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An Algorithm for Diagnosis and Treatment of Status Epilepticus in Adults.

Abstract: Convulsive or generalized tonic-clonic status epilepticus (SE) is a neurological emergency that can lead to transient or permanent brain damage or even death. A conceptual model was developed to assist nurses and other medical professionals to differentiate between convulsive and nonconvulsive SE. An algorithm was then designed to aid nursing and medical staff in decision making about the type of SE and pharmacological intervention needed to stop prolonged or repetitive seizures occurring in patients undergoing video electroencephalogram (EEG) monitoring.

A treatment algorithm for diagnosing and treating SE has clinical benefits in the practice setting of an inpatient comprehensive epilepsy program. Episodes of SE are more accurately classified and faster successful treatment of the episode occurs.

Introduction

With the advent of new technology for diagnosing patients with epilepsy, comprehensive epilepsy programs have multiplied in the United States and abroad over the past two decades. When patients are admitted to comprehensive epilepsy programs, continuous video electroencephalogram (video EEG) closed circuit television monitoring is done to record seizures so that increased knowledge may be gained about the patient's seizure type. In order to capture an epileptic seizure during a reasonable time period, it is often necessary to promote seizure activity by reducing antiepileptic drugs (AEDs) while the patient is in the hospital. This can put patients at risk for having multiple seizures or prolonged, life-threatening seizure events leading to status epilepticus (SE).

SE is a potentially life-threatening medical emergency that can result in transient or permanent brain damage. The frequency of SE in the United States alone is about 102,000 to 152,000 per year with adult mortality rates of 3-35%.[4,9,11,15,19] Generalized convulsive status epilepticus (GCSE), the most common and life-threatening form of SE requires immediate pharmacological and medical treatment. Effort should be made to prevent the occurrence of SE if possible. This article summarizes literature related to SE, describes a classification of SE, and discusses an algorithm for prompt pharmacologic intervention when patients are on an epilepsy unit. A conceptual model is described to assist nurses and other medical professionals to differentiate between convulsive and nonconvulsive SE and to facilitate treatment of life-threatening SE.

Because there are as many types of SE as there are types of seizures, it is critical that the nurse and physician be knowledgeable about the various types of SE so that proper treatment can be initiated. The Epilepsy Foundation of America's Working Group on Status Epilepticus defines SE as a continuous seizure lasting 30 minutes or more, or two consecutive seizures in a row without mental clearing.[19] In an epilepsy monitoring unit, where patients are routinely taken off medication to promote seizure activity, SE is a strong possibility. However, waiting 30 minutes to treat the patient is not an option. A protocol guiding interventions to prevent SE and quick treatment of the potentially serious complications of prolonged or repetitive convulsive seizures is necessary for state of the art care. Two major advantages of a protocol are a framework for a predetermined plan of action and decreased patient morbidity and mortality associated with SE.

Review of the Literature

Definitions of Status Epilepticus

The many types of status epilepticus require various approaches to management and also have different prognoses. The term, status epilepticus, was defined by the International League Against Epilepsy as a "seizure that persists for a sufficient length of time or is repeated frequently enough to produce a fixed and enduring epileptic condition" (p. 15).[5] This definition created difficulties in the practice setting because "sufficient length" cannot easily be translated into a distinct time period. In order to quantify the terms "sufficient length" and "repeated frequently," several investigators clarified the definition of status epilepticus, and recommended that a prolonged seizure be considered as status if it has lasted at least 30 minutes. Since then the Epilepsy Foundation of America's Working Group on Status Epilepticus has proposed the following definition: SE is 30 minutes of continuous seizure activity or two or more sequential seizures with out full recovery of consciousness in between.[19] Other investigators have proposed changing the definition to be five minutes of continuous seizure activity.[9]

Since any seizure can evolve into SE and can present as continuous seizure activity or as recurrent seizures, the practitioner must be knowledgeable about what type of status is occurring in order to provide the appropriate treatment. This can be confusing because SE often presents in the clinical setting as a combination of the various types. Most importantly, all of these types can lead to generalized convulsive status epilepticus (GCSE) which is life-threatening. Therefore, a nurse that can anticipate SE as a potential medical emergency is better equipped to intervene in a timely manner.

Physiological Effects

GCSE is a medical emergency that can lead to transient or permanent brain damage. Early treatment is a key factor in the outcome and prognosis of GCSE.[9,11,15] If seizures persist beyond 30 minutes, a vicious cycle of maladaptive physiological responses occurs. Oxygen demands increase secondary to increased oxygen consumption leading to hypoxia. As a consequence, the blood pressure rises to allow more oxygenated blood to reach the brain. Increased blood flow increases intracranial volume and may increase intracranial pressure. An increase in cerebral metabolic rate also results in more rapid glucose utilization causing an increase in glucose production followed by an increase in insulin secretion. This response leads to hypoglycemia. Many of the detrimental physiologic effects of SE are related to a mismatch between neuronal glucose and oxygen requirements and availability.[16]

Seizure-induced brain damage has been linked to excitotoxic neuronal injury seen after 30 minutes of continuous seizure activity. The prolonged epileptic seizure, which results in a lack of oxygen and glucose in brain cells, stimulates the production and release of excessive amounts of glutamate. The excessive glutamate alters the neuron's electrical balance and opens membrane channels, resulting in a calcium influx. The calcium overload triggers formation of oxygen free radicals which make the brain cells electrically unstable and cause cell injury.[2]

Epidemiology

In patients with known epilepsy, one half of the hospital reported cases of GCSE have been associated with subtherapeutic antiepileptic drug (AED) levels resulting from acute AED withdrawal.[11] Patients with frontal lobe epilepsy are at particular risk for developing status epilepticus, and that risk increases with acute AED withdrawal.[17]

Mortality and morbidity rates have been related to the etiology of status and the time from the onset of status until treatment has been initiated. The duration of the GCSE has also been related to the prognosis. In a retrospective study, Aminoff and Simon reviewed the charts of 98 patients with GCSE, ages 14-84 years, admitted to San Francisco General Hospital over a nine-year period.[1] Noncompliance with AED regimens accounted for 53% of SE in patients with a history of epilepsy. Other etiologies included alcohol withdrawal, infection, cerebrovascular disease and intracranial tumors. In 15 patients, the etiology was unknown. The duration of status prior to initiation of treatment ranged from several minutes to twelve hours. Clinical sequelae occurred in 10 of the patients; two patients died, six patients developed intellectual impairment and two patients developed evidence of cerebral atrophy as affirmed by computed tomography (CT) scan. In five of the six patients that developed intellectual impairment, duration of status exceeded 2 hours. The overall morbidity and mortality rates were 12% and 2.5% respectively.

In a study conducted by Scholtes et al, data were obtained from hospital records of 292 patients (346 hospital admissions) with GCSE in The Netherlands over a seven year period.[12] Data were collected from 50 different hospitals. Patients were ages 15 years or older with a minimal seizure duration of 30 minutes or more or successive generalized tonic clonic seizures without regaining consciousness in between. Sixty-eight percent of the patients in this study had a previous history of epilepsy; 28% of these patients developed SE because of noncompliance with AED regimens. Medical complications occurred in 41% of the cases including hyperthermia, cardiac arrhythmias, respiratory insufficiency, aspiration and acidosis. Thirty eight of these patients (13%) died as a result of one or more of the medical complications of status epilepticus.

Treatment

Improved clinical outcomes have been linked to early pharmacological, nursing and medical intervention. If GCSE results from rapid AED withdrawal, control is usually easy to obtain if appropriate pharmacologic treatment is initiated early in the course of the event.[11] Prolonged seizures have been associated with pharmacoresistance leading to an increased mortality rate.[10] Pharmacological interventions as well as efforts to maintain cardiac output and adequate oxygenation via intubation or oxygen supplementation are pivotal aspects of effective treatment.

Because of rapid peak brain concentrations and short administration times, the benzodiazepines such as diazepam and lorazepam have been shown to be more effective as first-line drugs in acute seizure control.[11] Benzodiazepines treat the episode of status and allow time for the practitioner to make decisions about instituting pharmacologic treatment for maintenance of seizure control. Lorazepam can also be administered rapidly as opposed to conventional AEDs, such as phenytoin and phenobarbital (Table 1).
Table 1. Comparison of Antiepileptics Drugs Used in SE

 Benzodiazepines

 Diazepam Lorazepam Phenytoin

Adult dose (mg/kg) 0.15-0.25 0.1 15-20

Usual adult dose (mg) 5-10 2 1000

Time to stop SE (min) 1-3 6-10 10-30

Duration of action (hrs) 0.25-0.5 12-24 24

Administration rate (mg/min) 5 2 50

 Phenobarbital Fosphenytoin

Adult dose (mg/kg) 20 10-20 PE(*)

Usual adult dose (mg) 120-600 1000PE(*)

Time to stop SE (min) 20-30 10-20

Duration of action (hrs) [is greater than] 48 24

Administration rate (mg/min) 100 100-150


Adapted from recommendations of the Epilepsy Foundation of America's Working Group on Status Epilepticus: Treatment of Convulsive Status Epilepticus. JAMA 1993; 270:(7): 856. American Medical Association [C] 1993. Data originally adapted from: Treiman DM: Pages 377-384 in: General principles of treatment: responsive and intractable status epilepticus in adults. Delgado-Escueta AV, Wasterlain CG, Treiman DM, Porter RJ eds. Advances in Neurology 34: Status Epilepticus: Mechanisms of Brain Damage and Treatment Raven Press, 1983. Also originally adapted from: Treiman DM: Special treatment problems in adults. Smith DB, ed. Pages 155-172 in: Epilepsy: Current Approaches to Diagnosis and Treatment Smith DB (editor) Raven Press, 1990.

(*) PE = Phenytoin Equivalents

Treiman noted that the pharmacokinetics of lorazepam provide for a longer duration of action in the management of SE than diazepam.[14] Diazepam is highly lipid soluble and serum levels drop quickly as compared to lorazepam which is less lipid soluble. Current practice, along with recommendations from the Epilepsy Foundation of America's Working Group on Status Epilepticus, advocates the use of lorazepam in the initial management of status epilepticus. It is noted that although SE is not recognized by the Food and Drug Administration as an approved indication for lorazepam, its use in SE is widely accepted by the medical community.[19]

Classification Schemes

Written reports on epilepsy and SE date back to Babylonian times. Despite a long list of historical references to epilepsy, it was only in the nineteenth century that SE was clearly differentiated from epilepsy. Literature related to epilepsy and the classification of epileptic seizures, however, was ambiguous and often inconsistent.

Eventually, a scheme for categorizing the types of SE was suggested by Gastaut in 1983. He proposed that there were three major classes of status: generalized, partial and unilateral. Generalized status included both convulsive and nonconvulsive types. Grand mal status was the label given to any form of status that included tonic-clonic seizures whether or not they had a generalized or secondarily generalized onset. The nonconvulsive subset included petit mal seizures and episodes of spike wave stupor. Partial status epilepticus was limited to repeated partial seizures without secondary generalization. Gastaut separated this category into elementary partial status epilepticus in which consciousness was preserved and complex partial status epilepticus in which consciousness was impaired. He coined the latter as temporal lobe or psychomotor status.[5] The last class included in Gastaut's scheme was unilateral status in which patients had clonic seizures affecting one side of the body.

Since that time, there have been several proposed ideas about classification, but no internationally recognized schemes have emerged. Treiman recognized three types of status is:

* generalized convulsive with subsets labeled overt and subtle

* nonconvulsive

* simple partial[15]

The generalized convulsive status category included not only tonic-clonic seizures but sub-clinical EEG seizures as well. The nonconvulsive category included generalized and partial types of seizures. Treiman referred to this as a simpler classification of SE because the distinction between primary and secondarily generalized seizures was difficult, therefore, they were grouped under the same category. This view, however, fails to separate generalized types of seizures from partial types, further clouding the comprehension of classification.

Proposed Conceptual Model for Classification of Status Epilepticus

Since any type of seizure can evolve into SE a more appropriate classification would be closely related to the international classification of seizures (Fig 1). In this conceptual model, SE is classified by the type of seizure manifested at the time of the status episode. The two subsets are nonconvulsive SE, which is not a life-threatening process, and convulsive SE, which is life-threatening and requires immediate treatment. Both partial and generalized convulsive types can further be broken down into type I or type II, further clarifying the severity of the event and indicating that each type of SE can be repetitive or continuous in nature.

[Figure 1 ILLUSTRATION OMITTED]

Type I SE includes seizures that occur in a repetitive nature whether or not consciousness is impaired. If a patient has repetitive simple partial or complex partial seizures they may still be experiencing status epilepticus even though consciousness remains intact in between seizures. Therefore, a definition that only encompasses GCSE is inadequate. In GCSE, consciousness is not regained in between seizures and immediate treatment should be initiated after 2-3 seizures. Other type I episodes are not treated emergently.

Type II includes continuous seizures. The proposed definition is a continuous seizure lasting longer than 3 minutes. This definition is intended for convulsive seizures occurring on the inpatient comprehensive epilepsy program unit as resources are available to diagnose this condition. In the general outpatient setting, it would be impossible to treat within 3 minutes. However, patients and family members should be taught to call for help if the seizure episode lasts longer than 3 minutes.

This proposed model also includes spike wave stupor, which is continuous spike and wave activity, under both partial and generalized types of SE because it is often seen in primary generalized and frontal lobe epileptic syndromes. Spike wave stupor usually involves alteration in consciousness. However, the patient may be able to carry out normal physical activities. Therefore, it is a condition that can be overlooked without concurrent EEG data. Most importantly, this conceptual model conveys the idea that any seizure type can eventually turn into generalized convulsive SE and that the progression towards that end should always be anticipated.

Clinical Algorithm

The nurses knowledge of a treatment protocol for effective management of GCSE on the general neurology patient care unit is critical but it is especially important when practicing in a high risk area such as an epilepsy unit. A predetermined plan of action increases the probability of a best outcome. Unambiguous, step by step instructions for solving clinical problems, such as clinical algorithms, have been very useful in the field of medical decision theory. Clinical algorithms have been shown to result in faster learning, higher retention and better compliance with practice standards than written text.[6]

Treatment Algorithm to Prevent SE

The treatment algorithm (Fig 2) used at Dartmouth Hitchcock Medical Center was developed with input from the clinical nurse specialist of the neuroscience unit and epileptologists involved in the comprehensive epilepsy program. Each patient entering the program as an inpatient is assessed for risk factors such as a prior history of SE, seizures that occur in clusters, medication noncompliance or a history of frontal lobe epilepsy. The protocol is initiated in those patients with the above risk factors. If type II SE occurs, the nurse automatically gives 2 mg of lorazepam before calling the physician in order to initiate treatment early. The physician is then called for further orders. If type I SE occurs, in which the patient has recurrent seizures, the physician is called prior to giving any medication. Since the purpose of the patient's admission is to record seizures, our criteria are altered to allow three, not two, repetitive seizures to occur without mental clearing before considering this as SE.

[Figure 2 ILLUSTRATION OMITTED]

Although this algorithm may seem simple, the knowledge required to get to the point of correct treatment must not be overlooked. Only experienced nurses and physicians are able to accurately and quickly diagnose this condition. Education in the form of didactic instruction with video-taped examples is necessary for high performance.

Summary

A treatment algorithm designed to provide early intervention to patients experiencing SE was imperative to provide state of the art care on our comprehensive epilepsy monitoring unit. Patients on a video EEG monitoring unit are admitted to record seizures, and most often antiepileptic medications must be reduced or discontinued in order to promote seizure activity in a short time frame. AED dose reduction puts patients at considerable risk for developing SE. Nurses working with this patient population must be educated about the various types of SE and must know when to take emergency action. A predetermined plan helps to take the "guess work" out of the decision-making process, thereby reducing potential patient morbidity and mortality.

References

[1.] Aminoff M, Simon R: Status epilepticus: Causes, clinical features, and consequences in 98 patients. Am J Med 1980; 69: 657-666.

[2.] Choi DW: Glutamate receptors and the induction of excitotoxic neuronal death. Prog Brain Res 1994; 100: 47-51.

[3.] Corsellis J, Bruton C: Neuropathology of status epilepticus in humans. Pages 129-139 in: Status Epilepticus: Mechanisms of Brain Damage and Treatment. Delgado-Escueta A, Wasterlain C, Treiman D, Porter R (editors). Raven Press, 1983.

[4.] Engel J: Status epilepticus, pages 256-280 in: Seizures and Epilepsy, Engel J (editor). FA Davis Company, 1989.

[5.] Gastaut H: Classification of status epilepticus. Adv Neurol 1983; 34:15-35.

[6.] Hadorn D, McCormick K, Diokno A: An annotated algorithm approach to clinical guideline development. JAMA 1992; 24:3311-3314.

[7.] Leppik I, Derivan A, Homan R: Double-blind study of lorazepam and diazepam in status epilepticus. JAMA 1983; 249:1452-1454.

[8.] Lothman E, Bertram E: Epileptogenic effects of status epilepticus. Epilepsia 1993; 34: (Suppl 1): S59-S70.

[9.] Lowenstein D, Alldredge B: Status Epilepticus. N Eng J Med 1998; 14:970-976.

[10.] Macdonald R: Acute cellular alterations in the hippocampus following status epilepticus. Proceedings of the seventeenth annual Merritt Putnam symposium, Boston, MA, 1997.

[11.] Ramsay E: Treatment of status epilepticus. Epilepsia 1993; 34 (suppl 1):71-81.

[12.] Scholtes F, Renier W, Meinardi H: Generalized convulsive status epilepticus: Causes, therapy, and outcome in 346 patients. Epilepsia 1994; 35 (5): 1104-1112.

[13.] Shorvon S: Pages 152-165 in: Status Epilepticus: Its Clinical Features and Treatment in Children and Adults. Cambridge University Press, 1994.

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

[15.] Treiman D: Generalized convulsive status epilepticus. Epilepsia. 1993; 34 (suppl. 1) S2-11.

[16.] Wasterlain C, Fujikawa D, Penix L, Sankar R: Pathophysiological mechanisms of brain damage from status epilepticus. Epilepsia 1993; 34 (suppl 1):37-53.

[17.] Williamson P: Frontal lobe seizures: Problems of diagnosis and classification. Adv Neurol 1992; 57:289-309.

[18.] Williamson P, Spencer D, Spencer S, Novelly R, Mattson R: Complex partial status epilepticus: A depth electrode study. Ann Neurol 1985; 18: 647-654.

[19.] Working Group on Status Epilepticus: Treatment of status epilepticus. JAMA 1993; 270: 854-859.

Questions or comments about this article may be directed to: Karen L. Gilbert, RN, BSN, 186 Orford Road, Lyme, New Hampshire 03768. She is the nurse coordinator of the Dartmouth Epilepsy Program at Dartmouth Hitchcock Medical Center in Lebanon, New Hampshire.
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Author:Gilbert, Karen
Publication:Journal of Neuroscience Nursing
Geographic Code:1USA
Date:Feb 1, 1999
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