Speaker 1:  Welcome to the ASHP Official  Podcast, your guide to issues related to medication use, public health, and the  profession of pharmacy.
Vicki Basalyga:     Thank you for joining us for Therapeutic  Thursdays Podcast. This podcast provides an opportunity to listen in as members  sit down to discuss what's new and ongoing in the world of therapeutics. My  name is Vicki Basalyga and I will be your host today for the ASHP Therapeutic  Thursdays Podcast. With me today, is Dr. David Zimmerman, who is an Associate  Professor of Pharmacy at Duquesne University School Pharmacy and Emergency  Medicine Pharmacist at UPMC Mercy Hospital. He has a scholarship focus on  medication dosing in obese patients and pain management in the ED. My second  guest today is Aimee Mishler. She is an Emergency Medicine Pharmacist and PGY2  Emergency Medicine Pharmacy Residency Program Director at Maricopa Integrated  Health Systems in Phoenix, Arizona. Thanks for joining us today Dave and Aimee.  Let's get started today by talking about the topic Intravenous lidocaine for  Pain Management. Aimee let's talk about why we use lidocaine for pain in the ED  and why it is an underutilized agent in certain patient populations.
Aimee Mishler:      That's a really good question Vicki.  There's a lot of different reasons that you might want to use a lidocaine in  the emergency department, especially right now with our opioid epidemic. Lidocaine  is really useful for a lot of different reasons. It can treat Non Neuropathic  pain and Neuropathic pain, both of those. It can be opioid sparing, it's  multimodal, it can be a monotherapy, or it can be used as an adjunct. It's fast  acting and there's only a few monitoring parameters that you need to take into  consideration. And it's good for both acute pain and acute exacerbations  of your chronic pain Vicki  Basalyga:   So Dave, most pharmacists are  familiar with lidocaine as an anesthetic or anti-arrhythmic agent. Can you tell  us more about how lidocaine works to relieve pain?
David Zimmerman:     Yeah, absolutely. So we know lidocaine is an Amino Amide Anesthetic that alters neuron signal conduction by modulation of sodium channels in both peripheral and the central nervous system. So this is where the thought that the analgesic activity comes from. This sodium channel blockade and CNS hyper excitability resulting in less painful stimulus response. It's not quite clear but it's also thought that lidocaine has some anti-inflammatory effects leading to the reduction of circulating inflammatory cytokines. We know this is how it works as anti-arrhythmic but does lead to the same analgesic mechanism. Does it have a, you know, vast clinical threshold. It's kind of unclear, but it is thought that the analgesic mechanism is a result of these two actions.
Vicki Basalyga:     When we're thinking about patients who  present to the ED for pain, what sort of patients would be good candidates to  use lidocaine to manage their pain?
Aimee Mishler:      lidocaine should be really added as an ALTO  therapy. So, ALTO being the alternatives to opioids, and it can be used by  itself or in conjunction with other non-opioid analgesics like NSAIDs,  Acetaminophen, sub-dissociative Ketamine and a lot of other options. As we know  there are various types of pain that exist, and lidocaine can be utilized for  several of those. Neuropathic pain conditions like postherpetic neuralgia and  acute pain conditions like renal colic have also demonstrated some of that  analgesic benefit. And then also lidocaine has demonstrated an opioid sparing  effect in the post-op setting as well. So, there's a lot of different options  that we should start looking at lidocaine for and there's a lot of different  organizations and institutions that are coming up with their own ALTO programs  and really promoting the use of lidocaine specifically for that Opioid sparing  or as an opioid alternative.
Vicki Basalyga:     Aimee, I'm so glad that you mentioned ALTO.  Dave, can you talk to us about lidocaine? Is it better than medications we're using  now including opioids versus non-opioids and then what is its role when it  comes to pain management? Do you use it as a single agent? Do you use it in  combination with other agents? Can you just tell us a little bit about how you  use lidocaine in your ED?
David Zimmerman:     And it kind of just depends on which pain  condition you're looking at. With some of our literature with Renal Colic we  know lidocaine has an equal efficacy and pain reduction compared to opioids and  that's why Aimee mentioned it's a great ALTO agent. When it was compared to  ketorolac, ketorolac was shown to be better than lidocaine. So, from my  standpoint, you know, a patient presents with Renal Colic, I'll still go with  an NSAID first and  then I can use lidocaine as a second line or as an add on option. And  certainly, there are patients out there that you may want to avoid  systemic NSAIDs .  So, then IV lidocaine would be an option. So, for Renal Colic we know it's as  good as an opioid. Those we can use it as an ALTO agent or avoid opioids all  together.
David Zimmerman:     When you look at a pain condition like acute  radiating low back  pain, IV lidocaine was shown to be similar to ketorolac. So, if a patient  presents with low back pain you can consider lidocaine as a first line option  or use it in conjunction with ketorolac or as a second line option. And then  there was an interesting study that looked at, and this was in the ICU, it  looked at opioid requirements for patients prior to and after a lidocaine  infusion and they noted that there was a decrease in opioid requirements after  the addition of lidocaine. So, I don't think we fully know for every acute pain  condition. We still certainly need evidence, but I think this is an agent that we can certainly  add to our arsenal. It may not be First Line everywhere, but I think it's a  good second agent or an add on the agent to something else first line.
Vicki Basalyga:     So Aimee patients present to the emergency  department for all sorts of pain. You briefly mentioned earlier talking about  Neuropathic pain and as Dave just mentioned is lower back pain. We also see  patients present to the ED for pain such as Cancer pain and those patients tend  to have already a lot of pain medication onboard and might not be opioid naive.  Can you talk to us a little bit more about these different kinds of pains,  particularly Neuropathic pain and pain for Cancer patients and the role that  lidocaine plays for this unique patient population?
Aimee Mishler:      Yeah, definitely. I think this one's a  little bit more difficult to talk about from an ED perspective because a lot of  these studies with these case reports were more on the chronic pain versus the  acute pain, but lidocaine has been studied for postherpetic pain, trigeminal neuralgia  and some cancer pain like you mentioned, and it looked like in these studies  that the pain score measured at different intervals decreased by about 50% from  the pre-infusion values and about 75% of those cases for those different  indications. But again, this may be more of an area that we need to look at for  future studies specifically in the emergency department because a lot of these  were more chronic pain. I don't know, Dave, if you have anything to add to  that.
David Zimmerman: I think you  summarized it well. There's a really good systematic review that was published  in Pharmacotherapy by Dalila Masic and Megan Rech and colleagues that kind of  goes through some of the conditions to summarize them.
Vicki Basalyga:     The next question that pharmacists receive  is, okay, I want to give this medication. How do I give it? In what dose? What  do you recommend starting at and how should it be administered, bolus, and then  a continuous infusion bolus alone or infusion alone?
David Zimmerman:     So, most of the dosing, if you look at doing  a bolus, we'll kind of do a weight-based of 1.5 mg/kg and this is usually capped  at 200 milligrams. So, if you have somebody that weighs like over 130 or 140  kilos you just cap it at 200mg. Some studies just did a flat dose of a hundred  milligrams. It's kind of either an option. What we did in our protocols, we did  1.5 mg/kg and  then we infuse that over at least 30 minutes. As you pointed out there's kind  of three different options, bolus only, bolus plus infusion or infusion only.  And it really kind of depends on what you're treating pain wise for the patient  and what's their game plan. You know, if it's somebody that's not, you're not  planning on admitting, you know, continuous infusion probably isn't going to be  the route that you go. Maybe just give a bolus dose.
David Zimmerman:     If you look at doing a continuous infusion  dosing here usually starts from the lower end of like 0.5  mg/kg/h and then can be titrated up. We do know that if you don't  bolus that may take a little bit longer for that continuous infusion to have  its analgesic effect. Again, another thing to look at is kind of just hospital  protocol. At my institution we in the ED are allowed to do boluses of lidocaine  for analgesia, but we are not allowed to do the continuous infusion part our  anesthesia and pain team has to do that. When you're initiating or looking to  at initiate  lidocaine and doing a bolus of it, you know, this is something we also want to make  sure everyone's onboard, pharmacy, nursing, emergency medicine, pain team, you  know, whoever else you want to bring to the table.
Vicki Basalyga:     Aimee, do you have at your institution  protocols or plans to introduce a protocol using lidocaine for pain?
Aimee Mishler:      Currently we don't have any protocols in  place for this, but we do use it primarily for renal colic and it is one thing  that we're looking at kind of as a whole institution in trying to, again, avoid  those opioids. So, we don't currently have any policies or protocols, but we do  use it for renal colic.
Vicki Basalyga:     Let's stop and talk a minute about  medication safety when it comes to lidocaine. We know that lidocaine comes in  different concentrations and sizes with different doses being used for  different indications. Can you guys share with me what you have in place at  your institutions to ensure safe administration?
David Zimmerman:     Yeah, absolutely. I'll kind of talk about  what we did, but first off, if you're looking at the bolus that should not be  given as an IV push. This would be given as an infusion, typically over 30  minutes. Some of the studies that are a little bit faster at 10 minutes. I  recommend at least doing 30 minutes if not longer, just 60 minutes. So, I know  lidocaine is stable in either normal saline or D5W. When kind of planning this,  we have tons of different lidocaine preparations as you mentioned Vicki and our  ED, you know, 1% 2% with EPI without EPI. So, what we did from a medication  safety standpoint, we don't have 24/7 ED pharmacy coverage. We always have a  pharmacist in the hospital but not always in the ED. So, we had to try to come  up with a plan to try to prevent, you know, any type of medication misadventure  from occurring.
David Zimmerman:     So we decided that it would always be  prepared by pharmacy, either our ED pharmacists or central pharmacy and then  sent down. We do not have a pharmacy satellite or anything like that in our ED.  So this is something where there might not be one size fits all approach. It  could depend on kind of your institution and coverage. I helped the hospital in  Arizona implement IV lidocaine in their ED and when I was talking about what we did and they said well  we don't always have a pharmacist in the hospital, but they said that's not as  feasible.
David Zimmerman:     So, what we came up with was creating an IV  lidocaine kit that pharmacy could prepare. It could be stocked in the safety cabinet in the  ED and then when ordered a nurse could remove it and it would give compounding  directions. It would have the IV lidocaine preparation in there. It would have  the bag of fluid and a label and then it could be prepared. So again, they're  not going to be one size fits all approach. But this is a situation where you  do have to consider a big med safety component because of the different  lidocaine preparations. When it comes to the continuous infusion this is a lot  easier because there is a pre-mix. So I would highly recommend utilizing that  if you're going to continuous infusion around.
Aimee Mishler:      I think we we're pretty similar to what  David was just explaining. Again, we don't have 24-hour ED pharmacy for us  either. So, when the ED pharmacist is not here, it does dispense from the main  pharmacy. But if I'm here or if my counterparts here then we’ll often make at  bedside for our nurses and we just use the prefilled syringes that you would  use like during a code is what we would use if I'm preparing it at bedside. But  I think David makes really great points about medication safety and there are  so many different products out there that when an ED pharmacist is not making  it, it really should be coming from the inpatient pharmacy.
Aimee Mishler:      We also have a satellite campus for us  that doesn't have 24-hour pharmacy. They're only there 12 hours a day. And so,  it's very similar to what David said. We stock it in the Pyxis for them to  dispense from and for the nurses to prepare it from. And we have for many of  our infusions we have a book for them that goes through step by step of how to  prepare it and how to label it and how to administer it and what to watch out  for. So even if the pharmacy is not there then they have some information that  they can use.
Vicki Basalyga:     Thanks Aimee and Dave. So what sort of  things should we be recommending to our physician and nursing colleagues to  keep an eye out when monitoring for adverse events?
Aimee Mishler:      Yeah, definitely. Like with any medication  there's always going to be side effects. Some of the more mild ones for a  lidocaine would be dizziness, nausea and vomiting, similar to a lot of our  other medications. And these are also the most commonly reported in that review  that David mentioned earlier. These are the most commonly reported side  effects. Some of the other more moderate ones that were mentioned were peri-oral numbnesssomnolence and this  happened in about 78% of the patients. And then the more severe side effects  that you should watch out for would be seizures or cardiac dysrhythmias and  these would be your higher doses kind of breaking that max dose recommendation.  And then the cardiac dysrhythmia as there was only one study in that review  that noted a cardiac event. And that was a patient who was on hospice who died  suddenly, and they couldn't determine specifically if it was from the lidocaine  or not, but they did mention that in the study.
Aimee Mishler:      But overall there aren't a lot of serious  or severe adverse events reported in those studies that we're looking at where  it's used for pain. And if a patient does develop a serious adverse effect from  the lidocaine the first thing, you'd want to do would be to just stop it  immediately. And if it was due to like an overdose situation or if it's a  seizure or something like that, then you could always administer intra lipid.  And for information on that you could visit the lipidrescue.org website.
Vicki Basalyga:     I'm so glad that you mentioned cardiac effects,  as most of us are familiar, lidocaine is often used to control arrhythmias.  From a monitoring standpoint with the ED and I'd also kind of like to know what  happens once you transfer those patients to the inpatient area if they're  admitted. Do you recommend telemetry monitoring for those who present the ED  for pain and you want to use lidocaine, do you rule out patients with  structural heart anomalies or are known to have dysrhythmias?
Aimee Mishler:      Yeah, sure. I think that my approach I  always ask the provider what’s the patient's history, do they have any cardiac  history are they otherwise pretty young and healthy or what else is going on  with them? Just so that I have an understanding of who we're going to be  administering this to and I always recommend that they get put on the cardiac  monitoring. In the renal colic study, they did exclude anyone that had cardiac  disease, renal disease or liver disease. But all of the other studies that were  in that review included those patients. 26% of those patients did have a cardiac  history and 10% did have an Arrhythmia history.
Aimee Mishler:      Those patients that did have that history  were included in those studies without any significant adverse effects, but I  think my approach is just a little bit more conservative and that I would  rather have them on the monitor just in case anything does go wrong. It can  alert somebody if they're not immediately in the room and having them on the  monitor is not very invasive or cumbersome and it may be that the benefit of  having them on a monitor out weighs the risk of not having them on the monitor,  but again in those studies they did include those patients with that history  and didn't see any significant effects from that.
Vicki Basalyga:     Great, thanks Aimee. Dave mexiletine is often considered the oral  lidocaine since we have patients who may be started on an IV lidocaine and we  find that it's effective, sometimes there's an interest to convert them from an  IV formulation to an enteral formulation. So I was just wondering what you guys  do when it comes to transition to these patients and if you ever recommend mexiletine 
David Zimmerman:     There's a little bit of evidence out there  with mexiletine for  chronic neuropathic pain. This is an area that I will defer to the inpatient  team or pain service or outpatient pain service. From my viewpoint, I don't  think it does in our purview as from an emergency medicine side. So, if I get  asked that I think that I'd say that's something you can consider, but also  typically defer to our pain team and let them make that recommendation if they  decided to add it or to not add it.
Vicki Basalyga:     So now we've given the medication, it's  been administered safely. The next question we often ask is when will we see  this drug start to work. Can you share with us what you guys tell your team  once you have administered IV lidocaine?
Aimee Mishler:      Yeah, that's a really good question. It's  difficult to say that all patients will respond by X time, especially with different  uses that we may be using the lidocaine for or the different dosing strategies  that are out there, but overall in the studies that are available, it looks  like the pain reduction was in about 30 to 60 minutes and it was pretty split  between those indications. So, somewhere between 30 and 60 minutes is usually  what I will tell the providers and the nurses if they're asking.
Vicki Basalyga:     Finally, in closing, what would be the  number one piece of information that you would want your colleagues to know  about using lidocaine in the pain free day?
Aimee Mishler:      I work a lot with the residents, and I  feel like at my institution it's still not very widely used. So, I think the  first thing that I always tell them is don't forget about it. I think that  oftentimes it's overlooked. Or even if I bring it up and recommend it, they're  like, Oh I've, I've never heard about that or what do you mean? So, I think the  first thing that I would say is just don't forget about it. And then if you do  want to use it, you know, just kind of everything that we've talked about that  there are benefits for using it. It can be opioid sparing and then you can see  some relief in about 30 to 60 minutes. So especially if you've tried something  else and it's not working, lidocaine can be an option.
David Zimmerman:     Yeah, I would echo that. I don't think  lidocaine is the wonder drug that's going to, you know, take all the pain away.  But I think it's a great addition to our treatment of pain in the ED. Going  back to what Aimee mentioned and the ALTO movement. You know alternative to  opioids one of the things we do is try to hit a multimodal effect. You know,  different receptors, different channels to treat a patient's pain and certainly  try to reduce our opioid use, as in lidocaine, is a good addition. I think you  can consider it. A lot of the studies look at lidocaine versus an opioid or  lidocaine versus ketorolac. I don't think it's wrong sometimes to give the  patient, especially if they come in in severe pain. Let's say it's Renal Colic  to give both ketorolac and IV lidocaine. So, it's something you can certainly  use up front and you know not always by itself.
Vicki Basalyga:     That's all the time we have today. I want  to thank both Dave and Aimee for joining us today to discuss IV lidocaine in  the ED for pain management. Join us here every Thursday while we will be  talking with ASHP member content matter experts on a variety of clinical  topics.
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