Valproate in status epilepticus: Correlation between loading dose, serum levels, and clinical response

Vijiala, Sergiu; André, Pascal; Buclin, Thierry; Décosterd, Laurent A.; Rossetti, Andrea O.; Nový, Jan

doi:10.1111/ene.15441

Cited by 4 publications

(3 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are several evidences that show that generally increasing ASMs dose to the greatest tolerated dose is counterproductive. In SE, there are multiple examples where administering maximal dose and reaching higher drug level brings little benefit [ 37 , 38 ]. Similar findings arose in chronic epilepsy, where no improved efficacy is found when titrating ASMs beyond a certain dose and plasma level [ 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Clonazepam Loading Dose in Status Epilepticus: Is More Always Better?

et al. 2023

Self Cite

View full text Add to dashboard Cite

Background and Objectives Benzodiazepines are the first treatment line in status epilepticus (SE). Despite their well-established benefit, benzodiazepines are frequently underdosed with potential detrimental consequences. In some European countries, clonazepam (CLZ) is commonly used as the first line treatment. The aim of this study was to explore the correlation between CLZ loading doses and SE outcome. Methods This study included a retrospective analysis of a prospective registry in Lausanne, Switzerland (CHUV Lausanne University Hospital), including all SE episodes treated between February 2016 and February 2021. Only adults (> 16 years old) were included with CLZ used as the first treatment line. Post-anoxic SE were excluded because of significant differences in physiopathology and prognosis. Patient characteristics, SE features, the validated SE severity score (STESS), and treatment characteristics were prospectively recorded. We considered loading doses of 0.015 mg/kg or higher (following commonly recommended loading doses) as high doses. We analyzed outcome in terms of number of treatment lines after the CLZ, proportion of refractory episodes, intubation for airways protection, intubation for SE treatment, and mortality. We performed univariable analyses to investigate the association between loading doses and clinical response. A multivariable stepwise backward binary logistic regression was applied for adjusting for potential confounders. Multivariable linear regression was similarly used to analyze CLZ dose as a continuous variable. Results We collected 251 SE episodes in 225 adult patients. Median CLZ loading dose was 0.010 mg/kg. CLZ high doses were used in 21.9% of SE episodes (in 43.8% for > 80% of the high dose). Thirteen percent of patients with SE were intubated for airways control, while intubation was needed in 12.7% for SE treatment. High CLZ loading doses were independently associated with younger age (median 62 versus 68 years old, p = 0.002), lesser weight (65 kg versus 75 kg, p = 0.001) and more frequent intubation for airways protection (23% vs 11%, p = 0.013), but differing CLZ dose was not associated with any outcome parameter. Conclusion CLZ high doses were more frequently used for SE treatment in younger patients with healthy weight and were more often associated with intubation for airways protection, probably as an adverse event. Varying CLZ dose did not alter outcome in SE, raising the possibility that commonly recommended doses are above what is needed, at least in some patients. Our results suggest that CLZ doses in SE may be individualized depending on the clinical setting.

show abstract

Section: Discussionmentioning

confidence: 99%

Clonazepam Loading Dose in Status Epilepticus: Is More Always Better?

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…Nonconvulsive SE in coma (NCSEC) is defined by an EEG clearly suggestive of SE (i.e., repetitive rhythmic or periodic discharges with evolution in amplitude or frequency or continuous periodic lateralized or generalized epileptiform discharges) [ 14 ]. Refractory SE (RSE) was considered after the failure of first- and second-line ASM to control seizures [ 15 ]. Resolution of SE was determined as the moment of seizure termination, assessed clinically, and confirmed by EEG documentation.…”

Section: Methodsmentioning

confidence: 99%

“…We considered clinical variables that were prospectively entered in the registry: demographics, occurrence of previous seizures, SE cause, worst seizure type, consciousness before treatment, STESS (Status Epilepticus Severity Score) [ 16 ], valproate loading dose/kg, valproate position in the treatment flow and mean maintenance doses, ASM and outcome at hospital discharge. We also retrieved history of liver disease or alcohol abuse, peak serum ammonia and valproate levels (typically reflecting residual values, as routinely taken in the morning before valproate administration) during the SE episode [ 15 ]. Hyperammonemia was defined at >50 µmol/L.…”

Section: Methodsmentioning

confidence: 99%

Acute Valproate-Induced Encephalopathy in Status Epilepticus: A Registry-Based Assessment

et al. 2023

Self Cite

View full text Add to dashboard Cite

Background Valproate-induced encephalopathy (VIE) affects between 0.1% and 2.5% of patients under long-term epilepsy treatment. Its frequency and characteristics in adults with status epilepticus (SE) is, however, unknown. Objective The aim of this study was to characterize the frequency and the clinico-biological characteristics of VIE in adult SE patients. Methods We reviewed all patients included in our institutional SE registry who were treated for an SE episode between November 2021 and February 2023 and identified 39 patients who received valproate for their SE treatment. Acute VIE was defined by worsening of consciousness having led to the discontinuation of valproate, and improvement of consciousness within 96 hours after discontinuation of valproate during acute hospital treatment. Results Patients had a mean valproate intravenous loading dose of 34.5 mg/kg and a mean maintenance dose of 15.3 mg/ kg/d (1078 mg/d). Four out of 29 patients with measured ammonium had hyperammonemia. We identified four (10%) patients fulfilling acute VIE criteria. Median time from administration of valproate to the occurrence of VIE, and to resolution of VIE after cessation of valproate treatment, was 2 days for each. Three of the four VIE patients had no associated hyperammonemia. Patients who developed VIE more frequently had a history of liver disease (p = 0.023), and tended to be younger, but other clinical variables did not differ significantly from patients without VIE, including valproate loading or maintenance doses, SE cause, duration or severity, other concomitant antiseizure medications (none received topiramate, phenobarbital, or primidone). Conclusion Pending larger studies, VIE in SE seems relatively frequent and difficult to foresee; clinical alertness to symptoms is mandatory, even without hyperammonemia, and valproate withdrawal should be considered in suspected cases.

show abstract

Valproate in status epilepticus: Correlation between loading dose, serum levels, and clinical response

Vijiala

André

Buclin

et al. 2022

Euro J of Neurology

View full text Add to dashboard Cite

Background and purpose Intravenous valproate (VPA) is an established treatment of status epilepticus (SE), but optimal loading dose was not fully assessed. We aimed at analyzing the correlation between VPA loading dose and subsequent plasma levels with clinical response in SE. Methods This was a retrospective study in one referral center of all consecutive VPA‐naïve SE episodes treated with VPA between January 2013 and June 2019, in which total VPA trough plasma levels after intravenous loading dose were available. Response to VPA, defined as last antiseizure medication introduced before SE resolution (without the need for additional treatment), was correlated with VPA loading dose and trough level. Correlations were adjusted for other SE characteristics. Results Among 128 SE episodes, 53 (41%) responded to VPA. Median VPA loading dose was 25.2 mg/kg (range, 7–58 mg/kg). Loading doses and total plasma levels were not associated with the probability of response or mortality. Correcting for other possible confounders (number of previously tried treatment, demographics, SE severity) did not alter these findings. Only 3.8% of SE episodes that responded to VPA received >30 mg/kg. Conclusions A high loading dose (>30 mg/kg) is not associated with a greater response rate in patients with SE. Therefore, it seems to bring little benefit. If confirmed in further studies, a dosage of 25–30 mg/kg appears adequate in SE.

show abstract

Valproate in status epilepticus: Correlation between loading dose, serum levels, and clinical response

Cited by 4 publications

References 27 publications

Clonazepam Loading Dose in Status Epilepticus: Is More Always Better?

Clonazepam Loading Dose in Status Epilepticus: Is More Always Better?

Acute Valproate-Induced Encephalopathy in Status Epilepticus: A Registry-Based Assessment

Valproate in status epilepticus: Correlation between loading dose, serum levels, and clinical response

Contact Info

Product

Resources

About