1619CHAPTER 134 Pediatric Delirium In addition to lowering the incidence of delirium, studies have also demonstrated decreased duration of mechanical ventilation and shorter PICU and hospital length o[.]
CHAPTER 134 Pediatric Delirium TABLE 134.1 Risk Factors for Delirium in Children PRECIPITATING RISK FACTORS Predisposing Factors Young age (,2 y) Developmental delay Poor nutrition Cyanotic congenital heart disease Nonmodifiable Modifiable Invasive mechanical ventilation Depth of sedation Benzodiazepines Restraints Red blood cell transfusion Pediatric intensive care unit environment rates demonstrated in children younger than years.27,34,36–38,40,42,45 In the largest study (n 1547), when delirium rates in older children were compared with those in children younger than years, adjusted odds ratios (AORs) decreased incrementally with age In children to years old, the OR was 0.6; in children older than years, the OR was 0.4.42 As another example, a singlecenter study that included 99 children after surgery on cardiopulmonary bypass showed that delirium risk decreased with each additional month of age (OR 0.35; 95% confidence interval [CI], 0.2–0.6).38 Children with baseline cognitive impairment are at higher risk for developing delirium in the setting of critical illness when compared with children with normal development Three separate studies demonstrated more than tripling of delirium risk after controlling for multiple confounders (AOR 3.3, 3.4, and 3.5).27,37,42 As stated previously, this may be analogous to the elderly population with underlying dementia, in whom critical illness can be conceptualized as a “stress test” that unmasks those patients with the least cognitive reserve.14 Other at-risk subgroups include children with cyanotic congenital heart disease (AOR 2.4; P 019) and children with poor baseline nutritional status (more than doubling of delirium risk in three separate studies).36–38,45 A major precipitating factor for delirium is IMV, which has been shown to be an independent risk factor for delirium irrespective of sedation practices or severity of illness A prospective study including 1547 children demonstrated an OR of 1.6 (P 006) in children who required IMV after controlling for age, cognitive impairment, probability of mortality, and depth of sedation.42 In an international point prevalence study, the effect of IMV was even stronger, with an adjusted OR of 1.7 (95% CI, 1.1–2.7) after controlling for multiple confounders.34 In contrast to IMV, which is most frequently not a modifiable risk factor, there are other treatment-related risk factors that are (at least potentially) modifiable An important example is use of restraints A multisite study of 994 subjects revealed a quadrupling of delirium risk (AOR 4.0; 95% CI, 2.0–7.7) after controlling for age, sedation, and IMV Although causality cannot be attributed based on the study design, it is likely that restraint use proceeded delirium development.34 Similar to adults, depth of sedation is an extremely important modifiable risk factor for pediatric delirium A burgeoning pediatric literature demonstrates that an analgosedation approach—in which pain control is optimized and sedation minimized—is not only feasible in critically ill children but also improves outcomes 1619 In addition to lowering the incidence of delirium, studies have also demonstrated decreased duration of mechanical ventilation and shorter PICU and hospital length of stay Importantly, there has been no statistical increase in serious adverse events (including unplanned extubations) that is attributed to this minimalist approach to sedation.46,47 When sedation is absolutely required, the pediatric literature favors avoidance of benzodiazepines in favor of alternative sedative classes (including the a-agonists) There are now seven separate pediatric studies that show an independent increase in delirium risk associated with benzodiazepine treatment, with AORs ranging from 2.2 (n 994) to 5.2 (n 1547).34,36–38,42,48,49 Two studies also demonstrate a dose-response effect, with an incremental increase in delirium risk based on benzodiazepine exposure.48,49 One study noted that for every 1-log increase in benzodiazepines received, there was a 43% increase in subsequent delirium.49 Rather than merely describing associations, a nuanced study by Mody et al used sophisticated statistical modeling to estimate the causal effect of benzodiazepines Marginal structural modeling creates a randomized sample from observational data to minimize both static and time-varying confounders.50 With this approach, benzodiazepines were shown to more than triple the risk for delirium development (OR 3.3; 95% CI, 1.4–7.8).49 Finally, there has been one high-quality randomized doubleblinded placebo-controlled trial comparing midazolam to dexmedetomidine in 42 critically ill adolescents after scoliosis surgery Not only was midazolam use associated with increased delirium rates (31% vs 12.5%; P , 05), total fentanyl use was significantly higher (P 002) and duration of mechanical ventilation was greater (P , 05) in this group as well.51 To summarize, the preponderance of evidence supports a causal inference between benzodiazepine use and delirium With alternative sedative choices available, this offers an important opportunity for modifying our traditional prescribing practices in order to decrease delirium risk in the PICU Another strong and modifiable risk factor for delirium is red blood cell (RBC) transfusion practices A single-center study demonstrated an independent association between receipt of RBCs (AOR 2.2; P 001) and delirium development This was not a function of anemia, as nadir hemoglobin prior to transfusion was not associated with delirium A biological gradient was noted, with odds of developing delirium rising with RBC dosage (ORs 1.4, 1.9, and 2.6 for mL/kg, 10 mL/kg, and 15 mL/kg, respectively).52 Adherence to strict transfusion criteria and transfusing as small a volume of RBCs as necessary may decrease delirium risk At this time, there is insufficient evidence to determine whether opiates, anticholinergics, and steroids independently increase delirium risk Further research is needed to clarify these potential associations Outcomes Pediatric delirium has been linked to delayed extubation, increased hospital and PICU length of stay, and increased hospital costs Most significantly, delirium has been related to excess mortality in PICU patients Delirium is associated with increased duration of mechanical ventilation In a cohort of 93 postoperative patients, early delirium (within the first postoperative days) predicted delayed time to extubation.39 Findings were similar in a separate cohort of 1620 S E C T I O N X I V Pediatric Critical Care: Anesthesia Principles in the Pediatric Intensive Care Unit 99 children after cardiac bypass surgery.38 A longitudinal cohort of 1547 children admitted to a general PICU showed that the duration of mechanical ventilation was longer (median vs day; P , 001) in children with delirium.42 At least five studies (n 93, n 99, n 194, n 300, n 1547) have demonstrated an independent association between delirium and PICU length of stay.37–39,42,48 In the largest study, the adjusted relative length of stay for children with delirium was 2.3 (P , 001) after controlling for IMV and severity of illness on admission.42 A prospective observational study investigating the effect of delirium on hospital costs included 464 consecutive PICU admissions Children were screened for delirium daily Hospital costs were analyzed (using cost-to-charge ratios in 2014 dollars) Results showed that median PICU costs increased 392% in children with delirium (P , 001), with an incremental increase in costs for each day with delirium After controlling for the usual drivers of ICU costs, delirium was independently associated with an 85% increased expense.53 Finally, delirium has been linked to excess mortality in children.42 In fact, in a 1547 patient cohort, delirium was a stronger predictor of mortality (AOR 4.4) than the widely accepted Pediatric Index of Mortality (PIM3; AOR 3.2).54 Although this is a strong and independent association, it is important to recognize that this does not establish a causal relationship Rather, it is likely that delirium is a sensitive marker for patients at high risk for poor outcome Early recognition of delirium will provide practitioners with the opportunity to focus their efforts on these fragile children Further research is needed to explore the longer-term effects of delirium on PICU survivors In adults, delirium has been linked to poor long-term outcomes in regard to cognitive and psychologic health Studies in children exploring the lingering effects of delirium after PICU discharge are underway Clinical Presentation Pediatric delirium is complex and multifactorial, further complicated by developmental variability Normal behavior in a 2-yearold would be considered highly abnormal behavior in a 12-yearold Thus, the developmental context is integral to the diagnosis of delirium in children In fact, in early pediatric delirium research, questions were raised regarding the reliability of the DSM criteria in the diagnosis of delirium in young children, particularly preverbal children To address this issue, Silver and colleagues investigated the reliability of the criterion standard (delirium diagnosis by psychiatric examination using the DSM-IV criteria) by performing 38 paired psychiatric evaluations of children at risk for delirium by two different psychiatrists Of the children in this cohort, 50% were younger than years Interrater reliability of the paired psychiatric assessments was excellent, with a k of 0.95, demonstrating the reliability of the standard criteria for diagnosis of delirium in children.55 The diagnosis of delirium may be challenging in the developmentally delayed child As such, this at-risk subgroup is often omitted from research This is unfortunate and unnecessary, as delirium can be distinguished from static encephalopathy With attention to the child’s prehospital baseline and focus on fluctuation (a hallmark of delirium) in current symptoms, delirium can be reliably diagnosed even in this difficult-to-assess population.41,55,56 Children with delirium can present with a range of alterations in psychomotor activity, including fidgetiness and self-stimulating behavior or sluggish responses to interactions Children and adolescents may have disordered emotional states, with extreme tearfulness, inconsolability, or inappropriate calmness relative to their circumstances In addition, pediatric delirium is often marked by profound sleep disturbance that, when present, further worsens the delirium.57 Delirium in children is most often of the hypoactive or mixed subtypes A large prospective study of 1547 children showed that only 8% of children had hyperactive delirium; 46% had hypoactive delirium and 45% had mixed delirium.42 A study of 99 children in a cardiothoracic ICU had a similar phenotype distribution: 5% hyperactive, 52% hypoactive, and 43% mixed.38 A study focusing on younger patients (n 300, ages months– years) also showed that only 7% of delirious children presented with the hyperactive subtype.40 Although hyperactive delirium represents only a small portion of pediatric delirium, it is the most readily recognized, as the child is actively interfering with the medical team’s interventions In the past, these children frequently received large doses of sedatives, which further contributed to the evolving delirium.58 However, it is the docile child, often termed the “good patient,” who lies in bed without protest and allows the care team to perform multiple uncomfortable interventions, whose condition often goes unnoticed This is markedly abnormal behavior for a preschool- and school-age child and likely represents hypoactive delirium.56 As discussed previously, hypoactive delirium is often missed without routine screening and has been linked to the worst prognosis in several studies in adult patients.3,59 Pediatric delirium (similar to adult delirium) is often shortlasting, with a median duration of days (interquartile range [IQR] 1–5).42 This short-lasting delirium cannot be dismissed, as even day with delirium has measurable negative effects on outcomes.39,40,42 Epidemiologic studies have shown that pediatric delirium often occurs early in the PICU stay, highlighting the importance of screening every patient every day, even on the day of admission.37,39,42 Recurrent delirium is also common, with 27% of children with delirium having repeat discrete episodes within a PICU stay.42 With timely recognition and intervention, the duration of delirium can be decreased Diagnosis Until recently, the only way to diagnose delirium in children was via a psychiatric interview and examination using the DSM criteria This is time-consuming, expensive, and relies on a limited resource (pediatric psychiatrists) This explains why, historically, only children with hyperactive delirium were recognized and received appropriate attention The advent of bedside delirium screening tools presents an opportunity to assess all critically ill children for delirium.12,60,61 Two validated tools are currently available for use in the PICU The Pediatric Confusion Assessment Method for the ICU (pCAM-ICU) is a tool derived from the well-validated and widely used CAM-ICU It uses yes/no questions, hand signals, and pictures and has been designed for use in children older than years who not have significant developmental delay.35 There is a preschool version available, the Preschool Confusion Assessment Method for the ICU (psCAM-ICU), for children months to years of age.40 The pCAM-ICU and psCAM-ICU are point-intime interactive and cognitively oriented assessments Delirium is scored as present or absent CHAPTER 134 Pediatric Delirium 1621 Please answer the following questions based on your interactions with the patient over the course of your shift: Never Rarely Sometimes Often Always Never Rarely Sometimes Often Always Score Does the child make eye contact with the caregiver? Are the child’s actions purposeful? Is the child aware of his/her surrounding? Does the child communicate needs and wants? Is the child restless? Is the child inconsolable? Is the child underactive–very little movement while awake? Does it take the child a long time to respond to interactions? TOTAL • Fig 134.2 Cornell Assessment for Pediatric Delirium (From Traube C, Silver G, Kearney J, et al Cornell Assessment of Pediatric Delirium: a valid, rapid, observational tool for screening delirium in the PICU Crit Care Med 2014;42:656–663.) The Cornell Assessment of Pediatric Delirium (CAPD) is a strictly observational tool, with eight questions that are scored by the bedside nurse on a Likert scale The elements of the tool are consistent with the diagnostic criteria for delirium It is designed to be applicable to children of all ages and cognitive levels.41 A Developmental Anchor Points chart is available for the nurse to use as a point-of-care reference when administering the tool in the youngest preverbal patients.56 The screen is scored on a numeric scale, with a score of or higher consistent with a diagnosis of delirium in a developmentally typical child The individual’s score can be trended over time to determine response to interventions The European Society of Pediatric and Neonatal Intensive Care (ESPNIC) has recommended routine delirium screening of all critically ill children with the CAPD twice daily throughout their PICU stay61 (Fig 134.2) With real-time bedside screening now available, a growing number of PICUs in North America and Europe have implemented delirium screening as part of their routine care Screening takes less than minutes per patient and is essential to ensure early detection (when delirium is most amenable to treatment) of hypoactive, mixed, and hyperactive delirium (Fig 134.3) well as the ability to identify children with delirium in real time, targeted interventions may be employed to minimize its duration and potentially ameliorate the long-term effects of delirium Just as delirium is caused by three associated triggers (underlying illness, complications of therapy, and the environment of care; see Fig 134.1), when delirium is diagnosed, attention should be focused on these three areas as well (Fig 134.4) Treatment Following assessment for previously undetected illness, attention should turn to the numerous clinical factors that can lead to delirium Pain control should be optimized with appropriate use of opiates and nonopiate analgesics.63 Sedation should be With increasing awareness in the pediatric critical care community of the prevalence and poor prognostic implications of delirium, as Underlying Illness Timely detection of delirium offers an early warning sign—a call to attention that something significant is occurring A positive delirium screen should lead to a series of clinical questions Is a new infection brewing? Delirium symptoms often precede the fever, heralding the new infection Is there evolving respiratory or hepatic or renal insufficiency leading to metabolic abnormalities? Is there a new, primary neurologic problem? A focused evaluation— including physical examination, neurologic examination, and appropriate laboratory workup—is indicated.62 Iatrogenic Factors 1622 S E C T I O N X I V Pediatric Critical Care: Anesthesia Principles in the Pediatric Intensive Care Unit • Cornell Assessment of Pediatric Delirium (CAPD) (in all PICU patients) • Pediatric Confusion Assessment Method for the ICU (pCAM-ICU) (in child >5 years old, with no developmental delay) Assess for delirium • Preschool Confusion Assessment Method for the ICU (psCAM-ICU) each shift: (in child months-5 years old) Delirium present if: • CAPD score of or higher* • pCAM-ICU positive • psCAM-ICU positive • Fig 134.3 Detection of delirium *In a child with developmental delay, must also establish alteration from baseline PICU, Pediatric intensive care unit Address underlying disease: • Assess for infection • Optimize pain control • Assess for hypoxemia • Assess for withdrawal Minimize iatrogenic factors: • Minimize sedatives • Avoid benzodiazepines • Avoid anticholinergics • Avoid restraints Optimize environment • Frequently reorient the child • Communicate clearly and concisely (as age appropriate) • Create a quiet, well-lit space with familiar objects from the child’s home • Encourage cognitive stimulation and mobilization during the day • Cluster care to allow for uninterrupted sleep Pharmacologic management of delirium may be indicated and can be implemented at the treating physician’s discretion • Fig 134.4 Delirium treatment algorithm minimized, as clinically appropriate A patient on invasive mechanical ventilation, whose sedative regimen has been steadily escalated over the course of hours to days, may be delirious as a direct result of the sedatives and will often improve with removal of the offending agents.64 As described previously, numerous studies have indicated that benzodiazepines are particularly problematic and that escalating dosages may result in increased risk for delirium and excess ventilator days In years past, clinicians hoped to decrease the traumatic effect of hospitalization by sedating the child; recent data indicate that this is counterproductive, interferes with the clinician’s ability to adequately recognize and treat pain, and may increase the risk of delusional memories and posttraumatic stress disorder.65,66 Many pediatric intensivists have adopted the philosophy that it is better for a critically ill patient to be awake and occasionally upset—with reassurance provided by the parents and the clinical care team—than to “sleep” through the ICU stay.67 Opiate and benzodiazepine withdrawal can precipitate delirium, but it is important to differentiate the physiologic signs of abstinence from the behavioral symptoms of hyperactive delirium In fact, a child with hyperactive delirium who has never been on an opiate will score positive on a number of withdrawal assessment tools.68,69 If delirium is triggered by opiate withdrawal, simply replacing the missing opiate is often insufficient to reverse the symptoms Judicious replacement of the opiate is necessary, but it is important to then approach the delirium as a primary problem rather than continue to escalate the opiate dosage, as this will simply prolong the delirium exposure.70 Reviewing the patient’s medication list is essential Anticholinergic agents and medications with anticholinergic effects may be routinely and often unnecessarily used in the PICU and can frequently be discontinued or replaced.71 If a child with hyperactive delirium is on corticosteroids, a taper should be considered Attention should be paid to minimizing the use of benzodiazepines and replacing these agents with dexmedetomidine when sedation is necessary Environment Optimizing the environment is an achievable goal.72,73 It is important to ensure that children who require corrective lenses have their glasses on when awake Creating a well-lit and uncluttered space during the day is feasible and effective Educating parents and staff to limit guests and avoid commotion at the bedside is essential Familiar items from home, such as a favorite blanket or stuffed toy, are more effective than new gifts Helium balloons can be disconcerting to a lightly sedated child as they move spontaneously and can contribute to hallucinations In adults, early mobilization has been shown to decrease delirium rates and shorten delirium once it occurs.74,75 Implementation CHAPTER 134 Pediatric Delirium 1623 of an early mobilization protocol in the PICU does not have to be as dramatic as walking an intubated child; it can start as a simple change in approach and mindset A child on invasive mechanical ventilation should be permitted to have periods of wakefulness as well as sleep; deep sedation should be avoided When awake, passive range-of-motion activities in bed can be performed by the nurse or an appropriately supervised family member Even young children can be safely maintained with a light level of sedation, awake on the ventilator, and interacting with caregivers, while older children and adolescents can often cooperate with a more aggressive mobilization strategy In these patients, getting out of bed to a chair and/or walking may be attainable goals.76 A difficult challenge is establishing a sleep-friendly environment within the PICU.77 Asking the parents to describe the child’s preferred sleep position can be helpful—a toddler who always sleeps in the prone position at home will have enormous difficulty remaining asleep on the back while critically ill; thus, repositioning may help (especially when mechanically ventilated) Attempts to ensure a quiet, dark environment at night and encouraging parents to continue their usual bedtime routines (such as a storybook or back rub) can help facilitate sleep, even in the ICU.78 Prevention of delirium remains the ultimate goal Data in adults suggest that early mobilization of critically ill patients will reduce the incidence of delirium and shorten its duration.74,75 In hospitalized adults who were not critically ill, delirium rates were decreased using a multicomponent intervention, with protocols for cognition, sleep, mobility, vision, hearing, and hydration.73 There is no evidence that prophylactic administration of antipsychotics decreases delirium rates in the general ICU population There are several prospective studies describing effective preventive strategies for the development of delirium in critically ill children A single-center PICU study decreased delirium rates by 19% with implementation of universal delirium screening and minimization of benzodiazepine-based sedation.27,42 A large quality improvement initiative in another PICU showed a stepwise decrease in delirium rates with implementation of universal delirium screening followed by protocol-based sedation and initiation of early mobilization.43 A systematic approach to family engagement, designed to operationalize the parents’ role in delirium prevention, has shown promising results in pilot studies.67 Further research on prevention of pediatric delirium is necessary and underway Pharmacotherapy Conclusion In 5% to 10% of cases, attempts to address the underlying illness, minimize therapeutic triggers, and optimize the environment are not enough, and persistent delirium symptoms interfere with necessary medical interventions In such instances, pharmacologic therapy for delirium may be considered.72 It is important to stress that this is an off-label use; currently, no drug has been approved by the US Food and Drug Administration to treat delirium in either adults or children Consensus approach is to use antipsychotic agents (either haloperidol or the atypical antipsychotics due to their more favorable side effect profiles) only when absolutely necessary.4 These procognitive drugs regulate neurotransmitters and can help organize thoughts and calm the delirious patient This may facilitate the patient’s cooperation with ongoing medical care and allow the opportunity for the patient to wean from other medications that promote delirium.79 Evidence for pharmacotherapy is scarce There are no published data showing that treatment with haloperidol reduces the duration of delirium in adults or children One randomized, placebo-controlled study showed a reduction in the duration of delirium with quetiapine (an atypical antipsychotic medication) in critically ill adults.80 There have been several case series describing the successful use of atypical antipsychotic agents (including olanzapine, quetiapine, and risperidone) to treat delirium in young children, but no prospective efficacy studies have been conducted to date.81–85 A retrospective study designed to evaluate the safety of quetiapine in treating delirium in critically ill children found no serious adverse events with greater than 2400 doses administered.86 Further research is needed to systematically assess the safety and efficacy of antipsychotics in the treatment of pediatric delirium Delirium is prevalent in critical illness and is associated with significant short- and longer-term morbidity Children are at significant risk of developing delirium while in the PICU With increased awareness of this common problem, pediatric intensivists can detect delirium sooner and implement strategies to treat and prevent this serious complication of PICU care Prevention Key References Mody K, Kaur S, Mauer EA, et al Benzodiazepines and development of delirium in critically ill children: estimating the causal effect Crit Care Med 2018;46(9):1486-1491 Patel AK, Biagas KV, Clarke EC, et al Delirium in children after cardiac bypass surgery Pediatr Crit Care Med 2017;18(2):165-171 Simone S, Edwards S, Lardieri A, et al Implementation of an ICU bundle: an interprofessional quality improvement project to enhance delirium management and monitor delirium prevalence in a single PICU Pediatr Crit Care Med 2017;18(6):531-540 Traube C, Silver G, Gerber LM, et al Delirium and mortality in critically ill children: epidemiology and outcomes of pediatric delirium Crit Care Med 2017;45(5):891-898 Traube C, Silver G, Reeder RW, et al Delirium in critically ill children: an international point prevalence study Crit Care Med 2017;45(4): 584-590 Traube C, Silver G, Kearney J, et al Cornell assessment of pediatric delirium: a valid, rapid, observational tool for screening delirium in the PICU Crit Care Med 2014;42(3):656-663 Meyburg J, Dill ML, Traube C, Silver G, von Haken R Patterns of postoperative delirium in children Pediatr Crit Care Med 2017;18(2):128-133 The full reference list for this chapter is available at ExpertConsult.com ... Pediatric Index of Mortality (PIM3; AOR 3.2).54 Although this is a strong and independent association, it is important to recognize that this does not establish a causal relationship Rather, it... delirium may be challenging in the developmentally delayed child As such, this at-risk subgroup is often omitted from research This is unfortunate and unnecessary, as delirium can be distinguished... interview and examination using the DSM criteria This is time-consuming, expensive, and relies on a limited resource (pediatric psychiatrists) This explains why, historically, only children with