Negative Pressure Wound Therapy With Instillation and Dwell Time and Standard Negative Pressure Wound Therapy in Complex Wounds: Are They Complementary or Competitive?

Negative pressure wound therapy (NPWT) has changed the management of wounds by promoting continuous wound drainage and facilitating faster granulation tissue growth.¹ This therapy prepares the wound either for split-thickness skin grafting or secondary healing. It can be used in traumatic, acute, and chronic wounds with bioburden, diabetic ulcer, and pressure injuries.^2-4 Reports have shown cost savings due to shorter hospital stay, fewer surgeries, reduced wound closure time, and increased limb salvage rates.¹

Negative pressure wound therapy with instillation and dwell time (NPWTi-d) is the latest modification in which a topical solution (eg, normal saline) is instilled in the wound and, after a specified interval, is evacuated by negative pressure. It is claimed to be better in controlling the bioburden of complex wounds.^4-7 This method also reduces the number of surgeries needed for debridement, especially in patients who are critically ill and might not withstand the stress of surgery. A review of the current literature suggests that NPWTi-d is a viable adjunct therapy in the management of infected wounds, especially in patients with medical comorbidities.^8-9 In India, NPWT is an accessory treatment recommended for a variety of acute and chronic complex wounds and has been used for the past 10 to 15 years, whereas NPWTi-d was introduced 5 years ago.

The aim of this case series is to study the effectiveness of NPWTi-d alone versus NPWTi-d plus NPWT in the treatment of patients with complex wounds with heavy bioburden and comorbidities. The objectives of this study were (1) reduction in bioburden, (2) reduction in number of surgeries, (3) faster appearance of healthy granulation tissue, and (4) cost savings.

The sample group was composed of patients with complex wounds and comorbidities who required admission to the hospital and/or intensive care. Written informed consent was obtained from every patient.

Inclusion criteria
Patients with complex wounds, such as diabetic ulcers, gangrene, infected traumatic wounds, necrotizing fasciitis, and pressure ulcers, with heavy bioburden and requiring multiple debridements were included in this study. Study patients also had serious comorbidities, such as uncontrolled diabetes, hypertension, multiorgan dysfunction syndrome (MODS), peripheral vascular disease, and renal failure.

Methods
The NPWTi-d equipment used was V.A.C. ULTA with V.A.C. VERAFLO (3M + KCI). Normal saline^8,10,11 was used for instillation on the wound bed with dwell time of 10 minutes and negative pressure of -125 mm Hg.^11-13 The cycles repeated every 6 to 8 hours per day. Fluid volume depended on the dimension of the wound and was calculated by covering the ulcer with a transparent, sterile, elastic polymer sheet. The sheet was punctured at the highest point, and 0.9% saline solution was injected with a hypodermic needle until no air was left in the cavity. The injected volume was measured, and it was considered 100%.Repeated volumetric measurements and photographs of the wounds were taken.

In 4 of 8 patients, NPWTi-d was stopped after 7 to 10 days and conventional NPWT was then initiated. Dressings were changed every 3 days. The endpoint was considered to have been met when the wound had contracted by approximately 50% with clearance of bioburden and appearance of healthy granulation tissue in the wound bed. All ulcers were then closed with a split-thickness skin graft. Definitive and supportive treatments were provided to all patients as per the requirements of their comorbid conditions.

The cases for NPWTi-d plus NPWT are shown in Table 1 and NPWTi-d alone cases are reported in Table 2.

NPWTi-d plus NPWT
Case 1: Complex infected diabetic foot. A 46-year-old man, with a history of diabetes mellitus for 15 years and poor arterial blood flow in the left foot, presented with a nonhealing ulcer on the left foot that had been present for 2 months. The ulcer was 8 cm × 6 cm, bone deep, and had a large amount of slough and foul-smelling pus discharge. The surrounding skin showed gangrenous changes (Figure 1A, 1B).

Results of blood tests showed hemoglobin A_1c (HbA_1c) of 7.8% and total leukocyte count of 16 900/µL. Culture and sensitivity testing of the pus showed growth of Klebsiella pneumoniae. Doppler ultrasound showed poor blood flow in the foot. Lateral and anteroposterior radiographs of the foot showed acute osteomyelitis changes in the bones of the ankle joint.

The patient underwent surgical debridement under anesthesia. Intravenous antibiotics were given as per the results of the culture and sensitivity report with all other supportive treatments. Blood glucose levels were monitored every 6 hours and controlled strictly using insulin and oral hypoglycemic medicines.  

After debridement, NPWTi-d was initiated with normal saline. The dressing was changed every third day. Four NPWTi-d dressings were applied. After the last dressing, there was maceration of the surrounding skin and frequent alarms in the vacuum pump due to leakage of instillation fluid and blockage of the drainage tubes. The NPWT dressings were applied and changed 3 times on every third day. After the third dressing, the wound was covered with healthy granulation tissue and there was a considerable decrease in the depth of the wound (Figure 1C, 1D). The patient underwent split-thickness skin grafting after 2 weeks. The NPWTi-d was helpful in reducing the bioburden and saving the patient from repeated debridement, but it caused maceration of the skin and frequent alarms due to leakage of fluid and blockage of tubes. Once slough was cleared, NPWT was helpful in fast granulation in the wound. It helped to save the foot from amputation.

Case 2: Complex infected traumatic wound. A 26-year-old woman was admitted 1 month after a motor vehicle accident. The patient presented with multiple infected large wounds measuring 25 cm × 25 cm on the left and right thighs (Figure 2A, 2B). The patient had comorbidities of septic shock with hypotension and metabolic acidosis, acute renal failure, anemia, and hypoproteinemia.

Results of blood tests showed the following values: hemoglobin, 7.4 g/dL leukocyte count, 23 000/µL; serum creatinine, 4.2 mg/dL; C-reactive protein, 237 mg/L; serum sodium, 125 mEq/L; and serum albumin, 1.1 g/dL. The culture and sensitivity report showed the presence of K pneumoniae, Pseudomonas aeruginosa, and Proteus vulgaris. Fungal culture showed growth of mucormycetes.

The patient was treated with bilevel positive airway pressure and ionotropic support. Broad-spectrum systemic antibiotics and antifungal drugs, intravenous fluids, and other supportive treatments were started. She underwent repeated hemodialysis and multiple blood transfusions. The patient’s condition stabilized. 

On the second day of admission, extensive debridement of wounds was performed followed by 2 NPWTi-d treatments on both thigh wounds at an interval of 3 days; this led to a considerable decrease in pus discharge and foul smell. However, there was recurrent troubleshooting due to fluid leakage and tube blockage. Therefore, standard NPWT therapy was applied 4 times at an interval of 3 days. After this, cultures showed no growth of bacteria or fungus, and healthy granulation tissue appeared in the wound (Figure 2C, 2D). After 6 weeks, split-thickness skin grafting was performed (Figure 2E, 2F). 

The patient’s general condition improved significantly, with 90% uptake of grafts. The patient was discharged after a 2-month hospital stay.

The combination of NPWTi-d plus NPWT was effective in the treatment of large, heavily infected wounds (resistant microorganism and mucormycosis) in this patient, and it also proved to be lifesaving. Repeated operation room visits for debridement were not required, and the dressings were less painful and fewer in number. 

Case 3: Complex wound of the right lower limb. A 70-year-old man with a history of an unsuccessful femoropopliteal bypass graft was admitted to the hospital 1 month after the surgery. At the time of this admission, the patient had gangrene of the left foot and leg as well as a large wound measuring about 25 cm x 18 cm on the medial aspect of the left thigh. The infection was spreading to the groin (Figure 3A). The patient had uncontrolled diabetes and peripheral vascular disease of the left lower limb arteries.

Results of blood tests showed a high total leukocyte count of 31 000/µL, serum creatinine level of 1.89 mg/dL, and HbA_1c of 9%. Pus culture showed growth of Staphylococcus aureus. 

Treatment with broad-spectrum antibiotics was started. Insulin and oral antidiabetic agents were given to control hyperglycemia. After the patient’s condition stabilized, he underwent above-the-knee amputation and debridement of the infected thigh wound, resulting in a large 20 cm x 14 cm wound with undermined edges (Figure 3A). 

Two NPWTi-d dressings were applied at an interval of 3 days, which substantially decreased the bioburden. Two NPWT dressings were then applied, after which the wound bed was covered with healthy granulation tissue (Figure 3B). The patient then underwent split-thickness skin grafting after 20 days.

Combined NPWTi-d plus NPWT was effective in the treatment of this complex and heavily infected ischemic wound of the thigh. It saved the patient from hind quarter amputation, giving him a chance to walk with a prosthesis. In addition, major high-risk surgery was avoided. 

Case 4: Complex wound of the left leg with necrotizing fasciitis. A 66-year-old male was admitted with the chief complaint of black discoloration of the skin of the left leg for 3 weeks, fever of 101°F, breathlessness, and anuria. On local examination, there was gangrene and skin blisters on the posterior aspect of the leg with crepitations (gas gangrene). The diagnosis was necrotizing fasciitis of the left leg. The patient’s comorbidities included diabetes, chronic renal failure, ischemic heart disease, septic shock, and anemia.

Results of blood tests showed hemoglobin, 6 g/dL; total leukocyte count, 42 000/µL; platelet count, 30 000/µL; and serum creatinine, 3.6 mg/dL. Liver function and coagulation profile were also abnormal (serum bilirubin, 3.8 g/dL; prothrombin time, 21.4 seconds; international normalized ratio, 1.8). Pus culture reported the presence of K pneumoniae and P aeruginosa. 

The patient was given intravenous fluids, broad-spectrum antibiotics, insulin, and ventilator support. Hemodialysis was also done for impaired renal function and anuria. Multiple blood transfusions and fresh frozen plasma were administered. Initially, dressings and minor debridement were done in the intensive care unit. When the patient’s condition stabilized, extensive debridement of gangrenous tissue was done in the operating room under anesthesia. Profuse foul-smelling discharge was still present (Figure 4A). 

One NPWTi-d dressing was applied for 3 days, but there was recurrent troubleshooting alarm due to leak. Therefore, NPWT dressings were used twice at an interval of 3 days. After removal of the second NPWT dressing, healthy granulation tissue covered the wound. Bioburden also was decreased to a great extent, and culture results were negative (Figure 4B). The overall condition of the patient improved significantly and he no longer needed ventilator support. After 2 weeks, split-thickness grafting was performed.

NPWTi-d plus NPWT used as adjunctive therapy proved to be limb- and life-saving in this patient with extensive necrotizing fasciitis with gas-forming organisms and multiple comorbidities. 

NPWTi-d alone
Case 1: Complex chest wound. A 70-year-old woman was admitted with a large gangrenous area (10 cm × 30 cm) on right side of the chest wall extending into the right breast (Figure 5A). The patient presented with breathlessness, dizziness, altered mental status, jaundice, and oliguria. Medical history revealed urinary sepsis and fever for 7 days. At the time of admission, she was hypotensive (70/50 mm Hg) and dehydrated with tachycardia 120 beats/minute, respiratory rate 35 breaths/minute, and fever reaching 102°F. The patient was diagnosed with necrotizing fasciitis of the right breast and back, diabetes, and MODS. The patient’s comorbidities included poorly controlled diabetes, hypertension, bronchial asthma, jaundice, and MODS.

Initial investigation showed hemoglobin, 10.9 g/dL; total leukocyte count, 22 520/µL; serum creatinine level, 7.66 mg/dL; bilirubin, 6.21 mg/dL; sodium, 125 mEq/L. Tissue culture results showed heavy growth of Enterococcus faecium and K pneumoniae.

The patient received ventilator and ionotropic support. Hemodialysis was performed, and broad-spectrum antibiotics, intravenous fluid, and blood transfusions were administered. After the patient’s general condition stabilized, she underwent aggressive debridement under general anesthesia. Postoperatively, the patient's serum creatinine decreased, and she was weaned from ionotropic support. She underwent extubation on postoperative day 3. After debridement, a dumbbell-shaped ulcer was present with remaining adherent slough and moderate discharge (Figure 5A), for which NPWTi-d was applied 3 times at an interval of 3 days. Gradually the wound began to heal, and healthy granulation tissue replaced necrotic tissue (Figure 5B). The patient underwent skin grafting 1 month later, and the wound healed completely (Figure 5C).

The NPWTi-d wound management system resulted in fast clearance of bioburden and the appearance of healthy granulation tissue. It contributed to saving the patient’s life. 

Case 2: Complex grade 5 diabetic foot ulcer. A 58-year-old man presented with gangrene of the distal part of the right foot that had been present for 1 week. He had decreased urine output for 5 days. Medical history showed diabetes mellitus for 16 years and hypertension for 12 years. He had undergone amputation of the left great toe 2 years before admission. 

On examination, there was blackening of 4 toes (excluding little toe) of the right foot. The surrounding skin of the distal half of the foot was inflamed. Dorsalis pedis artery pulsation was weak. The diagnosis was a grade 5 diabetic foot ulcer of the left foot with peripheral vascular disease. Comorbidities were hypertension, impaired renal function, and peripheral vascular disease.

Results of blood tests showed serum creatinine, 2.89 mg/dL; serum urea, 96 mg/dL; HbA_1c, 10.1%; and total leukocytes count, 14 380/µL. Doppler ultrasound showed poor blood flow in the foot and distal part of the right leg. Pus culture results showed heavy growth of S aureus.

Broad-spectrum antibiotics were started intravenously with supportive treatment of comorbidities. Glycemic control was achieved with parenteral insulin. The patient underwent amputation of 4 toes (excluding little toe) of right foot and debridement of gangrenous and necrotic tissue (Figure 6A). NPWTi-d was applied to the wound 3 times at an interval of 3 days. The patient also required intermittent hemodialysis. After the second dressing, the wound improved considerably with evident granulation (Figure 6B). Biochemical and hematological parameters also stabilized. The patient underwent split-thickness skin grafting after 10 days  with optimum graft uptake.

In this case of a patient with a grade 5 diabetic foot ulcer and compromised vascular supply, NPWTi-d was helpful in avoiding a foot amputation. It also saved time and reduced the overall cost of treatment.

Case 3: Necrotizing fasciitis of the leg. A 46-year-old man was admitted with a fever of 101°F and swelling of the right leg and foot with blackish discoloration and peeling of the skin for 1 week. He had breathlessness, anuria, and chronic liver disease. Local examination revealed superficial gangrene of the skin with blisters and excoriation in the lower half of right leg and foot (Figure 7A). The diagnosis was necrotizing fasciitis of the right leg and foot. Comorbidities included acute renal failure, cirrhosis of the liver, impaired coagulation profile, septicemia, and anemia.

The patient was given ventilator support and underwent immediate hemodialysis for anuria. Results of blood tests showed hemoglobin, 7 g/dL ; total leukocyte count, 31 000/µL; platelet count, 40 000/µL; serum creatinine, 4.6 mg/dL; impaired liver function and coagulation profile (serum bilirubin, 4.5 g/dL; prothrombin time, 28 seconds; international normalized ratio, 2.3). Pus culture results showed K pneumoniae, Acinetobacter baumannii, and P aeruginosa. 

The patient was given broad-spectrum antibiotics, multiple blood transfusions, and fresh frozen plasma along with other supportive care. The patient’s condition was managed medically, and debridement was performed on the third day. Adherent slough was still present on the dorsal aspect of the foot (Figure 7B). 

The NPWTi-d dressings were applied twice at an interval of 3 days, after which healthy granulation tissue filled the floor of the wound (Figure 7C). In addition, the patient’s general condition improved, culture results were negative, and improvement was seen in acute renal failure and respiratory depression. The patient underwent split-thickness skin grafting 1 week later.

In this case, NPWTi-d was useful in saving the life and limb of a patient with cirrhosis, necrotizing fasciitis, and septicemia. 

Case 4: Necrotizing fasciitis of the thigh. A 70-year-old woman was admitted to the hospital with fever 102°F and gangrene of the skin and superficial tissue of the right thigh for last 1 week in addition to anuria. On local examination, there was a 15 cm × 10 cm patch of dry gangrene on the medial aspect of the right thigh with foul smell (Figure 8A). The diagnosis was necrotizing fasciitis of the right thigh. Comorbidities included diabetes mellitus, hypertension, impaired renal function, and anemia.

Results of blood tests showed hemoglobin, 8 g/dL; total leukocyte count, 39 000/µL; blood glucose, 325 mg/dL; HbA_1C, 8%; serum creatinine, 2.6 mg/dL; and serum potassium, 6 mEq/L. The pus culture reported growth of S aureus.

The patient was given intravenous broad-spectrum antibiotics, intravenous fluids, hemodialysis, insulin, and blood transfusions along with other supportive care. After her condition stabilized, debridement was performed under general anesthesia. NPWTi-d dressing was applied twice at an interval of 3 days, after which bioburden was reduced and healthy granulation tissue appeared in the wound (Figure 8B). The general condition of the patient improved, and she underwent split-thickness skin grafting 1 week later.

Negative pressure wound therapy with instillation and dwell time was useful in treating necrotizing fasciitis. It arguably saved the life and limb of the patient, reduced hospital stay, and provided cost savings. 

Wound infections continue to be among the most expensive complications following surgery and are a major source of bacteria that increase the nosocomial infection rates in hospitals. Wounds with acute infection and biofilm are challenging problems that require an intensive multimodal approach, including systemic antibiotics, appropriate surgical intervention, and advanced wound management. Since its introduction, NPWT has drastically changed the management of such surgical wounds, promoting continued wound drainage and debridement while facilitating earlier growth of granulation tissue. As the next advancement of this therapy, NPWTi-d has proven superior in controlling the bioburden of complex infected surgical wounds while initiating beneficial cellular effects.¹³ Although NPWT has been used to successfully manage both acute and chronic wounds since 1997, it has only been used in India for the past 10 to 15 years due to unavailability. 

The benefits of regular wound cleansing between dressing changes to address healing impediments have become more apparent in recent years. Thus, instillation of a topical solution with removal via alternating negative pressure cycles is an important evolution of the NPWT concept. NPWTi-d equipment was made available in India in 2016 and has since been used to treat complex wounds.

In the present series of 8 cases of complex wounds in patients with serious comorbidities, 4 patients were treated with NPWTi-d alone; in the other 4 patients, NPWTi-d was used initially for 3 to 4 treatments and then replaced by NPWT. The causes of the wounds in these cases were variable and included diabetic ulcers with gangrene, necrotizing fasciitis with polymicrobial infections, and traumatic soft tissue injuries with significant bioburdens. All patients had comorbidities, including uncontrolled diabetes, renal failure, hypertension, septicemia, and MODS, which required hospital admission and intensive care. 

After initial debridement, NPWTi-d was effective in fast clearing of bioburden of the wound and preparing the wound for split-thickness skin grafting. In 4 patients, the wound dimensions were large and deep, requiring additional NPWT therapy after clearance of the bioburden. The outcomes for all 8 patients were satisfactory. Their lives were saved, and significant disabilities were averted. There were problems encountered in the initial stages of NPWTi-d and NPWT therapy, but solutions were created accordingly (Table 3).

It was observed that NPWTi-d was more effective in cleansing the wound and reducing the bioburden. None of the patients required a second surgery for debridement. It was also observed that for most wounds in this series, 2 to 3 treatments with NPWTi-d were sufficient and effective in reducing the bioburden. Addition of NPWT enhanced the effectiveness of the therapy by preparing the wound bed for skin grafting with minimal episodes of trouble shooting. At the same time, it was economical for the patients because the cost of standard NPWT dressing is almost half that of the NPWTi-d dressing.

Due to the limited sample size, it is difficult to draw a definitive conclusion that NPWTi-d alone or NPWTi-d complemented with NPWT is more effective in the management of complex wounds. Further studies with larger sample size are needed to make definitive recommendations. Also, because every wound is unique, standardizing therapy for a particular etiology is difficult in a limited case series.

From this case series, it can be inferred that NPWTi-d is effective in clearing the bioburden from the wound and promoting healthy granulation tissue for faster heating in acute and chronic wounds. It was seen that with NPWTi-d,the number of surgeries was reduced considerably (to 1). There were fewer troubleshooting episodes in the combined therapy after the application of NPWT dressing. Complementary use of both therapies also was cost-effective and economically beneficial to the patients.The combination of the 2 therapies can be considered in selected patients with complex wounds with heavy bioburden and comorbidities. 

The authors are thankful to the Director of Medical Services and Medical Superintendent along with the intensivist, nephrologist, diabetologist, and cardiologist of Apollo Hospital International Gandhinagar for allowing the authors to conduct this study and manage the comorbid conditions. A special thanks is extended to Madhulika Bardia for manuscript preparation and editing assistance.

Authors: Manjulata Anchalia, MBBS, MS (General Surgery), FIAGES; Swati Upadhyay, MBBS, MS (General Surgery), FICS; and Mohit Dahiya, MBBS, DNB Resident (General surgery)

Affiliation: Department of General Surgery, Apollo Hospitals, Gandhinagar, Gujarat, India

Correspondence: Dr. Manjulata Anchalia, MBBS, MS (General Surgery), FIAGES, Apollo Hospitals International Limited, Plot No. 1A, GIDC Bhat, Gandhinagar, Gujarat -382424 India; m_anchlia@yahoo.com

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