Adult Patients Presenting to the Emergency Department with Seizures

N E U R O L O G Y / C L I N I C A L P O L I C Y Policy statements and clinical policies are the official policies of the American College of Emergency Physicians and, as such, are not subject to the same peer review process as articles appearing in the jour- nal. Policy statements and clini- cal policies of ACEP do not necessarily reflect the policies and beliefs of Annals of Emergency Medicine and its editors. This clinical policy was devel- oped by the ACEP Clinical Policies Committee and the Clinical Policies Subcommittee on Seizures. For a complete list- ing of subcommittee and com- mittee members, please see page 614. Approved by the ACEP Board of Directors January 16, 2004. 0196-0644/$30.00 Copyright © 2004 by the American College of Emergency Physicians. doi:10.1016/ j.annemergmed.2004.01.017 Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients Presenting to the Emergency Department With Seizures M A Y 2 0 0 4 4 3 : 5 A N N A L S O F E M E R G E N C Y M E D I C I N E 6 0 5 This clinical policy focuses on critical issues in the evaluation and management of adult patients with seizures. The medical literature was reviewed for articles that pertained to the critical questions posed. Subcommittee members and expert peer reviewers also supplied articles with direct bearing on this policy. This clinical policy focuses on 6 critical questions: I. What laboratory tests are indicated in the otherwise healthy adult patient with a new-onset seizure who has returned to a baseline normal neurologic status? II. Which new-onset seizure patients who have returned to a normal baseline require a head computed tomography (CT) scan in the emergency department (ED)? III. Which new-onset seizure patients who have returned to normal baseline need to be admitted to the hospital and/or started on an antiepileptic drug? IV. What are effective phenytoin or fosphenytoin dosing strategies for preventing seizure recurrence in patients who present to the ED after having had a seizure with a subtherapeutic serum phenytoin level? V. What agent(s) should be administered to a patient in status epilepticus who continues to seize after having received benzodiazepine and phenytoin? VI. When should electroencephalographic (EEG) testing be performed in the ED? Recommendations for patient management are provided for each 1 of these topics on the basis of strength of evidence (Level A, B, or C). Level A recommendations represent patient management principles that reflect a high degree of clinical certainty; Level B recommendations represent patient management principles that reflect moderate clinical certainty; and Level C recommendations represent other patient management strategies based on preliminary, inconclusive, or conflicting evidence, or based on consensus of the members of the Clinical Policies Committee. This clinical policy is intended for physicians working in hospital-based EDs. [Ann Emerg Med. 2004;43:605-625.] I N T R O D U C T I O N Epilepsy is defined as recurrent unprovoked seizures. There are an estimated 2.5 mil- lion patients with epilepsy in the United States, based on a prevalence of about 6.6 per convulsive. To diagnose nonconvulsive status epilepti- cus (ie, complex partial status and absence status) and subtle convulsive status epilepticus (often the terminal stage of convulsive status), emergency physicians need to maintain a high index of suspicion.11 This policy is a scheduled revision of the American College of Emergency Physicians (ACEP) seizure clini- cal policy.12 This policy is not intended to be a complete manual on the evaluation and management of adult patients with seizures, but rather a focused look at criti- cal issues that have particular relevance to the practice of emergency medicine. In an attempt to maximize the usefulness of this policy, this revision is organized into “critical questions” that were determined by the com- mittee members to represent some of the most impor- tant and controversial issues related to the evaluation and management of adult patients who present to the ED with a seizure or a seizure-related complaint. It is the goal of the Clinical Policies Committee to provide an evidence-based recommendation when the medical literature provides enough quality information to answer a “critical question.” When the medical litera- ture does not contain enough quality information to answer a “critical question,” the members of the Clinical Policies Committee believe that it is equally important to alert emergency physicians to this fact. Recommendations offered in this policy are not intended to represent the only diagnostic and manage- ment options that the emergency physician should con- sider. ACEP clearly recognizes the importance of the individual clinician’s judgment. Rather, they define for the clinician those strategies for which medical litera- ture exists to provide strong support for their utility in answering the crucial questions addressed in this policy. M E T H O D O L O G Y This clinical policy was created after careful review and critical analysis of the medical literature. All articles were graded by at least 2 subcommittee members for strength of evidence. The medical literature (1960 to 2002) was reviewed for articles that pertained to each critical question posed. Subcommittee members and expert peer reviewers also supplied articles with direct bearing on this policy. The reasons for developing clinical policies in emer- gency medicine and the approaches used in their devel- opment have been enumerated.13 This policy is a prod- uct of the ACEP clinical policy development process, including expert review, and is based on the existing lit- C L I N I C A L P O L I C Y 1,000 Americans.1 Up to 28% of all epilepsy patients require treatment in emergency departments (EDs) annually.2 Patients with seizures or presenting com- plaints related to seizures represent approximately 1% to 2% of all ED visits in the United States.3 An estimated 2% to 5% of the population will have at least 1 nonfebrile seizure during their lifetime.1 In addition to patients who have an established seizure diagnosis, another 150,000 patients are diagnosed with a seizure each year, most often in the ED.4 A seizure can be the result of an acute process, in which case it is referred to as an “acute symptomatic seizure,” or it can result from a past intracranial insult such as stroke, trauma, or anoxia, in which case it is referred to as a “remote symptomatic seizure.” Re- sponsibilities of the emergency physician in evaluating and treating patients include providing stabilization and interventions to stop the seizure, preventing seizure-related complications, identifying life-threat- ening processes for which a seizure may be a symptom (eg, electrolyte abnormalities, intracranial hemor- rhage, meningitis), determining an appropriate and timely disposition (eg, hospital admission or outpatient follow-up), and minimizing future seizure-related mor- bidity and mortality. Status epilepticus is a life-threatening form of seizure. Generalized tonic-clonic status epilepticus occurs in 50,000 to 150,000 patients per year in the United States and most commonly occurs at the extremes of age.5 Between 5% to 17% of patients will have a seizure while in the ED, and up to 7% of patients in the ED will have status epilepticus. The reported mortality rate for patients in status epilepticus ranges from 5% to 22% and has been reported to be as high as 65% in those patients refractory to first-line therapies.5-8 Despite its frequency, there is no universally accepted definition of status epilepticus. According to the World Health Organization, status epilepticus is “a condition characterized by an epileptic seizure that is sufficiently prolonged or repeated at sufficiently brief intervals so as to produce an unvarying and enduring epileptic con- dition.”9 Status epilepticus has traditionally been defined as at least 30 minutes of persistent seizures or a series of recurrent seizures without complete return to full consciousness between the seizures. Some authors have proposed shortening the time criteria for diagnos- ing status epilepticus from 30 minutes to 5 minutes.7 Even when properly treated, patients with status epilepticus can have serious morbidity and mortality.10 Status epilepticus is more easily recognized when it is 6 0 6 A N N A L S O F E M E R G E N C Y M E D I C I N E 4 3 : 5 M A Y 2 0 0 4 C L I N I C A L P O L I C Y strength of prior beliefs, and publication bias, among others, might lead to such a downgrading of recommen- dations. Scope of Application. This guideline is intended for physicians working in hospital-based EDs. Inclusion Criteria. This guideline is intended for adult patients presenting to the ED with seizures. Exclusion Criteria. This guideline is not intended for pediatric patients. C R I T I C A L Q U E S T I O N S I. What laboratory tests are indicated in the otherwise healthy adult patient with a new-onset seizure who has returned to a baseline normal neurologic status? When confronted with an otherwise healthy adult patient who has had a first-time seizure, the emergency physician must determine if the seizure was the result of an acute event that requires immediate attention. The decision of which patients with a new-onset seizure need laboratory testing is determined by the informa- tion gathered through a careful history and physical examination. Patients with a first-time seizure that is suspected to be the result of concurrent alcohol use or alcohol withdrawal should be approached in a similar fashion.14 The diagnosis of an alcohol withdrawal seizure should be a diagnosis of exclusion, especially in patients presenting with a first-time seizure. Laboratory studies: The history and physical examina- tion will predict the majority of patients who will have a laboratory abnormality.15-18 Patients with altered mental status, fever, or a new focal neurologic deficit require more extensive evaluation. The controversial question is which laboratory tests are indicated in an otherwise healthy adult patient who presents to the ED after having a first-time seizure and is alert, oriented, and has no abnormal clinical findings. The literature suggests that laboratory testing is of very low yield in patients with a new-onset seizure who have returned to baseline. Glucose abnormalities and hyponatremia are the most frequent abnormalities identified and are usually predicted by the history and physical examination.15-17,19 In 1 prospective study of 163 patients, 1 unexpected case of hypoglycemia was discovered.16 In a prospective study of 136 patients, Turnbull et al15 found 4 cases of hypoglycemia and 4 cases of hyperglycemia. Two of the cases of hypo- glycemia were not suspected on the basis of the history and physical examination. Tardy et al18 found 1 case of erature; where literature was not available, consensus of emergency physicians was used. Clinical policies are scheduled for revision every 3 years; however, interim reviews are conducted when technology or the practice environment changes significantly. During the review process, all articles used in the for- mulation of this clinical policy were classified by the subcommittee members into 3 classes of evidence on the basis of the design of the study, with design 1 repre- senting the strongest evidence and design 3 represent- ing the weakest evidence for therapeutic, diagnostic, and prognostic clinical reports respectively (Appendix A). Articles were then graded on 6 dimensions thought to be most relevant to the development of a clinical guideline: blinded versus nonblinded outcome assess- ment, blinded or randomized allocation, direct or indi- rect outcome measures (reliability and validity), biases (eg, selection, detection, transfer), external validity (ie, generalizability), and sufficient sample size. Articles received a final grade (I, II, III) on the basis of a prede- termined formula taking into account design and grade of study (Appendix B). Articles with fatal flaws were given an “X” grade and not used in the creation of this policy. An Evidentiary Table was constructed and is included at the end of this policy. Clinical findings and strength of recommendations regarding patient management were then made accord- ing to the following criteria: Level A recommendations. Generally accepted principles for patient management that reflect a high degree of clinical certainty (ie, based on “strength of evidence class I” or overwhelming evidence from “strength of evidence class II” studies that directly address all the issues). Level B recommendations. Recommendations for patient management that may identify a particular strategy or range of management strategies that reflect moderate clinical certainty (ie, based on “strength of evidence class II” studies that directly address the issue, decision analysis that directly addresses the issue, or strong con- sensus of “strength of evidence class III” studies). Level C recommendations. Other strategies for patient management that are based on preliminary, inconclu- sive, or conflicting evidence or, in the absence of any published literature, based on panel consensus. There are certain circumstances in which the recom- mendations stemming from a body of evidence should not be rated as highly as the individual studies on which they are based. Factors such as heterogeneity of results, uncertainty about effect magnitude and consequences, M A Y 2 0 0 4 4 3 : 5 A N N A L S O F E M E R G E N C Y M E D I C I N E 6 0 7 and who have a first-time seizure, even if they are afebrile.17,24,26 In a retrospective cohort of 100 consec- utive HIV-positive patients, 14 cases of central nervous system infections were identified on lumbar puncture; however, clinical correlation was not provided.26 In a prospective cohort, Sempere et al17 reported on 8 HIV- positive patients found to have a central nervous system infection as a cause of their seizure, 2 of whom were afebrile with no meningeal signs. Patient Management Recommendations: What laboratory tests are indicated in the otherwise healthy adult patient with a new-onset seizure who has returned to a baseline normal neurologic status? Level A recommendations. None specified. Level B recommendations. 1. Determine a serum glucose and sodium level on patients with a first-time seizure with no comorbidities who have returned to their baseline. 2. Obtain a pregnancy test if a woman is of childbear- ing age. 3. Perform a lumbar puncture, after a head computed tomography (CT) scan, either in the ED or after admis- sion, on patients who are immunocompromised. Level C recommendations. None specified. II. Which new-onset seizure patients who have returned to a normal baseline require a head CT scan in the ED? The indications and timing of head CT scans in patients with a first-time seizure are controversial. Three percent to 41% of patients with a first-time seizure have abnormal head CT scan results.18,27 In 1 retrospective review, 22% of patients with a first-time seizure who had a normal neurologic examination had abnormal head CT scan results.27 In a study of 259 patients with suspected alcohol withdrawal seizure, 58% had abnormal CT scan results, of which 16 (6%) had a clinically significant lesion.28 Of the 16 patients with abnormal CT scan results, 7 were alert, had a nor- mal neurologic examination, and no signs of head trauma. Management changed in 10 patients as a result of the abnormal finding.28 The question remains whether identifying the abnor- mality in patients with nonfocal neurologic examina- tions who are evaluated in the ED has an effect on out- come. This, of course, depends on the outcome measure used; clearly, identifying a lesion may direct disposition and argues in favor of ED neuroimaging. For example, Tardy et al18 reported that 23% of patients with a new- onset seizure had an acute stroke or tumor demon- C L I N I C A L P O L I C Y unsuspected hypoglycemia in 247 patients. Sempere et al17 found 1 case of unsuspected hyponatremia in a patient with psychogenic water ingestion in a cohort of 98 patients that was prospectively studied. Tardy et al,18 in a retrospective review of patients with new- onset seizures, found 4 cases of hyponatremia, only 1 of which was not suspected on the basis of history and physical examination. There are no prospective studies in either children or adults at this time to support more in-depth routine lab- oratory testing such as serum calcium, magnesium, or phosphate levels of otherwise healthy patients evalu- ated in the ED.20 Of note, Turnbull et al15 did find 2 patients with hypocalcemia in 136 patients with new- onset seizure who were prospectively studied; 1 with cancer, and 1 with renal failure. Tardy et al18 reported 1 case of hypocalcemia, but clinical correlation was not provided. There are inconclusive data to direct appro- priate laboratory testing in patients with known medi- cal disorders such as renal insufficiency or malnutri- tion, and in patients taking diuretics. Identification of pregnancy in a patient with a first- time seizure is important because it may affect testing, disposition, and initiation of antiepileptic drug therapy. In 1 study of 59 patients with new-onset seizures in pregnancy, 14 patients were diagnosed with gestational epilepsy (ie, seizure disorder that occurs only during pregnancy).21 A drug of abuse screen is a consideration in patients with a first-time seizure; however, there are no prospec- tive studies that demonstrate a benefit of routine use.22-24 Dhuna et al,22 in a retrospective review, reported that 69 of 90 admitted patients with cocaine-related seizures had no prior seizure history. Pesola and Westfal24 re- ported 4 cases of cocaine-related seizures in 120 patients studied, although not all patients received the same tests nor was a direct correlation demonstrated. Lumbar puncture: There are no prospective studies that support performing a lumbar puncture as part of the diagnostic evaluation in the ED on patients who are alert, oriented, afebrile, and not immunocompromised. There are no adult studies, but in 1 retrospective pedi- atric case series of 503 cases of meningitis in children aged 2 months to 15 years, there was no case of occult bacterial meningitis manifesting solely as a simple seizure.25 Sempere et al17 reported that 5 of 9 patients with a first seizure who had a fever had a central ner- vous system infection. There is evidence to support performing a lumbar puncture in patients who are immunocompromised 6 0 8 A N N A L S O F E M E R G E N C Y M E D I C I N E 4 3 : 5 M A Y 2 0 0 4 C L I N I C A L P O L I C Y of patients with new-onset seizures in the ED, and most of this literature uses an abnormal laboratory or diag- nostic test as the outcome measure. There are no studies that have looked at the 24-hour morbidity or mortality of first-time seizure patients discharged from the ED. There are no prospective studies and only 1 retrospec- tive study that looked at the recurrence rate in the first 24 hours of admitted patients.18 The majority of studies that look at recurrence rates begin by excluding patients with acute symptomatic seizures, whereas the majority of studies that look at diagnostic testing group all types of seizure patients together. The focus of this question is patients who are alert with a normal neurologic ex- amination.30 The chance of a patient having a recurrent event after 1 unprovoked seizure varies depending on the patient’s age and the seizure’s underlying etiology.30-33 Seizure etiology, combined with electroencephalographic (EEG) findings, are the best predictors of recurrence. When no etiology is identified and the EEG findings are normal, the recurrence rate is 14% at 1 year and 2