I was providing a general anesthetic to a patient for bilateral blepharoplasties (eyelid lifts) in a plastic surgery center operating room recently, and I asked the surgeon how frequently she performed this surgery in her office under local anesthesia without an anesthesia professional. She answered that in her office setting, her anesthesia plan was to sedate patients for this surgery by administering a sublingual tablet called an MKO Melt, a formulation of 25 mg ketamine, 3 mg midazolam, and 2 mg ondansetron. The MKO Melt delivers its medication via sublingual troche over a 2-minute release period. The surgeon told me that the MKO Melt successfully brought on a state of mild to moderate sedation during which the patient tolerated of the injection of local anesthesia. Anesthesiologists and Certified Registered Nurse Anesthetists typically achieve this level of sedation by starting an intravenous line and titrating intravenous sedation with medications such as midazolam, fentanyl, propofol, and/or ketamine. This use of sublingual anesthesia was a simpler technique for obtaining sedation without the need for an intravenous line or an anesthesia professional. It was a technique I’d never heard of nor read about. I suspect you haven’t heard or read of it either. It’s never been reported in our peer-reviewed anesthesia journals or textbooks.
What is a troche?
A troche is a small, hard tablet designed to dissolve slowly when placed under the tongue. A key difference is the way a troche is processed by the body. Medicines introduced into the body via a troche bypass the digestive system and deliver their ingredients directly into the bloodstream. Medicinal troches enter the blood stream via blood vessels located in the tissue directly under the tongue and in the walls of the cheek. The only other places on the body where the blood vessels are this close to the surface are the vagina and the rectum.
The MKO Melt is a compounded drug and is not available from pharmacies. It’s available from ImprimisRx, an ophthalmic-focused division of Imprimis Pharmaceuticals, Inc. Per their press release, “the MKO Melt (midazolam/ketamine/ondansetron) is a non-invasive, non-opioid, patented, sublingual troche used typically by physicians for short term procedures, with potentially 100 million addressable procedures in the U.S. annually across multiple verticals and a potential multi-billion-dollar opportunity. Imprimis Pharmaceuticals recently formed a new subsidiary, Melt Pharmaceuticals, Inc., which is pursuing the development of 505(b)(2) drug candidates for FDA approval based on the underlying technology of the MKO Melt.”
Use of the MKO Melt sedation has been described in the ophthalmology literature for facilitating cataract surgery cases. The conscious sedation effects are evident after 2 to 3 minutes, peak at about 15 minutes, and provide adequate sedation for up to 1 hour. The combination of ketamine and midazolam offers a level of sedation that is effective for patient sedation and comfort. The ondansetron adds an antiemetic to the compound. Ophthalmologists find the advantages of the sublingual anesthesia troche include a) it is nonopioid, b) it is easier for patients than IV sedation, c) most patients prefer it, d) it is quick to administer, e) it has a rapid, reliable onset, and f) it lasts long enough to keep the patient comfortable during a typical cataract procedure. In this publication, the ratio of patients treated with the MKO Melt versus patients treated with IV sedation varied from 50/50 to 70/30 on any given surgical day. The authors acknowledged there were times when a patient needed more sedation than the troche provided—for example if the case was prolonged—and on those occasions an IV was started and IV sedation was supplemented. When the authors compared the effects of the MKO Melt with the effects of IV sedation on patients’ vital signs, they observed statistically significant improvements in preoperative and postoperative systolic blood pressure and postoperative heart rates in patients who received the MKO Melt. They concluded that the MKO Melt was safe, effective, well tolerated, and a viable alternative to intravenoussedation. An additional benefit was that MKO Melt sedation was a cheaper method, as it eliminated the need for intravenous tubing and intravenous solutions, and reduced the personnel costs associated with IV insertion and removal.
In a second retrospective study, 1111 patients underwent cataract surgery and received either MKO Melt (n = 991) or traditional intravenous sedation (n = 120). No clinically and statistically significant differences were found in vital signs during or after the two sedation methods. The MKO Melt was a safe and effective alternative to intravenous sedation.
Since the release of the MKO Melt in 2018, it seems the technique has not made a significant market share advance into conscious sedation practice. I’m curious if any of my readers have any experience with the technique.
Don’t expect the development of a sublingual troche to induce general anesthesia or deep sedation. The addition of respiratory depressant drugs such as fentanyl or propofol would increase the risk of hypoxic complications. The risk of losing the airway due to obstructive apnea or oversedation without an anesthesia provider present would be too great. I wrote a previous column discussing the risks of administering the sublingual narcotic sufentanil. The safety profile of the current MKO Melt is assured by the fact that neither midazolam nor ketamine has a significant risk of respiratory cessation in moderate doses. The inclusion of ondansetron in the MKO Melt formulation is perplexing, since neither midazolam nor ketamine has a significant incidence of causing nausea. The troche could conceivably have been an “MK Melt” without any difference in efficacy or side effects.
I’m surprised by the lack of prospective randomized trials testing the MKO Melt versus intravenous conscious sedation. I’d be interested in the results of such trials for oculoplastic surgery procedures like the ones my surgeon colleague does in her office. I’d also be interested in trials of the MKO Melt for elective colonoscopies, in which the current standards of anesthesia care are intravenous sedation with midazolam/fentanyl, or propofol sedation administered by an anesthesia professional. If patients tolerated endoscopy with MKO Melt instead of intravenous propofol sedation administered by an anesthesia professional, the cost savings would be substantial.
As anesthesiologists we are unlikely to administer the MKO Melt because we utilize intravenous catheters and intravenous medications on our patients, but in the future non-anesthesiologists may find increasing uses for sublingual sedatives like the MKO Melt for instances when no anesthesia professional is available.