Effects of non contact low‐frequency ultrasound on healing of suspected deep tissue injury: a retrospective analysis

Abstract

The purpose of this study was to assess the effectiveness of non contact low‐frequency ultrasound on the healing of suspected deep tissue injury (SDTI). Participants were adults ranging in age from 28 to 93 years old, with multiple diagnoses including anaemia, diabetes mellitus and hypertension. Data were examined retrospectively on 85 patients (intervention group = 43 and non intervention group = 42) with 127 SDTI (intervention group = 64 and non intervention group = 63). Participants in both groups received standard of care for treating pressure ulcers. A severity score was used to assess SDTI severity before treatment and healing/progression after treatment. This scale measures surface area, wound colour/tissue assessment, and skin integrity with potential scores of 3 to 18 (higher scores indicate greater severity). A significant difference in changes in wound severity was found (t = 5·67, P < 0.000). Difference in mean change scores was 2·52 on the 3–18 severity scale. The decrease in wound severity for the intervention group was 1·45. Severity in the non intervention group increased by 1·06. This exploratory study of the effect of the non contact low‐frequency ultrasound provides initial findings that support its use with SDTI.

INTRODUCTION

Suspected deep tissue injury (SDTI) is a new pressure ulcer stage that was added to the National Pressure Ulcer Advisory Panel's (NPUAP) staging system in 2007. An SDTI is a ‘purple or maroon localised area of discoloured intact skin or blood‐filled blister due to damage of underlying soft tissue from pressure and/or shear’(1). The National Database for Nursing Quality Indicators (NDNQI) identified in 2010 that there was a 10·9% prevalence of SDTI out of a 375 613 patient sample (2). The NPUAP held a consensus conference in 2005 on SDTI and pressure ulcer staging. One of the goals was to identify how the addition of SDTI would impact clinical practice. As a result of this consensus conference, the attendees identified and agreed that the addition of SDTI would guide clinicians to implement more aggressive measures earlier in hope of improving outcomes for patients with SDTI (3). Current literature suggests that SDTI represent the early pathogenesis of a full thickness stage 3 or 4 pressure ulcer 4, 5. The SDTI phenomenon is still poorly understood despite advances in knowledge from current research. The causes of SDTI development are multi‐factorial and follow a complex series of events at the bone/muscle interface that include tissue deformation, ischaemia, ischaemic reperfusion injury, impaired lymph drainage, alteration in interstitial fluid flow, alteration in capillary wall permeability leading to tissue oedema, and inflammatory changes conducive to apoptosis 6, 7, 8. In addition, there is a dearth of literature that describes specific patient populations or conditions that pre‐dispose patients for developing SDTI. Despite advances in understanding the pathophysiology of SDTI, there is a paucity of information in the literature guiding the clinician regarding how to appropriately treat an SDTI and alter the normal progression to full thickness ulceration. Current recommendations follow accepted standard of care for treating pressure ulcers. These include repositioning schedules, support surfaces, topical dressing application, and nutritional support. At this time, there are no new treatment options identified in the literature for SDTI 9, 10.

The incorporation of ultrasound therapy as an adjuvant therapy has been identified in the literature as an option for the treatment of pressure ulcers. Based on a Cochrane review, there is no current evidence supporting the use of ultrasound as an adjuvant therapy in the treatment of pressure ulcers. Given the small number of studies conducted in the area, reviewers were unable to conclude whether adjuvant ultrasound therapy would be beneficial or harmful. They also identified a number of methodological limitations in the studies reviewed (11). Therapeutic ultrasound is a type of biophysical agent that uses sound waves emitted from a transducer to deliver energy to the treatment location (12). The mechanism by which ultrasound benefits wound healing is a result of non thermal effects. The ultrasound therapy causes cavitation and acoustic streaming of the tissue stimulating cellular and molecular activity that is conducive to wound healing 13, 14. Some potential non thermal benefits that are applicable to SDTI may include increased tissue perfusion, increase of collateral circulation, suppression of inflammatory response, and stimulation of cell survival mechanisms (15). Non contact low‐frequency ultrasound (NLFU) (MIST™ Therapy System, Celleration, Eden Prairie, MN) delivers ultrasound at a low intensity of 0·2–0·6 W/cm (2) and a low frequency of 40 kHz. These settings are conducive for producing the non thermal effects mentioned above. The low‐frequency ultrasound wave form is able to penetrate into the deeper tissues secondary to the longer wave length. In comparison, high‐frequency (megahertz) ultrasound has a shorter wave length and often the energy is absorbed more at the skin surface (16). Therefore, the NLFU is more advantageous in comparison to using megahertz ultrasound to treat SDTI as the ultrasound is able to penetrate deeper into the tissue where the ischaemic injury occurred (15). A review of relevant literature showed three retrospective analysis studies, one prospective analysis study, and one meta‐analysis that studied the affects of NLFU on chronic wounds 17, 18, 19, 20, 21. The research studies had a total of 17 pressure ulcers (21). These articles were studying the effect of adjunctive NLFU with patients who have chronic wounds. These studies did not specify the stage of the pressure ulcers that were treated with NLFU. Although a pressure ulcer stage is not mentioned, the median chronicity of the wounds in the study ranged from 7 to 8 weeks 17, 18, 19, 20, 21. This may suggest that these wounds were likely stage 3, stage 4 or unstageable pressure ulcers. In addition, two case studies showed the use of NLFU on stage 2, stage 4 and unstageable pressure ulcers 22, 23. This research team reported the first use of NLFU with SDTI with six case study series (15). However, the use of NLFU specifically with the treatment of SDTI has not been researched. NLFU has been studied in populations experiencing chronic wounds such as diabetic, arterial and venous ulcers with statistical findings supporting their use as part of the plan of care 17, 18, 19, 20, 21.

Owing to the recent addition of SDTI to the NPUAP staging system, opportunities for further research in therapeutic modalities that are effective at halting the visual progression of the SDTI to an unstageable pressure ulcer have emerged. Identifying an effective treatment for SDTI is essential because of the impact that pressure ulcers have on a patient's quality of life and the subsequent resource taxation that pressure ulcers have on the health care system (24). The presence of an SDTI that progresses to a stage 3 or 4 pressure ulcer alone is not an independent predictor of mortality, but is representative of underlying disease severity and other comorbidities 25, 26. The presence of pressure ulcers may increase morbidity (26). Therefore, further research is needed to identify an optimal treatment regimen for SDTI. The purpose of this study was to retrospectively review and compare the clinical results of patients with SDTI from 2008 to 2009 in the acute care setting to identify the clinical outcomes of patients that received standard of care and those receiving standard of care plus adjunctive NLFU.

MATERIALS AND METHODS

Delivery of NLFU

The NLFU was delivered using the MIST™ Therapy System (Celleration). Ultrasound requires a delivery medium in order to deliver the ultrasound waveform directly to the treatment site, as air can deflect the waveform (12). The ultrasound is continuous and emitted from a transducer. Normal saline from the saline bottle, attached to the treatment head, is used as the delivery medium. NLFU was added to the SDTI protocol if the SDTI was able to be treated within 5 days of onset. Within our facility, the physical therapist (PT) performed the treatments. The wound, ostomy and continence (WOC) nurses identified the SDTI and paged the wound care PT to notify them regarding the treatment of SDTI. They would treat the patient with NLFU the same day if possible.

Treatment protocol/methods

Participants in both the control and NLFU groups received the standard of care for pressure ulcers, including repositioning schedule with assistive repositioning/turning devices, trypsin‐balsam‐of‐Peru ointment twice daily or soft‐silicone bordered foam, low‐air‐loss support mattress for non‐ICU patients, addition of static‐air overlay on an intensive care unit (ICU) beds, dietetic consultation, heel‐off‐loading boots, and institutional pressure ulcer prevention policy. The topical regimen was determined by the ability for a dressing to stay in place. Trypsin‐balsam‐of‐Peru would be used if the SDTI location was not conducive for dressing adherence and the patient was frequently incontinent of stool and urine. The purpose of the topical treatment was to promote protection against external variables such as shear, friction or incontinence that might disrupt the wound healing process and to promote a moist wound bed conducive to healing. In addition, participants in the NLFU group received NLFU treatments daily for 5 days and then every other day thereafter. If the SDTI were caught early and NLFU initiated early, then this may lead to a better outcome for the NLFU group (3). As both the control and NLFU groups received timely initiation of the standard of care, there is likely no bias due to SDTI onset time. The only difference between the groups is that the NLFU group would only receive the ultrasound treatment if it was less then 5 days of onset as the researchers believed that past this time range would exceed clinical benefit. NLFU treatment time was based on total surface area (TSA) of the SDTI, which corresponds to pre‐programmed ranges on the NFLU device. For purple non blanchable discolouration, TSA was determined and the next level up on the device's pre‐set treatment time was chosen to give SDTI extra ultrasound time. NLFU treatment continued until purple/maroon discolouration disappeared and the wound bed was red, moist, and beginning to re‐epithelialise, or the patient was discharged from the hospital. Treatment time could range from 3 to 20 minutes depending on the TSA ranges that were from 10 to 180 cm (2).

Data assessment

Study population and setting

A retrospective chart review was conducted in all SDTI patients treated in 2008, who received standard of care (control group), and SDTI patients treated between March 2009 and March 2010, who received NLFU in addition to standard of care (NLFU group). All participants were patients who gave general consent upon admission to Central Baptist Hospital, Lexington, KY. Participants eligible for the control group consisted of SDTI patients evaluated by WOC nurses who had a minimum of three evaluations, the researchers believed that this number of evaluations would capture the evolution of the SDTI. These evaluations occurred over a 10‐ to 14‐day period of time allowing sufficient time to identify if the SDTI would progress (unstageable versus stage 2). A total of 60 charts were reviewed of patients treated in 2008, and 42 patients were considered controls. The NLFU group consisted of SDTI patients evaluated by WOC nurses and whose SDTI was identified within 5 days of onset. All patients who received adjunctive NLFU were included in the treatment group between March 2009 and March 2010. Patients who were ineligible for the NLFU group consisted of patients that had standard contraindications for the ultrasound therapy, including those with lesions over electronic devices/implants, pregnant uterus, malignancy near the treatment area or any area located on the face or head. There were no patients with SDTI that had any of these associated conditions thereby limiting their ability to be eligible for the NLFU group.

A standardised data collection sheet was used to review electronic medical records (EMR) and photographs (Figure 1). Data were examined retrospectively for 85 patients (42 control group and 43 NLFU group) with a total of 127 SDTIs (63 control and 64 NLFU). Following the data collection, the decision support analyst used The Precision Alternative (TPA) decision support software to obtain data from the patient's charts, using medical record numbers, to identify any data points that showed any potential significance. Data points of interest were how the NLFU treatment affected the facility financially and its impact on discharge disposition. Other data points that were evaluated were admit source, re‐admission and cases by financial group (i.e. insurance). In addition, the measurements of the wound from the data collection tool would be used to gather data regarding the SDTI at initial assessment and at discharge to identify median TSA, largest TSA and smallest TSA. The study protocol was approved by the Central Baptist Hospital Institutional Review Board as an expedited review.

Figure 1.

A standardised data collection sheet.

SDTI severity assessment

At present, instruments to assess the severity of SDTI are not available. For this study, three characteristics of SDTI were used to identify their severity: TSA, skin integrity and wound colour/tissue assessment. The severity scale tool needed to capture the potential variables when the SDTI was first assessed and at the discharge assessment to adequately identify a change in the wound. The TSA consisted of a scoring from 1 to 8 and covered a range of wound sizes. The skin integrity section consists of a scoring from 1 to 3 and reflects the potential characteristics identified with SDTI assessment. The wound colour/tissue assessment category consisted of a scori from 1 to 7 and was a reflection of the possibilities of having normal skin characteristics to bone, muscle, tendon exposure. The NPUAP staging system was used as a reference when identifying the level of tissue loss identified when the severity scale score was determined. This guide ascribed a severity score based on the type of tissue assessed in the wound. These categories were given numerical scorings to represent the potential ranges of how an SDTI could present and progress. The total combined score for all three categories ranges from 3 to 18, with higher scores reflecting greater severity (Figure 2). Data collected from the EMR were used to assign a severity score at the time of initial assessment and upon discharge in order to collect data of severity of SDTI upon initial treatment and to identify the progression of the SDTI at discharge.

Figure 2.

Honaker suspected deep tissue injury severity scale.

Statistical analysis

Inferential and descriptive statistics were used to describe the population and examine the effect of the NLFU intervention. To test the probability that adjunctive NLFU therapy would have an effect on SDTI severity, Student's t test was used to test for significant differences between SDTI severity at initial assessment and at discharge assessment between the control and NLFU groups. SPSS version 19 (IBM Corp., Armonk, NY) was used to perform the statistical analysis. In addition, outcomes were measured using the current NPUAP staging system to identify what tissue would be visible during our final assessment of the wound. A power analysis P < .05, with a moderate effect size determined that 63 SDTI were required in each group in order to have an 85% chance of achieving significance.

RESULTS

Patient characteristics

Patient demographic and clinical characteristics are shown in Table 1. Study patients were adults ranging in age from 28 to 93 years old (mean 72 years), with a slight predominance of women in both treatment groups. A majority of study patients in both treatment groups shared comorbidities of anaemia, diabetes, hypertension, low albumin/pre‐albumin and foecal incontinence. Other clinically relevant factors present in a substantial minority of patients in both treatment groups included congestive heart failure, end‐stage renal disease, urinary incontinence, use of vasopressors, and need for ventilator support. More patients in the NLFU group had diabetes mellitus and peripheral vascular disease. More patients in the control group had chronic obstructive pulmonary disease, a history of cigarette smoking and had received end‐of‐life or palliative care. The average length of stay (LOS) for the control group was 19 days and the LOS for the treatment group was 21 days. Both groups were similar in regards to shared comorbidities and secondary conditions. There was an average of ten NLFU treatments in the treatment group, which covered a 15‐day span (Table 1). There were no adverse events associated with patients that received NLFU. Once the patient was transferred or discharged from our facility, no follow up occurred unless the patient was readmitted to the facility for medical care. The sample size was insufficient to perform inferential statistics that would have statistical power (27).

Table 1.

Patient demographics and clinical characteristics

	Control group N = 42	NLFU group N = 43
Female gender (%)	52	58
Mean age (years)	69	75
Mean length of stay (days)	19	21
Diabetes (%)	48	60
End‐stage renal disease (%)	26	28
Congestive heart failure (%)	24	19
Chronic obstructive pulmonary disease (%)	26	16
Peripheral vascular disease (%)	17	33
Hypertension (%)	71	79
Anaemia (%)	83	88
Smoker (%)	43	28
Low albumin/pre‐albumin (%)	67	70
Fecal incontinence (%)	67	74
Urinary incontinence (%)	26	28
End‐of‐life/palliative care (%)	45	33
Operating room time >3·5 hours (%)	5	5
Vasopressors (%)	36	35
Ventilator support (%)	50	44

Wound outcomes

The median TSA size for the control group was 11·25 cm (2) and the NLFU group was 8·25 cm (2) at the first assessment. The median TSA size for the control group was 8 cm (2) and the NLFU group was 2·1 cm (2) at the final assessment. At baseline, the control group was 3 cm (2) larger than the NLFU group. Although the control group had slightly larger wounds, the researchers believed that the difference was not large enough to be significant. However, the final assessment time for the NLFU group indicated a 6·24 cm (2) decrease in size in comparison to the 3·25 decrease noted in the control group. The largest size wound for the control group was 161 cm (2) at the first assessment and 241 cm (2) at the final assessment. The largest size wound for the NLFU group was 77 cm (2) for the first assessment and 72·5 cm (2) for the final assessment. The smallest size wound for the control group was 0·25 cm (2) for the first assessment and 0 cm (2) for the final assessment. The smallest size wound for the NLFU group was 0·2 cm (2) for the first assessment and 0 cm (2) for the final assessment. In the control group, 15 of the SDTI were maroon non blanchable and 48 were purple non blanchable upon the first assessment. In the NLFU group, 13 of the SDTI were maroon non blanchable and 51 were purple non blanchable upon the first assessment. Upon the first assessment, 35 of the SDTI had intact skin and 28 had denudation of the epidermis for the control group. The first assessment for the NLFU group showed that 32 of the SDTI had intact skin, 25 had denudation and 7 had blisters. Of the 43 patients treated with NLFU, 12 patients experienced multiple SDTI. Of the 12 patients that had multiple SDTI, 3 of the patients had an SDTI to have a positive and negative outcome as manifested by evolution to an advanced stage ulcer. Furthermore, 6 of the 12 patients with 2 or more SDTI had all SDTI to resolve for a positive outcome and only 3 of the 12 patients had all SDTI progress to a poor outcome. The remainder of the 43 patients had only one SDTI treated. The sample size for the above items was insufficient to perform any inferential statistics that would have statistical power (27). See Table 2 for summary of the above data. As shown in Figure 3, substantially more SDTIs in the NLFU group resolved spontaneously or evolved to no more than a stage 2 pressure ulcers compared with the control group. The average severity score for the control group at the first assessment was 9·62 and at the final assessment the average score was 10·68. The difference between the two scores showed an increase in severity by 1·06. The average severity score for the NLFU group at the first assessment was 9 and the final assessment average severity score was 7·55. The difference between the two scores showed a decrease by 1·45. The tests of between‐subjects effects for severity scale time 1 showed a P < 0·913 indicating no statistical difference between the NLFU and control groups with the initial assessment. Finally, the total difference noted between the two groups accumulated showed a significant decrease in wound severity (2·52 on the 3–18 point severity scale) between the NLFU and control group for the discharge assessment (t = 5·67, P < 0·000) (Figure 4).

Table 2.

Wound attributes

	Control group N = 63	NLFU group N = 64
Median total surface area, initial assessment	11.25	8.25
Median total surface area, discharge assessment	8	2.1
Largest wound (cm2), initial assessment	161	77
Largest wound (cm2), discharge assessment	241	72.5
Smallest wound (cm2), initial assessment	0.25	0.2
Smallest wound (cm2), discharge assessment	0	0
Maroon SDTI	15	13
Purple SDTI	48	51
SDTI with intact skin, initial assessment	35	32
SDTI with blister, initial assessment	0	7
SDTI with denudation, initial assessment	28	25

SDTI, suspected deep tissue injury.

Figure 3.

Final pressure ulcer stage after suspected deep tissue injury resolved.

Figure 4.

Change in suspected deep tissue injury severity from initial assessment to discharge assessment.

Discharge disposition

In attempting to identify the impact of adding the therapy to this facility, data of both the control and treatment groups were analysed to potentially identify a positive financial impact for this hospital. The financial analysis did not show any significant data. The average LOS for the control group was 19 and the treatment groups was 21. The presence of an SDTI or pressure ulcer did not appear to impact discharge plans. The discharge plans were influenced by overall medical status and bed availability at the selected discharge facility that the patient and family had selected. However, a greater proportion of NLFU patients (21%) than control patients (12%) were discharged to home health care. Conversely, a smaller proportion of NLFU patients (10%) than control patients (33%) were discharged to a long‐term care facility.

DISCUSSION

This exploratory study has added to the body of literature surrounding the use of ultrasound therapy with pressure ulcers, but more specifically the use of NLFU during the early onset of the SDTI. The findings of this study suggest that NLFU may have a beneficial effect on the progression of SDTI. This is an initial attempt to validate the use of NLFU as an affective treatment for SDTI. Future studies could examine the impact of treatment times (minutes) on SDTI, impact of day of onset and treatment time initiation on the SDTI progression, affect of comorbidities or patient condition on SDTI and its response to NLFU.

In order to elucidate the possible mechanisms of action that low‐frequency ultrasound may have the SDTI environment, a literature review was performed to review the pressure ulcer development process and the variables that NLFU may be able to affect (15). An SDTI or pressure ulcer develops as a result of tissue deformation from non uniform pressure that alters the cellular environment as a result of impeding normal circulation and cellular processes within skeletal muscle over top of bony prominences. SDTI or pressure ulcers can be a result of a single event or a cycle of ischaemic/ischaemic‐reperfusion‐injury cycles. Subsequently, the bodies response to this ischaemic injury sets off a complex set of events that could further destabilise the cellular environment promoting necrosis and/or apoptosis to the injury site and the tissue surrounding the injury as a result of the ensuing inflammatory processes and tissue oedema that occurs following reperfusion of the environment 28, 29. Low‐frequency ultrasound has been shown to upregulate endothelial nitric oxide synthase (NOS) secondary to the shear stress induced by cavitation and microstreaming (30). Endothelial NOS has been found to be cytoprotective in I‐R injury, when sufficient levels of l‐arginine are available, by increasing NO with subsequent increased blood flow, suppression of oxygen‐ and nitrogen‐derived free radical development, inhibition of leukocyte extravasation secondary to decreased endothelial expression of leukocyte adhesion molecules, and balances microvascular permeability by maintaining tight endothelial cell–cell junctions. The upregulation of endothelial NOS has beneficial effects on improving blood flow to the area in the form of decreased muscular reperfusion oedema, blunted inflammatory response by decreasing leukocyte extravasation and free radical‐induced leukocyte chemotaxis, and decreased nitrogen‐ and oxygen‐derived free radical formation 31, 32. Another potential benefit of low‐frequency ultrasound is the stimulated upregulation of vascular endothelial growth factor through monocyte stimulation 16, 33. Nitric oxide and vascular endothelial growth factor have an impact on stimulating both vasodilatation and angiogenesis with the subsequent beneficial removal of metabolic waste products, delivering key nutrients required for normal cellular processes, and as a result normalising the pH level 16, 31, 33. In addition, NLFU has been found to stimulate a balance of both the JNK and ERK signal transduction pathways that promote cellular survival and repair mechanisms following injury (34). When these pathways are stimulated through shear stress, intracellular communication initiates a cascade of events leading to mechanisms of cellular repair and survival following oxidative stress 34, 35, 36, 37. In addition, NLFU has been found to suppress the p38 MAPK signal transduction pathway with subsequent suppression of tumour necrosis factor (TNF)‐alpha secretion (38). When the p38 MAPK pathway is inhibited, there is a decrease in the release of TNF‐alpha and interleukin 1, both of which stimulate upregulation of matrix metalloproteinases (MMPs) 39, 40. Therefore, the inflammatory response can be modified by directly influencing the release of pro‐inflammatory cytokines. This may be beneficial in a pressure ulcer environment where, as the inflammatory phase progresses, the build‐up of cytokines that in turn increase the release of MMP can potentially harm healthy cells as the MMPs breakdown the extracellular matrix to prepare the wound bed for repair. Clearly, more research is needed to fully elucidate the mechanisms by which ultrasound energy may contribute to the tissue repair process on a cellular level. However, the currently available literature does suggest that low‐frequency ultrasound is capable of stimulating cellular activity through mechanical energy in the absence of key growth factors, ATP, cytokines or other enzymes.

A limitation of this study is a sample size that was not large enough to statistically analyse difference in comorbidities between the control and experiment group. Not only does a pressure ulcer significantly impact a patients quality of life, but also a stage 4 hospital acquired pressure ulcer can cost up to $129,248 to treat (41). An additional area of interest would be financial impact to acute care settings and the continuum of care. The ability to alter the progression of SDTI to an advanced stage is essential because it directly impacts a patient's quality of life. Future research is suggested to add to the body of knowledge supporting the efficacy of this modality to be added to the treatment plan.

ACKNOWLEDGEMENTS

The author was financially support by Central Baptist Hospital. Editorial assistance for the manuscript was supported by Central Baptist Hospital. The author would like to thank Dr. Dorothy Brockopp and Dr. Karen Hill for editorial assistance in guidance in organizing the research project.