Dr. Gurvich Article


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Dr. Gurvich Article

  1. 1. CASE SERIES Synergism in Using Negative Pressure Wound Therapy With Alternated Applications of Autologous Platelet-derived Growth Factors in Treating Post-acute Surgical Wounds Leon Gurvich, ANP, MS, MPH, CWS WOUNDS 2009;21(5):134–140 Abstract: Chronic and acute wounds with long tunneling or undermin- ing are always a challenge to wound care providers. One of the most From L. Weiss Memorial Hospital frequently employed treatments for closing tunneled or undermined Wound Healing Center, Chicago, wounds is negative pressure wound therapy (NPWT). The benefits of Illinois this treatment system are widely discussed in the professional litera- ture, and will not be covered here. Even though NPWT allows for faster Address correspondence to: wound healing initially, in some cases, progress to wound closure is Leon Gurvich, ANP, MS, MPH, CWS limited and healing stops after reaching a maximum potential, which L. Weiss Memorial Hospital Wound may occur after just a few weeks. This adverse phenomenon is more Healing Center common when the wound exhibits deep tunneling or has been exten- 4646 N. Marine Dr. sively undermined. Trying variations of NPWT strategies geared toward Chicago, IL 60640 closing these wounds is usually unsuccessful. This article describes Phone: 847-529-2407 cases where combined therapy, using the V.A.C.® Therapy System E-mail: leon_gurvich@hotmail.com (KCI, San Antonio, Tex) and the autologous platelet-derived gel, AutoloGel™, (Cytomedix, Rockville, Md) was employed. he efficacy of negative pressure wound therapy (NPWT) to promote T healing of open wounds has considerable support in the literature. NPWT promotes wound healing through multiple actions: removal of exudate from the wound to help establish fluid balance, provision of a moist wound environment, removal of slough to decrease wound bacterial burden, reduction in edema and third-space fluids, increase of blood flow to the wound, increase in growth factors, and promotion of white cells and fibrob- lasts within the wound. Negative pressure brings tissue together, promoting coaptation, which allows the tissues to stick together through natural tissue adherence and increases healing. It is postulated that this combination treatment affects the wound healing rate by creating a well-oxygenated, angiogenic tissue bed using NPWT and then activating fibroblasts with platelet-rich plasma gel (PRP). The idea behind applying this particular combination was to increase, according to Chen et al2, angiogenesis in the hypoxic tissue with NPWT and then to “sow” 134 WOUNDS www.woundsresearch.com
  2. 2. Gurvich the growth factors from the PRP into the new hypervas- Case Reports cular tissue like seeds into “enriched soil.”The NPWT pre- Case 1. A 62-year-old man presented to the wound pares the “ground” by creating numerous new microcap- center with extensive necrosis of the lateral-anterior illaries for the platelet-derived growth factors, which portion of a skin graft that had been applied to his right then function as natural fertilizer causing proliferation of leg 6 weeks earlier. The patient had a history of exten- the fibroblast “crop.” sive peripheral vascular occlusive disease, having had an Niezgoda et al3 provided further evidence for this aortobifemoral bypass graft and bilateral lower extremi- approach. They found that using NPWT therapy stimu- ty infrainguinal revascularization several years previous. lates the development of angiogenesis in the adjacent tis- He had multiple treatments to his left leg, which ulti- sues underlying and surrounding the wound base to a mately led to an above knee amputation. The patient greater degree than can be achieved with standard rehabilitated well with prosthesis. Six months before he wound healing efforts, such as enzymatic treatments, sur- arrived at the wound center, he underwent surgery on a gical debridements, and local wound care. Chen et al2 femoral-popliteal graft above his right knee, which had reported that using NPWT promotes capillary blood thrombosed. After successful revascularization of the flow velocity, increases capillary caliber and blood vol- graft, the patient developed multicompartment fascioto- ume, stimulates endothelial proliferation and angiogene- my of his right leg, which was ultimately skin-grafted. sis, narrows endothelial spaces, and restores the integrity His medical history included hypercholesterolemia— of the capillary basement membrane. the patient carries prescriptions for Coumadin (Bristol- Studies in basic science have demonstrated a dose- Myers Squibb Company, Princeton, NJ) and Lipitor response relationship between platelet concentration (Pfizer, New York, NY). and levels of secretory proteins, and between platelet Treatment course. The right lateral leg wound concentration and certain proliferative events of signifi- exhibited an exposed anterior tibialis tendon. cance to the healing wound.1 The platelet is a natural source of myriad growth factors and cytokines that pro- mote wound healing. Platelet-derived angiogenesis factor Week 0 is a polypeptide capable of stimulating new capillary • 62-year-old man with necrosis of a skin graft growth by inducing migration of endothelial cells. The • Necrotic tissue was debrided platelet-derived epithelial cell growth factor is partially Weeks 2–4 • Maggot therapy in week 2, which improved the responsible for the initial influx of neutrophils into the wound wound space; it is also a mitogen for many cells, includ- • NPWT weekly for 3 weeks ing epithelial cells and fibroblasts.4,5 Week 5 Four wound treatment cases are presented. These • Healing stagnated patients were treated with a combination of two wound • PRP applied Week 6 healing products: NPWT (V.A.C.® Therapy System, KCI, • NPWT San Antonio, Tex) and an autologous PRP (AutoloGel™ Week 7 Cytomedix, Rockville, Md). The application of PRP was a • NPWT key component in the treatment plan. The bedside treat- • 50% reduction in wound volume ment was achieved by first drawing a small amount of Week 8 • PRP blood (5 cc–15 cc based on the size of treated wound), Week 9 extracting the platelets and plasma.This extract was then • NPWT mixed with calcified thrombin, which caused the extract • 75% healed to “gel” and the platelets to release a number of factors Week 10 that initiated the process of fibroblast migration to the • PRP Week 11 wound. The plasma-rich gel, with its fibrin scaffold, was • NPWT applied topically to the wound under a protective cover Weeks 12–20 dressing. • Collagen to maintain The cases described here illustrate healing rates of • Completely healed at week 20 post-surgical wounds after treatment with NPWT and Figure 1. Treatment progression in case 1. PRP. Vol. 21, No. 5 May 2009 135
  3. 3. Gurvich Case 1: Week 1 Case 1: Week 2 Case 1: Week 3 Case 1: Week 7 Case 1: Week 13 Case 1: Week 20 Dimensions of the wound were 11 cm x 3.4 cm x 1.5 had not closed from the time of injury to her admission cm. At the wound center, necrotic tissue was debrided at at the wound center. The wound dimensions were 0.8 initial exploration of the muscle tissue. Due to the exten- cm x 0.7 cm x 4.0 cm and had a sinus tract extending in sive amount of necrotic tissue remaining after debride- ment and the severe pain experienced, maggot therapy was introduced in the second week of therapy, after Week 0 which significant improvement was noted. NPWT thera- • 75-year-old woman py was also started during week 2 and continued on a • One-year-old hip wound with sinus tracts Week 1 weekly basis for 3 weeks. Healing stagnated at this point. • Special packing in tracts In week 5, autologous PRP was added to the regimen. • Iodosorb dressing applied This application of PRP combined with 2 subsequent Weeks 2–7 weekly NWPT applications restarted the healing • NPWT weekly process; a 50% reduction in wound volume was noted. • No healing Weeks 8–9 The next treatment (week 8 after admission) applied • PRP weekly was PRP gel alone.At the end of week 8, 75% healing was Weeks 10–11 described. Subsequently, in weeks 9 to 11, NPWT therapy • NPWT weekly was alternated on a weekly basis with PRP. At week 12, Week 12 because of the significant reduction in wound size and • PRP • 50% closure depth, only collagen maintenance therapy was applied. Week 13 The patient’s wound healed completely in 20 weeks. • NPWT Figure 1 shows the treatment progression timeline. Week 14 Case 2. A 75-year-old woman presented to the treat- • PRP ment center with an open wound on her left hip, which Week 15 • Wound and both sinuses closed had lasted for 1 year.The wound resulted from a fall after which she developed a hematoma. The hip area then Figure 2. Treatment progression in case 2. became infected and was surgically drained. The wound 136 WOUNDS www.woundsresearch.com
  4. 4. Gurvich reduced by 50%. The treatment was finished with one more NPWT and one more PRP application. Both sinuses closed completely fol- lowing this treatment. Although there is a photograph of the wound at week 18, the wound was Case 2: Week 12 actually healed at week 15 with minimal dimensions. It was pur- posefully not closed at that time Case 2: Week 2 since the patient’s comorbidities— rheumatoid arthritis and depres- sion—were thought to contribute to closure issues. When the patient returned at week 18, the wound had officially closed. Case 3. An 88-year-old woman presented to the wound center with a left buttock ulcer that had developed 2 months previously. Initially, the patient experienced Case 2: Week 18 Case 2: Week 21 painful erythema and swelling over the ulcerated area. Three 2 directions: at a position corresponding to 9 o’clock (9.5 weeks before admission to the wound center, the cm), and at 12 o’clock (7.5 cm). A small amount of gran- patient had the infected abscess surgically drained and a ulated tissue was present external to the wound but moderate amount of purulent discharge was removed. there was no slough or other evi- dence of necrotic tissue. The patient’s medical history included rheumatoid arthritis and depres- sion. Treatment course. In her first week in the clinic, the patient’s wound was treated with Iodosorb (Smith & Nephew, Fort Lauderdale, Fla). Special packing sponges were placed inside both sinus tracts. In Case 3: Week 1 Case 3: Week 4 week 2, NWPT was started. After 5 weeks of NPWT, visible healing effects on the wound were negligi- ble. Since NPWT did not result in any significant improvement, PRP was added to the treatment regi- men. The PRP was applied weekly for the first 2 weeks. At this point, intermittent weekly dosing of NPWT and PRP was used (Figure 2). After 5 weeks of this alternating Case 3: Week 19 Case 3: Week 23 treatment, the wound volume was Vol. 21, No. 5 May 2009 137
  5. 5. Gurvich Week 0 Week 0 • 88-year-old woman • 56-year-old woman • Left buttock ulcer (2-month duration) • Open surgical wound on left breast from • 3 weeks before admission, wound was drained implant removal and purulent discharge removed Weeks 2–3 Weeks 1–4 • PRP weekly • Wound debridement performed weekly • 50% healed (week 3) Weeks 5–6 Weeks 4–5 • NPWT weekly • PRP weekly Weeks 7–8 • No further healing • PRP weekly Weeks 6–7 • 25% wound closure (week 8) • NPWT weekly Weeks 9–10 Weeks 8–11 • PRP weekly • PRP weekly • > 50% healed (week 10) • 75% healing (week 11) Weeks 11–19 Weeks 12–16 • Collagen treatment for maintenance only • Maintenance therapy (5 weeks) • Wound completely healed (week 19) • Complete healing (week 16) Figure 3. Treatment progression in case 3. Figure 4. Treatment progression in case 4. The patient’s medical history included ulcerative colitis, Case 4. A 56-year-old woman presented to the wound seizure disorder, heart disease, Parkinson’s disease, and center with an open post-surgical wound on her left osteoarthritis. Upon presentation, the wound dimen- breast.The wound was the result of the surgical removal sions were 1.5 cm x 1.5 cm x 3 cm, with 4 cm of tun- of an infected breast implant.The patient had been diag- neling at the 10 o’clock position. nosed with breast cancer 3 years previously, at which Treatment course. Wound debridements were per- time she underwent prophylactic bilateral mastectomy, formed weekly for 1 month over which time, most of the and a course of chemotherapy and radiation. One year necrotic tissue was removed. Other wound care was also per- formed during this time, including cadexomer iodine gel and pad, but the deep cavity still showed no signs of healing. NPWT was started at week 5 to improve local micro- circulation and increase the amount of granulated tissue.After 2 weeks of NPWT treatment without significant improvement, PRP ther- Case 4: Week 1 Case 4: Week 6 apy began and was performed each week. After 2 weeks of PRP treatment, a 25% reduction in wound volume was recorded. At this point, the wound steadily improved and after 2 more weeks of PRP treatment and 7 weeks of collagen mainte- nance (a total of 19 weeks from admission), the wound closed. Figure 3 shows the treatment pro- Case 4: Week 11 Case 4: Week 16 gression timeline. 138 WOUNDS www.woundsresearch.com
  6. 6. Gurvich after her mastectomy, she had breast implants inserted tion of the wound and the effect of the previous treat- and did well for the next 2 years. Two weeks prior to ment. Criteria used for wound condition included the presentation at the wound center, the patient noticed amount of granulating tissue and the level of tissue “vas- signs of an infection in the left implant—local swelling, cularity,” which was assessed before and after each redness, and fever. No culture was taken to identify the debridement. Hypervascular tissue showing multiple specific pathogen(s), but the acute infection was treated new microvessels has a red, beefy appearance and has a with a course of oral antibiotics; the infected implant tendency to bleed easily for prolonged periods. PRP ther- was then removed. The resultant wound measured 2.6 apy was considered appropriate for wounds with hyper- cm x 0.3 cm x 1.5 cm with tunneling (6.8-cm) at the 4 vascularization, and was applied until hypervascular o’clock position, and undermining (3.9-cm) at the 9 granulating tissue was significantly reduced. NPWT was o’clock position. initiated and continued until a positive change in tissue Treatment course. PRP therapy was initiated in the quality was achieved if the wound showed a pale, avas- second week after admission and was repeated weekly cular appearance and tended not to bleed during for the following 4 weeks. After 2 weeks of this therapy, debridement. When signs of infection were noticed, a tis- a 50% reduction in the wound was noted. During the sue culture was obtained and an appropriate oral course next 2 weeks of treatment, no improvement in wound of antibiotics was prescribed. dimensions, tunneling, or undermining was achieved. The data analysis has shown that there was a signifi- Two courses of weekly NPWT was applied, followed by cant change in wound volume (20%–50%) 2–6 weeks 4 weeks of PRP therapy. At week 10 of treatment (11 after beginning one or both of these treatment modali- since admission), wound volume had reduced by 75%. ties. In the first three cases, the advanced wound care One more PRP treatment was applied, and then mainte- began with NPWT. After lack of significant progress, PRP nance with standard treatment was continued. At 15 was added. In the fourth case, the first treatment was PRP weeks, all tunneling and undermining had dissipated. where there was initial improvement after 2 weeks of Figure 4 shows the treatment progression timeline. therapy but then after 2 more weeks, the healing did not progress so NPWT was initiated. In these 4 cases, using Discussion NPWT and PRP treatments alternately resulted in suc- In this 4-patient case series, the use of both NPWT and cessful wound healing. None of these patients’ wounds PRP in various combinations had a positive effect on have reopened after 2 years. wound healing rates (Figure 5). Treatment courses in Topical application of autologous PRP may play an these cases included weekly applications of either PRP important role in complicated, limb-threatening wounds. or NPWT at some time during the patient’s stay in the Wound volumes decreased after the first application in clinic. These treatments were sufficiently spaced (7 days most cases, with continued wound contraction observed apart) to prevent NPWT from removing activated weekly until complete wound healing was achieved. platelet-rich plasma platelet releasate, growth factors, and fibrin scaffolding from the wound bed. The decision Conclusion on the appropriate length of each treatment and the vari- This case series illustrates positive clinical outcomes ation in treatment was made based on the clinical condi- that are possible when using alternating treatment com- binations of PRP and NPWT. These cases represent some of the more recalcitrant wounds that we see—all of the wounds exhibited tunneling or sinus tracts. No serious adverse events were noted with either treatment, and patients expressed no discomfort during the treatments. None of the wounds in these cases have reopened after 2 years. Other clinical data have shown the significant effects platelet growth factors have on wound healing in enriched hypervascular environments.1,4,5 The use of NPWT to promote healing of open wounds has consid- Figure 5. Wound healing rates. erable support in the literature as well.2,3 Previously Vol. 21, No. 5 May 2009 139
  7. 7. Gurvich reported data,4,5 along with the results from this case series, suggest that larger trials may support both effica- cy and safety of this alternating treatment regimen. Such trials would need to establish more precise standards and treatment protocols and offer clinical guidelines to optimize the combined therapy. References 1. Carter CA, Jolly DG, Worden CE Sr, Hendren DG, Kane CJ. Platelet-rich plasma gel promotes differentiation and regeneration during equine wound healing. Exp Mol Pathol. 2003;74(3):244–255. 2. Chen SZ, Li J, Li XY, Xu LS. Effect of vacuum-assisted clo- sure on wound microcirculation: an experimental study. Asian J Surg. 2005;28(3):211–217. 3. Niezgoda JA, Cabigas EB, Allen HK, Simanonok JP, Kindwall EP, Krumenauer J. Managing pyoderma gan- grenosum: a synergistic approach combining surgical debridement, vacuum-assisted closure, and hyperbaric oxygen therapy. Plast Reconstr Surg. 2006;117(2):24e–28e. 4. Pietrzak WS, Eppley BL. Platelet-rich plasma: biology and new technology. J Craniofac Surg. 2005;16(6):1043–1054. 5. Wrotniak M, Bielecki T, Gazdzik TS. Current opinion about using the platelet-rich gel in orthopaedics and trauma surgery. Ortop Traumatol Rehabil. 2007;9(3):227–238. 140 WOUNDS www.woundsresearch.com