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548  |  wileyonlinelibrary.com/journal/pan Pediatric Anesthesia. 2022;32:548–555.© 2022 John Wiley & Sons Ltd.
Received: 20 May 2021  | Revised: 23 December 2021  | Accepted: 7 January 2022
DOI: 10.1111/pan.14395 
R E S E A R C H R E P O R T
The relationship between nitrous oxide sedation and 
psychosocial factors in the pediatric outpatient setting
Mohammad Moharrami1  | Samina Ali2  | Bruce D. Dick3  | Fardad Moeinvaziri1 | 
Maryam Amin1
1Faculty of Medicine & Dentistry, School 
of Dentistry, University of Alberta, 
Edmonton, Alberta, Canada
2Department of Pediatrics, Faculty 
of Medicine & Dentistry, Women and 
Children's Health Research Institute, 
University of Alberta, Edmonton, Alberta, 
Canada
3Department of Anesthesiology and 
Pain Medicine, Faculty of Medicine 
& Dentistry, University of Alberta, 
Edmonton, Alberta, Canada
Correspondence
Maryam Amin, Alberta Dental Association 
& College Chair in Clinical Dentistry 
Research, University of Alberta, 5513– 476 
Edmonton Clinic Health Academy, 11 405– 
87 Avenue NW, 5th Floor, Edmonton AB 
T6G 1C9, Canada.
Email: maryam.amin@ualberta.ca
Section Editor: Joseph Cravero
Abstract
Background: Moderate sedation using nitrous oxide (N2O) has become common in 
pediatric dentistry. However, less is known regarding the role of patients' characteris-
tics and psychosocial factors in their cooperative behavior during dental procedures 
with N2O.
Aims: This study aimed to examine pediatric dental patients' behaviors while under-
going N2O sedation and to measure the associations between child's cooperative be-
havior and demographic, physiological responses, and psychosocial factors.
Methods: In this within- subject observational study, participants received 40% N2O/
O2, by nasal hood, for non- surgical dental procedures. The main outcome measure 
was the extent of cooperative behaviors, as assessed by the Frankl scale at five time-
points, namely T1: pre- administration of N2O, T2: post- administration of N2O, T3: 
dental injection, T4: dental treatment, and T5: post- procedure administration of 100% 
O2. Predictors included age, sex, psychosocial factors reported using the Parenting 
Style and Dimension Questionnaire and Spence Children Anxiety Scale, as well as 
pulse rate, respiratory rate, and oxygen saturation. The Wilcoxon signed- rank test and 
generalized estimation equation were used for data analyses.
Results: In 80 children with a mean age of 7.2 (2.2) years, administration of N2O was 
significantly associated with cooperative behaviors (odds ratio [OR]:2.62, confidence 
interval [CI]: 1.46– 4.70, p = .001) when adjusted for other predictors. There was no 
interaction between any of the predictors and N2O sedation on behaviors. Except for 
the authoritative parenting style (OR: 1.96, CI: 1.16– 3.31, p = .012), which predicted 
more cooperative behaviors, other predictors were not associated with behavioral 
outcomes.
Conclusion: In children sedated with N2O, behavior was independent of the child's 
demographic and psychosocial factors. While sedated, demographics, vital signs, and 
anxiety did not contribute to behavior management. However, screening for parent-
ing style may help predict the child's behavioral response.
K E Y W O R D S
anxiety, behavior, nitrous oxide, parenting style, vital sign
https://orcid.org/0000-0002-4364-7969
https://orcid.org/0000-0002-0595-364X
https://orcid.org/0000-0003-0404-4927
mailto:
https://orcid.org/0000-0003-2249-5465
mailto:maryam.amin@ualberta.ca
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    |  549MOHARRAMI et Al.
1  |  INTRODUC TION
Moderate sedation using nitrous oxide (N2O) is common in outpa-
tient dentistry.1 N2O is effective in providing analgesia and anxi-
olysis but does not induce loss of consciousness.2 Given its safety 
profile and rapid onset and reversibility upon discontinuation, 
N2O is a favorable sedation option in many settings, including 
dentistry.3 The American Academy of Pediatrics and the American 
Academy of Pediatric Dentistry (AAPD) recognized N2O as a safe 
and useful method for reducing anxiety and pain.4,5 Although N2O 
may result in reducing pain and distress,6,7 the behavior manage-
ment of pediatric patients during painful procedures can still be 
challenging.
It has been shown that demographics, anxiety, and parenting 
style may predict cooperative behaviors in children. For example, 
older child age is associated with more cooperative behaviors in 
outpatient clinics.8 Authoritative parenting style has been shown 
to associate positively with cooperative behaviors but inversely 
with children's anxiety.9 Moreover, the anxiety and distress of chil-
dren, regardless of their age, can have an impact on their behaviors 
during dental treatments.10 It has been also reported that children 
are often less cooperative when treatment duration increases.11 
Currently, the association between these factors with behaviors is 
not clear, in the context of N2O sedation. Moreover, the possible 
interactions between the effect of N2O and the aforementioned 
predictors on children's cooperation have not been fully studied; 
such interactions may moderate the effect of N2O on children's 
behaviors.
Most previous studies in outpatient clinical settings evaluated 
the effect of N2O in combination with other sedative agents, which 
may lead to deeper sedation. The additive effects of anesthetic 
drugs might manifest in different behavioral responses. Few studies 
have evaluated the effect of N2O on behaviors without combining 
it with other sedative agents,12– 16 but even some of these studies 
either targeted adults or did not follow children's behaviors through-
out the entire dental process.12– 14 A recent Cochrane review found 
that from 50 studies on sedative agents that focused on behavior 
management of children, 81% had a high risk of bias. There was con-
siderable heterogeneity in terms of method, dose, mode, and time 
of administration. Consequently, a meta- analysis could not be con-
ducted for N2O.17
The primary objective of this study was to determine pediatric 
dental patients' behaviors before and after administrating N2O as 
well as throughout the dental treatment to recovery with 100% ox-
ygen. The secondary objectives were to explore the relationship of 
N2O sedation- related behaviors with patients' characteristics and 
psychosocial factors. The null hypotheses were (1) there is no dif-
ference between pediatric dental patients' behaviors before and 
after administrating N2O as well as between different timepoints 
of dental treatment and (2) there is no relationship between N2O 
sedation- related behaviors with patients' characteristics and psy-
chosocial factors.
2  |  METHODS
2.1  |  Ethics statement
This study was approved by the Health Research Ethics Board- 
Health Panel of the University of Alberta (ID: Pro00093184); writ-
ten informed consent and assent for children aged 7 or older were 
obtained from all participants.
2.2  |  Study design and participants
A convenience sample of participants for this within- subject obser-
vational study was recruited from a private pediatric dental practice 
(Edmonton, Alberta, Canada) from October 2019 to February 2020. 
Healthy (ASA- 1) English- speaking children aged 2– 12 years who re-
ceived N2O/O2 as part of their standard treatment for non- invasive 
dental treatments such as pulpotomy, stainless- steel crowns, 
and amalgam and composite fillings were included. Dental visits 
were scheduled during the morning, and fasting was not required. 
Children were excluded if they had previously been exposed to N2O 
or had dental injections within the last 30 days or needed invasive 
surgical dental procedures such as dental extractions. Children who 
waited in the waiting room for more than 1 h, had a prior diagnosis of 
post- traumatic stress disorder (PTSD) related to dental settings, had 
severe or chronic orofacial pain, or had chronic systemicdiseases 
were also excluded.
2.3  |  Surveys and questionnaires
2.3.1  |  Parenting styles and dimensions 
questionnaire
The 32- item short English version of the Parenting Styles and 
Dimension Questionnaire (PSDQ- 32) 18, which classifies parenting 
What is already known about this topic
• N2O is a favored sedative agent for minor procedures 
and is recognized as a safe and useful method for reduc-
ing pain and anxiety.
What new information this study adds
• The effect of N2O sedation on child behavior is not 
moderated by patients' characteristics or psychosocial 
factors. Clinicians may administer N2O for behavior 
management in outpatient clinical settings regardless of 
children's age, sex, vital signs, anxiety, and their caregiv-
ers' parenting style. Screening parenting style may in-
form predicting of behaviors while children are sedated.
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550  |    MOHARRAMI et Al.
style into authoritarian (e.g., scold when child's behavior does not 
meet our expectation), authoritative (e.g., give child reasons why 
rules should be obeyed), and permissive (e.g., to spoil child) was 
used to assess parental factors. The Cronbach's alpha value for the 
authoritative, authoritarian, and permissive parenting scales has 
shown to be 0.86, 0.82, and 0.64, respectively.19
2.3.2  |  Spence children's anxiety scale
This widely used validated scale provides two related parent- report 
questionnaires categorized based on the age of participants.20 The 
Spence Children's Anxiety Scale, Parent report (SCAS- P), used for 
school- age children aged 6– 12 years, consists of 38 items with 
scores of 0 (never) to 3 (always) and has a maximum score of 114. 
The Preschool Anxiety Scale (PAS), used for preschool- age children 
aged 2– 5 years, consists of 28 items with scores of 0 (not true at 
all) to 4 (very often true) and has a maximum score of 112. In both 
scales, higher scores indicate more severe anxiety symptoms. The 
Cronbach's alpha value for SCAS has been reported to be 0.92.21
2.3.3  |  Demographics and treatment duration
Demographic information collected included age and sex as re-
ported by caregivers.
2.4  |  Procedure
After consent and assent were obtained, caregivers completed the 
questionnaires in the waiting room. Clinical data collection took 
place at 5 different time points (Figure 1): (T1) pre- administration of 
N2O, (T2): post- administration of N2O, (T3) during dental injection 
(T4) during dental treatment, and (T5) post- procedure administration 
of 100% O2.
At T1, audio- visual distraction was provided by dental assistants 
using a TV above the dental unit and headphones. At T2, the dentist 
applied a nasal hood (MRX, Porter Instrument C0, USA) delivering 
40% nitrous oxide and 60% oxygen at the flow of 5 liters/minute. 
This dose of nitrous oxide was continued for the remainder of the 
study at which point children received 100% oxygen. At T3, ben-
zocaine 20% (Master Dent Topical Anesthetic Gel) was applied to 
dried mucosa for 1 min. Then, local anesthesia, 2% lidocaine and 
1:100 000 epinephrine (Cook- Waite Lidocaine, Septodont), with 
a maximum dose of 4.4 mg/kilogram,22 was administrated using a 
controlled local anesthetic delivery system (The Wand, Milestone 
Scientific). At T4, the planned dental treatments were delivered. In 
T5, after finishing the dental treatment, N2O/O2 was discontinued 
and 100% O2 was provided.
2.5  |  Clinical measurements and instruments
Children's behaviors were scored using the Frankl scale at each time-
point (i.e., T1, T2, T3, T4, and T5) separately. The Frankl scale classi-
fies behavior based on cooperation during dental treatment into four 
ordinal levels of definitely positive (F- score: 4), positive (F- score: 3), 
negative (F- score: 2), and definitely negative (F- score: 1).23
Pulse rate and oxygen saturation (SpO2) were measured every 4 s 
using an FDA- listed digital pulse oximeter (Lookee Pulse Oximeter) 
attached to the thumb or index finger of the children. The mean 
values for each of the five points were calculated by adding all the 
recorded values and dividing them by the number of records during 
each time point. The mean value for the whole procedure, beginning 
of T1 to end of T5, was reported by the pulse oximeter automatically. 
The respiratory rate (RR) was calculated by counting excursions of 
the reservoir bag as the system is patient- driven.
2.6  |  Sample size
The sample size was calculated using GPower v3.1.9 software.24 
Considering power (1−β) of 0.80 and alpha error of 0.05, the mini-
mum number of 70 samples was needed to reach a small effect 
size of dz = 0.35 for behaviors (ordinal variable) to be used in the 
Wilcoxon signed- rank test. We chose to over- recruit to 80 partici-
pants to allow for attrition in data collection due to participant with-
drawal or other unforeseen circumstances.
2.7  |  Data analysis
The Statistical Package for the Social Sciences (SPSS, IBM Corp. 
Version 25.0) was used to perform the analyses. The descriptive 
analysis was reported for the continuous data by mean and standard 
deviation and for the discrete data by frequency and percentage. The 
outcome variable of interest was behavior (ordinal). Also, there were 
eight predictors in this study namely age (scale), and sex (categorical), 
anxiety (scale), parenting style (scale), timepoints of the study, that is, 
F I G U R E 1  Description of the five time points of study (T1– T5)[Colour figure can be viewed at wileyonlinelibrary.com]
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    |  551MOHARRAMI et Al.
T1, T2, T3, T4, and T5 (categorical), and vital signs including pulse rate 
(scale), respiratory rate (scale), and SpO2. (scale). Since there was high 
collinearity between the mother's and father's parenting style, only the 
mother's parenting style was entered into the models. Further, SCAS 
and PAS scores were combined into a single variable using standardi-
zation by converting them into a Z score.
The Friedman test was used to compare the results between the 
five timepoints (T1, T2, T3, T4, and T5) with the Wilcoxon singed- rank 
test for pairwise comparisons. Using the ordinal model in generalized 
estimation equation (GEE), which is an extension of generalized linear 
models (GLM) for longitudinal and repeat- measures studies, the rela-
tionship between behaviors and predictors of the study was assessed. 
The interactions between timepoints of the study (T1, T2, T3, T4, and 
T5) and other predictors on the behaviors were also entered into the 
model. p- values of62 
(77.5%) had an F- Score of 4, and the least level of cooperation was 
seen at T3 in which only 44 (55.0%) children showed an F- Score 
of 4. The detailed analyses of the outcome measures are shown in 
Table 2.
3.2  |  Inferential
Behavioral data pertaining to each time point are illustrated in 
Figure 2. The Friedman test showed that there was a statisti-
cally significant difference between time points regarding the 
level of cooperative behaviors of children χ2(2) = 20.31, p0.07 1.40 1.08 0.94 1.25
Respiratory rate 0.03 0.02 1.00 0.93 1.08
Anxiety 0.17 0.31 0.90 0.63 1.28
Abbreviation: SpO2, oxygen saturation.
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AUTHOR BIOG R APHIE S
Mohammad Moharrami is a dentist (DDS) who has been active 
clinical research since graduation in 2014. Dr. Moharrami ob-
tained his MSc in Dentistry (Research) from the University of 
Alberta in 2020. Dr. Moharrami has 22 peer- reviewed publica-
tions in the dental and medical fields.
Samina Ali is a pediatric emergency physician, Professor of 
Pediatrics & Emergency Medicine and the Research Director 
for Pediatric Emergency Medicine at the University of Alberta 
(Edmonton, Canada). She is a clinician- scientist with a nationally- 
funded research program focused on better treatment of chil-
dren's acute and procedural pain, as well as responsible use of 
opioids in the acute care setting.
Bruce Dick is a Professor and Clinical Psychologist in the 
Department of Anesthesiology and Pain Medicine at the 
University of Alberta. His research interests focus primarily on 
pain's effects on humans across the lifespan. He is also Chief of 
Psychology at the Multidisciplinary Pain Centre at the University 
of Alberta Hospital.
Fardad Moeinvaziri is a pediatric dentist in Edmonton Alberta 
and the surrounding areas ( FRCDC, DMD). He has been prac-
ticing pediatric dentistry since 2014 after finishing his pediatric 
residency program from Stony Brook University Hospital.
Maryam Amin is a Professor and Associate Chair of Research, 
and Director of Dentistry Graduate Program at the University of 
Alberta. She is also the Alberta Dental Association and College 
clinical dentistry research chair. Her research interests are clin-
ical, social and behavioral aspects of oral health with a focus on 
understanding the psychosocial, behavioral, community, and so-
cietal influences on the oral health of children particularly from 
disadvantaged marginalized populations.
How to cite this article: Moharrami M, Ali S, Dick BD, 
Moeinvaziri F & Amin M, . The relationship between nitrous 
oxide sedation and psychosocial factors in the pediatric 
outpatient setting. Pediatr Anaesth. 2022;32:548–555. 
doi: 10.1111/pan.14395
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