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Journal of Neuroscience Nursing:
doi: 10.1097/JNN.0b013e31828a414b
Article

To Provoke or Not Provoke: Ethical Considerations in the Epilepsy Monitoring Unit

Updyke, Monica; Duryea, Barbara

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Author Information

Barbara Duryea, MSN, is Director of Research and Development at the John P. Murtha Neuroscience and Pain Institute, Conemaugh Health System, Johnstown, PA.

Questions or comments about this article may be directed to Monica Updyke, MSN ACNP-BC, at nursecop1@gmail.com. She is a Nurse Practitioner, Palliative Care, Conemaugh Memorial Medical Center, Johnstown, PA.

The authors declare no conflicts of interest.

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Abstract

ABSTRACT: Epilepsy is the second most common neurological disorder after migraines and headaches, with an economic burden of 15.5 billion dollars annually. Most patients with epilepsy can be controlled with antiepileptic drugs. Those who remain uncontrolled are considered refractory and are often admitted to an epilepsy monitoring unit for definitive diagnosis. Nonepileptic seizures are a common differential diagnosis in persons with refractory seizures. It is helpful for providers to witness the patients’ seizures to make a definitive diagnosis for seizure classification. Frequently, unstandardized practice-provocation techniques are employed in an epilepsy monitoring unit setting. The purpose of these techniques is to elicit a seizure. A debate is occurring on whether the use of provocation techniques is ethical and necessary. This article will review the literature related to the current evidence and moral opinions swirling around this topic. It is important for the neuroscience nurse to be familiar with both sides of the seizure provocation debate as he or she will be on the front lines of shaping future policy and practice to come.

Patients with refractory seizures present clinical care and ethical challenges. Epilepsy is a common neurological disorder that, in most patients, can be well controlled. Those who continue to experience seizures despite treatment are intractable or refractory. It is the refractory seizure patient that the neuroscience nurses will generally care for more often. The setting in which they are evaluated include outpatient office visits for monitoring and medication adjustment. Some patients with epilepsy are admitted to an inpatient epilepsy monitoring unit (EMU) for diagnosis and classification of their seizures, the goal of the admission being the patient having a seizure. If the patient does not have a seizure during their EMU admission, provocation techniques to induce a seizure may be employed. This article will focus on the current literature regarding the use of provocation techniques and the ethical dilemmas and safety considerations surrounding a typical EMU admission for a patient with refractory epilepsy.

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Background: Seizures Versus Epilepsy

A seizure is a transient paroxysmal event because of abnormal neuronal discharge in the cerebral cortex. Presentations of the abnormal electrical discharge will depend on the location in which they arise and can vary from dramatic convulsions to occurrences that are not readily detectable to observers (Aminoff & Kerchner, 2010; Fisher & Long, 2007; Lowenstein, 2008). It is estimated that approximately 5%–10% of the population will experience at least one seizure in their lifetime with the highest incidence occurring in early childhood and late adulthood (Fisher & Long, 2007; Lowenstein, 2008). Epilepsy is a condition in which a person has recurrent unprovoked seizures that are caused by a chronic biochemical, anatomical, and/or physiological change (Fisher & Long, 2007; Lowenstein, 2008). Causes of epilepsy are many and may include disease such as neoplasm, degenerative disorders, infection, traumatic brain injury, and stroke. Stroke or vascular diseases have become an increasingly frequent cause of epilepsy in people greater than 60 years old (Aminoff & Kerchner, 2010; Lipe, 2001). There are 200,000 new cases of epilepsy diagnosed each year with 70% of those cases having no apparent cause (Epilepsy Foundation, 2009a; Lipe, 2001). The incidence is greater in African American and socially disadvantaged populations, and the reasons for the ethnic/racial differences have not been identified (National Institute of Neurological Disorders and Stroke, 2011). It is estimated that 3 million people in the United States are currently diagnosed with epilepsy. The burden of epilepsy in the United States is projected at 15.5 billion dollars a year. Treatment using antiepileptic drug(s) (AEDs) accounts for 30% of direct medical costs. About 70% of patients diagnosed with epilepsy will have their seizures controlled with AEDs and have a marked reduction or seizure freedom for 5 years after treatment is initiated. However, 30% of patients fail to gain control of seizures despite optimal medical management.

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Medically Refractory Epilepsy and the EMU

Medically refractory, intractable, or drug-resistant epilepsy has been simply defined as patients who continue to have seizures while receiving AEDs (Kwan & Brodie, 2000). Medically refractory epilepsy contributes to a disproportionate amount of cost with 25% of patients who are drug resistant incurring 86% of all costs. Treatment of uncontrolled epilepsy costs approximately $11,000 per year, whereas treatment of controlled epilepsy is approximately $3,000 annually (Ivanova et al., 2010).

A common differential diagnosis in medically refractory patients is psychogenic nonepileptic seizures (PNES). These are episodes of altered movements or sensation that appear to be epileptic in nature but are not associated with abnormal electrical discharges within the brain (Brown, Syed, Benbadis, Lafrance, & Reuber, 2011; Reuber & Elger, 2003). Although PNES is commonly used in the literature to classify epileptic seizures without an electrical focus in the brain, it has been suggested to refer to PNES simply as nonepileptic seizures (NES), as the diagnosis itself implies that the person is not sincere or is faking events when, in reality, they experience real seizures (Epilepsy Foundation, 2009b).

In medically refractory patients, long-term video electroencephalography (V-EEG) in an EMU is the gold standard and enables providers to both visualize the patients’ motor behavior during the seizure while simultaneously evaluating the electrical activity within the brain. Valuable information can be gained, which may permit diagnosis, classification of epilepsy syndromes (including NES), and surgical localization of epileptic focus (Cascino, 2001; Ghougassian, d’Souza, Cook, & O’Brien, 2004; Gilliam et al., 1997) and is the next diagnostic step. The importance of V-EEG lies in its ability to classify epilepsy and differentiate between seizures that are associated with an abnormal electrical discharge and those which are not. This is important as the treatment approaches are very different. The diagnostic yield of the EMU in establishing a definitive diagnosis in patients is 76%–88% (Friedman & Hirsch, 2009; Smolowitz et al., 2007). Patients with epilepsy are admitted to an EMU for the sole purpose of having a seizure so it can be captured on video and through EEG. However, the crucial piece to the EMU admission is that the patient must have a typical event/seizure during this admission. It is important for the nurse caring for patients in an EMU to realize that the goal of the admission is to capture an event or seizure. Provocation techniques, or practices, which may cause a seizure to occur, may be employed. Because the neuroscience nurses are frontline in caring for patients in an EMU, it is vital that they understand and are familiar with the latest evidence and ethical considerations associated with these techniques.

Nurses who care for patients in an EMU must realize that the ultimate goal of the admission is to capture a seizure event even when this involves strategies to provoke seizures despite the ethical concerns that envelop provocation.

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Provocation: What Does it Mean?

The International League Against Epilepsy defines a “provocative factor” as an “element capable of augmenting seizure incidence in persons with chronic epilepsy and evoking seizures in susceptible non-epileptic individuals” (Engel, 2001). A number of techniques have been used to provoke typical events while patients are admitted to an EMU. More common techniques used to provoke all patients with seizures include hyperventilation, photic stimulation, sleep deprivation, and AED withdrawal. The use of these techniques has been a common place, and they are considered relatively safe. The exact mechanism in seizure provocation with hyperventilation is unknown, but it is thought that hypocapnia, which occurs during hyperventilation, causes vasoconstriction and some degree of hypoxia that triggers neurons to abnormally fire or discharge. Research has shown some effectiveness of this technique during an EMU admission without provoking events that were different or more severe than the patient’s typical event (Arain, Arbogast, & Abou-Khalil, 2009; Guaranha et al., 2005). Photic stimulation has been implicated in seizure induction and has been shown to induce generalized seizures. A well-known account in which photic stimulation caused seizures occurred in Japan in 1997. A large number of children were taken for medical attention for symptoms that were believed to be seizures after watching a televised animated cartoon (Fisher, Harding, Erba, Barkley, & Wilkins, 2005; Takada et al., 1999). Sleep deprivation is often used in provocation of seizures; however, there is no evidence to support its usefulness during an EMU admission (Malow, Passaro, Milling, Minecan, & Levy, 2002). The most common practice to induce seizures is a planned reduction of AED(s). It is important to note that rapid reduction of AEDs increases a patient’s risk, and many patients who have never had a generalized seizure will have one (Marciani, Gotman, Andermann, & Olivier, 1985; Marks, Katz, Scheyer, & Spencer, 1991). There is no clinical consistency or standardization among epilepsy centers regarding how or when to withdraw AEDs. A national survey was conducted asking 257 physicians and 39 nurses who practice in EMUs their protocol for AED withdrawal. Forty-eight percent of physicians stated that they withdraw medication before admission on “some of the patients,” whereas 11% reported that they withdraw AEDs on “most patients” before admission to the EMU, as opposed to admitting them then withdrawing therapy during their EMU stay. Sixty percent of those surveyed reported that they occasionally withdraw AEDs on the day of admission. Eighty percent of the physician respondents and 74% of the nurses reported that they did not have any specific protocols for drug withdrawal (Buelow, Privitera, Levisohn, & Barkley, 2009). Other techniques used to attempt to provoke seizures include physical exercise, alcohol consumption, and mental concentration tasks. However, there is no evidence to support their usefulness.

As mentioned above, these techniques may be used in all patients with epilepsy during an EMU admission; however, different provocation techniques may be employed when NES is suspected. Some of the more common provocation techniques for NES include placing an alcohol pad on the skin, a tuning fork applied to the forehead, psychiatric interviewing, head-up tilt testing, inhalation of ammonia fumes, intravenous saline injections, and administration of placebo with the suggestion that it may cause a seizure (Bazil et al., 1994; Cohen, Howard, & Bongar, 1992; Cohen & Suter, 1982; Drake, 1985; Gates, 2000; Khan et al., 2009; Lancman, Asconape, Craven, Howard, & Penry, 1994; LeVine & Ramierz, 1980; McGonigal, Oto, Russell, Greene, & Duncan, 2002; Ribai, Tugendhaft, & Legros, 2006; Stagno & Smith, 1996). These particular techniques require some form of deception of the patient on the part of the practitioner, and not all practitioners agree with using them. There is literature supporting the effectiveness and use of these techniques in diagnosing NES (Benbadis et al., 2000; Chen et al., 2011; McGonigal et al., 2002; Slater, Brown, Jacobs, & Ramsay, 1995). When some of these techniques are used, actual epileptic events have been elicited in patients who believed to have NES (Walczak, Williams, & Berten, 1994).

Regarding provocation techniques, overall, no standard or evidence-based guidelines or large clinical trial results are available regarding the use of any one provocation technique over another or even if provocation should be used at all. In fact, current guidelines state only this regarding provocation: “Provocation by suggestion may be used in the evaluation of non-epileptic attack disorder. However, it has a limited role and may lead to false positive results in some individuals” (National Clearinghouse Guidelines, 2009).

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The Debate: To Provoke or Not Provoke

At the core of this debate is a question of ethics. Ethics, or moral philosophy, addresses concepts like good and evil and right and wrong. The arguments for and against use of seizure provocation techniques revolve around the concepts of trust/autonomy and nonmaleficence (do no harm). Of importance for the neuroscience nurse, the American Association of Neuroscience Nurses Core Curriculum lists three desired patient-centered outcomes for all treatments of epilepsy. The first outcome considered as “prime importance” is that the patient with epilepsy experiences no seizures. The second is that the patient does not experience side effects to any of the treatments, and the third is that the patient has a perceived high-level quality of life (Buelow, Long, Maushard, & Gilbert, 2004). Ethics and desired clinical response sometimes clash in the ongoing debate regarding the use of provocation.

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Ethical Debate to Provoke: Do No Harm

In his article, Benbadis reviews past literature and brings an argument for provocation (Benbadis, 2009). The most common reason for a patient to complete a full EMU admission without a definitive diagnosis being determined is because a typical event has not been captured. A second EMU admission is costly, and provocation to elicit an event can be cost effective (reducing length of stay).

Another compelling argument for provocation is to provide early definitive diagnosis and initiation of appropriate treatment, especially in patients with NES. Patients with NES are often misdiagnosed as epileptic. This misdiagnosis means appropriate treatment is withheld while the patient is exposed for a longer time to AEDs that can be toxic and produce varied side effects, both acute and chronic, such as osteoporosis, risk of pregnancy complications in women, aplastic anemia, and Steven Johnson syndrome. Use of AEDs alone has been reported as the major reason for lower quality of life (Gilliam, 2002; Toledano & Gil-Nagel, 2008). In a study by Martin, Gilliam, Kilgore, Faught, and Kuzniecky (1998), 20 patients with V-EEG had confirmed NES and the authors reviewed the financial impact of a definitive NES diagnosis by V-EEG. They found an average reduction of 84% in total seizure-related charges in the 6-month post-NES diagnosis. There was an average medication charge reduction of 69% and a reduction of emergency department visits by 97% representing a substantial decrease in healthcare utilization costs (Martin et al., 1998). Smolowitz performed a retrospective review of 213 patients to determine in part if EMU admission resulted in change in diagnosis or treatment in patients with medically refractory epilepsy. The NES were diagnosed in 15.5% of the EMU admissions. These NES patients had an average of 10 years since their diagnosis, and 48% had been treated with three or more AEDs (Smolowitz et al., 2007). This delay in diagnosis leads to a delay in mental health treatment, which has been shown to be effective in the NES patient, and the potential for adverse effects from medications they do not otherwise need. With both cost considerations and definitive accurate diagnosis and its influence on appropriate treatment, the importance of a patient having an event while in the EMU is obvious. Therefore, getting a diagnosis earlier by utilizing a provoking technique that has little risk associated with it, although deceptive, is considered more ethical than allowing the patient to continue a treatment that is not effective and could produce harm, therefore satisfying the principle of nonmaleficence or do no harm (Benbadis, 2009).

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Ethical Debate Not to Provoke: Autonomy/Trust

In her article, Leeman discusses the counter argument to provocation. At the forefront of the argument, provocation techniques are not the issue; it is the deception required for some of the techniques that is necessary to carry them out (Leeman, 2009). Physicians and medical staff mislead the patient to believe that an agent that will produce a seizure will be given. In specific situations, the deception carried out by the healthcare team can be quite dramatic. Patients with epilepsy refractory to treatment and those with NES are vulnerable. They may have been marginalized throughout their lives, and in a vast majority, there is a personal history of physical and/or sexual abuse as well as other trauma. Therefore, they are distrustful of others already. For a patient to find out that their healthcare team lied or created a deception, no matter what the reason, can cause irreparable damage by violating the very trust on which they relied. Many of these patients experience ongoing depression and anxiety that can potentially be made worse, not to mention an increase in distrust of the medical community, which may hinder all future treatment, especially psychotherapy, no matter how effective it may be. In addition, the evidence does not show that provocation procedures actually produce the event or that the techniques used may produce atypical events. In a study by Walczak et al., 23% of patients (epilepsy and NES) who were injected with saline for provocation had events that were not typical for them or false-positive results (Walczak et al., 1994). Ribai and Bazil both reported in their studies using saline provocation that an average of 32% and 40% of subjects, respectfully, had no response to the provocation (Bazil et al., 1994; Ribai et al., 2006). Proponents of provocation may argue that it will induce an event sooner, decreasing length of stay; however, a study by Rose et al, evaluating 514 patients from five epilepsy centers, showed that the average time to generalized or complex partial seizure was 2.1 days and the average number of days to a nonepileptic event was 1.2 days (Rose et al., 2003).

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Summary

Arguments on both sides are compelling. Our ethical position may drive us to “do no harm.” However, as this review suggests, when are you doing no harm? Is it when you avoid unnecessary AED use or when you refuse to deceive your patient? Clinically, our goal as nurses caring for a patient with epilepsy is to achieve a goal of no seizures, to reduce side effects related to any treatment, and to help the patient achieve a high quality of life. Provocation may provide a solution that helps identify seizures and epilepsy for more effective treatment, which would aid in reducing side effects and increase quality of life. However, provocation may create an environment in which a person, who has been ostracized throughout their life, feels their trust has been violated, and more likely, they feel even more marginalized because even their healthcare providers chose to lie to them. The bottom line of the debate on provocation is that there are no standards and no evidence to support its widespread use. Furthermore, the research that has been conducted does not help to identify who would benefit (all refractory patients or just those suspected with NES) and when they would benefit. (Should it be implemented early in the admission or only after a period of time, such as 2 days has passed without a seizure occurring naturally?) Conversely, research is equally lacking in regards to not supporting its use. Clearly, more investigations must be undertaken to answer these questions and develop evidence-based practice. Neuroscience nurses are in a unique position to be the catalyst for much of this research. Although the bedside nurse is not the person ordering the provocation, he or she will be involved in the process and must be aware of the clinical and ethical concerns. This is not an easy situation, and a solution is not readily apparent. Regardless of the use of provocation or not, we, as nurses, need to continue to advocate on our patients’ behalf, providing high-quality, evidence-based care with respect for human dignity.

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Keywords: EMU; epilepsy monitoring unit; nonepileptic seizures; provocation techniques; refractory seizure

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