Deep tissue injuries (DTIs) became a distinct classification of pressure injuries (PI) in 2009 following recognition that their presentation and pathogenesis differed from those of normal PI (Fletcher et al, 2017).
DTIs have been defined as:
‘purple or maroon localized area of discoloured 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.’
While the epidemiology of deep tissue injury remains to be fully elucidated, the clinical impact of these injuries can be significant. Recent retrospective studies have indicated that full thickness tissue loss can be expected in 9–14% of DTI cases. This illustrates the potentially significant impact of DTI on patients' physical and psychological health as well as economic burdens on healthcare services (Sullivan, 2013; Tescher et al, 2018).
Current understanding of PI pathology does not explain why some PIs, particularly DTIs, can develop rapidly and undermine viable tissue, whereas ‘normal’ PIs such as those defined within the I–IV grading system created by Shea (1975) in many cases affect only superficial tissues despite the higher vulnerability of deeper muscle tissues to pressure (Oomens et al, 2015).
A recent retrospective review of pressure ulcer root cause analyses challenged the previous consensus that 95% of grade II-IV PIs are avoidable, instead reporting that only 43% of grade II-IV PI are likely to have been avoidable had best practice been followed (Downie et al, 2013).
A later analysis conducted after reimbursement for hospitals for costs associated with hospital-acquired PI was ended in the US found that the incidence of grade III and IV PIs reduced after these payments were ended (Padula et al, 2015).
Notably, neither of these analyses included DTI as a distinct category of injury. It is possible, however, that DTIs that evolved may have been re-graded as grade III or IV PI and consequently included in these studies. This indicates the potential financial impact that evolved DTI may have on healthcare services even though it remains unclear why some DTIs become deep wounds and others do not. It is also possible that DTIs were included in statistics on non-DTI grade III-IV PIs that were prevented; this makes it difficult to determine if clinical outcomes associated with DTI can be influenced by preventive intervention.
It is also unclear if DTI is an appropriate name for injuries that often do not result in full thickness tissue loss (Tescher et al, 2018).
Overall, these issues indicate the controversial nature of DTI from epidemiological, clinical and economic perspectives.
This article discusses the current understanding of the aetiologies associated with deep tissue injury in contrast to normal PI based on evidence from clinical studies.
Animal studies
One of the earliest studies investigating the nature of pressure-related injuries was conducted by Husain (1953). This focused on the relationship between PI and bacterial infections rather than on the aetiology of the injury. Husain (1953) made two key observations that challenged the understanding of PI and indicated a potential explanation for the nature of DTI, which was not defined until much later in 2009 (Fletcher et al, 2017). These observations were: dermal tissue suffers more vascular damage than skeletal muscle when subjected to pressure; but skeletal muscle suffers more structural damage because of pressure than dermal tissue. This study used murine models, however, which potentially limits the extrapolation of these observations to human subjects because there are structural differences between murine and human tissues (Ansell et al, 2012).
A review by Bouten et al (2003) investigated whether PI starts in muscle tissues or can be only ‘skin deep’ as suggested by the most recent guidelines (EPUAP/NPIAP/PPPIA, 2019). The review established four key pathologies associated with PI, which are: occlusion of capillaries; occlusion of lymph vessels, mechanical deformation; and reperfusion injury. Bouten et al (2003) suggested that muscle may be more susceptible to PI because skeletal muscle has higher metabolic activity than dermal tissue. These metabolic requirements would make the tissue more prone to damage following a restriction of blood supply and amplify the accumulation of metabolic waste created by lymphatic occlusion (Bouten et al, 2003). They concluded that future studies should adopt a ‘hierarchic’ approach, using a combination of computer modelling and in vivo methodologies to yield more information on the nature of PI on deeper tissues; this is in recognition of the limitations of animal models and the ethical challenges inherent in testing on live human subjects.
This review was later supported by Berlowitz and Brienza (2007), who reviewed both computer model and animal studies as well as human punch biopsy studies on PI aetiology. According to the authors, stress (force applied per unit area) and strain (amount of tissue deformation) were demonstrably higher at the interior bone-buttock interface than at the skin surface, which suggests that deeper muscle structures are more susceptible to mechanical deformation damage as described by Bouten et al (2003).
It had been reported in porcine models that increased heat may lead to rises in metabolic activity, increasing the strain on muscle tissues because of the effects of vascular occlusion (Berlowitz and Brienza, 2007).
Despite the known limitations of animal models, porcine tissue is widely considered to be most like human and therefore most indicative of how human tissues may react to any given clinical phenomena (Vlig et al, 2019). This may indicate a potentially increased risk of DTI in human patients experiencing pyrexia, where muscle tissue may be prone to more damage because of the metabolic consequences of increased temperature combined with the lack of lymphatic draining and oxygen supply to dermal tissues caused by pressure. However, pyrexia is not recognised as a risk for PI in contemporary risk assessments tools (Coleman et al, 2013).
Finally, a punch biopsy study by Berlowitz and Brienza (2007) reported that grade I PIs, as per EPUAP/NPIAP/PPPIA guidance (2019), showed necrosis in subcutaneous tissues and subdermal haemorrhage, indicating that deeper damage may already be present in PI considered clinically to be superficial.
Ultimately, Berlowitz and Brienza (2007) concluded that superficial lesions commonly associated with pressure may be more likely to be caused by friction or moisture.
Although this review supports the developing concept that pressure universally creates damage in deeper tissues, it does not explain the differences in clinical presentation of deep PI compared to DTI as per the EPUAP/NPIAP/PPPIA (2019) definition. Specifically, these include the variation in skin colour changes and the ability of DTI to either ‘resolve’ or ‘evolve’, a phenomenon not observed in non-DTI PI.
A primary study by Stekelenburg et al (2008) adopted the hierarchic approach recommended by Bouten et al (2003). This study used a combination of in vitro and in vivo techniques to model the effects of pressure at cellular and tissue levels. According to Stekelenburg et al (2008), tissue necrosis is an apparent consequence of tissue acidification because of ischaemia and glucose depletion. This study used a murine model, which has been criticised in clinical studies investigating muscle function because of differences in mechanical structures of the tissues between mice and humans (Hu et al, 2017).
However, a primary in vitro study by Jacobs et al (2013) comparing the metabolism of murine and human muscle reported no statistically significant difference in mitochondrial activity between the species. This suggests that, although the effects of mechanical deformation on murine tissues may not be comparable to the those on human muscle, the impact of pressure on the metabolic processes within muscle cells may be similar in mice and humans.
Notably, Jacobs et al (2013) did not compare differences in cellular function between murine and human dermal tissues, making it unclear whether the observed deeper tissue damage observed in mice reflects the patterns of damage that may occur in human subjects exposed to the same pressures.
Overall, the Stekelenburg et al (2008) study reinforces the concept of metabolic stress and subsequent tissue necrosis as central mechanisms associated with the development of DTI and suggests that patients with impaired glucose metabolism may be at increased risk of deeper tissue damage.
Although diabetes and malnourishment are recognised as risk factors for PI development, other conditions potentially affecting glucose metabolism such as high melatonin levels (Garaulet et al, 2020), reductions in physical activity (Von Ah Morano et al, 2019) or dietary fat-induced impairments in glycaemic control (Parry et al, 2019) are not considered in current PI risk assessment tools (Coleman et al, 2013); this may impact the tools' clinimetric sensitivity by underestimating risk in patients who are at genuine risk for DTI.
Compartment syndrome theory of DTI development
According to Smart (2013), skeletal muscle is more vulnerable to reperfusion injuries than dermal tissue.
Smart (2013) illustrates this with data indicating that most DTIs occur on the heel (41%) and, to a lesser extent, the sacrum (19%). These areas have no distinct main blood supply and rely on dense collateral capillaries for their perfusion (Anderson, 1978). Smart (2013) argued that owing to the small and stiff musculature surrounding the sacrum and heel covering a rigid underlying fascia in both cases, these areas are prone to compartment syndrome following swelling caused by ischaemia and vascular occlusion. Ultimately, it is suggested that DTI should be referred to as ‘hypoxic reperfusion ulcers’ based on the proposed aetiology, with the outcome of pressure applied over the affected areas being entirely dependent on the metabolic situation of the patient (Smart, 2013).
The impact of the pathologies associated with PI, such as vascular occlusion, metabolic changes and increased mechanical strain in deeper tissues, suggest that deep damage to muscle and deeper tissues is inevitable in cases of prolonged exposure to pressure (Bouten et al, 2003; Stekelenburg et al, 2008). Smart's (2013) conclusion suggests that all DTIs are unavoidable from a nursing perspective and may be prevented only by medical intervention to create changes to the metabolic state of the patient.
However, this does not explain why normal PIs can occur in the same anatomical locations (heel or sacrum) as well as with the use of medical devices in anatomical locations that do not fit the compartment syndrome theory of DTI (Kayser et al, 2018).
Notably, in a review looking at whether PI are avoidable, Downie et al (2013) argued that DTI are often categorised as grade III ulcers or are not reported until a wound bed is visible, which does not always develop. For example, a retrospective study by Sullivan (2013) reported that in a sample of 128 patients with DTI, only 9.3% (n=12) experienced full-thickness tissue loss. This means that current incident reporting data is unlikely to support the view of Smart (2013) that DTI are largely unavoidable if the patient's metabolic status is not optimised because of inconsistencies and potentially inappropriate reporting of DTI as other types of PI. Inconsistencies in reporting will confound data indicating the proportion of DTIs considered avoidable.
In addition to this, root cause analyses for PI are often inconsistent in design and are likely to be poor indicators of patterns in clinical presentation and outcomes because they are widely perceived as a mechanism to apportion blame for clinical events (Samuriwo, 2015).
Animal model of DTI deterioration
A murine study by Sari et al (2015) produced the first model of DTI deterioration. The authors took a hierarchic approach, using a murine model in combination with a computer finite element model (FEM) in which the distribution of pressure through tissues was simulated and measured. Notably, the FEM results demonstrated higher levels of shear stress in deeper tissues at a simulated bone-tissue interface, supporting the early observations that deeper tissues are more vulnerable to pressure than dermal tissues (Husain, 1953).
Results from histological analysis and observation of the deterioration of induced DTI as per the EPUAP/NPIAP/PPPIA (2019) definition suggested that these wounds showed little infiltration of inflammatory cells or denaturation of dermal collagen (Sari et al, 2015). These findings are consistent with damage starting within the deeper tissues.
However, Sari et al (2015) also reported that 100% of the DTI produced in the murine models deteriorated to produce deep wounds. This is inconsistent with the retrospective study by Sullivan (2013), in which only 9.3% of DTI deteriorated to form wounds. This may reflect variations in clinical assessments of PI, which are most often carried out by nurses whose training and understanding of PI are often inconsistent (Aydin et al, 2019; De Mayer et al, 2019).
Alternatively, the clinical appearance of the injuries created in Sari et al's (2015) study may be a result of bruising because mice have a loose skin (Vlig et al, 2019), which is more prone to bleeding into tissues when compressed (Vanezis, 2001). Notably, Sari et al (2015) concluded that the darker appearance of DTI was likely due to bleeding into the tissues owing to the shearing of blood vessels.
Ultimately, it is unclear if the wounds created in Sari et al's (2015) murine model are representative of the pathology involved in DTI in humans, which has been hypothesised to be related to metabolic stresses (Berlowitz and Brienza, 2007) or a potential compartment syndrome effect (Smart, 2013), or be more comparable to the simpler pathology of traumatic bruising (Vanezis, 2001). The current consensus on the development of DTI suggests that tissue damage is not typically visible for 24-72 hours after the exposure to pressure (Fletcher et al, 2017); this is in contrast to the Sari et al (2015) study in which ‘superficial ulcers’ were reported in all of the test animals from the day of wounding. This is more suggestive of a traumatic injury than the pathology typically associated with DTI.
Novel approaches
More recent studies have adopted other methodologies to demonstrate the aetiology of DTI. These include the use of magnetic resonance imaging (MRI) (Nelissen et al, 2018) and biomarkers to indicate the source and magnitude of tissue damage (Traa et al, 2019).
Notably, Nelissen et al (2018) demonstrated that damage to deep muscle is visible on an MRI scan for up to 2 weeks following mechanical deformation periods of only 2 hours. This was later supported by a study by Traa et al (2019), who demonstrated that concentrations of myoglobin and troponin in blood and urine samples rise following mechanical compression, which provides strong evidence of damage to muscle tissues even in the absence of clinically visible tissue damage at the skin surface. However, in both studies, no prospective observation of changes in the superficial tissues was conducted, making it difficult to conclude that the damage to muscle tissues observed or determined by biomarkers is unique to DTI or inevitable in all mechanically loaded tissues.
Challenges in DTI diagnosis
Issues associated with the unique clinical appearance of DTI and how this may relate to its aetiology were investigated in a case series by Solmos et al (2019). They highlighted the significant number of potential alternative diagnoses to DTI that are consistent with the purpura-type lesions described in the EPUAP/NPIAP/PPPIA (2019) definition of DTI, which include vasculitis, warfarin-induced necrosis and calciphylaxis.
Solmos et al (2019) concluded that lesions caused by non-pressure related pathologies may frequently be confused with DTI as there is a lack of effective assessment methods to differentiate between DTI and other lesions because DTI aetiology is poorly understood.
This reflects current methodologies adopted to investigate DTI; these rely on FEM or animal models and seek to demonstrate damage in deep tissues caused by mechanical deformation, vascular shearing or metabolic stresses but do not demonstrate any clear differences in aetiology between ‘normal’ PI and DTI because of a lack of concurrent observations of changes in the skin or use of human subjects (Nelissen et al, 2018; Traa et al, 2019).
Conclusion
Clear aetiological processes have been described, observed and measured in cases of PI (Bouten et al, 2003; Stekelenburg et al, 2008; Traa et al, 2019). These processes include the mechanical deformation of cells with concurrent occlusion of vascular structures, which put additional metabolic and biochemical strain on tissues, leading to inflammation and necrosis (Berlowitz and Brienza, 2007).
However, controversies over the aetiological features of DTI remain. More recent reviews have suggested the unique clinical presentation of DTI may be due to a compartment syndrome effect created by the higher metabolic requirements of deep muscle tissue combined with a limited vascular supply and stiff fascia surrounding the areas where DTIs are commonly found (heels and sacrum) (Smart, 2013). However, this does not explain why DTIs caused by medical devices may occur at any location on the body (Kayser et al, 2018).
Primary studies aiming to elucidate the aetiology of DTI rely heavily on animal models and FEM to demonstrate the distribution of pressure (Sari et al, 2015; Traa et al, 2019). Ultimately, it may not be possible to extrapolate the results from these studies to human subjects because of structural differences in tissues between animals and humans (Ansell et al, 2012). Notably, the loose skin of mice has a high risk of bruising (Vanezi, 2001), so murine models may mimic the clinical appearance of DTI when exposed to pressure, which explains the early observation of DTI in studies modelling DTI deterioration (Sari et al, 2015).
Currently, there are no major studies are investigating the impact of comorbidities on tissue responses to pressure in humans and DTI may consequently be diagnosed inappropriately where other pathologies are the cause of similar purpuric lesions (Solmos et al, 2019). Future studies should focus on the aetiological differences between normal PI and DTI, taking into consideration the presence of comorbidities not included in FEM or animal studies.
It is also notable that before the 2009 definition and inclusion of DTI by the EPUAP in the widely used PI grading system (Fletcher et al, 2017), varying definitions of DTI were used in studies investigating its aetiology, which potentially limits the value of these studies and whether they were investigating injuries consistent with the current definition of DTI.
Consistent reporting and follow-up of DTI may, ultimately, help provide a data set from which to better establish the epidemiological features of DTI to help guide future prospective studies investigating potential aetiologies of these unusual injuries.