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Status epilepticus in the elderly patients: A national data study in Thailand
JNS-14925; No of Pages 5 Journal of the Neurological Sciences xxx (2016) xxx–xxx
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Clinical Short Communication
Status epilepticus in the elderly patients: A national data study in Thailand Somsak Tiamkao a,c, Sineenard Pranboon b,c, Kaewjai Thepsuthammarat d, Kittisak Sawanyawisuth a,e,f,⁎ a
Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand Nursing Division, Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand Integrated Epilepsy Research Group, Khon Kaen University, Khon Kaen, Thailand d Clinical Epidemiology Unit, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand e Research Center in Back, Neck Other Joint Pain and Human Performance (BNOJPH), Khon Kaen University, Khon Kaen, Thailand f Non-communicable Diseases Research Group, Khon Kaen University, Khon Kaen, Thailand b c
a r t i c l e
i n f o
Article history: Received 10 March 2016 Received in revised form 6 November 2016 Accepted 8 November 2016 Available online xxxx Keywords: Incidence Status epilepticus Elderly Outcomes National
a b s t r a c t There are limited data in terms of incidence, clinical features, and outcomes in elderly patients with status epilepticus (SE) in national level. We retrospectively explored national data in Thailand for reimbursement of all SE in elderly patients admitted in the fiscal year 2004–2012. SE in elderly patients (age N 60 years old) were diagnosed and searched based on ICD 10 (G41) from the national database of from the National Health and Security Office. There were 3326 SE in elderly patients. The national incidence of SE was highest at 8.78 patients/100,000/year in 2012. The average age was 72.02 years and most were males (1379 patients; 58.8%). At discharge, 66% of patients had improved and in-hospital mortality rate was 14.5%. Predictors of poor outcomes were older age ≥ 80 years, being female, hospital levels, chronic renal failure, central nervous system infection, respiratory failure, pneumonia, septicemia, shock, acute renal failure, and hyperkalemia. In conclusion, the number of cases of SE in elderly patients in Thailand has been increasing annually. Increasing age was associated with poor outcome in admitted elderly SE patients. © 2016 Elsevier B.V. All rights reserved.
1. Introduction The incidence rate of epilepsy may increase in the future due to a higher. proportion of elderly people in the population [1,2]. Epilepsy and its complications may cause the elderly to suffer an increasing of economic burden [2]. Status epilepticus (SE), a serious complication of epilepsy and a major public health problem [3], may also be increasing in the elderly similar to epilepsy. SE in the elderly may be more intractable and have high morbidity and mortality compared with the general population [4]. Several studies have shown that the incidences of SE in people over 60 were higher than in the general population [4–7]. The incidence rate of SE in the elderly (over 60 years old) was 39.2/100,000 population and higher than that in the younger age group (20–59 years) of 14.7/ 100,000 population [5]. The SE incidence rates from Virginia (over 60 years old) and Minnesota (over 75) were 86/100,000 population and 4/1000 population, respectively [6,8]. There are limited data in term of incidence, characteristics, demographics, comorbidity,
⁎ Corresponding author at: Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. E-mail address: [email protected] (K. Sawanyawisuth).
outcomes and prognostic factor and in-hospitalized mortality of SE in the elderly patients as longitudinal data at the national level. 2. Methods 2.1. Study design A retrospective study explored national data from the National Health and Security Office. The study period was from the fiscal years 2004 and 2012. Data from the reimbursement section of all admitted SE in elderly patients aged 60 and over were studied. The ICD-10 code (G41) was used to identify eligible patients. The G41 code indicated Grand mal SE excluding epilepsia partialis continua, petit mal SE, complex partial SE, other SE, and SE unspecified. Medical discharge forms were used to retrieve clinical data, co-morbid diseases, complications, procedures, and discharge status. The Universal Health Coverage Insurance is the main health care insurance system in Thailand and is supported by the government. Approximately 77% of the entire Thai population is covered under this plan. The other two health care insurance systems in Thailand are social security system and civil servant medical benefit system (CSMBS).·One person can have only one type of health insurance. There were three hospital categories in Thailand including primary or community, secondary, and tertiary hospitals. The primary or
http://dx.doi.org/10.1016/j.jns.2016.11.013 0022-510X/© 2016 Elsevier B.V. All rights reserved.
Please cite this article as: S. Tiamkao, et al., Status epilepticus in the elderly patients: A national data study in Thailand, J Neurol Sci (2016), http:// dx.doi.org/10.1016/j.jns.2016.11.013
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S. Tiamkao et al. / Journal of the Neurological Sciences xxx (2016) xxx–xxx
community hospitals serve at the district or community levels and usually have 10–30 beds. The secondary hospitals provide healthcare at the provincial level, while the tertiary hospitals, such as university hospitals or large provincial hospitals, are referral centers. Attending physicians categorized the discharge statuses of all admitted patients as follows: complete recovery, improved, not improved, and death. The first two categories were classified as improved or good outcomes, while the latter two were not improved or poor outcomes. All eligible patients were divided into two groups based on whether they their outcomes were considered good or poor. 2.2. Statistical analysis Descriptive statistics were used to analyze the baseline data. The incidence rates of SE in each year were calculated and adjusted by the structure of population in the year of 2012. Three age groups were used as reference values (age group 60–69, 70–79, and 80 and over). Factors associated with discharge status were calculated by descriptive statistics. Univariate and multivariate logistic regression analyses were used to identify significant factors associated with poor discharge status. All data analyses were performed by STATA software version 10 (College Station, Texas, USA) on a personal computer. A p value of b 0.05 was considered statistically significant. 3. Results 3.1. Demographics There were 3326 Elderly SE patients examined in the study period. 1957 of the patients were male (58.8%) and 1369 were female (41.2%). The mean age (SD) was 72.02 years (7.55) (range 61– 103 years). Most were admitted into tertiary care (1701 patients; 51.1%) followed by secondary care (967 patients; 29.1%) and primary care (658 patients; 19.8%). 3.2. National incidence of SE The number of SE in elderly patients was increasing every year from 113 patients in 2004 to 717 patients in 2012. The national incidence rate of SE was lowest at 1.84 patients/100,000/year in 2004 and highest at 8.78 patients/100,000/year in 2012 as shown in Table 1. 3.3. Comorbidities and in-hospital complications The three most common comorbidities were hypertension, diabetes mellitus and previous stroke (Table 2), while the three most common complications were respiratory failure, pneumonia and septicemia (Table 3). Table 1 Incidence rates of status epilepticus (SE) in elderly patients admitted throughout Thailand during the 9-year study period from 2004 to 2012. Years SE, n
Age group 60–69
Age group 70–79
Age group ≥80
Rate/100,000 populationsa
2004 2005 2006 2007 2008 2009 2010 2011 2012 Total
65 76 78 115 149 170 216 247 304 1420
33 64 68 90 149 174 243 242 264 1327
15 26 28 36 58 69 97 101 149 579
1.84 2.63 2.67 3.60 5.14 5.74 7.40 7.55 8.78
113 166 174 241 356 413 556 590 717 3326
a The rate was adjusted by three age groups (60–69, 70–79, and 80 and over) by using the population of each age group in the year of 2012 as the reference.
Table 2 Co-morbid conditions of status epilepticus in elderly patients admitted throughout Thailand during the 9-year study period from 2004 to 2012. Co-morbid conditions
Numbers (%)
Hypertension Diabetes mellitus Previous stroke Chronic renal failure Traumatic brain injury Cirrhosis CNS infection Schizophrenia Brain tumor Psychosis Depression
1072 (32.2) 543 (16.3) 423 (12.7) 219 (6.6) 45 (1.4) 43 (1.3) 38 (1.1) 24 (0.7) 21 (0.6) 12 (0.4) 8 (0.2)
3.4. Outcomes of treatment The most cases of treatment of SE in elderly patients were classified as having good outcomes 66.6% (2215 patients; categorized as complete recovery 17 patients or 0.5% and improved 2198 patients or 66.1%), while poor outcomes accounted for 33.4% (1111 patients; categorized as not improved 630 patients or 18.9% and dead 481 patients or 14.5%). The mean (SD) hospital stay was 7.74 (16.36) days. Predictors of poor outcome were age N 80 years, female sex and hospital levels. Out of 11 co-morbid conditions, chronic renal failure and central nervous system infection were significantly associated with poor outcomes. Additionally, six complications including respiratory failure, pneumonia, septicemia, shock, acute renal failure, and hyperkalemia. There were 251 patients who received at least one treatment procedures such as Foley catheterization, or cardiopulmonary resuscitation. Only cardiopulmonary resuscitation was a significant factor of poor outcomes as shown in Table 3. The mortality rate was slightly increasing by years (Table 4). No death was reported in 2004. The age group of ≥ 80 years had highest mortality rate except in 2006; highest in 2005 (26.92%).
4. Discussion This study showed the trend of SE incidence rates in the elderly over a nine-year period based on the national data. SE incidences and mortality rate increased slightly over this period (Table 1). The incidence rates in this study were lower than previous reports from the Western countries [4–10]. In 2012, the incidence rate of SE in the Thai elderly population was 8.78/100,000 population, while a study from California found an incidence rate there of 22.3/100,000 population in a generalized tonic clonic SE in the elderly aged 75 years and older [10]. The reported SE incidence rates in the Thai elderly population may be under-reported mainly due to the limited number of laboratories and epileptologists [11, 12]. Nonconsulvive SE may be difficult to diagnose, particularly in the elderly. Electroencephalography (EEG) and experienced neurologists or epileptologists are required to examine SE patients who have subtle or minor symptoms of SE. Clinical suspicion of SE is crucial and the lack of clinical suspicion may lead to misdiagnosis. EEG is not available in all healthcare facilities. Additionally, the low incidence of SE in this study may be due to source of data in this study. We collected data from discharge documents which depended on summary by attending physicians and also correct code for SE. These errors may slightly result in lower incidence of SE. The present study indicated that SE in Thai elderly patients had good outcomes (66.6%) and in-hospital mortality was 14.5%. Compared with other studies in Thailand, the mortality rate in this study was somewhat lower [13–15]. In a study from the southern
Please cite this article as: S. Tiamkao, et al., Status epilepticus in the elderly patients: A national data study in Thailand, J Neurol Sci (2016), http:// dx.doi.org/10.1016/j.jns.2016.11.013
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Table 3 Factors affecting discharge status of status epilepticus in elderly patients admitted throughout Thailand during the 9-year study period from 2004 to 2012. Variables
Discharge Status
Age group 60–70 years 70–80 years ≥80 years Gender Male Female Hospital level Primary care Secondary care Tertiary care Co-morbid conditions Hypertension Diabetes mellitus Previous Stroke Chronic renal failure Traumatic brain injury Cirrhosis CNS infection Schizophrenia Brain tumor Psychosis Depressive Complications Respiratory failure Pneumonia Septicemia Pressure sore Shock Acute renal failure Hyperkalemia Hyperglycemia Procedures* Foley's catheter CPR
Total n (%)
Adjusted odds ratios (95%CI)
404 (36.4) 464 (41.8) 243 (21.9)
1420 (42.7) 1327 (39.9) 579 (17.4)
1 1.19 (0.99, 1.44) 1.58 (1.26, 1.99)
1379 (62.3) 836 (37.7)
578 (52.0) 533 (48.0)
1957 (58.8) 1369 (41.2)
1 1.52 (1.29, 1.80)
383 (17.3) 654 (29.5) 1178 (53.2)
275 (24.8) 313 (28.2) 523 (47.1)
658 (19.8) 967 (29.1) 1701 (51.1)
1 0.29 (0.23, 0.38) 0.22 (0.17, 0.28)
719 (32.5) 362 (16.3) 261 (11.8) 111 (5.0) 27 (1.2) 26 (1.2) 18 (0.8) 16 (0.7) 16 (0.7) 9 (0.4) 7 (0.3)
353 (31.8) 181 (16.3) 162 (14.6) 108 (9.7) 18 (1.6) 17 (1.5) 20 (1.8) 8 (0.7) 5 (0.5) 3 (0.3) 1 (0.1)
1072 (32.2) 543 (16.3) 423 (12.7) 219 (6.6) 45 (1.4) 43 (1.3) 38 (1.1) 24 (0.7) 21 (0.6) 12 (0.4) 8 (0.2)
0.91 (0.75, 1.09) 0.85 (0.66, 1.08) 1.17 (0.91, 1.49) 1.79 (1.30, 2.47) 1.55 (0.76, 3.17) 1.44 (0.72, 2.88) 2.18 (1.07, 4.44) 0.97 (0.36, 2.57) 0.64 (0.21, 1.92) 0.88 (0.21, 3.61) 0.45 (0.05, 4.15)
0.323 0.181 0.203 b0.001 0.238 0.335 0.029 0.964 0.460 0.964 0.471
884 (39.9) 310 (14.0) 109 (4.9) 58 (2.6) 24 (1.1) 51 (2.3) 51 (2.3) 26 (1.2)
672 (60.5) 259 (23.3) 278 (25.0) 43 (3.9) 49 (4.4) 122 (11.0) 70 (6.3) 26 (2.3)
1556 (46.8) 569 (17.1) 387 (11.6) 101 (3.0) 73 (2.2) 173 (5.2) 121 (3.6) 52 (1.6)
2.37 (1.94, 2.90) 1.35 (1.08, 1.69) 5.24 (4.03, 6.81) 1.03 (0.65, 1.63) 3.49 (1.99, 6.12) 3.24 (2.20, 4.78) 2.04 (1.33, 3.14) 1.87 (0.99, 3.55)
b0.001 b0.001 b0.001 0.865 b0.001 b 0.001 0.001 0.057
100 (4.5) 9 (0.4)
70 (6.3) 83 (7.5)
170 (5.1) 92 (2.8)
0.88 (0.60, 1.29) 15.54 (7.52, 32.10)
0.600 b0.001
Good n (%)
Poor n (%)
1016 (45.9) 863 (39.0) 336 (15.2)
p-value
b0.001
b0.001
b0.001
Note. CNS: central nervous system; CPR: cardiopulmonary resuscitation; *only 251 patients received at least one treatment procedure.
Thailand, the rates poor outcomes and mortality were 62.2% and 26.7%, respectively [13], while studies from central and northeastern Thailand reported mortality rates of 25% and 35% [14,15]. However, there have been several studies that have found similar SE mortality rates as were found in this study (range 14.5%–16%) [16–18]. Note that populations examined in the above studies were not limited to elderly patients. These three studies were conducted in university or referral hospitals which may have more severe SE patients. The results of this study should be more generalized for Thailand in overall. Only 45% of the patients in the study from central Thailand were 60– 90 years of age [14]. We found the national mortality rate of SE to be 11.96% for all age groups [19], which was lower than in this elderly population (14.5%). Several factors were independently associated with poor outcomes at discharge (Table 3). Age was one significant positive factor, with the rate of poor outcomes increasing with the age of the patients. Patients 70–80 years old had an adjusted OR of 1.24 (1.03,
1.49), while those over 80 had higher the adjusted OR of 1.67 (1.33, 2.10). These findings were similar to previous studies with smaller sample sizes [18,20–26]. Elderly patients over 75 years old had unfavorable outcomes in 50% of cases if the patients had experienced deterioration of mental status [21]. Female gender was also another poor prognostic factor as previously reported [23]. The mortality rate increased by 34% (95% CI 1.04–1.73) in females [23], while the adjusted OR in this study was quite similar at 1.53 (95% CI 1.29, 1.80) as shown in Table 3. Hospital category was also significantly associated with poor outcomes. The tertiary care hospitals had the highest rate of poor outcomes compared with secondary or primary care hospitals (24.8% vs 28.2% vs 47.1%) as shown in Table 3. These findings were mainly explained by the fact that there were more severe cases at tertiary hospital level. But, the adjusted odds ratios for secondary and tertiary care hospitals were b1 (Table 3). In other words, the secondary and tertiary care hospitals may have better outcomes. These findings may be due to better
Table 4 Mortality rates of status epilepticus (SE) in elderly patients admitted throughout Thailand during the 9-year study period from 2005 to 2012. Years
Age group 60–69, n (%)
Age group 70–79, n (%)
Age group ≥80, n (%)
Total death, n
SE, n
Mortality rate
Mortality/100,000 populationsa
2005 2006 2007 2008 2009 2010 2011 2012
8 (10.53%) 16 (20.51%) 14 (12.17%) 17 (11.41%) 16 (9.41%) 33 (15.28%) 30 (12.15%) 37 (12.17%)
9 (14.06%) 14 (20.59%) 7 (7.78%) 25 (16.78%) 24 (13.79%) 43 (17.70%) 31 (12.81%) 39 (14.77%)
7 (26.92%) 3 (10.71%) 8 (22.22%) 11 (18.97%) 16 (23.19%) 23 (23.71%) 23 (22.77%) 27 (18.12%)
24 33 29 53 56 99 84 103
166 174 241 356 413 556 590 717
14.46% 18.97% 12.03% 14.89% 13.56% 17.81% 14.24% 14.37%
0.38 0.51 0.43 0.77 0.78 1.32 1.08 1.26
a
The rate was adjusted by three age groups (60–69, 70–79, and 80 and over) by using the population of each age group in the year of 2012 as the reference.
Please cite this article as: S. Tiamkao, et al., Status epilepticus in the elderly patients: A national data study in Thailand, J Neurol Sci (2016), http:// dx.doi.org/10.1016/j.jns.2016.11.013
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S. Tiamkao et al. / Journal of the Neurological Sciences xxx (2016) xxx–xxx
diagnosis and management in higher hospital levels. The tertiary care hospitals have experienced neurologists, while the primary care hospitals do not. Additionally, non-convulsive SE requires an EEG to diagnose, and is quite difficult to control seizures particularly if a referral process is delayed. Generally, elderly people with epilepsy have 2–3 times greater mortality than the general population [27]. SE was presented in 30% of acute seizures in the elderly with a mortality rate of 40% particularly refractory SE [8,20,28,29]. In addition, primary care hospitals have a limited amount of anti-epileptic drugs to control refractory or non-convulsive SE [17,19,30]. The most common co-morbid conditions of SE in elderly patients were cerebrovascular disease at 45%–50% [2,5,31]. Our nationwide data showed that the three most common co-morbid conditions were hypertension (32.2%), diabetes mellitus (16.3%), and previous stroke (12.7%). These factors may not be the primary cause of SE in the elderly patients. However, they may be a contributing factor for other SE-related conditions such as stroke instead. Therefore, elderly people who develop new-onset seizures should undergo assessment for the presence of cerebrovascular risk factors and treat these conditions accordingly with the aim of stroke prevention [2]. Common SE complications were respiratory failure (46.8%), pneumonia (17.1%) and septicemia (11.6%) as shown in Table 3. These factors, once again, related with poor outcomes as previously reported by Hocker et al.. [20]. SE, particularly non-convulsive SE in elderly patients was associated with a high rate of hospital-acquired infections [32]. The study of non-convulsive SE on 25 elderly patients found a mortality rate of 52% and death was associated with the number of acute life-threatening medical problems [32]. Our study found that the mean (SD) hospital stay was 7.74 (16.36) days. The length of hospital stay was longer than adult SE patients at the national level at 5.48 (SD 11.44) days [30]. These results confirmed that cases of SE in the elderly were more severe and required longer hospitalizations than the general population. The mortality rate tends to increase by years (Table 4). These findings may be due to elderly community in Thailand. Even though the healthcare is better, the elderly patients had more co-morbid diseases. Additionally, the mortality rates tended to be higher in age group of N 80 years in almost all years (Table 4). Advanced age is one factor associated with mortality other than disability status [33]. The strengths of this study were large sample size at the national level and longitudinal data over a nine-year period. This study is a subgroup analysis of the previous study [31]. Another national study included all adult SE patients with all types of health insurance and treated in 2010 [19] which may be a part of this study. Some limitations exist, however. The patients enrolled in this study were only those who were admitted and reimbursed through the national insurance system. However, these populations accounted for N77% of Thai population. Due to retrospective data collection, some specific clinical factors, such as laboratory results, were not included in the analysis. Additionally, data were collected from discharge summary forms. Some factors were not recorded such as duration of seizure, anticonvulsant therapy, or depth of coma. Finally, even though discharge summary form was routinely double checked or audited according to the standard of the hospital accreditation, using the ICD code in the discharge summary may not have the 100% accuracy. The sensitivity and specificity for epilepsy by the ICD-code were 98.8% and 69.6%, respectively [34]. SE in the elderly had a high rate of incidence and severity. Factors associated with poor outcomes in admitted SE in elderly patients were age, sex, hospital level, co-morbid conditions, complications of SE, and procedural intervention by the national data.
Financial disclosure None declared by all authors.
Conflicts of interest None declared by all authors. Acknowledgement The authors would like to thank Mr. Dylan Southard for his English language editing and the Thailand Research Fund (TRF) for their kind support (IRG 5780016). This research was also funded in part by grants from the Higher Education Research Promotion National Research University Project of Thailand Office of the Higher Education Commission through the Health Cluster (SHeP-GMS), Thailand; the Faculty of Medicine, Khon Kaen University grant number TR57201; and the TRF Senior Research Scholar Grant, Thailand Research Fund grant number RTA5880001. References [1] H. Stefan, T.W. May, M. Pfäfflin, et al., Epilepsy in the elderly: comparing clinical characteristics with younger patients, Acta Neurol. Scand. 129 (2014) 283–293. [2] M.J. Brodie, A.T. Elder, P. Kwan, Epilepsy in later life, Lancet Neurol. 8 (2009) 1019–1030. [3] E.J. Waterhouse, R.J. DeLorenzo, Status epilepticus in older patients: epidemiology and treatment options, Drugs Aging 18 (2001) 133–142. [4] T. De Assis, T.M.R. de Assis, G. Costa, A. Bacellar, M. Orsini, O.J.M. Nascimento, Status epilepticus in the elderly: epidemiology, clinical aspects and treatment, Neurol. Int. 4 (2012), e17. [5] V. Govoni, E. Fallica, V.C. Monetti, et al., Incidence of status epilepticus in southern Europe: a population study in the health district of Ferrara, Italy, Eur. Neurol. 59 (2008) 120–126. [6] D.C. Hesdorffer, G. Logroscino, G. Cascino, J.F. Annegers, W.A. Hauser, Incidence of status epilepticus in Rochester, Minnesota, 1965–1984, Neurology 50 (1998) 735–741. [7] R.J. DeLorenzo, J.M. Pellock, A.R. Towne, J.G. Boggs, Epidemiology of status epilepticus, J. Clin. Neurophysiol. 12 (1995) 316–325. [8] R.J. DeLorenzo, W.A. Hauser, A.R. Towne, et al., A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia, Neurology 46 (1996) 1029–1035. [9] A.R. Towne, Epidemiology and outcomes of status epilepticus in the elderly, Int. Rev. Neurobiol. 81 (2007) 111–127. [10] Y.W. Wu, D.W. Shek, P.A. Garcia, et al., Incidence and mortality of generalized convulsive status epilepticus in California, Neurology 58 (2002) 1070–1076. [11] H. Stefan, Epilepsy in the elderly: facts and challenges, Acta Neurol. Scand. 124 (2011) 223–237. [12] S. Tiamkao, S. Towanabut, K. Dhiravibulyn, S. Pranboon, K. Sawanyawisuth, The Epilepsy Society of Thailand, et al., Is the Thailand epilepsy service adequate to help patients? Neurology Asia 18 (2013) 271–277. [13] K. Phabphal, A. Geater, K. Limapichart, P. Sathirapanya, S. Setthawatcharawanich, Adult tonic-clonic convulsive status epilepticus over the last 11 years in a resource-poor country: a tertiary referral centre study from southern Thailand, Epileptic Disord. 15 (2013) 255–261. [14] K. Kulkantrakorn, W. Moonman, Treatment outcome of status epilepticus in Thammasat University Hospital, Thailand, Neurology Asia 19 (2014) 257–262. [15] S. Tiamkao, P. Suko, N. Mayurasakorn, Srinagarind Epilepsy Research Group, Outcome of status epilepticus in Srinagarind Hospital, J. Med. Assoc. Thail. 93 (2010) 420–423. [16] H.J. Skinner, S.A. Dubon-Muricia, A.R. Thompson, et al., Adult convulsive status epilepticus in the developing country of Honduras, Seizure 19 (2010) 363–367. [17] A.O. Rossetti, S. Hurwitz, G. Logroscino, E.B. Bromfield, Prognosis of status epilepticus: role of aetiology, age, and consciousness impairment at presentation, J. Neurol. Neurosurg. Psychiatry 77 (2006) 611–615. [18] A.C.F. Hui, G.M. Joynt, H. Li, K.S. Wong, Status epilepticus in Hong Kong Chinese: aetiology, outcome and predictors of death and morbidity, Seizure 12 (2003) 478–482. [19] S. Tiamkao, S. Pranbul, K. Sawanyawisuth, K. Thepsuthammarat, A national database of incidence and treatment outcomes of status epilepticus in Thailand, Int. J. Neurosci. 124 (2014) 416–420. [20] S.E. Hocker, J.W. Britton, J.N. Mandrekar, E.F. Wijdicks, A.A. Rabinstein, Predictors of outcome in refractory status epilepticus, JAMA Neurol. 70 (2013) 72–77. [21] F.J. Bottaro, O.A. Martinez, F. Pardal, et al., Nonconvulsive status epilepticus in the elderly: a case–control study, Epilepsia 48 (2007) 966–972. [22] A. Neligan, S.D. Shorvon, Prognostic factors, morbidity and mortality in tonic-clonic status epilepticus: a review, Epilepsy Res. 93 (2011) 1–10. [23] M. Koubeissi, A. Alshekhlee, In-hospital mortality of generalized convulsive status epilepticus: a large US sample, Neurology 69 (2007) 886–893. [24] D. Rudin, L. Grize, C. Schindler, S. Marsch, S. Rüegg, R. Sutter, High prevalence of nonconvulsive and subtle status epilepticus in an ICU of a tertiary care: a threeyear observational cohort study, Epilepsy Res. 96 (2011) 140–150. [25] Y. Li, L. Tian, T. Zeng, J. Chen, L. Chen, D. Zhou, Clinical features and outcome of super-refractory status epilepticus: a retrospective analysis in West China, Seizure 23 (2014) 722–727.
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Clinical Short Communication
Status epilepticus in the elderly patients: A national data study in Thailand Somsak Tiamkao a,c, Sineenard Pranboon b,c, Kaewjai Thepsuthammarat d, Kittisak Sawanyawisuth a,e,f,⁎ a
Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand Nursing Division, Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand Integrated Epilepsy Research Group, Khon Kaen University, Khon Kaen, Thailand d Clinical Epidemiology Unit, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand e Research Center in Back, Neck Other Joint Pain and Human Performance (BNOJPH), Khon Kaen University, Khon Kaen, Thailand f Non-communicable Diseases Research Group, Khon Kaen University, Khon Kaen, Thailand b c
a r t i c l e
i n f o
Article history: Received 10 March 2016 Received in revised form 6 November 2016 Accepted 8 November 2016 Available online xxxx Keywords: Incidence Status epilepticus Elderly Outcomes National
a b s t r a c t There are limited data in terms of incidence, clinical features, and outcomes in elderly patients with status epilepticus (SE) in national level. We retrospectively explored national data in Thailand for reimbursement of all SE in elderly patients admitted in the fiscal year 2004–2012. SE in elderly patients (age N 60 years old) were diagnosed and searched based on ICD 10 (G41) from the national database of from the National Health and Security Office. There were 3326 SE in elderly patients. The national incidence of SE was highest at 8.78 patients/100,000/year in 2012. The average age was 72.02 years and most were males (1379 patients; 58.8%). At discharge, 66% of patients had improved and in-hospital mortality rate was 14.5%. Predictors of poor outcomes were older age ≥ 80 years, being female, hospital levels, chronic renal failure, central nervous system infection, respiratory failure, pneumonia, septicemia, shock, acute renal failure, and hyperkalemia. In conclusion, the number of cases of SE in elderly patients in Thailand has been increasing annually. Increasing age was associated with poor outcome in admitted elderly SE patients. © 2016 Elsevier B.V. All rights reserved.
1. Introduction The incidence rate of epilepsy may increase in the future due to a higher. proportion of elderly people in the population [1,2]. Epilepsy and its complications may cause the elderly to suffer an increasing of economic burden [2]. Status epilepticus (SE), a serious complication of epilepsy and a major public health problem [3], may also be increasing in the elderly similar to epilepsy. SE in the elderly may be more intractable and have high morbidity and mortality compared with the general population [4]. Several studies have shown that the incidences of SE in people over 60 were higher than in the general population [4–7]. The incidence rate of SE in the elderly (over 60 years old) was 39.2/100,000 population and higher than that in the younger age group (20–59 years) of 14.7/ 100,000 population [5]. The SE incidence rates from Virginia (over 60 years old) and Minnesota (over 75) were 86/100,000 population and 4/1000 population, respectively [6,8]. There are limited data in term of incidence, characteristics, demographics, comorbidity,
⁎ Corresponding author at: Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. E-mail address: [email protected] (K. Sawanyawisuth).
outcomes and prognostic factor and in-hospitalized mortality of SE in the elderly patients as longitudinal data at the national level. 2. Methods 2.1. Study design A retrospective study explored national data from the National Health and Security Office. The study period was from the fiscal years 2004 and 2012. Data from the reimbursement section of all admitted SE in elderly patients aged 60 and over were studied. The ICD-10 code (G41) was used to identify eligible patients. The G41 code indicated Grand mal SE excluding epilepsia partialis continua, petit mal SE, complex partial SE, other SE, and SE unspecified. Medical discharge forms were used to retrieve clinical data, co-morbid diseases, complications, procedures, and discharge status. The Universal Health Coverage Insurance is the main health care insurance system in Thailand and is supported by the government. Approximately 77% of the entire Thai population is covered under this plan. The other two health care insurance systems in Thailand are social security system and civil servant medical benefit system (CSMBS).·One person can have only one type of health insurance. There were three hospital categories in Thailand including primary or community, secondary, and tertiary hospitals. The primary or
http://dx.doi.org/10.1016/j.jns.2016.11.013 0022-510X/© 2016 Elsevier B.V. All rights reserved.
Please cite this article as: S. Tiamkao, et al., Status epilepticus in the elderly patients: A national data study in Thailand, J Neurol Sci (2016), http:// dx.doi.org/10.1016/j.jns.2016.11.013
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community hospitals serve at the district or community levels and usually have 10–30 beds. The secondary hospitals provide healthcare at the provincial level, while the tertiary hospitals, such as university hospitals or large provincial hospitals, are referral centers. Attending physicians categorized the discharge statuses of all admitted patients as follows: complete recovery, improved, not improved, and death. The first two categories were classified as improved or good outcomes, while the latter two were not improved or poor outcomes. All eligible patients were divided into two groups based on whether they their outcomes were considered good or poor. 2.2. Statistical analysis Descriptive statistics were used to analyze the baseline data. The incidence rates of SE in each year were calculated and adjusted by the structure of population in the year of 2012. Three age groups were used as reference values (age group 60–69, 70–79, and 80 and over). Factors associated with discharge status were calculated by descriptive statistics. Univariate and multivariate logistic regression analyses were used to identify significant factors associated with poor discharge status. All data analyses were performed by STATA software version 10 (College Station, Texas, USA) on a personal computer. A p value of b 0.05 was considered statistically significant. 3. Results 3.1. Demographics There were 3326 Elderly SE patients examined in the study period. 1957 of the patients were male (58.8%) and 1369 were female (41.2%). The mean age (SD) was 72.02 years (7.55) (range 61– 103 years). Most were admitted into tertiary care (1701 patients; 51.1%) followed by secondary care (967 patients; 29.1%) and primary care (658 patients; 19.8%). 3.2. National incidence of SE The number of SE in elderly patients was increasing every year from 113 patients in 2004 to 717 patients in 2012. The national incidence rate of SE was lowest at 1.84 patients/100,000/year in 2004 and highest at 8.78 patients/100,000/year in 2012 as shown in Table 1. 3.3. Comorbidities and in-hospital complications The three most common comorbidities were hypertension, diabetes mellitus and previous stroke (Table 2), while the three most common complications were respiratory failure, pneumonia and septicemia (Table 3). Table 1 Incidence rates of status epilepticus (SE) in elderly patients admitted throughout Thailand during the 9-year study period from 2004 to 2012. Years SE, n
Age group 60–69
Age group 70–79
Age group ≥80
Rate/100,000 populationsa
2004 2005 2006 2007 2008 2009 2010 2011 2012 Total
65 76 78 115 149 170 216 247 304 1420
33 64 68 90 149 174 243 242 264 1327
15 26 28 36 58 69 97 101 149 579
1.84 2.63 2.67 3.60 5.14 5.74 7.40 7.55 8.78
113 166 174 241 356 413 556 590 717 3326
a The rate was adjusted by three age groups (60–69, 70–79, and 80 and over) by using the population of each age group in the year of 2012 as the reference.
Table 2 Co-morbid conditions of status epilepticus in elderly patients admitted throughout Thailand during the 9-year study period from 2004 to 2012. Co-morbid conditions
Numbers (%)
Hypertension Diabetes mellitus Previous stroke Chronic renal failure Traumatic brain injury Cirrhosis CNS infection Schizophrenia Brain tumor Psychosis Depression
1072 (32.2) 543 (16.3) 423 (12.7) 219 (6.6) 45 (1.4) 43 (1.3) 38 (1.1) 24 (0.7) 21 (0.6) 12 (0.4) 8 (0.2)
3.4. Outcomes of treatment The most cases of treatment of SE in elderly patients were classified as having good outcomes 66.6% (2215 patients; categorized as complete recovery 17 patients or 0.5% and improved 2198 patients or 66.1%), while poor outcomes accounted for 33.4% (1111 patients; categorized as not improved 630 patients or 18.9% and dead 481 patients or 14.5%). The mean (SD) hospital stay was 7.74 (16.36) days. Predictors of poor outcome were age N 80 years, female sex and hospital levels. Out of 11 co-morbid conditions, chronic renal failure and central nervous system infection were significantly associated with poor outcomes. Additionally, six complications including respiratory failure, pneumonia, septicemia, shock, acute renal failure, and hyperkalemia. There were 251 patients who received at least one treatment procedures such as Foley catheterization, or cardiopulmonary resuscitation. Only cardiopulmonary resuscitation was a significant factor of poor outcomes as shown in Table 3. The mortality rate was slightly increasing by years (Table 4). No death was reported in 2004. The age group of ≥ 80 years had highest mortality rate except in 2006; highest in 2005 (26.92%).
4. Discussion This study showed the trend of SE incidence rates in the elderly over a nine-year period based on the national data. SE incidences and mortality rate increased slightly over this period (Table 1). The incidence rates in this study were lower than previous reports from the Western countries [4–10]. In 2012, the incidence rate of SE in the Thai elderly population was 8.78/100,000 population, while a study from California found an incidence rate there of 22.3/100,000 population in a generalized tonic clonic SE in the elderly aged 75 years and older [10]. The reported SE incidence rates in the Thai elderly population may be under-reported mainly due to the limited number of laboratories and epileptologists [11, 12]. Nonconsulvive SE may be difficult to diagnose, particularly in the elderly. Electroencephalography (EEG) and experienced neurologists or epileptologists are required to examine SE patients who have subtle or minor symptoms of SE. Clinical suspicion of SE is crucial and the lack of clinical suspicion may lead to misdiagnosis. EEG is not available in all healthcare facilities. Additionally, the low incidence of SE in this study may be due to source of data in this study. We collected data from discharge documents which depended on summary by attending physicians and also correct code for SE. These errors may slightly result in lower incidence of SE. The present study indicated that SE in Thai elderly patients had good outcomes (66.6%) and in-hospital mortality was 14.5%. Compared with other studies in Thailand, the mortality rate in this study was somewhat lower [13–15]. In a study from the southern
Please cite this article as: S. Tiamkao, et al., Status epilepticus in the elderly patients: A national data study in Thailand, J Neurol Sci (2016), http:// dx.doi.org/10.1016/j.jns.2016.11.013
S. Tiamkao et al. / Journal of the Neurological Sciences xxx (2016) xxx–xxx
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Table 3 Factors affecting discharge status of status epilepticus in elderly patients admitted throughout Thailand during the 9-year study period from 2004 to 2012. Variables
Discharge Status
Age group 60–70 years 70–80 years ≥80 years Gender Male Female Hospital level Primary care Secondary care Tertiary care Co-morbid conditions Hypertension Diabetes mellitus Previous Stroke Chronic renal failure Traumatic brain injury Cirrhosis CNS infection Schizophrenia Brain tumor Psychosis Depressive Complications Respiratory failure Pneumonia Septicemia Pressure sore Shock Acute renal failure Hyperkalemia Hyperglycemia Procedures* Foley's catheter CPR
Total n (%)
Adjusted odds ratios (95%CI)
404 (36.4) 464 (41.8) 243 (21.9)
1420 (42.7) 1327 (39.9) 579 (17.4)
1 1.19 (0.99, 1.44) 1.58 (1.26, 1.99)
1379 (62.3) 836 (37.7)
578 (52.0) 533 (48.0)
1957 (58.8) 1369 (41.2)
1 1.52 (1.29, 1.80)
383 (17.3) 654 (29.5) 1178 (53.2)
275 (24.8) 313 (28.2) 523 (47.1)
658 (19.8) 967 (29.1) 1701 (51.1)
1 0.29 (0.23, 0.38) 0.22 (0.17, 0.28)
719 (32.5) 362 (16.3) 261 (11.8) 111 (5.0) 27 (1.2) 26 (1.2) 18 (0.8) 16 (0.7) 16 (0.7) 9 (0.4) 7 (0.3)
353 (31.8) 181 (16.3) 162 (14.6) 108 (9.7) 18 (1.6) 17 (1.5) 20 (1.8) 8 (0.7) 5 (0.5) 3 (0.3) 1 (0.1)
1072 (32.2) 543 (16.3) 423 (12.7) 219 (6.6) 45 (1.4) 43 (1.3) 38 (1.1) 24 (0.7) 21 (0.6) 12 (0.4) 8 (0.2)
0.91 (0.75, 1.09) 0.85 (0.66, 1.08) 1.17 (0.91, 1.49) 1.79 (1.30, 2.47) 1.55 (0.76, 3.17) 1.44 (0.72, 2.88) 2.18 (1.07, 4.44) 0.97 (0.36, 2.57) 0.64 (0.21, 1.92) 0.88 (0.21, 3.61) 0.45 (0.05, 4.15)
0.323 0.181 0.203 b0.001 0.238 0.335 0.029 0.964 0.460 0.964 0.471
884 (39.9) 310 (14.0) 109 (4.9) 58 (2.6) 24 (1.1) 51 (2.3) 51 (2.3) 26 (1.2)
672 (60.5) 259 (23.3) 278 (25.0) 43 (3.9) 49 (4.4) 122 (11.0) 70 (6.3) 26 (2.3)
1556 (46.8) 569 (17.1) 387 (11.6) 101 (3.0) 73 (2.2) 173 (5.2) 121 (3.6) 52 (1.6)
2.37 (1.94, 2.90) 1.35 (1.08, 1.69) 5.24 (4.03, 6.81) 1.03 (0.65, 1.63) 3.49 (1.99, 6.12) 3.24 (2.20, 4.78) 2.04 (1.33, 3.14) 1.87 (0.99, 3.55)
b0.001 b0.001 b0.001 0.865 b0.001 b 0.001 0.001 0.057
100 (4.5) 9 (0.4)
70 (6.3) 83 (7.5)
170 (5.1) 92 (2.8)
0.88 (0.60, 1.29) 15.54 (7.52, 32.10)
0.600 b0.001
Good n (%)
Poor n (%)
1016 (45.9) 863 (39.0) 336 (15.2)
p-value
b0.001
b0.001
b0.001
Note. CNS: central nervous system; CPR: cardiopulmonary resuscitation; *only 251 patients received at least one treatment procedure.
Thailand, the rates poor outcomes and mortality were 62.2% and 26.7%, respectively [13], while studies from central and northeastern Thailand reported mortality rates of 25% and 35% [14,15]. However, there have been several studies that have found similar SE mortality rates as were found in this study (range 14.5%–16%) [16–18]. Note that populations examined in the above studies were not limited to elderly patients. These three studies were conducted in university or referral hospitals which may have more severe SE patients. The results of this study should be more generalized for Thailand in overall. Only 45% of the patients in the study from central Thailand were 60– 90 years of age [14]. We found the national mortality rate of SE to be 11.96% for all age groups [19], which was lower than in this elderly population (14.5%). Several factors were independently associated with poor outcomes at discharge (Table 3). Age was one significant positive factor, with the rate of poor outcomes increasing with the age of the patients. Patients 70–80 years old had an adjusted OR of 1.24 (1.03,
1.49), while those over 80 had higher the adjusted OR of 1.67 (1.33, 2.10). These findings were similar to previous studies with smaller sample sizes [18,20–26]. Elderly patients over 75 years old had unfavorable outcomes in 50% of cases if the patients had experienced deterioration of mental status [21]. Female gender was also another poor prognostic factor as previously reported [23]. The mortality rate increased by 34% (95% CI 1.04–1.73) in females [23], while the adjusted OR in this study was quite similar at 1.53 (95% CI 1.29, 1.80) as shown in Table 3. Hospital category was also significantly associated with poor outcomes. The tertiary care hospitals had the highest rate of poor outcomes compared with secondary or primary care hospitals (24.8% vs 28.2% vs 47.1%) as shown in Table 3. These findings were mainly explained by the fact that there were more severe cases at tertiary hospital level. But, the adjusted odds ratios for secondary and tertiary care hospitals were b1 (Table 3). In other words, the secondary and tertiary care hospitals may have better outcomes. These findings may be due to better
Table 4 Mortality rates of status epilepticus (SE) in elderly patients admitted throughout Thailand during the 9-year study period from 2005 to 2012. Years
Age group 60–69, n (%)
Age group 70–79, n (%)
Age group ≥80, n (%)
Total death, n
SE, n
Mortality rate
Mortality/100,000 populationsa
2005 2006 2007 2008 2009 2010 2011 2012
8 (10.53%) 16 (20.51%) 14 (12.17%) 17 (11.41%) 16 (9.41%) 33 (15.28%) 30 (12.15%) 37 (12.17%)
9 (14.06%) 14 (20.59%) 7 (7.78%) 25 (16.78%) 24 (13.79%) 43 (17.70%) 31 (12.81%) 39 (14.77%)
7 (26.92%) 3 (10.71%) 8 (22.22%) 11 (18.97%) 16 (23.19%) 23 (23.71%) 23 (22.77%) 27 (18.12%)
24 33 29 53 56 99 84 103
166 174 241 356 413 556 590 717
14.46% 18.97% 12.03% 14.89% 13.56% 17.81% 14.24% 14.37%
0.38 0.51 0.43 0.77 0.78 1.32 1.08 1.26
a
The rate was adjusted by three age groups (60–69, 70–79, and 80 and over) by using the population of each age group in the year of 2012 as the reference.
Please cite this article as: S. Tiamkao, et al., Status epilepticus in the elderly patients: A national data study in Thailand, J Neurol Sci (2016), http:// dx.doi.org/10.1016/j.jns.2016.11.013
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diagnosis and management in higher hospital levels. The tertiary care hospitals have experienced neurologists, while the primary care hospitals do not. Additionally, non-convulsive SE requires an EEG to diagnose, and is quite difficult to control seizures particularly if a referral process is delayed. Generally, elderly people with epilepsy have 2–3 times greater mortality than the general population [27]. SE was presented in 30% of acute seizures in the elderly with a mortality rate of 40% particularly refractory SE [8,20,28,29]. In addition, primary care hospitals have a limited amount of anti-epileptic drugs to control refractory or non-convulsive SE [17,19,30]. The most common co-morbid conditions of SE in elderly patients were cerebrovascular disease at 45%–50% [2,5,31]. Our nationwide data showed that the three most common co-morbid conditions were hypertension (32.2%), diabetes mellitus (16.3%), and previous stroke (12.7%). These factors may not be the primary cause of SE in the elderly patients. However, they may be a contributing factor for other SE-related conditions such as stroke instead. Therefore, elderly people who develop new-onset seizures should undergo assessment for the presence of cerebrovascular risk factors and treat these conditions accordingly with the aim of stroke prevention [2]. Common SE complications were respiratory failure (46.8%), pneumonia (17.1%) and septicemia (11.6%) as shown in Table 3. These factors, once again, related with poor outcomes as previously reported by Hocker et al.. [20]. SE, particularly non-convulsive SE in elderly patients was associated with a high rate of hospital-acquired infections [32]. The study of non-convulsive SE on 25 elderly patients found a mortality rate of 52% and death was associated with the number of acute life-threatening medical problems [32]. Our study found that the mean (SD) hospital stay was 7.74 (16.36) days. The length of hospital stay was longer than adult SE patients at the national level at 5.48 (SD 11.44) days [30]. These results confirmed that cases of SE in the elderly were more severe and required longer hospitalizations than the general population. The mortality rate tends to increase by years (Table 4). These findings may be due to elderly community in Thailand. Even though the healthcare is better, the elderly patients had more co-morbid diseases. Additionally, the mortality rates tended to be higher in age group of N 80 years in almost all years (Table 4). Advanced age is one factor associated with mortality other than disability status [33]. The strengths of this study were large sample size at the national level and longitudinal data over a nine-year period. This study is a subgroup analysis of the previous study [31]. Another national study included all adult SE patients with all types of health insurance and treated in 2010 [19] which may be a part of this study. Some limitations exist, however. The patients enrolled in this study were only those who were admitted and reimbursed through the national insurance system. However, these populations accounted for N77% of Thai population. Due to retrospective data collection, some specific clinical factors, such as laboratory results, were not included in the analysis. Additionally, data were collected from discharge summary forms. Some factors were not recorded such as duration of seizure, anticonvulsant therapy, or depth of coma. Finally, even though discharge summary form was routinely double checked or audited according to the standard of the hospital accreditation, using the ICD code in the discharge summary may not have the 100% accuracy. The sensitivity and specificity for epilepsy by the ICD-code were 98.8% and 69.6%, respectively [34]. SE in the elderly had a high rate of incidence and severity. Factors associated with poor outcomes in admitted SE in elderly patients were age, sex, hospital level, co-morbid conditions, complications of SE, and procedural intervention by the national data.
Financial disclosure None declared by all authors.
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