Dear Editor,

Status epilepticus (SE) is among the most common life-threatening neurological emergencies in childhood, with an incidence of approximately 17-23 episodes per 100.000 children annually, peaking within the first five years of life.¹ SE carries a significant risk of neurological morbidity and an overall mortality rate of up to 3%.¹ We read with great interest the recently published protocol titled “2025 SE in Critically Ill Children” by Özcan et al.² in the Journal of Pediatric Emergency and Intensive Care Medicine. We commend the authors for their valuable contribution. Compared to previous protocols, a notable difference in the new guideline is the omission of intravenous (IV) midazolam as a first-line treatment option for SE, with IV diazepam recommended exclusively.³ It is worth noting that if IV lorazepam were readily available in our country, this debate might have been less pronounced. Nonetheless, a national survey conducted prior to the protocol’s publication could have provided a more comprehensive reflection of current practice patterns across Türkiye.

The article offers an up-to-date and comprehensive overview of SE management in critically ill children; however, several methodological aspects merit further consideration. Notably, the absence of details regarding systematic literature search strategies, database usage, and study selection criteria represents a gap in methodological transparency. Furthermore, the omission of evidence levels and recommendation strength impedes an independent evaluation of the proposed therapeutic strategies. Although references to meta-analyses and systematic reviews are made, the findings of these studies are not analyzed in depth. Practical factors-such as cost-effectiveness, feasibility, and the limitations imposed by local resources-are also insufficiently addressed, potentially affecting real-world applicability. Additionally, the lack of visual treatment algorithms limits the accessibility and ease of clinical implementation. Patient heterogeneity (e.g., preterm infants, metabolic disorders) is another critical factor inadequately discussed, creating gaps in individualized care strategies. Similarly, the application hierarchy for immunomodulatory therapies remains undefined, potentially complicating clinical decision-making. While a detailed long-term follow-up protocol is not mandatory, including a brief recommendation to refer patients to pediatric neurology or related specialties for longitudinal care would have enhanced the protocol’s scientific robustness and patient safety considerations. Addressing these issues would strengthen the methodological rigor and clinical applicability of the protocol within an evidence-based framework.

A comprehensive review of the literature reveals that IV midazolam is at least as effective as diazepam, and in some cases, it may even be considered superior. According to international recommendations, if IV access is available, IV lorazepam (0.1 mg/kg, max 4 mg/dose), IV diazepam (0.2-0.3 mg/kg, max 10 mg/dose), or IV midazolam (0.1 mg/kg, max 5 mg/dose) can all be considered as first-line agents.⁴ Their effects typically become apparent within 0.5 to 5 minutes. Current evidence does not strongly favor one over the others in terms of seizure control efficacy.^{5, 6}

Although the 2018 Cochrane review and a 2016 network meta-analysis found no clear differences in efficacy or safety among diazepam, lorazepam, and midazolam,^{5, 7} heterogeneity in study designs and patient populations may affect the generalizability of these results. Furthermore, no significant difference in seizure cessation rates has been observed when comparing IV midazolam with IV diazepam or lorazepam, or IV lorazepam with the combination of IV diazepam and phenytoin.^{5, 8-11} However, studies have reported that fewer second doses were required when lorazepam was used compared to diazepam, although no significant difference was noted between midazolam and the other agents.⁶ Importantly, IV lorazepam is associated with fewer adverse events, including respiratory depression and excessive sedation, compared to IV diazepam.^{5, 12}

National variations are also notable. A nationwide survey conducted by the Italian Paediatric SE group revealed that approximately 90% of physicians preferred midazolam as the first-line treatment.¹³ The Canadian guidelines recommend either midazolam or lorazepam, Australian protocols favor midazolam, and Japanese protocols support the use of all three benzodiazepines.^14-16 These differences likely reflect variations in drug availability, healthcare infrastructure, and physician training across countries. Future protocols could benefit from including alternative treatment pathways that account for these factors to enhance relevance and applicability.

In conclusion, while we advocate for the inclusion of IV midazolam as a first-line treatment option based on its efficacy, safety, and route flexibility, we also underscore the importance of developing adaptable, evidence-based protocols that reflect national practice variations and evolving literature.