A Clinical Practice Guideline for the Recognition, Diagnosis, and Management of Neonatal Delirium

Purpose. The objective of this project was to create a clinical practice guideline (CPG) in order to standardize the assessment and treatment of neonatal delirium in a newborn intensive care unit (NICU) environment. Methods. An evidence-based CPG was developed using literature pertaining to pediatric and neonatal delirium within the past 10 years. Key stakeholders were invited to participate in the educational program. Participants included neonatologists, neonatal fellows, neonatal nurse practitioners (NNPs), child psychiatrists, and palliative care practitioners. Pre- and posttest questionnaire results were analyzed using a paired t-test to assess learning of participants. Results. The results from the pre- and post-education surveys showed that all but two participants agreed or strongly agreed that neonatal delirium is a disease process with recognizable symptoms that requires intervention. The educational presentation significantly increased knowledge and confidence in recognizing signs and symptoms of delirium, identifying risk factors, using the CAPD screening tool to aid in diagnosis of delirium, understanding environmental measures that prevent and treat delirium, and pharmacologic management principles for delirium. An unexpected finding was that participants with fewer than five years' experience had greater confidence than more experienced practitioners in recognizing the signs and symptoms of delirium, identifying risk factors, identifying environmental measures that prevent and treat delirium, and using pharmacologic management. Conclusions. The results suggest that providing education to key stakeholders increased the recognition, diagnosis and management of neonatal delirium. The CPG will need to be evaluated after implementation into the NICU setting to assess its effectiveness in recognizing and managing neonatal delirium.

Running head: NEONATAL DELIRIUM A Clinical Practice Guideline for the Recognition, Diagnosis, And Management of Neonatal Delirium Krista Schulte, RN, BSN Project Chair: Pamela Phares, PhD, APRN, CNM Content Expert: Lisa Giles, MD The University of Utah College of Nursing In partial fulfillment of the requirements for the Doctor of Nursing Practice 1 NEONATAL DELIRIUM Abstract 2 Purpose. The objective of this project was to create a clinical practice guideline (CPG) in order to standardize the assessment and treatment of neonatal delirium in a newborn intensive care unit (NICU) environment. Methods. An evidence-based CPG was developed using literature pertaining to pediatric and neonatal delirium within the past 10 years. Key stakeholders were invited to participate in the educational program. Participants included neonatologists, neonatal fellows, neonatal nurse practitioners (NNPs), child psychiatrists, and palliative care practitioners. Pre- and posttest questionnaire results were analyzed using a paired t-test to assess learning of participants. Results. The results from the pre- and post-education surveys showed that all but two participants agreed or strongly agreed that neonatal delirium is a disease process with recognizable symptoms that requires intervention. The educational presentation significantly increased knowledge and confidence in recognizing signs and symptoms of delirium, identifying risk factors, using the CAPD screening tool to aid in diagnosis of delirium, understanding environmental measures that prevent and treat delirium, and pharmacologic management principles for delirium. An unexpected finding was that participants with fewer than five years' experience had greater confidence than more experienced practitioners in recognizing the signs and symptoms of delirium, identifying risk factors, identifying environmental measures that prevent and treat delirium, and using pharmacologic management. Conclusions. The results suggest that providing education to key stakeholders increased the recognition, diagnosis and management of neonatal delirium. The CPG will need to be evaluated after implementation into the NICU setting to assess its effectiveness in recognizing and managing neonatal delirium. Running head: NEONATAL DELIRIUM Introduction 3 Problem Description Delirium is an acute neuropsychiatric syndrome in the setting of serious illness that is well studied in the adult and geriatric populations but has not been extensively studied in the neonatal and pediatric population. Delirium is defined as an acute and fluctuating change in awareness and cognition that often occurs as the result of serious medical illness (Groves, Traube, & Silver, 2016). Studies have shown that the prevalence of delirium in critically and/or chronically ill infants from birth to 24 months of age may be as great as 20% and can be associated with a worse functional outcome, a longer and more costly hospital stay and a higher mortality rate (Traube, Silver, Reeder, et al., 2017). Available Knowledge The etiology of delirium is often multifactorial and can include "circulating cytokines and locally acting chemokines, impaired oxidative metabolism, abnormal neurotransmitter release, and alteration in complex neurotransmitter interactions" (Turkel, Jacobsen, & Tavaré, 2013, p. 352). However, factors placing both critically and chronically ill infants at high risk for developing delirium include severity of illness, iatrogenic drug withdrawal, mechanical ventilation, use of restraints, underlying neurologic pathology, developmental delay and postoperative recovery. High dosing or prolonged use of benzodiazepines, opioids, anticholinergics, steroids also put an infant at risk for developing delirium (Traube, Silver, Gerber, et al., 2017; Traube, Silver, Reeder, et al., 2017). Early diagnosis and treatment of delirium is important to minimize the morbidity of ongoing delirium and its associated disruption in care. In many NICUs, delirium is a diagnosis that is rarely considered and therefore underdiagnosed (Schieveld & Leentjens, 2005). Because NEONATAL DELIRIUM of their high vulnerability to the development of delirium and their exposure to many of the risk 4 factors, high-risk neonates should be frequently screened to allow for early diagnosis and treatment (Silver, Kearney, Kutko, & Bartell, 2010). The most important step in delirium management is early recognition. Because infants are preverbal, it is necessary to use appropriate developmental milestones when assessing highrisk infants. With this in mind, the Cornell Assessment of Pediatric Delirium (CAPD) (Figure 1) was created with developmental anchor points for newborns as well as infants at four weeks, six weeks, eight weeks, 28 weeks, 12 months and 24 months of age (Figure 2). These anchor points help guide the nursing assessment to determine if the infant is exhibiting clinical signs of delirium including deficits in awareness, cognition, and arousal. In validity studies, the CAPD tool was found to have both high sensitivity and specificity (92%; CI, 85.7-98.3% and 86.5%; CI, 75.4-97.6%, respectively) in infants without significant developmental delay (Traube et al., 2014). A CAPD score of 9 or higher, or an increase in score above the infant's established baseline, represents a positive screen; the diagnosis is then confirmed by the physician (Traube et al., 2017). While the CAPD scoring is a reliable and valid assessment tool, the gold standard for diagnosis of infant delirium is a formal assessment by a child psychiatrist using the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. The DSM-IV characterizes delirium by four features: (1) inattention and disturbance of consciousness; (2) change in cognition; (3) acute onset and fluctuating course; and (4) pathophysiological cause (Schieveld et al., 2009). When the diagnosis of delirium is made in an infant, the first goal of treatment is to minimize or eliminate predisposing factors such as benzodiazepines, anticholinergics, opioids, NEONATAL DELIRIUM barbiturates, steroids, and restraints (Silver et al., 2010). Researchers also suggest following a 5 three-pronged approach that includes investigating for underlying illness, iatrogenic causes, and abnormal environment before initiating pharmacologic treatment (Traube, Silver, Reeder, et al., 2017). If the infant remains delirious after the clinician has addressed these factors, pharmacologic treatment with an atypical antipsychotic such as quetiapine should be considered. In one study, researchers conducted an international point prevalence study to determine the prevalence of delirium in critically ill infants and young children and to explore associated risk factors (Traube, Silver, Reeder, et al., 2017). They studied infants and children in 25 pediatric critical care units in the United States, the Netherlands, New Zealand, Australia, and Saudi Arabia. Infants were screened for delirium using the CAPD. It was discovered that delirium is a frequently occurring complication of critical illness in infants and young children with a point prevalence of 25% across multiple institutions. The highest percentage of cases occurred in infants younger than 24 months, those with infectious/inflammatory disorders and those requiring prolonged mechanical ventilation (MV) with increased exposure to sedatives. They also found that CAPD scoring was a reliable and valid method for assessing delirium in infants and young children. Researchers in another study described cases of three infants in the neonatal intensive care unit at corrected gestational ages of four, 11, and 17 weeks who presented with typical symptoms of delirium (Groves et al., 2016). All three infants had complex medical problems and were receiving multiple analgesic and sedative medications. They exhibited agitation that was unresponsive to increasing doses of medications, and they all appeared to improve after treatment with quetiapine, allowing weaning of mechanical ventilation and analgesic and sedative medications. The authors of the study stated that although neonates are likely at risk, NEONATAL DELIRIUM delirium is not currently recognized as a common complication of the NICU environment. The 6 authors also contended that with increased vigilance, delirium will be increasingly recognized in newborns, thus allowing tailored intervention. Rationale Researchers have strongly advocated for standardized assessment and clinical screening tools for the detection of delirium in all critically ill patients, regardless of age (Silver et al., 2015). The purpose of a clinical practice guideline (CPG) is to promote evidence-based interventions in an effort to improve the consistency and quality of care. Such guidelines also benefit healthcare professionals by offering recommendations when one is uncertain about how to proceed (Woolf, Grol, Hutchinson, et al., 1999). Clinical guidelines also save time by synthesizing the most current research evidence to guide diagnosis and treatment. A CPG for the assessment and treatment of neonatal delirium may reduce morbidity and mortality associated with delirium and improve clinical outcomes for this population. Specific Aims The purpose of this project was to create a CPG in order to standardize the assessment and treatment of neonatal delirium in a NICU environment. The specific aims included: (1) identifying characteristics of delirium, diagnostic criteria, and best practices related to delirium management in neonates, (2) applying an evidence-based approach for developing the CPG with stakeholders, and (3) beginning the process of implementation, and testing its feasibility. Methods Context This CPG was developed for implementation at a 52-bed level IV surgical NICU in the intermountain west region of the U.S. The NICU at Primary Children's Hospital (PCH) in Salt NEONATAL DELIRIUM Lake City, Utah cares for infants aged 23 weeks gestation at birth to 24 months of age. This 7 NICU cares for critically ill infants with myriad diagnoses including those requiring open-heart surgery, neurosurgery, GI surgery and ECMO. Additional input for the development of this CPG was elicited from approximately 20 neonatologists, nine neonatal fellows, 60 neonatal nurse practitioners (NNPs), eight members of the palliative care team and a pediatric child psychiatrist who is experienced in diagnosing and treating neonatal and pediatric delirium. Five cases of neonatal delirium were recently recognized and treated in this NICU guided by the child psychiatrist prior to the development of this CPG. It was determined at that time that a CPG specific to recognizing, diagnosing and managing neonatal delirium in infants would be beneficial. It would also allow for increasing awareness and knowledge of delirium in the NICU in order to facilitate prompt diagnosis and treatment of the disorder while also standardizing the care that these infants receive. A standardized approach also allows for a more accurate analysis of the efficacy of the treatment in terms of improving the patient's cognitive and emotional status and reducing the risk of adverse short and long-term health outcomes. Intervention Because there are no data regarding the safety of treatment of delirium with an atypical antipsychotic for premature infants who are fewer than 37 weeks of age, the proposed CPG was not intended for use in this population. The CPG was developed for use in infants who are greater than 37 weeks corrected gestational age including infants up to 24 months of age at the time they begin exhibiting symptoms of delirium. While all project participants were educated on delirium and able to provide feedback about the CPG, the primary investigator, two neonatologists, two NNPs, and a child psychiatrist worked as a multidisciplinary team to develop the CPG (Appendix A). NEONATAL DELIRIUM The CPG was developed based on the most current evidence from a review of the 8 literature regarding neonatal and infant delirium in a NICU or PICU setting. The first section of the CPG contains guidelines for the recognition of delirium and identifies factors that place an infant at high risk for developing delirium. Risk factors include high severity of illness frequently involving infectious and inflammatory disorders, underlying neurologic issues, prolonged mechanical ventilation, iatrogenic drug withdrawal, pharmacologic treatment with benzodiazepines, opiates, sedatives, anticholinergics, or steroids, post-operative recovery, the use of restraints, and prolonged hospitalization. In many cases, a combination of these risk factors contributes to the development of delirium. This section also outlines common signs and symptoms. The second section of the CPG outlines principles to guide clinicians in the diagnosis of delirium using the CAPD scoring system previously discussed. The CAPD is a valid and reliable screening tool that detects changes in cognition and aids in the diagnosis of delirium in infants. A CAPD score of nine or greater indicates a positive screen. For infants with a baseline at or above nine, an increase in score from the infant's baseline represents a positive screen. For infants with a positive screen, a definitive diagnosis of delirium is made by a child psychiatrist who evaluates the child using DSM-IV criteria. The final section of the CPG outlines treatment recommendations for delirium once a diagnosis has been made. Initial treatment includes non-pharmacologic interventions such as assessing for and treating underlying illness, minimizing and/or eliminating use of deliriuminducing medications and implementing therapeutic environmental measures. Environmental measures are focused on promoting healthy sleep patterns, encouraging activation during the day, and promoting a calm, supportive, and consistent environment (Appendix A). However, if non- NEONATAL DELIRIUM pharmacological management is insufficient, pharmacologic therapy with an atypical 9 antipsychotic agent such as quetiapine should be considered. Study of the Interventions Due to time constraints for implementation of this project, final system approval of the CPG was not possible. The goal for this project was to inform and educate the stakeholders about neonatal delirium and introduce the CPG to them for feedback. After stakeholder feedback was incorporated and the final draft was approved by content experts, formal submission of the CPG for institutional approval was initiated. The implementation phase as well as the assessment of the effectiveness of the CPG in clinical practice will be explored in a later project. To assess the impact of the educational program on preparing stakeholders to recognize, diagnose and manage neonatal delirium and to obtain feedback on the CPG, pre- and postsurveys were completed with a group of neonatologists, neonatal fellows, NNPs, palliative care team and a pediatric child psychiatrist. This data was useful for establishing further educational needs of clinicians and modifications of the CPG before it is integrated into practice at the system level. Measures Participants for the interviews were recruited by email invitation. The goal was to recruit a minimum of ten neonatologists, five neonatal fellows, and ten NNPs. There is not currently a survey tool to assess the effectiveness of education on this topic so survey questions were developed using a Likert scale and piloted with a small group at Primary Children's Hospital (PCH) which was comprised of two neonatologists, two NNPs one neonatal fellow and the child psychiatrist who are familiar with diagnosing and treating neonatal delirium. Three NNPs who NEONATAL DELIRIUM are unfamiliar with neonatal delirium were also included. The survey questions were edited 10 based on feedback from the pilot group to assure clarity and appropriateness of questions. A 45-minute educational session was offered to participants followed by 15 minutes of discussion on February 26, 2018. Participants were asked to complete pre- and post-education surveys to compare understanding of and confidence in the recognition, diagnosis and management of neonatal delirium (Appendix B). The education was based on information included in the clinical practice guideline (CPG). The pre- and post-education surveys required no more than 10 minutes to complete and feedback was also elicited. The data gathered was analyzed to determine if the educational session increased understanding and confidence in the recognition, diagnosis and management of neonatal delirium. It was also used to evaluate whether the group viewed the CPG as an effective tool for clinical practice. Participant feedback was used to make revisions and improvements to the program and the CPG. Analysis A paired t-test was used to measure the change between pre- and post-survey scores. The level of significance was set at p < 0.05. Qualitative responses were evaluated for content and summarized. Ethical Considerations This project was determined to be non-human subject research by the University of Utah Institutional Review Board and was therefore exempt from IRB approval. Participants were not compensated for their time. Results E-mails were sent to 20 neonatologists, nine neonatal fellows, 60 neonatal nurse practitioners (NNPs), eight members of the palliative care team and a pediatric child psychiatrist NEONATAL DELIRIUM 11 at Primary Children's Hospital. Of those, 57 (58%) potential participants indicated they would be willing to attend the educational presentation and participate by completing pre- and posteducation surveys. A follow up e-mail was sent again to all 98 potential participants three days before the presentation to remind them of the date, location and time and thank them for their willingness to participate. On the day of the presentation, 37 (38%) of the invited participants were present. Of those, 12 (32%) were neonatologists, 6 (16%) were neonatal fellows, 14 (38%) were NNPs, and 5 (14%) were members of the palliative care team/child psychiatrist. Demographic characteristics of participants are described in Table 1. Participants scored each pre- and posttest question using a five-point Likert scale ranging from strongly disagree to strongly agree. For analysis purposes these responses were numbered from 1 to 5 in which 1 = "strongly disagree", 2 = "disagree", 3 = "neither agree nor disagree" and 5 = "strongly agree". The pre-test scores showed that participants viewed neonatal delirium as a disease process that needs to be treated (4.3 ± 0.7) and they believed a CPG would increase their confidence in the recognition, diagnosis and management of delirium (4.3 ± 0.7). The results also showed need for improvement in recognizing signs/symptoms of delirium (2.4 ± 0.8), understanding high-risk factors (3.3 ± 0.9), using CAPD screening tool to aid in diagnosis (2.1 ± 1.1), understanding therapeutic environmental measures to prevent/treat delirium (3.1 ± 1.2) and using pharmacologic management (2.4 ± 0.8). After the presentation there was there was no significant change in participants' belief that delirium was a disease process that needed to be treated (p=0.96) and if they thought a CPG would be helpful in clinical practice (p=1.0). Pre-test scores were already high so posttest differences were difficult to detect in the small sample size. There was one participant who stated NEONATAL DELIRIUM 12 they were less confident that delirium was a disease process that needed to be treated and there were four participants who were less confident that a CPG would be helpful in clinical practice. The educational presentation did increase knowledge and confidence in recognizing signs and symptoms (p=0.0001), understanding high-risk factors (p=.0001), using CAPD screening tool to aid in diagnosis (p=.0001), understanding what environmental measures help prevent or treat delirium (p=.0001) and using pharmacologic management (p=.0001). Two participants indicated that they were less confident in using the CAPD screening tool to aid in the diagnosis of delirium after the presentation and one participant was less confident in using pharmacologic treatment to manage delirium. The second data analysis compared scores according to job title. Group one included neonatologists, group two included neonatal fellows, group three included NNPs, and group four included palliative care and psychiatry providers. Neonatal fellows and palliative care and psychiatry providers were more likely than neonatologists and neonatal nurse practitioners to view delirium as a problem requiring treatment. There were no significant differences in the recognition, diagnosis or management of neonatal delirium or perceived benefit of a CPG among the different groups. The third data analysis compared groups according to years of experience in neonatology. Group one included participants with fewer than five years of experience, group two included those with six to 15 years' experience and group three included participants with greater than 15 years of experience. In the pre-survey, participants in group one were more likely than those in groups two and three to view delirium as a disease process that needs to be treated. Those in group one were also more likely to feel confident in recognizing signs and symptoms, identifying high risk factors, understanding what environmental measures help prevent and treat delirium, NEONATAL DELIRIUM using pharmacologic management and viewing a CPG as helpful in the clinical setting. There 13 was no significant difference in confidence using the CAPD to aid in diagnosis. There were also no significant differences among scores in the pre-survey between groups two and three or difference between pre-survey and post-survey results in any group. Question eight on the survey asked participants to state anticipated barriers to implementation and effectiveness of the CPG. The number one barrier listed was lack of knowledge and education about delirium. Belief in delirium as a disease process affecting the neonatal population and lack of study about the phenomenon were also commonly identified barriers. Other barriers included lack of concordance among staff acknowledging the phenomenon of neonatal delirium, difficulty changing the unit's culture, inconsistency in daily patient care assignments, nurses not implementing environmental measures, unknown risks of atypical antipsychotic use in neonates, inconsistencies in staff education, and varying interpretation of neonatal behavior. Factors that may have affected the confidence of participants in the recognition, diagnosis and management of neonatal delirium include doubt that young infants in the NICU experience delirium, a lack of conclusive evidence or prospective studies about delirium in this population, low prevalence rates in the NICU leading to infrequent clinician exposure to the phenomenon, and a lack of formal education on neonatal delirium. Reasons for not attending the educational session per verbal and e-mail replies included working at an outlying hospital during the presentation, other work or family commitments, long distance to travel for a one hour meeting, and forgetting to attend. NEONATAL DELIRIUM Discussion 14 Summary Results indicated that there is a lack of confidence and knowledge among providers and key stakeholders in the NICU setting regarding the recognition, diagnosis and management of neonatal delirium. Providing education on neonatal delirium, resulted in increased knowledge and confidence of participants. That there was no significant change in the belief that delirium is a disease process requiring treatment after the educational intervention was unexpected. Feedback provided by participants suggested that the lack of clinical trials and prospective studies on the prevalence and treatment of neonatal delirium was a major reason for this finding. It was also unexpected to find that those with fewer years of experience in neonatology were more likely to view neonatal delirium as a disease process that needed to be treated. They were also more likely to feel confident in the recognition, diagnosis and management of neonatal delirium. Delirium in the neonatal population is only recently being recognized nationally as a disease process that affects infants and this may have influenced these findings. Interpretation Many articles have been published on the recognition, diagnosis and management of pediatric delirium in an ICU setting. Most studies include infants from birth to more than 24 months of age with several focusing solely on this population. There are currently only a handful of articles that focus specifically on neonatal delirium in the NICU setting. The paucity of relevant studies illustrates the need for more research in the NICU population. The proposed CPG was created by synthesizing data from both the pediatric and neonatal literature. It can be used to guide the provider in preventing as well as managing neonatal delirium. Although multiple case studies showed that atypical antipsychotics are safe to use and have relatively few NEONATAL DELIRIUM side effects in neonates studied, care should be taken when prescribing them since no large 15 controlled clinical trials have been done to definitively determine their safety. Findings confirmed that neonatal delirium is under-recognized and under-diagnosed as the literature suggests. By providing education to providers, we found that providers are more confident in their knowledge and ability to recognize, diagnose and manage neonatal delirium. Most participants were receptive to the education. Some voiced opinions regarding their doubt that delirium is a common problem in this population, though many agreed that some of the recommended environmental interventions recommended by the CPG would be beneficial in this population to prevent onset of delirium. Limitations This study is limited in several ways. First, the participants in this study were all providers which excluded registered nurses and neonatal pharmacists who are key health care team members. Because registered nurses are at the bedside, they are better equipped to notice acute changes in cognition that may be related to delirium. Registered nurses also complete the CAPD screening tool each shift and report concerning findings to the providers. Neonatal pharmacists who manage all medications that infants receive as well as any atypical antipsychotics that are prescribed, are critical for advising on the management and weaning of delirium-inducing medications. Further study with these two groups of professionals is recommended. Another limitation is the lack of conclusive evidence and prospective studies. Many studies show the effectiveness of environmental measures in treating delirium but there are no clinical studies in this population on treatment with atypical antipsychotics. All information used for this CPG is based on case studies presented in the literature. Another limitation is that the NEONATAL DELIRIUM 16 CAPD screening tool was studied in the pediatric population. Developmental anchor points were created in an effort to aid nurses in understanding normal development for a given age but no studies have been done to validate the exclusive use of this screening tool in a NICU setting. More research needs to be conducted to determine the validity and reliability of the CAPD as a neonatal screening tool. Finally, the time constraints imposed by the timeline for implementation of the project contributed to a reduced number of participants. Inclusion of all caregivers in the NICU setting was not possible in the timeframe allotted for implementation and evaluation. Conclusions The educational intervention was effective for increasing providers' confidence in their knowledge and ability to recognize, diagnose and manage neonatal delirium. The use of a CPG is expected to help providers translate that education into clinical practice. More education needs to be done to include clinicians who were unable to attend as well as neonatal nurses, respiratory therapists, and pharmacists. Through education and clinical use of the CPG, awareness and prevention of delirium are predicted to increase, thus reducing morbidity in neonates. Further study is recommended to determine the prevalence of delirium in the NICU setting, the safety and efficacy of treatment with atypical antipsychotics, and the reliability and validity of the CAPD screening tool in the NICU population. NEONATAL DELIRIUM References 17 Groves, A., Traube, C., & Silver, G. (2016). Detection and management of delirium in the neonatal unit: A case series. Pediatrics, 137(3), e1-e4. doi: 10.1542/peds.2015-3369 Schieveld, J.N., & Leentjens, A.F. (2005). Delirium in severely ill young children in the pediatric intensive care unit (PICU). Journal of the American Academy of Child and Adolescent Psychiatry, 44(4), 392-394. doi: 10.1097/01.chi.0000153231.64968.1a Schieveld, J.N., van der Valk, J.A., Smeets, I.A., Berghmans, E., Wassenberg, R., Leroy, P.L., … van Os, J. (2009). Diagnostic considerations regarding pediatric delirium: A review and a proposal for an algorithm for pediatric intensive care units. Intensive Care Medicine, 35(11), 1843-1849. doi: 10.1007/s00134-009-1652-8 Silver, G.H., Kearney, J.A., Kutko, M.C., & Bartell, A.S. (2010). Infant delirium in pediatric critical care settings. American Journal of Psychiatry, 167(10), 1172-1177. doi: 10.1176/appi.ajp.2010.09111606 Silver, G., Kearney, J., Traube, C., & Hertzig, M. (2015). Delirium screening anchored in child development: The cornell assessment for pediatric delirium. Palliative & Supportive Care, 13(4), 1005-1011. doi:10.1017/S1478951514000947 Traube, C., Silver, G., Gerber, L.M., Kaur, S., Mauer, E.A., Kerson, A. …Greenwald, B.M. (2017). Delirium and mortality in critically ill children: Epidemiology and outcomes of pediatric delirium. Critical Care Medicine, 45(5), 891-898. doi: 10.1097/CCM.0000000000002324 Traube, C., Silver, G., Kearney, J., Patel, A., Atkinson, T.M., Yoon, M.J., … Greenwald, B. (2014). Cornell Assessment of Pediatric Delirium: A valid, rapid, observational tool for NEONATAL DELIRIUM screening delirium in the PICU. Critical Care Medicine, 42(3), 656-663. 18 doi:10.1097/CCM.0b013e3182a66b76. Traube, C., Silver, G., Reeder, R.W., Doyle, H., Hegel, E., Wolfe, H.A., … Bell, M.J. (2017). Delirium in critically ill children: An international point prevalence study. Critical Care Medicine, 45(4), 584-590. doi: 10.1097/CCM.0000000000002250 Turkel, S.B., Jacobson, J.R., & Tavaré, C.J. (2013). The diagnosis and management of delirium in infancy. Journal of Child and Adolescent Psychopharmcology, 23(5), 352-356. doi: 10.1089/cap.2013.0001 Woolf, S.H., Grol, R., Hutchinson, A., Eccles, M. & Grimshaw, J. (1999). Potential benefits, limitations and harms of clinical guidelines. BMJ, 318(7182), 527-530. PMC1114973 NEONATAL DELIRIUM Figure 1. Cornell Assessment of Pediatric Delirium (CAPD) (Silver et al., 2010) 19 NEONATAL DELIRIUM 1. Does the child make eye contact with the caregiver? 20 NB 4 weeks 6 weeks 8 weeks 28 weeks 1 year Fixates on face Holds gaze Holds gaze Follows moving object/caregiver past midline, regards examiner's hand holding object, focused attention Holds gaze. Prefers primary parent. Looks at speaker Holds gaze. Prefers primary parent. Looks at speaker Holds gaze. Prefers primary parent. Looks at speaker briefly Follows 90 degrees 2 years 2. Are the child's actions purposeful? Moves head to side, dominated by primitive reflexes Reache s (with some discoordination) Reaches Symmetric movements, will passively grasp handed object Reaches with coordinated smooth movement Reaches and manipulates objects, tries to change position, if mobile may try to get up Reaches and manipulates objects, tries to change position, if mobile may try to get up and walk 3. Is the child aware of his/her surroundings? Calm awake time Awake alert time Increasing awake alert time Turns to primary caretaker's voice May turn to smell of primary care taker Facial brightening or smile in response to nodding head, frown to bell, coos Strongly prefers mother, then other familiars. Differentiates between novel and familiar objects Prefers primary parent, then other familiars, upset when separated from preferred care takers. Comforted by familiar objects especially favorite blanket or stuffed animal Prefers primary parent, then other familiars, upset when separated from preferred care takers. Comforted by familiar objects especially favorite blanket or stuffed animal Turns to primary caretaker's voice May turn to smell of primary care taker 4. Does the child communicate needs and wants? Cries when hungry or uncomfort able Cries when hungry or uncomfortable Cries when hungry or uncomfortable Cries when hungry or uncomfortable Vocalizes /indicates about needs, eg. hunger, discomfort, curiosity in objects, or surroundings Uses single words, or signs 3-4 word sentences, or signs. May indicate toilet needs, calls self or me 5. Is the No sustained No sustained No sustained No sustained No sustained No sustained No sustained child restless? 6. Is the child inconsola ble? awake alert state Not soothed by parental rocking, singing, feeding, comforting actions Little if any flexed and then relaxed state with primitive reflexes calm state calm state calm state calm state calm state calm state Not soothed by parental rocking, singing, feeding, comforting actions Little if any reaching, kicking, grasping (still may be somewhat discoordinated) Not soothed by parental rocking, singing, feeding, comforting actions Little if any reaching, kicking, grasping (may begin to be more coordinated) Not soothed by parental rocking, singing, comforting actions Not soothed by usual methods eg. singing, holding, talking Not soothed by usual methods eg. singing, holding, talking, reading Not soothed by usual methods eg. singing, holding, talking, reading (May tantrum, but can organize) Little if any purposive grasping, control of head and arm movements, such as pushing things that are noxious away Little if any reaching, grasping, moving around in bed, pushing things away Little if any play, efforts to sit up, pull up, and if mobile crawl or walk around Little if any more elaborate play, efforts to sit up and move around, and if able to stand, walk, or jump Not making sounds or reflexes active as expected (grasp, suck, moro) Not kicking or crying with noxious stimuli Not cooing, smiling, or focusing gaze in response to interactions Not babbling or smiling/laughing Not following simple directions. If verbal, not engaging in simple dialogue with words or jargon Not following 1-2 step simple commands. If verbal, not engaging in more complex dialogue 7. Is the child underactive- very little movement while awake? (Child should be sleeping 8. Does it take the child a long time to respond to interactions? comfortably most of the time) Not making sounds or reflexes active as expected (grasp, suck, moro) in social interactions (or even actively rejecting an interaction) Figure 2. Developmental Anchor Points for CAPD (Silver et al., 2010) 21 NEONATAL DELIRIUM Job Title Neonatologists 12/37 (32%) Neonatal Fellows 6/37 (16%) Neonatal Nurse Practitioners Palliative Care/Psychiatry 14/37 (38%) 5/37 (14%) Table 1 Demographic characteristics of participants by job title Years of Experience <5 Years 13/37 (35%) 5-15 Years >15 Years Table 2 15/37 (41%) 9/37 (24%) Demographic characteristics of participants by years of experience 22 NEONATAL DELIRIUM Appendix A Clinical Practice Guideline: Recognition, Diagnosis and Management of Neonatal Delirium Introduction: Delirium is an acute and fluctuating change in awareness and cognition that is underdiagnosed and undertreated, especially in pediatrics. This can lead to prolonged mechanical ventilation, lengthened hospital stay and increased morbidity and mortality. The etiology is often multifactorial, including infection, hypoxia, and exposure to benzodiazepines, opioids, steroids and/or anticholinergics. Risk factors include age < 2yrs, severity of illness, post-op recovery, restraints, iatrogenic withdrawal, and mechanical ventilation. Environmental interventions such as promoting uninterrupted sleep, providing appropriate developmental stimulation, minimizing sedation and addressing pain will help prevent as well as treat delirium. If delirium persists after implementing environmental interventions, pharmacologic treatment may be indicated. Aim: To aid in the recognition, diagnosis and management of neonatal delirium. Definition of Terms: Delirium: Delirium is a disturbance in attention and awareness that develops as a change from baseline over a short period of time (hours to days) and tends to fluctuate in severity during the course of the day. This disturbance in cognition is a direct physiologic consequence of a medical condition, substance withdrawal, exposure to toxin or multiple etiologies. Prevalence: An emerging body of research indicates that delirium in critically ill infants <2 yrs of age has prevalence rates greater than 20%. Recognition/Diagnosis: Identifying high-risk infants • Identifying high-risk infants and initiating screening using the Cornell Assessment for Pediatric Delirium (CAPD) screening tool (see diagnosis) allows for earlier recognition of neonatal delirium. In addition to elevated scores that screen positive, use of the CAPD tool allows nurses and providers to more easily recognize fluctuations in mental status from baseline. • Factors that put an infant at high risk for delirium include: o High dosing or prolonged use of benzodiazepines, opioids, anticholinergics or steroids o Severity of illness o Mechanical ventilation o Hypoxemia o Iatrogenic drug withdrawal o Underlying neurologic issues (i.e. seizures) or developmental delay o Difficult or prolonged post operative recovery o Located in an isolation room or a room with no windows o Frequent disruptions of sleep cycles Clinical signs/symptoms NEONATAL DELIRIUM 23 • Delirium usually has an acute onset of signs/symptoms that vary from an infant's baseline. Signs/Symptoms include: o Agitation and/or anxiety o Disturbance in state regulation (lack ability to be awake, alert and calm) o Inconsolability with usual comfort measures o Sleep disturbance or insomnia o Regression in developmental skills (i.e. no longer able to make eye contact or track objects) o Reduced appetite o Purposeless movement o Increased sensitivity to sounds and touch or underresponsiveness to stimuli Scoring Tools and Diagnosis: Overview: Cornell Assessment of Pediatric Delirium (CAPD) • The CAPD is a rapid and reliable observational tool scored by the bedside nurse to detect changes in cognition that aid in the diagnosis of delirium. This tool has been previously validated, with an overall sensitivity of 94.1% and a specificity of 79.2% in pediatric patients, with a large proportion of those studied <2 years of age. • Because of concerns about accurate screening in children under 2 years old, developmental anchor points were delineated. Based on classic texts and established scales of child development, each anchor point characterizes the normal developing infant for each item on the CAPD. • The CAPD has never been formally tested in a NICU population but has been validated in infants. CAPD Scoring • A recent position article published by the European Society of Paediatric and Neonatal Intensive Care recommends use of CAPD to assess for delirium every 8-12 hours (Q Nursing shift). • A CAPD score of 9 or higher represents a positive screen. For infants with a baseline at or above 9, an increase in score from the infant's baseline represents a positive screen. DSM-5 criteria • The CAPD scoring is simply a screening tool to suggest delirium is more likely. • The "gold standard" diagnosis for pediatric delirium is an assessment by a child psychiatrist using the DSM-5 criteria that require acute onset, fluctuating course, and disturbance of awareness and cognition. Management (See clinical algorithm) Goal of management • Management should focus on improving the patient's cognitive and emotional status and reduce the risk of adverse outcomes such as prolonged mechanical ventilation, lengthened hospital stay and increased morbidity and mortality. • When a diagnosis of delirium is suspected, minimization and/or elimination of predisposing and precipitating factors should be the main focus. Assess for and treat underlying illness • Infection/Meningitis • Inflammatory disorders • Hypoxia/Respiratory failure • Electrolyte or acid-base imbalance • CNS pathology (bleed, seizures, infarct) • Cardiac failure NEONATAL DELIRIUM • End organ dysfunction • Iatrogenic drug withdrawal 24 Minimize/eliminate use of deliriogenic medications • Wean deliriogenic medications as able o Benzodiazepines o Anticholinergics o Opioids o Barbiturates o Steroids • Priority medications to wean include benzodiazepines and anticholinergic medications followed by opioids and other sedatives. • If needed, consider use of dexmedetomidine as an alternative sedating agent. Minimize other potential causes • Prolonged mechanical ventilation • Restraints Implement environmental measures • Promote healthy sleep patterns o Lights off and quiet at night o Consistent bedtime o Cluster cares and minimize disruptions during sleep • Promote activity during the day o Increased presence of family, primary caregivers, and/or "aunt/uncle" o Involve child life, music therapy, developmental therapists, Rainbow Kids and cuddlers o Turn lights on during the day. Place near window if possible o Avoid long daytime naps • Promote a calm, supportive and consistent environment and routines o Implement a consistent daily routine including a nap and activity schedule o Get infant out of bed several times a day if able o Engage in developmentally appropriate activities o Calm/comfort infant quickly when upset o Introduce and utilize a comfort object • Address Pain Overview: Pharmacologic Treatment • If delirium persists after treating the underlying cause, minimizing/eliminating predisposing and precipitating factors, and implementing environmental measures, pharmacologic treatment with an atypical antipsychotic may be indicated. • The goal of pharmacologic treatment is to reduce agitation and improve state control, allow for weaning of potentially offending agents, limit the time the patient is delirious, decrease any associated trauma, distress, and/or potential toxicity, and to reduce the length of hospital stay. • Atypical antipsychotics are the preferred pharmacologic treatment over typical antipsychotics due to the lower risk for extrapyramidal side effects and QT prolongation Before Initiating Pharmacologic Treatment • If the physician is confident in the diagnosis of delirium and non-pharmacologic treatment has not alleviated symptoms, a child psychiatrist should be consulted to evaluate the patient and assist in dosing and management of the atypical antipsychotic. NEONATAL DELIRIUM 25 • A baseline EKG, CBC and CMP should be done before starting treatment with atypical antipsychotics since a prolonged QT, neutropenia, anemia, electrolyte abnormalities, hyperglycemia and elevated liver enzymes are potential side effects • Review current medications for other medications that may put the infant at risk for a prolonged QT. • Assess for hypoxia, electrolyte abnormalities and/or infection. These, in combination with an atypical antipsychotic, increase the risk for prolonged QT Monitoring During Pharmacologic Treatment • Obtain a baseline EKG and an EKG 7 days after starting Quetiapine. • Monitor infant for prolonged QT or other arrhythmias. • Monitor for signs/symptoms of NMS or EPS • Follow electrolytes and assess for hypoxia or infection (these can increase the risk of prolonged QT while on an antipsychotic). • Continue CAPD scoring to monitor efficacy of treatment • Continue to wean deliriogenic medications as able during treatment. Quetiapine (Seroquel) • Quetiapine has a high affinity for both dopamine D2 receptors and serotonin 5-HT2 receptors. It also has a moderate affinity for serotonin 5- HT1A, dopamine D1, histamine H1, and a1 and a2 receptors. It has no affinity for muscarinic or benzodiazepine receptors. • Peak: 0.5-3 hours • Elimination half life: 5.3 hours • Common adverse effects: Drowsiness, agitation, dry mouth, constipation, • Rare adverse effects: Prolonged QT, neuroleptic malignant syndrome (NMS) (fever, sweating, autonomic dysfunction, and muscular rigidity), and/or extrapyramidal symptoms (EPS) (muscle spasms and irregular jerky movements). These are generally seen at much higher dosing than typically used for delirium. • Dosing: Consult with a child psychiatrist to assist with dosing and management of this medication. Risperidone (Risperdal) • Risperidone has a high affinity for both dopamine D2 receptors and serotonin 5-HT2 receptors. It also has a moderate affinity for serotonin 5-HT1A, 5- HT1C and 5-HT1D receptors as well as a weak affinity for dopamine D1 receptors. It has no affinity for muscarinic or beta 1 and beta 2 receptors. • Peak: 1-3 hours • Elimination half life: 5.3 hours • Dosing: Consult with a child psychiatrist to assist with dosing and management of this medication. • Common adverse effects: Drowsiness, agitation, dry mouth, constipation, vomiting, tremors, dystonia, bradycardia, elevated liver enzymes, hyperglycemia, anemia • Rare adverse effects: Prolonged QT, neuroleptic malignant syndrome (NMS) (fever, sweating, autonomic dysfunction, and muscular rigidity), and/or extrapyramidal symptoms (EPS) (muscle spasms and irregular jerky movements). These are generally seen at much higher dosing than typically used for delirium. Olanzapine (Zyprexa) • Olanzapine has a high affinity for dopamine D1-4, serotonin 5-HT2A and 5-HT2C, histamine H1, and alpha1-adrenergic receptors. It also has a moderate antagonism of serotonin 5-HT3 and muscarinic M1-5 receptors and a weak affinity for GABA-A, BZD, and beta-adrenergic receptors. • Peak: 2-7 hours NEONATAL DELIRIUM 26 • Elimination half life: 37 hours • Dosing: Consult with a child psychiatrist to assist with dosing and management of this medication. • Common adverse effects: Drowsiness, agitation, dry mouth, nasal congestion, diarrhea, vomiting, abdominal pain, elevated liver enzymes • Rare adverse effects: Prolonged QT, neuroleptic malignant syndrome (NMS) (fever, sweating, autonomic dysfunction, and muscular rigidity), and/or extrapyramidal symptoms (EPS) (muscle spasms and irregular jerky movements). These are generally seen at much higher dosing than typically used for delirium. Need for Further Research • The available evidence in infants <2 years of age is largely based on case reports/ series and retrospective studies with a lack of prospective trials to assess efficacy of interventions, including medications. • The unique combination of the vulnerability and resiliency of children's developing brains makes it imperative that research on prevention, diagnosis, treatment, and follow-up of this complication of pediatric medical illness and treatment be vigorously pursued. Companion Documents: • Clinical Algorithm for Diagnosis and Management of Neonatal Delirium • CAPD screening tool with developmental anchor points NEONATAL DELIRIUM 27 NICU Delirium Algorithm Does infant have clinical triggers or high-risk triggers? No Continue to monitor clinically Yes Begin CAPD Scoring. No CAPD >_ 9 and/or clinical suspicion of delirium? Yes Identify and treat potential causes Continue environmental measures Review sedation target and modify medications • Remove deliriogenic medications if possible (Benzos, opiates, anticholinergics, steroids) • Transition from midazolam to dexmedetomidine if appropriate Review Pain control • Assess for withdrawal if weaning • Assess pain score to determine adequate analgesia or over medication Consider electrolyte or acid-base issues Consider a CNS pathology (bleed, seizures, infarct, metabolic toxicity) Consider inflammation or infection Assess for and treat other end organ dysfunction Review oxygenation status Confirm environmental measures are in place. Promote healthy sleep patterns • Lights off and quiet at night • Consistent bedtime • Cluster cares and minimize disruptions Promote activation during the day • Increased presence of family and/or "aunt/uncle" • Involve child life, music therapy, PT/OT, and cuddlers • Lights on during the day, place next to window if possible • Avoid long daytime naps Promote a calm, supportive and consistent environment and routines • Institute a consistent daily routine including a nap schedule • Get infant out of bed several times a day • Engage in developmentally appropriate activities • Calm/comfort infant quickly when upset • Introduce and utilize a comfort object Address Pain Are symptoms improving? Yes Continue current treatment No Request a psychiatry eval NEONATAL DELIRIUM 28 Appendix B Pre-Presentation Survey on Neonatal Delirium Strongly Disagree 1. I believe delirium is a disease process that needs to be treated (environmentally and/or pharmacologically). 2. I feel confident in my ability to recognize the signs/symptoms of delirium. 3. I know what factors place an infant at high-risk for developing delirium. 4. I feel confident in using the CAPD screening tool to aid in the diagnosis of delirium. 5. I know what environmental interventions can help prevent/treat delirium. 6. I feel confident in managing a patient with delirium using atypical antipsychotics. 7. A clinical practice guideline would increase my confidence in the recognition, diagnosis and management of neonatal delirium. 8. What do you see as potential barriers to recognizing and treating neonatal delirium? 9. What information do you think would be helpful to include in a clinical practice guideline on neonatal delirium? Disagree Neither Agree nor Disagree Agree Strongly Agree NEONATAL DELIRIUM Post-Presentation Survey on Neonatal Delirium Strongly Disagree Disagree 1. I believe delirium is a disease process that needs to be treated (environmentally and/or pharmacologically). 2. I feel confident in my ability to recognize the signs/symptoms of delirium. 3. I know what factors place an infant at high-risk for developing delirium. 4. I feel confident in using the CAPD screening tool to aid in the diagnosis of delirium. 5. I know what environmental interventions can help prevent/treat delirium. 6. I feel confident in managing a patient with delirium using atypical antipsychotics. 7. A clinical practice guideline would increase my confidence in the recognition, diagnosis and management of neonatal delirium. 8. What do you see as potential barriers to recognizing and treating neonatal delirium? (In addition to those you stated in the prepresentation survey. You do not need to repeat any answers.) 9. What feedback do you have on the clinical practice guideline (i.e. what needs to be added, taken out, changed, elaborated on, etc.) Neither Agree nor Disagree Agree 29 Strongly Agree