A Comparison of Pre-oxygenation Techniques in Pregnant Patients Prior to a Cesarean Delivery - A Randomized Clinical Trial
Phase: NA
Conditions: Preoxygenation
Sponsor: University of British Columbia

 
 
 
 
 
 
 
 
 
 
A Comparison of Pre-oxygenation Techniques in Pregnant Patients Prior to a 
Cesarean Delivery - A Randomized Clinical Trial  
 
NCT03310723 
10/23/2019 

Study Protocol and Statistical Analysis 
Study was approved by the University of British Columbia Children's and 
Women's Research Ethics Board  
Inclusion criteria: healthy, term (≥ 36 weeks gestation), non‐labouring parturients 
admitted for elective caesarean delivery or induction of labour  
Exclusion criteria: ASA physical status 3 or above; any medical condition that 
could affect gas exchange; BMI ≥ 40 kg/m2; known airway pathology; obstructed 
nasal airway; or unable to tolerate a tight‐fitting facemask. 
Microsoft Excel 2010 was used to generate a randomisation sequence with 1:1 
allocation to either HFNO or control groups.  
All patients were first placed in a 30‐degree head up position using the Troop™ 
(Goal Medical, LLC, Eugene, OR, USA) elevation pillow and with a right lateral 
pelvic wedge to minimise aortocaval compression. A nose clip was applied and 
each patient was asked to breathe 21% oxygen at 12 l.min−1 through a 
standardised mouthpiece using tidal volume breathing. The mouthpiece was 
connected to an anaesthetic circle system with a two‐litre reservoir bag, heat 
moisture exchange filter and an oxygen analyser. At the end of 30 s, baseline 
values for oxygen saturation, respiratory rate, heart rate and EtO2 were recorded. 
Patients in the standard oxygen flow rate facemask group (control) were then 
pre‐oxygenated with 100% oxygen, using tidal volume breathing and a tight‐fitting 
facemask attached to a circle system, with an oxygen flow rate of 15 l.min−1. End‐
tidal carbon dioxide waveform analysis was monitored to ensure a tight seal was 
achieved between the patient and the facemask. After 3 min, patients were asked 
to hold their breath for a few seconds and the nose clip was re‐attached. The 
patients then exhaled fully and continued to breathe for several breaths via the 
mouthpiece (delivering 21% oxygen) to ensure the highest value for EtO2 was 
measured. 
Patients in the HFNO group were pre‐oxygenated with 100% oxygen using tidal 
volume breathing and the Optiflow™ HFNO nasal high‐flow cannula system 
(Fisher and Paykel Healthcare Ltd, Auckland, New Zealand). The oxygen flow 
rate was initially started at 30 l.min−1and gradually increased to a maximum of 
70 l.min−1 over the first 30 s. If a patient did not tolerate the flow rate, it was 

Study Protocol and Statistical Analysis 
reduced to a level the patient could tolerate, typically 50–60 l.min−1. Patients were 
specifically instructed to breathe via their nose with a closed mouth and the 
percentage of time this was achieved was recorded (0%, 25%, 50% or 100%). 
After 3 min, the patients were asked to hold their breath for a few seconds while 
the HFNO was quickly removed and the nose clip re‐attached. The patients then 
exhaled fully and continued to breathe for several breaths via the mouthpiece 
(delivering 21% oxygen) to ensure the highest value for EtO2 was measured. 
Patients in both groups then underwent a washout period for up to 5 min until the 
EtO2returned to within 10% of their baseline value. Once washout was 
completed, both groups repeated 30 s of tidal volume breathing followed by eight 
vital capacity breaths using their respective pre‐oxygenation methods. During the 
initial 30 s of tidal volume breathing, the oxygen flow rate in the HFNO group was 
increased from 30 to 70 l.min−1 and EtO2 was measured at the conclusion of eight 
vital capacity breaths. The time taken to complete 30 s of tidal volume breathing 
and eight vital capacity breaths was also recorded. 
Immediately after the study, patient satisfaction was assessed using a 5‐category 
Likert scale for acceptability (acceptable, slightly acceptable, neutral, slightly 
unacceptable or unacceptable) and comfort (completely comfortable, slightly 
comfortable, neutral, slightly uncomfortable or completely uncomfortable).  
 
Outcomes 
The primary outcome was EtO2 after pre‐oxygenation, with factorial comparisons 
also being made between HFNO and standard flow rate facemask, and also 
between 3 min of tidal volume breathing and eight vital capacity breaths.  
The Secondary outcomes were the proportion of patients achieving an 
EtO2 ≥ 90%, percentage of time patients had their mouths closed during HFNO 
pre‐oxygenation and tolerability (comfort and acceptability) of both pre‐
oxygenation techniques. 
 
Sample Size Calculation 

Study Protocol and Statistical Analysis 
The study sample size was determined based on a prior study demonstrating that 
the mean (SD) EtO2 achieved following 3 min of pre‐oxygenation in healthy, non‐
pregnant subjects with HFNO and facemask was 85.6% (6.4%) and 88.5% 
(6.2%), respectively. We initially powered the study for a non‐inferiority 
comparison. The criterion for non‐inferiority with respect to EtO2 concentration 
achieved after 3 min was considered to have been met if the upper limit of a two‐
sided 95%CI for the absolute difference of EtO2 concentration between groups 
was less than 10%. Using a non‐inferiority design, assuming a non‐inferiority 
margin of 10 and a standard deviation of 6.3, and that the HFNO group would 
have a mean approximately 3% lower than the control group, 26 patients (13 per 
group) were required to achieve a power of 90% with a type‐1 error of 0.05. To 
account for attrition and study dropouts due to equipment errors (i.e. lack of a 
tight seal for waveform analysis), the sample size was increased to 40 (20 per 
group).  
After patient recruitment we realised that as a physiological and not clinical study, 
a standard superiority design was more appropriate. Using a superiority analysis 
with 20 patients per group there would have been approximately 31% power to 
detect a difference in means of 3% with a standard deviation of 6.3. 
Consequently, data for primary outcomes were analysed using mixed‐effects 
linear regression. Mixed‐effects models take into account the repeated‐measures 
aspect of the data and control for correlations among measurements from the 
same patient. To determine if there was a difference in how the treatment groups 
responded, we tested for an interaction term between group and time‐point. If a 
significant interaction was found, we followed it up with pairwise tests of the 
estimated marginal means between the groups at each time‐point (e.g. HFNO 
baseline vs. control baseline) using the Kenward–Roger method to estimate 
confidence intervals, and controlling for multiple comparisons using Tukey's 
method. The proportion of patients achieving an EtO2 ≥ 90%, comfort and 
acceptability was compared using Fisher's exact test. A p value < 0.05 was 
considered statistically significant. Statistical analysis was performed using 
RStudio version 1.0.153 (Integrated Development for R. RStudio, Inc., 
USA; http://www.rstudio.com) and R version 3.4.1, release date June 30, 2017 
(The R Foundation for Statistical Computing, Austria).