Brief Research Report
Empiric Acyclovir Is Infrequently Initiated in the Emergency Department to Patients Ultimately Diagnosed With Encephalitis

https://doi.org/10.1016/j.annemergmed.2005.07.019Get rights and content

Study objective

We evaluate the frequency of empiric acyclovir administration to patients in the emergency department (ED) who are ultimately diagnosed with encephalitis.

Methods

We conducted an explicit retrospective medical record review of consecutive patients discharged with a final diagnosis of herpes simplex encephalitis or viral encephalitis not otherwise specified for the period 1993 to 2003. The frequency of ED administration of empiric acyclovir was measured for patients who met the inclusion criteria of fever, neuropsychiatric abnormality, and cerebrospinal fluid pleocytosis with a negative Gram's stain result in the ED.

Results

Of the 90 patients reviewed, 24 (27%) met the inclusion criteria of fever, neuropsychiatric abnormality, and cerebrospinal fluid pleocytosis with a negative Gram's stain result in the ED. Of these 24 patients, 7 (29%) received empiric acyclovir in the ED, 6 (86%) patients after cerebrospinal fluid results were available, with a median time to administration of 1.5 hours (95% confidence interval [CI] 0 to 3.1 hours). The remaining 17 (71%) patients did not receive acyclovir in the ED, with median times of 16 hours (95% CI 7.5 to 44 hours) before initiation of acyclovir in inpatient settings.

Conclusion

The majority of patients in our institution who were ultimately diagnosed with encephalitis did not receive empiric acyclovir in the ED, despite clinical presentations consistent with encephalitis.

Introduction

Encephalitis and meningitis describe inflammatory processes involving the brain (encephalitis) and the meninges (meningitis). The cardinal features of meningitis are headache, fever, and neck stiffness, whereas encephalitis is characterized by headache, fever, and neurologic or psychiatric alteration. Although the most common cause in both cases is infectious, the differentiation between meningitis and encephalitis in the emergency department (ED) is not always clear. Both are acute illnesses with evidence of central nervous system inflammation on analysis of cerebrospinal fluid. Although the 2 conditions may be differentiated with further testing, including magnetic resonance imaging (MRI), specialized cerebrospinal fluid analysis, and electroencephalography (EEG), these modalities are often unavailable in the time required to make decisions about empiric therapy in the ED. Moreover, the 2 conditions may overlap. In this case, the term “acute meningoencephalitis” is preferred because it broadens the differential diagnosis and resultant empiric therapies.

Although therapy for acute encephalitis is supportive in most cases, intravenous acyclovir has been shown to be highly effective in the treatment of herpes simplex encephalitis (HSE). Herpes simplex encephalitis is a hemorrhagic, necrotizing encephalitis caused by herpes simplex virus type 1. It is the most common cause of sporadic encephalitis, with an incidence of more than 2,000 cases annually in the United States.1 An additional 1,500 cases occur as disseminated herpes simplex virus type 2 disease in neonates, bringing the total burden of serious disease to more than 3,500 cases per year.2 Furthermore, newer highly sensitive assays are detecting subacute, atypical, and less severe cases of herpes simplex encephalitis that were previously undiagnosed.3

With treatment, mortality decreases dramatically from approximately 75% to approximately 25%.1, 4, 5 Significant neurologic impairment in survivors is also markedly decreased with treatment, with many patients reporting minor or no neurologic impairment at follow-up.4 Two groups of patients are known to have poorer outcomes: those presenting with severe symptoms and signs and those in whom treatment with acyclovir is delayed for several days.4, 6 For this reason, it is recommended that antiviral therapy be initiated early, before a delay in treatment adversely affects outcome in patients ultimately determined to have herpes simplex encephalitis. Despite multiple articles in the neurologic, pediatric, infectious disease, and psychiatric literature emphasizing the need for prompt empiric acyclovir therapy to patients with encephalitis of unclear cause, we were unable to find mention of such a practice in the emergency medicine literature (PubMed 1965 to 2004).4, 7, 8, 9, 10 In contrast, there are many articles in the emergency medicine literature advocating immediate empiric antibacterial therapy to patients with suspected bacterial meningitis.11, 12, 13

The goal of this study is to determine how frequently empiric therapy with acyclovir is initiated in the ED in patients who are ultimately diagnosed with encephalitis before discharge. We hypothesized that empiric acyclovir is underused in patients presenting to the ED despite findings consistent with encephalitis. We further hypothesized that omissions or delays of empiric antibacterial administration would be less common.

Section snippets

Study Design

We conducted an explicit retrospective medical record review of patients discharged from the Los Angeles County–University of Southern California Medical Center with a diagnosis of herpes simplex encephalitis or viral encephalitis not otherwise specified for the period July 1, 1993, to June 1, 2003. In this case, “discharge” referred to anyone discharged home or to another facility for extended care, as well as to the morgue in fatal cases. The study was approved in advance by the University of

Characteristics of Study Subjects

Ninety-nine (99) medical records were requested, of which 90 were available for review. Of the original 90 reviewed, 24 met the inclusion criteria. Fifty-six (82%) of the cases excluded were because of an absence of fever at or before the decision point. An inability to obtain a cerebrospinal fluid specimen from the ED before admission accounted for 8 excluded cases (12%), and 2 (3%) were excluded because of a normal initial cerebrospinal fluid examination result. Of the 24 included patients,

Limitations

We chose a rather conservative definition of encephalitis that substantially increased the likelihood of a central nervous system source of infection. We did this because we wanted to examine the practice of emergency physicians in situations in which empiric acyclovir was most likely to be considered. Empiric acyclovir may be a consideration in a larger group of patients, such as those that met only 2 of the 3 inclusion criteria used for this study. In fact, of the 66 patients reviewed who

Discussion

Our findings suggest that, although empiric treatment for bacterial pathogens occurred regularly in the ED, empiric treatment of encephalitis with acyclovir did not. Only 29% of patients ultimately diagnosed with encephalitis received acyclovir while in the ED, despite clinical presentations consistent with encephalitis. Moreover, the clinical diagnosis of acute encephalitis or acute meningoencephalitis was made in our ED in only 17% of these cases.

McGrath et al,8 in their study of 42 patients,

References (15)

There are more references available in the full text version of this article.

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Supervising editor: Gregory J. Moran, MD

Author contributions: PCB was solely responsible for the medical record reviewing, data analysis, and the literature search. PCB and SPS wrote and revised the manuscript. PCB takes responsibility for the paper as a whole.

Funding and support: The authors report this study did not receive any outside funding or support.

Presented at Society for Academic Emergency Medicine Western Regional Conference, Oakland, CA, April 2004, and American College of Emergency Physicians Scientific Assembly, San Francisco, CA, October 2004.

Reprints not available from the authors.

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