Good morning. Today I'll be discussing a case of post-intubation tracheal laceration. My name is Ani Danielian. I'm a third-year pulmonary and critical care medicine fellow at Aventura Hospital. I have no financial disclosures. The objectives for today is to describe the diagnosis and classification of tracheal injuries as well as establishing the role of surveillance bronchoscopy in patients with tracheal injury. Tracheobronchial injury is a rare complication of endotracheal intubation with a reported incidence of 0.005%, although this is thought to be underreported. Most of these lacerations are longitudinal in nature and located in the middle to distal trachea. Some of the risk factors documented in the cardiothoracic literature include female gender and age of greater than 65 as being non-modifiable risk factors. It's also documented that emergent procedures account for an incidence upwards of 15%. I present the case of an 88-year-old female. She presented out of hospital cardiac arrest. She was endotracheally intubated in the field and resuscitated with a mechanical compression device with successful return of spontaneous circulation. Upon arrival to our ER, she had developed a tension pneumothorax, which was confirmed by radiograph, and had a chest tube placed on the right side. After the chest tube was placed, she was hemodynamically stable. She underwent a CT angio of the chest, abdomen, and pelvis, which showed extensive subcutaneous emphysema, bilateral rib fractures, a pneumomediastinum, and a right pneumothorax residually after the chest tube was placed, as well as a focal defect of the distal posterior trachea. Another chest tube was placed in the ER. This is imaging, figure one and figure two, which are CT angios. Figure one is an axial view demonstrating the posterior tracheal defect. And figure two is also demonstrating the degree and extent of abnormalities that I discussed in the prior slide. And here you can appreciate that the patient is intubated. Her hospital course, specifically on day six, is when she initially underwent surveillance bronchoscopy, which showed a 2-centimeter level 2 to level 3A tracheal laceration, which was 1 centimeter above the carina. There was no evidence of fistula formation at that time. She also underwent an EGD that did not show evidence of esophageal perforation or fistula formation. Here's a timeline of her hospital course, appreciating day one was her arrival day. Day six was her initial bronchoscopy and EGD, and then day nine and 14, which I'll show you on the next slide. Throughout her hospital course, she underwent a total of five surveillance bronchoscopies. This was her bronchoscopy on the left of day six, and then subsequently on day 14. And we can appreciate here the degree of tracheal injury just above the carina as described, two centimeters in length and just right above the carina. So as I said before, she underwent a total of five surveillance bronchoscopies. The last one was done on day 28, which showed a decrease in size to 0.5 centimeters. Throughout her hospital course, she failed multiple spontaneous breathing trials. And after multidisciplinary discussion, it was decided that since the size of her laceration had decreased, that percutaneous tracheostomy was safe at that time. Shortly after she underwent tracheostomy, she was discharged from LTAC. So the diagnosis of tracheal injury requires CT chest imaging, because you have to assess for pneumo-mediastinum, rib fractures, and other injuries that can cause tracheal injury. And it helps with classification of this type of injury, as well as bronchoscopy, which is the gold standard. Bronchoscopy helps us identify the location, the size, extent of injury, and if the patient is amenable to any endoscopic treatments. There is to date lack of formalized guidelines in the cardiothoracic literature or in anesthesia literature in regards to the management of tracheal injuries. But majority do say that this is a multidisciplinary approach that needs to be taken into account with a patient's comorbidities and extent of injury. Classification of tracheal injury was described by Cardio. This is well described in the literature. Level 1A tracheal injury is submucosal. Level 2A on the top right is full thickness injury with subcutaneous emphysema. Level 3A is full thickness injury with herniation of the soft tissue, but without esophageal injury. And level 3B on the bottom right includes esophageal injury with full thickness injury. Historically, all tracheal injuries were managed surgically. However, this did carry a high morbidity and mortality. Historically, we've leaned towards more conservative management, especially in cases of level 1 and even up to level 3A injury, as is the case for my patient. Conservative management includes observation, intubation, tracheostomy, and fiber and sealant application. Observation was the approach for my patient specifically. This allows time for the laceration to heal. It includes antitussives and rest. Intubation, when patients require mechanical ventilation or in respiratory failure, tracheostomy, as this can reduce the airway pressures, and fiber and sealant application, which allows for the laceration to be sealed and healed in that way. There's still a lack of evidence to support the role for surveillance bronchoscopy to assess tracheal laceration, as in the case for my patient. In conclusion, I believe surveillance bronchoscopy should be considered as a safe tool in assessing these patients, especially in those who are managed conservatively. I'm open for any questions. Yes. I wanted to ask about the functional status and the nutritional status of the patient, because you inquired for a long hospitalization, but also there was a healing that was ongoing. Right. You wouldn't expect to see someone who was more frail. Yes, she was definitely frail. I think in the beginning, you can appreciate how kyphotic she was as well. Very frail, elderly woman, very weak, but she was undergoing physical therapy. She was getting nutrition. Eventually, had to get a PEG-2 placed during the hospital course as well. And so, that was basically. Just a quick reminder. We do have a mic for questions, so if we can use it, it'll benefit everybody. Any other questions? Sorry, Surgeon General, can you please use the microphone? If the tracheal injury wouldn't have been decreased and inside at that point, would you, would the patient be a candidate for surgery? At that point, just due to her comorbidities, her frailty and age, multidisciplinary discussion was against doing any type of surgical intervention. Perhaps some sort of endoscopic intervention, but that would have required her to be transferred to another facility. Thank you. Mm-hmm. We have time for one more. Any details about the intubation that led you to be more concerned about a tracheal injury? So I know that she was intubated in the field by EMS. I wasn't able to get any much more information other than that because she arrived at our facility already intubated. But I suspect it was a traumatic one in the setting of CPR. All right. So my name's Henry Mayo-Molaski. When I submitted this, I was a fellow, but I'm currently an attending. So please excuse me if there's any gaps. Anyway, so we're going to talk about a serious complication of norepinephrine infusion via peripheral IV intravenous access and a successful treatment. So I imagine many people in this room practice critical care medicine and maybe have dealt with this complication. And so we'll talk about how we addressed it at the bedside. Again, I'm working now at Northwell Health Montefiore Medical Center and also with the United States Navy. So there's my relevant disclaimers and nothing to disclose. So the lesson objectives here discuss the safety of infusion of norepinephrine through peripheral IV access. Where I did my fellowship training, Long Island Jewish Hospital, we published on this. And we'll go over that paper. And then we'll define what peripheral IV access extra extravasation of norepinephrine is like and what the clinical presentation is. And then we'll outline the management of how to treat it. So this is a typical patient that we would often see in our Long Island Jewish Hospital emergency department in Queens, New York, a mid-60s male with just a, you know, some pretty straightforward comorbidities, including class III obesity, COPD, chronic hypoxemic respiratory failure, HEF-PEF, atrial fibrillation, hypertension, hyperlipidemia, alcohol use disorder. There was a few more, but I was just running out of space. And this patient represented to our emergency department hypotensive, pallorous, tachycardic, and with a history of hematokizia. So he's having quite a substantial upper GI bleed, which was later determined. And he was being resuscitated in the emergency department with IV fluid, blood, and a GI consult had been placed. And the emergency department team placed a peripheral IV, 18 gauge, 2 centimeters, in the right basilic vein under ultrasound guidance. And this is, you know, a standard practice in our emergency department to start IV pressers that if they can see, have a good active vein to target on ultrasound, rather than going for a central line, they will attempt to do a peripheral guided IV. And I'll just not mention here, this patient was orthostatic and was also on bi-level. So we were involved in the case because, you know, obviously the patient was put on pressers to the consult at the MICU. It's a busy MICU. We received the consult. I was the consult fellow at the time. The resident would typically go down to see the patient, and then, you know, come and present to me, and then I would go down and see the patient. So essentially, there was about a 20-minute period after the initiation of the norepinephrine infusion and the point of contact with the ICU, where we received a phone call that there were some changes occurring to the patient's right upper extremity. And, you know, it became pretty apparent early on that the peripheral IV had exited the target vein, and there had been not a small amount of extravasation of norepinephrine. And it was reported to me over the phone that, you know, the peripheral IV, rather, the right upper extremity was mottled and cooled. So we had been consulted. We hadn't accepted care of the patient, but, of course, we went to help immediately because we have a protocol on how to deal with norepinephrine extravasation in the ICU, and this is, like, these images were used with permission, and this is the right upper extremity of the patient. And it may be hard to appreciate here, but this is definitely not what his left upper extremity looked like, and this is a gentleman who, later on in the hospitalization, I was joking with him that he needed to invest in, like, some sunblock because he was a very bright red individual, but here you can see his right upper extremity is pallorous. It's swollen, and this was not good, and he was experiencing some pain in the emergency department. So a physical exam in the emergency department, performed by me. There were no radial or ulnar pulses, and the nurses came to the bedside with one of those Doppler's machines. Pow, pow, pow. There was no signal on the right upper extremity. There was definitely swelling and tenseness right in the distal, bacillic vein region, and then there was complete lack of capillary refill on the right upper extremity physical exam. So what's the diagnosis? I mean, probably 15 to 20 minutes of norepinephrine extravasation in the right upper extremity with, at that time, probably impending loss of limb situation. And what are the treatment options? So in our ICU, we typically do a mixture of two things. We do the fentolamine, five milligrams mixture. It's in 10 mLs of normal saline, and then this is injected in, like, a circular motion around the site of injury, and then we also do topical nitroglycerin mixed with 10 mLs of normal saline. It's, like, topically applied. You kind of, like, rub it on there. I don't know, probably some of you have done it. And I did that immediately. I brought all those things down with me and did it in the emergency department, and, you know, those interventions can take, you know, a few minutes to a little bit longer to work. So we immediately transported the patient to the intensive care unit, and upon arrival, there was no improvement. In fact, his arm was worse now, much more swollen. He was having pain. And so now the question is, what are the options from here? Pretty standard was call the vascular consult. So we did, and they had called in the emergency department, and the vascular team arrived, saw the hypotension, saw the AFib with RVR in the 150s, saw the patient on BiPAP. No acute surgical intervention. Raised the arm and some warm compresses, okay? And we needed to do something else. This man was going to lose his arm. So at this point, on the BiPAP, he was still coherent, and he knew something was wrong with his arm, one, because it probably hurt a lot, and two, because there was a lot of people in there examining his arm. And so what we did is that there is a literature here that we'll discuss that in cardiac catheterization through the radial artery. There's a phenomena where there's a vasospasm effect once the initial needle insertion occurs, and it can cause a massive vasoconstriction, vasospasm of the radial artery. And that can be very, very problematic because it quickly leads to, you know, not only decreased flow and perfusion, but thrombosis. And in the, you know, Circulation Cardiovascular Interventions, it's like a very prominent journal, there's a treatment protocol that's discussed that involves intra-arterial injection of verapamil and nitroglycerin. This is not part of our ICU protocol, but we made the determination at the bedside that we had to do something because this gentleman was going to lose his arm. So under sterile technique, we inserted a 10-centimeter, 20-gauge arterial catheter under ultrasound guidance, right into the right brachial artery, right in the, just, it would be proximal to the insertion site of the peripheral IV. And then we injected 2.5 milligrams of verapamil and 0.2 of nitroglycerin. And that's the dosage that was used in, or was mentioned, rather, in the Cardiovascular Interventions article. And you can see on the left side, that is what his hand looked like before the procedure. And then you can see on the right side, that's our right, not the patient's right, or it is the patient's right, rather. Anyway, you can see this is the improvement that we saw in literally minutes. Change in color, return of pulses, return of Doppler signal. And it was pretty miraculous. Moving on from there, you can see just an additional photo. This really brings out the contrast of what we saw on, initially, which was a dead and dying limb. And I think maybe several of, maybe some of the more senior intensivists, no offense, have maybe seen where extravasation of norepinephrine can lead, with an ischemic limb, attempts at amputation, often overwhelming sepsis can develop. And here we avoided that. And so the, like I said, within minutes of injecting these two medications, we had return of pulses. We had return of Doppler signals. And then a formal upper extremity ultrasound was performed of the right upper extremity. And you can see that his arm was literally clotting off, right in front of our eyes, with thrombosis in the brachial, radial, and ulnar veins, superficial thrombosis. And so after the, you know, just to move on to the discussion, you know, we, this is the article I mentioned before that actually came from the Long Island Jewish Medical Center Working Group. It showed the safety of peripheral IV administration of vasoastive medications. It's Jose Cardenas-Garcia and Paul Mayo et al, with 734 patients. We showed that there was a, only a 2% complication rate for extravasation of vasopressors. And with local fentanylamine injection and application of topical nitroglycerin paste, all of those extravasation events were managed medically without any loss of limb or, and I think this is a good demonstration that you can use peripheral IV access for pressors, and it's safe. However, you should have a treatment protocol if something goes awry. And so just for a conclusion, norepinephrine extravasation is uncommon, but it can result in potentially catastrophic limb ischemia. And if your local antidote is not sufficient, then a consensual to the option of direct intra-arterial injection of vasodilators, Barapimil and nitroglycerin to the supply artery. Thank you. Just real quick, can you tell me where you put the A-line to put the infused, just to re-clarify that? We went to the brachial artery, which was just proximal to the location of their initial peripheral IV, because we wanted to be proximal to the injury site, because we knew that the injuries to the vessels and was going to be distal to that. So we wanted there to be complete optimal circulation of the vasodilators from the proximal entry point down into the extremity. And this gentleman survived this admission. He survived his GI bleed. He had no short-term or long-term complications from this event, which we were very pleased about. Why would the point of collapse of the artery be further down? Why wouldn't it be closer to where the presser actually extravasated? And is it possible that your arterial line, a 10-centimeter arterial line, was stenting open that artery? You know, it's definitely possible. I think that the way that we thought about it is that there was a, that there was, like the basilic vein was accessed, and there was probably a period of time when you had still continuous infusion of norepinephrine into the basilic vein. And then as the peripheral IV probably started to slip out, there was damage to the endothelium in the surrounding area, and then local leak of the extravasation of the vasopressor. And this probably caused the catecholating cascade that went down through the, so at some point through this whatever the mechanism is, this ended up not only being a venous event, but also a vascular event. So we wanted to be as proximal as possible to get the vasodilators down going through the arterial tree and then back up through the venous tree. What I meant was is why did you believe that the point of occlusion of the artery wasn't at the exact same place as where the pressor extravasated? So you're asking like why we thought that the injury was here? No. Why didn't you think it was here? Because if it was here and you put the art line in, then did the medications do anything or did that art line do it? Oh, so I mean, just to demonstrate, the peripheral IV was placed here towards the antecubital fossa, and we were proximal to that in the brachial artery, as high as we could go. Got it. Yeah. All right. Thank you very much. Thank you. All right, we're going to hear about LAST. Good morning, everyone. So today I'm going to be talking about a rare case of cardiac arrest due to local anesthetic systemic toxicity, which is LAST syndrome. My name is Sally Tyle. I'm currently PGY-3 chief resident at Vassar Brothers Medical Center in Newmans Health at Upstate New York in Poughkeepsie. I have no financial disclosures for this presentation. So the objectives today is to recognize the clinical presentation of LAST syndrome, understand the pathophysiology behind it, and the cornerstones of therapy for LAST syndrome. Currently local anesthetics are used widely in many settings, either inpatient or outpatient medical settings, and they prove to have impressive efficacy and safety. However, local anesthetic systemic toxicity, which is LAST syndrome, is a very rare life-threatening complication that can happen from those medications with a percentage of like 0.03% as far as the literature review says. Of the local anesthetics, bupivacaine was shown to have the highest incidence of cardiac toxicity because it has long-acting properties. It has vasodilator effects, so tend to be prolonged in the circulation and tend to cause more toxicity than other medications used. For the case presentation, our patient was a 20-years-old male. He had no significant past medical history. He sustained the left distal radius fracture while doing some sports and was planned to go in an outpatient setting for a regional nerve block to repair his fracture with. The anesthetics that were used at that setting were bupivacaine and mipivacaine. Soon within a few minutes after he received a regional nerve block, he developed acute encephalopathy. He was confused, then started having seizures. After that, he developed respiratory arrest and went into a V-fib cardiac arrest, a ventricular fibrillation cardiac arrest. Of course, ACLS was initiated right away. The patient was emergency intubated at that scene to protect his airway. He received one shock at that point, and he had return of the spontaneous circulation within three minutes of the ACLS initiation. He was then maintained intubated on sedation with metazolam and fentanyl. When they started intralipid infusion immediately, and that's the cornerstone of therapy for this last syndrome, then he was transferred to our hospital to the emergency department. This is when ICU was contacted to come and see the patient in the emergency room. So when we saw him in the ED, his vitals were kind of hemodynamically stable except for soft blood pressure of 99 over 55, most likely in the setting of his sedation. He was intubated on the sedation, mentioned the metazolam and fentanyl. He was in full ventilation support. He was minimally responsive to verbal stimuli. He was not completely sedated. He was able to respond to us. And the lab work done at that point when he first came in was within normal limits. There was no interesting findings in his CBC, CMP. His troponin was negative. Repeated troponins were negative. The first one was 12. The second one was 10. EKG was done. It showed normal sinus rhythm. There was no, like, any forms of arrhythmia or prolongation of the QTC or anything abnormal in his EKG findings. While in the ED, he had a CT head that showed no acute intracranial findings. And then he was transferred at that point to the ICU. They did an echo. Echo showed normal ventricular function, size. There was no, like, abnormal valvular disease, no pulmonary hypertension, no any abnormalities in his echo. He was gradually removed of sedation within a few hours. He was successfully extubated shortly after he arrived to the ED. And then after that, he was admitted to the ICU for close monitoring. Remained hemodynamically stable within the ICU stay for 24 hours. After that, he was transferred to medical floors. His remainder of the hospital course was an eventful, and the patient was successfully discharged with no complications after his cardiac arrest incidents. So to take points and to understand from Last Syndrome, how does this happen? So local anesthetics tend to block the sodium channels. This will result in disruption of the inhibitory pathway of the neuron depolarization. So when we lose the inhibitory pathway, you tend to have more excitatory features. And this mostly happens in the CNS. So they will tend to have the excitatory clinical features in the CNS, which is in the form of seizures mostly. And then the cardiac to assist in the form of conduction disruption, arrhythmias, and then eventually cardiac arrest can happen. How does Last Syndrome present? So 40% of the cases can have atypical presentations. However, the typical presentation will start with CNS toxicity, which is 68% to 77% as far as the literature says. So CNS toxicity is the most common feature, and it's typically the first clinical manifestation. Patients can have agitation, they can have psychosis, they can have hallucinations, they can have confusion, and then eventually will have seizures. Then comes the cardiac manifestations, which is the second most common manifestation of Last Syndrome. It tends to happen of arrhythmias because of the disruption of the sodium channels, potassium channels. Those patients will tend to have arrhythmias. And cardiac arrest will develop after the neurological symptoms. The most common type of cardiac arrest that usually happens is asystole. However, our patient had ventricular fibrillation cardiac arrest. One-fifth of the last episodes can just present with isolated cardiovascular disturbances. So from the risk factors for developing Last Syndrome, we have extremes of age. This is most likely related to the availability of binding proteins and the circulation where the drug will bind to, the muscle mass, the clearance, the hepatic and renal clearance in elderly patients. The low muscle mass tends to affect this too, like the amount of binding protein is still a storage of the medication in the system. Pregnancy because those patients tend to have high cardiac output, so they tend to distribute the medication into the system quicker and more than the usual. Renal hepatic dysfunction because of the clearance. Cardiac disease patients who tend to have already conduction abnormalities, and those medications will affect the potassium channels, the sodium channels, they will tend to have arrhythmias. The medication effect itself depends on the dosage of the medication. As I said, like Bupivacaine has more vasodilator properties, so it tends to go widely to the system and has long-acting properties. So the type of medication we're giving also is a risk factor. The site of injection is one of the other risk factors as the proximity to it to the vascular axis can still be a risk factor for developing the toxicity. How do we manage LAS syndrome? The first initial step is to directly discontinue the drug, and this is mostly if it's like a continuous infusion with patients having catheter infusions for local anesthesia, epidurals, and all of that. So we'll discontinue the drug immediately. Then we have ACLS for cardiac arrest. Intubation is really important because hypoxia and hypercapnia will tend to make the drug distribute quicker into the system, so protecting the airway and providing adequate oxygenation is important. Seizure suppressions, benzodiazepines is the medication for the seizures. And then comes the LRT, which is the lipid rescue therapy, or the lipid emulsion therapy as they call it. So how does this act? So lipid emulsion therapy, it's an intralipid infusion. The way it acts is that it creates like a lipid phase, or like a film in the circulation known as the lipid sink. This will help draw the medication, because it's lipid soluble, out of the vital organs as the CNS and the cardiac tissue, allowing the medication to be distributed to other organs like the liver for the medication to be detoxified, or the muscles for the medication to be stored there. So you're taking medication away from the heart and the CNS. It was also shown to improve cardiac output, the lipid emulsion therapy, and this will help reduce mortality, in addition, of course, to the ACLS and resuscitation measures, because when you improve the cardiac output, you're going to get more clearance of the medication at that point. Early administration, 20% of the intralipid infusion should be the immediate priority in such situations after ACLS right away. So we'll start with ACLS, airway protection, and directly starting the intralipid infusion. This is how it acts. It acts as a film within the blood vessels, as, you know, coding the medication, taking it away from the heart and the brain, and basically distributing it to the other organs as the liver and the muscle. Adverse effects of lipid rescue therapy, there are some adverse effects. Patients sometimes tend to have allergic reaction, hyperlipidemia, some cases reported acute pancreatitis after the infusion, acute respiratory distress syndrome, and then the most common that is usually to be seen is interference with lab values, like transient elevation of the liver function test. This was not seen in our patients, but this tends to be the most common to happen a lot of times, and will mislead us if we do the lab work at that point, so we'll just give it a chance and repeat the blood work and see how things will improve afterwards. So the conclusion from this case is that we have to be aware that we use local anesthetics widely in different settings, but we have to keep in mind that this is a rare complication but still can happen. To follow protocol and have ACLS as your first thing to do, and then availability of the lipid rescue therapy to be in every outpatient setting, well, they tend to give local anesthetics, like with the nerve blocks, with tap blocks, everything that we use as local anesthetic, they tend to happen. So we just need to be aware and have it available all the time, and that immediate starting of the treatment will help prevent any outcomes, as we've seen in outpatients, within two to three hours from the event, he was completely extubated, off sedation, he was doing fine, no post findings in the EKG or his echo, so it does help. Not sure if we didn't give the medication, how would the outcome for this patient would have been, so that's what we need to learn at that setting. Any questions? Great presentation. I actually have a last poster presentation this afternoon, so I'm curious about some of the things, just to compare notes. Did you guys send a level of the local anesthetic, a blood level, number two would be that prior to starting the lipid emulsion therapy, what were your differentials, how did you zero in on lidocaine being the cause of his seizures or his arrest? Yeah, so this happened in an outpatient setting, so we don't know as much about the level of the medication that was given or how much he received from the local anesthetic, and we didn't check how much of the local anesthetic was in his system at that point because he was already started on the lipid infusion therapy before even coming to our emergency department. As far as how do we think this was the most common diagnosis, because this patient was young, he was a 20 years old male, he had no significant past medical history, no known heart disease or arrhythmias or conduction abnormalities, and this happened right after he received the local anesthetic, and the way they present it is having confusion, then he developed the cardiac arrest, so it's the typical presentation of how that syndrome will present, so this was basically the most likely diagnosis, and the fact that he was started directly on the intralipid infusion and he managed to be extubated and recover afterwards makes it more clear that this is most likely the cause of the event that happened to the patient. You're welcome. Thank you. Thank you. Moving on to our next speaker, Yana Zemkova. Oh, he's not, he's not here. Good morning, everyone. My presentation is titled Mimics of Sepsis, a rare complication of ceftriaxone presenting with cholestatic liver injury and drug-induced hemolytic anemia. My name is Yana Zemkova, and I'm a second year fellow at the University of Iowa. I have no conflicts of interest or financial disclosures in relation to this presentation. So our objectives today will be to discuss a case presenting with complications of a very common antibiotic, to identify lesser-encountered adverse effects of ceftriaxone and describe their mechanisms, and to highlight the importance of recognizing these adverse effects. So the case presentation is how we'll start. We have a 65-year-old male who is admitted with presumed septic shock to the medical ICU. He's currently two weeks into a six-week course of ceftriaxone that was started for a group B streptococcal prosthetic joint infection. On presentation to the ICU, he's noted to be febrile to 38.7, tachycardic to 135, and hypotensive to 84 over 66, despite five liters of fluids in the emergency department. On physical exam, he's noted to have scleral icterus, diffused jaundice. His left knee, which is the one that had the prosthetic joint infection previously, was noted to be warm, erythematous, and edematous, without any evidence of drainage from the incision or anything like that. The PIC site where he was getting his antibiotics was without erythema or drainage. And then from a neurologic perspective, the patient was very somnolent, however arousable. I'll proceed to review the data. So two weeks prior when the patient was discharged, his labs, as you can see, were fairly unremarkable normal kidney function, normal hemoglobin, and normal liver function tests. On presentation to the ICU, I'll point your attention to several salient features, including a new AKI with a creatinine of 6.5 and a BUN of 115, hemoglobin of 6.8, there was no evidence of bleeding at that time anywhere, and a direct hyperbilirubinemia to 9.7, total bili of 10.8, and then an alkaline phosphatase of 255. Additional workup that was done to elucidate the etiology of the presentation. So for hematologic workup, the reticulocyte count was 2.8% with an index of 0.5, indicating a hypoproliferative state, LDH was elevated at 460, the haptoglobin was undetectably low, and a direct antiglobulin test was positive for C3. Hematologic workup, the right upper quadrant ultrasound revealed cholelithiasis, but no evidence of duct dilation. We did obtain a HIDA, which showed slow clearance, but no other evidence of cholecystitis, and then a hepatic autoimmune workup was negative as well. From a musculoskeletal perspective, the joint was tapped, and ultimately the culture was negative, and blood cultures were also obtained without any positivity to them. So based on the presentation, our working diagnosis was suspected medication-induced cholestatic liver injury and hemolytic anemia. Here I have a pictorial representation of the trend. I'll point your attention to hospital day negative 12, which is when the patient was started on ceftriaxone. As you can see, there's a steady increase in the bilirubin and creatinine. Patient on admission was actually transitioned to cefepime due to suspected failure of ceftriaxone with evidence of ongoing increased levels. When the patient was transitioned to an alternate class of antibiotics, there was a plateau of these levels and then subsequent resolution. And then additional workup revealed positive results for ceftriaxone and cefepime-dependent antibodies in the presence of the drug on blood samples. So at this point, I'll discuss the mechanisms of toxicity. So ceftriaxone in and of itself is actually a soluble drug. However, when it binds to calcium, the calcium cation, it becomes poorly soluble. And understanding the pattern of excretion of the drug will help us understand where it precipitates and the resulting effects. So ceftriaxone is about 60% renally excreted, and the rest is excreted unchanged in the enterohepatic circulation, which helps us explain where deposition will occur when these precipitants happen, which will result in nephrolithiasis and biliary sludge, otherwise known as pseudolithiasis. Some of the risk factors for these complications include prolonged duration of the antibiotic for greater than five days, high doses, greater than four grams per day, delayed gallbladder emptying, things that promote stasis, TPN. Some of these precipitants are more often seen in pediatric populations, and that's where most of the data comes in. But in adults, the incidence of the gallbladder findings are about 8.6% in some of the studies that I had seen, with a lower incidence of nephrolithiasis. Subsequently, I'll talk about the anemia, since that was one of the more salient features in this patient's presentation. And so this patient had a drug-induced hemolytic anemia, and it was immune-mediated, of which there's two types. There are drug-independent, and there are drug-dependent reactions. And so the drug-independent, excuse me, the drug-dependent, there's the penicillin type, which is a covalent bonding, immune complex, which is a looser binding, but tends to be more severe because it activates the complement cascade, and then passive absorption, which induces a change in the RBC membrane and results in extravascular hemolysis. In our case, this was an immune complex process. So very briefly, just talking about the mechanism, you have ceftriaxone binding to the antibody and the C3b component. This complex binds to the C3b receptor on the red blood cell, activates the complement cascade, and results in intravascular hemolysis. Drug-induced hemolytic anemia, in and of itself, is actually a very rare occurrence. There are about three to four cases per million per year, but a good majority of these cases are actually triggered by anti-infectives and antimicrobials, as you can see in the 2017 British guidelines. So you can see that ceftriaxone, as well as other cephalosporins, are very commonly implicated, although it is a rare occurrence in and of itself. It's important to note the mortality rate is about 30%, and it can cause significant sequelae such as ARDS, DIC shock, and liver and renal failure in the absence of sepsis. And because of these sequelae, that's why it's crucial to recognize, because it can be confused for septic shock or a failure of treatment and other infections. Interestingly, it is also notable that patients, about a third of patients who presented with a severe hemolytic episode actually had a weaker self-limited preceding episode of hemolysis in the past and with other exposures. So why do we care? In the context of precipitance, it can prevent, recognition of this adverse effect can prevent avoidable interventions such as cholecystectomy in the context of cholelithiasis. Additionally, it is a fully reversible condition when the precipitation does occur, and stones tend to dissolve within weeks to months. And then drug-induced hemolytic anemia is fairly rare, but it is associated with a high mortality, and it's important to recognize because it can be confused for sepsis and septic shock. So in key points, ceftriaxone, a very commonly used antibiotic in many of our toolboxes, but it's not without harm. It's important to maintain a very high index of suspicion, and adverse effects can be reversible with drug cessation, but mimic other presentations. Those are my references, and that is all I have. Are there any questions? Okay. Could you use the mic? I was wondering about the low blood pressure on admission. What was that from? What was that attributed to? So we suspected that that was a sequela of the hemolytic anemia as well because it can present with shock states as a result of the complement cascade and subsequent inflammatory responses. So we didn't feel like it was secondary to under-resuscitation as the patient had received adequate fluids. We initially thought it was secondary to inappropriately treated infection, however, a source was never found, and so ultimately we felt like it was secondary to the hemolytic anemia and the shock state as a result. Thank you. So is the hemolytic anemia and the precipitation causing the cholestasis, are they two separate processes? Is that what you're saying? Yes. They were two separate processes, and we felt like our patient had both of them, and then ultimately after cessation of the drug, the patient had resolution of his kidney function, his LFTs, and his hemoglobin without other interventions. When a very long time ago, probably 20 years ago in my intensive care, a patient was given Keftraxone and they were getting TPN, and they developed an acute precipitation reaction with an ARDS-type picture and ended up on ECMO. They survived that, but since that time I've always used Keftraxone just because I think we give so many drugs in the ICU, which, you know, calcium-containing or the TPN, et cetera, so the chance of the precipitation with Keftraxone I think is less likely, but that sort of reinforced my view on that. Thank you. Actually, one of the things I did see was that TPN was listed as a risk factor for the development of the precipitation, so thank you for bringing that case. I think that goes to highlight the frequency that this could happen, with which this could happen. Okay. Thank you. I think anybody who knows me will be shocked that I had an IT solution. Hi, everyone. My name is Beenish. Today I'm going to be talking a little bit about a case of itrogenic botulism. Nothing to disclose. Okay. So botulin toxin is commonly used for a variety of purposes. It has both cosmetic use as well as therapeutic uses, so it's been used for neurogenic bladder, hyperhidrosis, spasticity, and one of the more rare side effects of its use can be the development of hydrogenic botulism. This is a variety in terms of how it presents, so anywhere from mild symptoms like doses all the way to respiratory distress. So my case is of a 37-year-old female with a past medical history of hyperhidrosis. She presented to our emergency room with a three-and-a-half-week history of generalized weakness, fatigue, headache, dysphagia, intermittent blurring of her vision. On speaking with her, she told us that a month prior to the onset of these symptoms, she was actually receiving treatment with botulin toxin for hyperhidrosis. Her first session consisted of 10 injections, and then she went back for a second session one-and-a-half week later for another round of 10 injections, and then two days later after the second session is when she first started noticing her symptoms. On her physical exam, she had easy fatigability and nystagmus bilaterally. She had generalized weakness, 4x5 muscle strength in both her upper and lower extremities. Her gait was normal, but she kept stopping because she felt very weak. We got neurology on board. They evaluated her, got an EMG, and that EMG actually showed a presynaptic neuromuscular junction disorder. That finding plus her history of botulin use and the abrupt onset of her symptoms made us very clinically suspicious for possible botulism. She was admitted to our ICU for closer respiratory monitoring, was given the antitoxin, had significant improvement in her symptoms, and then was eventually discharged with a completely normal physical exam. So there have been cases in the literature that have reported on the systemic toxicity with botulin use. Looking at the literature, a lot of the things that have been associated with increased chances of developing this toxicity include when it's used for more therapeutic purposes versus cosmetic reasons, more likely with more frequent injections, higher doses, and then patients who have underlying severe comorbidities. Some of the clinical points that we really wanted to highlight with our case was the fact that the presentation can be very varied. So a systematic review that looked at about 400 patients with botulism, only 40% of them actually presented with respiratory distress, 39% of them had cranial palsies. And so this is something to keep in mind, that not all patients will present with the classical symptoms that are associated with botulism. And some of their maximal deficits can be very mild, just some doses, some dysphagia, and can go all the way up to respiratory distress, which can be the leading cause of death in these patients. Another thing to take away is that the time to presentation can also be very varied among So it's been reported up to six hours, all the way up to 10 days post-treatment is when patients can present. The only current treatment right now is the antitoxin, which can be asked for, requested from the CDC. And so the way this works is, and this little blurb is actually from the CDC's website, so any case that's clinically suspicious for botulism should be reported to the state public health department as well as to the CDC. And based on clinical suspicion alone is when the antitoxin should be requested and patients should be treated. It's been shown that the sooner the treatment in terms of their disease process, the better in terms patients are in terms of their fatality as well as shorter duration of their symptoms. And so it's been recommended at least within the first 72 hours of their onset of symptoms is when they should receive the antitoxin. That being said, if patients have progressive symptoms, they should still be given the antitoxin and there's no specific cutoff after which the toxin's not been shown to improve symptoms. In our patient, it's likely that just given the frequency of her injections, she probably had some super therapeutic dose that she received of the toxin causing her symptoms. And then just to highlight once again that the presentation as well as the time onset to presentation can be very varied and that's something to just keep in mind when looking at patients who you're suspecting for possible botulism. My references. Thank you. Any questions?

Botulinum toxin

iatrogenic botulism

cosmetic purposes

therapeutic purposes

side effect

hyperhidrosis

neuromuscular junction disorder

antitoxin treatment

respiratory distress