Risk factors for malnutrition in refractory convulsive status epilepticus

Purpose: To study the risk factors and prognosis of malnutrition in patients with refractory convulsive status epilepticus. Methods: A total of 73 patients with refractory convulsive epileptic status in West China Hospital from January 2017 to May 2019 were collected. All patients met the 2016 International Anti-epileptic Alliance diagnostic criteria for refractory convulsive status epilepticus. A logistic regression model was used to evaluate the risk factors of malnutrition in refractory convulsive status epilepticus. Results: Of the 73 patients with refractory convulsive status epilepticus, 33 (45.21%) suffered from malnutrition during hospitalization, and hospitalization days (OR =1.251; 95% CI: 1.067-1.384; P =0.007), nasal feeding (OR =22.623; 95% CI: 1.091-286.899; P =0.013), and malnutrition on admission (OR =30.760; 95% CI: 1.064-89.797; P =0.046) were risk factors for malnutrition in patients with refractory convulsive status epilepticus. Conclusion: Malnutrition is a common complication during hospitalization in patients with refractory convulsive status epilepticus. Hospitalization days, nasal feeding, and malnutrition at admission are risk factors for malnutrition in patients with refractory convulsive status epilepticus. Further longitudinal studies are needed to identify the relationship between refractory convulsive status epilepticus and adverse outcomes.

resulting in physical and mental functional defects [9]. A large number of studies show that the nutritional status of patients will deteriorate continuously during hospitalization. Despite receiving nutritional support, various nutritional parameters are still on a downward trend, and this decrease in nutrition may be related to the poor prognosis of patients [9][10][11][12][13]. The risk factors of malnutrition in patients with RCSE during hospitalization have not yet been reported. The nutritional status of the patients is evaluated at the time of admission; it may be important for treatment to discover the risk of malnutrition as soon as possible. Therefore, this study aims to explore the risk factors and prognosis of malnutrition in patients with RCSE during hospitalization to develop strategies and purposeful early interventions and to improve the prognosis.

Research Object
This study included 73 cases of RCSE patients from the NICU, Neurology and other departments in West China Hospital from January 2017 to May 2019. The diagnosis of all patients met the latest diagnostic criteria of the International Anti-epilepsy Alliance (ILAE) [1][2]. According to the standards of the Helsinki Declaration, this study strictly abided by the principle of patient's willingness and knowledge. If the patient did not have conscious autonomy, the willingness and knowledge of his immediate family members were obtained. Exclusion criteria: 1. Age 18 years old; 2. No informed consent; 3. Primary psychosis or serious anxiety and depression disorder; 4, Liver cirrhosis or renal insufficiency and a need to limit protein intake; and 5. Hospitalization days fewer than 2 weeks.

Research methods
According to the inclusion and exclusion criteria, the general patient data (including demographic information, hospitalization time and expenses) included serum albumin detected within 36 hours of admission and at the time of discharge, collected retrospectively; height and weight; body mass index (BMI); clinical characteristics at admission (including whether there is consciousness disorder, dysphagia, diet reduction, stress ulcer and nutritional status, etc.); and dysphagia status, i.e., the ability of the patient to drink 30 ml of water in the sitting position. Results Classification: Grade 1 is smooth swallowing, no choking coughs or pauses. Grade 2 consists of swallowing twice without choking coughs or pauses or prolonged to more than 5 s; Level 3 indicates being capable of swallowing once but with a choking cough. Grade 4 is divided into more than two swallows but still with a choking cough; Grade 5 is frequent choking cough, and a full swallow is difficult [22][23].
Dysphagia is considered to exist if the symptoms of dysphagia are present and if the drinking water test is ≥3 grade or there is consciousness disorder [22]. The Glasgow score is used for the evaluation of consciousness level.
Nutritional status assessment: nutritional status assessments were carried out by special personnel 24 hours after admission and discharge, including measurements of body weight and height and calculation of body weight index (BMI) BMI = body weight (kg)/height (m 2 )]. The indexes of serum albumin, serum transferrin and serum prealbumin were detected. The Mini Nutrition Assessment Form (MNA) was completed [16]. Diagnostic criteria for malnutrition: meet ≥1 of the following 4 criteria: (1) BMI < 18.5 kg/m 2 ; (2) serum albumin concentration < 35 g/l; (3) weight loss at discharge was greater than 6% of the weight at admission; Mna < 17. An MNA score of 17-23.5 indicates the risk of malnutrition [9][10].

Data statistics and analysis
An SPSS 22.0 logistic regression model was mainly used for the statistical data. Fisher's exact test was used for counting data. Measurement data are expressed as the means and standard deviations (x s). The measurement data were tested by t-test. Multivariate logistic regression analysis was carried out on the factors with statistical significance in single-factor analysis. P < 0.05 was considered to have statistical significance.

Results
A total of 33 out of 73 patients with RCSE were malnourished. There was no significant difference between the demographics of 33 patients with malnutrition (16 males, age 39 ± 21 years) and 40 patients without malnutrition (28 males, age 40 ± 20 years).
Patients suffering from malnutrition have longer hospitalization time, more hospitalization expenses and lower body weight and albumin when discharged from the hospital than patients without malnutrition.
There were 7 patients (9.59%) with malnutrition at the time of admission, including 4 patients with BMI < 18.5 kg/m 2 and 3 patients with albumin < 35 g/l. There were 33 malnourished patients (45.21%) at the time of discharge, including 15 patients with weight loss greater than 6% of their body weight at the time of admission, 18 patients with BMI < 18.5 kg/m 2 , 19 patients with albumin < 35 g/l, 33 patients with MNA < 17 points, and 11 patients with MNA 17-23.5 points. The incidence of malnutrition at discharge was significantly higher than that at admission (all p < 0.05). The ratio of serum albumin < 35 g/l at discharge was significantly higher than that at admission (all p < 0.01). Multivariate logistic regression analysis showed that patients with malnutrition or risk of malnutrition had worse prognosis than patients with good nutrition (p < 0.05).

Discussion
During hospitalization, although RCSE patients received nutritional support, various nutritional parameters still showed downward trends. The malnutrition rates were 9.59% at the time of admission and 45.21% at the time of discharge in this study. At present, there is no universally accepted definition of malnutrition, and there is no gold standard for nutrition assessment. Previous studies have found that serum albumin is the most significant indicator to reflect nutritional status and is often used to assess nutritional status, but the half-life is relatively long, approximately 14-20 days [14][15]. In addition, the use of a variety of nutrition assessment tools, such as MNA, may help to make a broad estimate of malnutrition [16]. There are many reasons for malnutrition during hospitalization, which are related to insufficient intake, gastrointestinal tract malabsorption and increased energy consumption.
In RCSE patients who fast due to consciousness disorder, gastrointestinal hemodynamics is affected due to lack of food stimulation, and gastrointestinal digestion and absorption function weaken or even disappear; thus, malnutrition occurs due to poor nutrient absorption [9,17]. When gastrointestinal dynamics are weakened, it can lead to an increase in gastrointestinal pressure, coupled with damage to the gastrointestinal mucosal structure caused by ischemia. A large amount of bacteria and toxins in gastrointestinal tract can enter the blood, causing systemic infection and poisoning symptoms, aggravating the body's energy consumption and leading to malnutrition [17]. In this study, the level of consciousness in the malnutrition group decreased more obviously after admission; the functional status of daily activities was lower; there were more gastrointestinal complications, such as pulmonary infection, heart failure, and electrolyte disturbance; and gastrointestinal function was poor.
This study shows that malnutrition at admission, nasal feeding and hospitalization days are risk factors for malnutrition during hospitalization for patients with RCSE. Malnutrition on admission is the basis of malnutrition, which indicates that pneumonia, other infections, gastrointestinal hemorrhage, and other related conditions are more likely to occur during hospitalization, leading to decreased food consumption in patients and malnutrition. The longer the stay in the hospital is, the more likely the patients are to suffer from nosocomial infection, bedsores, gastrointestinal hemorrhage and other complications; moreover, the nutritional intake during hospitalization is worse than that after discharge. The diet accepted by nasal-feeding patients is mainly a liquid diet, such as protein powder, rice flour, etc., which carries a high risk of diarrhea.
Previous studies have shown that dysphagia is a risk factor for malnutrition after stroke, which is inconsistent with the conclusion of this study [18][19][20][21][22][23]. The reason for this difference may be that only 5 patients with RCSE caused by cerebral infarction were included in this study, and the study sample was small. More patients with cerebral infarction can be included in a follow-up study, and the sample size can be expanded and analyzed separately. Decreased consciousness levels in patients during hospitalization may also be a risk factor for malnutrition in patients with refractory epilepsy. When the patient's consciousness level decreases, nutrition intake may decrease, and decreased intestinal peristalsis during long-term bed rest may lead to poor absorption. However, this study did not reach this conclusion, which may be because the included patients were seriously ill, and most patients had decreased levels of consciousness.
In addition to the malnutrition, nasal feeding and hospitalization days shown in this study, there may be other related risk factors. These factors include (1) concomitant consumptive diseases. In addition, (2) some patients with intractable convulsive epilepsy continued to use ketogenic diet, mainly high-fat diet, lacking protein involvement. This study shows that malnutrition patients have a high incidence of poor prognosis. Patients with malnutrition may be more prone to hospital infection, gastrointestinal dysfunction and other complications, which may have occurred accidentally due to the small sample size or due to the limitations of evaluation tools. This conclusion requires further longitudinal study with larger samples.
There are still some limitations to this study. First, these data are all from West China Hospital.
Although they can reflect the risk factors of malnutrition in patients with RCSE in western China to some extent, their generalizability is lower since this is a single-center study. At present, there is no universally accepted definition of malnutrition and no gold standard for nutritional assessment. Thus, these research results have certain limitations. In subsequent research, the sample size will be further expanded, and a subgroup analysis related to etiology will be conducted. Only patients over 18 years old were included in this study. These patients may have some differences with other age groups in the results of this study.

Conclusion
The risk of malnutrition during hospitalization in RCSE patients is 45.21%. Malnutrition, nasal feeding and hospitalization days are risk factors for malnutrition. Malnourished patients at admission are more likely to develop malnutrition during hospitalization, and early intervention is required for these patients.

Ethics approval and consent to participate
The protocol was approved by the West China hospital ethics Committee

Availability of data and material
I can confirm I have included a statement regarding data and material availability in the declaration section of my manuscript.

Competing interests
The authors declare no conflicts of interest.

Funding
Funding information is not applicable.

Authors' contributions
Dr Zhang collects data and writes articles Dr Chen and Dr Zhu are responsible for collation and statistics Dr Liu reviews articles