The Consistent Delivery of Negative Pressure to Wounds Using Reticulated, Open Cell Foam and Regulated Pressure Feedback

Abstract: Negative pressure wound therapy (NPWT) is used to manage wounds and promote wound healing. The most common form of NPWT utilizes reticulated, open cell foam (ROCF). Pressure is transferred to the wound by ROCF using T.R.A.C.™ Technology (regulated pressure feedback [RPF]) creating an environment that promotes healing. This study examines the effectiveness of ROCF versus gauze in inducing macrostrain and investigates the ability of NPWT/ROCF/RPF to consistently deliver negative pressure to the wound, compensating for constantly changing wound fluid characteristics. In an in-vitro model, ROCF induced significantly greater macrostrain than gauze demonstrating a 57% decrease in dressing surface area following negative pressure application. The decrease measured with gauze under suction (GUS) was insignificant. The NPWT/ROCF/RPF system consistently delivered negative pressure to the wound when compared to GUS or ROCF without RPF. Further, with the negative pressure source elevated 36 in (90 cm) above surrogate wounds, GUS demonstrated a 7- to 10-fold pressure drop when compared to NPWT/ROCF/RPF. Systems without RPF are limited because they cannot sense or measure pressure delivered at the wound. In situations where pressure drop occurs, neither the clinician nor patient would necessarily know that suboptimal pressure was being delivered to the wound. Therefore, a system with ROCF and RPF capability that effectively monitors and maintains the NPWT environment plays a crucial role in the optimal induction of macrostrain and microstrain. The ability of the NPWT/ROCF/RPF system to monitor and maintain controlled, consistent delivery of negative pressure would seem important to achieve desired clinical outcomes.
Address correspondence to: Amy McNulty, PhD Kinetic Concepts, Inc. 8023 Vantage Dr. San Antonio, TX Phone: 210-515-4336 Email: amy.mcnulty@kci1.com Disclosure: The authors are employees of Kinetic Concepts, Inc.

     Both acute and chronic wounds are a major issue in healthcare today. In the United States alone the annual incidence rate for foot ulcers in persons with diabetes is estimated between 1%–4%.^1–3 By 2025 it is believed that nearly 300 million people will have diabetes.⁴ Vacuum-assisted Closure Therapy (V.A.C.® Therapy, Kinetic Concepts, Inc., San Antonio, TX) is widely used to promote wound healing. During this therapy, negative pressure is transferred to the wound surface using a reticulated open cell foam (NPWT/ROCF). Two methods via which NPWT/ROCF is recognized to promote wound healing are through the generation of macrostrain and microstrain.^5–7 Macrostrain is the visible change of wound shape and size that occurs upon application of negative pressure through ROCF. As the negative pressure reaches 30 mmHg, the ROCF begins to collapse. As it continues to collapse, wound edges are drawn together creating a smaller wound. A smaller wound size requires less granulation tissue formation to fill.      Microstrain may be defined as a stress induced change in the length of cells in a particular direction. It has long been known that cells under strain tend to divide.^7–9 It is believed that the application of NPWT/ROCF induces average tissue microstrain between 5%–20%.⁷ Levels of microstrain between 5%–20% are consistent with those levels known to induce cellular responses such as proliferation in vitro.^10,11 Recent work has shown that mechanical forces in the wound bed mediates the appearance of functional vasculature.¹² In addition to stimulating proliferation, studies have associated NPWT/ROCF with angiogenesis.^13,14 Greene et al¹⁴ demonstrated that the tissue in contact with ROCF exhibited significantly higher microvessel density as opposed to tissue without direct ROCF contact. The microstrain generated by NPWT/ROCF was believed to be the causal factor in the increased microvessel density.¹⁴      During NPWT/ROCF, edema is removed from the wound through specialized tubing. This fluid has weight, and lifting it can cause a reduction in the negative pressure being delivered to the wound. This reduction in negative pressure at the dressing/wound interface is termed a pressure drop, and if large enough, could result in a loss of efficacious therapy. To compensate for pressure drop and to allow for controlled delivery of NPWT/ROCF, Therapeutic Regulated Accurate Care™ (T.R.A.C.™ [Kinetic Concepts, Inc.]) technology (regulated pressure feedback [RPF]) is incorporated. Sensing lumens in the RPF Dressing enable the therapy unit to monitor and modify the pressure being transferred to the wound site. The therapy unit is thus able to compensate for the continually changing fluid characteristics and levels in the central tubing, providing consistent pressure delivery to the wound.      Since pressure transferred to the wound may be translated into cellular responses, it is important that pressure delivery be both controlled and consistent across the entire wound bed. The current study assesses the ability of NPWT/ROCF and RPF to consistently deliver a set negative pressure to the wound bed. This ability is then compared to that of gauze under suction, where the therapy does not include RPF.

Methods

     Macrostrain experiments. To assess the change in dressing surface area upon application of negative pressure, 130 cm² pieces of GranuFoam® Dressing (Kinetic Concepts, Inc.) or fan-folded gauze were cut using a template. Ensuring that dressing surface area was equal across groups prior to the application of negative pressure eliminated any size bias in the experiment. Dressings were covered top and bottom with KCI drape in an airtight fashion. An incision was made in both of the dressing assemblies for application of the T.R.A.C. Pad dressing. Assemblies were then connected to a V.A.C. Freedom® Therapy System (Kinetic Concepts, Inc.) via a Y adaptor. Next, 125 mmHg negative pressure was applied continuously to the dressings. Surface area measurements were made before and after negative pressure application.      Horizontal pressure drop experiments. To assess pressure distributions horizontally away from a vacuum source, a planar test grid consisting of a 36-in x 36-in array of luer ports (2.0-in spacing) on a 0.5-in thick polycarbonate sheet was used. All dressings were of a uniform size to eliminate any size bias. Pressure transferred through the dressings was measured via a MPX5100 integrated pressure sensor (Motorola Semiconductor) having a range of 0–750 mmHg. Pressure sensor calibration and airflow measurements were conducted through a FMA-1608 Flowmeter (Omega Engineering, Inc.). Data acquisition and control utilized a CIO-DAS08-PGH board (Omega Engineering) installed on a PC (Microsoft Windows 95) and a custom user interface in Microsoft Excel (via Microsoft Visual Basic for Applications [VBA]). Data were logged at approximately 1-second intervals.      Pressure profiles at the simulated wound were acquired during therapy mode operation of the following dressing-therapy unit systems. For NPWT/ROCF, pressure was delivered to GranuFoam using a V.A.C. ATS® Therapy System. For gauze under suction, pressure was delivered through a Versatile 1 Pump (BlueSky Medical) to layered gauze and used Chariker-Jeter Wound Drainage Kits incorporating Jackson-Pratt drains.      Vertical pressure drop experiments. For the experiment, 4 units with 4 surrogate wound set-ups were run for each therapy unit type (V.A.C. Therapy with ROCF and RPF Technology [RPFT] or Versatile 1 systems with gauze). Wound surrogates were composed of dressings attached to Plexiglas sheets using V.A.C. Drape. The set up of the dressing was according to manufacturer’s instructions. Dressings were constantly infused with an albumin-based fluid (14 ± 2 centipoise) using a peristaltic pump connected to ports in the Plexiglas sheet. This fluid was used to simulate wound fluid in the surrogate wound. NPWT units were elevated 36 in (90 cm) above surrogate wounds to simulate a scenario of a person with a foot ulcer. This is due to the fact that portable NPWT units may be worn on or above the waist. Units were initially set to 80 mmHg negative pressure for 5 minutes. The units were then switched to 125 mmHg negative pressure for 5 minutes and finally set to deliver 200 mmHg for 5 minutes. Data were continually logged at 1-second intervals during the experiment. At each new pressure setting, therapy unit and wound readings were averaged following an approximate 2-minute equilibration period. Negative pressure readings at the therapy unit and surrogate wound were averaged for 2 minutes of continuous therapy at the particular setting following the 2-minute equilibration period.      Experiments to assess the impact of T.R.A.C. technology. For this segment of the pressure drop analysis, 4 units with 4 surrogate wound set-ups were run using the V.A.C. Therapy system. Two units were elevated to 36 in and 18 in (90 cm and 45 cm) above surrogate wounds to simulate the height differential, which is often seen in the situation of a person with a foot wound. To differentiate between V.A.C. Therapy with and without T.R.A.C. Technology, sensing lumens in the V.A.C. Therapy tubing were disabled. Wound bed treatment simulations included those with the complete V.A.C. Therapy system with GranuFoam and T.R.A.C. Pad technology, V.A.C. Therapy with GranuFoam without T.R.A.C. Pad technology using a Jackson-Pratt drain inserted into the center of the GranuFoam (ROCFD) and NPWT, which utilized a V.A.C. Therapy Unit delivering pressure to layered gauze with a Jackson-Pratt drain placed in the center of the gauze. Units were initially set to 50 mmHg negative pressure for 5 minutes. The units were then switched to 80 and 125 mmHg negative pressure for 5 minutes and finally set to deliver 200 mmHg for 5 minutes. Data were continually logged at 1-second intervals during the experiment. At each new pressure setting, therapy unit and wound readings were averaged following an approximate 2-minute equilibration period. Negative pressure readings at the therapy unit and surrogate wound were averaged for at least 2 minutes of continuous therapy at the particular setting following the 2-minute equilibration period. Average readings for ROCFD and gauze were compared to those for the complete V.A.C. Therapy System.

Statistical Analyses

     A Wilcoxon/Kruskal-Wallis test, a non-parametric analogue of a one-way ANOVA based on rank order of the data was utilized to detect differences among treatment groups. All direct comparisons were evaluated at an alpha level of 0.05. The Tukey-Kramer method was implemented in order to adjust for multiplicity when appropriate.

Results

     Prior to application of negative pressure, all dressings used in the macrostrain experiment were of equal size. Figure 1 shows that following application of negative pressure, there was a significant difference as demonstrated by a 57% decrease in ROCF area (P < 0.05). Application of -125 mmHg to gauze did not lead to any decrease in surface area. On the contrary, the area of the dressing increased 0.4% when negative pressure was applied.      Figure 2 shows that for NPWT/ROCF, the horizontal pressure drop at 3.6 cm from the vacuum source was between 2.9% and 5.3%. In contrast, the horizontal pressure drop at 3.6 cm from the vacuum source was between 23.9% and 38% for gauze under suction. For all pressures tested, the pressure drop at 3.6 cm was always significantly higher for gauze under suction than for NPWT/ROCF (P < 0.05). In fact, the pressure drop for gauze under suction was generally 7 to 10 times higher than for NPWT/ROCF.      To assess vertical pressure drop, pressure was measured at the therapy unit and at the wound surface following application of negative pressure. Figure 3 illustrates that the percent pressure drop recorded at each pressure for gauze under suction was significantly greater than that recorded for NPWT/ROCF (P < 0.05). At all pressures tested, the percent pressure drop was approximately 2 fold greater for gauze under suction than for NPWT/ROCF. The greatest pressure drop (90%) was recorded for gauze under suction at -80 mmHg. For NPWT/ROCF, the therapy unit was able to accurately measure and display the pressure being delivered to the wound site. There was no difference between pressure registered at the therapy unit and the pressure measured at the surrogate wound (P > 0.05).      The impact of the RPF Dressing in helping to consistently deliver pressure to the wound was assessed using NPWT/ROCF without RPFT. Pressure delivery in this set up was compared to that of gauze under suction. Instead of using RPFT to connect the ROCF to the NPWT pump, a Jackson-Pratt Drain was attached to the NPWT canister tubing and placed in the center of the ROCFD. This was similar to the way pressure was transferred from the NPWT pump to gauze dressings. The pressure drop observed for systems without RPF was normalized to values for NPWT/ROCF using RPFT. Figure 4 shows that there was no significant difference between pressure drop values measured for ROCFD when compared to those measured for gauze under suction (P > 0.05) at therapy unit heights of 36 in (90 cm) or 18 in (45 cm) above the surrogate wounds. Fold change pressure drops from control (NPWT/ROCF) were approximately between 2- and 10-fold greater for dressings without RPFT.

Discussion

     The effects of NPWT/ROCF on wound healing have been documented in over 470 peer reviewed articles.¹⁵ A key mechanism of action for NPWT/ROCF is the mechanotransduction of mechanical forces such as macrostrain and microstrain into cellular responses. The generation of macrostrain is dependent upon the mechanical properties of the dressing.⁵ With ROCF, as air initially evacuates the dressing, tissue is drawn against the ROCF. The mechanical structure of ROCF is initially able to resist the force of the tissue but at some point the inward force of the tissue becomes greater than the force of the ROCF pushing outward, causing the foam to collapse. As a result of this process, the size of the defect decreases. This bulk tissue deformation is macrostrain. The use of macrostrain for tissue generation has been successfully used for decades with bone distraction and tissue expansion.^8,9,16,17      Macrostrain experiments assessing the area reduction occurring in either gauze or ROCF in response to application of -125 mmHg pressure demonstrated that the tissue interface used has a tremendous effect on the amount of macrostrain delivered to the wound. Indeed, little or no macrostrain was generated when gauze was used. In comparison, ROCF experienced an over 50% decrease in surface area upon application of -125 mmHg pressure. Using a cadaveric model, Argenta et al18 attained similar surface area changes in wounds when comparing gauze versus ROCF.¹      The generation of microstrain at the wound is dependent upon the ability of the tissue interface to transfer pressure to the tissue. As negative pressure is transferred to the tissue using ROCF, tissue is pulled into the pores of the foam and compressed at the struts of the foam. The stretch and compressive forces create microstrain at a cellular level. Mechanotransduction occurs when microstrain is sensed by the cells and translated into physiological or biochemical responses.^7,19,20 This mechanotransduction of mechanical forces may affect virtually all aspects of cell physiology including increases in proliferation,^7,21,22 angiogenesis,¹⁴ protein synthesis,²¹ gene expression,^20,23 and cellular energetic status21; all of which are important to the generation of granulation tissue. It therefore follows that if mechanotransduction of mechanical forces is important to the generation of cellular response during NPWT/ROCF, then it is important to consistently deliver negative pressure to the foam in a controlled fashion. This point is shown through a previous randomized clinical trial by Wild et al²⁴ where the delivery of inconsistent negative pressures to wounds using Redon drains produced less granulation tissue (P = 0.001) than did the NPWT/ROCF group even though the same dressing was used in both therapy groups.²⁰      To enable consistent and uniform delivery of negative pressure, the wound filling material cannot significantly impair the delivery of negative pressure to the wound site. Previous in-silico modeling indicated that ROCF generated significantly more microstrain than gauze at all negative pressures tested.⁶ The current study confirmed this by showing in vitro that ROCF is a more efficient material for transferring pressure than is gauze. At 3.6 cm from the vacuum source ROCF was able to transfer a significantly higher percentage of the set pressure to the surrogate wound than was gauze. In fact, the pressure drop was 7 fold higher for gauze at a set pressure of -50 mmHg and 10 fold higher for gauze at a set pressure of -125 mmHg. As an example, at a set pressure of -125 mmHg, gauze only transferred -96 mmHg to the wound. Therefore when gauze is used as a wound filling material, tissues 3.6 cm or more from the vacuum source may not receive the prescribed level of negative pressure.      The ability of NPWT/ROCF to consistently deliver negative pressure to the wound bed is also influenced by the presence and amount of exudate. Due to the fact that fluid has mass, and the movement of fluid against gravity inversely influences the delivered pressure, it is important that the NPWT system is able to sense and compensate for the constantly changing fluid properties at the wound. In fact, for systems that cannot compensate for changing fluid properties at the wound, -22.4 mmHg pressure drop could occur for every foot that fluid travels against gravity. The current study showed that when therapy units were elevated 36 in (90 cm) above simulated wounds, the NPWT system using ROCF with RPFT was able to accurately monitor the pressure delivered to the wound site. This is an important feature of NPWT/ROCF. The ability to sense and respond to changing pressure delivery at the wound site allows for consistent pressure delivery and application of intended therapy. This is not necessarily the case for gauze under suction where RPFT is not utilized. The present study showed that the therapy delivered at the gauze dressing using the Versatile 1 pump was decreased by 90% at -80 mmHg; 68% at -125 mmHg and 51% at -200 mmHg. To illustrate, at a prescribed pressure of -80 mmHg an average of -8.2 mmHg was actually delivered to the surrogate wound model in this experiment using the Versatile 1 pump with the gauze. For systems without RPFT since pressure delivered at the wound cannot be sensed and measured, in situations where pressure drop occurs, neither the clinician nor patient would necessarily be aware of the fact that suboptimal pressure was being delivered to the wound.      To more specifically determine the role of RPFT in the consistent delivery of negative pressure therapy an experiment was conducted whereby the NPWT therapy unit was elevated either 18 in (45 cm) or 36 in (90 cm) above the simulated wound. Pressure was transferred to the simulated wound using either ROCF or gauze. Neither of the dressings was connected to the therapy unit using RPFT. Regardless of dressing used in this experiment, pressures delivered to the wound site were between 2- and 10-fold less than pressures delivered with NPWT when RPFT utilized. For example, when the NPWT unit was 18 in (45 cm) above the surrogate wound and set to deliver -80 mmHg, approximately 60 mmHg was delivered to the wound irrespective of wound filling material. This experiment illustrates the fact that it is not simply the foam, which allows for the consistent and controlled delivery of pressure to the wound; rather, it seems that the complete NPWT System including RPFT as incorporated in T.R.A.C technology is required.

Conclusion

     The present study showed the interface material used to transfer negative pressure to tissue is important to the generation of macrostrain. ROCF was able to generate more macrostrain than was gauze. Both the interface material and the use of RPFT were shown to be important to the consistent delivery of negative pressure to the surrogate wound. ROCF transferred pressure horizontally more efficiently than gauze. Without RPFT, an equivalent amount of pressure drop was recorded for both ROCF and gauze when vacuum pumps were placed above the surrogate wounds. When RPFT was utilized with ROCF, significantly less pressure drop occurred than under gauze. The transfer of negative pressure to the wound leads to the generation of macrostrain and microstrain. Therefore, delivering prescribed negative pressure therapy to the wound site ensures optimal therapy for the wound. The complete V.A.C. Therapy System including T.R.A.C. Technology and ROCF was shown to more consistently deliver negative pressure than either gauze under suction or when using ROCF without T.R.A.C. Technology. This ability to deliver consistent negative pressure to the wound site is important in order to achieve the desired the clinical outcomes associated with V.A.C. Therapy.