Monday, December 28, 2015

Status epilepticus management

Continuous intravenous therapy versus intermittent bolus therapy for pediatric refractory status epilepticus (RSE)   Authors: Kevin Chapman, Howard Goodkin, R Tasker, Ivan Sanchez Fernández, Alexis Topjian, Angus Wilfong, Ashley Helseth, Jessica Carpenter, Joshua Goldstein, Katrina Peariso, Korwyn Williams, Mark Wainwright, Michele Jackson, Mohamad Mikati, Nicholas Abend, James N. Brenton, Ravindra Arya, Tracy Glauser, William D. Gaillard, Tobias Loddenkemper

Rationale: Children in convulsive RSE are often treated with continuous intravenous infusions (CI). We examined escalation to CI and challenge the hypothesis that RSE that fails to respond to 2 antiepileptic drugs (AEDs) always requires escalation to CI.

Methods: A prospective cohort study of pediatric RSE in 9 tertiary pediatric hospitals in the US from June 2011 to June 2013 including children 1 month to 21 years with initial convulsive seizures and failure of ≥2 AEDs to stop seizures or the initiation of CI. Exclusions: Non-convulsive SE on EEG without initial convulsive seizures or non-convulsive SE with motor manifestations limited to infrequent myoclonic jerks. Each center followed its own procedure for management of RSE. Data included first- and second-tier AEDs and use of CI. Seizures were dichotomized into continuous or intermittent. A stratification of in-hospital SE >30-mins was used for comparative analyses.

Results: Of 111 cases of RSE in 111 patients, 55 (49.5%) received CI therapy. There was no difference in age, sex distribution, ethnicity or known epilepsy of patients receiving CI compared to those receiving AED boluses. All patients were admitted to a PICU and remained for 3 [2 – 12] days (median [interquartile range]). SE started out-of-hospital in 38/55 (69%) cases that went on to receive CI treatment; this proportion was no different to those who received boluses of AEDs (36/56 65%). Duration of convulsive seizures in all patients was 141 [70 – 357.5] mins. Overall, there was no difference in duration comparing those receiving CI to those receiving AED boluses (162 [70 – 1200] vs 123.5 [70 – 240] mins). There were 95/111 (85.6%) cases with a duration of SE >30-mins in-hospital. Of these, the interval to seizure cessation was longer in the 45 receiving a CI as compared to the 50 cases with AED boluses: 155 [119.3-460] vs 110.5 [54-217] mins (P<0.01). Hypotension and the use of vasopressors were more frequent in CI therapy (CI vs non-CI: hypotension19/45 vs 8/50, P<0.01; vasopressors 15/45 vs 3/50, P<0.001). PICU length of stay was increased in those receiving CI therapy (CI vs non-CI: 10 [3-19] vs 2 [2-3] days, P<0.001), despite no difference in the proportion mechanically ventilated (CI vs non-CI: 37/45 vs 35/50). Overall, continuous SE was present in 34/110 (31%). In the 25 cases with in-hospital RSE >30-mins, the use of CI was not more frequent in those with continuous seizure activity (9/30 vs 16/31).

Conclusions: CI therapy for RSE was used in half of cases and its use did not differ between those with continuous versus intermittent SE. However, CI was associated with more PICU interventions and longer length of stay. Interestingly, patients with in-hospital seizures longer than 30 minutes treated with CI infusions had a longer time to seizure cessation than those with intermittent dosing. Given this variation in response and morbidity, CI therapy may not be appropriate for all RSE patients - further research is warranted. (This study was funded by an AES/Epilepsy Foundation of America infrastructure award)

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  1. Factors associated with status epilepticus duration in childrenAuthors: Tobias Loddenkemper, Iván Sánchez Fernández, Michele Jackson, Nicholas Abend, Ravindra Arya, J. Nicholas Brenton, Jessica Carpenter, Kevin Chapman, William D. Gaillard, Tracy Glauser, Joshua Goldstein, Howard Goodkin, Ashley Helseth, Mohamad Mikati, Katrina Peariso, Alexis Topjian, Mark Wainwright, Angus Wilfong, Korwyn Williams, Robert Tasker


    Rationale: The aim of this study was to identify factors associated with the duration of pediatric convulsive status epilepticus (SE).

    Methods: Prospective observational descriptive study performed from June 2011 to May 2015. Pediatric subjects (1 month to 21 years) with refractory convulsive SE were enrolled. We considered the duration of convulsive seizures as the main outcome and evaluated predictors for SE duration.

    Results: We enrolled 190 subjects (54.2% males) with a median (p25-p75) age of 4.1 (1.3-10.2) years. The median (p25-p75) duration of SE was 140 (60-300) minutes. SE etiology was structural (36.9%), genetic or metabolic (21.9%), and unknown (41.3%). 94 subjects had developmental delay, 83 subjects had epilepsy, 33 subjects had at least a prior episode of SE, 18 subjects had cerebral palsy, and 18 subjects had history of febrile seizures. The SE episode was continuous in 29.7% of subjects and intermittent in 70.3% of subjects. On univariate analysis, SE duration was associated with AED choice (non-recommended versus recommended treatment strategy) (p= 0.0123), time to first BZD (p<0.001), time to first non-BZD AED (p<0.001), time to EMS arrival at the patient (p= 0.0103), time of hospital arrival for the patient (p<0.001), age (p= 0.0218), type of SE (intermittent versus continuous) (p<0.001), and SE onset (out-of the hospital versus in-hospital) (p= 0.0188). SE duration was note associated with gender (p= 0.4925) or etiology (structural versus genetic or metabolic versus unknown) (p= 0.7266) (Table 1). All variables were included in multivariable regression due to our a priori analysis plans. Multivariable median regression analysis showed that the only variables which remained significantly associated with SE duration were structural etiology (versus genetic/metabolic or unknown etiology) (p=0.005), time to first BZD (p<0.001), and time to first non-BZD AED (p<0.001). However, the regression coefficient for etiology is considerably larger (structural vs. others: 35.82, SE: 12.45) compared to those for other predictors (time to first BZD: 0.72, SE: 0.03, and time to first non-BZD: 1.59, SE: 0.02). Hence, clinically the etiology would be the most important predictor of the duration of SE. AED choice (non-recommended versus recommended treatment strategy) (p=0.016) was not associated with SE duration (Table 2).

    Conclusions: The main determinants of convulsive SE duration in our series were structural etiology, time to first BZD, and time to first non-BZD AED, but not AED choice (non-recommended versus recommended treatment strategy) (This study was funded by an AES/Epilepsy Foundation of America infrastructure award).

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