The association of patient weight and dose of fosphenytoin, levetiracetam, and valproic acid with treatment success in status epilepticus.

The Established Status Epilepticus Treatment Trial was a blinded, comparative-effectiveness study of fosphenytoin, levetiracetam, and valproic acid in benzodiazepine-refractory status epilepticus. The primary outcome was clinical seizure cessation and increased responsiveness without additional anticonvulsant medications. Weight-based dosing was capped at 75 kg. Hence, patients weighing >75 kg received a lower mg/kg dose. Logistic regression models were developed in 235 adults to determine the association of weight (≤ or >75 kg, ≤ or >90 kg), sex, treatment, and weight-normalized dose with the primary outcome and solely seizure cessation. The primary outcome was achieved in 45.1% and 42.5% of those ≤75 kg and >75 kg, respectively. Using univariate analyses, the likelihood of success for those >75 kg (odds ratio [OR] = 0.9, 95% confidence interval [CI] = 0.54-1.51) or >90 kg (OR = 0.85, 95% CI = 0.42-1.66) was not statistically different compared with those ≤75 kg or ≤90 kg, respectively. Similarly, other predictors were not significantly associated with primary outcome or clinical seizure cessation. Our findings suggest that doses, capped at 75 kg, likely resulted in concentrations greater than those needed for outcome. Studies that include drug concentrations and heavier individuals are needed to confirm these findings.

Long-term outcomes after epilepsy surgery, a retrospective cohort study linking patient-reported outcomes and routine healthcare data.

OBJECTIVE: The objective of the study was to assess the long-term outcomes of epilepsy surgery between 1995 and 2015 in South Wales, UK, linking case note review, postal questionnaire, and routinely collected healthcare data. METHOD: We identified patients from a departmental database and collected outcome data from patient case notes, a postal questionnaire, and the QOLIE-31-P and linked with Welsh routinely collected data in the Secure Anonymised Information Linkage (SAIL) databank. RESULTS: Fifty-seven patients were included. Median age at surgery was 34 years (11-70), median: 24 years (2-56) after onset of habitual seizures. Median follow-up was 7 years (2-19). Twenty-eight (49%) patients were free from disabling seizures (Engel Class 1), 9 (16%) experienced rare disabling seizures (Class 2), 13 (23%) had worthwhile improvements (Class 3), and 7 (12%) had no improvement (Class 4). There was a 30% mean reduction in total antiepileptic drug (AED) load at five years postsurgery. Thirty-eight (66.7%) patients experienced tonic-clonic seizures presurgery verses 8 (14%) at last review. Seizure-free patients self-reported a greater overall quality of life (QOL; QOLIE-31-P) when compared with those not achieving seizure freedom. Seizure-free individuals scored a mean of 67.6/100 (100 is best), whereas those with continuing seizures scored 46.0/100 (p < 0.006). There was a significant decrease in the median rate of hospital admissions for any cause after epilepsy surgery (9.8 days per 1000 patient days before surgery compared with 3.9 after p < 0.005). SIGNIFICANCE: Epilepsy surgery was associated with significant improvements in seizures, a reduced AED load, and an improved QOL that closely correlated with seizure outcomes and reduced hospital admission rates following surgery. Despite this, there was a long delay from onset of habitual seizures to surgery. The importance of long-term follow-up is emphasized in terms of evolving medical needs and health and social care outcomes.

Phenytoin versus other antiepileptic drugs as treatments for status epilepticus in adults: a systematic review and meta-analysis.

AIM: Status epilepticus (SE) is a life-threatening neurological emergency. There is insufficient evidence regarding which antiepileptic therapy is most effective in patients with benzodiazepine-refractory convulsive SE. Therefore, this study aimed to evaluate intravenous phenytoin (PHT) and other intravenous antiepileptic medications for SE. METHODS: We searched PubMed, the Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi for published randomized controlled trials (RCTs) in humans up to August 2019. We compared outcomes between intravenous PHT and other intravenous medications. The important primary composite outcomes were the successful clinical cessation of seizures, mortality, and neurological outcomes at discharge. The reliability of the level of evidence for each outcome was compared using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: A total of 1,103 studies were identified from the databases, and 10 RCTs were included in the analysis. The ratio of successful clinical seizure cessation was significantly lower (risk ratio [RR] 0.89; 95% confidence interval [CI], 0.82-0.97) for patients treated with intravenous PHT than with other medications. When we compared mortality and neurological outcomes at discharge, we observed no significant differences between patients treated with PHT and those treated with other medications. The RRs were 1.07 (95% CI, 0.55-2.08) and 0.91 (95% CI, 0.72-1.15) for mortality and neurological outcomes at discharge, respectively. CONCLUSIONS: Our findings showed that intravenous PHT was significantly inferior to other medications in terms of the cessation of seizures. No significant differences were observed in mortality or neurological outcomes between PHT and other medications.

Efficacy, Safety, and Economics of Intravenous Levetiracetam for Status Epilepticus: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate efficacy, safety, and economics profiles of intravenous levetiracetam (LEV) for status epilepticus (SE). METHODS: We searched PubMed, Embase, the Cochrane Library, Clinicaltrials.gov, and OpenGrey.eu for eligible studies published from inception to June 12th 2019. Meta-analyses were conducted using random-effect model to calculate odds ratio (OR) of included randomized controlled trials (RCTs) with RevMan 5.3 software. RESULTS: A total of 478 studies were obtained. Five systematic reviews (SRs)/meta-analyses, 9 RCTs, 1 non-randomized trial, and 27 case series/reports and 1 economic study met the inclusion criteria. Five SRs indicated no statistically significant difference in rates of seizure cessation when LEV was compared with lorazepam (LOR), phenytoin (PHT), or valproate (VPA). Pooled results of included RCTs indicated no statistically significant difference in seizure cessation when LEV was compared with LOR [OR = 1.04, 95% confidence interval (CI) 0.37 to 2.92], PHT (OR = 0.90, 95% CI 0.64 to 1.27), and VPA (OR = 1.47, 95% CI 0.81 to 2.67); and no statistically significant difference in seizure freedom within 24 h compared with LOR [OR = 1.83, 95% CI 0.57 to 5.90] and PHT (OR = 1.08, 95% CI 0.63 to 1.87). Meanwhile, LEV did not increase the risk of mortality during hospitalization compared with LOR (OR = 1.03, 95% CI 0.31 to 3.39), PHT (OR = 0.89, 95% CI 0.37 to 2.10), VPA (OR = 1.28, 95% CI 0.32 to 5.07), and placebo (plus clonazepam, OR = 0.73, 95% CI 0.16 to 3.38). LEV had lower need for artificial ventilation (OR = 0.23, 95% CI 0.06 to 0.92) and a lower risk of hypotension (OR = 0.15, 95% CI 0.03 to 0.84) compared to LOR. A trend of lower risk of hypotension and higher risk of agitation was found when LEV was compared with PHT. Case series and case report studies indicated psychiatric and behavioral adverse events of LEV. Cost-effectiveness evaluations indicated LEV as the most cost-effective non-benzodiazepines anti-epileptic drug (AED). CONCLUSIONS: LEV has a similar efficacy as LOR, PHT, and VPA for SE, but a lower need for ventilator assistance and risk of hypotension, thus can be used as a second-line treatment for SE. However, more well-conducted studies to confirm the role of intravenous LEV for SE are still needed.