38 episodes

Bite size chunks of critical care medicine targeted at fellowship exam preparation

Tasty Morsels of Critical Care Andy Neill

    • Medicine

Bite size chunks of critical care medicine targeted at fellowship exam preparation

    Tasty Morsels of Critical Care 037 | Serotonin Syndrome

    Tasty Morsels of Critical Care 037 | Serotonin Syndrome

    Welcome back to the tasty morsels of critical care podcast. A meandering monologue through critical care fellowship exam preparation.

    This week: serotonin syndrome. Much talked about, very common in an exam, quite rare in real life. It doesn’t really get much coverage in Oh’s manual so the following is prepared from the hodge podge of resources listed at the end.

    In normal circumstances we produce serotonin from tryptophan. There are a bunch of complicated pathways and mechanisms that are as usual more beyond my comprehension as opposed to beyond the scope of this article. Serotonin does masquerade under its alternate name of 5-hydroxytriptamine which in turn has bred a whole range of receptors of which most relevant is the 5HT2A receptor.

    The other piece of the puzzle here is monoamine oxidase (MAO). This enzyme is responsible for metabolism of serotonin. So when we give drugs that inhibit MAO we can also get into trouble

    So in summary 5HT (pseudonym for serotonin) stimulates neurons through a variety of receptors but the 5HT2A receptor is the one that gets us into bother with serotonin syndrome. We can get into bother by having too much 5HT stimulating the 5HT2A receptor or we can get into bother by not getting rid of 5HT with MAO when we need to. Clear as mud I’m sure.

    This is all very interesting but it’s clear from the now somewhat dated 2005 NEJM review article that this piece of knowledge is only the tip of the iceberg in terms of its pathophysiology. Though rest assured the tip of the iceberg is likely to be enough for exam purposes.

    In terms of clinical presentation it’s clear that it exists as a spectrum from mild to ICU level. A common mnemonic used is CAN



    * CNS dysfunction

    * Autonomic disturbance

    * Neuromuscular effects



    To flesh this out in bullet point form, these are the type of features we’re looking for:



    * onset 24 hrs

    * big pupils

    * tremor

    * clonus (esp spontaneous)

    * hyperreflexia

    * fever

    * autonomic issues

    * rapid resolution within 24 hrs with treatment

    * hyperactive bowel sounds (you may snigger at the inclusion of BS here but in terms of distinguishing this from its examinable partner, NMS, the presence of hyperactive bowel sounds may be one of the few if only indication to listen for them)



    The proposed algorithm for diagnosis here is the Hunter criteria. Named for the lush area of NSW where they make nice semillion wine and have the Hunter Valley Toxicology service that named this a few years ago. It is a step wise algorithm that in the limited science available claims a 95% specificity for diagnosis. This is one of those algorithms (like the CAM-ICU) that refuses to stay in my brain so invariably I end up looking it up. Sadly this is not an option in an exam.

    It is important to remember that this algorithm only applies in the presence of a serotonergic agent. There is, it seems a quite large number of agents to populate this list. Some of them are obvious with the clues in the name like Selective Serotonin Reuptake Inhibitors (SSRIs) or Monamine Oxidase Inhibitors (MAOI). There are however, a few unusual ones such as linezolid (which acts as an MAOI), fentanyl (which is serotonergic) and usual tox favourites such as cocaine. Tramadol is on the list, which is unsurpising given that it won 1st prize at the recent Toxicology awards for filthiest side effect and interaction profile ever. The final two worth noting are lithium (which can increase sensitivity to 5HT) and methylene blue which sort of acts like a toxicology double agent by playing the hero in methhaemolobinaemia then stabbing you in the back with a serotonin syndrome.

    Overall expect to see this in 2 scenarios



    * the overdose of a single serotonergic agent – th...

    • 6 min
    Tasty Morsels of Critical Care 036 | Oxygen

    Tasty Morsels of Critical Care 036 | Oxygen

    Welcome back to the tasty morsels of critical care podcast. A meandering monologue through critical care fellowship exam preparation.

    Today we’re talking a little about that most vital of gases – oxygen. This is going to be back to some very basic physiology from Oh’s Manual Chapter 28, that I probably should have learnt in medical school but honestly looking back I’m not sure I learnt anything in medical school except how to scrape by with the minimum of effort and knowledge. My post graduate career has been somewhat more enthusiastic I might add.

    Oxygen is that vital substance that we need in order to conduct oxidative phosphorylation which is the body’s most efficient means of producing ATP.

    For oxygen to get from, say, my left nostril, to a skeletal myocyte in my right tibialis anterior, it has to go through roughly 5 steps



    * convection of O2 to alveoli (this is ventilation)

    * diffusion through alveolar membrane

    * reversible bonding with Hb

    * transport to tissues (CO dependant)

    * diffusion to cells and organelles



    Let’s run through that in a  little more detail. Oxygen is drawn in through the big bellows of the lungs and at the alveolus it meets its first real challenge – how to get across the membrane. Here, it obeys Fick’s law of diffusion, where “the rate of diffusion is proportional to both the surface area and concentration difference and is inversely proportional to the thickness of the membrane”. In other words when there’s lots of membrane that is very thin, and not very much oxygen on the other side of the membrane then diffusion is at its best. In apnoea for example the continued blood flow through the lungs draws away any O2 increasing the gradient across the membrane. O2 is drawn through the membrane and in turn more O2 is drawn from the larger airways. This is one reason why apnoeic oxygenation works so well, we see this perhaps most dramatically during the apnoea testing for brainstem death. Simply maintaining a high concentration of O2 in the airways will continue to keep a patient oxygenated even in the absence of bulk flow of gas through breathing.

    Once diffused into the blood it then joins up with its best friend forever – haemoglobin. Oxygen would much rather be joined to Hb than merely dissolved in the blood. At this stage I am legally required to mention the oxygen-Hb dissociation curve. Despite years of doing this I still cannot get my the left and right shifts stuck in my head. What has stuck in my head is the intelligent adaptation of a system that encourages oxygen offload in areas of the body that are hot, full of CO2 and acidotic – for example muscles working at high load. This might be a rightward or a leftward shift, I really can’t remember but thankfully the human body seems to do it without my input so all is well.

    This oxy-Hb relationship allows us to move large amounts of oxygen around the body fairly easily. However, of course it is dependant on the cardiac output to get it to where it needs to go. The amount of oxygen the pump can deliver is dependant on flow but also on the oxygen content of the blood. An Hb of 15 will carry more oxygen for a CO of 5L/min than an Hb of 10 for a CO of 5L/min. The oxygen carrying capacity of the blood combined with the CO can be put together to form the oft cited DO2. DO2 is one of those abbreviations for a physiologic concept that has an off little dot above one of the letters and superscript 2 making it altogether difficult to reproduce online without a bewildering number of keyboard shortcuts. DO2 is also best discussed with reference to its partner VO2, indeed combined you can use the term DO2:VO2 relationships in a physiology discussion on a ward round and pray no one asks a follow up question. Perhaps something actually worth knowing is that resting oxygen delivery (DO2) comes in at roug...

    • 5 min
    Tasty Morsels of Critical Care 035 | When to start CRRT

    Tasty Morsels of Critical Care 035 | When to start CRRT

    Welcome back to the tasty morsels of critical care podcast. A meandering monologue through critical care fellowship exam preparation.

    Today we’ll talk about CRRT timing. When should your critically ill patient take a spin on the green machine?

    From an exam point of view this can go a few directions. You can go core physiology or you can go down the literature route. I think both are worth covering.

    Oh Chapter 48 has a list of indications that include:



    * volume overload

    * electrolyte issues – classically refractory hyperkalaemia

    * severe acidosis

    * uraemic symptoms inc pericarditis

    * progressive AKI (oliguia or anuria, high creat/urea)

    * Oh also has temp>40 as an indication

    * Dialysable toxin



    These all seem fairly reasonable.

    There is an interesting concept called the furosemide stress test that was first described by Chawla in 2013 and then repeated by Rewa in 2019. The concept here is that you can use the response to furosemide to predict the need for CRRT. The dose is between 1 and 1.5mg/kg of furosemide looking for >200 mls of urine in the first 2 hrs. If it’s less then wheel out the green machine and get started. Of note it is not used to determine who is ready to stop CRRT which seems to be a much slippier beast that i’ll mention at the end.

    Physiology over and done with for now let’s look at the literature that looks at this question. The papers here are all classics in intensive care and a careful student of the discipline should have a passing familiarity with all of them (and I am not even going to cover all of them!)

    Once upon time there was the AKIKI trial led by Gaudry and published in NEJM in 2016. This was a French study (side bar – i know the locations are largely irrelevant to the science here but the location makes it so much easier for me to remember as I can picture a polo necked french man with onions round his neck as a means to remember the paper). Anyhow. Once you had stage III AKI then you could be randomised to CRRT or wait till a solid indication like hyperkalaemia developed. They included 600 mainly medically septic and ventilated patients. Mortality was pretty much the same and of note only 50% actually ended up needing CRRT in the delayed group which is a recurrent theme worth noticing.

    In the same year, Zarbock and the Germans published in JAMA the ELAIN trial. Again, randomised but single centre and enrolled patients at an earlier stage (stage 2 by KDIGO). They got 200 pts with a 40% v 50% mortality favouring early CRRT. Of note these were almost all surgery patients but the mortality benefit was big enough to attract attention with the idea that getting in early with CRRT was key.

    Next enter the IDEAL-ICU trial by Barbar in 2018 which is yet another French multi centre RCT which randomised septic shock patients to CRRT or not at 12 hrs after meeting the F on the RIFLE criteria. They wanted 800 pts and got 500 pts and abandoned it due to futility with no difference between the groups. Of note again almost half in the delayed group did not end up getting CRRT.

    Now enter the START-AKI trial, the most recent and potentially practice changing study in the field. This is one of the current generation of ICU mega trials where all the great and good critical trials groups get together and put out a trial to end all trials. They randomised at 170 different sites, and included patients with a stage 2 or 3 AKI to either immediate CRRT or wait till a traditional indication developed. This trial took in 3000 patients and found no benefit of the early CRRT but again noted that 40% in the delayed group never needed CRRT.

    Putting this altogether it seems that we probably pull the trigger on CRRT a little early. I know when i see someone on 2 pressors that are both escalating and ...

    • 5 min
    Tasty Morsels of Critical Care 034 | Chemotherapy agents and intensive care

    Tasty Morsels of Critical Care 034 | Chemotherapy agents and intensive care

    Welcome back to the tasty morsels of critical care podcast. A meandering monologue through critical care fellowship exam preparation.

    If you were tuning in to try and pick up some core exam level content then this is probably not it. However, it is what came up in my non-random, semi alphabetical by system, trawl through my notes that forms the basis for the order I write these in.

    We’re going to spend 5 minutes on chemo agents in the ICU. Roughly hewn from the stone tablet of Oh Chapter 46 on solid tumours in intensive care.

    This is perhaps not something that will be top of the list in exams and certainly for clinical practice you are not going to be prescribing any of these agents. However a passing familiarity with some of the commoner ones, (or at least the ones that are more likely to run the risk of an ICU admission) is probably worth while.

    Table 46.1 has a table that covers two pages of scrolling on my browser and includes many drugs that I have never heard of or can’t pronounce or both. Thankfully the next segment has a much smaller selection of “specific chemo induced toxicities” and we’ll try and cover at least that much today.

    First up – bleomycin lung injury. Bleomycin is actually an antimicrobial used in a variety of head and neck and gynae tumours and Hodgkins. The pneumonitis can occur in up to 40% (though the corresponding up to date article puts it at more like 15%) and can be fatal. There is generation of oxygen free radicals with corresponding fibrosing alveolitis that is actually worsened with oxygen therapy. If this sounds familiar, then the insecticide paraquat does a very similar thing but is, I suspect, much less useful in treating cancer. In terms of treatment it seems that just like in ARDS, the terms fibrosing alveolitis and high dose pulsed methyl pred are inexplicably connected.

    Second on our list is ifosfamide related neurotoxicity. Ifosfamide is an alkylating agent used in a broad range of tumours and is well known for causing an encephalopathy in 10-20% of patients. It is a diagnosis of context and exclusion. I have heard it discussed, if not diagnosed on several occasions by oncologists with patients in the ICU and one was even given methylene blue which is a somewhat established antidote of sorts through some mechanism of MAO activity. However it turns out that guidelines from the European Society for Medical Oncology specifically recommend against giving it so maybe forget i just said that and instead cite them in opposition to any oncologists wandering into your ICU with little blue vials.

    Coming in at number 3 is anthracycline related cardiomyopathy. There are a number of drugs in this category all ending in rubicin and seem to be used fairly widely. There are two parts to this. Firstly, there can be an acute cardiomyopathy, sometimes with arrhythmias that happens early and secondly, a more chronic cardiomyopathy that can happen months to years after the drug has been given. The mechanism has too many proposed options to be memorable but reactive oxygen species seem to have at least some role.

    Last but by no means least are the immunotherapy agents. This is chemo Jim, but not as we know it. Melanoma appears to be the poster child for the agents here. There seem to be a broad variety of agents and mechanisms that fall under the term immunotherapy but the check point inhibitors are probably the most well known. The immune system has various check points as such to stop the cellular militia getting too carried away. The check point inhibtors effectively remove these check points and let the immune system go wild on whatever foreign tumour antigen it can get its hands on. Mechanistically this is genius as a therapy but as you can imagine there can be a few issues with getting the g...

    • 4 min
    Tasty Morsels of Critical Care 033 | Pre-eclampsia

    Tasty Morsels of Critical Care 033 | Pre-eclampsia

    Welcome back to the tasty morsels of critical care podcast. A meandering monologue through critical care fellowship exam preparation.

    Today we’re looking at Oh Chapter 64 covering some of the absolute basics of pre eclampsia. ICU level pre eclampsia is rare. In Ireland most of it is managed in separate obstetric hospitals by the obstetricians and the anaesthetists. And given that the definitive treatment is removing the baby from the mother, it turns out that this will typically have been done before we even get involved. Unfortunately its rarity does not get us out of having to know it very well as it is an exam favourite.

    Firstly some definitions. To have pre eclampsia you’ll need to have



    * new onset of hypertension with proterinuria OR

    * new onset of hypertension with end organ damage (inc foetal growth issues)



    Hypertension here defined as BP >140/90 and proteinuria as >300mg/24hrs or protein +ve on a dipstick.

    To have eclampsia you simply need to have seizures in addition to the above.

    To summarise the cause and pathogenesis, the short answer is we don’t know. The longer answer is – we still don’t know but we have lots of science to show it and the medium length, exam appropriate answer answer that I might be able to reproduce is a straight quote from deranged physiology:

    [pre eclampsia is] a systemic response to placental hypoperfusion, with increased activation of the potent vasoconstrictor endothelin-1, as well as an increased sensitivity to vasoconstrictors in general, and a down-regulation of vasodilatory mechanisms such as nitric oxide synthase.

    The clinical presentation of pre-eclampsia from a critical care perspective is best split into organ systems



    * Cardiovascular: hypertension is the main player here. You’ll see increased SVR also

    * Neurological: early signs can be headache and visual symptoms. You will see hyperreflexia if you look for it and you probably should. But with progression you’ll start seeing seizures, cerebral oedema and even ICH

    * Renal: protein loss is obvious but the fancy term to pull out is renal endotheliosis which is a form of thrombotic microangiopathy or TMA. A topic that deserves its own post.

    * Haematologic: low platelets but also impaired function. This might come as part of HELLP syndrome

    * Hepatic: HELLP syndrome is part of this but the most dramatic complication can be hepatic rupture which as you can imagine is somewhat bleedy



    While rare you can even get pre eclampsia in the post partum patient and I always liked the quip from Mel Herbert of EMRAP fame, that the usual definitive treatment of pre eclampsia is of course to deliver the baby but if it’s post partum what are we meant to do? put it back in again?

    We are unlikely to be given the job of ridding the woman of the placenta so we can instead usefully occupy ourselves with supporting the various failing organ systems. The priorities here will be



    * seizure prevention and treatment.

    * BP control

    * maintaining placental perfusion



    Seizure control here should lead to a brainstem level reflex of magnesium prescription. The indication is described as eclampsia or imminent risk of eclampsia and BP is often in the 160/110 range by this stage. Recommendations are 4g magnesium over 5 mins followed by 1g/hr as an infusion. Any further seizures can be treated with another 2g of magnesium. The NICE guidance on this has a carefully worded phrase t...

    • 5 min
    Tasty Morsels of Critical Care 032 | Nutritional requirements in ICU

    Tasty Morsels of Critical Care 032 | Nutritional requirements in ICU

    Welcome back to the tasty morsels of critical care podcast. A meandering monologue through critical care fellowship exam preparation.

    Today’s podcast is mostly taken from Oh’s manual Chapter 96 covering critical care nutrition. Something we all know and love deeply for exams and then immediately outsource to our dieticians the moment we get the chance.

    Perhaps the first take home figure is 25kCal/kg/day. This has been around as a recommended energy intake since the late 90s. And like most nutritional things it’s not exactly stellar in its support from the literature. There has been a recent tread in trials towards hypocaloric feeding that have hinted towards benefit at feeding to a lower target with purported mechanisms including that higher targets suppress autophagy which is an important part of killing nasty organisms. The lower target has not panned out as yet but it is worth pointing out that we rarely actually achieve the 25kCal/kg/day that we aim for, so we are probably inadvertently underfeeding people at baseline. On the other side of this it’s clear that if we have prolonged periods of not meeting targets then patients clearly do worse.

    We could, of course, measure the energy requirements the patient needs instead of a blanket recommendation for all. And there are a variety of methods for doing this. Oh describes indirect calorimetry as “a rather burdensome gold standard” and it seems all the units I have worked in have taken this on board and simply not bothered with getting the metabolic cart needed for doing it. This device, when connected to the vent allows measurement of O2 consumption and CO2 production, and can calculate energy expenditure.

    The other options for estimating energy expenditure include a bunch of equations of which the Penn-State one is recommended as the best of a bad bunch and finally you can calculate using the reverse Fick method which needs a PA catheter to measure O2 consumption. I mention these only as useful options for a candidate to scribble down in answer to a question rather than perform them in real life.

    As the good book says, man shall not live by kCal alone so we need to consider what else the patient needs nutritionally. First off – protein. For normal people walking around their everyday business not attached to pressors or a ventilator the daily protein intake is around 0.8g/kg/day. In the critically ill this has been bumped up to at least 1.2g/kg/day or even has high 2g/kg/day in some of the super catabolic patients such as major burns.

    For bonus points remember that patients require all the micronutrients such as vitamins, thiamine and elements that come as part of a healthy diet. Most enteral formulations will contain these and it’s really in those on parenteral nutrition that you need to stress a little more about it.

    When calculating the energy intake we need to consider all the sources of intake. Energy is not just glucose but will include the protein that we give and also some of the infusions we use for example the fats in the propofol infusion (which comes in at ~1kCal/ml) and the glucose in the 5% dextrose we’re giving to correct the hypernatraemia.

    References

    Oh’s Manual Chapter 96

    Deranged Physiology – there is a lovely section on the theoretical maximum and minimum amounts of each class needed including some lovely stuff on inuits and zero carb diets

    • 3 min

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