Evaluating the Use of NPWT to Reduce Infections in Lower Extremity Fracture Care
In a multicenter study from the UK, researchers compared deep surgical site infections in patients who had incisional negative pressure wound therapy versus patients with a standard dressing following surgery for lower limb fracture due to major trauma.
Blake Schultz, MD, and Philipp Leucht, MD, PhD
Costa ML, Achten J, Knight R, et al. Effect of incisional negative pressure wound therapy vs standard wound dressing on deep surgical site infection after surgery for lower limb fractures associated with major trauma: the WHIST randomized clinical trial. JAMA. 2020 Feb 11;323(6):519-526.
Patients with fractures caused by major trauma events are at high risk for postoperative infection due to the extensive soft tissue injury and general systemic inflammatory response associated with the trauma. The consequences of deep infection can be severe, including:
- Return trips to the operating room for debridement
- Removal or revision of hardware
- Increased risk of non-union
Various wound care strategies – including incisional negative pressure wound therapy (NPWT) – have been investigated in an attempt to lower the infection rate.
NPWT works by 2 main mechanisms:
- The first is reduction of the local inflammatory response caused by damaged tissues. The subatmospheric environment of the NPWT acts at the level of the interstitium, decreasing edema and inflammatory mediators.  Decreasing edema is important for facilitating arterial inflow and delivery of nutrients and oxygen, as well as for venous outflow.
- In addition, the strain created by the vacuum stimulates increased recruitment of growth factors/cytokines, such as VEGF, FGF-2, and IL-8, which promotes cellular chemotaxis, angiogenesis, and granulation tissue formation. [2 ] The subatmospheric environment also affects genomic transcription, up-regulating proto-oncogenes required for granulation tissue formation. 
Negative pressure wound therapy has been effective in providing temporary wound coverage when definitive primary wound coverage is not possible. This success prompted the use of NPWT as an incisional dressing in wounds that could be primarily closed but that were considered high risk due to the amount of soft-tissue injury, fracture location, or patient factors such as BMI.
A prior randomized control trial in 249 patients demonstrated a decreased risk of deep infection (P=0.049) and wound dehiscence (P=0.044) in high-risk lower extremity fractures (calcaneus, pilon, tibial plateau) when incisional NPWT was used for 2 or 3 days compared with standard dressing.  Specifically, the rate of late deep infections, defined as occurring after the initial hospitalization, was reduced 6%, from 15% with standard dressings to 9% with incision NPWT. 
The aim of the WHIST trial was to evaluate outcomes in patients undergoing surgery for lower limb fracture due to major trauma, defined as involvement of more than 1 organ system or severe trauma to an isolated limb. The study was powered to show a clinically important reduction in deep surgical site infections. The authors’ survey of members of the UK Orthopedic Trauma Society showed that a 6% reduction in late deep infections would be sufficient to change clinical practice with regard to wound dressing choice. This number was used by the study authors to power the WHIST trial to 1540 participants.
The multicenter, randomized controlled trial was conducted across 24 hospitals in the UK Major Trauma Network, enrolling 1584 patients over age 16 who had surgery for a lower extremity fracture caused by major trauma. Exclusion criteria were:
- Open fractures with wounds that would not close
- Presentation to the hospital more than 72 hours after injury
- Inability to adhere to trial procedures or complete questionnaires (ie, pre-existing dementia)
Patients were randomized to incisional NPWT (n=785) or standard dressing (n=763). The standard dressing had to be sterile, but the dressing choice was otherwise left to the discretion of the treating healthcare team as per routine care at their center.
The primary outcome was deep surgical site infections at 30 and 90 days based on criteria from the Centers for Disease Control and Prevention (CDC):
- First criteria: Drainage, pus
- Second criteria: Wound dehiscence, painful wound, fever
- Third criteria: Signs of abscess or infection on exam or imaging
Secondary outcomes collected included:
- Patient-reported disability (Disability Rating Index)
- Quality of life (EuroQol 5-level EQ-5D)
- Surgical scar assessment (Patient and Observer Scar Assessment Scale)
- Chronic pain (Douleur Neuropathique Questionnaire)
Secondary outcomes were collected at 3 and 6 months, except for surgical scar assessment, which was also collected at 1 month. Any local wound healing complications that did not meet the CDC’s criteria for a deep infection were also recorded.
The statistical model was stratified based on open versus closed fracture, Injury Severity Score (15 or less vs 16 or more), age, sex, and recruitment center. The patient groups were similar in wound location (categorized as above or below knee) and social demographic factors considered high risk for infection (BMI, diabetes, smoking status, and alcohol consumption).
No significant difference in the rate of deep surgical site infections was seen at either 30 or 90 days:
- 30 days: 5.84% (45/770) for NPWT vs 6.68% (50/749) for standard dressing (odds ratio, 0.87 [95% CI, 0.57 to 1.33]; absolute risk difference, −0.77% [95% CI, −3.19% to 1.66%]; P=0.52)
- 90 days: 11.4% (72/629) for NPWT vs 13.2% (78/590) for standard dressing (odds ratio, 0.84 [95% CI, 0.59 to 1.19]; absolute risk difference, −1.76% [95% CI, −5.41% to 1.90%]; P=0.32)
No significant differences were observed between the groups for any of the secondary outcome measures. In addition, there were no differences in other wound healing complications that did not meet the CDC criteria for deep surgical site infections.
This study showed no difference in the rate of deep infection between use of incisional NPWT and standard dressing in patients who underwent lower extremity fracture surgery secondary to major trauma. There were also no differences in patient-reported disability, chronic pain, cosmesis, or quality of life outcomes. These findings call into question the role of incisional NPWT in trauma surgery.
Limitations of the study include the inability to blind the patient or surgeon to the treatment group. In addition, although the specific wound sites were recorded (ie, tibia/fibula vs acetabulum), the number of patients per group was too small to justify a sub-group analysis of wound site-specific outcomes between the NPWT and standard dressing groups. We encourage the authors to publish long-term follow-up results broken down by site of injury, specific fracture type (eg, pilon), and surgical intervention, which could provide better insight into treatment of fractures that are at higher risk for infection.
It is important to note that there may be additional outcomes to consider with incisional NPWT that were not recorded in this study. Although NPWT is more expensive than standard dressings, Stannard et al  found that patients who had NPWT were ready for discharge approximately half a day earlier than control patients based on the condition of their surgical site.
Cost-analysis studies on NPWT would be interesting, including the time needed to place the NPWT dressing in the OR, time spent changing the NPWT dressing on the floor every few days versus daily changes of standard dressings, and costs associated with length of stay.
Blake Schultz, MD, is a Resident in the Department of Orthopaedic Surgery and Philipp Leucht, MD, PhD, is an Associate Professor of Orthopaedic Surgery and Cell Biology at NYU Grossman School of Medicine and Langone Orthopedic Hospital, New York, New York.
Disclosures: The authors have no disclosures relevant to this article
- Gage MJ, Yoon RS, Egol KA, et al. Uses of negative pressure wound therapy in orthopedic trauma. Orthop. Clin. North Am. 2015 Apr;46(2):227–234.
- Labler L, Rancan M, Mica L, et al. Vacuum-assisted closure therapy increases local interleukin-8 and vascular endothelial growth factor levels in traumatic wounds. J Trauma. 2009 Mar;66(3):749–757.
- McNulty AK, Schmidt M, Feeley T, et al. Effects of negative pressure wound therapy on fibroblast viability, chemotactic signaling, and proliferation in a provisional wound (fibrin) matrix. Wound Repair Regen. 2007 Dec;15(6):838–846.
- Stannard JP, Volgas DA, McGwin G, et al. Incisional negative pressure wound therapy after high-risk lower extremity fractures. J Orthop Trauma. 2012 Jan;26(1):37–42.