Any study in a paediatric population is not easy to design and implement, particularly in vulnerable children as a result of the often-catastrophic symptoms associated with convulsive status epilepticus (CSE). The child's guardians are frequently asked to consent, at very short notice, to a barrage of tests and therapies with uncertain results. Yet treatment must be urgently administered since it is well known that CSE, if untreated, may lead to severe neuropsychological impairments and a reduction in quality of life.¹ The possible adverse long-term consequences with increased treatment resistance, morbidity, and mortality,² leaves no option for all those involved, but to try and try again. In the absence of alternative options, benzodiazepines have been the mainstay of treatment for decades. Yet studies, to date, have mostly been limited to prospective observational adult cohorts and their use in paediatrics is largely based on anecdotal evidence.³

The study by Colmard et al.⁴ seeks an innovative, yet still preliminary, way in which to use practice-based research in order to obtain more solid data on the outcomes following the administration of benzodiazepines, in this case varying doses of intravenous clonazepam, in managing CSE. It describes a very interesting study which is, however, undermined by the fact that the data were collected retrospectively and in just one centre. It involved children with a huge age range (0 months to 16 years). This is unfortunately too common in paediatric studies, and the underlying pharmacokinetic and pharmacodynamic characteristics of the children involved was thus extremely heterogenous. In addition, the fact that the seizure cessation rate was not different between the low- and high-dose groups may also put into question the interpretation of the results, especially since time from seizure to the first clonazepam dose could not be evaluated because it was not systematically recorded. It is also not clear why clonazepam was preferred among all the benzodiazepines available. The authors limit themselves to stating that clonazepam was chosen since it has similar pharmacokinetic properties to lorazepam which had been tested in similar cases in adults. These shortcomings may indicate possible bias in the results described. However, as a preliminary investigation, this paper provides a sound basis for future studies.

Future studies would also need to provide more information on how the absence of clinical signs of seizures was determined by the medical team. Indeed, in the data provided, it is also not clear whether the child had already been diagnosed with epilepsy, what type (if any) of medication the child was already on, which could have resulted in a possible drug–drug interaction with the clonazepam administered in this present treatment. The authors acknowledge these and other lacunae in this study, and admit that the data from this monocentric retrospective study needs to be confirmed and extended in a randomized prospective multicentric controlled study.

Despite this, such papers must be published since they highlight the urgent need to develop studies which lead to better evidence-based data so as to identify the optimal dosing regimen of drugs used for the treatment of CSE in children.⁵ This serious medical condition cannot be left to trial and error. Pharmacometric studies and population pharmacokinetics have a key role to play in such future studies. These will determine the exact impact of the huge interindividual variation in this heterogenous population, especially in determining the individual dose needed.

The lack of IV clonazepam outside Europe may prevent such larger and more sound studies. Yet, funding must be made available if CSE in paediatrics is to be managed successfully. This is an urgent unmet need, and these vulnerable children demand this.