The Role of Negative Pressure Wound Therapy in Managing Chinese Patients With Wound-derived Acute Severe Illness

Introduction. Resulting mostly from major injury or infection, severe acute wounds are often accompanied by septic shock or multiple organ failure and associated with high disability and mortality rates. In managing Chinese patients with wound-derived acute severe illnesses, salvage treatment in the emergency department has traditionally prioritized life support and protection of vital organs before wound repair. Objective. This retrospective review evaluated the outcomes of patients with wound-derived acute severe illness who were treated with a new salvage protocol that combined proactive wound care with simultaneous life-support measures. Materials and Methods. Records from 2011 to 2013 at Peking Union Medical College Hospital (PUMCH) in Beijing, China, were reviewed to identify patients with wound-derived acute severe illness treated with the new protocol. The plastic surgery department, emergency department, and intensive care unit developed the protocol, which included proactive wound treatment with negative pressure wound therapy (NPWT), interdepartmental cooperation, and comprehensive patient treatment. Results. Fifty-six patients were managed with the new protocol. At presentation, all patients were in septic shock and 29 of 56 (51.8%) required mechanical ventilation. Of the treated patients, 21 (37.5%) fully recovered and 29 (51.8%) improved sufficiently enough for transfer to a general ward. Six patients (10.7%) died of causes unrelated to NPWT. Conclusions. At PUMCH, the new collaborative salvage protocol with proactive use of NPWT with simultaneous life-support methods resulted in greater therapeutic effects than traditional salvage treatment could offer.

As living standards and medical conditions improve, the spectrum of disease widens with increasing numbers of patients with complex acute wounds. No longer merely a clinical problem, wounds have become a social concern, and wound care has expanded into a new clinical discipline. Treatment of complex acute wounds resulting from injury, infection, and iatrogenic factors remains a challenge in clinical practice. Acute wound infections and bacteremia are significant risks for sepsis and septic shock, both of which are recognized global health challenges. Sepsis-associated in-hospital mortality has been estimated to be ≥ 10% and septic shock-associated has been projected at ≥ 40%.¹

Although wound repair is a vital task for plastic and reconstructive surgery, in China, patients with complex acute wounds have traditionally missed the best, earliest opportunities for wound treatment. Until recently, conventional salvage treatment applied life-saving measures first, while wound treatment involving multiple disciplines was the last work to be performed. With this method, the authors observed longer patient treatment times, prolonged medical expenses, reduced quality of life due to poorer prognosis, and persistent wound issues that resulted in a vicious cycle of new infections and fluid loss, among other factors.

In China, patients with a wound that is the primary cause of their critical illness are classified as patients with wound-derived acute severe illness. Often hospitalized in an emergency department or an intensive care unit (ICU), these patients have wounds resulting mainly from injury and infection. If the wound is caused by an iatrogenic factor, the patient usually has an underlying disease as well as a history of surgeries and is critically ill with septic shock and organ failure. Iatrogenic factors are treatment-related factors that compromise wound healing, such as poor wound management, regular disruption of the wound through inappropriate cleansing, improper removal of dressings, applying cytotoxic topical agents, cross-contamination, improper use of sterile and clean techniques, lack of proper hand washing, shear injuries from transfers, and ischemia from unrelieved pressure.² Treatment of the illness typically calls for consultation with clinicians and physicians from multiple specialties, who often determine the need for complex surgeries with significant morbidity, such as amputation. In these cases, not only are decision-making and treatments complicated, but patient prognosis also is quite poor.

Over the past 2 decades, negative pressure wound therapy (NPWT; V.A.C. Therapy; KCI, an Acelity Company, San Antonio, TX) has advanced wound treatment. Negative pressure wound therapy (also referred to as vacuum-assisted wound closure^3,4) is an integrated system that involves placing a polyurethane foam dressing (V.A.C. GRANUFOAM Dressing; KCI, an Acelity Company) into an open wound, sealing the area with an adhesive film, and connecting a tube attached to the dressing to a therapy unit that provides continuous or intermittent negative pressure (monitored by SENSAT.R.A.C. Technology; KCI, an Acelity Company) at the wound site. Exudate is collected into an attached canister.

Negative pressure wound therapy is intended to create an environment that prepares the wound bed for closure and promotes wound healing by secondary or tertiary (delayed primary) intention.^5,6 Both macrostrain and microstrain are applied to the wound bed during NPWT to promote healing. Macrostrain occurs when the negative pressure contracts the open pore foam dressing; it draws wound edges together, provides direct wound bed contact, distributes negative pressure evenly, and removes exudate and infectious materials.⁵ Microstrain is microdeformation at the cellular level, leading to cell stretch, an increase in cellular proliferation and migration, enhanced perfusion, reduction in edema, and promotion of granulation tissue formation.⁶

From 2011 to 2013 at Peking Union Medical College Hospital (PUMCH) in Beijing, China, the plastic surgery department collaborated with the emergency department and the ICU team to establish a new salvage treatment protocol that included proactive wound treatment with NPWT, interdepartmental cooperation, and comprehensive patient care.

The purpose of this retrospective review was to report the authors’ early experiences with interventional NPWT and simultaneous basic or advanced life support in patients with wound-derived acute severe illness.

From 2011 to 2013 at PUMCH, deidentified patient data were gathered according to institutional guidelines; patients consented to use of deidentified wound photos. Patients with wound-derived acute severe illness were admitted to the hospital following consultation with the plastic surgery department. Wounds were cleansed, disinfected, and debrided at the bedside. A polyurethane foam dressing was placed in the wound and covered with an adhesive drape and tubing; continuous NPWT was applied to the wound at -125 mm Hg to -200 mm Hg with dressings changed every 3 to 4 days. Negative pressure wound therapy was intended as a key step in the treatment for these patients and was only discontinued once sepsis was under control or septic shock was reversed. The emergency department and ICU administered adjunctive therapies, including surgical or nonsurgical wound treatment, as necessary after use of NPWT.

Fifty-six patients with wound-derived acute severe illness were treated with NPWT; 29 (51.8%) were male and 27 (48.2%) were female. Median age was 45 years (range, 17–82 years), with 2 patients < 20 years. No first visits originated in the plastic surgery department. Acute wound types included in the analysis were iatrogenic invasive manipulation, acute open wound, open abdomen, blast injury, skin and soft tissue infection, and crush injury. Etiologies are detailed in Table 1. Of the mediastinitis wounds, 5were cases of coronary artery bypass grafts, 3 were aortic or mitral valve replacements, and 2 were cases of ascending aortic dissection. Of the abdominal surgery patients, 2 were acute intestinal obstruction status post cancer and the other 2 were superior mesenteric artery embolization.

Duration of NPWT treatment ranged from 3 to 29 days, with a median of 11.5 days. During use of NPWT, 37 of 56 (66.1%) patients underwent surgical procedures, including debridement, primary suture, split-thickness skin grafting (STSG), and skin flap transfer. Nineteen (33.9%) patients were treated with only NPWT with regular dressing changes and received no surgical procedures. Their wounds closed via secondary intention.

As demonstrated herein, with early, proactive use of NPWT and adjunctive therapy, most patients improved considerably, either in terms of general physical condition or local condition of the wound. Of the 56 patients, 21 (37.5%) fully recovered and were discharged; to note, these were mostly young or middle-aged patients with wounds or soft tissue infections.

A total of 29 of 56 (51.8%) patients improved and were transferred to general wards for continued treatment of their primary disease and/or reconstruction. Six patients (10.7%; all > 40 years) died of multisystem organ failure (MSOF) unrelated to NPWT. Forty-four of 56 (78.6%) patients left the hospital with healed wounds, either by hospital discharge or transfer to a different hospital (Table 2).

The following 2 cases demonstrate successful use of the new salvage treatment protocol.

Case 1: Necrotizing soft tissue infection of the upper arm

A 38-year-old man presented with furuncles on his right upper arm that were rapidly developing into severe skin and soft-tissue infections and necrotizing fasciitis, and causing septic shock. The skin swelled prominently, resulting in tension blisters over its surface. Despite incision and drainage performed previously in a different hospital, the patient did not improve. While being transported to PUMCH, the patient was conscious but indifferent, and his noninvasive blood pressure was not detected. At the emergency room, antishock and other life-support systems were administered. Peripheral blood leukocytes were 60 × 10⁹/L at peak, and leukemoid reactions occurred. The culture of a sample taken from the deep arm wound (Figure 1A, 1B) as well as a blood culture revealed pan-drug resistant Acinetobacter baumannii. Intravenous (IV) imipenem/cilastatin (500 mg every 8 hours) was administered for 7 days.

The plastic surgery and orthopedic departments were invited to an emergency consultation, during which emergency department surgeons proposed to remove the focus of infection with an immediate above-the-elbow amputation to help control the septic shock. Because this patient was a manual laborer and the only able-bodied person in his household, both the patient and his family expressed a strong desire for limb salvage. During physical examination, the plastic and orthopedic surgeons observed relatively good sense and mobility of the distal end of the limb, great vessels and nerves exposed on the wound surface, some necrotic muscle and skin, and copiously draining exudate (> 2000 mL every 24 hours). The wound measured 15 cm x 15 cm.

The multidisciplinary team ultimately decided to initiate NPWT (Figure 1C) and postpone amputation of the right arm. After 2 weeks of NPWT at -125 mm Hg, the wounds were filled with beefy red granulation tissue and considerably smaller (Figure 1D). After 3 weeks of NPWT at -125 mm Hg, the drainage volume significantly decreased to 100 mL every 24 hours, and the tension blisters disappeared. With a gradual decrease in the dosage of vasoactive drugs (IV noradrenalin [2 µg/kg/min] and dopamine [5 µg/kg/min]), which had been administered for 13 days in the emergency room, the patient’s vital signs were stable, and the number of the peripheral blood leukocytes returned to normal a level.

At 4 weeks, the wound measured 14 cm x 11 cm and was ready for a STSG (Figure 1E) and NPWT was discontinued. After the wound was surgically debrided, an STSG was applied and bolstered with petrolatum gauze, dry gauze, cotton pad, and cast from shoulder to metacarpophalangeal joints for 12 days. The patient fully recovered and was discharged with a healed upper arm 3 weeks post STSG application (Figure 1F).

Case 2: Osteofascial compartment syndrome (OCS) and crush syndrome in lower leg with acute renal failure

A 31-year-old woman presented to a local hospital with a swollen left lower leg and reported sensory and movement disturbance below the knee joint. She had arrived home severely intoxicated the night before, collapsed near furniture, and slept for 22 hours prior to awakening to this pain. At the hospital, the patient was diagnosed with OCS. Incision, drainage, and debridement were performed, but after 5 days, the patient’s condition had not improved. The patient then was admitted to PUMCH.

Upon admittance, the patient suffered from hypovolemic shock, metabolic acidosis, hyperpotassemia, anuria (volume of the deep red urine was < 100 mL for 24 hours), and significantly increasing levels of serum creatinine, myoglobin, and creatine kinase. On the patient’s swollen left leg, 2 symmetrical incisions, each about 30 cm in length, touched the muscular layers (Figure 2A, 2B). Below the knee joint there was significant weakness of deep and superficial sensibility, a myodynamia of grade 0, and foot drop. The wound measured 20 cm x 13 cm. Blood and wound secretion cultures revealed Escherichia coli. A diagnosis of crush syndrome with acute renal failure was clear.

Immediately, the patient was admitted to the ICU where she received bedside continuous renal replacement therapy and anti-infection therapy for 15 days. In tandem with these therapies, the plastic surgery department applied NPWT at the bedside at -125 mm Hg (Figure 2C, 2D). As a large amount of deep red drainage was discharged into the canister, the urine color gradually lightened, and serum myoglobin and creatine kinase levels decreased. Within 2 weeks of NPWT application, the urine volume gradually increased, the serum creatinine level gradually returned to normal, and both the sensibility and myodynamia of the limb were recovered to some extent.

At about 2 weeks post initiation of NPWT, granulation tissue covered the wound surface and the wound size was reduced to 18 cm x 9 cm (Figure 2E, 2F). At this time, NPWT was discontinued, surgical debridement was performed, and a single STSG was applied. The STSG was bolstered with petrolatum gauze, dry gauze, cotton pad, and cast extending from above the knee joint to the ankle joint for 7 days. Postoperatively, physical therapy was prescribed 3 times per week for 2 weeks.

Two weeks later, the patient was discharged and able to walk on crutches. Four months post STSG placement, the wounds achieved full closure (Figure 2G, 2H).

The top priority in the salvage treatment of patients with wound-derived acute severe illness is to save their life and then conserve limb function. The key to the emergency treatment paradigm evaluated in this study was to balance the relationship between improving the patient’s general physical condition and repairing the wound. In these patients, wound treatment is of particular importance as it can influence the whole body. Better wound treatment generally results in improved physical condition for these patients. Therefore, wound treatment should be incorporated early into the whole treatment paradigm and should proceed simultaneously with, and be as important as, life support. During the intervention and treatment of wound-derived acute severe illness, plastic surgeons should not only focus on wound repair but also cooperate with other departments to proactively ameliorate local areas, improve the patient's general physical condition, and alleviate illnesses.

For example, if traditional salvage treatment methods at PUMCH had been followed, the patient in case 1 would have received an amputation of the right arm. Subsequently, the amputation might have been expanded because of tissue edema, obscured boundary of necrosis, and other issues. Primary wound closure would have been highly unlikely, and wound repair would have been the last work conducted by the plastic surgery department. In addition, the patient would have run the risk of a surgery during the acute phase and suffered from great pain and loss, as acute necrotizing fasciitis is often accompanied by whole-body toxic shock with a reported mortality rate of 15% to 45% with late diagnosis and treatment.⁷ The key to proper treatment for this patient was to immediately remove the focus of infection, ease tissue edema, and reduce circulatory burden.

The patient in case 2 was diagnosed with relatively uncommon OCS, crush syndrome, and acute renal failure. Because crush syndrome is commonly seen in construction accidents, traffic accidents, and earthquakes, it was speculated that the patient (who was not overweight and likely did not suffer from her own body pressure while she was lying down) may have been under pressure for long periods beneath tables, chairs, or other pieces of furniture that were knocked down and not removed by anyone else.

With evident myoglobinuria, shock, hyperkalemia and kidney failure, the patient in case 2 was critically ill with a life-threatening injury. Considering such rapid deterioration, some surgeons on the PUMCH multidisciplinary team believed that, for severe cases with evident myonecrosis that could not be eased by incision and drainage, amputation should be administered immediately to eliminate pathologic and physiological cascade reactions resulting from widespread myonecrosis.⁸ Since amputation was unacceptable to the patient, the keys to proper treatment in this case were elimination of her internal necroses, restoration of renal function, and maximum preservation of her affected limb. Restoration of renal function was noted by closely monitoring the reduction level of serum creatinine and myoglobin and monitoring changes in volume and color of urine. As urine volume increased and entered into polyuria stage, the color became pale.

Playing an active role in intervention, the plastic surgery department applied NPWT, and the reticulated open-cell foam dressings worked with stable and controllable negative pressure.^3,9 In October 2010, the NPWT device used was approved for commercialization in China. With it being easy to operate and monitor, it can be applied at the bedside without the risks associated with anesthesia and surgery. In addition, NPWT does not typically affect the therapies administered by other departments.

In the authors’ experiences, once the sepsis and infection were brought under control during early stages with application of NPWT, the NPWT could be discontinued. They discontinued the therapy once sepsis was under control to save on therapy costs. Also, in their experience, progression of sepsis and infection was halted with the application of NPWT in the early stages, after which the therapy was no longer required. Based on their experience and existing clinical reports,^5,6 NPWT allows sufficient drainage and reduction of tissue edema. Although NPWT has widely been applied to wounds, most of the reports concern chronic wound treatment versus complex acute wound treatment. Its adjunctive use in wounds with infection is a subject of ongoing research; cautious and judicious use has been recommended.¹⁰ Debridement and appropriate antibiotics always should be administered as needed.

Results from this uncontrolled retrospective data analysis showed a survival rate of 89.3% in this acute injury population with the new salvage treatment protocol. The authors have continued with NPWT use in their practice based on their observational experience that this technology has improved outcomes and survival rates. Between 2008 and 2011, about 23 patients with wound-derived acute severe illness were treated at PUMCH with traditional salvage treatment protocol. Of these 23 patients, death was reported in 12 (52.2%) patients, and 3 of the 11 (27.3%) who survived received an amputation. Outcomes of patients who received the traditional protocol are listed in Table 3. These results suggest survival rates with the new protocol were improved over previous survival rates in patients with wound-derived acute severe illness, but controlled research is needed to confirm a statistical correlation.

There have been several reports on the application of NPWT to treat crush syndrome.^8,11,12 Further, anecdotal clinical evidence and controlled animal study data have demonstrated a decrease in serum myoglobin levels in the presence of crush/ischemia injury during NPWT use.¹² A skeletal muscle injury such as muscle compression and crush leads to a disruption of the integrity of the muscle cell wall with release of intracellular contents, including myoglobin, potassium, phosphate, and creatine kinase, into the interstitial fluid space. Without active removal, the released myoglobin eventually enters the systemic circulation and frequently leads to acute renal failure.¹³ Removal of myoglobin and other nephrotoxic agents from the wound site before entry into the systemic circulation has been postulated to help prevent obstruction in the distal tubules and the direct cytotoxic effect of myoglobin uptake in the proximal tubule by endocytosis.¹² Myoglobin levels in this case series decreased during use of NPWT even after acute renal failure diagnosis. In the authors’ experiences, compared with open incision and drainage, NPWT appeared to remove infectious materials more effectively.

Wound treatment is often the primary problem in the traditional salvage treatment protocol of patients with wound-derived acute severe illness. It is necessary to take into account the beneficial impact of the improvement of local areas on general physical conditions and to choose a proper approach early to deal with the primary problem first. The traditional treatment approach of treating the wound last is changing in China but has not yet been completely abandoned.

Rather than isolating their focus to their own specialized area, clinicians from multiple departments in a general hospital should collaborate, think creatively, and organize a highly cooperative team for wound treatment, so that a view of comprehensive treatment can be adopted. For patients with wound-derived acute severe illness, wound healing is a critical factor in the whole treatment because it is a key part of patient survival, especially in the early days. The longer a wound remains open, the greater the risk for infection, which may potentially result in amputation, life-threatening illness, longer hospital stay, and higher treatment costs.^14,15 In this case series of critically ill patients, NPWT appeared to be an essential tool in accomplishing the goal of wound healing.

Affiliation: Chinese Academy of Medical Sciences, Peking Union Medical College Hospital, Beijing, China

Correspondence: Xiaojun Wang, MD, Peking Union Medical College Hospital (East), No.1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, China 100730; pumchwxj@163.com

Disclosure: The authors disclose no financial or other conflicts of interest.