This observational study aims to determine the incidence of delirium among children in a pediatric intensive care unit (PICU) and to identify associated risk factors.

Research Questions:

What is the incidence of delirium among children in a pediatric intensive care unit? What are the identifiable risk factors that predispose children in a pediatric intensive care unit to developing delirium?

Study Background and Rationale Delirium, an acute neurocognitive syndrome, is characterized by a sudden onset of fluctuating mental states, reflecting a deterioration in brain function. Its clinical manifestations include impaired attention span, sleep disturbances, acute confusion, impaired concentration, decreased level of consciousness and responsiveness, increased irritability, apathy, or agitation. The duration of delirium can vary from short periods to several days and may fluctuate throughout hospitalization. The presence of delirium can significantly contribute to an increased length of hospital stay and can exacerbate suffering for both the pediatric patient and their family. In Swedish pediatric intensive care units (PICUs), a systematic assessment of delirium using a standardized, validated assessment instrument has historically been absent. This gap in practice hinders the early identification of affected children, which is crucial for improving care and mitigating adverse outcomes. Recognizing this need, an assessment instrument, the Cornell Assessment of Pediatric Delirium (CAPD), has been rigorously translated and culturally adapted from English to Swedish. This study is designed to implement this newly translated instrument to establish the incidence of delirium in children within Swedish PICUs. Furthermore, a critical objective is to identify associated risk factors, which will inform the development and implementation of targeted care strategies aimed at reducing the risk and burden of delirium. The proactive assessment and management of delirium are well-established standard practices in adult intensive care settings, underscoring the imperative for similar advancements in pediatric critical care.

Study Objectives and Research Questions Aim: This observational study aims to determine the incidence of delirium among children in a pediatric intensive care unit (PICU) and to identify associated risk factors.

Research Questions

• What is the incidence of delirium among children in pediatric intensive care units?
• What are the identifiable risk factors that predispose children in a pediatric intensive care unit to developing delirium?

Study Design and Setting This is a prospective, longitudinal multicenter observational study conducted across multiple pediatric intensive care units in Sweden. The study design is optimized for capturing real-world data on delirium incidence and associated factors in a diverse PICU population.

Participant Eligibility Participant eligibility criteria are comprehensively detailed in a separate protocol section. Briefly, the study will include children admitted to participating PICUs with an expected duration of care exceeding one over night stay. The primary consideration for inclusion is the ability for children (with assent as appropriate) and/or their parents/legal guardians to be informed about the study's purpose and provide consent. A deferred consent procedure will be utilized in emergency situations preventing immediate consent, wherein provisional inclusion occurs, followed by formal consent/assent at the earliest calm moment. In cases of consent withdrawal, all previously collected data for that participant will be immediately destroyed. Given the observational nature of the study, without any direct intervention, the risk of privacy violation under the deferred consent procedure is considered minimal.

Study Procedures and Data Collection Prior to the commencement of data collection, comprehensive education regarding pediatric delirium and the standardized administration of the CAPD instrument will be delivered to all nursing staff in participating PICUs. This initial training will ensure consistent application of the assessment tool across all sites. Continuous training modules will also be available for newly hired staff and accessible on demand, through both in-person sessions and remote online platforms, to maintain proficiency and adherence to protocol.

Delirium Assessment Following ethical approval, CAPD assessments will be systematically performed once per nursing shift for all eligible children admitted to the unit. This assessment will continue for each participant for a period of up to 24 months.

Clinical Data Elements

In addition to the CAPD assessment for delirium incidence, a comprehensive set of clinical data will be collected through direct inquiry with treating staff and through detailed electronic health record (EHR) review. Data elements considered relevant for identifying risk factors for delirium, characterizing delirium subtypes, and calculating delirium duration include, but are not limited to:

• Demographics: Age (at admission), gender.
• Medical History: Documented pre-existing conditions (e.g., neurological disorders, developmental delays).
• Clinical Course Data: Laboratory analyses (e.g., inflammatory markers, electrolyte levels, drug levels). Diagnostic findings (e.g., neurological diagnoses, infection status). Functional assessments (e.g., baseline functional status, mobility). Imaging results (e.g., cranial CT/MRI findings). Physiological Parameters: Continuously recorded vital signs (e.g., blood pressure, heart rate, respiratory rate, oxygen saturation), urine output, pain scores. Complications: Documented occurrences of renal failure, thrombotic events, episodes of decreased level of consciousness. Treatments: Initiation and duration of therapies such as dialysis, mechanical ventilation, specific medications (e.g., sedatives, analgesics, corticosteroids, vasopressors, anti-infectives). Nursing Interventions: Use of physical restraints, documented parental presence at the bedside, environmental modifications.

Data Management System Data will be collected by PICU nurses during the delirium assessment and subsequently managed by a designated research contact (1-2 persons) at each unit. All collected data will be entered into a secure, validated electronic Case Report Form (eCRF) database. Initial data will be captured via CAPD scores and select clinical variables. Subsequent retrospective EHR review will complement this initial dataset, with additional relevant clinical and historical data collected and entered into the same eCRF database.

Data Dictionary A comprehensive data dictionary will be maintained, providing detailed descriptions of each variable collected within the eCRF. This includes variable names, definitions, data types, allowable ranges, coding information (e.g., ICD-10 codes, MedDRA terms if applicable), and normal physiological ranges where relevant. The source of each variable (e.g., CAPD score, EHR abstraction) will also be documented.

Standard Operating Procedures (SOPs)

Detailed SOPs will govern all aspects of the study operations and analysis activities, including:

• Patient recruitment and screening.
• Informed consent/assent procedures, including deferred consent.
• Standardized CAPD assessment administration.
• Clinical data collection and EHR abstraction.
• Data entry into the eCRF.
• Data management, including data cleaning and validation.
• Handling and reporting of adverse events (if any related to study procedures).
• Change management for protocol amendments.

Study Staff Roles Each pediatric intensive care unit will designate 1-2 nurses primarily responsible for patient inclusion, informed consent processes, and consistent CAPD assessments. Additionally, a research assistant or nurse will be allocated to assist with meticulous EHR review and data entry to ensure accuracy and completeness. Permissions for EHR review will be formally sought from each participating hospital in accordance with local regulations and ethical guidelines.

Quality Assurance and Data Integrity Data entered into the eCRF system will undergo manual validation by personnel independent of the primary data collection team. A minimum of 10% of the entered records will be thoroughly reviewed. This manual review, will include assessment of data ranges, formats, and consistency across related data fields to minimize entry errors.

Source Data Verification (SDV) A proportion of the eCRF data, particularly critical variables related to delirium incidence and key risk factors, will undergo source data verification by comparing it against original medical records (EHRs). This will assess the accuracy and representativeness of the registry data.

Site Monitoring and Auditing Regular monitoring visits (remote or on-site, as determined by the study's scope and resources) will be conducted to ensure protocol adherence, proper CAPD administration, and data quality. Independent auditing may be performed to ensure compliance with regulatory and ethical standards.

Statistical Analysis Plan The sample size assessment will be performed to ensure adequate statistical power for the primary objectives, particularly for estimating the incidence of delirium with a specified precision and for identifying significant risk factors through multivariable logistic regression.

A plan will address missing data. Strategies for handling missing variables will include: Documentation of reasons for missingness. Assessment of patterns of missing data (e.g., Missing Completely at Random, Missing at Random, Missing Not at Random). Implementation of appropriate imputation techniques (e.g., multiple imputation) if deemed necessary and justifiable, following sensitivity analyses to assess the impact of missing data.Data will be analyzed using standard statistical software.

Descriptive Statistics Baseline characteristics of the study population will be summarized using descriptive statistics (e.g., means with standard deviations or medians with interquartile ranges for continuous variables; frequencies and proportions for categorical variables). The incidence of delirium will be presented as a proportion of children experiencing at least one episode of delirium during their PICU stay, along with its 95% confidence interval. The cumulative duration of delirium will be described using measures such as mean, median, and range of days. Delirium subtypes (hypoactive, hyperactive, mixed) will be reported using frequencies and proportions.

Inferential Statistics To identify risk factors, multivariable logistic regression models will be constructed. To explore associations with delirium duration, linear regression or other generalized linear models will be considered. Associations between risk factors and delirium subtypes may be analyzed using multinomial logistic regression or chi-square tests. Potential covariates, including demographic, clinical, and treatment-related factors identified during data collection, will be considered for inclusion in the models. Model selection will be based on established statistical criteria. Subgroup analyses may be performed if indicated by the data. All statistical tests will be two-sided, with a significance level set at p < 0.05.

Inclusion Criteria:

• Expected time of care at the pediatric intensive care unit for at least one overnight stay

Exclusion Criteria:

• Care at the very end of life

All children admitted to a pediatric intensive care unit with an expected time of care for at least one over night stay

De-identified individual participant data underlying the results reported in publications from this study will be made available. This will include baseline characteristics, clinical course variables (such as physiological parameters, laboratory analyses, diagnostic findings, and complications), treatment exposures (e.g., medications, mechanical ventilation, nursing interventions), and delirium outcome data (incidence, cumulative duration, and subtype characterization based on CAPD assessments). All data will be fully anonymized at the individual level so that no participant can be identified.

Data will be available beginning 12 months after publication of the primary results and will remain available upon reasonable request for at least 5 years thereafter.

Access to the de-identified dataset will be granted to qualified researchers upon reasonable request. Requests must include a brief description of the research question, analysis plan, and intended use of the data. All requests will be reviewed by the PADI steering committee. Data will be shared only for scientifically sound projects and for purposes consistent with the original study objectives and ethical approvals. Data will be shared through secure data transfer following approval of a data sharing agreement. No direct identifiers or site-specific identifiers will be included in the shared dataset.