Antipsychotic Medications for Delirium Treatment in the Pediatric Intensive Care Unit: A Systematic Review

Pediatric delirium (PD) is a common but underdiagnosed condition in pediatric intensive care units (PICUs), affecting 17-66% of patients. It is associated with prolonged ventilation and hospitalization, increased healthcare costs, and mortality. While nonpharmacological approaches are considered first-line treatments, pharmacological interventions are used in refractory cases despite limited pediatric-specific evidence. The objective of this systematic review was to evaluate the efficacy and safety of pharmacological treatments for PD in PICUs.

Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (International Prospective Register of Systematic Reviews [PROSPERO]: CRD42024504618), PubMed, Embase, Scopus, CINAHL, Cochrane, and Web of Science databases were searched for studies published up to February 2024. Eligible studies included children aged 1 month-18 years, diagnosed with PD in the PICU using validated scales or psychiatric evaluation and receiving pharmacologic treatment. Outcomes included delirium improvement or resolution and safety. Risk of bias was assessed using the Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I) scale.

Of 7,309 records, 10 studies involving 283 patients receiving pharmacological treatment met inclusion criteria. All but one of the studies were retrospective and no randomized controlled trials (RCTs) were identified. Pharmacological treatment was administered to 283 patients, with the most used agents being quetiapine (36%), risperidone (20%), haloperidol (20%), and olanzapine (11%). Seven studies reported variable efficacy, with olanzapine showing significant symptom improvement in one study (olanzapine: N = 31; control: N = 28; F(1,20) = 28.62, r = 0.77, 95% confidence interval [CI] = 0.50-0.90) and the other drugs reporting a trend toward improvement in delirium severity. Adverse events were inconsistently measured and reported throughout studies: 22 cases were reported, with QTc prolongation (11 cases) and dystonia (7 cases) being the most frequent. Dystonia was observed in patients receiving haloperidol, whereas QTc prolongation was reported in those treated with quetiapine or risperidone. Complete resolution of the events was reported in 21/22 cases and occurred after dose adjustment or treatment interruption.

Pharmacological interventions for PD in PICU patients showed variable efficacy, and adverse events were reported in a minority of treated patients. The limited sample size, the only modest quality of the studies, and the lack of replication preclude definitive conclusions about the drugs' efficacy. In addition, haloperidol, risperidone, and quetiapine raised some safety concerns. Further research is needed to establish stronger evidence for the pharmacologic treatment of PD in the PICU and to address specific treatment on the basis of delirium subtype.