Antipsychotic Treatment of Delirium in Critically Ill Children: A Retrospective Matched Cohort Study

Abstract

OBJECTIVE To describe the use of pharmacologic treatment in critically ill children treated according to a delirium protocol and compare those treated with antipsychotics to those treated non-pharmacologically. METHODS The study included a retrospective matched cohort describing patients who were pharmacologically treated for delirium compared to those with delirium but not treated in a PICU from December 2013 to September 2015, using a delirium management protocol. Patients were matched by age, sex, diagnosis, mechanical ventilation (MV), and presence of delirium. RESULTS Of 1875 patients screened, 188 (10.03%) were positive for delirium. Of those, 15 patients (8%) were treated with an antipsychotic for delirium. Patients with delirium treated with antipsychotics were younger, had more delirium days (6 vs. 3, p=0.022), longer MV days (14 vs. 7, p=0.017), and longer PICU length of stay (34 vs. 16 days, p=0.029) than in the untreated group. Haloperidol, risperidone, and quetiapine were used in 9, 6, and 2 patients, respectively. Two patients were treated with multiple antipsychotics. Antipsychotic treatment was initiated on day 2 of delirium for 8 of 15 patients (53.3%). Ten patients in the treatment group had improved delirium scores by day 2 of treatment. No significant differences in sedation exposure between groups. No significant adverse effects were reported. CONCLUSIONS No significant adverse events seen in this small cohort of critically ill pediatric patients with delirium treated with antipsychotic therapy. Patients with early-onset delirium refractory to non-pharmacologic treatment may have a more effective response to antipsychotic therapy than patients with late-onset refractory delirium.

Current State of Analgesia and Sedation in the Pediatric Intensive Care Unit

“…Antipsychotics (haloperidol, chlorpromazine, risperidone, olanzapine, and quetiapine) are useful treatments for refractory delirium [ 181 ]. First-generation antipsychotics, such as haloperidol and chlorpromazine, have high rates of extrapyramidal symptoms (EPS) due to their strong dopamine D 2 antagonism [ 181 ]. Haloperidol is popular in the critical care setting because of its IV formulation.…”

“…Second-generation antipsychotics such as risperidone, olanzapine, and quetiapine have lower rates of EPS and tardive dyskinesia but with long term use they are associated with an increased risk of weight gain, metabolic side effects, and dyslipidemia. Risperidone and quetiapine are often favored for their favorable side effect profile in the treatment of delirium [ 181 , 182 , 183 ].…”

“…Treating delirium may involve non-pharmacologic and pharmacologic approaches. A retrospective matched cohort study in the PICU suggests that antipsychotics may be more effective for early vs late-onset delirium refractory to non-pharmacologic treatment [ 21 , 181 ]. Table 1 depicts a comparison of pediatric delirium screening tools [ 30 ].…”

The ICU Liberation Bundle and Strategies for Implementation in Pediatrics

“…Antipsychotics can be helpful for symptomatic management when a child continues to experience delirium despite the optimal management of the underlying illness and minimizing iatrogenic triggers. Although this represents offlabel use, quetiapine was shown to be safe and effective in a randomized controlled trial [61], and case studies suggest the same for risperidone and olanzapine [62][63][64].…”

An Evaluation of Risperidone Dosing for Pediatric Delirium in Children Less Than or Equal to 2 Years of Age

“…Typical (haloperidol) and atypical antipsychotics (risperidone, olanzapine, quetiapine) have been studied for the management of pediatric delirium focusing on both efficacy and safety. 2-5,9-12 Very few patients <2 years old were included in these studies or dosing was described for the entire study population with no specific data for younger infants. Based on the data available, there is no universally accepted agent recommended for treatment of PICU delirium.…”