In this episode of Interventional Mindset, Dr. John Berdahl, an ophthalmologist at Vance Thompson Vision in Sioux Falls, South Dakota, and inventor of MELT, discusses advancements in sedation for cataract surgery related to MELT.
Minimizing opioid exposure in cataract surgery
Approximately 5 million cataract surgeries are performed in the United States,1 and fentanyl is one of the most commonly used forms of sedation.2 Dr. Berdahl believes that, despite being one of the most commonly used agents in cataract surgery, fentanyl offers little benefit for routine cases and exposes patients to avoidable risk.
Studies have shown that prolonged anesthesia recovery is associated with intra-operative fentanyl use, post-operative pain, and opioid requirements.2 Additionally, opioids prescribed during this period can lead to long-term use—the opioid paradox—where more intra-operative opioids result in increased post-operative needs.2 Because of this, Dr. Berdahl asserts that there are better ways to sedate patients than with midazolam and fentanyl.
MELT and multimodal pain management
The sublingual MELT, containing compounded midazolam and ketamine, is an effective non-opioid sedative for cataract surgery. Multimodal analgesia effectively manages pain following cataract extraction by utilizing two or more medications or nonpharmacologic interventions that work through different mechanisms of action to alleviate post-operative discomfort.2
In one study by Jeffries et al., there were no significant differences in surgical or discharge times, satisfaction, or side effects among patient groups.2,3
For Dr. Berdahl, MELT provides an excellent, consistent sedation with several major advantages, including:
- Avoiding opioid exposure and associated recovery delay (ex., no fentanyl)
- Enabling fully oral/sublingual sedation workflows because IV is not required
- Producing predictable anxiolysis and dissociation without respiratory depression
- Offering the benefits of ketamine, as it may help patients look at light more comfortably, reduce squinting, and induce mild euphoria1
Findings from clinical trials on MELT
While Dr. Berdahl invented MELT and has a financial interest in it, Harrow Health owns the MELT product and, in combination with Melt Pharmaceuticals, ran a phase II clinical trial for FDA approval of MELT (midazolam and ketamine).1
The study was a four-arm trial comparing midazolam with ketamine, midazolam only, ketamine only, and placebo:1,4
- The rescue rate in the midazolam-ketamine arm was half that of midazolam alone or ketamine alone, and one-third that of placebo alone
- The combination of medications was twice as effective at preventing the need for rescue sedation
In the phase III trial, MELT-300 performed better than midazolam alone and placebo, and the rescue sedation half of midazolam mirrored the findings from phase II trials.5
Vance Thompson Vision uses the MELT for almost all eye surgeries, including cataract surgery, DSEK/DMEK, and MIGS, and also uses it as a sedative for blocks. In Dr. Berdahl’s experience, using the MELT provides a measurable and impactful improvement for patients because they can avoid the painful part of cataract surgery—getting poked for an IV.
It also improves the staff experience by avoiding delays when starting an IV on a patient. However, it is ideal to have an anesthetist or anesthesiologist present.
Addressing anesthesia concerns
Using MELT can make the anesthetist's day more efficient, allowing them to do more cases. Dr. Berdahl acknowledges that the primary objection to non-IV sedation is the perceived loss of rescue access; however, in real-world use, IV access is required in fewer than 2% of cases and can be rapidly established if needed.
At Vance Thompson Vision, the practice uses an IV with a Hep-lock in 1 to 2% of cases if a patient is "particularly squirrely," but they seldom need to use it. For new surgeons with hesitant anesthetists, Dr. Berdahl’s advice is to start the IV, Hep-lock it, and, after 50 or 100 cases without needing an IV push, the anesthetist will realize it's unnecessary.
According to Dr. Berdahl, an IV is not necessary for billing Monitored Anesthesia Care (MAC). Billing for MAC is based on the patient receiving an anesthetic that requires monitoring, regardless of how it is administered. Since ketamine is classified as an anesthetic, it falls under this category. However, be sure to check the specific requirements for your state.
Note: Dr. Berdahl warns against using Valium (diazepam) for oral or sublingual sedation, especially in older people, because its half-life is 6 to 7 days, increasing the risk of falls.6 If using a single drug, midazolam is the better choice.
Conclusion
Given the scale of cataract surgery in the United States and the established risks of even brief opioid exposure, continued routine use of fentanyl is increasingly difficult to justify.
Non-opioid multimodal sedation using MELT, a sublingual midazolam-ketamine, offers an evidence-based alternative that improves workflow, enhances patient comfort, and reduces opioid reliance without compromising surgical efficiency.
Financial Disclosure: As the co-inventor of MELT, John Berdahl, MD, has a vested financial interest in this product, which is manufactured by ImprimisRx, a subsidiary of Harrow, Inc. (formerly Imprimis Pharmaceuticals, Inc).
