Parkinson's Disease
Parkinson's disease is important to the anaesthetist for a variety of pathophysiological and pharmacological reasons that go far beyond remembering to prescribe their usual medications.
Describe the pathophysiology of Parkinson's disease
- Loss of dopaminergic pathways
- In the pars compacta of the substantia nigra
- Need to lose around 70% of dopaminergic neurons before symptoms develop
What are the classic features of Parkinsonism?
- Muscle rigidity
- Resting tremor
- Bradykinesia
What are some other symptoms of Parkinson's disease?
This is a big question, so break it down into groups:
Autonomic
- Postural hypotension
- Urinary and sexual dysfunction
- Sweating
Motor
- Gait disturbance
- Instability
- Dysphagia
- Micrographia
- Mask-like face (lack of expression)
- Quiet speech
Constitutional
- Disturbed sleep
- Fatigue
Cognitive and psychiatric
- Low mood
- Dementia
- Cognitive impairment
What would be on the differential diagnosis?
- Idiopathic Parkinson's disease (85%)
- Multisystem atrophy
- Progressive supranuclear palsy
- Vascular parkinsonism
- Wilson's disease
- Trauma
- Infection
- Neoplastic
- Antipsychotic medication
Remember every differential diagnosis has vascular, infective, neoplastic, traumatic and iatrogenic causes.
What perioperative complications are associated with Parkinson's?
- Increased perioperative mortality
- Falls
- Aspiration pneumonia
- Venous thromboembolism
- Respiratory failure
- Length of stay
- Delirium
Tell me about Dopamine
You love it.
No literally, you love it.
It's a natural catecholamine neurotransmitter and hormone present throughout the CNS and periphery as well, with a wide variety of effects from cognition and motor control, to renal perfusion and blood pressure management.
Long story short:
- Start with the amino acid phenylalanine
- This is converted by phenylalanine hydroxylase into tyrosine
- Tyrosine is actively transported into adrenergic neurons
- Here it is metabolised by tyrosine hydroxylase into DOPA
- This is the rate limiting step, and that gets asked in the exam
- DOPA is then converted to dopamine by DOPA-decarboxylase
Simple enough.
Here's our video on catecholamines
So what's particularly complex?
We don't yet have any disease-modifying treatments, it's all symptom control by trying to replace the lost dopamine functionality.
You're trying to replace lost dopamine, but you can't just give dopamine because it's too charged to cross the blood brain barrier to get to where it needs to be.
Therefore you have to give a precursor that can cross the BBB (levodopa), to then be converted by DOPA decarboxylase into the dopamine that we actually want.
Great, sorted!
Not quite. You also have peripheral DOPA decarboxylase that is also going to start spewing out reams of dopamine in the rest of the body, leading to:
- Nausea
- Vomiting
- Tachycardia
- Arrhythmias
So you have to combine it with a DOPA decarboxylase inhibitor (that won't cross the blood brain barrier), and that's why we have co-careldopa and co-beneldopa combination therapy.
To complicate things further, levodopa has a short half life of only a couple of hours, meaning you have to give it regularly on a strict timetable.
Alternatively you can just hammer the dopamine receptors directly, using dopamine agonists like ropinirole or pramipexole, but since dopamine is a ubiquitous and powerful neurotransmitter and hormone, these have their own host of side effects as well.
Outline the pharmacological management of Parkinson's disease
- Dopamine precursor and DOPA decarboxylase inhibitor - co-careldopa, co-beneldopa
- Dopamine agonist - pramipexole, ropinirole, rotigotine*
- MAO-inhibitors - selegiline, rasagiline
- COMT-inhibitors - tolcapone, entacapone
- Glutamate antagonists - amantadine
*Rotigotine transdermal patches are often the go-to option for patients that cannot take or absorb oral medications while in hospital. The other option is subcutaneous apomorphine, but it's highly emetogenic so might require domperidone prophylaxis.
What are the main side effects of Parkinson's medications?
These are all the things you would expect of elevated dopamine concentrations:
- Nausea and vomiting
- Dyskinesia
- Hallucinations
- Poor impulse control
- Somnolence
- Headaches
The tricky balancing act of side effects vs treatment means patients with Parkinson's disease are usually on a tight schedule of extremely powerful drugs that they have to take orally within a narrow time window to avoid withdrawal symptoms.
So once you insert a laparotomy for bowel obstruction into the equation, it's easy to see why this is a very difficult perioperative challenge.
What does withdrawal from Parkinson's medication look like?
- Parkinson-hyperpyrexia syndrome (levodopa withdrawal) - fever, rigidity, altered mental status, labile blood pressures
- Dopamine agonist withdrawal - anxiety, depression, nausea, hypotension
Tell me about Parkinsonism-hyperpyrexia syndrome
- Triggered by abrupt withdrawal of levodopa
- Looks a lot like neuroleptic malignant syndrome
- Carries up to 20% mortality if not treated promptly
- Symptoms include
- Hyperthermia
- Severe rigidity
- Altered consciousness
- Autonomic instability
- Can be avoided by careful timing of levodopa and other PD meds
And that's just the drugs
Now let's look at the actual disease process itself and how it might impact on your day as the patient's anaesthetist.
Parkinson's disease is a multisystem disease with anaesthetic implications for many body systems.
What are the airway implications of Parkinson's?
- Laryngeal dyskinesia
- Sialorrhoea
- Fixed flexion deformity makes laryngoscopy harder
- Increased chance of laryngospasm after extubation
What are the respiratory implications?
- Respiratory muscle rigidity causes restrictive respiratory disease
- Obstructive sleep apnoea is also common
- These then lead to pulmonary hypertension
What are the cardiovascular implications?
- Hypotension - this can be from the disease or the drugs
- Increased risk of arrhythmias
What are the neurological implications?
- Post-operative delirium - up to 60%
- Increased risk of hallucinations
What are the GI implications?
- Malnutrition from dysphagia
- Increased incidence of reflux
- Post operative ileus will impact absorption of Parkinson's meds
Pharmacological considerations
Can I use propofol?
Yes absolutely. It can cause excitatory neurological reactions in any patients during induction, but this isn't a contraindication to its use in patients with Parkinson's.
Ketamine is also safe, as is thiopentone.
What about my volatiles?
Sevoflurane is fine. Just don't get the halothane out the cupboard (why would you?) because it can worsen arrhythmias triggered by levodopa.
And rocuronium?
Also fine, just don't give neostigmine, which you won't, because it's 2026 and we all use sugammadex now.
What about opioids?
All fine except for pethidine which can trigger serotonin syndrome.
What antiemetics can you use?
- Ondansetron
- Dexamethasone
- Cyclizine
- Domperidone (doesn't cross the blood brain barrier)
Avoid all the other dopaminergic antiemetics (metoclopramide, haloperidol, droperidol, prochlorperazine, chlorpromazine).
What are the benefits and drawbacks of regional anaesthesia in patients with Parkinson's?
- Faster return to being able to take oral medications
- Can give oral medications during the procedure if needed
- Lower opioid requirement
- Avoids PONV and increased risk of pneumonia seen with general anaesthesia
- Avoids aspiration risk in patients with increased reflux and airway dysfunction
But
- Might be technically tricky with tremor and rigidity
- Patient may not be sufficiently stationary for surgery if not under general anaesthesia if the rest of their body is tremulous
Your Plan
Here's the section where you answer the Final SOE examiner's question "How are you going to anaesthetise this patient?"
'I'll divide my plan into preoperative, intraoperative and postoperative components.'
Preoperative
- Elderly patient with comorbidities - needs thorough history, examination and relevant investigations such as ECG, Echo and chest xray
- Need review and optimisation by Parkinson's disease specialists
- Should be first on the list to reduce fasting times and risk of cancellation and allow quicker return to normal oral intake
- Need a specific plan for the perioperative management of their regular medication - take oral meds during nil by mouth period
- Need to plan how their Parkinson's medications will be administered or substituted in the postoperative period
- Some patients will have deep brain stimulators, which need to be switched off if diathermy is needed for the operation.
What are your intraoperative concerns?
Monitoring
- Association of Anaesthetists minimum standards
- Consider invasive arterial blood pressure monitoring in light of autonomic dysfunction
- Tremor can interfere with ECG and NIBP monitoring
Airway plan
- Prepare for difficult airway
- Consider RSI if increased risk of aspiration
Positioning
- Cautious positioning in presence of stiffness and weakness
- Careful when adjusting bed tilt - orthostatic hypotension
Blood pressure control
- Judicious use of IV fluids
- Caution with adrenergic agents that may cause exaggerated response
Intraoperative PD meds
- May need to give NG, IV or transdermal medications during particularly long procedures
What are your postoperative priorities?
- Have a low threshold for HDU admission postoperatively
- The priority is recommencing Parkinson's meds as soon as possible
- Levodopa can be given via NG tube if needed
- If enteral route is not available, consider rotigotine or apomorphine parenterally
- Multimodal, opioid-sparing analgesia including use of regional anaesthesia where applicable (as always with any patient)
- Just note that a patient with Parkinson's disease may struggle to use a PCA
- Postop delirium and hallucinations are common, and you can't give haloperidol, so use quetiapine or lorazepam instead
References and Further Reading
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