BT PO 1.120 Pharmacology of anticoagulant drugs

One winter’s day in 1933, a young farmer named Ed Carlson drove 200 miles in a blizzard, to the biochemistry building at the University of Wisconsin with a dead cow, a bucket of un-clotted blood and a truckload of old sweet clover. He carried the bucket of blood into the only office that was open, and pleaded with the researcher, one Karl Link, to help him with his dying cattle.

So begins a wonderful story of scientific discovery, Vitamin K, newborn haemorrhagic disease, and of course rat poison (years later, Link was recuperating from tuberculosis in a facility with a rat problem and he got to thinking…) with the eventual development of a drug that has saved countless lives from stroke and DVT over the last 60 years.

Prof Karl Link was known for his fine dress sense

I once by chance sat next to a professor of medical history from Wisconsin in a restaurant in New York. He didn’t know any of this. I gave him a short tutorial …

More clinically, although many consider warfarin’s days to be numbered, there are a lot of patients out there who will be on it for years to come, and there’s a fair chance that in the middle of the night, if the anaesthetist does not know how to correctly manage a patient on warfarin, then nobody else in theatre will be able to either.

T/F 3mg intravenous Vitamin K will bring the INR down to 1.4 in 90% of patients within 12 hours

T/F Macrolide administration to a patient on warfarin will invariably make the INR increase to dangerously high levels

T/F Acute increases in the dose of warfarin can cause catastrophic skin necrosis

T/F Reversal of warfarin with Prothrombinex works in 5 minutes but costs 500 times as much as Vitamin K

T/F A raised INR due to hepatic liver disease does not imply the same degree of coagulopathy as the same INR caused by warfarin

References:

Peck & Hill has the basic facts on warfarin & reversal.

Australian reversal protocols here: An update of consensus guidelines for warfarin reversal. The Medical Journal of Australia, 198(4), 198–199.2013, Tran, H. A., et al

For those of you with oodles of time, you can read more of the history online here, or here, or in Wardrop & Keeling (2008) – The story of the discovery of heparin and warfarin. British Journal of Haematology, 141(6), 757–763.

And for the true Karl Link enthusiast, here is a home movie film of him visiting the Wisconsin Alumni Research Foundation, complete with his dog and some ears of corn.

IT_GS 1.5 Colloids and Crystalloids

Which contains more salt?

Even healthy elective patients at my hospital seem to routinely get a litre of crystalloid connected to their cannula, which invariably all runs into them before they get back to day surgery. Why is this?

Do they really need the water? They certainly don’t need the salt. If you were fluid deplete and thirsty from an overnight fast, would your choice be to drink salty water? How salty is normal saline? Have you ever tasted it?

T/F The first patient on the morning list, who has fasted since midnight, is no more dehydrated than the registrar, who has drunk a mild diuretic.

T/F 1 litre of Hartmann’s contains more salt than your recommended daily intake.

T/F The volume of distribution of Normal Saline is about 12 litres

T/F 1 litre of Normal Saline contains more salt than 100g of Vegemite.*

T/F The main reason that elective patients get i.v. fluids is so the anaesthetist doesn’t need to flush in each drug manually.


* Marmite has slightly less salt than Vegemite, but the answer remains the same. But supposing you did eat 100g of it, as part of some sort of slightly perverse primary exam self-study project, how much water do you think you would need to drink to compensate, and would that water take more than a just little while to excrete?

Congratulations, Dr Richard Harris – Australian of the Year

Australia Day was celebrated on Saturday, 26th January. Today is the corresponding public holiday.

I’m sure you have all heard by now that Dr Richard Harris has been named joint Australian of the Year for 2019. Dr Harris is a consultant anaesthetist working in Adelaide, who was instrumental in the rescue of 12 boys from a flooded cave in Thailand. No doubt an advanced understanding of respiratory physiology was one of the many attributes he needed to safely undertake that dangerous rescue!! He shares the Australian of the Year award with his diving colleague, Dr Craig Challen, a retired vet. Click here to read the Sydney Morning Herald article.

Dr Harris has also received the Star of Courage (Australia’s second highest civilian bravery decoration), and the Medal of the Order of Australia (OAM).

Dr Richard Harris SC OAM

Feeling inspired by the above, I though I would do a post on diving physiology. I have to admit that there does not appear to be an LO in the curriculum specifically on diving physiology. BT_PO 1.37 mentions the effect of altitude, and BT_SQ 1.5 covers gas laws. Even so, Nunn’s Chapter 16 covers diving it extremely well, and it’s quite interesting, so let’s do this one just for fun.

T/F underwater, at a depth of 10 m below sea level, the pressure exerted on a diver would be 2 ATM

T/F at this depth, alveolar PO2 would be 264 mmHg (see Note 1)

T/F During a SCUBA dive, the PaN2 increases, so more and more N2 progressively dissolves into tissues, including the brain (see Note 2). This can cause nitrogen narcosis – with effects ranging from mild confusion to unconsciousness.

T/F During ascent from a SCUBA dive, the extra dissolved N2 can no longer remain in solution so there is potential for it to form gas bubbles in the tissues and blood stream. (see Note 3)

T/F Breath holding during rapid ascent from a dive (maybe you panicked when you saw a shark) can cause a pneumothorax (see Note 4)

T/F very deep or prolonged dives can be made safer by using a mixture of helium and oxygen (rather than nitrogen and oxygen). (see Note 5)

Notes

1. Why doesn’t the alveolar PO2 just double?
2. Can you use a gas law to explain why this happens?
3. Decompression sickness is also called “the bends” and “Caisson disease”. Why did it get those names?
4. Can you use a gas law to explain why this happens?
5. Can you explain why helium is better for this situation? There is more than 1 reason.

What’s this?

What on earth would this historical instrument have been used for in anaesthesia?

BT_PM 1.21 Describe the pharmacology of opioid antagonists

T/F  naloxone is a competitive opioid antagonist, which binds covalently to opioid receptors

T/F  in the presence of an agonist, a competitive antagonist has the effect of making the agonist less potent

T/F  the structure of naloxone is almost identical to morphine

T/F  naloxone has zero efficacy, and low receptor affinity

T/F  using small titrated doses of naloxone, it is possible to reverse respiratory depression without reversing analgesia

T/F  especially at high doses, the partial agonist buprenorphine can act as an antagonist to other opioids

T/F  Suboxone™ contains a mixture of buprenorphine and naloxone, and is used in the management of opioid abuse (can you explain why the naloxone is added?)

References

• any decent pharmacology book will contain the answers to the above
• general information about agonists and antagonists would be found in the chapter(s) on pharmacodynamics

BT_RA 1.7 Describe the pain and sensory pathways

T/F  the sensory pathway (including pain) consists of three separate neurons: 1. periphery to spinal cord, 2. spinal cord to thalamus, 3. thalamus to cortex (see also Discussion Point 1)

T/F  sharp, well localised pain is transmitted via A-delta nerve fibres

T/F  C fibres are polymodal, and respond to thermal, chemical and mechanical stimuli

T/F  C fibres synapse in the dorsal horn at laminae I and II

T/F  all sensory information (including pain) is transmitted in the spinal cord via the spinothalamic tract

T/F  the primary sensory cortex (in the brain) lies anterior to the primary motor cortex

References:

1. Kam & Power 3rd edition Chapter 13
2. Ganong 24th Edition Chapter 8

Discussion Point 

• does this basic scheme still apply for sensation/pain transmitted via cranial nerves?

BT_RA 1.8 Describe the principles of ultrasound imaging and the safe use of ultrasound equipment for regional anaesthesia

T/F  the frequency and amplitude of a wave are synonymous terms

T/F  one Hertz = 100 cycles per second

T/F  ultrasound consists of high frequency sound waves above the human hearing range (medical ultrasound is 2.5 – 15 MHz)

T/F  Ultrasound waves are produced by a piezo-electric crystal *. The crystal vibrates in response to an electric current.

T/F  choosing an ultrasound transducer with a higher frequency will produce a higher resolution image, at a greater depth **

T/F ultrasound waves are propagated through all tissues at the same velocity

T/F  when using ultrasound for an invasive procedure, the probe must be covered by a sterile cover, and sterile gel must be used (see ANZCA PS 28)

References

1. Cross & Plunkett 2nd ed, page 87-88
2. Magee & Tooley 2nd ed, page 148-150
3. ANZCA PS 28 – Infection Control in Anaesthesia, 2015

* What does “piezo” mean?

** Have a look at your ultrasound machine(s) at work. What is the frequency of the probes you usually use for nerve blocks or line insertions, compared with probes for obstetric scans, or FAST trauma scans?

BT_RT 1.14 Discuss cerebral perfusion pressure

T/F  cerebral perfusion pressure = mean arterial pressure – intracranial pressure

T/F  cerebral perfusion pressure is the only determinant of cerebral blood flow

T/F  PEEP can decrease cerebral perfusion pressure

T/F  after traumatic brain injury, the recommended range for cerebral perfusion pressure is 60-70 mmHg (see reference 2)

T/F  sevoflurane may decrease CPP, but increase CBF

T/F  the cerebral circulation has minimal sympathetic innervation

References:

1. Miller 8th edition, Chapter 17
2. Brain Trauma Foundation. Guidelines for the management of severe traumatic brain injury, 4th edition. 2016, page 181

Do you know any great primary teachers?

Because they could become great primary examiners.

Do you have any tutors who have been fellows of the college for at least 3 years? Who have a contagious passion for the sciences underpinning anaesthesia? Who seem to know a bit about the topic? Who might be reluctant to apply without a bit of a nudge? Or are you a tutor reading this?

We have vacancies for primary examiners. First step is to email primaryexam@anzca.edu.au to get the application documents and ask any questions. The applications are considered twice a year and and successful fellows are invited to a weekend training workshop before the following vivas. At the workshop they are allocated a mentor who helps them prepare for and at their first viva examination. If someone applied now they’d be considered in May. It’s hard work but satisfying.

We’d love you to encourage any tutors you admire.

BT_PO 1.69 Describe the physiological effects and clinical assessment of renal dysfunction

Late, AND only 4 today. They range from a simple fact (in Hemmings and Egan), through to more complex statements. Statement 4 is TRUE, more important is that you know why.

Neonates have a higher serum potassium due to poor renal excretion  TRUE/FALSE

Urea concentration is a measure of renal function independent of hepatic function  TRUE/FALSE

Creatinine is a reliable indicator of renal function in an 80 year old TRUE/FALSE

Positive pressure ventilation contributes to intra-operative oliguria  TRUE/FALSE