Hello everyone, we are going to talk about sedation and analgesia. I'm Dr. Sarah Kacoma and I work at Rush University Medical Center in Chicago, Illinois. I'm an anesthesiologist and an intensivist there. I have no disclosures. In this presentation, the objectives to keep in mind are as follows. We are going to learn how to measure anxiety, agitation, and pain using validated scales, establish goals of therapy, monitor not only the process of care, considering the route, drug, and dose, but also the outcome compared with the goal. For example, on rounds, you would want to be able to tell the patient's score, indicate which scoring system you used, and state what was being achieved compared with the goals that were set. The triad of agitation consists of pain, delirium, and anxiety. Each of these factors can cause internal discomfort leading to agitation. It is, however, important to acknowledge that a patient can experience these symptoms without demonstrating agitation as an external distress. Agitation is common. For most critically ill patients, a safe and effective strategy addressing pain, agitation, and delirium while maintaining a light level of sedation is associated with better clinical outcomes. Approximately 70% of ICU patients experience agitation. Agitation is associated with negative outcomes like longer ICU stays, more days on the ventilator, ventilator desynchrony, increased oxygen demand, and inadvertent removal of devices and catheters. Several validated scales are available to measure agitation. The Ramsey, Riker, and Richmond scales are among the most widely used. The Ramsey sedation scale was the first one developed to quantify the level of consciousness. The scale uses a score of 1 to 6 with 2 indicating a patient who is cooperative, oriented, and tranquil. The Riker scale uses 7 items ranging from 1 being dangerously agitated to 7 being unarousable. With 4 representing a patient who is calm and cooperative. The Richmond agitation sedation scale is the most widely used. This is a 10-point scale with 0 being the pivot point where the patient is calm and alert. As you move towards more positive values, agitation increases with a positive 4 score being the highest level of agitation. This is the other half of the scale recalling that 0 is our pivot point representing the calm patient. We see that moving in the negative direction moves from drowsy to unarousable. Question number 1, which of the following must be a major focus of sedation and analgesia plan for ICU patients? Number 1, attaining a subjective pain score of 0. Number 2, monitoring only the route of drug administration. Number 3, formal iterative evaluation using validated scales. Number 4, monitoring only the drug and dose. Number 5, titration to avoid delirium. The answer is 3. Using validated scores is one of the key goals from the first slide. You do want to monitor the drug and dose, but you want to do more than that. You want to compare the patient's actual score to the goal that you've set for that patient. When considering an optimal level, the ideal is a patient who is calm, comfortable, and easily arousable. On the scales we just looked at, this level corresponds to a 2 on the Ramsey scale, a 4 on the Rikers scale, and a 0 on the Richmond scale. When using the Richmond agitation sedation scale, which of the following is the most common goal? Number 1, attain a score of negative 3 to negative 4. Number 2, a score of 0 to minus 2. Number 3, a score of plus 1 to minus 1. Number 4, a score of plus 2 to minus 2. Number 5, avoid nurse titration of medications. Remembering that on the RAS scale, we want to be as near to 0 as possible. The answer is 3, attain a score of plus 1 to minus 1. Once you've chosen your scoring system and selected the goal based on that system, the next step is deciding what sedation strategy to use. You want to aim for sedation protocols with daily sedation interruptions or maintenance of light sedation. Today, the approach is less is more, which is very different from what it used to be. Bedside protocols are very useful for titrating sedation and analgesia, and daily checklists that serve as reminders are also very useful. Sedation protocols have been associated with significant clinical benefits, including decreased duration of mechanical ventilation. This is a trial of 128 patients who were divided into two groups. The interventional group had daily interruption of all sedatives until the patient was awake, while the control group had interruption of sedatives at the discretion of the clinician. The researchers found that for all the variables that were monitored, duration of mechanical ventilation, ICU length of stay, hospital length of stay, and percentage of days awake, the intervention group did much better. Taking the previous study one step further, this trial looked at what happens when you combine daily interruptions of sedation with spontaneous breathing trials. The investigators found that this combined intervention was associated with fewer ventilator days, fewer ICU days, fewer hospital days, and improved survival at one year. If it's appropriate to wake the patient, is it okay to initiate early physical and occupational therapy? In this study, the therapy intervention group did better in all the variables measured, including ICU delirium days, hospital delirium days, ventilator-free days, and the duration of mechanical ventilation. Although continuous IV sedation is widely used in ICU patients, this trial of 242 patients demonstrated that continuous IV sedation increased mechanical ventilation days and increased both ICU and hospital length of stay. Question number three, intubation and mechanical ventilation. Number one, cause such anxiety that patients require sedation and sometimes neuromuscular blockade. Number two, cause such pain that patients require aggressive analgesic regimens. Number three, require significant doses of sedatives and analgesics. Number four, obligate the care team to ensure that they can awaken most patients daily. Number five, always lead to complications. The answer is number four, intubation and mechanical ventilation obligate the care team to ensure that they can awaken most patients daily. It's been demonstrated that many patients who don't have a source of pain in the ICU can be managed without any anxiety or pain medicines, so they do not need sedatives to tolerate mechanical ventilation. Moving on to sedatives. A sedative is a substance that depresses the central nervous system, resulting in calmness, relaxation, reduction of anxiety, and sleepiness in most patients. Sedatives may also cause slowed breathing, slurred speech, staggering gait, poor judgment, slowed reflexes, so we must think carefully about using them and monitoring patients who receive them. Sedatives are anxiolytic and amnestic, both of which can be beneficial, although some believe that the amnestic effect contributes to delirium. The sedatives that we're going to discuss do not have any analgesic properties except for dexmedetomidine and ketamine, both of which offer some analgesia and the possibility of sparing opioid use. Opioids do not have anxiolytic or amnestic properties, but we should always consider pain as a driver of agitation, and if we believe that a patient has pain, it should always be treated first prior to providing sedatives. Remember that before selecting a drug, we should first think about non-pharmacological interventions. These include psychological support, such as frequent orientation, day and night cycles, and reassurance. Physical intervention, such as touch, physical or occupational therapy, and ambulation or mobility when possible, and compassionate nursing. With a variety of sedatives available, how do you select the appropriate one to use? These are some of the factors that you need to consider. What is the patient's level of pain? Will the patient have procedures later in the day? Does the patient need to be transported, and do you want them to be sedated during transport? What is the expected duration, that is, how long do you think the patient will need to remain sedated? What is the patient's organ function like, and how is it affecting their metabolism? Do the agents induce drug withdrawal? Finally, you need to consider your formulary. Now we can begin to look more closely at some of the specific agents. Benzodiazepines are sedative, hypnotic, amnestic, anxiolytic, and anticonvulsant. So they offer a variety of effects, which may or may not be beneficial for your patient. They do not provide any analgesia. Many benzodiazepines are lipid soluble. They are metabolized in the liver and excreted in the urine. They have synergistic respiratory depression with opiates. So if you combine these agents, you'll have to monitor closely and be mindful of pulse oximetry, deciding whether N-tidal CO2 may be beneficial. Benzodiazepines can have active metabolites, for instance. Midazolam has a metabolite that is about 50% active. If the metabolite accumulates, midazolam can act as a long-acting drug rather than a short-acting drug. Patients can develop tolerance to benzodiazepines, and benzodiazepines are often associated with higher rates of delirium. Therefore, you should minimize the use of these agents when possible. The three most common benzodiazepines in the ICU are diazepam, lorazepam, and midazolam. This slide shows a comparison amongst the three agents. Midazolam has a fast onset and the shortest duration. Since you want to avoid benzodiazepines if you can, you need to consider some other agents, and propofol is one that you might want to think about. Propofol is a sedative, an anesthetic, an amnestic, and an anticonvulsant. Again, it has no analgesic effect, and it does cause respiratory and cardiovascular depression. This agent has a very rapid onset of under a minute, as well as a short duration with a half-life of only four to eight minutes. Its clearance changes very little in liver and kidney disease. In addition to respiratory depression that we mentioned, other side effects include hypotension, increased triglyceride levels, which need to be monitored if you select this agent, and infusion syndrome, which includes all or several of the following complications listed here. Metabolic acidosis, hyperkalemia, cardiomyopathy with acute cardiac failure, myopathy, and hepatomegaly. Dexmedetomidine is being used more and more widely in ICUs. This agent is an alpha-2 agonist that is highly protein-bound. Side effects include bradycardia and lower blood pressure by decreasing both vascular resistance and cardiac output. Dexmedetomidine is approved only for sedation of 24 hours or less, although it's frequently used longer. Patients tend to appear asleep, but they can be easily aroused. This effect is diminished with higher doses. In a study comparing dexmedetomidine and lorazepam, dexmedetomidine was associated with more days alive without delirium and coma, a lower prevalence of coma, and a greater success at meeting sedation goals. Ketamine can also be used in the ICU. Keep in mind that ketamine is a PCP derivative, and it's highly lipid soluble, which means it crosses the blood-brain barrier faster. It's a non-competitive antagonist at the NMDA receptor, and it can be a bronchial smooth muscle relaxant, which means it could be of benefit in patients with asthma. Ketamine has been associated with nightmares, although that typically does not occur at doses used for pain management in ICU. Ketamine is generally not used for continuous infusions unless it's combined with other agents. Automadate is not used anymore for ongoing sedation. It's associated with adrenal suppression, even as a single dose. And importantly, it's also associated with myoclonus. That could be an important consideration in specific patients. For instance, in a patient with a hormone-secreting tumor, myoclonus could result in increased secretion of that hormonal agent. Finally, in this quick review, we have the butyrophenones. Haloperidol is perhaps the most widely recognized. These are antipsychotic tranquilizers, typically with a slow onset of about 20 minutes. There tend to be less respiratory depression or hypotension with these agents. They can be useful in agitated, delirious, or psychotic patients. However, they can prolong the QT segment, which can be very concerning in some patients, especially those who are on multiple medications that can cause QT prolongation, where the risk of torsades can be dramatically increased. Although useful in some situation, brain function monitoring is not recommended for routine use. However, you might want to consider it in patients receiving neuromuscular blockade and deeper sedation. The BIS Monitor is one example of a brain function monitoring tool. This monitoring device uses a modified EEG to produce a numerical indication of a patient's level of consciousness. As an important reminder of what was mentioned earlier in this presentation, the goal is to address pain and discomfort first, and then add a hypnotic agent or other sedative or anesthetic agent. You might hear this approach called by a couple different names, such as the ones listed here. Since pain management is paramount, let's look more closely at pain. Pain is defined as an unpleasant sensory or emotional experience associated with actual or potential tissue damage, or described in terms of such damage. Pain can be extremely subjective, and the literature shows that pain is very much unrecognized and undertreated in ICU patients. Pain is very common in ICU patients. This is a study that looked at 154 surgical and 76 medical ICU patients who were assessed twice daily. Pain was assessed using a numerical rating scale or behavioral rating scale. Agitation was measured using the Richmond scale or the RAS. The researchers found that the incidence of pain was about 51%, and there was no difference between surgical or medical patients in terms of pain prevalence. Despite that, 36% of surgical and 63% of medical patients received no preventative analgesics. Also in this study, the medical patients had higher pain scores and relatively slightly less pain medicine. Aside from its association with agitation, pain can augment the stress response and lead to prolonged catabolism, ileus, ADH release, immune dysregulation, hypercoagulable state, and increased myocardial workload. Question number four. Important components of pain assessment include, number one, relying on changes in vital signs. Number two, increasing dosing strategies only when a patient appears to be in pain. Number three, having a clear understanding of how much each type of procedure should hurt. Number four, minimizing analgesics in patients who are asleep. Or number five, using a validated scale, establishing a goal, and measuring against that goal. The answer here is number five, using a validated scale, establishing a goal, and measuring against that goal. It's important to break old myths. Pain assessment is not relying on changes in vital signs. Vital signs should not be used as markers of pain, which again is subjective. Noting that a patient does not look in pain, knowing how much a procedure or disease should hurt, assuming sleeping patients do not have pain, or assuming patients will tell you they have pain, all of these are myths. There are a variety of pain scales you can use. Some institutions use a descriptive scale, whereas others prefer a numerical scoring system. There's also a visual scale that's used in some places. Most commonly, behavioral pain scales are used. That includes paying attention to the patient's facial expressions, monitoring upper lip movements, and considering mechanical ventilation-related issues. You've selected your standardized scale and you've determined that the patient is having pain that is outside of your goal, it's time to start thinking about analgesics, which are designed to blunt or eliminate pain or noxious stimuli. To make your selection, you're going to think about whether the patient needs any adjuvants, whether regional or neuroaxial analgesia is available or appropriate, for instance, epidural analgesia or peripheral nerve blocks, and finally, whether to use opioids, and if so, which one. Adjuvants are especially important today because of widespread use of multimodality pain management, where you may be using opioids in addition to other agents, such as nonsteroidals, ketamine, or other anti-pain medications. For an adjuvant strategy, you want to initiate that strategy early, avoid as-needed dosing, and use regular dosing when possible. As-needed dosing is a common mistake with an agent like Tylenol, which works better when used around the clock. Be aware of all of your options, such as topicals, acetaminophen, NSAIDs, Celecoxib, steroids, anticonvulsants, antidepressants, and long-acting local anesthetics. Since opioids are the mainstay of pain management, it's very important to remember that they are metabolized by the liver and excreted in the urine. Comparing different opioids, morphine has the potential for histamine release, hypotension, and dysphoria. Fentanyl is perhaps the most widely used opioid. It's lipid-soluble, with 100 times the potency of morphine, and it has a more rapid onset. Meparidine is not a good analgesic, and it's not commonly used. It has the potential for abuse, and it's associated with hallucinations, and its metabolites can build up and lead to seizures. Hydromorphone is potent, and it's associated with euphoria, and it has a slower onset and longer half-life. Methadone is a good analgesic, but it can take days to load, and thus carries a risk of respiratory depression. You need to have a lot of experience in titrating this agent before using it. Like all drugs, opioids have side effects, including respiratory depression, hypotension from sympatholysis or histamine release, decreased gastrointestinal motility, and pruritus. This chart provides a handy comparison of these agents for your review, including mechanism of action, onset times, elimination times, metabolic pathways, whether the agent has an active metabolite, and the agent's equal analgesic dose. Depending upon the patient, a regional or neuroaxial approach may be very useful as a primary strategy or an adjunctive strategy. Options include spinal, epidural, regional blocks, and nerve catheters, which are becoming more common. Some concerns include the potential for vasodilation and hypotension, principally with spinal or epidural options. You must have knowledge of local anesthetic toxicity with regard to the space where the anesthetic is being administered, and catheter removal with anticoagulation is an important consideration in terms of timing. 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 and avoiding benzodiazepine. There is no recommendation for pharmacological prophylaxis. They also cover treatment with dexmedetomidine or propofol infusions. They recommend dexmedetomidine, especially in patients with delirium who are mechanically ventilated and agitation is precluding weaning or extubation. If you're going to use antipsychotics, the guidelines stress that you must be aware of the risk for torsades and do not use these agents when that risk is present. They also talk about consideration of other strategies, like daily sedation interruption or light target level of sedation, analgesia-first sedation, and the promotion of normal sleep patterns. Finally, the key points of this presentation that we talked about at the very beginning are shown here as reminders. We need to measure anxiety, agitation, and pain using validated scales. We need to establish goals of therapy that are individualized for the patient and potentially individualized for the day. And we need to monitor not only the process of care, but also the outcome compared with the goal. Thank you very much. Any questions?

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