Abstract
This study assesses whether patients with status epilepticus are receiving first-line treatment consistent with current guidelines.
The American Epilepsy Society guideline recommends that paramedics use midazolam (10 mg intramuscularly), lorazepam (4 mg intravenously), or diazepam (6-10 mg intravenously) as first-line treatment for status epilepticus.1 Small cohort studies suggest that patients are frequently undertreated, but this has not been examined broadly across the United States.2
Methods
This study used data from ESO, a prehospital electronic health record used by approximately 5% of emergency medical service agencies in the United States. Agencies are responsible for prehospital care within defined geographic regions (county, city, or smaller). Agencies using ESO cover all 9 Census divisions in urban and rural settings. Data are recorded during evaluation, deidentified, and available in a public use research data set.3 We identified patients aged 18 years or older with a paramedic impression of status epilepticus treated with midazolam, lorazepam, or diazepam from January 1, 2019, to January 1, 2020. We excluded 164 encounters for cardiac arrest. The University of California, San Francisco, institutional review board approved the study with waiver of consent because patient data were deidentified.
We examined dose and route of the first benzodiazepine administered. We created 3 binary variables indicating whether the dose, the route, and the dose-route combination were consistent with guidelines. We then calculated the proportion of encounters in which treatment was consistent with expert guidelines for each variable, along with their corresponding 95% CIs (Box).1 To examine whether dosing variability reflected between-agency differences as opposed to within-agency paramedic and patient differences, we focused on patients given midazolam, who made up the majority. We estimated a mixed-effects model with an agency random intercept to calculate mean dose and determine the proportion of variance in dosing at the agency level. Statistical analyses were performed using Stata version 15.1 (StataCorp).
Box. Guideline Recommendations for Treatment of Adults With Status Epilepticusa.
First-line Therapy Options
Midazolam
Administer 10 mg intramuscularly as a single, 1-time dose.
Lorazepam
Administer 4 mg intravenously as a single 1-time dose that may be repeated once.
Diazepam
Administer 6 to 10 mg intravenously as a single 1-time dose that may be repeated once.
Results
Of the 9176 prehospital encounters we identified for status epilepticus across 743 agencies, 7665 patients (83.6%) were treated with midazolam, 1264 (13.8%) with lorazepam, and 245 (2.7%) with diazepam. Each agency had a median of 38 (IQR, 11-128) encounters. Patients were a mean age of 46 years (SD, 18 years), 4526 (49.3%) were women, and 2730 (29.8%) received a subsequent dose of benzodiazepine. There were 357 (3.9%; 95% CI, 3.5%-4.3%) encounters for which initial treatment was concordant with expert guidelines in the recommended dose and route. For midazolam, treatment was guideline concordant for 310 encounters (4.0%; 95% CI, 3.6%-4.5%), 2641 (34.5%; 95% CI, 33.4%-35.5%) were route concordant, and 541 (7.1%; 95% CI, 6.5%-7.7%) were dose concordant (92.9% <10 mg). For lorazepam, treatment was guideline concordant for 18 encounters (1.4%; 95% CI, 0.9%-2.2%), 928 (73.4%; 95% CI, 70.9%-75.8%) were route concordant, and 35 (2.8%; 95% CI, 2.0%-3.8%) were dose concordant (96.8% <4 mg). For diazepam, treatment was guideline concordant for 29 encounters (11.8%; 95% CI, 8.3%-16.5%), 191 (78.0%; 95% CI, 72.3%-82.7%) were route concordant, and 38 (15.5%; 95% CI, 11.5%-20.6%) were dose concordant (84.5% <6 mg) (Table).
Table. Prehospital Benzodiazepine Use for Status Epilepticus.
| Benzodiazepine type and dose | No. (%) of encounters | ||||
|---|---|---|---|---|---|
| All (N = 9174)a | Intramuscular route | Intranasal route | Intravenous route | Other routeb | |
| Midazolam, mg | |||||
| <5 | 3289 (42.9) | 648 (8.5) | 559 (7.3) | 2061 (26.9) | 21 (0.3) |
| 5 | 3809 (49.7) | 1677 (21.9) | 788 (10.3) | 1331 (17.4) | 13 (0.2) |
| >5 and <10 | 22 (0.3) | 6 (0.1) | 3 (<0.1) | 13 (0.2) | 0 |
| 10 | 541 (7.1) | 310 (4.0)c | 154 (2.0) | 72 (1.0) | 5 (0.1) |
| >10 | 4 (0.1) | 0 | 0 | 4 (0.1) | 0 |
| Total | 7665 | 2641 | 1504 | 3481 | 39 |
| Lorazepam, mg | |||||
| <2 | 331 (26.2) | 40 (3.2) | 18 (1.4) | 268 (21.2) | 5 (0.4) |
| 2 | 890 (70.4) | 188 (14.9) | 47 (3.7) | 640 (50.6) | 15 (1.2) |
| >2 and <4 | 2 (0.2) | 1 (0.1) | 0 | 1 (0.1) | 0 |
| 4 | 35 (2.8) | 13 (1.0) | 2 (0.2) | 18 (1.4)c | 2 (0.2) |
| >4 | 6 (0.5) | 3 (0.2) | 2 (0.2) | 1 (0.1) | 0 |
| Total | 1264 | 245 | 69 | 928 | 22 |
| Diazepam, mg | |||||
| <6 | 207 (84.5) | 18 (7.4) | 25 (10.2) | 162 (66.1) | 2 (0.8) |
| ≥6 and <10d | 38 (15.5) | 2 (0.8) | 2 (0.8) | 29 (11.8)c | 5 (2.0) |
| Total | 245 | 20 | 27 | 191 | 7 |
All percentages represent the proportion relative to the total number of administrations for a given benzodiazepine type.
Route was intraosseous or unspecified.
Indicates guideline-concordant benzodiazepine dose and route.
There were no patients who received a diazepam dose greater than 10 mg.
For midazolam, the mean dose was 4 mg (SD, 2 mg) across all agencies. Between-agency variability accounted for 47% of variance in dosing (intraclass coefficient, 0.47; 95% CI, 0.43-0.51).
Discussion
Prehospital status epilepticus treatment was rarely consistent with expert guidelines. The majority of patients received benzodiazepine doses lower than recommended, and many were treated via a route not recommended. For midazolam, the most common treatment, guidelines recommend intramuscular administration, bypassing the need for intravenous access.1 However, only 34.5% were treated intramuscularly, potentially resulting in treatment delays and less effective seizure cessation.4
The high proportion of variance attributed to the treating agency suggests that benzodiazepine dose is not arbitrarily determined by paramedics responding to particular clinical situations; rather, factors such as agency policy or treatment algorithms, which are rarely guideline concordant, influence treatment decisions. Efforts to modify these policies could improve outcomes.5
This study has several limitations. The data set could not confirm that benzodiazepine treatment was for status epilepticus; however, specificity for the target population was increased by restricting the cohort to those diagnosed with status epilepticus who had received a benzodiazepine.6 Excluding patients without benzodiazepine treatment underestimated the degree of undertreatment. Also, ESO may not be nationally representative; thus, generalizability is unknown because studies comparing ESO patients with the broader prehospital population are lacking.
This study suggests that reasons for the variation in care between emergency medical service agencies should be examined to improve the real-world prehospital care of patients with status epilepticus.
Section Editors: Jody W. Zylke, MD, Deputy Editor; Kristin Walter, MD, Associate Editor.
Footnotes
Level A evidence from the American Epilepsy Society guidelines for adults weighing 40 kg or more.1
References
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