Outcome Of Refractory Status Epilepticus Research Articles

OUTCOMES OF REFRACTORY STATUS EPILEPTICUS IN CHILDREN

Objective: To determine the outcome of Refractory Status Epilepticus (RSE) in children and the factors affecting the outcome. 
 Study Design: Cross-sectional study.
 Place and Duration of Study: High Dependency Unit of Pediatrics Neurology Department at the Children’s Hospital and Institute of Child Health, from Aug 2019 to Mar 2020.
 Methodology: This study was conducted on the children presenting with refractory status epilepticus. Structured proforma was used for recording predictive factors. Modified Rankin scale prior to the presentation and Glasgow Coma Scale at presentation were documented and compared with the discharge scores.
 Results: Out of 75 children, 46 (61.4%) were males with mean age of 4.43 ± 3.47 years. Common etiologies were acute symptomatic in 37 (49.3%), progressive encephalopathy in 19 (25.3%), static encephalopathy in 9 (11.9%), remote symptomatic in 4 (5.3%), acute on remote symptomatic in 3 (4.0%), idiopathic and unclassified in remaining patients. Mean time between seizures onset and first benzodiazepine injection was 44 ± 36 minutes. Duration of RSE was <24 hours in 17 (22.7%), 24-48 hours in 15 (20.0%), 48-72 hours in 14 (18.6%), 72-96 hours in 12 (16%) and >96 hours in 17 (22.7%). At discharge 33 (44%) returned to baseline, 31 (41%) developed neurological disability while 11 (15%) expired during the stay. Etiology and duration of status epilepticus had significant impact on outcome with p-value of 0.021 and 0.041, respectively.
 Conclusion: Acute etiology was associated with higher mortality whereas return to baseline was also fair among survivors. This poses implications for emergency management to significantly............

Impact of timing of continuous intravenous anesthetic drug treatment on outcome in refractory status epilepticus

BackgroundPatients in refractory status epilepticus (RSE) may require treatment with continuous intravenous anesthetic drugs (cIVADs) for seizure control. The use of cIVADs, however, was recently associated with poor outcome in status epilepticus (SE), raising the question of whether cIVAD therapy should be delayed for attempts to halt seizures with repeated non-anesthetic antiepileptic drugs. In this study, we aimed to determine the impact of differences in therapeutic approaches on RSE outcome using timing of cIVAD therapy as a surrogate for treatment aggressiveness.MethodsThis was a retrospective cohort study over 14 years (n = 77) comparing patients with RSE treated with cIVADs within and after 48 h after RSE onset, and functional status at last follow-up was the primary outcome (good = return to premorbid baseline or modified Rankin Scale score of less than 3). Secondary outcomes included discharge functional status, in-hospital mortality, RSE termination, induction of burst suppression, use of thiopental, duration of RSE after initiation of cIVADs, duration of mechanical ventilation, and occurrence of super-refractory SE. Analysis was performed on the total cohort and on subgroups defined by RSE severity according to the Status Epilepticus Severity Score (STESS) and by the variables contained therein.ResultsFifty-three (68.8%) patients received cIVADs within the first 48 h. Early cIVAD treatment was independently associated with good outcome (adjusted risk ratio [aRR] 3.175, 95% confidence interval [CI] 1.273–7.918; P = 0.013) as well as lower chance of both induction of burst suppression (aRR 0.661, 95% CI 0.507–0.861; P = 0.002) and use of thiopental (aRR 0.446, 95% CI 0.205–0.874; P = 0.043). RSE duration after cIVAD initiation was shorter in the early cIVAD cohort (hazard ratio 1.796, 95% CI 1.047–3.081; P = 0.033). Timing of cIVAD use did not impact the remaining secondary outcomes. Subgroup analysis revealed early cIVAD impact on the primary outcome to be driven by patients with STESS of less than 3.ConclusionsPatients with RSE treated with cIVADs may benefit from early initiation of such therapy.

Refractory status epilepticus: Impact of baseline comorbidity and usefulness of STESS and EMSE scoring systems in predicting mortality and functional outcome

PurposeLittle has been published on the prognostic value of the Status Epilepticus Severity Score (STESS) or the Epidemiology-based Mortality score in Status Epilepticus (EMSE) in refractory status epilepticus (RSE). We sought to analyze the prognostic value of STESS and EMSE and the impact of baseline comorbidities in mortality and functional outcome in RSE. MethodsWe designed an observational retrospective study of patients diagnosed with RSE between August 2013 and September 2017. For each patient, we analyzed prospectively recorded demographic, clinical, comorbidity, electroencephalographic, treatment, and hospital stay–related data and calculated STESS and EMSE. All variables were compared statistically between patients with good and poor functional outcome at discharge and between patients who died in hospital and those who were alive at discharge. ResultsFourty-nine patients had RSE; 35.4% died in hospital and 88% showed functional decline at discharge. Mortality was associated with baseline chronic kidney disease (CKD) (OR 19.25, p = 0.006), baseline modified Rankin scale score (mRS) (OR 3.38, p = 0.005), non-convulsive status epilepticus (NCSE) with coma (OR 11.9, p = 0.04), STESS (OR 2, p = 0.04), and EMSE (OR 1.3, p = 0.02). Functional outcome was associated with baseline mRS (OR 13.9, p = 0.02), and EMSE (OR 1.3, p = 0.02). The optimal cutoff scores for predicting mortality were 4 for STESS and 60 for EMSE. EMSE predicted functional outcome with an optimal cutoff of 40. ConclusionsCKD, NCSE with coma and STESS were associated with mortality. mRS and EMSE were associated with mortality and functional outcome. EMSE was useful for predicting functional outcome, while EMSE and STESS were useful for predicting in-hospital mortality.

A Comparative Study of Midazolam and Target-Controlled Propofol Infusion in the Treatment of Refractory Status Epilepticus.

Background:The recommended treatment for refractory status epilepticus (RSE) is the use of anesthetic agents, but evidence regarding the agent of choice is lacking. This study was designed to compare target-controlled infusion of propofol versus midazolam for the treatment of RSE regarding seizure control and complications.Methods:This prospective, randomized study recruited 23 adult patients with RSE due to any etiology and treated with either propofol or midazolam titrated to clinical seizure cessation and gradual tapering thereafter. The primary outcome measure was seizure control and the secondary outcomes were duration of the Intensive Care Unit stay and duration of mechanical ventilation, occurrence of super RSE (SRSE), and complications.Results:We recruited 23 patients (male:female = 18:5) into this study (propofol Group-11; midazolam Group-12). Overall, seizure control was noted in 34.8%, with successful seizure control in 45% of patients in the propofol group and 25% in midazolam group (P = 0.4). Mortality was similar in both the groups (propofol group [8/11; 72.7%] compared to the midazolam group [7/12; 58.3%] [P = 0.667]). The duration of hospital stay was significantly shorter in the propofol group compared to midazolam (P = 0.02). The overall incidence of SRSE was 69.5% in this study. The complication rate was not significantly different between the groups.Conclusions:The choice of anesthetic agent does not seem to affect the overall outcome in RSE and SRSE. Target-controlled propofol infusion was found to be equal in its efficacy to midazolam for the treatment of RSE. High mortality might be due to SRSE secondary to the underlying brain pathology.

Clinical predictors and outcomes of refractory status epilepticus in a large urban hospital. (P4.226)

Clinical predictors and outcomes of refractory status epilepticus in a large urban hospital. (P4.226)

Hypocapnea with mechanical ventilation and poor outcome of refractory status epilepticus (P6.067)

Hypocapnea with mechanical ventilation and poor outcome of refractory status epilepticus (P6.067)

Long-term outcome of refractory status epilepticus in adults: A retrospective population-based study

PurposeRefractory status epilepticus (RSE) is a neurological emergency with significant morbidity and mortality. We aimed to analyze the long-term outcome of intensive care unit (ICU)-treated RSE and super-refractory status epilepticus (SRSE) patients in a population based cohort. MethodsA retrospective study of ICU- and anesthesia-treated RSE patients in Kuopio University Hospital’s (KUH) special responsibility area hospitals in the central and eastern part of Finland from Jan. 1, 2010 to Dec. 31, 2012 was conducted. KUH’s catchment area consists of five hospitals—one university hospital and four central hospitals—and covers a population of 840 000. We included all consecutive adult (16 years or older) RSE patients admitted in the participating ICUs during the 3-year period and excluded patients with postanoxic etiologies. We used a modified Rankin Scale (mRS) as a long-term (1-year) outcome measure: good (mRS 0–3, recovered to baseline function) or poor (mRS 4–6, major functional deficit or death). Key findingsWe identified 75 patients with ICU- and anesthesia-treated RSE, corresponding to an annual incidence of 3.0 (95% confidence interval (CI) 2.4–3.8). 21% of the patients were classified as SRSE, with the annual incidence being 0.6/100 000 (95% CI 0.4–1.0). For RSE, the ICU mortality was 0%, hospital mortality was 7% (95% CI 1.2%–12.8%) (n=5), and one-year mortality was 23% (CI 95% 13.4%–32.5%) (n=17). 48% (n=36) of RSE patients recovered to baseline, and 29% (n=22) showed neurological deficit at 1year. Poor outcome (mRS 4–6) was recorded for 52% (n=39) of the patients. Older age was associated with poorer outcome at 1year (p=0.03). For SRSE, hospital mortality was 6% (n=1) and 1-year mortality was 19% (n=3) (95%CI 0%–38.2%). SignificanceDuring 1-year follow-up, nearly 50% of the ICU-treated RSE patients recovered to baseline function, whereas 30% showed new functional defects and 20% died. SRSE does not have a necessarily poorer outcome. The outcome is worse in older patients and in patients with progressive or fatal etiologies. SE should be treated with generalized anesthesia only in refractory cases after failure of adequately used first- and second-line antiepileptic drugs.

Propofol versus thiopental sodium for the treatment of refractory status epilepticus.

This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (Issue 6, 2015).Failure to respond to antiepileptic drugs in patients with uncontrolled seizure activity such as refractory status epilepticus (RSE) has led to the use of anaesthetic drugs. Coma is induced with anaesthetic drugs to achieve complete control of seizure activity. Thiopental sodium and propofol are popularly used for this purpose. Both agents have been found to be effective. However, there is a substantial lack of evidence as to which of the two drugs is better in terms of clinical outcomes. To compare the efficacy, adverse effects, and short- and long-term outcomes of refractory status epilepticus (RSE) treated with one of the two anaesthetic agents, thiopental sodium or propofol. We searched the Cochrane Epilepsy Group Specialized Register (16 August 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 16 August 2016), MEDLINE (Ovid, 1946 to 16 August 2016), ClinicalTrials.gov (16 August 2016), and the South Asian Database of Controlled Clinical Trials (16 August 2016). Previously we searched IndMED, but this was not accessible at the time of the latest update. All randomised controlled trials (RCTs) or quasi-RCTs (regardless of blinding) assessing the control of RSE using either thiopental sodium or propofol in patients of any age and gender. Two review authors screened the search results and reviewed the abstracts of relevant and eligible trials before retrieving the full-text publications. One study with a total of 24 participants was available for review. This study was a small, single-blind, multicentre trial studying adults with RSE receiving either propofol or thiopental sodium for the control of seizure activity. This study was terminated early due to recruitment problems. For our primary outcome of total control of seizures after the first course of study drug, there were 6/14 patients versus 2/7 patients in the propofol and thiopental sodium groups, respectively (risk ratio (RR) 1.50, 95% confidence interval (CI) 0.40 to 5.61, low quality evidence). Mortality was seen in 3/14 patients versus 1/7 patients in the propofol and thiopental sodium groups, respectively (RR 1.50, 95% CI 0.19 to 11.93, low quality evidence). Our third primary outcome of length of ICU stay was not reported. For our secondary outcomes of adverse events, infection was seen in 7/14 patients versus 5/7 patients in the propofol and thiopental sodium groups, respectively (RR 0.70; 95% CI 0.35 to 1.41). Hypotension during administration of study drugs and requiring use of vasopressors was seen in 7/14 patients versus 4/7 patients in the propofol and thiopental sodium groups, respectively (RR 0.87; 95% CI 0.38 to 2.00). The other severe complication noted was non-fatal propofol infusion syndrome in one patient. Patients receiving thiopental sodium required more days of mechanical ventilation when compared with patients receiving propofol: (median (range) 17 days (5 to 70 days) with thiopental sodium versus four days (2 to 28 days) with propofol). At three months there was no evidence of a difference between the drugs with respect to outcome measures such as control of seizure activity and functional outcome. Since the last version of this review we have found no new studies.There is a lack of robust, randomised, controlled evidence to clarify the efficacy of propofol and thiopental sodium compared to each other in the treatment of RSE. There is a need for large RCTs for this serious condition.

Neuroprotective effects of deep hypothermia in refractory status epilepticus.

Pharmacoresistance develops quickly during repetitive seizures, and refractory status epilepticus (RSE) remains a therapeutic challenge. The outcome of RSE is poor, with high mortality and morbidity. New treatments are needed. Deep hypothermia (20°C) is used clinically during reconstructive cardiac surgery and neurosurgery, and has proved safe and effective in those indications. We tested the hypothesis that deep hypothermia reduces RSE and its long-term consequences. We used a model of SE induced by lithium and pilocarpine and refractory to midazolam. Several EEG measures were recorded in both hypothermic (n = 17) and normothermic (n = 20) animals. Neuronal injury (by Fluoro-Jade B), cell-mediated inflammation, and breakdown of the blood-brain barrier (BBB) (by immunohistochemistry) were studied 48 h following SE onset. Normothermic rats in RSE seized for 4.1 ± 1.1 h, and at 48 h they displayed extensive neuronal injury in many brain regions, including hippocampus, dentate gyrus, amygdala, entorhinal and pyriform cortices, thalamus, caudate/putamen, and the frontoparietal neocortex. Deep hypothermia (20°C) of 30 min duration terminated RSE within 12 min of initiation of hypothermia, reduced EEG power and seizure activity upon rewarming, and eliminated SE-induced neuronal injury in most animals. Normothermic rats showed widespread breakdown of the BBB, and extensive macrophage infiltration in areas of neuronal injury, which were completely absent in animals treated with hypothermia. These results suggest that deep hypothermia may open a new therapeutic avenue for the treatment of RSE and for the prevention of its long-term consequences.

Drug-induced EEG pattern predicts effectiveness of ketamine in treating refractory status epilepticus.

Refractory status epilepticus (RSE) can lack overt clinical manifestation and is usually treated with continuous infusion of intravenous anesthetic drugs (IVADs), where the use of continuous electroencephalography (cEEG) is imperative. Ketamine has recently been shown to be effective in the treatment of RSE. We retrospectively review a cohort of 11 patients receiving ketamine as part of their treatment regimen for RSE. We report on the presence of a characteristic EEG rhythm consisting of a generalized archiform theta to beta rhythms (7-20 Hz) appearing after ketamine administration. This pattern was seen in five patients, four of whom achieved successful resolution of RSE. Ketamine-induced EEG pattern may serve as a biomarker predictive of successful treatment outcome in RSE.

Short- and Long-Term Outcomes After Status Epilepticus.

Refractory Status Epilepticus Frequency, Risk Factors, and Impact on Outcome Mayer SA, Claassen J, Lokin J, Mendelsohn F, Dennis LJ, Fitzsimmons B-F Arch Neurol 2002;59:205–210 Refractory status epilepticus (RSE) is a life-threatening condition in which seizures do not respond to first- and second-line anticonvulsant drug therapy. How often RSE occurs, risk factors that predispose to this condition, and the effect of failure to control seizures on clinical outcome are poorly defined. Objective To determine the frequency, risk factors, and impact on outcome of RSE. Design Retrospective cohort study. Setting Large academic teaching hospital. Patients Consecutive sample of 83 episodes of status epilepticus in 74 patients (mean age, 63 years). Main outcome. Methods Refractory status epilepticus was defined as seizures lasting longer than 60 minutes despite treatment with a benzodiazepine and an adequate loading dose of a standard intravenous anticonvulsant drug. Factors associated with RSE were identified using univariate and backward stepwise logistic regression analyses. Results In 57 episodes (69%), seizures occurred after treatment with a benzodiazepine, and in 26 (31%), seizures occurred after treatment with a second-line anticonvulsant drug (usually phenytoin), fulfilling our criteria for RSE. Nonconvulsive SE (P = .03) and focal motor seizures at onset (P = .04) were identified as independent risk factors for RSE. Eleven (42%) of 26 patients with RSE had seizures after receiving a third-line agent (usually phenobarbital). Although mortality was not increased (17% overall), RSE was associated with prolonged hospital length of stay (P < .001) and more frequent functional deterioration at discharge (P = .02). Conclusions Refractory status epilepticus occurs in approximately 30% of patients with SE and is associated with increased hospital length of stay and functional disability. Nonconvulsive SE and focal motor seizures at onset are risk factors for RSE. Randomized controlled trials are needed to define the optimal treatment of RSE. Long-term Mortality After a First Episode of Status Epilepticus Logroscino G, Hesdorffer DC, Cascino GD, Annegers JF, Bagiella E, Hauser WA Neurology 2002;58:537–541 Objective To evaluate long-term mortality among people with status epilepticus (SE). Methods The authors performed a population-based retrospective cohort study to determine long-term mortality after SE. Between January 1, 1965, and December 31, 1984, all first episodes of SE receiving medical attention were ascertained through the Rochester Epidemiology Project Records-Linkage System. Cases surviving the first 30 days (n = 145) were followed until death or study termination (February 1996). Results At 10 years, cumulative mortality among 30-day survivors was 43%. The standardized mortality ratio (SMR) at 10 years was 2.8 (95% CI, 2.1–3.5). The mortality rate of those with idiopathic/cryptogenic SE was not increased (SMR = 1.1; 95% CI, 0.5–2.3). The following characteristics of SE increased long-term risk for mortality: SE ≥ 24 hours in duration vs. SE < 2 hours (relative risk [RR] = 2.3; 95% CI, 1.1–5.1); acute symptomatic etiology vs. idiopathic/cryptogenic etiology (RR = 2.2; 95% CI, 1.0–5.1); myoclonic SE vs. generalized convulsive SE (RR = 4.0; 95% CI, 1.3–13). Conclusion Forty percent of subjects who survived the first 30 days after an incident episode of SE die within the next 10 years. The long-term mortality rate was threefold that of the general population over the same time period. The long-term mortality rate at 10 years was worse for those with myoclonic SE, for those who presented with SE lasting more than 24 hours, and for those with acute symptomatic SE. The long-term mortality rate was not altered in those with idiopathic/cryptogenic SE. We conclude that SE alone does not modify long-term mortality.

Outcome of Refractory Status Epilepticus

Neurology| April 01 2002 Outcome of Refractory Status Epilepticus AAP Grand Rounds (2002) 7 (4): 44. https://doi.org/10.1542/gr.7-4-44 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Outcome of Refractory Status Epilepticus. AAP Grand Rounds April 2002; 7 (4): 44. https://doi.org/10.1542/gr.7-4-44 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search nav search search input Search input auto suggest search filter All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: grand mal status epilepticus, refractory Source: Sahin M, Menache CC, Holmes GL, et al. Outcome of severe refractory status epilepticus in children. Epilepsia. 2001;42:1461–1467. The records of 22 children, ages 4.5 months to 18 years, treated for refractory status epilepticus (RSE) between 1992 and 2000, were reviewed retrospectively at Children’s Hospital, Boston, Massachusetts. Treatment consisted of high-dose anesthetic agents, including pentobarbital, midazolam, propofol, and phenobarbital, alone or in combination, for periods ranging from 2 to 146 days (mean 31 days). Outcome correlated with duration of treatment: of 8 children treated for <7 days, only 2 died and 4 returned to baseline neurologic state, whereas of 7 children requiring treatment of RSE for >31 days, 4 died and only 1 returned to baseline. A total mortality of 32% (7 cases) was related to etiology, age, and EEG. The most frequent etiology was presumed or known viral encephalitis affecting 10 children, of whom 4 died. Of 4 children <3 years of age, none returned to baseline, 3 died, and 1 had new neurologic deficits after RSE. Of 6 children older than 10 years, 4 returned to baseline, and only 1 died. Mortality was 25% in 12 children with focal EEG abnormalities at onset of RSE, and 40% in 10 with multifocal or generalized EEG abnormalities. No deaths occurred in 5 seizure-susceptible children with symptomatic seizures not due to an acute provocation; their diagnoses were mental retardation, Rett’s syndrome, old intracranial hemorrhage, atypical Rasmussen encephalitis, and developmental delay. The findings of the above study are similar to a study of 346 adolescent and adult patients with status epilepticus reported from the Netherlands.1 A poor outcome was related to the underlying cause and status associated with an acute illness, a duration of >4 hours, the occurrence of medical complications, and inadequate therapy. Of 38 patients who died, 44% received insufficient therapy. A study in 74 adults with 83 episodes of status epilepticus at the Neurological Institute, New York City,2 found a mortality of 21% which was correlated with increased age and acute symptomatic seizures. Increased length of hospitalization and acute symptomatic seizures were predictors of functional disability in 23% of patients with nonfatal episodes. Regarding long-term outcome, the occurrence of status with recovery had no adverse effects in a cohort of 342 children followed prospectively for a mean of 72 months.3 It appears that mortality with status is related particularly to the cause of the status and the association of an acute illness such as encephalitis or encephalopathy and, sometimes, to inadequate therapy. Although the majority of single, generalized tonic-clonic seizures are self-limiting and of no more than 2 to 4 minutes duration, a seizure lasting 5 minutes or more may progress to status and should be treated aggressively. The prevention of status and the effective treatment of status are dependent upon the avoidance of delay in initiating anticonvulsant therapy and the adherence to a well-defined protocol for managing prolonged seizures outlined for emergency room physicians.4 RSE may not... You do not currently have access to this content.