Thanks, Joanna. Thank you all for being here and making it to warm Phoenix. I know where I'm from. It's a little bit cooler. So we're going to be talking about a balancing act, managing opioid use in critically ill patients. My disclosures, I have some internal funding related to marijuana and invasive fungal infections, as well as a pilot on some deprescribing work. So my objectives for the next 15 or so minutes, we're going to compare and contrast opioid agonist therapy with respect to analgesic properties and utility for management of opioid use disorder, and then design a plan for an algo sedation in patients with OUD admitted to the ICU. So we've all seen this before. We're pharmacists, physicians, nurse practitioners in the ICU. We know pain is common. So pain is common at rest. Pain is common with routine care in the ICU. And that incidence of significant pain or pain that patients say they want to go away is over half of our patients, if not more, in both medical and surgical ICU settings. We know that's also influenced by psychosocial factors. We don't have a really good understanding of all those, and there's some work that needs to be done there. So that's psychology of individual patients, as well as some of their demographic and cultural factors that we need to take into account. So the PADIS guidelines recommend that we use a protocol-based pain assessment and management program, which we know reduces mechanical ventilation length, ICU length of stay, pain intensity. And we should be using self-report as the gold standard. We know that in a lot of our patients, especially those that are mechanically ventilated or those that are non-verbal, we need to use our validated behavioral pain scales, not our vital signs. So we have our BPS, our behavioral pain scale, and then our CBOT, or the Critical Care Pain Observation Tool. So what does PADIS say about analgesia? It recommends the analgesia-first or analgesia-based sedation strategy. And opioids are our usual analgesic choice, despite mounting evidence showing that opioids increase delirium in a dose-dependent manner. But where do the guidelines fall on patients that come in with a pre-existing opioid use disorder? So their exact quote is, generalizability of study findings can be improved by including heterogeneous samples of ICU patients, specifically those with a known opioid use disorder. Okay, we're off to a great start. We have no data in the latest set of guidelines. And they recognize that as an evidence gap. What are potential safety concerns associated with our protocol-based analgesia protocols, specifically post-hospital opioid use disorder? And Bill did a great job showing where some of this data is going. So as practitioners, one of our most important roles in patients that have opioid use disorder or potential opioid use disorder is a thorough patient assessment. Pain assessment, specifically patient-recognized pain, again, is our gold standard. But we need to make sure that we're also setting goals with patients. For individuals that are actively using opioids, individuals that are in recovery from opioid use disorder, we need to talk with them about what they should be expecting during their ICU stay and what their goals are during ICU recovery. So for some patients, that's, I want to remain abstinent of opioids during my ICU stay. For others, it's using opioids as a bridge to treat pain to get out of the ICU. For others, it's their first time being in a center like this and being given those choices. So we really need to be talking to our patients. And I know it's difficult. You have patients that are coming in intubated. They were intubated in an outside hospital, and we don't always have that opportunity. We need to assess throughout the ICU stay. So one of the questions you can use, are you currently using opioids? Which ones are you using? How much are you using? How often? Patients should be able to ballpark what they're using. You may need to become familiar with street terms for what patients are using, how much is in a dime bag, et cetera. But this will help you figure out what your baseline is for what patients are using, what their expected tolerance levels are, and what you should be giving them in order to effectively manage their pain. And remember that patients don't always differentiate between prescribed opioids and opioids that they obtain from the black market or illicit means. Also keep in mind that some patients will have concomitant use of other substances that may complicate their management. So stimulant use disorder, cannabis use disorder may be problematic here as well. The next question, do you want to stop using in patients that are actively using? You need to reevaluate this throughout the ICU and hospital stay. This determines whether or not we should be furnishing things like methadone and buprenorphine during ICU stay, or if we should just be bridging with active, full opioid agonist therapy. And then what are you using or what have you used in the past for individuals that are trying to stay sober or trying to avoid opioid use disorder in order to figure out what medications they're on, how we can effectively manage them during their ICU stay, and what we need to do to bridge them back to outpatient therapy. A strong medication reconciliation, whether that's done by a pharmacist, a nurse, or the physician, is extremely important. And this is a case where you need to go into places you don't normally go for medication reconciliation. A lot of the data will be in your PDMP in your states that you can pull for controlled substances. But things like naltrexone use, methadone that comes from a clinic, are not going to be populated into PDMP. So just doing a PDMP search will often leave you lacking for the amount of data that these patients will have. It's important that you contact the pharmacy or for patients that are using methadone for therapy to contact their methadone clinic for multiple reasons. At the beginning, that is the most reliable source for patient dose, especially with methadone. These patients are titrated on a daily or weekly basis, and they are not the usual doses that you would see for individuals that are using methadone for pain. So contacting the clinic, letting them know that the patient has been admitted to the ICU, and that you need to reconcile their dose so that they can maintain opioid agonist therapy during their ICU stay is extremely important. They can also document that the patient has had an encounter with the ICU, that they may be receiving opioid agonist therapy, because if they are required to have urine toxicology screens, they are now going to flag positive for using, which in individuals that are getting opioids for acute pain in the ICU is a very different circumstance than individuals that are using in a recreational site. It's important to note that stigma from healthcare professionals can lead to barriers to patient access to care and to harm reduction strategies. So utilizing patient-centered language, talking to them about what is important to them is important to making sure that they can access care. So why do we need this thorough assessment? We know that if we're not getting what patients are actually taking, we are putting them at risk for ineffective analgesia or undertreating their pain. We can also precipitate withdrawal in individuals that may or may not be using buprenorphine as an outpatient. This is also important for your staff safety. Individuals that are undertreated are more likely to become agitated, pull at lines, and become violent. That is a nursing and care practitioner safety standard. And then you can also put individuals at risk of relapse. But it's important to note that adequate analgesia in the setting of acute pain is less likely to induce relapse than individuals that have inadequate pain therapy, who would then be seeking for analgesia when they leave the hospital. So precipitation of withdrawal. Bill mentioned this briefly, but we have the Clinical Opioid Withdrawal Scale. Not those cows, but we abbreviate it as COWS. It's a 48.11 domain scale, which includes resting heart rate, sweating, GI upset, yawning, and irritability. Anybody that's had a patient that's intubated will know that most of these things you can't really tell. How do you tell what a resting pulse rate is in a patient that's on three pressers? I don't know. So this is not really useful in the ICU. It's a gap in our care. We have to utilize some of the domains in order to determine whether or not our patients are in withdrawal when they're coming into the ICU. So what are our medications? We have three mainstay medications for management of opioid use disorder that you need to be aware of in your patients. There's four lines. We'll talk about it. Methadone is a mu-receptor agonist, or a full agonist, and also has weak NMDA agonist activity. It's available orally and intravenously, and usually is dosed daily. It's important to note that for individuals that may be having issues with QTC prolongation, methadone is known to prolong the QTC interval, and it also blocks serotonin reuptake. So it is not a good choice in individuals that are at risk for serotonin syndrome. Buprenorphine is a partial mu-receptor agonist and a weak kappa and delta agonist. It is available in sublingual, injectable, transdermal, and intradermal formulations. That can be given on a daily or monthly basis. Buprenorphine is the one drug that should be available in your PDMP so you can get usually accurate doses on this just by doing your normal searches. But it's important to note that this has the potential to precipitate withdrawal. Because you have partial agonism, but it is a very strong binder at the mu-opioid receptor, you are likely that if you treat patients that are on buprenorphine with a strong mu-agonist, you can knock buprenorphine off and get rid of a lot of that agonism and precipitate withdrawal despite giving opioid therapy. And when you initiate it in the hospital, there is an induction protocol that we will talk about. The second half is buprenorphine with naloxone. This is literally just a misuse suppressant so that individuals do not crush it up and inject it. And then naltrexone is our antagonist. This is not used as commonly as the other two, but this is for individuals that want to remain opioid-free as an outpatient. This is available as a monthly intramuscular injection that is provided at a care center. So again, will not show up in the PDMP, and you need to go looking for this in order to figure out how to treat these patients. So what's our care plan? A recent survey of ICUs found that only 7% of ICUs have a protocolized plan for taking care of our patients with OUD. We need to make sure that we're titrating our opioid analgesia to effect, and then using our non-opioid adjuvants that are in the PADIS guidelines. So patients that are maintained on methadone before they come in, you can either administer the oral dose at the full dose that you would. You can give this down an NG tube or an OG tube, and then furnish additional opioid and non-opioid analgesics in order to titrate to pain relief. It is, again, important to notify the methadone maintenance program at admission and at discharge that the patient is in the hospital. And for individuals that do not have oral access, you can administer a total of one-half to two-thirds of the dose in divided daily doses, usually three times a day. For patients that are on naltrexone, nobody freak out that I put a chemical structure on the slide, please. This is, the important thing to do is determine when the last dose of naltrexone was and the route of administration. Some patients are using oral naltrexone, in about three days it'll be gone. The intramuscular injection lasts for about a month, and you're going to be using high dose, extremely tight binding mu-opioid agonists in order to try to overcome that. It's very important in these patients to furnish non-opioid analgesics because of the blocking of the mu-opioid receptor. And then you want to consider those strong mu-opioids. So what are strong mu-opioids? The smaller the bar, the stronger the binding. So please avoid codeine in these patients. But things like fentanyl, morphine, hydromorphone, and intravenous buprenorphine or sublingual buprenorphine can be used in patients that are on naltrexone to potentially overcome that. But again, keep in mind that not all of these drugs have a ceiling effect on respiratory depression. And if you have patients that don't have a maintained airway, you're going to need to be monitoring for respiratory depression. So patients that are on buprenorphine as an outpatient, there are actually four different recommended ways of handling this. You can continue their buprenorphine at the outpatient dose and then titrate short-acting opioids. This does have a higher risk of respiratory depression because of how buprenorphine occupies those mu-opioid receptors. You can split the buprenorphine dose and give it every six to eight hours. You can stop buprenorphine and then titrate a full opioid agonist to effect. But keep in mind buprenorphine has a long half-life, so this will probably take you about a week for buprenorphine to wear off, and you're going to be titrating doses daily as you go through. And then when you start them back on buprenorphine, you have to go back through the induction protocol. Or you can convert to methadone at 30 to 40 milligrams per day and titrate opioid therapy. So the dosing for patients that are over 16 milligrams a day, it's recommended to drop to 16. For patients that are at 16 or under, you can keep them at their current dose. If pain control is inadequate, the recommendation is actually to decrease the buprenorphine because of the way it occupies that mu-opioid receptor and then titrate up their other opioids. So does buprenorphine continuation work? A single-center retrospective study of 117 patients found that when they kept patients on buprenorphine, the amount of opioids they used both in the ICU and out of the ICU were significantly less than in patients that did not receive buprenorphine therapy. So we know that it decreases the use of full mu-opioid agonist therapy, which may be important when we talk about delirium rates. We talked about buprenorphine induction. There is a lot of literature out there. But in patients that you want to induce, this is a multi-day process. You have to monitor the patient for two hours after each dose, increasing the dose daily until you do not have withdrawal symptoms and they're maintained throughout the day. And then Bill talked about this data, but in patients that are receiving opioid agonist therapy prior to hospitalization, we know that furnishing buprenorphine decreases the likelihood of patients coming back to the hospital. This is not something that we know about inpatient buprenorphine therapy, but if we start patients when they first come, the thought is that they will be on buprenorphine when they come back and hopefully will decrease readmissions on subsequent encounters with the ICU. So for all of you looking for the money slide, this is the one to look at. Patients actively using opioids should be monitored for withdrawal and you should consider initiation of medications for opioid use disorder. For those that are already receiving therapy for buprenorphine, 16 mg per day or less is the recommendation. For methadone, continue their dose, either give it as a full dose in the morning or divide it throughout the day for its analgesic properties. And the patients that are on naltrexone, do not give more and anticipate that they will have higher needs for opioids than your other patients. So where do we go from here? Sorry, my personal plans got in here. But epi studies are needed for using MOUD in the ICU. What happens when we continue therapy from the community? What are our best practices for newly initiated therapy within the ICU? We need comparative effectiveness studies specifically between methadone and buprenorphine, but also looking at our other opioid agonists in the hospital. Is there a difference if we're giving patients hydromorphone versus fentanyl? And we really need to follow these patients for their post-ICU outcomes. We know about readmission, but the problem with a lot of our readmission studies is they're retrospective and patients are lost to follow up. So we're not sure if they are living in the community or if they've gone and continued their opioid use and have died from other manners. With that, I will pass it along.

opioid use disorder

ICU management

opioid therapy

methadone buprenorphine

withdrawal prevention