Oral Sucrose for Pain Management During Flexible Nasolaryngoscopy
Phase: NA
Conditions: Infant Conditions
Sponsor: The Hospital for Sick Children

 
Be Sweet during Flexible Nasolaryngoscopy 
 
 
Version Date:September 13, 2024  
 
 
 
 
 
 
           1 
Oral Sucrose for Pain Management During Flexible Nasolaryngoscopy 
 
Principal Investigator:  
Nikolaus Wolter MD, MSc, FRCSC, FACS 
Staff Otolaryngologist, Department of Otolaryngology – Head and Neck Surgery, Hospital for Sick 
Children 
 
Associate Professor, Department of Otolaryngology – Head and Neck Surgery, University of Toronto 
555 University Avenue, Toronto, ON, M5G 1X8 
Phone: 416-813-2190 
FAX: 416-813-5036 
Email: nikolaus.wolter@sickkids.ca 
 
Co-Investigators:  
Mary-Elizabeth Vanderpost, Otolaryngology Nurse, Department of Otolaryngology – Head and 
Neck Surgery, Hospital for Sick Children, Toronto, ON 
 
Meghan Tepsich, Complex Airway Nurse Practitioner, Department of Otolaryngology – Head 
and Neck Surgery, Hospital for Sick Children, Toronto, ON 
 
Jennifer Siu, MD, MPH, FRCSC,  Staff Otolaryngologist, Department of Otolaryngology – Head 
and Neck Surgery, Hospital for Sick Children 
 
Evan Propst, MD, MSc, FRCSC, Staff Otolaryngologist, Department of Otolaryngology – Head 
and Neck Surgery, Hospital for Sick Children 
 
 
Study Site(s): Hospital for Sick Children 
Funded By: Gnat/Bastable-Potts Chair in Otolaryngology 
 
 
 

 
Be Sweet during Flexible Nasolaryngoscopy 
 
 
Version Date:September 13, 2024  
 
 
 
 
 
 
           2 
 
Statement of Compliance 
 
The Principal Investigator (PI) will assure that no deviation from, or changes to the protocol will take place without 
prior agreement from the sponsor and documented approval from the Research Ethics Board (REB) of Record, except 
where necessary to eliminate an immediate hazard(s) to the study participants. All personnel involved in the conduct 
of this study have completed the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans 
Training.  
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be submitted to the 
REB of Record for review and approval. Approval of both the protocol and the consent form(s) must be obtained 
before any participant is enrolled. Any amendment to the protocol or consent materials will require review and 
approval by the REB of Record before the changes are implemented to the study. All changes to the consent form 
will be REB approved; a determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form. 
 
This page should be signed by the Principal Investigator at each site. If this is a single center study conducted only 
at SickKids, delete the site address below. 
 
Principal Investigator: 
Name:  
 Nikolaus Wolter 
 
Signed:  
  
  Date:    06/08/2024 
 
<DD Month YYYY> 
 
 
Hospital for Sick Children Department of Otolaryngology – Head and Neck Surgery 
555 University Avenue, Toronto, ON, M5G 1X8 
Phone: 416-813-2190 
FAX: 416-813-5036 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Be Sweet during Flexible Nasolaryngoscopy 
 
 
Version Date:September 13, 2024  
 
 
 
 
 
 
           3 
Table of Contents 
1 PROTOCOL SUMMARY 
4 
1.1 SYNOPSIS 
4 
1.2 SCHEDULE OF ACTIVITIES (SOA) 
5 
1.3 KEY ROLES 
6 
2 INTRODUCTION, BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE 
6 
2.1 BACKGROUND INFORMATION AND RELEVANT LITERATURE 
6 
2.2 RATIONALE 
8 
2.3 POTENTIAL RISKS & BENEFITS 
8 
2.3.1 
Potential Risks 
8 
2.3.2 
Potential Benefits 
9 
3 OBJECTIVES AND PURPOSE 
10 
3.1 PRIMARY OBJECTIVE 
10 
3.2 SECONDARY OBJECTIVES 
10 
4 STUDY DESIGN AND ENDPOINTS 
11 
4.1 DESCRIPTION OF STUDY DESIGN 
11 
4.2 DURATION OF STUDY PARTICIPATION 
13 
4.3 TOTAL NUMBER OF PARTICIPANTS AND SITES 
13 
5 STUDY ENROLLMENT AND WITHDRAWAL 
13 
5.1 PARTICIPANT INCLUSION CRITERIA 
13 
5.2    PARTICIPANT EXCLUSION CRITERIA 
13 
5.3 STRATEGIES FOR RECRUITMENT AND RETENTION 
14 
5.4 PARTICIPANT WITHDRAWAL OR TERMINATION 
14 
5.4.1 
Reasons for Withdrawal or Termination 
14 
5.4.2 
Handling of Participant Withdrawals or Termination 
15 
6 STUDY ASSESSMENTS AND PROCEDURES 
15 
7 STUDY PROCEDURES / EVALUATIONS 
15 
8 STATISTICAL CONSIDERATIONS 
16 
8.1  STUDY HYPOTHESES 
16 
8.2  SAMPLE SIZE DETERMINATION 
16 
8.3  STATISTICAL METHODS 
17 
9 SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA / DOCUMENTS 
17 
10 STUDY OVERSIGHT 
17 
11 ETHICS / PROTECTION OF HUMAN PARTICIPANTS 
17 
11.1 ETHICAL STANDARD 
17 
11.2 INFORMED CONSENT PROCESS AND DOCUMENTATION 
17 
11.3 CONSENT / ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO PARTICIPANTS 
18 
12 DATA HANDLING AND RECORD KEEPING 
19 
12.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES 
19 
12.2 STUDY RECORDS RETENTION 
19 
13 PROTOCOL DEVIATIONS 
19 
14 PUBLICATION AND DATA SHARING POLICY 
19 
15 REFERENCES 
20 
16 APPENDIX A 
22 

 
Be Sweet during Flexible Nasolaryngoscopy 
 
 
Version Date:September 13, 2024  
 
 
 
 
 
 
           4 
1    PROTOCOL SUMMARY  
1.1 Synopsis  
 
Title 
Oral Sucrose for Pain Management during Flexible Nasolaryngoscopy 
Short Title 
Be Sweet to Babies during Flexible Nasolaryngoscopy 
Study Description 
This study aims to evaluate the impact of oral sucrose on pain or distress in 
outpatient infants undergoing flexible nasolaryngoscopy during a scheduled 
appointment at the SickKids Pediatric Otolaryngology Clinic.  
Objectives 
The primary objective of this study is to determine the impact of using oral 
sucrose solutions on clinical pain scores after FNL in infants under 12 months 
of age. The secondary objectives of this study are to evaluate the impact of 
oral sucrose on crying times, maximum heart rate, and skin conductance 
during FNL in infants under 12 months of age. 
Study Design  
This is double-blinded randomized controlled trial. The intervention in this 
study is the provision of 0.5 ml 0.24% oral sucrose solution, which is a 
standard procedure for acute painful procedures in infants and widely 
available, compared to a control group of 0.5 ml water. The practice of giving 
sucrose during FNL has not yet been established, with inconsistent use 
across sites due to a lack of data, which this study aims to provide. 
Approximately 30 participants will be randomized into each arm. 
Participant Population, 
Selection Criteria 
Inclusion criteria: 
● 
Patient  <12 months of age;  
● 
Scheduled for an appointment with Dr. Nikolaus Wolter, Dr. Evan 
Propst or Dr. Jennifer Siu, who are Staff Pediatric 
Otolaryngologists at the Hospital for Sick Children, or Meghan 
Tepsich, a complex airway Nurse Practitioner at SickKids; 
● 
Requiring flexible nasolaryngoscopy for diagnostic purposes; 
● 
Accompanied by caregivers who provided consent. 
Exclusion criteria: 
● 
Patient >12 months of age 
● 
Infants <37 weeks corrected gestational age 
● 
Infants with decreased level of consciousness or delayed 
neuromuscular development with limited pain response 
● 
Infants with the following conditions, where oral sucrose is 
contraindicated or ineffective (detailed under Exclusion Criteria).  
● 
Infants whose parents did not consent to enrolling their child in 
the study, including randomization into either arm of the study 
due to preference for a given intervention  
● 
Any other circumstance in which consent for participation in the 
study was not obtained prior to the scope 
Infants will also be excluded from the study if they present with conditions in 
which FNL is contraindicated (detailed under Exclusion Criteria). 
  
Study Sites 
Sickkids Pediatric Otolaryngology Clinic 

 
Be Sweet during Flexible Nasolaryngoscopy 
 
 
Version Date:September 13, 2024  
 
 
 
 
 
 
           5 
Participant Duration 
All participant observations will be completed on one day, during their 
scheduled appointment. 
Number of participants 
The goal is to enroll approximately 30 participants into arm of the study for a 
total of 60 participants. 
Study Phases 
(Screening, Study 
Treatment, Follow-Up) 
1) Screening: Screening will be completed by a member of the research 
team prior to a given clinic day, and eligible patients will be flagged on Epic. 
(2) Enrollment and Consent: Consent and study intervention will be 
completed on the same day. Prior to their scheduled appointment, parents or 
guardians of the potential participant will be approached by a member of the 
circle of care to introduce the study. If they are interested in participating, a 
member of the research team will obtain informed consent.  
(3) Study Treatment: For consenting participants, patients will be 
randomized into intervention (sucrose) or control (water) prior to undergoing 
nasolaryngoscopy. The administration of intervention or control will be 
integrated into their appointment and data will be collected concurrently by an 
independent observer. 
(4) Follow-up: No follow-up of patients will be required for the study 
purposes.  
(5) Data analysis will be completed once the target number of randomized 
patients (n=60) is reached. 
Efficacy Evaluations 
EVENDOL scale, heart rate, duration of cry, and skin conductance will be 
used to evaluate the analgesic efficacy of oral sucrose. 
Safety Evaluations 
Children will be undergoing flexible nasolaryngoscopy which is a part of a 
routine physical exam. Children will be administered sucrose which is 
recommended by the Hospital for Sick Children for any non-sedated painful 
procedures in infants. No safety evaluations are required 
Statistical Analysis 
The primary and secondary outcome measures will be assessed for normalcy 
and compared by Student’s T test or Kruskal Wallace test as appropriate.  
Data and Safety 
Monitoring Plan 
As the principal investigator, Dr. Nikolaus Wolter will be responsible for data 
quality management and ongoing assessment of the study conduct.  
 
1.2 Schedule of Activities (SOA)  
The study will take place during previously scheduled outpatient visits requiring routine 
diagnostic flexible nasolaryngoscopy (FNL) at the Hospital for Sick Children Otolaryngology 
Clinic. Screening patients for eligibility may occur up to 2 months prior to their appointment 
dates and on a rolling basis until study objectives are met. Consent will be obtained on the 
scheduled appointment day, while patients wait to see the clinician. FNL is a routine part of the 
pediatric otolaryngological exam but will only be initiated if clinically indicated for the patient. 
A routine visit will include: visiting with the otolaryngologist and or nurse practitioner, team 
review, physical exam including endoscopy, review of findings and formulation of a plan. A visit 
takes approximately 30-45 minutes and participation in the study will not alter the duration. For 
the purposes of gaining consent to participate in the study, the clinical indication must already be 
ascertained prior to the encounter. The study intervention and data collection will occur during 

 
Be Sweet during Flexible Nasolaryngoscopy 
 
 
Version Date:September 13, 2024  
 
 
 
 
 
 
           6 
the clinical encounter. Incoming data will be reviewed for completeness and study acceptability 
after the appointments, at least every 2-4 weeks for the duration of the study. 
1.3 Key Roles  
Principal Investigator: Nikolaus E Wolter, MD, MSC, FRCSC, FACS 
Associate Professor, Department of Otolaryngology – Head and Neck Surgery, University of 
Toronto 
Hospital for Sick Children 
555 University Avenue, Toronto, ON, M5G 1X8 
Phone: 416-813-2190 FAX: 416-813-5036 
Email: nikolaus.wolter@sickkids.ca 
 
No other sites will be involved in the study. 
2 Introduction, Background Information and Scientific Rationale 
2.1 Background Information and Relevant Literature 
 
Flexible nasolaryngoscopy (FNL) is a common, painful procedure performed as a routine part of 
the upper airway exam in children. FNL is used to examine the nose, nasopharynx, oropharynx 
and supraglottis for a wide range of presenting complaints in the Otolaryngologist’s office. As 
these areas cannot be examined with the naked eye and are poorly captured on x-ray and static 
cross-sectional images, FNL is essential. It must be done in the awake, spontaneously breathing 
child to observe the dynamic airway changes that occur actively and passively with airflow.  
Although it is felt to be safe and is generally short in duration, it is a painful procedure and can 
be quite distressing for the infant. A clinical nurse typically assists with the procedure, with the 
infant sitting in their lap and holding their head and hands to minimize movement (Figure 1). It is 
not uncommon for children to require multiple FNL 
examinations over time to assess the evolution of 
their underlying condition or recovery. In addition, 
the painful nature of the procedure often limits the 
visualization of these structures due to poor 
compliance and the anatomical limitations of the 
pediatric airway often obscures distal structures 
(narrow nasal aperture, obstructing adenoids, 
hooding of the vocal cords by the supraglottis, etc.) 
Friedman noted that a single FNL was inadequate 
for diagnosis in 20% of children under the age of 3 
years.1 It is now well established that untreated or 
undertreated pain can lead to infant and parental 
distress during procedures.2 Repeated exposures to 
pain early in life can alter long term pain responses 
and negatively impact a child’s future relationship 
with the healthcare system.3-6 Similarly, watching an infant go through a painful procedure can 
be quite distressing for caregivers. Although FNL is an essential part of the evaluation of the 

 
Be Sweet during Flexible Nasolaryngoscopy 
 
 
Version Date:September 13, 2024  
 
 
 
 
 
 
           7 
pediatric airway, it is the responsibility of the health care team to prevent or minimize the pain 
involved with this procedure whenever possible.7,8  
Attempts to anesthetize the nasal and oral mucosa have been considered but are quite 
unpalatable, often making the experience worse. Participants who have received topical 
anesthesia (topical decongestant/anesthetic spray) will not be included in this research study.  
This effect can last up to two hours and patients must be kept fasting during this time which can 
be problematic for infants who must feed frequently, particularly in our population, where 
caloric demands are increased due to increased work of breathing. As painful procedures for 
young children are not uncommon in the inpatient setting, e.g. venipuncture, heel sticks, eye 
exams, nasogastric tube insertion; various non-pharmacological pain management methods have 
been studied. Strategies include breastfeeding, non-nutritive sucking, kangaroo care, and oral 
sucrose.2,4,12 None of these interventions have been assessed for FNL in infants. Of these options, 
considering the limitations imposed by patient positioning during FNL and need for access to the 
nasal cavity, oral sucrose is the only feasible option.  
Oral sucrose is an easily accessible, non-pharmacological molecule given by syringe or pacifier 
prior to painful procedures in children less than 12 months of age in various clinical settings13 at 
the Hospital for Sick Children.14 A recent Cochrane review did not find any serious side effects 
associated with oral sucrose in infants.15 Multiple mechanisms of action for oral sucrose have 
been proposed. The sweet taste of sucrose may cause the release of endogenous opioids that may 
sufficiently attenuate nociceptive stimuli from painful procedures.13 The nearly immediate 
response of intraoral administration suggests that stimulation of gustatory cells may also simply 
temporarily divert the infant’s attention from painful stimuli.16,17 Despite its widespread use and 
positive safety profile, randomized control trials and meta-analyses have shown only variable 
results of oral sucrose on pain owing to the inherent challenges of measuring pain in infants but 
also the varying degrees of pain that are caused by the procedures. A Cochrane review showed 
effective pain management for heel lance and venipuncture in infants.12,15 For other painful 
procedures such as circumcision and ocular exams, however, oral sucrose alone did not seem to 
sufficiently reduce pain on a consistent basis.18 The use of oral sucrose for nasogastric tube 
insertion has also been studied and may be the closest correlate to FNL as they stimulate similar 
structures upon entry. Results here are similarly variable but encouraging2. In contrast to a 
nasogastric tube, upon insertion a FNL is visually guided through the nose and can be steered 
away from sensitive anatomical structures. Additionally, the FNL sits above the larynx to 
examine it from a distance and does not collide with it like a nasogastric tube. For these reasons, 
oral sucrose may be even more effective in FNL than nasogastric tube insertion.  
We have recently started using oral sucrose in clinic for some infants less than 12 months of age 
undergoing routine diagnostic FNL.  While oral sucrose may have a positive safety profile and 
demonstrated efficacy in some contexts, its effectiveness specially for FNL has not been 
conclusively established, thus there is equipoise to randomize patients to not receive the oral 
sucrose solution to determine whether it provides significant benefits 
Our objective is to understand the analgesic efficacy of oral sucrose on pain in infants undergoing 
FNL compared to placebo (water). Our hypothesis is that oral sucrose will reduce pain and crying 
duration in infants undergoing FNL compared to placebo.  

 
Be Sweet during Flexible Nasolaryngoscopy 
 
 
Version Date:September 13, 2024  
 
 
 
 
 
 
           8 
Our primary outcome measure will be the impact on infant pain measured by: validated infant 
pain scores, vital signs, time to cessation of crying, and skin conductance algesimetry (SCA). In 
order to evaluate the analgesic efficacy of oral sucrose in this context, procedural pain must be 
reliably and consistently assessed. Numerous pain scales have been validated for the assessment 
and management of pain in pre-verbal children. In a position statement by the Canadian Pediatric 
Society, the Evaluation Enfant Douleur (EVENDOL) scale was noted to carry a lower risk of 
bias compared to other frequently employed behavioral pain scales.19 Initially designed for 
evaluating pain in the emergency department, components of the EVENDOL scale are simple to 
assess in the outpatient setting. Five measures are each rated between 0-3 for a total out of 15 
points at rest, during the procedure, and at interval reassessments depending on the context. The 
measures are vocal or verbal expression, facial expression, movements, postures, and 
interactions with the environment. The EVENDOL scale is appropriate for evaluating acute, 
procedural, and chronic pain in children aged 0-7.20  
The SCA is a safe and noninvasive validated tool that uses electrodermal activity to complement 
behavioral pain scale data in infants. The SCA uses surface electrodes on the skin, which can be 
easily applied and removed in the outpatient setting. Driven by cholinergic muscarinic receptors, 
the autonomic response to pain causes bursts of increased skin conductance due to increased 
perspiration. Measuring these changes in peaks per second on the algesimeter provides an 
objective, physiologic marker of pain or distress. In contrast to vital signs such as heart rate and 
oxygen saturation, skin conductance changes per second are not influenced by respiratory 
rhythm, vasoactive drugs, or environmental temperature.21,22 The SCA will be used as a 
physiologic counterpart to the EVENDOL scale. 
2.2 Rationale 
 
This study aims to address the question: does oral sucrose reduce pain in infants undergoing 
flexible laryngoscopy (FNL)?  
 
FNLs are essential to evaluating a pediatric airway and provide rapid, diagnostic information in 
an outpatient setting. Addressing procedural pain and distress is a key component of providing 
developmentally appropriate and family-centered care. 
 
While there is substantial evidence to support the use of oral sucrose for venipuncture or heel 
lances, to our knowledge, there is no research published on the analgesic efficacy of sucrose in 
infants undergoing FNL. There is limited and variable but encouraging evidence for the use of 
oral sucrose during nasogastric tube insertion, which may be the closest clinical correlate. A pilot 
retrospective analysis of use of sucrose in FNL in our clinic demonstrated improvements in 
scores and parental satisfaction but was limited by imperfect blinding and lack of placebo.  
 
The results of this study could inform clinical practice with respect to minimizing infant distress 
during FNL. 

 
Be Sweet during Flexible Nasolaryngoscopy 
 
 
Version Date:September 13, 2024  
 
 
 
 
 
 
           9 
2.3  Potential Risks & Benefits 
2.3.1 Potential Risks 
 
One potential risk to conducting the study is that randomization and pain assessment may 
lengthen the duration of the appointment and/or FNL procedure. Consent would be obtained 
while patients are waiting for endoscopy, study solutions will be made readily available, and 
both the EVENDOL and SCA are designed for rapid assessment. Nevertheless, the cumulative 
effect of these study components could alter clinical workflow and increase waiting times. A 
pilot retrospective study done in our clinic demonstrated no significant increase in clinic visit 
time. 
 
The procedure for both groups would involve administering a few drops of study solution onto 
the tip of the baby’s tongue. This is standard practice throughout the Hospital for Sick Children 
where sucrose is used routinely used in the ED, on the ward and in the critical care unit for acute 
painful procedures such as heel lances. This method carries a low risk of aspiration compared to 
breast or bottle feeding.  
 
The risk of being randomized into the intervention group is related to the potential risks of oral 
sucrose solution. Oral sucrose solutions have been used for a variety of other indications in 
reducing pain during acute minor painful procedures among newborns and young infants. These 
procedures include heel lances, vaccinations, venipuncture, frenuloplasty, NG tube insertion etc. 
Several studies, including a Cochrane systematic review have shown that there is no evidence to 
support that administration of sucrose prior to painful procedures causes any significant side 
effects.15 Although not impossible, it is highly unlikely that infants in an outpatient setting would 
present with an undiagnosed contraindication to sucrose such as a rare metabolic condition. The 
risk is no higher in the inpatient or ED setting where sucrose use is routinely used. All children 
undergo thorough systematic review including review of perinatal genetic testing prior to 
assessment in our clinic and screening for eligibility will include these precautions.  
 
The risk of being randomized into the control group is that an infant who may have otherwise 
received oral sucrose may experience more pain or parental distress if they were given water 
instead. Provision of oral sucrose is not currently the standard of care and its analgesic efficacy 
in this context is unknown. Therefore, there is sufficient clinical equipoise to justify 
randomization into either group. 
 
As the intervention (FNL) is a routine part of our clinical exam, there are no foreseeable long-
term risks to participating in this study. 
2.3.2 Potential Benefits 
 
All infants who participate in this study will be directly observed for signs of pain and distress, 
prompting caregivers to respond accordingly when FNL is completed. Additionally, caregivers 
will learn about the potential applications of oral sucrose for procedural pain in other contexts, 
such as heel lances or immunizations. Consequently, they may be more likely to advocate for 
appropriate non-pharmacological measures aimed at reducing distress during future painful 
procedures. 

 
Be Sweet during Flexible Nasolaryngoscopy 
 
 
Version Date:September 13, 2024  
 
 
 
 
 
 
           10 
 
If our hypothesis is correct, then infants who are randomized to the intervention group may 
experience less procedural pain or distress during the FNL compared to routine practice.  
 
Although there will be no financial compensation, families may benefit from learning more 
about initiatives to make FNL less distressing for our youngest patients. Long term, the results of 
this study could justify the practice of providing oral sucrose to infants undergoing FNL. 
Conclusions drawn from this study could then inform future policies regarding procedural pain 
management for infants. 
3 Objectives and Purpose 
 
The purpose of this study is to determine the analgesic effect of oral sucrose in infants 
undergoing FNL. The data from this study will help inform our potential future use of oral 
sucrose for FNL in clinical practice. The data may also help guide future studies. 
The primary objective of this study is to determine the impact of using oral sucrose solutions on 
clinical pain scores after FNL in infants under 12 months of age. 
Objective 
Brief Description / Justification of 
Outcome Measure 
Outcome Measured 
By 
Time Frame 
Determine the 
impact of using 
oral sucrose 
solutions on 
clinical pain 
scores after FNL 
in infants under 12 
months of age. 
Pain scores are used to 
quantitatively evaluate infant 
distress and tolerance of 
procedures. There is little data on 
infant pain or distress during FNL, 
which often forms the basis of 
physical examination in pediatric 
otolaryngology clinics. 
Blinded research team 
member (not the clinical 
MD) will directly 
observe participants 
during the procedure 
and assign a pain score 
using the EVENDOL 
scale.* 
Scores obtained 
during the 
scheduled 
appointment for 
each participant. 
* The EVENDOL scale is a validated 15-point scale developed for children with 
presenting, prolonged, or procedural pain. Infant pain observations are ranked 
from 0-3 based on 5 different observations: (1) vocal or verbal expression, (2) 
facial expression, (3) movements, (4) postures, and (5) interactions with the 
environment. 
3.1 Secondary Objectives  
 
The secondary objective(s) of this study are to: 
1. Determine the impact of using oral sucrose solutions on crying time after FNL in infants 
under 12 months of age. 
2. Determine the impact of using oral sucrose solutions on the infant’s maximum heart rate 
and time to return to baseline as measured by a pulse oximeter during FNL.   
3. Determine the impact of using oral sucrose solutions on the infant’s palmar or plantar skin 
conductance during FNL as measured by maximum peaks per second. 
4. Determine if the administration of oral sucrose prolongs clinic visits. 

 
Be Sweet during Flexible Nasolaryngoscopy 
 
 
Version Date:September 13, 2024  
 
 
 
 
 
 
           11 
5. Determine the impact of using oral sucrose on caregiver impression of infant discomfort. 
 
Objective 
Brief Description/Justification of 
Outcome Measure 
Outcome 
Measured By 
Time Frame 
Determine the impact 
of oral sucrose 
solutions on crying 
time after flexible 
nasolaryngoscopy in 
children under 12 
months of age.  
Crying time is another measurable 
indicator of infant pain and distress. It 
may provide additional data points when 
evaluating the impact of oral sucrose 
solutions. 
The crying time 
will be defined as 
the time from 
cessation of FNL 
to when the infant 
stops crying for a 
period of 10 
consecutive 
seconds. Crying 
will be measured 
for a maximum of 
5 minutes. 
Will be 
assessed and 
documented at 
the same time 
as the primary 
outcome.  
Determine the impact 
of using oral sucrose 
solutions on the 
infant’s maximum 
heart rate during FNL.  
Changes in the baby’s heart rate is an 
additional indicator of infant pain or 
distress frequently employed in pain 
scales. This may provide additional data 
when evaluating the impact of oral 
sucrose solutions. 
The heart rate 
will be measured 
using a portable 
pulse oximeter 
for a maximum of 
5 minutes. 
Will be 
assessed and 
documented at 
the same time 
as the primary 
outcome.  
Determine the impact 
of using oral sucrose 
on the infant’s palmar 
or plantar skin 
conductance during 
FNL. 
Painful stimuli trigger the release of 
norepinephrine, which stimulates 
muscarinic cholinergic receptors to 
increase perspiration. Perspiration 
improves local skin conductance, which 
is a sensitive measure for pain. This 
may provide additional data when 
evaluating the analgesic effect of oral 
sucrose solutions.  
Skin conductance 
is measured 
through 
electrodes 
attached to the 
baby’s hand or 
foot and recorded 
on the 
algesimeter. 
Will be 
assessed and 
documented at 
the same time 
as the primary 
outcome. 
Determine if 
administration of oral 
sucrose prolongs 
clinic visits. 
Whether or not oral sucrose prolongs 
the length of the encounter helps 
evaluate the feasibility and acceptability 
of implementing oral sucrose into FNL 
procedures. 
The length of the 
clinical encounter 
will be assessed 
in both arms of 
the study. 
The duration of 
the clinical 
encounter will 
be assessed at 
the same time 
as the primary 
outcome. 
Determine the impact 
of using oral sucrose 
on caregiver 
impression of infant 
discomfort. 
Watching an infant go through a painful 
procedure can be distressing for 
caregivers. This can impact their 
relationship with the healthcare team. 
Wong-Baker 
FACES pain 
rating scale 
After the FNL is 
completed, 
caregivers will 
be given the 
FACES scale 
to rate their 
child’s pain. 

 
Be Sweet during Flexible Nasolaryngoscopy 
 
 
Version Date:September 13, 2024  
 
 
 
 
 
 
           12 
4 Study Design and Endpoints 
4.1 Description of Study Design 
 
This is a double-blinded randomized controlled trial evaluating the analgesic effect of oral 
sucrose on pain scores in outpatient infants undergoing FNL during a scheduled appointment. 
These appointments take place at the Pediatric Otolaryngology Clinic at SickKids. There are no 
other study sites. Recruitment will continue on a rolling basis from the above clinics with the 
goal of recruiting thirty patients in each arm. This is anticipated to take place over the course of 
approximately 12 months. As such, recruitment is anticipated to occur between May 2024-2025. 
 
The intervention in this study is the provision of 0.5 ml 0.24% oral sucrose solution, which is a 
standard procedure at SickKids for acute painful procedures in infants and widely available, 
compared to a control group of 0.5 ml water. The practice of giving sucrose during FNL has not 
yet been established, with inconsistent use across sites due to a lack of data, which this study 
aims to provide.  
 
Following evaluation for eligibility, the clinical team will introduce the study to the patient’s 
caregivers and introduce the study coordinator. Informed consent will be obtained by the study 
coordinator during team review. The study coordinator will randomize the participant to sucrose 
or water using an open-source random number generator. Sucrose or water will be hand-
delivered to the clinical team immediately prior to endoscopy in identical, unmarked syringes 
prepared and provided by the study coordinator who performs consent. The clinical team, 
parents, and a separate evaluator will be blinded to sucrose vs. water. 
 
Pain assessment will involve validated infant pain scores, vital signs, time to cessation of crying, 
and skin conductance algesimetry (SCA). EVENDOL is an excellent pain scale for non-verbal 
children noted to carry a lower risk of bias compared to other frequently employed behavioral 
pain scales and is recommended by the Canadian Pediatric Society.19 Initially designed for 
evaluating pain in the emergency department, components of the EVENDOL scale are simple to 
assess in the outpatient setting. Five measures are each rated between 0-3 for a total out of 15 
points at rest, during the procedure, and at interval reassessments depending on the context. The 
measures are vocal or verbal expression, facial expression, movements, postures, and 
interactions with the environment. The EVENDOL scale is appropriate for evaluating acute, 
procedural, and chronic pain in children aged 0-7.20  
We will also measure time to cessation of crying or “settling” which is defined as a period of 10 
consecutive seconds of no crying. Finally, the infant’s maximum heart rate will be measured by a 
pulse oximeter. These outcome measures will be recorded by a member of the research team 
during the participant’s appointment along with the identification number of the study solution 
they were given. Crying will be measured to a maximum of 5 minutes after the procedure.  
 
The SCA is a safe and noninvasive validated tool that uses electrodermal activity to complement 
behavioral pain scale data in infants. The SCA uses surface electrodes on the skin, which can be 
easily applied and removed in the outpatient setting. Driven by cholinergic muscarinic receptors, 
the autonomic response to pain causes bursts of increased skin conductance due to increased 

 
Be Sweet during Flexible Nasolaryngoscopy 
 
 
Version Date:September 13, 2024  
 
 
 
 
 
 
           13 
perspiration. Measuring these changes in peaks per second on the algesimeter provides an 
objective, physiologic marker of pain or distress. In contrast to vital signs such as heart rate and 
oxygen saturation, skin conductance changes per second are not influenced by respiratory 
rhythm, vasoactive drugs, or environmental temperature.21,22 The SCA will be used as a 
physiologic counterpart to the EVENDOL scale.  
We will compare the pain scores of infants from each study arm. We will also compare the time 
spent during the appointment to determine the impact of sucrose administration in the clinic. 
Finally, we will compare the caregiver’s impression of their child’s pain using the Wong-Baker 
FACES scale.  
4.2 Duration of Study Participation 
 
Potential participants will be screened prior to each clinic day and approached for consent after 
introduction by the clinical team while they are waiting for their physician or nurse practitioner 
during the team review. Participants will be observed by the evaluator for up to 5 minutes 
following FNL during their scheduled appointment time. The duration of patient participation is 
limited to their scheduled appointment at the clinic. No follow-up is required from the 
participants for this study. As such, participation is limited to the day of their appointment. 
Although some participants will be followed for clinical reasons, participation in the study will 
not impact their next visit. Caregivers will be given the option to opt out of being approached for 
re-enrollment at future appointments if the patient is still eligible. 
4.3 Total Number of Participants and Sites  
 
Recruitment will end when approximately 30 participants are enrolled to each arm. 
5 Study Enrollment and Withdrawal 
5.1 Participant Inclusion Criteria 
● Patient  <12 months of age;  
● Scheduled for an appointment with Dr. Nikolaus Wolter or Dr. Jennifer Siu, who are 
Staff Pediatric Otolaryngologists at the Hospital for Sick Children, or Meghan 
Tepsich, a complex airway Nurse Practitioner at SickKids; 
● Requiring flexible nasolaryngoscopy for diagnostic purposes; 
● Accompanied by caregivers who provided consent. 
5.2 Participant Exclusion Criteria 
● Patient >12 months of age 
● Infants <37 weeks corrected gestational age 
● Infants with decreased level of consciousness or delayed neuromuscular development 
with limited pain response 
● Infants who have received acute/urgent /emergent airway assessment such as 
respiratory distress or a foreign body, etc. 

 
Be Sweet during Flexible Nasolaryngoscopy 
 
 
Version Date:September 13, 2024  
 
 
 
 
 
 
           14 
● Infants who have received topical anesthesia (topical decongestant/anesthetic spray) 
● Infants with the following conditions, where oral sucrose is contraindicated or 
ineffective: 
▪ 
Carbohydrate intolerance 
▪ 
Decreased level of consciousness or heavy sedation  
▪ 
Absent gag reflex 
▪ 
Non-functional gastrointestinal tract 
▪ 
History of aspiration, tracheoesophageal fistula 
▪ 
Necrotizing enterocolitis 
● Infants whose parents did not consent to enrolling their child in the study, including 
randomization into either arm of the study due to preference for a given intervention  
● Any other circumstance in which consent for participation in the study was not 
obtained prior to the scope 
 
Infants will also be excluded from the study if they present with conditions in which FNL is 
contraindicated: 
● Severe respiratory distress 
● Post-palliative systemic artery to pulmonary artery shunt 
● Single ventricle congenital heart disease 
5.3 Strategies for Recruitment and Retention 
 
Potential participants are the patients scheduled to see Dr. Wolter, Dr. Propst, Dr. Siu, or 
Meghan Tepsich NP at the SickKids Pediatric Otolaryngology clinic. The clinic schedule of 
these practitioners will be reviewed on Epic prior to the appointment date, and patients <12 
months old will be screened for eligibility. Specifically, the provider’s referral note and clinical 
chart for the patient may be reviewed to determine whether FNL is indicated during their 
appointment, and whether the patient has any medical conditions impacting their eligibility. 
Parents of potential participants will be introduced to the study by someone in the circle of care 
and consent will be obtained by the study coordinator prior to seeing their physician or nurse 
practitioner during team review. As such, the consent process should not interfere with the 
clinic’s scheduled patient care. All patients will be seen as scheduled and the intervention will be 
integrated into the clinical visit to minimize inconvenience to the patient and caregivers.  
 
Parents of potential participants will be asked to confirm whether their child has any of the 
medical conditions listed in the exclusion criteria. Demographic information (age, sex, birth 
weight, current weight, history of previous endoscopy, history of previous surgery, and reason 
for clinic appointment) will be obtained using Epic after obtaining participant consent. A 
member of the research team will accompany consenting participants for the duration of the 
FNL; however, the research team will not be present for the remainder of the appointment.  
 
An overview of the study including the primary objective, inclusion criteria, and implications on 
clinical flow (i.e. speaking with parents of eligible patients in the clinic room prior to being seen 

 
Be Sweet during Flexible Nasolaryngoscopy 
 
 
Version Date:September 13, 2024  
 
 
 
 
 
 
           15 
by the doctor or nurse practitioner) will be provided to nurses working at the SickKids Pediatric 
Otolaryngology Clinic. No marketing or media services will be required. If the FNL is 
interrupted for any reason, the consenting participant’s data will not be included in the data 
analysis. No data will be stored for non-consenting patients; however, the number of non-
consenting patients will be tracked to review study acceptability and participant flow. The 
patient’s participation in the study ends once their clinic appointment is over. Participating will 
not impact any future visits, and they are not committing to participating again even if the next 
visit will also include FNL as part of the baby’s evaluation.  
5.4 Participant Withdrawal or Termination 
5.4.1 Reasons for Withdrawal or Termination 
 
Parents or caregivers are free to withdraw their infant from participating in this study at any time 
upon request. Additionally, an investigator may terminate a patient’s participation in the study if: 
● The participant meets an exclusion criterion, either newly developed or not previously 
recognized 
● A clinical adverse event (AE) occurs when administering the intervention such that it 
would not be advisable to proceed with the scoping procedure 
● A situation occurs such that continued participation in the study would not be in the best 
interest of the participant 
 
No participant data will be included in the analysis if FNL needs to be interrupted for any reason. 
5.4.2 Handling of Participant Withdrawals or Termination 
 
If a caregiver withdraws consent for their child to participate, or if participation is terminated due 
to meeting any criteria described in 5.4.1, then all participant data will be removed from study 
documentation. Efforts will be made to document reasons for study withdrawal in the interest of 
periodically assessing the acceptability of the study. Likewise, the reason for termination will be 
documented in the participant flow sheet.  
6 Study Assessments and Procedures 
 
Participants will be screened for eligibility by a REB-approved research team member no more 
than 28 days prior to their appointment at the Outpatient Otolaryngology Clinic. The 
appointment schedules for Dr. Wolter, Dr. Siu, or Meghan Tepsich NP on a given clinic day will 
be reviewed to screen for participant eligibility. Patients who are less than 12 months of age will 
be further screened using the Chart Review and Summary views on Epic to look for inclusion 
and exclusion criteria. Potential participants will be flagged accordingly to be approached by a 
member of the research team. 
 
No pre-consenting process for screening is indicated. Parents of eligible infants will be 
approached in the clinic, while they are waiting to see their doctor or nurse practitioner. The 
nature of the study, anticipated risks or benefits, and possible outcomes of randomization will be 
reviewed. Questions will be answered to their satisfaction, and parents will be able to withdraw 
consent at any time without impacting their child’s care. This consent process will occur in a 

 
Be Sweet during Flexible Nasolaryngoscopy 
 
 
Version Date:September 13, 2024  
 
 
 
 
 
 
           16 
private clinic room to respect confidentiality. The consent form will be stored in a locked file 
cabinet for the duration of the study. Information from patients who decline participation in the 
study will not be recorded; however, the number of eligible patients who declined will be 
recorded for the purpose of evaluating study acceptability and participant flow. 
7 Study Procedures/Evaluations 
7.1 Procedures / Evaluations 
 
Consented participants will be given the randomized solution and observed during FNL. Collection 
of EVENDOL pain scores and crying time is part of routine standard procedure.  
 
Randomization: 
Each participant will be randomized into the intervention or control group by an online random 
number generator (https://www.random.org/)  
 
Intervention:  
Each participant will be administered a previously prepared 1cc syringe containing either the 
sucrose solution or sterile water depending on their randomization. The expiry dates of sucrose 
solutions will be verified prior to drawing-up 0.5mL of the solution into a 0.5 mL syringe. The 
control group will receive 0.5 mL of sterile water via syringe in the mouth, which will be 
prepared in identical syringes to maintain the blinded nature of this study. An equal number of 
intervention and control syringes will be prepared prior to initiating the study, and each syringe 
will each be labeled using an identification number. A log of the solution contained in each 
syringe will be kept in a separate folder, which will not be opened until after completion of study 
activities. During the study, each participant’s study solution identification number will be 
recorded along with their pain scores. The log will then be accessed and participants will be 
matched into the intervention or control group for data analysis. 
 
Study Solution Administration: 
We will follow the standard procedure for oral sucrose administration in infants undergoing 
other acute painful procedures, such as heel lances. Approximately 0.5 mL of either solution is 
placed on the tip of the baby’s tongue, or on their pacifier. The solution is administered within 2 
minutes prior to FNL. 
 
Outcome Data Collection: 
A member of the research team will apply the non-invasive skin algesimeter stickers and 
portable pulse oximeter prior to the procedure. A blank printed EVENDOL scale and a timer will 
be used to obtain the pain scores and crying times, respectively. Maximum heart rate during the 
procedure will also be documented. This data will be collected on a printed paper (Appendix A) 
with the participant’s study ID and study solution number. It will be shredded after transferring 
the data to the password-protected Excel spreadsheet. 
 
Flexible Endoscopy: 
This procedure will be performed by a single endoscopist for all eligible participants to reduce 
potential provider-dependent variations. The research team member obtaining the data will not 

 
Be Sweet during Flexible Nasolaryngoscopy 
 
 
Version Date:September 13, 2024  
 
 
 
 
 
 
           17 
comment, interfere, or interact with the participant during this procedure. This single endoscopist 
will be blinded to the randomization. 
8 Statistical Considerations 
8.1 Study Hypotheses 
The study hypothesis is that oral sucrose administration in infants undergoing FNL will result in 
lower pain and distress as measured by the EVENDOL pain score, heart rate, crying time, and 
skin conductance as compared to infants who receive sterile water instead. 
8.2 Sample Size Determination 
 
Based on our retrospective review completed earlier in 2023, we anticipate needing 30 
participants per study arm for a total of 60 participants. This sample size should be sufficiently 
powered to evaluate both primary and secondary outcomes. This sample size is also comparable 
to similar studies that sought to evaluate the analgesic efficacy of oral sucrose for nasogastric 
tube insertions.23 Participants who withdraw from the study will be replaced.  
8.3 Statistical Methods 
 
Demographic data including sex, age, birthweight, current weight, and history of 
endoscopy/surgery will be summarized using means and proportions where appropriate. Chi-
squared test will be used to ensure balanced arms after randomization, and study arms will be 
compared statistically by Wilcoxon rank sum tests or Student’s T-test as appropriate.  
 
To evaluate the study hypothesis the pain scores, vital signs, cry duration, algesimetry, and 
parent Wong-Baker FACES scores will be assessed for normalcy and compared by Student’s T-
test or Kruskal Wallace depending on whether the data is parametric. These are all continuous 
variables. Analysis of data will be done using SPSS statistical analysis software (Version 24.0 
for Macintosh; SPSS, Chicago, Illinois). 
9   Source Documents and Access to Source Data/Documents 
 
Access to study records will be limited to REB-approved members of the study team. The PI will 
permit study-related monitoring, audits, and inspections by the REB and/or University 
compliance and quality assurance groups of all study related documents (e.g. source documents, 
data collection instruments, study data etc.). Participation as a PI in this study implies acceptance 
of potential inspection by REB and/or applicable University compliance and quality assurance 
offices. 
10 Study Oversight 
 
Study oversight will primarily be done by the principal investigator and the Otolaryngologist in 
Chief at SickKids, Dr. Blake Papsin.  
 
Preliminary data will be reviewed every month. If a clear difference in pain scores is observed 

 
Be Sweet during Flexible Nasolaryngoscopy 
 
 
Version Date:September 13, 2024  
 
 
 
 
 
 
           18 
between the two groups, the study will be terminated on the basis of lacking clinical equipoise to 
continue. No other sites are involved in the study. As such, there will be no dissemination of data 
outside of the SickKids Otolaryngology Clinic. 
11 Ethics/Protection of Human Participants 
11.1 Ethical Standard 
Respect for persons – Consent will be obtained in a way that respects their rights to self-
advocacy and privacy. There will be no coercion to participate in this study. The decision to 
participate or decline participation will not affect their present or future care at the 
Otolaryngology Clinic. If the parent would like their child to receive sucrose during FNL 
rather than a blinded study solution, their preference will be respected and the patient will 
not be enrolled in the study. 
 
Concern for welfare – This study was designed to minimize the inconvenience and time 
burden on participants. Participant safety and wellbeing must be prioritized over 
recruitment. 
 
Social and clinical value – the intent of this study is to evaluate a potential method to reduce 
infant pain and distress during FNL, which is often a central component of the physical 
exam when assessing the airway and nasal passages. While there are no direct benefits for 
study participants, the data from this study may improve the future quality of care and 
inform future research on pain management strategies during FNL.  
11.2 Informed Consent Process and Documentation  
 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in 
the study and continues throughout the individual’s study participation. A clinic nurse or another 
member of the patient’s circle of care will introduce the study before any member of the research 
team gets involved. The research coordinator or an appointed member of the research team will 
be responsible for obtaining consent in a private clinic room to respect patient privacy. Extensive 
discussion of study’s purpose, possible risks, and alternative choices will be provided to the 
participant’s decision-maker. A language line or translation iPad may be used for translation if 
needed; the need for translation would be documented as well. As all study participants will be 
infants, consent will be obtained from their parent, guardians, or appointed clinical decision-
maker. Consent forms will be REB approved and the potential participant’s decision-maker will 
be asked to read and review the document. The study coordinator will explain the research study 
to the potential participant and answer any questions that may arise. The family will be given 
sufficient time to carefully review the written consent form and ask questions about the study. 
Their decision to participate or decline will be respected. The parent will sign the informed 
consent document prior to any procedures being done specifically for the study. They may 
withdraw consent at any time throughout the course of the study. A copy of the signed informed 
consent document will be given to the participant’s decision-maker for their records. The rights 
and welfare of the participants will be protected by emphasizing to them that the quality of their 
medical care will not be adversely affected if they decline participation in this study. 
 

 
Be Sweet during Flexible Nasolaryngoscopy 
 
 
Version Date:September 13, 2024  
 
 
 
 
 
 
           19 
A copy of the signed informed consent document will be stored in the participant’s research 
record. The consent process, including the name of the individual obtaining consent, will be 
documented in the participant’s research record. Any alteration to the standard consent process 
(ex. use of a translator, consent from a legally authorized representative, consent document 
presented orally, etc.) and the justification for such alteration will likewise be documented.  
11.3  Consent/Assent and Other Informational Documents Provided to Participants 
 
Consent forms detailing the study intervention, procedure, potential risks, and the option to 
decline without affecting their care are given to the participant’s decision-maker. Written 
documentation of informed consent is required prior to administering the intervention. The 
Parent Consent Form is provided with this protocol for review. No further materials will be 
produced for the study. 
12 Data Handling and Record Keeping 
12.1 Data Collection and Management Responsibilities 
 
Data collection is the responsibility of the study staff at the site under the supervision of the site 
PI. The PI is responsible for ensuring the accuracy, completeness, legibility, and timeliness of the 
data reported. 
 
Consent forms will be stored in a locked cabinet for the duration of the study.  Any paper data 
obtained during research activities (for example, an EVENDOL pain scoring tool) will be 
shredded on site after entering data into a password-protected Excel file. Each participant will be 
assigned a Study ID, and data will be stored on a password-protected Excel file using the 
SickKids Microsoft 365 Sharepoint. All data entered into this Excel file will be de-identified and 
will not contain any identifiable information. We will be responsible for creating and 
maintaining a log that links the Study ID of the patient to the patient’s identifiable information 
(i.e., name, hospital MRN) for auditing purposes. The master linking log will be kept separately 
from the study data.  
12.2 Study Records Retention 
 
Paper records of the consent forms will be retained in a locked cabinet for 7 years from the last 
publication prior to disposal in SickKids confidential disposal bins. All electronic records will be 
stored in a password-protected file for the same duration, and destroyed by contacting the 
SickKids IS help desk.  
13 Protocol Deviations 
 
Research activities will be reviewed and an informal debriefing will occur after each clinic day 
to ensure compliance with the approved protocol. Any deviations that were detected will be 
reported to the Research Ethics Board for approval.  
 

 
Be Sweet during Flexible Nasolaryngoscopy 
 
 
Version Date:September 13, 2024  
 
 
 
 
 
 
           20 
If evidence of information dissemination is discovered, our team would contact the 
Otolaryngology – Head and Neck Surgery Chief along with the SickKids Hospital Research 
Ethics office and the SickKids Privacy Office. We would also contact the participants that may 
be affected by the data breach. 
14 Publication and Data Sharing Policy 
 
Dr. Wolter is the Principal Investigator and as such, he will be responsible for resolving any 
authorship issues that may arise. This is a single site study, and data will not be shared with 
outside institutions. The final analysis will be summarized in a manuscript for publication. A 
summary of the data analyzed from this study may also be presented at national and international 
meetings. 
 
15 References 
 
1. 
Friedman EM. Role of ultrasound in the assessment of vocal cord function in infants and 
children. Ann Otol Rhinol Laryngol. Mar 1997;106(3):199-209. doi:10.1177/000348949710600304 
2. 
Chen S, Zhang Q, Xie RH, Wen SW, Harrison D. What is the Best Pain Management During 
Gastric Tube Insertion for Infants Aged 0-12months: A Systematic Review. J Pediatr Nurs. May-Jun 
2017;34:78-83. doi:10.1016/j.pedn.2016.12.015 
3. 
Taddio A, Katz J. The effects of early pain experience in neonates on pain responses in infancy 
and childhood. Paediatr Drugs. 2005;7(4):245-57. doi:10.2165/00148581-200507040-00004 
4. 
Harrison D, Reszel J, Bueno M, et al. Breastfeeding for procedural pain in infants beyond the 
neonatal period. Cochrane Database Syst Rev. Oct 28 2016;10(10):CD011248. 
doi:10.1002/14651858.CD011248.pub2 
5. 
Ravishankar A, Thawani R, Dewan P, et al. Oral dextrose for analgesia in neonates during 
nasogastric tube insertion: a randomised controlled trial. J Paediatr Child Health. Feb 2014;50(2):141-5. 
doi:10.1111/jpc.12392 
6. 
Ranger M, Grunau RE. Early repetitive pain in preterm infants in relation to the developing brain. 
Pain Manag. Jan 2014;4(1):57-67. doi:10.2217/pmt.13.61 
7. 
Trottier ED, Dore-Bergeron MJ, Chauvin-Kimoff L, Baerg K, Ali S. Managing pain and distress 
in children undergoing brief diagnostic and therapeutic procedures. Paediatr Child Health. Dec 
2019;24(8):509-535. doi:10.1093/pch/pxz026 
8. 
Keels E, Sethna, N., Watterberg, K. L., Cummings, J. J., Benitz, W. E., Eichenwald, E. C., 
Poindexter, B. B., Stewart, D. L., Aucott, S. W., Goldsmith, J. P., Puopolo, K. M., Wang, K. S., Tobias, J. 
D., Agarwal, R., Anderson, C. T. M., Hardy, C. A., Honkanen, A., Rehman, M. A., Bannister, C. F. . 
Prevention and Management of Procedural Pain in the Neonate: An Update. Pediatrics. 2016;137(2) 
9. 
Sunkaraneni VS, Jones SE. Topical anaesthetic or vasoconstrictor preparations for flexible fibre-
optic nasal pharyngoscopy and laryngoscopy. Cochrane Database Syst Rev. Mar 16 2011;(3):CD005606. 
doi:10.1002/14651858.CD005606.pub2 
10. 
De Vito A, Carrasco Llatas M, Ravesloot MJ, et al. European position paper on drug-induced 
sleep endoscopy: 2017 Update. Clin Otolaryngol. Dec 2018;43(6):1541-1552. doi:10.1111/coa.13213 
11. 
Doherty LS, Nolan P, McNicholas WT. Effects of topical anesthesia on upper airway resistance 
during wake-sleep transitions. J Appl Physiol (1985). Aug 2005;99(2):549-55. 
doi:10.1152/japplphysiol.01221.2004 
12. 
Liu Y, Huang X, Luo B, Peng W. Effects of combined oral sucrose and nonnutritive sucking 
(NNS) on procedural pain of NICU newborns, 2001 to 2016: A PRISMA-compliant systematic review 
and meta-analysis. Medicine (Baltimore). Feb 2017;96(6):e6108. doi:10.1097/MD.0000000000006108 

 
Be Sweet during Flexible Nasolaryngoscopy 
 
 
Version Date:September 13, 2024  
 
 
 
 
 
 
           21 
13. 
Yaprak D, Karagol BS, Bozat AD, Kar I. The role of time interval elimination on pain control of 
preterm infants by sucrose administration. Eur J Clin Pharmacol. Jun 2023;79(6):841-848. 
doi:10.1007/s00228-023-03496-2 
14. 
Members PMTF. Hospital for Sick Children: Pain Management Clinical Practice Guideline. 
webpage. Hospital for Sick Children. 2023. http://my.sickkids.ca/learning/learning-opportunities/nursing-
education/Nursing%20Education%20Documents/Pain%20mgmt%20policy.pdf#search=oral%20sucrose 
15. 
Stevens B, Yamada J, Ohlsson A, Haliburton S, Shorkey A. Sucrose for analgesia in newborn 
infants undergoing painful procedures. Cochrane Database Syst Rev. Jul 16 2016;7(7):CD001069. 
doi:10.1002/14651858.CD001069.pub5 
16. 
Ramenghi LA, Evans DJ, Levene MI. "Sucrose analgesia": absorptive mechanism or taste 
perception? Arch Dis Child Fetal Neonatal Ed. Mar 1999;80(2):F146-7. doi:10.1136/fn.80.2.f146 
17. 
Bellieni CV, Bagnoli F, Perrone S, et al. Effect of multisensory stimulation on analgesia in term 
neonates: a randomized controlled trial. Pediatr Res. Apr 2002;51(4):460-3. doi:10.1203/00006450-
200204000-00010 
18. 
Labban M, Menhem Z, Bandali T, Hneiny L, Zaghal A. Pain control in neonatal male 
circumcision: A best evidence review. J Pediatr Urol. Feb 2021;17(1):3-8. 
doi:10.1016/j.jpurol.2020.09.017 
19. 
Best practices in pain assessment and management for children. Canadian Paediatric Society. 
https://cps.ca/en/documents/position/pain-assessment-and-management 2022, November 4.  
20. 
Fournier-Charrière, E. , Tourniaire, B. , Carbajal, R. , Cimerman, P. , Lassauge, F. , Ricard, C. , 
Reiter, F. , Turquin, P. , Lombart, B. , Letierce, A. & Falissard, B.  (2012).  Pain,  153 (8),  1573-1582.  
doi: 10.1016/j.pain.2012.02.024. 
21.  
Gokulu, G., Bilgen, H., Ozdemir, H., Sarioz, A., Memisoglu, A., Gucuyener, K., & Ozek, E. 
(2016). Comparative heel stick study showed that newborn infants who had undergone repeated painful 
procedures showed increased short-term pain responses. Acta paediatrica (Oslo, Norway : 1992), 
105(11), e520–e525. https://doi.org/10.1111/apa.13557 
22.  
Passariello, A., Montaldo, P., Palma, M., Cirillo, M., Di Guida, C., Esposito, S., Caruso, M., 
Pugliese, M., & Giliberti, P. (2020). Neonatal painful stimuli: skin conductance algesimeter index to 
measure efficacy 24% of sucrose oral solution. The Journal of Maternal-Fetal & Neonatal Medicine, 
33(21), 3596–3601. https://doi.org/10.1080/14767058.2019.1580690 
23.  
McCullough S, Halton T, Mowbray D, Macfarlane PI. Lingual sucrose reduces the pain 
response to nasogastric tube insertion: a randomised clinical trial. Arch Dis Child Fetal Neonatal 
Ed. 2008;93(2):F100-F103. doi:10.1136/adc.2006.110338 
 
 
 
 
 
 
 

 
Be Sweet during Flexible Nasolaryngoscopy 
 
 
Version Date:September 13, 2024  
 
 
 
 
 
 
           22