Nasogastric TubeIntroduction
How to approach a patient with PD
Management of neuropsychiatric manifestations of PD
Neuroleptic malignant syndrome
Dyskinesias
Management of PD who cannot swallow their medications or are nil by mouth
Peri-operative management of PD patients
Management of orthostatic hypotension in PD
Management of PD in end of life
Conclusion  

 

Introduction

Patients with Parkinson’s disease (PD) are one and a half times more likely to be admitted to hospital and their hospital stay is 2–14 days longer than non-PD patients.1 Patients with PD are admitted in frequencies of 7–28% per year.

There are many causes that lead PD patients to be acutely admitted to hospital, some of them are directly related to PD such as motor fluctuations with on-off periods, reduced mobility or immobility, psychiatric symptoms such as delirium, hallucinations, psychosis or dementia and dysphagia leading to aspiration pneumonia.

Other causes of admission are indirectly related to PD such as chest or urinary tract infections (UTI) or falls due to orthostatic hypotension.

PD patients can also be admitted for PD unrelated causes such as cardiovascular diseases like angina, myocardial infarction (MI), arrhythmias, stroke and TIA or gastrointestinal (GI) diseases such as diarrhoea and vomiting and GI bleed.

In one study, 367 patients with PD who were admitted as an emergency to a district general hospital elderly care ward over a period of four years were analysed.2 The commonest cause for admission was falls in 14%, followed by pneumonia 11%, then UTI 9%, decreased mobility 8%, psychiatric causes 8%, angina 6%, heart failure 6%, fractures 4%, orthostatic hypotension (OH) 4%, surgical 4%, upper GI bleed 3%, stroke/transient ischaemic attack (TIA) 2%, and MI 2%.

The mean length of stay for PD patients was 21.3 compared to 17.8 days for non-PD patients on the same ward for the same period. There was increased discharge to nursing homes from 37 for non-PD patients to 52 for PD patients.3,4

It is important that doctors who deal with PD patients when they are admitted acutely to hospital, whether in the emergency department, on a medical, surgical, orthopaedic or other wards, know how to approach a PD patient and should have access to local guidelines available on hospital intranet. They should also refer to the Parkinson’s team as soon as possible in order to reduce morbidity and length of stay.

 

How to approach a patient with PD

It is important that these patients should not miss their medications as a result of the admission and should not to be given medications that may worsen their condition. Patients should take the same dosage of PD medication at the same time as they take them at home. This may be different from nurses’ drug rounds. NICE guidance advocate self medication as a way of ensuring medications are taken at the right time.5

The Parkinson’s UK “Get it on time” campaign also advocates drug concordance by providing a checklist and an audit toolkit that is available online.6

PD medication should never be stopped. Some patients may tolerate missing a dose or two, but others may become very rigid and less mobile or may fall. Others may become more dysphagic and aspirate.

Rarely patients develop neuroleptic malignant syndrome (NMS) with a high temperature, raised creatine kinase and neuropsychiatric manifestations, which can be fatal.

In addition, drugs that may worsen a patient’s underlying motor symptoms should be avoided. These include:

Anti-emetics

Metoclopramide and prochlorperazine should be avoided as they worsen parkinsonian symptoms, instead domperidone should be used for nausea or vomiting in a dose of 10mg up to three times a day orally. Higher doses may cause prolonged QT interval. Alternatively ondansetron could be used.

Antipsychotics

Haloperidol, chlorpromazine and other first generation antipsychotics should be avoided.

Drugs that may worsen a patient’s confusion like anticholinergics or sedatives should also be avoided particularly in patients with Parkinson’s disease dementia unless absolutely necessary.

 

Management of neuropsychiatric manifestations of PD

Patients with PD, especially those with some degree of dementia, can develop neuropsychiatric symptoms like delirium and psychosis. Common causes for delirium in PD are infections such as pneumonia and UTI, urinary retention, dehydration, electrolyte disturbances, constipation and drug side effects. This includes non-PD medications like anticholinergics and sedatives.

Patients should be screened for causes of delirium like infection, dehydration, electrolyte disturbances, constipation and medications such as anticholinergics, sedatives and opiate-derived analgesics.

If no cause is found and the patient is experiencing visual hallucinations, a staged reduction of PD medications should be considered.

Anti-parkinsonian medications most likely to cause delirium are in the following order anticholinergics, amantadine, the monoamine oxidase inhibitors (MAOI), selegeline3 and then dopamine agonists (DA). These should be gradually reduced and replaced by levodopa, which is less likely to cause confusion than other anti-Parkinson medications.

If a patient is on levodopa, already consider cutting the dose slightly using the approach of ‘last in first out.’ However, the drug should never be stopped completely otherwise there would be risk of developing NMS.

If hallucinations persist or reduction of PD drugs is not possible rivastigmine could be added in a dose of 1.5mg bd, which could be increased gradually after two weeks to 3mg bd. Alternatively, rivastigmine patch 4.6mg daily can be used.

If the patient is experiencing psychotic symptoms with delusions or is severely agitated, lorazepam 0.5–1mg orally or intramuscularly can be given.

Quetiapine 25mg orally can be given in severe cases, as it has a lower incidence of extrapyramidal side effects and this could be increased to twice daily if necessary.

Clozapine has the best evidence-based treatment for PD psychosis,4 but its use is restricted as the patient will need frequent monitoring of full blood count because of the risk of agranulocytosis. Clozapine can only be prescribed by a registered prescriber. Very few specialists caring for PD patients have experience with clozapine.

 

Neuroleptic malignant syndrome

This is a rare complication of PD, which can be caused by the abrupt stopping of dopaminergic medications or the use of first-generation antipsychotic medications like haloperidol in PD patients. It can also be precipitated by infection or electrolyte disturbances like hypo or hypernatraemia. Clinical features include fever >380 in the absence of source of infection, stupor, autonomic disturbances such as labile blood pressure, and severe rigidity. Laboratory tests would show raised CK with leucocytosis and abnormal liver function tests. If untreated the condition may progress to rhabdomyolysis and acute renal failure that may lead to death.

Treatment consists of rehydration with intravenous fluids, lowering core body temperature with antipyretics and cooling and giving dopaminergic drugs orally or via NG and thromboprophylaxis. Dantrolene can be used for rigidity and hyperpyrexia. Transdermal rotigotine or subcutaneous infusion of apomorphine can be used if enteral route is not possible or in combination with levodopa.3,4 In severe cases admission to intensive care may be needed.

 

Dyskinesias

Dyskinesias are choreic or choreoathetoid movements that occur in advanced PD when there is significant striatal denervation. It is commoner in younger PD patients who have had prolonged treatment with levodopa, especially when the patient is on high doses. It is usually (but not exclusively) caused by peak plasma and possibly high striatal level of levodopa. This varies in severity from a mild form that is tolerated by the patient, but only noticed by spouse or friends or may cause weight loss due to excessive movements, to severe forms which could be disabling and affect the patient’s quality of life. Rarely, it can be life threatening causing exhaustion and necessitating hospital admission.3,4

It usually affects the torso, limbs, head, speech and respiratory muscles. Management is difficult. Cutting the dose of levodopa may help but may increase the off periods. Amantadine can be used in a dose of 100mg once or twice daily up to maximum of 400mg per day, but higher doses can cause confusion.

Use of long acting dopamine agonist or catecholo- methyl transferase (COMT) inhibitor like entacapone can help with reduction of levodopa dose. In severe cases with motor fluctuations (on-off) effect, constant subcutaneous infusion of apomorphine should be considered.7 Deep brain stimulation can be used in selective patients.4

 

Management of PD patients who cannot swallow their medications or are nil by mouth

Dysphagia is a common symptom of PD. It happens usually later on in the disease. It can worsen if medications are omitted or the doses of medications are inadequate. Swallowing can also worsen when the patient has an acute infection. It is important that patients with swallowing problems are referred to a speech and language therapist for swallowing assessment.

Algorithm for PD patients with swallowing problems or are NBM

If the patient cannot take tablets or capsules then some of the medications like for example cobeneldopa can be given in dispersible form and cocareldopa can be dissolved in water. The pharmacist can advise on which other Parkinson’s medications can be given as liquid.

If the patient cannot take anything orally, then a nasogastric (NG) tube should be inserted and medications should be given via the tube using equivalent dose of dispersible co-beneldopa to the patient’s usual medication.

If the patient does not tolerate an NG tube or is nil by mouth due to gastrointestinal disease or surgery, equivalent dose of the transdermal dopamine agonist, rotigotine, should be used. (See figure 1)

The OPTIMAL calculator has been developed by a team of Parkinson’s specialists and pharmacists with the support of the Southampton/Isle of Wight Excellence Network regional working group and the British Geriatrics Society Movement Disorders Section.8 It is useful for the non specialist to use to calculate the equivalent dose of co-beneldopa given via NG tube for those who can have NG tube or the equivalent dose of transdermal rotigotine if they cannot have NG tube. Doctors should be trained to use the calculator in order to be able to prescribe the medication without delay until PD specialist advice is available.

The links below are for calculator 1 for patients with NG tube and calculator 2 for those without NG tube.

  • http://www.parkinsonscalculator.com/ calculator1-withNG.html
  • http://www.parkinsonscalculator.com/ calculator2-withoutNG.html 

Rotigotine is a dopamine agonist given via transdermal patch over a 24-hour period. It is available in 2mg, 4mg, 6mg and 8mg patches. The patch should be removed temporarily during MRI and DC cardioversion. If the patient has dementia, then a lower dose of rotigotine should be used as it is a dopamine agonist and may worsen neuropsychiatric symptoms. The dose of rotigotine should be reviewed every 24–48 hours to see if it needs to be increased if symptoms are not well controlled or reduced if the patient is having hallucinations or is becoming agitated. Increments or reductions should be gradual, usually 2mg at a time.

The maximum dose of rotigotine is 16mg; if the dose is not adequate to control PD symptoms then a PD specialist should be contacted to see if apomorphine is appropriate. Pre-treatment with domperidone for at least 48 hours is required usually.

Once patients can take oral medications they should be put back on the same medications at the same dosage and times they were taking before the conversion.

Apomorphine is a dopamine agonist that is given by intermittent injection or continuous infusion subcutaneously. Patients who are established on apomorphine routine need to be continued at the prescribed dose. Apomorphine should not be started on apomorphine naïve patients without advice from PD specialist. Like other dopamine agonists, apomorphine can worsen neuropsychiatric symptoms in patients with pre-existing cognitive decline. It can also cause severe vomiting as a side effect and hence patients will need to be pre-treated with domperidone.

 

Peri-operative management of PD patients

PD patients undergoing surgery are at risk of aspiration pneumonia and post-operative respiratory failure or laryngeal spasm on extubation. They are also at risk of inadvertently missing doses of their medication due to pre-operative fasting and the misconception that they can’t have oral medications prior to surgery. The following is useful advice in these cases.

  • For elective cases, if the medications are likely to clash with the timing of the operation specialist advice should be sought to see if timing of medications could be changed.
  • If possible, regional anaesthesia should be considered instead of general as it allows symptoms assessment and medications administration.
  • PD patients should ideally be put first on the list to facilitate greater predictability over the time of fasting and surgery.9
  • PD medication should be given before the surgery up to the point of anaesthetic induction. They should be given as soon as possible on recovery.
  • If the operation is prolonged >3 hours, intra or perioperative co-beneldopa via NG tube should be given. If NG is not possible due to ileus or gastro-intestinal surgery then equivalent dose of rotigotine intraoperatively should be given.
  • If the patient has deep brain stimulation, the surgeon should be made aware as diathermy is contraindicated.

 

Management of orthostatic hypotension in PD

Orthostatic hypotension (OH) is common in PD due to the disease itself, as well as a side effect of the medications, especially dopamine agonists. It is present in 48% of PD patients5 and is asymptomatic in 60%. This could cause falls, which may lead to injuries or fractures. OH is defined as drop in systolic blood pressure >20mmHg or to below 90mmHg or drop of diastolic BP>10mmHg.

It is important to look for infection or dehydration that may worsen the condition. Patients should be encouraged to drink plenty of fluids and increase salt intake. If necessary they should be rehydrated intravenously if not drinking enough or have swallowing problems or are hypovolaemic due to infection.

Patients’ medications should be reviewed and antihypertensives or drugs that have hypotensive side effects should be gradually reduced or stopped. If it doesn’t improve, non-pharmacological measures should be used. Patients should avoid sudden change in posture and should be advised to sit at the edge of the bed for few minutes before standing up. Compression leg stockings could be used and tilting the head of bed by 30o–40o when lying down can help.

Pharmacological measures can be used such as fludrocortisone 50–300 microgram daily, starting with lower dose and increasing gradually according to response and tolerability.

If there is no response to this or if it is not tolerated due to side effects like leg swelling, the sympathomimetic agent midodrine can be used starting at dose of 2.5mg three times a day. The last dose should be at least four hours before bed time to avoid supine hypertension. The dose should be reviewed weekly and increased gradually according to blood pressure to maximum of 10mg three times daily.

If the patient is still symptomatic, a referral to a PD specialist is helpful to see if some reduction or change of PD medications can help as DA agonists are more likely to cause OH than levodopa.

 

Management of PD in end of life

Patients with advanced PD who become terminal need early input from the palliative care team who have knowledge of the needs of PD patients in terminal stages as some of the palliative drugs can worsen parkinsonian symptoms. In addition, their PD medications should be gradually reduced as they would become very sensitive to the side effects and they become less effective in the terminal stage of PD. While all other non-essential medications are usually stopped at the end of life stage, Parkinson’s medications should never be stopped but smaller doses should be given to control symptoms.10

For treatment of nausea or vomiting, domperidone can be given orally or rectally. Alternatively, ondansetron could be used. If the patient is on syringe driver, cyclizine subcutaneously could be given with caution as it may occasionally worsen extrapyramidal symptoms. Haloperidol and levomepromazine should be avoided. Hyoscine, glycopyrronium, midazolam and opiates are all safe in PD and could be given when needed.

If the patient can swallow, dispersible cobeneldopa can be given. Co-careldopa can also be dissolved in water and given orally.

If the patient cannot swallow, rotigotine 2–4mg patch can be used to control rigidity. The dose should be reviewed every 24–48 hours and increased gradually by 2mg increments if the patient is still rigid or cut down by 2mg at a time if the patient is agitated or is hallucinating.

 

Conclusion

Parkinson’s disease patients have a greater risk of being admitted to hospital and their length of stay is longer than non-PD patients. The risk of being admitted to a nursing homes after discharge from acute admission is also higher than non-PD patients. In addition, they are more likely to develop postoperative complications from emergency or elective surgical procedures.

It is important that patients do not miss their medications and they get them on time otherwise they would end up with complications such as falls, dysphagia or even neuroleptic malignant syndrome.

Patients should be referred early to the Parkinson’s specialist to reduce morbidity and length of stay. Doctors and staff who deal with PD patients should have access to local Parkinson’s guidelines through the hospital intranet. They should also have teaching sessions especially to enable them to deal with patients who are nil by mouth to minimise complications.

Parkinson disease (PD) is the second most common neuro-degenerative disease that affects 2% of the population above the age of 80 years. Patients with PD have a higher rate of hospitalisation than the general population and their length of stay is longer. Early involvement of the multidisciplinary team is important to reduce morbidity and length of stay.

 

Dr Farid Munim, Consultant Physician and Geriatrician at Frimley Park Hospital NHS Foundation Trust
Conflict of interests: none declared.

 

References

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4. MacMahon MG, MacMahon DG. Management of Parkinson’s disease in the acute hospital environment. J R Coll Physicians Edinb 2012; 42: 157–62

5. NICE. Parkinson’s disease. National clinical guidelines for diagnosis and management of in primary and secondary care. NICE, 2006. https://www.nice.org.uk/guidance/cg35/ evidence/full-guideline-194930029 (accessed 20/04/17)

6. Parkinson’s UK.”Get it on time” campaign” https://www.parkinsons.org.uk/content/get-it-time (accessed 20/04/17)

7. Thanvi B, Lo N, Robinson T. Levodopa induced dyskinesia in Parkinson’s disease: clinical features, pathogenesis, prevention and treatment. Postgrad Med J 2007; 83(980): 384–88

8. OPTIMAL Parkinson medication guideline and conversion calculator,. https://www.parkinsons.org.uk/professionals/resources/optimal-parkinsons-medication-guideline-and-conversion-calculator (accessed 20/04/17)

9. Brennan KA, Genever RW. Managing Parkinson’s disease during surgery. BMJ 2010; 341: c5718

10. Campbell C, Jones E, Merrills J. Palliative and end-of-life care in advanced Parkinson’s disease and multiple sclerosis. Clinical Medicine 2010: 10(3): 290–92