Using complementary and alternative medicines to prevent and treat pressure ulcers:a systematic review

Ali Safdari,Abdollah Abolfathi,2,Davood Hekmatpou,Fatemeh Mehrabi*

1Student Research Committee, Arak University of Medical Sciences, Arak 3819693345, Iran.2BSc of Nursing, Iranian Social Security Organization, Arak 3817793164,Iran.3Department of Nursing,School of Nursing and Midwifery,Arak University of Medical Sciences,Arak 3848176941,Iran.

Abstract Background: Pressure ulcers are skin lesions generated by ischemic conditions caused by pressure on soft tissues.Several studies have investigated complementary and alternative medicine (CAM) as preventative and treatment measures for pressure ulcers.Therefore, we systematically reviewed the CAM literature in preventing and treating pressure ulcers.Methods:All clinical trial studies which used CAM were included.We searched different databases,including Scientific Information Database, Irandoc, Google Scholar, PubMed, Medline, Scopus,Cochrane Library, Embase, and Science Direct.The following keywords were used:“complementary and alternative medicine-CAM”, “integrative medicine”, “traditional medicine”, “pressure ulcer”, “bedsore”, “pressure sore healing”, and “prevention”.A Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2015 checklist was used to perform analyses.Results: After screening, 35 studies were selected.Our investigations suggested that honey, medicinal plants, such as resin salve, Angelica dahurica, Aloe vera, fruits, herbal oils, a combination of several traditional medicine methods, sheepskin, maggot therapy, massage,charcoal, and acupuncture were the most common CAM methods.Conclusion: CAM strategies can prevent and treat pressure ulcers.They reduce wound size, exudate and necrotic tissue levels, inflammation, pain, bleeding, and infections.

Keywords: complementary therapies; traditional medicines; prevention;healing;pressure ulcer;systematic review

Tradition

Complementary and alternative medicine has been used for thousands of years to prevent and treat pressure ulcers in Egypt,China,Greece,India,and Iran.One of the oldest medical manuscripts,the Sumerian clay tablet of Mesopotamia,dates back to 2200 B.C.E.,describes healing process methods,i.e.,washing wounds,wound dressing,and wound bandaging.According to some sources,in Mesopotamian cultures,including the Sumerians and Akkadians,wounds were washed with beer or wine.They also used sesame infusions,which were first purified and pulverized before being applied with beer.Thus,probably one of the oldest known complementary and alternative medicine applications is beer.According to Majno,in 1911,in Mesopotamia,wounds were washed in water or milk and dressed with honey or resin.Similarly,conifer,myrrh and frankincense may also have been used for wound bandaging.

Background

Pressure ulcers are skin lesions that arise from ischemic conditions caused by pressure applied to soft tissues.This pressure results from the soft tissue being pressed between hard tissue and bone tissue [1,2].Globally, pressure ulcers occur in more than 1.3 million adults annually [3].Its prevalence in hospitals is 8.3% in Spain, 8.9% in France, 10.2% in Germany, 12.5% in Portugal, 12% in Jordan, 18.5%in Ireland, 21.1% in Belgium, 22.7% in Denmark, 23% in Sudan, and 1.58% in China.The condition is reported at 5% in general in Iran and 10.1%–21% in specialized wards [4–6].When a pressure ulcer diagnosis is delayed, the patient’s health deteriorates, and costs related to controlling possible infections increase.Approximately 2.5 million patients contract pressure ulcers annually in the USA, which translates to an estimated 9–11.5 million dollars in treatment costs.Approximately 60,000 patients die annually from pressure ulcer complications.In Europe, this equates to almost 18% of total hospitalized patients in public and private hospitals.Treatment costs for these patients are approximately 15,000–17,000 euros[7].

Pressure ulcers arising from cancer and cardiovascular disease are the third most expensive condition.Physical, financial, and social consequences of pressure ulcers can also affect different individuals and groups, including patients, caregivers, families, and medical personnel.Similarly, pain and dependency on caregivers are also inevitable complications.Evidence from the USA has suggested that developing pressure ulcers is associated with an increased hospitalization rate of more than four days, a 25% increased risk of hospital-acquired infection,and a 55%increase in mortality rates[8,9].

Pressure ulcers typically occur in prominent bony areas such as the sacrum, anterior superior iliac spine bumps, trochanter, heel, shoulder area, and occipital.Lesions have also been reported in the lips, nose,and ears [10].Despite improvements in ameliorating pressure ulcers,patient numbers with these lesions are increasing [2].In addition to the high financial costs of addressing the condition, healthcare institutions must endure other consequences, including loss of clinical credibility, staff training, increased nurse workloads of up to 50%,increased hospitalization days, pain, infection, stress, recovery delays,and impaired mental image in patients [10].Therefore, preventing and treating this complication is essential [9].

There are many suggested treatments for pressure ulcers; however,most are ineffective.Machado et al.reported that lasers were ineffective for the condition [11].Similarly, another study reported no pharmacological effects on pressure ulcers [12].In terms of treatment costs, complementary and alternative medicines (CAM) may be reasonable and effective and become increasingly popular treatments[8, 9].A study reported that approximately half of Europe’s population were interested in CAM methods [8].In Iran, CAM is deep-rooted in ancient beliefs and traditions, contributing to the success of different treatments.CAM prevalence across different countries is 33% in the UK, 46% in Australia, 34% in the USA, 75% in Belgium, 49% in France, and 18%–30% in Germany [13–15].

There are two types of CAM treatments for pressure ulcers: (1)treatments applied locally to wounds, and/or (2) treatments such as massage, acupuncture, and larval therapies.Local treatments comprise dressings or layers of materials placed directly or indirectly on wounds for specified periods [16, 17].Local CAM treatments include herbal compounds and their products (e.g., henna,Aloe vera,olive oil, or combinations of two or more different ingredients, e.g.,Aloe veraand honey used as gels, creams, and ointments [8–20].

Wound management is an art and as old as humanity, with CAM used for thousands of years to prevent and treat pressure ulcers in Egypt, China, Greece, India, and Iran.One of the oldest medical manuscripts isthe Sumerian clay tablet of Mesopotamia, which dates back to 2200 B.C.E.This tablet describes healing process strategies,i.e., washing, dressing, and bandaging wounds.In Mesopotamian cultures, including Sumerians and Akkadians, wounds were washed with beer or wine.They also used sesame infusions which were first purified and pulverized before being applied with beer.Therefore, and quite possibly, the oldest known CAM could be beer [21].In the ancient Greek epic poem from 800 B.C.E., Song of Ilion or Song of Ilium, believed the oldest extant work in Western literature, Homer documented the management of various battle wounds at Troy where bitter healing herbs were used [21–23].In Mesopotamia, according to Majno, wounds were washed with water or milk and dressed with honey or resin.Similarly, conifer, myrrh, and frankincense were also used for wound bandaging[23].

In this research, we systematically reviewed studies using CAM methodologies to prevent and treat pressure ulcers.

Methods

Inclusion and exclusion criteria

Inclusion criteria.The review included all CAM clinical trials using control groups with a placebo arm or comparing other treatments.

Exclusion criteria.The Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2015 checklist was used in this study.Studies using animal models, articles with more than one intervention,articles using native Chinese plants, articles not in English, repeated articles, articles with obscure statistical results, incomplete articles,and studies with small sample numbers were excluded.

Document retrieval

Study sources were chosen according to published articles in Iranian and foreign journals.Studies were chosen from the following databases: Scientific Information Database, Irandoc, Google Scholar,PubMed, Medline, Scopus, Cochrane Library, Embase, and Science Direct.Bibliographies from identified papers were scanned to identify more sources.Keywords were “complementary and alternative medicine-CAM”, “integrative medicine”, “traditional medicine”,“pressure ulcer”, “bedsore”, “pressure sore”, “healing”, and“prevention”.No time limitations were set for electronic searches.

Search strategy

Search terms were used individually or in combination with the title,abstract and keywords, such as “complementary and alternative medicine” OR “integrative medicine” OR “traditional medicine” AND“pressure ulcer” OR “pressure sore” OR “bedsore” AND “randomized controlled trial” OR “clinical trial”.The specific search strategy for PubMed is shown(Table 1).

Table 1 Retrieval strategy for PubMed

Data extraction

Extracted information was classified and aggregated.Information on CAM and pressure ulcers was collated, and the number of selected studies counted.These were divided into several groups: studies using medicinal plants, fruits, herbal oils, a product or combined products derived from several traditional medicine methods, particular animal compounds, and other traditional medicine methods.Articles for each category were reported separately.

Results

Of the 75 selected studies, 15 were performed in animals, six were inaccessible or written in non-English,eight used native Chinese herbs,and eight had limited sample numbers with poor statistical quality.These studies were excluded, and the remaining 34 studies assessed(Figure 1).

Figure 1 Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist for study selection.CAM, complementary and alternative medicines.

Articles were divided into several groups: medicinal plants, fruits,herbal oils, products or combinations derived from several traditional medicine methods, particular animal compounds, and other traditional medicine methods.

Among the selected 35 studies, seven articles focused on honey and its comparisons, eight focused on medicinal plants, two studied fruit,eight used herbal oils, three used products or combinations derived from several traditional medicine methods, two focused on sheepskin and five used other traditional medicine methods (Supplementary Table 1–3).

Supplementary Table S1 A partial information table for the core targets

Supplementary Table 1 Analysis of studies using combination of several medicinal plants for PU

Supplementary Table 2 Analysis of studies using sheepskin for PU

Supplementary Table S2 Molecular docking result of targets with daidzein

Supplementary Table 3 Analysis of studies using other methods for PU

Honey

Seven studies investigating pressure ulcer treatments used honey as a therapy (Table 2) [24–30].Honey is an ancient treatment for pressure ulcers and has been used as an ointment to heal wounds and skin inflammation.Moreover, honey acts as a bridge between different active immune cells in response to infection.Honey also activates protein-digesting enzymes, which have important roles during healing processes.Due to its acidic properties, high sugar, and nutrient content, honey promotes new tissue growth by increasing free oxygen compounds at wound sites [31].

Table 2 Analysis of studies using honey for PU

In the seven selected studies, honey’s antibacterial effects were greater than insulin, betadine, nitrofurantoin, and silver sulfadiazine dressings.It reduced healing and hospitalization times and resolved infections at wound sites [24–29, 31].Honey was also used to treat grade 2 and 3 wounds.However, no differences were observed between honey and a hydrocolloid dressing [25].

Medical plants

Medicinal plants have also been exploited as CAM treatment methods used for biological treatments.For centuries, herbal medicines were the only available cures for pain and other complications [32].CAM plants used to prevent and treat pressure ulcers includingAloe vera,henna,Angelica dahurica, resin salve from spruce trees, andPlantago majorL.(Table 3).

Table 3 Analysis of studies using medicinal plants for PU

Aloe vera.Aloe verabelongs to the liliaceous family and is similar in appearance to cacti.It is a perennial herbaceous plant with thick,fleshy, long leaves [33].There are 75 compounds identified inAloe veraplants, including 20 minerals, 20 amino acids, vitamins, and water [33–35].In laboratory studies and studies in living organisms,Aloe verainhibited thromboxane (wound healing inhibitor), promoted healing, and decreased inflammation [36].In addition, magnesium lactate in the gel fromAloe verainhibited histamine reactions and prevented itching and skin irritation.Moreover, it also improved immune system activity and cytokine synthesis.Aloe veraalso inhibited inflammatory reactions by inhibiting interleukin-6 and interleukin-8, reducing leukocyte adhesion and tumor necrosis factor-α levels, and increasing interleukin-10 levels [17].

The plants healing properties are primarily related to glucomannan which is rich in polysaccharides, such as mannose.This affects fibroblasts and promotes collagen production.Aloe veragel increases collagen in the wound and changes its composition by increasing cross-linking between collagen fibers, thereby accelerating wound healing [37].Aloe veraalso prevents wound formation due to mucopolysaccharides, amino acids, and zinc, which cause skin cohesion, maintain moisture, reduce erythema, and prevents skin lesion formation [17, 38].Moreover,Aloe verawas also more effective than saline gas dressing, phenytoin, and common treatments [20,37–43].However, only one study identified no differences between the two groups, which may have been due to limited sample numbers[38].Thus,Aloe verareduced pain, bleeding, and healing times [42,43].

Henna.Henna plants (Lawsonia inermis) belong to the Lythraceae family and are native to the Mediterranean, Middle Eastern, Indian,and southern Iran regions.The most commonly used parts of the plant are the adult leaves.The plant contains effective ingredients such as colored materials, tannins, resins, volatile oils, and fats.When its leaves are powdered and made into a dough, it is used in cosmetics and remedies for traditional medicine.In some Middle East countries,henna is used to treat burns, wounds, and some fungal infections.It also targets infections caused by Gram-positive bacteria, treats acne and abscesses, and has strong antifungal, antiviral, antiparasite, and anti-inflammation effects [43–46].

In 2008, Khatem et al.investigated the antimicrobial effects of henna and showed its antibacterial effects were similar to common antibiotics [47].In 2007, Saedabi et al.reported that henna was a source of antimicrobial materials which exhibited high activities against a wide range of microorganisms, includingStaphylococcus aureus,Bacillus subtilis,Escherichia coli,Pseudomonas aeruginosa, and fungi.The plant killed bacterial and fungal pathogens without side effects or bacterial resistance[46, 48].

These studies suggested that when henna was used as a pressure ulcer treatment, it reduced redness, inflammation, and local heat from affected areas (P< 0.0001).When preparing henna for wounds, 50 g henna powder should be mixed with 500 mL water, placed on the area for 30 minutes, and then washed.This should be performed for seven days.Moreover, henna also effectively treats first-degree pressure ulcers in the sacrum area [8–16].

Angelica dahurica.This plant is native to Siberia,Russia,the Far East,Mongolia, northeast China, Japan, Korea, and Taiwan.The roots are used extensively due to their medicinal properties, and it is known as a furocoumarin and angelicotoxin medication.A.dahuricaexhibited improved healing effects in treating degree 1 and 2 pressure ulcers after four weeks when compared with clotrimazole.The plant induced wound healing by increasing interleukin-8, epidermal growth factor,transforming growth factor-beta, and vascular endothelial growth factor levels; this increased cells in the G0/G1 phase and cyclin D and cyclin-dependent kinases levels.A.dahuricaalso provided an effective clinical treatment for phase I and II pressure ulcers.The plant also increased angiogenesis, improved wound status, and exerted positive effects on diabetic wounds.A 2–4 mg dose is recommended [49, 50].

Resin salve.Resin salve from the Norwegian spruce tree was also used to treat pressure ulcers.The authors reported that the salve reduced the size of degree 4 ulcers after two weeks of treatment.Moreover, after a 6-month treatment regime, ulcers had completely healed [51].To treat degrees 2, 3, and 4 ulcers, a resin layer of approximately 1 mm diameter under sterile cotton is sufficient.The resin resulted in 73% complete healing, which was significant when compared with the control group (P= 0.013).Similarly, ulcer cultures were negative for bacterial infection [52].

Plantago major L..Plantago majorL.is used to treat skin diseases,respiratory diseases, digestive disorders, reproduction issues, blood circulation problems, cancer, pain relief, and infections.The plant contains biologically active compounds such as polysaccharides, lipids,caffeic acid derivatives, flavonoids, iridoid glycosides, and terpenoids.Also, alkaloids and some organic acids have also been characterized.Plant extracts have been used for wound healing, with anti-inflammatory, analgesic, antioxidant, weak antibiotic,immune-modulating, and anti-inflammatory roles reported.Because of these effects, the plant has been successfully used as a suitable medicine for folk remedies [53, 54].

Fruit

Two studies suggested that kiwi and mango were effective for treating pressure ulcers (Table 4).Kiwi healed grade 2 and 3 ulcers in three weeks by increasing granulation and angiogenesis (P< 0.02) [55].Mango was more effective in debriding grade 3 and 4 ulcers with less bleeding, and it had higher success rates when cleaning necrotic tissue[56].

Table 4 Analysis of studies using fruits for PU

Herbal oils

Massaging the skin with herbal oils is an important tradition in some countries [55].Herbal oils used for pressure ulcers include olive,sunflower seed, tea tree, sesame, coconut, almond, and henna [57–64](Table 5).The most frequently used oil is olive oil, which in most studies, effectively prevented pressure ulcers.Preventing and treating pressure ulcers is clinically beneficial, and because olive oil is easy to access, this approach may be effective in targeting pain and reducing treatment costs [64].One study used sweet almond oil for pressure ulcers.The oil contains 54% oil and 26% carbohydrates.It is rich in vitamin E(26 mg vitamin per 100 g of oil),group B vitamins, different amino acid types, and minerals, which can be used as skin massage oil[62].Sunflower seed oil effectively treated grade 1 and 2 pressure ulcers over a 21-day period [58].In another study, tea tree oil also efficiently reduced ulcer sizes [63].Coconut and henna oils were also beneficial in reducing the risk of pressure ulcers.

Table 5 Analysis of studies using herbal oils for PU (Continued)

Table 5 Analysis of studies using herbal oils for PU

Medicinal plant combinations

The most frequent combinations wereAloe veraand olive oil, poppy and plant cellulose, honey andAloe vera, and sesame, honey, and camphor.

Poppy and plant cellulose combinations exerted antimicrobial effects toward ulcers, withP.aeruginosa,E.coli, andS.aureussensitive to preparations [65].Similarly,Aloe veraand olive oil exerted positive effects by decreasing ulcer size and depth and reducing exudate and tissue edema around the ulcer when compared with phenytoin [20].Ointments containing honey, sesame oil and camphor accelerated the treatment of pressure ulcers in the sacrum, ischium, and heel protrusion in patients with diabetes (P<0.001) [18].

Sheepskin

Two Australian articles investigated sheepskin to ameliorate pressure ulcers [66, 67].Preparations were particularly useful in the sacrum area as they reduced the incidence of pressure ulcers by up to 8.9%[66, 67].Preparations were also used to treat grade 1 and 2 ulcers.The method acted as a pressure-reducing agent to reduce pressure by up to 27 mmHg and absorbed moisture.These characteristics of sheepskin will not disappear until 50–65 washes in a washing machine[66].

Other methods

Maggot therapy, acupuncture, charcoal, and mummy solution were some of the other CAM methods used for pressure ulcers.Maggot therapy was primarily used to treat diabetic wounds, but some studies have suggested its utility for healing pressure ulcers, debriding, and wound granulation [68, 69].In the past, charcoal was used to heal chronic wounds.Other studies associated it with decreased exudate from pressure ulcers and effective treatment [70, 71].The mummy solution reduced ulcer size, discharge rate, and redness in grade 2 and 3 ulcers [72].Some studies listed acupuncture, but these were excluded because they did not meet our inclusion criteria.A fire needle was used in a randomized controlled trial with positive effects[73, 74].

Limitations

Our review had some limitations.The most relevant was reduced access to some articles and unpublished reports.Another limitation involved the lack of precise, high-quality, and useful information in some articles, making it difficult to completely and accurately analyze and compare data.

Conclusion

Different CAM methods preventing and treating pressure ulcers have been widely investigated in the literature.This systematic review demonstrated that various methods were used to prevent and treat pressure ulcers.Of all the CAM approaches, honey,Aloe vera, and olive oil were the predominant methods.Importantly, sheepskin as a pressure-reducing agent and moisture-absorbent exhibited major effects on ameliorating pressure ulcers.We also investigated the effects of these methods on different ulcer characteristics, including ulcer depth and size, edema, exudate levels, necrotic tissue [37],inflammation,pain,bleeding,and infection.Critically,in 90%of cases,CAM demonstrated positive effects and reduced complications.Hospitalization times, treatment costs, and redness and itching at wound sites were some of the secondary aims evaluated in several studies, suggesting herbal compounds and CAM methods are often more effective when compared with other treatments.