Adverse drug reactions of haloperidol used in critically ill children for the treatment of delirium

BACKGROUND: As delirium in critically ill children is increasingly recognized, more children are treated with the antipsychotic drug haloperidol. However, little is known about its safety in this context. The objective of this study was to investigate the incidence and nature of adverse events associated with the use of haloperidol and its possible relationship with dose. METHODS: We identified all patients admitted to the PICU between January 2000 and July 2011 who received haloperidol. Patients were included when haloperidol was prescribed for delirium. Medical and nursing charts were evaluated for a predefined list of known haloperidol adverse events. When a symptom possibly related to haloperidol was identified, the probability of causality was evaluated using the Naranjo score. In addition, each event was evaluated for causality by two clinical pharmacologists and by the Dutch Pharmacovigilance Institute. RESULTS: Fifty-two patients [median age 10.6 (0.3-18.8) yrs] received the drug for treatment of delirium. In six patients (11%) possible adverse events were documented. These included extrapyramidal reactions (n=2), extrapyramidal reactions + hyperpyrexia (n=1), neuroleptic malignant syndrome (n=1), long QT (n=1), and isolated muscle rigidity (n=1). Adverse events were rated as doubtful (n=1), possible (n=2), probable (n=2) and definite (n=1). The median (range) haloperidol dose was similar between patients with and without adverse events [0.03 (0.02-0.06) mg/kg/d vs 0.02 (0.003-0.08) mg/kg/d, p=0.08]. CONCLUSION: To our knowledge, this is the largest pediatric cohort studied for haloperidol-related adverse events. Our study suggests that a significant proportion of patients develop adverse events with haloperidol. As haloperidol adverse events are correlated with dose in adults, our findings suggest that dosing in our pediatric population is suboptimal. Therefore, studies are needed to determine the optimal haloperidol dose for ICU delirium in children