A Final FRCA station on MedMock, start to finish

Good afternoon. We'll start with the first short case. A 74-year-old man with Parkinson's disease is listed for an emergency laparotomy for adhesional small bowel obstruction. He was diagnosed twelve years ago and takes co-careldopa five times a day and rasagiline. He's been vomiting for two days and hasn't kept his tablets down since yesterday. What are the implications of his Parkinson's disease for his anaesthetic?

I'd think about the disease, his drugs and the surgery. The disease affects several systems. Motor: rigidity, tremor and bradykinesia, which matter for positioning, cause ECG artefact and slow his mobilisation afterwards, and severe rigidity can impair his breathing if his levodopa lapses. Bulbar: dysphagia and pooling of saliva, so a high aspiration risk on top of his obstruction. Respiratory: upper airway dysfunction and a weak cough, with a risk of laryngospasm and post-operative chest infection. Autonomic: postural hypotension, which makes him prone to marked hypotension at induction and with fluid shifts, and gastroparesis, urinary retention and poor temperature control. And neuropsychiatric: cognitive impairment, depression and hallucinations, which put him at high risk of post-operative delirium, so I'd assess his capacity and involve his family early. His drugs: levodopa has a short half-life, so missed doses quickly worsen his rigidity and swallowing, and NICE warns that letting antiparkinsonian drugs fail through poor absorption, including after abdominal surgery, risks acute akinesia or a neuroleptic malignant syndrome. Rasagiline is an MAO-B inhibitor, so pethidine must be avoided, and sympathomimetics can cause a hypertensive reaction, particularly indirect-acting ones such as ephedrine, so I'd avoid ephedrine and titrate any vasopressor carefully with an arterial line. And I'd avoid the centrally acting dopamine antagonists: metoclopramide, prochlorperazine, haloperidol and droperidol. I'd also ask whether he has a deep brain stimulator, because that changes how we use diathermy. Then the surgery: this is a high-risk emergency laparotomy, so I'd calculate his NELA risk, and at 5% or more he needs a consultant anaesthetist and surgeon present and a critical care bed afterwards. His fluid and electrolyte deficits need correcting, and he'll need a rapid sequence induction after aspirating his nasogastric tube.

Thank you. He's missed his last two doses. How will you manage his Parkinson's medication around the operation?

This is time-critical, so I'd involve the Parkinson's specialist nurse or neurology team and a pharmacist now, not after theatre. The problem is that he can't absorb anything reliably: levodopa is absorbed from the small intestine, which is obstructed, and his nasogastric tube is on free drainage. So he needs a non-oral route. The usual choice is a rotigotine patch, a transdermal dopamine agonist, with the dose worked out from his total daily levodopa-equivalent dose using a conversion calculator and checked with the Parkinson's team. I'd put it on before theatre rather than wait, using the lowest effective dose, because at his age it can cause confusion and hallucinations. It has to come off for an MRI scan or cardioversion, because the backing contains aluminium. Apomorphine by subcutaneous infusion is an alternative in specialist hands. After the operation I'd restart his co-careldopa as soon as his gut is working, at his usual times and prescribed as a time-critical medicine, and if he's absorbing, a dispersible levodopa preparation can go down the nasogastric tube. The rasagiline can wait until he's taking tablets again. For nausea I'd use ondansetron or cyclizine, remembering that ondansetron must be avoided if he's given apomorphine, because together they can cause severe hypotension, and that cyclizine adds to the risk of delirium. Once he's absorbing, low-dose domperidone is an option, because it barely crosses the blood-brain barrier, though I'd check his QT interval first.

Thank you. The operation goes well. On the second night on the ward he's agitated and says there are people in his room. The ward doctor wants to give haloperidol. What's your advice?

Please don't. Haloperidol can cause a severe worsening of his parkinsonism, and NICE's delirium guideline flags its risks in people with Parkinson's disease. This is most likely delirium, so I'd look for the cause: hypoxia, sepsis, including an aspiration pneumonia or a surgical complication, pain, urinary retention, constipation, an electrolyte disturbance, particularly of sodium, and his drugs. The drugs cut both ways: under-treatment, if the patch dose is too low or it has come off, and over-treatment, because dopaminergic drugs cause hallucinations themselves, as do opioids and anticholinergics such as cyclizine. So I'd check the patch and the drug chart and review the doses with the Parkinson's team. Non-drug measures come first: a calm, well-lit room, his glasses and hearing aids, his family, reorientation and sleep. If he's still a danger to himself or others, a small dose of lorazepam is generally preferred to an antipsychotic in Parkinson's disease, although it can itself add to the confusion. If hallucinations persist after the delirium has settled, quetiapine is sometimes used in Parkinson's disease, but that would be a specialist decision. And I'd involve the older people's medicine team.

Thank you. Let's turn to the linked science question. How is dopamine made, and how is it broken down?

It's made from the amino acid tyrosine. Tyrosine hydroxylase converts tyrosine to L-DOPA, which is the rate-limiting step, and aromatic L-amino acid decarboxylase, often called DOPA decarboxylase, converts L-DOPA to dopamine. In noradrenergic neurones, dopamine is taken up into vesicles and converted to noradrenaline by dopamine beta-hydroxylase, and in the adrenal medulla noradrenaline is methylated to adrenaline by PNMT. In dopaminergic neurones, dopamine is stored in vesicles and released, and its action is ended mainly by reuptake through the dopamine transporter. It's broken down by monoamine oxidase and catechol-O-methyltransferase, and the main end product is homovanillic acid, which is excreted in the urine.

Thank you. Which receptors does it act on, and what do they do?

There are two families of G protein-coupled receptors. The D1-like receptors, D1 and D5, are coupled to Gs and increase cyclic AMP; the D2-like receptors, D2, D3 and D4, are coupled to Gi and reduce it. In the brain there are four main pathways. The nigrostriatal pathway controls movement, and loss of its neurones causes Parkinson's disease. The mesolimbic and mesocortical pathways are involved in reward and behaviour; excess dopaminergic activity there is linked to psychosis, which is why antipsychotics block D2 receptors, and why his Parkinson's drugs can cause hallucinations. The tuberoinfundibular pathway inhibits prolactin release, so D2 antagonists raise prolactin. And the chemoreceptor trigger zone in the area postrema has D2 receptors and lies outside the blood-brain barrier, which is why dopamine agonists cause nausea and D2 antagonists are antiemetics. Peripherally, D1 receptors dilate the renal and mesenteric vessels. As an infusion, dopamine also stimulates beta-1 and then alpha-1 receptors as the dose rises, but low-dose renal dopamine doesn't protect the kidneys: the ANZICS trial found no benefit in critically ill patients with early renal dysfunction.

Thank you. How do his drugs work, and why is his levodopa combined with carbidopa?

Dopamine itself doesn't cross the blood-brain barrier, but levodopa does, carried by the large neutral amino acid transporter, and it's converted to dopamine in the surviving nigrostriatal neurones. Given alone, most of an oral dose would be decarboxylated in the periphery, causing nausea, vomiting and postural hypotension and leaving little for the brain. Carbidopa is a peripheral decarboxylase inhibitor that doesn't cross the blood-brain barrier, so it blocks that peripheral conversion and allows a lower dose with fewer side effects; benserazide does the same in co-beneldopa. Rasagiline irreversibly inhibits MAO-B, reducing the breakdown of dopamine in the brain and prolonging the effect of each dose, which is also why it interacts with pethidine, with a risk of serotonin toxicity. The dopamine agonists, like the rotigotine patch, act directly on dopamine receptors and don't need conversion, which is why they're useful when he can't absorb levodopa. And domperidone is safer than metoclopramide in Parkinson's disease because it blocks D2 receptors at the chemoreceptor trigger zone, outside the blood-brain barrier, without reaching the striatum.

Thank you. That's the end of the station.