Seizures

KEYPOINTS

  • Seizures are relatively common in the palliative care population, occurring in up to 10% of patients
  • Most seizures are brief, self-limited and rarely harmful themselves
  • Pethidine/meperidine, if used on an ongoing basis, can cause seizures due to an accumulation of normeperidine, a neurotoxic metabolite. Pethidine/meperidine should, therefore, be avoided in palliative care patients
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  • Can be extremely frightening to family
  • Quite common at the end of life in children

ASSESSMENT

(see Foreword)

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Treatment is usually symptomatic and a full seizure workup is, in most cases, not necessary
  • Causes of seizures include:
    • Brain tumours
    • Drug toxicity (e.g. pethidine/meperidine)
    • Metabolic or electrolyte abnormality
      • Hypoglycemia
      • Hyponatremia
      • Hypercalcemia
    • Hypoxia
    • Severe hepatic failure
    • Infections of the central nervous system
    • Epilepsy
  • Cancers most likely to metastasize to the brain are lung, breast and malignant melanoma
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  • Where appropriate treat correctable causes of seizures
  • In children with a longer prognosis a review by a neurologist to optimise prophylactic treatment might be appropriate

MANAGEMENT

  • Most seizures are brief, self-limited and rarely harmful in themselves

Acute Treatment of Seizures (Status Epilepticus)

  • Clear airway
  • Diazepam 10 mg PR. Repeat after 15 and 30 minutes if needed. If no response consider doubling the dose
  • Lorazepam 2-4 mg SL, SC or IV. Repeat after 15 and 30 minutes if needed
  • Midazolam 5-10 mg SC or IV. Repeat after 15 minutes if needed. If no response consider doubling the dose
  • Phenobarbital 100-200 mg SC or IV (slowly by IV over 30 minutes with 100 cc of saline). May repeat if necessary. Follow this with 100 mg tid SC

Prophylactic Management of Seizures

  • Seizure prophylaxis with anticonvulsants has only been proven useful in patients with brain metastasis due to malignant melanoma and patients with brain metastasis from other cancers who have already had a seizure

Anticonvulsant medication

  • Phenytoin 300 mg PO followed by 100-200 mg tid PO
  • Carbamazepine 100 mg bid PO
  • Valproate 200 mg tid PO
  • Others options exist (lamotrigine, gabapentin, toprimate)

Corticosteroids

  • Are helpful in the prevention and management of seizures which are secondary to brain metastasis, by decreasing the oedema surrounding a tumour mass

Radiation

  • Can be helpful in preventing seizures in patients with metastatic brain disease

Opioid rotation

  • Opioids very rarely cause seizures (except pethidine/meperidine which can cause cerebral excitation and seizures)
  • Switching to another opioid can be helpful in this situation
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Acute treatment

  • Diazepam 0.3-0.5 mg/kg/dose PR/SC/IV
  • Lorazepam 0.06-0.1 mg/kg/dose PR/SC/SL/IV
  • Midazolam 100 mcg/kg SC over one minute, then if necessary 300-700 mcg/kg over 24 hours by continuous SC infusion
  • Phenobarbital 10-20 mg/kg IV or PO, followed by 3-5 mg/kg/day IV/SC/PO

Prophylactic treatment

  • Phenytoin 4-8 mg/kg/24h bid or tid PO in divided doses
  • Carbamazepine
    • Less than 6 years: 10-20 mg/kg/24h bid or tid PO in divided doses
    • Over 6 years: 100 mg bid PO
  • Valproate
    • Initial: 10 mg/kg/24h tid PO in divided doses
    • Increment: 5-10 mg/kg/24h at weekly intervals
    • Maintenance: 20 mg/kg/24h tid in divided doses (monotherapy). Higher doses (30-60 mg/kg/24h) are often required in patients on polytherapy

PITFALLS/CONCERNS

  • There are many drug-drug interactions that occur with anticonvulsant medications
  • It is important to monitor the dose and duration of treatment with corticosteroids frequently, especially when used for more than 4 weeks, to prevent long-term side effects such as steroid myopathy, hyperglycemia and gastrointestinal bleeding among others
  • Pethidine/meperidine can cause cerebral excitation and seizures
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  • Parents should be trained in administering medications by SL and PR routes if there is a likelihood of child having prolonged seizures at home

PALLIATIVE TIPS

  • Prophylactic anticonvulsant therapy for all patients with cerebral metastases is unnecessary as most patients are unlikely to seize due to their metastases. If they do indeed seize, anticonvulsant therapy should then be started
  • If seizures last longer than 5 minutes, or if they occur at frequent intervals and the patient does not recover fully between intervals, the patient is considered to be in status epilepticus (see Acute Treatment of Seizures)
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  • Rectal administration can be given by syringe with a small feeding tube cut at 5 cm to deliver medication up to 4 to 5 cms beyond the anal margin for an older child and less for an infant

SOURCES/REFERENCES

  1. Heafield M. Managing status epileptics. BMJ 2000;320(7240):953-954. http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1117894
  2. Watson M, Lucas C, Hoy A, Back I. Oxford handbook of palliative care. Oxford: Oxford University Press; 2005.
  3. Weil S, Noachtar S. Epileptic seizures and myoclonus. In: Voltz R, Bernat JL, Borasio GD, Maddocks I, Oliver D, Portenoy R, editors. Palliative care in neurology. New York: Oxford University Press; 2004. p. 178-18.
  4. Ziai WC, Hagen N. Headache and other neurolgic complications. In: Berger AM, Portenoy RK, Weissman DE, editors. Principles and practice of palliative care and supportive oncology. Philadelphia: Lippincott Williams & Wilkins; 2002. p. 515-531.

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