Tasty Morsels of Critical Care

Welcome back to the tasty morsels of critical care podcast. Today we’re going to have a quick overview of the oesophageal balloon. If you’re directed to a patient in your long case who has an oesophageal balloon in, then you’re probably having a bad day. It would seem very unfair to have too many questions on this but an awareness of their existence and some cliff notes on their basic use might come in handy especially if you’re doing well and you’re in the medal type territory of the exam. Exams aside they’re a useful gateway drug into some important respiratory mechanics that are relevant to all of us. At their most basic these are fancy NG tubes with an inflatable balloon that should end up in the lower third of the oesophagus. Inflating the balloon with a small amount of air allows you to transduce the pressure at the area the balloon lies. While that sounds straightforward there are large sections of review papers dedicated to troubleshooting placement and means of assuring the number you generate is actually accurate. I refer you to the below references for further reading. The pressure measured is called the oesophageal pressure, often abbreviated to Pes because it seems the Americans won the spelling war on that one. Oesophageal pressure is a reasonable surrogate (with assumptions of course) for pressure within the pleural space. Once we have an estimate of pleural pressure we can subtract that from the plateau pressure displayed on the vent and we end up with a fancy number called the transpulmonary pressure. The transpulmonary pressure or Ptp is the distending pressure applied to the lung either from the muscles of spontaneous ventilation or from positive pressure ventilation from the ventilator. Whoopdy do says the examiner – you now have another number you don’t really know what to do with. What should we use this data for, the examiner is asking? Well a short list of useful aspects you can look at with the oesophageal balloon include compensating for the effect of the chest wall on respiratory mechanics appropriate titration of PEEP assessing the contribution of respiratory muscle use to potential lung injury assessing triggering and synchrony issues At this stage you’d be hoping the examiner is satiated and you can move on to something else but in the unlikely and terrifying event that they ask for more detail you might want to mention some of the following. Our typical approach to safe ventilation in the passively ventilated patient is to look at driving pressures and tidal volumes. But this takes no account for the contribution of the chest wall. In the very obese patient there is a lot of flesh pressing down on the chest wall, this leads to an increasingly positive pleural pressure. It would make sense that we would need more pressure to distend the lungs in this scenario. The balloon in this scenario will allow you to set your PEEP appropriately. The Ptp at end expiration needs to sit somewhere in the 0-10cmH20 range to avoid derecruitment and in end inspiration it needs to be less than 25cmH20. This may need a lot more PEEP or less driving pressure than you’re used to giving and the balloon can help you feel safe about doing that. In the patient weaning from the ventilator in a spontaneous mode the oesohpageal balloon can be used to make an estimate of the contribution of the patients muscular effort to the transpulmonary pressure. Your patient may be on 10/5 on a pressure support mode and you may well be lulled into a false sense of security that because the pressure numbers on the vent are modest then the pressures being exerted across the lung are also modest. What we are not measuring in this scenario is the distending pressure being applied to the lungs by the respiratory muscles, the Pmus. The balloon in this scenario can give an estimate of this as it reflects the negative pleural pressure generated by the patients inspiratory efforts allowing us to come up with a Ptp number that takes Pmus into consideration. Sometimes this might encourage you to increase the support from the vent, sometimes this might encourage you to increase the sedation depending on the context. So given all the wonderful things the balloon can do for us why are we not doing it on everyone? A list of reasons not to use oesophagaeal balloons might include cost – these fancy NG tubes are pricier than you would think compatible software on the ventilators. These frequently don’t come as standard appropriate placement. These are tricky to get right and knowing that the number generated is valid is not entirely straightforward. Lots of assumptions are made the Pes number reflects pleural pressure only at a single location and does not take account of heterogeneity. the evidence base is unclear if this adds anything over doing something like simply following the high PEEP table from ARDSnet. Interestingly several research groups (thinking the folk from Toronto or Luigi Camporata in london)  have used balloons to identify surrogate ways of measuring recruitment or estimating Pmus that we can easily measure on a standard ventilator set up. This may well be a way of bringing the important concepts of transpulmonary pressure to the bedside. Reading: The Toronto Mechanical Vent Course was an excellent intro for resp mechanics for me. They offer a virtual version Mauri, T. et al. Esophageal and transpulmonary pressure in the clinical setting: meaning, usefulness and perspectives. Intens Care Med 42, 1360–1373 (2016). Yoshida, T., Grieco, D. L. & Brochard, L. Guiding ventilation with transpulmonary pressure. Intensive Care Med 45, 535–538 (2019). Mireles-Cabodevila, E., Fischer, M., Wiles, S. & Chatburn, R. L. Esophageal Pressure Measurement: A Primer. Respir. Care respcare.11157 (2023) doi:10.4187/respcare.11157. Jonkman, A. H., Telias, I., Spinelli, E., Akoumianaki, E. & Piquilloud, L. The oesophageal balloon for respiratory monitoring in ventilated patients: updated clinical review and practical aspects. Eur. Respir. Rev. 32, 220186 (2023). Deragned Physiology LITFL  

Welcome back to the tasty morsels of critical care podcast. This is the second of 2 parts on PE in critical care. The first focused on risk stratification and this one will focus on management. There is a link to a transcript of a more comprehensive talk with references on emergencymedicineireland.com for those keen enough to dive a little deeper. As noted in the last podcast this one leans very heavily on “in the my experience” level of the evidence pyramid and should be weighted as such. For this discussion I’m going to assume your patient is in the ESC High risk category, ie hypotensive with a PE on imaging and you’re satisfied that the PE is causing the hypotension. I do believe there is a tiny cohort of the PE population who warrant aggressive reperfusion even with a normal appearing BP but at this stage I cannot say I have any evidence or guidance to really identify who they are and back that up. For the original talk I gave on this to an EM audience, I split the interventions into helpful , distractions, and not helpful. It was probably a little bit of a provocative division if I’m honest. The slide is on the site for reference and viewing it will likely make what follows more edifying. For the resus room patient in the first 30-60 mins I feel comfortable to standby my assertion that a short list of “helpful interventions” should includes lysis, anticoagulation, noradrenaline, oxygen and some CPR. In the ICU however we’re often present both at the first 30-60 mins but over next hours and many of the items on the “distraction” list become a little more relevant with time. Number 1 on my list of helpful interventions is thrombolysis. As mentioned, if you have found PE and you have satisfied yourself that the sickness and hypotension you’re seeing is caused by that PE then you need to have a good reason not give thrombolysis. The evidence base is not high level RCTs but it is a class 1 recommendation on the ESC guidelines and the list of class 1 interventions is really quite short. In the 25 year old in resus with a massive PE day 3 after an arthroscopy the decision here seems pretty straightforward. However in the post trauma patient in the ICU with massive PE with a small traumatic SAH and an improving SDH and a recent laparotomy then the decision is orders of magnitude more complex and you may well find a very good reason why lysis is not an option. There is not a straightforward answer to lysis because it will vary from patient to patient but I would emphasis that it is a question worth dedicating a decent chunk of your cognitive bandwidth to. Dosing in an unstable patient is often 10mg of alteplase followed by 90mg over 2 hrs. Dosing in a cardiac arrest situation is typically a 50mg bolus. Anticoagulation is one of the other class 1 recommendations on the ESC list. Opinions vary on agent of choice. With my ICU hat on I will almost always advocate for UFH as I feel confident that if i stop it, the heparin effect will be gone in a couple of hours when the inevitable bleeding starts. Opinions vary and I know smart people who advocate for LMWH in this scenario with one of the arguments being you probably get more reliable and quicker anti Xa effect. Both the guidelines and your esteemed narrator recommend against volume resuscitation. Dumping a litre of crystalloid into the venous circulation will shift the IVS further towards the left impairing cardiac filling and doing the opposite of what you intended. A much better resuscitation fluid would be noradrenaline. This is remarkably effective in improving BP and perfusion and I have often used it when I am 90% sure the patient has a PE but haven’t quite got the CT scan to prove it. The noradrenaline can also buy you a little time to make a better decision about the lysis and reperfusion, converting what would have been an immediate decision into something that you maybe have more like 30 mins to make. Certainly if the noradrenaline dosage is rising and the right heart is struggling then adrenaline would be my add on inotrope of choice. Of course we know in the ICU we have a plethora of other agents available to us with lots of theoretical advantage on pulmonary vascular resistance etc. They would rarely be my first line, certainly not in the ED population but I would often reach for them a little further down the line once i have a better handle on the physiology and what they might tolerate. Enough to say that staring someone on 0.5mcg/kg/min milrinone as a single agent with a starting BP of 60/40 is not likely to end well in this context Oxygenation is strongly endorsed given its proclivity for reduction in PVR, however intubating someone in this context to facilitate oxygenation is likely to result in a catastrophic haemodynamic collapse. The adage “resuscitate before you intubate” or even “reperfuse before you intubate” has some relevance here. I find CPR to be helpful in the context of massive PE, not simply for the usual reasons of preserving some degree of forward flow but I suspect there is a mechanical effect of breaking up or moving clot more distally. I have frequently seen stuttering intermittent ROSC in this context. I would suggest caution with the mechanical CPR devices as the presence of a liver lac in the context of tPA is unlikely to be well tolerated. While not available or that relevant to the emergency medicine population I do think the addition of nitric in the ventilated ICU patient who develops nasty PE seems like a low risk intervention with potentially massive gains. There is a small RCT of nitric in the spontaneous breathing PE population that did not however show benefit. I put mechanical devices in the “distraction” category in my original talk as I don’t think they have much relevance in the early stage of resuscitation. However if you have kept them alive long enough or if you have a true contraindication to lysis or a failed lysis then they may well have a role. I have found the evidence base so far here decidedly underwhelming and for catheter directed lysis in particular i struggle to see how a mg/hr tpa via a pulmonary catheter is any different than a mg/hr of tpa via a peripheral IV line given that the entire venous return ends up in the pulmonary circulation either way. The thrombectomy devices are certainly more compelling from a physiological perspective and the obvious and dramatic changes in physiology on removal of clot are quite compelling. But they are a tremendous faff requiring a catheter akin to an ECMO catheter to be threaded into the pulmonary circulation. The recent PEERLESS trial gave an average 90 min procedure time emphasizing the need to keep the patient alive long enough to receive the intervention. I do feel this has a role in our management quiver I am just unsure what that role is, but more evidence in the coming years will likely clarify VA ECMO is undoubtedly a fantastic physiological support for a dying PE patient but bear in mind it is almost definitely not available to you in the vast majority of hospitals in the Ireland and the UK. PERT teams are groups of relevant physicians willing to weigh in on difficult PE cases to advise on management. I put PERT teams in the distraction category. And I feel bad about that because they’re usually filled with knowledgeable and enthusiastic people . But there are 2 errors I’ve seen on this that we should be aware of. One is on us as primary clinicians where we outsource the decision to lyse in someone who has a clear indication. This is not necessarily the fault of the PERT team but there is risk to the patient in delaying as it is a tremendous faff trying to get hold of the relevant people and then get them to agree. The second distraction that can happen is the recommendation for interventions in a patient that they have not seen and are not present to. A couple of times I have had to talk people out of IR interventions that frankly were not needed because the patient was getting better with conventional treatment. Do not underestimate the importance of being at the bedside and seeing the patient and evaluating response to treatment. Surgery, in terms of pulmonary embolectomy is the third and final class 1 recommendation in the ESC guidelines for high risk PE. All be it with a very low evidence rating. It gets talked about in papers and guidelines but you’re talking about taking someone who is already mostly dead into theatre, lined, anaesthetised, chest opened and onto bypass. There probably is a role for it somewhere and in certain institutions and it’s often raised in the context of contraindications to lysis but those same contraindications to lysis usually apply to the 30000 units of heparin you need to get them on bypass. It seems to suffer from the old goldilocks flaw of “not sick enough” for theatre or “too sick” for theatre I have clearly done way beyond my usual brevity in this scenario but honestly didn’t think anyone could tolerate a 3rd part on PE. Full refunds are available on request For further reading it is probably best to visit the original lecture post where the relevant papers are all listed with a little smattering of critical appraisal thrown in for good measure.

Welcome back to the tasty morsels of critical care podcast. I haven’t managed to cover PE on the podcast yet. I have been involved in lots of small PE projects over the years and have developed something of an interest in it. I got invited to give a talk to the national EM conference this year and these podcasts are sort of the cliff notes version of that lecture. The full talk is linked to on the emergencymedicineireland.com website for those interested. I would emphasise that beyond the mention of the ESC guidelines this is an evidence lite podcast and more than usual represents opinions rather than hard science. The original talk was about PE in the resus room but I definitely think PE in the ICU in an established ICU patient is quite a different beast and I will try to highlight that as we go through it. PE is so ubiquitous that I’m skipping a lot of the core pathophys and work up and instead want to split it into 2 parts, the first today on risk stratifying PE and the second on nuances of management in critical care. PE is common in critical care. Either as a referral from ED with a patient with a nasty PE and bad physiology as the sole problem (less common) or as a finding in an ICU patient with other clinical issues, eg trauma or a surgical patient in whom you have now found a PE (a much more common scenario). From our perspective in ICU the test we need is a CT scan. I think all the other discussion about dimers etc is moot for us and if you need to exclude the diagnosis then CTPA is the way to go. I think for the majority of the ICU population found to have a PE they are relatively innocuous. Yes they have PE but it is frequently quite small and not really contributing to their physiology. Yes they need anticoagulation but rarely anything more. There are a small cohort who need aggressive management of the clot and the physiology but these are much less common. In terms of identifying the sick ones or risk stratifying them you need to be able to cite the ESC 2019 guidelines on PE. This is a substantial piece of work and is well worth a read. In that you will find PE can be split into low risk, intermediate risk, intermediate-high risk and high risk patients. However while a good starting place for risk stratification they remain a little blunt and don’t really tease out the super sick PE patients where the subtleties of management really come out. Most of the ICU cohort will fall in the intermediate risk group who generally do very well as long as you anticoagulate them. It starts getting interesting in the intermediate-high and the high risk group. The intermediate-high group are identified with some form of right heart strain on CT or echo and a bump in a biomarker like troponin and BNP. If you add in low blood pressure then you’re in the high risk group. As noted this risk stratification is, in my opinion, a little too blunt to be of use in the ICU population where there are so many other reasons that the right heart might look funny or the BP low or the troponin raised. How can we be a bit smarter with our risk stratification? Well firstly we need to decide if the low BP is being caused by the PE. Size of clot can be helpful here. If very small then it’s unlikely to be that significant. Especially if we have a much more clinically apparent cause of hypotension like the large empyema also seen on the CT scan. Particularly in the ICU population with multiple reasons for hypotension the pressure is on us to tease out which of the pathologies is causing the hypotension. If they are genuinely hypotensive because of the PE then lysis is probably inidicated – more on that next time. With regards to clot size, however the opposite does not seem to be true: ie the presence of large clot, especially in the ED population does not seem to predict outcomes especially well. Instead of looking in the report for the size of the clot we would better served paying attention to the size of the right heart versus the left and for evidence of contrast reflux into the IVC. These are more useful in predicting right heart dysfunction. An even more useful method is to look at the heart itself with an echo. I’m pretty sure this has little evidence to support it but I find that the echo gives a more accurate description of the impact that the PE is having on the physiology as I think (very much an opinion here) the CT scan often over calls the right heart strain. The obvious confounder here is that the echo is often done after the CT where the right heart has had a little time to recover so I’m very willing to be wrong on that. The useful things to look for on the echo are RV size, TAPSE and septal flattening. While i do love all the other nerdy measures of RV function I remain skeptical of their additive value in making a decision on something as significant as thrombolysis. The other reason I think echo has some advantages over CT on risk stratification is that it’s easy to see the response to therapies on the echo. Does the RV look a bit healthier after an inotrope or lysis etc. ECG can certainly be used to risk stratify and right heart strain on ECG, (think deep inverted T waves anteriorly and inferiorly) seems to predict CT and echo changes quite well. However I know my ECG skills are lacking and even when I do see the changes I see the ECG as a reason to order another test (ie CT/echo) rather than make the definitive diagnosis or thrombolyse. While trop and BNP get a lot of attention in the ESC guidelines for risk stratification I find them to be less than helpful in the critically ill as all of our patients already have a raised trop and BNP even before they get a PE. I do pay attention to our universal badness-metre the lactate. A rapidly rising lactate in a PE patient with a bad RV is certainly worrisome. Next time we’ll look at management options For further reading it is probably best to visit the original lecture post where they are all listed with a little smattering of critical appraisal thrown in for good measure.

Welcome back to the tasty morsels of critical care podcast. Hypertriglyceridaemua induced pancreatitis came up at a recent trainee presentation and I thought despite it being pretty niche and rare, it’s still common enough that it might be fair game for an SAQ or perhaps a side bar in a viva discussion. Pancreatitis is of course a common presentation to the ICU and can range from the straightforward to the never ending complication fest that carries a not insubstantial mortality rate. This is not the post that will cover the full gammut of pancreatitis. So what is the deal with the cumbersomely named “hypertriglycerdiaemia induced pancreatitis”. UTD has the helpful statement that this is the causative factor in “1-35%” of cases of pancreatitis. This tells me nothing except that we don’t know how common it is. In terms of cases coming to your unit you should probably consider it if you can’t find gallstones and they don’t ingest alcohol. It should probably come higher on your differential than scorpion bites for example. I’ve seen a few of these and the main trigger for the diagnosis was the lab ringing and saying that the blood is so lipaemic that they can’t process it. There are some lovely images online of the bizzare appearance of the blood. It’s one of the few diagnoses you can make by simply looking at the blood as it fills the bottle (the other being methaemogobinaemia) The higher the trigs, the worse the pancreatitis generally. It may be a familial thing to do with generation and metabolism of trigs or it may be secondary hypertriglyceridaemia due to something common like diabetes or even pregnancy. How does the fatty stuff cause the pancreatitis? At this stage in the viva expectations will be low – no one expects detail though a complete silence is likely not going to be well received. A statement along the lines of “well now, it’s not the trigs themselves that are toxic but instead the fatty acids produced by lipases that are the precipitating agent”. This is likely to pacify any potential predatory examiner and you can move onto something more relevant like how it might change your management. Your management will be the same as for almost all pancreatitis with organ support, and some fluids etc…. The subtleties of management of pancreatitis associated with hypertriglyceridaemia are somewhat predictable. You should restrict fats in your nutrition till things are under control. If they’re severe enough to be in ICU they’re often hyperglycaemic and on some insulin already but as we know insulin can help reduce fatty acid release, therefore being aggressive with insulin (maybe in the 5-10 unit/hr range) , and supporting with dextrose if needed, would seem prudent. The more eye catching therapy that you should be aware of is plasmapheresis. As one can imagine removing all of the plasma from the person will result in removal of the triglycerides from the blood. Indeed a 50-80% reduction is quoted in the available observational studies used to support the practice. There are no RCTs to support its use in this scenario though if you’ve been around for long enough you’ll of course note that most of what we do is not supported by RCT level evidence. Neither the 2013 APA guidance or the 2019 WSES guidance mentions plasmapheresis Somewhat surprisingly, the classic outpatient lipid drugs like the statins, the fibrates and ezetimibes etc do not seem to play a prominent role in the acute management but are naturally important in prevention of recurrence in the longer term. Reading heavy dependence on the doctor’s little helper here (otherwise known as UTD) Oh Chapter 43 covers pancreatitis generally and I am sure we will return here in due course  

Welcome back to the tasty morsels of critical care podcast. Today we’re going to try and cover the not insubstantial topic of acute liver failure from Oh’s Manual chapter 44. As you can imagine this will be a superficial skim of the topic so set your expectations appropriately. First point is differentiating acute from acute on chronic liver failure. This has a massive impact on presentation, diagnosis and management and I must confess for many years as a trainee my understanding of the distinction between the two was a little cloudy and it was only really in fellowship that it became clear to me. Oh describes it as a massive parenchymal liver injury with multi system impact and organ failure. Coagulopathy and encephalopathy with various degrees of hypotension and renal failure are the main presentations. Encephalopathy and coagulopathy are needed to make the diagnosis. This happens in the context of a previously normal liver. Acute on chronic liver failure occurs when someone with pre-existing liver disease eg cirrhosis has a decompensation. This may be a consequence of portal hypertension like bleeding or encephalopathy or sometimes it’s infection. Encephalopathy may or may not be a part of it. Portal hypertension is a substantial feature whereas it is typically absent in acute liver failure. So what we’re expecting to see to make a diagnosis of acute liver failure in the critical care environment is a patient with what is thought to be a previously normal liver present with a rapid progression of symptoms and jaundice leading to encephalopathy. Now “acute” can be within 6 weeks from jaundice to encephalopathy but they’re not typically the type of patients that come to us. The rapid outpatient to ICU trajectory is typically within days and a differential arranged by prevalence in the western world should include paracetamol the commonest and is not always obvious and can be large single overdose or a staggered intentional overdose or even a therapeutic misadventure on the ward in someone with a low BMI idiopathic while a common end point of the work up it is not a helpful diagnostic category drugs idiosyncratic reactions to any number of medications including things as simple co amoxiclav or an NSAID viral these are the alphabet soup of hepatitides. This is no doubt commonest world wide but is much less likely in our part of the world. The tests should definitely be sent but don’t expect much autoimmune vascular the commonest liver injury we see is usually ischaemic as part of sometihng like OOHCA. But usually it’s not the liver on its own that causes the mortality as the brain injury usually kills them first portal vein thromboses and budd chiari (blockage of venous outflow) do happen and why the imaging is important Heat related we’ve had a couple of these in the past few years related to exertional heat injury. The context is obvious and the care largely supportive pregnancy HELLP syndrome and acute fatty liver of pregnancy fall under this banner mushrooms i have never looked after an amanita poisoning but they do exist in Ireland. You are orders of magnitude more likely to get in trouble with paracetamol than mushrooms but you should still keep mushrooms on your list. When investigating this there is a long list of labs that should be sent but beyond the routine labs you get on anyone you should check for the hepatitis viruses, have a look at eosinophil count if you’re thinking about drug reactions and if you really are unsure then they all end up getting urinary copper and ceruloplasmin to look for Wilson’s. Imaging with either US or more likely US and CT is important. Liver biopsy is often indicated but it is disappointing in it’s yield and comes with bleeding complications Encephalopathy is assessed with a specific 4 level grading system known either as the West Haven or Parson’s Smith scale. Grades 3-4 is where we’re likely to get involved. There are multiple reasons for the encephalopathy – ammonia is obviously part of it but there are other factors involved. Ammonia is taken up by astrocytes and deamination to glutamine  which in turn draws in water leading to astrocyte swelling. In addition there is likely loss of autoregulation and integrity of the blood brain barrier as part of inflammatory response to acute liver injury. Ultimately this means that these patients are at risk of an ICP crisis (unlike acute on chronic liver failure where the brain has been able to compensate). The ICP crisis can be a real source of morbidity and mortality and all of our usual arsenal of ICP management strategies have been employed in supporting these patients. The coagulopathy is often profound in terms of the numbers measured. Thombocytopaenia is typically consumptive. The INR is prognostic and correcting it routinely does not seem of much benefit. Indeed we should remember that levels of both pro and anticoagulant factors are depressed though we only measure the procoagulant ones typically. As a result the coagulopathy may have a degree of balance to it that we simply don’t measure. Surgical procedures probably need attempted correction of coagulopathy but simple things like CVC insertion are probably safe. NAC is a truly life saving and effective drug in paracetamol overdose and should be used liberally. It is unclear how helpful it is in other forms of liver failure but given its benign side effect profile it is used early and liberally and a decision to give some should not be something to spend too much time on. Kidney injury is common but we should probably be filtering earlier than we might conventionally do so. The idea is that CRRT can wash the blood of some of the foul humors that the liver isn’t dealing with. The dose of CRRT here is typically a lot higher at 45ml/kg or higher rather than our usual 25. This has a limited evidence base but it is published on and frequently used. On a similar vein (pun intended) of removing evil humors, plasma exchange has been used and a small open label RCT exists. An SAQ or viva may raise the existence of MARS – Molecular Absorbent Recirculating System. This was thought of as “liver dialysis” but does not seem to have panned out and does not seem to be in regular use Finally it is critical to consider liver transplant as an option for these patients. Unlike in heart or lung transplant where you need a stable patient with limited organ failures to be a candidate, in acute liver failure you can be in the throes of severe multiorgan failure and still be a candidate for liver transplant. Hopefully your liver physicians will have made the referral for you but if not you should be making the phone call. Reading Oh chapter 40 Larsen, F. S. et al. High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial. J Hepatol 64, 69–78 (2016).

Welcome back to the tasty morsels of critical care podcast. Today we look at the other diabetes. We are of course all familiar with the sweet urine of diabetes mellitus but this time we will look at the tasteless or insipid urine of diabetes insipidus. This will as always be a critical care type primer on the topic designed to help you survive a critical care fellowship exam. I would certainly not claim endocrine as my strong suit. There are 2 forms we’re likely to encounter in the ICU. The first is a deficiency or absence of antidiuretic hormone.The second is an resistance to ADH. You’ll notice this is just like diabetes mellitues where type I is an absence of insulin and type II a resistance to insulin. However because endocrinology has to be the most obtuse and complex specialty they refrain from calling it type I and type II and instead refer to them as cranial DI (deficiency of ADH) and nephrogenic DI (resistance to ADH). Just to note ADH also goes by the moniker of  arginine vasopressin (AVP) or even argipressin. For the sake of simplicity I’ll just refer to it as ADH. Given the number of TBI and ICH we see in the ICU we obviously see a lot more of the cranial DI than the nephrogenic DI. We’ll come back to the 2 types of DI later, but a brief section on the function of ADH is unfortunately warranted. As the name suggests ADH reduces urine output. It does this by promoting free water reabsorption in the kidneys. It does this by stimulating V2 receptors in the kidney increasing the number of aquaporin channels in the tubules. Hence more ADH, more water reabsorption, less urine. ADH is released primarily in response to a rise in osmolality. For example in hot weather you get dehydrated, your osmolality rises, your pituitary releases ADH, you reabsorb more water slowing the rise in osmolality. In diabetes insipidus either absence of ADH or resistance to ADH will lead to reduced water reabsoprtion in response to increased tonicity. Ongoing free water loss will result in rising tonicity driven by a rising sodium concentration. So that’s the basics of the pathophysiology, lets’s go back to our 2 types, cranial DI and nephrogenic DI. Cranial DI happens when the pituitary is so injured that we lose production of ADH. This could be something rare like infarction or an auto immune issue of the pituitary or much more likely in our context some devastating intracranial event leading to a massive rise in ICP. The urine starts pouring out at 300-400 ml/hr and then the Na starts rising. The patient may or may or may not continue to progress towards brainstem herniation. The context makes the diagnosis here usually fairly obvious but it’s worth sending a urinary Na and osmolality and in this case we’re expecting to see a very dilute urine (eg an osm <200 ) with a low Na which is inappropriate when the serum Na is high. Treatment is relatively straightforward in the acute stage. We should give some ADH replacement typically in the form of DDAVP but you could of course vasopressin or argipressin because they’re the same thing really. Replacing the ADH will allow water reabsorption and correction of the tonicity. We will usually have to replace some of the free water and 5% dextrose is a reasonable way to do this, just be sure to control the urine output with the DDAVP first. Chasing a 600 ml/hr urine output with 1000ml/hr of 5% dextrose will lead to a dextrose driven diuresis making things even worse. Of note there are different phases to this type of DI and if the patient survives the first few days then you may well see some lessening of the polyuria for a period. Management of cranial DI beyond the first week is certainty beyond the scope of this podcast. Nephrogenic DI is more often going to be a label that comes with a patient to the ICU who is coming often for another reason rather than a diagnosis we make de novo in the ICU. Top of the list here is going to be chronic lithium use with a distant 2nd of hypercalcaemia. In this scenario ADH continues to be produced appropriately in response to a rise in tonicity but the drugs involve interfere with aquaporin function resulting in a failure of water reabsorption. Nehprogenic DI is less severe and more chronic than central DI and as a result patients themselves will compensate for it quite well by simple drinking more water. We see it when we have them intubated in the ICU for whatever reason and have removed their ability to drink. Over the next day or two the Na continues to drift up with only a modest increase in the urine output. Treatment for these is primarily replacing their free water loss and restarting their chronic meds for DI. Involvement of an endocriniologist or nephrologist or whoever manages such issues in your jurisdiction would seem wise. Reading Oh’s Manual Chapter 60 and 95    

Welcome back to the tasty morsels of critical care podcast. Following on from the recent post on Heparin, today we’re going to talk about one of its more significant complications – Heparin Induced Thromboyctopaenia or HIT for short. In my notes I had it down as HITTS for hepain induced thrombotic thrombocytopaenia syndrome which I kind of liked as it included the important presence of thrombosis in the context of low platelets. But HIT is definitely snappier There are incidentally 2 forms of HIT. Type 1 is an entirely benign phenomenon where the platelets transiently drop in the first few days of heparin exposure and spontaneously recover even with ongoing heparin use. There is no thrombosis associated and no doubt it happens all the time and we miss it. From our perspective we’re only interested in type 2 HIT which is a serious immune phenomenon where the major concern is not bleeding but clotting despite the low platelet count. Unsurprisingly a necessity for this condition is an exposure to heparin. This can be UFH or LMWH. It is an immune phenomenon so you don’t typically get it on the first exposure but it’s the ongoing or repeat exposure can cause the immune reaction. As part of normal heparin function it, at various points binds to something on platelets called PF4 – platelet factor 4. For reasons beyond the comprehension of this narrator, the body can produce IgG against this heparin-PF4 complex. The IgG has now labelled these platelets for destruction by macrophages hence the thrombocytopaenia. Again, for reasons beyond this narrator’s comprehension there is also activation of other platelets resulting in both arterial and venous thrombosis. Incidence is estimated about 1-5% of those on UFH and <1% on those on LMWH. Interestingly the antibody reaction is quite common but even when present only ~10% of those with the antibody develop HIT properly. The classic presentation is a fall in platelets somewhere 5-10 days following first heparin exposure. Counts usually are between 40 and 80 but 10% can be under 20. The 4T score has been developed as a means of establishing a pre-test probability for HIT. I’ll outline the 4 categories briefly severity of the thrombocytopaenia. ie platelets of 10  or 120 make it unlikely while platelets of 50 are in the zone timing of the fall – 5-10 days being the sweet spot. The catastrophic fall in the first 48hrs of overwhelming sepsis for example would not be consistent with HIT presence of thrombosis. This can a bit equivocal as it can be difficult to find all the clot and a clotted CRRT filter maybe shouldn’t carry as much weight as a clotted femoral artery is presence of another reason for thromboyctopaenia likely – this is of course like the wells score very open to interpretation A high 4T score usually prompts formal testing and usually a switch to an alternate anticoagulation regime pending the results. This is frequently misunderstood as it seems most are happy to stop heparin pending the test but disregard the fact that clotting is actually the problem so alternate anticoagulation is really needed. Testing usually comes in 2 stages. The first is a more rapid easily available screening test which i believe is a PF4 immunoassay. This can be followed up by a fancier (checks notes) Heparin Induced Platelet Activation functional assay. I can attest that we have two tests available in our place but I wouldn’t swear they are the ones described above. The main dilemma we’re left with, is when we suspect HIT but have not got a definitive test to confirm it. We need to make a probability and risk based decision on whether to commit to the diagnosis or not. Let’s say we’ve decided it’s HIT and we need to anticoagulate. We have a few options, we can use direct thrombin inhibitors (DTIs) like bivalarudin or anti xa agents like fondaparinoux. In our place we reach for argatroban, one of the DTIs. We will of course seek expert advice from our coagulation colleagues but the critical take homes here are suspicion of HIT, knowing the probability and tests and ensuring we anticoagulate despite the off putting low platelet count. Reading LITFL Deranged Physiology Shore-Lesserson, L. et al. The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines ∗ —Anticoagulation During Cardiopulmonary Bypass. Ann Thorac Surg 105, 650–662 (2018). Lubnow, M. et al. Prevalence and outcomes of patients developing heparin-induced thrombocytopenia during extracorporeal membrane oxygenation. Plos One 17, e0272577 (2022).  

Welcome back to the tasty morsels of critical care podcast. Following on from our initial post in this entirely accidental series on “things you don’t want to find in the chest drain” we turn our eyes (if not our noses) to empyema. Many penumonias will develope a parapneumonic effusion. This is largely reactive and inflammatory but by no means does it mean there is infection. On the other hand parapneumonic effusions can become the seed for an empyema proper, something seen relatively commonly with something like strep pneumo. The commonest bugs described in empyema are strep pneumo and staph aureus, both of which occur as complications of pneumonia with said bugs. If on the other hand you have perforated your oesophagus into your pleural space then expect to find a different selection of microbiological beasties. While perhaps obvious, the clinical features we’ll be looking for are fever and pleural effusion either on CXR, CT or US. Fever despite appropriate antibiotics always should make us think about source control so if the CXR looks funny then put the probe on or run them through the CT scanner. You can see pleural enhancement on CT scans which in my somewhat limited experience seems quite specific but not especially sensitive. Similarly loculations can be very easily seen with ultrasound, better than CT it seems but again don’t necessarily correlate that well with empyema. As such the best thing to do it seems is to get a sample. It is my contention that if you’re going so far as to get a sample then why not leave a little teeny weeny drain in there while you’re at it. The advent of US guidance and pig tails and a substantial literature base all suggest that small. bore drainage is actually often quite effective and the old days of just assuming everyone needs a 28fr drain are probably past. My own practice is to use an 8Fr pigtail and see what happens. I have in my notes a list of fluid criteria that apparently define an empyema. I am unclear of the provenance of this list but it seems to have been drawn loosely from the 2017 thoracic surgery guidelines and some the intereventional trials we’ll talk about later. So definitionally if we have pus it’s an empyema, if we have a positive gram stain it’s an empyema, if we have growth it’s an empyema. Other features suggestive on pleural fluid analysis include pH<7.2 LDH>1000 Sugar <2.2 high lactate So now let’s assume you’ve got your sample and you’ve tried small bore drainage and you still have a big collection there. What are your options? Well, adding extra or bigger drains is all very reasonable and it would seem wise to involve a thoracic surgeon at some point. Unresolved these empyemas develop into what is known as the “rind” causing a trapped lung and many will need the rather brutal procedure of decortication to strip it away. However in the early days we’re likely to more interested in simply getting source control and sometimes it’s the loulcations that are our enemy. There are a number of trials and indeed published guidelines suggesting the use of injected pleural therapies to aid drainage. This consists of 2 agents 1) DNAase 2) our old friend tPA The intervention involves placing a small drain then injecting DNAase and tPA into the drain every 12 hrs. This has been moderately well studied with MIST-2 2011 and the Picollo trial (2014) being  commonly quoted trials suggesting benefit. There is a cochrane review looking at tPA on its own that also suggests less need for surgery The major downside, understandably is pleural bleeding, that occurs in about 2-5% in the studied cohorts. This can be clinically significant though very rarely does it seem to be life threatening. The major barrier to implementation in the ICU setting is the almost complete absence of ICU patients from these trial cohorts. And as we all know if there is a complication possible it’s almost definitely going to happen with greater frequency in the ICU cohort. I have not mentioned it so far, which is somewhat remiss of me,  but if it’s not obvious you will also need some antibiotics here… To answer an SAQ with lots on definitions and drainage and fail to mention antibiotics would be poor form. Reading Deranged Physiology has this covered as always – Piccolo, F. et al. Intrapleural Tissue Plasminogen Activator and Deoxyribonuclease for Pleural Infection. An Effective and Safe Alternative to Surgery. Ann. Am. Thorac. Soc. 11, 1419–1425 (2014). – M., R. N. et al. Intrapleural Use of Tissue Plasminogen Activator and DNase in Pleural Infection. N. Engl. J. Med. 365, 518–526 (2011). – Altmann, E. S., Crossingham, I., Wilson, S. & Davies, H. R. Intra‐pleural fibrinolytic therapy versus placebo, or a different fibrinolytic agent, in the treatment of adult parapneumonic effusions and empyema. Cochrane Database Syst.Rev. 2019, (2019). – Shen, K. R. et al. The American Association for Thoracic Surgery consensus guidelines for the management of empyema. J. Thorac. Cardiovasc. Surg. 153, e129–e146 (2017).      

Welcome back to the tasty morsels of critical care podcast. Today we look at quite a niche topic, that of chylothorax. We are used to many things in the pleural space, like simple fluid or blood or air but the presence of the myseterious substance chyle is a much more unusual and note worthy event. As a reminder of the basics which I of course knew implicitly and definitely did not have to resort to wikipedia to check… Chyle is largely formed in the small intestine as the gut transports free fatty acids from the intestinal lumen. This combined with lymphatic flow is transported via the thoracic duct to the vasculature where it enters the circulation proper. The lipids in the chyle are transported in the form of wonderfully named chylomicrons. The cisterna chyli is akin to the gall bladder of the lymphatic system, situated in the upper abdomen it drains a lot of the lymphatics from the gut before sending it on it’s jolly way through the diaphragm into the thoracic duct. Once in the thorax the thoracic duct has to run the gauntlet of the posterior mediastinum where it is frequently hunted and subjected to extreme violence by cardiothoracic or upper GI surgeons who are purportedly there for completely unrelated reasons. If the thoracic duct survives this odyssee then it drains into the sub clavian vein on the left. As suggested, the commonest time we find chyle in the pleural space is when we notice the milky stuff in the drains that were left in place after said surgery. The other common context is apparently lymphoma or a number of other malignancies. Chyle in the chest drain can be a yellowy milky thing or blood tinged. As a Deranged Physiology post quotes one group “to our surprise a quantity of fluid which resembled pale tomato soup was withdrawn” To be definitive about the fluid you can measure triglycerides or even use electrophoresis to identify the above named chylomicrons. Assuming we’re comfortable with the diagnosis, let’s turn to management. The duct is a fragile little beast, apparently too fragile for the surgeons to spot when they’re doing their original surgery and certainly not amenable to surgical repair. So like a lot of things in medicine it’s best to let the body sort it out itself and the body is best able to do this if we can reduce the flow through the duct. Perhaps number one is the low fat diet, or at least providing fats in the form of medium chain fatty acids that can be absorbed through the portal vein bypassing the thoracic duct altogether. PN is naturally an option here. Our universal secretion dryer upper octreotide has also been used frequently and to effect. This strategy appears effective in a certain somewhat undefined proportion cases. If it is not settling and still causing issues then our beloved friends in IR now have techniques allowing them to embolise the duct and our surgical colleagues, while not able to repair the duct can at least tie it off. Reading Deranged Physiology is excellently referenced, detailed and humorous in equal proportion LITFL

Welcome back to the tasty morsels of critical care podcast. We’re going to cover a bit of an environmental/tox topic today and look at carbon monoxide poisoning from Oh’s manual chapter 83 on burns. I have previously covered this on the old tasty morsels of EM series back when i was doing my EM fellowship exams. As you no doubt remember from school chemistry classes, carbon monoxide is a colourless, odourless, tasteless gas produced when combustion occurs with insufficient oxygen. We’re likely to see this in a couple of contexts. 1) the house fire victim, pulled from the fire unconscious and sick 2) the sub acute or chronic poisoning in a patient presenting with headaches and flu symptoms that seem to get better when they leave the problem environment. The classic EM example is the whole family who present with flu symptoms and no fever and even the dog is sick. We’re much less likely to see this cohort in the critical care side of things. How does it make people sick? Haemoglobin is a fickle little protein, while evolved to carry oxygen to needy tissue beds it actually has a distinct preference not for our beloved oxygen but for carbon monoxide. Introduce some carbon monoxide at the alveolus and the haemoglobin molecule will bind to CO with an affinity 240 times that than for oxygen. I take that number of 240 somewhat at face value but I presume someone got a PhD from working that out. In visual form my preferred means of explanation for this would be the distracted boyfriend meme where the haemoglobin boyfriend looks longingly over his shoulder at the carobon monoxide while his oxygen girlfriend looks on in horror. Hopefully you get the idea. So instead of having lots of circulating oxyhaemoglobin we’re instead left with lots of not especially useful carboxyhaemoglobin. Let’s imagine 50% of our Hb is now carboxyHb and 50% is OxyHb we’re left with a sort of severe fucntional anaemia where half of our Hb is out of action. One might be inclined to think that this is the major cause of morbidity and mortality in CO poisoning but in fact this is only a small portion of the problem. CoHb actually has a direct cytotoxic effect on things cytochrome oxidase and myoglobin function. As such it interrupts the whole process of oxidative metabolism and life as we know it. We can measure the level of CO fairly easily, any blood gas machine worth its salt should be able to give you a break down of the types of Hb present in the sample. This is co-oximetry and typically it’ll show you oxy, deoxy, carboxy and met haemoglobins. All these different forms of Hb absorb different wavelengths of light. The lowly pulse oximeter does not have the subtlety to distinguish the different wavelengths as it only functions at wavelengths of 940 and 660nm. Indeed the pulse ox often demonstrates a non diagnostic number somewhere in the 80s rather than a true reflection of the CarboxyHb or OxyHb present. Severe CO poisoning resulting in obtundation is going to have high level of COHb on our cooximeter. >10% is quoted but it’s more often over 30%. Patients are going to be pretty sick often from multiple pathologies but COHb on its own is enough to produce severe neurological injury, shock and even cardiac injury is also quite prevalent. Expect a high lactate given the disruption of oxidative metabolism. Resuscitate and investigate as you would any sick patient. Treatment is nice and simple in that we just give loads of oxygen. Oxygen reduces the half life of CO in the blood quite dramatically, commonly quoted numbers are the haf-life of COHb in an FiO2 of 0.21 is 300 minutes the half-life of COHb in an FiO2 of 1.0 is 60-90 minutes  There is a substantial rationale and literature on the use of hyperbaric oxygen as a means of accelerated clearance of COHb. But the RCTs that have been done don’t seem (to me at least) to give a clear benefit. The Lindell Weaver NEJM RCT in 2002 did suggest a neuro benefit but only 8% of the patients in this trial were intubated. A follow up trial in 2011 by ICU steroid guru Djilalli Annane did not find a benefit . So if anyone should get this it might be the non intubated isolated COHb poisoining. This is not really our cohort. Our cohort is likely to be tubed, shocked, with multiple injuruies and not someone you want to transport cross county to put in a single person hyperbaric chamber for hours at a time. Reading Oh Manual Chapter 83 Weaver, L. K. et al. Hyperbaric oxygen for acute carbon monoxide poisoning. The New England journal of medicine 347, 1057–1067 (2002). Annane, D. et al. Hyperbaric oxygen therapy for acute domestic carbon monoxide poisoning: two randomized controlled trials. Intensive Care Medicine 37, 486–492 (2011).      

Welcome back to the tasty morsels of critical care podcast. We’ve been talking about pulmonary hypertension, last time we had a pretty broad overview with a focus on group 1 or pulmonary arterial hypertension. This time we’re going to go through some management strategies that might keep you between the hedges on a night on call or a fellowship exam viva. We briefly mentioned the PH specific drugs that someone might be on. The evidence base for these is almost exclusively in group 1 PH. But what should we do with these meds in someone with group 1 PH who has just arrived back from theater after a laparotomy and a hartmans and they’re on a bit of noradrenaline? The simple answer is continue them. The more complicated answer is you should usually continue them. For example there will be the very rare patient whose pulmonary vascular resistance is kept low in the community with a PICC line and an epoprostenol pump. They are critically dependent on this drug with a very short half life and it should be continued at all costs. Think about it like an adrenaline infusion running at 10mcg/min, not something you can tolerate a break in. A recurring message from the review papers on critically ill patients with PH is to focus on treating PVR not PA pressures. This is a somewhat philosophical approach that reminds us that the PA pressures themselves don’t prognosticate especially well but a failure of flow from right to left will result in cardiogenic shock and death. We have a lot of vasoactives to choose from in helping with this, most of which have varying impacts on the PVR. Vasopressin has some animal data suggesting it causes less rise in PVR than our beloved noradrenaline but take that with an appropriately loosely defined portion of salt given that animal data is not ICU patients. Milrinone seems like a great idea as an inotrope that is easy on the PVR but the often dramatic drop in SVR is often a disaster. Dobutamine has the benefit of at least having substantial clinical experience in PH patients even if the tachycardia and even worse the a fib is less than desirable. The ventilator is a bit of a poisoned chalice. Not only do you have to tolerate a significant risk of peri-intubation cardiac arrest even once you get them on the vent you have to deal with the adverse effects of positive pressure on the RV. The only upside of the vent is that it might make them easier to oxygenate but only if the cause of the hypoxia was a big shunt physiology like a pnuemonia. Oxygen is a great tool for reducing PVR so if we can leverage that then that’s great. However, a lot of hypoxia in end stage PH is reduced mixed venous oxygenation due to low cardiac output and the vent does nothing good for this. Once on the vent we want a goldilocks’s zone of lung unit recruitment. Too little PEEP we have atelectasis and shunt and hypoxia and vasoconstriction. Too much PEEP and we have overdistension which itself can raise PVR by squeezing the pulmonary vasculature. Finding that sweet spot for the PEEP is a whole post or 10 on its own. While on the vent it’s a good opportunity to deliver some inhaled therapies. The original gangster here is of course nitric oxide which is one of our target molecules in PH. In a crisis and a failing RV, this might get you out of a tricky spot. But given its expense and not being widely available its worth considering other inhaled options, particularly intermittent nebs of iloprost or a continuously nebulised eporprostenol solution both of which i have seen implemented to good effect. In terms of monitoring should we be reaching for a PAC? Well, take a step back to start with. We probably need the CVP more. The RV is the first downstream organ that suffers under the burden of worsening PH and if the RV is failing then the CVP will be rising. Like any monitoring tool, a PAC in itself is going to do nothing but provide you with scary looking numbers, particularly the PA pressures which, remember, you should largely ignore. But picking up a severely raised wedge for example might push you to be much more aggressive with your diuresis and left heart management. A continuous cardiac output monitor will allow you to titrate your vasoactives with a great deal more confidence and accuracy The other monitor I would reach for would be echo. I am a self confessed echo phile so take that into consideration but one of my targets of treatment is going to be how the heart looks. Is the IVS becoming less flattened, is the RV less distended, is the TAPSE improving etc… Echo early, echo often in my book. Atrial fibrillation is something of a right of passage in the ICU. Have you really been critically ill if you haven’t even had an episode of fast AF? When it comes to PH it’s often poorly tolerated and the approach to rhythm and rate control probably needs to be a bit more aggressive than usual. Our usual choice of vitamin A, amiodarone is a good start but you may need other agents like dig or even DCC to get control. A consistent message from the reviews is to avoid beta blockers. The negative inotropic effect on an RV that is already functioning at peak capacity is not going to be good. Our first reaction when faced with hypotension is often to load with fluid, this makes sense when we think of the frank starling mechanism, we want to be sure our LV is appropriately pre loaded. But in PH the issue is a failure to deliver volume or flow from the right heart to the left. We can dump a litre into the venous side of the circulation but the PVR just stops it getting efficiently through to the LV. If your patient is hypotensive then the RV is already failing in its basic function of delivering volume and flow to the LV while keeping the CVP low. More fluid is almost never going to fix this. Indeed diuresing the hypotensive patient may well be the way to go. If you can decongest the right side and reduce the bowing of the septum you’ll get both the RV and the LV working more efficiently This is only a taster of things you might want to try in a critically ill patient with severe PH. It is important to emphasis that they are not evidence based overall. Most of it is interpretation of clinical physiology at the bedside and applying the available manipulations. Which is of course what makes it so much fun.2 Reading My own rambling review of pulmonary hypertension on JFICMI website. 2022 ESC Guidance McLaughlin, V. V., Shah, S. J., Souza, R. & Humbert, M. Management of Pulmonary Arterial Hypertension. J. Am. Coll. Cardiol. 65, 1976–1997 (2015). Jentzer, J. C. & Mathier, M. A. Pulmonary Hypertension in the Intensive Care Unit. J. Intensiv. Care Med. 31, 369–385 (2015). Johnson, S. et al. Pulmonary Hypertension: A Contemporary Review. Am. J. Respir. Crit. Care Med. 208, 528–548 (2023). Barnett, C. F., O’Brien, C. & Marco, T. D. Critical care management of the patient with pulmonary hypertension. Eur. Hear. J. Acute Cardiovasc. Care 11, 77–83 (2022).

Welcome back to the tasty morsels of critical care podcast. This time we’re looking at pulmonary hypertension. Mainly cause I recently had to give a talk on it so it’s fresh in my rapidly diminishing brain cells and thought I should get it all written down before I forget it. We’re going to try it as a 2 parter. Part 1 will cover a broad overview of pulmonary hypertension and part 2 will focus on management strategies for a PH patient in the ICU. Saying a patient has PH does not really tell you very much. All we mean is that pressures in pulmonary circulation are higher than they should be. Saying someone has PH and not quantifying it is a little like saying someone has cancer but not saying which organ or how advanced it is. We need to go a bit further than just say they have PH and quantify the cause or rather which group of PH they’re in. We also need some way of quantifying the severity of it. The definition of PH since the 2022 ESC guidelines is a mean PAP of 20mmHg on a right heart catheter. Echo can be used to screen for “probability” of PH but the right heart cath is needed to make the diagnosis. Once you’ve defined that the pressure is high the real doctory work begins as you have to figure out the likely cause. The language the guidelines use is “group”. You should be able to put your patient into 1 of 5 groups. To give an example you are handed over someone who has known PH. You dig a little deeper and see they have an mPAP of 27 on a recent right heart cath. Their echo shows a poorly functioning LV and severe MR. The PH here is going to be group 2, PH secondary to left heart disease. This is by far the commonest. Or another example, you are told someone has PH. You dig a little deeper and see an echo report that says the left heart works well but the right side is dilated. You dig a little deeper and see the clinic letters describing severe end stage emphysema. This is likely to be group 3 PH, PH secondary to lung disease. In both those examples the PH is a problem but it is a downstream effect of other disease. And unless you can fix the heart or lung disease then the patient is in trouble, indeed if the patient dies in the coming weeks to months it’s likely going to be the left heart disease or the lung disease that kills them. Let’s spend a few minutes talking about group 1 PH, sometimes called PAH. This is rare but often very severe and progressive and comes with some unique medications so it’s worth discussing. These people should have normal lung parenchyma and normal left hearts. There are a variety of specific causes in group 1 but a lot of it is described as “idiopathic”. It is a progressive pulmonary vasculopathy where the tiny arterioles suffer intimal proliferation and eventual fibrosis due to a variety of vasoactive molecules. This transforms the pulmonary circulation from a very compliant, low resistant circuit into a narrow and stiff group of pipes. The right heart is evolved and very comfortable with assisting large volumes of blood through a low resistance circuit. In hroup 1 PH, the change in pulmonary vascular resistance is more than the right heart can cope with and the right heart over time starts to fail in its primary purpose of maintaining a low CVP while delivering preload to the LV. Over the past decades a number of classes of drugs have been developed that target the vasoactive molecules that cause the vascular changes. These can be split into 3 classes 1) endothelin receptor angtagonists which do exactly what the name says: reducing endothelin. Drugs like macitentan fall in that category 2) PDE5 inhibitors. These inhibit the enzyme you expect from the name but the key outcome is that there is an increase in nitric oxide something that causes pulmonary vasodialtion. Sildenafil or tadalafil are two common drugs in this group 3) prostacyclins. These vasodilate and reduce proliferation in the vascular bed and typically IV epoprostenol is the drug of choice here. These drugs have proven disease modifying benefit but only in group 1 PH. We have not been able to prove any benefit for those with PH from left heart disease or lung disease. The more severe their disease the more drugs they might be on. Some patients are even on IV epoprostenol in the community to keep their PVR compatible with life. These 3 classes of drugs have had a significant impact on both length and quality of life in PH. But the prognosis in group 1 PH is still one of progressive irreversible disease in the longer run. There are lots of features that are well validated on an outpatient basis to determine prognosis however that is rarely the question we’re faced with. For example we know ICU admission is a poor prognostic sign in severe PH but this is generally the very point we get involved at. As usual i suspect decisions about prognosis in the ICU setting are typically decisions about limitation or withdrawal of life sustaining therapy and they all depend on reversibility. If someone with severe PH has a pneunonia then we can probably turn that around then that’s something to consider. However if the right heart and liver are failing due to worsening congestion from progressive PH then that’s a different question. That’s enough for today and to give you an overview of PH, next time we’ll focus on some management strategies. Reading My own rambling review of pulmonary hypertension on JFICMI website. 2022 ESC Guidance

Welcome back to the tasty morsels of critical care podcast. Last time i was butchering my way through a diagnostic approach to hyponatraemia, particularly the forms likely to end up in the critical care end of the hospital. This time we’ll take a punt at how you might approach management. In an ideal world of course you would have all of the diagnostic tests back and you’ve been able to make a very solid diagnosis of the cause of hyponatraemia and you would institute a bespoke treatment course for the underlying disease and the resultant hyponatraemia. But as we all know in critical care we often work with less than ideal information and have to begin treatment while the diagnostic process is ongoing. Hopefully what follows will provide enough broad brush strokes to get you through a night on call or even worse a viva. We’ll start with truly emergent situations. Older person presents to the ED after being unwell for several weeks. They have a seizure on arrival and a Na comes back at 105. This is a fairly solid indication to give hypertonic saline. In this scenario they are seizing because of the low Na and rapid increase of the Na is needed to stop the seizure. The European Hyponatraemia Guidelines would suggest 150mls of 3% saline over 20 mins aiming for a rise in the Na of 5mmol/L. This bit is usually pretty straightforward. The sodium rises, the patient stops seizing everyone relaxes but then the Na continues to rise, well above the 5mmol we wanted and a panic ensues. The guidelines suggest a max rise of 10mmol in the first 24 hrs and 8 mmol/day after that. It is hard to overemphasise how easy it is to blow past that target unless you are paying attention. So how do you control the rise in the Na? If it’s rising too quick it’s often because the patient is losing lots of water through the kidneys which concentrates the plasma raising the Na in the blood. You can replace that water loss by giving a decent bolus of free water in the form of something like 5% dextrose. An alternative method involves using the wonderfully named DDAVP clamp. In this scenario you’re using the DDAVP to tell the kidneys to excrete less water therefore limiting the rise of the Na. I have not seen particularly strong data on one method vs the other for limiting the rise and indeed I have seen clinicians use either or indeed both to good effect. The European guidelines do use the phrase “severe symptoms” as an indication for a bolus of hypertonic. Unfortunately it’s a little less clear what constitutes severe symptoms. A seizure seems fairly easy to define but “coma” is a little bit more vague.  The guidelines are clear that you have to be able to put the symptoms down to the hyponatraemia and not some other cause. But as we all know patients often have multiple reasons to be obtunded including sepsis or intoxication or multiple other causes. As such the decision to give hypertonic can be a little subjective and fudgeable. For many patients the best thing you can do is very little. A former consultant I worked for had somewhat facetious plans to start a hyponatraemia clinic that involved locking the patient in a room and denying them access to water and letting the body sort it out over several days. There is an element of truth to that as for many of the hyponatraemics simple fluid restriction and time will correct things. Lastly, our hypertonic of choice is typically 3% saline with an osmolality somewhere in the range of 1000 or so. Typically we’re a bit reticent to give such concentrated solutions through a peripheral IV but there are a few papers suggesting that this is fine at least on a limited basis. I will say that once the hypertonic is in and you’re reaching for a 2nd or a 3rd you should probably be thinking about a CVC as the access for administration and indeed regular sampling is really helpful. Reading European Hyponatraemia Guidelines Oh Chapter 95 Khasiyev, F., Hakoun, A., Christopher, K., Braun, J. & Wang, F. Safety and Effect on Intracranial Pressure of 3% Hypertonic Saline Bolus Via Peripheral Intravenous Catheter for Neurological Emergencies. Neurocritical Care 1–6 (2024) doi:10.1007/s12028-024-01941-3.

Welcome back to the tasty morsels of critical care podcast. Today we cover an incredibly common inpatient issue – hypnatraemia. We’ll often find 1 or 2 of these in our high dependency unit at any given time, mainly due to the requirement for frequent testing of Na levels that seems beyond the remit of normal ward level care. The approach I describe here is neither comprehensive or especially robust but it is how I approach it. Caveat emptor and all that. The over bearing demyelinating elephant in the room in hyponatraemia is the risk of osmotic demyelinating syndrome (the pathology formerly known as central pontine myelinolysis). If we correct the Na too fast will our patients end up with a severe brain injury? This is rare but is a very real phenomenon.The brain is actually quite good at adapting to sodium levels that have lowered over a few days or weeks. Hence why the slow developing sodium of 120 often causes minimal or no symptoms. However once the patient is in this adapted state (as mentioned this probably is after a few days at a minimum) then a rapid return to baseline sodium can cause ODS. By contrast a rapid drop in sodium, eg over a few hours drinking litres of unnecessary water during a marathon, is poorly tolerated but the plus side is it can be corrected fairly rapidly without harm. Most of the hyponatraemia we see admitted through the ED will be hypoosmotic hyponatraemia. The bucket here will include heart failure, cirrhosis, SIADH, tea and toast and beer potomania. I’m going to put these common ones to one side for a minute and look at some of the niche exam ones. For example, i said hypoosmotic hyponnatraemia there, so presumably there could be an isotonic and a hypertonic verison. There is indeed. The isotonic hyponatraemias are usually from spurious results. For example, when you have high lipids (super high, like high enough to cause pancreatitis high) or high proteins (eg high paraproteins like myleoma) the measurement method can underestimate the sodium. You can work this out by always sending a serum osmolality. If this is normal but the Na is 125 and your calculated osmolality is low, then you have an isoosmotic hyponatraemia. You should then check the lipids and the protein. Hypertonic hyponatraemia is another strange beast. This time the tonicity is high from something else such as high glucose or mannitol drawing water from cells into plasma. Again a mix of clinical context and a serum osm will help you out here. Let’s go back to the bread and butter (or should i say the “tea and toast”) hyponatraemia, the hypotonic or hypoosmotic hyponatraemia. Context as always will give you lots of clues, if the patient has consumed nothing but beer for weeks then the likely causes is beer potomania. If the patient has a new cancer then SIADH is high up your list. I confess I lean heavily on the approach you can see on Deranged Physiology and have Alex Yartsev’s flow diagram saved on my phone and i look at it almost every time i’m trying to work this out. The first test (assuming you’ve confirmed this is hypotonic hyponatraemia) in this algorithm is urinary osm, the question you are asking here is whether the kidneys are doing what they’re meant to be doing in the face of a low sodium. A normal sane and functioning kidney will try and lose water to conentrate the plasma in order to bring the sodium back up to normal, in other words the kidney should be producing a dilute urine with a low osm. Next step is to check the concentration of sodium in this dilute urine. If the kidney is doing what it should be doing it should be holding onto to all the sodium it can and urine sodium should be low. The problem here is too much water, not enough solute. Think, beer potomania, tea and toast, and polydipsia. If the urine is dilute but the sodium is high then you know something has gone wonky in the kidney itself, typically AKI or resolving ATN. On the other side of the algorithm we have a concentrated urine, in other words, a high urine osm. The kidney is holding onto water and concentrating the urine. This may be a very sane and sensible response by the kidney if you are frankly hypovolaemic from eg gastroenteritis. The kidney also gets tricked by a few conditions into thinking its hypovolaemic, things like CHF or cirrhosis where the kidney itself just mightn’t be being perfused very well.  In this scenario you should have a concentrated urine with a high osm and a low urinary Na as the kidney holds onto Na for all its worth in an effort to maintain effective circulating volume. On the other hand you might find a concentrated urine with a high osm but a high sodium also. This tells us that the kidney is handling water reabsorption OK but has lost the run of itself when it comes to regulating sodium. Something may be strong arming the kidney into losing more sodium than it should, like thiazides or an external actor like ADH, in this case it would be inappropriate ADH, hence the syndrome of inappropriate ADH. In addition a lack of steroid (and in particular the mineralocorticoid part) or a dodgy thyroid may cause the kidney to lose sodium when you shouldn’t. Or of course this scenario could be due to intrinsic renal disease. So that’s 8 or 900 hundred words running through the deranged physiology algorithm and you can imagine that simply looking at the algorithm would probably be a better use of your time so go do that. Next time we’ll have a look at how we might manage hyponatraemia Reading Deranged Physiology – Wonderfully titled ” A Lazy Man’s Classification” Oh Chapter 95

Welcome back to the tasty morsels of critical care podcast. Today we’ll cover some key exam content, all be it not something you’re likely to run into in the ICU too often. The thyroid is a deceptive little organ, tucked in the neck, quietly secreting hormones and interfering in negative feedback loops. It usually restricts its mischief to outpatient clinics by running hot or cold on a chronic basis, occasionally hypertrophying and interfering with its more important neighbour the airway. But every now and then in a pique it decides it’s fed up of this low level mischief and uses its deeply embedded relationship with the rest of the body to wreak havoc. We’ll split this into 2 parts, one when the thyroid goes on strike and is under active and the other when it goes bananas and secretes far too much hormone Some basic physiology. Thyroid hormones are essential for all organ systems. The active forms are T3 and T4. T3 is generally the more active one. They are synthesised by incorporating iodine into tyrosine residues in thyroglobulin in the thyroid gland. Hence how iodine deficiency can cause a deficit in thyroid hromone. Their release into the circulation is stimulated by TSH. TSH causes endocytosis of this thyroglobulin into the follicular cells where they undergo hydrolysis into T3 and T4 which is released into the circulation. Both are highly protein bound to thyroid binding globulin. Our first relevant condition is the wonderfully named thyroid storm. Most commonly you might see this as part of untreated Grave’s disease. It can be precipitated by the usual physiological stressors such as surgery or sepsis etc… Expect to see (at least in an exam scenario) fever tachycardia or fast AF jaundice delirium heart failure eye signs or a goitre consistent with thyroid disease For awareness there is a clinical prediction tool that rejoices in the name Burch-Wartofsky Point Scale. This includes most of the features listed above. It’s clear that the features listed above are fairly non specific and like always it’s likely just sepsis. But if something in the spidey sense tingles then finding undetectable TSH and high T3 or T4 should really get you going. In reality this is an incredibly rare diagnosis, one which in its fulminant form i have yet to see. Or perhaps more accurately one that i have failed to diagnose as yet. This is of course hardly surprising as it is hopefully clear by now on this podcast that I am not especially good at what i do and continue to put my appointment to my current job down as some kind of administrative error that is yet to be detected. Once you’ve decided you’ve made the diagnosis then you’ll need a few basic principles of treatment. Firstly do a bit of resuscitation. There may well be some co existing sepsis so give some antibiotics. If they’re hypoxic give some oxygen. They may need some fluid or indeed they may be in congestive heart failure. The key is to do an assessment, this likely includes having a sneaky peak at the heart and the lungs with ultrasound. A commonly recommended treatment is propanolol to help with the tachycardia. Many patients will be hyperdynamic and tachycardic and giving a beta blocker may well be a good idea but giving a negative inotrope to someone who’s heart is a bit clapped out is generally considered bad form. The key message is to assess comprehensively and then decide. For specific therapies, your list should include some steroids, this reduces the release of thyroid hormone from the gland. There is occasionally some coexisting adrenal insufficiency so you’ll treat that as well.  You’ll need to use something like PTU (propylthiouracil) or carbimazole in order to block new production of thyroid hormone. Good luck finding PTU at 3am. Having performed one miracle in locating PTU you are now expected to perform a further miracle and find something that sounds more like a tonic you’d buy from a wild west apothecary. This is of course “Lugol’s Solution”. Only give this once thyroid production has been blocked (recommendations suggest an hour afterward). It contains typically a bunch of iodine and will block the release of any T3/4 left in the gland. Your next patient in your exam viva comes from the opposite end of the spectrum. Myxoedema coma. As an aside, myxoedema coma is a terrible name, the patient may not have oedema or be in a coma. Again, Farkas on the IBCC uses the term “decompensated hypothyroidism” which i think is much more descriptive and accurate. This is hypothyroidism but not as you’ve seen it before. Typical features or as Josh Farkas calls them “cognitive triggers” to consider myxoedema coma include neuromusclular features like reduced consciousness, delirium, slow reflexes and weakness hyothermia. the classic is someone found unresponsive with a much lower temp than expected for the environmental conditions endocrine issues like low sugars and low sodiums cardiovascular features such as bradycardia, hypotension and pericardial effusion respiratory features like alkalosis and pleural effusions GI issues like ileus and weight gain Again lots of these are non specific so keep the differential broad before anchoring too early. As expected TFTs will be helpful and in general expect to find a high TSH and low T3/4 Management will involve your usual assessment and resuscitation but the specific therapy here is IV thyroid hormone. It does exist but is also hard to track down at 3am. Your ICU probably has it and you’ve typically only seen it as part of management of a potential organ donor in brain death. T4 is the one typically recommended (which will converted intracellularly to the more active T3). But in Ireland the most commonly available will be T3. These people also need steroid, typically some hydrocortisone for the ubiquitous adrenal insufficiency. Indeed giving thyroid hormone without steroid may cause an adrenal crisis. Reading: Oh Chapter 61 Tasty Morsels of EM 130 The IBCC Deranged Physiology

Welcome back to the tasty morsels of critical care podcast. Today we’ll talk about one of the niche and shall I say “advanced” in inverted commas therapies in intensive care practice. ECMO. And to be precise we’ll be talking about VV ECMO. Indeed saying that you are “putting someone on ECMO” is a woefully incomplete sentence as the support and physiological difference between venovenous ECMO and venoarterial ECMO is really rather profound. The post will be an intentionally broad description of the therapy and perhaps less on the nuances of managing a patient on VV ECMO, as at fellowship exam level I suspect you’d only be expected to have an overview of what it it is, what it can (and can’t do) and when to ask for it. I acknowledge the glaring gaps in the post and the likely criminal omission of the oxygen carrying capacity calculation. It would be fair to call this an idiot’s guide. And given that these posts are generated from my own notes then we all know who the idiot in that title it refers to is. We’ll start at its simplest level, which is how i try to describe to friends and non medical people about how ECMO works. Blood is removed from the veins in one pipe and put through an artificial lung type device where CO2 is removed and Oxygen added, then blood is returned to the veins via a second pipe. If you’re lungs don’t work so well then the device can replace a lot of their function in the short term. Lay person explanation ends. The degree to which we can replace lung function, primarily the degree to which we can oxygenate, is determined by the amount of the venous return coming back to the heart we can divert through the machine. Let’s say the cardiac output is a healthy 5L/min. That means that 5L/min is being ejected from the left ventricle and 5L/min is returning to the right ventricle. If the lungs aren’t working well then we need to capture at least 60% or so of this venous return and stick it through the oxygenator in order to maintain tolerable saturation of haemoglobin with oxygen. So in our example we’ll have to be siphoning off at least 3L/min from the venous return, putting it through the oxygenator and returning it back to the right side of the heart. With me so far? It is at this stage that we immediately run into one of the physics challenges of VV ECMO. Pulling off 3L/min of blood requires pipes of substantial diameter. Typically these are in the 23 to 27Fr range. (ie 8-9mm internal diameter). You want to place this drainage pipe somewhere where there is a high flow of blood in a large vessel capable of accommodating it. Typically this will be in the SVC or the IVC, typically reached by an insertion point in the IJ or femoral vein respectively. It becomes really quite tricky to drain more than 3L/min of blood (or 60% of the venous return) with a single pipe as you can really only drain either the SVC (venous return from the upper body) or the IVC (venous return from the lower body) and as should be obvious the venous return from the body is split between these. In addition to the limitations of the physical size of the pipes you have to remember that the vessels within which these pipes are placed are not rigid fixed stented things, they dilate and contract in response to intravascular volume and intravascular tone. If you try to suck blood out of them with too much negative pressure the vessels will collapse around the pipe blocking all the holes and stopping all drainage. All this to say that oxygenation is determined by the proportion of venous return we can divert through the ECMO machine. And capturing that venous return should be the priority when it comes to deciding on drainage pipe size and placement. once the blood is out of the body and through the oxygenator it turns out that it’s quite east to get it back into the budy. Pushing blood back into the body is much easier and can be done with a much smaller pipe. Pulling is harder than pushing in this context. The key factor in returning blood back to the body in VV ECMO is 1) it has to return to a vein, hence the second V in VV ECMO and 2) it needs to return to the venous circulation at a healthy distance from the drainage pipe. It would be bad form to return 3L/min of beautifully oxygenated blood directly into the inlet holes of the drainage pipe and through the circuit for a second entirely pointless run. We call this re circulation and we get around it by placing the tip of our return pipe somewhat remote to the access pipe. For example we could drain blood from the SVC and return it to the IVC or if both of our pipes were in the IVC we could ensure that the return of blood happens much closer to the heart in the IVC or even in the RA but importantly a healthy distance away from where the drainage pipe is in the IVC. Why would one want to initiate such a therapy? There are a number of indications, or should i say circumstances where VV ECMO might have a role. A reasonable list for examination purposes might run as follows. Refractory hypoxaemia is a good coverall term but better teased out into some specifics below; ARDS where you can’t maintain safe settings on a ventilator or safe numbers in terms of oxygenation and CO2 clearance of note you can squeeze in almost every pathologic lung condition under the ARDS umbrella so think pneumonia, pulm vasculitis etc… this is the vast majority of VV ECMO runs. primary graft dysfunction post lung transplant refractory asthma a bronchopleural fistula where continuing to ventilate with pressure is probably not the best thing for healing the hole in the lung. refractory hypercapnoea where the hypercapnoea is causing life threatening problems despite a thorough effort to fix it the occasional slightly bonkers airway surgery where you may have no means to oxygenate or ventilate for a substantial period of time There is lots of debate and indeed variations in practice on when you might initiate VV ECMO. There are a number of published criteria for when ECMO is indicated but you have to remember that a single PaO2 of 6.5kPa on 100% does not actually tell you how sick a patient is or if you’ve truly exhausted your conventional management. Either way at the end of a viva question on management strategies for severe ARDS, once you’ve been through high PEEPs, permissive hypercapnoea, diuresis, proning, and a nuanced discussion on steroids and nitric you should probably mention VV ECMO. It’s worth noting some reasons when doing VV ECMO is not a great idea. As with almost all intensive care organ supports there’s not much point in adding it if you don’t have a way to fix the underlying organ. For example, if you have ARDS from pneumonia we can probably fix that, however if you have end stage COPD we can’t fix that. Adding the device will not change things. There are some programs who will use VV ECMO as a bridge to transplant but this is beyond the scope of this post. But it is commonly used in the immediate post lung tx phase when the new lungs are a bit heavy, wet and not working too well. If your circulation is falling apart and you’re on 2mcg/kg/min of noradrenaline and the LV is clapped out from septic cardiomyopathy then it’s hard to see how fixing the hypoxic part of the multiorgan failure is going to turn things around. That being said if you’re hypoxic with a struggling RV then adding VV ECMO might be enough to correct the circulatory issues simply by fixing the hypoxia and hypercarbia. If you wanted to end your SAQ with a flourish and add some complications then a convenient top 5 might run as follows bleeding bleeding bleeding clotting bleeding I am of course being a little bit facetious here but i’m not that far off the mark. Anticoagulation is typically used to keep the VV ECMO circuit running but even on those without anticoagulation they still bleed. And the bleeding is often spontaneously into non compressible sites like the pleura, GI tract or retroperitoneum. References: Oh chapter 41 The ELSO red book Alfred ECMO Site

Welcome back to the tasty morsels of critical care podcast. Way back in the way back in tasty morsel number 43 we discussed inotropes and vasopressors but there was a noticeable AHD analogue shaped hole in that post that i promised to discuss at a future stage. Well, that time has come and it’s time to run through vasopressin. You probably first encourntered vasopressin when you heard about ADH in medical school. Anti diruetic hormone, named for what it stops Its discussion in medical school involved delving into the world of endocrinology and negative feedback loops. Something we will be studiously avoiding here. Vasopressin is an ADH analogue, very simillar in structure with very similar effects. As such vasopresin exhibits the same ADH effects but this maxes out at very low doses, much lower than what we use in sepsis. At the very high doses we use, much higher than the pituitary can secrete, it acts as a pure pressor without the inotropic effect we’re use to when using more familiar agents like noradrenaline or adrenaline. How does it work? Well this is where the fun beings. We’re used to messing around with the adrenergic receptors but vasopressin opens up a whole new bunch of confusing letters that have a whole myriad of effects. Some of these receptors are even shared with other molecules like oxytocin. The main we’re interested in is the V1 receptor, this is found throughout vascular smooth muscle. Stimulating it causes calcium release from the sarcoplasmic reticulum leading to increased vascular tone. Note noradrenaline has the same mechanism (ca release) just through a different receptor. This vasoconstriction affects pretty much all the vasculature including things like the coronaries (not so good) but does seem to spare the pulmonary arteries meaning it may be good in those with pulmonary hypertension. What other receptors is it worth knowing about? both for exams and the all important one-upmanship on the ward round. V2 receptors are mainly in the renal collecting ducts, this is where we get the ADH effect primarily be increasing the number and effect of something called aquaporin 2 channels. The V3 receptor causes increased ACTH, increasing cortisol secretion, and then there are the OTR and P2 receptors which my notes make no elaboration upon and i will make the dangerous assumption that they have no relevance to what we do in ICM. Why pull out the vaso when we can get the same vasopressor effect from our beloved noradrenaline. In theory the vasopressin receptors should remain fully funcitonal in the depths of horrific metabolic acidosis that has led your patient into intensive care, the same acidosis in theory should be causing issues with the effectiveness of your catecholamines. It should cause less pulmonary arterial constriction than a catecholamine and should even have less tachyphylaxis. the above list of advantages seems to come straight from the manufacturers advert, so why doesn’t it come pre attached to every patient? The issue gets a bit clouded due to the somewhat clouded evidence base. I’m going to run through a few of the bigger name trials that one may trot out in a viva type setting, and with all good controversial issues in ICM you could easily go the track of “on the one hand this and the other hand that” and come up with an answer with both buttocks firmly on the fence of the issue. First up is the VASST trial, (Russel et al 2008 NEJM). Done in North America and Oz, they enrolled septic patients and randomised them to vasopressin vs a blinded infusion of 15mcg/min of norad. Once maxed out on the study drug, then open label additional norad could then be titrated to keep the MAP at target. Enrolled 800 fairly typical ICU patients, and found a 35% vs 39% mortality benefit favouring the vaso but of course this was below the somewhat arbitrary statistical significance. A somewhat underwhelming start Second is the VANISH trial by Gordon et al, JAMA 2016. This was closer to home in the UK, with 18 ICUs. Septic patients randomised similar to the VASST trial, vaso vs blinded norad, this time at 12mcg/min. Primary outcome here was kidney based rather than mortality. 400 pts here, no clear benefit for vaso. Again, hardly compelling Enter the meta analysis. Nagendran 2019 in CCM. This was of a decent standard being not just a mix of numbers from the trials but an individual patient meta analysis that takes individual patient data points rather than the trial aggregate. This included all the trials but unsurprisingly VASST and VANISH make up most of the numbers. No mortality benefit found but there was less need for CRRT and less arrhythmias. There was some more digital ischaemia but no clear sign of increased mesenteric ischaemia. Hence the “on the one hand this, on the other hand that” and widely varying opinions on use of vaso. It would be perfectly reasonable to say this drug adds nothing to usual practice and i’ll stick with my catecholamines. And lots of other reasonable people look at the data and say, well this is a catecholamine sparing agent and is a balanced approach to receptor manipulation and just might spare a few filters. As you can imagine (though please don’t actually imagine this) my buttocks remain firmly on the fence getting splinters. Reading Deranged Physiology LITFL Russell, J. A. et al. Vasopressin versus norepinephrine infusion in patients with septic shock. New Engl J Medicine 358, 877–87 (2008). Gordon, A. C. et al. Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial. Jama 316, 509–518 (2016). Nagendran, M. et al. Vasopressin in septic shock: an individual patient data meta-analysis of randomised controlled trials. Intens Care Med 45, 844–855 (2019).

Welcome back to the tasty morsels of critical care podcast. Today we’re going to verge into challenging territory for an audio podcast in that we’re going to the discuss the very visual topic of dynamic LV outflow tract obstruction. This is something fairly dependent on echocardiography for diagnosis which as you can imagine translates poorly to audio format.  This also means you’ll be denied my interpretative dance as i simulate the mitral valve leaflets being pulled over towards the septum via the Venturi effect. But alas i digress. In essence dynamic LVOTO occurs when the closure point and tips of mitral valve tips are pulled into the left ventricular outflow tract during systole forming an anatomic obstruction to LV outflow thus reducing SV, CO, perfusion etc… This is reflected in poor blood pressure to which we respond by giving more catecholamines which makes this whole thing worse in a horrible cycle of nastiness. Perhaps it’s best to start by identifying contexts where we should be on the look out for this. We’ll start with sepsis. Sepsis is a state of low systemic vascular resistance leading to reduced preload and afterload in the heart. The LV receives less than usual volume to stretch it and the low afterload makes it incredibly easy for the LV to empty itself of this load. This results in a small cavity LV where the LVOT and the mitral valve find themselves in much closer proximity than they are normally used to. If it gets out of hand bits of the mitral valve find themselves in the LVOT itself causing all kinds of bother. The incidence of dynamic LVOTO in those with septic shock  is remarkably high and is reported to be  20% in one study from ICU echo guru Michel Slama. Even if it’s not that common it’s yet another reason why the super shocked patient should get a timely echo. So let’s say we’re worried about our septic patient: within that cohort who is at risk? Classically it would be the older person with LVH or a thickened septal bulge, sometimes called a sigmoid septum. Going with that is a stiff ventricle that fills poorly and has diastolic dysfunction. As noted at the beginning it’s clear that echo is a key part of the diagnosis here and if you do one you may see some of the baseline features just mentioned but with the addition of SAM or systolic anterior motion of the mitral valve. Most dynamic LVOTO has SAM but not all SAM has LVOTO. SAM can be quite a common out patient echo finding and so in addition to SAM you might want to look for flow acceleration. Just as a river approaching a narrow point accelerates and becomes turbulent so does blood flow in the LVOT approaching an unwelcome and intrusive mitral apparatus. This flow acceleration can be easily measured with doppler and produces characteristic patterns that get echo nerds like me all hot under the collar and is largely beyond the scope of the podcast. Before we get onto management I want to mention another at risk cohort. These are usually easy to spot as they return from theatre with a big sternotomy following an AV replacement or mitral valve repair. To take the example of the aortic valve. Aortic stenosis leads to severe LVH as the LV has to generate an enormous pressure to get the crusty calcified stenotic valve to open. The heart slowly adapts and learns to live with this very high afterload. Then one day someone opens their chest and pops in a nice shiny new valve that opens like a dream. The LV is not used to this and continues to eject blood like pompeii on a bad day. This hyperdynamic contraction in an LV not used to it has a tendency to drag the mitral apparatus into the LVOT forming an obstruction. Patients following MV repair are also at risk as the change in shape of the annulus and final position of the coaptation point at end repair can also lead to the MV getting pulled into the LVOT. If you’ve ever done the TOE board examinations you will curse yourself learning the 8 echocardiographic risk factors for SAM post MV repair… So we’ve talked about what it is, and a few at risk populations (sepsis and cardiac surgery). The clinical appearance is typically rapidly worsening shock and rising pressors, hypotension and rising lactate. Let’s say you’ve even managed to diagnose it using echo. How should you manage the thing? Increasing the preload can help, typically best done with volume expansion. Part of the mechanism here is an empty LV so filling it up can help. You can of course increase preload with noradrenaline but it comes with the unfortunate side effect of inotropy which is how we got into this mess in the first place. As such you find yourself having to do something quite uncomfortable and reduce or stop your catecholamines even when you think they might be keeping the patient alive. If that’s not bad enough, you probably want to swap them out for…. eughhh, and i struggle to say this… phenylephrine… Much derided and neglected it may well have a role here and it does hold the title of “pure alpha” and as such gives pressor effect without inotropy. Vasopressin is of course a reasonable option but as you know it is not the most titratable drug. The next step might make you even more uncomfortable. Understandably these patients are often very tachycardic. This tachycardia leaves less time for diastole, less time for cardiac filling, again worsening the LVOTO. As such beta blockers become a very attractive option. Even though beta blocking a very sick patient seems like a slightly insane idea. But of course you’ll only be doing this after a high quality, well interpreted echo that shows a hyperdynamic LV so that should give you a little reassurance. Esmolol is probably the agent of choice here given it’s titratability. The dosing can be tricksy as it’s in the mcg/kg/min range and is not a daily use drug for most of us. I tend to skip the loading dose. In other words look it up. Usually with filling and removal of inotropy and chronotropy you can ride it out and you should see some improvement in your haemodynamics. A failure to respond to treatment should make you question your diagnosis, that high lactate may well be due to dead gut rather than low output due to LVOTO. References Chapter 13, Oxford Textbook of Advanced Critical Care Echocardiography covers this nicely. Chauvet, J.-L. et al. Early dynamic left intraventricular obstruction is associated with hypovolemia and high mortality in septic shock patients. Critical Care 19, 1–8 (2015). Slama, M., Tribouilloy, C. & Maizel, J. Left ventricular outflow tract obstruction in ICU patients. Current Opinion in Critical Care 22, 260–266 (2016). Pollick, C., Shmueli, H., Maalouf, N. & Zadikany, R. H. Left ventricular cavity obliteration: Mechanism of the intracavitary gradient and differentiation from hypertrophic obstructive cardiomyopathy. Echocardiogr Mt Kisco N Y 37, 822–831 (2020). Deranged Physiology. (Also contains mention of the wonderfully named Brockenbrough–Braunwald-Morrow phenomenon, which seems ripe for morning ward round pontification)  

Welcome back to the tasty morsels of critical care podcast. Following hot on the heels of tasty morsel number 72 on cardio renal syndrome is its partner in nephron injury: hepatorenal syndrome. This gets covered in a sub section of Oh’s manual chapter 44 on liver issues but there are a variety of other sources mentioned at the end that are worth a read. It can be a little tricky to pin down this diagnosis. A lot of that comes because it is a “syndrome”, ie a collection of clinical findings that someone has put into a big bucket and mixed around without paying too much attention to hard core diagnostic information like histology or a true pathological diagnosis. To start with we need context. We should have an AKI in the setting of advanced chronic liver disease and portal hypertension ie cirrhosis. But of course there are multiple reasons for AKI in this context so we have to work through them a little before the label of hepatorenal gets attached. Our friends in the international club of ascites (yes that’s a thing, i didn’t make it up) suggest that you need an AKI with a failure to respond to simple things like withdrawal of nephrotoxic agents, treatment of infection and, importantly a decent trial of albumin. You also have to exclude intrinsic renal diseases that lose protein and blood but this is usually fairly straightforward to exclude. However you can quickly see that a lot of this is pretty nebulous and it can be hard to really draw a line under. As such it’s fair to say that your patient may have several causes for their AKI in cirrhosis and hepatorenal may only be part of the problem. To take hepatorenal per se, what’s the purported pathogenesis? Well we think that increasing portal venous pressures and cirrhosis leads to splanchnic vascular vasodilation. The vessels in our gut lose tone and we develop this chronic high output, low SVR state. This state of reduced pressure leads to activation of the RAAS causing increased resistance in the renal arteries (in distinction to the very low resistance state of the splanchnic vasculature). As such, perfusing pressure to the glomerulus falls and GFR falls. This is reflected in oliguria and the usual renal response to a crisis of hanging onto Na for all its worth with a urine Na typically <10 if you do go looking for it. In the background you’ve got all this chronic ascites that is adding to the compartment pressure in the abdomen making things worse. That’s the basic bedtime story version of the pathophys that i received, I understand there’s a competing theory where the chronic bacterial translocation of a leaky liver leads to a chronic inflammatory process buggering the kidneys but i digress. At this stage, it’s worth noting that just like our cardiorenal syndrome we can split hepatorenal into a couple of types. This is all about timing of onset. The in-patient with a rapidly rising creatinine in the hospital setting is more likely to have type I or acute HRS while the stable out patient cirrhotic with a gradually rising creatinine is going to have the type II or chronic HRS. HRS itself can be precipitated by the usual chronic liver disease decompensations – ie , bleeding, infection, SBP and also large volume paracentesces without appropriate albumin replacement. How should we treat. First off an important reminder that cirrhosis is not a reversible pathology and if you’re decompensating then the only real treatment to turn the whole thing around is a transplant. All the rest of it is a little bit like rearranging the deck chairs on the Titanic. I don’t mean to imply that the deck chairs should not be rearranged; rearranging the deck chairs may well lead to some meaningful short term outcomes and quality of life improvement but the hole in the hull from the iceberg isn’t going to get any better without the transplant. As mentioned in the diagnostic bit, they probably should’ve got some albumin. I don’t deny that albumin has a limited role in the ICU, gone are the days where we could make bold assertions about colloid osmotic pressures and how albumin was better than crystalloid. We studied it and it turns out it doesn’t seem to be any better than salty water. But i still think that in the livers it still has an important role and HRS is probably one of those scenarios. The data for its use in HRS is not exactly stellar, and no where near as good as it is say for albumin in ascites drainage in SBP where it has a mortality benefit. I confess i have done the sneaky move “push the MAP up to 75 mmHg” for a few days to see if that makes a difference but i can’t say I’m standing on solid ground doing that but it does get a mention in the relevant UpToDate article.  Of course given that we have access to terlipressin in Ireland and the UK, these types of haemodynamic manipulations could even be done on the ward before rushing to commit yourself to CRRT and an ICU admission. TIPS has been described to be helpful in improving renal function in HRS but only on a very limited basis so probably worth a discussion with your local liver experts but not something you can use evidence to make a compelling argument for. If the HRS fails to respond to such therapies then the option of CRRT is usually raised. This will indeed replace the failing kidney but like many things in intensive care, there’s not much point in starting it if there’s no chance of reversibility. Some HRS may be in the context of something like acute alcoholic hepatitis where the chance of recovery of some hepatic function is reasonable and hence a trial of the CRRT while the liver settles is reasonable. In addition if the patient is already on the transplant list then keeping them going with CRRT pending the transplant would also be reasonable. However the more common scenario is the burnt out cirrhotic who is having increasing frequency of decompensations. The prognosis here is dismal and adding more machines at the end of life is probably not going to help. The tricky bit for us is teasing out so much of what we’ve discussed above, eg is this one of the many other eminently reversible causes of AKI in the context of cirrhosis or is this all driven by the chronic progressive liver failure. This as you’ve probably discovered by now is a core part of ICM and best learnt in the unit and on the wards rather than on the podcast. Reading ICA Guidelines Deranged Physiology LITFL CCC

Welcome back to the tasty morsels of critical care podcast. Today we tackle a somewhat nebulous syndrome. Something we throw around with a few hand wavy explanations but often light on detail. Hopefully in a few minutes you’ll at least have a few morsels more of information to stave off all the trainees who are undoubtedly much smarter than you on the ward round. But perhaps I’m getting too autobiographical already. This does not appear with any great frequency in Oh’s manual but there is a nice scientific statement from the AHA that is referenced below. Though when you call it a statement you imagine some nervous spokesman in front of a camera trying to explain why is boss has done something naughty. Instead this is a 39 page epic review of the topic. To start with there are apparently 5 types of cardiorenal syndrome. I’ll let that sink in. You all thought there was one didn’t you? Type 1 is the acute deterioration in kidney function seen in cardiogenic shock from ACS. Type 2 is the slow and chronic deterioration of kidney function in the chronically failing heart. They get sneaky with type 3 calling it renocardiac syndrome. You see what they did there they just reversed cardiorenal syndrome and called it renocardiac syndrome. In this scenario the kidney has acutely been injured and the consequences such as fluid overload cause heart failure. Type 4 is again renocardiac with the kidneys causing the heart failure but on a chronic basis. With me so far? Type 5 is the big bucket where they put all the left over disease that cause both kidney and heart failure eg things like amyloid, or sepsis or cirrhosis. Certainly when i use the term in daily practice i was only ever thinking of types 1 and 2 and that’s what we’re going to focus on in this  tasty morsel. Why does this happen. I’ll paraphrase the opening part of the pathophys section from the scientific statement. Conventionally we focus on poor forward flow from the heart causing poor renal perfusion, poor GFR and activation of the RAAS. But in the style of a telemarketing TV advert “wait there’s more”. Poor forward flow is by no means the only pathology and in fact high pressures on the venous side likely contribute to the phenomenon of cardiorenal syndrome. for example we know that a MAP of 65mmHg is a generic target for perfusion pressure for most organ beds. However the actual calculation of perfusion pressure is probably better represented as MAP-CVP. Therefore in those with CVPs chronically sitting in the 10-15 range, you are going to struggle to effectively perfuse their kidneys. You’ll even here this called congestive renal failure on occasion. Along the same lines it’s worth thinking about the impact of intrabdominal pressure on renal perfusion, those with tense ascites from heart failure are also going to struggle. There are of course much more complex neurohumoral, inflammatory type cytokiney thingies going on but as you can tell they are well over my head so I’ve skipped them for now. You might think that diagnosis of cardiorenal syndrome might be straightforward. We just check a creatinine and if it’s high it’s a problem. But there are a fairly bewildering array of tests available for assessing renal function beyond the very blunt stick of creatinine. Things that rejoice in names like NGAL or cystatin C or looking at albuminuria; all may have a role in teasing out CRS from other issues. Valuable as it is for filling the 39 pages of the scientific statement i can’t see any great relevance to the jobbing intensivist. Of note in the paper, and perhaps obscured by the detail of the available biomarkers is the note that fluctuations in creatinine are often poor representations of actual kidney injury. I took home from this discussion that as long as they are still diuresing effectively we shouldn’t be in a rush to hold the diuretics purely because the creatinine bumped. Of note as part of the diagnostic work up the statement does give a shout out to the much maligned and greatly missed PAC. This might allow us to effectively assess congestion while avoiding the terrors of hypoperfusion from volume removal. Moving swiftly on to management strategies I think it’s clear that diuretics have a clear role in congested heart failure patients. However there does seem to be a reluctance to give diuretics once the creatinine bumps up anywhere above the normal range. There is a pervasive (and unfounded) belief that loop diuretics are directly nephrotoxic and as such should not be given. But if we’ve been paying attention so far we’ll realise that congestion itself may be causing the kidney injury and decongestion may well fix things. Now of course we need to be a doctor about this and have a think about other causes of AKI beyond simple congestion but for the sake of the podcast we will assume that we have the correct diagnosis. Let’s say we have done the right thing and given a decent dose of loop diuretic despite the bump in the creatinine, we often encounter something called the “braking phenomenon”. This refers to the idea that we get less and less response to each successive dose of diuretic, and this can develop over hours. The pathophys of this is beyond the scope of this podcast but involves the nephron doing what it does best in a crisis and tries to hold on to more sodium. You can get around this by making a flanking attack on the nephron by bringing in something like a thiazide in addition. Indeed the concept of the Nephron Bomb covered in tasty morsel 68 (first made popular to me by Joel Topf known as kidneyboy on twitter) is a clinically compelling and somewhat entertaining way to approach pharmacology of diuresis. Of note there comes a certain point where no matter the diuretic stratgey the volume of wee wee produced is insufficient. And this indeed portends a poor prognosis. Ultrafiltration with whatever mode of RRT you choose seems a compelling option but has performed poorly in most trials to date. Either because it simply doesn’t work or possibly because those sick enough to qualify for an ultrafiltration trial have already found themselves in a category of patients likely to do poorly no matter what. This segues relatively nicely into a section of the document on palliative care. It is important to realise that a referral to ICU for refractory cardiorenal syndrome may simply be a sign that the patient is reaching end of life. Adding an extra machine to a patient at end of life is not good form and it is incumbent upon us to do the work to figure out if we have some degree of reversibility (eg from acute congestion) or if this is just progression of an underlying irreversible disease process Reading: – Rangaswami, J. et al. Cardiorenal Syndrome: Classification, Pathophysiology, Diagnosis, and Treatment Strategies: A Scientific Statement From the American Heart Association. Circulation 139, e840–e878 (2019). – Mullens, W., Verbrugge, F. H., Nijst, P. & Tang, W. H. W. Renal sodium avidity in heart failure: from pathophysiology to treatment strategies. Eur Heart J 38, 1872–1882 (2017). – Mullens, W. et al. Evaluation of kidney function throughout the heart failure trajectory – a position statement from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 22, 584–603 (2020).