Tasty Morsels of Critical Care

Welcome back to the tasty morsels of critical care podcast. Today we look at blunt cerebrovascular injury or BCVI. I added this to my list to cover for unclear reasons as when i looked back at my notes i had about 8 bullet points and a couple of referenced articles. So this will be shorter than usual I suspect. Effectively this refers to injuries to the carotids and vertebral arteries in the context of trauma. The pathology here is typically a pinch, twist or stretch of the vessel leading to an intimal tear in the vessel. The exposed endothelium then is a nidus for thrombus formation. The main downstream consequence is stroke and it’s a real shame to have a successful haemostatic and surgical resus of a major trauma patient only to have them suffer a life changing stroke 3 days into their hospital stay. They’re also pretty tricksy injuries as there are rarely obvious clinical signs to indicate their presence until they you find the dense hemiplegia, so this is one of those things were the term “index of suspicion” comes into play. It is especially important seeing as we have now effectively outsourced all diagnosis to the radiologists and these injuries are not picked up on the typical trauma pan scan that we so love. Given that I described the pathology of the injury as pinching, twisting and stretching we can probably get a sense of the mechanism of injury associated with these injuries. Top of the list here are c-spine injuries – if the neck has moved enough to break it you should think about the delicate blood vessels beside the c-spine. This is particularly pertinent to the vertebrals whose course, evolution in her wisdom, placed inside the tiny little vertebral foramen transversarium of the c spine itself. To make life more difficult for the poor little vertebrals they have to navigate a few 90 degree turns to get between C1 and the skull to get into the foramen magnum. This is reflected in the higher incidence of BCVI in high spine injuries. Obvious other associations are with severity of TBI and complex facial fractures (remember the carotid has to navigate its way past these). You might get some pointers to diagnosis from your clinical exam. Horner’s syndrome would be a classic (disruption to sympathetic neurons in the carotid) but if you’re diagnosing a Horner’s syndrome in your primary survey then you’re either over achieving or doing it wrong or possibly both. They may have stroke features on arrival which would be an obvious trigger for imaging. A bruit is also listed as a sign of injury but I think that’s a sign for better clinicians than you or I. Most of the time you will have an injured patient without specific symptoms of BCVI. Who do we pursue further imaging on given that I’ve already noted the initial trauma pan scan will often not pick up this? Enter stage left the geographically titled criteria each named after the academic centre that developed it. Denver, Memphis and Boston have all contributed a published criteria. The Denver criteria appear to be the most commonly used and referenced. I think listing the individual components is probably beyond the scope of the post but I’d emphasise the main headlines c-spine injuries facial fractures complex base of skull severe TBIs hanging Once you’ve decided the patient needs imaging then you should be reaching for our trusty friend the CT scanner. in this case a well done CT angiogram of the neck vessels extending into the intracranial vessels. It is not (unsurprisingly) a perfect test but it is a very good test and certainly where you should start. If you do find a BCVI you may even have the joy of seeing it classified I to V according to the wonderfully named Biffl classification system. It covers things like intimal tears and degrees of narrowing and occlusion. once you’ve found a BCVI it’s unclear who your go to specialist might be and I have seen vascular, neurosurgery and stroke all give opinions on treatment. Overall risk of stroke in BCVI is ~8% but changes significantly depending on grade with higher grades having higher stroke risk. For the vast majority of patients your treatment options come down to heparin vs aspirin. There does not appear to be a clear proven superiority of one strategy over the other. Some form of antithrombotic does, in observational data, seem to reduce stroke rate and is probably worth doing. Aspirin is generally easier delivered and seems to be the most common choice in our region. Many of the injuries would actually be amenable to surgical repair but the vast majority are surgically inaccessible hence the antithrombotic treatment as next best thing. The decision to give something that makes clotting more difficult in a patient who is either still bleeding or at risk of major bleeding is not an easy one. Hence there is typically a day or two of hand wringing amongst several specialties till we are all comfortable giving it. Observational work suggests that we’re likely a little overcautious on this in a similar way to our reluctance to commence VTE prophylaxis in TBI. Reading Doctor’s Little Helper Radiopaedia      

Welcome back to the tasty morsels of critical care podcast. Today we look at something we do fairly frequently in ICU, especially in the post COVID era: prone positioning or to use its preferred technical term: adult tummy time. This has been around for a long time but was uncommonly done in the pre COVID days and was always a talking point when it did happen. But then 2020 came and you’d spend significant portions of the day proning and supinating patients in the unit. Fair to say it’s something we should have a keen understanding of. Firstly we’ll talk about the physiology and potential mechanism of benefit behind proning. This comes from the proning chapter in Tobin’s mechanical ventilation textbook. Written by none other than the late, great Gattanoni. He argues that there are 3 mechanisms by which proning affects ventilation and oxygenation changes in inflation redistribution of ventilation redistribution of perfusion A lot of this comes from Gattanoni’s early work where they managed to do a whole bunch of CT scans on critically people with ARDS in both the supine and the prone position. Yes you heard that right they did the CT scan prone. The typical CT scan for many ARDS patients is a basal dorsal distribution of disease. One would think that flipping the patient might redistribute this atelectasis to the ventral surface. But what seems to happen is more of a homogenisation of the lung with an overall improved inflation of the lung tissue. No longer are you just hyperinflating the baby lung and doing nothing for the atelectatic lung. This should lead to better recruitment, better perfusion/ventilation matching, better oxygenation and in turn better clinical outcomes. There are some suggestions it may also aid secretion clearance which in a paralysed supine patient is obviously a problem. Proning (as we shall we see) does seem to improve outcomes but the precise mechanism is unclear. Improved oxygenation seems plausible but it may also be a reduction in VILI by having a more homogenous lung that is less prone to injury of the baby lung. Guerin (lead PROSEVA author) wrote a nice review article in 2020 highlighting that proning can make chest wall compliance worse. The anterior ventral wall is normally more mobile than the dorsal chest wall. When prone the ventral bit is now wedged and immobile against the bed hence the fall in chest wall compliance. However lung compliance is probably improved and now that the chest wall is moving less it’s probably increased diaphragmatic movement that recruits the bases. Overall compliance should improve. We turn now to the evidence base for proning our patients. This, like many critical care interventions, this has a little bit of a narrative to it with some early trials lacking benefit followed by the paradigmatic trial that shapes practice. What follows is a brief summary of some of the important studies and is neither intended nor considered to be comprehensive. Back in the early noughties there were a flurry of RCTs looking at prone positioning in ARDS. The late and great Gattanoi was of course involved in some. The “dose” of proning was variable with sometimes only short periods like 6 hours being used. Results were variable and a 2011 meta analysis of 7 RCTs did not show a definitive mortality benefit but did suggest that those with the sicker lungs had a benefit Enter PROSEVA. A name, that if you’re going into an ICU viva, is probably something that you should keep in your head. This was 26 centres in France who were already experienced with proning. They took people with severe ARDS and randomised them to 16 hrs a day of proning vs no proning. They used mortality at 28 days as a primary outcome and they were looking for a 15% absolute reduction in mortality (which is pretty huge). It was, for obvious reasons, an open label trial. They enrolled 450 patients and found a 32% vs a 16% mortality favoring proning. It’s possible this trial found a benefit due to the dose – they proned for much longer than many of the other trials. It’s worth having some problems related to proning in your back pocket to pull out. The list of potential contraindications was initially quite long pre-COVID but it turns out that when your back is up against the wall we all became a little bolder with our proning. While you can prone the vast majority of patients it’s not going to be possible in those with unstable spinal injuries. One would think that abdominal surgery or advanced pregnancy might be a problem but you can usually work round this with some discussion with your surgeons. The main downsides (beyond the hassle factor) are related to safety. The facial oedema and skin injuries are not insignificant and no matter how careful you are some people just aren’t a great shape for proning. There is a chance that the ET tube can kink or dislodge either on the proning or on the head turns so you need to have a good plan in your head how to confirm this and get someone flipped back if they need it.   Reading Tobin Chapter 49 Deranged Physiology Prone Position and Mechanical Ventilation Guerin, C. et al. Prone Positioning in Severe Acute Respiratory Distress Syndrome. New England Journal of Medicine 368, 2159–2168 (2013). Guérin, C. et al. Prone position in ARDS patients: why, when, how and for whom. Intens Care Med 46, 2385–2396 (2020).

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. 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 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 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. 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. 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. 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 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. 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. 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).  

Welcome back to the tasty morsels of critical care podcast. Today we’re covering the ambitious topic of CRRT in the ICU. Something that occupies a central part of the daily job, but also occupies Oh Chapter 48, Irwin and Rippe chapter 201 and a few other review papers thrown in for good measure. We’re only going to get so far as the modes today so let’s not get too carried away. The obvious initial distinction in RRT modes is between IHD and CRRT with IHD being intermittent as the name suggests and CRRT being continuous. These are obvious temporal discriminators to do with how long the machine is attached to the patient but under the hood there are more fundamental differences between how the two modes work. In broad terms we can compare dialysis (the movement of small molecules across a membrane along an osmotic gradient) with ultrafiltration (the squeezing of plasma through a big sieve that retains the big bits of the plasma and lets the other bits leak out). The best analogy I’ve seen for this comes from one of my colleagues in his yearly introduction talk to RRT. Dialysis is the tea bag as ultrafiltration is to the espresso machine. Alas such simply categorisations fall by the way side when we encounter the actual workings of one of the big green machines in the unit as it often presents several modes to us. We can run a continuous heamofiltration, a continuous haemodialysis or a combo mode of continuous haemodialfiltration. These rejoice in the acronyms CVVH, CVVHD and CVVHDF respectively. Lets start with CVVH, continous venoveno heamofiltration. In this set up blood is drained from the venous side and entered a circuit initially under negative pressure then post pump becomes positive pressure. This positive pressure is used to force blood through a haemofilter containing many hollow fibre microtubules making up around a metre squared squeezed into that tiny plastic cylinder. Hydrostatic pressure drives the water into the filter compartment from the blood compartment with “solute drag” bringing along small and middle molecules with it. The principle here is convection with both the transmembrane pressure and the semipermeable barrier characteristics both contributing to how much filtrate is generated. The filtrate produced looks just like urine and collects in a big bag at the bottom of the machine. The yellow stuff contains things we want out of the body like potassium and urea. It is very easy to remove water from the body in this manner and in general if left to filter without replacement fluid then your patient will become very negative very quickly, hence the large 5L bags of replacement crystalloid fluid that run simultaneously as the yellow stuff is being produced. At its simplest the yellow ultrafiltrate has all the same concentrations in it as the plasma minus the large molecules like albumin. In pure CVVHD (continuous venovenous haemodialysis) the patient’s blood is on one side of a membrane with a dialysate fluid running in the opposite direction on the other side of the membrane. In this scenario solutes (such as Na and K and urea) leave the blood compartment to the dialysate compartment down a concentration gradient. In this scenario the water follows the solute which is in distinction to haemofiltration. When running CVVHD the dialysate flow rates are usually very modest at maybe 30ml/min in distinction to IHD dialysate flow rates of 500-800ml/min CVVHDF is a combination of the two with a little bit from column A and little bit from column B so to speak, with plasma being squeezed through the haemofilter and a modest counter current dialysate flow happening at the same time. The yellow stuff produced in this mode is a combination of ultrafiltrate and the spent dialysate that has passed through the filter. One would think that we’ve already covered enough acronyms for one day but unfortunately there are several other important ones still to cover, thankfully they use most of the physiological principles already covered. Let’s start with SCUF, slow continuous ultrafiltration. Simply put this is CVVHaemofiltration without fluid replacement. Blood enters a haemofilter and through the interaction of hydrostatic pressure and membrane characteristics ultrafiltrate is produced and the remaining blood is returned to the body minus some electrolytes and water. Because the electrolyte concentration in the ultrafiltrate is the same concentration as that in the blood there’s no major drops in Na or K to worry about as long as you don’t remove too much fluid. Solute clearance overall is very poor as effluent rates are more like 100-200/hr (~2ml/kg/hr) vs the usual 2000ml/hr (25ml/kg/hr) produced in CRRT. But this is not an issue as this is a mode that you use in someone who has reasonably working kidneys but has about 10 or 15 kg of water to remove. Removing 100-200ml of ultrafiltrate an hour will rapidly dry out your patient as you might imagine. The final ICU specific mode of RRT is probably SLED. Slow, Low efficiency Dialysis. It must be said that they’re really not selling it with a name like that and perhaps the inventors need to up their branding game a little. Unlike all the other modes so far this needs a standard IHD machine and the plumbing that goes with it. The idea here is to run the blood and dialysate flows at a much lower rate over a longer period of time. Given that it’s a diffusion mode it is much more effective at solute removal than CRRT. The idea is that your ICU patient can have a busy day with trips to CT, line changes, rehab activities and then get plugged in for the night shift to SLED to give the blood a nice wash ready for another day of clinical progress the next day. I have zero experience with this but people who do have it feel it’s the best thing since loaves came pre-cut up and ready for the toaster. CRRT is clearly ubiquitous in every day ICU practice and one might think this is due to an overwhelming collection of evidence suggesting its superiority over IHD but perhaps unsurprisingly such an evidence base supporting a mortality benefit does not exist and the stability and availability of CRRT has led to its current market leading position. There does seem to be a suggestion of better renal recovery with CRRT over IHD which might be related to less kidney hypoperfusing episodes of hyoptension when CRRT is used. Reading: Oh Chapter 40 Iriwin and Rippe 201 Deranged Physiology