Effect of Opioids on Ventilation in Children With Obstructive Sleep Apnea
Conditions: Respiratory Depression, Obstructive Sleep Apnea
Sponsor: Baylor College of Medicine

 
 
Institutional Review Board for Baylor College of Medicine and Affiliated Hospitals
 
Protocol Number:    H-45486
Status:                        Closed
Initial Submit Date:  4/2/2019
 
A1.  Main Title
     EFFECT OF OPIOIDS ON VENTILATION IN CHILDREN WITH OBSTRUCTIVE SLEEP APNEA
A2.  Principal Investigator
 
     Name:  
ADAM ADLER
Phone:  
832-824-5800
     Id:  
195273
Fax:  
     Department:  ANESTHESIOLOGY: BCM
Email:   
acadler@bcm.edu
     Center:  
Mail Stn:  BCM320
A3.  Administrative Contact
 
     Name:
KIMBERLY MAYFIELD
Phone:  
832-824-5800
     Id:  
160158
Fax:  
     
Email:   
kmayfiel@bcm.edu
     
Mail Stn:  BCM320
 
A4.  Co-Investigators
 
     Name:  
ARVIND CHANDRAKANTAN
Phone:  
832-824-5800
Id:  
195204
Fax:  
Department:  ANESTHESIOLOGY: BCM
Email:   
chandrak@bcm.edu
Center:  
Mail Stn:  BCM320
A5.  Funding Source:
     Baylor College of Medicine (Internal Funding Only)
A6a.  Institution(s) where work will be performed:
     TCH: Texas Children's Hospital
A6b.  Research conducted outside of the United States:
     
Country:  
Facility/Institution:  
Contact/Investigator:  
Phone Number:  
If documentation of assurances has not been sent to the Office of Research, please explain:
A7.  Research Category:
     
A8. Therapeutic Intent
Does this trial have therapeutic intent?
     Not set yet
 
A9. ClinicalTrials.gov Registration
 
B.  Exempt From IRB Review
     Not Applicable
 
     
Ventilatory suppression in children following opioid administration is of obvious concern, especially following routine surgical
procedures (i.e. adenotonsillectomy). It is thought that patients with obstructive sleep apnea (OSA) have increased sensitivity to
opioids, and especially in opioid naïve patients. Recent evidence in adults suggests that patients with moderate to severe OSA
may not predispose patients to increased opioid sensitivity in the form of respiratory depression when compared with patients that
do not have OSA. It is well known that OSA in children is significantly different from OSA in adults (e.g. gender predilection, central
vs. peripheral causation). The manifestation and etiologies are very different in pediatric OSA making it a vastly different disease
process. The aim of this study is to identify if children with known OSA experience opioid induced respiratory depression with
greater incidence then in children without OSA.
 
     
The sole objective in this study is to evaluate if routine amounts of opioids given for tonsillectomy in children have greater amounts
of respiratory depression in children with documented obstructive sleep apnea when compared with patients that do not have
obstructive sleep apnea
 
E1.  Risk Category
     Category 3: Research involving greater than minimal risk and no prospect of direct benefit to the individual subject, but likely to
yield generalizable knowledge about the subject's disorder or condition.
E2.  Subjects
Gender:
     Both
Age:
     Child (3-12 yrs), Infant/Toddler (0-36 mos)
Ethnicity:
     All Ethnicities
Primary Language:
     English, Spanish
Groups to be recruited will include:
     Asymptomatic patients with chronic conditions, healthy; Patients
Which if any of the following vulnerable populations will be recruited as subjects?
     Children
Vulnerable populations require special protections.  How will you obtain informed consent, protect subject confidentiality, and prevent
undue coercion?
     
Parents will be approached as ask to participate in the study. They will be informed that this is completely voluntary and that they
can choose to avoid participation and or revoke their participation at any point. Their participation or lack there of will not change or
alter the care their child will receive. The risks include loss to confidentiality and we will reduce this risk by only having the PI and
co-investigators collect data which will be stored only on the BCM firewall. Additionally, there is a risk of apnea with all opioids
however this risk is routinely managed by pediatric anesthesiologists and encountered in nearly all anesthetics.
E3.  Pregnant woman/fetus
Will pregnant women and/or fetuses (as described in 45 CFR 46 Subpart B) be enrolled in the research?
     No
E4.  Neonates
Will neonates of uncertain viability or nonviable neonates (as described in 45 CFR 46 Subpart B) be enrolled in the research?
     No
E5.  Children
Will children be enrolled in the research?
     Yes
 
F1.  Design
Select one category that most adequately describes your research:
     c) Pilot
Discuss the research design including but not limited to such issues as: probability of group assignment, potential for subject to be
randomized to placebo group, use of control subjects, etc.
     
The Principal and/or co-investigators will identify children meeting enrollment criteria from the daily operative list at Texas
Children's Hospital main campus. Those meeting enrollment criteria will be approached by the PI and or co-investigators. 
The study is a prospective randomized trial to identify the effect of opioids on children with obstructive sleep apnea
Inclusion Criteria:
     -Patients undergoing tonsillectomy or adenotonsillectomy at Texas Childrens Hospital main campus. -Ages 2 to 8 years -
Polysomnography with AHI >6 (study group) -Polysomnography with AHI =0 or negative OSA 15 questionnaire (control group)
Exclusion Criteria:
     
Ages >8 years Patients requiring pre-medication Parental refusal Opioid allergy/intolerance Patients requiring propofol for
intubation Patients with known or suspected difficult airway Obesity ¿ body mass index exceeding 30- (control group only) Known
cardiovascular disorders Known pulmonary disorders aside from asthma Patients with chronic oxygen requirement History of
Prematurity <35 weeks of gestation Personal of family history of malignant hyperthermia Recent Illness
F2.  Procedure
     
Patient Identification The Principal and/or co-investigators will identify children meeting enrollment criteria from the daily operative
list at Texas Childrens Hospital main campus. Those meeting enrollment criteria will be approached by the PI and or co-
investigators. 
Control Group: -Patients requiring tonsillectomy/adenotonsillectomy without suspected OSA Children presenting for tonsillectomy/
adenotonsillectomy for recurrent infection. Children with negative sleep studies will be included. Those without formal sleep studies
will be screened using the OSA 18 questionnaire, a validated clinical assessment score for pediatric sleep‐disordered breathing.
Those with negative questionnaire scores will be included. 
Study Group: -Patients with Moderate to Severe OSA as documented by formal polysomnography For the study group, patients will
be included if they have undergone formal sleep study evaluations. Stratification will be based on the polysomnography testing
using the apnea hypopnea index (AHI) and or the number desaturation events according to the McGill Scoring system for pediatric
OSA. Patients with AHI greater than 6 will be considered to have moderate to severe OSA and thus eligible for inclusion 
All patients will undergo general anesthesia per the usual practice at Texas Childrens Hospital according to the preferences of the
anesthesiology attending physician. Induction will be with sevoflurane+/-nitrous oxide followed by intravenous access securement.
Endotracheal intubation using a RAE endotracheal tube will be performed with the size selected using the formula: Predicted Size
Cuffed Tube = (Age / 4) + 3. Following endotracheal intubation, spontaneous ventilation will be maintained without the use of
continuous positive pressure. Sevoflurane will be reduced to maintain between 0.5-0.7 MAC according to the Drager Apollo
anesthesia machine. The patient will be allowed to establish their respiratory equilibrium for 3 minutes following intubation on
0.21% oxygen. Baseline tidal volume (TV), respiratory rate (RR) and end-tidal carbon dioxide (ETCO2) will be recorded. fentanyl
1mcg/kg will be administrated as a bolus (usual clinical practice). The TV, RR, ETCO2 will be recorded, at 5 and 10 minutes
following opioid administration. Apnea or desaturation <92%) will be treated by assisting ventilation as required (standard practice).
After 10 minutes,(to study a repeated dose effect) a second dose of 1/mcg/kg will be administered with the same TV, RR, ETCO2
recorded for 5 minutes. 
Surgery will commence as usual with additional medication to be administered at the discretion of the anesthesiology providers. No
change to standard practice will occur the research portion will be prospectively recording the TV, RR, ETCO2 following opioid
administration to calculate change from baseline (pre-opioid). routine fentanyl administration for these procedures is 2 mcg/kg
 
G1.  Sample Size
How many subjects (or specimens, or charts) will be used in this study?
     Local: 50              Worldwide: 50
Please indicate why you chose the sample size proposed:
     Our sample size is based on a recent 2019 landmark paper investigating a similar question in adults with obstructive sleep apnea
we propose to enroll 20 control patients and 30 patients with documented obstructive sleep apnea
G2.  Data Analysis
Provide a description of your plan for data analysis. State the types of comparisons you plan (e.g. comparison of means, comparison
of proportions, regressions, analysis of variance). Which is the PRIMARY comparison/analysis? How will the analyses proposed relate
to the primary purposes of your study?
     
The primary outcome will be measurement of continuous variables of tidal volume, respiratory rate and end tidal CO2. these will be
reported as means with SD. regression analysis will be performed for patients falling into the moderate and severe categories of
obstructive sleep apnea by sleep study.
 
Describe and assess any potential risks/discomforts; (physical, psychological, social, legal, or other) and assess the likelihood and
seriousness of such risks:
     
The risks include loss to confidentiality and we will reduce this risk by only having the PI and co-investigators collect data which will
be stored only on the BCM firewall. Additionally, there is a risk of apnea with all opioids however this risk is routinely managed by
pediatric anesthesiologists and encountered in nearly all anesthetics. 
There is no long term follow up or patient related efforts required to participate.
 
Describe potential benefit(s) to be gained by the individual subject as a result of participating in the planned work.
     There is no planned benefit for the patient enrolled
Describe potential benefit(s) to society of the planned work.
     the societal benefit is understanding the impact of opioids based on obstructive sleep apnea. The risk of opioid induced respiratory
depression can be significant and even lethal as it has been demonstrated repeatedly over recent years
Do anticipated benefits outweigh potential risks? Discuss the risk-to-benefit ratio.
     
This study is a risk category 3, moderate risk which in this case is apnea. The risks to the patient is apnea which occurs in nearly
all anesthetics and routinely managed by pediatric anesthesiologists. There is also the risk of loss of confidentiality which will be
minimized by limiting data access to those on the protocol only
 
J1.  Waiver of Consent
Will any portion of this research require a waiver of consent and authorization?
     NA
 
J1a.  Waiver of requirement for written documentation of Consent
Will this research require a waiver of the requirement for written documentation of informed consent?
     NA
J2.  Consent Procedures
Who will recruit subjects for this study?
     PI
PI's staff
Describe how research population will be identified, recruitment procedures, any waiting period between informing the prospective
participant and obtaining consent, steps taken to minimize the possibility of coercion or undue influence and consent procedures in
detail.
     
The PI and Co-investigator will identify patients prior to the day of surgery that meet inclusion/exclusion criteria.
Participants/parents will be approached in the preoperative area for potential enrollment. The study will be explained to the
participants parent/guardian and we will explain that all care will be standard regardless of their participation. They will be informed
that their participation is optional, and can be revoked at any time without penalty. They will also be informed that no cost is
associated with participation.
Are foreign language consent forms required for this protocol?
     Yes
Which of the following ways will you document informed consent in languages other than English?
     Short-Form consent documents
J3.  Privacy and Intrusiveness
Will the research involve observation or intrusion in situations where the subjects would normally have an expectation of privacy?
     No
J4.  Children
Will children be enrolled in the research?
     Yes
J5.  Neonates
Will non-viable neonates or neonates of uncertain viability be involved in research?
     No
J6.  Consent Capacity - Adults who lack capacity
Will Adult subjects who lack the capacity to give informed consent be enrolled in the research?
     No
J7.  Prisoners
Will Prisoners be enrolled in the research?
     No
 
Will research data include identifiable subject information?
     NA
Information from health records such as diagnoses, progress notes, medications, lab or radiology findings, etc.
     NA
Specific information concerning alcohol abuse:
     NA
Specific information concerning drug abuse:
     NA
Specific information concerning sickle cell anemia:
     NA
Specific information concerning HIV:
     NA
Specific information concerning psychiatry notes:
     NA
Demographic information (name, D.O.B., age, gender, race, etc.):
     NA
Full Social Security #:
     NA
Partial Social Security # (Last four digits):
     NA
Billing or financial records:
     NA
Photographs, videotapes, and/or audiotapes of you:
     NA
Identifiable biospecimens
     NA
Other:
     NA
At what institution will the physical research data be kept?
     NA
How will such physical research data be secured?
     NA
At what institution will the electronic research data be kept?
     NA
Such electronic research data will be secured via BCM IT Services- provided secured network storage of electronic research data
(Non-Portable devices only):
     NA
Such electronic research data will be secured via Other:
     NA
Will there be anyone besides the PI, the study staff, the IRB and the sponsor, who will have access to identifiable research data?
     NA
Please describe the methods of transmission of any research data (including PHI, sensitive, and non-sensitive data) to sponsors
and/or collaborators.
     NA
 
Will you obtain a Certificate of Confidentiality for this study?
     No
Please further discuss any potential confidentiality issues related to this study.
     the only risk to this study is potential loss of confidentiality which will be minimized by only using BCM/TCH behind the BCM firewall
using BCM Box and keeping all information with the PI and Con-investigator
 
Delineate clinical procedures from research procedures. Will subject's insurance (or subject) be responsible for research related
costs? If so state for which items subject's insurance (or subject) will be responsible (surgery, device, drugs, etc). If appropriate,
discuss the availability of financial counseling.
     none
If subjects will be paid (money, gift certificates, coupons, etc.) to participate in this research project, please note the total dollar amount
(or dollar value amount) and distribution plan (one payment, pro-rated payment, paid upon completion, etc) of the payment.
Dollar Amount:
     0
Distribution Plan:
     
 
How would you classify your genetic study?
     
Discuss the potential for psychological, social, and/or physical harm subsequent to participation in this research. Please discuss,
considering the following areas: risks to privacy, confidentiality, insurability, employability, immigration status, paternity status,
educational opportunities, or social stigma.
     
Will subjects be offered any type of genetic education or counseling, and if so, who will provide the education or counseling and under
what conditions will it be provided? If there is the possibility that a family's pedigree will be presented or published, please describe
how you will protect family member's confidentiality?
     
 
None
 
Does the research involve the use of ANY drug* or biologic? (*A drug is defined as any substance that is used to elicit a
pharmacologic or physiologic response whether it is for treatment or diagnostic purposes)
     No
Does the research involve the use of ANY gene transfer agent for human gene transfer research?
     No
O1.  Current Drugs
 
Is this study placebo-controlled?
     No
Will the research involve a radioactive drug?
     No
 
Does this study need an IDE?
     No
Regarding your device study, could potential harm to subjects be life-threatening?
     No
Regarding your device study, could potential harm to subjects result in permanent impairment of a body function?
     No
Regarding your device study, could potential harm to subjects result in permanent damage to a body structure?
     No
 
Research Study on Narcotics and sleep apnea
 
None
 
Section Aa:  Title & PI
Section Ab:  General Information    
Section B:  Exempt Request
Section C:  Background Information
Section D:  Purpose and Objectives
Section E:  Protocol Risks/Subjects
Section F:  Design/Procedure
Section G:  Sample Size/Data Analysis
Section H:  Potential Risks/Discomforts
Section I:  Potential Benefits
Section J:  Consent Procedures
Section K:  Research Related Health Information and Confidentiality
Section L:  Cost/Payment
Section M:  Genetics
Section N:  Sample Collection
Section O:  Drug Studies
Section P:  Device Studies
Section Q.  Consent Form(s)
Section R:  Advertisements