Okay. Next, I have a case with questions integrating pharmacology and concepts from the toxicology lecture. The case, a 20-year-old man, no other past medical history, is brought in by EMS, status post single GSW to the chest. The FAST, or the focused assessment of its sonography in trauma exam, was negative, and he's stabilized prior to transport to the surgical trauma ICU. In the ICU, again, he's, as a temperature of 38 degrees Celsius, he's tachycardic, slightly hypertensive if the baseline is normal, but 130 over 60, respiratory rate of 26, and an O2 sat of 92% on room air. Serum creatinine is noted to be 2.5, and urine tox demonstrates a BAC, or a blood alcohol concentration of 0.2%, as well as an anion gap. Metabolic acidosis examination is noted for disorientation and confusion. He's agitated after the staff give him a couple of doses of intravenous lorazepam via the CEWA scale. The patient becomes more cooperative. However, then his O2 sats decrease to 85%, and the ICU team has decided to intubate the patient. So the question is, which of the following would be the initial analgesia sedation regimen to initiate dexmedetomidine infusion, lorazepam infusion, fentanyl IV push PRN and propofol, ketamine IV push as needed, and then fentanyl IV push as needed, plus midazolam infusion. How many takers for A? Okay, a couple. So the dexmedetomidine, it's interesting in terms of evolution, but it kind of originally came out with this sedative, completely different mechanism, similar to clonidine as an alpha-2 agonist, and then kind of evolved initially with just utilization and label less than to equal of 24 hours. And quickly the studies came out comparing it, whether it's against midazolam infusion or lorazepam infusion, and subsequently we noticed the duration of the therapy extend days, maybe in some patients weeks. There is one smaller study, I believe it's 20 or 23 patients, I believe out of the group in Denver, that looked at it specifically for alcohol withdrawal, and they didn't really find much of a difference. And the actual study which was then tried, it was replicated by other groups and found no difference in comparing it to lorazepam. But initially it was found to be different, but it was against lorazepam infusion versus boluses. It could be used as an adjunct for alcohol withdrawal, but that was the key word, an adjunct, right? So it won't replace the mechanism of GABA amino butyric acid or GABA. So it's, again, maybe helpful as an adjunct, could help reduce lorazepam or a benzodiazepine total quantity, but maybe that's probably about it. But here, the reason is because it's outlining it as a sole therapy or monotherapy. How many for lorazepam infusion? That's fine. So of course it would address the alcohol withdrawal piece, but maybe not necessarily, as Dr. Balk went over earlier, the light analgesia sedative approach now that the patient's on mechanical ventilation. But again, it can be potentially an option, again, maybe in the right setting, but not for this patient as sole therapy. And probably as a sole therapy, very little. There were a couple of papers retrospective many years ago that utilized lorazepam, IV push, PRN in comparison to the infusion. But again, nothing since then. Fentanyl IV push, PRN, and propofol? Okay, several more. Again, it would allow you to achieve, and the answer is C, allow you to achieve light sedation, analgo sedation, right? So pain and a sedative combination approach for now that the patient's on mechanical ventilation. And your propofol infusion, right, will address the GABAminobutyric acid, kind of the withdrawal concept, if that was to be a factor. And easily titratable, which is the other key factor. Ketamine IV push, PRN? Again, there's a similar to actually dexmedetomidine. There's some actually pretty good literature using it, again, as an adjunct. So that's the key. In addition to other therapies, maybe to help limit the amount of lorazepam infusion or IV push quantities that the patient's needing. And again, IV push ketamine would help achieve that, again, as an adjunct, but probably not as a sole therapy. Fentanyl IV push, PRN, and midazolam? Again, the key differentiating factor in the question is the acute kidney injury. And so, again, even though fentanyl IV push, as needed, would help achieve the RAS balance of minus one to plus one, the midazolam infusion is the problematic piece in that answer. Any questions on that one? So if there was no patient with acute kidney injury, which one would you pick, the propofol? Yeah, no, so that's a good question. So if there was not acute kidney injury, the answer actually still would be the fentanyl push and the propofol. But that has to do with, there was a number of studies, CEDCOM and Midex, and there's many that looked at infusion-based approach to PRN-based. The reason I put in infusion specifically is there are trials where they've looked at fentanyl IV push PRN with midazolam IV push PRN. That probably would be, you'd achieve the goal, but then you're going on the concept of, we're trying to reduce overall benzodiazepine exposure. But it would be acceptable in this patient because you actually have a reason to give a benzodiazepine because that's probably the cause of the agitation. But IV push PRN could be an option for this patient, but normally the kind of approach is to avoid continuous infusions as much as possible and then err on keeping them a little bit more interactive and awake, if you can. So now the, and I spoke a little bit about this, but the patient gets trialed on a few days of lorazepam infusion. So we switch gears a little bit. The other unique properties that lorazepam, to kind of keep in mind, and this was the other reason not to select it, is not to forget, and this goes into a little bit of the tox piece, but it's the propylene glycol content. So likely the patients, unless they're getting really high doses and frequent of IV push lorazepam, but once it's utilized as in a continuous infusion, generally it could be within 48 hours. Generally most of the literature now is if it's on continuously for at least 96 hours or four days at a higher dose, then that propylene glycol can be problematic as well. So a lot of the adjuncts have been helpful. Any other adjuncts folks can think of to treat the alcohol withdrawal? Either generally, maybe in the IV push realm. Phenobarbital. Yeah, the phenobarbital will be the other one. Anything problematic with phenobarbital? You'll have a little bit of, there's a content there, but not nearly as significant as the others, but it can be utilized in as an adjunct, especially if you have a known history of high amount of alcohol intake or history in general chronic use. There's a couple of papers utilizing either five to 10 milligram per kilogram doses, like a loading dose actually up front, and then a much significant smaller quantity twice a day for two or three days. The key with phenobarbital, and this is actually, I don't know if they'll have a question about this, but one of the key features is once you, it's a stacking phenomenon in the sedative effect. Once you start having lorazepam IV push, plus or minus ketamine, plus or minus dexmedetomidine, plus or minus phenobarbital, it's more the consciousness state. So if the patient's GCS score, they're again become more, less and less interactive. The airway tends to be a kind of an issue. So it is quite actually popular, I think in the, or ED, kind of in the urgent situation immediately, but it can be utilized as an adjunct. Again, I probably generally err on the side of lower doses of milligram per kilogram of phenobarbital versus, I think there's at least a couple of papers now using 10. It's quite a bit. If you're not as familiar with how much they're getting as an adjunct in addition to it, maybe not necessarily by itself. So, but it can be an option as well. Over the next couple of days, the serum creatinine improved, but only gets a little bit better. But now you have laboratory findings. You're getting reports of a triglyceride of 515 and a lactate of 15, and the patient is likely observing which of the following? Pancreatitis, alcohol withdrawal, rhabdo, propofol infusion syndrome, or abdominal compartment syndrome. Yeah, Chris, and it tends to be a common question for sure. The hypertriglyceridemia, lactic acidosis, and the other notable findings are, does anybody, there's two more. Yeah, you can have hemodynamic instability. So either bradycardia, arrhythmias is the other one. Again, one of the other things that's noted, and with propofol infusion syndrome, and we actually observed this, I believe a lot during COVID, is in the younger population, even on less than 48 hours of the infusion, just saw the triglycerides go from either, maybe they weren't checked at baseline, but normal, presumably to like in the five, six hundreds, or even sometimes thousands. If you did, and this is a question that does come up, and could be asked, when is, if you're checking it, maybe not daily, but every three days in a patient getting the infusion, what is your likely threshold, and when would you want to stop therapy, if it's just based on triglycerides? Yeah, so most of the literature, it's, initially, folks got, and rightfully so, a little bit excited and worried when it hit around 300, 400. More of the collective, I would say, analyses around that kind of phenomena, and if it would have the clinical impact, or closer to 500. But there's a couple of key things. If you have a patient you know right away, they're going to be on it for at least 96 hours, or longer. Getting a baseline is very helpful, because for many of the patients, we don't have that. So you, and more so, so you can observe the second phenomena, issue is the trend. So if looking at the trend helps a little bit, versus just getting an isolated number. But yes, greater than when you're encroaching, or getting closer to 500, or higher, probably a good idea to start thinking about other therapies, or alternatives. And that was the rationale, and I think, oh, I did have the propofol dose in there. You'll see it commonly, either as a rounded number, or 67. But in, I don't know if they'll last, but it is very commonly cited. The 67 mics per kilo per minute. But you'll also see another number. It's four milligram per kilogram per day, and that, this is just a translation of that number. So if you come across either the 67 as a threshold, or the four milligram, that's why. The 67 is in micrograms, but there's references and papers that have both, or could have either. So just something to note. But those are usually the two dosing threshold limits, if it's going to go beyond that kind of time period to look out for. If your baseline is, say, 300, do you still look at 500? Oh, baseline is 300. Baseline is already elevated than normal. Oh, it's elevated than normal. I would say yes, because I don't know exactly, unless it's a known chronic, but I don't know the exact etiology. Generally, error on the side of safety. We have alternative sedatives that you can employ, versus maybe, you know, a couple decades ago, where it really was propofol. So now you have many other options, or alternatives. So I would say yes, Sway-A-Way. It was a little bit, I would say, for sure, and I'm not sure what kind of questions in detail to get around COVID or COVID-19 management for patient's event, that is sedated. But it was much more common around that time, to even when they were getting around four, 400, 450, you just let it, I would just see patients, right, just because there wasn't, they were on maximum doses of everything else, which there are actually some pretty good review papers on, but no, it's a good question. I would say avoid. And some references, and I think that's it. Thank you.

gunshot wound

propofol infusion syndrome

tachycardia

sedative regimens

metabolic acidosis