Anapod™ Humi-Therm Heated Humidification System Breathing Circuit Versus Bair Hugger™ Warming Blanket for Intraoperative Maintenance of Body Temperature in Pediatric Patients Undergoing Dental Procedures: a Prospective Randomized Non-Inferiority Study
Phase: NA
Conditions: Temperature Change, Body
Sponsor: University of Minnesota

PROTOCOL TITLE: Anapod™ Humi-Therm Heated Humidification System Breathing Circuit versus Bair 
Hugger™ Warming Blanket for Intraoperative Maintenance of Body Temperature in Pediatric Patients Undergoing 
Dental Procedures: a Prospective Randomized Non-Inferiority Study 
VERSION DATE: Version 3, 4/28/2020
PROTOCOL TITLE: 
Anapod™ Humi-Therm Heated Humidification System Breathing Circuit versus Bair 
Hugger™ Warming Blanket for Intraoperative Maintenance of Body Temperature in 
Pediatric Patients Undergoing Dental Procedures: a Prospective Randomized Non-
Inferiority Study 
PRINCIPAL INVESTIGATOR 
Benjamin Kloesel MD 
Department of Anesthesiology 
Assistant Professor 
612-301-1245 
bkloesel1@umn.edu 
Co-Investigator 1 
Kumar Belani MD 
Department of Anesthesiology 
Professor 
612-624-9996 
belan001@umn.edu 
Co-Investigator 2 
Soraya Beiraghi, DDS, MSD, MS 
Department of Developmental and Surgical Sciences 
Professor 
612-624-5997 
Beira001@umn.edu 
Support Personnel  
Melissa Cohen 
Jason Hall 
Ryan Eskuri DO 
VERSION NUMBER/DATE: 
Version 3 
4/28/2020 
 
Page  of 
 
Revised: April 19, 2017
1
21

PROTOCOL TITLE: Anapod™ Humi-Therm Heated Humidification System Breathing Circuit versus Bair 
Hugger™ Warming Blanket for Intraoperative Maintenance of Body Temperature in Pediatric Patients Undergoing 
Dental Procedures: a Prospective Randomized Non-Inferiority Study 
VERSION DATE: Version 3, 4/28/2020
REVISION HISTORY 
Revision #
Version Date
Summary of Changes
Consent Change?
1
6/27/19
See stipulation letter
YES
2
4/28/2020
Updated contact information, length 
of enrollment period, and also see 
stipulation letter for more
YES
 
Page  of 
 
Revised: April 19, 2017
2
21

PROTOCOL TITLE: Anapod™ Humi-Therm Heated Humidification System Breathing Circuit versus Bair 
Hugger™ Warming Blanket for Intraoperative Maintenance of Body Temperature in Pediatric Patients Undergoing 
Dental Procedures: a Prospective Randomized Non-Inferiority Study 
VERSION DATE: Version 3, 4/28/2020
Table of Contents 
After completing your protocol, right click on the Table of Contents below and select “Update 
Field.” If prompted, select “Update entire table.” This will automatically update the protocol 
sections and page numbers for you. Do this also each time you modify your protocol after initial 
approval. 
1.0  Objectives 
 
.................................................................................................................................6
2.0  Background 
 
...............................................................................................................................7
3.0  Outcomes 
 
..................................................................................................................................8
4.0  Study Intervention(s)/Investigational Agent(s) 
 
........................................................................9
5.0 Procedures Involved 
 
................................................................................................................10
6.0  Data and Specimen Banking 
 
...................................................................................................12
7.0 Sharing of Results with Participants 
 
........................................................................................12
10.0  Vulnerable Populations 
 
.........................................................................................................14
11.0  Local Number of Participants 
 
...............................................................................................14
12.0  Local Recruitment Methods 
 
.................................................................................................15
13.0  Withdrawal of Participants 
 
...................................................................................................15
14.0  Risks to Participants 
 
.............................................................................................................16
15.0  Potential Benefits to Participants 
 
..........................................................................................16
16.0  Data Management 
 
.................................................................................................................17
17.0  Confidentiality 
 
......................................................................................................................17
18.0  Provisions to Monitor the Data to Ensure the Safety of Participants 
 
...................................17
19.0  Provisions to Protect the Privacy Interests of Participants 
 
...................................................18
20.0  Compensation for Research-Related Injury 
 
.........................................................................18
21.0  Consent Process 
 
....................................................................................................................19
22.0  Setting 
 
...................................................................................................................................20
23.0  Multi-Site Research  N/A  This study is only being conducted at the University of 
Minnesota 
 
......................................................................................................................................20
24.0  Resources Available 
 
..............................................................................................................20
25.0  References ............................................................................................................................21
 
Page  of 
 
Revised: April 19, 2017
3
21

PROTOCOL TITLE: Anapod™ Humi-Therm Heated Humidification System Breathing Circuit versus Bair 
Hugger™ Warming Blanket for Intraoperative Maintenance of Body Temperature in Pediatric Patients Undergoing 
Dental Procedures: a Prospective Randomized Non-Inferiority Study 
VERSION DATE: Version 3, 4/28/2020
ABBREVIATIONS/DEFINITIONS 
Include any abbreviations or definitions for key or technical terms you use in your 
protocol. 
•
MRN 
= 
Medical Record Number 
•
IV  
= 
Intravenous 
•
PACU 
=  
Post Anesthesia Care Unit (Recovery Room) 
 
Page  of 
 
Revised: April 19, 2017
4
21

PROTOCOL TITLE: Anapod™ Humi-Therm Heated Humidification System Breathing Circuit versus Bair 
Hugger™ Warming Blanket for Intraoperative Maintenance of Body Temperature in Pediatric Patients Undergoing 
Dental Procedures: a Prospective Randomized Non-Inferiority Study 
VERSION DATE: Version 3, 4/28/2020
STUDY SUMMARY  
Study Title
Anapod™ Humi-Therm Heated Humidification 
System Breathing Circuit versus Bair Hugger™ 
Warming Blanket for Intraoperative Maintenance of 
Body Temperature in Pediatric Patients Undergoing 
Dental Procedures: a Prospective Randomized Non-
Inferiority Study
Study Design
Prospective randomized non-inferiority study
Primary Objective
Determine non-inferiority of Anapod™ Humi-Therm 
Heated Humidification System Breathing Circuit 
compared to Bair Hugger™ Warming Blanket
Secondary Objective(s)
Need for hyperthermic or hypothermic rescue 
intervention 
Correlation of 3M SpotOn Temperature Monitoring 
with rectal temperatures 
Research Intervention(s)/
Investigational Agents
Anapod™ Humi-Therm Heated Humidification 
System Breathing Circuit and BairHugger ™ 
Warming System
IND/IDE # (if applicable)
N/A
Investigational Drug Services 
# (if applicable)
N/A
Study Population
Pediatric patients undergoing dental procedures
Sample Size (number of 
participants)
256 (128 patients per study arm)
Study Duration for Individual 
Participants
Duration of one dental procedure (1-6 hours) 
including recovery period in the postoperative care 
unit until discharge home or admission to the floor.
 
Page  of 
 
Revised: April 19, 2017
5
21

PROTOCOL TITLE: Anapod™ Humi-Therm Heated Humidification System Breathing Circuit versus Bair 
Hugger™ Warming Blanket for Intraoperative Maintenance of Body Temperature in Pediatric Patients Undergoing 
Dental Procedures: a Prospective Randomized Non-Inferiority Study 
VERSION DATE: Version 3, 4/28/2020
1.0  Objectives 
Purpose:  Temperature management is an important aspect of perioperative care that falls under 
the purview of the anesthesiologist. Temperature is recognized as one of four primary vital 
signs and significant deviations from normal values may result in patient harm. General 
anesthesia disrupts the body’s temperature homeostasis by inhibiting temperature 
regulation mechanisms such as vasoconstriction/-dilation, shivering and behavioral 
interventions (donning clothes or leaving an area with excessive heat, for example). 
Anesthetized patient have a tendency to become hypothermic, especially during long 
surgical procedures.  This results from both the redistribution of cooler peripheral 
temperatures into the cord (due to vasodilation) as well as actual temperature loss to a cold 
operating room environment (which is maintained at a lower temperature for the comfort 
of fully gowned surgeons and nurses).  In addition, large surgical incisions predispose the 
patient to hypothermia through evaporation and convection.   
 
Hypothermia is a recognized risk factor that predisposes the patient to an increased 
metabolic rate, increased oxygen demand, coagulopathies, impaired wound healing, 
impaired immune function and increased risk of infection. Therefore, maintenance of 
normal body temperature is an important goal of every general anesthetic - and is a well-
accepted quality metric associated with patient care.  Because of the greater surface area to 
volume relationship, children are thought to be a greater risk of intraoperative 
hypothermia. 
 
The most widely used method of maintaining body temperature during surgery (and a 
routine at this institution) is by using a forced-air warming blanket (Bair Hugger warming 
blanket, 3M). Despite its widespread use, the forced-air warming blanket has its 
limitations.  For example, during certain surgical procedures, the location of the surgical 
field precludes placement of the warming blanket.  In addition, the warming blanket often 
cannot be placed immediately after the induction of anesthesia (when complex patient 
positioning is required) - leaving the patient exposed to hypothermic conditions for short 
(10-15min) or long (30-60min) periods of time.  There is hence a need for alternative 
warming systems that could be implemented immediately following anesthetic induction. 
 
Westmed, Inc. has developed an alternative system that utilizes a heated, humidified 
breathing circuit to regulate a patient’s body temperature in the intraoperative setting. This 
system is active from the moment the trachea is intubated following anesthetic induction, 
i.e. there are no delays in instituting thermal management. 
 
Our goal is to evaluate the efficacy of the Westmed system vs the Bair Hugger Blanket.   
 
Page  of 
 
Revised: April 19, 2017
6
21

PROTOCOL TITLE: Anapod™ Humi-Therm Heated Humidification System Breathing Circuit versus Bair 
Hugger™ Warming Blanket for Intraoperative Maintenance of Body Temperature in Pediatric Patients Undergoing 
Dental Procedures: a Prospective Randomized Non-Inferiority Study 
VERSION DATE: Version 3, 4/28/2020
2.0  Background 
Significance of Research Question/Purpose:  The Westmed Inc Anapod system used a 
humidified warming unit that is located within the anesthesia breathing circuit.  The 
manufacturer has supported studies to evaluate the performance of the Anapod Humi-
Therm Heated Humidification System Breathing Circuit in adult subjects.  But while the 
system is being used nationwide in pediatric populations, there have been no studies in 
pediatrics, nor studies evaluating its performance compared to another well-established 
warming method (i.e. forced-air warming blanket). 
Preliminary Data: The Anapod Humi-Therm Heated Humidification System Breathing Circuit 
has been evaluated in three studies  
 
Seo et al., Effect of electrically heated humidifier on intraoperative core body 
temperature decrease in elderly patients: a prospective observational study, 
Anesthesiology and Pain Medicine 2016; 11: 211-216 
 
Kaneyuki et al., A comparison of the effectiveness of transtracheal heating and 
humidification system in maintaining body temperature during general anesthesia 
with low flow gases, Masui. 2001 Jan;50(1):76-9 
 
Bean et al., Active Humidification and Perioperative Temperature Regulation Using a 
Novel Heated Airway Circuit after Deep Hypothermic Circulatory Arrest, Society for 
Cardiovascular Surgery Annual Meeting poster, 2017).  
All three of these studies demonstrated that the Anapod system was capable of preventing the 
development of intraoperative hypothermia.   However, as noted, there are no studies 
evaluating the device in the pediatric population, nor have any of the aforementioned 
studied compared the Anapod system to other warming methods currently in use.  
Existing Literature:  
See above 
 
Page  of 
 
Revised: April 19, 2017
7
21

PROTOCOL TITLE: Anapod™ Humi-Therm Heated Humidification System Breathing Circuit versus Bair 
Hugger™ Warming Blanket for Intraoperative Maintenance of Body Temperature in Pediatric Patients Undergoing 
Dental Procedures: a Prospective Randomized Non-Inferiority Study 
VERSION DATE: Version 3, 4/28/2020
3.0  Outcomes 
Primary Endpoint/Outcome: Last measured core temperature at conclusion of the procedure 
(measured with rectal temperature probe) in patients assigned to the two warming systems. 
Secondary Endpoint/Outcomes: 
 
The need for hyperthermic or hypothermic rescue (see Section 5.0 for further explanation) 
 
Cummulative degree-minutes above and below 37oC in the two treatment groups (based 
on both 3M SpotOn and rectal temperatures. 
Correlation of intraoperative 3M SpotOn temperature values with rectal temperatures. 
 
Page  of 
 
Revised: April 19, 2017
8
21

PROTOCOL TITLE: Anapod™ Humi-Therm Heated Humidification System Breathing Circuit versus Bair 
Hugger™ Warming Blanket for Intraoperative Maintenance of Body Temperature in Pediatric Patients Undergoing 
Dental Procedures: a Prospective Randomized Non-Inferiority Study 
VERSION DATE: Version 3, 4/28/2020
4.0  Study Intervention(s)/Investigational Agent(s) 
Description: This study will utilize the Anapod™ Humi-Therm Heated Humidification System 
Breathing Circuit from WestMed,and compare its efficacy in maintaining a patient’s body 
temperature with an established warming method (Bair Hugger™ Warming Blanket). 
Drug/Device Handling: The Anapod™ Humi-Therm Heated Humidification System Breathing 
Circuits will be stored in a separate section in the anesthesia equipment room. They will 
be clearly labeled “research use only, not for routine patient care”. Anesthesia aides will 
set up the breathing circuit for study patients as directed by the study coordinator.  
IND/IDE:   N/A 
Biosafety: N/A  
 
Page  of 
 
Revised: April 19, 2017
9
21

PROTOCOL TITLE: Anapod™ Humi-Therm Heated Humidification System Breathing Circuit versus Bair 
Hugger™ Warming Blanket for Intraoperative Maintenance of Body Temperature in Pediatric Patients Undergoing 
Dental Procedures: a Prospective Randomized Non-Inferiority Study 
VERSION DATE: Version 3, 4/28/2020
5.0 Procedures Involved 
Study Design: Prospective randomized non-inferiority study comparing Anapod™ Humi-
Therm Heated Humidification System Breathing Circuit versus Bair Hugger™ Warming 
Blanket 
Study Procedures: The study participants will be randomized to one of the following 
temperature management groups: 
 
Group 1.) Anapod™ Humi-Therm Heated Humidification System Breathing Circuit, with 
a starting circuit temperature set at the standard 45°C (note, this is temperature at the unit - 
NOT the temperature of the gas reaching the trachea).   
 
Group 2.) Bair Hugger™ Warming Blanket with a starting temperature set at HIGH 
 
All aspects of anesthetic care will be as per routine except that a second temperature 
recording device will be used (3M SpotOn™ Forehead Temperature probe, used routinely 
in the operating rooms and postoperative recovery areas) in addition to the standard rectal 
thermister probe.  In both groups, both Anapod™ and a BairHugger™ systems will be 
placed and ready for use prior to the induction of anesthesia.   Randomization will occur 
immediately after anesthetic induction and endotracheal intubation. 
 
For Group 1.), the BairHugger™ blanket will be connected a warming unit, but the unit 
will not be turned on.  Patient warming will be provided via the Anapod™ system. In the 
event that the patient’s rectal temperature falls below 35.6°C (96.08F), the BairHugger™ 
warming system will be activated ("Hypothermic Rescue").  In the event that rectal 
temperature increases to a value of ≥37.5°C (99.5), the Anapod system will be turned off - 
and the BairHugger turned on with the warming unit set to "ambient" (meaning cool 
operating room temperature will be blown over the patient ("Hyperthermic Rescue"). 
 
For Group 2, the BairHugger™ unit will be attached to the warming unit and started as 
soon as possible.  In the event that the patient’s rectal temperature falls below 35.6°C, the 
Anapod™ warming system will be activated ("Rescue").  In the event that rectal 
temperature increases to a value of ≥37.5°C (99.5°F), the BairHugger™ warming unit will 
be set to "ambient" (meaning cool operating room temperature will be blown over the 
patient ("Hyperthermic Rescue"). 
All drugs and devices required for participation:   
A standard Bairhugger™ warming unit, an Anapod™ Humi-Therm Heated 
Humidification System Breathing Circuit, and two temperature measurement systems 
(rectal and SpotOn forehead) 
 
Page 
 of 
 
Revised: April 19, 2017
10
21

PROTOCOL TITLE: Anapod™ Humi-Therm Heated Humidification System Breathing Circuit versus Bair 
Hugger™ Warming Blanket for Intraoperative Maintenance of Body Temperature in Pediatric Patients Undergoing 
Dental Procedures: a Prospective Randomized Non-Inferiority Study 
VERSION DATE: Version 3, 4/28/2020
Data to be collected about participants and the source records that will be used to collect those 
data:    
From Epic: MRN, Name, Date of birth, Date of procedure, Height, Weight, procedure 
performed, and procedure duration.  Preop Temperature (in preop area),  Initial post-
induction temperature (both rectal and SpotOn), final rectal and SpotOn temperatures 
prior to leaving the OR - as well as all rectal and SpotOn™ temperatures recorded 
intraoperatively, first PACU temperature (SpotOn only)   Note:  patient temperature 
data are recorded every minute in the Epic Anesthesia system and will be extracted 
from the record by manual record review.   
Directly Collected (via research Case Report Forms):  Warming device set-points, Rescue 
interventions (time and temperature when the rescue protocols are initiated. 
Individually Identifiable Health Information:  See above.  PID including name, MRN, and 
other demographic information including date of procedure will be collected.   
HIPPA Agreement:  Attached 
Use of radiation: None 
Use of Center for Magnetic Resonance Research: N/A  
 
Page 
 of 
 
Revised: April 19, 2017
11
21

PROTOCOL TITLE: Anapod™ Humi-Therm Heated Humidification System Breathing Circuit versus Bair 
Hugger™ Warming Blanket for Intraoperative Maintenance of Body Temperature in Pediatric Patients Undergoing 
Dental Procedures: a Prospective Randomized Non-Inferiority Study 
VERSION DATE: Version 3, 4/28/2020
6.0  Data and Specimen Banking 
Specimen Banking: N/A 
Data Banking: See above for all collected data.  See below for data and data form handling 
7.0 Sharing of Results with Participants 
None 
8.0 Study Duration 
Individual Subject Participation Duration: For the duration of the dental procedure (typically 
1-6 hours), from induction until discharge from the hospital. 
Total Study Duration (all Participants): about 2 years 
Total Study Duration Including Data Analysis: about 2.5 years 
9.0 Study Population 
Inclusion Criteria: Pediatric patients (ages 0-18 years) undergoing elective, scheduled 
dental procedures at Masonic Children’s hospital requiring general anesthesia with 
endotracheal intubation, anticipated to last a minimum of 1hr. Procedures may 
include dental x-rays, dental exams, dental extractions, dental filling and dental 
restorations. Eligible procedures may last up to 6hrs or longer.  
Vulnerable Populations:  Children, Children with developmental delay, Children with 
behavioral disorders  
Exclusion Criteria:  
•
Parent refusal of consent 
•
Patient refusal of assent (if applicable) 
•
Additional procedures (combined procedures) that involve other specialties 
besides dentists and other parts of the patient's body other than the oral cavity.  
•
History of diseases associated with temperature dysregulation (active 
hyperthyroidism, dysautonomia, osteogenesis imperfecta, history of malignant 
hyperthermia) 
•
Patients that will not be intubated for the procedure 
Screening: Patients will be seen in dental clinic and scheduled for a dental procedure in the 
operating room. We will inform the dental clinic staff and make flyers available to 
patient families (flyer attached), which will introduce them to our study. Patients will 
be identified before the procedure by either the participating anesthesiologists or 
 
Page 
 of 
 
Revised: April 19, 2017
12
21

PROTOCOL TITLE: Anapod™ Humi-Therm Heated Humidification System Breathing Circuit versus Bair 
Hugger™ Warming Blanket for Intraoperative Maintenance of Body Temperature in Pediatric Patients Undergoing 
Dental Procedures: a Prospective Randomized Non-Inferiority Study 
VERSION DATE: Version 3, 4/28/2020
research team by review of the posted operating room schedule (specifically by 
identifying the dental procedure list and the planned procedure). The research assistant 
responsible for discussing the research and obtaining the consent will call the patient’s 
family the day before the procedure and determine whether they will consider 
participation.  If the family expresses a willingness to consider participation, the 
research assistant or anesthesiologist will meet with the family on the day of the 
procedure to obtain consent and answer any additional questions.  
 
Page 
 of 
 
Revised: April 19, 2017
13
21

PROTOCOL TITLE: Anapod™ Humi-Therm Heated Humidification System Breathing Circuit versus Bair 
Hugger™ Warming Blanket for Intraoperative Maintenance of Body Temperature in Pediatric Patients Undergoing 
Dental Procedures: a Prospective Randomized Non-Inferiority Study 
VERSION DATE: Version 3, 4/28/2020
10.0  Vulnerable Populations 
Vulnerable Populations 
☒ Children 
☐ Pregnant women/Fetuses/Neonates 
☐ Prisoners 
☐ Adults lacking capacity to consent and/or adults with diminished capacity to 
consent, including, but not limited to, those with acute medical conditions, 
psychiatric disorders, neurologic disorders, developmental disorders, and behavioral 
disorders 
☐ Approached for participation in research during a stressful situation such as 
emergency room setting, childbirth (labor), etc. 
☐ Disadvantaged in the distribution of social goods and services such as income, 
housing, or healthcare 
☐ Serious health condition for which there are no satisfactory standard treatments 
☐ Fear of negative consequences for not participating in the research (e.g. 
institutionalization, deportation, disclosure of stigmatizing behavior) 
☐ Any other circumstance/dynamic that could increase vulnerability to coercion or 
exploitation that might influence consent to research or decision to continue in 
research 
☐ Undervalued or disenfranchised social group 
☐ Members of the military 
☒ Non-English speakers 
☐ Those unable to read (illiterate) 
☐ Employees of the researcher 
☐ Students of the researcher 
☐ None of the above 
Adults lacking capacity to consent and/or adults with diminished capacity to consent: None 
Additional Safeguards: N/A 
11.0  Local Number of Participants 
Local Number of Participants to be Consented: 256 
Basis for Sample Size Calculation:  Since the BairHugger is the most widely used 
intraoperative warming system in used today (at UMN and around the country), this study 
is based on examining the non-inferiority of the Anapod system vs the BairHugger.  A 
review of recent pediatric dental cases managed using the BairHugger shows an end-of-
case rectal temperature median of 37°C (98.6°F), with an IQR of (36.9°F-98.4°F)- 
37.3°(99.2°F); means and SD are comparable (with a 95% CI for the mean of 
36.9-37.1)98.7°F-.  However, general clinical practice does not demand this kind of tight 
 
Page 
 of 
 
Revised: April 19, 2017
14
21

PROTOCOL TITLE: Anapod™ Humi-Therm Heated Humidification System Breathing Circuit versus Bair 
Hugger™ Warming Blanket for Intraoperative Maintenance of Body Temperature in Pediatric Patients Undergoing 
Dental Procedures: a Prospective Randomized Non-Inferiority Study 
VERSION DATE: Version 3, 4/28/2020
control - and to construct a non-inferiority trial with a lower boundary of 36.9°C (98.4°F) 
would require an impossibly large sample size.  We have therefore selected a non-
inferiority boundaries of 0.3°C (32.54°F) , i.e. the Anapod would be considered "non-
inferior" to the BairHugger if the mean end-of case temperatures were ≥36.6°C (97.8°F).  
For these conditions, a total sample of 256 patients (128 per group) are required to achieve 
and alpha of 0.05 and beta of 0.8. 
12.0  Local Recruitment Methods 
Recruitment Process:  
Patients/families that are scheduled for procedures and willing to participate are invited to 
take part in the study.  The research team will make attempts to contact the child’s parent 
or guardian prior to the day of the procedure.  The research team which also includes 
dentistry personnel, Dr. Soraya Beiraghi will try and speak with the patient and their 
family to consent them for the study at their dental visit prior to the procedure.  If they 
decide to consent the dentistry staff will do so at that time. If they want to learn about the 
study at this visit and take the consent home for further consideration whether or not to 
participate, study personnel (from anesthesia) will  contact the parents by phone on the 
day prior to the procedure to discuss their willingness to participate. Formal consent will 
then  be obtained by direct conversation on the day of the procedure.  
In addition, we have created a handout about the study to provide families in the dental 
clinic prior to their child’s procedure.  The researchers (PI from Anesthesia and study team 
from anesthesia) will have their contact information available on the brochure.  Hopefully, 
they will have had time to review the handout and the consent so when the research team 
attempts to contact them before surgery, their questions will be answered.  We will review 
the study again on the day of surgery.   
Source of Participants: Dental surgery patients being performed on the West Bank of the 
University of Minnesota, Masonic Children’s Hospital . 
Identification of Potential Participants: Patients will be identified in dental clinic as far in 
advance as possible and  by daily review of the surgical schedules in Epic. 
Who will make initial contact with potential participants:   Again, the Research team members 
will make attempts by phone to contact the parent or guardian to describe the study prior 
to the date of the procedure. 
Recruitment Materials: Attached in Ethos 
Payment: None 
13.0  Withdrawal of Participants 
 
Page 
 of 
 
Revised: April 19, 2017
15
21

PROTOCOL TITLE: Anapod™ Humi-Therm Heated Humidification System Breathing Circuit versus Bair 
Hugger™ Warming Blanket for Intraoperative Maintenance of Body Temperature in Pediatric Patients Undergoing 
Dental Procedures: a Prospective Randomized Non-Inferiority Study 
VERSION DATE: Version 3, 4/28/2020
Withdrawal Circumstances:  Parents/Patients may withdraw from the study at any point prior 
to the induction of anesthesia by the principle investigator for any reason.   At this point, 
the parents possibly will not be present (in the OR) and the patient will be unconscious. If 
this is the case the research team will inform the family immediately.    
Withdrawal Procedures: Group randomization will take place immediately after anesthetic 
induction.  If a parent/patient withdraws after providing consent but prior to the induction 
of anesthesia and randomization, no further data will be collected (and any data forms 
started prior to induction will be destroyed).   
Termination Procedures: the Principle investigator has the right to terminate the study at any 
time during the study.                                                                                                                   
14.0  Risks to Participants 
Foreseeable Risks:  
Overall, the proposed study does not carry any identifiable risks for patients beyond those 
normally encountered with anesthesia and surgery.   Both the BairHugger and Anapod 
systems are approved for clinical use and are being used for their approved and marketed 
purposes.   There is a potential for both devices to result in unintended hyperthermia - but 
since body temperature is monitored and recorded continuously, and because Rescue 
Protocols are in place for all patients, body temperatures outside of the desired ranges 
(≤35.6°C and ≥37.5°C) will be prevented or corrected quickly.  NOTE:  this attention to 
close temperature maintenance EXCEEDS what is done during routine care.    
The Anapod™ Humi-Therm Heated Humidification System Breathing Circuit uses 
warmed, inspired air to warm the patient.  It is theoretically possible that the device might 
malfunction, resulting in excessively warmed inspired gases and airway injury.  However, 
the device has passed extensive safety testing and has built in safety systems (which shut 
down the warming system if excessive temperatures are noted).  The device will be used 
only in its FDA approved manner according to all manufacturer specifications and 
directions.  To date, no such failures have been reported to the manufacturer. 
Reproduction Risks: None 
Risks to Others: None 
15.0  Potential Benefits to Participants 
Potential Benefits: Participation will not have any direct benefit for the subject. 
  
 
Page 
 of 
 
Revised: April 19, 2017
16
21

PROTOCOL TITLE: Anapod™ Humi-Therm Heated Humidification System Breathing Circuit versus Bair 
Hugger™ Warming Blanket for Intraoperative Maintenance of Body Temperature in Pediatric Patients Undergoing 
Dental Procedures: a Prospective Randomized Non-Inferiority Study 
VERSION DATE: Version 3, 4/28/2020
16.0  Data Management 
Data Analysis Plan: Describe the data analysis plan, including any statistical procedures.   
 
Our primary outcome variable is the patient’s rectal temperature at the end of the surgical 
procedure.  Since this is a continuous and generally normally distributed variable, 
intergroup comparisons will be via a simple unpaired t-test. 
 
Our primary secondary variable will the incidence of hypothermia and hyperthermic 
rescue which will be compared between groups via a 2 x 2 Chi-Square Test (or depending 
on numbers, a Fisher's Exact Test) [Hypo and Hypothermic Rescue, Yes/No for the two 
groups). 
 
Cummulative degree-minutes below or above our target values are again expected to be a 
continuous, normally distributed value and hence can be tested by t-test. 
 
The relationships between rectal and Spot-on intraoperative temperatures will be 
examined by both correlation analysis (linear regression) and via a repeated-measures 
Bland-Altman method.   
Data Integrity: Objective data will be digitally collected from the EMR and extracted by 
members of the research team.  These extracted data, as well as protocol compliance and 
the incidence of Rescue interventions will be reviewed by the PI or Co-PI each week. A 
detailed review of all patients collected to date will be conducted in monthly intervals by 
the PI.  Group assignment will be blinded with the data set (Group A vs B) for review 
purposes - although it is important to note that true blinding of the providers (including on 
PI and Co PI) is impossible for this procedural study.   
17.0  Confidentiality 
Data Security: Only the core study team (PI, Co-PI, support personnel) will be handling PHI 
during the initial collection process.  Data will be collected on paper forms.  Each paper 
form will be given a code number.  When data are transferred into REDCap (for later 
analysis) ONLY this code number will be included. The PHI which might be connected 
with a specific patient (e.g name, MRN, date of surgery) will be placed in REDCap on a 
separate data sheet that will include the study number so that if necessary for data 
correction purposes we can go back and verify our data. The source documentation and 
consent documents (with identifying information) will be stored in a locked cabinet in the 
locked research office - accessible only to the core study team.  
18.0  Provisions to Monitor the Data to Ensure the Safety of Participants 
Data Integrity Monitoring:  
 
As noted above, a detailed review of all patients/patient data will be conducted at monthly 
intervals by the PI or Co PI, to insure that all required information is being captured 
correctly.   Any missing data or unexplained "out of range" data will immediately trigger a 
 
Page 
 of 
 
Revised: April 19, 2017
17
21

PROTOCOL TITLE: Anapod™ Humi-Therm Heated Humidification System Breathing Circuit versus Bair 
Hugger™ Warming Blanket for Intraoperative Maintenance of Body Temperature in Pediatric Patients Undergoing 
Dental Procedures: a Prospective Randomized Non-Inferiority Study 
VERSION DATE: Version 3, 4/28/2020
detailed review of the source data (Epic) and the RAs will be re-educated as to correct 
procedures to minimize the chance of recurrence.   The PI or Co PI will also review the 
Epic records of EACH patient to verify that the designated protocols were followed - in 
particular whether any "rescue" interventions were implemented correctly (i.e. at the 
correct trigger temperatures).    
 
Any adverse events occurring in any patient - whether or not related to the study or to 
temperature management - will be reported to the study team (or, if not reported, will be 
captured by case-by-case chart reviews).  An adverse event log will be maintained and 
events  will be reported to the IRB. If there is any question as to whether the event was 
related to the study, the case will be referred to Dr. Michael Todd, the Department of 
Anesthesiology's Vice Chair for Research and the Departments Quality Assurance Event 
monitor, for review and adjudication.  Dr. Todd will be empowered to temporarily halt 
enrollment if any safety concerns are noted - although the final decision re. halting or 
resuming the study will be referred to the Departments DSMB.   
Data Safety Monitoring:  The Department of Anesthesiology has a designated "DSMB" 
headed by Dr. Joyce Wahr and including Drs. Richard Prielipp and Michael Todd.  Given 
the low risk nature of this study, our plan is for the DSMB to receive blinded (A vs B) 
data after the completion of the 128th patient (the half-way point).   While statistical 
stopping rules for non-inferiority studies remain uncertain, we will use a well-established 
O'Brien-Fleming procedure and will stop the study if the SUPERIORITY of either 
method is established, based on an intergroup Z-score difference of 2.78.    
19.0  Provisions to Protect the Privacy Interests of Participants 
Protecting Privacy: Patients/ families will be provided written information about the study and 
contacted by phone to assess their willingness to participate, hence minimizing the amount 
of direct interaction until the decision is made to participate. The patient/ family will 
interact directly with the research assistant who will obtain consent and collect data. After 
the procedure is concluded, there is no planned additional follow-up. The collected 
information will be handled according to HIPPA rules and regulations as detailed before. 
As noted above, all data gathered in the course of the study, other than the paper forms 
completed at the time of surgery, will be coded and constructed in such a way as to 
eliminate all patient identifiers.   
Access to Participants: Review of the child’s Epic anesthesia record is required for the 
successful completion of this study. Patients/ families will be consented and will give 
permission for the research team to use specifically defined information. 
20.0  Compensation for Research-Related Injury 
In the event that this research activity results in an injury, treatment will be available, including 
first aid, emergency treatment and follow-up care as needed.  Care for such injuries will be billed 
 
Page 
 of 
 
Revised: April 19, 2017
18
21

PROTOCOL TITLE: Anapod™ Humi-Therm Heated Humidification System Breathing Circuit versus Bair 
Hugger™ Warming Blanket for Intraoperative Maintenance of Body Temperature in Pediatric Patients Undergoing 
Dental Procedures: a Prospective Randomized Non-Inferiority Study 
VERSION DATE: Version 3, 4/28/2020
in the ordinary manner to the subjects insurance. Under some circumstances the sponsor of the 
study will pay for care for injuries resulting directly from being in the study.  If the child’s parent 
or guardian  want information about those circumstances or if they think their child has suffered 
a research related injury let the study physicians know right away. 
21.0  Consent Process 
Consent Process:  Attempts will be made to try and contact the patients parents or guardian 
with written information prior to the procedure. The research team, which also includes 
dentistry personnel (Dr. Soraya Beiraghi and reseach staff) will try and speak with the 
patient and their family at the initial dental visit prior to the procedure.  If the parents 
decide to consent they will do so at that time. If they want to learn about the study at this 
visit and take the consent home to further evaluate whether or not to participate, study 
personnel (either from dentistry or anesthesia) will contact the parents by phone on the 
day prior to the procedure to discuss their willingness to participate. If the parents decide 
to participate, formal consent will be obtained by direct conversation on the day of the 
procedure. The study staff will explain the differences between the system we are studying 
and the standard of care (BairHugger).  We will have pictures of both systems to facilitate 
the discussion.  We will also emphasize that for patient safety, the study requires the 
placement of both systems at the beginning of the dental procedure so that the Bairhugger 
warming-blanket (standard of care) serves as a back-up in case the studied system is 
unable to maintain body temperature.  The randomization process will inform the 
physician which system will be used as a primary warming device.  The standard of care  
rectal temperature probe will also be placed in all children to monitor their temperature 
throughout the case.  If the system assigned is not performing optimally, the physician can 
choose to switch to the other system.  The research staff will be present and decisions will 
be thoroughly discussed; any changes will be documented in the subject’s chart.    
Waiver or Alteration of Consent Process:  N/A 
Non-English Speaking Participants: Patients with any primary language will be considered for 
inclusion, so long as there is a professional interpreter available for the consent process 
and other aspects of the study.  The study is not targeting any subjects that have a specific 
language.  The short form will be used if the subject is non-English speaking. 
Participants Who Are Not Yet Adults:  See above.  This is a pediatric study.  Ninety Percent of 
the dental cases performed under anesthesia are under the age of 7.  The capability of these 
children (taking into account the ages, maturity and psychological state of the children involved) 
is so limited that they cannot reasonably be assented.  For children aged 7 years and above, the 
majority of participants have neurodevelopmental conditions that impact cognition and behavior. 
They will be undergoing medically necessary dental procedures under anesthesia with parental 
consent, where child assent is not obtained. It is in our clinical judgment that to attempt to obtain 
 
Page 
 of 
 
Revised: April 19, 2017
19
21

PROTOCOL TITLE: Anapod™ Humi-Therm Heated Humidification System Breathing Circuit versus Bair 
Hugger™ Warming Blanket for Intraoperative Maintenance of Body Temperature in Pediatric Patients Undergoing 
Dental Procedures: a Prospective Randomized Non-Inferiority Study 
VERSION DATE: Version 3, 4/28/2020
assent for this study might cause the child unnecessary confusion, emotional upset and harm, 
when they have not been allowed to refuse the medical procedure itself. In these cases, we will 
obtain parental/LAR consent only, and document the underlying diagnosis. For the few cases 
where there is no neurodevelopmental condition, we will obtain child assent for the study  
Cognitively Impaired Adults, or adults with fluctuating or diminished capacity to consent:  
 Not Eligible 
Adults Unable to Consent: Not Eligible 
22.0  Setting 
Research Sites:  
o
Dental procedures are performed in the surgical suites at the University of 
Minnesota West Bank medical center (Masonic Children’s Hospital) 
o
Data analysis will be conducted in the Anesthesiology offices at the East Bank 
(Mayo building) and by the Department of Anesthesiology's statistician (Alex 
Kaizer PhD) 
23.0  Multi-Site Research  N/A  This study is only being conducted at the University of 
Minnesota 
24.0  Resources Available 
Resources Available: Research Assistants to aid in consent and data acquisition. 
Available Patients: During a typical week at the West Bank Medical Center, approximately 
10-20 qualifying patients undergo appropriate elective dental surgery.  Note however, that 
logistics will probably limit us to enrolling at maximum of 2 patients on any given day.   
Time to Devote:  We anticipate this will require approximately 10-20% effort on the part of the 
principle investigator.  This will also require 50% -75%effort of a research assistant’s 
effort. 
Describe your facilities: All procedures will be performed in the clinical facilities of M Health 
West Bank operating room arena. Data storage and analysis can be done using desktop 
equipment which is available in the Research Office located on the East Bank Mayo 
Memorial Building. This office is locked at all times with only research staff having 
access. Data will be stored on the university-supported secured Box cloud storage drive.  
Only the research staff and PI will have access to the Box.   
Describe your process to ensure that all persons assisting with the research are adequately 
informed about the protocol, the research procedures, and their duties and functions: RAs 
and other support faculty will be trained by the principle investigator (Kloesel) and the 
 
Page 
 of 
 
Revised: April 19, 2017
20
21

PROTOCOL TITLE: Anapod™ Humi-Therm Heated Humidification System Breathing Circuit versus Bair 
Hugger™ Warming Blanket for Intraoperative Maintenance of Body Temperature in Pediatric Patients Undergoing 
Dental Procedures: a Prospective Randomized Non-Inferiority Study 
VERSION DATE: Version 3, 4/28/2020
Co-PI (Belani). Training will include a review of the protocol, consent form and data 
collection forms as well as hands-on instructions on the used devices. 
25.0  References 
Seo et al., Effect of electrically heated humidifier on intraoperative core body temperature 
decrease in elderly patients: a prospective observational study, Anesthesiology and Pain 
Medicine 2016; 11: 211-216;  
Kaneyuki et al., A comparison of the effectiveness of transtracheal heating and humidification 
system in maintaining body temperature during general anesthesia with low flow gases, Masui. 
2001 Jan;50(1):76-9;  
Bean et al., Active Humidification and Perioperative Temperature Regulation Using a Novel 
Heated Airway Circuit after Deep Hypothermic Circulatory Arrest, Society of Cardiovascular 
Anesthesiologists annual meeting poster, 2017 
Sessler, DI. Perioperative thermoregulation and heat balance, Lancet 2016(387):2655-64 
Sessler, DI. Temperature Monitoring and Perioperative Thermoregulation, Anesthesiology 
2008(109):318 –38 
Kurz, A. Physiology of Thermoregulation, Best Practice & Research Clinical Anaesthesiology 
2008; 22(4): 627–644
 
Page 
 of 
 
Revised: April 19, 2017
21
21