Stage IV Perineal Pressure Ulcers in Immobile Patients Treated With Surgical Flap Closure Augmented With Cryopreserved Placental Membrane Containing Viable Cells

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Stage IV pressure ulcers (PUs) around the perineum, including ischial, sacral, gluteal, and trochanteric ulcers, develop as the result of prolonged pressure, shear, moisture, and/or frictional forces. When pressure increases due to external forces, localized ischemia occurs, resulting in tissue damage and potential necrosis.¹ Risk factors include impaired circulation, immobilization, malnutrition, and incontinence. Infections often occur in these wounds and may lead to the development of osteomyelitis, necrotizing fasciitis, and sepsis. This is especially detrimental to the immobilized/paraplegic patient with comorbidities. In these patients, PUs are hard to treat by surgical intervention because of their impaired potential for postoperative healing.^2-4

A flap or muscle closure is a standard treatment option for chronic, late-stage (stage 4) PUs. Reconstruction of a PU is aimed at improving patient quality of life, preventing or resolving infection, reducing fluid and protein loss, and preventing future malignancy. In general, stages III and IV PUs often require flap reconstruction to achieve closure.

Surgical intervention includes radical excision of the ulcer, bursa, surrounding scar tissue, and any heterotopic calcification. Underlying bone is debrided to ensure there is no retained niche of osteomyelitis. Surgeons may choose to perform a staged surgery in the presence of osteomyelitis; however, most surgeons prefer debridement and reconstruction at the same time to minimize risks to the patient, time, and resources. Once the wound has been appropriately debrided, it may be closed in a variety of ways, depending on the location, any previous scars or operations, and the surgeon’s clinical preference. Options for surgical management of PUs include direct closure (rarely used due to its high rate of wound recurrence), skin grafting, skin flaps, and musculocutaneous flaps.^5,6

The aim of this study is to evaluate the outcomes associated with the use of a cryopreserved placental membrane containing viable cells (vCPM) graft for the augmentation of surgical flap closure in nonhealing PUs.

A retrospective analysis was conducted on 4 immobile patients with paraplegia with perineal PUs who received surgical treatment with muscle flap augmented with vCPM. The study included 2 men and 2 women with an average age of 61 years (range, 44–77 years). Patients were all from various nursing facilities in the Pittsburgh, PA area, and accurate wound measurements were not available. Pressure ulcers were staged according to the National Pressure Ulcer Advisory Panel staging guidelines.⁷ Ulcers were located on either the ischial, gluteal, or sacral area with a mean duration of 4 years (range, 0.5–10 years). All PUs were treated with surgical debridement followed by the application of intraoperative vCPM (Grafix CORE; Osiris Therapeutics, Inc, Columbia, MD) to the wound bed prior to muscle flap closure.

As a human tissue allograft regulated by the US Food and Drug Administration under 21 CFR Part 1271 Part 361 Human Cells, Tissues, and Cellular- and Tissue-based Products, vCPM can be utilized as a wound cover or barrier for a broad variety of acute and chronic wounds at all locations. Human placental membrane (HPM) has unique anti-inflammatory, antifibrotic, and antimicrobial properties.^8-10 It has low immunogenicity and can be used as an allograft without matching between donors and recipients.¹¹ The vCPM graft contains a 3-dimensional extracellular matrix, growth factors, and retains viable neonatal fibroblasts and mesenchymal stem cells native to fresh placental membrane.^8-10 The vCPM graft is conforming and easily adheres to moist wound beds as well as deep anatomic structures such as bone and tendon.

In this series, vCPM was applied to the debrided perineal wound bed without the need for anchoring or suturing. The myocutaneous flap then was closed primarily over the graft. In situations where the graft may migrate, it can be anchored in place with sutures, staples, or fibrin adhesive.

Following muscle flap closure augmented with vCPM, all 4 patients achieved complete wound closure in an average of 7 weeks (range, 6–8 weeks) without complications or recurrence (Table). Complete muscle flap incorporation was demonstrated in all patient cases and surgical wound closure was maintained for an average follow-up of 12 months. Figure 1, Figure 2, Figure 3, and Figure 4 show the preoperative PUs, intraoperative muscle flap with skin closure placement, and follow-up with ulcer and skin closure maintained.

Immobility is a key risk factor for PU development. About 70% of all PUs occur in immobile or elderly patients whose tissue is less resistant to external insults; of these, the incidence of sacral ulcers is 23%.¹² Spinal cord injury, severe illness, poor nutritional status, trauma, impaired consciousness, or prolonged surgery also increase PU risk.^6,13-16

Individuals who develop PUs have a 3.6-times greater risk of death within 21 months.¹⁷ Patients are at substantial risk for ulcer recurrence at the same location if preventative measures, such as proper offloading, reduction of friction, control of microenvironment, monitoring of nutritional status, psychosocial status, and infection control are not enforced. Kuwahara et al¹⁸ showed 37.5% of operated patients will have a recurrence of the PU and that mortality with associated ulcers was 68.8%.

Because of the risk for such complications, there is ongoing demand for novel techniques that augment surgical closure of PUs in compromised patients. Recent vCPM clinical studies reported durable closure of chronic wounds of various etiologies.^19,20 Most recently, Frykberg et al²¹ and Suzuki et al²² reported the positive clinical outcomes of vCPM in the management of complex wounds with exposed tendon and/or bone. Frykberg et al,²¹ in a prospective, multicenter, open-label study, showed 96.3% of patients achieved 100% granulation and 59.3% achieved complete wound closure by 16 weeks; similarly, Suzuki et al²² demonstrated 100% wound closure using vCPM without concomitant use of negative pressure, hyperbaric oxygen treatment, or surgical intervention.

Based on these clinical evidences, the benefit of vCPM was evaluated after augmenting surgical repair of late-stage PUs in immobile patients with underlying comorbidities. The results were compared with muscle flap procedures that did not utilize augmentation with allograft. Results of vCPM use in this study showed better clinical outcomes in comparison with historically known outcomes.^23,24In a 10-year study of 78 patients with spinal cord injuries with PUs, Ahluwalia et al²³ showed a 16% complication rate and a 7% recurrence rate was observed following surgical flap closure, while a separate study of 119 patients treated with a similar method of flap closure showed complication and recurrence rates of 26% and 11%, respectively.²⁴

In addition to procedure selection and the adjunct use of beneficial biologic products to aid in durable wound closure, proper postoperative offloading can define the outcome of the ulcer reconstruction. In the present cases, air-fluid beds were utilized for offloading. From the time of transfer from the operating table to an air-fluid bed, care must be exercised to prevent shearing and tension across the flap repair. Patients are positioned supinely in the air-fluid bed for 6 weeks followed by gradual progression through semi-sitting position, graduated mobility sitting, and self-lifting to relieve pressure.

This series demonstrates a novel use of vCPM used in conjunction with standard myocutaneous flap techniques to improve healing outcomes in immobilized patients with perineal wounds. Historical comparisons show complication risks in this population; therefore, procedures that utilize viable graft tissue may improve wound closure rates in these patients.

While the vCPM-augmented flap reconstruction technique should be considered to augment surgical repairs, the lack of active or historical patient comparator, small sample size, and retrospective nature of data collection present significant limitations to the reported outcomes.

All patients with chronic, stage IV perineal PUs in the current study proceeded to complete closure of the vCPM-augmented flap reconstruction sites without complications or recurrence during a 12-month follow-up period. This report demonstrates that a vCPM allograft can be used in conjunction with standard muscle flap repair techniques to decrease complications and recurrence rates and yield satisfactory outcomes for defects repaired by muscle flap reconstruction. Larger clinical studies are needed to compare this technique with others to gain a better understanding of its applicability to surgical practice. This case series presents a novel use of vCPM combined with standard myocutaneous flap reconstruction, demonstrating clinical benefits for immobile patients, resulting in complete wound closure and avoiding the need for surgical revision or rehospitalization.

Authors: Dinakar Golla, MD¹; and Dorothy H. Kurtz Phelan, DPM²

Affiliations: ¹Dinakar Plastic Surgery, Pittsburgh, PA; and ²Osiris Therapeutics, Inc, Columbia, MD

Correspondence: Molly Saunders, Senior Manager, Clinical Operations, Osiris Therapeutics, Inc, 7015 Albert Einstein Drive, Columbia, MD 21046; MSaunders@osiris.com

Disclosure: At the time of acceptance, Dr. Kurtz Phelan was a full-time employee of Osiris Therapeutics Inc.