Impact of co-morbidities on the mortality of patients with status epilepticus and the utility of RCBI score in evaluating the mortality of status epilepticus CURRENT STATUS: POSTED

Background: To investigate the influential factors of complications on prognosis of patients with status epilepticus, modify the Complication Burden and analyze its practicability in status epilepticus in western China. Method: A total of 396 patients with status epilepticus were studied from December 2016 to January 2019 in West China Hospital. The clinical data were collected, including demographic characteristics, status epilepticus characteristics. Statistical analysis was performed using SPSS 22.0 and MedCalc ROCand logistic regression was used to analyze the influencing factors of hospitalization death and poor prognosis (GOS scale is 1-3). Results: Of the 396 patients with status epilepticus included in the study, 43 (10.9%) died in hospital and 114 (28.8%) had poor prognosis. Using ROC curve analysis, when RCBI > 3, the area under the ROC curve of hospitalization death was 0.914 , p < 0.0001; When RCBI > 3, the area under ROC curve for poor prognosis was 0.882, p < 0.0001. There were 327 people with convulsive status epilepticus, including 41 deaths. When RCBI>3, the area under the hospital mortality curve was 0.915 (p<0.0001). A total of 100 patients had a poor prognosis. When RCBI>3, the area under the poor prognosis curve was 0.867 (p<0.0001). Conclusions: The hospital mortality rate of patients with status epilepticus is 10.9%. RCBI >3 points had a certain significance for predicting hospitalization death and poor prognosis of status epilepticus. There were no significant differences in for and nonconvulsive status epilepticus.

formulate and revise the medical care plan, improve the quality of medical care, and make rational use of medical resources. In recent years, there have been many studies on the prognosis of status epilepticus, including a variety of scales and biological markers [3-5, 8, 11]. At present, five commonly used international scoring scales for predicting the prognosis of patients with status epilepticus include the epidemiology-based mortality scale in status epilepticus EMSE [3][4] ENDtracheal intubation scale END-IT [8] status epilepticus severity scale STESS [2,4] modified Rankin scale-status epilepticus severity scale mSTESS [11] and Complication Burden Index CBI [5].
Systemic complications are very common in patients with status epilepticus, and the types and number of complications may influence the prognosis of patients [5,[9][10][16][17][18][19]24]. In 2018, Leena et al [5] proposed the CBI and evaluated patients for 13 types of complications: respiratory system, cardiovascular system, nervous system, kidney, liver, coagulation function, gastrointestinal and musculoskeletal system, and electrolyte/acid-base balance, infection, hypoglycemia/hyperglycemia, skin/allergic reaction, and mental disorders. Using the receiver operating characteristic (ROC) curve, the maximum CBI scale was 13 points, the average CBI was 3.8 points, and the cutoff point for poor prediction function was 3 points [5]. The CBI scale established by Leena et al. included a small number of patients, and only included convulsive epileptic patients with seizure time > 30 min.
Therefore, the purpose of this study was to investigate the influencing factors of co-morbidity of patients with epileptic status on their prognosis, modify CBI scale into the RCBI scale, and evaluate whether it is applicable to the population in western China, as well as its feasibility in non-convulsive epileptic status.  [25] and 13 complications included in the CBI scale that were summarized and screened at discharge, such as hyperglycemia and hypoglycemia, which can be counted as electrolytes. Electrolyte imbalance and acid-base imbalance can be counted as one category, and the etiology of epileptic seizures needs to be removed. Therefore, comorbidity is defined as a disease that is comorbid during the status epilepticus but does not include the factors that cause status epilepticus, including skin allergy, musculoskeletal-related diseases, digestive system diseases, thyroid function diseases, respiratory system diseases, immune system diseases, kidney and urinary system diseases, electrolyte/acid-base balance disorders, hypoglycemia/hyperglycemia, hypoproteinemia, infection, blood system diseases, mental diseases, nervous system diseases (excluding the causes of status epilepticus, such as brain tumors, acute stroke, etc.), and cardiovascular system diseases. Regardless of the severity of the common disease or the involvement of multiple systems, it is only calculated once, and the total number of diseases is up to 15 ( Table 1). The outcome variables were hospitalization death and poor prognosis. The evaluation index of poor prognosis was GOS scale of 1-3.    (Table 3 ) 3. There were 2 patients suffering from 9 kinds of comorbidities, including 1 death in hospital and 1 case of poor prognosis ( Table 2). The average number of common diseases is 2.98. A total of 43 people died. MedCalc ROC curve was used for analysis.
When RCBI>3, the specificity was 71.37%, the sensitivity was 97.67%, the AUC was 0.914, the standard error was 0.020, and the P value was <0.0001, 95% confidence interval was 0.881-0.939, and the accuracy was high (Figure 1-1). A total of 114 patients had a poor prognosis. When RCBI>3, the specificity was 81.56%, the sensitivity was 79.82%, the AUC was 0.882, the standard error was 0.016, the P value was <0.0001, the 95% confidence interval was 0.846-0.912 and the accuracy was medium (Figure 1-2 ).

4.
Comparative analysis of persistent status of convulsive epilepsy and non-convulsive epilepsy. There were 327 people with convulsive status epilepticus, including 41 deaths. When RCBI>3, the specificity was 70.38%, the sensitivity is 97.50%, the AUC was 0.915, the standard error was 0.021, the P value is <0.0001, the 95% confidence interval was 0.880-0.943, and the accuracy was high (Figure 2-1). The prognosis was poor in 100 patients. When RCBI>3, the specificity was 79.74%, the sensitivity was 78.00%, the AUC was 0.867, the standard error was 0.018, the P value was <0.0001, the 95% confidence interval was 0.825-0.902. The accuracy was medium (Figure 2-2). There were 43 non-convulsive epilepsy states, including 2 deaths. When RCBI>3, the specificity was 75.76%, the sensitivity is 100.00%, the AUC was 0.919, the standard error was 0.057, and the P value was <0.0001. The 95% confidence interval was 0.828-0.971, and the accuracy was high (Figure 3-1). The prognosis included 14 patients. When RCBI>3, the specificity was 89.09%, the sensitivity was 92.86%, and the AUC was 0.955. The standard error was 0.024, the P value is <0.0001, the 95% confidence interval was 0.876-0.990, and the accuracy was high (Figure 3-2).

Discussion
Status epilepticus is one of the most common neurological critical illnesses, often leading to permanent neurological damage, with high morbidity and mortality [ This study showed that the digestive system, respiratory system, immune system, kidney and urinary system, electrolyte/acid-base imbalance, and infection are the risk factors for hospitalization death in status epilepticus. The musculoskeletal system diseases, digestive system, thyroid function, respiratory system, immune system, kidney/urinary system, electrolyte/acid-base imbalance, hypoglycemia/hyperglycemia, infection, blood system, nervous system, and cardiovascular system diseases are risk factors for poor prognosis of patients with status epilepticus. Therefore, we improved the CBI scale and added three new complications: immune system diseases, thyroid function diseases and hypoproteinemia, because these three diseases also have certain influence on the prognosis of patients, such as hyperthyroidism/hypofunction, etc. In addition, the liver system and gastrointestinal diseases are combined into the digestive system to avoid double counting.
Coagulation function should be expanded to include diseases of the blood system,such as anemia.
The renal system and urinary system are combined into one item. This study did not consider tumor (excluding the cause of status epilepticus), which obviously affects the prognosis of patients, because it probably existed before status epilepticus. This was a single-center study. The patients included in the study were all from a hospital in western China, which may have certain selection bias. This study was scaled by a doctor's own judgment, and there may be some deviation. In the subsequent study, it is expected that two doctors will scale at the same time to obtain more accurate scoring results. Therefore, more scales or indicators may be needed to evaluate the prognosis of patients with epilepsy, and large-scale multicenter studies are needed to further verify our findings.

Conclusion
The in-hospital mortality rate of patients with status epilepticus in western China is approximately 10.9%, and RCBI > 3, which is of certain significance for predicting in-hospital death and poor prognosis of status epilepticus. Regarding the status of convulsive epilepsy and non-convulsive epilepsy, RCBI has no significant difference in predicting hospital death and poor prognosis(GOS 1-3).

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

Consent for publication
I can confirm I have consent for publication and study participants was written

Availability of data and material
The datasets generated or analysed during the current study are not publicly available due not have consent from all patients, but are available from the corresponding author on reasonable request.

Competing interests
The authors declare no conflicts of interest.   Figure 1 Total hospital deaths and poor prognosis NCSE hospital deaths and poor prognosis