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Pediatric Delirium
Introduction
In everyday parlance, delirium is a familiar term. For example, one might say someone is delirious with grief, or someone else might be described as deliriously happy. Although these forms of delirium may look different (i.e., one is somnolent and sad and the other is frenetically gleeful), these behaviors share a common definition that is encapsulated using the term delirium (i.e., an incoherence of thought and speech accompanied by behavioral dysregulation). As this chapter will discuss, the medical definition of delirium is not far from this colloquial one in terms of its phenotypic variability.
Pediatric delirium is a medical emergency that requires immediate management; however, in the hospital and outpatient settings, it often goes underdiagnosed. Mortality rates in untreated delirium range from 12.5% to 29% in affected children. There is ongoing effort to codify the clinical presentation of pediatric delirium with age-appropriate assessment tools to allow for more timely diagnosis and treatment. Adult and pediatric delirium types share many similarities; however, pediatric practitioners should be familiar with the significant differences.
The goal of this chapter is to provide an overview of medical delirium, as it relates to the pediatric population. It is intended for physicians and healthcare providers in primary care and hospital settings. Topics addressed include definition and symptom criteria, epidemiology, pathophysiology, assessment and screening, diagnostic dilemmas, treatment, sequelae, prevention, and integrative care. The incidence of delirium has been shown to be decreased by improving multidisciplinary education and collaboration, which is an additional aspiration of this chapter.
Definition/Symptom Criteria
Delirium is a neuropsychiatric condition involving acute behavioral and mental status changes associated with underlying medical illness. The symptoms that meet the Diagnostic and Statistical Manual , Fifth Edition ( DSM-5 ) diagnostic criteria (see Table 12.1 ) are applicable to both adults and children. As in adults, pediatric delirium may present with three motoric subtypes: hyperactive, hypoactive, and mixed delirium (see Table 12.2 ). Of note, there is a new fourth “informal” category identified in adults called a nonmotoric subtype; however, this has not been described in children. The frequency of these subtypes is well studied in adult populations ; however, a gap in the literature exists for pediatric patients.
TABLE 12.1
DSM-5 Definition of Delirium
From Neurocognitive Disorders . 5th ed. Washington, DC: American Psychiatric Association; 2013. Diagnostic and statistical manual of mental disorders , with permission.
| A | Disturbance in attention (i.e., reduced ability to direct focus, sustain, and shift attention) and awareness (reduced orientation to the environment). |
| B | The disturbance develops over a short period (usually hours to a few days), represents an acute change from baseline attention and awareness, and tends to fluctuate in severity during the course of a day. |
| C | An additional disturbance in cognition (e.g., memory deficit, disorientation, language, visuospatial ability, or perception). |
| D | The disturbances in Criteria A and C are not better explained by a preexisting, established, or evolving neurocognitive disorder and do not occur in the context of a severely reduced level of arousal, such as coma. |
| E | There is evidence from the history, physical examination, or laboratory findings that the disturbance is a direct physiologic consequence of another medical condition, substance intoxication or withdrawal (i.e., due to a drug of abuse or a medication), exposure to a toxin, or is due to multiple etiologies. |
TABLE 12.2
Motoric Subtypes of Delirium
Adapted from Meagher D, Moran M, Raju B, et al. A new data-based motor subtype schema for delirium. J Neuropsychiatry Clin Neurosci . 2008;20(2):185–193, with permission.
| Hyperactive |
|
| Hypoactive |
|
| Mixed motor | Proof of hyperactive and hypoactive features over the prior 24 hours that deviate from baseline |
To date, the most comprehensive data regarding pediatric delirium are from a descriptive study of patients seen by a single pediatric intensive care unit (PICU) psychiatric consult service over a 4-year period at the University Hospital of Maastricht in the Netherlands. These data are presented below; however, further studies are needed to strengthen these preliminary findings.
Hyperactive delirium is characterized by an elevated level of psychomotor activity and mood liability. Symptoms include confusion, psychosis, disorientation, agitation, hypervigilance, hyperalertness, fast or loud speech, combativeness, and behavioral problems, such as pulling out catheters and lines. Patients with hyperactive delirium are often quite disruptive and quickly come to the attention of caregivers. Hyperactive delirium is reported to have a prevalence rate of 35% by Schieveld and colleagues in the above study.
Hypoactive delirium, in contrast, is notable for reduced levels of psychomotor activity, ranging from sluggishness and apathy to lethargy, confusion, and stupor. These patients are more sedate and less disruptive, and consequently their delirium is more likely to be overlooked by care providers or misdiagnosed as depression. The aforementioned study identified 22.5% of patients in the cohort with this subtype.
Mixed delirium describes patients with features of both hyper- and hypoactive delirium or those who fluctuate between the two states. These patients can also present with relatively normal psychomotor activity and solely express disruption of attention and awareness. Mixed delirium can also masquerade as generalized systemic symptoms, possibly presenting with pain, anxiety, and nausea, which occasionally makes it more difficult for medical professionals to recognize. The majority of cases (42.5%) in the Schieveld study were classified with this subtype.
A 2008 study comparing the phenomenology of pediatric delirium with that of adult delirium found delirium in children to have faster onset and more severe perceptual disturbances, mood lability, and agitation. Less severe cognitive deficits, sleep-wake cycle disturbance, and variability of symptoms over time were noted in pediatric patients when compared with adults.
Prevalence/Epidemiology
The epidemiology and risk factors associated with pediatric delirium remain difficult to determine because of a lack of universal hospital screening and recognition. (See Table 12.3 for general risk factors for developing delirium.) However, several studies in the recent years elucidate this area. In a prospective, 10-week, observational study, all children in Cornell University’s PICU were assessed for delirium over the course of their hospitalization. Silver and colleagues showed that the prevalence of delirium was 21% among this cohort of patients (newborns to 21-year-olds). The greatest risk factors for developing delirium included the presence of developmental delay (odds ratio [OR] = 3.45 [1.54, 7.76]), the need for mechanical ventilation (OR = 3.86 [1.81, 8.24]), and age 2–5 years (OR = 8.80 [1.82, 42.53] compared with adolescents >13 years of age).
TABLE 12.3
Risk Factors for Developing Delirium
From Wolfe J, Hinds P, Sourkes P. Textbook of Interdisciplinary Pediatric Palliative Care E-Book: Expert Consult Premium Edition . Philadelphia: Elsevier Health Sciences; 2011, with permission.
| Predisposing Factors | Precipitating Factors | Environmental Factors |
|---|---|---|
| Age Genetic predisposition Neurologic disease Psychiatric illness Visual impairment Hearing impairment Surgery |
Electrolyte imbalance Hypoxia Acidosis Hypoalbuminemia Fever Hypotension Sepsis Infection Polypharmacy Oversedation Medication withdrawal Sleep deprivation |
Immobility Light/noise Reduced social interaction Pain Use of IV lines Physical restraints |
In a similarly designed study looking at delirium in Columbia University’s pediatric cardiothoracic intensive care unit (ICU), the prevalence of delirium (49%) was significantly higher. Patel and colleagues corroborated that developmental delay was a risk factor for delirium in their patients (OR = 3.38 [1.18–9.66]). Better nutrition (OR = 0.19 [0.04–0.84] with albumin >3 mg/dL) and older age (compared with 0–2 years, 2–5 years had OR = 0.30 [0.12–0.72], 5–13 years with OR = 0.30 [0.10–0.87], and >13 years with OR = 0.06 [0.02–0.22]) were protective factors. The risk factors identified in these two studies parallel risk factors identified in adults, which include preexisting cognitive impairment, medications with high anticholinergic effects, sleep deprivation, hypoxia, metabolic abnormalities/poor nutrition, and a history of alcohol or drug abuse.
As expected with patients studied in more acutely ill settings (i.e., PICU and cardiothoracic ICU), these two studies report a prevalence of pediatric delirium that is much higher than earlier reports (see Chapter 28: Delirium by Wolfe and colleagues, for an in-depth comparison of these earlier studies). The largest of these earlier single-center, retrospective studies reported a 9% prevalence of delirium in a sample of 1027 pediatric patients referred for psychiatric consultation. Another study in a pediatric sample of 877 critical care patients reported an even lower prevalence of 4.6%. These older, more conservative estimates are likely more representative of delirium frequencies among generally hospitalized children. That said, these newer studies use more sensitive screening techniques that likely identify patients who would have previously gone undiagnosed. The true prevalence of delirium among hospitalized children probably falls between these estimates. A later section in this chapter discusses some of the new advances made in screening for improved sensitivity in diagnosis of pediatric delirium.
Pathophysiology/Etiology
Delirium is a behavioral manifestation of global encephalopathy and cognitive slowing caused by multiple dysregulated neural pathways and physiologic processes (see Table 12.4 for some of the most common etiologies). No single mechanism of delirium has yet been identified, although numerous theories have been put forward. Neurotransmitter deficiency/dysregulation, neuroinflammation, and oxidative stress are among the most substantiated mechanisms pertinent to children. Most cases of delirium likely arise from a mix of some or all of these factors. For those seeking a more detailed discussion of these topics, see Maldonado.
TABLE 12.4
Common Etiologies of Delirium
Adapted from Rockwood K. Causes of delirium. Psychiatry . 2008;7(1):39–41; Francis J, Young B, Aminoff MJ, Schmader KE, Wilterdink JL. Diagnosis of delirium and confusional states. UpToDate . 2014, with permission.
| Infectious |
|
| Metabolic |
|
| Neurologic |
|
| Iatrogenic |
|
Neurotransmitter Deficiency/Dysregulation
Delirium is conceptualized as a by-product of aberrations in a number of different neurotransmitters, many of which are the downstream consequences of acetylcholine (ACh) and dopamine (DA) dysregulation. In animal models, a deficiency in cholinergic function relative to other neurotransmitters has been shown to alter arousal, attention, and memory. Samples of plasma and cerebrospinal fluid (CSF) taken directly from delirious patients show low levels of ACh, and resolving delirium correlates with decreased serum anticholinergic activity. Inversely, DA levels are increased in delirium, as measured by increased homovanillic acid (a DA metabolite) in the CSF of delirious patients. Dopaminergic antagonists are often effective in treating delirium, further suggesting this axis is critical to the pathogenesis of delirium. Glutamine, gamma-aminobutyric acid (GABA), and serotonin have also been implicated in the pathogenesis of delirium, perhaps as upstream or downstream consequences of ACh and DA dysregulation. For example, GABAergic agents such as benzodiazepines and barbiturates are shown to exacerbate delirium, probably at least in part by interrupting central cholinergic muscarinic transmission in the basal forebrain and hippocampus, and excess DA is known to potentiate the neurotoxic excitatory effects of glutamate that contribute to delirium.
Neuroinflammation
Peripheral inflammation is theorized to play a large role in the pathogenesis of delirium. Infection, surgery, and trauma induce brain parenchymal cells to release proinflammatory cytokines that increase blood-brain barrier permeability, which allows inflammatory cytokines and chemokines to enter the central nervous system. These cytokines, which include interleukin (IL)-1, IL-2, interferon, and tumor necrosis factor, activate microglia to deleteriously modulate astrocyte and neuronal activity. By a separate mechanism, these cytokines also set in motion a cascade of neurodegenerative metabolites: they activate indoleamine-2,3-dioxygenase, which decreases tryptophan levels and subsequently 5-hydroxytryptamine and melatonin production, which ultimately leads to increased kynurenine and other neurotoxic metabolites in the brain. These cytokines also exacerbate neurotransmitter dysregulation by inhibiting ACh-dependent neuronal pathways, which, as discussed above, precipitates agitation, perceptual disturbances, seizures, and delirium.
Oxidative Stress
Oxidative metabolism is required in many biologic processes to convert toxic chemicals into benign ones, such that when insufficient oxygen is available, these toxins (i.e., oxygen-free radicals, arachidonic acid metabolites, and cytokines) accumulate within tissues and cause potential damage. This process, oxidative stress, can occur in a multitude of conditions, ranging from trauma, severe illness, frank hypoxia, to infection. The brain is particularly susceptible to oxygen-free radical damage, which chemically alters lipids in the myelin sheaths. Impaired oxidative metabolism has been shown to be a predisposing factor for delirium ; this is supported by epidemiologic findings indicating that patients requiring ventilation are at a greater risk for developing delirium. It seems likely that the residual cognitive deficits reported in many recovered delirious patients are at least in part due to this irreversible, oxidative stress–induced brain damage.
Assessment
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