Sernekos, PhD, MSN, ANP-BC (Lecturer B)1,2 1 2
University of Pennsylvania School of Nursing, Philadelphia, Pennsylvania Advocare Gigliotti Family Medicine, Berlin, New Jersey
Keywords Geriatric; long-term care (LTC); nutrition; wound care. Correspondence Loretta A. Sernekos, PhD, MSN, ANP-BC, University of Pennsylvania School of Nursing, Claire M. Fagin Hall, 418 Curie Boulevard, Philadelphia, PA 19104-4217. Tel: 856-694-0377; E-mail: [email protected] Received: July 2012; accepted: January 2013 doi: 10.1002/2327-6924.12025 To obtain CE credit for this activity, go to www.aanp.org and click on the ce Center. Locate the listing for this article and complete the post-test. Follow the instructions to print your CE certificate. Disclosures The author reports no competing interests.
Abstract Purpose: To review the literature on the nutritional treatment of pressure ulcers, with an emphasis on long-term care issues. The focus is on studies that have used high energy or high protein diets, supplementation with vitamin C, zinc, or arginine, or some combination of those four approaches. The goal of this review is to clarify the evidence (if any) supporting each nutritional treatment. Data sources: A search of the literature was conducted including PubMed, CINAHL, and MEDLINE. Search terms included “pressure ulcers,” in combination with “treatment,” “nutrition,” “supplements,” “Vitamin C,” “zinc,” and “arginine.” Conclusions: Studies of high energy and high protein intake provide some evidence that those may be useful interventions, but the evidence is not strong. Although we have basic science providing evidence of the role of vitamin C, zinc, and arginine in wound healing processes, data on those nutrients related to pressure ulcer healing is equivocal. Implications for practice: Nurse practitioners should assess the nutritional status of patients with pressure ulcers and treat deficiencies within current guidelines. At this time, there is not strong evidence to support the use of specific nutritional supplements.
Pressure ulcers remain a vexing and distressingly common problem in older adults who are residents of longterm care (LTC) facilities, and nurse practitioners (NPs) practicing in those settings are likely to have reason to treat them. They cause significant pain and reduction in the quality of life, as well as increased mortality (Horn et al., 2004). Additionally, they are costly to treat: total cost of treating pressure ulcers in the United States is estimated to be over $11 billion annually (White-Chu, Flock, Struck, & Aronson, 2011). Recent pressure ulcer prevalence estimates range from 11% to 14.4% of all nursing home residents (Park-Lee & Caffrey, 2009; VanGilder, MacFarlane, & Meyer, 2008). The incidence rate in a 2004 study of 95 LTC facilities was 29% (Horn et al., 2004). Risk factors for developing a pressure ulcer include: being bedfast or chairfast, comorbidities including stroke and renal failure, significant weight loss, eating difficulties, incontinence, and use of positioning devices (Horn et al., 2004; Kwong, Pang, Aboo, & Law, 2009; Park-Lee & Caffrey, 2009). Risk for a pressure ulcer increases with age, with one large 2005
survey of multiple institution types finding that 27.2% of persons over 70 and 33.8% of persons over 80 had a pressure ulcer (VanGilder et al., 2008). Healing a pressure ulcer is a complex cellular, molecular, and biochemical process that requires a multipronged approach to care. The most recent European Pressure Ulcer Advisory Panel (EPUAP) and American National Pressure Ulcer Advisory Panel (NPUAP) treatment guidelines address: assessment and monitoring, nutrition, support surfaces, cleansing, debridement, dressing choice, assessment and treatment of infection, biophysical agents (e.g., ultraviolet light, ultrasound, etc.), and surgery (EPUAP & NPUAP, 2009). Although this article focuses on nutritional approaches to pressure ulcer treatment, it should be viewed in the larger context of malnutrition and weight loss as indicators of underlying pathologies, evaluation, and treatment of which may ameliorate concomitant nutritional deficiencies. Some possible causes of malnutrition and weight loss include: chronic obstructive pulmonary disease, cancer, malabsorption syndromes, peptic ulcer
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disease, atrophic gastritis, oral disease, dysphagia, renal failure, cardiac failure, Parkinson’s disease, thyroid dysfunction, chronic pain, alcoholism, dementia, and depression (Chapman, 2007; Visvanathan & Chapman, 2009). Medications may also contribute to anorexia, weight loss, and malnutrition and consideration should be given to strategies for overcoming age-related changes, including reduced smell and taste sensation and early satiety (Alibhai, Greenwood, & Payette, 2005).
Nutritional considerations in pressure ulcer healing Increased energy and protein requirements The phases of wound healing place great demands on the body’s energy resources. Cell proliferation, protein synthesis, and the activities of enzymes consume energy (i.e., kilocalories) and protein reserves. A 2011 systematic review and meta-analysis of studies of energy balance in patients with pressure ulcers demonstrated that patients with pressure ulcers have a significantly higher resting energy expenditure than patients without pressure ulcers (Cereda, Klersy, Rondanelli, & Caccialanza, 2011). Dietary protein is of special concern in older adults, because sarcopenia may be accelerated under the stress of disease and the demands of wound healing (Dorner, Posthauer, Thomas, & NPUAP, 2009). For these reasons, the EPUAP and NPUAP guidelines recommend providing 30–35 kcal/kg body weight per day and 1.25–1.5 g protein/kg body weight for patients with a pressure ulcer. In patients with renal disease, appropriateness of increasing protein intake must be considered (Dorner et al., 2009; EPUAP & NPUAP, 2009).
Weight loss and malnutrition concerns in the LTC setting Estimates of unintended weight loss and malnutrition in the LTC setting vary widely and range up to 85% of resident populations (Ahmed & Haboubi, 2010; Dorner et al., 2009). Research on the relationship between weight loss, malnutrition, and pressure ulcers has tended to focus on the influence of malnutrition on development, as opposed to healing, of pressure ulcers (Harris & Fraser, 2004). Horn et al. (2004) found that significant weight loss was associated with a greater likelihood of developing a pressure ulcer. A 2005 study of one Veterans Administration nursing home found that 13 of 23 (56.5%) older male residents (mean age 79 ± 1 years) with pressure ulcers who were screened with the Mini Nutritional Assessment (MNA ) Screening Form were malnourished and an additional seven (30.4%) were at risk for malnutrition (Langkamp-Henken, Hud R
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gens, Stechmiller, & Herrlinger-Garcia, 2005). Shahin et al. (2010) found that of 290 residents with pressure ulcers in German nursing homes (mean age 82.3 years) and hospitals (mean age 65.2 years), 14% had had an undesired weight loss of 5%–10% in 6 months or less and 3.7% had had an undesired weight loss of greater than 10%. Sixteen percent had a body mass index of less than 18.5 kg/m2 . There is a paucity of data on the influence of malnutrition or weight loss on pressure ulcer healing. But because malnutrition is likely to complicate pressure ulcer healing, EPUAP and NPUAP guidelines recommend performing a nutritional assessment on admission for persons with a pressure ulcer, with any condition change and/or when pressure ulcer healing is not progressing. Anyone with a pressure ulcer should be referred to a registered dietician immediately. Additionally, weight status, weight loss, ability to eat independently, and adequacy of total nutrient intake should be assessed (EPUAP & NPUAP, 2009).
Relevant studies Only one study has examined the effect of increased caloric intake alone on pressure ulcer healing, and it is confounded by the fact that the supplement administered had additional vitamins and trace elements. Ohura, Nakajo, Okada, Omura, and Adachi (2011) conducted an open randomized trial of 60 Japanese tube-fed bedbound older adults (mean age 81.4 ± 8.13 years) with Stage III or IV pressure ulcers. The control group (N = 30) received the same daily calories as before the study. The treatment group (N = 30) received an individualized additional caloric supplement based on basal energy expenditure multiplied by two factors that take the stress of wound healing and being bedbound into account. The primary outcome was reduction in the size of the pressure ulcer surface and the depth of the ulcer. In both cases, patients who received greater calories had statistically significant greater reductions in wound surface size and depth. Few studies have examined increased protein supplementation in isolation as it relates to pressure ulcer healing. In a pilot study, Chernoff, Milton, and Lipschitz (1990) randomized 12 tube-fed patients (mean age 71.5 years) with pressure ulcers to either a high protein (16% of calories) or very high protein (25% of calories) dietary formula. The outcome measure was the reduction in mean surface area of the ulcer after 8 weeks. Patients in the very high protein cohort had a 73% reduction in mean surface area, compared to 42% in the high protein group. The difference was statistically significant, but the small sample size limits generalizability.
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Breslow, Hallfrisch, Guy, Crawley, and Goldberg (1993) studied 28 malnourished tube-fed and orally fed nursing home residents (mean age 72 ± 18 years) with truncal pressure ulcers (Stages II through IV); participants were nonrandomized. Fifteen residents received a 24% protein oral supplement and 13 received a 14% protein oral supplement. There was a statistically significant decrease in the total pressure ulcer surface area of the residents taking the 24% protein supplement, as compared to the 14% protein supplement cohort. Lee, Posthauer, Dorner, Redovian, and Maloney (2006) randomized 89 residents of LTC facilities with Stage II, III, or IV pressure ulcers to receive a commercial concentrated, fortified, collagen protein hydrolysate supplement or placebo; the study was double-blinded. Seventy-one residents completed the study. Wound healing was measured using the Pressure Ulcer Scale for Healing (PUSH) validated tool (Stotts et al., 2001), which scores pressure ulcers on a scale ranging from 0 (complete healing) to 17 (greatest severity). At the end of 8 weeks the statistically significant change in PUSH scores in the treatment group was 3.55 ± 4.66 vs. 3.22 ± 4.11 in the control group. The treatment group also had a significantly higher rate of healing at 2, 6, and 8 weeks.
The role of vitamin C Vitamin C, in the form of ascorbic acid, is needed for the hydroxylation of proline and lysine in the synthesis, cross-linking, and structural stabilization of collagen. Vitamin C also is required for immune response, cell mitosis, and monocyte migration into wound tissue, in addition to its role as an antioxidant (Collins, 2004; Wild, Rahbarnia, Kellner, Sobotka, & Eberlein, 2010). Vitamin C deficiency is known as scurvy and can result in fatigue, weakness, swollen gums, and capillaries that rupture easily. Its role in maintaining the integrity of skin has been known since at least the 1930s and was suspected long before (Magiorkinis, Beloukas, & Diamantis, 2011). The National Academy of Sciences (2011a, 2011b) has set the required dietary allowance (RDA) for vitamin C at 75 mg/day for women over age 70 and 90 mg/day for men over age 70. The Tolerable Upper Limit (TUL) for both sexes is 2000 mg/day (Collins, 2004). Vitamin C deficiency can be expensive to diagnose via assay, but the supplement is generally well tolerated and is frequently prescribed as part of a wound care regimen (Doley, 2010). At doses of 10 times the RDA or higher, nausea, diarrhea, and abdominal cramps may occur. It should be used cautiously in patients who tend to get kidney stones or who have iron overload (Collins, 2004). EPUAP and NPUAP (2009) guidelines do not recommend routine prescribing of vitamin C for
pressure ulcer management, unless there is a known or suspected deficiency.
Relevant studies There have been only two studies of vitamin C’s effect on pressure ulcer healing. Both studies are older and came to contradictory conclusions. Taylor, Rimmer, Day, Butcher, and Dymock (1974) carried out a double-blind, randomized controlled trial with 20 postsurgery patients (mean age 74.5 years) with pressure ulcers. Half the patients received 500 mg ascorbic acid twice daily for 4 weeks, while the other half received a placebo. At the end of 4 weeks, patients in the treatment group had a statistically significant mean reduction in the surface area of their pressure ulcers of 84%; the placebo group had a 42.7% reduction. In contrast, ter Riet, Kessels, and Knipschild (1995) conducted a blinded, randomized controlled trial with 88 patients (from 11 nursing homes and one hospital) with pressure ulcers. Patients in the treatment group received 500 mg ascorbic acid twice daily for 12 weeks. Patients in the control group received 10 mg ascorbic acid twice daily. There were no statistically significant differences between the groups in wound surface area, volume, relative healing rates, healing velocities, or overall improvement (as judged by a panel viewing slides of the wounds).
The role of zinc Zinc, a trace element, is a cofactor for many reactions involved in the synthesis of RNA and DNA and thus, proteins (Wild et al., 2010). It is needed for the formation of granulation tissue and epithelial tissue; it also has anti-inflammatory and antimicrobial effects (Doley, 2010). Zinc deficiency can result in hair loss, diarrhea, poor appetite, decreased taste sensation, skin lesions, and erectile dysfunction (Gray, 2003). The National Academy of Sciences (2011a, 2011b) has set the RDA for elemental zinc at 8 mg/day for women over age 70 and 11 mg/day for men over age 70. The TUL for both sexes is 40 mg/day. Commercially available zinc sulfate is made in doses of 110 and 220 mg, which contain 25 and 50 mg of elemental zinc, respectively. Assays of zinc can be unreliable, but plasma zinc levels of less than 60 µg/dL are generally considered indicative of deficiency (Jamshed & Schneider, 2010). Excessive zinc intake can result in copper deficiency, immunosuppression, and gastrointestinal distress (Jamshed & Schneider, 2010). One brief 2001 report of the use of a 100 mg elemental zinc supplement in 25 older adults with pressure ulcers (Stages II through IV) 283
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compared them to 43 observational controls who also had pressure ulcers. The participants taking the zinc supplement were 12.5 times more likely to have nausea and vomiting and, paradoxically, were 7.8 times more likely to acquire an infection requiring an antibiotic (Houston, Haggard, Williford, Meserve, & Shewokis, 2001). EPUAP and NPUAP (2009) guidelines do not recommend routine prescribing of zinc for pressure ulcer management, unless there is a known or suspected deficiency.
Relevant studies There is very little data available regarding zinc’s effect on pressure ulcer healing. Norris and Reynolds (1971) conducted a randomized, double-blind, crossover study with 14 hospitalized patients (mean age 59.3 years) with pressure ulcers. Participants received 200 mg zinc sulfate three times a day or placebo for 24 weeks. Crossover occurred after 12 weeks. Pressure ulcer volume was measured by filling the ulcers with a rapid-setting alginate hydrocolloid. Although a statistically significant difference in the net pressure ulcer volume is reported, only three patients completed the full crossover study, making it impossible to draw any clinically relevant conclusions. There have been two other brief reports published as abstracts or letters. Watkin and Waldron (1981) randomized 29 male Veterans Administration hospital patients with pressure ulcers to receive 220 mg zinc sulfate daily and an additional 28 patients to receive placebo. After 10 weeks, healing was assessed by measuring changes in the area of the pressure ulcers, evaluated both by serial photographs and ulcer border tracings. There were no statistically significant differences in each group’s result. As previously described, Houston et al. (2001) compared 25 older adults with pressure ulcers who took 100 mg elemental zinc daily to 43 adults with pressure adults who did not take zinc. There were no statistically significant differences in wound healing between the two groups.
The role of arginine Arginine is a semiessential (also known as conditionally essential) amino acid. This means that the human body can make its own arginine, but that during times of physiological stress, the amount made may be insufficient and arginine must be supplied through the diet (Collins, 2001; Crowe & Brockbank, 2009). Arginine has several functions that are important to wound repair:
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it is a precursor of proline, which is converted to hydroxyproline and then collagen; it is also a precursor of polyamines, the “building blocks” of proteins; and it is the only substrate for nitric oxide (NO) synthesis. NO is crucial to wound healing because it is toxic to bacteria, contributes to angiogenesis, and acts as a vasodilator, immune response mediator, and neurotransmitter (Collins, 2001; Crowe & Brockbank, 2009; Doley, 2010). There is a strong relationship between the availability of NO and the quality of collagen deposited in a wound (Curran, Winter, & Bouchier-Hayes, 2006).
Average dietary intake of arginine is 5–6 g/day, but older adults living in nursing homes have been reported to have much lower arginine intakes, in the range of 2.4– 3.3 g/day (Crowe & Brockbank, 2009). Arginine is available as a powdered drink supplement from multiple manufacturers. Maximum safe dosages of arginine have not been established and the EPUAP and NPUAP guidelines state that additional research is needed before arginine alone or in combination can be recommended to treat pressure ulcers (Dorner et al., 2009; EPUAP & NPUAP, 2009).
Relevant studies There have been no studies of the effect of arginine in isolation on pressure ulcer healing. Commercial preparations such as Cubitan , Argiment , and Arginaid contain arginine in combination with additional protein, various vitamins, minerals, and other nutrients, and these are the types of preparations that have been studied (trade names and/or manufacturers are usually, but not always, identified in published studies). Frias Soriano et al. (2004) conducted an open intervention study of 39 patients in Spanish hospitals (mean age 74.7 ± 12.9 years) with Stage III or IV pressure ulcers. They were given an oral supplement that contained 20 g of protein, of which 3 g were arginine. The supplement also included vitamin C, vitamin E, zinc, and other unnamed “essential micronutrients” (p. 320). Patients were given a variable amount of supplement, based on their calculated energy needs; average intake was 1.9 ± 0.5 packages per day. Primary outcome was a reduction in surface wound area at 3 weeks compared to baseline; the statistically significant median reduction was 29%. Desneves, Todorovic, Cassar, and Crowe (2005) randomized 16 patients from spinal cord and geriatric hospital units in Australia with Stage II through IV pressure ulcers to one of three diets: (a) standard hospital diet (mean age 63.0 ± 9.9 years); (b) standard hospital diet plus two R
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daily high calorie, high protein supplements containing vitamin C and zinc (mean age 75.6 ± 5.9 years); or (c) standard hospital diet plus two daily supplements containing the same contents as the second diet, but containing an additional 9 g of arginine (mean age 83.2 ± 1.1 years). Pressure ulcers were evaluated using the PUSH tool for 3 weeks. Patients receiving the arginine supplement had statistically significant improvement in pressure ulcer healing versus the other two groups. The small number of patients in each group limits generalizability. Heyman, Van De Looverbosch, Meijer, and Schols (2008) conducted an open study in which they enrolled 245 residents (mean age 82.2 ± 10.1 years) of LTC facilities in Belgium and Luxembourg; all had Stage II, III, or IV pressure ulcers. All received their normal diet or enteral feeding plus three servings of a 200 mL supplement containing 20 g total protein, 3 g arginine, 250 mg vitamin C, 38 mg vitamin E, and 9 mg zinc, plus “other micronutrients” (p. 477). Primary outcome was a reduction in mean pressure ulcer surface area. There was a significant reduction in surface area after 9 weeks. Cereda, Gini, Pedrolli, and Vanotti (2009) conducted a study of 28 residents of LTC facilities in Italy (mean age 82.1 ± 9.6 years); both tube-fed and nontube-fed residents were eligible. The treatment group (N = 13) received, if orally fed, a standard hospital diet plus 400 mL of an oral supplement that contained 34 g total protein, 6 g of arginine, 500 mg vitamin C, and 18 mg zinc. If tubefed, residents received 1000 mL of a supplement containing 55 g total protein, 8.5 g of arginine, 320 mg vitamin C, and 20 mg zinc. The control group (N = 15) received a standard hospital oral- or tube-fed diet. The primary outcomes were pressure ulcer healing, measured with the PUSH tool and reduction of ulcer surface area. The PUSH score was significantly lower, and the reduction in surface area was significantly higher in the treatment group. Van Anholt et al. (2010) randomized 43 European hospital and LTC facility patients (mean age 76.2 ± 3.2 years) with Stage III or IV pressure ulcers to one of two groups: the treatment group (N = 22) received a 200 mL supplement containing 20 g total protein, 3 g arginine, 238 mg vitamin A, 250 mg vitamin C, 38 mg vitamin E, 9 mg of zinc, plus carotenoids, selenium, copper, and folic acid. Supplementation was three times a day. The control group (N = 21) received a noncaloric flavored placebo. The primary endpoint was a reduction in pressure ulcer surface area over 8 weeks; a secondary endpoint was the change in the PUSH score. Pressure ulcer surface area and PUSH scores both declined significantly in the treatment group versus the controls. Leigh et al. (2012) randomized 23 Australian hospital and rehabilitation patients with Stage II through IV
ulcers to receive either of (a) a supplement containing 4.5 g arginine, 155 mg vitamin C, and 40.5 mg vitamin E or (b) a supplement containing 9 g arginine, but also twice as much vitamins C and E. The average age of Group (a) (N = 12) was 69.8 ± 5.2 years; Group (b) (N = 11) was 67.5 ± 4.9 years old. Primary outcome was pressure ulcer healing, measured via PUSH scores. After 3 weeks, both groups had statistically significant reductions in PUSH scores compared to baseline, but there was no statistically significant difference in the rates of healing of both groups. The authors concluded that a lower dose arginine supplement was as effective as a higher dose supplement.
Strengths and weaknesses of literature reviewed Strengths Studies included in this review had several strengths that will be of value to NPs who treat patients with pressure ulcers. All of the studies evaluated a nutritional intervention with specific reference to treatment of pressure ulcers and not to wounds more broadly defined. Generally speaking, the studies focused on older adults, although not all studies gave the demographics of participants. Many of the studies included or focused on residents of LTC facilities, where NPs are likely to encounter residents with pressure ulcers. The arginine combination supplement studies employed commercially available supplements, making it possible for NPs to investigate using these supplements clinically. However, no study gave cost data, which is an important consideration.
Weaknesses A number of weaknesses of the literature reviewed are evident. Some studies, such as Norris and Reynolds (1971), Taylor et al. (1974), and Desneves et al. (2005) had very small numbers of participants. This weakens the generalizability of the studies and makes it difficult to draw meaningful conclusions about their clinical relevance. Few studies were fully randomized, blinded, and placebo-controlled, which raises issues of nonrandom bias. Measurement of healing of pressure ulcers varied among studies, making cross-study comparisons difficult. The two most common methods of evaluating pressure ulcer healing were the measurement of surface area and the PUSH validated tool. Further, some studies had participants with Stage II, III, and IV pressure ulcers (now referred to as Category II, III, and IV pressure ulcers;
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EPUAP & NPUAP, 2009). There is a significant difference between a Category II and Category III or IV pressure ulcer, and a single approach to treating them may be less than optimal. An additional weakness of the literature on arginine supplementation is that the studies used commercial preparations that included other vitamins and minerals, including vitamin C and zinc. As noted above, there is very little evidence to support the use of vitamin C and zinc in pressure ulcer treatment. The addition of vitamin A, vitamin E, and other nutrients confounds the data, as we do not know their effect on pressure ulcer healing. Many studies did not detail the participants’ baseline nutrition status. In view of the fact that malnutrition is known to contribute to pressure ulcer development (Horn et al., 2004) and the fact that malnourished patients would likely require additional nutrition beyond the needs of well-nourished patients, this is a major oversight. As detailed above, malnutrition is a very common problem in LTC facilities. Some studies (Cereda et al., 2009; Heyman et al., 2008) mixed oral-fed and tube-fed participants, without giving details about those participants’ mobility status; both feeding route and mobility status would affect their energy requirements. Finally, other pressure ulcer treatment was nonstandardized across these studies, introducing another confounding variable. For example, ter Riet et al. (1995) noted that they used enzymatic or surgical debridement on some wounds during their vitamin C study. Some studies refer to patients receiving “standard” pressure ulcer care, without outlining the details of that care (Heyman et al., 2008; van Anholt et al., 2010). While recognizing that pressure ulcer treatment is a multimodal undertaking, details on the type of care would help the reader make decisions about the clinical applicability of the nutritional intervention.
Conclusion and implications for practice Adequate nutritional intake is an important part of pressure ulcer treatment, and current guidelines recommend assessing patients’ nutritional status and insuring their energy and protein intake meets certain minimum standards (EPUAP & NPUAP, 2009). Studies of high energy and high protein intake provide some evidence that those may be useful interventions, but the evidence is not strong, given the small number of studies and their overall methodological weakness. Although we have basic science providing evidence of the role of certain nutrients in wound healing in general, data on those nutrients related to pressure ulcer healing is more equivocal. In the case of vitamin C, we have only
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two older studies drawing opposite conclusions. Data on zinc are so sparse (and not peer reviewed) that it is impossible to make generalizations about the utility of zinc in pressure ulcer healing. It is for these reasons that the EPUAP and NPUAP (2009) guidelines do not recommend use of vitamin C or zinc unless there is a deficiency. Further research is needed in this area before any recommendations regarding their use can be made. The evidence for arginine supplementation is generally favorable, but it is confounded by the addition of other nutrients in commercially available preparations. There may be a degree of synergy occurring among all the ingredients of the supplements. We do not know if arginine, in isolation, is beneficial for pressure ulcer healing. NPs, in collaboration with a registered dietician, should assess the nutritional status of patients with pressure ulcers and develop nutritional plans to treat deficiencies within current guidelines. Several validated tools are available for screening and assessing nutritional status of geriatric patients and are also appropriate for use in LTC facilities. Screening tools include the Malnutrition Screening Tool (MST), Malnutrition Universal Screening Tool (MUST), Mini Nutritional AssessmentShort Form (MNA -SF), and Simplified Nutritional Assessment Questionnaire (SNAQ). Two widely used and validated tools for assessing nutritional status are the Subjective Global Assessment (SGA) and MNA (Isenring, Banks, Ferguson, & Bauer, 2012). The MNA in particular is recommended for LTC residents, as it has been the extensively studied in geriatric populations and in the LTC setting (Thomas, 2008); it also provides data to support a diagnosis of malnutrition on the Minimum Data Set (MDS) 3.0 active diagnoses list (Skates & Anthony, 2012). The MNA and MNA -SF, as well as user guides for their implementation, are available for download (www.mna-elderly.com). A finding of malnutrition or high risk for malnutrition resulting from any of these screening tools should prompt a comprehensive nutritional assessment by a registered dietician or other qualified nutrition expert (Skates & Anthony, 2012). At this time, there is not strong evidence to support the use of specific nutritional supplements in the treatment of pressure ulcers. More scientifically rigorous studies with larger participant populations and standardized interventions are needed to create an evidence-based model of nutritional interventions in the treatment of pressure ulcers. R
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Acknowledgments The author wishes to thank Susan Renz, DNP, CRNP, and Melissa Taylor, MSN, CRNP, for their mentoring
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and comments on an earlier version of this manuscript. Many thanks also go to the anonymous reviewers and the Editor.
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