Is Treating Patients With Stage 4 Pressure Ulcers With Vitamins A and C, Zinc, and Arginine Justified?

Introduction. Management of patients with pressure wounds often may entail the administration of vitamins A and C, zinc, and arginine. Supplementing these nutrients as part of a standard wound care protocol may increase the risk for toxicity and unnecessarily increase the cost of health care. Objective. This study aimed to correlate the nutritional status represented by albumin and prealbumin levels with aforementioned nutrient levels. This understanding would determine whether albumin and prealbumin levels have good predictive value in identifying patients with vitamin deficiencies in this population. Materials and Methods. Twenty patients aged 18 to 90 years were included, patients had to be admitted in the acute hospital setting with stage 4 pressure ulcers on their sacrum, hips, or heels. Patients already on vitamin supplements were excluded from the study. An odds ratio (OR) was used to assess the association between vitamin deficiency and albumin/prealbumin status. Fisher exact test was performed to test the significance of the association. Results. The OR of vitamin A deficiency vs albumin deficiency was 0.27, but the association was not significant (95% CI, 0.004–3.68; P = .34). The OR of zinc deficiency vs albumin deficiency was 25.67 (95% CI, 1.2–568.9), and the association was significant (P = .01). The odds of a patient with vitamin C deficiency also having albumin deficiency was 0.62 times greater than that for patients without vitamin C deficiency. Vitamin A deficiency was more likely to be associated with prealbumin deficiency. Zinc deficiency was more likely to be associated with albumin deficiency. While arginine deficiency was more likely to be associated with albumin deficiency, and less likely to be associated with prealbumin deficiency, the results were not statistically significant. Conclusions. This study showed that routine treatment with vitamins A and C, zinc, and arginine in patients with stage 4 pressure ulcers is not justified.

Introduction

The lack of adequate treatment for chronic pressure ulcers remains one of the most prominent public health issues to date. Chronic pressure ulcers affect more than 6.5 million people in the United States and are associated with significant morbidity, cost, and suffering for patients.¹ As the prevalence of diabetes, obesity, and cardiovascular disease continues to increase, treatment of chronic pressure ulcers is expected to become increasingly important. Pressure ulcers are defined as skin injuries and/or underlying tissue damage localized over a bony prominence, resulting from pressure force and/or pressure combined with shear.¹ They are often highly burdensome for health care providers as they require weeks to months of complex treatment regimens and a multidisciplinary approach to promote healing.² Currently, nutritional management of nearly all patients with pressure wounds includes administration of vitamins A and C, zinc, and arginine because these patients are understood to be vitamin-deficient, although the standard of care is to first measure blood levels of these nutrients before starting patients on supplements. However, there are no high evidence-based studies to support the benefits of administering supplements to these patients. Many of these patients may be otherwise well nourished and will ingest sufficient amounts of these vitamins and essential nutrients as part of their diet. Administration of these supplements to patients with chronic pressure ulcers not only increases the cost of health care but may yield toxic side effects that could otherwise be avoided by not prescribing them unnecessarily. As such, this study aimed to determine whether patients with chronic pressure ulcers are overtreated with vitamins A and C, zinc, and arginine. In addition, the authors aimed to identify correlations between and among albumin, prealbumin, and vitamin levels.

Materials and Methods

After approval by an institutional review board, the study included 20 patients, aged 18 to 90 years, who presented to ProMedica Toledo Hospital with stage 4 pressure ulcers of any size on the sacrum, hips, or heels. Patients who were already on vitamin A or C, zinc, and/or arginine supplementation were excluded from the study. Upon admission to the hospital, each patient’s blood was drawn to determine nutritional status as per levels of vitamins A and C, zinc, arginine, albumin, and prealbumin. Normal serum values of nutrients were as follows: vitamin A, 20 to 60 mcg/dL; vitamin C, 0.6 to 2.0 mg/dL; zinc, 0.66 to 1.1 µg/mL; and l-arginine, 81 to 113 mmol/L in men and 72 to 88 mmol/L in women. An odds ratio (OR) was used to assess the association between vitamin deficiency and albumin/prealbumin status. The OR is a statistic that quantifies the strength of association between 2 events. In this case, the OR quantifies the strength and direction of the association between each vitamin level with albumin and prealbumin levels (ie, albumin level vs vitamin A level). An OR of greater than 1 indicates a positive association while an OR less than 1 indicates a negative association. Furthermore, a Fisher exact test was performed to test the significance of the association. A P value of less than .05 was considered to be significant, and a 95% CI was constructed to describe the level of confidence that the true association lies within the interval if repeated intervals were constructed.

Results

The OR of nutrient deficiency as correlated with albumin and prealbumin deficiencies are shown in the Table. The OR of vitamin A deficiency vs albumin deficiency was 0.27 (95% CI, 0.004–3.68), which means the odds of having albumin deficiency (albumin < 3.2 g/dL) for patients with vitamin A deficiency (vitamin A < 0.3 mcg/dL) was 0.27 that for patients without vitamin A deficiency. That is to say, vitamin A deficiency was less likely to be associated with albumin deficiency, but the association was not significant (P = .34). In terms of percentage change, the odds of having albumin deficiency for patients with vitamin A deficiency was 73% lower than the odds for patients without vitamin A deficiency; the deficiency percentages for albumin levels are shown in Figure 1. The OR was 23.0 for vitamin A deficiency vs prealbumin deficiency, suggesting the odds of having prealbumin deficiency in patients with vitamin A deficiency is 23.0 times greater than that in patients without vitamin A deficiency; the deficiency percentages for prealbumin levels are shown in Figure 2.

With zinc deficiency vs albumin deficiency, the OR was 25.67 (95% CI, 1.2–568.9), which means the odds of having albumin deficiency in patients with zinc deficiency was 25.67 times greater than that for patients without zinc deficiency. That is to say, zinc deficiency was more likely to be associated with albumin deficiency. The association was significant (P = .01). If interpreted in terms of percentage change, the odds of having albumin deficiency for patients with zinc deficiency were 240.67% higher than the odds for patients without zinc deficiency. Although not as high, the odds of having prealbumin deficiency in patients with zinc deficiency were also higher than in patients without zinc deficiency, as the OR was 1.47.

Although not statistically significant, the findings indicated that the odds of having albumin deficiency for patients with arginine deficiency were 1.09 times greater than those for patients without arginine deficiency. Arginine deficiency was more likely to be associated with albumin deficiency. On the other hand, arginine deficiency was less likely to be associated with prealbumin deficiency (OR, 0.76).

Furthermore, the authors found that the odds of having albumin deficiency for patients with vitamin C deficiency were 0.62 times greater than the odds for patients without vitamin C deficiency. As such, vitamin C deficiency was less likely to be associated with albumin deficiency. To the contrary, vitamin C deficiency was more likely to be associated with prealbumin deficiency (OR, 1.47).

Discussion

It is estimated that up to 50% of hospitalized patients are malnourished. Malnutrition related to reduced intake of nutrients, underlying comorbidities, inflammation, and metabolic alterations related to disease states has been found to be a significant factor influencing pressure injury risk and wound healing.³ Pressure injuries can present as intact skin or as a painful open wound commonly located on the back, sacral, coccyx, buttock, and heel areas. Although pressure injury prevention requires multidimensional complex care, it has long been understood hospitalized patients benefit from interventions that focus on improving oral nutrition to enhance wound healing and reduce pressure injury risk. In 2019, Citty et al³ suggested that although patients at risk for pressure injuries should obtain adequate vitamins and minerals, evidence for recommendations on vitamin supplementation is limited. Despite the fact that vitamin C supplementation in wound healing is believed to impact collagen formation, immunomodulation, and antioxidant function, the current study found that the OR for vitamin C deficiency vs albumin deficiency was only 0.62.⁴ This suggests that the odds of having albumin deficiency (a marker of nutritional deficiency) is only 0.62 times greater than the odds for patients without vitamin C deficiency. In other words, the odds of patients with vitamin C deficiency also having albumin deficiency is 38% lower than the odds for patients without vitamin C deficiency. As such, the question becomes whether nutritionally depleted patients with healing wounds should receive vitamin C supplementation without first checking vitamin C levels. Vitamin C toxicity from oversupplementation may manifest as diarrhea, nausea, vomiting, heartburn, abdominal cramps, headache, and insomnia.

Similarly, vitamin A is believed to be helpful in wound healing, especially in patients who have a documented deficiency or who have inadequate intake of foods rich in vitamin A.⁵ This study, however, found that vitamin A deficiency is less likely to be associated with albumin deficiency, as the odds of patients with vitamin A deficiency also having albumin deficiency is 73% lower than the odds for patients without vitamin A deficiency. Therefore, it seems likely that many hospitalized patients with pressure wounds may be overtreated with vitamin A. Oversupplementation with vitamin A may yield toxic symptoms, including vision changes, bone pain, skin changes, liver damage, and increased intracerebral pressure.

On the contrary, the current study found the odds of patients with zinc deficiency also having albumin deficiency are 25.67 times greater than those for patients without zinc deficiency. The odds of having albumin deficiency for patients with zinc deficiency is 240.67% higher than those without zinc deficiency. Although immediate zinc supplementation seems appropriate for patients with healing pressure wounds due to the strong correlation between nutritional status and zinc deficiency, it may still be appropriate to obtain zinc levels first as zinc toxicity is associated with impaired neutrophil and lymphocyte function. It is also associated with gastrointestinal tract irritation, nausea, vomiting, and diarrhea.⁶ Similarly, this study showed that patients with arginine deficiency were more likely to have albumin deficiency than patients without arginine deficiency. However, it should also be noted that arginine supplementation has been associated with nausea, vomiting, and blood abnormalities that should be considered before treating patients with complex pressure wounds.

Limitations

Although the authors’ data help to reveal whether patients with chronic pressure wounds are being overtreated with vitamins A and C, zinc, and arginine, the small sample size was a limitation of the study. Future studies must be done to further correlate nutritional status with vitamin levels in patients with chronic pressure ulcers.

Conclusions

Overall, the treatment of pressure ulcers will continue to be increasingly relevant as the population ages and chronic disease becomes more prevalent. The findings of the current study suggest that albumin and prealbumin deficiency are variably correlative with vitamin deficiency; therefore, patients may need to undergo more adequate assessment of deficiency before vitamin supplementation is begun in the context of nutritional depletion. For example, in this analysis, arginine and zinc deficiencies are positively correlative with albumin deficiency, but vitamin C deficiency was less likely to be correlated with albumin deficiency. Therefore, why should vitamin C supplementation be initiated in chronic wound patients simply on the basis of presumed albumin deficiency? It is increasingly important to gather evidence elucidating the effectiveness of treatment mechanisms for patients suffering from chronic wounds. Additional research will hopefully uncover whether protocoled vitamin supplementation in patients with chronic pressure ulcers and wounds is, in fact, justified.

Acknowledgements

The authors would like to acknowledge Mariam Abouahmed for preparing and editing the manuscript.

Authors: Kunaal Bafna, MS¹; Tian Chen, PhD²; and Richard Simman, MD, FACS, FACCWS^3,4

Affiliations: ¹University of Toledo College of Medicine, Toledo, OH; ²University of Toledo, Department of Mathematics and Statistics, Toledo, OH; ³Wright State University School of Medicine, Dayton, OH; ⁴Jobst Vascular Institute/ProMedica Health system, Toledo, OH

Correspondence: Richard Simman, MD, FACS, FACCWS, 2109 Hughes Drive, Suite 400, Toledo, OH 43606; richard.simmanmd@promedica.org

Disclosure: The authors disclose no financial or other conflicts of interest.

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