Tasty Morsels of Critical Care – Details, episodes & analysis

Welcome back to the tasty morsels of critical care podcast.

We’re going to cover a bit of an environmental/tox topic today and look at carbon monoxide poisoning from Oh’s manual chapter 83 on burns. I have previously covered this on the old tasty morsels of EM series back when i was doing my EM fellowship exams.

As you no doubt remember from school chemistry classes, carbon monoxide is a colourless, odourless, tasteless gas produced when combustion occurs with insufficient oxygen.

We’re likely to see this in a couple of contexts.

1) the house fire victim, pulled from the fire unconscious and sick

2) the sub acute or chronic poisoning in a patient presenting with headaches and flu symptoms that seem to get better when they leave the problem environment. The classic EM example is the whole family who present with flu symptoms and no fever and even the dog is sick. We’re much less likely to see this cohort in the critical care side of things.

How does it make people sick? Haemoglobin is a fickle little protein, while evolved to carry oxygen to needy tissue beds it actually has a distinct preference not for our beloved oxygen but for carbon monoxide. Introduce some carbon monoxide at the alveolus and the haemoglobin molecule will bind to CO with an affinity 240 times that than for oxygen. I take that number of 240 somewhat at face value but I presume someone got a PhD from working that out. In visual form my preferred means of explanation for this would be the distracted boyfriend meme where the haemoglobin boyfriend looks longingly over his shoulder at the carobon monoxide while his oxygen girlfriend looks on in horror. Hopefully you get the idea.

So instead of having lots of circulating oxyhaemoglobin we’re instead left with lots of not especially useful carboxyhaemoglobin. Let’s imagine 50% of our Hb is now carboxyHb and 50% is OxyHb we’re left with a sort of severe fucntional anaemia where half of our Hb is out of action. One might be inclined to think that this is the major cause of morbidity and mortality in CO poisoning but in fact this is only a small portion of the problem. CoHb actually has a direct cytotoxic effect on things cytochrome oxidase and myoglobin function. As such it interrupts the whole process of oxidative metabolism and life as we know it.

We can measure the level of CO fairly easily, any blood gas machine worth its salt should be able to give you a break down of the types of Hb present in the sample. This is co-oximetry and typically it’ll show you oxy, deoxy, carboxy and met haemoglobins. All these different forms of Hb absorb different wavelengths of light. The lowly pulse oximeter does not have the subtlety to distinguish the different wavelengths as it only functions at wavelengths of 940 and 660nm. Indeed the pulse ox often demonstrates a non diagnostic number somewhere in the 80s rather than a true reflection of the CarboxyHb or OxyHb present.

Severe CO poisoning resulting in obtundation is going to have high level of COHb on our cooximeter. >10% is quoted but it’s more often over 30%. Patients are going to be pretty sick often from multiple pathologies but COHb on its own is enough to produce severe neurological injury, shock and even cardiac injury is also quite prevalent. Expect a high lactate given the disruption of oxidative metabolism. Resuscitate and investigate as you would any sick patient.

Treatment is nice and simple in that we just give loads of oxygen. Oxygen reduces the half life of CO in the blood quite dramatically, commonly quoted numbers are

• the haf-life of COHb in an FiO2 of 0.21 is 300 minutes
• the half-life of COHb in an FiO2 of 1.0 is 60-90 minutes 

There is a substantial rationale and literature on the use of hyperbaric oxygen as a means of accelerated clearance of COHb. But the RCTs that have been done don’t seem (to me at least) to give a clear benefit. The Lindell Weaver NEJM RCT in 2002 did suggest a neuro benefit but only 8% of the patients in this trial were intubated. A follow up trial in 2011 by ICU steroid guru Djilalli Annane did not find a benefit . So if anyone should get this it might be the non intubated isolated COHb poisoining. This is not really our cohort. Our cohort is likely to be tubed, shocked, with multiple injuruies and not someone you want to transport cross county to put in a single person hyperbaric chamber for hours at a time.

Reading

Oh Manual Chapter 83

Weaver, L. K. et al. Hyperbaric oxygen for acute carbon monoxide poisoning. The New England journal of medicine 347, 1057–1067 (2002). Annane, D. et al. Hyperbaric oxygen therapy for acute domestic carbon monoxide poisoning: two randomized controlled trials. Intensive Care Medicine 37, 486–492 (2011).

 

 

 

Welcome back to the tasty morsels of critical care podcast.

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

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

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

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

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

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

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

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

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

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

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

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

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

Reading

My own rambling review of pulmonary hypertension on JFICMI website.

2022 ESC Guidance

McLaughlin, V. V., Shah, S. J., Souza, R. & Humbert, M. Management of Pulmonary Arterial Hypertension. J. Am. Coll. Cardiol. 65, 1976–1997 (2015). Jentzer, J. C. & Mathier, M. A. Pulmonary Hypertension in the Intensive Care Unit. J. Intensiv. Care Med. 31, 369–385 (2015). Johnson, S. et al. Pulmonary Hypertension: A Contemporary Review. Am. J. Respir. Crit. Care Med. 208, 528–548 (2023). Barnett, C. F., O’Brien, C. & Marco, T. D. Critical care management of the patient with pulmonary hypertension. Eur. Hear. J. Acute Cardiovasc. Care 11, 77–83 (2022).

Welcome back to the tasty morsels of critical care podcast.

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.

Oh Chapter 37 is dedicated to NIV in the ICU and is probably worth some time given that this is a common respiratory support both in the ICU and throughout the hospital.

Many of the benefits of NIV are similar to those seen with ventilation with the blue plastic tube through the vocal cords.For example you still get:

• positive airway pressure which recruits alveoli and improves oxygenation
• improved alveolar ventilation which improves minute volume and lowers CO2
• reduction in work of breathing as the machine is doing some of the work
• stabilisation of the chest wall eg in rib fractures
• reduction in transmural LV pressures acting as a sort of poor man’s IABP (more on that later)

The big advantage of course is that you get all the positives but avoid the blue plastic tube through the cords and all the hassle and complications that come with that.

But it’s not all unicorns and rose petals, the mask itself has a tendency to macerate the face over time and patients who are already feeling breathless and suffocating often don’t take kindly to having a plastic mask shoved over their face. Even if they do tolerate the mask it is frequently difficult to make a decent seal and maintain that lovely positive mean airway pressure that you’re looking for.

And while i did wax lyrical about the potential positives of positive pressure ventilation at the beginning of the post, it seems only fair to point out the negatives of positive pressure ventilation. It is clear that positive pressure ventilation is non physiological and is known to cause its own form of lung injury when applied through a plastic tube through the cords. The alveoli only see the pressure and care not which device it’s being delivered through, so there’s no good reason why NIV wouldn’t cause similar problems.

This of course brings up the unanswered and quite entertaining controversy over P-SILI or patient self induced lung injury that hit its zenith during the worst days of the COVID-19 pandemic. There were back and forth letters in the journals between some of the heaviest hitters in the ventilation world bouncing back and forth whether they actually believed self induced lung injury was a thing. Now this is not the post to explore it, but perhaps suffice to say that someone sitting with a resp rate of 30 for a week on 80% O2 and a PEEP of 10 on NIV may well be undergoing some of the same lung stress that any typical ventilated ARDS patient may be undergoing. NIV is not necessarily a free pass.

When it comes to modes, the names are, as ever, confusing and baffling. Overall they split into some kind of CPAP mode where airway pressure is constant throughout the respiratory cycle and a mode with pressure support set above the PEEP where the pressure increases above the baseline CPAP when the patient inspires. To make matters worse there’s no clear consensus in how the numbers are described. For example, our portable, single limb circuit, ward based NIV machines use the terminology EPAP and IPAP to describe the pressures with both numbers starting from zero. for example 10/5 would be a CPAP of 5 with an additional 5cmH2O pressure support whenever the patient expires. On an ICU vent this would be described as 5/5.

When would you reach for NIV over say one of the aforementioned blue plastic tubes through the cords? Well there are a number of now well established indications where it is entirely appropriate to try and temporise with NIV rather than just putting the tube in. I’ll give a brief summary of a few of them below:

Pulmonary oedema.

• the heart is poor, the lungs are wet and heavy and the sats are low. The patient is crying out for some CPAP. How might it help, let me count the ways.
  1. by increasing intrathoracic pressure you are decreasing the gradient of pressure between the low pressure at end disastole in the LV and the high pressure at end diastole in the aorta. As a result the LV has to do less work to pop open the AV and get blood moving forward to the aorta. This mechanism is somewhat akin (though probably not nearly as effective)  to the afterload reduction with an IABP. hence the description of CPAP as the poor man’s balloon pump
  2. improving oxygenation by recruiting alveoli
  3. reducing work of breathing by giving a little boost as the chest wall tries to expand those wet and heavy lungs
  4. applying a little +ve hydrostatic pressure to the alveoli to get the fluid back into the vasculature where the furosemide can do its glorious work of diuresis.
• there is a clearly proven benefit for reducing intubations and improving oxygenation though the signal for mortality improvement is not as clear.

Exacerbations of COPD

• in this scenario the lungs are scarred and the airways constricted and obstructed. A minor sniffles can be enough to push them over the edge of respiratory failure and the CO2 is rising and the pH is falling and they do not have the respiratory reserve to up their work of breathing
• NIV, and in particular a mode with increased support during inspiration can improve the minute volume and clear the CO2 and wake them from their CO2 narcosis.
• This is a very well supported intervention with 14 or so RCTs showing benefit and an NNT to avoid intubation and death of 4 and 10 respectively .

Asthma

• now we have rapidly strayed into the evidence lite zone. It seems somewhat counterintuitive that a disease where the main issue is difficulty breathing out would be helped by adding positive pressure down the airway but it may be that the extrinsic PEEP is helping them overcome the intrinsic PEEP, or it could be that its reducing the work of breathing or it could be any number of  potential arguable benefits. Still to be proven but commonly tried.

ARDS

• For a long time this was firmly in the controversial box and many would have argued that ARDS needs low volume low pressure ventilation, all of which we can not control in NIV. Meaningful trials were lacking. Then COVID came along and we all went mad with the old CPAP handing out CPAP masks with the coffee and dexamethasone on the morning ward round. Allowing that the bilateral infiltrates of COVID meet the definition of ARDS by any standard then it seems that NIV had found a role in the world of ARDS. That role and how far you might push CPAP before biting the bullet and tubing them remains to be defined. Yes I can keep this person going for 2 weeks on 90% FiO2 and a PEEP of 10 but is that really the best thing to do? There’s no sarcasm here, i really don’t know the answer to that…

Post extubation support

• so you’ve taken the tube out and they’re struggling, should you stick an NIV mask on or just put the tube back in? Again, data not exactly clear on that but it seems that if they’re failing extubation due to either pulmonary oedema or bronchospasm/COPD then it’s probably worth a go. hardly surprising seeing as they’re the two most solid indications we have already. If its’ not either of those then probably best just to put the tube back in.

 

Reading:

Oh’s Manual of intensive Care chapter 37

 

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

 

Welcome back to the tasty morsels of critical care podcast.

Nestled towards the end of Oh Chapter 51 we have a section dedicated to SAH. Given that a lot of ICU bed days are given over to managing SAH, I felt it might have warranted its own chapter. Indeed, looking at its prevalence in fellowship examinations it does seem that a fair deal of attention should be given to SAH. It stands apart from the usual intracranial bleeding where the typical  treatment and discussions are all focussed on supportive care and the the nuance only comes in when you get to BP management. Whereas in SAH you have a whole bunch of interesting and well proven interventions that can improve outcome for the lucky patients who haven’t already prognosticated themselves by presenting with a GCS of 3.

As a starter for 10: in which meningeal space in the brain do you find an SAH? The clue, thankfully  is in the name. The space between the brain adhering pia matter and the filmy arachnoid matter is where you’ll find an SAH. This is the space that CSF flows in from it’s genesis in the choroid plexi of the ventricles on its journey to reabsorption in the arachnoid granulations. Also in this space lies the cerebral vasculature that has a tendency to become aneurysmal and rupture arterial blood into this space.

Blood in the sub arachnoid space is easily seen on a simple dry CT scan, particularly in the first few hours. It has now become a test so good that people would suggest that if you have a negative CT in the first 6 hrs then you probably can skip the de rigeur LP that has been all the rage for the past century. Though i’ll admit that that question is delving much more into the realm of EM than hard core crit care.

In a critical care exam type stem you might be faced with someone in their 60s with a history of poorly controlled hypertension, who smokes, takes cocaine and has polycstic kidneys. All of these are identified as risk factors for SAH, though such a combination, i imagine only exists on exams. In the stem they’re likely to have a reduced GCS in the 13-14 range with a BP of somewhere north of 170mmHg. You’ll be given a CT scan showing some diffuse SAH but you’re waiting on an angio etc… Imagine a question like: what are your immediate priorities in management.

Given that 85% of SAH is aneurysmal, and they need definitive treatment likely not available in your hospital then getting that angio done is certainly a priority. But probably more acutely will be the basics of assessments of ABCs with particular attention to getting that BP under control. The biggest risk to life in the first few hours is going to be a rebleed which happens in maybe 20% of patients. Getting the BP down to somewhere south of 160 is likely a good idea with the ubiquitous labetalol probably being the most accessible and available option. Avoid the GTN and the foil wrapped madness of nitroprusside as both can cause a little cerebral vasodilation that you want to avoid. Bonus points for a decent analgesic (which will help the pain) and an antiemetic as vomiting does indeed tend to make the BP spike a little.

The stem continues and the plot thickens. While waiting for the CT angio the patient becomes obtunded gets intubated (where great attention was paid to the heamodynamics). Now the CT shows more blood, some hydrocephalus and a big posterior communicating aneurysm. What now genius?

Hydrocephalus is a relatively common event in SAH and the theory is that blood in the CSF space blocks up the arachnoid granulations preventing reabsorption and with ongoing production and failure to reabsorb you get hydrocephalus. There may be other reasons including a clot in one of the intricate drainage canals in the brain but either way you get more CSF than you want with a concomitant rise in ICP that quickly becomes life threatening if not drained with an EVD. Now if you’re a neurosurgeon and someone gives you the story of GCS 13-14 with SAH and an aneurysm your interest is definitely piqued but this is likely to be a transfer within 24 hrs to get some coiling done but is unlikely to require any surgery per se by the neurosurgeon at 3am. However if you give them that same story but now add some hydro and a falling GCS you have the type of thing that will buy your patient an emergency blue light transfer over to the OT in the neurosurgical centre.

So what’s going to happen with the aneurysm? Assuming we keep the BP under control and correct any coagulopathy then it needs secured. If possible this should be done by a neurointerventionalist with a coiling procedure, and not by craniotomy and clipping of aneurysm. This is now well defined and supported by randomised controlled level evidence. Given the complexity of these procedures the timescales provided for which it has to be secured is generally in the 24-48hr range and this allows them to be done as day time procedures most of the time.

The scene fades and the time jumps and the question stem now is in the ICU on day 5. On your daily sedation break it is noted the patient is not moving the left side. What pray tell is this new calamity? Has the poor soul now had a big embolic stroke in addition to his SAH? While this is definitely cerebral ischaemia it is not stroke and instead rejoices in the name of “Delayed cerebral ischaemia”  or DCI to its friends or “vasospasm” to the people it knew in high school but haven’t bothered to stay in touch.  DCI is a clearly recognized phenomenon in SAH patients and is typically found to co exist with the radiological phenomenon of vasospasm where the artery spasms and has reduced flow. Vasospasm itself is very common in up to 70% of SAH patients but only about 30% of vasospasm is DCI. DCI requires a focal deficit or drop in GCS in addition to imaging findings of ischaemia.

The typical response in days of yore would have been “triple H therapy” consisting of hypervolaemia, hypertension and high haemoglobin. Over the passage of years the only remaining tenet of the grlorious trio is induced hypertension which does seem to have some kind of effect on improving those ischaemic symptoms. Don’t be surprised to find your neurosurgeons requesting MAP targets like 90 or 100mmHg in these scenarios. The single best treatment for DCI we have is actually a prophylactic treatment in the form of the calcium channel blocker nimodipine. 60mg given 4 hrly is the standard recommended from day of rupture given for 3 weeks or so. It’s not entirely clear how this works but it’s fairly clear that it does. lastly it’s worth noting that DCI is not a day 1 concern for your SAH patient with incidence peaking in the 4-10 day range.

Reading:

As a broad overview Oh Chapter 51 covers all the bases.

Welcome back to the tasty morsels of critical care podcast.

Today we are going to talk about triggering on the ventilator. Now given the ubiquity of the word “triggering” in contemporary discourse I must confess that i do find it quite “triggering” to walk up to a vent and see the pressure support set at 11 or some other horror show like a PEEP of 7… I mean, who would do such a thing. But let me clear we are talking about a very different type of triggering.

If i was on a ventilator and somewhat engaged in the process of respiration at least at a brainstem level, I would feel a much more content if the ventilator cycled to inspiration whenever I requested it to. Indeed I would also find myself greatly contented if said ventilator did not randomly produce new inspirations any time it detected the slightest change in airway pressure. All of this is dependant on ventilator triggering.

Let’s start with the basics, the ventilator can be triggered to cycle to inspiration in a number of ways:

1. time (in the case of mandatory ventilation, in fairness this is not really a trigger as the patient has no input)
2. pressure trigger. The patient must produce enough negative pressure in the circuit to trigger the vent
3. flow. The patient must produce a certain amount of inspiratory flow in the circuit to trigger the vent

My experience has been overwhelmingly with the ubiquitous servo ventilators found in many ICUs in Ireland. On the servo-i when you scroll through the menus you’ll see a dial for trigger. This dial is defaulted to flow trigger with a dimensionless number from 1-10 based on a proprietary software from Maquet. The more clockwise you turn the knob the lower the flow in the circuit the patient has to generate and therefore the easier it is to trigger inspiration. Swing it all the way right for the poor GBS patient who struggles to trigger. As the dial is turned left (or anticlockwise) then the trigger will magically switch to a pressure trigger with actual numbers in cm H20. These define the negative pressure in the circuit that has to be generated before the vent will trigger a breath. Thus flow triggers are easier for the patient and pressure triggers harder.

But when would you ever want to make the trigger harder for the patient? Typically it’s not actually that you want to make it harder for the patient, it’s more that you want to avoid autotriggering. A good example of auto triggering is commonly seen in the patient who has become dead by neurological criteria. The story at handover will typically be a  devastating brain injury with some haemodynamic instability and loss of pupilary and cough reflexes but the trainee notes that brain death cannot have occurred because they are still triggering the vent. In this scenario it is quite common for the ventilatory to be auto triggering due to the minor fluctuations of flow within the circuit caused by the substantial cardiac oscillations of the hyperdynamic circulation of the person undergoing  brain death. Simply switching from a flow trigger to a pressure trigger typically eliminates these auto triggers. Alternate sources of auto triggering can be the big air leaks of a bronchopleural fistula or a water logged circuit with a meniscus of rained out water oscillating back and forth in the tubing.

Failure of triggering is very common. In this scenario there has been a neurological trigger that may have even initiated some diaphragmatic contraction but it was missed by the ventilator. An oesophageal balloon is probably the gold standard here and you can use it to see if a negative deflection on the balloon is matched by a breath.

In the absence of a balloon (and aren’t we all?) we have to use some surrogates. It’s hard to detect but in some patients you can see a -ve deflection in the pressure waverform that is not matched by a breath. This may be the patient trying to trigger but failing. The flow waveform is similar but this time we’re looking for a +ve deflection of the expiratory slope. There are some nice pictures in the multiple references at the end of the post.

While it may seem inconceivable to many there is always the option of actually examining the patient. A hand on the sternocleidomastoid or tummy might make patient generated effort easier to recognise.

Intrinsic PEEP or gas trapping is one of the commonest causes of a failed trigger. Let’s say a COPD patient is emerging from propofol and fentanyl induced haze of 3 or 4 days on the vent for pneumonia. They are transitioning to a spontaneous mode as their respiratory drive increases. Unfortunately their obstructive lung disease is still an issue and the expiratory flow has not returned to zero before they try and take their next breath. Air is still exiting their body at a certain flow and pressure so they need to generate enough flow and pressure to reverse this gas in the circuit in order for gas flow to move from expiratory to inspiratory limb to allow the vent to recognize a trigger. You can often see this as artefact in the flow waveform.

There is an interesting technology called NAVA or Neurally Adjusted Ventilatory Assist . This involves a fancy NG tube that is placed in the distal oesophagus and picks up electrical signals from the diaphragm. This is then connected to the vent and allows the vent to know with a high degree of precision when the diaphragm is contracting and match the beginning of the breath to this. So even if the diaphragm is weak and ineffective the NAVA can pick up on the neural signal to breathe. Like most such things it’s been tricky to bring to widespread practice and trials showing signficant benefit are sparse.

Moving on from failed triggers there are 2 more concepts to discuss. 1) double triggering 2) reverse triggering. These can look quite similar at times and are often mistaken from each other but are quite distinct. Double triggering can be seen when neural inspiration is longer than mechanical inspiration; in other words the patient wants to take a really long drawn out breath in but the vent for any number of reasons has cycled to expiration before the patient was finished. This will be particularly common in partially controlled mode of vent where you’ve tried to set a small and “safe” tidal volume but the patients brainstem is having none of it.

The second one, reverse triggering is much more recently described and can be really quite subtle. It is usually seen in deeply sedated patients undergoing a control mode of ventilation. In this scenario the vent triggers the breath itself based on the set program. During the mandatory breath the diaphragm is activated and so as soon as the mandatory breath is over the vent senses the diagphrgm induced flow change and cycles into inspiration again.  If you have something like NAVA or an oesophageal balloon you can see the diaphragmatic activation on the trace. Without one of these it can look almost like a hiccup. In addition look for a mandatory breath followed by a triggered breath during the expiratory phase.

As always this is by no means a comprehensive review of triggering but hopefully a little intro to some potential very examinable topics.

Reading:
– Georgopoulos, D. & Roussos, C. Control of breathing in mechanically ventilated patients. Eur Respir J 9, 2151–2160 (1996).
– Good lecture on triggering from Brochard at the Toronto course
– Dres, M., Rittayamai, N. & Brochard, L. Monitoring patient–ventilator asynchrony. Curr Opin Crit Care 22, 246–253 (2016).
– Artigas, R. M. et al. Reverse Triggering Dyssynchrony 24 h after Initiation of Mechanical Ventilation. Anesthesiology 134, 760–769 (2021).
– Oto, B., Annesi, J. & Foley, R. J. Patient–ventilator dyssynchrony in the intensive care unit: A practical approach to diagnosis and management. Anaesth Intens Care 49, 86–97 (2021). [images above]

Welcome back to the tasty morsels of critical care podcast.

Today we are going to do our best to charm the yellow snake of the intensive care unit and cover the pulmonary artery floatation catheter. Like a lot, indeed practically all of these topics, I do not in any way consider myself to have great expertise in the topic but I have had to upskill as much as I possibly can in lieu of the typical mis spent youth doing cardiac anaesthesia that most of my colleagues have had.

As such the source list for this post is quite varied in terms of its references.

The focus here will be on the basis, the nuts and bolts of how to put in and what type of numbers you might obtain from a PAC.

The insertion carries a lot of similar complications to any typical central vascular access procedure. But the big ones come from the fact that you’re trying to place the catheter through the heart rather than in close proximity to it. Perforation is of course a real possibility but perhaps more likely are nasty arrhythmias precipitated by the catheter irritating the myocardium. Expect to see this more in the cold, shocked post bypass patient or in someone who’s already having a lot of arrhythmias.

The PAC is also famous for the knots it can manage to tie itself into that can make extraction more than a little challenging.

There are lots of good materials online on insertion so I’ll only mention a few basics in passing. The tiny little balloon at the tip catches the flow of the venous return and pulls the catheter along with the flow.

In the absence of flurosocopy it can be tricky to know quite where the tip of the catheter is at any given time so we use the changes in waveforms to tell us what chamber or vessel the tip is at any given time. The pattern we expect to see should be CVP waveform, RV waveform then PA waveform and finally a wedged waveform. If all plays ball the you should those patterns at roughly 20cm, 30cm, 40cm and 50 cm respectively. The challenge is usually transitioning from the RV to the PA and the key change in waveform to look for is the “step up” in the diastolic pressure from the RV waveform which has a diastolic in the low single digits to a PA diastolic which is in the low double digits.

Once the procedure bit is done we typically take a CXR looking for the tip. Typically the natural curve of the catheter leads it to ending up in the right PA most commonly though this is by no means guaranteed. It can be tricky to tell from a simple CXR but ideally we want the tip in a West zone 3 part of the lung, typically in the inferior portions. West zones may be a distant memory from medical school but for our purposes the estimate of the left atrial pressure produced by our pulmonary capillary wedge pressure is only valid when the alveolar pressure is less than the pulmonary venous pressure, a situation that exists only in West zone 3. If you’re in zone 3 you should be able to see a and v waves (analagous to the a and v waves of the CVP waveform)

In some of the linked papers at the end there are some excellent images of troubleshooting various waveforms. One of the more useful ones was dealing with the failing RV (the very scenario where a PAC is likely to be needed) In this scenario, the RV diastolic pressures can approach the PA diastolic pressures with a loss of the “step up” as you move into the PA. The key difference to note in this scenario is that when the PAC is in the RV the diastolic run off (the period before the next ejection) is upsloping and the disatolic run off is downsloping when the PAC is in the PA.

There are lots of measurements we can take from the PAC. Directly measured PA pressures are of course useful but the typical catheters used these days also have a thermodilution filament built in so that we can measure continuous cardiac output (on the principle that the RV cardiac output is equivalent to the LV cardiac output). The contemporary catheters use semi random pulses of heat (up to 44 degrees) in order to calculate a thermodilution cardiac output. In general it needs at least a 15% difference in CO to be detectable and it averages things over 5-10 minutes rather than from beat to beat. There is often a “stat CO” measure that averages it over a more like 60 seconds.

In another success of marketing over function there is typically a continuous oxygenation sensor at the tip of the catheter. This gives a continuous reading of the true mixed venous oxygenation but is probably worth calibrating with an actual co-oximetry reading from a blood gas taken from the tip of the catheter.

With a PAC in place we have the potential for measuring the pulmonary capillary wedge pressure which given a long number of assumptions can allow us to infer things like a left atrial pressure or left ventricular end diastolic pressure, key variables for assessing the filling status of the left heart. The principle involves the tip being in a west zone 3 branch vessel, the balloon is then blown up creating a theoretical continuous column of blood between the tip of the catheter and the left atrium. Once wedged the displayed number will typically be a mean, however the PAOP should be obtained at end expiration and in end diastole which often means reviewing a screenshot with your monitor and using a cursor to identify the pressure, timed at the onset of the QRS. There of course are lots of subtleties and caveats to the number obtained and even more about how to respond to it.

Finally if you want to be really hard core there is a way of compensating for the effect of high levels of PEEP (>10) on the PAOP. The transmission index (TI) gives you a “corrected” PAOP taking this into account. The TI is calculated by looking at the PAOP  in inspiration and expiration. The difference between these two numbers is then divided by the driving pressure on the ventilator, this is your TI. The corrected PAOP is then the measured PAOP minus the total PEEP multiplied by the TI. This type of maths does not translate well to audio format and indeed there are actually several of these calculations available just to make it even more confusing.

There is a substantial literature behind the utility, or lack thereof of the PAC that has led to a massive decline in its use preceding the mid noughties when i started practicing. However they remain a key tool in the intensivists arsenal and if you deal with sick hearts on a regular basis it’s vital you have a decent grasp on charming the yellow snake.

Reading:

Irwin & Rippe Chapter 19 (an excellent source of a textbook if you want detail on any topic not particularly well served by Oh)

Deranged physiology has as expected an even higher level of excruciating details for those interests, presented of course in an excellent fashion.

LITFL

– Bootsma, I. T., Boerma, E. C., Scheeren, T. W. L. & Lange, F. de. The contemporary pulmonary artery catheter. Part 2: measurements, limitations, and clinical applications. J Clin Monitor Comp 1–15 (2021) doi:10.1007/s10877-021-00673-5. – Bootsma, I. T., Boerma, E. C., Lange, F. de & Scheeren, T. W. L. The contemporary pulmonary artery catheter. Part 1: placement and waveform analysis. J Clin Monitor Comp 1–11 (2021) doi:10.1007/s10877-021-00662-8. – Teboul JL, Pinsky MR, Mercat A, Anguel N, Bernardin G, Achard JM, Boulain T, Richard C. Estimating cardiac filling pressure in mechanically ventilated patients with hyperinflation. Crit Care Med. 2000 Nov;28(11):3631-6. doi: 10.1097/00003246-200011000-00014. PMID: 11098965

Welcome back to the tasty morsels of critical care podcast.

The subject of solid tumours in the ICU gets a whole chapter in Oh’s hallowed pages, number 46. I suppose the term solid is in place to distinguish it from the “liquid” tumours of the bone marrow and domain of the haematologists, something we covered in tasty morsel number 58

Historically the idea of admitting people to the ICU with malignancy was somewhat unusual and the idea of admitting someone with some degree of metastatic disease even more heretical. But now on a daily occurrence I find people admitted post op from debulking surgery, or hepatic resections for metastases or the slightly “out there” concept of HIPEC procedures (heated intraperitoneal chemotherapy). Many of these patients are on a potentially curative trajectory not thought possible 20 years ago.

That being said many patients with disseminated malignancy, even those on active treatment are typically approaching end of life when the old multi organ failure and ICU referral appears.

An intensive care unit admission is bad for cancer as there is a sort of immunosupression that comes about with being critically ill, leading to depletion in things like natural killer cells who were rightfully killing off cancer cells till the pneumonia, steroids and blood transfusions came along. For example the beta stimulation from adrenergic agents has a direct effect on reducing cytotoxic t cells and natural killer cells.

Let’s look at some complications of chemotherapeutic agents that might land a patient in the ICU. One would hope that the oncologist will pick this up but it’s still important for us to have an awareness of the potential issues. I’m going to skip over the most common presentation to us , that of neutropaenic sepsis from a beaten down bone marrow, and instead focus on the niche ones.

Bleomycin is a relatively commonly used agent for multiple malignancies, perhaps most famous for its potential to cause lung injury, namely a form of pulmonary fibrosis. The pneumonitis associated has been reported in up to 40% of patients according to Oh, but a quick review of the relevant UTD article suggests it’s more like 10%. Will generally be seen in the first 6 months since treatment but can occasionally be late. So the cancer patient with new diffuse alveolitis has a very broad differential including multiple infections but perhaps wise to keep bleomycin in your head. Don’t be surprised if someone gives lots of steroids as that might be beneficial.

Ifosfamide (a sort of cyclophosphamide in disguise) is another agent commonly used in multiple cancer types and is famously associated with an encephalopathy (and also a nephrotoxicity that i mention only in passing). This neurotoxicity can happen in around 20% of patients and is thought to be related to a break down product rejoicing in the name chloroacetaldehyde. Both Oh’s manual, and the oncologists in the two cases i saw gave methylene blue as there was a suggestion it might help. Interestingly the European society for oncology guidelines recommend specifically against using it.

The anthracyclines are a broad group of drugs including such tongue twisters as daunorubicin, doxorubicin, and epirubicin. These are the kind of drugs that can bring a patient to the ICU 5 years after their cancer treatment with severe heart failure and dilated cardiomyopathy. This type of toxicity is one reason for the pre treatment echo requested on these patients and the interest in things like global longitudinal strain to predict early signs of complications of treatment.

Finally I’ll mention some cautions with regards to platinum based chemo agents, easily identified by the “platin” at their end, the most common one being cisplatin. I’ve noticed our chemo protocols have specific note not to use gentamicin in neutropaenic sepsis associated with platinum based chemo agents. Given that gentamicin is one of my top 10 drugs, up there with propofol and steroids, and noradrenaline, it made me intrigued as to why. After a brief and really quite shallow rabbit hole it seems that the prohibition is all related to ototoxicity. Aminoglycosides, we all know are associated with ototoxicity and it seems cisplatin does the same by a very similar mechanism. There doesn’t seem to be any kind of synergy or pharmacological trickery here, it’s simply that giving two drugs with risk to the inner ear is simply a bad idea.

The massive monoclonal antibody shaped hole in this post is the immunotherapeutic agents now so common in much of modern oncology. They have their own list of very specific complications that are deserving of their own post but for now I would point you towards the excellent IBCC post and podcast that cover the topic beautifully.

Reading:

Oh’s Manual Chapter 46

Schacht J, Talaska AE, Rybak LP. Cisplatin and aminoglycoside antibiotics: hearing loss and its prevention. Anat Rec (Hoboken). 2012 Nov;295(11):1837-50. doi: 10.1002/ar.22578. Epub 2012 Oct 8. PMID: 23045231; PMCID: PMC3596108.

Welcome back to the tasty morsels of critical care podcast.

This time we look at Oh Chapter 52, focused on cerebral protection. There is, I must admit some repetition and cross over here, particularly with tasty morsels 20 and 39 respectively which cover more with regards to TBI. But in all honesty a little repetition is often very helpful for such subjects. We talk a lot about cerebral protective measures in the ICU and hopefully this will give you a little of the basic physiological background.

We’ll start with a few basic factoids. The brain apparently receives 15% of the cardiac output, though I imagine by the end of a typical ICU on call shift, that proportion will have dropped quite significantly. The squishy pale blob of folds and ridges in our skulls uses a surprising amount of glucose and oxygen and is very dependent on a continuous and uninterrupted supply of glucose, or ketones to allow ATP generation. It is not an organ able to tolerate an oxygen debt and has no real capacity for anaerobic metabolism. Basically it’s a bit of a diva and seems to take the position that as its the only organ capable of producing consciousness and self awareness that therefore it’s a bit special.

It’s circulation has some redundancy built in with 4 separate vessels (2 verts and 2 internal carotids) all filtering into the big round about that is the circle of Willis. However once you take the branches off this circle the redundancy and collaterals are somewhat lacking.

As a reminder cerebral perfusion pressure is equal to MAP – ICP. So for most normal humans from day to day this works out at a perfusion pressure of ~60mmHg. Autoregulation of blood supply to brain is very well controlled being able to control perfusion and flow very precisely anywhere in the ranges of MAPs from 60-160mmHg. It does this by vasoconstricting when arterial pressure is high and vasodilating when pressure is low. As expected chronicity will have some effect on the brain’s response here.

There is an intricate mechanism called “flow-metabolism coupling” that allows the brain to match supply with demand. The mechanism for this is described in Oh as unclear with lots of intriguing theories but it remains hard to grasp how metabolic products being washed away on the venous side cause a neatly matched dilation of the arterial side of things.

Outside of that broad pressure range of 60-160mmHg, flow becomes more linear with higher pressures leading to higher flow and lower pressures to less flow. In the injured brain (either traumatically or medically) this autoregulation becomes much more challenged and we find ourselves stepping into augment MAPs with things like vasopressors in order to ensure a reasonable CPP.

There are also systemic (ie non local factors) that can significantly affect cerebral blood flow. Most notably CO2 and temperature. CBF (cerebral blood flow) increases 3-4% for each mmHg increase in PaCO2. For those of us tied to kPa it’s perhaps easier to express it as a doubling of PaCO2 will double the cerebral blood flow and having the CO2 will have an equivalent effect. The overall metabolic rate of the cerebral tissues is lowered 8% for every degree celcius that the body temperature is lowered. Being able to reduce flow to the brain (either by hyperventilating or cooling) is a nifty trick when you’re in trouble with the ICP. However hyperventilating is reducing flow to a brain that needs it while temperature control is reducing the actual need for the flow and therefore clearly seems the more elegant of the two. As mentioned in prior posts it’s fairly definitive at this stage that therapeutcially cooling the injured brain to sub normal temps does not improve outcomes but it would still seem prudent to take the TBI with a temp of 39 down to a more normal range. Equally, hyperventilating to a PaCO2 of 3kPa might buy you an ICP drop on the lift to theatre but is not something you want to be doing as a definitive strategy.

Osmolality is another manipulable physiological variable we can tinker with. Oh states that a 3mosm drop in osmolality can lead to a 7% increase in overall cerebral volume as fluid shifts into the brain. An overnight sodium drop in a TBI patient from 135 to 130 all of a sudden seems a little more significant now. The most basic implications of this are to avoid hypotonic fluids in the brain injured patient and the more advanced might be manipulating the serum Na north of 150 in the hope of shriveling the brain up like a prune so it fits within the cranium instead of herniating out the foramen magnum.

As a little bit of a bonus, I’ve been working through Thomas Woodcock’s highly recommended “Fluid Physiology” textbook. The focus on this for me has been the revised starling mechanism, best described elsewhere online but there is a nice chapter on the CNS. He points out that recent studies suggest there is a form of lymphatic system in the brain (previously it was thought to be non existent) that probably helps with CSF re circulation beyond the traditional understanding of re absorption through the arachnoid granulations. He describes 3 forms of cerebral oedema evident.

1) vasogenic due to disruption of the blood brain barrier

2) cytotoxic due to plasma hypoosmolality, mostly thought to be related to failure of various ion pumps.

3) interstitial due to CSF circulation issues.

He also makes a nice point about mannitol. We claim this works by osmotic reabsorption. Something he says does not normally occur across an intact blood brain barrier. But if the endothelium and glycocalyx is damaged only then mannitol will becomes effective by the mechanism of osmotic reabsorption. Of no clinical import but interesting none the less.

Reading

Oh’s manual Chapter 52

Fluid Physiology by Thomas Woodcock.