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Epilepsy monitoring units can be safe places; a prospective study in a large cohort
Epilepsy & Behavior 102 (2020) 106718
Contents lists available at ScienceDirect
Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh
Epilepsy monitoring units can be safe places; a prospective study in a large cohort Fieke Cox ⁎, Elise Reus, Guido Widman, Jack Zwemmer, Gerhard Visser Department of Clinical Neurophysiology, Stichting Epilepsie Instellingen Nederland (SEIN), the Netherlands
a r t i c l e
i n f o
Article history: Received 15 October 2019 Revised 12 November 2019 Accepted 13 November 2019 Available online xxxx Keywords: EMU Safety Diagnostic utility Adverse events Video-EEG recording
a b s t r a c t Objective: No international guideline is available for minimum safety measures at epilepsy monitoring units (EMUs), although recommendations for preferred practices exist. These are mostly based on expert opinion, without evidence of effectiveness. We do not apply all of these preferred practices at our EMU setting. We audited adverse events and diagnostic utility at our EMU over one year. Methods: From May 2018 to May 2019, we prospectively collected data concerning adverse events and diagnostic utility of all EMU admissions (noninvasive video-electroencephalogram (EEG) recordings); during these admissions, individuals can be ambulant within their EMU room. Results: There were 1062 admissions comprising 1518 EMU days. In 2% of the admissions, a complication occurred, mostly a fall without injury (n = 6). In almost half of the falls, this was from the bed. Complications occurred most often during admissions for presurgical evaluation. Antiseizure medication (ASM) was tapered in 86% of presurgical cases, but no serious injury occurred, and occurring seizures were effectively treated with intranasal midazolam if needed. Conclusions: The overall adverse event rate was low. Falls are the most common adverse event comparable with previously published fall rates at other EMUs where people are restricted to their bed. We showed that restricted ambulation at a well-monitored EMU is not necessary and possibly unwanted. No serious injury due to tapering of ASM occurred, and intranasal midazolam was shown to be effective as acute seizure treatment. © 2019 Elsevier Inc. All rights reserved.
1. Introduction In epilepsy monitoring units (EMUs), people are admitted for prolonged video-electroencephalogram (EEG) recording. Aims included the following: finding interictal EEG abnormalities if standard EEG recording is inconclusive; recording clinical events, diagnosing epilepsy or mimickers; or evaluating individuals for epilepsy surgery by recording ictal events. To increase the effectiveness of EMU admissions, provocation measures (such as, drug tapering or night sleep deprivation) are often used to induce (epileptic) events. Because of the nature of epilepsy and the type of admission, people admitted to EMUs are prone to specific adverse events (AEs). Adverse events due to the habitual events include falls or injury; Because of provocative measures, seizure frequency and severity can be increased. Faster propagation to bilateral tonic–clonic activity, seizure clustering, and status epilepticus can also occur [1,2]. Postictal psychosis and even SUDEP have been described in EMU settings [2,3]. A systematic review including 33 studies reporting AEs at EMUs showed a pooled proportion of AEs of 7%, with ⁎ Corresponding author at: Stichting Epilepsie Instellingen Nederland, PO Box 540, 2130 AM Hoofddorp, the Netherlands. E-mail address: [email protected] (F. Cox).
https://doi.org/10.1016/j.yebeh.2019.106718 1525-5050/© 2019 Elsevier Inc. All rights reserved.
significant heterogeneity [4]. Minimal safety guidelines and recommendations for EMUs have been published [5–7], but these reflect expert opinion and are consensus-based; additionally, not all preventive measures have been shown to be effective. There is still no general accepted guideline concerning (minimum) safety measures, and there is large variation in safety measures at different EMUs. We have not implemented all safety measures previously suggested (e.g., intravenous (IV) access, restricted ambulation) in our EMU. A previous study showed that a nonrestrictive EMU setting can be as efficient for individuals safety as limiting their mobility [8]. We prospectively assessed the safety and quality of care at our EMU in a tertiary epilepsy center in the Netherlands as a service evaluation. 2. Methods 2.1. The epilepsy monitoring unit The EMU comprises 8 single-patient bedrooms (including a bathroom with outswing doors) open from Monday to Friday. Two beds are reserved for presurgical evaluation. The other beds are used for up to 24-hour video-EEG recording for (interictal) diagnostic/classification purposes and multiple-day video-EEG recording for event recording (to
2
F. Cox et al. / Epilepsy & Behavior 102 (2020) 106718
Fig. 1. The central observation post at the EMU:
classify events); most are planned for 2–3 days. Only noninvasive videoEEG monitoring is performed. Adults and children (accompanied by a caregiver) are admitted. The EMU is designed so that the rooms are within a 20-second walk from the central observation post (Fig. 1). The two rooms where presurgical evaluation is performed are the nearest and can be reached within 10 s. Rooms are designed to minimize fall-related injury (no sharp points, (not-padded) guard rails) (Fig. 2). Where there is a history of tonic–clonic seizures, nocturnal hyperkinetic events or antiseizure medication (ASM) tapering, soft mattresses are placed on the floor next to the bed, which is lowered
during the night. Individuals can use a seizure alarm button if they anticipate an event. Patients may walk about but should not go outside the room. They are continuously observed by trained nurses in the central observation room: 3 nurses from 7 am to 11 pm and 2 nurses from 11 pm to 7 am. Observation includes use of 4 adjustable full-HD cameras (including infrared during the night), EEG, single-lead electrocardiogram (ECG), and sound per individual, but online seizure detection software is not used. Four neurologists/clinical neurophysiologists are responsible for the EMU, and the team also has 10 EEG technologists, a physician assistant and a technical physician. Each patient is
Fig. 2. A patient room at the EMU, designed to minimize injury in case of a fall.
F. Cox et al. / Epilepsy & Behavior 102 (2020) 106718
interviewed on admission concerning epilepsy characteristics and comorbidities, and a risk evaluation is made (previous falls, tonic–clonic seizures, nocturnal hyperkinetic events, status epilepticus, use of anticoagulants). Clinical rounds with nurses, EEG technicians, physician assistant, technical physician, and supervising neurologists are carried out twice daily. A local guideline for ASM tapering is used (generally reduction of one ASM per day by one third to half the daily dose); ASM tapering is individualized based on this guideline, influenced by the type of ASM, seizure frequency, history of status epilepticus, seizure clustering, and seizure type. A protocol for neurocognitive testing during a seizure is also used. Each patient has an individualized protocol for acute seizure treatment and seizure clustering, also based on the history. Intranasal midazolam is usually prescribed for acute seizure treatment as no IV medication is used. In the Netherlands, intranasal midazolam is currently prepared in a hospital pharmacy as a special preparation. During ASM tapering, acute seizure rescue treatment is prescribed for use if tonic–clonic activity lasts for more than 2 min. Oxygen and an automated external defibrillator are available, and the complete EMU team has yearly training in resuscitation. A neurologist is on duty 24 h a day in case of medical emergencies. If status epilepticus does not respond to treatment, individuals can be transferred to the nearby general hospital for IV treatment and further cardiorespiratory support.
3
3. Results 3.1. General findings There were 1062 admissions, comprising 1518 EMU days. A total of 183 recordings were done with the primary goal of event recording (83 for presurgical evaluation — 8% of all admissions). In 423 of all admissions (40%), one or more habitual events occurred, of which 252 were of epileptic origin (60%) and 62 were with diagnosed psychogenic nonepileptic seizures (PNES) (15%). Demographic data and other admission characteristics are shown in Table 1. For safety issues, in 5 individuals (4 for presurgical screening, one for event recording), ambulation was restricted as the risk of falling was considered very high (onset of seizures with tonic–clonic activity in combination with ASM tapering); they called for a nurse if they wanted to move around in the room. In these four presurgical patients, ASM was tapered and the recording was considered successful. In none of these individuals did a complication occur. All presurgical patients where acute seizure treatment was required (n = 12) responded successfully to first-line seizure treatment (intranasal midazolam).
2.2. Adverse events From May 2018 to May 2019, AEs were prospectively collected after each admission at the time of finalizing the EEG report. We predefined the following three most commonly observed AEs [2]: • Status epilepticus, defined following the International League Against Epilepsy (ILAE) criteria [9] • Falls and fall-related injuries classified using the National Database of Nursing Quality Indicators (NDNQI) classification [10] • Postictal psychosis during or directly following the EMU visit. Injury levels were classified as follows: none (no signs or symptoms of injury); minor (resulting in pain, bruise, or abrasion, or requiring minor treatment); moderate (resulting in muscle/joint strain or requiring suturing, steristrips, skin glue, or splinting); major (resulting in internal injury or requiring neurological consultation, surgery, casting, or traction). The location of any falls was noted. Other, nonpredefined AEs occurring were noted. We also collected demographic data (age, gender), risk factors for AEs (previous tonic–clonic seizures, falls, or status epilepticus), ASM use, type of video-EEG recording, duration of recording, occurrence and classification of habitual events, and individualized safety measures. Diagnostic gain in case of event recording was noted and defined as follows: • For presurgical recordings, whether sufficient focal seizures occurred to make a hypothesis of the seizure onset zone, enabling a next step in the presurgical evaluation. • For 2–3 day event recording for other diagnostic purposes, whether sufficient events occurred to classify habitual events. For event recording and presurgical recordings, ASM tapering was noted, and the use of acute seizure rescue treatment in presurgical patients was also noted. Informed consent was not required, as the data were used as service evaluation. Data were entered in a database anonymously. For statistical analysis, IBM SPSS Statistics 23 was used. A Chi-square test for independence (with Yates continuity correction) was used to determine the statistical significance of the association between recording type and occurrence of an AE.
Table 1 General findings (N = 1062). Age in years (median and range) Gender M F Risk factors History of TCa Previous fall History of SEa ASM use Type of recording Diagnostic/classification Presurgical Other event recording Duration recording 0.5 day 1 day 2 days 3 days 4 days 5 days Recordings with events Types of event during recordings (N = 423) Epileptic PNESa Epileptic and PNES Uncertain Other Unknown Classification of epilepsy where seizures occurred (N = 256) Focal Generalized Focal and generalized Uncertain Unknown ASM tapering Presurgical (N = 83) b1/3 daily dose per day ≥1/3 daily dose per day Other event recording (N = 100) b1/3 daily dose per day ≥1/3 daily dose per day Individualized preventive measures Lowering beds, mattresses on floor Restricted ambulation Use of acute seizure treatment (presurgical recordings only) (N = 83)
26 (1–92) 510 (48%) 552 (52%) 579 (55%) 395 (37%) 63 (6%) 702 (66%) 879 (83%) 83 (8%) 100 (9%) 30 (3%) 851 (80%) 35 (3%) 71 (7%) 6 (1%) 69 (6%) 423 (40%) 252 (60%) 62 (15%) 4 (0.9%) 34 (8%) 67 (16%) 4 (0.9%) 167 (65%) 51 (20%) 3 (1%) 18 (7%) 17 (7%) 71 (86%) 22 (31%) 49 (69%) 11 6 (55%) 5 (45%) 646 (61%) 5 (0.5%) 12 (14%)
a ASM = antiseizure medication, TC = tonic–clonic seizure, SE = status epilepticus, PNES = psychogenic nonepileptic seizure.
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F. Cox et al. / Epilepsy & Behavior 102 (2020) 106718
the EEG electrodes. She was transferred back to the general ward for further treatment of the postictal psychosis.
3.2. Adverse events In total, 20 AEs occurred (total complication risk of 2%). Details are shown in Table 2. In presurgical recordings, 5 AEs were noted (complication risk in presurgical group: 6%). For other event recordings, there were 4 AEs (4% complication risk). For the shorter, diagnostic recordings, 11 AEs occurred (1% complication risk).There was a significant association between type of recording (diagnostic versus event recording) and the occurrence of AEs (p = .003). The most frequent complications were a fall (n = 10) and prescheduled ending of the recording by own will (n = 3). Of the falls (n = 10), six were classified as resulting in no injury and four with minor injury. Four occurred from lying in bed, four while standing in the room, one while standing in the bathroom, and one while sitting on the ground. In the four individuals who fell from the bed, the bed had been lowered and mattresses were on the ground as precautionary measures; only one of these falls was classified as producing a minor injury (pain neck/jaw area). In two children, status epilepticus occurred. A 6-year-old boy with a known SCN1A mutation had a history of frequent focal status epilepticus. Acute seizure treatment stopped the focal status episode successfully. The other, a 4-year-old girl, also with a history of focal status epilepticus (no known genetic cause) was transferred to a general hospital, after a 2.5-mg intranasal midazolam rescue medication, as a precautionary measure as she was known to have severe desaturations with higher doses of midazolam. In two cases, a postictal psychosis occurred. One individual was admitted to the EMU for presurgical recording. This individual had medically refractory focal epilepsy (with focal aware seizures and focal to bilateral tonic–clonic seizures), and a history of seizure clustering and postictal psychosis. During the EMU admission ASM was tapered, and 5 focal to bilateral tonic–clonic seizures occurred. Because of the previous history of postictal psychosis, after 5 days in the EMU, he was transferred to the general ward for observation. He developed postictal psychosis and was medically treated with consultation of a child psychiatrist. The other individual, with a prior diagnosis of focal epilepsy, was admitted for event recording. She had stopped her ASM 6 weeks previously as she experienced adverse effects. She was admitted to the general observation ward to optimize treatment, and was then transferred to the EMU for event recording to further classify the seizures and monitor seizure frequency. Two days prior to admission at the EMU, she had a focal to bilateral tonic–clonic seizure. During the EMU admission, progressive agitation and hallucinations developed, and she removed all
3.3. Diagnostic utility 3.3.1. Presurgical recordings In 71 (86%) of the 83 recordings, one or more seizures occurred, with a median of 4 seizures (range 0–40) per recording. Sixty-two (75%) recordings were considered to be successful; the diagnostic question could be answered. The median duration of recording was 5 days (range 2–5 days). 3.3.2. Other event recordings In 56 of the 100 recordings, one or more events occurred, with a median of one event (range 0–20) per recording. Classifications of events were as follows: epileptic (n = 23), PNES (n = 22), other (n = 4), and uncertain (n = 7). Forty-seven (47%) recordings were considered as successful, where the diagnostic question could be answered. The median duration of recording was 3 days (range 0–5 days). 4. Discussion We showed that the overall complication rate at our EMU is low. As was expected, the complication rate is the highest in admissions for presurgical evaluation, as the seizure frequency is usually high, and ASM is often tapered in order to provoke seizures. The complication rate in our presurgical patients was 6%, but without serious injury. This rate is comparable with studies from other EMUs, ranging from 5 to 9% [8,11–14], although comparing AEs between different EMUs is challenging. The occurrence of AEs is dependent on the type of monitoring and individuals monitored as shown above, factors that may differ between centers. Only one serious AE (postictal psychosis) occurred in a patient after ASM tapering. The diagnostic utility at our EMU was comparable with a previous study [11]. We conclude that our protocol of ASM tapering is effective, with a reasonable rate of AEs. A recent survey [15] showed that 70% EMUs in the E-PILEPSY network across 22 European countries use restricted ambulation. At our EMU, individuals are ambulant within the room. The overall fall risk was low, and none resulted in major injury. Previous studies at EMUs where ambulation is restricted describe fall rates of 2–3% [12,16]. Two retrospective studies describe serious injuries as a result of falls. One study describes AEs in 507 individuals only allowed to leave their bed
Table 2 Complications per case. Case
Adverse event
Gender
Age
Type of recording
ASM tapering
No. of events
Classification event
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Fall, minor injury Fall, minor injury Postictal psychosis Unhabitual tonic–clonic seizure Unhabitual clustering seizures Fall, no injury Fall, minor injury Postictal psychosis Prescheduled ending recording Fall, no injury Fall, no injury Fall, no injury Fall, no injury Fall, no injury Fall, minor injury SEa SE, transfer general hospital Prescheduled ending recording Prescheduled ending recording Puncture accident with sharp attribute in game
F F M F M M M F F F M F M F F M F M M M
56 7 13 9 17 66 25 23 17 5 16 20 28 9 77 6 4 33 40 7
Presurgical Presurgical Presurgical Presurgical Presurgical Event, other Event, other Event, other Event, other Diagnostic Diagnostic Diagnostic Diagnostic Diagnostic Diagnostic Diagnostic Diagnostic Diagnostic Diagnostic Diagnostic
≥1/3 No tapering ≥1/3 ≥1/3 ≥1/3 No ASM b1/3 No ASM No ASM – – – – – – – – – – –
8 17 5 5 9 1 5 0b 0 22 1 3 2 7 6 1 1 0 0 0
Epileptic Epileptic Epileptic Epileptic Epileptic PNESa Epileptic – – Epileptic Epileptic Epileptic and PNES Other Epileptic Other Epileptic Epileptic – – –
a b
ASM = antiseizure medication, PNES = psychogenic nonepileptic seizure, SE = status epilepticus. Tonic–clonic seizure 2 days prior to EMU admission.
F. Cox et al. / Epilepsy & Behavior 102 (2020) 106718
to go to the toilet in the company of a nurse [12]. How ASM were tapered is not described. Fourteen falls occurred with minor injury, of which almost half were from the bed. In two cases, nasal fractures occurred (one due to a fall from the bed, one after a toilet visit). In one case, an epidural hematoma resulted from a fall in the toilet. In the other study of 524 EMU admissions [14], one seizure-related fall outside the bed resulted in a nose fracture (restrictions concerning ambulation not further specified, ASM tapering generally half a dose per day). Other studies where individuals can leave their bed without assistance of staff report fall rates of 0.5–9.5% [8,11,14]. In a previous large prospective study with a similar design [8], but where individuals could be ambulant even outside their rooms, fall rate also was also very low (1.9%) with no injury requiring intervention. One study [17] showed that being restrained to the bed did not lead to fewer falls. Being ambulant is more comfortable than being restrained in bed, and compression stockings or administration of subcutaneous low molecular weight heparin is not necessary. Being ambulant also prevents complications of being bedridden, such as, pressure sores [18] and deep venous thrombosis. Therefore, we believe individuals admitted for noninvasive recording at a well-monitored EMU should be ambulant, unless there is a risk of severe falls. Consensus-based recommendations for patient safety in epilepsy monitoring units describe the need for IV access from the beginning of the monitoring period in all patients [6] or in those in whom ASM is tapered [7,19]. Intravenous line-related AEs have previously been described (9.5% of all AEs) at an EMU [14]. We showed that the use of a non-IV seizure rescue treatment, mostly intranasal midazolam, is effective as acute seizure treatment in preventing status epilepticus. This was also shown by another study [20], which found that intranasal midazolam is comparable with IV lorazepam for the treatment of prolonged seizures and prevention of status epilepticus and seizure clustering. We believe that intranasal midazolam should be the first choice treatment for seizure rescue medication at EMUs. 5. Conclusion As in our EMU, EMUs are safe places if preventive safety measures are in place. We believe that if EMU safety measures are in place (proper surveillance, safely designed rooms), people undergoing noninvasive video-EEG recordings should be ambulant, and there is no need for preventive placing of IV lines. Declaration of competing interest The authors report no conflict of interest. References [1] Rose AB, McCabe PH, Gilliam FG, Smith BJ, Boggs JG, Ficker DM, et al. Occurrence of seizure clusters and status epilepticus during inpatient video-EEG monitoring. Neurology 2003;60:975–8. https://doi.org/10.1212/01.WNL.0000053748.83309.28.
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[2] Shafer PO, Buelow J, Ficker DM, Pugh MJ, Kanner AM, Dean P, et al. Risk of adverse events on epilepsy monitoring units: a survey of epilepsy professionals. Epilepsy Behav 2011;20:502–5. https://doi.org/10.1016/j.yebeh.2010.12.048. [3] Ryvlin P, Nashef L, Lhatoo SD, Bateman LM, Bird J, Bleasel A, et al. Incidence and mechanisms of cardiorespiratory arrests in epilepsy monitoring units (MORTEMUS): a retrospective study. Lancet Neurol 2013;12:966–77. https://doi. org/10.1016/S1474-4422(13)70214-X. [4] Sauro KM, Wiebe N, Macrodimitris S, Wiebe S, Lukmanji S, Jetté N. Quality and safety in adult epilepsy monitoring units: a systematic review and meta-analysis. Epilepsia 2016;57:1754–70. https://doi.org/10.1111/epi.13564. [5] Labiner DM, Bagic AI, Herman ST, Fountain NB, Walczak TS, Gumnit RJ. Essential services, personnel, and facilities in specialized epilepsy centers — revised 2010 guidelines. Epilepsia 2010;51:2322–33. https://doi.org/10.1111/j.1528-1167.2010.02648.x. [6] Shafer PO, Buelow JM, Noe K, Shinnar R, Dewar S, Levisohn PM, et al. A consensusbased approach to patient safety in epilepsy monitoring units: recommendations for preferred practices. Epilepsy Behav 2012;25:449–56. https://doi.org/10.1016/j. yebeh.2012.07.014. [7] Hamandi K, Beniczky S, Diehl B, Kandler RH, Pressler RM, Sen A, et al. Current practice and recommendations in UK epilepsy monitoring units. Report of a national survey and workshop. Seizure 2017;50:92–8. https://doi.org/10.1016/j.seizure.2017.06. 015. [8] Craciun L, Alving J, Gardella E, Terney D, Meritam P, Cacic Hribljan M, et al. Do patients need to stay in bed all day in the epilepsy monitoring unit? Safety data from a non-restrictive setting. Seizure 2017;49:13–6. https://doi.org/10.1016/j.seizure. 2017.05.006. [9] Trinka E, Cock H, Hesdorffer D, Rossetti AO, Scheffer IE, Shinnar S, et al. A definition and classification of status epilepticus — report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia 2015;56:1515–23. https://doi.org/10.1111/epi. 13121. [10] Staggs VS, Mion LC, Shorr RI. Assisted and unassisted falls: different events, different outcomes, different implications for quality of hospital care. Jt Comm J Qual Patient Saf 2014;40:358–64. https://doi.org/10.1016/S1553-7250(14)40047-3. [11] Sauro KM, Macrodimitris S, Krassman C, Wiebe S, Pillay N, Federico P, et al. Quality indicators in an epilepsy monitoring unit. Epilepsy Behav 2014;33:7–11. https:// doi.org/10.1016/j.yebeh.2014.01.021. [12] Dobesberger J, Walser G, Unterberger I, Seppi K, Kuchukhidze G, Larch J, et al. VideoEEG monitoring: safety and adverse events in 507 consecutive patients. Epilepsia 2011;52:443–52. https://doi.org/10.1111/j.1528-1167.2010.02782.x. [13] Ley M, Vivanco R, Massot A, Jiménez J, Roquer J, Rocamora R. Safety study of longterm video-electroencephalogram monitoring. Neurol (English Ed) 2014;29:21–6. https://doi.org/10.1016/j.nrleng.2013.03.001. [14] Fahoum F, Omer N, Kipervasser S, Bar-Adon T, Neufeld M. Safety in the epilepsy monitoring unit: a retrospective study of 524 consecutive admissions. Epilepsy Behav 2016;61:162–7. https://doi.org/10.1016/j.yebeh.2016.06.002. [15] Kobulashvili T, Höfler J, Dobesberger J, Ernst F, Ryvlin P, Cross JH, et al. Current practices in long-term video-EEG monitoring services: a survey among partners of the EPILEPSY pilot network of reference for refractory epilepsy and epilepsy surgery. Seizure 2016;38:38–45. https://doi.org/10.1016/j.seizure.2016.03.009. [16] Dobesberger J, Höfler J, Leitinger M, Kuchukhidze G, Zimmermann G, Thomschewski A, et al. Personalized safety measures reduce the adverse event rate of long-term video EEG. Epilepsia Open 2017;2:400–14. https://doi.org/10.1002/epi4.12078. [17] Spanaki MV, McCloskey C, Remedio V, Budzyn D, Guanio J, Monroe T, et al. Developing a culture of safety in the epilepsy monitoring unit: a retrospective study of safety outcomes. Epilepsy Behav 2012;25:185–8. https://doi.org/10.1016/j.yebeh.2012.06. 028. [18] Noppornprom C, TY. Quality and safety in adult epilepsy monitoring unit of Prasat Neurological Institute epilepsy center. Poster presentation 33rd International Epilepsy Congress, Bangkok Thailand; 2019. [19] Pressler RM, Seri S, Kane N, Martland T, Goyal S, Iyer A, et al. Consensus-based guidelines for video EEG monitoring in the pre-surgical evaluation of children with epilepsy in the UK. Seizure 2017;50:6–11. https://doi.org/10.1016/j.seizure.2017.05. 008. [20] Owusu KA, Dhakar MB, Bautista C, McKimmy D, Cotugno S, Sukumar N, et al. Comparison of intranasal midazolam versus intravenous lorazepam for seizure termination and prevention of seizure clusters in the adult epilepsy monitoring unit. Epilepsy Behav 2019;98:161–7. https://doi.org/10.1016/j.yebeh.2019.07.021.
Contents lists available at ScienceDirect
Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh
Epilepsy monitoring units can be safe places; a prospective study in a large cohort Fieke Cox ⁎, Elise Reus, Guido Widman, Jack Zwemmer, Gerhard Visser Department of Clinical Neurophysiology, Stichting Epilepsie Instellingen Nederland (SEIN), the Netherlands
a r t i c l e
i n f o
Article history: Received 15 October 2019 Revised 12 November 2019 Accepted 13 November 2019 Available online xxxx Keywords: EMU Safety Diagnostic utility Adverse events Video-EEG recording
a b s t r a c t Objective: No international guideline is available for minimum safety measures at epilepsy monitoring units (EMUs), although recommendations for preferred practices exist. These are mostly based on expert opinion, without evidence of effectiveness. We do not apply all of these preferred practices at our EMU setting. We audited adverse events and diagnostic utility at our EMU over one year. Methods: From May 2018 to May 2019, we prospectively collected data concerning adverse events and diagnostic utility of all EMU admissions (noninvasive video-electroencephalogram (EEG) recordings); during these admissions, individuals can be ambulant within their EMU room. Results: There were 1062 admissions comprising 1518 EMU days. In 2% of the admissions, a complication occurred, mostly a fall without injury (n = 6). In almost half of the falls, this was from the bed. Complications occurred most often during admissions for presurgical evaluation. Antiseizure medication (ASM) was tapered in 86% of presurgical cases, but no serious injury occurred, and occurring seizures were effectively treated with intranasal midazolam if needed. Conclusions: The overall adverse event rate was low. Falls are the most common adverse event comparable with previously published fall rates at other EMUs where people are restricted to their bed. We showed that restricted ambulation at a well-monitored EMU is not necessary and possibly unwanted. No serious injury due to tapering of ASM occurred, and intranasal midazolam was shown to be effective as acute seizure treatment. © 2019 Elsevier Inc. All rights reserved.
1. Introduction In epilepsy monitoring units (EMUs), people are admitted for prolonged video-electroencephalogram (EEG) recording. Aims included the following: finding interictal EEG abnormalities if standard EEG recording is inconclusive; recording clinical events, diagnosing epilepsy or mimickers; or evaluating individuals for epilepsy surgery by recording ictal events. To increase the effectiveness of EMU admissions, provocation measures (such as, drug tapering or night sleep deprivation) are often used to induce (epileptic) events. Because of the nature of epilepsy and the type of admission, people admitted to EMUs are prone to specific adverse events (AEs). Adverse events due to the habitual events include falls or injury; Because of provocative measures, seizure frequency and severity can be increased. Faster propagation to bilateral tonic–clonic activity, seizure clustering, and status epilepticus can also occur [1,2]. Postictal psychosis and even SUDEP have been described in EMU settings [2,3]. A systematic review including 33 studies reporting AEs at EMUs showed a pooled proportion of AEs of 7%, with ⁎ Corresponding author at: Stichting Epilepsie Instellingen Nederland, PO Box 540, 2130 AM Hoofddorp, the Netherlands. E-mail address: [email protected] (F. Cox).
https://doi.org/10.1016/j.yebeh.2019.106718 1525-5050/© 2019 Elsevier Inc. All rights reserved.
significant heterogeneity [4]. Minimal safety guidelines and recommendations for EMUs have been published [5–7], but these reflect expert opinion and are consensus-based; additionally, not all preventive measures have been shown to be effective. There is still no general accepted guideline concerning (minimum) safety measures, and there is large variation in safety measures at different EMUs. We have not implemented all safety measures previously suggested (e.g., intravenous (IV) access, restricted ambulation) in our EMU. A previous study showed that a nonrestrictive EMU setting can be as efficient for individuals safety as limiting their mobility [8]. We prospectively assessed the safety and quality of care at our EMU in a tertiary epilepsy center in the Netherlands as a service evaluation. 2. Methods 2.1. The epilepsy monitoring unit The EMU comprises 8 single-patient bedrooms (including a bathroom with outswing doors) open from Monday to Friday. Two beds are reserved for presurgical evaluation. The other beds are used for up to 24-hour video-EEG recording for (interictal) diagnostic/classification purposes and multiple-day video-EEG recording for event recording (to
2
F. Cox et al. / Epilepsy & Behavior 102 (2020) 106718
Fig. 1. The central observation post at the EMU:
classify events); most are planned for 2–3 days. Only noninvasive videoEEG monitoring is performed. Adults and children (accompanied by a caregiver) are admitted. The EMU is designed so that the rooms are within a 20-second walk from the central observation post (Fig. 1). The two rooms where presurgical evaluation is performed are the nearest and can be reached within 10 s. Rooms are designed to minimize fall-related injury (no sharp points, (not-padded) guard rails) (Fig. 2). Where there is a history of tonic–clonic seizures, nocturnal hyperkinetic events or antiseizure medication (ASM) tapering, soft mattresses are placed on the floor next to the bed, which is lowered
during the night. Individuals can use a seizure alarm button if they anticipate an event. Patients may walk about but should not go outside the room. They are continuously observed by trained nurses in the central observation room: 3 nurses from 7 am to 11 pm and 2 nurses from 11 pm to 7 am. Observation includes use of 4 adjustable full-HD cameras (including infrared during the night), EEG, single-lead electrocardiogram (ECG), and sound per individual, but online seizure detection software is not used. Four neurologists/clinical neurophysiologists are responsible for the EMU, and the team also has 10 EEG technologists, a physician assistant and a technical physician. Each patient is
Fig. 2. A patient room at the EMU, designed to minimize injury in case of a fall.
F. Cox et al. / Epilepsy & Behavior 102 (2020) 106718
interviewed on admission concerning epilepsy characteristics and comorbidities, and a risk evaluation is made (previous falls, tonic–clonic seizures, nocturnal hyperkinetic events, status epilepticus, use of anticoagulants). Clinical rounds with nurses, EEG technicians, physician assistant, technical physician, and supervising neurologists are carried out twice daily. A local guideline for ASM tapering is used (generally reduction of one ASM per day by one third to half the daily dose); ASM tapering is individualized based on this guideline, influenced by the type of ASM, seizure frequency, history of status epilepticus, seizure clustering, and seizure type. A protocol for neurocognitive testing during a seizure is also used. Each patient has an individualized protocol for acute seizure treatment and seizure clustering, also based on the history. Intranasal midazolam is usually prescribed for acute seizure treatment as no IV medication is used. In the Netherlands, intranasal midazolam is currently prepared in a hospital pharmacy as a special preparation. During ASM tapering, acute seizure rescue treatment is prescribed for use if tonic–clonic activity lasts for more than 2 min. Oxygen and an automated external defibrillator are available, and the complete EMU team has yearly training in resuscitation. A neurologist is on duty 24 h a day in case of medical emergencies. If status epilepticus does not respond to treatment, individuals can be transferred to the nearby general hospital for IV treatment and further cardiorespiratory support.
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3. Results 3.1. General findings There were 1062 admissions, comprising 1518 EMU days. A total of 183 recordings were done with the primary goal of event recording (83 for presurgical evaluation — 8% of all admissions). In 423 of all admissions (40%), one or more habitual events occurred, of which 252 were of epileptic origin (60%) and 62 were with diagnosed psychogenic nonepileptic seizures (PNES) (15%). Demographic data and other admission characteristics are shown in Table 1. For safety issues, in 5 individuals (4 for presurgical screening, one for event recording), ambulation was restricted as the risk of falling was considered very high (onset of seizures with tonic–clonic activity in combination with ASM tapering); they called for a nurse if they wanted to move around in the room. In these four presurgical patients, ASM was tapered and the recording was considered successful. In none of these individuals did a complication occur. All presurgical patients where acute seizure treatment was required (n = 12) responded successfully to first-line seizure treatment (intranasal midazolam).
2.2. Adverse events From May 2018 to May 2019, AEs were prospectively collected after each admission at the time of finalizing the EEG report. We predefined the following three most commonly observed AEs [2]: • Status epilepticus, defined following the International League Against Epilepsy (ILAE) criteria [9] • Falls and fall-related injuries classified using the National Database of Nursing Quality Indicators (NDNQI) classification [10] • Postictal psychosis during or directly following the EMU visit. Injury levels were classified as follows: none (no signs or symptoms of injury); minor (resulting in pain, bruise, or abrasion, or requiring minor treatment); moderate (resulting in muscle/joint strain or requiring suturing, steristrips, skin glue, or splinting); major (resulting in internal injury or requiring neurological consultation, surgery, casting, or traction). The location of any falls was noted. Other, nonpredefined AEs occurring were noted. We also collected demographic data (age, gender), risk factors for AEs (previous tonic–clonic seizures, falls, or status epilepticus), ASM use, type of video-EEG recording, duration of recording, occurrence and classification of habitual events, and individualized safety measures. Diagnostic gain in case of event recording was noted and defined as follows: • For presurgical recordings, whether sufficient focal seizures occurred to make a hypothesis of the seizure onset zone, enabling a next step in the presurgical evaluation. • For 2–3 day event recording for other diagnostic purposes, whether sufficient events occurred to classify habitual events. For event recording and presurgical recordings, ASM tapering was noted, and the use of acute seizure rescue treatment in presurgical patients was also noted. Informed consent was not required, as the data were used as service evaluation. Data were entered in a database anonymously. For statistical analysis, IBM SPSS Statistics 23 was used. A Chi-square test for independence (with Yates continuity correction) was used to determine the statistical significance of the association between recording type and occurrence of an AE.
Table 1 General findings (N = 1062). Age in years (median and range) Gender M F Risk factors History of TCa Previous fall History of SEa ASM use Type of recording Diagnostic/classification Presurgical Other event recording Duration recording 0.5 day 1 day 2 days 3 days 4 days 5 days Recordings with events Types of event during recordings (N = 423) Epileptic PNESa Epileptic and PNES Uncertain Other Unknown Classification of epilepsy where seizures occurred (N = 256) Focal Generalized Focal and generalized Uncertain Unknown ASM tapering Presurgical (N = 83) b1/3 daily dose per day ≥1/3 daily dose per day Other event recording (N = 100) b1/3 daily dose per day ≥1/3 daily dose per day Individualized preventive measures Lowering beds, mattresses on floor Restricted ambulation Use of acute seizure treatment (presurgical recordings only) (N = 83)
26 (1–92) 510 (48%) 552 (52%) 579 (55%) 395 (37%) 63 (6%) 702 (66%) 879 (83%) 83 (8%) 100 (9%) 30 (3%) 851 (80%) 35 (3%) 71 (7%) 6 (1%) 69 (6%) 423 (40%) 252 (60%) 62 (15%) 4 (0.9%) 34 (8%) 67 (16%) 4 (0.9%) 167 (65%) 51 (20%) 3 (1%) 18 (7%) 17 (7%) 71 (86%) 22 (31%) 49 (69%) 11 6 (55%) 5 (45%) 646 (61%) 5 (0.5%) 12 (14%)
a ASM = antiseizure medication, TC = tonic–clonic seizure, SE = status epilepticus, PNES = psychogenic nonepileptic seizure.
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the EEG electrodes. She was transferred back to the general ward for further treatment of the postictal psychosis.
3.2. Adverse events In total, 20 AEs occurred (total complication risk of 2%). Details are shown in Table 2. In presurgical recordings, 5 AEs were noted (complication risk in presurgical group: 6%). For other event recordings, there were 4 AEs (4% complication risk). For the shorter, diagnostic recordings, 11 AEs occurred (1% complication risk).There was a significant association between type of recording (diagnostic versus event recording) and the occurrence of AEs (p = .003). The most frequent complications were a fall (n = 10) and prescheduled ending of the recording by own will (n = 3). Of the falls (n = 10), six were classified as resulting in no injury and four with minor injury. Four occurred from lying in bed, four while standing in the room, one while standing in the bathroom, and one while sitting on the ground. In the four individuals who fell from the bed, the bed had been lowered and mattresses were on the ground as precautionary measures; only one of these falls was classified as producing a minor injury (pain neck/jaw area). In two children, status epilepticus occurred. A 6-year-old boy with a known SCN1A mutation had a history of frequent focal status epilepticus. Acute seizure treatment stopped the focal status episode successfully. The other, a 4-year-old girl, also with a history of focal status epilepticus (no known genetic cause) was transferred to a general hospital, after a 2.5-mg intranasal midazolam rescue medication, as a precautionary measure as she was known to have severe desaturations with higher doses of midazolam. In two cases, a postictal psychosis occurred. One individual was admitted to the EMU for presurgical recording. This individual had medically refractory focal epilepsy (with focal aware seizures and focal to bilateral tonic–clonic seizures), and a history of seizure clustering and postictal psychosis. During the EMU admission ASM was tapered, and 5 focal to bilateral tonic–clonic seizures occurred. Because of the previous history of postictal psychosis, after 5 days in the EMU, he was transferred to the general ward for observation. He developed postictal psychosis and was medically treated with consultation of a child psychiatrist. The other individual, with a prior diagnosis of focal epilepsy, was admitted for event recording. She had stopped her ASM 6 weeks previously as she experienced adverse effects. She was admitted to the general observation ward to optimize treatment, and was then transferred to the EMU for event recording to further classify the seizures and monitor seizure frequency. Two days prior to admission at the EMU, she had a focal to bilateral tonic–clonic seizure. During the EMU admission, progressive agitation and hallucinations developed, and she removed all
3.3. Diagnostic utility 3.3.1. Presurgical recordings In 71 (86%) of the 83 recordings, one or more seizures occurred, with a median of 4 seizures (range 0–40) per recording. Sixty-two (75%) recordings were considered to be successful; the diagnostic question could be answered. The median duration of recording was 5 days (range 2–5 days). 3.3.2. Other event recordings In 56 of the 100 recordings, one or more events occurred, with a median of one event (range 0–20) per recording. Classifications of events were as follows: epileptic (n = 23), PNES (n = 22), other (n = 4), and uncertain (n = 7). Forty-seven (47%) recordings were considered as successful, where the diagnostic question could be answered. The median duration of recording was 3 days (range 0–5 days). 4. Discussion We showed that the overall complication rate at our EMU is low. As was expected, the complication rate is the highest in admissions for presurgical evaluation, as the seizure frequency is usually high, and ASM is often tapered in order to provoke seizures. The complication rate in our presurgical patients was 6%, but without serious injury. This rate is comparable with studies from other EMUs, ranging from 5 to 9% [8,11–14], although comparing AEs between different EMUs is challenging. The occurrence of AEs is dependent on the type of monitoring and individuals monitored as shown above, factors that may differ between centers. Only one serious AE (postictal psychosis) occurred in a patient after ASM tapering. The diagnostic utility at our EMU was comparable with a previous study [11]. We conclude that our protocol of ASM tapering is effective, with a reasonable rate of AEs. A recent survey [15] showed that 70% EMUs in the E-PILEPSY network across 22 European countries use restricted ambulation. At our EMU, individuals are ambulant within the room. The overall fall risk was low, and none resulted in major injury. Previous studies at EMUs where ambulation is restricted describe fall rates of 2–3% [12,16]. Two retrospective studies describe serious injuries as a result of falls. One study describes AEs in 507 individuals only allowed to leave their bed
Table 2 Complications per case. Case
Adverse event
Gender
Age
Type of recording
ASM tapering
No. of events
Classification event
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Fall, minor injury Fall, minor injury Postictal psychosis Unhabitual tonic–clonic seizure Unhabitual clustering seizures Fall, no injury Fall, minor injury Postictal psychosis Prescheduled ending recording Fall, no injury Fall, no injury Fall, no injury Fall, no injury Fall, no injury Fall, minor injury SEa SE, transfer general hospital Prescheduled ending recording Prescheduled ending recording Puncture accident with sharp attribute in game
F F M F M M M F F F M F M F F M F M M M
56 7 13 9 17 66 25 23 17 5 16 20 28 9 77 6 4 33 40 7
Presurgical Presurgical Presurgical Presurgical Presurgical Event, other Event, other Event, other Event, other Diagnostic Diagnostic Diagnostic Diagnostic Diagnostic Diagnostic Diagnostic Diagnostic Diagnostic Diagnostic Diagnostic
≥1/3 No tapering ≥1/3 ≥1/3 ≥1/3 No ASM b1/3 No ASM No ASM – – – – – – – – – – –
8 17 5 5 9 1 5 0b 0 22 1 3 2 7 6 1 1 0 0 0
Epileptic Epileptic Epileptic Epileptic Epileptic PNESa Epileptic – – Epileptic Epileptic Epileptic and PNES Other Epileptic Other Epileptic Epileptic – – –
a b
ASM = antiseizure medication, PNES = psychogenic nonepileptic seizure, SE = status epilepticus. Tonic–clonic seizure 2 days prior to EMU admission.
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to go to the toilet in the company of a nurse [12]. How ASM were tapered is not described. Fourteen falls occurred with minor injury, of which almost half were from the bed. In two cases, nasal fractures occurred (one due to a fall from the bed, one after a toilet visit). In one case, an epidural hematoma resulted from a fall in the toilet. In the other study of 524 EMU admissions [14], one seizure-related fall outside the bed resulted in a nose fracture (restrictions concerning ambulation not further specified, ASM tapering generally half a dose per day). Other studies where individuals can leave their bed without assistance of staff report fall rates of 0.5–9.5% [8,11,14]. In a previous large prospective study with a similar design [8], but where individuals could be ambulant even outside their rooms, fall rate also was also very low (1.9%) with no injury requiring intervention. One study [17] showed that being restrained to the bed did not lead to fewer falls. Being ambulant is more comfortable than being restrained in bed, and compression stockings or administration of subcutaneous low molecular weight heparin is not necessary. Being ambulant also prevents complications of being bedridden, such as, pressure sores [18] and deep venous thrombosis. Therefore, we believe individuals admitted for noninvasive recording at a well-monitored EMU should be ambulant, unless there is a risk of severe falls. Consensus-based recommendations for patient safety in epilepsy monitoring units describe the need for IV access from the beginning of the monitoring period in all patients [6] or in those in whom ASM is tapered [7,19]. Intravenous line-related AEs have previously been described (9.5% of all AEs) at an EMU [14]. We showed that the use of a non-IV seizure rescue treatment, mostly intranasal midazolam, is effective as acute seizure treatment in preventing status epilepticus. This was also shown by another study [20], which found that intranasal midazolam is comparable with IV lorazepam for the treatment of prolonged seizures and prevention of status epilepticus and seizure clustering. We believe that intranasal midazolam should be the first choice treatment for seizure rescue medication at EMUs. 5. Conclusion As in our EMU, EMUs are safe places if preventive safety measures are in place. We believe that if EMU safety measures are in place (proper surveillance, safely designed rooms), people undergoing noninvasive video-EEG recordings should be ambulant, and there is no need for preventive placing of IV lines. Declaration of competing interest The authors report no conflict of interest. References [1] Rose AB, McCabe PH, Gilliam FG, Smith BJ, Boggs JG, Ficker DM, et al. Occurrence of seizure clusters and status epilepticus during inpatient video-EEG monitoring. Neurology 2003;60:975–8. https://doi.org/10.1212/01.WNL.0000053748.83309.28.
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[2] Shafer PO, Buelow J, Ficker DM, Pugh MJ, Kanner AM, Dean P, et al. Risk of adverse events on epilepsy monitoring units: a survey of epilepsy professionals. Epilepsy Behav 2011;20:502–5. https://doi.org/10.1016/j.yebeh.2010.12.048. [3] Ryvlin P, Nashef L, Lhatoo SD, Bateman LM, Bird J, Bleasel A, et al. Incidence and mechanisms of cardiorespiratory arrests in epilepsy monitoring units (MORTEMUS): a retrospective study. Lancet Neurol 2013;12:966–77. https://doi. org/10.1016/S1474-4422(13)70214-X. [4] Sauro KM, Wiebe N, Macrodimitris S, Wiebe S, Lukmanji S, Jetté N. Quality and safety in adult epilepsy monitoring units: a systematic review and meta-analysis. Epilepsia 2016;57:1754–70. https://doi.org/10.1111/epi.13564. [5] Labiner DM, Bagic AI, Herman ST, Fountain NB, Walczak TS, Gumnit RJ. Essential services, personnel, and facilities in specialized epilepsy centers — revised 2010 guidelines. Epilepsia 2010;51:2322–33. https://doi.org/10.1111/j.1528-1167.2010.02648.x. [6] Shafer PO, Buelow JM, Noe K, Shinnar R, Dewar S, Levisohn PM, et al. A consensusbased approach to patient safety in epilepsy monitoring units: recommendations for preferred practices. Epilepsy Behav 2012;25:449–56. https://doi.org/10.1016/j. yebeh.2012.07.014. [7] Hamandi K, Beniczky S, Diehl B, Kandler RH, Pressler RM, Sen A, et al. Current practice and recommendations in UK epilepsy monitoring units. Report of a national survey and workshop. Seizure 2017;50:92–8. https://doi.org/10.1016/j.seizure.2017.06. 015. [8] Craciun L, Alving J, Gardella E, Terney D, Meritam P, Cacic Hribljan M, et al. Do patients need to stay in bed all day in the epilepsy monitoring unit? Safety data from a non-restrictive setting. Seizure 2017;49:13–6. https://doi.org/10.1016/j.seizure. 2017.05.006. [9] Trinka E, Cock H, Hesdorffer D, Rossetti AO, Scheffer IE, Shinnar S, et al. A definition and classification of status epilepticus — report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia 2015;56:1515–23. https://doi.org/10.1111/epi. 13121. [10] Staggs VS, Mion LC, Shorr RI. Assisted and unassisted falls: different events, different outcomes, different implications for quality of hospital care. Jt Comm J Qual Patient Saf 2014;40:358–64. https://doi.org/10.1016/S1553-7250(14)40047-3. [11] Sauro KM, Macrodimitris S, Krassman C, Wiebe S, Pillay N, Federico P, et al. Quality indicators in an epilepsy monitoring unit. Epilepsy Behav 2014;33:7–11. https:// doi.org/10.1016/j.yebeh.2014.01.021. [12] Dobesberger J, Walser G, Unterberger I, Seppi K, Kuchukhidze G, Larch J, et al. VideoEEG monitoring: safety and adverse events in 507 consecutive patients. Epilepsia 2011;52:443–52. https://doi.org/10.1111/j.1528-1167.2010.02782.x. [13] Ley M, Vivanco R, Massot A, Jiménez J, Roquer J, Rocamora R. Safety study of longterm video-electroencephalogram monitoring. Neurol (English Ed) 2014;29:21–6. https://doi.org/10.1016/j.nrleng.2013.03.001. [14] Fahoum F, Omer N, Kipervasser S, Bar-Adon T, Neufeld M. Safety in the epilepsy monitoring unit: a retrospective study of 524 consecutive admissions. Epilepsy Behav 2016;61:162–7. https://doi.org/10.1016/j.yebeh.2016.06.002. [15] Kobulashvili T, Höfler J, Dobesberger J, Ernst F, Ryvlin P, Cross JH, et al. Current practices in long-term video-EEG monitoring services: a survey among partners of the EPILEPSY pilot network of reference for refractory epilepsy and epilepsy surgery. Seizure 2016;38:38–45. https://doi.org/10.1016/j.seizure.2016.03.009. [16] Dobesberger J, Höfler J, Leitinger M, Kuchukhidze G, Zimmermann G, Thomschewski A, et al. Personalized safety measures reduce the adverse event rate of long-term video EEG. Epilepsia Open 2017;2:400–14. https://doi.org/10.1002/epi4.12078. [17] Spanaki MV, McCloskey C, Remedio V, Budzyn D, Guanio J, Monroe T, et al. Developing a culture of safety in the epilepsy monitoring unit: a retrospective study of safety outcomes. Epilepsy Behav 2012;25:185–8. https://doi.org/10.1016/j.yebeh.2012.06. 028. [18] Noppornprom C, TY. Quality and safety in adult epilepsy monitoring unit of Prasat Neurological Institute epilepsy center. Poster presentation 33rd International Epilepsy Congress, Bangkok Thailand; 2019. [19] Pressler RM, Seri S, Kane N, Martland T, Goyal S, Iyer A, et al. Consensus-based guidelines for video EEG monitoring in the pre-surgical evaluation of children with epilepsy in the UK. Seizure 2017;50:6–11. https://doi.org/10.1016/j.seizure.2017.05. 008. [20] Owusu KA, Dhakar MB, Bautista C, McKimmy D, Cotugno S, Sukumar N, et al. Comparison of intranasal midazolam versus intravenous lorazepam for seizure termination and prevention of seizure clusters in the adult epilepsy monitoring unit. Epilepsy Behav 2019;98:161–7. https://doi.org/10.1016/j.yebeh.2019.07.021.