Tasty Morsels of Critical Care

Welcome back to the tasty morsels of critical care podcast. Condensing all of “inotropes and vasopressors” into a single 5 minute podcast is of course doomed to fail but that’s never stopped me before. The main reference for this is Oh’s Manual Chapter 92 by John Myburg who is known to me  for describing adrenaline as “God’s own inotrope” and in the same lecture describing dobutamine as “the Devil’s semen”. i have also heard him say with regards to fluid choice in the ICU that you can give any cat’s piss if you like as long as you do it carefully. The chapter begins with a brief discourse on some of the physiology noting that ~ 20% of blood volume is held in the large conducting arterial vessels, meaning that the majority is held in the smaller vessels and venous structures. This larger venous proportion is often referred to as the unstressed volume. I think of it like the lazy river in a swimming pool, slowly meandering it’s way back to the RV while the arterial side is the flumes that you weren’t allowed on till you were 7 years old and you always had some unconscious fear that you’d enter in and never leave again. But that’s enough about my childhood. Blood in this lazy river of unstressed volume returns on the venous side along a gradient from something called the mean systemic filling pressure (MSFP) to the lower right atrial pressure (RAP). Maintenance of a lowish CVP will therefore aid venous return. In terms of improving cardiac output, autotransfusion of this unstressed volume (and increasing preload to LV) is the easiest and quickest and most effective way of improving CO. Altering vascular tone and cardiac output can be done through a variety of systems: the adrenergic system renin angiotensin, aldosterone system (RAAS) Vassopressinergic Glucocorticoid Local systems such as nitric oxide and endothelin Finally the determinants of cardiac output are stroke volume and heart rate. Heart rate in particular is easy to measure and causes issues at either end of the spectrum. When it’s too low the oveerall CO is too low, at some point it’s too fast, impairing cardiac and coronary filling and hence impairing stroke volume. Pretty much all vasoactive medications have the same end point – that is the release, utilisation or sequestration of intracellular calcium. There are various methods to get there, many of which are cAMP dependant,  but calcium is the end point. First off our beloved catecholamines. There are typically our first line in the fight against MAP<65. We have a fairly bewildering range of options available to us all with their own nuances.The nuances stem from the variety of catecholamine receptor biology we have evolved over the millenia. We know the basics of α and β but these can be extensively sub divided further in forms that only reinforces how little I understand about medicine despite over 20 years studying it. For exam purposes I find having a rudimentary understanding of the differences between α and β stimuli is useful. Following a β receptor stimulus, there is increased cAMP while following an α receptor stimulus something called phospholipase C is engaged. Tachyphylaxis is a common clinical phenomenon with the adrenergic drugs and reduced receptor density, sequestration and enzymatic uncoupling are all part of down regulation. Of note steroids act as pressors probably by increasing receptor sensitivity to catecholamines. Both adrenaline and noradrenaline are predominantly β in action at lower doses with the α effect coming in at higher doses. Pretty much all the synthetic catechols are β in action with the obvious exception being phenylephrine as a pure α. Myburgh is keen to make the point that at the doses we use, the catecholamines have no effect on arterial tone and CABG or vascular grafts, which is a frequent concern of our surgical colleagues who are understandably somewhat precious about their grafts and anastamoses. However it seems that when they go iscahemic it’s not the use of catecholamines is to blame but rather the severity of illness that requires the use of catecholamines. It is acknowledged that necrosis is common but more likely due to microthrombosis from sepsis rather than vasoconstriction from pressors. Next let’s look at the phosphodiesterase inhibitors. Milrinone, enoxamone and levosimendan are all in this bucket.  They work by non-receptor mediated inhibition of PDE, ultimately resulting in increased cAMP. They are thought to be unique in that they may improve lusitropy (ability of heart to relax). All come with potent vasodilation so expect to have to crank up your pressor to compensate. They do not seem to suffer from tolerance and tachyphylaxis. It’s reported that they can inhibit platelet aggregation but unclear how significant this is in real life.  A major downside is their prolonged half life and dependance on working kidneys for excretion. Vasopressin is another obvious category to discuss but I’ll save that for its own entry. References Oh’s Manual 92 Ashley Miller’s short video on MacroCirculation physiology    

Irish Critical Care legend, Martin Tobin, discusses the use of nitric oxide in critical care, exploring its mechanisms, dosages, risks like adverse effects and rebound hypoxemia, and potential anticoagulant effects.

Welcome back to the tasty morsels of critical care podcast. Today we’re going to talk about a fairly rare and niche issue in critical care – gas embolism. The venerated stone tablets of Oh’s Manual do not mention it in any great detail but my alternative and go to textbook has been Irwin & Rippe’s weighty tome/deadweight, and chapter 177 here is dedicated to gas embolism syndromes. This can quickly be split into venous and arterial emboli and we’ll start with the venous side There are a few causes for this and a reproducible short list might include Surgical causes sitting awake craniotomy the classic case where air gets into a venous sinus any procedure with an open vein it is worth noting that when this is searched for in surgeries that are considered high risk it is very common to find signs of air in the venous circulation on doppler. It is a testament to the lungs as a protective filter that it doesn’t cause more issues Traumatic causes a stab wound to a big vein major thoracic injury Procedural CVC being the most obvious one we think of it has been reported with peripheral IVs and even epidurals (though I can’t quite get my head around the mechanism there) Ultimately there needs to be some kind of pressure gradient between the atmosphere and the vein in question hence why position and vigorous respiratory effort are risk factors as both induce a pressure gradient and rapid flow toward the right atrium. The air can get trapped anywhere between the entry point and the pulmonary circulation and it is then obstruction of flow through and out of the right heart that causes all the drama. 100mls is considered to be a fatal “dose” in case you were wondering. Paradoxical emboism is a very real concern here. 1 in 5 of us is walking around with a PFO  and generally it’s not a problem as the slightly higher pressure in the LA vs the RA ensures that the little flap of tissue sits closed. However in the scenario of raised right heart pressures (say when there is 50 mls of air trapped in the RV) then the PFO can blow open and air can enter the left sided circulation converting the scenario from a venous gas embolism to the as yet unmentioned arterial gas embolism situation. In terms of making the diagnosis the context is everything – what was the situation when the haemodynamic collapse occurred? Did they rip out their vascath while sitting upright attacking staff with an IV pole prior to their cardiac arrest? There is apparently a mill-wheel murmur that has been described that i suspect is useful only as an answer in an exam. In reality this will probably be a tricky echo diagnosis or a slightly late and embarrassing CT diagnosis. Hopefully you’ll have nailed it at the context stage and proceded to treatment. Treatment involves stopping any further gas entering the circulation which will likely involve clamps on vascular devices or sticking a finger on the hole in the vessel. The ninja move that is needed next is to lie the patient on their left side in the hope that the air lodges in the RV apex and allows an unobstructed conduit from RA through RV and on to PA. Next try and get a catheter into the RV and aspirate some air. This always make me think of some form of reverse John Travolta/Uma Thurman in Pulp Fiction precordial syringe stab but in reality it’ll be a CVC placed in a rush. 100% O2 is considered a good idea as physiologically you might replace the insoluble nitrogen in the apex of the RV with pure metabolisable O2 but this didn’t really pan out in PTX and I suspect is useful only in theory. This is another time to suggest hyperbaric oxygen but again, in reality, taking a critically ill dying patient to a single person compression chamber seems like a recipe for disaster but perhaps it is something that is done. Let’s turn to the arterial side. Overall the venous side will tolerate gas somewhat better than the arterial side, with the lungs acting as a giant filter however once it gets big enough you can obstruct your RV and the usual RV spiral of death beings. Air in the left side is much less problematic haemodynamically but neurologically is devastating. The list of causes is similar to those for venous gas embolism as many of them can shunt through a PFO In addition some important ones to note include cardiac surgery angiography traumatic injuries like a bronchovenous fistula will rapidly entrain blood into the LA and LV decompression sickness carotid endarterectomy The pathophys is one of simple obstruction to flow in the brain but there is a corresponding endothelial injury that has its own consequences The treatment here is much less exciting as all we can really do is give 100% O2 as a strategy and consider HBO. And by HBO i mean hyperbaric oxygen not the TV channel. References: Irwin & Rippe’s Intensive Care Chapter 177    

Exploration of respiratory monitoring including lung mechanics, esophageal balloons, intrinsic peep, patient-ventilator asynchrony, and neuromuscular function measurement methods, providing comprehensive insights into ventilator management techniques

Welcome back to the tasty morsels of critical care podcast. This is part of Oh’s Manual Chapter 77 on head injury and we covered ICP monitoring before in number 20. A key principle here is cerebral perfusion pressure or CPP. This is easily calculated at the bedside as MAP-ICP. Of course this is only easy if you actually have an ICP monitor.  The CPP should probably be around 60-70 which assuming your patient is unconscious means that the ICP is probably north of 20mmHg and therefore your MAP should be around the 80-90mmHg range. If you actually have a monitor then you can be much more scientific about your MAP target. A moment’s thought about the complexities and unknowns of cerebral blood flow and perfusion in the acutely head injured patient should hopefully make you realise that targeting a CPP is an incredibly blunt tool for so fine tuned an instrument, but given the lack of anything better and strong recommendations from international guidelines then we better stick to it. Oh splits TBI into two phases which I find useful as a concept even if I still find it unclear when a patient transitions from one phase to the next. the early hypo-perfusion phase: after a bump to the noggin there is a rise in pressure from extra axial lesions or oedema that necessitates a bump in your MAP to keep CPP in the right range. the hyperaemic phase: about a quarter will have this at around day 3-7 and it seems ill defined but it’s suggestive you can lower your MAP targets here a bit Overall the basic bundle of interventions in the ICU for ICP include: sedation – this is needed for the tube but also it reduces metabolic rate considerably and reduces ICP. There is no clear advantage of one agent over another although the ileus inducing agent thiopentone is useful in refractory settings SUP – this is one of the groups particularly at risk of GI bleeding keeping the head up 30-40 degrees can promote venous drainage and indeed you’ll see ET tubes taped to the cheeks rather than circumferential ties in many neurosurgical units. DVT prophylaxis should be given – the timing of which is a topic in itself and frequently delayed longer than it should be. The phrase used typically is when the appearances on CT are “stable” whatever that means but it probably does include the absence of fresh bleeding at the very least. CO2 should be in the normal range and same goes for oxygenation. Now is not the time for permissive hypercapnoea and so for your patients with head injury and ARDS this can be really challenging The BTF guidance is the key guideline document that should be referenced and it is well worth a read for any exam candidate and indeed any clinician dealing with TBI. The following summarises some of the headlines. Decompressive craniectomy a bifrontal cranitoyomy is not recommended to improve neuro outcomes, which is a way of acknowledging the important DECRA trial. if done then a large frontotemporal craniectomy is recommended of note these were published before the results of the RESCUE-ICP were available Hypothermia there is a substantial literature and a compelling physiologic argument that cooling would be good however a sequence of trials have put this to rest with the key ones being Eurotherm 2015 RCT ICP>20, 400 pts small impact on ICPs POLAR 2018 500 pts RCT no difference, again little impact on ICP also. There was a decent increase in pneumonia here. Hyperosmolar mannitol effective controlling high ICP but reserve it for those who look like they are near herniating importantly they have no recommendation on hypertonic saline. Doesn’t mean it doesn’t work just that not enough data yet to sell it over mannitol CSF Drainage an EVD can be useful to drain CSF (and lower pressure) in the early period Steroids no, no and no again… Seizure prophylaxis not recommended for preventing late epilepsy (which is an obscure answer to a question no one asked as we use it typically to prevent early seizures) phenytoin is recommended to reduce early (within 1 week) seizures when “benefit outweighs risk” (though early seizures not shown to worsen outcomes) not enough evidence to recommend keppra over phenytoin but you can guess what happens in real life Tagged onto the end of this post on ICP management I’ve included recommendations from a separate BTF guidance that covers when to operate on TBI. In reality this should maybe have been covered first as managing an expanding extradural with mannitol and thio is doing it all wrong. These particular guidelines can be printed out and rolled up and used as a stick to beat your neurosurgeons into operating. But i jest. SDH clot >10 mm, >5mm shift, regardless of GCS those with less severe numbers but low GCS or unequal/fixed pupils should also get surgery EDH Conservative: <30cm3, <15mm depth, <5mm shift and GCS>8 Surgical: all >30cm3 should be evacuated. Parenchymal TBI any >50cm3 >20cm3 and shift >5mm with GCS 6-8 Posterior fossa most of these get evacuated (due to mass effect or reduced GCS) Depressed fractures open and depressed >thickness of the skull generally get surgery (though not all) In reality I find this guidance is viewed somewhat loosely by our neurosurgical colleagues and given the level of evidence it’s based on they may well be right but we do run into the usual neurocrit care dilemma of self fulfilling prophecy.  Managing these patients with medical therapy when they should have had surgery inevitably results in bad outcomes. In closing, I realise I have neglected to mention the 3 tiered approach to ICP management where you provide therapies in a step wise fashion but alas i have ran over time already. References: Oh’s Manual 77 BTF Guidance BTF Surgical Guidance    

Dive into the fascinating world of lung transplantation! Learn about survival rates, the complexities of patient selection, and the unique role of ECMO as a bridge. Discover the latest in ex vivo lung perfusion and delve into respiratory challenges faced post-transplant. Unpack the concerns of right heart response and the risks of infection in donor pairs. The discussion also sheds light on surgical complications and post-transplant lymphoproliferative disorders. It's an engaging exploration filled with critical insights!

Welcome back to the tasty morsels of critical care podcast. A meandering monologue through critical care fellowship exam preparation. This week: serotonin syndrome. Much talked about, very common in an exam, quite rare in real life. It doesn’t really get much coverage in Oh’s manual so the following is prepared from the hodge podge of resources listed at the end. In normal circumstances we produce serotonin from tryptophan. There are a bunch of complicated pathways and mechanisms that are as usual more beyond my comprehension as opposed to beyond the scope of this article. Serotonin does masquerade under its alternate name of 5-hydroxytriptamine which in turn has bred a whole range of receptors of which most relevant is the 5HT2A receptor. The other piece of the puzzle here is monoamine oxidase (MAO). This enzyme is responsible for metabolism of serotonin. So when we give drugs that inhibit MAO we can also get into trouble So in summary 5HT (pseudonym for serotonin) stimulates neurons through a variety of receptors but the 5HT2A receptor is the one that gets us into bother with serotonin syndrome. We can get into bother by having too much 5HT stimulating the 5HT2A receptor or we can get into bother by not getting rid of 5HT with MAO when we need to. Clear as mud I’m sure. This is all very interesting but it’s clear from the now somewhat dated 2005 NEJM review article that this piece of knowledge is only the tip of the iceberg in terms of its pathophysiology. Though rest assured the tip of the iceberg is likely to be enough for exam purposes. In terms of clinical presentation it’s clear that it exists as a spectrum from mild to ICU level. A common mnemonic used is CAN CNS dysfunction Autonomic disturbance Neuromuscular effects To flesh this out in bullet point form, these are the type of features we’re looking for: onset <24 hrs big pupils tremor clonus (esp spontaneous) hyperreflexia fever autonomic issues rapid resolution within 24 hrs with treatment hyperactive bowel sounds (you may snigger at the inclusion of BS here but in terms of distinguishing this from its examinable partner, NMS, the presence of hyperactive bowel sounds may be one of the few if only indication to listen for them) The proposed algorithm for diagnosis here is the Hunter criteria. Named for the lush area of NSW where they make nice semillion wine and have the Hunter Valley Toxicology service that named this a few years ago. It is a step wise algorithm that in the limited science available claims a 95% specificity for diagnosis. This is one of those algorithms (like the CAM-ICU) that refuses to stay in my brain so invariably I end up looking it up. Sadly this is not an option in an exam. It is important to remember that this algorithm only applies in the presence of a serotonergic agent. There is, it seems a quite large number of agents to populate this list. Some of them are obvious with the clues in the name like Selective Serotonin Reuptake Inhibitors (SSRIs) or Monamine Oxidase Inhibitors (MAOI). There are however, a few unusual ones such as linezolid (which acts as an MAOI), fentanyl (which is serotonergic) and usual tox favourites such as cocaine. Tramadol is on the list, which is unsurpising given that it won 1st prize at the recent Toxicology awards for filthiest side effect and interaction profile ever. The final two worth noting are lithium (which can increase sensitivity to 5HT) and methylene blue which sort of acts like a toxicology double agent by playing the hero in methhaemolobinaemia then stabbing you in the back with a serotonin syndrome. Overall expect to see this in 2 scenarios the overdose of a single serotonergic agent – the Saturday night young person presentation the cumulative effect of poor prescribing in a hospitalised patient The archetypal case of the second presentation was with Libby Zion, the young New York lady who died from unrecognised serotonin syndrome due to inadvertent combination prescribing of serotonergic agents by undersupervised and overtired junior doctors. It is thought to be the key case that led to reforming residency hours in the US from life threatening indentured servitude to the more modern underpaid and overworked trial by fire that it seems today. Once you’ve made the diagnosis then you should fill the rest of the answer with something like this supportive care – usual ICU issues, you can split by organ system to cover everything. This might be a good opportunity to wax lyrically about controlling temp either with a bellevue ice bath or a CRRT circuit. specific/antidotal therapy Cyproheptadine is the drug that is listed in all the books. This is an ancient 1st gen antihistamine that has an affinity for the 5HT2A receptor greater than that of serotonin. Like all talks about toxicology it provides an excellent reason to use the distracted boyfriend meme, an example of which is shown below. As you can imagine an early generation antihistamine is probably not the ideal agent for this these days, especially with a dosing regime of NG administration every few hours of a drug that you will probably not be able to locate after hours.  It persists, likely due to the challenging evidence base that tox has to work off. The same Hunter Valley Tox people who came up with the criteria have published their experience with chlorpromazine and olanzapine as alternate agents to cyproheptadine. There is little data to support one over the other but a bit like COVID vaccines, the best one is the one you can get. (This is a comparison that may not hold up over time…) References: NEJM 2005 Review article LITFL Deranged Physiology Geoff Isbister et al (from Hunter Valley…) review from 2014  One of the early Hunter Criteria papers from 2003

Welcome back to the tasty morsels of critical care podcast. A meandering monologue through critical care fellowship exam preparation. Today we’re talking a little about that most vital of gases – oxygen. This is going to be back to some very basic physiology from Oh’s Manual Chapter 28, that I probably should have learnt in medical school but honestly looking back I’m not sure I learnt anything in medical school except how to scrape by with the minimum of effort and knowledge. My post graduate career has been somewhat more enthusiastic I might add. Oxygen is that vital substance that we need in order to conduct oxidative phosphorylation which is the body’s most efficient means of producing ATP. For oxygen to get from, say, my left nostril, to a skeletal myocyte in my right tibialis anterior, it has to go through roughly 5 steps convection of O2 to alveoli (this is ventilation) diffusion through alveolar membrane reversible bonding with Hb transport to tissues (CO dependant) diffusion to cells and organelles Let’s run through that in a  little more detail. Oxygen is drawn in through the big bellows of the lungs and at the alveolus it meets its first real challenge – how to get across the membrane. Here, it obeys Fick’s law of diffusion, where “the rate of diffusion is proportional to both the surface area and concentration difference and is inversely proportional to the thickness of the membrane”. In other words when there’s lots of membrane that is very thin, and not very much oxygen on the other side of the membrane then diffusion is at its best. In apnoea for example the continued blood flow through the lungs draws away any O2 increasing the gradient across the membrane. O2 is drawn through the membrane and in turn more O2 is drawn from the larger airways. This is one reason why apnoeic oxygenation works so well, we see this perhaps most dramatically during the apnoea testing for brainstem death. Simply maintaining a high concentration of O2 in the airways will continue to keep a patient oxygenated even in the absence of bulk flow of gas through breathing. Once diffused into the blood it then joins up with its best friend forever – haemoglobin. Oxygen would much rather be joined to Hb than merely dissolved in the blood. At this stage I am legally required to mention the oxygen-Hb dissociation curve. Despite years of doing this I still cannot get my the left and right shifts stuck in my head. What has stuck in my head is the intelligent adaptation of a system that encourages oxygen offload in areas of the body that are hot, full of CO2 and acidotic – for example muscles working at high load. This might be a rightward or a leftward shift, I really can’t remember but thankfully the human body seems to do it without my input so all is well. This oxy-Hb relationship allows us to move large amounts of oxygen around the body fairly easily. However, of course it is dependant on the cardiac output to get it to where it needs to go. The amount of oxygen the pump can deliver is dependant on flow but also on the oxygen content of the blood. An Hb of 15 will carry more oxygen for a CO of 5L/min than an Hb of 10 for a CO of 5L/min. The oxygen carrying capacity of the blood combined with the CO can be put together to form the oft cited DO2. DO2 is one of those abbreviations for a physiologic concept that has an off little dot above one of the letters and superscript 2 making it altogether difficult to reproduce online without a bewildering number of keyboard shortcuts. DO2 is also best discussed with reference to its partner VO2, indeed combined you can use the term DO2:VO2 relationships in a physiology discussion on a ward round and pray no one asks a follow up question. Perhaps something actually worth knowing is that resting oxygen delivery (DO2) comes in at roughly 1000ml/min. This is the supply half of the relationship. The oxygen consumption comes in at around 250ml/min. This is the demand half of the relationship. We see this reflected in the normal venous saturations of around 65%. If the body was ran by a socially funded health service in English speaking Western Europe, then I doubt we’d see such generous reserves. Why are we going to all this effort supplying 4 times the amount of oxygen than the body actually needs in any given minute? But the body is smart, having learnt its way through natural selection that the best way to avoid a sabre tooth tiger eating you is to have a large reserve of oxygen supply in the event that you need to get away from said Tiger in a hurry. The nationalised health services that we know and love could do with a lesson in supply and demand from the perspective of DO2:VO2 relationships. But I digress. Having navigated the rushing rivers of the circulation our intrepid hero, the oxygen molecule is nearing its final destination – the mitochondria. It has to cross the cell membrane and get to the mitochondria and again it finds benefit in Fick’s principles of diffusion in addition to the shift in the oxy-Hb curve mentioned above. In my head I pictured oxygen tensions in the mitochondria similar to that taken from my arterial blood gas. If I had been guessing in a medical school undergraduate exam (which was generally my default position) I would have said the PO2 would be in 8-10 kPa range. In reality when we have measured oxygen tensions in the mitochondria we find it to, quite staggeringly, to be as low as 0.133 kPa. Below this the mitochondria gets a little upset and tends towards anaerobic respiration. So next time the med reg is trying to get someone into ICU with a PaO2 of 7.5 kPa you can always be smug and say “call me back when it’s less than 0.133 kPa…” and hang up. References: Oh’s Manual Chapter 28    

Explore when is the best timing to start CRRT in critically ill patients, considering factors like volume overload and electrolyte imbalances. Learn about the furosemide stress test as a predictor for CRRT necessity and the complexities in determining the most beneficial timing for CRRT initiation in patients with AKI.

Welcome back to the tasty morsels of critical care podcast. A meandering monologue through critical care fellowship exam preparation. If you were tuning in to try and pick up some core exam level content then this is probably not it. However, it is what came up in my non-random, semi alphabetical by system, trawl through my notes that forms the basis for the order I write these in. We’re going to spend 5 minutes on chemo agents in the ICU. Roughly hewn from the stone tablet of Oh Chapter 46 on solid tumours in intensive care. This is perhaps not something that will be top of the list in exams and certainly for clinical practice you are not going to be prescribing any of these agents. However a passing familiarity with some of the commoner ones, (or at least the ones that are more likely to run the risk of an ICU admission) is probably worth while. Table 46.1 has a table that covers two pages of scrolling on my browser and includes many drugs that I have never heard of or can’t pronounce or both. Thankfully the next segment has a much smaller selection of “specific chemo induced toxicities” and we’ll try and cover at least that much today. First up – bleomycin lung injury. Bleomycin is actually an antimicrobial used in a variety of head and neck and gynae tumours and Hodgkins. The pneumonitis can occur in up to 40% (though the corresponding up to date article puts it at more like 15%) and can be fatal. There is generation of oxygen free radicals with corresponding fibrosing alveolitis that is actually worsened with oxygen therapy. If this sounds familiar, then the insecticide paraquat does a very similar thing but is, I suspect, much less useful in treating cancer. In terms of treatment it seems that just like in ARDS, the terms fibrosing alveolitis and high dose pulsed methyl pred are inexplicably connected. Second on our list is ifosfamide related neurotoxicity. Ifosfamide is an alkylating agent used in a broad range of tumours and is well known for causing an encephalopathy in 10-20% of patients. It is a diagnosis of context and exclusion. I have heard it discussed, if not diagnosed on several occasions by oncologists with patients in the ICU and one was even given methylene blue which is a somewhat established antidote of sorts through some mechanism of MAO activity. However it turns out that guidelines from the European Society for Medical Oncology specifically recommend against giving it so maybe forget i just said that and instead cite them in opposition to any oncologists wandering into your ICU with little blue vials. Coming in at number 3 is anthracycline related cardiomyopathy. There are a number of drugs in this category all ending in rubicin and seem to be used fairly widely. There are two parts to this. Firstly, there can be an acute cardiomyopathy, sometimes with arrhythmias that happens early and secondly, a more chronic cardiomyopathy that can happen months to years after the drug has been given. The mechanism has too many proposed options to be memorable but reactive oxygen species seem to have at least some role. Last but by no means least are the immunotherapy agents. This is chemo Jim, but not as we know it. Melanoma appears to be the poster child for the agents here. There seem to be a broad variety of agents and mechanisms that fall under the term immunotherapy but the check point inhibitors are probably the most well known. The immune system has various check points as such to stop the cellular militia getting too carried away. The check point inhibtors effectively remove these check points and let the immune system go wild on whatever foreign tumour antigen it can get its hands on. Mechanistically this is genius as a therapy but as you can imagine there can be a few issues with getting the genie back in the bottle. This can affect all kinds of body systems and is best summarised in an excellent IBCC post by Josh Farkas that you can find linked in the show notes. If this podcast does nothing but direct you to better resources then it’s 5 minutes well spent. References: Oh’s manual Chapter 46 UpToDate articles on the relevant toxicities IBCC Check Point Inhibitors