Sevoflurane Shows Promise as Topical Analgesic for Intractable Pain

By Scott Baltic

August 03, 2020

NEW YORK (Reuters Health) - The widely used inhalational anesthetic sevoflurane was effective as a topical analgesic in treating otherwise refractory pain in an elderly patient with a severe leg ulcer, in a case report newly published by Spanish physicians.

In addition, there are indications that the medication accelerated healing of the year-old ulcer, Dr. Manuel Geronimo-Pardo of Complejo Hospitalario Universítario, in Albacete, and colleagues report in the BMJ Supportive and Palliative Care.

"Sevoflurane produces a rapid, intense, and long-lasting analgesic effect when it is irrigated on painful wounds, regardless of the etiology of the ulcer and the nature of the pain," Dr. Geronimo-Pardo told Reuters Health by email. "Mild and transient itching at the wound edges is the most frequent adverse effect, so the risk-benefit profile is favorable."

An 87-year-old woman was under palliative treatment for advanced endometrial cancer, but also had numerous comorbidities, including type 2 diabetes, hypertension, acute coronary syndrome with a stent, chronic kidney failure, and peripheral arterial occlusive disease. Her living will barred hospital admission or any invasive procedures.

For the previous 13 months, the patient had severe pain from a mixed vascular ulcer (7 cm by 2 cm, and 1 cm deep at presentation to the authors) on the back of her right foot.

Minor and major opioids, adjuvant analgesics and conventional systemic analgesics were either ineffective or were abandoned because of adverse events. The patient declined leg amputation.

The patient's pain was so severe it interfered with sleep, precluded physical activity, and produced depression and suicidal ideation. Further, daily dressings were extremely painful.

The patient consented to topical sevoflurane 6 ml, applied at home from pre-filled syringes. Within about three minutes of the first application, her pain fell from 9/10 to 2/10. Because the analgesic effect lasted longer than 24 hours and sevoflurane was applied daily, the patient's pain remained below 2/10 thereafter.

Systemic analgesics were tapered, the patient's suicidal ideation disappeared, and her physical activity, sleep and mood improved, until her death four months later of neoplastic disease.

Dr. Geronimo-Pardo said the available evidence is insufficient to recommend sevoflurane for the management of non-complicated wounds. His advice to health workers is to try sevoflurane for the management of complicated chronic wounds in which usual therapies have failed, such as ulcers causing refractory pain, ulcers superinfected by multidrug-resistant organisms, or hard-to-heal ulcers.

The report notes that although the patient had had the leg ulcer for 13 months before starting topical sevoflurane therapy, the wound healed completely after 35 days of such treatment.

"We are fully convinced that sevoflurane promotes healing, as several hard-to-heal ulcers healed after a few weeks of being treated with it," Dr. Geronimo-Pardo said. He noted, however, that evidence of this is sparse and that healing is a time-consuming process that's influenced by multiple factors.

Dr. Geronimo-Pardo said he accidentally discovered sevoflurane's topical anesthesia capacity while he was studying the drug's in vitro antimicrobial properties. A drop of sevoflurane fell on his lip, which was immediately anesthetized.

Dr. Thomas J. Smith, director of palliative medicine at Johns Hopkins Medical Institutions, in Baltimore, told Reuters Health by email that most practitioners in the palliative care community have never heard of using topical sevoflurane.

"That said," he continued, "it appears to be uniquely effective at relieving the pain of skin and deeper ulcers, allowing for successful debridement and even healing." He pointed out that its effect is quick (minutes), long lasting (hours), and persistent for over weeks or even months if applied regularly.

Sevoflurane's U.S. price of as low as $102 for a 250 ml bottle makes the drug "highly attractive economically," Dr. Smith commented.

"This is definitely a new technique that I will see if we can add here for palliative and hospice patients, although it may have bigger applications in vascular medicine," he concluded. Dr. Smith was not involved with the case in question or the case report.

The authors declared no specific funding in connection with this case report. Dr. Geronimo-Pardo has financial ties to Vapogenix, Inc., which develops topical, non-narcotic medications to treat pain.

SOURCE: BMJ Supportive and Palliative Care, online June 29, 2020.