Pediatr Blood Cancer 2014;61:1121–1123
BRIEF REPORT Neuroblastoma and Pediatric Delirium: A Case Series Chani Traube,
MD,
1
* Julie Augenstein,
2 MD,
Bruce Greenwald, Gabrielle Silver, MD4
Delirium occurs frequently in critically ill children, and children with neuroblastoma may be at particular risk. Early diagnosis and treatment may improve short- and long-term outcomes. In this case series, we present four critically ill children with neuroblastoma who were diagnosed with delirium in the post-operative period. In all four
MD,
1
Michael LaQuaglia,
3 MD,
and
patients, the diagnosis of delirium facilitated targeted intervention and improvement. Heightened awareness by pediatric oncologists, surgeons, and intensivists may lead to earlier diagnosis and improvement in clinical outcomes. Pediatr Blood Cancer 2014;61: 1121–1123. # 2013 Wiley Periodicals, Inc.
Key words: delirium; neuroblastoma; pediatrics; critical care
INTRODUCTION Delirium is a common and serious sequela of critical illness. Children with neuroblastoma may be at particular risk during the postoperative period. Unfortunately, most pediatric oncologists, surgeons, and intensivists are not aware of this issue, and do not routinely screen children for the development of delirium. In our pediatric intensive care unit, we admit approximately 35 children with stage 4 neuroblastoma each year for post-operative management after extensive thoracoabdominal resection. In this case series, we highlight some typical patients who were diagnosed with delirium, discuss risk factors, and suggest a treatment plan (Table I). The institutional review board reviewed this report and waived the need for approval. Delirium is defined as an acute and fluctuating change in mental status, associated with disordered cognition and attention, due to an underlying medical condition or treatment there-of [1]. There are three subtypes of delirium: hyperactive, hypoactive, and mixed. In adults, delirium is associated with increased mortality, increased length of hospitalization, and post-discharge cognitive impairment [2]. An emerging pediatric literature suggests a prevalence of 15–20% in critically ill children, with associated long-term morbidity [3–6]. Pediatric delirium is complicated by developmental variability— normal behavior in a 2-year old is clearly abnormal in a 12-year old— but with attention to developmental expectations, it can be diagnosed as reliably as in adults [3,4,7]. Delirium in children is notable for changes in psychomotor activity (restlessness in hyperactive delirium, and underactivity in hypoactive delirium). In extremely young or mechanically ventilated children, delirium may present as refractory agitation [8–10]. Neuroblastoma is the third most common pediatric cancer, and accounts for 15% of all pediatric cancer deaths. More than 600 cases are diagnosed in the US annually, with median age at presentation of 17 months. A tumor of the sympathetic nervous system, it is composed of primitive sympathetic ganglion cells. Multi-modality treatment consists of chemotherapy, radiation, surgical resection, and stem cell transplantation [11–12]. Children with neuroblastoma possess many underlying risk factors thought to predispose patients to delirium. These include high severity of illness at admission, underlying malignancy, sympathetic overdrive, mechanical ventilation in post-operative period, and need for opiates and sedatives [2,6,13]. In our pediatric intensive care unit, we screen for delirium twice daily using the Cornell Assessment of Pediatric Delirium, an 8-item rapid bedside observational tool completed by the nurse [4].
C
2013 Wiley Periodicals, Inc. DOI 10.1002/pbc.24917 Published online 28 December 2013 in Wiley Online Library (wileyonlinelibrary.com).
Positive screens are flagged for evaluation by the pediatric intensivist or child psychiatrist who use the gold-standard criteria of the Diagnostic and Statistical Manual of Mental Disorders to diagnose delirium [1]. Children diagnosed with delirium are then treated in four ways: (1) Treat the underlying disease processes predisposing to delirium (i.e., sepsis with inflammatory cascade, or fever). (2) Address iatrogenic factors, particularly those that are medication-related. Minimize anticholinergics and benzodiazepines, titrate opiates to treat pain (not agitation), and consider dexmedetomidine (an alpha-2 agonist with anxiolytic effect) for sedation. (3) Mitigate the environmental triggers: minimize sleep interruptions, facilitate early mobilization, exposure to natural light when possible, use of eyeglasses when appropriate, and introduction of familiar and comforting objects (i.e., favorite blanket or music). (4) When modification of medications and environmental factors are insufficient, employ pharmacologic intervention, specifically quetiapine, an atypical antipsychotic with a favorable risk profile [14,15] (as compared to typical antipsychotics such as haloperidol). With early detection and treatment, the duration of delirium can be shortened, thereby facilitating weaning from mechanical ventilation and post-operative recovery.
CASE EXAMPLES Case 1 A 3-year-old male with Soto syndrome and stage IV neuroblastoma was admitted to the PICU for post-operative care following thoracoabdominal resection, including right adrenalectomy, lymph node dissection, and liver biopsy. At baseline, the patient was nonverbal with significant developmental delay. Post1
Division of Pediatric Critical Care Medicine, Weill Cornell Medical College, New York, New York; 2Department of Pediatrics, NY Prebyterian Hospital, New York, New York; 3Department of Pediatric Surgery, Memorial Sloan Kettering Cancer Center, New York, New York; 4Department of Pediatric Psychiatry, Weill Cornell Medical College, New York, New York Conflict of interest: Nothing to declare.
Correspondence to: Chani Traube, Division of Pediatric Critical Care Medicine, Weill Cornell Medical College, 525 East 68th Street, M-508, New York, NY 10065. E-mail: [email protected] Received 13 November 2013; Accepted 6 December 2013
1122
Traube et al.
TABLE I. Summary of Patient Data Patient 1
Patient 2
Patient 3
Patient 4
Age
3 years
2 years
3 years
7 months
Gender
Male
Female
Female
Female
Possible risk factors
Neuroblastoma Post-operative status Developmental delay Opiates Benzodiazepines
Neuroblastoma Post-operative status Prolonged intubation Opiates Benzodiazepines Anticholinergics
Neuroblastoma Post-operative status Acute renal failure Shock Opiates Benzodiazepines
Neuroblastoma Post-operative status Opiates Anticholinergics
Treatment
Benzodiazepines discontinued
Benzodiazepines and anticholinergics discontinued Opiates decreased Care clustered
Benzodiazepines discontinued
Benzodiazepines and anticholinergics discontinued Dexmedetomidine added Care clustered
Quetiapine added
BUN and electrolytes normalized Care clustered Quetiapine added
Opiates decreased Care clustered to avoid sleep disruption Quetiapine added
operative course was notable for extreme agitation, treated with high dose midazolam (approximately 0.2 mg/kg/hour) and fentanyl (approximately 4 mcg/kg/hour) infusions to prevent self-extubation. When sedation was decreased, patient-ventilator dyssynchrony was noted. The patient had sporadic restless movements of the arms and legs, minimal eye contact, and no appreciable sleep/ wake cycle. His mother described him as “possessed” and claimed that he did not seem to recognize her. On the fifth post-operative day, he was diagnosed with delirium. Anticholinergic mediations and benzodiazepines were discontinued, and he was started on quetiapine. He improved within 24 hours and was successfully extubated the following day.
Case 2 A 27-month-old female with cervical neuroblastoma encasing the aorta and vagus, hypoglossal, and recurrent laryngeal nerves was admitted for post-operative care after resection. PICU course was complicated by vocal cord paresis and prolonged intubation. On sixth post-operative day, she was noted to have worsening agitation, with ventilator dyssynchrony, thrashing in bed, no eye contact or purposeful activity, and no sustained sleep. She was diagnosed with delirium, weaned from benzodiazepines, and started on quetiapine. Within 24 hours agitation subsided, and she had improved eye contact and communication. This facilitated weaning of opiates and sedatives and successful extubation.
Case 3 A 3-year-old female with stage IV neuroblastoma was admitted for post-operative care following extensive thoracoabdominal resection complicated by acute renal failure. In the immediate post-operative period, she required extensive volume resuscitation, vasopressors for hypotension, and stress dose steroids for adrenal insufficiency. When shock resolved, sedation was lightened and she was noted to have a fluctuating mental status, sometimes extremely agitated and combative, and other times withdrawn, with delayed Pediatr Blood Cancer DOI 10.1002/pbc
Opiates decreased Dexmedetomidine added
Quetiapine added
motor response to interactions. Her mother described her as “in a trance”. Delirium was diagnosed and targeted interventions ensued, including replacing benzodiazepines with dexmedetomidine for sedation, minimizing opiates, avoiding anticholinergics, optimizing continuous veno-venous hemofiltration (CVVH) to normalize blood urea nitrogen, and clustering care to avoid nighttime awakenings. Agitation improved but she remained withdrawn and confused. With initiation of quetiapine, confusion improved. Quetiapine was continued for approximately 10 days, and tapered off prior to discharge home.
Case 4 A 7-month-old female with neuroblastoma was admitted after extensive pelvic mass resection, involving paraspinal and paraaortic regions. Initial post-operative course was unremarkable, with expected third-spacing of fluids and volume resuscitation. On postoperative Day 2, she was hemodynamically stable with a modest alveolar-arterial oxygen gradient and she was successfully extubated. The patient’s mother stated that she was not interactive, did not seem to recognize her parents, was not comforted by usual maneuvers, and “could not seem to settle down.” She was diagnosed with hyperactive delirium and successfully treated with a combination of dexmedetomidine and quetiapine.
CONCLUSION Delirium is the most frequently diagnosed neuropsychiatric complication of advanced cancer in adults, and an independent risk factor in predicting short-term survival [16–17]. The prevalence of delirium in pediatric oncology patients is not well-described, largely due to the absence of widespread screening. Pediatric oncologists are at the front lines with respect to detecting delirium in their high-risk patient population. Widespread screening is feasible, even in extremely young and mechanically ventilated patients. Targeted treatment may shorten the duration of delirium and mitigate associated morbidities. Heightened awareness by pediatric oncologists, surgeons, and
Neuroblastoma and Delirium intensivists may lead to earlier diagnosis and improvement in clinical outcomes. Children with neuroblastoma have underlying factors that may constitute an increased risk for delirium, especially in the postoperative period. A prospective multi-institutional trial to investigate the prevalence of delirium in neuroblastoma patients, and identify modifiable risk factors, is warranted.
REFERENCES 1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV-TR, 4th edition, text revision. Washington, DC: American Psychiatric Association; 2000. 2. Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med 2013;41:278–280. 3. Silver G, Traube C, Kearney J, et al. Detecting pediatric delirium: Development of a rapid observational assessment tool. Intensive Care Med 2012;38:1025–1031. 4. 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 2013 [Epub ahead of print]. 5. Smith HAB, Brink E, Fuchs DC, et al. Pediatric delirium. Pediatr Clin North Am 2013;60:741–760. 6. Smith HA, Fuchs DC, Pandharipande PP, et al. Delirium: An emerging frontier in the management of critically ill children. Crit Care Clin 2009;25:593–614.
Pediatr Blood Cancer DOI 10.1002/pbc
1123
7. Turkel SB, Braslow K, Tavare CJ, et al. The delirium rating scale in children and adolescents. Psychosomatics 2003;44:126–129. 8. Schieveld JN, Staal M, Voogd L, et al. Refractory agitation as a marker for pediatric delirium in very young infants at a pediatric intensive care unit. Intensive Care Med 2010;36:1982–1983. 9. Silver GH, Kearney JA, Kutko MC, et al. Infant delirium in pediatric critical care settings. Am J Psychiatry 2010;167:1172–1177. 10. Turkel SB, Tavare CJ. Delirium in children and adolescents. J Neuropsychiatry Clin Neurosci 2003;15:431–435. 11. Brodeur GM, Hogarty MD, Mosse YP, et al. Neuroblastoma. In: Pizzo PA, Poplack DG, editors. Principles and practice of pediatric oncology. Philadelphia, PA: Lippincott Williams & Wilkins; 2011: 886–922. 12. Goodman MT, Gurney JG, Smith MA, et al. Sympathetic nervous system tumors. In: Ries LA, Smith MA, Gurney JG, et al., editors. Cancer incidence and survival among children and adolescents: United States SEER Program, 1975–1995. Bethesda, MD: National Cancer Institute; 1999: 65–72. 13. Creten C, Van Der Zwaan S, Blankespoor RJ, et al. Pediatric delirium in the pediatric intensive care unit: A systematic review and an update on key issues and research questions. Minerva Anestesiol 2011;77:1099. 14. Devlin JW, Roberts RJ, Fong JJ, et al. Efficacy and safety of quetiapine in critically ill patients with delirium: A prospective, multicenter, randomized, double-blind, placebo-controlled pilot study. Crit Care Med 2010;38:419–427. 15. Traube C, Witcher R, Mendez-Rico E, et al. Quetiapine as treatment for delirium in critically ill children: A case series. Pediatr Intensive Care 2013. In press. 16. Lawlor PG, Bruera ED. Delirium in patients with advanced cancer. Hematol Oncol Clin North Am 2002;16:701–714. 17. Caraceni A, Nanni O, Maltoni M, et al. Impact of delirium on the short term prognosis of advanced cancer patients. Cancer 2000;89:1145–1149.
BRIEF REPORT Neuroblastoma and Pediatric Delirium: A Case Series Chani Traube,
MD,
1
* Julie Augenstein,
2 MD,
Bruce Greenwald, Gabrielle Silver, MD4
Delirium occurs frequently in critically ill children, and children with neuroblastoma may be at particular risk. Early diagnosis and treatment may improve short- and long-term outcomes. In this case series, we present four critically ill children with neuroblastoma who were diagnosed with delirium in the post-operative period. In all four
MD,
1
Michael LaQuaglia,
3 MD,
and
patients, the diagnosis of delirium facilitated targeted intervention and improvement. Heightened awareness by pediatric oncologists, surgeons, and intensivists may lead to earlier diagnosis and improvement in clinical outcomes. Pediatr Blood Cancer 2014;61: 1121–1123. # 2013 Wiley Periodicals, Inc.
Key words: delirium; neuroblastoma; pediatrics; critical care
INTRODUCTION Delirium is a common and serious sequela of critical illness. Children with neuroblastoma may be at particular risk during the postoperative period. Unfortunately, most pediatric oncologists, surgeons, and intensivists are not aware of this issue, and do not routinely screen children for the development of delirium. In our pediatric intensive care unit, we admit approximately 35 children with stage 4 neuroblastoma each year for post-operative management after extensive thoracoabdominal resection. In this case series, we highlight some typical patients who were diagnosed with delirium, discuss risk factors, and suggest a treatment plan (Table I). The institutional review board reviewed this report and waived the need for approval. Delirium is defined as an acute and fluctuating change in mental status, associated with disordered cognition and attention, due to an underlying medical condition or treatment there-of [1]. There are three subtypes of delirium: hyperactive, hypoactive, and mixed. In adults, delirium is associated with increased mortality, increased length of hospitalization, and post-discharge cognitive impairment [2]. An emerging pediatric literature suggests a prevalence of 15–20% in critically ill children, with associated long-term morbidity [3–6]. Pediatric delirium is complicated by developmental variability— normal behavior in a 2-year old is clearly abnormal in a 12-year old— but with attention to developmental expectations, it can be diagnosed as reliably as in adults [3,4,7]. Delirium in children is notable for changes in psychomotor activity (restlessness in hyperactive delirium, and underactivity in hypoactive delirium). In extremely young or mechanically ventilated children, delirium may present as refractory agitation [8–10]. Neuroblastoma is the third most common pediatric cancer, and accounts for 15% of all pediatric cancer deaths. More than 600 cases are diagnosed in the US annually, with median age at presentation of 17 months. A tumor of the sympathetic nervous system, it is composed of primitive sympathetic ganglion cells. Multi-modality treatment consists of chemotherapy, radiation, surgical resection, and stem cell transplantation [11–12]. Children with neuroblastoma possess many underlying risk factors thought to predispose patients to delirium. These include high severity of illness at admission, underlying malignancy, sympathetic overdrive, mechanical ventilation in post-operative period, and need for opiates and sedatives [2,6,13]. In our pediatric intensive care unit, we screen for delirium twice daily using the Cornell Assessment of Pediatric Delirium, an 8-item rapid bedside observational tool completed by the nurse [4].
C
2013 Wiley Periodicals, Inc. DOI 10.1002/pbc.24917 Published online 28 December 2013 in Wiley Online Library (wileyonlinelibrary.com).
Positive screens are flagged for evaluation by the pediatric intensivist or child psychiatrist who use the gold-standard criteria of the Diagnostic and Statistical Manual of Mental Disorders to diagnose delirium [1]. Children diagnosed with delirium are then treated in four ways: (1) Treat the underlying disease processes predisposing to delirium (i.e., sepsis with inflammatory cascade, or fever). (2) Address iatrogenic factors, particularly those that are medication-related. Minimize anticholinergics and benzodiazepines, titrate opiates to treat pain (not agitation), and consider dexmedetomidine (an alpha-2 agonist with anxiolytic effect) for sedation. (3) Mitigate the environmental triggers: minimize sleep interruptions, facilitate early mobilization, exposure to natural light when possible, use of eyeglasses when appropriate, and introduction of familiar and comforting objects (i.e., favorite blanket or music). (4) When modification of medications and environmental factors are insufficient, employ pharmacologic intervention, specifically quetiapine, an atypical antipsychotic with a favorable risk profile [14,15] (as compared to typical antipsychotics such as haloperidol). With early detection and treatment, the duration of delirium can be shortened, thereby facilitating weaning from mechanical ventilation and post-operative recovery.
CASE EXAMPLES Case 1 A 3-year-old male with Soto syndrome and stage IV neuroblastoma was admitted to the PICU for post-operative care following thoracoabdominal resection, including right adrenalectomy, lymph node dissection, and liver biopsy. At baseline, the patient was nonverbal with significant developmental delay. Post1
Division of Pediatric Critical Care Medicine, Weill Cornell Medical College, New York, New York; 2Department of Pediatrics, NY Prebyterian Hospital, New York, New York; 3Department of Pediatric Surgery, Memorial Sloan Kettering Cancer Center, New York, New York; 4Department of Pediatric Psychiatry, Weill Cornell Medical College, New York, New York Conflict of interest: Nothing to declare.
Correspondence to: Chani Traube, Division of Pediatric Critical Care Medicine, Weill Cornell Medical College, 525 East 68th Street, M-508, New York, NY 10065. E-mail: [email protected] Received 13 November 2013; Accepted 6 December 2013
1122
Traube et al.
TABLE I. Summary of Patient Data Patient 1
Patient 2
Patient 3
Patient 4
Age
3 years
2 years
3 years
7 months
Gender
Male
Female
Female
Female
Possible risk factors
Neuroblastoma Post-operative status Developmental delay Opiates Benzodiazepines
Neuroblastoma Post-operative status Prolonged intubation Opiates Benzodiazepines Anticholinergics
Neuroblastoma Post-operative status Acute renal failure Shock Opiates Benzodiazepines
Neuroblastoma Post-operative status Opiates Anticholinergics
Treatment
Benzodiazepines discontinued
Benzodiazepines and anticholinergics discontinued Opiates decreased Care clustered
Benzodiazepines discontinued
Benzodiazepines and anticholinergics discontinued Dexmedetomidine added Care clustered
Quetiapine added
BUN and electrolytes normalized Care clustered Quetiapine added
Opiates decreased Care clustered to avoid sleep disruption Quetiapine added
operative course was notable for extreme agitation, treated with high dose midazolam (approximately 0.2 mg/kg/hour) and fentanyl (approximately 4 mcg/kg/hour) infusions to prevent self-extubation. When sedation was decreased, patient-ventilator dyssynchrony was noted. The patient had sporadic restless movements of the arms and legs, minimal eye contact, and no appreciable sleep/ wake cycle. His mother described him as “possessed” and claimed that he did not seem to recognize her. On the fifth post-operative day, he was diagnosed with delirium. Anticholinergic mediations and benzodiazepines were discontinued, and he was started on quetiapine. He improved within 24 hours and was successfully extubated the following day.
Case 2 A 27-month-old female with cervical neuroblastoma encasing the aorta and vagus, hypoglossal, and recurrent laryngeal nerves was admitted for post-operative care after resection. PICU course was complicated by vocal cord paresis and prolonged intubation. On sixth post-operative day, she was noted to have worsening agitation, with ventilator dyssynchrony, thrashing in bed, no eye contact or purposeful activity, and no sustained sleep. She was diagnosed with delirium, weaned from benzodiazepines, and started on quetiapine. Within 24 hours agitation subsided, and she had improved eye contact and communication. This facilitated weaning of opiates and sedatives and successful extubation.
Case 3 A 3-year-old female with stage IV neuroblastoma was admitted for post-operative care following extensive thoracoabdominal resection complicated by acute renal failure. In the immediate post-operative period, she required extensive volume resuscitation, vasopressors for hypotension, and stress dose steroids for adrenal insufficiency. When shock resolved, sedation was lightened and she was noted to have a fluctuating mental status, sometimes extremely agitated and combative, and other times withdrawn, with delayed Pediatr Blood Cancer DOI 10.1002/pbc
Opiates decreased Dexmedetomidine added
Quetiapine added
motor response to interactions. Her mother described her as “in a trance”. Delirium was diagnosed and targeted interventions ensued, including replacing benzodiazepines with dexmedetomidine for sedation, minimizing opiates, avoiding anticholinergics, optimizing continuous veno-venous hemofiltration (CVVH) to normalize blood urea nitrogen, and clustering care to avoid nighttime awakenings. Agitation improved but she remained withdrawn and confused. With initiation of quetiapine, confusion improved. Quetiapine was continued for approximately 10 days, and tapered off prior to discharge home.
Case 4 A 7-month-old female with neuroblastoma was admitted after extensive pelvic mass resection, involving paraspinal and paraaortic regions. Initial post-operative course was unremarkable, with expected third-spacing of fluids and volume resuscitation. On postoperative Day 2, she was hemodynamically stable with a modest alveolar-arterial oxygen gradient and she was successfully extubated. The patient’s mother stated that she was not interactive, did not seem to recognize her parents, was not comforted by usual maneuvers, and “could not seem to settle down.” She was diagnosed with hyperactive delirium and successfully treated with a combination of dexmedetomidine and quetiapine.
CONCLUSION Delirium is the most frequently diagnosed neuropsychiatric complication of advanced cancer in adults, and an independent risk factor in predicting short-term survival [16–17]. The prevalence of delirium in pediatric oncology patients is not well-described, largely due to the absence of widespread screening. Pediatric oncologists are at the front lines with respect to detecting delirium in their high-risk patient population. Widespread screening is feasible, even in extremely young and mechanically ventilated patients. Targeted treatment may shorten the duration of delirium and mitigate associated morbidities. Heightened awareness by pediatric oncologists, surgeons, and
Neuroblastoma and Delirium intensivists may lead to earlier diagnosis and improvement in clinical outcomes. Children with neuroblastoma have underlying factors that may constitute an increased risk for delirium, especially in the postoperative period. A prospective multi-institutional trial to investigate the prevalence of delirium in neuroblastoma patients, and identify modifiable risk factors, is warranted.
REFERENCES 1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV-TR, 4th edition, text revision. Washington, DC: American Psychiatric Association; 2000. 2. Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med 2013;41:278–280. 3. Silver G, Traube C, Kearney J, et al. Detecting pediatric delirium: Development of a rapid observational assessment tool. Intensive Care Med 2012;38:1025–1031. 4. 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 2013 [Epub ahead of print]. 5. Smith HAB, Brink E, Fuchs DC, et al. Pediatric delirium. Pediatr Clin North Am 2013;60:741–760. 6. Smith HA, Fuchs DC, Pandharipande PP, et al. Delirium: An emerging frontier in the management of critically ill children. Crit Care Clin 2009;25:593–614.
Pediatr Blood Cancer DOI 10.1002/pbc
1123
7. Turkel SB, Braslow K, Tavare CJ, et al. The delirium rating scale in children and adolescents. Psychosomatics 2003;44:126–129. 8. Schieveld JN, Staal M, Voogd L, et al. Refractory agitation as a marker for pediatric delirium in very young infants at a pediatric intensive care unit. Intensive Care Med 2010;36:1982–1983. 9. Silver GH, Kearney JA, Kutko MC, et al. Infant delirium in pediatric critical care settings. Am J Psychiatry 2010;167:1172–1177. 10. Turkel SB, Tavare CJ. Delirium in children and adolescents. J Neuropsychiatry Clin Neurosci 2003;15:431–435. 11. Brodeur GM, Hogarty MD, Mosse YP, et al. Neuroblastoma. In: Pizzo PA, Poplack DG, editors. Principles and practice of pediatric oncology. Philadelphia, PA: Lippincott Williams & Wilkins; 2011: 886–922. 12. Goodman MT, Gurney JG, Smith MA, et al. Sympathetic nervous system tumors. In: Ries LA, Smith MA, Gurney JG, et al., editors. Cancer incidence and survival among children and adolescents: United States SEER Program, 1975–1995. Bethesda, MD: National Cancer Institute; 1999: 65–72. 13. Creten C, Van Der Zwaan S, Blankespoor RJ, et al. Pediatric delirium in the pediatric intensive care unit: A systematic review and an update on key issues and research questions. Minerva Anestesiol 2011;77:1099. 14. Devlin JW, Roberts RJ, Fong JJ, et al. Efficacy and safety of quetiapine in critically ill patients with delirium: A prospective, multicenter, randomized, double-blind, placebo-controlled pilot study. Crit Care Med 2010;38:419–427. 15. Traube C, Witcher R, Mendez-Rico E, et al. Quetiapine as treatment for delirium in critically ill children: A case series. Pediatr Intensive Care 2013. In press. 16. Lawlor PG, Bruera ED. Delirium in patients with advanced cancer. Hematol Oncol Clin North Am 2002;16:701–714. 17. Caraceni A, Nanni O, Maltoni M, et al. Impact of delirium on the short term prognosis of advanced cancer patients. Cancer 2000;89:1145–1149.
