Predictors of Maladaptive Behaviors in Children Undergoing Procedural Sedation
Conditions: Procedural Sedation and Analgesia
Sponsor: London Health Sciences Centre Research Institute

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Study Title: PRedictors Of maladaptive behaviors in children 
undergoing procedural SEDation 
 
Or 
 
Short Title: PRoSEED 
 
Version Number: V.3.0 
2026 FEBRUARY 02 
Logo 
 
 
 
Principal Investigator 
Naveen Poonai, Western University 
 
Co-Principal Investigator 
Noha Gomaa, Western University 
 
Co-Investigators 
Amy Drendel, Medical College of Wisconsin 
Daniel Tsze, Columbia University 
Kyna Patterson, London Health Sciences Centre (LHSC) 
Emma Parent, LHSC 
Heather Maddocks, LHSC 
Michael Miller, Western University 
Maala Bhatt, University of Ottawa 
Samina Ali, University of Alberta 
Mohamed Eltorki, University of Calgary 
Vikram Sabhaney, University of British Columbia 
Evelyne Doyon-Trottier, Universite de Montreal 
Gopakumar Nair, Western University 
Rana Swed Tobia, University of British Columbia 
 
OSF Registration 
Pending 
 
Funding 
Academic Medical Organization of Southwestern Ontario 
 

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Table of Contents 
AMENDMENTS ............................................................................................................... 4 
LAY SUMMARY ............................................................................................................... 4 
ABSTRACT ...................................................................................................................... 5 
RESEARCH QUESTION ................................................................................................... 5 
OBJECTIVES ............................................................................................................... 5 
HYPOTHESES ............................................................................................................. 5 
HEALTHCARE IMPACT ................................................................................................. 6 
BACKGROUND ............................................................................................................... 6 
RATIONALE AND SIGNIFICANCE ................................................................................. 7 
EXPECTED OUTCOMES ............................................................................................... 8 
DESIGN ......................................................................................................................... 8 
ELIGIBILITY ................................................................................................................. 8 
SCREENING AND ENROLLMENT ................................................................................. 8 
DATA COLLECTION ..................................................................................................... 8 
PRIMARY OUTCOME ................................................................................................... 9 
SECONDARY OUTCOMES ........................................................................................... 9 
EXPOSURE VARIABLES ................................................................................................ 9 
COMPENSATION ...................................................................................................... 10 
SCHEDULE OF ACTIVITIES ............................................................................................ 10 
ANALYSIS ..................................................................................................................... 11 
SAMPLE SIZE CONSIDERATIONS ............................................................................... 11 
SEX & GENDER-BASED ANALYSIS .............................................................................. 12 
PATIENT ENGAGEMENT ................................................................................................ 12 
PILOT WORK ................................................................................................................ 12 
RATIONALE FOR RECRUITMENT TARGETS .................................................................. 12 
TEAM ........................................................................................................................... 13 
TIMELINE ..................................................................................................................... 14 
REFERENCES ............................................................................................................... 15 

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AMENDMENTS 
Version (Date) 
Description 
Version 2.0 
(09JAN2026) 
- Updated sample size from 2152 to 2113 
- Modified the ILCTI to include copyrighted material 
- Added telephone, email, and SMS scripts 
- Replaced PHBQ with the PHBQ-AS 
- Changing the PPPM with the PPPM-SF 
- Removed FPS-R and included all ages for the PPPM-SF 
- Adding Day 1 to the follow-up data collection 
- Miscellaneous updates 
Version 3.0 
(02FEB2026) 
- Added the PROMIS Pediatric Family Relationships – Short Form 8a & Parent 
Proxy 8a survey 
- Added the Pain Catastrophizing Scale – Parent (PCS-P) 
- Specified that anxiolysis can also be used for sedation 
- Updated the sample size calculation from n=2113 to n=2145 
 
LAY SUMMARY 
Procedural sedation for children outside of the operating room is a common practice in 
emergency departments, outpatient clinics, radiology suites, and dental offices for painful and 
anxiety-provoking procedures. However, there is emerging evidence that so-called “delayed 
maladaptive behaviors” (disordered sleep, anxiety, and aggression) affect nearly a quarter of 
children for up to 2 weeks following sedation. This can lead to poor school attendance, reduced 
extracurricular involvement, disruptions to caregivers’ employment obligations, and poor patient 
satisfaction. As this phenomenon has only recently been identified, very little is known about 
what factors predispose children to delayed maladaptive behaviors, however, small studies 
suggest younger age and pre-procedural anxiety may be involved. The aim of our study is to 
characterize risk factors for delayed maladaptive behavior in a large multicentre study involving 
emergency departments, dental offices, and hospital sedation services. Understanding these risk 
factors may help healthcare workers prevent delayed maladaptive behaviors and provide patients 
with anticipatory guidance, akin to post-operative recovery instructions. 
 
There is emerging evidence that maladaptive behaviors, including significant negative behavioral 
changes, can occur in children following procedural sedation. These include disordered sleep, 
anxiety, and aggression)1,2 and affect up to 24% of children following inhalational anesthetics3 
and intravenous sedatives such as ketamine.1 Moreover, these appear to be more pronounced in 
children <4 years4 and can persist for up to 2 weeks post-sedation. Unfortunately, only two trials 
have reported delayed maladaptive behaviors.1,2 Data on immediate and delayed AEs are 
urgently needed for safe clinical decision-making and anticipatory guidance surrounding ED 
anxiolytics. In a prospective cohort study of children undergoing emergency department 
procedural sedation with intravenous ketamine, 22% exhibited significant negative behavioral 
changes 1–2 weeks after discharge, as measured by the Post-Hospitalization Behavior 
Questionnaire. High pre-procedure anxiety have been identified as independent predictors of 

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these maladaptive behaviors.5 Additionally, irritability, hyperactivity, and hallucinations during 
recovery have been reported and are associated with lower parental satisfaction.6 
 
ABSTRACT 
Background: Procedural sedation in children outside of the operating room (OR) is routine. 
There is emerging evidence that delayed maladaptive behaviors (disordered sleep, anxiety, and 
aggression) can manifest in up to a third of children. No study has characterized the risk factors 
for delayed maladaptive behaviors following procedural sedation. 
Methods: Multicentre prospective cohort study. The primary outcome is the proportion of 
children with delayed maladaptive behaviors based on a Post-Hospital Behavior Questionnaire – 
Ambulatory Surgery (PHBQ-AS) score of >3.2 negative changes on day 3 post-
sedation/anxiolysis. 
Expected Outcome: This study is expected to provide actionable data on modifiable and non-
modifiable risk factors for maladaptive behavioral outcomes with the overarching aim of 
informing safer and more personalized sedation practices in children. 
RESEARCH QUESTION 
What are the risk factors for delayed maladaptive behaviors in children and adolescents 1-17 
years undergoing procedural sedation or anxiolysis? 
 
OBJECTIVES 
i) Characterize the risk factors associated with delayed maladaptive behaviors in children 
undergoing procedural sedation or anxiolysis in the ED and dental clinics. 
ii) Determine the proportion of children with delayed maladaptive behaviors following 
procedural sedation or anxiolysis. 
iii) Determine the degree to which delayed maladaptive behaviors are associated with post-
sedation pain. 
 
HYPOTHESES 
i) An increased risk of delayed maladaptive behaviors (> 3 in negative behaviors score from pre-
sedation to 3-days post-sedation) will be associated with younger age, greater pre-sedation 
anxiety (Modified Yale Pre-Operative Anxiety Scale score > 40), greater pre-sedation pain 
(Parent’s Post-Operative Pain Measure – Short Form), sedative drug combinations, and baseline 
temperament (Integrative Childhood Temperament Screener - age < 8 years) and Integrative Late 
Childhood Temperament Inventory - age > 8 years). This hypothesis is based on previous 
associations identified in children receiving inhalational anesthetics.7-9 

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ii) The proportion of children with delayed maladaptive behaviors will be > 20% based on prior 
literature.5,10 
iii) Delayed maladaptive behaviors will be associated with greater post-sedation pain. 
 
HEALTHCARE IMPACT 
Delayed maladaptive behaviors following procedural sedation/anxiolysis or hospitalization in 
children and adolescents have adverse implications for family well-being and the child's overall 
functioning. Parental reports consistently identify behavioral issues as among the most frequent 
post-discharge events, and symptoms such as irritability, prolonged sleepiness, and hyperactivity 
are associated with lower caregiver satisfaction and increased family stress, indicating a direct 
impact on family well-being.11,12 This underscores the need for systematic screening for anxiety 
in high-risk children prior to sedation and mitigate maladaptive behaviors through targeted 
pharmacologic and non-pharmacologic interventions. Now more than ever, healthcare systems 
are challenged with providing comprehensive care in the context of a growing population, fewer 
bedside nurses, and spiraling costs. Our findings will enable healthcare systems to focus their 
efforts through individualized risk assessment, tailored sedation plans, and pain/anxiety 
mitigation strategies to minimize delayed maladaptive behaviors, ultimately improving quality 
and safety in pediatric procedural sedation.11,13 
 
BACKGROUND 
Procedural sedation in children outside of the operating room (OR) is routinely performed for 
orthopedic reductions, laceration repairs, diagnostic imaging, and other painful or anxiety-
provoking procedures.[3-6] Data from the Pediatric Sedation Research Consortium identified 
432,842 outpatient pediatric procedural sedation encounters over an 11-year period, reflecting 
widespread use in settings such as emergency departments (EDs), radiology suites, and dedicated 
sedation units.14,15 Most sedations are performed in children under 10 years of age.[3-4] Ketamine 
is the most commonly used agent,16 but other common sedatives include propofol, nitrous oxide, 
and dexmedetomidine.15,17 Children also receive anxiolysis (nitrous oxide; midazolam) for 
procedural distress. Typically, these agents do not sedative children but may be associated with 
delayed maladaptive behaviors. 
 
Although procedural sedation outside the OR is widely regarded as safe,18-20 there is emerging 
evidence that delayed maladaptive behaviors, manifesting as disordered sleep, separation 
anxiety, and aggression towards authority2,5 can affect up to a third of children.5,10,21 Delayed 
maladaptive behaviors have been described following general anesthesia in the perioperative 
setting,7,8 where they can persist for up to a month post-anesthesia.8 Moreover, they appear to be 
more pronounced in children under 4 years of age.7 However, only two studies have 
characterized delayed maladaptive behaviors following procedural sedation outside the OR.2,5 A 
prospective single-center study of 97 children undergoing ED procedural sedation with 
intravenous ketamine found that 22% of children exhibited significant negative behavioral 
changes up to 2 weeks after discharge with high pre-procedural anxiety identified as a risk 

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factor.5 Another study of 60 children found that 20% exhibited delayed maladaptive behaviors 
that persisted for one week following ED discharge.10 
 
Although there are similarities between the ED and perioperative setting, there are some 
important differences. Unlike the OR, procedural sedation in the ED is largely unscheduled, and 
with a relatively short time period from decision to performance of the procedure. This together 
with the time constraints of busy EDs often precludes the ability of healthcare workers to enact 
measures to reduce pre-procedural anxiety and provide anticipatory guidance to families. In 
addition, procedural sedation in the ED is often performed to facilitate low morbidity procedures 
with an anticipated short recovery time. In contrast to surgical procedures in the OR, children are 
often expected to resume normal activities shortly after an ED visit. Thus, the frequency, 
severity, and functional impact of delayed maladaptive behaviors on children and their caregivers 
may be significantly greater. 
 
RATIONALE AND SIGNIFICANCE 
Procedural sedation and anxiolysis is frequently performed in children and preliminary evidence 
suggests delayed maladaptive behaviors are common. These behaviors may reduce school 
attendance and participation in extracurricular activities and compromise caregivers’ abilities to 
fulfill employment responsibilities. Characterizing the risk factors for delayed maladaptive is 
essential to extending the care of children and supporting their caregivers following ED 
discharge. The Canadian Paediatric Society (CPS) strongly recommends managing distress 
during medical procedures, but lacks guidance for pre-sedation pain and anxiety,22 which may 
contribute to delayed maladaptive behaviors. Our study will fill this unmet need and identify 
modifiable risk factors such as pain and pre-procedural anxiety that can be addressed through 
interventions by certified child life specialists (CCLSs) and bedside nurses. Currently, measures 
to reduce anxiety and pain-related procedural distress in children are inconsistently used.23,24 Our 
findings will also inform more comprehensive amendments to existing pain and anxiety 
management recommendations set by the CPS.22 
 
Characterizing risk factors for delayed maladaptive behaviors in children undergoing procedural 
sedation or anxiolysis is highly innovative because current research has focused primarily on 
immediate adverse events and neurodevelopmental outcomes, leaving a significant gap in 
understanding the behavioral sequelae of procedural sedation outside the OR.6,20,25,26 Recent 
large-scale studies have identified risk factors for acute adverse events and prolonged recovery, 
such as higher body weight, prior sedation history, and specific sedative agents, but have not 
systematically addressed delayed maladaptive behavioral changes.17,20 The American Academy 
of Pediatrics highlighted the need for further work to determine the magnitude and causation 
of behavioral and executive function deficits in children with repeated sedation exposures, 
especially those with developmental disabilities.27 Our work will fill this unmet need. Moreover, 
parental dissatisfaction and negative recovery experiences are associated with behavioral 
symptoms that persist into the post-sedation period, yet these outcomes remain poorly 
characterized in the literature.6 By prospectively identifying modifiable and non-modifiable risk 
factors for delayed maladaptive behaviors, this study will address critical knowledge gaps and 
inform safer, more personalized sedation practices for children and adolescents. 
 

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EXPECTED OUTCOMES 
Overall, the study is expected to provide actionable data on modifiable and non-modifiable 
risk factors for maladaptive behavioral outcomes with the overarching aim of informing safer 
and more personalized sedation practices in children. In the short-term, we expect to 
characterize risk factors that increase the risk for delayed maladaptive behaviors in children and 
adolescents undergoing procedural sedation or anxiolysis, identify the prevalence of maladaptive 
behaviors, and identify links with post-sedation pain. In the long-term, we expect to use this 
knowledge to implement practice change through i) education of certified child life specialist and 
nurses on the importance of measures to reduce pre-procedural anxiety such as providing age-
appropriate anticipatory guidance, distraction, and caregiver involvement; ii) education of 
physicians on the importance of screening for at-risk patients and choosing sedative or anxiolytic 
and doses that are associated with a lower risk of maladaptive behaviors; iii) standardizing pre-
procedural analgesia through nurse-initiated medical directives for common indications such as 
orthopedic manipulation, laceration repair, and dental procedures. We will evaluate the impact of 
the study’s findings using a quality improvement (QI) framework. 
 
DESIGN 
Multicenter prospective cohort study involving 5 sites across the Pediatric Emergency Reseach 
Canada (PERC),28 a national research network with experience supporting impactful, multicentre 
research.29,30 Potential sites include Children’s Hospital LHSC (ED and dental clinics), BC 
Children’s, Stollery Children’s, CHU Ste Justine, and Children’s Hospital of Eastern Ontario 
(CHEO). 
 
ELIGIBILITY 
We will include children and adolescents 1-17 years undergoing procedural sedation or 
anxiolysis with any agent for any indication in the ED and dental clinics. We will exclude 
patients where the primary caregiver lacks English or French (if applicable to site) 
comprehension in the absence of a native language interpreter, lack a smartphone able to receive 
SMS text messages, caregiver and/or patient are not available for all of the planned follow-up 
dates, or were previously enrolled in the study. 
 
SCREENING AND ENROLLMENT 
A research assistant (RA) will consecutively screen and enroll participants during hours of 
availability. 
 
DATA COLLECTION 
Data will be stored in on Research Electronic Data Collection platform (REDCap) by the RA. 
Data collection on days 1, 3, 7, 10, and 14 will be obtained via SMS text messages using Twilio 

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containing links to REDCap surveys. If the participant is experiencing issues accessing the 
surveys over text message, the surveys will be completed by the participant over the phone with 
the research assistant or research coordinator. 
 
PRIMARY OUTCOME 
Maladaptive behavior on day 3 post-sedation/anxiolysis using the Post-Hospital Behavior 
Questionnaire for Ambulatory Surgery (PHBQ-AS).31 The PHBQ-AS is a caregiver-reported 11-
item measure of post-hospitalization behavioral changes. The PHBQ-AS is a revision of the 
original PHBQ with 11 items, no subscales, and a different scoring approach that treats 
behavioral change as a continuous overall construct, based on average item scores, rather than 
relying on a count of “severe” behaviors or a threshold meant to imply clinical severity. To score 
the PHBQ-AS, items are averaged by summing the items for each respondent and dividing by the 
total number of items. The total PHBQ-AS score produces a continuous variable with higher 
values above 3 (the midpoint) indicating greater maladaptive behavioral changes, lower values 
below 3 indicating improvements in behavioral change, and values equal to 3 indicating no 
behavioral change. A cut-off score of 3.2 on the PHBQ-AS for the diagnosis of negative behavior 
has been published.33 The original PHBQ was designed to measure behavior changes after 
surgery or hospitalization, and has been used in the ED setting.5,10 However, several items were 
not applicable to older children. The PHBQ measures general anxiety, separation anxiety, 
aggression toward authority, eating disturbance, apathy and withdrawal, or sleep anxiety. 
Caregivers compare their child’s current behavior to pre-sedation behavior on a 5-point Likert-
type scale.5 Each behavior can show an improvement, deterioration or no change. The number of 
deteriorations is summed across the 11 items to determine the magnitude of behavior change. 
 
SECONDARY OUTCOMES 
Prevalence of maladaptive behaviors on days 1, 7, 10, and 14 post-sedation or anxiolysis based 
on a significant deterioration (> 3.2 negative changes on the PHBQ-AS).31 
 
EXPOSURE VARIABLES 
i) Age 
ii) Sex 
iii) Gender or gender identity. Young children may not be able to report gender so caregivers will 
be asked to report their child’s gender using the Gender Identity Questionnaire for Children34 
(GIQC). The GIQC has sensitivity of 87% in age 2-12 years and specificity of 95%.36 
iv) Sedative/anxiolytic +/- analgesic agent 
v) Sedative/anxiolytic +/- analgesic dose (mg/kg, mcg/kg, or % nitrous oxide) 
vi) Sedation duration (drug administration to discharge time) 
vii) Adequacy of sedation (yes/no based on physician report) 
viii) Procedure grouping based on a modification of the Pediatric Sedation Research Consortium 
categories.17 The modification categorizes procedures as painful and non-painful. 
ix) Pre-sedation child temperament based on the Integrative Child Temperament Screener (ICTS; 
age < 8 years)37 and Integrative Late Childhood Temperament Inventory (ILCTI; age > 8 

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years).38 The ICTS is a brief 9-item parent-report measure designed to assess three core 
temperament dimensions in children aged 2 to 8 years: frustration, behavioral inhibition, and 
attention/persistence, and was developed to be a more practical version of the much longer 
Integrative Child Temperament Inventory. Its psychometric properties have been evaluated 
across large, multinational samples. Specifically, the ICTS demonstrates adequate internal 
consistency for its subscales, as well as strong test-retest reliability and interrater reliability 
(across teachers and parents).37 The ICTS shows robust convergent validity with established 
temperament measures and criterion validity with behavioral problem scales (e.g., Child 
Behavior Checklist). It effectively discriminates between general population and clinically 
referred children with emotional or behavioral disorders.37 The ILCTI is a brief parent-report 
measure designed for children aged 8–14 years. It assesses six temperament dimensions: 
frustration, behavioral inhibition, attention/persistence, activity level, sensory sensitivity, and 
affiliation. The ILCTI has strong internal consistency across all subscales, robust confirmatory 
factor analytic support for its six-factor structure, and adequate convergent validity with 
established temperament and personality measures. The ILCTI also demonstrates criterion 
validity through significant associations with externalizing and internalizing problems, as well as 
school failure, supporting its clinical utility for risk assessment in late childhood and early 
adolescence.38 
x) Child’s pre-procedural anxiety based on a Modified Yale Pre-Operative Anxiety Scale 
(mYPAS) score > 40. The mYPAS is a widely used scale validated in children39 to assess anxiety 
prior to anesthesia21 and procedural sedation.5 It has been validated in children > 6 months.40 
xi) Most severe pain over a 24-hour period on days 1, 3, 7, 10, and 14 post-sedation using the 
parent reported Parent’s Post-Operative Pain Measure – Short Form (PPPM-SF).43  
xii) The PROMIS Pediatric Family Relationship – Short Form 8a and Parent Proxy 8a will be 
used to measure family dynamics. The measure is scored on a T-score metric with a mean of 50 
and standard deviation of 10. Higher scores indicate better family relationship quality. A 3-point 
difference in T-scores is generally considered a minimally important different. 
xiii) The Pain Catastrophizing Scale – Parent (PCS-P) will be used to measure parental 
catastrophizing. It has a score range from 0-44 with each item scored on a 5-point scale ranging 
from 0 (not at all) to 4 (all the time). Higher scores indicate greater parental catastrophizing. 
COMPENSATION 
Participants will be provided with a $30 Amazon gift card as a token of appreciation for their 
participation. The gift card will be emailed to the participant/caregiver after their participation in 
the study has ended. 
SCHEDULE OF ACTIVITIES 
 
 
 
 
      
 
      
 
      

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ANALYSIS 
Variables will be summarized with counts and percentages for categorical data and means and 
standard deviations (or medians and IQRs for non-normal distributions) for continuous data. The 
primary outcome will be reported as the proportion of participants with > 3 negative changes on 
the PHBQ-AS. Bivariate and multivariable analyses will be used to explore the associations 
between the primary outcome of maladaptive behaviors (defined as > 3 negative changes on the 
PHBQ-AS on day 3 post-sedation) and age, sex, gender/gender-identity, sedative drug, sedative 
dose, pain, pre-sedation anxiety, pain catastrophizing, family relationships, and temperament. 
Adjusted multivariable ORs and 95% CIs will be obtained from a mixed-effects logistic 
regression model with the predictors as fixed effects and site as a random effect using a simple 
variance components covariance structure with a random intercept (to adjust for clustering of 
procedures within sites). To avoid overfitting, predictors with p>0.2 will be dropped from the 
model through a stepwise, backwards-elimination method. If issues of separation are detected in 
the mixed effects model (e.g. encounters involving low frequency predictors), we will 
incorporate a Bayesian method with a weak informative prior to estimate fixed-effect 
parameters.44,45 Tolerance <0.1 will be used to rule out multicollinearity. Standardized residual 
errors will be examined to identify potential outliers. Area under curve, Akaike information 
criterion, and conditional R-squared will be used to assess model fit. Analyses will be conducted 
using SPSS version 30 (IBM Corp., Armonk, NY, USA). A type I error rate of 0.05 will be used 
to reject the null hypothesis of no association. All p-values will be two-tailed. To assess the 
credibility of potential effect modifiers, we will use the Instrument for assessing the Credibility 
of Effect Modification Analyses.46 
 
SAMPLE SIZE CONSIDERATIONS 
Based on 10 outcome events per degree of freedom,47 a sample size of 1500 (300 outcome 
events) would permit 30 degrees of freedom in the multivariable model. Considering 
maladaptive behavior as the primary outcome (>3 change score on the PHBQ-AS on Day 3) with 
15% prevalence,10 a conservative estimated OR=1.5, 80% power, 5% two-sided alpha, 10 fixed 
effects: age, sex (2 levels), sedative (5-6 levels), pre-sedation child anxiety (mYPAS, 2 levels), 
emergence agitation (2 levels), temperament (ICTS/ILCTI), adequacy of sedation (2 levels), pain 
at day 3, caregiver anxiety (PCS-P, 2 levels), and family dynamics (PROMIS), with 1 random 

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effect of site (5 anticipated sites in total), we calculate a needed sample size of N=1,650. 
Accounting for 30% attrition, the target sample size is N=2,145. 
 
SEX & GENDER-BASED ANALYSIS 
Female sex and feminine gender are associated with greater pain sensitivity48 and pain can be an 
effect modifier for PHBQ-AS scores. For the PHBQ-AS score, we will present a stratified 
analysis for sex, gender (masculine vs. feminine vs. non-binary), and gender-expression (trans- 
vs. cis-gendered) and adjust for these covariates in separate multivariable models to overcome 
collinearity. We will report sex and gender-based analyses using the Sex and Gender Equity in 
Research Guidelines.49 
PATIENT ENGAGEMENT 
LHSC’ Family Advisory Council (FAC) consists of caregivers of children and persons with lived 
experience. The FAC was engaged to inform patient facing materials (study brochure, consent, 
and assent), outcome measures, and knowledge mobilization (KM) plan. Engagment involved 
reviewing the study materials, protocol, and three in-person (virtual) question and answer 
sessions. 
PILOT WORK 
Two of our sedation trials used the PHBQ to measure delayed maladaptive behaviors on day 3 
post-sedation. The original scale consisted of 27 items. The results suggest that a completed day 
3 post-sedation PHBQ-AS using the Twilio and REDCap platforms is feasible. 
 
Trial 
Eligibility 
Day 3 PHBQ 
Completion (%) 
PHBQ-related protocol 
compliance1 (%) 
Ketamine plus 
dexmededetomidine for 
procedural sedation 
(KETODEX) - 
completed 
4-17 years 
(orthopedic 
reduction) 
147/152 (97) 
151/152 (99.3) 
Anxiolysis for 
laceration repair in 
children (ALICE) 
N=115/315 
2-12 years 
(laceration 
repair) 
108/115 (94) 
113/115 (98.3) 
1Compliance defined as completion of the PHBQ on day 3 
 
RATIONALE FOR RECRUITMENT TARGETS  
Our estimated consent rate is based on our KETODEX and ALICE trials (72%) and a recent 
feasibility assessment. The lead site performs an average of 3.4 procedural sedations per day 
during research assistant hours and estimate that 80% of patients would be eligible. This forms a 
conservative basis upon which to estimate enrollment as the lead site has the lowest ED census 

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(39,000 visits). Western University’s dental clinic performs 5.2 procedural sedations per day. 
This totals (3.4 x 5 sites + 5.2 dental clinic) x 0.8 eligibiliy x 0.7 consent rate = 12.4 potential 
participants per day. Research assistants will enroll patients for 6 hours per day, 5 days per week, 
for 48 weeks a year, making enrollment of 2,145 participants within 2 years entirely feasible. 
TEAM 
Dr. Noha Gomaa (early career researcher) is an Assistant Professor of Dentistry, Western 
University. She is a co-principal investigator and site lead for the Western University’s dental 
clinics. 
 
Dr. Amy Drendel is a Professor, Medical College of Wisconsin. She is an international expert on 
acute paediatric pain and was a senior author on one of only two studies on delayed maladaptive 
behaviors in children. 
 
Dr. Dan Tsze is a Professor, Columbia University. He is an international expert in paediatric 
procedural sedation and anxiety and pain scales. 
 
Kyna Patterson is a child life specialist at LHSC. She will inform the non-pharmacologic aspects 
of the medical directive to reduce pre-sedation anxiety and help provide education for healthcare 
staff. 
 
Emma Parent is a nurse educator at LHSC. She will help develop the medical directive and 
facilitate healthcare provider education as part of the QI project. 
 
Heather Maddocks is a knowledge visualization specialist in the Department of Paediatrics at 
Western. She will help create KT materials. 
 
Michael Miller is a biostatistician, Western University. He developed the statistical analysis plan 
and will conduct the final analysis. 
 
Dr. Maala Bhatt is an Associate Professor, University of Ottawa. She is the potential CHEO site 
lead and expert in sedation-related adverse events.50,51 
 
Dr. Samina Ali is a Professor at the University of Alberta. She is the potential Stollery Children’s 
site lead. 
 
Dr. Vikram Sabhaney (early career researcher) is an Assistant Professor, University of British 
Columbia. He is the potential BC Children’s site lead. 
 
Dr. Evelyne Doyon-Trottier is an Associate Professor at the Universite de Montreal. She is the 
potential the CHU Ste Justine site lead. 
 
Dr. Gopakumar Nair (early career researcher) is a paediatric anesthesiologist at LHSC. He has 
expertise in post-anesthetic maladaptive behaviors. He will inform the anxiety management 
aspects of the medical directive. 

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Dr. Rana Swed Tobia (early career investigator) is an Assistant Professor at University of British 
Columbia. She has experience in Healthcare Quality. She will guide the QI project. 
TIMELINE 
 
AMOSO Funding Year 
Year I 
Year II 
Calendar Year 
2026 
2027 
Study Activities 
Q1 
Q2 
Q3 
Q4 
Q1 
Q2 
Q3 
Q4 
Submission of protocol for publication 
 
 
 
 
 
 
 
 
Lead site research personnel training 
 
 
 
 
 
 
 
 
Lead site enrollment 
 
 
 
 
 
 
 
 
Subsite agreements, approvals, & training 
 
 
 
 
 
 
 
 
Subsite enrollment 
 
 
 
 
 
 
 
 
Data verification and analysis 
 
 
 
 
 
 
 
 
Manuscript & abstract preparation  
 
 
 
 
 
 
 
 
Knowledge Translation 
Submission of main manuscript 
 
 
 
 
 
 
 
 
Social media posts & podcasts 
 
 
 
 
 
 
 
 
Media releases (Western Media Relations) 
 
 
 
 
 
 
 
 
Presentation at academic conferences 
 
 
 
 
 
 
 
 
Educational materials for healthcare providers 
and families 
 
 
 
 
 
 
 
 
KT materials on Western Open  
 
 
 
 
 
 
 
 
Children’s Healthcare Canada webinar 
 
 
 
 
 
 
 
 
Education for healthcare providers 
 
 
 
 
 
 
 
 
Solutions for Kids in Pain website, social media, 
and partner blogs 
 
 
 
 
 
 
 
 
Presentation of final results at PERC meeting 
 
 
 
 
 
 
 
 
Update to CPS Practice Guideline 
 
 
 
 
 
 
 
 
MSc student-led sub-studies 
 
 
 
 
 
 
 
 
Quality Improvement  
PERC site agreements and approvals 
 
 
 
 
 
 
 
 
Focus groups to identify facilitators and barriers 
to uptake  
 
 
 
 
 
 
 
 
Root cause analysis 
 
 
 
 
 
 
 
 
Development of medical directive 
 
 
 
 
 
 
 
 
Intervention mapping exercise 
 
 
 
 
 
 
 
 
Data collection 
 
 
 
 
 
 
 
 
Data verification and analysis; manuscript 
preparation; conference presentations 
 
 
 
 
 
 
 
 
 
 

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REFERENCES 
 
1. 
Pearce JI, Brousseau DC, Yan K, Hainsworth KR, HoYmann  RG, Drendel AL. 
Behavioral changes in children after emergency department procedural sedation. 
Acad Emerg Med 2018;25(3):267-74. 
2. 
Brodzinski H, Iyer S. Behavior changes after minor emergency procedures. Pediatr 
Emer Care;29(10):1098-101. 
3. 
Stargatt R, Davidson AJ, Huang GH, et al. A cohort study of the incidence and risk 
factors for negative behavior changes in children after general anesthesia. Paediatr 
Anaesth 2006;16(8):846-59. 
4. 
Keaney A, Diviney D, Harte S, Lyons B. Postoperative behavioral changes following 
anesthesia with sevoﬂurane. Paediatr Anaesth 2004;14(10):866-870. 
5. 
Pearce JI, Brousseau DC, Yan K, Hainsworth KR, HoYman RG, Drendel AL. 
Behavioral changes in children after emergency department procedural sedation. 
Acad Emerg Med 2018;25(3):267-74. 
6. 
Cortellazzo Wiel L, Monasta L, Pascolo P, et al. Recovery characteristics and 
parental satisfaction in pediatric procedural sedation. Paediatr Anaesth 
2022;32(3):452-461. DOI: 10.1111/pan.14390. 
7. 
Keaney A, Diviney D, Harte S, Lyons B. Postoperative behavioral changes following 
anesthesia with sevoﬂurane. Paediatr Anaesth 2004;14(10):866-70. DOI: 
10.1111/j.1460-9592.2004.01310.x. 
8. 
Stargatt R, Davidson AJ, Huang GH, et al. A cohort study of the incidence and risk 
factors for negative behavior changes in children after general anesthesia. Paediatr 
Anaesth 2006;16(8):846-59. DOI: 10.1111/j.1460-9592.2006.01869.x. 
9. 
Kain ZN WS, Mayes LC, Caramico LA, Hofstadter MB Distress during the induction of 
anesthesia and postoperative behavioral outcomes. Anesth Analg 1999;88:1042-7. 
10. 
Brodzinski H, Iyer S. Behavior changes after minor emergency procedures. Pediatr 
Emerg Care 2013;29(10):1098-101. DOI: 10.1097/PEC.0b013e3182a5Y07. 
11. 
Roher K, Becke-Jakob K, Eich C. Safety and quality in paediatric procedural 
sedation: what really matters? Curr Opin Anaesthesiol 2023;36(3):340-346. DOI: 
10.1097/ACO.0000000000001255. 
12. 
Thorburn M, Dishman D, Glick A, Pazmino K, Chiquet B. Identifying Post-Discharge 
Events in Pediatric Sedation Patients. Pediatr Dent 2025;47(2):108-113. 
(https://www.ncbi.nlm.nih.gov/pubmed/40296262). 
13. 
Erumbala G, Anzar S, Deiratany S, Blackie B, Powell C, Al Ansari K. Procedural 
sedation programme minimising adverse events: a 3-year experience from a tertiary 
paediatric emergency department. Arch Dis Child 2024;109(2):88-92. DOI: 
10.1136/archdischild-2023-326021. 
14. 
Grunwell JR, Travers C, Stormorken AG, et al. Pediatric Procedural Sedation Using 
the Combination of Ketamine and Propofol Outside of the Emergency Department: 
A Report From the Pediatric Sedation Research Consortium. Pediatr Crit Care Med 
2017;18(8):e356-e363. DOI: 10.1097/PCC.0000000000001246. 

Version: V.3.0 (02FEB2026) 
16 
15. 
Kamat PP, McCracken CE, Simon HK, et al. Trends in Outpatient Procedural 
Sedation: 2007-2018. Pediatrics 2020;145(5). DOI: 10.1542/peds.2019-3559. 
16. 
Green SM, Roback MG, Kennedy RM, Krauss B. Clinical practice guideline for 
emergency department ketamine dissociative sedation: 2011 update. Annals of 
emergency medicine 2011;57(5):449-61. DOI: 
10.1016/j.annemergmed.2010.11.030. 
17. 
Beach ML, Cohen DM, Gallagher SM, Cravero JP. Major Adverse Events and 
Relationship to Nil per Os Status in Pediatric Sedation/Anesthesia Outside the 
Operating Room: A Report of the Pediatric Sedation Research Consortium. 
Anesthesiology 2016;124(1):80-8. DOI: 10.1097/ALN.0000000000000933. 
18. 
Green SM, Emergency Dept Ketamine M-A, Emergency Department Ketamine Meta-
Analysis Study G. Predictors of airway and respiratory adverse events with ketamine 
sedation in the emergency department: an individual-patient data meta-analysis of 
8,282 children. Ann Emerg Med 2009;54(2):158-168.e4. DOI: 
10.1016/j.annemergmed.2008.12.011. 
19. 
Green SM, Emergency Dept Ketamine M-A, Emergency Department Ketamine Meta-
Analysis Study G. Predictors of emesis and recovery agitation with emergency 
department ketamine sedation: an individual-patient data meta-analysis of 8,282 
children. Ann Emerg Med 2009;54(2):171-180.e4. DOI: 
10.1016/j.annemergmed.2009.04.004. 
20. 
Bhatt M JD, Barrowman N, Chan J, Farion KJ, Ali S, Beno S, Dixon A, McTimoney CM,  
Dubrovsky AS, Sourial N, Roback MG; for the Sedation Safety Study Group of 
Pediatric Emergency Research Canada (PERC). Predictors of Adverse Events in 
Pediatric Emergency Department Sedation: A multi-center safety surveillance study 
from the PERC network. Abstract presented at the American Academiy of Pediatrics 
Annual Conference 2015 2015. 
21. 
Fortier MA, Del Rosario AM, Rosenbaum A, Kain ZN. Beyond pain: predictors of 
postoperative maladaptive behavior change in children. Paediatr Anaesth 
2010;20(5):445-53. DOI: 10.1111/j.1460-9592.2010.03281.x. 
22. 
Doyon-Trottier E, Doré-Bergeron MJ, Chauvin-KimoY L, Baerg K, Ali S. Managing pain 
and distress in children undergoing brief diagnostic and therapeutic procedures. 
Paediatr Child Health 2019;24(8):509-21. 
23. 
Trottier ED AS, Le May S, Gravel J. . Treating and reducing anxiety and pain in the 
pediatric emergency department: The TRAPPED survey. Paediatr Child Health 
2015;20(5):239-44. 
24. 
Poonai N, Brzozowski V, Stang AS, et al. Pain management practices surrounding 
lumbar punctures in children: A survey of Canadian emergency physicians. CJEM 
2019;21(2):199-203. DOI: 10.1017/cem.2018.382. 
25. 
Turner AD, Sullivan T, Drury K, et al. Cognitive Dysfunction After Analgesia and 
Sedation: Out of the Operating Room and Into the Pediatric Intensive Care Unit. 
Front Behav Neurosci 2021;15:713668. DOI: 10.3389/fnbeh.2021.713668. 
26. 
Cui Y, Wu Q, Tang M, et al. Incidence and risk factors of prolonged recovery during 
procedural sedation in pediatrics. Front Med (Lausanne) 2024;11:1466205. DOI: 
10.3389/fmed.2024.1466205. 

Version: V.3.0 (02FEB2026) 
17 
27. 
Sarvas E, Webb J, Landrigan-Ossar M, et al. Oral Health Care for Children and Youth 
With Developmental Disabilities: Clinical Report. Pediatrics 2024;154(2). DOI: 
10.1542/peds.2024-067603. 
28. 
Pediatric Emergency Research Canada (PERC). (https://perc-canada.ca/). 
29. 
Schuh S, Sweeney J, Rumantir M, et al. EYect of nebulized magnesium vs placebo 
added to albuterol on hospitalization among children with refractory acute asthma 
treated in the emergency department: a randomized clinical trial. JAMA 
2020;324(20):2038-47. 
30. 
Freedman SB, Williamson-Urquhart S, Farion KJ, et al. Multicenter Trial of a 
Combination Probiotic for Children with Gastroenteritis. N Engl J Med 
2018;379(21):2015-2026. DOI: 10.1056/NEJMoa1802597. 
31. 
Jenkins BN, Kain ZN, Kaplan SH, et al. Revisiting a measure of child postoperative 
recovery: development of the Post Hospitalization Behavior Questionnaire for 
Ambulatory Surgery. Paediatr Anaesth 2015;25(7):738-45. DOI: 10.1111/pan.12678 
32. 
Vernon DT, Schulman JL, Foley JM. Changes in children's behavior after 
hospitalization. Some dimensions of response and their correlates. Am J Dis Child 
1966;111(6):581-93. DOI: 10.1001/archpedi.1966.02090090053003. 
33. 
Lee-Archer PF, Gibbons K, Reade M, von Ungern-Sternberg BS, Long D. Comparison 
of two measures of behavior change in children after day surgery. Paediatr Anaesth 
2022;32(1):62-66. DOI: 10.1111/pan.14321 
34. 
Karling M, Stenlund H, Hägglöf B. Behavioural changes after anaesthesia: validity 
and liability of the Post Hospitalization Behavior Questionnaire in a Swedish 
paediatric population. Acta Paediatr Scand 2006;95(3):340-6. 
35. 
Kain ZN ML, O’Connor TZ, Cicchetti DV. Preoperative anxiety in children: predictors 
and outcomes. Arch Pediatr Adolesc Med 1996;150:1238-1245. 
36. 
LL Johnson, SJ Bradley, AS Birkenfeld-Adams, et al. A parent-report gender identity 
questionnaire for children. Arch Sex Behav 2004;33:105-16. 
37. 
Zentner M. Identifying child temperament risk factors from 2 to 8 years of age: 
validation of a brief temperament screening tool in the US, Europe, and China. Eur 
Child Adolesc Psychiatry 2020;29(5):665-678. DOI: 10.1007/s00787-019-01379-5. 
38. 
Biedermann V, Zentner M. Assessing Temperament Risk Factors in Late Childhood 
and Early Adolescence: Development and Validation of the Integrative Late 
Childhood Temperament Inventory. Child Psychiatry Hum Dev 2024. DOI: 
10.1007/s10578-024-01675-5. 
39. 
Kain ZN, Mayes LC, Cicchetti DV, Bagnall AL, Finley JD, Hofstadter MB. The Yale 
Preoperative Anxiety Scale: how does it compare with a "gold standard"? Anesth 
Analg 1997;85(4):783-8. DOI: 10.1097/00000539-199710000-00012. 
40. 
Kuhlmann AYR, Lahdo N, Staals LM, van Dijk M. What are the validity and reliability 
of the modiﬁed Yale Preoperative Anxiety Scale-Short Form in children less than 2 
years old? Paediatr Anaesth 2019;29(2):137-143. DOI: 10.1111/pan.13536 
41. 
Bulloch B, Tenenbein M. Assessment of clinically signiﬁcant changes in acute pain 
in children. Academic Emergency Medicine 2002;9(3):199-202. 
42. 
von Baeyer CL. Children's self-reports of pain intensity: Scale selection, limitations 
and interpretation. Pain Research and Management 2006;11(3):157-162. 

Version: V.3.0 (02FEB2026) 
18 
43. 
von Baeyer CL, Chambers CT, Eakins DM. Development of a 10-item Short Form of 
the Parents' Operative Pain Measure: The PPPM-SF. J Pain 2011 Mar;12(3):401-406. 
DOI: 10.1016/j.pain.2010.10.002 
44. 
Gelman A, Jakulin A, Pittau MG, Su YS. A weakly informative default prior 
distribution for logistic and other regression models. Ann Applied Stat 2008;2:1360-
83. 
45. 
José Cortiñas A, Aerts M. A solution to separation for clustered binary data. Stat 
Model 2012;12(1):3-27. 
46. 
Schandelmaier S, Briel M, Varadhan R, et al. Development of the Instrument to 
assess the Credibility of EYect Modiﬁcation Analyses (ICEMAN) in randomized 
controlled trials and meta-analyses. CMAJ 2020;192(32):E901-E906. DOI: 
10.1503/cmaj.200077. 
47. 
Altman D, Machin D, Bryant T, Gardner M. Statistics with conﬁdence: conﬁdence 
intervals and statistical guidelines: John Wiley & Sons, 2013. 
48. 
Bartley EJ, Fillingim RB. Sex diYerences in pain: A brief review of clinical and 
experimental ﬁndings. Br J Anaesth 2013;111(1):52-8. 
49. 
Heidari S, Babor TF, De Castro P, Tort S, Curno M. Sex and Gender Equity in 
Research: rationale for the SAGER guidelines and recommended use. Res Integr 
Peer Rev 2016;1:2. 
50. 
Bhatt M, Johnson DW, Chan J, et al., On behalf of the Sedation Safety Study Group of 
Pediatric Emergency Research Canada (PERC). Risk factors for adverse events in 
emergency department procedural sedation for children. JAMA Pediatr 
2017;171(10):957-964. DOI: 10.1001/jamapediatrics.2017.2135. 
51. 
Bhatt M, Kennedy RM, Osmond MH, et al., Consensus Panel on Sedation Research 
of Pediatric Emergency Research Canada and the Pediatric Emergency Care Applied 
Research Network. Consensus-based recommendations for standardizing 
terminology and reporting adverse events for emergency department procedural 
sedation and analgesia in children. Ann Emerg Med 2009;53(4):426-435.e4. DOI: 
10.1016/j.annemergmed.2008.09.030.