Status epilepticus (SE) is one of the most common neurological emergencies in children, with 23 cases per 100,000 children and a mortality of up to 7%¹. Children are at a particularly elevated risk for refractory status epilepticus (RSE), with up to 40% of pediatric cases developing RSE.² Furthermore these cases have a greater mortality, with a rate as high as 44%.³ It is therefore imperative to appropriately diagnose and treat these patients in a timely manner. The selection of medications to treat SE in children is of the utmost importance, as particular pediatric populations are especially vulnerable to the adverse effects of certain antiseizure medications (ASMs) (e.g. valproic acid) and anesthetic infusions (e.g. propofol).

The use of ketamine for SE has gained renewed interest in the realm of pediatric neurocritical care in recent years. These efforts culminated in a meta-analysis we published earlier this year, featuring the possible role of ketamine in the management of SE in children.⁴ The following patient case highlights the advantages of ketamine as a potentially safer alternative to traditional GABAergic anesthetic infusions (e.g., benzodiazepines, propofol, and barbiturates) in a patient population particularly vulnerable to their deleterious adverse effects.

This patient case highlights the clinical implementation of ketamine based on our recent meta-analysis supporting the use of ketamine for pediatric SE.⁴ In this study published in Epilepsia, we demonstrated that the addition of ketamine resulted in cessation of SE in 51% of cases. While this is similar to the clinical effectiveness of other infusions, there is an additional safety benefit, as none of the included studies reported significant side effects with the use of ketamine. Only minor and/or rare side effects were reported, including increased oral secretions, hypertension, and delirium.

When evaluating the specific patient factors from the case above in the context of our meta-analysis, a few noteworthy details should be highlighted. First, in terms of seizure types, most patients had focal seizures with secondary generalization in three of the included studies^5,6,7, which was the case for the patient presented here. Second, some patients receiving ketamine never required intubation. In the largest cohort included in the meta-analysis, Jacobwitz and colleagues found that 4% of patients who received ketamine were not intubated⁸. Although this is not a large number, it is more notable to recognize that most patients were already intubated before ketamine initiation, and that other anesthetic infusions ubiquitously require intubation. Meanwhile, a study by Ilvento et al. found that the majority of patients from their cohort did not require intubation⁹. In the case above, one of the biggest benefits of ketamine for this patient was circumventing the need for a potentially risky intubation. In addition, given his cardiovascular history and episodes of profound hemodynamic instability with other ASMs that required vasopressors and admission to the CICU, there was concern that other anesthetic infusions could exacerbate his cardiovascular pathophysiology. Of note, in the aforementioned study by Jacobwitz et al., only 35% of patients receiving ketamine developed hypotension, of whom 92% developed hypotension prior to ketamine initiation (with their hemodynamics eventually stabilizing after the initiation of ketamine)⁸. These considerations factored into the decision to trial ketamine in the case presented above. While ketamine proved effective in this case, the potential risks and benefits of ketamine for patients with SE and concurrent underlying cardiovascular disease should be evaluated on a case-by-case basis.

Although our meta-analysis distilled the available literature for ketamine in pediatric SE, it is important to recognize that the quality of evidence of the studies included remains low, with no clinical trials currently available. The only clinical trial attempted thus far was halted due to poor recruitment⁸. Nevertheless, ketamine remains a promising option for pediatric patients, but more research is necessary to better elucidate its role in the treatment of pediatric SE and RSE, ideally with randomized controlled trials.