Determination of the Predictors of Nocturnal Desaturation in Postpartum Women
Phase: NA
Conditions: Sleep Disordered Breathing, Nocturnal Oxygen Desaturation, Upper Airway Edema
Sponsor: Massachusetts General Hospital

PARTNERS HUMAN RESEARCH COMMITTEE DETAILED PROTOCOL  
 
Title:  
Incidence of sleep-disordered breathing and upper airway collapsibility in postpartum 
patients and its intervention  
 
I.  
BACKGROUND AND SIGNIFICANCE  
Post-partum airway obstruction is a main cause of anesthesia related maternal 
death in North America. 
1 A significant decrease in oral volume and pharyngeal area 
after labor and delivery, as well as a potential impairment of upper airway dilator muscle 
control are mechanisms that likely contribute to a decrement in upper airway patency 
during and after labor. We aim to conduct a randomized controlled study to evaluate the 
effects of posture during the first post partum night on the incidence and severity of 
sleep apnea. In addition, we will further examine the anatomical and physiological risk 
factors that contribute to post-partum upper airway obstruction.  
Sleep-disordered breathing has been identified as an issue of national interest; 
the NIH has recently decided to request RO1 applications related to this topic (effective 
as of May 2011).  
 
The function of the upper airway  
The upper (supralaryngeal) airway is the pathway located between the 
nose/mouth and the base of the epiglottis
2. Its main function is not only to conduct air, 
but also to take part in other processes such as air conditioning (through warming and 
humidification), swallowing, speech and smell. The muscles in the upper airway 
comprise those of the external nares, soft palate, pharynx and larynx. Their function is 
to promote patency of the upper airway during inspiration, when the respiratory pump 
muscles evoke a negative pharyngeal pressure that puts the upper airway at risk of 
collapse in its retropalatal and retroglossal segments. The genioglossus, a fan-shaped 
muscle that runs dorsally from the ventral portion of the mandible to the tongue and 
protrudes the tongue when it contracts, protects the retroglossal part of the airway from 
collapsing during inspiration.  
While the activity in the chest-wall muscles increases progressively during 
inspiration and reaches its peak at or near the cessation of inspiratory flow, activity in 
the alae nasi, genioglossus and posterior cricoarytenoid starts rather abruptly, reaches 
its peak early after the onset of inspiration and declines well before cessation of 

inspiratory flow. Furthermore, the activity onset of these muscles usually precedes the 
diaphragmatic activity and, when negative pressure is applied selectively to the upper 
airway, a reflex increase in peak inspiratory activity and a greater lead time relative to 
the onset of diaphragmatic activity occurs. This pattern of contraction allows the upper 
airway to stabilize or dilate throughout the period when it is subjected to the negative 
intraluminal pressure produced by contraction of the inspiratory chest wall muscles. If 
the forces generated by the upper airway dilating muscles are not sufficient to oppose 
the negative intraluminal pressure, the upper airway will decrease in size and may 
collapse during sleep.  
 
Problems of airway change in parturients  
Dynamic changes in respiratory anatomy and physiology occur in the parturient 
3. 
Mucosal edema, hyperemia, capillary congestion, and fragility of the upper airway begin 
in the first trimester, persist throughout pregnancy, and peak in the third trimester. There 
is also gestational weight gain and decreased functional residual capacity in pregnant 
women. With labor, there is a significant increase in Mallampati airway classification 
score 
4 and there is a well-documented reduction in the oropharyngeal volume following 
delivery 
3. These anatomic and physiologic changes may place the parturient at 
increased risk for sleep-disordered breathing and upper airway obstruction. Sleep-
disordered breathing and upper airway collapsibility 
5 are important causes of 
respiratory distress. Peripartum patients may be at particular risk for these 
complications. A review of anesthesia-related maternal deaths in Michigan from 1985 to 
2003 identified five deaths resulting from airway obstruction or hypoventilation after 
general anesthesia, and this was the leading cause of anesthesia-related maternal 
mortality 
1.  
While it is recognized that parturients may have an elevated risk for sleep- 
disordered breathing and upper airway obstruction 
3, there are is little data regarding the 
incidence and risk factors for these disorders during the peripartum period. Parturient 
are frequently exposed to neuraxial and systemic narcotics, both of which may interact 
synergistically with sleep-disordered breathing to cause respiratory complications. 
Therefore, understanding the magnitude of the risk of airway obstruction and respiratory 
failure has important implications for monitoring in the peri-delivery period. We have 
previously conducted a research study evaluating the postoperative upper airway 
obstruction by quantifying its incidence
6.  
The absolute risk of death particularly without general anesthesia is low, but 

airway size is decreased in parturients, increasing the risk for temporary sleep apnea 
during pregnancy in some patients.  
Posture strongly predicts airway collapsibility during sleep and anesthesia.
7,8 
Recently it has been observed that postural changes from supine to sitting significantly 
improve collapsibility of the pharyngeal airway. Therefore, we hypothesize that a 45 
degrees bed head elevation in parturients after delivery stabilizes the airway patency 
and consequently prevents nocturnal deoxygenation. We believe that the insights 
gained from these studies may lead to novel strategies to improve the safety of peri- 
partum patients presenting with airway obstruction, and eventually reduce the morbidity 
and mortality of postpartum patients.  
 
II.  
SPECIFIC AIMS  
Aim 1 To compare respiratory outcomes in post-partum women on 45 degrees bed 
head elevation or supine (flat) position to determine its association with changes on the 
Apnea-Hypopnea Index (AHI) and Oxygen Desaturation Index (ODI) within 48 hours 
and after 3-6 months post-partum.  
 
Aim 2 To further elucidate the anatomical and physiological risk factors that contribute in 
the upper airway obstruction in post-partum patients compared with healthy female 
volunteers.  
 
III.  
SUBJECT SELECTION  
Inclusion criteria:  
Postpartum mothers within 24 hours of delivery, over 18 years old.  
 
Inclusion Criteria for Control Group:  
Healthy female volunteers, between 20- 40 years  
 
Exclusion criteria:  
1. Age under 18 years.  
2. History of pre-existing pulmonary and cardiac diseases, including bronchial asthma, 
cystic fibrosis, chronic obstructive lung disease, neck and chest tumors (thyroid, 
mediastinal, etc.), and congenital airway deformities.  
3. Stillbirth, child in NICU or maternal ICU admission, remaining on “Labor and Delivery” 
floor for bleeding monitoring or preeclampsia.  

4. In case of C-section delivery, mother will be excluded from the tests involving 
respiratory effort monitoring through abdominal belt.  
 
IV. SUBJECT ENROLLMENT  
We anticipate recruiting a total of 260 subjects. Written, informed consent will be 
obtained by co-investigators after subjects/health care proxy have considered the study 
consent form and detailed explanation of the study purpose, procedures, risks and 
discomforts. Consent will be obtained not earlier than 2 hours after delivery and until 10 
PM of the same day. We will enroll patients from Ellison 13 and Blake 13.  
 
V. STUDY PROCEDURES  
In the first part of the study, upper airway patency during inspiration was 
assessed by spirometry, with the ratio of the maximum expiratory and inspiratory flow at 
50% vital capacity (MEF50/MIF50 ratio). This variable that can be used to detect dynamic 
inspiratory flow limitation, defined as MEF50/MIF50 ratio greater than one
9-11. In addition, 
pharingometry was used to assess upper airway cross sectional area (CSA). Finally, 
apnea-hypopnea index (AHI) was evaluated with a standard monitor for conducting 
ambulatory PSG; this non-invasive monitor (Alice PDX, Respironics, Inc) measures 
pulse oximetry, respiratory flow, and respiratory effort (respiratory belt movements). 
Spirometry and pharyngometry were measured on the evening, and on the morning 
after the first post-partum night. PSG was taken during the first night post-partum. If the 
patient is deemed to have significant sleep apnea, a letter was written to inform the 
patient of this result and to consider further testing by her primary care provider. The 
first part of the study has been already finished.  
 
In the second stage of this study, we will test an additional group of 100 subjects 
with a wrist worn pulse oximeter to calculate their Oxygen Desaturation Index (ODI) and  
estimate the content of oxygen in their blood while they are sleeping either in a supine 
position or at 45 degree bed head  
elevation.  
 
Experimental design:  
Patient condition (Table 1)  
The information listed in Table 1 will be obtained at the time of enrolment, which 
is during 2-8 h after delivery.  
 

Table 1 
Demographic details  
Age  
 
Race  
 
Weight (on the day of admission)   
 
Pre-pregnancy weight  
 
Height  
 
BMI  
 
ASA physical status score  
Anatomical airway inspections  
Inter-incisor gap  
 
Thyromental distance  
 
Sternomental distance  
 
Neck Circumference  
Physical examination  
Vital Signs at 28-32weeks  
 
Vital Signs at admission  
Gestational age at delivery  
 
Allergies  
Latex, drugs, food, other allergies  
Social history  
Smoking (patient, family)  
Medications  
Tocolysis  
 
Magnesium therapy  
 
Beta blockers  
 
Betamethasone  

 
Other medications  
Mother complications  
HELLP  
 
Eclampsia 
 
Preeclampsia 
 
Gestational DM 
 
Anemia 
 
Recent upper respiratory infection  
Labor 
Length of labor (hours)  
The first stage begins with the onset of 
contractions that cause progressive 
changes in the cervix and ends when 
the cervix is fully dilated. This stage is 
divided into two phases: early (or latent) 
and active labor.  
During early labor, the cervix gradually 
effaces (thins out) and dilates (opens). 
During active labor, the cervix begins to 
dilate more rapidly and contractions are 
longer, stronger, and closer together. 
People often refer to the last part of 
active labor as "transition."  
The second stage of labor begins once 
the cervix is fully dilated and ends with 
the birth of the baby. This is sometimes 
referred to as the "pushing" stage.  
The third and final stage begins right 
after the birth of the baby and ends with 
the separation and subsequent delivery 

of the placenta. 
 
Induction  
 
CS following labor vs. CS without labor 
vs. vaginal 
Anesthetic management 
Neuraxial anesthetic (epidural vs. spinal 
vs. CSE)  
 
Neuraxial narcotics (medication, dose, 
route, time)  
 
General anesthesia  
 
Other 
Postoperative pain management  
Narcotics (medication, dose, route, 
time)  
 
Other  
Newborn outcome  
Gender  
 
APGAR scores at 0 and 5 min  
 
NICU admission 
 
IUGR  
Number of days hospitalized  
 
Methods:  
Aim 1: To compare respiratory outcomes in post-partum women on 45 degrees 
bed head elevation or supine (flat) position to determine its association with changes on 
the Apnea-Hypopnea Index (AHI) and Oxygen Desaturation Index (ODI) within 48 hours 
and after 3-6 months post-partum.  
This study will be performed in two stages. In the first part, a cross-over study 
was performed. Patients were randomly assigned to at least 2.5 hours on supine 
position or at 45 degrees bed head elevation during the first postoperative night.  

An overnight polysomnography (PSG) to measure the apnea-hypopnea index 
(AHI) was conducted. The AHI estimated the incidence of sleep disordered breathing in 
the night following delivery, and is calculated from pulse oximetry and capnography, a 
waist-bound respiratory belt to determine respiratory effort, and an EEG study. An 
ambulatory PSG device that has been designed to be self-applied by the patient prior to 
going to sleep will estimate the above-mentioned parameters. A research fellow, an 
anesthesia resident or Staff member set the device on the patient. All members of the 
obstetric anesthesia team were briefed on the study and a study team member will 
always be immediately available to answer any questions that the patient or the nursing 
staffs have about the study or the monitor. Whenever an obstruction in the upper airway 
was found, a letter to her primary care physician was mailed from Dr. Matthias 
Eikermann (see submitted document: OSA letter).  
 
In the second stage of this study, we will assess the Oxygen Desaturation Index 
(ODI) by means of a wrist-worn pulse oximeter (WristOx2 3150). The device probe will 
be placed on the index finger to measure the amount of oxygen in the blood during the 
night while the patient is sleeping supine or at 45 degree bed head elevation. The 
device will be placed by a research fellow, anesthesia resident, or an anesthesia staff 
member and it will not interfere with medical care, childcare, or self-care.  
 
Aim 2: To elucidate the anatomical and physiological risk factors that contribute 
in the upper airway obstruction in post-partum patients compared to healthy female 
volunteers.  
 
1. Upper airway patency during forced inspiration (MEF50/MIF50):  
MEF50/MIF50 is the ratio of maximal expiratory flow and maximal inspiratory flow 
at 50% vital capacity. MEF50/MIF50 is a variable derived from spirometry that can be 
used to detect dynamic inspiratory flow limitation
6,11 9-10). Upper airway obstruction will 
be defined as MEF50/MIF50 ratio greater than one ([MEF50/MIF50]>1)
6. Within 48 hours 
following delivery, we will measure three valid spirometric readings via face 
mask/mouth-piece; FEV1, FVC and MEF50/MIF50 will also be done at that time. Patients 
will be instructed to take deep breaths and forcefully exhale into the measuring device.  
 
2. Upper airway cross sectional area:  
To measure cross section area (CSA) of the pharynx, we will perform acoustic 

pharyngometry (EccoVision Acoustic Pharyngometer-E. Benson Hood laboratories, 
Pembroke, MA 
13 14,15) after the pulmonary function tests are completed. The device will 
be positioned in the mouth using a mouthpiece designed to secure the tongue in place. 
The pulse emitter will produce five pulses per second. Two microphones will detect the 
amplitude and temporal changes of the reflected pulse. Data will be collected and 
analyzed by a single investigator (research fellow). During the measurements, the 
subject's head position will be fixed.  
Upper airway-cross sectional area will be determined at end expiration as the 
mean area between the nasal and oropharyngeal junction (velum) and the glottis 
16. A 
standard adult mouthpiece will be used. Acoustic pharyngometry has been validated 
against CT scanning 
17 and MRI 
18 for assessment of the cross-sectional area in non- 
snorers and in snorers with and without OSA in both the supine and upright positions 
19- 
22. At least 4 curves will be obtained and will be considered valid if the CSA differed by 
10% or less.  
 
VI. BIOSTATISTICAL ANALYSIS  
Continuous variables will be compared by a two-sample, and paired- 
measurements t-test, as appropriate. Categorical variables will be compared by using 
Fisher’s exact test or Pearson's chi-square test. Data will be reported as mean (±SD), 
and P<0.05 will be considered statistically significant. The primary criterion is AHI, and 
comparisons will be made within an individual between two body positions. We powered 
the study for detecting changes AHI between body positions. As for power analysis, we 
expect based on the finding of Tagaito Y, and co-workers 
8. Accordingly, a sample size 
of 50 patients will provide a 90 per cent power to identify a difference between groups. 
We plan to conduct an interim analysis on 25 patients to make sure a potentially helpful 
intervention (elevated body position) will be provided to all patients in the case of clinical 
significance.  
 
VII. RISKS AND DISCOMFORTS  
There are no significant risks from the tests on this study. The investigation of the 
ability to swallow normally is part of the routine care in these patients. In addition, we 
will perform pulmonary function tests, grip strength measurement, and an acoustic 
pharyngometry test.  
1. Spirometry is not associated with any notable risk.   
2. Acoustic pharyngometry, overnight oximetry and respiratory effort monitoring are 

 not associated with any notable risk.   
3. Intervention (bed head positioning) is not associated to any notable risk, but the 
 pre-defined body position may induce some discomfort. In addition, the patient 
will be woken up once during the night in order to change the upper body position 
between supine and 45 degrees elevated.   
 
VIII. POTENTIAL BENEFITS  
Understanding the risk of sleep-disordered breathing associated with the 
peripartum period may help clinicians to determine which patients need monitoring 
following delivery with pulse-oximetry or other assessments to prevent respiratory 
complications. By investigating the beneficial effect of intervention (i.e. bed head 
positioning), we aim to eventually improve upper airway patency in our patient 
population.  
 
IX. MONITORING AND QUALITY ASSURANCE  
As our study is observational in nature, no formal quality assurance program 
needs to be implemented. In addition, any adverse events will be reported to the Human 
Research Committee for review.  
 
X. Flow sheet  
Stage 1:  
 
Part 1 (2-8 h after delivery): enrollment, vital signs recording.  
 
Part 2 (48 hours post-delivery): AHI, PSG and pharyngometry:  
 

 
 
 
 
 
 
 
 
 
 
 
 
*For the intervention we will apply a supine (flat)
23 or 45° semi-recumbent position 
24. 
**For the determination of AHI, overnight pulse oximetry, nasal pressure, abdominal 
wall motion and electroencephalography (EEG) will be measured in both Group A and 
Group B patients.  
*** After enrollment (for the control group)  
 
Stage 2:  
 
On the day after 
delivery, 5-10 PM 
***  
From 10 pm to 7 
am  
Morning after 
delivery  
Group A  
Screening for 
eligibility and 
consent form. 
Questionnaires 
(Epworth 
ODI evaluation 
with wrist-worn 
pulse oximeter, 
45° bed head 
elevation*  
Removal of the 
device, 
questionnaire 
(Quality of sleep 
score).  
 
 
On the day 
after delivery, 
5-10 PM ***  
 
From 10 pm 
to 1:30 am  
From 1:30 am 
to 5 am  
Morning 
after delivery  
**Group A  
MEF50/MIF50 
and upper 
airway cross 
sectional area  
PSG, 45° 
elevated*  
 
PSG Supine  
MEF50/MIF50 
and upper 
airway cross 
sectional 
area  
**Group B  
PSG, Supine  
 
PSG, 45° 
elevated *  
  
Control 
Group  
MEF50/MIF50 
and upper 
airway cross 
sectional area  
-----------------  
--------------- 
--------------- 
Follow up 
Group  
--------------------  PSG  
  
PSG 
 
----------------  

Group B  
Sleepiness Scale, 
Pittsburgh Sleep 
Quality Index)  
ODI evaluation 
with wrist-worn 
pulse oximeter, 
Supine  
   
 
 
    
Version 5  
 
 
 

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