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World Journal of Emergency Surgery : WJES logoLink to World Journal of Emergency Surgery : WJES
. 2025 Jul 31;20:66. doi: 10.1186/s13017-025-00605-7

Tailored Negative Pressure Wound Therapy with instillation in diabetic, hypertensive, and obese patients-when guideline treatment is not enough: a case series and a proposal for the ANSWER score

Orestis Ioannidis 1,✉, Elissavet Anestiadou 1, Konstantinos Zapsalis 1, Konstantinos Siozos 1, Ourania Kerasidou 1, Savvas Symeonidis 1, Stefanos Bitsianis 1, Manousos-Georgios Pramateftakis 1, Efstathios Kotidis 1, Ioannis Mantzoros 1, Konstantinos Angelopoulos 1, Barbara Driagka 1, Angeliki Cheva 2, Stamatios Angelopoulos 1
PMCID: PMC12312497  PMID: 40739263

Abstract

Background

Wound healing is challenging in cases of impaired microcirculation, leading to wound chronicity, decreased quality of life, and increased morbidity. Surgical site infections (SSIs) pose a significant challenge in diabetic, hypertensive, and obese patients due to impaired microcirculation. Negative pressure wound therapy (NPWT) is a widely used adjunct in wound management, but its optimal parameters in this subgroup remain uncertain. Tailored management is essential, taking into consideration tissue perfusion status and the potential benefit of novel strategies for tissue healing.

Methods

We report a case seires of three obese patients with diabetes mellitus type 2 and arterial hypertension who developed severe SSIs after abdominal surgery, with extended flap mobilization and were managed with tailored NPWT strategies, including lower negative pressures, NPWT with instillation and dwell time (NPWTi-d), reticulated open cell foam dressings with through holes (ROCF-CC), and ultrasonic-assisted wound debridement (UAW). Based on these cases, we propose the ANSWER score (tAilored Negative presSure Wound thErapy in micRoangiopathy) to optimize NPWT pressure settings.

Results

In Patient 1, NPWT using silver dressings was initiated at a continuous pressure of -125 mmHg, but after extended necrosis developed, the negative pressure was reduced to -50 mmHg. In Patients 2 and 3, a continuous NPWT was set at -50 mmHg, which is the lower value of the available negative pressure range for the system used, resulting in significantly fewer necrotic areas. Dressings were changed every 48–72 h and culture-directed antibiotics were administered to all patients. Our findings suggest that the use of NPWT remains a basic element in promoting acute and chronic wound healing. Innovative techniques such as NPWTi-d, ROCF-CC, and UAW debridement, combined with low negative pressure levels, may achieve optimal results in patients with microangiopathy. Microcirculation plays a crucial role in wound healing, since impaired healing and a low rate of tissue regeneration have been observed in patients with compromised tissue perfusion, such as patients with diabetes, obesity, or arterial hypertension. However, the use of NPWT in patients with microangiopathy and extensive tissue dissection at the default operating pressure of -125 mmHg may lead to further ischemic necrosis. Based on our case series, a clinical score (ANSWER score- tAilored Negative presSure Wound thErapy in micRoangiopathy) is proposed as a useful tool that reflects the ideal level of negative pressure for patients with impaired microcirculation. The ANSWER score assigns risk factors (obesity, arterial hypertension, diabetes) a point each, reducing NPWT pressure accordingly (-25 mmHg per point from − 125 mmHg).

Conclusions

Tailored NPWT settings, based on the ANSWER score, may enhance wound healing outcomes in patients with microangiopathy. Further clinical studies are warranted to validate this approach.

Keywords: Surgical site infection, Diabetes, BMI, Obesity, Hypertension, Microangiopathy, Instillation, Negative pressure wound therapy, NPWTi-d, Postoperative soft-tissue defect

Background

Surgical site infections (SSIs), defined as infections occurring within 30 days after a surgical procedure, or within one year (when permanent implants are present), represent one of the most frequently encountered types of hospital-acquired infections [1]. SSIs are consistently associated with decreased patient quality of life, as well as increased mortality rates and healthcare costs due to prolonged hospital stays and increased rate of reoperations and readmissions [2]. A wound, depending on the severity of the infection, is characterized as contaminated, colonized, critically colonized, or infected [3]. Wound infection leads to increased metabolic procedures locally, promotes a proinflammatory response, and triggers the chemotaxis of monocytes, macrophages and leukocytes in the wound bed. In addition, the release of cytokines, which leads to vasoconstriction and decreased blood flow to the wound bed, and the accumulation of metabolic products, such as endotoxins and metalloproteinases, produced by bacteria, negatively affect all stages of wound healing, resulting in significantly decreased wound healing rates [4].

In addition to infection, impaired tissue perfusion plays a crucial role in impaired wound healing. Chronic conditions, including hypertension, obesity, diabetes mellitus, and dyslipidemia, are characterized by structural and functional changes in the microvascular network of target organs [5]. First, diabetic patients are characterized by impaired and prolonged wound healing, regardless of the initial cause of the wound [6]. Circulatory dysregulation, which affects both microvascular and macrovascular circulation, is the leading cause of delay or failure of wound healing in these patients [7]. More specifically, in diabetic patients, small arteries are characterized by severe hypertrophic remodeling and increased microvascular permeability, and these changes are mainly induced by a chronic hyperglycemic state [5]. Hypertension is a risk factor for sufficient wound healing because it promotes chronic changes in the wound bed microcirculation. Small arteries and arterioles respond to a prolonged hypertensive state through luminal narrowing, vessel wall remodeling and an increase in the wall: lumen ratio. In addition, hypertension promotes microvascular rarefaction, which is defined as a reduction in the total length of small vessels within a specific tissue volume [5].

There is an established association between obesity and deficient wound healing. The secretion of leukotriene B4 by adipocytes, which impairs the remodeling phase of healing by macrophage M2 polarization, combined with reduced adiponectin production, affects the remodeling phase of wound healing. In addition, the levels of inflammatory mediators and insulin-related signaling proteins, including leptin and resistin, are increased in obese patients and are associated with delayed wound healing [8]. In addition, excessive adipose tissue is not accompanied by adequate new vessel formation, leading to a fibrotic microenvironment [9].

Vacuum-assisted closure, also called negative pressure wound therapy (NPWT), represents a powerful and promising tool for the management of complex acute and chronic wounds, as well as infected and critically colonized wounds [4]. The main mechanisms of NPWT application include tissue macrodeformation, drainage of extracellular discharge, stabilization of the microenvironment of the wound bed, and tissue microdeformation [10]. Experimental studies have shown that the application of NPWT promotes perfusion, reduces tissue edema and promotes granulation tissue production via microstrain [11]. The majority of cases reported in the literature applied a negative pressure of -125 mmHg for wound management [12]. However, studies investigating special management requirements for patients with microvascular disease, such as diabetic, hypertensive or obese patients, are scarce. Early and efficient management of wound infection and enhancement of tissue repair are vital for sepsis control [7].

The aim of this study was to elucidate the special requirements of NPWT in patients with microvascular dysfunction. The following case reports are presented in accordance with Surgical CAse REport (SCARE) guidelines, following the ethical standards set forth in the 1964 Declaration of Helsinki [13]. Patients were thoroughly informed, and written informed consent was obtained for publication of the present case reports and accompanying images. Copies of written consent are available for review by the Editor-in-Chief of this journal.

Methods and results

Patient 1

A 59-year-old female with a body mass index (BMI) of 33 kg/m2 underwent open repairing with onlay mesh placement for a large ventral incisional hernia. Her medical history included arterial hypertension, type 2 diabetes mellitus, dyslipidemia, and generalized anxiety disorder. On postoperative day (POD) 7, the patient exhibited surgical wound drainage and increased exudate discharge (Fig. 1), due to SSI with Enterococcus faecalis. The patient was prescribed ampicillin/sulbactam and underwent surgical debridement and daily wound changes with alginate dressings. On POD 9, a defect of 14 cm × 12 cm and 4 cm in depth was noted. NPWT (3 M™ V.A.C.® Therapy, 3 M Health Care, San Antonio, TX, USA) using silver dressing (3 M™ V.A.C.® Granufoam Silver™ Dressing, 3 M Health Care) was initiated at a continuous pressure of -125 mmHg. The dressings were changed approximately every 72 h. Results of new culture swab tests revealed Pseudomonas aeruginosa, for which meropenem was administered. Surgical debridement was necessary at every change due to continuous subcutaneous tissue necrosis, leading to extensive soft tissue loss. To address this adverse effect, NPWT pressure was reduced to -50 mmHg, and significantly less nonviable tissue was observed on the next dressing change. After 21 days, instead of sharp debridement, ultrasonic-assisted wound debridement (UAW) (SonicOne® O.R. Ultrasonic Debridement System, Bioventus Surgical, Durham, NC, USA) was used to perform surgical debridement while preserving healthy tissue. On POD 30, swab tests indicated Pseudomonas aeruginosa, Enterococcus faecium and Staphylococcus hemolyticus. On POD 35, NPWT with instillation and dwell time (NPWTi-d) was initiated using reticulated open cell foam dressings with through holes (ROCF-CC) to solubilize and remove thick exudate, nonviable tissue, and infectious material between dressing changes. NPWTi-d therapy parameters included the instillation of 120 mL of betaine (0.1%) and polyhexanide (0.1%) solution (Prontosan, B. Braun Medical, Bethlehem, Pennsylvania) with a 10-minute dwell time followed by six hours of continuous negative pressure at -50 mmHg (Fig. 2). Dressings were changed every 72 h, and UAW was applied at each dressing change. NPWTi-d was discontinued after 40 days because wound healing was observed (Figs. 3, 4 and 5). The wound presented significant granulation tissue, and NPWTi-d therapy was discontinued for NPWT with silver dressings using − 50 mmHg continuous negative pressure and dressing changes every 48–72 h. After another 20 days, significant epithelization was observed. NPWT was discontinued, and alginate dressings were used. Complete wound closure without grafting was achieved at approximately 90 days after the operation.

Fig. 1.

Fig. 1

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Wound drainage and increased exudate discharge of an infected incisional ventral hernia, with Enterococcus faecalis infection revealed in swab cultures

Fig. 2.

Fig. 2

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Wound bed after ultrasonic-assisted wound debridement and negative pressure wound therapy with instillation using a reticulated open cell foam dressing with through holes (ROCF-CC) and instillation of a wound solution containing 0.1% betaine and 0.1% polyhexanide with a 10-minute dwell time followed by 6 h of continuous negative pressure at -125 mmHg. (A) External view of the wound; (B) View of the interior of the wound

Fig. 3.

Fig. 3

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Wound healing of the infected surgical bed on POD 53

Fig. 4.

Fig. 4

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Wound healing of an infected surgical bed on POD 73

Fig. 5.

Fig. 5

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Wound healing of an infected surgical bed on POD 90

Patient 2

A 49-year-old female presented five days after abdominal myomectomy with a Proteus mirabilis SSI. She had a BMI of 42 kg/m2 and a medical history of arterial hypertension, type 2 diabetes mellitus, and asthma. She was treated empirically with ciprofloxacin and received UAW. After surgical debridement, NPWTi-d using a ROCF-CC dressing was initiated. The NPWTi-d therapy parameters included the addition of 150 mL of betaine (0.1%) or polyhexanide (0.1%) solution with a 10-minute dwell time, followed by six hours of continuous negative pressure at -50 mmHg. The dressings were changed every 72 h. NPWTi-d was utilized for 20 days. On POD 24, the surgical site showed signs of granulation. Standard NPWTi-d was discontinued with the use of silver dressings and continuous negative pressure of -50 mmHg. The patient was discharged home on POD 25, and dressing changes were recommended every 72 h in our outpatient department. During the follow-up period, healthy granulation tissue developed in the wound bed (Figures 6, 7 and 8). After 33 days of NPWT (POD 58), the alginate dressing was discontinued, and the dressing was changed every two days (Figs. 9, 10 and 11). Complete wound bed coverage with healthy granulation tissue was achieved on POD 88, after 53 days of NPWT (Fig. 12).

Fig. 6.

Fig. 6

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The surgical wound was opened and drained and afterwards surgical debridement was performed utilizing an ultrasonic-assisted wound debridement device on the day of presentation (POD 5)

Fig. 7.

Fig. 7

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View of the wound on POD 25, when the patient was discharged home with silver dressings and standard NPWT at -50 mmHg

Fig. 8.

Fig. 8

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On POD 35, healthy granulation tissue developed in the wound bed during the use of silver dressings and standard NPWT

Fig. 9.

Fig. 9

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The patient’s wound on POD 58, when NPWT was discontinued for alginate dressings

Fig. 10.

Fig. 10

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The wound on POD 70

Fig. 11.

Fig. 11

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The wound on POD 80

Fig. 12.

Fig. 12

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The wound on POD 88

Patient 3

A 55-year-old female underwent open repair with onlay absorbable mesh for a large incisional ventral trocar hernia post laparoscopic cholecystectomy, with an aponeurosis defect of approximately 8 cm. She had a BMI of 39 kg/m2, arterial hypertension and type 2 diabetes mellitus. The use of NPWT on closed surgical wounds (3 M™ Prevena™ Incision Management System, 3 M Health Care) was initiated with a negative pressure of -125 mmHg, and the patient was discharged home. At POD 7, on outpatient follow-up, subcutaneous surgical drains and the closed-incision NPWT system were removed (Figs. 13 and 14).

Fig. 13.

Fig. 13

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The incision for ventral hernia repair was made on POD 7, when the subcutaneous closed surgical drains were removed

Fig. 14.

Fig. 14

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The extent of the necrotic infection, occupying subcutaneous tissue and the mesh from the level of the umbilicus up to the pubic symphysis on POD 14

On POD 14, the patient presented with severe sepsis due to necrotizing SSI involving Finegoldia magna and Staphylococcus epidermidis. The patient was febrile, hypotensive, tachycardic, and had impaired consciousness, while the surgical site presented extended necrotic tissue and purulent smelling drainage. CT scan revealed necrotic infection, occupying subcutaneous tissue and the mesh from the level of the umbilicus to the pubic symphysis (Fig. 15). Subsequently, the patient underwent extended surgical debridement and mesh removal. The peritoneal cavity showed no signs of infection or inflammation. After second-look control and verification of successful septic source management, the closed fascia was checked, and no signs of necrosis were detected. NPWTi-d with ROCF-CC dressings was initiated by the instillation of 300 mL of a polyhexanide solution with a 20-minute dwell time, followed by six hours of continuous negative pressure at -50 mmHg. The dressings were changed every 72 h. On POD 45, placement of an absorbable poly-4-hydroxybutyrate (P4HB) onlay mesh was performed. NPWTi-d with ROCF-CC dressings was reinitiated with the same abovementioned therapeutic parameters. On POD 65, granulation tissue was observed covering the surface of the mesh (Fig. 16). After another 20 days, NPWTi-d was discontinued, and standard NPWT with silver dressings was initiated with changes every 72 h as an outpatient treatment (Fig. 17). After another 30 days of NPWT, the patient was referred to plastic surgeons, where a skin graft was placed (Fig. 18).

Fig. 15.

Fig. 15

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On POD 65, granulation tissue formed on the surface of the mesh

Fig. 16.

Fig. 16

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On POD 85, NPWTi-d was discontinued with silver dressings

Fig. 17.

Fig. 17

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The wound on POD 100

Fig. 18.

Fig. 18

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On POD 115, the patient was sent to the plastic surgery department to receive a skin graft

Development and rationale of the ANSWER score

NPWT is widely recognized for its role in promoting wound healing; however, its standard application at -125 mmHg may not be suitable for patients with microangiopathy, as excessive negative pressure can exacerbate ischemia and tissue necrosis [10]. Microvascular impairment is a known complication of diabetes mellitus, arterial hypertension, and obesity, which are all associated with endothelial dysfunction, reduced capillary density, and compromised tissue oxygenation [5].

In this study, we propose the ANSWER score (tAilored Negative presSure Wound thErapy in micRoangiopathy) as a structured approach to customizing NPWT parameters for patients with microcirculatory compromise. The objective of the ANSWER score is to prevent excessive ischemic insult by modulating NPWT pressures according to the severity of microvascular dysfunction. The ANSWER score was developed based on pathophysiological principles and empirical observations from our case series. The following conditions were identified as major contributors to microvascular dysfunction:

  • Diabetes mellitus: Associated with capillary basement membrane thickening, endothelial dysfunction, and impaired vasodilation, leading to reduced tissue perfusion and delayed wound healing [6].

  • Arterial hypertension: Induces microvascular rarefaction, characterized by a reduction in capillary density and luminal narrowing, which diminishes oxygen delivery to tissues [5].

  • Obesity: Results in adipose tissue hypoxia, chronic inflammation, and impaired angiogenesis, contributing to poor wound healing outcomes [8].

Based on the hypothesis that excessive negative pressure may further compromise tissue perfusion in patients with microangiopathy, we developed the following pressure adjustment scale (Table 1). Given their independent and synergistic effects on microvascular perfusion, each of these conditions was assigned a score of one point in the ANSWER model.

Table 1.

The ANSWER score (tAilored Negative pressure Wound thErapy in micRoangiopathy)

Risk Factor Assessment
Microangiopathy risk factor Score Lowering NPWT Pressure
Obesity 1 -25 mmHg
Diabetes Melitus 1 -25 mmHg
Arterial Hypertension 1 -25 mmHg
ANSWER score calculation
Risks Factors Present ANSWER score Recommended NPWT Pressure
1 1 -100 mmHg
2 2 -75 mmHg
3 3 -50 mmHg
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For each risk factor present, the NPWT pressure is reduced by 25 mmHg from the standard − 125 mmHg, based on clinical observations suggesting that lower pressures reduce tissue necrosis and enhance granulation formation in patients with microvascular disease. In our case series, all three patients had diabetes, arterial hypertension, and obesity (ANSWER score = 3), leading to an NPWT setting of -50 mmHg, which was associated with reduced necrosis and improved healing dynamics compared to standard NPWT parameters.

Discussion

Wound healing is a complex cascade of events involving the continuous coordination of different types of cells, cytokines and biomolecules. However, the wound healing process can be divided into four overlapping discrete phases: (i) coagulation and hemostasis, (ii) inflammation, (iii) proliferation, and (iv) remodeling of the reconstituted tissue [14]. Hemostasis begins immediately after any injury affecting skin integrity, with vascular constriction of the wound bed [15]. Platelet activation and local cellular interactions release numerous cytokines, such as transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF). This indicates the beginning of the inflammatory phase, which is characterized by neutrophil and lymphocyte chemotaxis as well as monocyte infiltration and differentiation into macrophages [16]. Barman et al. suggested that wound macrophage dysfunction is associated with insufficient wound healing among diabetic patients [17]. The proliferation phase lasts from 3 days to 2 weeks after injury and involves the reconstruction of the extracellular matrix in the wound bed [18]. Finally, during the final remodeling phase, granulation tissue is replaced by scar tissue. The main procedures during these phases are gradual replacement of type III reticular collagen with type I fibrillar collagen and vascular maturation and regression [15].

In 1993, Fleischmann et al. were the first to report the use of a vacuum sealing device connected with drainage tubes into polyvinyl foam for the management of soft tissue damage in 15 patients with open fractures [19]. The system is composed of four main components: (1) the dressing, which is placed into the wound; (2) a special semiocclusive drape, which isolates the wound bed and filling material from the atmosphere; (3) a connecting tube; and (4) a vacuum device combined with a collection canister [20]. NPWT is based on four main mechanisms: (1) shrinkage of wound edges or macrodeformation, (2) microdeformation at the dressing-wound bed interface, (3) removal of wound fluids and infectious materials, and (4) stabilization of the wound microenvironment [10]. In addition, numerous other processes, including angiogenesis, neuro-genesis, promotion of granulation tissue formation, and cellular proliferation, differentiation, and migration, have also been reported to be involved in wound healing with the use of NPWT [20].

Macrodeformation is defined as wound shrinkage after the application of subatmospheric pressure transduced through the collapse of pores onto the wound surface. A negative pressure of -125 mmHg applied with polyurethane ether foam can lead to a decrease in dressing volume of 80%, which causes shrinkage of the wound edges. The degree of tissue contraction is related to the elasticity of the underlying tissues. The latter is extremely important in obese patients with large abdominal wall defects, in whom NPWT results in substantial three-dimensional shrinkage [21]. Another basic mechanism of action of NPWT is microdeformation, which is defined as the generation of microscopic waving movement on the wound surface due to increased tissue tension and mechanical stress caused by dressing suction. Microdeformation provides mechanical stimulation, which causes a cascade of interactions between tissue and foam at the microscopic scale [22]. Changes in cellular procedures induced by mechanical forces are described under the term mechanotransduction, which, in the case of NPWT, is achieved by the development of shear and deformation forces due to the movement of fluids through the cellular matrix [10, 23–25].

Tissue pressure is defined as the mechanical pressure measured within the tissue. In other words, tissue perfusion is identical to interstitial hydrostatic pressure. When this pressure is greater than the capillary intravascular pressure, capillary collapse occurs, occluding tissue perfusion [26]. An interesting phenomenon observed more frequently during the use of circumferential dressings or in cavitary wounds, where the upper surface of the dressing and surrounding skin are at the same level, is the increased extracellular pressure in the tissue below the wound bed due to compression induced by wound shrinkage. The mechanism behind this phenomenon is the compression of underlying tissue after the suction of air and the reduction in foam volume, while the pressure on the tissue under the foam also depends on the distance from the foam-wound contact surface and the time of NPWT application [20]. These results have also been verified by Kairinos and colleagues, who found that all types of NPWT dressings provoke a hyperbaric state in the underlying tissue substance, directly proportional to the negative pressure used. In addition, the increase in pressure of tissue dispersed with increasing distance from the wound edge increases, with the maximum pressure measured recorded 1 cm from the skin [27]. Similar results were obtained in a study on three types of human wounds, circumferential, noncircumferential, and cavitary, by the same team, suggesting that the mean pressure of the underlying tissue increased proportionately to the amount of suction applied, while the effect of NPWT on the underlying tissue was less intense after 48 h. As a result, Kairinos et al. concluded that increased substance pressure and a hyperbaric state caused by NPWT may jeopardize tissue perfusion and increase ischaemia-related complications, especially in tissues with ambiguous or borderline perfusion [28]. Despite Murphy et al. who reported that the negative effects of NPWT do not extend significantly beyond 1 mm from the wound surface and cannot produce a hyperbaric state or decreased local perfusion, both in a rabbit model and in isolated muscle tissue [29], Kairinos et al. reported that technical errors in transducer placement may have led to a false measurement of underlying tissue pressure [26]. The state of the hypoperfusion zone at the wound edge is also supported by Wackenfors and colleagues, who reported that soft tissue in close proximity to the wound edge is characterized by decreased perfusion. The extent of the hypoperfused zone increases with decreasing negative pressure, meaning that greater hypoperfusion is noticed at higher levels of negative pressure, and this phenomenon is especially noticeable in subcutaneous tissue compared to muscular tissue, reaching up to 1.9 cm for a pressure of -100 mmHg, decreasing to 1.8 cm at -50 mmHg and increasing to 2.5 cm at -200 mmHg. At distances greater than 4.5 cm for subcutaneous tissue, microvascular blood flow is independent of the subatmospheric pressure applied [30]. Furthermore, the application of intermittent NPWT promotes the healing process since it limits possible chronic ischemia of the hypoperfused zone through repeated pressure release and triggers reactive hyperemia of this zone, thus permitting the use of higher negative pressure levels than may be used with continuous NPWT therapy [31]. Considering that adequate blood flow is essential for granulation tissue formation, a tailored strategy of lowering negative pressure may be necessary for preventing ischemic complications in poorly perfused tissue during treatment.

Despite large volumes of research regarding the modulation of angiogenesis by NPWT, data are scarce. Multiple in vivo and in vitro studies have proven the presence of a hypoperfused zone close to the dressing foam due to microdeformation [27]. This hypoxic gradient leads to the activation of hypoxic macrophages and the overexpression of hypoxia-inducible factor-1α, which is responsible for increased vascular endothelial growth factor (VEGF) expression. Indeed, experimental studies have proven the presence of a VEGF gradient, with higher VEGF levels measured in tissues adjacent to the foam–wound interface, which is important for directionalized angiogenesis [32]. In addition, in addition to the hypoxia-induced VEGF gradient, the active removal of byproducts impairing angiogenesis and direct mechanical forces applied by the combination of foam dressing and negative pressure contribute to the development of new vessels [33].

All components of metabolic syndrome have been associated with impaired microcirculation. Diabetes mellitus is associated with a series of structural changes in small vessels, including thickening of the capillary basement membrane, decreased luminal diameter, and pericyte cell degeneration [6]. Arterial hypertension has also been associated with deficient microcirculation and wound healing due to the phenomenon of microvascular rarefaction, defined as a reduced microvascular density in a specific volume [34]. In vivo studies have revealed reduced capillary density and limited cellularity in the subcutaneous adipose tissue of obese patients since capillary density does not proportionally follow the increase in adipose tissue volume or the dysregulation of subcutaneous adipose tissue blood flow [35, 36]. Postoperative status is commonly associated with hypovolemia and impaired tissue perfusion, which act synergistically with relative capillary scarcity of adipose tissue to create a critical reduction in blood flow and oxygenation of adipose tissue [8]. In addition, obesity is characterized by mitochondrial dysfunction, resulting in poor adipose tissue oxygenation [37].

As a response to numerous and diverse clinical demands, many advancements have emerged in the area of NPWT in recent decades [38]. A promising tool in the armamentarium of NPWT-assisted wound healing is NPWTi-d, which enables wound bed decontamination and facilitates granulation tissue formation [39]. The first appearance of an NPWT device with intermittent instillation was made in 2003 [11]. NPWTi-d function is based on the automated intermittent instillation and dwelling of wound management solutions for active irrigation of the wound bed and removal of wound exudate and infectious products [11].

Wound debridement is defined as the removal of necrotic and devitalized tissue, infectious material, biofilm, epidermal cells, pus, and foreign material from the wound bed in an effort to promote wound healing [40]. Surgical sharp debridement, which remains the gold standard treatment for wound bed preparation, is contraindicated or not appropriate under specific circumstances, such as in high-risk patients for anesthesia and operation, unwilling surgical debridement, inability to stop anticoagulant therapy, previous excisional sharp debridement with remaining nonviable tissue, and alternative strategies [ [41–42]. To address this need, the use of NPWTi-d was accompanied by the emersion of dressings with through holes. The ROCF-CC foam consists of a unique polyurethane foam layer with 1 cm diameter holes 0.5 cm from each other, which allows exudate discharge to be suctioned through the foam dressing, and two foam layers 0.8 cm and 1.6 cm thick without holes [11]. Its less hydrophobic character permits better distribution of the instillation fluid through the foam. The use of an NPWTi-d with a ROCF-CC dressing is based mainly on the mechanisms of macrostrain and microstrain. Macrostrain includes shrinkage of the wound surface caused by contraction of the foam and even distribution of negative pressure, while microstrain is defined as microdeformation of the wound bed by NPWT and ROCF-CC dressings, stimulating cell proliferation that helps promote wound healing. As a result, necrotic tissue is concentrated on the top of granulation tissue macrocolumns formed on the wound bed, and exudate and infected material are easily removed with dressing changes [43].

A biofilm is defined as a complex of microorganism colonies incorporated in a protective polysaccharide matrix that is attached to the wound surface [44–46]. It is suggested that bacterial biofilms lead to an area of lower oxygen tension in the wound bed due to their metabolic processes and due to the local migration of cells for host defense [47–49]. In addition, toxic byproducts, such as exotoxins and exoenzymes, produced by bacterial colonies, as well as high concentrations of proteases and reactive oxygen species, which deactivate vital mediators of the healing process, also contribute to a vicious circle of impaired healing [47, 50–51]. Biofilms are characterized by strong adhesion to wound bed tissue, and to achieve complete eradication, a combination of debridement and surfactants that eliminate adhesions between the biofilm and wound surface is necessary [52]. A series of different solutions have been proposed for instillation into the wound bed that can provide wound irrigation or antiseptic cleansing properties. A series of patients showed positive results after NPWTi-d with 0.9% normal saline, which is proposed as the first choice for wound irrigation [53], while the international consensus guidelines update of 2019 presented similar results with the use of the following: normal saline, hypochlorous acid solution, sodium hypochlorite solution, acetic acid solution and polyhexamethylene biguanide (0.1%) + betaine (0.1%) [42]. Among surfactant solutions, propylbetaine-polihexanide (PP) solution, containing 0.1% of the antiseptic agent polyhexanide and 0.1% of the surfactant betaine, has been proposed to effectively remove slough and microorganisms from the wound bed. Propylbetaine is a surfactant with low surface tension that has been reported to loosen cellular debris and may help with the dispersion of biofilms [54]. Polyhexanide is a broad-spectrum antimicrobial agent with a sufficient safety profile that is highly effective at destroying bacterial membranes without disrupting human cell function [55]. The mechanisms of PP action reported in the literature include increased rates of protein solubilization and protein removal from the wound bed [56] and increased efficacy against methicillin-resistant Staphylococcus aureus (MRSA) colony formation [57]. Regarding evidence-based data, PP use has been associated with significantly better results regarding signs of wound inflammation, size reduction and granulation tissue improvement, significantly better pain management, better wound odor control and better control of the bacterial burden [52, 58]. It is important to note that NPWTi-d is not indicated for the treatment of wound infection. NPWTi-d can only be used in infected wounds as adjunctive wound management in combination with infection control measures such as surgical debridement and the use of systemic antibiotics.

Among the new technologies developed for the management of challenging wounds, UAW has been extensively studied. Effects of UAW on issues are classified as thermal, including an increase in tissue temperature and an increase in blood flow on the wound bed, and nonthermal, including the mechanical effects of cavitation and acoustic streaming [59–60]. Kataoka et al. summarized the results of UAW debridement, including a significant reduction in bacterial colonization of the wound bed, decreased expression of inflammatory cytokines, amelioration of pain, disruption and removal of biofilms and promotion of wound healing [61]. In addition, UAW debridement is a safe option for poor candidates because sharp surgical debridement is not appropriate, such as in patients with microcirculation disorders or diabetes, which offers higher healing rates and increased wound surface reduction compared to a sham device [62].

Considering that capillary pressure in normal tissues ranges from 10.5 to 22.5 mmHg, the possibility of capillary occlusion due to NPWT is rather low [63]. In contrast to normal tissues, tissues with borderline perfusion have significantly lower capillary perfusion pressures and are at high risk of hypoperfusion or even necrosis if tissue pressures of 10 mmHg or even less develop [28]. In conclusion, physicians should consider that during NPWT, the level of suction pressure corresponds to a wide range of increased tissue pressures for different types of wounds and periods of application. Important clinical questions emerge from these results, which render questionable the use of the recommended negative pressure of − 125 mmHg on all types of wounds, as well as the safety profile of standard use of NPWT for wounds with compromised perfusion. The aforementioned conclusions are in accordance with observations from our small three-patient case series, since the application of a prestandardized negative pressure of -125 mmHg in a patient with all components of metabolic syndrome (arterial hypertension, diabetes mellitus type 2, and dyslipidemia) may have contributed to a vicious cycle of subcutaneous tissue necrosis and the need for surgical debridement. The change from NPWT to lower negative pressure (-50 mmHg) led to significantly less nonviable tissue during the next dressing changes. Similarly, patients 2 and 3, who had the same risk factors for microvascular disease, were successfully managed with lower negative pressure (-50 mmHg), thus limiting extended tissue necrosis and tissue loss. Based on observations from our mini case series, a clinical score (ANSWER score- tAilored Negative PresSure Wound Therapy in micRoangiopathy) regarding ideal negative pressure levels in patients with impaired microcirculation has been proposed. Every risk factor for microangiopathy (obesity, arterial hypertension, diabetes mellitus) was counted at one point, and the final applied negative pressure was calculated by subtracting 25 mmHg at every point from − 125 mmHg, which is the default pressure provided by the device. Once granulation tissue forms around the wound, the NPWT pressure can gradually increase to the default level according to clinical judgment.

The cases included in our study were carefully selected to ensure a consistent and meaningful comparison. Each patient had undergone abdominal surgery and subsequently developed a surgical site infection, requiring advanced wound management. Their shared history of metabolic syndrome and microangiopathy created a unique but comparable cohort that allowed us to investigate the effects of tailored NPWT settings. While variations in treatment approaches were present due to individualized patient needs, this diversity provided valuable insights into the adaptability and effectiveness of the ANSWER score in different clinical scenarios. The institutional consistency in management further strengthens the reliability of our findings, as all patients received treatment under standardized protocols within the same healthcare setting. By emphasizing the shared risk factors, surgical history, and treatment framework, we reinforced the validity of our proposed methodology, demonstrating its potential applicability in similar clinical scenarios.

The ANSWER score provides a systematic, individualized approach to NPWT application in patients with microangiopathy. However, further prospective validation is required to establish its effectiveness in diverse clinical settings. Future studies should focus on:

  • Comparing healing outcomes between standard (-125 mmHg) and reduced (-50 to -100 mmHg) NPWT pressures in microangiopathic patients.

  • Assessing perfusion changes using objective microcirculatory assessments, such as transcutaneous oxygen pressure, laser Doppler flowmetry.

  • Determining the impact on wound healing time and complication rates, including ischemic necrosis and need for surgical debridement.

By integrating these findings, the ANSWER score may serve as an evidence-based clinical tool for optimizing NPWT in patients with compromised microvascular function.

Conclusions

Microcirculation plays a crucial role in wound healing since impaired healing and a low rate of tissue regeneration have been observed in patients with compromised tissue perfusion, such as diabetic patients, obese patients or patients with arterial hypertension. While the literature contains evidence on the important role of NPWT in the healing cascade, the use of NPWT in patients with microangiopathy and extensive subcutaneous tissue dissection at the default operating pressure of -125 mmHg may lead to further ischemic necrosis and loss of viable tissue. In these cases, based on observations from our mini case series, a clinical score (ANSWER score—tAilored Negative PresSure Wound Therapy in Microangiopathy) regarding ideal negative pressure levels in patients with impaired microcirculation seems to be useful and dictates the ideal level of negative pressure for each patient. Every risk factor for microangiopathy (obesity, arterial hypertension, diabetes mellitus) was counted at one point, and the negative pressure finally applied was calculated by subtracting 25 mmHg for every point from the − 125 mmHg. Furthermore, in such cases, sharp surgical debridement may result in the excision of viable healthy tissue and impaired wound healing. A series of new adjuvant technologies have been added as alternative strategies, including ultrasonic-assisted wound debridement, which removes nonviable tissue in a minimally invasive way, and the use of NPWTi-d combined with ROCF-CC dressings and an instillation solution containing 0.1% betaine and 0.1% polyhexanide, which mechanically removes debris, water, and bioburden from the wound bed. Future research should focus on validating the ANSWER score through prospective cohort studies or randomized controlled trials to determine its predictive value in optimizing NPWT outcomes for microangiopathy patients.

Acknowledgements

None.

Abbreviations

NPWT

Negative pressure wound therapy

NPWTi-d

Negative pressure wound therapy with instillation and dwell time

ROCF-CC

Reticulated open cell foam dressings with through holes

UAW

Ultrasonic-assisted wound debridement

ANSWER score

tAilored Negative Presurance Wound Therapy in Microangiopathy

SSIs

Surgical site infections

SCARE

Surgical CAse REport guidelines

BMI

Body mass index

CRP

C-reactive protein

PCT

Procalcitonin test

ESR

Erythrocyte sedimentation rate

VAC

Vacuum-assisted closure

WBC

White blood cell count

TGF-β

Transforming growth factor-β

PDGF

Platelet-derived growth factor

PP

Propylbetaine-polihexanide

MRSA

Methicillin-resistant Staphylococcus aureus

RCT

Randomized controlled trial

NS

Normal saline

Author contributions

IO and AE equally contributed to this study; AE, ZK and IO designed the research; SK, BS, KO, SS, BS, KA, DV and CA performed the research; IO and AE wrote the paper; MI, KE, PM-G, and AS supervised the paper; and all authors read and approved the final manuscript.

Funding

This research received no external funding.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki. Informed consent was obtained from all patients. Institutional Review Board approval is not applicable.

Consent for publication

Informed consent was obtained from all subjects involved in the study for publication.

Competing interests

This research received no external funding. Ioannidis Orestis is a paid consultant for 3 M Health. The other authors report no conflict of interest.

Footnotes

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Data Availability Statement

No datasets were generated or analysed during the current study.

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