Faculty of Medicine and Faculty of Public Health, University of Toronto, Toronto, ON

Introduction

Herpes simplex virus (HSV) is responsible for an infection around the lips (herpes labialis) that often occurs with a longer primary infection and then may result in shorter recurrences (cold sores, fever blisters).¹ Herpes simplex infection is ubiquitous in the adult population with various studies documenting between 60-90% of tested individuals having previous infections.² Currently available treatments include prescription and non-prescription drugs in topical and oral formulations, with antiviral medications representing a mainstay of treatment. They are reviewed below, as are data from a clinical trial of a new formulation of topical 5% acyclovir with 1% hydrocortisone cream (Xerese®).

Background

• Most herpes labialis lesions are caused by herpes simplex type 1 (HSV-1). Genital herpes simplex is predominantly herpes simplex type 2 virus (HSV-2).²
• With an increase in oral sex, there are more cases (although still a minority) of herpes labialis associated with type 2 infections.²
• Primary HSV infection in children or young adults may cause severe stomatitis and pharyngitis with an erosive, painful infection of the buccal mucosa and gums.²
• Primary infections may be associated with pain on swallowing and lymphadenopathy.
• In adults, the primary infection may be limited to a pharyngitis without involvement of the mouth (gingival- stomatitis).²
• Some primary infections are completely asymptomatic.
• Viral shedding and potential spread of infection is most common with an open lesion.
• After the primary infection, the virus remains latent in the sensory nerve (Trigeminal) ganglion of the facial nerve for life.³ It may re-activate at a later date, in a non-primary episode, with a clinical course that is often less severe than a primary episode but more severe than a typical recurrence.⁴
• Asymptomatic viral shedding can occur sporadically between acute episodes and result in spread of the infection.
• Recurrent infections follow a shorter time period and have a number of identifiable stages, specifically:³
  1. Prodrome: tingling, itching, burning or local pain may occur for a few hours up to a couple of days prior to the development of local erythema.
  2. Day 1 of the eruption is often associated with virus replication at the end of the nerve and in the epithelial cells resulting in local erythema and swelling.
  3. Days 2-3 (or sooner) results in the appearance of tender papules and subsequent vesicles usually around the lips but the lesions may appear on the nose, chin or cheeks.
  4. Day 4 or sooner, a painful ulcer may develop from ruptured vesicles that may coalesce into a larger single ulcer with the characteristic herpetiform edges that have a semi-circular peripheral appearance similar to the outline of a cluster of grapes. The serous or serosanginous discharge is loaded with viral particles and represents the most contagious stage of the cold sore. Submental lymphadenopathy may be present but is less severe than signs associated with a primary infection. Secondary bacterial infection with staphylococcus or streptococcus may result in a pustular element to the discharging fluid.
  5. Days 5-8 is the crusting stage (serosanginous, occasionally pustular) which forms from the dried exudate.
  6. The healing stage can take from day 9 to day 14 but is variable. It may be shorter with aborted recurrent episodes or with early treatment at the prodrome or early lesion stage.

Diagnosis

• The diagnosis of herpes labialis is often recognized by the clinical appearance alone.
• If a lesion is atypical, laboratory investigations can be ordered that will identify HSV-1, HSV-2, or return a negative result (more common from late lesion samples).⁵

Patient Impact

A recent survey of 231 patients (age >18 years) with recurrent herpes labialis (outbreaks at least once a year) revealed that cold sores had a severe negative influence on social life/self-image in 55.5% of survey respondents.⁶ Additional findings include:

• The most troublesome aspects of the cold sores are the blister/ulcer and the subsequent crust formation.
• The duration of the cold sores can be prolonged and more significant than acknowledged by many clinicians.
• The majority of infected individuals (65.9%) preferred topical treatment, either over-the-counter or prescription treatment for cold sore recurrences.
• 77.2% preferred a topical preparation for the first sign of an outbreak (46.2% prescription, 31% non-prescription) and 9.6% would prefer not to prevent or treat outbreaks. Oral prophylaxis was preferred by 19.8% with a topical agent for a breakthrough.

Treatment of Recurrent Herpes Simplex Labialis

Topical Prescription Drugs

• A recent, multicenter, randomized, double-blind study identified the combination of 5% acyclovir with 1% hydrocortisone cream (Xerese®) as effective and well tolerated in the control of herpes simplex labialis recurrences in adults.²
• Topical acyclovir (Zovirax®) is a nucleoside antiviral agent that targets the viral replication stage.² The 1% hydrocortisone component is anti-inflammatory, designed to decrease the host response time post viral replication.²
• The study compared a new base of 5% acyclovir with 1% hydrocortisone cream to 5% acyclovir base and the Xerese® vehicle base cream. The study included 1,443 treated subjects with 601 receiving combination 5% acyclovir / 1% hydrocortisone cream, 610 receiving topical acyclovir cream, and 232 placebo cream for a randomization ratio of 2.7/ 2.7 to 1.
• The number of patients not progressing to the ulcerative stage compared to non-ulcerative recurrences was 42% for the acyclovir combined with 1% hydrocortisone (Fig. 1) compared to 35% for acyclovir cream alone (p=0.14) and 20% for Xerese® vehicle alone (p=0.001). This is the first study to demonstrate effectiveness of topical acyclovir cream compared to the vehicle alone.
• The enhanced effect was likely due to the reformulation with the partial replacement of propylene glycol with isopropyl myristate that enhances stratum corneum penetration of the topical acyclovir.
• The addition of the anti-inflammatory effect of topical 1% hydrocortisone further enhanced the effectiveness of the topical acyclovir in the new cream formulation.
• The cumulative lesion area in the study was calculated from the area of the ulcerative lesions that were added from daily measurements. The combination of 5% acyclovir with 1% hydrocortisone had a cumulative lesion area that was 50% smaller than the placebo cream cumulative area (p<0.0001), and the 5% acyclovir area was 25% smaller than the placebo cream cumulative area.
• Healing of lesions with the combination cream occurred in 3 vs. 4 days for acyclovir cream and 5 days for the placebo cream.
• The average lesion tenderness duration with the combination cream was 5 days, similar to acyclovir cream but less than the 6 day average for placebo cream (p=0.019). Positive cultures for herpes simplex were no higher with the combination cream (22%) compared to acyclovir cream alone (24%) and less than the placebo cream (40%).
• Overall adverse event rates were similar in all 3 groups.
• The combination cream is applied 5 times per day for 5 days.
• These results can be compared favourably to a previous study by Shaw et al, using an original vehicle formulation of topical acyclovir.⁷ This older formulation of topical acyclovir in the relatively small number of subjects failed to demonstrate benefit in 45 patients with 72 recurrences.
• Spruance et al, combined the results of two randomized clinical trials (RCTs) comparing the original topical 5% acyclovir cream with placebo cream in 1,385 subjects, and found a reduced time to healing with the 5% acyclovir preparation, from 5 to 4.4 days.⁸

Significantly reduced cold sore ulceration and duration of ulcerative lesions£,Δ

ΔHull CM, Brunion S. The Role of topical 5% Acyclovir and 1% hydrocortisone Cream (Xerese) in the Treatment of Recurrent Herpes Simplex Labilias: Postgraduate Medicine. Vol 122. June 5, Sept 2010. ISSN = 0032-5481.

£ Adapted from Spruance et al. High-Dose, Short Duration Early Valacyclovir Therapy for Episodic Treatment of Cold Sores: Results from Two Randomized, Placebocontrolled, multicenter studies.

Figure 1: Similar efficacy between Xerese® and Valtrex® in preventing ulcerative lesions

Topical Non-Prescription Formulations

• Topical docosanol (Abreva®) is a saturated fatty alcohol proposed to be effective in preventing the HSV envelope from attaching to the host cell.
• Sacks et al, published results of an RCT with 737 patients comparing the 10% docosanol cream to a placebo (polyethylene glycol) in the prodromal stage.⁹
• Treatment with docosanol cream significantly (p=0.002) shortened the duration of pain, itching, tingling or burning and reduced the time to complete healing (p=0.002).⁹
• Docosanol cream has a low risk of drug resistance.
• Symptomatic relief may be obtained by preparations with local anesthetic effects including Blistex® with menthol, phenol and camphor and zilactin with benzoyl alcohol.¹⁰
• Propolis extract from honey is the active component in ColdSore-FX® with in vitro anti-inflammatory and antimicrobial properties.¹⁰

Oral Prescription and Non-Prescription Drugs

• Effective oral antiviral medications that can speed the healing of labial herpes simplex recurrences include acyclovir and penciclovir.
• Spruance et al, conducted an RCT of 114 subjects with recurrent herpes labialis treated with oral acyclovir 400 mg 5 times a day for 5 days compared to 60 patients given a similar course of placebo treatment. The lesions treated with acyclovir were less painful and healed faster compared to placebo.¹¹
• Valacyclovir (Valtrex®) is the prodrug of acyclovir. It increases gastrointestinal absorption of the antiviral agent. Spruance et al, conducted a high-dose, short duration, early valacyclovir treatment RCT for recurrent episodes of labial cold sores vs. placebo. The dose of valacyclovir was either 2 grams twice daily for 1 day or with the addition of 1 gm twice daily on day 2.¹² There were more aborted episodes with both of these treatment regimens compared with placebo, but the episode duration was reduced by a half to one day.
• Famciclovir, (Famvir®) the prodrug of penciclovir, increases the gastrointestinal absorption of this antiviral agent. An RCT conducted with high dose famciclovir (750 mg twice daily or 1500 mg in a single dose) vs. placebo showed that recurrences healed in both active groups in 4 vs. 6 days with placebo. ¹³
• The newer, high dose, short treatment duration studies have shown better therapeutic efficacy compared to the traditional treatment of lower doses over 5-7 days.
• One non-prescription drug, oral lysine, is available in most health food stores. This medication has been popular with patients for the treatment or prevention of herpes labialis based on in vitro studies but the evidence supporting this treatment in humans is inconclusive.

Prevention

• A study by Rooney et al, utilizing an experimental system of ultraviolet light to induce reactivation of herpes labialis lesions did not produce any lesions in 35 patients using sunscreen but reactivated a herpes lesion in 27 of 38 patients (71%) utilizing the placebo sunscreen.¹⁴
• Continuous prophylaxis is often considered for individuals with 6 or more herpes lesions per year. Twenty patients completed a randomized, 4-month crossover trial with oral acyclovir 400 mg twice daily or placebo.¹⁵ Placebo treatment was associated with 1.8 reactivation episodes per subject while the continuous prophylaxis had 0.85 reactivation episodes.¹⁵
• Similar continuous prophylaxis has also been proposed for valacyclovir at a dose of 500 mg or 100 mg p/day or famciclovir 250 mg or 500 mg daily.¹²

Conclusion

Because oral antivirals have a narrow therapeutic window, they should be initiated at the prodromal stage. However, if the antiviral medication is taken after the prodromal stage, efficacy is decreased significantly. The oral medication has no effect on the inflammatory component of a cold sore. A way to optimize treatment is to offer patients two options, i.e. oral therapy and the topical treatment that contains acyclovir 5% and hydrocortisone 1% (Xerese®). The combination would address not only the viral replication but the inflammatory response. This strategy could potentially optimize patient outcomes.

References

1. Lee C, et al. Cochrane Database of Systematic Reviews. Published Online: 5 OCT 2011. DOI: 10.1002/14651858.CD009375
2. Hull CM, et al. ME-609 Study Group. J Am Acad Dermatol. 2011;(64):696.
3. Bruce AJ, et al. Clin. Dermatol. 2004;(22):520–527.
4. Opstelten W, et al. J Canadian Fam Physician. 2008;(54):1683–1687.
5. Sterling JC. Herpes labialis. In:Lebwohl MG, Heymann WR, Berth-Jones J, Coulson I. Treatment of skin disease; comprehensive therapeutic strategies. 3rd ed. Saunders Elsevier. 2010;303-305.
6. Sibbald RG. Evaluation of patient concerns and quality of life aspects of early cold sores treatment in 231 subjects. Poster presentation: Derm Update. 2013. Montreal, Canada.
7. Shaw M, et al. Br Med J (Clin Res Ed). 1985;(291):7-9.
8. Spruance SL, et al. Antimicrob Agents Chemother. 2002;(46):2238-2243.
9. Sacks SL, et al. J Am Acad Dermatol. 2001;(45):222-230.
10. Harmenberg J, et al. Acta Dermato Venereologica. 2010;(90):122–130.
11. Spruance SL, et al. J Infect Dis. 1990;(161):185-190.
12. Spruance SL, et al. Antimicrob Agents Chemother. 2003;(47):1072-1080.
13. Spruance SL, et al. J Am Acad Dermatol. 2006;(1):47-53.
14. Rooney JF, et al. Lancet.1991;(338):1419-1422.
15. Rooney et al. Ann Intern Med. 1993;(118):268-272

¹Department of Medicine, University of Toronto, Toronto, ON, Canada
²Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
³Dermatology Day Care and Wound Healing Clinic, Sunnybrook and Women’s College Health Sciences, Toronto, ON, Canada
⁴Toronto Regional Wound Healing Clinics, Toronto, ON, Canada
⁵Shoppers Home Health Care, Toronto, ON, Canada
⁶Wound & Skin Care Consultant, York, PA, USA
⁷School of Nursing, Excelsior College, Albany, NY, USA
⁸The John A. Hartford Institute for Geriatric Nursing, New York University College of Nursing, New York, NY, USA

ABSTRACT

Pressure ulcer prevention and treatment remains a challenge for interprofessional teams in all health care sectors. Evidence based pressure ulcer guidelines can be simplified with a bedside enabler utilizing the wound bed preparation paradigm. Key steps involve treatment of the cause, addressing patient-centered concerns, and administering local wound care (debridement, infection/ inflammation control, and moisture balance before considering advanced therapies with the edge effect). Optimal outcomes are achievable with a multi-disciplinary approach that supports patients and their circle of care, which is central to every evaluation and course of treatment decisions.

Key Words:
algorithm, pressure ulcers, prevention, wound bed preparation, wound healing

Introduction

This best practice for the prevention and treatment of pressure ulcers (PrU) has been developed with the expertise of the authors and utilizing:

• The 2009 evidence-based guidelines developed in collaboration between the National Pressure Ulcer Advisory Panel and the European Pressure Ulcer Advisory Panel (NPUAP-EPUAP)^1,2
• The Registered Nurses Association of Ontario’s guideline for the prevention and treatment of pressure ulcers^3,4
• Canadian Association of Wound Care’s best practices for pressure ulcers⁵
• Wound Bed Preparation Update 2011⁶

The best approach to pressure ulcer management includes the patient and their circle of care along with an interprofessional team of health professionals including physicians, nurses, rehabilitation specialists, dietitians, and other allied health specialists.

Prevention

The holistic assessment to identify persons at risk of a pressure ulcer includes:

• Review of comorbidities and historical events (e.g., previous history of a pressure ulcer)
• Assessment of the patient’s skin, particularly over bony prominences
• Medication profile
• Use of a validated risk assessment tool

The routine assessment interval is based on patient acuity (e.g., daily in acute care units to weekly assessments in chronic care for the first 4 weeks and then monthly to quarterly). High risk individuals include those with advanced age, spinal cord injuries or other causes of immobility, and low body mass index (i.e., BMI below 20).

For adult patients there are three validated risk assessment scales: Braden, Waterlow, and Norton:

• Braden scale with 6 subscales (sensory/perception, moisture, activity, mobility, nutrition, and friction/shear) is most commonly used in North America⁷
• Waterlow scale with 9 subscales: (BMI, continence, skin type, mobility, appetite, tissue malnutrition, neurological deficit, major surgery/trauma, and medications)⁸
• Norton scale with 5 subscales (physical condition, mental condition, activity, mobility, and incontinence)⁹

The Braden scale scores between 6 and 23. A score of 18 or lower indicates an increased risk of developing a pressure ulcer. It is important to institute prevention strategies for each low scoring or high risk subscale item and use clinical judgment in addition to any risk assessment tool scores.

Despite optimal care, not all pressure ulcers are preventable as outlined in a recent consensus document (Skin Changes At Life’s End=SCALE).¹⁰

Pressure Ulcers

The international NPUAP-EPUAP defines a pressure ulcer as “Localized injury to the skin and/or underlying tissue usually over a bony prominence as a result of pressure, or pressure in combination with shear.”¹

Findings from international PrU prevalence audits (447,930 patients) reported incidence rates of 9.2-27.3%.¹¹ Pressure ulcers are a significant financial burden on healthcare systems. Nonhealing/ chronic wounds are associated with increased length of hospital stay and mortality, and patients are at greater risk for developing complications such as cellulitis, osteomyelitis, and sepsis.

Determine Healability⁶

Categorization of wound healability (i.e., healable, maintenance, or non-healable) is of particular importance. This designation defines for the clinician, patient, and family an expected course of action, plan of care, and predictable healing rate. As a prerequisite to setting realistic treatment objectives, wounds are differentiated as:

• Healable wound: the cause is corrected, there is enough blood supply to heal; moist interactive healing
• Maintenance wound: the wound could heal, but the cause is not corrected due to patient unwillingness to adhere to treatment or a lack of required system resources
• Non-healable wound: the patient is ill or may have negative protein balance or inadequate blood supply that is not bypassable or dilatable

Other cofactors/comorbidities such as systemic disease, nutrition, and medications may also delay or inhibit healing in all of the above groups. For maintenance and non-healable wounds, moisture balance is contra-indicated and antiseptics including povidone iodine, chlorhexidine or its derivative polyhexamethylene biguanide (PHMB) may be prudent choices in a gauze or packing format. Conservative debridement of slough can, however, be undertaken to prevent spread of infection to local or deeper surrounding tissues through moisture and bacterial reduction.

Treat the Cause: Pressure and Shear

The foundation of the prevention and management of pressure ulcers is to reduce the forces of pressure and shear that damage the skin in the deep tissue compartments, particularly subcutaneous fat and muscle. Pressure is defined as the “force per unit area exerted perpendicular to the plane of interest.”¹² Shear is the “force per unit area exerted in parallel to the plane of interest.” Appropriate pressure reduction is outlined in Table 1. To minimize shear (the axial skeleton moves in opposite direction to the skin surface), do not raise the head of the bed more than 30 degrees and avoid slipping or sliding with transfers or in various types of seating.

Nutrition¹⁵

The nutritional assessment should include body mass index (BMI), hemoglobin (Hgb), and serum albumin level. The BMI is normal between 20-25, with levels <30 obese, and <40 morbidly obese. A BMI of >20 poses an increased risk of pressure ulcer development. Investigations of nutritional status should include Hgb (110-120 normal, ≥100 for normal healing, 80-100 for delayed healing, and 60-80 will severely impair the wound healing process). The albumin measures the protein status over the past few months in the peripheral circulation. Normal albumin levels are above 30-33, with delayed healing at levels between 20-30, and at <20 it will be very difficult to heal a wound. Nutritional support should include adequate protein intake of 10-20 g/kg/day. Zinc deficiency is uncommon in adults and its supplementation can interfere with absorption of other nutrients.

Immobility, Level of Activity and Positioning

Persons with spinal cord injuries (SCI)¹⁶ and neuromuscular degenerative disease are at an increased risk of developing a pressure ulcer. Interprofessional team members can offer patient-specific strategies for safe and optimal activity levels for individuals with a pressure ulcer. These consultations should actively engage input from both the patient and their circle of care with respect to an exercise program (e.g., in bed, movements or positioning during seating, assisted ambulation, and training equipment). Even with therapeutic surfaces, persons with PrU’s require a regular turning program based on their risk level and ability to perform voluntary changes in position.

Moisture and Friction¹⁷

Excess moisture may be due to sweat but is more often associated with urinary or fecal incontinence. Fecal incontinence is most harmful in the sacral area and a bowel routine or external collection device should be considered, as well as prompt changing of wet underwear or diapers. Urinary incontinence may be controlled with intermittent catheterization, a condom catheter, or an indwelling catheter; however, their use is associated with other complications including infections.

Friction is “the resistance to motion in a parallel direction relative to the common boundary of two surfaces.”¹² Moisture and friction are often responsible for the superficial breakdown of the skin in the sacral area, where incontinence associated dermatitis (IAD), a form of contact irritant dermatitis, is often misdiagnosed as a pressure ulcer.

Patient-centered Concerns¹⁸

Pain is often underestimated by wound care providers. Controlling pain promotes wound healing as well as renders patients more comfortable. Pain can be either nociceptive (gnawing ache, tender, and throbbing) stimulus dependant or neuropathic (burning, stinging, shooting, and stabbing) non-stimulus dependent. The former can be treated with the WHO’s pain ladder, starting with acetylsalicylic acid and nonsteroidal anti-inflammatory drugs and progressing to weak and stronger narcotic agents. Short acting drugs are used for initial dosing and breakthrough with longer acting agents for sustained and adequate pain control. Neuropathic pain can be spontaneous and is best controlled with tricyclic compounds high in anti-noradrenaline activity (e.g., nortriptyline or desipramine 10-30 mg at night, titrating higher if required) or anti-epileptic agents (e.g., gabapentin, pregabalin, or carbamazepine). Pain can also be minimized at dressing change with modern, easily removable dressings featuring soft silicone rather than traditional adhesive products.

Odor from a wound dressing is often concerning to patients and may indicate the need for treatment against gram-negative or anaerobic bacteria.

Smoking can decrease cutaneous blood flow by as much as 40%, inducing ischemia and impaired healing.¹⁹ Smoking one cigarette creates a vasoconstrictive effect for 90 minutes.²⁰

Bed rest resulting in physical and mental deterioration can be one of the most harmful strategies for the treatment of pressure ulcers.²¹ The facilitation of daily living activities will help promote a return to normal function.

Classification of Pressure Ulcers2

Pressure ulcers previously identified as grades or levels are now known as categories (outlined in Table 2). It is worth noting that the NPUAP considers suspected deep tissue injury (sDTI) and unstageable ulcers as a separate category, whereas the EPUAP designates both conditions as category 4.

A sDTI is characterized by a purple or maroon localized area of intact skin that may feature a blood filled blister due to damage of the underlying soft tissue from pressure and/or shear. Not all sDTIs subsequently ulcerate or breakdown, as they can selfresolve.

Location and Size

It is important to document the location and size of the wound. This facilitates objective assessment of progress or deterioration, especially when several care providers are involved with patient care. Wounds should be measured at the longest length and then the widest width at right angles to the measured length. Depth can be measured with a cotton tip applicator or wooden stick, where the deepest depth is measured a notch should be made on the disposable measuring instrument, and then the length should measured.

Arterial Insufficiency

Heel ulcers, although triggered by pressure, may be due in large part to lower limb arterial insufficiency.⁶

Treatment6

Local Wound Care

Gently cleanse wounds with low-toxicity solutions, i.e., saline, water, or acetic acid (0.5-1.0%). Wounds should not be irrigated when seepage of the solution is not visible or retrieval (or aspiration) of the irrigation solution is not possible. Under these conditions, use compresses applied with forceps on gauze ribbon as an alternative.

Debridement

Debridement can be accomplished surgically with scalpel, curette, or scissors. Sharp techniques may help remove bacterial burden on the surface of the wound, particularly when it is arranged in biofilms. Autolytic debridement is often facilitated with dressings (e.g., calcium alginates, hydrogels or hydrocolloids). Enzymatic (e.g., collagenase) or biological debridement with maggots are additional alternatives.

Moisture Balance

Achieving optimal moisture balance is essential in wound healing, which promotes new tissue growth by encouraging cellular proliferation and collagen formation.²² Moisture balance dressings are listed in Table 3 along with their autolytic debridement properties.

Infection

Bacteria can critically colonize wounds, leading to stalled healing. Critically colonized wounds can be identified with the presence of any three clinical signs in the mnemonic NERDS (non-healing, exudate increase, red friable or easily bleeding granulation tissue, new slough or debris on the wound surface, and smell).²³

Topical antimicrobials for healable wounds include silver dressings (combined with foams, alginates or hydrogels, as well as grid or cloth-like structures), PHMB foam and gauze, iodine (cadexomer iodine or povidone iodine), and honey (alginate, hydrogel or hydrocolloid).

The mnemonic STONEES (size increase, temperature of surrounding skin elevated, os-probing or exposed bone, new satellite areas of breakdown, erythema and/or edema = cellulitis, exudate increase, and smell),²¹ indicate infection that may be superficial, deep, or both, particularly if increased exudate and smell are present. Treatment with systemic antibiotics is required in these situations. The choice of antibiotic should preferably be based on bacterial swab results. Wounds that have been present for >4 weeks or if the patient is immunocompromised require antimicrobial coverage for gram-positive, gram-negative and anaerobic organisms. Osteomyelitis (OM) must be considered as a complication of pressure ulcers, especially if the ulcer probes to bone or the bone surface is rough, gritty or contains bone fragments. Supporting evidence for OM can be simply achieved by X-ray or MRI in some cases, along with elevated sedimentation rate (>40 mmHg/h) may be helpful in making this determination. Positive parameters should be followed and corrected prior to stopping systemic antibiotics.

Inflammation

Persistent inflammation due to excess harmful cytokines (e.g., matrix metalloproteinase 9) can result in delayed wound healing. This can be treated topically with dressings containing silver, collagen, oxidized regenerated cellulose, or ibuprofen.

Edge Effect

If the cause of a healable wound has been corrected and patientcentered concerns are addressed (including receiving optimal local wound care), but healing is stalled, advanced therapies can be considered. The edge effect refers to the cliff-like edges of a wound that is often seen with stalled healing, which contrasts the tapered edges and peripheral rim of purple new epithelium of a healing wound. If a wound does not exhibit a 30% reduction by week 4, it is unlikely to heal by week 12.⁶

Advanced Therapies

There is RCT evidence of advanced therapies in pressure ulcers, including electrical stimulation and therapeutic ultrasound.²⁴ Surgery is also considered when deep ulcers have bone, muscle or fascia base, and granulation tissue involvement, or healing cannot be easily stimulated with local measures. Surgery is often a major procedure that is accompanied by a structured rehabilitation program to prevent dehiscence. Some patients with heel pressure ulcers and peripheral vascular disease may benefit from hyperbaric oxygen therapy. Additionally, there may be a role for negative pressure wound therapy when a healable wound is stalled with excessive exudate.

Conclusion

Most pressure ulcers can be prevented, but not all can be avoided. A comprehensive assessment and treatment of PrUs can be completed with the wound bed preparation paradigm (Figure 1) outlined in this article. These assessments and interprofessional collaboration are important for the early identification and optimal PrU treatment. Local ischemia or incontinence associated dermatitis are often misdiagnosed as PrUs. Coordinated PrU treatment needs to combine an awareness of appropriate surfaces, turning schedules, correction of shear, and implement strategies for adequate protein intake/correction of nutritional deficiencies, enhanced mobility, manageable pain levels, and improved activities of everyday living. Empowering patients and their circle of care are key factors to treatment adherence and successful program outcomes.

Figure 1: Wound bed preparation for the prevention and treatment of pressure ulcers

References

1. European Pressure Ulcer Advisory Panel and National Pressure Ulcer Advisory Panel. Prevention and treatment of pressure ulcers: quick reference guide. Washington DC: National Pressure Ulcer Advisory Panel; 2009.
2. European Pressure Ulcer Advisory Panel and National Pressure Ulcer Advisory Panel. Treatment of pressure ulcers: quick reference guide. Washington DC: National Pressure Ulcer Advisory Panel; 2009.
3. Registered Nurses’ Association of Ontario (RNAO). Risk assessment & prevention of pressure ulcers. Guideline supplement. Nursing best practice guideline. Toronto, ON: Registered Nurses’ Association of Ontario; 2011 Sep. Available at: http://rnao.ca/sites/rnao-ca/files/Risk_Assessment_and_Prevention_of_Pressure_Ulcers.pdf. Accessed: July 17, 2012.
4. Registered Nurses’ Association of Ontario (RNAO). Assessment and management of stage I to IV pressure ulcers. Summary of recommendations. Nursing best practice guideline. Toronto, ON: Registered Nurses’ Association of Ontario; 2007 revision. Available at: http://rnao.ca/sites/rnao-ca/files/Pressure_Ulcers_I_to_IV_Summary.pdf. Accessed: July 17, 2012.
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