FormalPara Key Summary Points

Why carry out this study?

Prolonged seizures are emergency cases, but currently no data is available on the burden of epileptic and pediatric febrile seizures (PFS) occurring in the prehospital emergency medical services (EMS) setting.

A total of 171,275 epileptic seizures and 28,500 PFS occur in the prehospital EMS setting, which are associated with a high hospital admission rate of up to 81% and impact society with costs of 56.6 million EUR in 2019.

What was learned from the study?

The results of this study indicate that a high number of seizure cases occur in the prehospital setting, which are associated with a high patient and economic burden.

Therefore, seizure action plans for the prehospital EMS setting are needed.

Introduction

Epilepsy is a neurological disorder characterized by recurring seizures and affects 46 million people worldwide [1, 2]. When seizures are not well controlled, patients often need emergency treatment in addition to their antiseizure medication (ASM). Seizures encompass self-resolving brief seizures, prolonged seizures (PS), seizure clusters (SC), and status epilepticus (SE) [3], and account for 1–3% of all emergency department visits [4,5,6].

Treatment and care of epilepsy are associated with high costs. Treatment of patients with epilepsy in an outpatient unit in Germany led to total annual costs of 10,000 EUR per patient [7]. A second study identified mean costs of 5551 EUR per 3 months per patient, including direct costs of 1861 EUR and indirect costs of 3690 EUR [8].

About one-third of patients with epilepsy have drug-resistant epilepsy, despite using multiple ASMs [9, 10]. Patients with refractory epilepsy often experience emergencies like PS, SC, or SE, which are associated with increased morbidity and mortality [11, 12]. Complications of SE are not restricted to neurological sequelae and can result in neurocardiogenic, pulmonary, musculoskeletal, or renal injury and death [13].

Febrile seizures are the seizures most often observed in humans, are one of the most common neurological disorders in children, and a main reason for pediatric emergencies. In the first 2 years of life, febrile seizures occur in 2–5% of all children in Western countries [14, 15]. Furthermore, 8% of febrile seizures lasted longer than 15 min and prolonged febrile seizures represent 25% of all SE episodes in infancy [16].

Seizures are a common reason to call an ambulance and often epilepsy is the underlying reason [17]. German guidelines recommend that emergency medical services (EMS) are called if an epileptic seizure has a duration longer than 5 min [17]. Often, EMS arrive during the postictal phase, but in the case of PS, SC, or unconsciousness, the patient needs transportation to hospital. Most pediatric febrile seizures (PFS) are of short duration and do not require medical intervention. However, seizures lasting longer than 5–10 min should be interrupted with medication [18].

Prehospital EMS personnel use standardized processes to treat patients experiencing seizures, with benzodiazepines often used as first-line treatment for PS or febrile seizures [17, 19]. EMS are regulated by the federal states in Germany. In Hesse, EMS personnel should arrive at the scene of a medical event within 10 min after the emergency call [20].

Prehospital EMS plays a major role in handling patients with PS. Hospitalization is the main driver of direct costs in patients with epilepsy, but little is known about the prehospital situation for patients with seizures. Therefore, this study had the following objectives:

  1. 1.

    To identify the number of patients with seizures treated by prehospital EMS staff and percentage of patients transported to hospitals

  2. 2.

    To describe the acute medical status of patients with seizures and number of cases with prehospital EMS physician involvement

  3. 3.

    To analyze data on time passed from emergency call to arrival at hospital for patients with seizures

  4. 4.

    To calculate costs related to transportation of patients to hospital

Methods

Study Design and Data Sources

This was a population-based, cross-sectional analysis of prehospital EMS data on suspected epilepsy-related seizure (ES) and PFS cases, recorded by IVENA system-generated log-files for seizure emergency events in the federal state of Hesse, Germany, in 2019 [21]. Log-file information from EMS coordination centers of Hesse for research has also been used as per recent publications [22, 23].

In the German federal state of Hesse, using the IVENA system, prehospital EMS staff can electronically transmit a suspected diagnosis from patient location via prehospital coordination centers to hospitals. For transmission, a patient assignment code (PAC) is generated for each case and forwarded to the coordination center, which afterwards registers the patient at the hospital. The PAC consists of a three-number response indication number (RIN) representing the suspected diagnosis, age of patient (1–99 years), and hospital admission priority (0 = no transportation; 1 = patient requires immediate intervention; 2 = inpatient hospital stay [≥ 24 h in hospital]; 3 = outpatient hospital treatment [< 24 h in hospital]).

For the suspected diagnosis, EMS staff select an RIN from a predefined list of medical disorders. Then, prehospital EMS staff submit the acute medical condition of patients using a six-digit response code (RC). The digits represent the following systems and symptoms: 1 = consciousness; 2 = breathing; 3 = circulatory system; 4 = injuries; 5 = neurology; and 6 = pain. Medical status of each system or symptom is rated using a 5-level scale ranging from 1 = indicating unnoticeable/none; through 5 = most severe function impairment. Additionally, coordination centers and prehospital EMS staff document operation times of prehospital EMS staff (operating time signifies time starting from emergency call, driving to patient’s site, handling patient at the site, driving patient to hospital, and handing them over to hospital) [24, 25].

Classification of Study Population

RIN codes included in the study were those related to seizures: RIN411 (seizure with known seizure disorder [SEPI]); RIN412 (first seizure [1stS]); RIN513 (PFS); or RIN514 (pediatric epilepsy [PEPI]). Data for ES; RIN411, 412, and 514 were obtained from the coordination centers of nine counties or cities in the federal state of Hesse, covering a region with 3.05 million inhabitants, and for PFS from coordination centers of three counties or cities, covering 0.74 million people in Hesse, respectively.

Coordination centers, as owners of the prehospital EMS data, were informed about the study’s purpose and provided data voluntarily. This study was conducted in accordance with national data protection regulations and the Declaration of Helsinki. As a result of the nature of the data, it was not possible to obtain patient consent for usage of the data in this analysis. The analysis was based on emergency data and the emergency situation did not allow consent to be requested. The data was stored with minimum personal information (age and county) and no names were available to identify the patients to obtain retrospective patient consent. In addition, patient consent for retrospective analysis of anonymized, secondary data is not mandatory. Finally, a review board of the HSD Hochschule Döpfer Cologne, Germany, reviewed the protocol and decided that patient consent based on the available data was not necessary. The conduct of this study using public data for neurologic disorders was also approved by the ethical commission of the Faculty of Medicine of Goethe University Frankfurt (application reference 313/16).

Data Analysis

Data for demographic and clinical characteristics of seizure cases were analyzed using descriptive statistics. For continuous variables, mean and standard deviation [SD] were calculated. Categorical variables were summarized as percentage. Analyses were performed using RIN code and/or by combining ES (SEPI, 1stS, PEPI), as current German treatment guidelines differentiate between ES and PFS [17, 19, 26].

Incidences of seizure cases were calculated for ES and each RIN, respectively, based on population of included counties or cities taken from the Hessian State Office of Statistics [27]. Results were reported by age group and expressed in units of cases per 100,000 population. Results were age-specifically extrapolated to the 2019 German population published by the federal Statistics Office of Germany [28] to estimate national number of ES (RIN411, 412, 514) and PFS cases (RIN513). For extrapolation, age-specific extrapolation factors were calculated by dividing the population in Germany by population size of the areas included in the analysis. Age-specific extrapolation factors were then multiplied by number of cases in respective age groups. Finally, mean (SD) time prehospital EMS staff (physician, nonphysician) needed from time they received the emergency call until arrival of staff at the patient’s location, from emergency call until leaving the patient’s location for transportation to the hospital, from emergency call until arrival at hospital, as well as time spent at the patient’s location, and transportation time from the location to the hospital were calculated. In addition, age-adjusted number of seizure cases per 100,000 population were calculated using the New European Standard Population [29].

Total costs of seizure-related emergency missions were calculated using proportions of seizure-related emergency cases (ES, PFS) identified in this study for all emergency cases in the analyzed area. The proportions were then multiplied by the total costs of all prehospital emergency missions in Germany, obtained from the Federal Ministry of Health [30]. Analyses were performed using Excel and JASP software [31].

Results

Characteristics of Cases and Hospital Admission Priorities

In total, 6534 suspected cases (SEPI, 4122; 1stS, 1924; PFS, 270; PEPI, 218) were identified and included in the analysis (Table 1). Median age of seizure cases was 42.5 years for SEPI; 51.0 years for 1stS; 1.0 year for PFS; and 4.0 years for PEPI. For PFS and PEPI, most cases were aged 0–3 years (88.2% and 49.5%, respectively) and 4–11 years (10.4% and 39.5%, respectively). Most SEPI cases were aged 18–44 years (45.3%) and 45–64 years (27.0%), and 1stS cases were predominantly coded for patients aged 18–44 years (32.5%) and those aged over 65 years (32.0%). Prehospital EMS physicians were involved in 39.7% of suspected SEPI, 46.0% of 1stS, 49.1% of PEPI, and 54.4% of PFS cases.

Table 1 Characteristics of included cases
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Incidence of Seizure Cases and Extrapolation to Germany

Highest age-specific incidence of suspected seizure cases per 100,000 inhabitants was seen for (a) SEPI in those aged 18–44 years (175.4 [95% confidence interval [CI] 167.5–183.5]); (b) 1stS in those aged over 65 years (103.6 [95% CI 95.6–112.1]); (c) PFS in those aged 0–3 years (787.8 [95% CI 691.3–894.1]); and (d) PEPI in those aged 0–3 years (86.0 [95% CI 70.5–103.8]) (Table 2 and Fig. 1).

Table 2 Incidence per 100,000 (95% CI) of suspected seizure cases by RIN and age-specific extrapolation to German population
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Fig. 1
figure 1

Incidence of seizure case by response indication number per 100,000 inhabitants. There were no cases 45+ years of age for PFS and PEPI. 1stS first seizure (RIN412), ES epilepsy-related seizures (combined RINs 411, 412, 514), PFS pediatric febrile seizure (RIN513), PEPI pediatric epilepsy (RIN514), RIN response indication number, SEPI seizure with known seizure disorder (RIN411)

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Extrapolated to the German population in 2019, a total of 171,275 suspected ES cases (SEPI, 1stS, PEPI) have occurred in the prehospital EMS setting in 2019 in Germany (Table 2). Most cases were in the 18–44 years age group (63,306 cases), 45–64 years (45,032 cases), and in those over 65 years of age (43,055 cases). For PFS, a total of 28,500 suspected cases in the prehospital EMS setting were extrapolated to have occurred in Germany (Table 2), with most of the cases in the 0–3 years age group (25,049 cases), followed by those aged 4–11 years (3019 cases) and aged 12–17 years (222 cases).

Medical Condition of Cases

On the basis of prehospital EMS coding, the majority of suspected seizure cases were transported to hospital and admitted for inpatient stay of ≥ 24 h (total 70.7–80.9%) (Fig. 2). An “immediate intervention needed” at hospital was coded for 15.8% of 1stS, 13.8% of PEPI, 6.6% of SEPI, and 4.1% of PFS cases. No transport by prehospital EMS staff was needed for 18.7% of cases with SEPI, 12.3% with PFS, 6.0% with PEPI, and 2.3% with 1stS.

Fig. 2
figure 2

a Percentage of suspected seizure cases not transported to hospital by the emergency medical services (EMS) staff and b hospital admission priority of suspected seizure cases based on coding of prehospital EMS staff. 1stS first seizure (RIN412), PFS pediatric febrile seizure (RIN513), PEPI pediatric epilepsy (RIN514), RIN response indication number, SEPI seizure with known seizure disorder (RIN411)

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Most patients (≥ 80%) with any of the investigated seizure codes were in an inconspicuous or slightly impaired status for consciousness, breathing, circulatory system, injury, and pain status (Table S1). Regarding neurological impairment, 34.5% of those with an ES indicated an acute neurological dysfunction, whereas only 18.7% with PFS were coded as having an acute neurological dysfunction. No fatal cases during transportation were identified in the analysis.

Operating Times of Prehospital EMS Staff

Mean time that prehospital EMS staff needed from emergency call to arrival at the patient’s location for ES cases (SEPI, 1stS, PEPI) was 8:24 min:s (SD 7:24 min:s; n = 5004) for all cases with time stamp, irrespective of transport. For ES cases transported to hospital, average time from emergency call until leaving for hospital was 33:06 min:s (SD 12:30; n = 3518) and 45:34 min:s (SD 57:29; n = 3452) until arrival at hospital. Thus, time at the patient’s location for transported ES cases was 25:22 min:s (SD 11:31; n = 3502); whereas transportation time from the patient’s location to hospital was on average 12:38 min:s (SD 55:59; n = 3418). Time spent at the patient’s location was comparable for SEPI (25:17 [SD 11:53] min:s; n = 2145), 1stS (25:48 [SD 10:53] min:s; n = 1217), and PEPI cases (22:59 [SD 10:56] min:s; n = 140).

For PFS cases, average time needed by prehospital EMS staff (a) from emergency call until arrival at the patient’s location was 10:58 min:s (SD 27:39; n = 321) for all cases with time stamp, regardless of transport to hospital; (b) from emergency call until leaving for hospital was 30:20 min:s (SD 28:40; n = 299); and (c) from emergency call until arrival at hospital was 46:58 min:s (SD 16:50; n = 207) for transported cases. Average time needed at the patient’s location for transported PFS cases was 19:22 min:s (SD 9:44; n = 294) and transportation from the patient’s location to hospital was 18:36 min:s (SD 12:03; n = 207).

Costs of Seizure-Related EMS Missions

Based on total number of EMS cases (any indication 482,940 cases) in the eight included counties, the proportion of ES cases (SEPI, 1stS, PEPI) ranged from 1.04% to 1.47% (mean 1.20%). In the three counties or cities that provided data for PFS cases, the total number of EMS operations with any indication was 132,676, and the proportion of PFS cases ranged from 0.17% to 0.23% (mean 0.20%). Based on these proportions and total annual costs for EMS in Germany in 2019 of 4.043 billion EUR [30], total costs for ES cases in Germany were 48.5 million EUR and for PFS were 8.1 million EUR.

Discussion

This retrospective analysis of prehospital EMS data indicates that 171,275 ES cases (SEPI, 1stS, PEPI) and 28,500 PFS cases were handled by prehospital EMS staff in Germany in 2019. Depending on the type of seizure, 71% (SEPI) to 81% (1stS) of these patients were admitted to hospital for inpatient stay and 4% (PFS) to 16% (1stS) needed immediate hospital intervention. Nevertheless, persons with SEPI and children with PFS were less often transported to hospital than patients with 1stS or PEPI (Fig. 2a).

Although prehospital EMS data only relate to suspected seizure cases, the total number of 171,275 extrapolated ES cases, of which 77% (SEPI) to 97% (1stS) were admitted to hospital for inpatient stay or immediate intervention, was comparable with the confirmed diagnosis of 155,746 seizures/epilepsy cases (G40.x[epilepsy], G41.x[status epilepticus]) in German hospitals in 2019 [32]. This is in line with a recent study showing that numbers of suspected femoral neck fracture cases based on prehospital EMS data were comparable with hospital diagnosis of femoral neck fractures [23]. Therefore, prehospital EMS data represent a valid data source for epidemiological studies on seizure disorders.

EMS data indicate that in 40–54% (SEPI and PFS, respectively) of seizure-related emergency cases, an EMS physician participated in the mission. An analysis on prehospital EMS data for any indication showed that during 2013 through 2017, EMS physicians participated in 24–28% of all prehospital EMS missions in the federal state of Hesse, Germany [33]. On the basis of these data, we conclude that seizure cases are considered more severe than other indications in the prehospital EMS setting. Nevertheless, none of the analyzed febrile and ES cases received a coding for being in respiratory arrest, without pulse and comatose grade IV, which can be considered a fatal case (Supplementary Table S1). This is supported by hospital diagnosis data showing that only 1.8% of patients with seizure/epilepsy die in hospital [32, 34]. Absence of fatally coded seizure cases in prehospital EMS data can also be explained by the fact that patients who die before arrival of prehospital EMS personnel do not receive an RIN for seizure and were not included into the analysis. Furthermore, overall risk of death in epilepsy is low, although patients with epilepsy have an increased risk for fatal outcomes compared with the general population. From German hospital data, a high proportion of fatal outcomes is observable for SE with almost 10% in 2019 [32], which is in line with other recent publications [34,35,36]. Absence of fatal cases during transportation is explainable with the treatment algorithm for refractory SE after treatment with benzodiazepines. Usually, in cases where a convulsive SE is not terminated by initial treatments, patients are intubated, receive general anesthesia, and are transported to hospital [17].

A previous study of prehospital EMS missions indicated that 10% of all missions are related to neurological disorders [37]. In our study, the proportion of febrile and ES cases was 0.2% and 1.2% of all cases in the analyzed regions, respectively. Thus, the proportion of seizures cases can be considered lower compared with a study from Munich, Germany, showing that 4.9% of EMS missions were seizures [38].

Age distribution of suspected seizure cases within each RIN code was as expected, because epilepsy affects all ages and has a bimodal distribution with peaks at a young and at an older age. In addition, we assume that the much higher number of suspected seizure cases in adults compared to children is a result of an aging German population with 83.6% of German being adults in 2019 [39]. The age distribution of 1stS can be explained by the increasing risk of brain diseases with epileptogenic potential with increasing age and may also be provoked by acute or remote symptomatic factors, such as metabolic derangements and drug toxicity. This group of suspected cases also had the highest percentage with acute neurologic dysfunction.

Finally, we found that annual health care costs associated with seizure-related emergencies was 56.6 million EUR in Germany in 2019. Therefore, EMS for patients with seizures is associated with significant costs for the health care system. To reduce the need for some seizure-related emergency calls, it is important that patients and caregivers take appropriate actions during an acute seizure emergency. Seizure action plans can reinforce timely and appropriate care in such situations, as they provide clear instructions on appropriate use of an individual’s rescue ASM and when to call EMS [40]. In any event, they can help EMS staff with emergency seizure management. Therefore, individualized seizure action plans may reduce unnecessary health care utilization as well as direct and indirect costs.

Even though the analysis is solely based on German data, countries with comparable population structures in terms of age distribution like Germany might benefit from the results. The reported age-specific suspected seizure incidence rates can be used to extrapolate number of seizure cases and even costs in the respective countries. In addition, the relatively high number of cases which were not transported to hospital and those being outpatient treated (hospital stay < 24 h) can be considered unnecessary EMS transports and thus costs. This likely applies to other countries with comparable EMS and/or population structures and the presented results might help to develop and implement new treatment pathways, and paradigms as well as seizure action paths.

Limitations

This study has several limitations. RIN and RC data only provide suspected diagnoses, and we have no information on whether these diagnoses were confirmed in hospital. Prehospital EMS data used for this study did not provide any information on sex of patients. Also, the study could only use information on a case-by-case basis; therefore, the exact number of patients with seizure-related emergencies is not available. Furthermore, data for patients who may have died because of seizures or SE before arrival of the EMS were not included under codes studied here, so we have no data on seizure-related death.

Conclusions

This study presents analysis of log-file information from EMS coordination centers of the German federal state of Hesse. Evidence from this health care area is scant, and so this study provides new data in the field of seizure-related emergencies in Germany from a different perspective. Our analysis identified 6534 seizure-related emergency cases, which were extrapolated to 171,275 epilepsy-related and 28,500 PFS cases in Germany. Depending on RIN, in 40% (SEPI) to 54% (PFS) of these cases, a prehospital EMS physician was involved. Additionally, 71% (SEPI) to 81% (1stS) of cases were admitted to hospital for inpatient stay and 4% (PFS) to 16% (1stS) needed immediate intervention. Nevertheless, cases with known seizure disorder and children with febrile seizures were less often transported, indicating less severe conditions. Costs for prehospital EMS for seizure-related cases in Germany were 56.6 million EUR in 2019. Finally, comparison of prehospital EMS data with hospital data provided comparable numbers and thus we concluded that prehospital EMS data provided a useful data source for analysis of seizure-related emergencies.