Monday, April 5, 2010

#229 Seizure Management in the Dying Patient

FAST FACTS AND CONCEPTS #229

SEIZURE MANAGEMENT IN THE DYING PATIENT

Jennifer Connelly MD and David E Weissman MD

Background
 Management of seizures in the dying patient without intravenous access, such as is in the home environment, is challenging. Seizures in this population can be due to primary or metastatic brain cancers, strokes, toxic/metabolic causes including hypoglycemia, or pre-existing seizure disorders. The actual incidence of seizures in dying patients is unknown, and while likely uncommon, they can cause tremendous distress to patients and families. This Fast Fact reviews management strategies for seizures near the end of life.



Seizure Prophylaxis
 Up to 40% of patients with brain tumors have a seizure at the time of diagnosis and another 20% develop seizures during the course of the illness. Although antiepileptic drugs (AEDs) are commonly started as prophylaxis at the time of brain tumor diagnosis, they have not been found to prevent seizures and the American Academy of Neurology Clinical Practice Guidelines do not support this practice (1). Thus, prophylactic AEDs can be safely discontinued in patients with brain tumors who have never had a seizure. For patients with a seizure history, including those with brain tumors, AEDs should be continued as long as possible. For patients who lose an enteric route and have no intravenous access, rectal administration of prophylactic AEDs is possible. Clinical judgment should be used as to whether to continue AEDs in this setting; it can be appropriate to simply stop them, particularly if the patient’s prognosis is very short. Phenobarbital, pentobarbital, carbamazepine, valproic acid, and lamotrigine can all be given rectally. Rectal absorption of other prophylactic AEDs is undefined and they should not be administered. None of the aforementioned AEDs need dose adjustments for rectal administration. Carbamazepine should be divided into small doses administered 6-8 times a day. Lamotrigone is administered rectally by crushing and suspending the chewable tablets in 10 mL of water. When clinically indicated, drug levels of lamotrigine should be monitored as rectal absorption is erratic.



Seizure Management

• Single self-limited seizure: Check for treatable causes such as hypoglycemia. If no reversible cause is identified, initiation of maintenance AED therapy should be considered, particularly if the patient is expected to survive more than a few weeks.

• Acute seizure or status epilepticus:

o Non-intravenous routes: Rectal diazepam (0.2 mg/kg or 10-20mg) is the drug of choice for status epilepticus and acute seizures lasting greater than two minutes due to its bioavailability, ease of administration, and short time to peak serum concentration (< 20 minutes). Diazepam can be repeated hourly until the seizure stops. Some authors suggest continuing 20 mg per rectum nightly to reduce the occurrence of further seizure events. Other rectal benzodiazepines are available (clonazepam, lorazepam, and midazolam), but take longer to reach peak serum levels. Sublingual lorazepam and intranasal midazolam are also available, but their use in the adult population is not well-studied.

o Parenteral therapy: When available, intravenous and subcutaneous benzodiazepines can be used and are usually effective at stopping a seizure in progress; intravenous lorazepam is preferred due to its long half-life. Clonazepam and midazolam can be given subcutaneously at doses similar to the intravenous route. If seizure activity persists, additional anti-epileptic medication should be provided using a loading and then maintenance dose. Patients with refractory seizures who have short prognoses and comfort-oriented goals of care should be considered for an anti-epileptic sedative such as midazolam or a barbiturate with the goal of deep sedation (see Fast Facts #106,107).



Parenteral AED Dosing and Routes:

Drug Status loading dose Maintenance dose

Diazepam 0.2 mg/kg or 10-20 mg PR 20 mg PR nightly

Lorazepam 0.1 mg/kg IV or IM



Midazolam 0.1-0.3 mg/kg IV or SC Titrate to control refractory seizures if needed

Clonazepam 1 mg IV or SC

Phenytoin 20 mg/kg IV 4-5 mg/kg/day IV divided TID

Fosphenytoin 20 mg/kg IV or IM 4-5 mg/kg/day IV or IM divided TID

Phenobarbital 10-15 mg/kg 1-3 mg/kg/day IV or IM

1200 mg/day SC (2)



Family Education
Family members should be counseled that all medications used to manage seizures can cause sedation and cardiopulmonary depression. Family members who have witnessed prior seizures often have great fear about seizure recurrence. Many hospice agencies have established seizure protocols and medication kits which can be stored at home, and will collaborate with physicians and families on establishing a ‘seizure plan’ for acute seizures. It is important to review with the family seizure safety, including not putting anything in the patient’s mouth and making sure the patient is in a safe environment.



References

1. Glantz MJ, Cole BF, Forsyth PA, et al. Practice parameter: anticonvulsant prophylaxis in patients with newly diagnosed brain tumors: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurol. 2000; 54:1886-1893.

2. Krouwer H, Pallagi J, Graves N. Management of seizures in brain tumor patients at the end of life. J Palliat Med. 2000;3:465-475.

3. Davis M, Walsh D, LeGrand S, et al. Symptom control in cancer patients: the clinical pharmacolog and therapeutic role of suppositories and rectal suspensions. Support Care Cancer. 2002; 10:117-138.

4. Brown L, Bergen DC, Kotagal P, et al. Safety of Diastat when given at larger-than-recommended doses for acute repetitive seizures. Neurol. 2001; 56:1112.

5. Voltz R, Borasio GD. Palliative therapy in the terminal stage of neurological disease. J Neurol. 1997; 244[Suppl 4]:S2-S10.

6. Droney J, Hall E. Status epilepticus in a hospice inpatient setting. J Pain Symptom Manage. 2008; 36:97-105.



Author Affiliations: Medical College of Wisconsin, Milwaukee, WI.



Fast Facts and Concepts are edited by Drew A. Rosielle MD, Palliative Care Center, Medical College of Wisconsin. For more information write to: drosiell@mcw.edu. More information, as well as the complete set of Fast Facts, are available at EPERC: http://www.mcw.edu/eperc. Readers can comment on this publication at the Fast Facts and Concepts Discussion Blog (http://epercfastfacts.blogspot.com).



Copyright/Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Connelly J, Weissman DE. Seizure Management in the Dying Patient. Fast Facts and Concepts. April 2010; 229. Available at: http://www.eperc.mcw.edu/fastfact/ff_229.htm.

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