Uncooperative Patient With an Infected Elbow Osteosynthesis: Alternative Management With Topical Sevoflurane

Introduction. Treatment of an infected osteosynthesis is usually a complicated process, with its complexity increasing when unforeseen situations appear. Typically, the therapeutic management of such situations is challenging because they are not anticipated in the medical literature and physicians have to look for and adapt novel solutions to a specific patient condition. Case Report. A 41-year-old, uncooperative, homeless man, presented to the emergency room with a left olecranon fracture. After planned surgery, the surgical wound became infected with a methicillin-sensitive Staphylococcus aureus because the treatment took place in an unhygienic outpatient hospital setting. The patient refused to remain in the hospital and also failed to complete antibiotic courses prescribed (culture-guided rifampicin 600 mg daily plus levofloxacin 500 mg daily). Instead of removing the osteosynthesis material, the infection was successfully treated by repeated applications of 5 mL of sevoflurane into the surgical wound. Subsequently, wound healing was achieved with a combination of a brief course of negative pressure wound therapy (NPWT), use of silver-impregnated dressings, and irrigation of the wound with sevoflurane. Sevoflurane also provided topical analgesic to ameliorate the pain caused by removing the NPWT sponge. Interestingly, despite extremely poor compliance by the patient to all standard treatment regimens, and the clinical decision to retain the implant, the infection was resolved, and the fracture was consolidated. Conclusions. Local application of sevoflurane in the wound bed appears to exhibit analgesic, antimicrobial, and positive healing effects. It could be a promising alternative treatment to be included as a therapeutic option for wound care.

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Wound management guidelines usually deal with ideal situations, in which health care providers are intended to control all aspects of therapy, including the patient and/or caregivers compliance to treatment.¹ However, this is not always the case in real-world clinical practice; sometimes it is necessary to face clinical situations not anticipated by the guidelines, such as noncompliant patients failing to follow the therapeutic plan. This setting represents a therapeutic challenge and forces the clinician to find proper and innovative solutions adapted to their particular patient. The authors present a successful experience of treating an uncooperative patient with an infected elbow osteosynthesis using ambulatory negative pressure wound therapy (NPWT) and topical sevoflurane.

The patient was a 41-year-old homeless man chronically infected with hepatitis C virus. He presented to the emergency room because of a fracture on his left olecranon. After 3 days of admittance, surgery consisted of a closed reduction and osteosynthesis, specifically a percutaneous cannulated screw was placed (Figure 1), and the fracture was immobilized with a plaster splint. The patient was discharged after 24 hours with an outpatient treatment plan consisting of primary caregiver follow-up visits every 2 to 3 days and a first review at the trauma center 3 weeks postoperatively.

Infectious complication

At the 3-weeks postop follow-up to the trauma center, it was noted the patient had failed to follow up at the outpatient clinic for dressing changes. At this time, the plaster was broken and extremely dirty, and the surgical wound was clearly infected with drainage of abundant purulent exudate. Analytical values were consistent with an infection; white blood cell count and C-reactive protein (CRP) were elevated (13 240 cells/µL and 54.7mg/L, respectively). Exudate was cultured and surgical debridement of the wound performed, finding the fracture stable. After consult with an infectious disease specialist, the patient received antibiotics with the goal of attempting implant retention. Antibiotic treatment consisted of 1 week of amoxicillin-clavulanate 1 g every 12 hours and linezolid 600 mg every 12 hours. After 1 week, due to the isolation of methicillin-sensitive Staphylococcus aureus (MSSA) from the exudate culture, the antibiotics were changed to rifampicin 600 mg daily plus levofloxacin 500 mg daily, which was maintained while he was admitted to the hospital. Despite this treatment modification, the clinical situation deteriorated; after 5 days of the rifampicin/levofloxacin treatment, the osteosynthesis became unstable due to osteolysis surrounding the cannulated screw.

The screw was removed, and a new surgical procedure performed. The procedure included the placement of 2 Kirschner wires and 8-cerclage with steel wire, covering the bone defect with gentamicin-loaded cement, and proceeding to primary wound closure (Figure 2). Again, MSSA was isolated from the wound and topical antimicrobial treatment with liquid sevoflurane was added to the aforementioned conventional antibiotics (rifampicin/levofloxacin). 

Since this treatment was off label, written informed consent of the patient was obtained. In addition, the Head Medical Office and the Pharmacy Service of the treating center approved the treatment in accordance with the country’s regulations for the Use of Medications in Special Situations. 

Daily applications of 5 mL of sevoflurane in the wound through the skin staples were initiated. After 5 days, the purulent exudate showed serous appearance and no microorganism grew from the new sample sent for culture. The wound was considered satisfactorily closed after 12 days of sevoflurane treatment. The patient was discharged with instructions to take rifampicin and levofloxacin for 10 days at the same aforementioned dosages and frequency until medical evaluation in an outpatient visit.

Mechanical complication

Ten days following discharge, the patient visited the outpatient clinic and wound dehiscence with exposure of the cement and osteosynthesis material was observed. The wound lacked any signs of infection, and infectious etiology was clinically ruled out. However, dehiscence was considered a mechanical complication due to the pressure of the cement on the skin (Figure 3A). The patient confessed he had not taken the prescribed antibiotics and refused to be admitted to the hospital.

An ad hoc plan consisting of irrigation of the wound with sevoflurane in an outpatient setting was carried out as follows: the wound was covered with a sterile plastic and 4 mL of sevoflurane were injected into the wound bed, letting it set for 4 to 5 minutes (Figure 3B); any residual sevoflurane was aspirated; then debridement was performed by pressure irrigation of sterile saline; and finally, the wound was covered with silver-impregnated dressings. This new treatment originally was scheduled for every 4 to 5 days, and the patient was expected to resume his conventional antibiotics. 

After 1 week, he presented to the emergency room with abundant, clear wound exudate that lacked clinical signs of infection. In addition, he again confessed to not having taken his antibiotics and refused to be admitted to the hospital. Therefore, samples for culture were taken, the wound was cleansed with 5 mL of sevoflurane, and exudate control was carried out with ambulatory intermittent NPWT (V.A.C. Therapy; KCI, an Acelity Company, San Antonio, TX) at -125 mm Hg at the homeless shelter where he now lived. Ambulatory care every 2 days to change the sponge was planned, but he first returned after 5 days. 

At that time, the sponge was completely adhered to the wound bed. The pain associated with its removal was controlled by soaking the sponge and irrigating the wound, all together, with 5 mL of sevoflurane. 

Five days afterwards, the same situation occurred. By that time, the patient had left the homeless shelter, therefore NPWT was discontinued. The wound exhibited granulation tissue and no signs of infection; there were no microbiological results from the exudate because the previous sample was lost by mistake.

The new therapeutic plan consisted of irrigating the wound with 5mL of sevoflurane at every visit (whenever it took place) and keeping the wound covered with silver-coated dressings between visits. These measures proved to be effective as the size of the wound progressively decreased until full closure wound after 3 additional weeks (35 days following sevoflurane initiation) (Figure 4).

Final outcome

Not surprisingly, after wound healing, the patient did not return for his scheduled ambulatory care. However, after 10 months he returned to the emergency room due to protrusion of the Kirschner wires. The fracture was consolidated and neither clinical nor analytical signs of chronic osteomyelitis were apparent (CRP: 2.5 mg/L). Therefore, the osteosynthesis material was removed (Figure 5). After 10 days, clinical examination of the elbow was normal except for a 10° deficit for extension. Since then, more than 3 years have passed without any further communication with the patient. 

Noncompliance

The most worrisome aspect of this case was the patient’s uncooperative attitude and unhygienic condition, which were largely responsible for his poor outcome and forced the authors to seek alternative treatments. Although other clinicians would have treated the patient’s complications differently, the authors encourage readers to always consider using an individualized treatment and management plan when dealing with complex and noncompliant patients.^2,3

Infectious complication

The initial osteosynthesis turned infectious, probably due to unhygienic conditions. It was decided to try wound debridement and an implant retention strategy,^4-6 providing the screw was well positioned, osteosynthesis was stable, and patient was uncooperative. In this case, debridement was performed, but antibiotics failed to control purulent discharge or to attain negative cultures. Therefore, the osteosynthesis became clearly unstable. 

At that point, the fracture was restabilized by placing new osteosynthesis material (wires) and removing the previous infected screw. Other authors have applied antibiotic-impregnated material to perform the new osteosynthesis over an infected fracture.^7,8 However, the present strategy consisted of administering antiseptics directly into the infected wound. Usually conventional antibiotics are administered for this purpose,^9,10 but irrigations of liquid sevoflurane were used herein. Sevoflurane is a nonflammable halogenated ether and known from in vitro studies that both ether and its halogenated derivatives have antimicrobial properties.^11-13 In addition, in the pre-antibiotic era, ether was applied locally to treat severe bacterial infections, such as peritonitis,¹⁴ septic arthritis,¹⁴ and wound infection.^14-16 More recently, published cases showed local irrigations of sevoflurane were associated with the healing of infected wounds.^17-19 

Due to its liquid formulation, sevoflurane has the ability to enter into the smallest areas of the wound, which has been documented as a great advantage in some clinical cases^17,19 and in the present case. In fact, the clinical outcome of the wound had been unfavorable even after 2 weeks of intravenous antibiotic treatment, but the infected appearance disappeared and cultures tested negative after only 5 days of sevoflurane application. Ether and its derivatives are solvents, and it is believed the antimicrobial effect is due to their ability to dissolve the lipid envelope of microorganisms.²⁰ By accepting this hypothesis, 2 main advantages arise.

The first advantage is it could be a useful drug to treat infections caused by microorganisms resistant to conventional antibiotics, which has already been documented in an immunocompromised patient with a subcostal postoperative wound infected by a multidrug-resistant Pseudomonas aeruginosa strain.¹⁹

And the second, in the authors’ opinion even more interesting a priori, it could be useful for dissolving biofilms adhered to prosthetic devices. Considering biofilm remains a major problem in trauma surgery,^21,22 this hypothesis is very attractive and should be studied further.

Mechanical complication

After the acute infectious complication was controlled, a mechanical complication due to the pressure of the cement on the skin appeared. To improve healing of the wound, a combination of sevoflurane irrigations, silver-impregnated dressings, and NPWT was used, however, due to the patient’s noncompliance, none of the treatments were used in ideal conditions. Negative pressure wound therapy was effective to control exudate, which usually is important to prevent wound superinfection.²³ Besides exudate control, NPWT has been applied to heal wounds, even with wounds infection and underlying orthopedic implants present.^24,25

However, NPWT should usually be applied over several weeks or months for wound healing to be achieved,^26,27 but this was not the case here. Short-term wound healing has been achieved by using silver-impregnated dressings,²⁸ and this could have been helpful in this case. However, in the authors’ opinion, sevoflurane irrigations were the main factor for the patient’s accelerated wound healing. Distaso and Bowen¹⁵ treated infected wounds in 3 ways: (1) covering them with ether-impregnated gauzes, (2) irrigating them with 1 L of 2% ether once daily, and (3) immersing them in 2% ether for 20 minutes once daily. These authors¹⁵ found irrigation and immersion were the most efficacious methods, specifically immersion, with quick resolution of pus (even after the first application), the appearance of granulation tissue, and wound epithelization.¹⁵ Regarding sevoflurane, some clinical cases involving chronic wounds treated with this agent suggest a beneficial effect promoting a quick healing.^18,29

Pain

An intense local analgesic/anesthetic effect of sevoflurane has been described following its topical application to the wound.^18,29-32 In the present case, this analgesic effect was observed at every wound cleansing procedure, being especially relevant to the removal of the NPWT sponges, which had adhered to the wound bed after 5 days of not being changed. Pain from the removal of adhered sponges is a very common problem when using NPWT. This pain can be alleviated by irrigating the sponge with the local anesthetic lidocaine,^33,34 but application of sevoflurane was used in this case. Thus, topical application of liquid sevoflurane could be a new field of study.

Adverse effects of topical sevoflurane

The most frequently reported adverse effect is itching or pruritus at the wound edges,³⁵ but this was not noted in the present case.

From a systemic point of view, treating wounds with topical sevoflurane seems to be a safe procedure since patients suffering from systemic effects (mainly hypnosis or hypotension) has not been reported. A protective pulmonary first-pass effect has been suggested to explain this: after absorption from the wound to the venous circulatory system, sevoflurane molecules reach the alveoli, and once there, volatilize to be exhaled trough respiration, which would protect the patient from systemic effects.³⁵ This hypothesis has not yet been confirmed by measuring sevoflurane blood or air concentrations.

Clinicians should note the risk for occupational exposure to sevoflurane could be reduced or even prevented by applying topical sevoflurane in a well-ventilated room.³⁶ In addition, work-place air pollution can be reduced by covering the wound with a plastic, injecting the liquid inside, and then aspirating the remains³⁶ as demonstrated herein (Figure 3B).

As this case report demonstrates, local application of sevoflurane in the wound bed appears to exhibit analgesic, antimicrobial, and positive healing effects. In the authors’ opinion, it could be a promising alternative treatment to be included as a therapeutic option for wound care. 

Authors: Sergio Losa-Palacios, MD¹; Ainara Achaerandio-de Nova, MD¹; Marcela Restrepo-Pérez, MD¹; and Manuel Gerónimo-Pardo, MD, PhD²

Affiliations: ¹Department of Orthopedic Surgery, Complejo Hospitalario Universitario of Albacete, Albacete, Spain; ²Department of Anesthesiology, Complejo Hospitalario Universitario of Albacete

Correspondence: Manuel Gerónimo-Pardo, MD, PhD, Department of Anesthesiology, Complejo Hospitalario Universitario of Albacete, Calle Hermanos Falcó 37, 02006, Albacete, Spain; sergepu@hotmail.com

Disclosure: Dr. Gerónimo-Pardo has acted as a consultant for Vapogenix Inc (Houston, TX). All other authors disclose no financial or other conflicts of interest.