Thank you, Dr. Feisal, for the introduction. As she mentioned, I will be discussing lidocaine. I don't have anything to disclose in regards to the content of the presentation, but similar to Luma, I did want to acknowledge that we will be discussing the off-label use of IV lidocaine. I've included three main objectives for this presentation. In brief, we're going to review the safety and efficacy of lidocaine, and we'll finish up by discussing some of the key aspects for implementation. And I'll also be sharing some of the experience we've had at our institution since implementing a lidocaine for pain protocol. So, lidocaine is known as an antiarrhythmic, but also a local anesthetic. There are numerous dosage forms available for a variety of subtypes of pain, but it's important to note that for the IV continuous infusion in particular, it's actually only FDA approved for ventricular arrhythmias. That being said, as Dr. Grewal discussed with the ongoing opioid epidemic, there has been an increased adoption of multimodal therapies and a renewed interest in utilizing agents such as lidocaine or ketamine, particularly in the ICU setting. Lidocaine exerts its analgesic effects via inhibition of sodium channels in the periphery in order to reduce nociception, but it also has additional anti-inflammatory properties. One of the benefits of lidocaine is that it does have a rapid onset of action and a very short half-life. This, however, can be prolonged in our patients that have severe hepatic and or renal failure due to the accumulation of active metabolite. Regarding dosing, I want to focus on three main things. First, there is a significant overlap between the dosing for ventricular arrhythmias and for pain. Typically, the dosing we use for ventricular arrhythmias might be a flat rate of 1 to 2 mgs per kg per hour, I mean, sorry, a flat rate, whereas the 1.5 to 2 mgs per kg per hour is typically what we're going to use more for pain. Secondly, I want to highlight the importance of weight and paying special attention to units. As you'll see as we kind of move forward in some rates, it's going to be put in mgs per kg per hour or micrograms per kilogram per minute, which can obviously lead to huge variation in the dosing. We will also discuss what the recommendations are based on in the coming slides. So first, SCCM currently does not recommend the use of systemic lidocaine for pain management due to limited evidence on efficacy and the known risk of adverse effects. However, recently, the Association of Anesthetists issued a consensus statement on the safety and efficacy and provides dedicated guidance to institutions who actually choose to use lidocaine. So now we'll move on to some of the evidence. Now I'm not going forward. There we go. Both of the systemic reviews that I've included here were performed by the same study team and essentially included any adult surgery patients as long as they required general anesthesia for their procedure. It included patients with no intervention, placebo, or thoracic epidural. And the primary end point was pain scores standardized to the visual analog scale. And the key thing to note is that the original trial found a statistically significant reduction in pain that was noted up to 24 hours. And additionally, they noted some other benefits to commonly seen postoperative issues such as ileus, nausea, and vomiting. However, I want to point out that in the latter study in 2018, that these findings were less pronounced. And even though there was a reduction seen with the pain reduction seen with lidocaine, it was deemed to be minimal and thus somewhat clinically insignificant. So given these inconclusive findings, I also looked at a few meta-analyses that reviewed lidocaine for more specific subtypes of surgery patients. And really the takeaway from this slide is similar to that first 2015 meta-analysis in that the patients that really seem to benefit the most are those that are undergoing abdominal surgeries. I've included a few trials here that are more recent but that weren't included in any of the meta-analyses previously discussed. And really without going through all of them in detail, the same kind of holds true as what the meta-analyses find, which that there may be a benefit, there may not be, but that patients that are undergoing abdominal surgeries seems more likely to benefit kind of in general. So the main challenge with interpreting the data so far is there's a high degree of variation, not only in the patient population but also in the primary outcome, the doses that were utilized, and the duration of therapy. And at what point a statistically significant reduction in postoperative pain becomes a clinically significant reduction and could drive us to use the medication more. Some efficacy, so since efficacy is somewhat mixed, the decision for use really becomes weighing the risk versus benefit. So is lidocaine really safe to use? I would say generally speaking, yes. However, it is a narrow therapeutic index medication, and if not used cautiously, it does carry the risk for serious adverse effects, which is where a lot of the hesitancy for use comes from. So you should be avoided in patients with unstable cardiac issues or severe hepatic impairment, as even within the therapeutic range, which is typically one to five, patients can experience some of the neurological side effects, although they're typically relatively minor, such as tinnitus. And really, any of the life-threatening complications are highly unlikely unless levels reach beyond five micrograms per milliliter. Regardless, if your institution chooses to use lidocaine, lipid sync therapy should be available for reversal if it's absolutely necessary. So while lidocaine is not without risk, the vast majority of trials reviewed suggest the risk for toxicity is actually fairly low, and that with appropriate patient selection, dosing, and monitoring, we can hopefully minimize that risk even further. The first study here is by Xu and colleagues. It helped a lot in answering the safety question, as it established that lidocaine actually has a two-compartment pharmacokinetic model, and the inclusion of weight really improved the overall accuracy. So these findings also indicated that a longer duration of therapy increases the risk of drug accumulation. So they actually came up with a regimen that starts off with higher doses, followed by incremental decreases in the dosing, and as the infusion continues on to help minimize the risk of accumulation. The second study looked specifically at obese patients, and interestingly, they used adjusted body weight and ideal body weight, and despite this higher dosing weight, their serum levels actually remained within our goal with no adverse effects reported. With all of that in mind, I think its most important points are that the dose, speed, duration of the infusion all really have a substantial impact on safe use, particularly keeping in mind that the longer the duration continues, the higher the risk of toxicity becomes, and if therapeutic drug monitoring is available, it may be important to implement a protocol with empiric rate decreases, particularly for those who actually don't have the ability to monitor levels so that as the infusion goes on for longer, you actually are decreasing the dose to preemptively prevent any chance of accumulation. Additional considerations are the use of other anesthetics. So administration must be separated from IV lidocaine use by at least four hours in order to avoid added toxicity. Even if laboratory monitoring is available, unfortunately, it's still not really a foolproof tool. We've run into issues at my institution with turnaround time that can be several hours, and so that obviously makes it a little bit impractical for clinical decision making. And then lastly, I want to just talk a little bit about what my institution has experienced since implementing the lidocaine for pain management protocol. It's been probably about four years now since we've had it. So we primarily use a lidocaine in the postoperative setting, so that would be our surgical and liver ICU for patients that are undergoing abdominal surgeries. We've historically initiated therapy in the ICU only at fairly conservative doses of 10 to 20 micrograms per kilogram per minute, and for that reason, as it does have safety risk, we restricted it to the ICU, but after an internal safety review, we've actually expanded the use of IV lidocaine specifically for pain to acute care floors as long as telemetry monitoring is available. We also do have the luxury of having levels available, and we've mandated an eight-hour check after initiation to try and catch any patients that may have early drug accumulation, and then after that, we move to every 12-hour monitoring. Our internal review last year included all comers, so they might not have been abdominal surgery transplant patients. It could have been any patient in the unit that had the lidocaine for pain protocol, and we found that most patients ended up on 20 microgram per kilogram per minute infusion for around 24 hours in total, which is fairly consistent with what guidelines recommend. We did note a reduction in pain scores when used in combination with other analgesic agents, including opioids and other multimodal therapies. So, in summary, lidocaine infusions may be beneficial adjunct therapy in select patients. The dose and duration is important, are probably the most important factors to ensure safe use. And lastly, the availability or lack of availability of therapeutic drug monitoring does not necessarily preclude the use of lidocaine as long as appropriate patient selection and therapy duration is taken into account. That is all I have. Thank you all so much for your time. Thank you.

lidocaine

off-label use

pain management

ICU setting

analgesic effects