Here is the link to our latest CRQs for the Final FRCA podcast episode on the Pharmacokinetics of sepsis, and below you can find the transcript of the recording.
Hello and welcome back to Anaestheasier, the social resource for learning all about anaesthetics!
Today we’re starting a new series on the podcast, specifically aimed at the Final FRCA exam, because James and I are both in the process of revising for the final written exam ourselves, and as part of that revision, I’m hoping that producing these podcasts will give me a new and interesting way to learn about the information, and hopefully I can use that time to provide value to our wonderful listeners as well.
If you’re revising for the Final yourself, then this should be right up your street, and if you’re not, it’s still useful information for any anaesthetist or anaesthesia enthusiast, so please do feel free to stick around – we’d be delighted to have you.
For this series, we are going to be addressing the CRQs or constructed response questions that feature in the MCQ paper, as these are a relatively new addition to the exam, replacing the older SAQs or short answer questions from previous years.
What I’m planning to do is address a single question topic per episode, and this is for two reasons:
- There’s more than enough material within each question to make a perfectly respectable podcast episode, and hopefully it will still be short enough to not feel overwhelming.
- I have found when listening to other podcasts myself, that when too much information is covered in one go I really struggle to maintain my focus, and ended up having to listen over and over again which frustrated me no end. So hopefully, we can strike a comfortable balance between informative and approachable, and please feel free to let us know if we’re anywhere near accomplishing this!
Now, the book I am using for these questions is the absolutely fabulous CRQs and SBAs for the Final FRCA: questions and detailed answers.
It is brand new, published this year and written by doctors Sumner, Allen, Feneley and Raithatha and I would highly recommend it. I have worked with Dr Sumner and his knowledge and attention to detail in his work are reflected in this book, and he has very kindly given me permission to sample some of the questions for this podcast, so without further faffing about – let’s crack on with question number one.
What I’ll do, is I’ll read out all the questions and how many marks they’re worth first, so if you’re revising for the exam you can pause as you go along and think or write down your answers first, then we can go through the answers afterwards.
Question one is the pharmacokinetics of sepsis.
Sepsis is one of the most common reasons for inpatient morbidity and mortality in the UK.
1. Define sepsis for two marks.
2. What underlying pathalogical features of sepsis contribute to end organ damage? For three marks.
3. Outline how the following pharmacokinetic principles would be altered in a patient with severe sepsis, and then it lists absorption for four marks, distribution for three marks, metabolism for one mark and elimination for one mark.
4. Explain the pharmacokinetics of propofol administration in patients with severe sepsis, for three marks and finally.
5. With prolonged sepsis, the doses of some vasoactive substances may need increasing to maintain the same degree of responsiveness. Explain the pharmacological mechanism for this, and that’s for three marks.
So this question is hard, and the pass mark is set at 10. The aim is to understand the changes in pharmacokinetics and drug handling that occurs in severe sepsis, specifically in a critical care setting. The main requirement to pass this question is ensuring you know the correct definition of sepsis and its underlying pathology.
So for two marks, define sepsis:
- An overwhelming and life threatening response to infection (gets you one mark)
- That can cause tissue damage, organ failure and ultimately death if left untreated (for the other mark)
This is the most recent definition according to the UK Sepsis Trust, and it neatly highlights the key points that it’s not so much the infection itself causing the trouble, but an overexaggerated response by the immune system, and there needs to be evidence that it’s causing damage to the tissues or evidence of organ dysfunction, such as acute kidney injury or respiratory failiure.
What underlying pathalogical features of sepsis contribute to end organ damage?
And this is for three marks, so we need to include something along the lines of:
- Widespread cytokine release and reactive oxygen species, leading to direct or indirect cellular damage
- Vasodilatation and capillary leak, giving the classic picture of distributive shock
- And finally impaired microcirculatory blood flow, causing poor perfusion, mitochondrial dysfunction and cellular hypoxia
The key here is a logical progression from infective trigger to celluar damage, and of course can be worded in your own style, but needs to include vasodilatation and mitochondrial dysfunction for full credit.
Next up we have the mega question:
Outline how the following pharmacokinetic principles would be altered in a patient with severe sepsis, including absorption, distribution, metabolism and elimination.
So for the four marks in absorption, you can choose four of the following:
- Delayed gastric emptying and ileus, both as a result of the illness itself and any opiates used
- Regular suctioning of NG tubes is likely to drag residual enteric medication back out of the patient’s system and reduce absorption
- Decreased splanchnic blood flow as a result of your vasopressors
- Mucosal oedema will affect absoprtion of sublingual and buccally administered drugs
- Reduced skin and muscle perfusion will reduce absorption from topical, subcut and intramuscular routes of administration as well
With regards to how distribution changes in severe sepsis, for the three marks you’re looking at:
- Changes in volume of distribution as a result of capillary leak and redistribution
- Changes in pH will influence drug behaviour based on the individual drug’s pKa, and the acidosis encountered in sepsis is no different
- Changes in plasma protein levels, particularly acute drops in albumin, will impact on drug binding and hence volume of distribution as well
Metabolism changes in severe sepsis can occur as a result of hepatic dysfunction, renal dysfunction or even pulmonary dysfunction as a result of being critically ill or directly from the infection itself, and elimination is particularly affected when we’re talking about renal excretion of drugs, in the context of acute kidney injury. This can be due to poor renal perfusion, intrinsic renal pathology or even changes in elimination that occur when a patient is on renal replacement therapy. Some drugs such as cefuroxime are completely cleared by haemofiltration, and should be dosed as if the patient has normal kidney function, while others such as aciclovir are not, and should be dosed as if the patient has a glomerular filtration, rate less than 10 ml/minute.
Phew, well done for making it this far, only two questions left.
Explain the pharmacokinetics of propofol administration in patients with severe sepsis, for three marks.
Here you have a bit of free reign to choose from anything vaguely resembling the following:
- Propofol is a very lipid soluble drug, with extensive protein binding
- Initially volume of distribution is decreased as a result of blood flow being diverted to the central parts of the body
- Furthermore there is a decrease in serum albumin, and this can lead to a higher concentration of free propofol in the plasma, with its subsequent cardiovascular side effects
- Add on top of this that you’ve got a reduced cardiac output anyway from the critical illness, and you can appreciate that induction of sedation or anaesthesia is likely to not only take longer, but you’re at greater risk of adverse side effects, because of an unexpectedly high plasma concentration
- And it’s worth mentioning that given these patients are often sedated for prolonged periods of time, there is an increased context-sensitive half life to take into consideration as well.
And last but not least:
With prolonged sepsis, the doses of some vasoactive substances may need increasing to maintain the same degree of responsiveness.
Explain the pharmacological mechanism for this, and that’s for a final three marks.
The underlying principle here is that there is down regulation of catecholamine remceptors, and increased production of vasoactive mediators by the endothelium, including nitric oxide and prostacyclin. So you’re going to need larger doses of vasopressors to achieve the same effect. So you could have the following points:
- Down-regulation of catecholamine receptors
- Increased production of nitric oxide and prostacyclin
- Generation of oxidative free radicals
- Tachyphalaxis occurs with vasopressors anyway, and you’re likely to be using them for a prolonged period of time in severe sepsis
- Activation of ATP-sensitive potassium channels as a result of prolonged acidaemia causes hyperpolarisation of the vasculature smooth muscle and vasodilatation
Any three of the above and you’re looking at a solid score.
So as a summary, we often see rather profound derangements in drug pharmacokinetics in severe sepsis, and understanding this is crucial to getting our management right, and avoiding over-sedating or under-squeezing our patients. You can see how this question takes your understanding of pharmacokinetics from a primary level, and adds some meaningful context, and gets you to apply that biochemical knowledge in a clinical scenario with appreciable patient outcomes.
If you’d like to read more about this specific topic, there is the BJA Eductation article entitled Pharmacokinetics in sepsis from 2019 written by Charlton and Thompson, which contains more than enough information for a really solid understanding required at a finals FRCA level.
I hope you have found this episode useful, I’ve certainly learned something while writing and recording it, and I would be really receptive to any feedback, comments or questions you may have, either comment directly or email at email@example.com. Otherwise, Happy gassing, and see you next time!