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Wound Instillation — The Next Step in Negative Pressure Wound Therapy. Lessons Learned from Initial Experiences

Empirical Studies

Wound Instillation — The Next Step in Negative Pressure Wound Therapy. Lessons Learned from Initial Experiences

Index: Ostomy Wound Manage. 2004;50(11):56-66.

    Negative pressure wound therapy (NPWT) using the V.A.C. System® (KCI, San Antonio, Tex.) to aid in wound healing was introduced for general use in the US in 1995 following receipt of FDA clearance for marketing.

The system consists of a reticulated sponge that is placed into a wound and sealed with a semi-occlusive dressing. Suction tubing is secured over a hole cut in the dressing, allowing contact with the sponge while the other end of the tubing is attached to a machine that delivers negative pressure as suction in a continuous or intermittent fashion. The negative pressure can be set from negative 50 mm Hg to 200 mm Hg, depending on the clinical situation. Generally, the entire dressing, including the sponge and tubing, is changed every 48 hours.

    Negative pressure wound therapy provided by this device is indicated for use with acute, subacute, chronic, traumatic, and dehisced wounds, as well as for diabetic ulcers, pressure ulcers, partial-thickness burns, flaps, and grafts.1 This therapy has been shown to aid wound healing in several ways. Animal studies have demonstrated that NPWT decreases bacterial burden in wounds, changing wounds from infected to colonized after 4 to 5 days of use.2 The therapy decreases wound edema and promotes the formation of granulation tissue as compared to wet-to-moist dressings; intermittent NPWT (5 minutes on, 2 minutes off) is even more effective in granulation tissue formation.2 Some evidence suggests that NPWT may help remove some inhibitory cytokines and activated polymorphonuclear leukocytes.3 Negative pressure wound therapy also has been shown to decrease the depth of deep wounds faster than wet-to-moist dressings.4 In a single-blind, randomized, controlled trial involving 24 patients with 36 wounds, NPWT resulted in a statistically significant (P = 0.00001) decrease in wound depth compared to wet-to-moist dressings.

    An evolution of NPWT, the V.A.C.® Instill™ has recently been introduced for the acute care setting (see Figure 1). It combines the “traditional” NPWT system with a method to intermittently instill a solution into the wound and is indicated for patients who would benefit from vacuum-assisted drainage and controlled delivery of topical wound treatment solutions and suspensions over the wound bed. Instead of the traditional single tubing, the NPWT with instillation uses two sets of tubing (see Figure 2).The instillation fluid drips by gravity through the first tubing to saturate the sponge and bathe the wound. Then the irrigation tubing is occluded. The fluid is allowed to sit in the wound for a predetermined period of time (from 1 second to 1 hour), after which the vacuum is applied to the suction tubing; thereby, removing the irrigation fluid and wound exudate and collapsing the sponge. Suction is continuously maintained until the entire cycle is repeated according to the amount of time programmed into the unit (1 minute to 12 hours). Typical instillation solutions include normal saline, antibiotics, antifungals, antiseptics, and local anesthetics. Clinical experience at the author’s institution suggests that the new system may decrease the pain that can be associated with the use of traditional NPWT, decrease the bacterial burden of infected wounds, and be more effective than traditional NPWT in “cleaning up” some infected wounds.

    Results of a retrospective analysis of case studies detailing the author’s initial experience using NPWT with instillation are presented and lessons learned after reviewing the cases are described.

Case Studies

    Case 1. Mr. M is a 48-year-old man who presented with wet gangrene of his right foot. His past medical history included insulin-dependent diabetes mellitus with diabetic retinopathy, neuropathy, nephropathy, and peripheral vascular disease. He had a 30-pack per year cigarette smoking history. He had a guillotine amputation of his right ankle on December 2, 2003 and the next day underwent a right below-knee amputation. Several weeks later, the wound became infected, including cellulitis and areas of necrosis. He underwent revision with conversion to an open below-knee amputation on February 9, 2004. Because clinicians were concerned about Mr. M’s circulation and resultant ability to heal the open below-knee amputation wound, a V.A.C.ATS (KCI, San Antonio, Tex.) was placed. The wound filled with healthy granulation tissue but Mr. M experienced moderate discomfort from the NPWT.

    Mr. M’s treatment was changed to NPWT with instillation on March 2, 2004 using a lidocaine solution to address the wound pain. The instillation solution (25 cc 1% lidocaine in 500 cc normal saline) was instilled for 30 seconds and held for 5 minutes. Suction was set at 125 mm Hg and kept on continuously until the entire cycle was repeated every 3 hours for a total treatment time of 7 days. Mr. M experienced significant, immediate wound pain relief. During this period, he was receiving pain medication from a patient-controlled anesthesia (PCA) device. His parenteral pain medication requirements with the ATS version averaged 3.21 mg to 4.26 mg morphine sulfate/hour. In addition, he needed a Fentanyl 100 µg/72 hour topical patch to control his pain. The day he was switched to NPWT with instillation with lidocaine irrigation, his PCA requirements decreased to an average of 2.5 mg morphine/hour. The next day his Fentanyl patch was able to be removed and his pain medication requirements decreased to an average of 0.95 mg morphine sulfate/hour; a >70% reduction in pain medication requirements.
Mr. M was discharged to an extended care facility on March 9, 2004 where traditional NPWT was placed to prepare the wound for a skin graft. A split-thickness skin graft was placed on March 29, 2004 and NPWT used to bolster the graft. Mr. M was discharged with NPWT in place the day after surgery and when it was removed on the post op day 4, nearly 100% take of the graft was noted.

    Case 2. Mr. C was a 41-year-old man who presented with osteomyelitis of his right foot. Past medical history included diabetes mellitus since age 11 with diabetic nephropathy and neuropathy. He underwent a kidney and pancreas transplant in 1998 and was on prednisone and immunosuppression (CellCept, Roche Pharmaceuticals, Nutley, NJ; and Rapamune, Wyeth Pharmaceuticals, Collegeville, Pa.). When infection of his right foot worsened, he underwent an open transmetatarsal amputation (TMA) on January 27, 2004. Hyperbaric oxygen therapy (HBOT) was used perioperatively. On February 2, 2004, he underwent debridement, irrigation, and wound closure of the TMA wound and 3 weeks later developed increased pain, swelling, and erythema at the wound site. On February 27, 2004, the wound was opened and he underwent incision, drainage, and debridement of the wound and the V.A.CATS was applied.

    After 21 days of NPWT, the wound was still infected. The tissue appeared gray (see Figure 3) and wound cultures were positive for Staphylococcus aureus (oxacillin-resistant — ORSA-sensitive to vancomycin) and Klebsiella pneumoniae. Mr. C was receiving IV antibiotics (vancomycin and metronidazole hydrochloride — Flagyl, SCS Pharmaceuticals, Chicago, Ill.) and undergoing hyperbaric oxygen treatments. He was switched to NPWT with instillation of vancomycin (1 g in 250 cc normal saline) for 15 seconds (held for 5 minutes) followed by continuous suction at 125 mm Hg. Instillation was repeated every 3 hours. After 3 days, when the first NPWT with instillation dressings were changed, only K. pneumoniae was cultured from the wound.
After 11 days of NPWT with instillation, the wound had a healthier appearance and only cultured normal flora (coagulase negative; Staphylococcus, light growth) (see Figure 4). Instillation of vancomycin into the wound did not change the pharmacokinetics of the IV vancomycin he also was receiving.

     Negative pressure wound therapy with instillation was discontinued and Mr. C was discharged on April 8, 2004 with a portable NPWT (V.A.C.Freedom, KCI, San Antonio, Tex.) in place. This therapy continued on an outpatient basis for 1 week. The wound has since been treated with local wound care, remains clean, and is slowly healing despite continued use of prednisone and immunosuppression (see Figure 5).

    Case 3. Ms. M, a 66-year-old woman, developed a left fifth toe infection. She previously had undergone a left second toe button amputation and left fourth toe ray amputation. Transcutaneous oxygen measurements (TCOM) were poor — single digit at all locations below her left knee with little if any response to oxygen. Past medical history included hypertension, insulin-dependent diabetes mellitus, and renal failure requiring chronic hemodialysis.

    On March 5, 2004, Ms. M underwent a fifth ray toe amputation. With progressive deterioration of the wound, she was readmitted March 23, 2004 to begin IV antibiotics (vancomycin and piperacillin sodium/tazobactam sodium - Zosyn, Lederle Laboratories, Pearl River, NY). The V.A.C.ATS was placed with Accuzyme (Healthpoint, Fort Worth, Tex.) applied at NPWT dressing changes and daily HBOT was initiated. During HBOT, her TCOM at pressure (2.0 ATA) was 568 mm Hg. After 9 days of treatment, wound cultures revealed the presence of S. aureus, (oxacillin resistant — ORSA-sensitive to vancomycin) and Enterococcus faecalis and Ms. M was taken to the OR because of extension of the infectious process. The wound was debrided (see Figure 6). Negative pressure wound therapy with instillation was started April 2, 2004, irrigating the wound with 1 g vancomycin + 25 cc 1% lidocaine in 250 cc normal saline for 15 seconds. The solution was retained for 5 minutes, followed by continuous suction set at 125 mm Hg. Instillation was repeated every 3 hours (see Figure 7). The lidocaine was extremely effective in minimizing the pain Ms. M had experienced with previous NPWT. After 10 days (fourth NPWT with instillation dressing change), wound culture results included S. aureus (light growth ORSA), E. faecalis, and yeast (not Candida albicans).

    On April 14, 2004, Ms. M required an amputation of her great toe, which had become gangrenous. She continued with IV antibiotics, NPWT with instillation, and HBOT. Her lateral foot wound continued to improve. On day 18, only yeast (not C. albicans) was cultured from the wound.

    Ms. M was discharged home on April 26, 2004 on antibiotics (vancomycin after dialysis, metronidazole hydrochloride, and fluconazole — Diflucan, Pfizer, Inc., New York, NY) to treat the yeast cultured from her wound. She was switched to the V.A.C.Freedom and completed 24 days of NPWT with instillation before discharge. Ms. M finished 40 HBOT treatments on May 12, 2004. Her wound continues to show significant signs of healing (see Figure 8). Negative pressure wound therapy was discontinued on June 15, 2004; however, her wound noticeably deteriorated after the NPWT had been off for a week, so NPWT was reapplied. The wound continues to slowly heal.

    Case 4. Ms. A, a 20-year-old woman, presented with body aches and a 35-lb weight loss. She had diffuse cervical, mediastinal, and retroperitoneal lymphadenopathy. She also had liver infiltration, and a right breast mass.

    On March 25, 2004, Ms. A underwent a right cervical lymph node biopsy and right breast biopsy. Pathology showed Hodgkin’s lymphoma (further work up revealed her Hodgkin’s Disease to be Stage IV), and a benign fibroademoma of her right breast. She had evidence of a hematoma in her right breast. Culture results following aspiration of the hematoma showed no growth. She was discharged receiving chemotherapy doxorubicin (Adriamycin, Pharmacia & Upjohn, Peapack, NJ); bleomycin sulfate; vincristine sulfate; and dexamethosone (Decadron, Merck & Co., Inc., West Point, Pa.) (ABVD protocol).

    On May 20, 2004, Ms. A was admitted with intractable nausea and vomiting following her second cycle of chemotherapy. The right breast incision had partially opened and had a foul odor. Wound culture results showed the presence of Pseudomonas aeruginosa (sensitive to all antibiotics tested). She was taken to the OR on May 25, 2004, for an incision and wound drainage (see Figure 9). Intraoperative aerobic and anaerobic culture results showed the presence of P. aeruginosa, Prevotella melaninogenica (Bacteroides), Peptostreptococus tetradius, and Actinomyces israelii. Negative pressure wound therapy with instillation was placed (see Figure 10). A solution of 80 mg gentamycin plus 25 cc 2% lidocaine in 500 cc normal saline was instilled for 15 seconds, held for 5 minutes, and followed by continuous vacuum set at 125 mm Hg. Instillation was repeated every 3 hours. The wound appeared cleaner and uninfected at the first NPWT dressing change and now only P. aeruginosa was cultured from the wound. Negative pressure wound therapy with instillation was stopped after 5 days (see Figure 11). At that time, no anaerobic bacteria and only coagulase-negative Staphylococcus (considered normal flora) was isolated. The wound appeared clean and Ms. A was discharged home with normal saline wet-to-moist dressing changes and IV antibiotics (gentamycin and cefepime).

    Case 5. Ms. C was a 62-year-old woman admitted from an extended care facility. Earlier in the year at another hospital, she underwent aortic valve replacement with coronary artery bypass grafting, complicated by postoperative Pseudomonas wound infections of both her sternum and saphenous vein donor site. These had been treated initially with NPWT. Five months later, at her most recent admission for a change in mental status, she was in renal failure, on chronic hemodialysis, and in respiratory failure. She was ventilator-dependent and had undergone a tracheotomy. Her medical history included: diabetes mellitus, history of congestive heart failure, morbid obesity, chronic obstructive lung disease with sleep apnea, and hypertension.

    A V.A.C.ATS was placed in the open wound of her left thigh where the saphenous vein had been harvested months before. After 11 days with continued infection after NPWT, the possibility of switching her to NPWT with instillation was assessed (see Figure 12). Instillation with 80 mg tobramycin and 25 cc 2% lidocaine in 500 cc normal saline every 3 hours was initiated. Following a 15- to 60-second instillation, the fluid was retained for 5 minutes, followed by NPWT (vacuum setting of 125 mm Hg). Cultures obtained during the first NPWT dressing change showed the presence of P. aeruginosa (sensitive only to amikacin and tobramycin) and Proteus mirabilis. After 12 days (fourth dressing change) P. aeruginosa and K. pneumoniae extended spectrum beta lactamase (ESBL) were cultured from the wound. The wound appeared noticeably cleaner and filled with healthy granulation tissue. A gelatinous exudate previously seen also disappeared (see Figure 13). After 18 days, only K. pneumoniae (light growth, not ESBL) was cultured from the wound and treatment was discontinued in anticipation of Ms. C’s transfer back to the extended care facility with normal saline gauze dressing treatment.

Discussion

    Negative pressure wound therapy has been shown to aid in wound healing. Decreasing the bacterial load of the wound is one of the proposed mechanisms of action. A recent modification of the NPWT system — NPWT with instillation — allows for intermittent instillation of solutions into the wound. Results of these five case studies suggest that instilling a dilute anesthetic solution effectively minimizes the pain that may be associated with NPWT. It also appears that instilling antibiotics, selected based on culture results, may help decrease the bacterial load of infected wounds. In two of the five cases described here, changing from a traditional NPWT system to NPWT with instillation facilitated a significant improvement in wound clinical appearance and culture results.

    The exact clinical role for wound irrigations and instillation remains unclear. Empirically, instilling antibiotic solutions into wounds seems to be a logical way to deliver high concentrations of antibiotics directly to the site of infection.5 Westaby6 described a closed wound irrigation system more than 20 years ago. The device used was believed to be a satisfactory alternative to once- or twice-daily dressing changes. More recently, Harris7 described a closed irrigation system for hand wounds that achieved resolution of the infection in all 12 of the study patients. Increasing the frequency of wound irrigations may help prevent wound infections.8

    It would be expected, as in the cases presented, that patients with seriously infected wounds would receive culture-directed antibiotic treatment both intravenously and as part of NPWT with instillation. At the author’s hospital system, IV dosing is adjusted by monitoring serum concentrations of vancomycin and aminoglycoside antibiotics. In the patient with a transmetatarsal amputation described in this series, significant systemic absorption of the wound irrigation solution containing vancomycin was not observed and pharmacokinetics did not change after the irrigations were started. Although the absorption of the antibiotic from most wounds is likely negligible, as in the above case, checking pharmacokinetics of any potentially toxic instilled antibiotic would be considered advisable until more clinical wound absorption data are available.

    Delivery Pressure. The delivery pressure of the irrigation seems to be an important factor. A delivery pressure of 5 to 10 lb per square inch (psi) is an accepted range to remove debris and bacteria from the wound while minimizing injury to the normal tissue in the area surrounding the wound.9 This pressure can be delivered by a variety of means, including a simple syringe and needle apparatus. Stevenson10 found that 8 psi of pressure can be delivered using a 35-cc syringe with a 19-gauge needle. In a rabbit model, irrigating with 150 cc to 200 cc of normal saline at this pressure was sufficient to dislodge bacteria from the surface of the wound and reduce the risk of infection. Rodeheaver11 found that 84% of soil infection potentiating factors could be removed from wounds with a continuous delivery pressure of 15 psi. High pressure pulsatile jet irrigation with a delivery pressure of 50 psi may more efficiently remove bacteria from wounds, but irrigation at this pressure has been reported to be deleterious to bone healing.12

    The NPWT with instillation system has only recently become available and is indicated for patients who would benefit from vacuum-assisted drainage and controlled delivery of topical wound treatment solutions and suspensions over the wound bed. Negative pressure wound therapy with instillation is a low-pressure delivery (gravity-feed) system for wound irrigations. However, wounds with significant debris and bacterial contamination can be irrigated at higher pressures at the time of NPWT dressing changes by one of the above methods.

    Solution type. The type of solutions that can be used for wound irrigation have been discussed for decades. Dakin and Carrel13 tested more than 200 chemicals before concluding that sodium hypochlorite 0.5% solution (“Dakin’s solution”) met the criterion of high bacterial activity and low toxicity. Tap water (adequate for drinking) has been satisfactorily used for cleansing wounds in the emergency setting.14-16 Sequential surfactant wound irrigations in a rat model were shown to effectively reduce the infection rate in an orthopedic implant contamination.17 Castile soap, benzalkonium chloride, and Bacitracin irrigation solutions also have been investigated for their effect on preventing or treating wound infections.18,19 The ordering physician can work with the hospital’s pharmacists and infectious disease physicians to determine which solution is appropriate for each particular patient and clinical situation, recognizing that some of the uses would be considered offlabel (see Table 1).

    Contraindications. Some solutions should be avoided or used with extreme caution. One death was thought to be attributed to wound irrigation with povidone iodine solution.20 D’Auria20 recommends that intermittent or continuous irrigation of large quantities of povidone iodine solution should be performed with caution. In another case, oxygen microbubbles after hydrogen peroxide irrigation were considered to be the cause of widespread embolization with shock and coma.21 Also, neomycin solutions must be used with caution. In a patient with hip a wound, this product was absorbed in serum concentrations associated with nephrotoxic and ototoxic reactions.22 Anaphylaxis has been reported in patients receiving Bacitracin irrigation23,24 and topical application of a polymixin B and Bacitracin topical mixture.25 Taking a detailed history of possible allergic reactions to antibiotics and topical preparations and continued monitoring is important for the possible development of an allergic reaction, side effect, or toxic reaction to the drug therapy.

    Alcohol-based solutions and solutions that contain alcohol are contraindicated for use with NPWT with instillation because of their effect on the sponge dressing. Hydrogen peroxide solutions also are contraindicated with this system.26 The effect of numerous other solutions on human wounds has not been extensively studied.

    A relatively short period of wound instillation (1 to 3 weeks) may suffice to favorably change a compromised wound to a wound that will heal successfully. Understanding the desired outcome for initiating NPWT helps guide when the therapy should be stopped — most often when near complete or complete wound closure has been achieved or when preparation for a graft, flap, or further surgery has been completed.

   In the past, NPWT has been discontinued when progress to achieving the desired goal is slow — eg, when an infected wound fails to show improvement or healing stalls. Negative pressure wound therapy also has been discontinued if the patient experiences too much pain or is unwilling to keep the unit on. The author’s experience suggests that, in these instances, NPWT with instillation may be an effective alternative to stopping traditional NPWT.

Conclusion

    Negative pressure wound therapy with instillation should strongly be considered for managing significant wound pain in patients with traditional NPWT (without instillation) currently in place. Dilute lidocaine solutions are extremely effective in pain control and may be combined with some antibiotic and antiseptic solutions. Negative pressure wound therapy with instillation also is indicated in the treatment of grossly infected wounds, especially if they do not show a significant improvement with a trial of traditional NPWT. Culture-directed antibiotic wound irrigation appears to effectively decrease the bacterial burden of infected wounds, change the appearance of some wounds from infected to clean, and convert wound culture data from positive cultures to no growth or normal flora.

    Negative pressure wound therapy with instillation should be used in conjunction with appropriate local wound care including irrigation, debridement, and systemic antibiotics, along with HBOT if indicated. Negative pressure wound therapy with instillation may be started initially to treat some “high-risk” wounds that appear severely infected and may be limb-threatening if located on an extremity.

    Clinicians should work with their hospitals’ clinical pharmacists to develop the appropriate solutions and concentrations to be administered at their facility. Culture-directed antibiotics may increase the success of irrigation in decreasing the wound bacterial burden. Consulting with an infectious disease specialist also may be helpful to select wound irrigation solutions for a particular patient. A detailed history of possible drug allergies and ongoing clinical monitoring are needed to avoid serious allergic or toxic reactions to the solution in use.

    Negative pressure wound therapy with instillation appears to help change the consistency of viscous wound exudates. Decreasing the viscosity of the wound drainage likely will make it easier for the system to remove the fluid from the wound.

    Because NPWT with instillation is a recently introduced wound care system, available clinical evidence regarding the effectiveness of the system and different irrigation solutions is limited. Controlled clinical studies are needed to look at this technology and compare it to other instillation/irrigation methods. Further studies to ascertain the benefits of NPWT and instilling solutions are needed.

Acknowledgments

    The author would like to thank Mike A. Dietrich, PharmD, BCPS, Associate Professor of Pharmacy Practice, Midwestern University College of Pharmacy, for his assistance in the preparation on this article. The author also would like to acknowledge and thank the compassionate and dedicated wound care staff at all the Scottsdale Healthcare sites.