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I haven’t managed to cover PE on the podcast yet. I have been involved in lots of small PE projects over the years and have developed something of an interest in it. I got invited to give a talk to the national EM conference this year and these podcasts are sort of the cliff notes version of that lecture. The full talk is linked to on the emergencymedicineireland.com website for those interested. I would emphasise that beyond the mention of the ESC guidelines this is an evidence lite podcast and more than usual represents opinions rather than hard science. The original talk was about PE in the resus room but I definitely think PE in the ICU in an established ICU patient is quite a different beast and I will try to highlight that as we go through it.

PE is so ubiquitous that I’m skipping a lot of the core pathophys and work up and instead want to split it into 2 parts, the first today on risk stratifying PE and the second on nuances of management in critical care.

PE is common in critical care. Either as a referral from ED with a patient with a nasty PE and bad physiology as the sole problem (less common) or as a finding in an ICU patient with other clinical issues, eg trauma or a surgical patient in whom you have now found a PE (a much more common scenario). From our perspective in ICU the test we need is a CT scan. I think all the other discussion about dimers etc is moot for us and if you need to exclude the diagnosis then CTPA is the way to go.

I think for the majority of the ICU population found to have a PE they are relatively innocuous. Yes they have PE but it is frequently quite small and not really contributing to their physiology. Yes they need anticoagulation but rarely anything more. There are a small cohort who need aggressive management of the clot and the physiology but these are much less common.

In terms of identifying the sick ones or risk stratifying them you need to be able to cite the ESC 2019 guidelines on PE. This is a substantial piece of work and is well worth a read. In that you will find PE can be split into low risk, intermediate risk, intermediate-high risk and high risk patients. However while a good starting place for risk stratification they remain a little blunt and don’t really tease out the super sick PE patients where the subtleties of management really come out.

Most of the ICU cohort will fall in the intermediate risk group who generally do very well as long as you anticoagulate them. It starts getting interesting in the intermediate-high and the high risk group. The intermediate-high group are identified with some form of right heart strain on CT or echo and a bump in a biomarker like troponin and BNP. If you add in low blood pressure then you’re in the high risk group. As noted this risk stratification is, in my opinion, a little too blunt to be of use in the ICU population where there are so many other reasons that the right heart might look funny or the BP low or the troponin raised.

How can we be a bit smarter with our risk stratification? Well firstly we need to decide if the low BP is being caused by the PE. Size of clot can be helpful here. If very small then it’s unlikely to be that significant. Especially if we have a much more clinically apparent cause of hypotension like the large empyema also seen on the CT scan. Particularly in the ICU population with multiple reasons for hypotension the pressure is on us to tease out which of the pathologies is causing the hypotension. If they are genuinely hypotensive because of the PE then lysis is probably inidicated – more on that next time.

With regards to clot size, however the opposite does not seem to be true: ie the presence of large clot, especially in the ED population does not seem to predict outcomes especially well. Instead of looking in the report for the size of the clot we would better served paying attention to the size of the right heart versus the left and for evidence of contrast reflux into the IVC. These are more useful in predicting right heart dysfunction.

An even more useful method is to look at the heart itself with an echo. I’m pretty sure this has little evidence to support it but I find that the echo gives a more accurate description of the impact that the PE is having on the physiology as I think (very much an opinion here) the CT scan often over calls the right heart strain. The obvious confounder here is that the echo is often done after the CT where the right heart has had a little time to recover so I’m very willing to be wrong on that. The useful things to look for on the echo are RV size, TAPSE and septal flattening. While i do love all the other nerdy measures of RV function I remain skeptical of their additive value in making a decision on something as significant as thrombolysis. The other reason I think echo has some advantages over CT on risk stratification is that it’s easy to see the response to therapies on the echo. Does the RV look a bit healthier after an inotrope or lysis etc.

ECG can certainly be used to risk stratify and right heart strain on ECG, (think deep inverted T waves anteriorly and inferiorly) seems to predict CT and echo changes quite well. However I know my ECG skills are lacking and even when I do see the changes I see the ECG as a reason to order another test (ie CT/echo) rather than make the definitive diagnosis or thrombolyse.

While trop and BNP get a lot of attention in the ESC guidelines for risk stratification I find them to be less than helpful in the critically ill as all of our patients already have a raised trop and BNP even before they get a PE. I do pay attention to our universal badness-metre the lactate. A rapidly rising lactate in a PE patient with a bad RV is certainly worrisome.

Next time we’ll look at management options

For further reading it is probably best to visit the original lecture post where they are all listed with a little smattering of critical appraisal thrown in for good measure.

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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.

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Today we’re going to try and cover the not insubstantial topic of acute liver failure from Oh’s Manual chapter 44. As you can imagine this will be a superficial skim of the topic so set your expectations appropriately.

First point is differentiating acute from acute on chronic liver failure. This has a massive impact on presentation, diagnosis and management and I must confess for many years as a trainee my understanding of the distinction between the two was a little cloudy and it was only really in fellowship that it became clear to me.

Oh describes it as a massive parenchymal liver injury with multi system impact and organ failure. Coagulopathy and encephalopathy with various degrees of hypotension and renal failure are the main presentations. Encephalopathy and coagulopathy are needed to make the diagnosis. This happens in the context of a previously normal liver.

Acute on chronic liver failure occurs when someone with pre-existing liver disease eg cirrhosis has a decompensation. This may be a consequence of portal hypertension like bleeding or encephalopathy or sometimes it’s infection. Encephalopathy may or may not be a part of it. Portal hypertension is a substantial feature whereas it is typically absent in acute liver failure.

So what we’re expecting to see to make a diagnosis of acute liver failure in the critical care environment is a patient with what is thought to be a previously normal liver present with a rapid progression of symptoms and jaundice leading to encephalopathy. Now “acute” can be within 6 weeks from jaundice to encephalopathy but they’re not typically the type of patients that come to us.

The rapid outpatient to ICU trajectory is typically within days and a differential arranged by prevalence in the western world should include

When investigating this there is a long list of labs that should be sent but beyond the routine labs you get on anyone you should check for the hepatitis viruses, have a look at eosinophil count if you’re thinking about drug reactions and if you really are unsure then they all end up getting urinary copper and ceruloplasmin to look for Wilson’s. Imaging with either US or more likely US and CT is important. Liver biopsy is often indicated but it is disappointing in it’s yield and comes with bleeding complications

Encephalopathy is assessed with a specific 4 level grading system known either as the West Haven or Parson’s Smith scale. Grades 3-4 is where we’re likely to get involved. There are multiple reasons for the encephalopathy – ammonia is obviously part of it but there are other factors involved. Ammonia is taken up by astrocytes and deamination to glutamine  which in turn draws in water leading to astrocyte swelling. In addition there is likely loss of autoregulation and integrity of the blood brain barrier as part of inflammatory response to acute liver injury. Ultimately this means that these patients are at risk of an ICP crisis (unlike acute on chronic liver failure where the brain has been able to compensate). The ICP crisis can be a real source of morbidity and mortality and all of our usual arsenal of ICP management strategies have been employed in supporting these patients.

The coagulopathy is often profound in terms of the numbers measured. Thombocytopaenia is typically consumptive. The INR is prognostic and correcting it routinely does not seem of much benefit. Indeed we should remember that levels of both pro and anticoagulant factors are depressed though we only measure the procoagulant ones typically. As a result the coagulopathy may have a degree of balance to it that we simply don’t measure. Surgical procedures probably need attempted correction of coagulopathy but simple things like CVC insertion are probably safe.

NAC is a truly life saving and effective drug in paracetamol overdose and should be used liberally. It is unclear how helpful it is in other forms of liver failure but given its benign side effect profile it is used early and liberally and a decision to give some should not be something to spend too much time on.

Kidney injury is common but we should probably be filtering earlier than we might conventionally do so. The idea is that CRRT can wash the blood of some of the foul humors that the liver isn’t dealing with. The dose of CRRT here is typically a lot higher at 45ml/kg or higher rather than our usual 25. This has a limited evidence base but it is published on and frequently used.

On a similar vein (pun intended) of removing evil humors, plasma exchange has been used and a small open label RCT exists.

An SAQ or viva may raise the existence of MARS – Molecular Absorbent Recirculating System. This was thought of as “liver dialysis” but does not seem to have panned out and does not seem to be in regular use

Finally it is critical to consider liver transplant as an option for these patients. Unlike in heart or lung transplant where you need a stable patient with limited organ failures to be a candidate, in acute liver failure you can be in the throes of severe multiorgan failure and still be a candidate for liver transplant. Hopefully your liver physicians will have made the referral for you but if not you should be making the phone call.

Oh chapter 40

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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.

Oh’s Manual Chapter 60 and 95

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Following on from the recent post on Heparin, today we’re going to talk about one of its more significant complications – Heparin Induced Thromboyctopaenia or HIT for short. In my notes I had it down as HITTS for hepain induced thrombotic thrombocytopaenia syndrome which I kind of liked as it included the important presence of thrombosis in the context of low platelets. But HIT is definitely snappier

There are incidentally 2 forms of HIT. Type 1 is an entirely benign phenomenon where the platelets transiently drop in the first few days of heparin exposure and spontaneously recover even with ongoing heparin use. There is no thrombosis associated and no doubt it happens all the time and we miss it.

From our perspective we’re only interested in type 2 HIT which is a serious immune phenomenon where the major concern is not bleeding but clotting despite the low platelet count.

Unsurprisingly a necessity for this condition is an exposure to heparin. This can be UFH or LMWH. It is an immune phenomenon so you don’t typically get it on the first exposure but it’s the ongoing or repeat exposure can cause the immune reaction. As part of normal heparin function it, at various points binds to something on platelets called PF4 – platelet factor 4. For reasons beyond the comprehension of this narrator, the body can produce IgG against this heparin-PF4 complex. The IgG has now labelled these platelets for destruction by macrophages hence the thrombocytopaenia. Again, for reasons beyond this narrator’s comprehension there is also activation of other platelets resulting in both arterial and venous thrombosis.

Incidence is estimated about 1-5% of those on UFH and <1% on those on LMWH. Interestingly the antibody reaction is quite common but even when present only ~10% of those with the antibody develop HIT properly.

The classic presentation is a fall in platelets somewhere 5-10 days following first heparin exposure. Counts usually are between 40 and 80 but 10% can be under 20. The 4T score has been developed as a means of establishing a pre-test probability for HIT.

I’ll outline the 4 categories briefly

A high 4T score usually prompts formal testing and usually a switch to an alternate anticoagulation regime pending the results. This is frequently misunderstood as it seems most are happy to stop heparin pending the test but disregard the fact that clotting is actually the problem so alternate anticoagulation is really needed.

Testing usually comes in 2 stages. The first is a more rapid easily available screening test which i believe is a PF4 immunoassay. This can be followed up by a fancier (checks notes) Heparin Induced Platelet Activation functional assay. I can attest that we have two tests available in our place but I wouldn’t swear they are the ones described above.

The main dilemma we’re left with, is when we suspect HIT but have not got a definitive test to confirm it. We need to make a probability and risk based decision on whether to commit to the diagnosis or not.

Let’s say we’ve decided it’s HIT and we need to anticoagulate. We have a few options, we can use direct thrombin inhibitors (DTIs) like bivalarudin or anti xa agents like fondaparinoux. In our place we reach for argatroban, one of the DTIs.

We will of course seek expert advice from our coagulation colleagues but the critical take homes here are suspicion of HIT, knowing the probability and tests and ensuring we anticoagulate despite the off putting low platelet count.

LITFL

Deranged Physiology

Shore-Lesserson, L. et al. The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines ∗ —Anticoagulation During Cardiopulmonary Bypass. Ann Thorac Surg 105, 650–662 (2018).

Lubnow, M. et al. Prevalence and outcomes of patients developing heparin-induced thrombocytopenia during extracorporeal membrane oxygenation. Plos One 17, e0272577 (2022).

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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

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.

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).

– 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).

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Today we look at quite a niche topic, that of chylothorax. We are used to many things in the pleural space, like simple fluid or blood or air but the presence of the myseterious substance chyle is a much more unusual and note worthy event.

As a reminder of the basics which I of course knew implicitly and definitely did not have to resort to wikipedia to check…

Chyle is largely formed in the small intestine as the gut transports free fatty acids from the intestinal lumen. This combined with lymphatic flow is transported via the thoracic duct to the vasculature where it enters the circulation proper. The lipids in the chyle are transported in the form of wonderfully named chylomicrons.

The cisterna chyli is akin to the gall bladder of the lymphatic system, situated in the upper abdomen it drains a lot of the lymphatics from the gut before sending it on it’s jolly way through the diaphragm into the thoracic duct. Once in the thorax the thoracic duct has to run the gauntlet of the posterior mediastinum where it is frequently hunted and subjected to extreme violence by cardiothoracic or upper GI surgeons who are purportedly there for completely unrelated reasons. If the thoracic duct survives this odyssee then it drains into the sub clavian vein on the left.

As suggested, the commonest time we find chyle in the pleural space is when we notice the milky stuff in the drains that were left in place after said surgery. The other common context is apparently lymphoma or a number of other malignancies.

Chyle in the chest drain can be a yellowy milky thing or blood tinged. As a Deranged Physiology post quotes one group “to our surprise a quantity of fluid which resembled pale tomato soup was withdrawn”

To be definitive about the fluid you can measure triglycerides or even use electrophoresis to identify the above named chylomicrons.

Assuming we’re comfortable with the diagnosis, let’s turn to management. The duct is a fragile little beast, apparently too fragile for the surgeons to spot when they’re doing their original surgery and certainly not amenable to surgical repair. So like a lot of things in medicine it’s best to let the body sort it out itself and the body is best able to do this if we can reduce the flow through the duct.

Perhaps number one is the low fat diet, or at least providing fats in the form of medium chain fatty acids that can be absorbed through the portal vein bypassing the thoracic duct altogether. PN is naturally an option here. Our universal secretion dryer upper octreotide has also been used frequently and to effect.

This strategy appears effective in a certain somewhat undefined proportion cases. If it is not settling and still causing issues then our beloved friends in IR now have techniques allowing them to embolise the duct and our surgical colleagues, while not able to repair the duct can at least tie it off.

Deranged Physiology is excellently referenced, detailed and humorous in equal proportion

LITFL

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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

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.

Oh Manual Chapter 83

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We’ve been talking about pulmonary hypertension, last time we had a pretty broad overview with a focus on group 1 or pulmonary arterial hypertension. This time we’re going to go through some management strategies that might keep you between the hedges on a night on call or a fellowship exam viva.

We briefly mentioned the PH specific drugs that someone might be on. The evidence base for these is almost exclusively in group 1 PH. But what should we do with these meds in someone with group 1 PH who has just arrived back from theater after a laparotomy and a hartmans and they’re on a bit of noradrenaline? The simple answer is continue them. The more complicated answer is you should usually continue them. For example there will be the very rare patient whose pulmonary vascular resistance is kept low in the community with a PICC line and an epoprostenol pump. They are critically dependent on this drug with a very short half life and it should be continued at all costs. Think about it like an adrenaline infusion running at 10mcg/min, not something you can tolerate a break in.

A recurring message from the review papers on critically ill patients with PH is to focus on treating PVR not PA pressures. This is a somewhat philosophical approach that reminds us that the PA pressures themselves don’t prognosticate especially well but a failure of flow from right to left will result in cardiogenic shock and death.

We have a lot of vasoactives to choose from in helping with this, most of which have varying impacts on the PVR. Vasopressin has some animal data suggesting it causes less rise in PVR than our beloved noradrenaline but take that with an appropriately loosely defined portion of salt given that animal data is not ICU patients. Milrinone seems like a great idea as an inotrope that is easy on the PVR but the often dramatic drop in SVR is often a disaster. Dobutamine has the benefit of at least having substantial clinical experience in PH patients even if the tachycardia and even worse the a fib is less than desirable.

The ventilator is a bit of a poisoned chalice. Not only do you have to tolerate a significant risk of peri-intubation cardiac arrest even once you get them on the vent you have to deal with the adverse effects of positive pressure on the RV. The only upside of the vent is that it might make them easier to oxygenate but only if the cause of the hypoxia was a big shunt physiology like a pnuemonia. Oxygen is a great tool for reducing PVR so if we can leverage that then that’s great. However, a lot of hypoxia in end stage PH is reduced mixed venous oxygenation due to low cardiac output and the vent does nothing good for this.

Once on the vent we want a goldilocks’s zone of lung unit recruitment. Too little PEEP we have atelectasis and shunt and hypoxia and vasoconstriction. Too much PEEP and we have overdistension which itself can raise PVR by squeezing the pulmonary vasculature. Finding that sweet spot for the PEEP is a whole post or 10 on its own.

While on the vent it’s a good opportunity to deliver some inhaled therapies. The original gangster here is of course nitric oxide which is one of our target molecules in PH. In a crisis and a failing RV, this might get you out of a tricky spot. But given its expense and not being widely available its worth considering other inhaled options, particularly intermittent nebs of iloprost or a continuously nebulised eporprostenol solution both of which i have seen implemented to good effect.

In terms of monitoring should we be reaching for a PAC? Well, take a step back to start with. We probably need the CVP more. The RV is the first downstream organ that suffers under the burden of worsening PH and if the RV is failing then the CVP will be rising. Like any monitoring tool, a PAC in itself is going to do nothing but provide you with scary looking numbers, particularly the PA pressures which, remember, you should largely ignore. But picking up a severely raised wedge for example might push you to be much more aggressive with your diuresis and left heart management. A continuous cardiac output monitor will allow you to titrate your vasoactives with a great deal more confidence and accuracy

The other monitor I would reach for would be echo. I am a self confessed echo phile so take that into consideration but one of my targets of treatment is going to be how the heart looks. Is the IVS becoming less flattened, is the RV less distended, is the TAPSE improving etc… Echo early, echo often in my book.

Atrial fibrillation is something of a right of passage in the ICU. Have you really been critically ill if you haven’t even had an episode of fast AF? When it comes to PH it’s often poorly tolerated and the approach to rhythm and rate control probably needs to be a bit more aggressive than usual. Our usual choice of vitamin A, amiodarone is a good start but you may need other agents like dig or even DCC to get control. A consistent message from the reviews is to avoid beta blockers. The negative inotropic effect on an RV that is already functioning at peak capacity is not going to be good.

Our first reaction when faced with hypotension is often to load with fluid, this makes sense when we think of the frank starling mechanism, we want to be sure our LV is appropriately pre loaded. But in PH the issue is a failure to deliver volume or flow from the right heart to the left. We can dump a litre into the venous side of the circulation but the PVR just stops it getting efficiently through to the LV. If your patient is hypotensive then the RV is already failing in its basic function of delivering volume and flow to the LV while keeping the CVP low. More fluid is almost never going to fix this.

Indeed diuresing the hypotensive patient may well be the way to go. If you can decongest the right side and reduce the bowing of the septum you’ll get both the RV and the LV working more efficiently

This is only a taster of things you might want to try in a critically ill patient with severe PH. It is important to emphasis that they are not evidence based overall. Most of it is interpretation of clinical physiology at the bedside and applying the available manipulations. Which is of course what makes it so much fun.2

My own rambling review of pulmonary hypertension on JFICMI website.

2022 ESC Guidance

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.

My own rambling review of pulmonary hypertension on JFICMI website.

2022 ESC Guidance