In this case, we present a situation in which 3D printing was used to design a patient specific device at the point-of-care, and placed under the FDA’s EAEU, in order to address a complex hemifacial wound from NF. The surgical management of NF involves early, aggressive debridement. The principles of wound management are to establish a healthy, uninfected wound bed for eventual reconstruction[1]. In facial NF, the proximity to vital structures may lead some to proceed with more cautious excision, but this can lead to persistence of disease, requiring more aggressive debridements in the future[15]. Even in the setting of aggressive initial debridement to healthy bleeding tissue, head and neck NF usually involves repeated debridements and a long course of local wound care prior to reconstruction.
In head and neck NF, previous case series have reported success with both frequent wet-to-dry dressing changes[3–5] or NPWT[6–9]. NPWT is thought to promote wound healing by removing secretions from the wound, decreasing the nidus for infection, reducing bacterial burden, and promoting vascularization of the wound bed and the formation of healthy granulation tissue[16]. While data comparing the use of standard wound care to NPWT are limited in the setting of acute infection, randomized evidence suggests accelerated wound healing time with the use of NPWT in other parts of the body[10].
In head and neck defects from massive infection and subsequent debridements, outcomes related to management of the wound bed are limited to case series. The original case series of this rare disease entity reported management of all types of wounds from NF with wet-to-dry dressing changes[3–5, 15]. NPWT has only recently been applied for management of NF in the head and neck[6–9]. These series found acceptable wound healing outcomes without recurrent or worsening infection. One group reported less aggressive debridement, keeping regions with discoloration or edema intact unless frankly avascular or necrotic[9]. All wounds eventually healed adequately for reconstruction, however, all patients required at least one additional debridement. In different series where standard debridement protocols were used and NPWT was applied, rates of repeated debridements were approximately 20% lower[6, 7].
NPWT is therefore a reasonable alternative to standard wound care in managing head and neck NF, particularly in the case of a large wound with suboptimal healing despite aggressive standard wound care, as presented in this case. Despite the potential benefits of NPWT, massive wounds in the HN present several unique difficulties to their application, which have previously been managed with various solutions[2, 7, 10, 13]. Particular challenges in this case include the proximity to the standard tracheostomy location and periorbita and risk of traction injury to the globe.
First, the proximity to a standard tracheostomy location in cases of cervical NF presents a challenge for long-term airway management. This is particularly relevant in the setting of NF of the HN as many present following Ludwig’s angina where airway management is an utmost concern[17]. Additionally, many patients with NF will require long-term ventilator support due to dissemination of and complications from infection, in which a tracheostomy may be indicated[5, 18]. In the presented case, the cervical portion of the wound extended near the midline and continued to expand despite aggressive local wound care. Placing tracheostomy through this area would have risked prolonged infection of the wound bed from tracheal secretions. Following NPWT, the wound decreased in size, allowing for safe tracheostomy placement without communication with the wound. Literature regarding NPWT in proximity to tracheostomy are limited. Balci et al. (2018) reported placement of foam to isolate the tracheostomy site from the wound bed[9]. Alternatively, a paramedian incision for tracheostomy has been reported in the case of a neck abscess[19], but these approaches are not well established. Therefore, delaying tracheostomy until the wound has decreased in size, which may be assisted by the use of NPWT, or been successfully reconstructed is reasonable and was pursued in this case.
Involvement of the orbit and periorbita with necrotizing fasciitis has previously been reported as a complication of pre-septal cellulitis[20, 21] or in the setting of facial necrotizing fasciitis[15]. Previous applications of NPWT to the periorbital region have been applied when the defect was superficial to the orbicularis oculi or in cases in which vision was already lost[15, 20]. Following NPWT for superficial periorbital infections, traction injury, vision loss, and permanent ectropion have not been reported[11, 20]. In contrast, in cases where facial NF extended to the deep periorbital tissue, debridement and local wound care have often resulted in permanent ectropion[15, 20]. To our knowledge, NPWT has not previously been applied to a periorbital wound bed deep to the orbicularis oculi in a patient with presumed intact visual function. The risk of potential eye injury related to the wound splint and NPWT use was weighed against the impending risk of infectious spread to the orbital compartment leading to vision loss, as previously reported. In this case, we successfully manufactured a patient-specific, 3D-printed wound splint separating the wound bed from the periorbita and allowing for safe application of NPWT. There was no obvious traction on the eye and the wound bed healed appropriately with preservation of vision and minimal ectropion due to wound contracture after reconstruction, and no wound splint related ocular complications. This concept has utility in relation to any vital or delicate structure, not just the periocular area.
Expanded Access for Medical Devices Emergency Use Mechanism (EAEU)
In acute, life-threatening scenarios such as NF, emergency devices may be used through the EAEU mechanism of the United States FDA[22, 23]. Under the EAEU mechanism, the clinicians also certify there is no acceptable treatment alternatives and, due to the life-threatening nature of the scenario, there is no time to use existing pathways for FDA approval. After a physician determines that the scenario meets the EAEU criteria and has assessed potential benefits and risks of unapproved device use, as many patient protections as possible should be followed (Fig. 2).
Importantly, the EAEU must be reported to the FDA within 5 days of device use, and thus does NOT require prior authorization. The report must include a description of the device, explanation of management options that were previously attempted and exhausted (Fig. 2), the patient protections that were followed, and any available patient outcome information. This pathway remains the most expedited option available for physicians to treat patients with an acute, extraordinary condition[24].
There is little precedent in the literature regarding 3D printed, point of care medical devices in head and neck surgery. One of the most well-known applications of the FDA’s EAEU pathway within Otolaryngology was reported by Zopf et al. (2013)[25]. An externally placed 3D printed splint was secured to a patient’s trachea who had failed all other management options for severe tracheobronchomalacia. Ultimately, this point-of-care manufactured device served as an excellent temporary solution for a condition that the patient ultimately outgrew and otherwise would not have survived.
In this case, the patient had begun to develop severe ectropion and keratitis of her right eye, which ultimately posed a threat to her vision. Furthermore, she was at risk of respiratory suppression from pain medication boluses due to the extent of the daily dressing changes, which required her to remain endotracheally intubated on mechanical ventilation for over a month. Due to involvement of the visceral space in the infection, a tracheostomy was not possible, which required a prolonged intubation and threatened development of subglottic stenosis and tracheal injury as well as ventilator associated pneumonia. The above justification was presented to the IRB for concurrence and included in the FDA EAEU follow-up report, leading to the successful application of a custom, 3D printed silicone wound splint and favorable clinical outcome for the patient.
Point of Care Device Development
Point-of-care, patient-specific device manufacturing, particularly 3D modeling and printing, allows for better device customization, and lower time to treatment with potential for rapid production[26, 27]. In-house manufacturing of personalized medical devices also allows for more adjustments to each device in rapidly changing clinical scenarios such as NF. In contrast, commercial producers have limited ability to adapt to patient-specific scenarios and require a longer time (weeks) for model creation and delivery, supporting the effectiveness of an in-house protocol[28].
Macielak et al. (2020) also report the use of two 3D printed custom silicone fistula plugs for wound stabilization in a multi-recurrent laryngeal cancer who developed post-operative wound dehiscence and pharyngocutaneous fistulae[29]. In this case, point of care 3D printed devices also led to wound stabilization and ultimately allowed for safe reconstruction. These reports along with our application of a patient-specific 3D-printed device points to the therapeutic potential of such devices in the future. Currently, use of 3D printing in otolaryngology-head and neck surgery is limited to surgical planning while therapeutic applications are rare[30, 31]. Given the complexity of head and neck defects and the increased availability of and familiarity with 3D printing technology among high-volume otolaryngology centers, 3D printed devices should be considered in assistance of management of complex defects of the head and neck. Furthermore, this example demonstrates the pathway to create custom devices for unprecedented patient situations with no alternative therapies through the EAEU, opening up the possibility of point of care customization to all patients at high volume centers.
In conclusion, this case is the first reported use of a patient specific 3D printed wound splint to allow application of NPWT in close proximity to the orbit while preventing orbital injury and vision loss. This case highlights the potential for point-of-care medical devices to be utilized in complex soft tissue defects, particularly in the head and neck where wounds in close proximity to vital structures is a common occurrence. Additionally, this case highlights the successful use of the FDA’s EAEU pathway to manage a rapidly changing, life-threatening clinical scenario where no existing therapy remained a viable option. Together, these tools represent a powerful option for clinicians faced with unprecedented medical condition and may provide significant benefit to patients when utilized appropriately.