Deep Tissue Injury from a Bioengineering Point of View

Abstract

The phrasing of the National Pressure Ulcer Advisory Panel’s (NPUAP) definition of deep tissue injury (DTI) was based on case reports, clinical observations, and experience. Although etiological studies of DTI, primarily related to characterizing biomechanical factors affecting onset and progression, support and strengthen parts of the NPUAP’s definition, some recent findings suggest a need to re-evaluate the wording and perhaps refine future definitions of DTI.

Application of existing bioengineering research to underlying biological, physical, biomechanical, and biochemical mechanisms involved in the definition of DTI suggests the following: 1) changes in skin color — ie, deviation of the local skin color from the surroundings — may indicate a DTI might be present, but color is not useful for quantifying the severity of injury; 2) the pressure and/or shear definition is inaccurate because it creates an artificial distinction between pressure and shear, which are physically coupled, and because it ignores tensional loads; 3) palpating tissue firmness at the wound site provides limited assessment information because tissue firmness will depend on the point in time along the course of DTI development. Damaged tissues might appear stiffer than surrounding tissues if examined when muscle tissue is locally contracted due to local rigor mortis but at a later stage damage might manifest as tissues that are softer than their surroundings when digestive enzymes start decomposing necrotic tissues; 4) skin temperature changes near the DTI site may reflect inflammatory response, causing local heating, or ischemic perfusion, causing local cooling; and 5) rapid deterioration of DTI is likely occurring due to muscle tissue stiffening at the rigor mortis phase; stiffened tissues abnormally deform adjacent tissues and this effect is amplified if muscles are atrophied. The application of interdisciplinary research may help clinicians and researchers move from evolving jargons, staging systems, and injury definitions to valid and reliable clinical instruments, which will improve clinical practice.

     On February 2007, the National Pressure Ulcer Advisory Panel (NPUAP) formally added a new definition to its pressure ulcer staging system: suspected deep tissue injury (DTI). This definition has since been published widely in the nursing literature^1–6 and is posted at the NPUAP’s website as follows⁷:

     Purple or maroon localized area of discolored intact skin or blood-filled blister due to damage of underlying soft tissue from pressure and/or shear. The area may be preceded by tissue that is painful, firm, mushy, boggy, warmer, or cooler as compared to adjacent tissue.

     The NPUAP added a “further description”:

     Deep tissue injury may be difficult to detect in individuals with dark skin tones. Evolution may include a thin blister over a dark wound bed. The wound may further evolve and become covered by thin eschar. Evolution may be rapid, exposing additional layers of tissue even with optimal treatment.⁷

     The addition of this definition of DTI was motivated by some clinicians’ criticism of Shea’s⁸ classic pressure ulcer staging system that sometimes allegedly led to inaccurate staging of ulcers, which consequently biased treatment.⁷ The NPUAP phrased and refined the definition using online evaluation from stakeholders with regard to face validity, accuracy, clarity, succinctness, utility, and discrimination. Phrasing based on the online input was discussed at a consensus conference and fine-tuned to create the final definitions published in 2007.⁷

     As reflected in the medical literature,^1-6 and from the definition itself,⁷ the phrasing of the definition of DTI was based on case reports, clinical observations, and experience. No validity or reliability testing was conducted. This author’s laboratory, which for several years has focused on etiological studies of DTI primarily related to characterizing biomechanical factors that affect the onset and progression of DTI, has gathered basic scientific information that explains, supports, and strengthens the NPUAP’s definition of DTI. However, some recent findings suggest that a re-evaluation of the wording and perhaps changes in future definitions of DTI are needed.

     The purpose of this paper is to: 1) analyze the definition of DTI from a bioengineering, basic science point of view by separating the definition into parts — each dealing with a different physical measure — and critically discussing each part relevant to underlying biological, physical, biomechanical, and biochemical mechanisms involved in DTI and 2) summarize and describe current DTI definition concerns and limitations.

Addressing Parts of the Definition

     Part 1: Purple or maroon localized area of discolored intact skin or blood-filled blister. This article assumes that DTIs occur in skeletal muscle layers adjacent to bony prominences. Considering the relatively high vulnerability of muscle to mechanical deformation and ischemia compared with, for example, subcutaneous fat and skin, this is the most probable scenario⁹ if heel injuries are excluded.

     The color of skeletal muscle tissue is an indicator of its oxygenation — red: normoxic, bluish: hypoxic or anoxic. Despite serving as a rough indicator and subjective measure that depends on illumination and temperature, documentation of muscle color (along with the experience of the observer) has been proven clinically useful in, for example, assessing the suitability of muscle flaps for implantation.¹⁰ In such flap evaluations, a rosy color indicates well-perfused tissue at the body’s temperature that has not swelled and will respond to finger pressure by rapid capillary refill when pressure has been removed. A pale color indicates a deviation from the body’s temperature, mild edema, and a delayed capillary refill in response to finger pressure. White or dark blue muscle tissues are also likely to show massive edema and no capillary refill.¹⁰

     Concerns and limitations. Salcido¹¹ recently noted that “alterations in skin color usually tell us about the degree of deep tissue injury,” which may be an extrapolation of techniques used by surgeons in flap evaluation. Unfortunately however, this is not straightforward, as demonstrated in computer-generated images (see Figure 1). Skin color as observed in ambient white light is a superposition of colors of overlying soft tissue layers. For example, the skin color visible to the observer in Figure 1a is a superposition of the red color of skeletal muscle, the white-yellowish color of a partially transparent layer of subcutaneous fat, and the rosy color of partially transparent skin (layer transparency level was taken as 50% in all of the simulations shown in Figure 1). If it is assumed that skeletal muscle tissue becomes locally ischemic in the process of DTI and subsequently turns bluish, this can be manifested on the skin surface as a purple spot if the skin is lightly pigmented (see Figure 1b) or as a maroon spot if the skin is tanned (see Figure 1c), despite the fact that the color of muscle itself is the same in these two simulation cases.

     Although necrotic muscle tissue is typically very dark (almost black), as simulated in Figure 1d,e, manifestation of muscle necrosis in terms of skin color is remarkably different for a lightly pigmented simulated skin (see Figure 1d) compared to a tanned skin (Figure 1e). It is interesting to note that because of the effect of skin pigmentation, the simulated skin colors in Figure 1c (ischemic muscle) and Figure 1d (necrotic muscle) appear similar, even though clinically, these are completely distinct conditions of muscle viability.

     Therefore, the simulations in Figure 1 indicate that a deviation of the local skin color from the surroundings is an indication that a DTI might be present but by no means can the color be used to quantify the level of injury or the prognosis. This also relates to the further description of a DTI provided by the NPUAP⁷ that “Evolution may include a thin blister over a dark wound bed” and “Deep tissue injury may be difficult to detect in individuals with dark skin tones”. These statements imply that the actual (deep) wound colors may be masked by the natural skin tone of the individual or by some superficial skin eruption. The information in Figure 1 specifically indicates not only that a DTI might be difficult to detect in individuals with dark skin, but also that it might be misleading to extrapolate from clinical experience gained while treating persons with a lightly pigmented skin to assess the skin of tanned individuals or persons with dark skin.

     In terms of technological development, in diagnosing and monitoring DTI, the computer images in Figure 1 indicate that automated color analyses of skin photographs taken in ambient white light will not work for diagnosis or severity assessment of DTI. Accordingly, future technological solutions to diagnose and quantify DTI based on photography perhaps should utilize invisible light photography techniques such as near-infrared¹¹ to bypass the problem of color masking and color mixing between semi-transparent tissue layers.

     Part 2: Damage of underlying soft tissue from pressure and/or shear. Soft tissues situated between a bony prominence and a support surface (eg, cushion or mattress) are focally distorted under the bone peak. A computer simulation demonstrates this effect using a rigid bone-like hemisphere model compressing a soft tissue layer (see Figure 2). Looking at a cross-section just under the bone peak model, it is possible to identify a site of highly intensified soft tissue deformations where tissues are simultaneously compressed, stretched, and sheared (see Figure 2b). Therefore, a DTI is formed in a soft tissue region subjected to compound mechanical loading. Thus, it is not practical or feasible (and perhaps meaningless) to separate individual contributions of pressure and shear loads from tissue damage. By processing magnetic resonance imaging (MRI) scans of patients with spinal cord injury or post limb amputation and scans of control subjects using computer models that are conceptually similar to the one used in Figure 2,^12-14 the author’s research group recently proved the co-existence of elevated compression, tension, and shear deformations and stresses in soft tissues overlying bony prominences, including both muscle and fat (see Table 1 for definitions for the components pressure and stress).

     Concerns and limitations. The current definition of DTI that refers to “pressure and/or shear” is inaccurate in the sense that it artificially separates pressure and shear and ignores tensional loads. Accordingly, a possible future improvement of the definition of DTI in this regard is to address “mechanical loading” or “tissue deformation” generically. Alternatively, it is possible to refer to each specific mechanical loading component that exists in the tissues — ie, compression, tension, and shear stresses. However, formal engineering terminology might be less appealing to the clinical community.

     Part 3: The area may be preceded by tissue that is painful, firm, mushy, boggy... In 2005 studies,¹⁵ the gracilis muscles (hindlimb adductors) of anesthetized rats were compressed in vivo to induce DTI. The stiffness of the gracilis was measured using an indentor probe pre-injury and after 15 minutes, 30 minutes, 1 hour, or 2 hours of continuous tissue deformation under pressure loads of 262.5 mm Hg or 525 mm Hg. With muscle cell death, the tissue was found to stiffen gradually by a factor of 1.2 for minimal pressure/time exposures (262.5 mm Hg for 15 minutes) and up to a factor of 3.3 for the maximal exposures (525 mm Hg for 2 hours). Researchers named this phenomenon local rigor mortis.¹⁶ Local rigor mortis is cell death-induced stiffening of muscle tissue that occurs locally in the wound site over the first several hours post-injury with a mechanism similar to rigor mortis in dead muscles of a corpse. Specifically, plasma membranes of apoptotic and necrotic muscle cells become more permeable than those of viable muscle cells, as recently demonstrated by Gawlitta et al¹⁷ in tissue-engineered model systems of DTI. Plasma membranes of dying muscle cells become more permeable to calcium ions (Ca2+). Unlike in living muscle cells, where energy is expanded to transport Ca2+ outward to the extracellular matrix, in dying cells, Ca2+ homeostasis is interrupted; calcium pumps function partially or not at all. The excessive Ca2+ activates the cross-bridge attachment between actin and myosin, which further causes a local “permanent” contraction area in the fresh wound site. The contraction area is stiffer than surrounding (non-damaged) muscle tissue and is probably the reason some clinicians report a firm region of tissue at the suspected DTI site.

     However, the firmness caused by contraction of dying muscle tissues only lasts until digestive enzymes start decomposing the necrotic tissues. Decomposition relaxes the local contractions and breaks down the tissue’s mechanical framework (ie, muscle fibers, collagen sheets) so eventually the wound site feels mushier or boggier than surrounding tissues when palpated. The forensic literature¹⁸ indicates that muscle tissue decomposition through activity of lysosomal intracellular digestive enzymes occurs 1 to 3 days post-mortem in a corpse. However, a longer time frame for decomposition is expected for a local nonviable inclusion in a living muscle tissue (contained within a living body) because the mass of the released digestive enzymes must be lower overall in a living body than in a corpse.

     Therefore, the process of local rigor mortis followed by tissue decomposition explains the diversity in qualitative descriptions of the biomechanical properties of the damaged tissues in the NPUAP’s definition of DTI — eg, firm versus mushy.

     Concerns and limitations. The result of a palpation examination will depend on the time point along the course of DTI development, as demonstrated schematically in Figure 3. Additionally, the mechanical stiffness of the wound site may serve as a useful indicator of the time of DTI occurrence. A firm wound site would indicate that the DTI was formed recently (several hours up to a day or so) before detection. A mushy or boggy wound site indicates the DTI is several days old. Therefore, the process described in the schematic curve in Figure 3 is implicated in litigation and reimbursement issues related to DTI, because in legal actions, the time when (which may imply where) the DTI occurred in a patient is important. A palpation examination of a DTI may be analogous to the technique used in forensic medicine for evaluation of the time elapsed since death, based on rigor mortis status.¹⁸ However, it should be emphasized that Figure 3 provides only general trends of changes in skeletal muscle stiffness as related to DTI based on animal model studies¹⁵ and the forensic literature.^18,19 The curve represented in Figure 3 is not suitable as presented for medical decision-making with regard to individual cases or for legal actions because of individual variations in the time course, which may depend on anatomical and biological variability in tissue responses to injury, ambient conditions (temperature, moisture), presence of diseases, the level of edema around the wound site, and other factors. More basic and clinical research is needed to characterize stiffness changes in and around DTI sites. Ultrasound-based elastography, which quantifies localized stiffness of deep tissues, is promising in this regard.^20,21

     Part 4: ...warmer or cooler as compared to adjacent tissue. Temperature is a useful physiological marker that can be measured with relative accuracy and monitored continuously in all clinical settings. In perfused tissues, local temperatures have been found to be a function of metabolic activity-related heat production, thermal conductivity, and heat convection.²² Heat convection, specifically, depends on microvascular perfusion; it has been shown empirically that a local temperature decrease of 2°C to 3°C in skeletal muscle may indicate an ischemic site.^23,24 Contrarily, active inflammation or infection leads to temperature increases of about 2°C²⁵ primarily caused by heat release from monocytes and inflammatory cells proportional to the local density of the cell population.²⁶

     Researchers recently measured the time course for development of pressure-related ischemia in deformed skeletal muscles in a rat model of DTI.²⁷ Specifically, the temperature of exposed gracilis muscles in hindlimbs of rats was measured immediately upon applying external pressures in the physiological range (90 mm Hg, 277.5 mm Hg, and 585 mm Hg) and every 10 minutes thereafter in 2-hour trials. The temperature of loaded muscle tissue was found to gradually decrease (on average) 2.4°C over 10 minutes after pressures were applied compared to the temperature in the contralateral, unloaded limb; the temperature then plateaued. The 10-minute time course was independent of the magnitude of the applied external pressure for the pressure range specified. A subsequent study by Liu et al²⁸ explained these findings by taking time-sequence micrographs of individual microvessels that were bent/stretched by external loads (loads on the capillaries were applied using restraining glass micropipettes in their experiments). Liu found that after capillaries were bent/stretched for approximately 3 minutes, erythrocytes accumulated at the curved capillary sites. After 10 minutes of bending/stretching, the capillaries were completely blocked by thrombi. Hence, these animal model studies^27,28 show that sustained soft tissue deformations, to an extent comparable to those occurring in human muscle tissues overlying the ischial tuberosities in seated paraplegic subjects,¹³ start to cause thrombosis in capillaries after approximately 10 minutes. This eventually causes perfusion failure that manifests as a 2°C to 3°C tissue temperature drop in the animal model.²⁷ A similar trend can be assumed for humans based on the study by Binzoni et al,²⁹ who compressed gastrocnemius (leg) muscles in subjects using an inflatable cuff and reported consequent localized temperature drops of ~2°C in the ischemic muscles.

     Concerns and limitations. Because the thermal status of deep tissues is masked by that of more superficial tissues, monitoring the perfusion status of deep tissues such as skeletal muscles by monitoring skin temperatures is impractical. For example, a local necrotic inclusion in muscle should be characterized by a locally lower temperature (caused by perfusion failure), but surrounding tissues may respond to the necrotic inclusion as inflammation. Thus, the involved area will produce heat because of macrophage activity that disintegrates the necrosis.³⁰ Hence, temperature measurements on the skin are unlikely to identify the true status of deep tissues because of interlayer masking effects analogous to the ones discussed with relation to wound color. A technological solution in this regard might be long-wave infrared imaging, which, unlike standard infrared thermography, can identify temperature changes in deep tissues.³¹

     Part 5: The wound may further evolve and become covered by thin eschar. Evolution may be rapid, exposing additional layers of tissue even with optimal treatment. The abnormal stiffening of injured muscle tissue during the first several hours of DTI has been discussed previously in this paper. The local changes in muscle tissue stiffness with onset of DTI, in turn, may affect the distributions of mechanical loads (such as tissue deformations) and the flow of forces per unit volume of tissue within and around the sites of initial injury (see Figure 3). For example, a relatively stiff inclusion that forms in skeletal muscle at the onset of DTI will increase tissue loads around it because of a basic principle from mechanical engineering that a stiff inclusion in a soft material causes stress concentrations around the inclusion (see Table 1 for the definition of stress concentrations). This effect can potentially expose additional, previously uninjured adjacent tissues to the intensified mechanical loads; thereby, widening tissue regions affected by sustained tissue deformations and obstruction or occlusion of capillaries. Eventually, additional cell death occurs at the margins of the newly formed DTI, which triggers additional tissue stiffening in an ongoing, positive-feedback injury spiral. This injury spiral of initial muscle tissue damage under bony prominences, causing a local rigor mortis stiffening effect that leads to additional muscle cell death, was identified by researchers in several studies using computer models.^15,16,32,33 These simulations were able to explain the clinical outcome of a crater-shaped injury, spreading and extending from the focal bone-muscle contact region throughout all soft tissue layers to the skin.^15,16,32

     Concerns and limitations. Recently, computer simulations¹⁶ demonstrated the time course of the spread of DTI depended on the level of muscle atrophy, radius of curvature of the ischial tuberosities, and mechanical properties of wheelchair cushions. DTIs were found to spread fastest between the first and second hour post initial injury. Thus, the evolution of a DTI via the above-described injury spiral may be rapid, particularly if an individual has atrophied muscles, which are more susceptible to deformation-induced damage.¹⁶ However, a point of concern is that computer simulations indicated a substantial variability in DTI progression rates depending on the internal anatomical characteristics of the individual, including (for example) thickness of gluteal muscle layers adjacent to the ischial tuberosities and radii of curvatures of the ischial tuberosities.^16,33 Because determining internal anatomical characteristics requires imaging (eg, ultrasound or MRI) and these measures often are not available to the medical staff at the point of care, it is difficult/impractical to identify the patients at the highest risk for DTI. Perhaps inexpensive imaging technologies specific for screening patients at potential risk for pressure ulcers and DTI could be developed for that purpose, based on recent advances in low-cost, high resolution ultrasound technology.³⁴ This will help identify patients with thin musculature and flattened ischial tuberosities — ie, persons at high risk for DTI on their buttocks according to biomechanical computer modeling¹⁶ — during routine patient evaluations that employ new DTI risk assessment scales that include internal anatomy characteristics as criteria.

Conclusion

     The phrasing of the relatively new NPUAP definition of DTI is based primarily on clinical experience. Reviewing the definition by separating the definition of DTI into parts — each dealing with a different physical measure — is convenient. The main part of the definition is neatly organized to describe changes to several physical measures of the affected tissues; it starts with color (purple or maroon), continues with mechanical loads (pressure and/or shear) and mechanical stiffness (firm, mushy, boggy), and ends with temperature (warmer or cooler). The analysis of the further description part of the definition used the same logical structure — ie, the basis of a physical measure or mechanism. Specifically, the parts that refer to skin/wound color (dark skin tones, dark wound bed) are reviewed in the context of color.

     Application of scientific data related to the biological, physical, biomechanical, and biochemical mechanisms involved in DTI strengthens some parts of the DTI definition but also suggests that future definitions should be refined with more succinct/accurate wording. For example, with regard to the anticipated biomechanical tissue stiffness changes at a DTI site described, it is suggested that in the future, accepted biomechanical terminology such as increased stiffness and decreased stiffness should be used to qualitatively describe changes in mechanical behavior of the tissues instead of using the somewhat graphic terms “mushy” or “boggy”. This is important because stiffness is a biomechanical variable that can be measured and expressed as a value, facilitating the development of medical instrumentation to evaluate the extent, progression, severity, and healing of DTI based on local tissue stiffness (eg, using ultrasound-based elastography^20,21) directly related to the formal definition of DTI. Through the interdisciplinary work of clinicians and bioengineers, basic science studies of DTI should quickly lead to the implementation of prevention programs and treatment options in the clinical setting. Such research and development requires a common ground of quantitative terminology and definitions across the different disciplines. Accordingly, at the present era of evolving jargons, staging systems, and injury definitions in the field of pressure ulcer studies, it appeared particularly important to provide this analysis of the recent definition of DTI from a bioengineering perspective for clinicians to use as a basis for future interdisciplinary discussions that hopefully will ensue.

Dr. Gefen is an Associate Professor, Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Israel. Please address correspondence to: Prof. Amit Gefen, Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, Tel Aviv 69978, Israel; email: gefen@eng.tau.ac.il.

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