Several treatments available for this brain dysfunction
By Mariela Herrera, MD, and Tatiana Falcone, MD
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Delirium is a brain dysfunction defined as a disturbance in attention and awareness with an acute onset and a fluctuating course, associated with alterations in cognition. Patients develop delirium as a direct physiological consequence of another medical condition, or due to substance intoxication or withdrawal. Emergence delirium follows emergence from anesthesia.
The prevalence of pediatric delirium (PD) in critically ill children varies between 4.5 and 28 percent. In one study, it constituted 10 percent of all inpatient referrals for a child and adolescent psychiatry consult and between 17 and 66 percent of psychiatry referrals from pediatric intensive care units (PICUs).
Behaviors associated with PD include auto-extubation, pulling out intravenous lines and climbing out of bed, all of which can impair a patient’s recovery. Research shows that delirium may prolong PICU stay by 2.4 days, with a cost increase of 1.5 percent. It is a traumatic experience for family and caregivers and can lead to post-traumatic stress disorder in the patient due to unrecognized delirious experiences.
PD is associated with high mortality rates, from 12.5 to 29 percent, but it is unclear if this association is independent of other factors. Disturbed perceptual-motor performance and electroencephalogram abnormalities after resolution of clinical PD have been reported.
Various proposed hypotheses for the etiology of delirium suggest that the contributing factors are complementary and act together to precipitate the neurobehavioral syndrome. These hypotheses are based on constructs of neuroinflammation, neuronal aging, oxidative stress, neurotransmitter alterations, neuroendocrine dysfunction, diurnal or melatonin dysregulation, and network disconnectivity.
Delirium is a multifactorial syndrome in which predisposing factors interact with precipitant factors. The greater the number of predisposing factors, the fewer precipitating factors are needed for delirium to occur. Different risk factors for PD are shown in Figure 1.
Delirium is classified according to the motor level of activity in hyperactive, hypoactive and mixed subtypes. The presentation of PD is similar to that observed in adults, with symptoms of sleep-wake disturbances, disorientation and inattention. Features more frequently or uniquely reported in PD and that are related specifically to the developmental stage of the child include purposeless actions, labile affect, unexplained lethargy, inconsolability, changes in the quality of parent-child interaction, developmental regression with transient loss of previously acquired skills and signs of autonomic dysregulation.
Delirium, especially the hypoactive form, is often underrecognized and undertreated. Routine screening is recommended for patients at high risk, such as those admitted to the PICU or those with neurological disorders. The assessment should start with a sedation scale, such as the Richmond Agitation Sedation Scale, to determine whether the patient can be evaluated.
Scales that have been validated in children for the diagnosis of PD include the Delirium Rating Scale, the Pediatric Confusion Assessment Method for the ICU (for critically ill children chronologically and developmentally at least 5 years of age both on and off mechanical ventilation) and the Cornell Assessment of Pediatric Delirium (for children ages 0 to 21 years; can also detect the hypoactive form).
The Pediatric Anesthesia Emergence Delirium Scale and the Postanesthetic Behavior Scale are specifically designed to detect emergence delirium.
The gold standard for diagnosis of PD is assessment by a child and adolescent psychiatrist based on DSM-5 criteria.
Treatment of delirium is achieved by promptly identifying and treating the underlying cause, which leads to resolution of symptoms. Infections and drug withdrawal are the most frequent causes of PD. Nonpharmacological and pharmacological approaches might be helpful for symptom management (Table 1).
Table 1. Nonpharmacological and pharmacological approaches for pediatric delirium.
Nonpharmacological strategies are focused on increasing support and orientation and mitigating modifiable risk factors.
The interplay among sedation, sleep, pain and delirium should be considered in the daily assessment of and goals for the patient. Regulation of sleep-wake homeostasis is essential and can be achieved with nonpharmacological and, if needed, pharmacological strategies such as the use of melatonin. Current medications administered should be reviewed, and avoiding or weaning the patient off benzodiazepines and other medications known to increase delirium risk is recommended.
Pharmacological interventions are indicated if the patient is distressed by the PD or is becoming dangerous because of his or her lack of cooperation with care. The research on pharmacological approaches to PD is scarce; recommendations mostly come from adult delirium and pediatric anesthesia literature. Currently there are no FDA-approved medications for delirium in either adult or pediatric populations.
Antipsychotics, both typical and atypical, have been used with some success (Table 1). In two retrospective reports the use of olanzapine and risperidone in infants (< 3 years old) with delirium, and the use of olanzapine, quetiapine and risperidone in children and adolescents with delirium, were effective, without significant adverse effects. However, the retrospective design and lack of control group in both studies limit the interpretation of the results.
Benzodiazepine use is indicated only for PD resulting from sedative or hypnotic withdrawal, or as an adjunct to antipsychotics for persistent agitation and insomnia. Emergence delirium might be reduced with the use of dexmedetomidine, ketamine, clonidine or propofol, but more research is needed to confirm these findings.
Dr. Herrera was a child and adolescent psychiatry fellow at Cleveland Clinic. She participated with Cleveland Clinic’s Delirium Task Force in the development of an institutional care path to standardize the detection, prevention and management of delirium.
Dr. Falcone is a child and adolescent psychiatrist at Cleveland Clinic and Assistant Professor of Medicine at Cleveland Clinic Lerner College of Medicine. She is the Principal Investigator for Project CARE (Coordination, Access, Resources, Education) 4 Epilepsy, a three-year Health Resources and Services Administration grant to enhance services, including mental health services, for children with epilepsy.
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