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New Therapies in the Management of Acute or Cluster Seizures and Seizure Emergencies.

Abstract: Acute repititive seizures, also known as cluster or serial seizures, may present considerable health risks, including death, to patients with epilepsy and often are a cause of psychosocial stigma. Fortunately, new formulations and drug-delivery systems approved by the Food and Drug Administration (FDA) over the past 5 years offer patients and health care providers greater control over acute repetitive seizures and emergency situations. Drugs that can be given intravenously, such as diazepam, phenytoin and valproate sodium solution, typically have the most rapid onset but are limited to use in clinical settings by health care professionals authorized to use them. In contrast, diazepam rectal gel can be administered to patients by their caregivers or family members in the home or in other non-hospital settings. Studies have shown that rectal diazepam used in such settings can reduce the number of emergency room visits, costs associated with emergent care and stress on the patient and family. Health education is necessary to help patients and families understand new treatment options and use them successfully. Additionally, facilitating patient compliance with prescribed treatment regimens may reduce the frequency and consequences of seizure emergencies.

Introduction

Despite advances in surgical techniques, drug therapy has remained the mainstay of treatment for patients with epilepsy. Because of limitations of many older antiepileptic drugs (AEDs), health care providers, patients and caregivers are seeking easier, safer ways to control seizures and increase patients' control over their lives. Fortunately, systematic drug development efforts have yielded medications that can achieve these goals. In addition to the introduction of several new agents suitable for chronic treatment, new formulations and drug-delivery systems approved by the Food and Drug Administration (FDA) over the past 5 years offer patients and health care providers greater control over acute repetitive seizures and emergency situations, such as status epilepticus.

Unfortunately, many patients and health care providers have not taken advantage of these new advances, perhaps because of a lack of awareness regarding these options. Nurses can play a critical role in helping patients and their families understand new treatment options available to them and how to respond to seizure emergencies. Nurses must also understand the multifaceted issues that can affect medication-taking behaviors. This will enable nurses to assess patient, family and caregiver learning needs more effectively and tailor educational strategies to meet these needs. This article highlights the new formulations of AEDs for acute treatment of seizures. Nursing assessment of factors affecting medication taking and strategies to improve compliance are discussed as well.

Overview of Epilepsy

Epilepsy is a diverse condition. Although most patients experience relatively uncomplicated courses of the disease, others are devastated by the disorder and experience difficulties finding effective management approaches. Living with uncontrolled seizures may pose significant psychosocial and financial burdens to individuals, families and society. Furthermore, frequent uncontrolled seizures may cause serious injuries, irreversible brain damage or death. Optimal management of the disorder must be directed toward stopping seizures and preventing seizure emergencies.

Many patients periodically experience acute repetitive seizures (ARS). Also known as seizure clusters or serial seizures, ARS are defined as multiple seizures occurring within a 24-hour period in adults or in a 12-hour period in children and distinguishable from the patient's other seizure type(s), with an onset that is readily recognizable by the patient's caregiver.[29]

ARS are associated with costly emergency room (ER) visits and hospitalizations.[25] They may precede prolonged seizures or status epilepticus (SE), one of the most serious, costly and life-threatening emergency situations that can occur in patients with epilepsy.[28] Status epilepticus is estimated to occur in 125,000-195,000 cases each year in the United States, with a mortality rate of approximately 22%.[11] Four to 16% of patients with epilepsy will report at least one episode of SE during their lifetime.[24]

Convulsive SE is typically defined as generalized seizures lasting longer than 10 minutes or sequential seizures lasting longer than 30 minutes without intervening recovery of consciousness.[20] SE occurs more often in the very young and the elderly. Recurrent febrile seizures in young patients carry the risk of the development of SE.[3]

New Formulations and Drug-Delivery Systems

Over the past 5 years, the FDA has approved several new formulations and drug-delivery systems for the treatment of acute seizure situations. Fosphenytoin (Cerebyx[R]) was approved by the FDA in 1995 as an injectable formulation of phenytoin (Dilantin[R]). Valproate sodium solution (Depacon[TM]), approved in 1997, was developed as an injectable formulation of valpoic acid (Depakene[R]) and divalproex sodium (Depakote[R]). A diazepam product formulated for rectal administration, diazepam rectal gel (Diastat[R]), was approved in 1997. Fosphenytoin, valproate sodium injection and diazepam rectal gel can be useful in certain acute seizure situations, as described below. A comparison of indications and usage of the three drugs is shown in Table 1.
Table 1
New Formulations for Acute Treatment of Seizures

 Cerebyx[R]
 (fosphenytoin)

Indications Status epilepticus
 Substitution

Use limited to Yes - IV, loading doses
hospital settings Maybe - IM substitution

Monitoring Yes
recommended

Improved safety profile Yes

Ease of use for Yes
health care provider(*)

Ease of use for No
patient/caregiver

 Depacon[TM]
 (IV valproate)

Indications Substitution

Use limited to Yes - IV
hospital settings

Monitoring Yes - for loading only
recommended

Improved safety profile Yes

Ease of use for Yes
health care provider(*)

Ease of use for No
patient/caregiver

 Diastat[R]
 (diazepam rectal gel)

Indications Cluster seizures
 Increased seizures

Use limited to No
hospital settings

Monitoring Yes
recommended

Improved safety profile Yes

Ease of use for Yes
health care provider(*)

Ease of use for Yes
patient/caregiver


(*) Relative to parent drug or standard formulation

Fosphenytoin Sodium

Fosphenytoin sodium was approved for intravenous (IV) or intramuscular (IM) administration in the treatment of SE, as well as for the prevention or treatment of seizures in patients who cannot take oral AEDs. Fosphenytoin is a prodrug of phenytoin, completely converted to phenytoin within 8-15 minutes after IV or IM administration regardless of plasma phenytoin or fosphenytoin concentration.[4] Unlike phenytoin, which must be dissolved at a high pH in a mixture of propylene glycol and ethyl alcohol, fosphenytoin is water soluble. As a result, the prodrug is better tolerated and can be administered at a faster rate than phenytoin. When given in IV form, fosphenytoin is much less likely to cause the tissue damage and vein irritation seen with IV phenytoin; this reduces patient discomfort and eliminates the need for frequent changes in IV infusion sites.

It is crucial that nurses understand the differences in dosing and administration between fosphenytoin and phenytoin. Fosphenytoin is measured in phenytoin sodium equivalents (PEs). A loading dose of fosphenytoin (~15 mg PE/kg) is essentially bioequivalent to phenytoin when infused at a rate of 150 mg PE/minute. Additionally, fast and consistent plasma total phenytoin concentrations can be achieved at this dose and infusion rate.[18,26,32] For treating patients in SE, fosphenytoin can be safely administered at rates of 150 mg PE/min. In less urgent situations, administering the drug at a slower rate of 50-100 mg PE/min may be appropriate.[5] Administration and dosing guidelines vary in patients with hepatic or renal disease, because in this group the conversion half-life is less than that of patients without hepatic or renal involvement.[2]

Therapeutic phenytoin levels are achieved within 7 minutes of IV infusion (150 mg PE/min) and within 30 minutes of IM injection. A recent review of fosphenytoin indicates that about 30% of patients treated with fosphenytoin report paresthesias and pruritis, usually in the perineal region, back, stomach or occasionally, head and neck.[5] These problems may be related to the rate of administration, are usually transient and resolve without intervention.

Fosphenytoin comes as a ready-mixed solution that is compatible with common IV solutions, including dextrose. It is generally accepted that fosphenytoin is stable at room temperature for 48 hours in vials. Fischer et al found that fosphenytoin sodium, when undiluted in polypropylene syringes or mixed with NaCL 0.9% or D5W in polyvinyl bags, can be kept for 30 days at room temperature, under refrigeration or frozen.[19] Additionally, the stability of fosphenytoin is maintained when the frozen solutions are thawed and kept at 4 [degrees] or 25 [degrees] C for 7 days and then refrozen for another week. The maximum time for stability of the drug in different preparations and conditions needs further study, but these data suggest that advance preparation of the drug is possible, and its use outside of the hospital may be more flexible than previously thought.

Fosphenytoin is intended primarily for hospital use in the treatment of patients with SE or acute seizures or in situations when IV or IM substitution is required. When given in IV form, a dedicated line is preferred to allow flexibility in adjusting dosages. Electrocardiogram and blood pressure monitoring are recommended during infusion because of the potential for cardiac arrhythmia and hypotension. Fosphenytoin can also be safely administered by the IM route at home or in other nonhospital settings; however, it is not approved for use by nonhealth professional caregivers. Equipment for IM injection is not furnished with the medication and must be obtained separately.

Depacon

Valproate sodium injection (Depacon) is indicated for use as monotherapy in the treatment of generalized seizures and as add-on therapy in the treatment of partial seizures.[12] It has been approved by the FDA as a substitution for oral divalproex sodium, for example in the treatment of acutely ill patients unable to take oral medications or during neurosurgical procedures.[12] It is also used in patients experiencing periods of increased seizure activity or requiring IV medication to achieve therapeutic levels quickly. The pharmacokinetics of valproate sodium injection are similar to those of divalproex sodium, with a mean half-life of 16 hours. Protein binding is about 90% at low serum concentrations but decreases with elevations in serum concentration. High plasma levels of valproate will thus yield higher free levels of the drug, creating potential for adverse effects. Also, protein binding is lower in the elderly, patients with hepatic disease or renal problems, women who are pregnant and patients taking certain drugs such as aspirin.[12,27] In these circumstances, dosages may need to be adjusted to minimize adverse effects from higher free levels.

Dosing is simple with 1:1 conversion from oral to IV dose. The dose should be administered over 1 hour at not more than 20 mg/min. Maximum concentrations are achieved at the end of the 1-hour infusion, compared to 4 hours after an oral dose. As replacement therapy, it is usually given every 6 hours. If valproate sodium injection is administered less frequently, more frequent monitoring of trough levels may be needed to maintain stable serum levels and seizure control.

Depacon's safety profile is similar to that of oral divalproex sodium. Patients receiving valproate sodium injection need monitoring only when loading doses are given. A multicenter safety trial of valproate sodium injection found no worsening of seizures related to the drug.[13] The most common adverse effects reported included nausea, vomiting, headache, dizziness, somnolence, injection-site reaction and change in taste.[13] Nurses should be aware that the risk of hepatic failure with valproic acid and its derivatives is greatest in the first 6 months of therapy and in children less than 2 years old.[6] Other risk factors should be evaluated, such as organic brain disease, congenital metabolic disorders, mental retardation and use of multiple AEDs.[12] Like all AEDs, valproate, can be teratogenic. The incidence of neural tube defects in offspring of women taking valproate is higher than with other AEDs, about 1%. Therefore, women of childbearing potential taking this medication should be counseled accordingly, and use of folic acid is recommended.

Patients receiving valproate, especially at high plasma concentrations, are at risk for thrombocytopenia and clotting abnomalities.[21] Thus, before a surgical procedure, patients receiving valproate sodium injection should have platelet count and clotting parameters monitored and be assessed for potential complications postoperatively.[12]

Valproate sodium injection is not intended for at-home administration. Its major benefit is as a substitute for patients when they are unable to take oral valproic acid. Previously, such patients had to use a different drug, such as phenytoin or phenobarbital, which could be given intravenously. Unfortunately, these drugs may also interact with valproic acid, thus complicating the substitution process. The use of valproate sodium injection will eliminate these problems for many people.

Diastat

Benzodiazepines, which include lorazepam and diazepam, are considered front-line treatment for acute seizures. Either IV diazepam (Valium[R]) or IV lorazepam (Ativan[R]) are the usual treatment when a patient is brought to an emergency care setting for treatment of seizures. Additionally, research shows that W lorazepam may be the most appropriate choice for treating acute seizures when IV administration is an option.[10,33] However, IV and oral administration may be difficult or impossible in certain situations, and an alternative route must be considered.

The rectal gel formulation of diazepam (Diastat[R]) is indicated for the management of patients with refractory epilepsy who are on stable regimens of AEDs and require intermittent use of diazepam to control acute seizure activity. Its use is not limited to a supervised or hospital setting. Rather, diazepam rectal gel is designed to allow patients and caregivers more control over managing acute seizures wherever they occur.

Table 2 compares administration and dosing for W diazepam, W lorazepam and diazepam rectal gel. After administration of IV diazepam, seizures should stop within 1-3 minutes.[34] The antiseizure effect of rectal diazepam appears to occur at serum concentrations ranging from 150-300 ng/ml.[1] After administering diazepam rectal gel, seizures usually stop within 15 minutes as diazepam levels of [is greater than or equal to] 200 ng/ml are reached.[7] Figure 1 compares plasma concentrations of diazepam after administration of W diazepam (7.5 mg) or diazepam rectal gel (15 mg).[7] Plasma concentrations differ most during the first hour after treatment. Intravenous diazepam demonstrates a rapid increase followed by a sharp decline after administration; the rise in diazepam levels is slower with diazepam rectal gel. Diazepam levels are highest within the first 90 minutes of treatment with rectal gel, then stabilize at a slightly higher level than is seen with IV diazepam.[14]
Table 2
Benzodiazepines for Treatment of Acute Seizures:
Administration and Dosing

 Ativan[R] Valium[R] Diastat[R]
 (IV loraze- (IV diaze- (diazepam
 pam)[33] pam)[33] rectal gel)

Adult dose (mg/kg) 0.1 0.15-0.25 0.2[14]

Maximum rate of 2 5 N/A
administration (mg/min)

Time to halt seizure (min) 6-10 1-3 15

Half-life 14 30 46(*)[14]


(*) Based on data on diazepam rectal solution

[Figure 1 ILLUSTRATION OMITTED]

The implications for these differences are clear. First, if IV access is difficult or impossible, or when the patient cannot get to a hospital, diazepam rectal gel is an optimal choice for acute treatment of seizures for both adults and children. Second, the slower and more stable concentration achieved with the rectal gel is less likely to increase the risk of sedation and respiratory compromise.

Diazepam rectal gel should not be used on a daily basis. For maximum effectiveness, patients and families should be instructed to use it not more than five times per month and not more than once every 5 days.[14] Patients who experience acute seizures or clusters more frequently may require further attention and evaluation of their AED regimen by their neurologist. The nurse should note that a treatment episode may include more than one dose. Patients and caregivers must be instructed if and when to give a second dose of diazepam rectal gel.

Diazepam rectal gel is pre-filled into a ready-to-use delivery system and is available in adult and pediatric sizes in various dosage strengths based on weight. Overall, diazepam rectal gel is easy to use; however, providers, caregivers and patients must have a thorough understanding of when and how it should be administered. There are no special storage issues. Although monitoring of respiratory status and recurrent seizures is recommended after administration, no special equipment is necessary. The availability of caregivers to remain with the patient until he or she is stable and able to resume usual activity must be considered.

Kriel and colleagues demonstrated significant cost savings associated with the use of rectal diazepam gel.[25] For instance, families who used rectal diazepam to manage acute seizure situations at home or in other nonhospital settings experienced fewer ER visits. The families also reported having more confidence in managing seizures, increased flexibility in managing their daily routines, greater independence and greater peace of mind.[25]

Factors Affecting Treatment Choice and Administration Route

A major consideration in choosing among the newer AEDs and AED formulations is the cost of medication and the impact of cost on patient access to the drug. Reimbursement issues are a challenge -- and often a barrier -- among physicians and patients operating in a managed care setting. Managed care networks may use restricted formularies that exclude newer medications. Nurses must know which epilepsy medications are covered by the patient's insurance and be aware of other sources for obtaining medications such as state-funded emergency plans, low-cost home pharmacies, or pharmaceutical patient-assistance programs. Nurses must also continually advocate on the patients' behalf to obtain coverage for new treatments for epilepsy.

Several factors bear consideration in the choice of administration routes. For seizure emergencies, the patient's location can dictate the choice. For example, patients prone to cluster seizures who live in rural areas may be unable to reach an ER easily, and treatment with a rectal benzodiazepine may be the safest, most rapid approach. Patients in whom it is difficult to obtain venous access, such as infants or patients in active convulsions, may also warrant an alternative administration route. However, IV medications such as fosphenytoin or lorazepam may be the first choice for patients with IV access treated for SE in a hospital setting. Other key factors to consider include the need for expedient treatment, differences in time required for an AED to reach therapeutic levels when given by different routes, ease of dosing and administration, tolerability, respiratory or cardiac monitoring needs and availability of resources for monitoring.

Patient and family preferences for the route of drug administration should be assessed. For example, the patient might prefer a medication that can be administered at home, but the person who would help administer it may not feel comfortable. Or, patients and family members might prefer one route, but the provider may not feel comfortable with their choice. In both of these scenarios, nurses may help Educate patients and families about their treatment options and facilitate communication of their preferences to the prescribing provider.

Learning Needs for Medication Management

Preventing acute repetitive seizures or seizure emergencies must also include educating patients and families about medication-taking behaviors that maximize seizure control. Compliance with a prescribed treatment regimen has been associated with a reduction in seizure emergencies, including SE.[17] Noncompliance can be a problem for anyone taking medications chronically and can be more of a problem for patients with seizures and memory deficits. Patients who do not adhere to their AED regimens may develop ARS or SE. Cramer et al found that patients with epilepsy took an average of 76% of their medicine as prescribed.[8] Additionally, compliance rates decreased as the number of AED doses given each day increased (Fig 2).[8] Subsequently, Cramer found that compliance rates were highest 5 days before and 5 days after a clinic visit, then decreased 1 month later.[9] These studies suggest that simplified dosing regimens and clinicians' interactions with patients can improve patient compliance with treatment.

[Figure 2 ILLUSTRATION OMITTED]

More recently, the nursing perspective on compliance has broadened to consider medication adherence as just one part of self-management.[16,32] Use of the self-management model encourages the nurse to evaluate the patient's health and daily life more comprehensively. Education can then be tailored to address medication-taking practices, seizure management and quality of life issues.

Assessing Learning Needs

A critical part of epilepsy self-management and compliance education begins with identifying the educational needs and preferences of the patient and family. Nurses should begin by asking patients and their caregivers what strategies might make medication taking easier and which have worked best for them. Too often, nurses may neglect the patient and family perspective, instead relying on AED blood level data or information from other health care providers. Understanding individual patient attributes such as knowledge, beliefs, skills, behavior, fears, expectations, feelings of control, self-efficacy and priorities for learning can faciliate the educational process.[30,32] For example, patients who feel they have no control over their seizures may be less motivated to learn how to improve compliance or treat seizure emergencies at home. Nursing interventions may need to address the patient's feelings of control and adjustment to epilepsy before trying medication changes.

Developing a partnership and setting realistic goals and expectations with the patient can enhance their understanding of available treatment options. Effective communication is crucial to the patient-provider relationship. Health behavior research studies have demonstrated that effective communication can reduce patient anxiety and increase satisfaction with care, the likelihood of remaining in care and care-seeking behaviors.[23] Additionally, patient-provider communication can improve the patient's understanding and adherence to treatment regimens.[23] Clear communication is crucial when educating patients and families about new therapies for cluster seizures and how to implement them outside of the hospital setting.

Providing support -- particularly epilepsy-specific support -- is a key factor for successful self-management.[15,22] Examples of regimen-specific support in epilepsy may include reminders to take medications, use of calendars or pillboxes to aid compliance, and showing how to administer diazepam rectal gel and monitor the patient post-treatment.

Perhaps most importantly, nurses need to reevaluate therapy choices whenever the patient's goals and satisfactory seizure control has not been reached. Reevaluation requires periodically revisiting the patient's diagnosis, seizure type and choice of therapy to ensure that the appropriate therapy for the patient's condition is being used. Education provided to patients and caregivers regarding medication management and other self-management practices should also be reevaluated periodically. Because this involves scrutiny of past and current treatment decisions, patients and providers need to be flexible and receptive to change.

Specific Concerns for Diazepam Rectal Gel Education

Because home administration of a rectal medication will be new for many providers (both nurses and physicians) and certainly for many patients, patient and family education must accompany any prescription for this therapy. Although diazepam rectal gel is easy to use, patients must understand exactly when and how to administer the drug. Most important, patients and caregivers must be able to distinguish between ordinary and cluster seizures, know how frequently to give the dose, and know when a second dose of diazepam rectal gel is indicated. Some providers may instruct patients and caregivers to give a second dose if seizures persist over a period of time. Nurses should also review seizure recognition and first aid with everyone involved. It is not safe to assume that this fundamental information has already been discussed. Teaching materials for diazepam rectal gel education are available from Elan Pharmaceuticals for use with patients and caregivers.

Some patients or providers may want to test the patient's response to diazepam rectal gel in the hospital setting under observation. Nurses can use this opportunity to alleviate concerns and teach patients and caregivers how to administer the drug and monitor the patient post-treatment. Current prescribing literature recommends that the patient be observed for 4 hours post-treatment to check for changes in respiration and further seizure activity. Caregivers need to know how to count the patient's breathing for 1 minute at rest (baseline respiratory rate), while asleep, and during a seizure. They must then be able to differentiate changes in breathing due to seizure activity or sleep from potential adverse effects of rectal diazepam. Monitoring for further seizure activity requires that caregivers be able to observe and differentiate seizure behaviors from postictal behaviors and to know when to call for additional help.

Patients or family members may express privacy concerns regarding use of diazepam rectal gel when seizures occur in public. Some people may be uncomfortable or embarrassed about administering a rectal medication in public, whereas others may be concerned with the stigma of having a seizure in public. For many, administering diazepam rectal gel in public is no more intrusive than breast-feeding or changing diapers in public. Patients and caregivers will need a chance to talk about their feelings and how to enhance privacy when giving diazepam rectal gel.

Summary

To enhance seizure control for people with epilepsy, nurses must remain up-to-date and knowledgeable about available treatment options, not only for chronic management but also for acute seizure situations. Patients and caregivers must also know what choices are available to them. Nurses can ensure that this occurs by continually assessing the patient's medication-taking behavior and compliance and by working together with the patient to find the best option. For information about available educational resources, providers and patients can contact the Epilepsy Foundation at 1-800-EFA-1000 or via the Internet at www.epilepsyfoundation.org.

References

[1.] Agurell S, Berlin A, Ferngren H, Hellstrom B: Plasma levels of diazepam after parenteral and rectal administration in children. Epilepsia 1975;16:277-283.

[2.] Aweeka F, Alldredge B, Boyer T et al: Conversion of ACC-9653 to phenytoin in patients with renal or hepatic diseases. Clin Pharmacol Ther 1989;45:152.

[3.] Berg AT, Shinnar S: Complex febrile seizures. Epilepsia 1996;37(2):126-133.

[4.] Browne RE, Kugler AR, Eldon MA: Pharmacology and pharmacokinetics of fosphenytoin. Neurology 1996;46 (suppl 1): 53-57.

[5.] Browne TR: Fosphenytoin (Cerebyx) [Review]. Clin Neuropharmacol 1997;20(1): 1-12.

[6.] Bryant AE, Dreifuss FE: Valproic acid fatalities. III. US experience since 1986. Neurology 1994;46:465-469.

[7.] Cloyd JC, Lalonde RL, Beniak TE, Novack GD: A single-blind, crossover comparison of the pharmacokinetics and cognitive effects of a new diazepam rectal gel with intravenous diazepam. Epilepsia 1998;39(5):520-526.

[8.] Cramer JA, Mattson RH, Prevey ML et al: How often is medication taken as prescribed? A novel assessment technique. JAMA 1989;261(22):3273-3277.

[9.] Cramer JA, Scheyer RD, Mattson RH: Compliance declines between clinic visits. Arch Intern Med 1990;150(7):1509-1510.

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[11.] DeLorenzo RJ, Hauser WA, Towne AR et al: A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia. Neurology 1996;46(4):1029-1035.

[12.] Depacon: Valproate Sodium Injection [package insert]. Abbott Laboratories, 1997.

[13.] Devinsky O, Leppik I, Willmore LJ: Intravenous Valproate Study Team: Safety of intravenous valproate. Ann Neurol 1995;38:670-674.

[14.] Diastat (diazepam rectal gel) Rectal Delivery System [package insert]. Athena Neurosciences, 1997.

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[16.] DiIorio C, Faherty B, Manteuffel B: Self-efficacy and social support in self-management of epilepsy. West J Nurs Res 1992;14:292-307.

[17.] Dreifuss FE: Prevention as it pertains to epilepsy. Arch Neurol 1995;52:363-366.

[18.] Eldon MA, Loewen GR, Voightman RE et al: Pharmacokinetics and tolerance of fosphenytoin and phenytoin administration intravenously to healthy subjects. Can J Neurol Sci 1993;20:5180.

[19.] Fischer JH, Cwik MJ, Luer MS et al: Stability of fosphenytoin sodium with intravenous solutions in glass bottles, polyvinyl chloride bags, and polypropylene syringes. Ann Pharmacother 1997;31:553-559.

[20.] Gastaut H: Classification of status epilepticus. Pages 15-35 in: Status Epilepticus: Mechanisms of Brain Damage and Treatment, Delgado-Escueta A, Wasterlain C, Treiman D et al (editors). Raven Press, 1983.

[21.] Gidal B, Spencer N, Maly M et al: Valproate-mediated disturbances of hemostasis: Relationship to dose and plasma concentration. Neurology 1994;44:1418-1422.

[22.] Glasgow RE, Toobert DJ: Social environment and regimen adherence among type II diabetic patients. Diabetes Care 1988; 11:377-386.

[23.] Gochman DS: Provider determinants of health behavior. Pages 397-417 in: Handbook of Health Behavior Research II: Provider Determinants, Gochman DS (editor). Plenum Press, 1997.

[24.] Hauser WA: Status epilepticus: Epidemiologic considerations. Neurology 1990;40(5 suppl 2):9-13.

[25.] Kriel RL, Cloyd JC, Hadsall RS et al: Home use of rectal diazepam for cluster and prolonged seizures: Efficacy, adverse reactions, quality of life, and cost analysis. Pediatr Neurol 1991;7:13-17.

[26]. Kugler AR, Knapp LE, Eldon MA: Rapid attainment of therapeutic phenytoin concentrations following administration of loading doses of fosphenytoin: a meta-analysis. Neurology 1996;46(suppl):A176.

[27.] Mattson RH: General principles: Selection of antiepileptic drug therapy. Pages 123-135 in: Antiepileptic Drugs, 4th ed, Levy RH, Mattson RH, Meldrum BS (editors). Raven Press, 1995.

[28.] Mitchell WG: Status epilepticus and acute repetitive seizures in children, adolescents, and young adults: Etiology, outcome, and treatment. Epilepsia 1996;37(suppl 1):S74-S80.

[29.] Morton LD, Rizkallah E, Pellock JM: New drug therapy for acute seizure management. Semin Pediatr Neurol 1997;4(1):51-63.

[30.] Ozuna J, Cammermeyer M: Learning needs of the epilepsy patient. Pages 133-151 in: Neurologic Care: A Guide for Patient Education, Van Meter MG (editor). Appleton Century Crofts, 1982.

[31.] Quon CY, Stampfli HE: In vitro hydrolysis of ACC-9653 (phosphate ester prodrug of phenytoin) by human, dog, rat, blood, and tissues. Pharm Res 1986;3(5 suppl):134S.

[32.] Shafer PO: Nursing support of epilepsy self-management. Clin Nurs Pract Epilepsy 1994;2:11-14.

[33.] Treiman DM: The role of benzodiazepines in the management of status epilepticus. Neurology 1990;40(suppl 2):32-42.

[34.] Working Group on Status Epilepticus: Treatment of convulsive status epilepticus: Recommendations of the Epilepsy Foundation of America's Working Group on Status Epilepticus. JAMA 1993;270(7):854-859.

Questions or comments about this article may be directed to: Patricia O. Shafer, RN, MN, Beth Israel Deaconess Medical Center, Comprehensive Epilepsy Center, KS-457, 330 Brookline Avenue, Boston, MA 02215. She is an Epilepsy Nurse Specialist.3
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Author:Shafer, Patricia O.
Publication:Journal of Neuroscience Nursing
Geographic Code:1USA
Date:Aug 1, 1999
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