Timing Status Epilepticus and Quantifying Delays to Effective Management: A Systematic Review of Clinical and Research Practices in Low- and Lower Middle-Income Countries
Introduction
Rationale: Time is of essence for preventing morbidity and mortality attributable to status epilepticus. There are studies which have documented delays in management of status epilepticus, from the seizure onset to its cessation. It was easier to quantify time when the cut-off for a seizure to be considered as status epilepticus was 30 minutes or more. But with the revised definition of 5 minutes or more, timing the seizure since its onset becomes difficult. Hence, to develop a uniform methodology on how to accurately time the seizure, it becomes imperative to understand the current practices on how a seizure was timed and recorded since its onset in the literature.
Research Question:
- How and how often are the timings of onset and duration of delays in the management of status epilepticus (SE) documented?
- What is the duration of delay in the management of SE at various stages of care: prehospital (at the community level), at the transit, initiation of treatment in the hospital (first, second and third line), time to regain consciousness and time of hospital discharge.
This review has been reported and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Inclusion criteria
Type of participants: Patients of all age groups (children, adults, mixed) who had status epilepticus- as per old and new definitions- including the patients of refractory and super refractory status epilepticus.
Exclusion criteria includes: Patients with post cardiac arrest status epilepticus
Phenomena of interest:
(i) The methodology for retrieving/ recording the time of onset and duration from onset of seizure associated with status epilepticus to call an ambulance or seek medical care, (ii) Time from seizure onset to presentation to emergency department. It includes an initial response or treatment at the community level along with time from patient transport to hospital arrival (transit phase), iii) Time from presentation to emergency department to first-line, second-line, and third-line treatment initiation upon hospital arrival, iv) Time from onset to jerks, v) onset to regaining the consciousness, vi)onset to recovery
Operational definitions:
- Prehospital phase: Time from seizure onset to presentation to emergency department. It includes an initial response or treatment at the community level along with time from patient transport to hospital arrival (transit phase).
- Hospital based treatment phase: Time from presentation to emergency department to first-line, second-line, and third-line treatment initiation upon hospital arrival.
- Time from onset to jerks, onset to regaining the consciousness, onset to recovery
Types of studies to be included: All descriptive (cross-sectional) and longitudinal studies conducted prospectively or retrospectively along with Randomized Controlled Trials; documenting data related to either (i) the methodology for retrieving/ recording the time of onset and duration from onset of seizure associated with status epilepticus to call an ambulance or seek medical care, or (ii) Time from seizure onset to presentation to emergency department. It includes an initial response or treatment at the community level along with time from patient transport to hospital arrival (transit phase); Time from presentation to emergency department to first-line, second-line, and third-line treatment initiation upon hospital arrival; Time from onset to jerks, onset to regaining the consciousness, onset to recovery or (iii) both will be included. We will include all studies irrespective of being based in hospital or community settings.
Studies documenting non-convulsive SE, reviews and meta-analysis along with studies published in languages other than English will be excluded from this review.
Search strategy
The search strategy will be developed under following steps:
- In the initial phase, a few relevant articles were reviewed to identify and develop a logical grid of keywords which included status epilepticus, seizures, duration, delay and healthcare seeking behaviour
- The Medical Subject Headings (MeSH) terms of these keywords were identified in PubMed to build a comprehensive and a specific search strategy.
- Preliminary strategy: Studies published from 1st Jan 2000 to 31st October 2024 using the following search strategies: (status epilepticus[Title]) AND (“time-to-treatment”[MeSH Terms] OR delays OR “time factors”[MeSH Terms]) FILTER: HUMANS, 2000-2024. The MeSH term ‘Time factors’ was used from 1981-2012; post which ‘time-to-treatment’ was introduced.
- The review of the cross references of all the included studies will be conducted for exhaustive search.
- Grey literature in the form of thesis/ dissertation and databases available at WHO library will also be searched for the relevant data.
Thereafter, the titles and abstracts of all retrieved studies will be screened independently by two authors, and irrelevant studies were discarded. The full-text version of the shortlisted studies will be analyzed for the presence of phenomena of interest. We will include only full-text articles in which detailed data would be available for extraction and analysis. A screening guide to be used to ensure that all review authors reliably applied the search, selection, and data extraction criteria.
Data extraction
A data extraction sheet will be prepared in Microsoft excel. It will be pretested by extracting data of 10 randomly chosen studies for pulling out data from the studies. The variables of data extraction will be pretested in 10 studies The following data will be extracted: study features – first author, year of publication, study setting, study period, study population (age), total sample size, sample size (male/female), whether the operational definition of delay was given (yes/no), duration of epilepsy among participants, duration (time interval) from the onset of SE to (i) recognition of SE among caregivers, (ii) arrival of ambulance, (iii) in-transit- till reaching the emergency care of the healthcare facility , (iv) initiation of treatment at the emergency care facility, (v) time from admission to regain consciousness and (vi) time from admission to discharge of the patient vii) onset to jerks, viii) onset to consciousness, ix) onset to recovery
Quality assessment of studies
We will assess the quality of descriptive studies by using the Joanna Briggs Institute’s critical appraisal tool for prevalence and Cochrane’s Risk of Bias (RoB 2) assessment tool for RCTs. The risk of bias will be categorized as low, unclear or high for all the studies by two reviewers independently. A group consensus will be reached to resolve disagreements.
Analysis: For research question 1: A scoring criterion will be developed to rate the studies on three point scale indicating their methodological robustness with respect to availability of data on timing the seizure in the prehospital phase (from onset to calling the ambulance or making decision to take the patient to the hospital), source of this data and verification of timing the seizure.
For research question 2: Summary mean, and standard deviation will be used as measure of effect for summarizing duration of delays in the management of Status Epilepticus (SE) at various stages of care, including the prehospital phase, transit phase, and hospital-based treatment. The heterogeneity of outcome measures between studies will be examined using I² statistics. The findings will be summarized only if atleast five studies will document a particular outcome. MetaXL or Stata will be used for performing the metanalysis.