Improving outcome of pressure ulcers with nutritional interventions: a review of the evidence

REVIEW ARTICLE

Improving Outcome of Pressure Ulcers with Nutritional Interventions: A Review of the Evidence David R. Thomas, MD, FACP From the St. Louis Health Sciences Center and Geriatric Research & Education Center, Veterans Administration, Division of Geriatric Medicine, St. Louis, Missouri, USA Pressure ulcers and malnutrition frequently co-exist in frail patients. Nutritional parameters have been correlated with development and with healing in chronic pressure ulcers, leading to suggestions that improving nutritional status can prevent or treat pressure ulcers. Despite a strong association, a causal relationship of poor nutritional status to development of pressure ulcers has not been established. Support for a causal relationship would include evidence that nutritional interventions improve general nutritional status, acute wound healing, or chronic wound healing. The data suggesting that nutritional intervention can improve clinical outcome are limited. No study has demonstrated that improvement in nutritional status can prevent pressure ulcers. There is at least suggestive evidence that improvement in nutritional status can improve outcome in pressure ulcer healing. Nutrition 2001;17:121–125. ©Elsevier Science Inc. 2001 Key words: pressure ulcers, malnutrition, wound healing

INTRODUCTION Pressure ulcers and malnutrition frequently co-exist in frail patients in both acute hospital and long-term care settings. In a prospective study of high-risk hospitalized patients, malnutrition, defined by an index of biochemical and anthropometric variables, was present in 29% of patients at admission. At 4 wk, 17% of these malnourished patients had developed a pressure ulcer, compared with 9% of non-malnourished patients. Patients malnourished at hospital admission were twice as likely to develop pressure ulcers as non-malnourished patients (Relative Risk 2.1, 95% confidence intervals [CI] 1.1, 4.2).1 In another long-term-care setting, 59% of residents were defined as malnourished, with 7.3% of those patients classified as severely malnourished. Pressure ulcers occurred in 65% of the most severely malnourished patients. No pressure ulcers developed in the mild-to-moderately malnourished or wellnourished groups.2 These data suggest a strong correlation between nutritional status and the development of pressure ulcers. Risk factors for development of a pressure ulcer in hospital populations include non-blanchable erythema, lymphopenia, immobility, dry skin, and decreased body weight.3 In long-term care facilities with a low incidence of pressure ulcers, difficulty in ambulation, difficulty feeding oneself, and male gender were associated with a higher risk of developing a pressure ulcer. In long-term care facilities with a higher incidence of pressure ulcers, difficulty with ambulation, fecal incontinence, difficulty feeding oneself, and diabetes mellitus predicted pressure ulcer development.4 In a chronic care setting, risk of developing a pressure ulcer was increased when the patients had a history of cerebrovascular accident, were bed- or chair-confined, or had impaired nutritional intake.5 The development of a pressure ulcer is multifactorial. Whereas

Correspondence to: David R. Thomas, MD, St. Louis Health Sciences Center, 1402 S. Grand Blvd., M238, St. Louis, MO 63104, USA. E-mail: [email protected] Date accepted: August 28, 2000. Nutrition 17:121–125, 2001 ©Elsevier Science Inc., 2001. Printed in the United States. All rights reserved.

it is clear that factors other than nutrition influence the risk of developing pressure ulcers, certain nutritional factors appear repetitively across different populations, including impaired nutritional intake,5 lower dietary protein intake,6 impaired ability to feed oneself,4 and recent weight loss.3 These factors suggest a role for nutrition in the development of pressure ulcers. Despite this strong association, a causal relationship of poor nutritional status to pressure ulcers has not been established. The important clinical question is whether this association is reversible. Reasoning intuitively, if malnutrition is due to a deficiency of protein or calories, the supply of these essentials in adequate amounts should reverse the deficiency. The reversal of the deficiency should either decrease the likelihood of pressure ulcer development or improve the healing rate. The evidence for this hypothesis is examined in relation to general complications, general nutritional status, supplemental nutrition, enteral and parenteral interventions.

MALNUTRITION AND COMPLICATIONS Patients with severe malnutrition are a higher risk for hospital death, sepsis, infections, and increased length of stay.7–9 Among other outcomes, malnutrition is an predictor of risk for early mortality.10 –13 Malnourished patients are more likely to have postoperative complications than well-nourished patients.9 This consistent relationship between poor nutritional status and risk of future complications forms the cornerstone of nutritional support. More data are available for acute wounds than for chronic wounds.

MALNUTRITION AND WOUND HEALING Acute wound healing has been associated with nutritional status. Severe protein-calorie malnutrition alters tissue regeneration, the inflammatory reaction, and immune function.3 Yet there is controversy about the ability of nutritional support to reduce complications or improve wound healing.14 After vascular surgery, hypoalbuminemia and low transferrin 0899-9007/01/$20.00 PII S0899-9007(00)00514-1

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levels predict wound healing complications.15 Other factors often associated with nutritional status, including body weight, low lymphocytes, immune function, and zinc levels, failed to predict complications in this study. Deposition of hydroxyproline in implanted polytetrafloroethylene tubes is impaired in malnourished patients.16 Even brief preoperative illness or reduced nutrient intake impairs fibroplasia in acute wounds.17 Brief and not necessarily full-target nutritional intervention can reverse or prevent decreased collagen deposition demonstrated with malnutrition.17 Although collagen deposition in Gore-Tex (W.L. Gore and Associates, Flagstaff, AZ, USA) tubes is improved by enteral feeding, there is little clinical advantage. Whereas collagen deposition is improved, enteral feeding in a small sample did not improve body composition (measured by tritiated water dilution), prevent weight loss, reduce postoperative fatigue, improve muscle function, reduce time-to-flatus, or reduce hospital length of stay.18 Most acute wounds heal, even in debilitated patients undergoing major surgical procedures.14 Clinical healing may be prolonged, particularly in patients with diabetes or following irradiation. However, the most important clinical outcome, complete wound healing, is rarely used as an endpoint in studies of nutritional effect. Surrogate outcomes for wound healing have potentially biased several studies. Thus, it is difficult to find evidence from the literature that supplemental nutrition improves, or fails to improve, acute wound healing.

GENERAL NUTRITIONAL STATUS Continued weight loss in long-term care facilities is common. In an academic nursing home, 60% of residents experienced a net weight loss following admission, despite efforts of a full-time dietitian.19 There is no consensus that poor outcomes in malnourished persons can be improved. Malnourished or high-risk surgical patients have not had postoperative complications reduced to that of well-nourished patients undergoing similar procedures by pre- or postoperative enteral or parenteral support.20 Improvement in clinical outcome in the longterm care setting is even more difficult to document. At best, small gains in weight have been shown but improvement in other commonly accepted parameters of malnutrition are more difficult to demonstrate. Improvement in functional status with nutritional repletion is even more difficult to demonstrate. Little data are available on either the nutritional condition of residents on admission to nursing homes or on the longitudinal outcome of long-term care residents identified as malnourished. Few studies document whether protein-energy malnutrition persists or improves in individual patients after admission to a longterm care facility. Malnutrition was present in 54% of subjects on admission to one long-term care facility.10 Residents who were malnourished at admission were prescribed 2240 ⫾ 620 calories compared with 2000 ⫾ 500 calories in the non–protein-energy malnourished group (NS). By 8 wk, residents with protein-energy malnutrition had been prescribed 2790 ⫾ 760 calories versus 2460 ⫾ 810 calories for the non–protein-energy malnourished group, indicating a revision upwards of initial dietary energy in both groups. By the end of the study, malnourished residents lost a mean of 1.4 kg whereas non-malnourished residents gained 2.2 kg (P ⬎ 0.05). The major difference between the group remaining malnourished and the non-malnourished group was in the acceptance of the diet; that is, the estimated amount of food consumed at each meal expressed as a percentage of the diet taken. The malnourished group consumed only 80% of their diet compared with 95% in the non-malnourished group. Although more food was offered, less was taken.

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ORAL SUPPLEMENTAL NUTRITION In community settings, improvements in body weight and skinfold thickness has been shown over 13 wk in malnourished patients with emphysema. The magnitude of the difference was small: a mean gain of 1.5 kg in weight and 2.7 mm in skinfold thickness. Other indices of well-being, including pulmonary functions and immunologic status, did not improve.21 In a long-term care geriatric hospital, 29% of patients were malnourished by index score on admission.22 Patients were randomized to receive either a standard hospital diet or hospital diet plus twice daily nutritional supplementation. Thirty-nine patients refused to take the supplement and 8 control patients received the supplement. At 8 wk, 41% of malnourished patients who received dietary supplements improved, whereas only 18% of malnourished patients who did not receive nutritional supplements improved. Stated differently, 59% of supplemented patients failed to improve during the course of follow-up. This failure rate may be higher, because patients who were offered supplementation but refused ingestion were not included. Both experimental and control groups showed a decrease in weight index, triceps skinfold thickness, and midarm circumference after 26 wk, although the initially non-malnourished group who received supplemental feedings showed less decline. There were no differences in prealbumin, albumin, or antitrypsin levels between groups. The mortality rate was higher in the initially malnourished group, 19% compared with 9%. A study in long-term institutions in France evaluated the effect of nutritional supplementation in 78 patients aged 67 y and older.23 Subjects were divided into four groups: one group was well nourished, one group was poorly nourished, and two groups were at risk of malnutrition. Oral supplements were given to one at-risk group and to the malnourished group, with one at-risk group serving as a control. After 60 d, there was little change in weight in the well-nourished and the non-supplemented at-risk group. In the supplemented group, a mean weight gain of 1.5 kg was seen. In the malnourished group, a mean weight gain of 2 kg was observed. Although there were differences in weight among the groups, the magnitude of the change was small. Similar changes in weight have been reported in meta-analysis of trials of nutritional supplements in adults. In 30 randomized controlled trials (2062 subjects), routine supplementation produced a weighted mean difference in body weight of 2.06% (95% CI 1.63–2.49%) and a weighted mean difference in anthropometry of 3.16% (95% CI 2.43–3.89%). No certain effect on mortality was seen24 (Table I). The logic behind nutritional supplementation and wound healing is almost irresistible. Poor nutritional status, at least defined by commonly used physiologic parameters, is consistently associated with risk of future complications. Nutritional support can improve nutritional status. Therefore, nutritional support should be able to reduce complications. Proof of this reasoning, however, remains elusive in the medical literature.

ENTERAL FEEDING Ciocon et al.25 reported the long-term effects of enteral feedings in a long-term care setting. Seventy tube-fed residents aged 65–95 y were studied prospectively for 11 mo in a 527-bed facility. The indications for enteral feeding were refusal to swallow (50%), dysphagia without obstruction (47%), and esophageal obstruction (3%). Complications of enteral feedings were divided into early problems (within first 2 wk) and late problems (after 2 wk). In residents fed by nasogastric tube, agitation and self-extubation occurred in 67% of residents, and aspiration pneumonia occurred 43% of residents. Early problems in residents fed by gastrostomy tube included aspiration pneumonia (56%), tube dysfunction (50%), and agita-

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TABLE I. RESULTS OF ORAL NUTRITIONAL SUPPLEMENTATION Malnourished Clinical trial 13-week supplementation in subjects with emphysema21 Long-term geriatric hospital22 Long-term care facility supplemented for 60 days23 Meta-analysis of supplement studies24

Non-malnourished

Weight gain

Anthropometric gain

Weight gain

Anthropometric gain

1.5 kg Weight index 86 2 kg 2.1%

2.7 mm TSF ⫺0.9 mm TSF — 3.2%

— Weight index 90 — —

— ⫺0.8 TSF — —

TSF, tricep skinfold thickness.

tion and self-extubation (44%). Late problems consisted of aspiration pneumonia in 44% of nasogastric tube-fed residents and 56% of gastric-fed residents. Late extubation was limited to the nasogastric tube group (38%). Death occurred in 28 patients, usually between the second and sixth months, for a mortality rate of 46%. Response to enteral feeding was observed in 56 patients for 11 mo. Weight remained stable for 6 mo, but weight loss was apparent beyond 6 mo. Only 6% of patients gained weight at any time. Serum albumin was stable for at least 1 mo after starting enteral feedings. Wide fluctuations occurred, but the mean albumin remained stable during the study. Serum albumin was not normalized, however. Mean hemoglobin concentration also remained stable during the 11-mo follow-up, but did not increase over the mean at the start of the study. This study in a long-term care setting shows that continuation of tube feedings for long periods of time is associated with a high frequency of complications. Aspiration pneumonia probably contributed to death in 40% of patients. Body weight may be maintained for 6 mo, followed by loss of weight. Serum albumin and hemoglobin concentration stabilized at 3 mo, but did not reach normal levels. Pressure ulcers occur particularly frequently in patients with hip fracture. Attempts to prevent development of pressure ulcers in this population by provision of enteral nutrition have not been successful.26 A 2-year follow-up of nursing home residents with advancing dementia who were fed enterally failed to show any survival benefit or benefit for pressure ulcers.27 A study of chronically tube-fed long-term care residents with pressure ulcers demonstrated continued weight loss and micronutrient measures despite provision of adequate calories and protein over a 3-mo period. No effect on pressure ulcer outcome was observed28 (Table II). Protein-energy malnutrition in long-term care facilities may not

RESULTS OF ENTERAL FEEDING IN SUBJECTS WITH PRESSURE ULCERS

Prevention of PU in hip fracture subjects.26 Survival benefit of enteral feeding in subjects with PU27 Outcome of subjects with PU at 90 days28

PU

PARENTERAL NUTRITION Improvement in nutritional parameters in small numbers of parenterally fed hospitalized patients with protein-energy malnutrition has been demonstrated.29 However, the response in the elderly to aggressive nutritional therapy is poor. If malnutrition is the simple absence of adequate provision of nutrients, correction of malnutrition should occur with the provision of these deficiencies. The response to aggressive feeding has been used as the gold standard to diagnosing malnutrition. In a study of 325 nutritionally at-risk patients receiving total parenteral nutrition, 219 patients were defined as malnourished using improvement in body cell mass with parenteral feedings as the standard for malnutrition. Non-responders, 106 patients, were defined as non-malnourished, based on no change in body cell mass with feedings. The outcome in elderly patients was dismal. In the 179 patients older than 65 y, no statistically significant improvement in body weight, body fat, lean body mass, extracellular mass, or body cell mass occurred.30 In a large clinical trial of preoperative total parenteral nutrition, the rate of major complications and mortality were similar in the parenterally fed and control groups. No beneficial effect on wound dehiscence, pressure ulcer formation, or wound infection was found.31 In a subgroup of 33 patients defined as severely malnourished using a combination of albumin and body weight, only the rate of non-infectious complications was lower in the parenterally fed group.

MALNUTRITION AND PRESSURE ULCERS

TABLE II.

Clinical trial

be as amenable to correction by enteral or parenteral means because of the risks of feeding tube complications, chronic disease, patient wishes, or ethical issues. There may be a reluctance to begin enteral feedings due to these risks.

No PU

No difference

No difference

RR of death 1.49 (1.2–1.8)

RR of death 1.06 (0.8–1.4)

65% PU at onset; 61% at end

PU, pressure ulcers; RR, relative risk; 95% confidence intervals in parentheses.

Experimental studies in animal models suggest a biologically plausible relationship between malnutrition and development of pressure ulcers. When pressure was applied for 4 h to the skin of well-nourished animals and malnourished animals, pressure ulcers occurred equally in both groups. However, the degree of ischemic skin destruction was more severe in the malnourished animals. At 3 d postinjury, epithelialization of the pressure lesions had occurred in normal animals, whereas massive necrosis of the epidermis was still present in the malnourished animals.32 These data suggest that whereas pressure damage may occur independently of nutritional status, malnourished animals may fail to initiate healing after a dermal injury. Further indication of a relationship is suggested by the finding that mitotic activity in normal epidermis is severely depressed in mice whose food intake was reduced to 70% of normal.33 Two studies have correlated development of pressure ulcers

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Nutrition Volume 17, Number 2, 2001 TABLE III.

TABLE IV.

EFFECT ON NUTRITIONAL FACTORS ON PRESSURE ULCERS: PREVENTION

EFFECT ON NUTRITIONAL FACTORS ON PRESSURE ULCERS: HEALING

Clinical trial

Factor

Development of PU6

Protein

Development of PU6

Total calories, vit A, vit C, iron, zinc Impaired intake

Development of PU5

PU

No PU

Protein intake Protein intake 93% RDA 119% RDA No difference No difference

RR 2.8 (1.0– 17.9)

—

PU, pressure ulcer; RDA, recommended daily allowance; RR, relative risk; 95% confidence interval in parentheses.

with dietary intake (Table III). Bergstrom and Braden6 reported that estimated percent intake of dietary protein predicted development of pressure ulcers. Patients with pressure ulcers ingested 93% of the recommended daily intake of protein compared with an intake of 119% of recommended protein in the non-pressure ulcer group. Only dietary intake of protein was predictive of pressure ulcer development in this study. The total dietary intake of calories or the calculated intake of vitamins A and C, iron, and zinc did not predict ulcer development.6 Berlowitz and Wilking5 reported that impaired nutritional intake (defined as a persistently poor appetite, meals held due to gastrointestinal disease, or a prescribed diet of less than 1100 kcal or 50 g protein per day) predicted pressure ulcer development. However, no other single nutritional variable reached univariate significance.6 In a trial of nutritional supplementation among 672 older persons, there was no difference in development of a Stage I or greater pressure ulcer between supplemented and control groups, although an increase in dietary intake was achieved in the supplemented group.34 Dietary interventions in healing pressure ulcers has been studied (Table IV). Total truncal pressure ulcer surface area decreased in patients fed an enteral formula containing 24% protein compared with a formula containing 14% protein.35 Total calorie intake, body weight, and traditional biochemical markers of nutrition did not, however, correlate with change in surface area. In a study of 12 enterally fed patients with pressure ulcers, the group who received 1.8 g/kg of protein had a greater decrease in pressure ulcer surface area than the group receiving 1.2 g/kg of protein (the current recommended daily allowance).36 Dietary recommendation for daily protein intake is 0.8 g 䡠 kg⫺1 䡠 d⫺1, which is probably too low. Current recommendations for dietary intake of protein in stressed elderly patients are between 1.2 and 1.5 g 䡠 kg⫺1 䡠 d⫺1. Yet half of chronically ill elderly persons cannot maintain nitrogen balance at this level.37 On the other hand, increasing protein intake beyond 1.5 g/kg per day may not increase protein synthesis and may cause dehydration.38 Thus, optimum protein intake for these patients has not been defined. Specific nutrients have been studied independently. Essential amino acids (histidine, lysine, methionine, phenylalanine, threonine, tryptophan) must be supplied by diet. Leucine seems to be important in severely ill patients. Glutamine is essential for the immune system function, but supplemental glutamine has not been shown to have noticeable effects on wound healing.39 Arginine enhances wound collagen deposition in healthy volunteers,40,41 but studies on sick wounded patients have not been conducted. No improvement in wound healing has been demonstrated by using high supplements of branched-chain amino acid formulations.42 Vitamin supplementation has been studied extensively. Vitamin C, for example, is essential for wound healing. Impaired

Clinical trial

Factor

PU

No PU

24% protein vs. 14% protein enteral feeding35 1.8 g/kg protein vs. 1.2 g/kg protein enteral feeding36 Vit C 10 mg vs. 1000 mg47

Protein

⫺4.2 cm2 vs. ⫺2.1 cm2 decrease in surface area 73% vs. 43% improvement in surface area No difference in complete healing

—

Vit C large dose vs. control, acute surgical subjects48 Development of PU in subjects with hip fracture54 Zinc supplementation v. control52

Vit C

Protein

Vit C

Zinc

Zinc

84% reduction surface area at 30 days No difference

No difference in rate of healing

—

No difference in complete healing 43% reduction surface area at 30 days No difference

No difference in rate of healing

PU, pressure ulcer; RDA, recommended daily allowance.

wound healing has been shown in clinical scurvy. However, clinically impaired wound healing requires 6 mo of an ascorbate-free diet.43 Even in animals who are vitamin C deficient, wound healing is abnormal at 7 d but completely normal at 14 d.44 In patients who are not vitamin C deficient, no evidence has been found of acceleration of wound healing by vitamin C supplementation.45 Similarly, supertherapeutic doses of vitamin C have not been shown to accelerate wound healing.46 Two clinical trials have evaluated the effect of supplemental vitamin C in the treatment of pressure ulcers. In a multicenter blinded trial, 88 patients with pressure ulcers were randomized to receive either 10 or 500 mg vitamin C twice daily. The pressure ulcer closure rate, relative healing rate, and ulcer improvement score was not different between groups.47 An earlier study in acute surgical patients reported a mean reduction in pressure ulcer surface area of 84% in patients treated with large doses of vitamin C compared with a mean reduction in surface area of 43% in the control group (P ⬍ 0.005).48 However, this study did not evaluate complete healing, and the absolute reduction in wound size is not given. Vitamin A deficiency results in delayed wound healing and increased susceptibility to infection.49 Vitamin A has been shown to be effective in counteracting delayed healing in patients on corticosteroids.50 Vitamin E deficiency does not appear to play an active role in wound healing.51 Zinc was first implicated in delayed wound healing in 1967.52 No study has shown improved wound healing in patients supplemented with zinc who were not zinc deficient.53,54 Zinc levels have not been associated with development of pressure ulcers in patients with femoral neck fractures.55 In a small study of patients with pressure ulcers, no effect on wound healing was seen at 12 wk in zinc-supplemented versus non–zinc-supplemented patients.56 High serum zinc levels may inhibit healing, impair phagocytosis, and interfere with copper metabolism.57–59

SUMMARY Wound nutrition is essentially whole body nutrition. Evaluation of the patient’s nutritional status and provision of the basic elements

Nutrition Volume 17, Number 2, 2001 of diet are the first principles of healing. It is clear that parameters commonly associated with poor nutritional status can predict future complications. There is at least suggestive evidence that improvement in nutritional status can improve outcome of pressure ulcer healing. More rigorous research on the relationship of nutrition and clinical healing outcome is needed. Studies to determine the optimum amount of protein for healing would be useful.

Improving Outcome of Pressure Ulcers

28.

29.

30.

REFERENCES

31.

1. Thomas DR, Goode PS, Tarquine PH, Allman R. Hospital acquired pressure ulcers and risk of death. J Am Geriatr Soc 1996;44:1435 2. Pinchcofsky-Devin GD, Kaminski MV Jr. Correlation of pressure sores and nutritional status. J Am Geriatr Soc 1986;34:435 3. Allman RM, Goode PS, Patrick MM, et al. Pressure ulcer risk factors among hospitalized patients with activity limitation. JAMA 1995;273:865 4. Brandeis GH, Morris JN, Nash DJ, Lipsitz LA. Epidemiology and natural history of pressure ulcers in elderly nursing home residents. JAMA 1990;264:2905 5. Berlowitz DR, Wilking SVB. Risk factors for pressure sore: a comparison of cross-sectional and cohort-derived data. J Am Geriatr Soc 1989;37:1043 6. Bergstrom N, Braden B. A prospective study of pressure sore risk among institutionalized elderly. J Am Geriatr Soc 1992;40:747 7. Young ME. Malnutrition and wound healing. Heart Lung 1988;17:60 8. Dempsey DT, Mullen JL, Buzby GP. The link between nutritional status and clinical outcome: can nutritional intervention modify it? Am J Clin Nutr 1988; 47(suppl 2):352 9. Detsky AS, Baker JP, O’Rourke K, et al. Predicting nutrition-associated complications for patients undergoing gastrointestinal surgery. JPEN 1987;11:440 10. Thomas DR, Verdery RB, Gardner L, Kant AK, Lindsay J. A prospective study of outcome from protein-energy malnutrition in nursing home residents. JPEN 1991;15:400 11. Lipschitz DA. Protein calorie malnutrition in the hospitalized elderly. Prim Care 1982;9:531 12. Rudman D, Feller AG, Nagraj HS, et al. Relation of serum albumin concentration to death rate in nursing home men. JPEN 1987;11:360 13. Volkert D, Kruse W, Oster P, Schlierf G. Malnutrition in geriatric patients: diagnostic and prognostic significance of nutritional parameters. Ann Nutr Metab 1992;36:97 14. Albina JE. Nutrition and wound healing. JPEN 1994;18:367 15. Casey J, Flinn WR, Yao JS, et al. Correlation of immune and nutritional status with wound complications in patients undergoing vascular operations. Surgery 1983;93:822 16. Haddock DA, Hill GL. Impaired wound healing in surgical patients with varying degrees of malnutrition. JPEN 1986;10:550 17. Goodson WH, Jensen JA, Gramja-Mena L, et al. The influence of a brief preoperative illness on postoperative healing. Ann Surg 1987;74:320 18. Schroeder D, Gillanders L, Mahr K, et al. Effects of immediate postoperative enteral nutrition on body composition, muscle function, and wound healing. JPEN 1991;15:376 19. Silver AJ, Morley JE, Strome LS, Jones D, Vickers L. Nutritional status in an academic nursing home. J Am Geriatr Soc 1988;36:487 20. Campos ACL, Meguid MM. A critical appraisal of the usefulness of perioperative nutritional support. Am J Clin Nutr 1992;55:117 21. Otte KE, Ahlburg P, D’Amore F, Stellfeld M. Nutritional repletion in malnourished patients with emphysema. JPEN 1989;13:152 22. Larsson J, Unosson M, Ek A-C, et al. Effect of dietary supplement on nutritional status and clinical outcome in 501 geriatric patients—a randomized study. Clin Nutr 1990;9:179 23. Laugue S, Arnaud-Battandier F, Mansourian R, et al. Protein-energy oral supplementation in malnourished nursing-home residents. A controlled trial. Age Ageing 2000;29:51 24. Potter J, Langhorne P, Roberts M. Routine protein energy supplementation in adults: systematic review. BMJ 1998;317:495 25. Ciocon JO, Silverstone FA, Graver LM, Foley CJ. Tube feedings in elderly patients: indications, benefits, and complications. Arch Intern Med 1988;148:429 26. Hartgrink HH, Wille J, Konig P, Hermans J, Breslau PJ. Pressure sores and tube feeding in patients with a fracture of the hip: a randomized clinical trial. Clin Nutr 1998;17:287 27. Mitchell SL, Kiely DK, Lipsitz LA. The risk factors and impact on survival of

32. 33. 34.

35. 36.

37.

38. 39. 40. 41. 42. 43. 44. 45.

46. 47. 48. 49. 50. 51. 52. 53. 54.

55. 56. 57. 58. 59.

125

feeding tube placement in nursing home residents with severe cognitive impairment. Arch Intern Med 1997;157:327 Henderson CT, Trumbore LS, Mobarhan S, Benya R, Miles TP. Prolonged tube feeding in long-term care: nutritional status and clinical outcomes. J Am Coll Nutr 1992;11:309 Lipschitz DA, Mitchell CO. The correctability of the nutritional, immune and hematopoietic manifestations of protein-calorie malnutrition in the elderly. J Am Coll Nutr 1982;1:17 Shizgal HM, Martin MF, Gimmon Z. The effect of age on the caloric requirement of malnourished individuals. Am J Clin Nutr 1992;55:783 VA Cooperative Study. Perioperative total parenteral nutrition in surgical patients. N Engl J Med 1991;325:525 Takeda T, Koyama T, Izawa Y, et al. Effects of malnutrition on development of experimental pressure sores. J Dermatol 1992;19:602 Bullough WS, Eisa EA. The effects of a graded series of restricted diets on epidermal mitotic activity in the mouse. Br J Cancer 1950;4:321 Bourdel-Marchasson I, Barateau M, Rondeau V, et al. A multi-center trial of the effects of oral nutritional supplementation in critically ill older inpatients. Nutrition 2000;16:1 Breslow RA, Hallfrisch J, Guy DG, Carwley B, Goldberg AP. The importance of dietary protein in healing pressure ulcers. J Am Geriatr Soc 1993;41:357 Chernoff RS, Milton KY, Lipschitz DA. The effect of a very high-protein liquid formula on decubitus ulcer healing in long-term tube-fed institutionalized patients. J Am Diet Assoc 1990;90:A-130 Gersovitz M, Motil K, Munro HN, Scrimshaw NS, Young VR. Human protein requirements: assessment of the adequacy of the current Recommended Dietary Allowance for dietary protein in elderly men and women. Am J Clin Nutr 1982;35:6 Long CL, Nelson KM, Akin JM Jr, et al. A physiologic basis for the provision of fuel mixtures in normal and stressed patients. J Trauma 1990;30:1077 McCauley R, Platell C, Hall J, McCulloch R. Effects of glutamine on colonic strength anastomosis in the rat. JPEN 1991;116:821 Barbul A, Lazarous S, Efron DT, et al. Arginine enhances wound healing in humans. Surgery 1990;108:331 Kirk SJ, Regan MC, Holt D, et al. Arginine stimulates wound healing and immune function in aged humans. Surgery 1993;114:155 McCauley C, Platell C, Hall J, McCullock R. Influence of branched chain amino acid solutions on wound healing. Aust NZ J Surg 1990;60:471 Crandon JH, Lind CC, Dill DB. Experimental human scurvy. N Engl J Med 1940;223:353 Levenson SM, Upjohn HL, Preston JA, et al. Effect of thermal burns on wound healing. Ann Surg 1957;146:357 Rackett SC, Rothe MJ, Grant-Kels JM. Diet and dermatology. The role of dietary manipulation in the prevention and treatment of cutaneous disorders. J Am Acad Dermatol 1993;29:447 Vilter RW. Nutritional aspects of ascorbic acid: uses and abuses. West J Med 1980;133:485 ter Riet G, Kessels AG, Knipschild PG. Randomized clinical trial of ascorbic acid in the treatment of pressure ulcers. J Clin Epidemiol 1995;48:1453 Taylor TV, Rimmer S, Day B, Butcher J, Dymock IW. Ascorbic acid supplementation in the treatment of pressure sores. Lancet 1974;2:544 Hunt TK. Vitamin A and wound healing. J Am Acad Dermatol 1986;15:817 Ehrlich HP, Hunt TK. Effects of cortisone and vitamin A on wound healing. Ann Surg 1968;167:324 Waldorf H, Fewkes J. Wound healing. Adv Dermatol 1995;10:77 Pories WJ, Henzel WH, Rob CG, et al. Acceleration of healing with zinc sulfate. Ann Surg 1967;165:423 Hallbrook T, Lanner E. Serum zinc and healing of leg ulcers. Lancet 1972;2:780 Sandstead SH, Henrikson LK, Greger JL, et al. Zinc nutrition in the elderly in relation to taste acuity, immune response, and wound healing. Am J Clin Nutr 1982;36(suppl):1046 Goode HF, Burns E, Walker BE. Vitamin C depletion and pressure ulcers in elderly patients with femoral neck fracture. BMJ 1992;305:925 Norris JR, Reynolds RE. The effect of oral zinc sulfate therapy on decubitus ulcers. J Am Geriatr Soc 1971;19:793 Goode P, Allman R. The prevention and management of pressure ulcers. Med Clin North Am 1989;73:1511 Prasad AS. Discovery of human zinc deficiency and studies in an experimental human model. Am J Clin Nutr 1991;53:403 Reed BR, Clark RAF. Cutaneous tissue repair: practical implications of current knowledge: II. J Am Acad Dermatol 1985;13:919

(For an additional perspective, see Editorial Opinions)