Good afternoon. My name is Dr. Heidi Smith. I will be presenting on the Assessment, Prevention, and Management of Delirium Recommendations from the 2022 SECM PEDS PANDEM Clinical Guidelines. I would like to disclose that I currently am receiving NIH funding for a pediatric sedation trial through NHLBI. The prevalence of delirium has become more accurately quantifiable with the validation and implementation of pediatric-specific delirium tools. The PANDEM Guidelines consolidated data from 15 large prospective cohort studies. With reported prevalence of ICU delirium ranging from 5 to 66 percent, more remote studies often reported on hyperactive delirium, which is the least common subtype of ICU delirium among pediatric patients. Reports of prevalence have increased with more recent validation studies of delirium tools that identify all motoric subtypes, including the most common hypoactive form. This form can be easily missed when patients are not routinely undergoing delirium monitoring. It is pertinent for the clinician to be aware of key risk factors that have been associated with ICU delirium in pediatric patients and encourage routine monitoring. Key predisposing or preexisting factors include younger age, shown to have a significant association with delirium in eight prospective cohort studies. Furthermore, presence of baseline neurodevelopmental delay was associated with a triple risk of delirium during critical illness compared to patients with normal development. Poor baseline nutritional status and cyanotic heart disease have also been associated with development of delirium. Precipitating factors, which include those that are related to the critical illness itself, but also iatrogenic or treatment-related factors, may be modifiable. Factors such as sedation, that includes a dose response component to benzodiazepine exposure and risk of ICU delirium. Also immobilization, additional to need for mechanical ventilation, and the length of cardiopulmonary bypass. Nine prospective cohort studies consistently demonstrate that children with delirium have increased PICU and hospital length of stay. Five prospective cohort studies demonstrated strong associations between delirium and prolonged duration of mechanical ventilation. Median costs were reported to be 85% higher in children who ever suffered from delirium in a large prospective cohort study of 484 patients. The association between delirium and mortality is not clear. In a high-quality prospective longitudinal study of around 1,500 patients, a strong and independent association between delirium and mortality was observed. However, in another large retrospective study of around 2,500 patients, there was no such association. Despite this uncertainty, the vigilance to both monitor and management is key, as there remain additional large knowledge gaps regarding delirium and potential long-term complications of cognitive impairment, attention deficits, and post-traumatic stress symptoms. We answered two specific delirium assessment questions. Which delirium screening tools have the best validity and reliability in critically ill pediatric patients? And should critically ill pediatric patients undergo routine delirium screening? Delirium is a state of acute brain dysfunction. A disturbance of both consciousness and cognition develops acutely with often a fluctuating course of altered mental status, a cardinal feature of inattention, sometimes disturbances in cognition, all triggered by a medical or surgical condition. A series of six pediatric-specific tools were reviewed based on validation literature. The task force focused on three main tools that were validated in a blinded fashion with use of a reference standard consisting of experts in the field of childhood and adolescent psychiatry employing DSM-IV or DSM-V criteria for delirium diagnosis. Additionally, strength of evidence for validation studies included appropriate cohort size, blinding, and easily reproducible methods. The Corneal Assessment for Pediatric Delirium and the Pediatric and Preschool Confusion Assessment Methods for the ICU were validated under robust methods and large cohorts to improve generalizability. The CAPD was adapted from the Pediatric Anesthesia Emergence Delirium Scale or PAED. The CAPD added three additional hypoactive elements including communication of needs, underactivity while awake, and prolonged response to interaction to meet the deficit of the PAED. The CAPD performed with a sensitivity of 94% and specificity of 79% compared with reference standard in a cohort of 111 patients. The tool is an observational using interaction over a nursing shift to grade these eight domains using a Likert scale. The Pediatric and Preschool Confusion Assessment Methods for the ICU are both interactive and observational point-in-time assessments for delirium adapted from the highly valid precursor, the adult CAM-ICU. These tools require the presence of DSM criteria for delirium including acute change or fluctuation from baseline mental status and inattention. The PCAM-ICU for patients five years and older was validated in a cohort of 68 patients and performed with a sensitivity of 83% and specificity of 99% against a reference standard. The preschool CAM-ICU was further adapted for use in infants and children developmentally less than five years of age and validated in a cohort of 300 patients aged six months to five years having a sensitivity of 75% and specificity of 91% compared to the reference standard. We recommend use of the PS or PCAM-ICU or the CAPD as the most valid and reliable delirium monitoring tools in critically ill pediatric patients. We further recommend routine screening for ICU delirium using one of these validated tools upon admission through ICU discharge or transfer. We answered three specific questions on prevention and management. Among critically ill pediatric patients, what non-pharmacologic or pharmacologic sedation strategies reduce the incidence and or decrease the duration or severity of delirium in critically ill pediatric patients? And does the use of haloperidol or atypical antipsychotics reduce the occurrence rate and or decrease the duration or severity of delirium in critically ill pediatric patients? Though the impact of the ICU environment is considerable, there remains a dearth of information regarding the impact of environmental modifications such as artificial light, minimization of noise, and bundling care on development or duration of delirium. As pediatricians, however, we can reflect on the importance of nutrition, sleep, and physical activity for healthy children, and therefore the ongoing push to assess these adages in the ICU setting are important. Family presence, despite our historical inclusion of family in the care for pediatric patients, there remains a lack of data regarding impact of family presence on delirium. Prevention strategies focused on vigilance of assessment and resolution of disease-related causes and iatrogenic sources that may exacerbate delirium is of great importance and can be quickly reviewed using the acronym BRAINMAPS, ranging from adequate oxygenation, remove or reduction of delirogenic drugs, the ICU atmosphere or environment, immobilization, new organ dysfunction, metabolic disturbances, and the three really hard ones, having patients more awake with less pain and exposure to less sedation. Less sedation seems like a simple request, but it's hard to follow through as being awake may not fit the needs of every critically ill pediatric patient, so we will discuss how we walk this line to both support patient needs and decrease risk of delirium. PEDS PANEM recommendations for non-pharmacologic strategies for delirium, given low patient risk and possible patient benefit to reduce the incidence and or decrease duration or severity of delirium, we suggest the following non-pharmacologic strategies, optimization of sleep hygiene, use of interdisciplinary rounds, family engagement on rounds, and family involvement with direct patient care. We further suggest performing early mobility when feasible to reduce the development of delirium. The pharmacologic management of delirium in some ways is relatively straightforward. There is no drug that cures delirium. It becomes complicated because the primary goal is treatment of underlying causes as we reflect on the acronym of BRAINMAPS. The secondary goals become patient safety and mitigation of severe manifestations. In many ways, the pathway to decrease sedation exposure in relation to its impact on delirium is through our response to agitation. The word itself seems harmless, except when you are in the pediatric ICU. This word is not only a symptom, but creates what seems like a never-ending dilemma, but to which the answers to three simple questions may be helpful in decreasing iatrogenic harm in relation to delirium. Agitation is a symptom. It may be due to pain, anxiety, fear, iatrogenic withdrawal, or delirium. This symptom, however, often drives the use of sedatives and opioids in the PICU. The dilemma is whether agitation needs treatment, if there is adequate patient-ventilator synchrony, and the patient is safe, hemodynamically or otherwise. The answer of three questions, which get back to the crux of the PANDEM guidelines, are where is my patient now, assessment, where are they going, reassessment, and how do I get them there, make a plan, meaning that maintaining a view of the overall path of the patient may allow the integration of other ways to address agitation than sedation alone, thereby impacting the development and duration of delirium. We incorporate what do we know with what do we do. Three larger prospective cohort studies have demonstrated that greater exposure to benzodiazepines is an independent risk factor for delirium. This does not mean that all patients who receive benzodiazepine will develop delirium, nor that other sedatives are not associated with delirium. We know that pediatric patients' needs are different, and only with a shift in the way we interpret agitation while providing adequate analgesia will we be able to impact avoidance or decrease of sedative exposure. We will need to be creative as a community to use non-pharmacologic approaches to support patient comfort. While we would all love for a new sedative to provide sedation without risk of adverse outcomes, we know without a change in our culture or expectation of sedation in the PICU that it will not matter what sedative we employ, the risk for delirium will remain. There may be a role for haloperidol or atypical antipsychotics in the treatment of severe manifestations of delirium resulting from an imbalance in excitatory and inhibitory neurotransmission. Excessive dopaminergic activity leads to hyperactive manifestations such as combativeness or severe agitation, or excessive GABA or cholinergic activation leads to hypoactive manifestations such as lability in mood, withdrawing from caregivers, or a child not acting like themselves. Haloperidol is often used in instances of severe hyperactive delirium as it works through dopaminergic blockade. The associated sedation and relief of severe agitation can decrease use of other sedatives that may further exacerbate these manifestations of delirium. Atypical antipsychotics can be used for both hyperactive and hypoactive delirium with their broader effects on dopaminergic, alpha-2, and serotonergic receptors. The task force reviewed 10 retrospective cohort studies and 7 case reports or series including around 350 pediatric patients receiving haloperidol or atypical antipsychotics for delirium manifestations. Generally, there was significant improvement in manifestations of delirium with few reports of significant adverse drug events. However, we are cautioned by the lack of prospective cohort studies or randomized control trials. Additionally, any use of haloperidol or atypical antipsychotics is off-label for pediatric delirium. When used, goal is short-term use with reassessment and monitoring of pertinent side effects. We recommend minimizing benzodiazepine-based sedation when feasible in critically ill pediatric patients to decrease incidence and or duration or severity of delirium. We suggest strategies to minimize overall sedation exposure whenever feasible to reduce coma and the incidence and or severity of delirium in critically ill children. We do not suggest routine use of haloperidol or atypical antipsychotics for the prevention of or decrease in duration of delirium. We do suggest, however, that in critically ill pediatric patients with refractory delirium, haloperidol or atypical antipsychotics are considered for the management of these severe delirium manifestations. When used, we recommend a baseline electrocardiogram followed by routine electrolyte and QTC interval monitoring for patients receiving haloperidol or atypical antipsychotics.

delirium

pediatric patients

ICU delirium

validated delirium screening tools

non-pharmacologic strategies