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Deep Dive #1 – Drug fever vs. Occult sepsis
- If there is an infection causing sepsis, it usually isn’t that hard to find, so if you can’t find an infection, you really need to think about other things including drug fever
- Look for other signs of drug fever:
- Rash, eosinophilia, LFT elevation, AKI, but not all drug fevers will have these signs
- <20% of patients with a drug fever will have eosinophilia
- Rash, eosinophilia, LFT elevation, AKI, but not all drug fevers will have these signs
- Which drugs are most likely to cause drug fever?
- Any antibiotic can, but beta lactams are most likely
- Consider older anti-epileptics as well
- If you really can’t decide between drug fever and sepsis then you can switch to another antibiotic class and decide on an empiric course based on the most likely infectious etiology
Deep Dive #2 – Neurotoxicity from antibiotics
- Cefepime neurotoxicity
- Which other antibiotics can cause neurotoxicity?
- All of the beta lactams
- Who is more at risk of antibiotic neurotoxicity?
Deep Dive #3 – What to do when someone has a surprising outcome?
- Think about code status in terms of plan of action rather than expected outcome
- Comfort measures only does not mean this patient will definitely die, it means we will focus on comfort
- While there is a high likelihood that they will die, we are still leaving room for all possible outcomes
- Comfort measures only does not mean this patient will definitely die, it means we will focus on comfort
- Give likelihoods
- Always being uncertain isn’t helpful for you or the family/patient
- You can still guide the patient/family with what you think is most likely to happen while leaving room for uncertainty
- “When we extubate your loved one, they most likely will not be able to support their breathing and will die; however, there is a possibility that they will be able to breathe on their own”
- Talk to your colleagues!
- Real time perspective from your colleagues can help you make more informed decisions/advice for families
- Reflecting with colleagues can help you learn for the next time
Ali: Welcome to Grey Matters, the podcast where we unpack how medical management is rarely black or white.
Jason: I’m Jason Freed and I’m a hematologist at Beth Israel Deaconess Medical Center.
Ali: I’m Ali Trainor and I’m a pulmonary and critical care fellow at the Harvard combined program at MGH and Beth Israel Deaconess. Jason, I had this case during my residency that I still think about because we made what seemed like an appropriate decision but it had a really unexpected outcome.
Jason: Oooo what happened?
Ali: It started like any other Monday morning in the ICU, long rounds, dehydration…
Jason: Oof, that’s why I didn’t go into critical care…
Ali: Hey! Everything has its pros and cons but yeah so I met her when she was in the ICU, but she was one of those patients we see all the time who is chronically ill and comes in to the hospital for one thing, but then ends up having multiple others issues while she’s in the hospital.
Jason: I know what you mean
Ali: Yeah, so this patient was a woman in her 50s who had cirrhosis from ongoing alcohol use and initially came in actually because of 20 pounds of unintentional weight loss. On the general medicine service, while they were working her up for her weight loss, she was found to have a portal hypertension with ascites, a pleural effusion and an AKI. She was getting treatment and workup for all of these when she developed a massive variceal bleed. They tried to do an EGD and banding, but were unsuccessful and she was intubated for airway protection and went to IR for an emergent TIPS.
Jason: Wow she sounds very sick but can we get back to the beginning? — one thing that strikes me here is that she came in with weight loss … usually people with portal hypertension and ascites come in with weight gain. Makes me wonder if there was something more going on.
Ali: Yeah definitely, her weight loss was really confusing when we typically think of patients with cirrhosis coming in with volume overload so it wasn’t really clear, but by the time I met her in the ICU, she did get a successful TIPS – her bleeding had resolved but now the puzzling part was that she had persistent fevers despite being started antibiotics on the floors.
Jason: Fevers while on antibiotics is my least favorite problem…
Ali: Right?? So she’s hypotensive on a low dose of vasopressors, has a mild leukocytosis and has these fevers. They hadn’t been able to find an infectious source yet, but at this point she had been on broad spectrum antibiotics for 3 days without any improvement in her clinical status or fevers. I’m curious about your thoughts on this because I know you’re constantly dealing with fevers in your neutropenic patients on the bone marrow transplant service.
Jason: For us, we’re constantly asking the question are they febrile because of their disease, i.e. B symptoms from lymphoma, or febrile from infection, or febrile because of a weird drug reaction, and sometimes it’s easy to tell but most often it’s hard
Deep Dive #1 – Drug fever vs. Sepsis
Ali: Right, I struggle with this too, I mean, I think we all do. I don’t want to go down the whole fever of unknown origin rabbit hole, because at this point our two main concerns were occult infection vs drug fever. She’s been on antibiotics at this point for about 3-4 days and she hasn’t improved with this treatment, but her fevers, hypotension and leukocytosis really seems like sepsis, so how do we tease out sepsis vs drug fever?
Dr. Stead: It’s so complicated. And, and sh, and she’s a perfect example of even added layers of complexity, right? Because she’s a cirrhotic patient. Um, and therefore we know her to be deeply immunocompromised. And so we’re already worried about some more serious infections and you know, opportunistic infections that can arise in her. You know, it sounds like people are trying to put together a picture of fevers, low blood pressure, and a white count and thinking, okay, all those things go together as sepsis. Um, and it’s hard to look away from that, but it’s super important to think about the other things that could be going on.
Ali: That was an Dr. Wendy Stead from the infectious disease division at BIDMC and it was tough at this point, she did not have evidence of SBP on paracentesis, her CXR still showed that pleural effusion, but it had already been sampled and had no evidence of infection, she didn’t have any obvious source but was on broad spectrum antibiotics and still having fevers.
Jason: This sounds like everyday on the leukemia service.
Ali: Yeah so at this point we felt a little stuck and again we’re wondering maybe this is drug fever or maybe there is still an infection that we just haven’t found.
Dr. Stead: I mean, we have great tests in the hospital to look for infection. Um, and usually by the time they’re in the ICU and they’re this sick, a lot of that very complete workup has taken place. You know, the blood cultures, the urine cultures, the chest imaging, it’s all been done, the body imaging, the, the CT torso, you know, a lot has been done to look for a source of infection. And so, you know, it’s really usually if there is a source of infection there that is serving as a sepsis source, it’s not that hard to find. And so typically we’re going to find it if the search has been done thoroughly and there hasn’t been an answer found, that is absolutely a situation where you should start opening your mind to think about these non infectious kind of mimics that can happen one of which is a drug fever.
Jason: That point speaks to me a lot: if there’s an infection that could produce sepsis it would be very likely to be found by the methods we have.
Ali: I agree, it makes so much sense when she says it, but in the moment, it’s so hard to pull myself away from thinking that it must be sepsis. And I often get worried about stopping abx, because even if I haven’t found an infectious source, there’s still this nagging in the back of my mind that what if I did miss something and stopping abx could be harmful. So I asked Dr. Stead and her big take away is to think about your patient’s trajectory and does it fit with what we’d expect from a typical infectious time course.
Dr. Stead: In the situation where you’ve started treating somebody, and maybe they got little bit better from the infection that they had, um, that you were treating, and then suddenly they start to take a turn for the worse, and maybe the fever comes back, or the white count that was going down. It starts to go up a little bit again. Um, but overall, they kind of look stable and you’re doing an additional search, and you’re not finding anything. That’s kind of a situation where I start to think about it. Maybe it’s the patient with the fever and the white count, but actually they kind of look clinically a little bit better than I would expect them to look if they had an infection that was getting worse over time. That’s another setting where I might think about it.
Ali: That time course didn’t really fit my patient because if anything she was doing a little bit worse, she’s now in the ICU on pressors, so when I’m looking at her med list which medications should I be focusing on as culprits for drug fever?
Dr. Stead: So there are a lot of different drug classes that can cause drug fever among the antimicrobials, the most likely drugs to cause drug fever are by far the beta lactam drugs. And it’s the whole class it’s penicillin, cephalosporins carbapenems any of them can cause drug fever. And it’s way more likely than a lot of the other classes. Some of the tetracyclines can cause drug fever as well, like minocycline. Um, but generally those are the ones, much more likely to do it than others. And so knowing that also increases the suspicion, if somebody happens to be on it, I never forget the anti epileptic drugs because that’s another class of drugs it’s very commonly associated with drug fever. Phenytoin, some of the older anti epileptics.
Ali: Okay sounds like all beta-lactams should be on our radar for drug fevers and didn’t know about the older antiepileptics. Dr. Stead some concrete signs to look out for that aren’t present in every patient with drug fever, but if they are there can be helpful.
Dr. Stead: Generally you’ll have a lot of other information at the tip of your fingers that might help guide you toward drug fever or drug reaction as opposed to infection. And so those would be things like looking for, um, a rash, because sometimes these are hypersensitivity reactions. And so probably in about a third or more of cases, you might find some kind of a rash there that’s gonna help you, or maybe you’ll find an eosinophilia. You know, maybe the team has seen that leukocytosis in the CBC, but they haven’t thought to send a diff for the last week. And you say, Hey, maybe you should add a diff to the next white count. And suddenly you realize, oh, there’s 18% eosinophils there. Um, and that’s what the white count of 20 was all about. And that sends you down a completely different road. Um, maybe the LFTs are climbing or they’ve got a little bit of a new AKI, which, you know, you’ve been explaining away from their hypotension, uh, but maybe they’re having some end organ manifestations of a more serious drug type reaction.
Jason: Ok, so did any of the things Dr. Stead mentioned come into play.. like did she have other signs that this could be a drug fever as opposed to sepsis?
Ali: She was on meropenem which is a beta-lactam, not on any antiepileptics. In terms of other things that are associated with drug fevers, she had a mild transaminitis, her bilirubin was mildly up, but she has cirrhosis, no eosinophilia, and she didn’t have a rash. So I’m still torn between drug fever and sepsis.
Jason: Yeah doesn’t sound like a slam dunk for drug fever
Ali: Yeah, so we still kept her meropenem thinking that’s the safest route. But I wanted to share with you something really powerful Dr. Stead had to say about when you’re considering drug fever.
Dr. Stead: If I’m starting to consider the diagnosis and no other source, a cult sepsis has been found, then it’s, it’s wrong not to think about stopping antibiotics in that setting because you’re starting to really think that you are truly causing the patient dangerous toxicity with the drugs that you’re giving. And I think, you know, we see antibiotics rescue people so that we tend to even among those of us who have seen tons of antibiotic reactions and toxicities, I think we still think of them as such a powerful weapon to jump in and save patient’s lives that we sometimes forget how dangerous they can be too. And so I think you really do have to keep your mind open to how incredibly dangerous and toxic these medications can be as well. And if you haven’t found a reason for which you’re giving them, then you should be thinking about peeling them back.
Jason: Wow, I mean with that framing, I’m worried we’re potentially doing more harm than good with keeping the antibiotics in, but she’s also a patient with cirrhosis in the ICU on vasopressors, so even though it seems like we should have found an infectious source by now, I’m still worried that we are treating something and stopping antibiotics could be harmful. So in that I honestly don’t know, but I might think of at least switching to a new antibiotic class so that I address the toxicity but am still treating infection.
Dr. Stead: I guess one of the possible outs that people can have in this situation too, Allie would be that if you are truly worried that you’re missing some, occult source of sepsis, and you feel like you cannot stop some kind of empiric antimicrobial coverage, then at the very least, you should be thinking about switching and pivoting to other antimicrobials that would not potentially share the same mechanisms of hypersensitivity. So if they’re on the beta lactam and the Vanco, you know, switch to something else that is not of those classes that might offer similar coverage for the things that you think you’re treating infection-wise. Um, but also removing that potential driver of the toxic reaction.
Ali: So just like you said, if you really can’t decide drug fever vs sepsis, then switching to another antibiotic class can be a good option
Jason: So is that what you ended up doing for her?
Ali: Well not exactly. Dr. Stead said another option to avoid these endless antibiotic courses is to come up with an empiric END course based on your most likely source. We had trouble with the most likely source part, but decided on 1 week of empiric antibiotics.
Jason: Ok, so I feel like we have a good handle on the concept of drug fever vs sepsis, but can you remind me again what else is going on with her. She sounded like she was pretty sick and I want to make sure I have the full picture
Ali: Yeah good point, there’s a lot going on. So her fever we’ve kind of beat to death here, but so she was declining at home for what sounds like several weeks and she’s now 3 weeks into her hospitalization and 1 week into her ICU stay with decompensated cirrhosis, on vasopressors, persistent fevers, just had a bad variceal bleed, and she was still intubated because of her altered mental status.
Jason: Wait, how were you even assessing her mental status? I thought you said she was intubated.
Deep Dive #2 – Neurotoxicity from antibiotics
Ali: Yeah great question, because we usually do have our intubated patients on sedation, but she was so obtunded and not interactive that she wasn’t actually requiring any sedation.
Jason: Oh, so what were you guys thinking for the altered mental status?
Ali: We did the standard workup of AMS – scanned her head, EEG, Rx of hepatic encephalopathy – the whole 9 yards – and then we raised the possibility that this is antibiotics associated neurotoxicity. I feel like this always gets raised on rounds but then I don’t know I feel I don’t know what to do about it or how assess if its antibiotic associated neurotoxicity, and thats why I want to talk about antibiotic associated neurotoxicity for our second deep dive.
Jason: Ali, I know you said she was on meropenem, but I feel like the first antibiotic causing neurotoxicity that comes to mind for me is always cefepime.
Dr. Stead: I think what’s important to remember when you start to go down the cefepime rabbit hole is that, um, that all beta Lactams can cause mental status changes in encephalopathy that is not unique to cefepime at all. Um, we know that penicillins do it. We know that Cephalosporins do it, probably the fourth generation Cephalosporins like cefepime more than the others, but we know they do it and we know that the carbapenems do it. Imipenem definitely more than the others, but in any of them can do it.
Jason: Ok, so we know she’s on meropenem which is a beta-lactam and could be a culprit for neurotoxicity.
Ali: True, but I don’t have a clear idea for when to suspect beta-lactam neurotoxicity.
Dr. Stead: And basically the spectrum of kind of CNS toxicity that you can get from cefepime is anything from just kind of global mental status change. And encephalopathy often myoclonus is described for reasons that I don’t think are very clear and then non convulsive status epilepticus
Ali: I didn’t realize just how broad the spectrum actually is
Jason: HAH! Broad the spectrum ! And on top of that, when we are thinking of it – think about all the times I’ve considered cefepime neurotoxicity – it’s never clear cut because if a patient is started on cefepime, there is A LOT going on with them- a lot going in and going out – so it’s never as clear cut as “oh we started cefepime 2 days ago, they got altered, we stopped it and they got better”… case closed.
Dr. Stead: But what’s been very characteristic of all of the reports of cefepime neurotoxicity so far is that there is a very particular group of patients in whom it seems to arise. And those are older patients, patients who have underlying renal problems where they’re not metabolizing the cefepime as they should and often have not been dosed reduced relative to their degree of kidney insufficiency, um, and patients with prior underlying CNS disease to begin with. So, you know, that poor substrate that probably makes them at more risk for a complication like this.
Jason: So it seems like in the exact situations where its really hard to tell, fluctuating renal function, older patients with a lot of other things going on – the ones where it’s the hardest to tell, those are the ones that are the most at risk for antibiotic-associated neurotoxicity
Ali: Yeah so to recap, we know that antibiotics neurotoxicity can happen with any of the beta-lactams and presentation can be super board – we should do an EEG to look for status epilepticus and we can also look for risk factors like older age, renal insufficiency and underlying CNS disease.
Jason: So Ali what happened next? Did you stop the meropenem?? Was it causing her fevers? Was it causing the neurotoxicity?
Ali: Well, we actually didn’t really have to decide because her family decided they wanted to make her comfort measures only.
Jason: Oh gosh she’s gonna pass away.
Ali: Yeah she had been so sick for so many days and her family really recognized that.
Jason: I don’t know how to say this, this is not important in the grand scheme of things, but the medical detective in me just still really wants to know if this was drug fever or neurotoxicity. We just spent 15 minutes learning all these interesting things and I’m just still so curious what happened to her.
Ali: So… there’s a little more to the story. What ended up happening was the family requests that we wait a few days to extubate her and take her off pressors until family members from out of state are able to arrive to come see her and say goodbye.
Jason: Yeah, I don’t know if it’s right or wrong but we keep people on life-sustaining support for family to say goodbye all the time, so what happened over those couple of days?
Ali: Well, it just so happened that her 1 week abx course ends the day we have this conversation with her family, but then we’re waiting a few days for people to come from out of state. And while we’re waiting, her fevers resolve, she comes off the vasopressors, and she actually wakes up.
Jason: She woke up?
Ali: Yeah, I mean it was amazing, but also gave me a kind of sickening feeling.
Jason: What do you mean.
Ali: I can’t help but wonder if we weren’t waiting for her family, we would have just stopped her pressors and terminally extubated her earlier while she was still dependent on these, and she prolly would have died.
Jason: Totally, that’s really heavy – she woke up but what was her MELD score? 40? Okay she survived the ICU but she sounds so sick, but I’m assuming if she made it out of the hospital she had another variceal bleed and dies within a few months.
Ali: You would think, but actually no! I took care of her several years ago now and she’s still alive! I actually still chart check her a few times a year to keep myself humble and last time I checked a few weeks ago she was alive and well, living independently actually back at work. Which is why this case haunts me, I mean what if there are other patients that I am making comfort measures, who maybe would have lived if we hadn’t done that. I don’t know but have you ever had something like this happen with one of your patients before?
Jason: Wow, not that I’m aware of, but now that I’m thinking of it thats the problem, right? Maybe I did make someone CMO who might have lived, but I won’t know because they passed away when we made them CMO.
Ali: Thats why I still think about this case. Im glad she’s alive but it makes me wonder about all the patients I’ve taken care of and made CMO.
Jason: Yeah it makes me wonder which of my patients if they only had family who had to travel across the country and we had to wait an extra day or two lived because they got an extra chance to unexpectedly recover.
Ali: Totally, it’s extremely unsettling.
Jason: I mean, in pretty much every other medical decision we make we know there’s going to be a “miss rate” and for each we kind of accept what that miss rate is (like you can’t look for aortic dissection in everyone with chest pain) but like how do you decide on an acceptable miss rate for making someone comfort measures when they might have had the small chance of living a quality life if you didn’t?
Ali: these are hard questions., we definitely need some expert help here so for our final deep dive I reached out to Dr. Emmy Rubin at MGH who is a pulmonary and critical care attending who also does ethics consults and research in ethics so I asked her to help us think through this idea of an acceptable “miss” rate for making someone comfort measures only.
Deep Dive #3 – Unexpected outcome after transition in care
Dr. Rubin: So I think to me, the, the representation of what you’re talking about with sort of a number needed to treat or a number needed to harm or a miss rate, um, comes into play often when we decide not to do things in the first place. So when we decide not to intubate somebody, right, and when they’re, when they’re failing not to send them to the ICU, not to put them on ECMO, not to do X, you know, put them on dialysis, whatever it might be. There are times when we will have been wrong and somebody could have survived with very intensive therapy. I think the problem is if the, and I think about this very, very often, cause this comes into play, you know, in many things that I do. I think if we, if absolute certainty is the threshold, we will do way too much for way too many people.
Jason: So I hear that but then how can you deprive people of the chance. Like how do we make those decisions. You know me, I love calculating probabilities to help me make medical decisions, but it seems like that’s really challenging to do in this scenario. I’m gonna try anyways, so if there’s only a 1 in 100 chance that aggressive care is going to benefit a certain type of patient. It means that 99 people got overaggressive care they wouldn’t have wanted. But were they really harmed? They were going to die either way. I feel like in order to not treat all 100 of those patients aggressively to save the 1, you have to believe you’ve subjected those 99 to a fate worse than death.
Ali: Yeah, it’s tough because I want to save people but I don’t want to cause suffering either. I really struggle with that balance.
Dr: Rubin: So you think about the aggregate harms of, of sort of either approach, right? The approach we tend to take is that if there’s any chance at all, and somebody wants to go to an ICU, for example, or be put on a breathing machine, we do it as a result. I think we do a lot. We do a lot of very aggressive things that don’t help. A lot of that comes from this sense that I share and that is very common and, and understandable that we don’t want to leave life on the table. Right? We don’t want to not save somebody who could have been saved and what we don’t think. Cause that feels like the worst thing. There are also other bad things, which are, you know, treating a lot of people very aggressively who wouldn’t have wanted to be treated that way if they weren’t going to get better. And there is no way to get that exactly right.
Jason: I guess that’s comforting because then you just do the best that you can to prognosticate based upon data and based upon experience, but at the same time it is still kinda troubling that I’ll never perfectly decide who should be CMO or DNR/DNI.
Dr. Rubin: I think people get bogged down in designations that are in a medical record, like comfort measures or DNR/DNI. So when I think about these things, I think about that in them in terms of what is the plan of action for this patient, as opposed to necessarily sort of what’s the code status, right?
Ali: This is helpful because when we made her comfort measures, in my mind that meant she was going to die.
Jason: Yeah, I mean that’s what CMO means to me.
Dr. Rubin: Judging by what happened, which was, she got better to everyone’s sort of surprise and delight, I assume in our family and for her, she got better against all that. So making her a quote unquote CMO didn’t actually affect her ability to get better. It affected the way you thought in your mind that you had decided she would likely die.
Ali: I really appreciate her being so blunt with me about my incorrect framing around what CMO means.
Jason: Ali, How has this case affected your practice? Are you less likely to make someone CMO?
Ali: Not necessarily, a big takeaway for me is to not equate CMO with death, but rather it’s a plan where certain outcomes are more likely, but we really need to be open to anything happening. But I’m still struggling with this idea of CMO potentially being wrong in this case.
Dr. Rubin: I guess the first thing I would say is to try to avoid thinking about it as right or wrong, based on what turns out to have happened. When you make a decision like designating her code status as CMO, and then she turns out to live for, for multiple more years, the decision that you made at the time feels like it was the wrong decision. That is a well known sort of cognitive bias where whatever happens afterwards, um, affects how you think about that decision at the time.
Ali: To be honest, I think I used my interview with Dr. Rubin a little like a therapy session to try and learn and move forward from this case because I needed a lot of reassurance to get past this idea that making her CMO was wrong.
Dr. Rubin: You didn’t snow her with medications. You didn’t prevent her from getting better. I think the thing that you feel like is wrong is that it was presented as if it was pretty black and white when maybe it wasn’t.
Ali: I think that really hit the nail on the head, which is that I want things to be black and white because I want to do the right thing for my patients, but as we’ve talked about, this being grey matters and all, things in medicine are rarely black and white. It just feels a heck of a lot harder when we’re talking about life or death scenarios.
Dr. Rubin: But it’s very hard. I mean, there’s a lot of pressure in medicine to always sort of feel like you’re getting everything right. And it’s a human endeavor. You’re not going to get everything right every time. Which again, just to come back to this is why I really encourage people to get groups of colleagues together in difficult situations and just check your own assumptions, um, because people bring their own assumptions and their own recency bias in cases that they just saw in both directions to all of these situations. And so I think you need to give yourself a break, realize that we’re human beings trying to do this and just try to continuously improve how you’re doing these things.
Jason: So Ali, you describe its been like therapy with Dr. Rubin. Does this case still haunt you?
Ali: Well I chart check her every 3 months like a crazy person, so I guess in some senses yes, but I think how I’ve thought about this has really changed. I think when I was resident I was checking her chart probably in a pathologic way just feeling so guilty.
Jason: Ali, that sounds awful, what makes you keep going back.
Ali: Well now when I look back i look back with a sense of humility. I look to be amazed and grateful that she is still doing okay.
Jason: You know I’m reading this book right now, “The Power of Regret” by Dan Pink and it’s really taught me think that verbalizing regrets out loud with someone is one of the best ways to diminish some of the emotion involved and helps you intellectualize the experience to decide what positives you can take away from the experience.
Ali: Definitely, it feels a lot better chatting with you than doing chart checks on her alone
Jason: So Ali, I know I seem to be fixated on this, but when you think back, do you think it was the antibiotics that were causing her fevers and encephalopathy and she got better because her antibiotics were stopped?
Ali: You just can’t let this one go… I guess we will never fully know but i do think that could have been a part of it.
Jason: Yeah we will never know unless we rechallenge her with meropenem and thankfully she hasnt needed it. Yeah maybe we should we recap what we learned with our deep dives?
Ali: Let’s do it. I’m gonna let you start with the deep dive on drug fever vs sepsis since this comes up all the time with your bone marrow transplant patients.
Jason: haha ok, Dr. Stead pointed out that an infection causing sepsis to the point of fevers, shock, etc, it really shouldn’t be that hard to find. So if you can’t find the infection you’re really obligated to start thinking about other causes of fevers, like drug fever because these drugs can be pretty toxic – as this case made very clear. And finally, if you really can’t decide if this is sepsis or a drug fever from antibiotics, then you can switch to a new antibiotic class
Ali: We also talked about neurotoxicity from antibiotics and how cefepime is the one that most of us think of first, but you can really get neurotoxicity with any of the beta lactams. Neurotoxicity can range from myoclonus, to reduced consciousness or confusion, up to non-convulsive status epilepticus. Some risk factors for developing neurotoxicity include patients who are older, have renal impairment, or who have cognitive dysfunction at baseline.
Jason: and what were your take aways from talking with Dr. Rubin?
Ali: Yeah, I think a big one for me was to think of the goals of care as more of a plan of action rather than the expected outcome. So I’m going to try to stop thinking of making someone comfort measures only as a transition to death and think of it really like the name says, focusing on their comfort, and then allowing for whatever outcome happens
Jason: And finally, like we’re doing here, talk to your colleagues. Debrief, especially when you feel regret about a decision you made. And yes give yourself feedback and follow up on how patients are doing but don’t punish yourself by checking EMR.
Ali: Thanks so much for talking through this case with me
Jason: any time, but no more drug fevers please.
Ali: And that is a wrap for today! But we also love going through other cases so if you have a case that you want to bring to Grey Matters please let us know. If you found this episode helpful, please share with your team and colleagues and give it a rating on Apple podcasts or whatever podcast app you use! It really does help people find us!
Jason: If you have a case you’d like to bring on air, please email us at email@example.com. Thank you to Daksh Bhatia for the audio editing. Opinions expressed are our own and do not represent the opinions of any affiliated institutions.
- MACKOWIAK, P. A., & LeMAISTRE, C. F. (1987). Drug fever: a critical appraisal of conventional concepts: an analysis of 51 episodes in two Dallas hospitals and 97 episodes reported in the English literature. Annals of Internal Medicine, 106(5), 728-733.
- Appa, A. A., Jain, R., Rakita, R. M., Hakimian, S., & Pottinger, P. S. (2017). Characterizing cefepime neurotoxicity: a systematic review. In Open forum infectious diseases (Vol. 4, No. 4, p. ofx170). US: Oxford University Press.
- Mackowiak, P. A. (1987). Southwestern internal medicine conference: drug fever: mechanisms, maxims and misconceptions. The American journal of the medical sciences, 294(4), 275-286.
- Payne, L. E., Gagnon, D. J., Riker, R. R., Seder, D. B., Glisic, E. K., Morris, J. G., & Fraser, G. L. (2017). Cefepime-induced neurotoxicity: a systematic review. Critical care, 21(1), 1-8.
Tags: antibiotics, comfort measures, DNR/DNI, drug fever, neurotoxicity, sepsis