Let's dive in here. I'm still Dr. Sarah Kacoma from Rush University Medical Center, and I still have no disclosures. Nothing happened in the last 40 minutes. OK, so right now we're going to talk about all things anxiety, agitation, and pain, and looking at different validated scales, measuring those things. We're going to establish goals of therapy, and we're going to monitor not only the process of care, considering the route, drug, and dose, but also the outcome compared with the goal. So goals of agitation therapy. So agitation, just to define it, motor restlessness resulting from any type of internal discomfort. The triad of it is pain, delirium, and anxiety. The goal is to treat the underlying internal discomfort while maintaining an awake patient who's able to follow commands. And agitation is associated with increased complications and length of stay. More ventilator days, ventilator desynchrony, and increased oxygen demand. There's a couple of different scales we're going to talk about that measures agitation. The Ramsey Sedation Scale was the first one developed. And then along came the Riker Sedation Agitation Scale, or the SAS as I like to call it. And then probably the most commonly used one is the Richmond Agitation Sedation Scale, or the RAS. This is one we used at Rush. It is a 10-point scale, just kind of with zero being the pivot point of calm and alert. More positive means more agitated. More negative means more sedated, all the way down to unarousable. I think I might skip the questions in here, just in consideration of time. Ideally, we're looking for a patient who's calm, comfortable, and easily arousable, and corresponds to the following scores on the different scales. On the Ramsey Sedation Scale, that would be a 2. On the Riker, the SAS, that would be a 4. And on the RAS, or the Richmond, that would be a 0. Different sedation strategies. Sedation protocols with daily interruptions of sedation or maintenance of light levels of sedation are thought to be the best thing for our patients. The pain sedation and delirium guidelines in 2013 and 2018 support that. Less is more strategy these days, compared to a historical perspective in the ICU, where more was better. Unarousable was what you wanted. And then using bedside protocols for titrating sedation and analgesia is best. And you should have daily checklists, where you're constantly, daily, several times a day, thinking about, can we detox at all? Can we go down on things? Can we lengthen the interval to try to get patients off sedation and pain meds? So this is one of my favorite studies. Just talked about it yesterday with my residents. Landmark critical care trial, way back in 2000. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. They had this crazy idea of turning off the sedation once a day and seeing what happened. Randomized trial of 120 patients in the medical ICU. Like I said, there was daily interruption of sedatives in the intervention group. And the control group was just interruption at clinician preference. And they showed better in all the parameters they were looking at. So decreased duration of mechanical ventilation, decreased ICU length of stay, and decreased hospital length of stay. Taking that one step further, if you can wake the patient up every day, then they thought, hey, wonder if we did a spontaneous breathing trial as well. And they found that if you did this, everything looks better in the intervention group. So more ventilator-free days, quicker time to discharge, and better one-year mortality. This was all kind of the genesis of the bundle that Dr. Cuppey was talking about. And to take both of those things one step further, if you can wake them up and if you can try to see if they're going to do well in a spontaneous breathing trial, then you can also get them up and moving earlier. I work in a surgical ICU, so early mobility is super important to us. We like to get patients up and going as soon as possible, even if that's just sitting on the side of the bed a couple times a day. Always good movement. But early mobilization has been shown time and time again to make most things better. So decreased delirium, decreased delirium in the ICU, increasing your ventilator-free days, decreasing your duration of mechanical ventilation, decreasing ICU length of stay. So even though most of us use continuous IV sedation in the ICU, there are some studies that show maybe it's better to kind of spot dose and whatnot. This is a study out of Barnes-Jewish Hospital where it looked at giving bolus medication instead of continuous infusions. But it was looking at fentanyl versus lorazepam. So I'm going to ding this study for that. So sedative. So sedative is a substance that depresses the central nervous system, resulting in calmness, relaxation, and reduction of anxiety and sleepiness. They do cause slowed breathing, slurred speech, staggering gait, poor judgment, and slowed reflexes. Sedatives are anxiolytic and amnestic. The sedatives discussed here do not have any analgesic properties except for dexmedetomidine ketamine, which kind of have weak ones. Opioids do not have anxiolytic or amnestic properties. But we should always consider treating pain as the genesis of their anxiety. I think non-pharmacological interventions are always good. We should definitely focus on those as well in addition to our medical things. So psychological. So frequent orientation. Any sort of familiar voice at the patient's bedside. The patients aren't going to know our voice, but they're going to know their family member's voice. If you can get them to be with them at the bedside, that's always great. Making sure their day-night cycles are maintained. Get those shades up. Close them at night. Reassuring them. Any sort of physical touch, physical therapy, occupational therapy, kind of the environmental stuff too, minimizing nighttime noise, family pictures. And then always compassionate nursing. So when you're choosing your choice of sedative, some things to think about. Think about a level of pain, any sort of procedures. Does your patient need to go off the unit, be transported somewhere? Are you going for long-term, several days in a row, or short-term to get through a procedure? Think about their organ function or dysfunction. Any sort of withdrawal that they might be experiencing. And then lastly, and probably not most popularly, but sometimes we're limited by our formulary. So you do have to take that into consideration. The first group I want to talk to you about are the benzodiazepines. These are sedative, hypnotic, amnestic, anxiolytic, and anticonvulsant. They have no analgesic effect. They're lipid soluble, metabolized in the liver and excreted in the urine. They have a synergistic respiratory depression with opioids, so use and caution with them. They do have active metabolites, most notably midazolam. You can develop a tolerance to them pretty quickly, and they do have higher rates of delirium, which is not our friend in the ICU. These are probably the three most commonly used ones in the ICU are listed here, diazepam, lorazepam, and midazolam. Hopefully, ideally, in any ICU that you're working in, you're not using a lot of these for anything. I think I finally got the spine surgeons that rushed to stop ordering diazepam for muscle spasms, but we're getting there. Lorazepam has a little bit of a longer acting effect compared to midazolam, but all of them can accumulate. Since we want to avoid benzodiazepines, some other agents to consider, probably most commonly propofol and dexmedetomidine. Propofol is a sedative anesthetic, amnestic and anticonvulsant. It has no analgesic effect, though. It does cause respiratory and cardiovascular depression. It has a rapid onset and a short duration, which is great in the anesthesia world, great in the ICU world. Some side effects of it, though, are respiratory depression, hypotension, and increased triglycerides. So after a couple of days, you've got to monitor those triglycerides. And there is something called propofol infusion syndrome. It's more common in children, but it can happen in adults. And the symptoms of this are metabolic acidosis, hyperkalemia, cardiomyopathy with acute cardiac failure, and myopathy and hepatomegaly. So watch out for that. Dexmedetomidine is also being more widely and commonly used in ICUs now. It's an alpha-2 agonist that's highly protein bound. The side effects are bradycardia and lower blood pressure. It is technically only approved for less than 24 hours of sedation, even though I think all of us use it for much longer than that. The patients appear to be asleep but can be easily aroused. And when a study looked at looking at dexmedetomidine versus lorazepam, more days alive without delirium, and coma, a lower prevalence of coma and greater success at meeting sedation goals. Ketamine is also used in ICU for sedation, especially in the COVID times. It is a PCP derivative, which can lead to some nightmares and PTSD from it. It is highly lipid soluble, crosses the blood brain barrier fast. It's a non-competitive antagonist with the NMDA receptor. It is a bronchial smooth muscle relaxant as well. So sometimes it's great for patients who do have a reactive airway disease. Dosing is listed here. And like I said, it can be associated with nightmares. We find that it's a good adjuvant to pain therapy in the operating room. And in the ICU, like I said, in COVID times, we were using lots of ketamine to help sedate people. Atominate's no longer used for ongoing sedation. It does cause adrenocorticoid suppression, as well as myoclonus. We just don't see a lot of infusions of that anymore. The last group that I just wanted to go over is the butyrophenones. Haloperidol is probably the most common one that we know. It's an antipsychotic tranquilizer, has a slow onset, about 20 minutes, causes less respiratory depression or hypotension. And it's useful in agitated, delirious, and psychotic patients. It does cause QT prolongation, neuroleptic malignant syndrome, and extrapyramidal symptoms. So you do have to monitor a couple things with it. Some places do use brain function monitoring, like a BIS monitor. Others don't. The studies on this are still kind of up for grabs. But regardless what your monitoring technique is, if you're just using validated scales or an actual BIS monitor, the goal is to address pain and discomfort first, and then add hypnotic agents or other sedatives to this. This is an analgesia first sedation. So pain is an unpleasant sensory or emotional experience associated with actual or potential tissue damage. And it's described in terms of such damage. It's very subjective, thought to be unrecognized and untreated in ICU patients. It is common in ICU patients. A study looking at 154 surgical and 76 medical patients were assessed twice a day. The incidence of pain was about 50%. There was no difference between medical and surgical patients. 36% of surgical and 63% of medical patients received no preventative analgesia. Medical patients had higher pain scores. So being in pain is not good for several reasons, and kind of the reasons listed here. It does put you into a catabolic state, can cause ileus, the release of all sorts of hormones, including ADH, causes immune dysregulation, hypercoagulable state, and more myocardial work and demand. There are a variety of pain scales you can use. Some institutions use descriptive scales, where others prefer numerical ones. I always tell the residents it's good to figure out where, well, first of all, what scale your nursing staff is using and where they're putting the information. So when they're asking for more pain medicine or more sedation on rounds, you can say, but hey, I see that you're documenting pain scores that are low here. So we always like to try to minimize as much as possible. Analgesia is defined as the blunting or absence of pain or noxic stimuli. Can kind of think about adjuvants, regional or neuroaxial analgesia, and then think of just your straight-up opioids. So a good adjuvant strategy is to start early. Like I said, I work in a surgical ICU. A lot of patients are being treated under the ERAS protocols now of early enhanced recovery after surgery. So we're kind of doing lots of things to get them up and moving quicker than usual. But a lot of that has to do with adjuvants that we start in the operating room. So certainly, if you can numb something up with any sort of topical agent, that's a great idea. Giving more Tylenol or NSAIDs, starting some gabapentin or Lyrica, looking at different antidepressants that have been shown to have good analgesia profiles, such as Cymbalta. And then, like I said, injecting long-acting local anesthetics in a peripheral nerve block or neuroaxial anesthesia. Since opioids are the mainstay of pain management, it's important to remember a couple of things here. They are metabolized by the liver, excreted in the urine. Morphine has a great potential for histamine release, hypotension, and dysphoria. Fentanyl is very lipid soluble. It's 100 times more potent than morphine as a very rapid onset. Meparidine or Demerol is not a very good analgesic. I think it has the FDA black box. It's taken off a lot of formularies now. Does cause hallucination and metabolites that can build up, leading to seizures. Hydromorphone or Dilaudid is potent. It's euphoric, slower onset, and longer half-life. And methadone is a great analgesic, but it can take days to load and carries a risk of respiratory depression. Need to have a little experience using methadone. We're starting to use it more and more at rush in the operating room. But it does require some more monitoring. Adverse effects of all opioids are listed here. Respiratory depression, hypotension, decreased GI motility, maybe even all the way to ileus, pruritus. I would also add altered mental status, delirium. Here's a table of different opioids. Provides a handy comparison of these different agents, including mechanism of action and onset of times. And kind of gives you the equivalent doses of each. I kind of touched on this before, but depending on the patient, regional or neuroaxial approach might be a great option for a patient. So calling the regional anesthesia team in your institution, or the anesthesia team in general, do some sort of peripheral nerve blocks. Maybe put in a thoracic epidural if somebody is having a really hard time taking deep breaths and breathing. Putting in a spinal is not the most common thing to do in ICU. But you do have to think about some local anesthetic toxicity when you're doing these things. Some of these different nerve blocks and epidurals can cause venodilation and hypotension. And then you also have to think about their coagulation status, if there's any sort of problem with their coags to begin with, or if you're going to use anticoagulation afterwards. Never great to have a catheter in the back if they're going to be fully anticoagulated. So this slide shows the SCCM's clinical practice guidelines for the management of pain, agitation, and delirium in the ICU. These guidelines include prevention strategies, such as early mobilization, avoiding benzos. No recommendation for pharmacological prophylaxis. We still don't have a good medicine to say, hey, we're going to give you this medicine, and that's going to prevent delirium. Maybe in the future, hopefully. But we do have different treatments for delirium. So that's kind of where your haloperidol, your atypical antipsychotics come in. For the treatment of delirium and sedation, we are going to be using dexmedetomidine and propofol infusions. We don't use antipsychotics when they are at risk for torsades, if they have prolonged QT. And then they just point or touch on the other strategies that Dr. Cuppey kind of talked about earlier, too. Daily sedation and eruption, that targets a light level of sedation. Using analgesia first in promotion of normal circadian rhythms. So finally, the key points of this presentation we talked about at the beginning are shown here. So we need to measure anxiety, agitation, and pain using validated scales. We need to establish goals of therapy and monitor not only the process of care, but also the outcome compared with the goal.

ICU patient management

sedation scales

sedatives

non-pharmacological interventions

delirium reduction