**1. Introduction**

Status epilepticus (SE) is broadly defined as a prolonged seizure and remains a common neurological emergency with an overall mortality approaching 20% [1]. Generalized convulsive SE is considered as the worst type of SE and may lead to neurological injury and risk of sequelae [2]. To an early seizure cessation, treatments could be aggressive and contribute to worsening consciousness, such as benzodiazepine or sedatives [3]. In addition, extra-neurological complications are frequent, especially respiratory infection, and may impact the prognosis [4,5]. Aspiration is common in patients with impaired consciousness and is probably more frequent in case of persistent convulsions [6]. Early identification of bacterial aspiration pneumonia (BAP) is needed to avoid useless treatments. In addition, BAP has been associated with acute respiratory distress syndrome and requires an early antibiotic therapy [6]. However, in the absence of a microbiological sample, it is impossible to differentiate BAP from pneumonitis. A previous study in patients with coma requiring MV did not find a relevant difference between patients, highlighting the need for early bacterial identification [7]. To our knowledge, no study has investigated the incidence of BAP and factors associated with the occurrence of BAP in patients with generalized convulsive SE requiring mechanical ventilation (MV).

**Citation:** Tortuyaux, R.; Wallet, F.; Derambure, P.; Nseir, S. Bacterial Aspiration Pneumonia in Generalized Convulsive Status Epilepticus: Incidence, Associated Factors and Outcome. *J. Clin. Med.* **2022**, *11*, 6673. https://doi.org/ 10.3390/jcm11226673

Academic Editors: Tamas Szakmany, Luca Brazzi and Giorgia Montrucchio

Received: 6 September 2022 Accepted: 9 November 2022 Published: 10 November 2022

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**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

We hypothesized that the incidence of aspiration syndrome and BAP would be high in a population at risk, as generalized convulsive SE patients are. Therefore, we conducted this retrospective study to determine the incidence of aspiration syndrome and BAP in order to identify factors associated with the occurrence of BAP and to study the impact of aspiration syndrome and BAP on MV duration, intensive care unit (ICU) length of stay, and 3-month outcomes.

### **2. Materials and Methods**

#### *2.1. Patients*

From January 2013 to February 2022, we retrospectively screened all patients older than 18 years who were admitted with a diagnosis of status epilepticus to the medical ICU of Lille University Hospital and requiring mechanical ventilation. Patients were screened to confirm the diagnosis of SE—meaning no other possible diagnosis could be considered—and the absence of exclusion criteria.

### *2.2. Inclusion and Exclusion Criteria*

The selected patients had generalized convulsive SE, defined as 5 or more minutes of continuous clinical seizure activity or two seizures without a return to baseline in the interval [2], and had received MV.

Exclusion criteria included post-anoxic SE due to the heterogeneity of their management [8].

According to French law, this database was declared at the institutional data protection board (DEC19-432, DEC20-354), and the study was approved by our local ethics committee (CE SRLF 21-38). This research has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. The authors have full access to all data and have the right to publish all data, separate and apart from the guidance of any sponsor.

#### *2.3. Data Collection*

For each patient, demographic characteristics and medical history were recorded. Severity at admission was defined using the Simplified Acute Physiology Score II (SAPS II) with exclusion of age studied separately: higher scores indicated greater severity of illness [9]. Clinical characteristics of SE were reported. Refractory status epilepticus was declared if the initial treatment failure included at least one benzodiazepine (i.e., clonazepam) and one intravenous long-duration antiepileptic drug (i.e., fos/phenytoin, levetiracetam, valproic acid, or phenobarbital) prior to intubation [10]. The etiology of SE was defined according to the international league against epilepsy (ILAE) classification: acute (e.g., stroke, intoxication, encephalitis), remote (e.g., poststroke, posttraumatic), progressive (e.g., brain tumor, dementias), and unknown [2]. Psychogenic non-epileptic seizure diagnosis was based on a paroxysmal event without ictal epileptiform EEG changes [11]. Due to a difficult diagnosis at ICU admission and a history of epilepsy frequently associated, these patients were not excluded. We also defined groups of etiology as vascular (acute SE related to ischemic or hemorrhagic stroke, cerebral venous thrombosis, and posterior cerebral encephalopathy), toxic (acute SE related to metabolic disturbance, alcohol, drug intoxication, or withdrawal), and brain tumor (progressive SE related to brain tumor).

Clinical, biological, radiological, and microbiological diagnostic criteria for BAP, as well as clinical outcomes (duration of MV, ICU length of stay, ICU mortality, 3-month mortality, and functional outcome), were collected. Functional outcome was evaluated by modified Rankin Scale (mRS) [12] during a face-to-face visit or by a telephone interview with the patient, the family, or the general practitioner. A poor functional outcome was defined as mRS score > 1 and was different from the pre-SE mRS score.

#### *2.4. Definitions*

#### 2.4.1. Aspiration Syndrome

The diagnosis of aspiration syndrome was based on the presence of at least two of the following criteria during the first 2 days after initiation of MV: body temperature of more than 38.5 ◦C or less than 35.5 ◦C; leucocyte count greater than 12,000 cells per μL or less than 4000 cells per μL, and purulent tracheal secretions; and the presence of new or progressive infiltrates on the chest X-ray. Chest X-rays were reviewed by at least two attending physicians. In the case of disagreement, a third physician was asked to interpret the chest radiograph. Of note, we collected macroaspiration, defined by history of vomiting before or during intubation, which was not required to define aspiration syndrome.

2.4.2. Bacterial Aspiration Pneumonia, Pneumonitis, and Ventilator-Associated Pneumonia All aspiration syndromes were classified as [7]


Ventilator-associated pneumonia (VAP) had the same diagnostic criteria as BAP but occurred at least 2 days after starting MV.

2.4.3. Measurements of Serum Levels of C-Reactive Protein (CRP), Procalcitonin (PCT), and Albumin during First 24 h after Admission

CRP was measured with the immunoturbidimetric method and a detection limit of 0.3 mg/L. PCT concentrations were determined using an electrochemiluminescence immunoassay with a detection limit of 0.02 ng/mL. Albumin concentrations were measured with the immunoturbidimetric method. All measurements were performed with Cobas 8000 modular analyzer series (Roche Diagnostics, Rotkreuz, Switzerland).

#### *2.5. Outcomes*

The primary outcome was the incidence of bacterial aspiration pneumonia, occurring during the first 2 days after starting invasive MV, among patients admitted to ICU with generalized convulsive SE requiring MV. The secondary outcomes were the incidence of aspiration syndrome in order to identify factors associated with BAP, as well as MV duration, ICU length of stay, functional outcome, and death at 3 months.
