SEIZURES |

Seizures (generalised or partial) occur in 10-15% of palliative care patients.

Causes

CNS – primary tumours, metastases, cerebrovascular disease, epilepsy, haemorrhage, or radiation necrosis
Biochemical abnormalities – hypoxia, hypoglycaemia, hyperglycaemia, hyponatremia, hypernatremia, hypocalcaemia, hypercalcemia, hypomagnesemia, uraemia, and hepatic failure
Medications – ondansetron, tramadol, antipsychotics, and chemotherapeutic agents, either through their proconvulsant effect or by lowering the seizure threshold

Assessment must determine the cause of loss of consciousness or abnormal limb/facial movement, effectiveness of treatment and impact on quality of life for the patient and their family (refer to the Guideline – Symptom Assessment)
Assessment should be done to exclude other causes of loss of consciousness or abnormal limb/facial movement. (e.g. vasovagal episode [syncope], postural hypotension, arrhythmia, hypoglycaemia, extrapyramidal side effects from dopamine antagonists, alcohol)
Ask for history of epilepsy, previous secondary seizure, and cerebrovascular disease
Enlist the medications the patient is on to look for drugs that can lower the seizure threshold
Assess if the patient is experiencing withdrawal from benzodiazepines or alcohol, or weaning from steroids
If the patient is already on anti-epileptic medications, check if there is a problem with the dose, frequency, compliance, drug interactions

Recommendations

Prophylactic anticonvulsant therapy in patients with brain tumours or metastases is not recommended
For patients with reversible causes, one episode of seizure does not warrant long-term anticonvulsants
For patients with irreversible causes long-term anticonvulsants are recommended only after the first seizure
For patients with brain tumours (primary or metastatic), the commencement or increase in dose of steroids, such as dexamethasone, could be considered alongside long-term anticonvulsant treatment
If patients require long-term anticonvulsants but are candidates for further chemotherapy, then institution of anti-epileptic medications which do not induce cytochrome P450 activity and thereby have little risk of interaction with the chemotherapeutic agents should be considered. Such medications include levetiracetam, gabapentin, lamotrigine, and pregabalin
Avoid medications which can lower seizure threshold
Phenytoin is no longer a first line drug for chronic seizure control in a palliative care setting, as it interacts with many drugs and is prone to cause side effects including sedation
Consultation with a second palliative care specialist is mandatory before initiating Midazolam
Setting of care should be discussed in the event of repeated seizures

Acute seizure management

Remove sharp objects to ensure that patient does not get hurt
Do not attempt to restrain the patient
Do not try to force anything into the patient’s mouth
When the seizure stops, turn the patient onto his/her side
Maintain airway by lifting the patient’s chin
The patient will be sleepy for a while after the seizure
If the seizure does not stop in about 5-10 minutes or if another seizure occurs soon after the first, call for medical assistance
Reassure the patient and family that the seizures can be brought under control

In acute setting, if seizures do not resolve within 5 minutes after the onset,

Inj. Lorazepam 4mg IV stat over 4 minutes (Lorazepam may be more beneficial than diazepam because it provides longer control of seizures and produces less cardio-respiratory depression)
or
Inj. Midazolam 5mg S/C stat
If seizures persist, then repeat dose after 10-20 minutes

If seizures persist, then

Inj. Midazolam 20-30mg CSCI/24 hours
or
Inj. Phenobarbital 100-200mg IM stat. followed if necessary, by 300-400mg by CSCI (using water as diluent) over 24 hours

If patient has known primary or secondary brain tumour,

Inj. Dexamethasone 8-16mg/24 hours S/C or IV divided q12h (before 4.00pm) should be considered along with anticonvulsants

Chronic seizure management

Starting dose – 50-100mg PO q12h, increase by 50-100mg every 1-2 weeks (Use m/r products for doses ≥ 100mg)
Usual effective dose – ≤ 800mg/24 hours
Maximum daily dose – 2g

Initial: 50mg PO OD for 2 weeks, then
100mg/day divided q12h for 2 weeks
At week 5 and beyond, may increase by 100mg/day PO every 1-2 weeks to 300 – 500mg/day PO divided q12h
Lamotrigine XR: Start 25mg PO OD for 2 weeks, then 25mg PO OD for 2 weeks, then 50mg PO OD (week 5), 100mg PO OD (week 6), 150mg PO OD (week 7), to maintenance (200-250mg PO OD)

Initial: 25mg PO OD A/D for 2 weeks, then
25mg PO OD for 2 weeks
At week 5 and beyond, may increase by 25-50mg/day PO every 1-2 weeks to 100 – 400mg PO OD or divided q12h
Lamotrigine XR: Start 25mg PO A/D for 2 weeks, then 25mg PO OD for 2 weeks, then 50mg PO OD (week 5), 100mg PO OD (week 6), 150mg PO OD (week 7), to maintenance (200-250mg PO OD)

Initial: 25mg PO OD for 2 weeks, then
50mg PO OD for 2 weeks
At week 4 and beyond, may increase by 50mg/day PO every 1-2 weeks to 225 – 375mg PO OD or divided q12h
Lamotrigine XR: Start 25mg PO OD for 2 weeks, then 50mg PO OD for 2 weeks, then 100mg PO OD (week 5), 150mg PO OD (week 6), 200mg PO OD (week 7), to maintenance 300-400mg PO OD

Levetiracetam can be considered when the first line treatments are not effective.

Dying patient (may not be able to take oral medications)

REFERENCES

Caraceni, A., Martini, C., Simonetti, F. (2015). Neurological problems in advanced cancer. Oxford Textbook of Palliative Medicine (pp. 885-905)
Medscape – Iamotrigine (Rx). Retrieved from ht tps://reference.medscape.com/drug/lamictal-lamotrigine-343012 on 3 January 2019.
Tradounsky, G. Seizures in palliative care. Canadian Family Physician. (2013) 59: 951-955
Twycross, R., Wilcock, A., Howard, P. (2014). Central Nervous System – Anti-epileptics. Palliative Care Formulary 5. (pp. 342-384)
Twycross, R. (2003). Drug Profiles – Benzodiazepines & Midazolam. Introducing Palliative Care. (pp. 166-167 & 170)

Palliative Care Guidelines