Prospective, Double-Blind, Randomized Controlled Trial of Quetiapine as a Treatment for Delirium in Critically Ill Children

Delirium is an acute syndrome with fluctuation in mental status with altered cognition and consciousness. It is a common occurrence (17% to 38%) in critically ill children with serious short-term consequences. Its pathophysiology is complex and incompletely understood. Dopaminergic, serotoninergic, glutaminergic, and cholinergic pathways in the cerebral cortex, striatum, substantia nigra, and thalamus have been implicated. Imbalance in the synthesis, release, and inactivation of neurotransmitters can result in altered cognitive function, behavior, and mood. The Society of Critical Care Medicine set the adult practice guidelines including widespread delirium screening as well as treatment to decrease duration of delirium and ameliorate its long-term effects (12). The cornerstone of pharmacologic therapy for delirium in adults is antipsychotics, both first and second-generation (13-20).

The current foundation of treatment for pediatric delirium is identifying and addressing the underlying etiology. Iatrogenic factors should be minimized, such as avoiding benzodiazepines and restraints, optimizing pain control, minimizing sedation, and treating withdrawal. The ICU environment should also be optimized to create a quiet, well-lit space with clustered care to allow for uninterrupted sleep. When non-pharmacologic treatment measures prove insufficient to manage the symptoms of delirium, we believe the second-generation antipsychotic (SGA) quetiapine may have a role in the treatment of delirium. However, there are currently no FDA-approved medications to treat delirium in this population.

The European Society of Paediatric and Neonatal Intensive Care (ESPNIC) has recently recommended that all children in the ICU be monitored for delirium but provided no guidance on recommended treatments (21), likely due to the lack of evidence of proven delirium treatment in children. An adult systematic review and meta-analysis by Kishi et al concluded that antipsychotics are superior to placebo in decreasing severity of delirium and time to response with there was no significant difference in the side effects between the two groups. Additionally, SGAs are associated with a shorter time to response and lower side effect profile than haloperidol (a first-generation antipsychotic).

A growing body of pediatric literature suggests that delirium is a serious and under recognized problem in critically ill children as well, however little research has been focused on treatment . A recent retrospective series looking at the use of quetiapine in suggested that quetiapine use for delirium treatment is a safe option in this population.

With proven efficacy in adults with delirium, an established track record in children for indications other than delirium, a favorable safety profile, and a wide therapeutic window, quetiapine is a logical choice for the next phase of research into pediatric delirium treatment. In this study are looking prospectively at the effectiveness of quetiapine as a treatment for pediatric delirium.