Introduction ® 1 2 5 3 6 7 8 9 10 12 13 The aim of this study was to investigate the incidence, patient and population characteristics, clinical presentation and response to treatment of delirium in a cohort of critically ill children admitted to a tertiary pediatric intensive care unit (PICU). Given the necessarily multidisciplinary approach to assessment and treatment of these children, the input of four disciplines – child psychiatry, pediatric intensive care medicine, child neurology and adult neuropsychiatry – was used. Methods Design, setting and patients A descriptive study was carried out over a 4-year period (January 2002 to December 2005) in an eight-bed tertiary PICU. This PICU is a tertiary referral center for both general and surgically critically ill children in the southeastern region of the Netherlands (population 1.4 million, 350 annual admissions). Critically ill children, acutely, non-electively and consecutively admitted, were prospectively sampled. Both mechanically ventilated and non-ventilated patients were included. Diagnostic approach 14 15 16 At the time the assessment for delirium was initiated, none of the patients had signs of imminent life-threatening respiratory, circulatory or neurological failure, while ongoing asphyxia, respiratory acidosis, metabolic disturbances, fighting the ventilator due to inappropriate ventilator settings and withdrawal syndrome all had been excluded systematically as an explanation for the observed behavior. The first step of the diagnostic approach was a systematic assessment by a child neuropsychiatrist (J.S.) using DSM-IV criteria for delirium. Criteria were evaluated on the basis of (1) hetero-anamnestic information from parents, nurses, intensivists, and child neurologists about behavior and behavioral changes and (2) child psychiatric examination. Based on the findings, patients were categorized as having a (probable) delirium or not. In a second step, the provisional diagnosis of delirium was further tested in a daily multidisciplinary consensus meeting. The team consisted of the child neuropsychiatrist, the attending pediatric intensivist, and occasionally a geriatric neuropsychiatrist specialized in delirium in geriatric patients and/or a child neurologist. If this team agreed that alternative explanations for a child's behavior were unlikely, the consensus diagnosis was delirium. 17 7 18 19 20 Therapeutic approach 21 11 22 23 Children were followed up for 6 weeks after discharge from the hospital either at the outpatient clinic or by contacting the parents by telephone. As the study solely involved the structured recording of routine clinical practice, under Dutch law no institutional review board approval was required. Results 1 Table 1 * Age * Patients with delirium Incidence (%) 0–2.99 years 513 14  2.7 Male 310  9  2.9 Female 203  5  2.5 3–5.99 years 106  4  3.8 Male  56  3  5.4 Female  50  1  2.0 6–8.99 years  80  6  7.5 Male  46  1  2.2 Female  34  5 14.7 9–11.99 years  77  3  3.9 Male  61  3  4.9 Female  16  0  0 12–14.99 years  70  7 10 Male  35  5 14.3 Female  35  2  5.7 15–18 years  31  6 19.4 Male  13  4 30.8 Female  18  2 11.1 Total 877 40  4.6 Male 521 25  4.8 Female 356 15  4.2 * 1 1 Fig. 1 Incidence of delirium in the sub-groups by age and gender  2 Table 2 n n Diagnosis 40 delirium  5 adjustment disorders with anxiety and depressed mood, post operative  4 psychological–psychiatric factors affecting the medical condition  3 anxiety disorder  3 emotional and behavioral problems during chronic ventilation  2 adjustment disorders with depressed mood  1 mood disorder  1 adjustment disorder with anxiety  1 sleeping problem  1 feeding problem 3 4 Table 3 Population characteristics of the 40 PICU cases with delirium, 2002–2005 Characteristics n Age (mean ± SD)  7.6 ± 5.9 Male  n 25  age (mean ± SD)  7.6 ± 6.1 Female  n 15  age (mean ± SD)  7.6 ± 5.8 Ethnicity   White 36 (90%)  African  3 (7.5%)  Asian  1 (2.5%) Mechanical ventilation 34 (85%) PIM score (mean ± SD) 9.96 ± 16.20 PRISM score (mean ± SD) 23.54 ± 24.94 Major somatic pharmacological features   Recent increase or decrease of analgosedative medication 22 (55%)  Neurological disorders 21 (52%)  Infectious disorders 20 (50%)  Respiratory disorders 12 (30%) PIM PRISM Table 4 Patient characteristics of the 40 PICU cases with delirium 2002–2005 No. Sex Age Primary diagnosis on admission PICU Mechanical ventilation Delirium type Treatment  1 M  3 months Multiple congenital malformations + Emerging Haloperidol  2 F  4 months Meningococcal septic shock + Emerging Risperidone  3 M  4.5 months Severe CLD + Emerging Risperidone  4 F 10 months Near drowning + Emerging Haloperidol  5 F  1 year Pneumonia + Emerging Haloperidol  6 M  1 year Sepsis due to perforated appendicitis + Emerging Haloperidol  7 M  1 year Subarachnoid bleeding + Emerging Haloperidol  8 M  1 year Pericardial effusion with pretamponade + Hyperactive Haloperidol  9 M  1 year Multiple dysmorphia, upper airway obstruction – Emerging Haloperidol 10 F  2 years Meningococcal septic shock + Hyperactive Haloperidol 11 M  2 years ADEM + Hyperactive Risperidone 12 M  2 years Cervical mass, upper airway obstruction + Emerging Haloperidol 13 M  2 years Aspiration and pneumothorax + Hypoactive – 14 F  2 years Meningococcal meningitis with sepsis and DIC + Hyperactive Haloperidol 15 F  3 years Cystic fibrosis and pneumonia + Hypoactive Haloperidol 16 M  4 years Intracerebral hemorrhage, Marfan syndrome + Hypoactive Haloperidol 17 M  5 years Medulloblastoma post surgery + Emerging Risperidone 18 M  5 years Upper respiratory tract infection + Hyperactive Haloperidol 19 M  6 years Multiple trauma + Emerging Risperidone 20 F  8 years Meningo-encephalitis + Hyperactive Risperidone 21 F  8 years Viral encephalitis + Hyperactive – 22 F  9 years Status asthmaticus + Hyperactive Risperidone 23 F  9 years TBI, gunshot wound + Hypoactive Risperidone 24 M  9 years Status asthmaticus + Hyperactive Haloperidol 25 M  9 years Neural tube defect and drain dysfunction – Emerging first Haloperidol, then Risperidone 26 M 11 years Hypovolemic shock, typhus abdominalis – Hyperactive Haloperidol 27 F 12 years TBI + Hypoactive Haloperidol 28 M 12 years TBI and fracture of lower leg + Emerging Haloperidol 29 M 13 years Sepsis, paronychia – Hyperactive Haloperidol 30 M 13 years Status epilepticus + Emerging Haloperidol 31 F 14 years TBI + Hyperactive Haloperidol 32 F 15 years Post TBI + Hypoactive Haloperidol 33 M 15 years Postoperative state + Hypoactive Risperidone 34 M 15 years Acute lymphoblastic leukemia – Hypoactive Haloperidol 35 M 15 years TBI + Emerging Haloperidol 36 F 15 years Status asthmaticus + Hyperactive Haloperidol 37 M 16 years Multiple trauma – Hypoactive Haloperidol 38 F 16 years Bacterial meningitis + Hyperactive Risperidone 39 M 16 years Respiratory failure, Duchenne disease + Emerging Haloperidol 40 M 17 years Septic shock + Emerging Haloperidol CLD ADEM DIC TBI n n n n 11 3 Discussion 2 1 11 24 25 2 always 17 26 27 17 28 29 32 33 1 34 35 36 37 This study has several limitations. First, it was a study of routine clinical practice. Observations were based on referrals emerging from care as usual. Although the focus on delirium may have altered referral paths and rates, we did not actively advocate any change, nor did we screen all admissions for delirium. In the absence of a hard clinical indication, no routine blood level measurements were performed to rule out persistent high levels of sedatives as a possible explanation for any neuropsychiatric symptom. Next, the lack of DSM-IV criteria for pediatric delirium and the disputed relevance of its main criterion in a (P)ICU setting make a standardized diagnosis difficult. Finally, treatment was provided in an open setting and based on consensus, especially among child psychiatrist, pediatric intensivist and child neurologist. In conclusion, critically ill children in a PICU can develop delirium, with a hyperactive, hypoactive or veiled presentation, despite adequate analgosedation and intensive psychosocial interventions. The approach using an algorithmic structuring and an intensifying of daily clinical care, including the use of multidisciplinary daily consensus meetings, appeared effective in assessing, diagnosing and treating childhood delirium at the PICU. The findings suggest that the incidence is much lower than in adults, but a likely explanation is that delirious states requiring child psychiatric referral are still frequently under-diagnosed. There is also still a great need for developing delirium criteria in critically ill patients, children and adults alike, in a (P)ICU setting. Treatment with haloperidol or risperidone was successful in all patients. Future research is necessary to identify the risk factors for pediatric delirium in a multivariate prospective approach, to develop “easy to use” bedside tools for non-psychiatric trained team members for the early detection of delirium in all pediatric PICU patients, and to study the effects of interventions in a double-blind and ideally placebo-controlled fashion. Disclosure Jim van Os is a speaker or member of the advisory board for Lilly, BMS, Janssen-Cilag and AstraZeneca. He received grant or research support from Lilly, GSK, BMS and AstraZeneca. Albert Leentjens participated in research for Boehringer Ingelheim and is on the advisory board of a study related to Parkinson's disease by the same company. The other authors have no financial relationships to disclose.