BT_RT 1.6 Describe the physiological basis of anaphylactic and anaphylactoid reactions

Relatives of the little guy hiding in the poppy, are big culprits in this department…

Anaphylaxis – arrgghh! I think this is one of the most awful complications associated with anaesthesia – its idiosyncratic nature mades it hard to avoid even with careful practice and, although rare, despite gold standard treatment a few patients will have a terrible outcome.

Anaphylaxis is obviously not a normal physiological response and hence tends not to be covered in physiology textbooks. Of those books on the reading list, Hemmings and Egan Ch 6 Adverse Drug Reactions and Miller Ch 34 Anaesthetic Implications of Concurrent Disease, both discuss it. Here  is and article from BJA Education and the Australian and New Zealand Anaesthetic Allergy Group have a wide range of resources especially for management of suspected anaphylaxis.

UPDATE SEPT 2018: following the comments after this post was originally published, I have amended the nomenclature of the statements. Unfortunately the LO remains as it is for now….

BT_RT 1.6 Describe the physiological basis of anaphylactic and anaphylactoid reactions

The first four of these statements are core and the answers and be found in the textbook references above

Allergic anaphylaxis is a Type 1 hypersensitivity reaction T/F

Following initial exposure to an allergen, IgE anitbodies are generated with circulate in the plasma until a repeat exposure T/F

Products of mast cells may be released en masse with both allergic and non-allergic anaphylactic reactions T/F

The symptoms of allergic anaphylaxis can all be attributed to histamine T/F

These two require a bit more thought (although the answer to the first in the books 😉 )

The severity of an non allergic but not allergic anaphylactic reaction may be reduced by giving a drug slowly T/F

Immediately after a life threatening allergic anaphylactic reaction, the same drugs may be given without risk if the same response T/F

BT_GS 1.12 Effect Site Modelling

BT_GS 1.12

If you read PS51 on medication safety, you will notice that it recommends the use of “Smart pumps”. Pharmacokinetic models are considered a fundamental part of modern anaesthetic practice, and you should understand their characteristics well.

The following question is important: 

This graph shows the curves calculated for individual patients in a Midazolam pharmacokinetics study. You will note that one of the curves looks strange. I suspect there was a transcription error with one of the constants. Apart from this patient though, this is neither a best, nor a worst case graph.

• T/F The predictive accuracy of a pharmacokinetic model is ±10%

The following concept is fundamental. You should be able to explain both what happens and why.

You can see here the effect of haemorrhagic shock on effect site concentrations after a bolus dose of propofol.  These graphs are based on pharmacokinetics from a pig study. You will note that pigs have different pharmacokinetics to humans. All the pigs were bled to a specific blood pressure, so the effect in a shocked patient might be less or more than this example.

Scroll down and look at the differences in the graphical representations of the control and shocked models. See if you can figure out why the curves are different.

• T/F Paradoxically the dose of propofol should be increased in haemorrhagic shock

The next concept is something you should understand.

Which of Schnider & Marsh has the larger central compartment? Now look at the difference between effect site and plasma concentrations with the Schnider and Marsh models.

• T/F The ratio of maximum plasma concentration to maximum effect site concentration is greater in models with a larger central volume of distribution

This is important because if you are using a model targeting plasma concentration, the initial bolus will be proportional to the size of the central compartment. Another issue to be aware of is that the central compartment size in the Schnider model is fixed. This means that all patients, regardless of size, would be given the same initial bolus if you used plasma concentration mode with the Schnider model.

This concept is interesting but less important.

Look at the difference between effect site and plasma concentrations with a model for vecuronium and for dexmedetomidine. Both have roughly the same central volume of distribution. Look at their times to peak effect. Try shortening the TTPE for dexmedetomidine and see what happens to the maximum plasma concentration.

• T/F The ratio of maximum plasma concentration to maximum effect site concentration is greater in drugs with a long time to peak effect

The last question tests your understanding of how these models work.

Take a look again at the time course of plasma concentration and effect site concentrations in the Schnider model for propofol. Take a look at some of the other drugs and see if it is the same.

• T/F Plasma concentration is equal to effect site concentration at ln(2) x the time to peak effect

I have put the following in small print because it is not a pass/fail concept.
When we look at the relationship between plasma concentration and effect, we notice that the effect lags the concentration in both onset and offset. We can correct for this by introducing a mathematical lag. The ‘effect’ site concentration is therefore a lag corrected plasma concentration rather than a real entity. If we could actually measure the concentration at the effect site, what would it be? The experiment is actually possible with microdialysis catheters. In this study, they found the actual tissue concentrations of cefazolin were about an order of magnitude less than the plasma concentrations.

It is not possible to simulate this using a standard mammillary model, as the effect site concentration in these models will always eventually approximate that of the central compartment.. How can you explain this discrepancy?

BT-PO 1.45 Factors affecting venous return

Sally lightfoot crab – Galapagos [no relevance except I might get crabby if don’t know this stuff…]

Effective venous return is clearly important for normal function of our cardiovascular system. It is inextricably linked to cardiac output, but I suspect that most of us spend more time thinking about factors affecting cardiac output rather than factors affecting venous return.

As with all questions of flow, if you are stuck for an answer think back to our friend, the hydraulic analogy of Ohm’s Law, Flow=ΔPressure/Resistance. Once you have done this, if you can work out the two important pressures, you should be able to think of some things that will alter them.

So what are the two important pressures for venous return? It is reasonably easy to work out that pressure at the final destination, the right atrium, is the lower pressure, but what is the driving pressure in the venous system?

BT-PO 1.45 Discuss the factors that determine and control cardiac output and the implications for clinical practice including:

• Cardiac output and vascular function curves

Power and Kam in their chapter on cardiovascular physiology, present this topic in a systematic way. The answers to these first really core statements can be found there.

Guyton ( the master of the cardiac function and venous return curves) and Hall in Chapter 20 also discuss this topic in depth.

Increased blood volume increases venous return, by increasing the mean systemic filing pressure (MSFP) T/F

The lower the right atrial pressure, the larger the venous return T/F

Venous return is more complicated than a simple passive hydraulic system as there are active components that come to its aid. Can you think about what these might be?

The skeletal muscle pump DOES NOT contribute in venous return whilst a person is standing still T/F

The decrease in intrapleural pressure with inspiration generally increases venous return to the right heart T/F

This one are a bit more conceptually difficult (it is discussed in Guyton and Hall)

An increase in venous tone causes a larger increase in resistance to venous return than the same increase in arterial tone, because the capacitance of the veins is much greater T/F

BT_SQ 1.16 Describe when a level 1 anaesthesia machine check is required. Refer to College professional document PS31: Recommendations on Checking Anaesthesia Delivery Systems

“Latex-free project 111.jpg” by Chrisjw is licensed under CC BY 2.0

Understanding the equipment used in anaesthesia is an important part of anaesthetic training and the primary exam.  Anaesthetic machines (or the more politically correct term – Anaesthetic Delivery Systems) have become increasingly sophisticated and complicated meaning, like cars engines, many of the components are now hidden away and require trained technicians to service and repair.  Gone are the days of owners fixing problems themselves.

The subject of this post is covered by a professional document produced by ANZCA, PS31 can be found here with a background paper here

T/F A level one check is done to verify that the system is functional and complies with the relevant Australian or New Zealand standards

T/F Intravenous and local anaesthesia delivery devices should be included in a level one check

T/F  A level one check should be performed at the start of every anaesthetic list

T/F Documentation of a level one check should include the date, the items checked, the results of the check, and the identity of the person performing the check

T/F Every step in a level one check is done because of a previous adverse event related to a failure of the component being checked

T/F  If a level one check has just been formed then a level two check is not required

Primary LO slice

Today a little something yummy to treat yourself to whilst studying.

In the notebook where I collect recipes this one is labelled Rachel’s Slice, after the friend who shared it with me. In her book it is called Vanessa’s slice for the same reason. If this one makes it into your repertoire perhaps you could call it Primary LO slice….

100g melted butter

140g crushed granita biscuits

1 cup shredded coconut

1 cup chocolate melts (I like dark)

1 cup pecans

1 tin condensed milk

Preheat oven to 180°C fan forced or 200°C conventional

Line a small tray (about 15×25 cm) with baking paper and it extend it up two sides to make removal of the slice easier

Layer all ingredients in the tray. Finish by drizzling the condensed milk over the top.

Bake for about 30 mins. I think the secret here is to wait until it is very brown. Don’t be tempted to remove it too early.

Allow to cool completely in the pan before slicing

It keeps pretty well (under lock and key….)

The slice isn’t particularly pretty so I have photographed it in one of my favourite cake tins.

I love the green of the tin. I think it is just as well I was born in the 20th century, as I suspect that green is quite similar to the infamous Scheele’s green. Scheele’s green, copper arsenite, was observed by Carl Wilhelm Scheele in 1775. Apparently at that time, it was very hard to manufacture a good green dye, so Scheele’s green went into mass production and was used to dye everything from wallpaper to artificial flowers to dress fabric. The problem was that it contained A LOT of arsenic. People started popping off the perch, prompting investigation by the medical profession through the mid 1800s. One sample of  dress fabric dyed with the pigment was found to contain 60 grains of arsenic per square yard (see Valeculla’s post to see exactly how much that is in modern terms). The compound was known to be poisonous by Scheele at the outset but even after there was fairly conclusive evidence that the pigment was harmful, no laws were ever passed to restrict arsenic’s use in paint. It you want to read more about this topic, including William Morris’s involvement have a look here or in the fabulous colour book I have mentioned previously, The Secret Lives of Colour.

Enjoy!

Bombay blood group

BT_RT 1.7 Describe blood groups and the physiological basis of transfusion reactions

I first heard of Bombay blood group this year. The H antigen is an intermediary in the production of A and B antigens, and is present in the red blood cells of those with O blood also. Bombay blood group has the recessive phenotype hh and does not express H antigens. It is very rare and will test falsely as O group unless specifically looked for. The antibody response to H antigens is predominantly IgM.

I don’t think this is examinable but I do think this is a useful concept to see how well you understand blood groups and transfusion reactions. You should be able to work out the answers given the above information.

A person with Bombay blood group is a universal donor      TRUE/FALSE

A person with Bombay blood group can safely receive blood from an O- donor      TRUE/FALSE

A person with Bombay blood group can safely receive blood from an AB- donor      TRUE/FALSE

In the soap opera General Hospital Monica was group A, her husband Alan AB and her child tested O. Was Monica cheating on Alan?*      YES/NO/MAYBE

Monica’s child was at risk of haemolytic disease of the newborn.      TRUE/FALSE

 

*thanks to Wikipedia for this gem!

Context Sensitive Half Time

BT_GS 1.12 Explain and describe the clinical application of concepts related to intravenous and infusion kinetics including: Concept of context sensitive half time

Context sensitive half time (CSHT) is a very important concept, and one which you should be prepared to discuss at length. This post discusses where these numbers come from.

All the textbooks show the same graph for CSHT of anaesthetic drugs. The graph comes from a paper by Hughes et al in 1992. You might be surprised to know that this graph is not of actual patient data, but the results of a simulation. The links in this post will allow you to reproduce these results, and also to see what happens if you use different pharmacokinetic models, or extend the time period.

This is the CSHT graph for midazolam using the data from Hughes’ paper. Click on the button labelled t_75%. This will show you the context sensitive time to fall to 1/4 of the original concentration.  t_87.5% shows the time to fall to 1/8 of the original concentration and t_93.5% the time to fall to 1/16. How do these times compare to the half time? How do they compare to the terminal elimination half life? (You can see it here).

• T/F The time to fall to 1/4 of the original concentration is equal to twice the CSHT

Look at the graph for fentanyl. Now change the timescale of the graph from 8 hours to 16 or 24 hours and see what happens.

• T/F The CSHT for fentanyl continues to increase indefinitely with length of infusion.

Have a think and see if you can answer this question:

• T/F Drugs with a very variable CSHT are inappropriate to administer as a bolus.

The minimum standard for a pass would be to know and be able to discuss the CSHT graphs which are in the textbooks. The following is for more advanced understanding.

Here is Hughes’ graph for propofol. Look at the CSHT at 4-8hours.  Now look at the same graphs using the Schnider and Marsh models. What do you notice? Which do you think correlates better with what we see clinically?

• T/F The CSHT for propofol after a 8 hour infusion is around 50 minutes

This is the graph for thiopentone. Have a look and see what happens with the prediction for 24 or 48 hour infusion. This certainly does not correspond with what we know clinically about thiopentone. See if you can work out the answer to the following question:

• T/F In Hughes’ graph, the CSHT for thiopentone increases steeply because it changes to zero order kinetics

The following is more of a question for a viva, as it does not have a simple answer:

Remifentanil is a better drug than oxycodone because it has a much shorter CSHT

BT_GS 1.30 Compartmental Modelling

BT_GS 1.30 Describe and compare the pharmacokinetics of intravenous induction and sedative agents, the factors which affect recovery from intravenous anaesthesia and the clinical implications of these differences

Pharmacokinetics of intravenous drugs is an important topic in the Primary. The following questions are based on standard compartmental modelling. You should have a solid understanding of the basic models, even if real life is more complicated.

The links are to an interactive page for compartmental models. If you can’t see the whole graph on the page, try making the page narrower.

Effect Site Concentrations, (Basic, Important)

These two questions are basic and important.

Here is a graph of “Effect site concentrations” after a bolus dose of propofol. Click on the 2x dose button to see what happens if you give a bigger dose.

• T/F Doubling the dose of propofol raises the effect site concentration by a factor of ln(2)

• T/F Doubling the dose of propofol speeds the time to peak effect

Compartment Modelling (Basic, Important)

A three compartment model can be expressed by the equation

C_t = Ae^-αt + Be^-βt + Ce^-ɣt

Look at the graphs here. Display them as both linear and semi-log graphs. How can the constants α, β & ɣ be calculated?

• T/F The constants α, β & ɣ are best calculated using a linear graph.

Look at the plasma concentration time graphs for two different models of Ketamine. Now look at the graphical display of the two models, Perrson and Olofson. You have probably not seen a 2D graphical comparison of models before, but the following concept is also basic and important.

• T/F The compartments in compartmental models refer to physical body compartments.

ke0 (Hard, Important)

ke0 is quite a difficult concept.  t_1/2ke0 is confusing because it has no simple relationship to any time that we use clinically. Do not conflate this with Time to Peak Effect!

Look at the different ke0 values for the Schnider and Marsh model for propofol.

• T/F The value for t_1/2ke0 is a constant for any given drug

So why is it called t_1/2ke0 if it doesn’t tell you the time to peak effect? It is the half life of the movement of drug to the hypothetical effect site. This movement is also affected by the plasma concentration, which in turn is affected by the other half lives. The calculation of time to peak effect involves a complicated function of all of them. TTPE is obviously a fixed property of the drug, so this means the ke0 is affected by the other half lives. Each ke0 is therefore specific to the model it has been calculated for. You cannot compare them between models.

 

BT_GS 1.51a Outline the aetiology of and measures to prevent intra- operative awareness under general anaesthesia.

This is an important topic yet much of it is more suited to the Final Fellowship. Be that as it may it in the LO’s so you will need to know something for the Primary, and ought to know a bit for your clinical practice anyway. There is a reasonable chapter in Miller 8e (chapter 50) on monitoring brain state in anaesthesia. This article by Michael Avidan is also well worth a read. Some of the material below comes from Spoors and Kiff but should be available in other places too.

T/F   End-tidal concentration of inhalational anaesthetics must be in use for every patient undergoing general anaesthesia where inhalational anaesthetic agents are delivered

T/F  The incidence of awareness with recall under general anaesthesia is about 0.12%

T/F  The risk of recall is higher with obstetric GA than with cardiac surgery

T/F  The risk of recall is higher with use of muscle relaxants

And now for some trickier ones:

T/F   Increase in autonomic arousal (pressure, rate, sweat, tears) is a sign of inadequate hypnosis

Hint: think about how you would treat this autonomic arousal in a patient on 1 MAC sevoflurane

T/F   The nociceptive-medullary-autonomic (NMA) circuit is comprised of the spinoreticular tract, brain stem arousal circuits and both sympathetic and parasympathetic efferents

Reading your feedback in 2018 – part 3

My hypothetical candidate was one of the 83.5% who passed the vivas at this exam. The vivas are in some ways easier than the SAQs as the examiners can prompt and rephrase questions to help you answer them, and in some ways more difficult as they test understanding. This candidate wasn’t able to compensate for their low SAQ mark, but should be very encouraged that they passed this component which requires both a breadth of knowledge and an ability to integrate the material.

This letter will have accompanying individual feedback sheets on questions/vivas that scored <40%, often with specific comments made by the marking examiner. It should be read in conjunction with the exam report too

This may be the first examination you have been unsuccessful in. This feedback, though difficult to read, can be a stepping stone to a successful attempt