BJA Education, 17 (4): 145–149 (2017)

doi: 10.1093/bjaed/mkw050
Advance Access Publication Date: 7 September 2016
Matrix reference
2A03, 2A07, 2G01

Parkinson’s disease
D J Chambers BM BCh DPhil MRCP FRCA1, J Sebastian BSc MBBS MRCP FRCA2, *,
and D J Ahearn MB ChB MRCP MSc3
1
Specialty Registrar in Anaesthesia, Salford Royal NHS Foundation Trust, Stott Lane, Salford M6 8HD, UK,
2
Consultant Neuroanaesthetist, Salford Royal NHS Foundation Trust, Stott Lane, Salford M6 8HD, UK, and
3
Consultant Physician/Geriatrician, University Hospital of South Manchester NHS Foundation Trust, Southmoor
Road, Manchester M23 9LT, UK
*To whom correspondence should be addressed. Tel: +44 161 2065870; E-mail [email protected]

classical motor symptoms of parkinsonism: bradykinesia, mus-

Key points cle rigidity, and asymmetric resting tremor. There is considerable
dopaminergic neuronal reserve—symptoms are often not seen
• Parkinson’s disease (PD) is associated with add-
until around 60–80% of dopaminergic neurones have degener-
itional perioperative morbidity and mortality.
ated. While the precise mechanism responsible for this cell
• Abrupt withdrawal or omission of anti-parkinson- death is unknown, age is the single most consistent risk factor.
ian medication can have serious consequences. Patients with PD are therefore typically older and, as patients
may live with PD for 20 yr or more, the prevalence in those
• The transdermal dopamine agonist rotigotine is es-
aged over 65 is ∼1%.
pecially useful in nil-by-mouth patients.
There is no specific diagnostic test for PD—the diagnosis is
• Many drugs used routinely in the perioperative per- essentially clinical, using the UK Parkinson’s Society Brain
iod are contraindicated in patients with PD. Bank Criteria,1 although brain imaging may be useful to exclude
structural lesions or to demonstrate features supportive of other
• Postoperative delirium is particularly common in
neurodegenerative disorders. A number of other rarer neurode-
PD, and is best managed by non-pharmacological
generative conditions (e.g. multiple system atrophy, progressive
methods.
supranuclear palsy) also present with parkinsonism, and are col-
lectively referred to as ‘Parkinson-plus’ syndromes.
It would be wrong to think of PD as simply a disorder of the
extrapyramidal nervous system—it is a multi-system neurologic-
Idiopathic Parkinson’s disease (PD) is a common neurodegenera-
al disorder which causes disabling motor, neuropsychiatric, and
tive disorder, affecting over 100 000 people in the UK. Patients
autonomic dysfunction. While many of the clinical features of PD
with PD are undergoing increasingly complex surgical proce-
are present at diagnosis, some develop years later as the number
dures, both elective and emergency. Perioperative management
of dopaminergic neurones continues to decrease (Table 1). Cogni-
poses specific challenges to the anaesthetist, not only because
tive impairment is common (but not ubiquitous) as the condition
the multi-system nature of PD increases perioperative mortality
progresses, with patients meeting criteria for PD dementia on
and morbidity, but also because of the difficulties of adequately
average 11 yr after diagnosis.2
maintaining anti-parkinsonian medication during the periopera-
tive period.

Pharmacological management
Pathophysiology, diagnosis, and clinical
There are no established disease-modifying or neuroprotective
features therapies for PD. Pharmacological management is therefore or-
The pathophysiology of PD is a loss of dopaminergic neurones in iented towards managing the symptoms of PD, to enable the pa-
the pars compacta region of the substantia nigra, leading to the tient to pursue as normal a lifestyle as possible. As the disease

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145
Parkinson’s disease

Table 1 Clinical features of PD progresses, it can be challenging to minimize the disability caused
by PD against the troublesome side-effects of anti-parkinsonian
Clinical features Timing drugs. For this reason, many PD patients have highly refined and
complex drug regimes consisting of three or more different medi-
Primary motor features
Resting tremor (usually asymmetrical) Usually at diagnosis
cations taken at different times throughout the day.
Bradykinesia As the predominant pathophysiology of PD is a lack of dopa-
Rigidity mine in the substantia nigra, it would make sense to give exogen-
Early non-motor features ous dopamine replacement. However, dopamine cannot pass
Fatigue May precede diagnosis through the blood–brain barrier (BBB)—there is no cell membrane
Depression/anxiety dopamine transport protein, and dopamine is too polar to diffuse
Sleep disturbance across. Instead, the dopamine precursor levodopa is given, which
Constipation crosses the BBB unaltered and is converted to dopamine within
Later features the central nervous system (CNS) by the enzyme dopa decarb-
Motor oxylase. This enzyme is also found within the peripheral nervous
Gait change: stooped posture, 5–10 yr after onset of system—levodopa must be administered with a peripherally act-
shuffling gait with small steps, symptoms ing (i.e. does not cross the BBB) dopa decarboxylase inhibitor
loss of arm-swing (DDI) to prevent peripheral dopaminergic side-effects such as
Dysphagia tachycardia, arrhythmias, nausea, and vomiting.
Expressionless face A number of drug classes are available for the treatment of
Small handwriting
PD3 (Table 2). Most anti-parkinsonian drugs increase the activa-
Soft speech
tion of CNS dopamine receptors, either by increasing dopamine
Postural instability, leading to
concentration or by acting as dopamine receptor agonists. Levo-
frequent falls
dopa remains the most effective treatment of motor symptoms
Neuropsychiatric
in PD, but the side-effects become increasingly troublesome as
Cognitive disturbance: slowed Increasing likelihood as
cognitive speed, inattention, time from diagnosis
the duration of treatment increases. For this reason, especially
poor problem solving increases in early-onset PD, dopamine agonists may be used as initial ther-
Dementia >80% at 20 yr after apy, and other drugs [monoamine oxidase type B inhibitors
diagnosis (MAOBIs), catechol-O-methyltransferase inhibitor (COMTIs)] are
Autonomic often used in combination with levodopa-DDI as ‘levodopa-spar-
Postural hypotension 5–10 yr after onset of ing’ adjuvants.
Sialorrhoea (drooling or excessive symptoms
salivation) Motor fluctuations
Urinary dysfunction
Sexual dysfunction An ‘on’ period refers to a phase of relatively good symptom con-
trol. An ‘off’ period refers to poor symptom control, which may be

Table 2 Common pharmacological management of PD

Drug Indication Side-effects Anaesthetic relevance

Dopamine agonist—acts at dopamine receptors, mimics the effect of dopamine

Pramipexole, Monotherapy in early and established Nausea, orthostatic Risk of DAWS on acute withdrawal
ropinirole PD, adjunct to levodopa-DDI regime hypotension, impulsive
Rotigotine ‘Bridging’ therapy in patients who are control disorders, Parenteral transdermal preparation
unable to take or absorb anti- somnolence
Apomorphine parkinsonian medication, adjuncts to Nausea, dyskinesias, cognitive Subcutaneous infusion or injectable ‘pen’
levodopa-DDI regime impairment, postural for patients with troubling motor
instability fluctuations, very emetogenic, risk of
severe hypotension

Dopamine precursors—levodopa converted to dopamine in CNS. Peripherally acting DDI prevents peripheral conversion of levodopa
Levodopa- Motor symptoms in established PD Nausea, orthostatic Risk of PHS on acute withdrawal; short half-
carbidopa, hypotension, dyskinesia, life (1.5 h)—need to continue enteral
levodopa- hallucinations administration in prolonged procedures
benserazide

Monoamine oxidase B inhibitors (MAOBIs)—prevents breakdown of dopamine by MAOB

Selegiline, rasagiline Used as monotherapy in early PD, or as Headache, arthralgia, Risk of serotonin syndrome (fever,
adjunct to levodopa-DDI regime exacerbation of levodopa hypertension, tachycardia, agitation)
side-effects when used as with meperidine
adjunct

Catechol-O-methyl transferase inhibitors (COMTIs)—prevents breakdown of dopamine by COMT

Entacapone Adjunct to levodopa-DDI regime Dark-coloured urine, Reduce dose of other drugs metabolized by
Tolcapone exacerbation of levodopa COMT pathways, for example,
side-effects epinephrine

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 Parkinson’s disease

experienced a few hours after dosing when the dopaminergic Table 3 Areas of focus in the anaesthetic assessment of a PD patient
medication is ‘wearing off’. Choreiform dyskinesia is experienced
by some patients (typically those having taken long-term levo- System Anaesthetic relevance
dopa therapy) 1–2 h after doses of dopaminergic medication
Airway – Upper airway dysfunction (due to laryngeal/
(‘peak dose dyskinesia’). These choreiform movements can be pharyngeal muscle dyskinesia) contributes
very disabling, and it is often difficult to find a balance between to retained secretions, atelectasis,
‘on’ and ‘off’ periods: increasing the dose of dopaminergic medi- aspiration, post-extubation laryngospasm
cation to treat ‘off’ periods can worsen the dyskinetic periods. In- – Fixed flexion deformity of neck, which may
stead, the dose of dopaminergic medication may be divided impair laryngoscopic view
further, or the dose of the dopaminergic drug may be reduced Respiratory – Restrictive pulmonary deficit, due to rigidity,
and an MAOBI or COMTI added. bradykinesia, or dyskinesia of respiratory
muscles
Withdrawal complications – Obstructive sleep apnoea common
Cardiovascular – Cardiac arrhythmias
Abrupt withdrawal of usual medication, as may occur in the peri- – Orthostatic or exercise-induced
operative period or during critical illness, can result in: hypotension, which may be due to PD or
anti-parkinsonian drugs, increased risk of
– parkinsonism-hyperpyrexia syndrome (PHS), due to
intraoperative hypotension
withdrawal of levodopa. Symptoms mimic those of neuro-
CNS – Greater risk of postoperative delirium and
leptic malignant syndrome: muscle rigidity, fever, cardio- hallucinations
vascular instability, altered mental status (agitation, Gastrointestinal – Dysphagia, which contributes to aspiration
delirium, coma). PHS carries a significant mortality, up pneumonia and malnutrition
to 20% in untreated cases. – Sialorrhoea (drooling) is a sign of advanced
– dopamine agonist withdrawal syndrome (DAWS). Symp- PD, but is thought to be a motor symptom
toms include: anxiety, nausea, depression, pain, and (which impairs swallowing), rather than an
orthostatic hypotension. Withdrawal of dopamine ago- excess of salivation. May need a drying
nists should be planned electively and simultaneously re- agent before operation, for example,
placed with levodopa-DDI regimes. glycopyrrolate. Antimuscarinic (e.g.
neostigmine) drugs increase the viscosity of
saliva, thus further impairing swallowing
Perioperative management – Increased prevalence of gastroesophageal
There is increasing evidence that PD is associated with an in- reflux
crease in perioperative mortality4 and morbidity, including – Postoperative ileus or delayed gastric
falls,5 aspiration pneumonia,4 venous thromboembolism,6 and emptying may result in reduced absorption
of enteral anti-parkinsonian drugs
respiratory failure,7 and also an increased postoperative length
Urological – Increased risk of postoperative urinary tract
of stay.4 Postoperative delirium is a particularly challenging prob-
infection
lem, with studies identifying rates as high as 60%; the onset is
often delayed.8 With the complexity and frequency of many PD
drug regimes, the perioperative management of dopaminergic
When PD patients present for emergency surgery, there is little
medication may be challenging, even for patients undergoing
time for optimization. In addition, those with intra-abdominal
relatively minor procedures. The consequences of missing medi-
pathology will likely be made nil-by-mouth or have reduced intes-
cation doses or inadequate absorption of administered medica-
tinal absorption. Abrupt withdrawal of dopaminergic medication
tion vary between patients: many experience the ‘off’ motor
can have disastrous consequences—hospitals should have agreed
symptoms of freezing and rigidity, with consequences such as
protocols for the pharmacological management of these patients,
falls, swallowing difficulties, rigidity of voluntary respiratory
or the means by which to seek urgent advice from PD specialists.
muscles, poor cough, and failure to clear oral secretions. Even
worse, the abrupt withdrawal of usual anti-parkinsonian medi-
cation may precipitate PHS or DAWS. Perioperative drug management
The guiding principle of the perioperative pharmacological man-
Preoperative assessment
agement of PD patients is to maintain CNS dopamine receptor ac-
When a PD patient is listed for elective surgery, the hospital’s tivation. In most cases, this can be achieved by continuing the
preoperative assessment service should be informed as soon as patient’s usual anti-parkinsonian drug regime into the peri-
possible to allow comprehensive anaesthetic assessment, opti- operative period: allowing patients to take their drugs up until
mization by PD physicians, discussion of perioperative risk, and anaesthetic induction, that is, within the ‘nil-by-mouth’ period
to plan perioperative dopaminergic drug management. The pa- with a sip of water, utilizing anaesthetic techniques which en-
tient should be warned of the potential for less-than-optimal able a rapid return to oral intake, for example, central neuraxial
PD symptom control during the perioperative period. PD nurse block, or by administering drugs enterally via a nasogastric
specialists play a crucial role in co-ordinating preoperative man- tube (NB for dispersible preparations only—due to the differing
agement plans, in particular prophylactic strategies to prevent bioavailabilities, a 30% dose reduction is suggested if the patient
postoperative delirium. In addition to undertaking a routine his- usually takes modified-release preparation). PD patients should
tory and physical examination, specific body systems require usually be placed first on the operating list, so that the timing
special focus in PD (Table 3). Additionally, most patients with of drug administration is predictable, the risk of cancellation is
PD are older and are therefore likely to have co-morbid disease minimized, and to ensure optimal early postoperative disease
which needs to be thoroughly assessed and optimized. management.

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Parkinson’s disease

In emergency and/or abdominal surgery, an early decision which treats parkinsonian symptoms without serious ad-
must be made about whether enterally administered dopamin- verse effects, for example, profound hypotension. The peri-
ergic drugs can be continued, or whether the patient must be operative apomorphine infusion is then commenced 24–48
converted to parenteral medication. Unfortunately, most anti- h before surgery, and continued until the patient’s usual PD
parkinsonian drugs can only be administered enterally. There drugs are re-established. Apomorphine is highly emeto-
are two main parenteral drug options: genic: patients are routinely pre-treated with 3 days of dom-
peridone before apomorphine challenge or therapeutic
– Subcutaneous apomorphine infusion. Apomorphine is a highly infusion, and throughout the duration of apomorphine
potent dopamine agonist with a number of side-effects, therapy.
and requires a high degree of planning. Dosing is difficult – Transdermal rotigotine. In recent years, rotigotine (a transder-
and should be overseen by a PD specialist: a preoperative mal dopamine agonist) has significantly simplified this
apomorphine challenge is recommended to find a dose complex clinical problem. Compared with apomorphine, ro-
tigotine patches are much easier to dose, with an improved
side-effect profile. However, they may not be sufficiently po-
Table 4 Pharmacological contraindications and cautions in PD tent to manage patients on higher-dose anti-parkinsonian
drug regimes. Ideally, conversion from a patient’s usual
Drug class (example) Effect
drugs should be overseen by a PD specialist, but if there is in-
Contraindicated sufficient time, a number of simple algorithms9 or online
Phenothiazines All are dopamine antagonists, calculators (e.g. http://www.parkinsonscalculator.com) are
( prochlorperazine) resulting in exacerbation of available. Many units adopt the approach of decreasing
Butyrophenones (droperidol) parkinsonian symptoms the initial rotigotine dose for acutely unwell or frail patients
Benzamides due to the risk of delirium and other neuropsychiatric
(metoclopramide) sequelae.
Typical anti-psychotics
(haloperidol)
Intraoperative anaesthetic considerations
Caution
Centrally acting May precipitate central A number of drugs commonly used in the perioperative period
anticholinergics (atropine) anticholinergic syndrome: are contraindicated in PD, and more still should be used with cau-
confusion, somnolence, tion (Table 4). Considerations for the anaesthetist are as follows:
restlessness; glycopyrrolate is a
safe peripherally acting – Regional anaesthesia. For suitable types of surgery, central
alternative neuraxial block offers many advantages (Table 5).
Halothane Sensitizes the heart to the action of – Monitoring. A significant tremor may induce monitoring
catecholamines: may potentiate artifacts: the ECG trace may mimic atrial flutter or ven-
levodopa-induced arrhythmias tricular fibrillation, and it may be difficult to measure ar-
Meperidine Interacts with selegiline (MAOBI) to terial pressure non-invasively. Excessive sweating due to
precipitate serotonin syndrome autonomic dysfunction may result in poor ECG electrode
Direct-acting Exaggerated vasoconstrictor effects contact.
sympathomimetics in – Induction of anaesthesia. Just as in the general population,
those taking MAOBIs propofol may cause dyskinetic movements in PD patients.
Epinephrine, in those taking Exaggerated sympathetic response But propofol is also an anti-emetic and temporarily sup-
COMTIs presses the parkinsonian resting tremor, and is therefore
Fentanyl, alfentanil Large doses may result in muscle
probably the best choice of induction agent in most situa-
rigidity
tions. Thiopental and ketamine have been used in PD
patients without harm, despite theoretical risks of

Table 5 Advantages and disadvantages of regional vs general anaesthesia

Mode of Advantages Disadvantages

anaesthesia

Central neuraxial Intraoperative monitoring of parkinsonian Muscle rigidity may make positioning difficult
block symptoms
Further oral medication may be given May be technically challenging with severe resting tremor
intraoperatively
Earlier return to postoperative oral intake Risk of hypotension, especially in those with autonomic dysfunction
Reduced use of systemic opioids, which may Tremor will only be abolished in the areas with motor block—tremor
otherwise decrease gastrointestinal absorption elsewhere may hinder surgery and affect monitoring
Neuromuscular blocking agents not required, so no
need for anticholinergic reversal agents
General Tremor is eliminated Postoperative nausea and vomiting may preclude adequate dosing of
anaesthesia anti-parkinsonian medication
General anaesthesia in combination with dysphagia and ineffective
cough is more likely to result in postoperative pneumonia

148 BJA Education | Volume 17, Number 4, 2017

 Parkinson’s disease

exacerbation of parkinsonian symptoms and exaggerated Delirium is ideally managed using both individualized mea-
sympathetic response, respectively. With the exception of sures agreed before operation and also by following local and na-
halothane, which potentiates levodopa-induced arrhyth- tional guidance.11 Non-pharmacological means are highly
mias, the volatile anaesthetic agents are safe. Whichever preferable, such as reorientation (explaining where the patient
drug is used for induction of anaesthesia, it is important is, the time of day, and your role) and providing a suitable care en-
that it is used judiciously: perioperative hypotension can vironment.11 Where drug management is absolutely necessary,
be difficult to manage, and is especially common in the typical anti-psychotics such as haloperidol should never be
presence of autonomic dysfunction or dehydration. used, due to their anti-dopaminergic effects; benzodiazepines
– Neuromuscular block. Neuromuscular blocking drugs are such as lorazepam are considered safer in PD. Quetiapine is
safe to use in PD. However, residual block in the immedi- often considered in clinical practice for troubling symptoms of
ate postoperative period can mask parkinsonian symp- psychosis, although evidence is lacking.
toms, and neostigmine should be used with caution due
to its thickening action on airway secretions. Perhaps, Declaration of interest
the ideal agent is rocuronium, as it may be reversed by
None declared.
sugammadex.
– Opioids. Meperidine should not be used for PD patients
who take selegiline, due to the risk of precipitating sero- MCQs
tonin syndrome. While all strong opioids have been used The associated MCQs (to support CME/CPD activity) can be
safely in PD patients, some cases of rigidity following high accessed at https://access.oxfordjournals.org by subscribers to
doses have been published. BJA Education.
– Airway management. Sialorrhoea can complicate airway
management, and may be reduced with glycopyrrolate. Podcasts
Intubation should be considered if dysphagia is sus-
pected. There is an increased prevalence of gastroparesis This article has an associated podcast which can be accessed
and gastrooesophageal reflux disease in PD patients, at https://academic.oup.com/bjaed/pages/Podcasts.
which may necessitate rapid sequence induction. Laryn-
goscopy may be difficult in the presence of a fixed flexion References
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