Effect of Peri-intubation Apneic Oxygenation Via Nasal Cannula on Pediatric Patients' Oxygen Saturation During Airway Management
Phase: NA
Conditions: Hypoxia
Sponsor: University of New Mexico

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 HRPO Protocol  
1) 
Protocol Title (Version Date 21 Oct 2015) 
Effect of peri-intubation apneic oxygenation via nasal cannula on pediatric 
patients’ oxygen saturations during airway management. 
Brief title: Apneic Oxygenation during Airway management in pediatric 
patients. 
2) 
IRB Review History 
The HRRC reviewed this study on 2/10/2015, and after requested 
modifications were completed, the HRRC approved it on 4/17/2015.  A 
modification to add research assistants was reviewed and approved by the 
HRRC on 5/19/2015.  Post-approval monitoring was conducted by the 
HRPO on 10/21/2015. 
3) 
Objectives 
We hypothesize that apneic oxygenation via nasal cannula during airway 
placement improves oxygen saturation in pediatric patients.  Patients who 
receive this treatment will be compared to patients managed under the 
current standard of care, which does not include apneic oxygenation 
during anesthetic induction and airway management. 
The primary outcome is the elapsed time between anesthetic induction and 
pulse oximetry (SPO2) falling to 95%, if it happens at all. 
The secondary outcomes are as follows: 
- whether the 95% threshold is met at all 
- whether intervention by attending or temporary mask ventilation is 
required 
- whether pulse oximetry falls to 90% 
- the lowest observed pulse oximetry during airway placement 
    
4) 
Background 
This observational study aims to investigate the effect of a planned 
practice change; instituting oxygenation via nasal cannula during 
induction of anesthesia.  The use of a nasal cannula during the peri-
intubation period is of minimal risk and is not considered a standard of 
care in pediatric anesthesia.  Some providers use it in certain clinical 
situations, but it is not broadly used and has virtually no pediatric 
literature to support or refute its use. 
At our institution, intubation of pediatric patients by inexperienced 
(learner) providers under expert supervision is routine.  The attending 

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physician intervenes if necessary before the patient experiences excessive 
loss of oxygenation. 
There has been increasing discussion of nasal cannula apneic oxygenation 
in the adult anesthesia and emergency medicine literature, but there is a 
paucity of pediatric literature to support or refute its use in the pediatric 
population. Weingart and Levitan 2012, discuss how Apneic oxygenation 
is based on the physiology of the lungs absorbing a greater volume of 
oxygen, 250 ml/min in an adult, than the volume of carbon dioxide, 8-20 
mL/min, that is released by the lungs as the majority of carbon dioxide is 
buffered in the blood stream during apnea.  With the imbalanced volumes 
of absorption and release of gasses in the lungs there is a lower than 
atmospheric pressure in the lungs, creating a passive movement of gases 
from pharynx to alveoli.  If the gas in the pharynx has a significantly 
higher percentage of oxygen instead of room air at 21% oxygen, a higher 
amount of oxygen can be passively delivered to the lungs for absorption 
prolonging the time to hemoglobin desaturation. 
Taha et al 2006, concluded the use of nasal cannula insufflation after 
preoxygenation can delay the onset of hemoglobin desaturation for a 
prolonged period of time during the subsequent apneic period in adults. 
Ramachandran et al 2009, demonstrated the ability to prolong oxygen 
saturations >95% and increase the lowest saturation level with use of a 
nasal cannula at 5 L/min during simulated difficult intubations in adult 
obese males.  Weingart and Levitan 2012, recommend that nasal cannula 
apneic oxygenation can extend the safe apnea period after the use of 
sedatives and muscle relaxants in adults.  With a variety of search terms 
only three relevant articles were found in pediatric anesthesia literature.  
Bhagwan 2013, in Pediatric Anesthesia, commented about Levitan’s 
NoDesat article in EPmonthy 2012, endorsing how her use of the nasal 
cannula adjunct in the peri-intubation period has led to fewer desaturations 
and bradycardic episodes in infant intubations by resident physicians.  Her 
opinions were based on her experiences, but no data was gathered or 
presented to support the claims in a form representing a true study.  T.M. 
Cook 1998, wrote a paper discussing blood gas results during pediatric 
apneic oxygenation in intubated pediatric patients undergoing undergoing 
cardiac catheterization.  The findings demonstrated that apneic 
oxygenation was likely safe for up to 10 minutes before hypoxia would 
occur.  An earlier study by Kernisan et al 1987,  also studied apneic 
oxygenation in pediatric patients.  Patients were intubated and not 
ventilated and they found desaturation via pulse oximetry did not occur in 
patients at 3 minutes.    
Physiologically, children have a higher oxygen consumption than adults, 
5-10 mL/kg/min, compared to adults, 3mL/kg/min.  This high metabolic 
rate leaves pediatric patients at higher risk for hemoglobin desaturation in 
the peri-intubation period.  In a Hospital setting there can be prolonged 
time periods as airway devices are placed in certain patients.  The current 

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adult literature indicates that peri-intubation nasal cannula oxygenation 
can decrease the occurrence of hemoglobin desaturation during prolonged 
intubations.  There is some pediatric literature supporting the physiologic 
safety of apneic oxygenation for a brief period of time after endotracheal 
intubation.  Our adaptation of using a nasal cannula in the peri-intubation 
period would be new to the pediatric literature and would hopefully 
further elucidate the potential effects during the peri-intubation period and 
investigate whether this benefit also extends to pediatric patients.  There 
are anatomical differences in the pediatric airway compared to adults 
which may make the use of nasal cannula apneic oxygenation less 
beneficial in the pediatric population.  
This minimal risk study would add to the literature extending this concept 
to the pediatric patient population.  If the same results were to be found as 
in the adult patient population there is the potential for an improved less 
stressful pediatric intubation learning environment and improved patient 
care with fewer and less severe desaturations during the peri-intubation 
period. 
 
 
5) 
Inclusion and Exclusion Criteria 
The study population would be infants and children with adjusted 
gestational age of 40 weeks or greater to 8 years of age, scheduled for 
surgery at UNM.  Patients to be excluded would be premature infants with 
adjusted gestational age of less than 40 weeks, those undergoing mask 
ventilation, and patients with ASA class 4-6.  Enrollment would occur for 
up to six months after HRRC approval and study commencement. 
6) 
Number of Subjects (Recruitment Target) 
A sample size estimate based on prior studies of apneic oxygenation in 
adults indicates that approximately 400 subjects would be appropriate for 
this study, 200 in the baseline group without nasal cannula adjunct and 
200 patients with implementation of nasal cannula adjunct during the peri-
intubation period.   
A power analysis (based on formulae in Statistics in Medicine 1982; 
1:121-9) indicated that if the baseline rate of reaching 95% SPO2 is 15% 
of patients and this procedure reduces that rate by half, 80% power at 
α=0.05 is reached for a one-tailed logrank test with a total of 371 patients.  
Rounding up to 400 patients to accommodate incomplete datasheets would 
provide power of 94%. 
Based on enrollment rate to date, we estimate that enrollment of 400 
patients will take approximately one year.  Because the planned evaluation 
of routine use of nasal cannula adjunct oxygenation is occurring 
independent of enrollment counts to the baseline study condition, data 

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may be gathered on more than 200 patients in that group.  In order to 
permit analysis without loss of power, we may need to enroll a higher total 
sample size in order to achieve an equal sample size in the group with the 
cannula.  To accommodate this reality, we may enroll a maximum of 500 
patients in the entire study. 
This period will also permit education of all relevant providers and staff 
on the use of peri-intubation nasal cannula oxygenation. 
7) 
Recruitment Methods 
Investigators will recruit participants from among their own patients.  All 
patients who meet the inclusion/exclusion criteria will be enrolled.  We are 
requesting waiver of consent. 
8) 
Study Timelines 
 Duration of individual patient participation: Patients will 
participate from the time when they are brought into the OR 
preoperative suite and it is determined they will have an 
endotrachaeal tube (ET) or laryngeal mask airway (LMA) placed.  
The study observation period will end once the airway has been 
secured. 
 The duration anticipated to enroll all study subjects will be 
sufficient time to enroll the target sample of patients. 
 An interim analysis will be conducted halfway through enrollment 
of the with-cannula group. 
 The estimated primary analysis will be done by December 2016. 
9) 
Study Endpoints 
As this study is of minimal intervention and minimal risk, we do not 
anticipate early study termination for research-induced adverse outcomes.  
The planned intervention may be suspended or canceled after the interim 
analysis if it is ineffective, or if we reach statistical significance on the 
primary outcome halfway through collecting our estimated number of 
patients.  “Ineffectiveness” is defined here as a failure to identify one-
tailed superiority of the with-cannula group with p<0.20 on any of the 
outcomes (primary or secondary) at the interim analysis. 
10) Research Setting 
Data will be collected at the UNM hospital pediatric surgical suites. 
11) Study Methods  
This is a prospective observational study.  Prospectively-recorded data are 
necessary because data on the outcomes of interest are not available in the 
medical record. 
Participants will be enrolled in the study once they have entered the pre-
operative area and they are determined by the attending anesthesiologist to 

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that they are an eligible study participant.  Participants enrolled in the first 
three months of the study will be assigned to the baseline condition as 
described below.  Participants enrolled in the second phase of the study 
will be assigned to the with-cannula condition described below. 
A patient sticker will be added to the data collection form.  Basic 
demographic information and vitals will be recorded before premedication 
is administered as is standard at entry to the pre-operative area.  Timing 
devices of the same make and model will be used consistently between all 
study cases. 
   
For the baseline group of this observational study, all intubation 
procedures will be performed as per usual practice.  Patients will receive 
premedication as determined by anesthesiologist/resident/midlevel, and 
the type and dose will be recorded.  
Once patients are brought to the operating room suite and vital signs are 
being monitored, patients will be preoxygenated via mask per standard of 
care, with an expired oxygenation concentration minimum of 0.75. Vitals 
will be recorded at the moment prior to removal of the face mask at the 
end of the preoxygenation period.  Anesthetic induction will then be 
performed with agents and dosages as per the provider’s clinical 
judgment.   
Airway management consisting of oral endotracheal intubation or 
laryngeal mask airway insertion will take place.  As per usual practice, an 
attending physician who is expert in pediatric airway management will 
supervise the procedure and intervene before the patient experiences 
excessive oxygen desaturation.  The lowest oxygen saturation and the time 
to either successful intubation or intervention by an attending physician 
will be recorded.   
For the with-cannula group, all of the above steps will be maintained.  
The sole difference will be nasal cannula placement after induction.  It 
will be set to deliver 5L of oxygen per minute.   
Airway management consisting of oral endotracheal intubation or 
laryngeal mask airway insertion will take place.  As per usual practice, an 
attending physician who is expert in pediatric airway management will 
supervise the procedure and intervene before the patient experiences 
excessive oxygen desaturation.  The lowest oxygen saturation and the time 
to either successful intubation or intervention by an attending physician 
will be recorded.  Apneic oxygenation will not be used as a long-term 
oxygenation strategy.  No patient will be allowed to cross any particular 
SPO2 threshold solely for research reasons.  
All intubation procedures in both study groups will proceed as per usual 
practice.  The goal of all intubation procedures has always been and 
remains the maintenance of adequate oxygen saturation. 

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12) List of Appendices 
Data collection form  
 
13) Data and Specimen Banking 
Deidentified data will be retained indefinitely in electronic format after study 
completion.  This retention will be only for possible use in preparation for future 
studies involving one or more of the investigators on this study, such as to inform 
power analyses.  While future studies are not currently planned, they may include 
investigations of the optimal use of and indications for pediatric apneic 
oxygenation, for example.  All retained data will be stripped of all 18 HIPAA 
identifiers and stored on UNMHSC password-protected servers.  The paper data 
collection forms and link to identity will not be retained, but will be shredded upon 
study completion.   
 
14) Data Management 
Only study investigators will have access to study data.  Study participants will be 
assigned a study number, and this number will be used in all data analyses.  The 
data will be entered into an electronic database that will be stored on UNMHSC 
password-protected servers.  The electronic data will only have study participant 
numbers and no identifiers that could link specific patients to the data.  All data 
forms that bear identifiers will be securely destroyed (shredded) upon application to 
HRRC for study closure, so that only deidentified data remain when that application 
is made. 

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As noted above, data to be gathered include basic demographic data, data about the 
anesthetic induction procedure, and data about the patient’s O2 saturation. 
 
Routine demographic data will be analyzed with t-tests and Wilcoxon rank-sum 
tests, as appropriate depending on normality of data distributions.  Categorical data 
will be analyzed with appropriate analyses, such as chi-square, Fisher’s exact, risk 
ratio, and/or odds ratio. 
 
The primary outcome of time to cross the 95% saturation threshold will be analyzed 
with Kaplan-Meier curves and survival analysis with “censoring” for cases in which 
the threshold was not crossed because of either successful intubation or intervention 
by the attending physician. 
 
Secondary outcomes with continuous data (e.g. the lowest observed O2 saturation) 
will be analyzed with standard t-tests or Wilcoxon rank-sum tests, as appropriate 
depending on normality of data distributions.  Secondary outcomes with binary data 
(e.g. whether intervention by the attending physician is required) will be analyzed 
with chi-square or Fisher’s Exact tests as appropriate depending on cell counts.  
 
15) Provisions to Monitor the Data to Ensure the Safety of Subjects 
NA; this is a minimal-risk study.  Patients will receive either usual care or 
usual care with additional oxygen. 
16) Withdrawal of Subjects 
As we are requesting waiver of consent and HIPAA authorization, there 
will not be withdrawals from the study. 
17) Risks to Subjects 
This study has minimal anticipated risk beyond the standard medical 
treatment which they are already consented to undergo for reasons outside 
of the study.  The control group is simply an observation of the current 
standard of care, documentation of vitals at specific times, and airway 
management success.   
The with-cannula part of the study has minimal risk and an unknown 
likelihood of delivering a very small benefit (see Benefits, section 18) to 
the patients.  It is routinely used in other clinical settings.  Some pediatric 
patients wear a nasal cannula chronically in the home environment without 
significant complications.  Other children may wear a nasal cannula for 
days on an inpatient medical service.  Nasal cannula placement has a very 
low probability of causing harm to the nares, eyes or to interfere with the 
ET or LMA placement process. 
  The risk of a breach of confidentiality is minimal, as no data that are 
usually considered “sensitive” will be gathered and all identifiable data 
will be destroyed upon study completion.     

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18) Potential Benefits to Subjects 
Subjects in the with-cannula group may have a small potential benefit during the 
study as they may experience improved oxygenation during the ET or LMA 
placement period, but it is not known whether the planned intervention is effective 
at all.  This hypothetical benefit is low for the individual patient, as it springs from 
any improvement in oxygenation that may result.  This benefit is expected to be low 
for several reasons: 1) even in the no-cannula group (current practice), an attending 
physician who is expert in pediatric airway management is always ready to 
intervene before the patient’s oxygen saturation reaches dangerous levels: therefore 
any temporary reduction in blood O2 saturation that may be avoided in the with-
cannula group is mild; 2)the rates of mild SpO2 reduction during intubation are 
already very low, and 3) rates of complications from any brief mild SpO2 reduction 
are extremely low.   
 
19) Vulnerable Populations 
The research will involve children from the age of birth to the age of 8 
years.  Permission will not be sought from the parents or assent from the 
children as this study is of a minimal intervention and of minimal risk to 
the participants.  The planned transition to use of routine oxygen 
cannulation during intubation will not modify the participants’ degree of 
risk to a level above that of standard medical treatment.  The standard of 
care will simply be observed with the participants in the baseline group, 
and during the implementation of the peri-intubation adjunct nasal cannula 
(a device considered standard care in various other clinical settings and 
that poses no foreseeable significant risk to the patient) the same readily 
available data will be collected for comparison.   
 
20) Multi-Site Research 
NA.  
21) Community-Based Participatory Research/Field Research 
NA.  
22) Sharing of Results with Subjects/Incidental Findings 
Study participation periods will be so brief that results analyzed after the 
fact would have no positive or negative effect for the patient. 
23) Resources Available 
This project will be completed at the UNM Children’s Hospital, which 
serves a large pediatric surgical population.  The investigators include: 
Codruta Soneru, M.D., Assistant Professor, Faculty Physician, UNM 
Department of Anesthesia and Critical Care 

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Ricardo Falcon, M.D., Associate Professor, Faculty Physician, UNM 
Department of Anesthesia and Critical Care 
Jimmy Windsor, M.D., Associate Professor, Faculty Physician, UNM 
Department of Anesthesia and Critical Care 
Darren Braude, M.D., MPH, EMT-P, Professor, Faculty Physician, 
UNM Department of Emergency Medicine 
Hans Hurt, M.D., Resident Physician, UNM Department of Emergency 
Medicine 
Timothy Petersen, Ph.D., Research Coordinator, UNM Department of 
Anesthesia and Critical Care 
UNMCH has all of the required supplies, equipment, facilities, and staff to 
perform pediatric surgery and provide intubation of pediatric patients. 
24) Prior Approvals/Attachments Requiring Signatures 
The departmental review form is included with this submission. 
This study has been registered with clinicaltrials.gov, and assigned record 
number NCT02437864. 
25) Confidentiality 
See section 12.  The link to identifiers will only be maintained for the 
duration of this research study.  Only investigators will have access to 
identifiable study data.  The link to identifiers will be destroyed upon 
application to HRRC for study closure. 
26) Provisions to Protect the Privacy of Subjects 
The transition to routine oxygen cannulation during intubation is planned 
regardless of this project.  This project therefore does not modify patient 
experience in any way, and there is no research-related contact between 
investigators and patients or parents. 
27) Compensation for Research-Related Injury 
NA. As this is an observation of the standard of care there is no potential for 
research specific related injuries. 
 
28)  Economic Burden to Subjects 
There will be no economic burden to the study participants or to a 3rd party 
payer.  The cost of the pediatric nasal cannula (NC) is included in the 
hospital facility fee and will not be billed extra to the subjects.  The 
potential cost of the nasal cannulas for the intervention group is negligible 
as it is standard of care to have a NC or face mask available for patients 
during their post operative time to provide oxygen supplementation as the 
anesthetic wears off, and the NC used during the peri-intubation period 
can still be used for that patient after extubation. 

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29) Consent Process (including waiver request for HIPAA, waiver of 
HIPAA for recruitment only, Waiver of Informed Consent, and 
Alteration of Informed Consent) 
Waiver or Alteration of Informed Consent:   
We are requesting waiver of consent for this study.  This research is not 
FDA-regulated, and does not involve non-viable neonates.  As noted above, 
this project presents minimal risk to participants.  Similarly, the available 
literature does not clearly indicate whether the planned intervention offers 
any benefit to patients at all.   Patients’ experience and clinical care will not 
be modified by to a level outside of standard medical care in this study.  The 
use of a nasal cannula is standard care in multiple clinical settings and will 
simply be monitored in another aspect of clinical care.  The risk of breach of 
confidentiality presented by the recordkeeping in this study is similar to that 
of normal practice, because normal practice involves the production and 
maintenance of both routine medical records and supplemental Quality 
Assurance datasets.  The information to be recorded is not particularly 
sensitive, and will not pose risks to participant employability or insurability. 
Similarly, waiver of consent for this study will not adversely affect the 
rights and welfare of the subjects.  This study consists of recording routine 
clinical data during routine medical care.  These data are already recorded 
for both patient-care and healthcare operations purposes. 
This study could not practicably be carried out without the waiver because 
the validity of observational studies depends on data capture as close to 
100% as possible.  Anything else introduces the possibility of bias, which 
would invalidate the results.  Parents of children of certain ages, or with 
certain types of medical conditions, may be more or less likely than others 
to provide consent.  Since this study does not modify patient care beyond 
minimal risk, it would not be appropriate to provide participants with 
extraneous information after participation. 
Waiver of HIPAA authorization:    
The PHI to be used for this study is described above, and includes basic 
demographic data, data about the anesthetic induction procedure, and data 
about the patient’s O2 saturation.  Only the specific measurements made for 
the outcomes themselves are not already found in the medical record. 
As noted above, the study data will be kept in a locked cabinet in 
Anesthesiology department offices.  Identifiable data will only be available 
to study investigators, and will be maintained only to permit completion of 
data for any cases in which data collection was incomplete or unclear.  The 

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identifiable datasheets will be destroyed upon application to HRRC for 
study closure.  Deidentified data may be retained for use in the preliminary 
stages of future research, but identifiable PHI will not be reused or disclosed 
to any other person or entity, except as required by law, or for authorized 
oversight of the research study. 
As noted above for waiver of consent, this research could not practicably be 
conducted without the waiver of HIPAA authorization because study 
validity depends on near-100% data collection.  Attempting to obtain 
authorization would invite bias.  Similarly, the study could not be conducted 
without access to and use of the PHI because it is a study of medical care.  It 
would not be possible to evaluate the planned intervention without access to 
these data. 
 
30) Drugs or Devices 
 
Medical Devices:   
This study records data on the clinically-indicated use of a nasal cannula for 
delivery of oxygen.  An IDE application has not been submitted to the FDA.  
Nasal cannulas are FDA-approved for marketing, and they are being used in 
accordance with their labeling.  The nasal cannulas to be used for this study 
will be supplied and maintained as per usual UNMHSC practice   
 
References: 
Weingart SD, Levitan RM. Preoxygenation and prevention of desaturation during 
emergency airway management. Ann Emerg Med. 2012 Mar;59(3):165-75.e1. 
doi: 10.1016/j.annemergmed.2011.10.002. Epub 2011 Nov 3. Review. PubMed 
PMID: 22050948. 
 
Ramachandran SK, Cosnowski A, Shanks A, Turner CR. Apneic oxygenation 
during prolonged laryngoscopy in obese patients: a randomized, controlled trial 
of nasal oxygen administration. J Clin Anesth. 2010 May;22(3):164-8. doi: 
10.1016/j.jclinane.2009.05.006. PubMed PMID: 20400000. 
 
Taha SK, Siddik-Sayyid SM, El-Khatib MF, Dagher CM, Hakki MA, Baraka AS. 
Nasopharyngeal oxygen insufflation following pre-oxygenation using the four 
deep breath technique. Anaesthesia. 2006 May;61(5):427-30. PubMed PMID: 
16674614 
 

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Bhagwan SD. Levitan's no desat with nasal cannula for infants with pyloric 
stenosis requiring intubation. Paediatr Anaesth. 2013 Mar;23(3):297-8. doi: 
10.1111/pan.12114. PubMed PMID: 23384304. 
 
Cook TM, Wolf AR, Henderson AJ. Changes in blood-gas tensions during 
apnoeic oxygenation in paediatric patients. Br J Anaesth. 1998 Sep;81(3):338-
42. PubMed PMID: 9861115 
 
Kernisan G, Adler E, Gibbons P, Runions D. Apneic oxygenation in pediatric 
patients. Anesthesiology 1987;3:A521.