gender-linked difference in blood oxygen saturation · •the difference remained significant even...

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GENDER-LINKED DIFFERENCE IN BLOOD OXYGEN SATURATION Sagi Levental , Elie Picard , Francis Mimouni, Leon Joseph, Shmuel Goldberg

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Page 1: GENDER-LINKED DIFFERENCE IN BLOOD OXYGEN SATURATION · •The difference remained significant even after considering age, BMI and BSA and was not related to respiratory rate, body

GENDER-LINKED DIFFERENCE IN

BLOOD OXYGEN SATURATION

Sagi Levental , Elie Picard , Francis Mimouni,

Leon Joseph, Shmuel Goldberg

Page 2: GENDER-LINKED DIFFERENCE IN BLOOD OXYGEN SATURATION · •The difference remained significant even after considering age, BMI and BSA and was not related to respiratory rate, body

תלמידי ישיבה-הבדלי סטורציה בין ירושלים לרחובות

Page 3: GENDER-LINKED DIFFERENCE IN BLOOD OXYGEN SATURATION · •The difference remained significant even after considering age, BMI and BSA and was not related to respiratory rate, body

תלמידי ישיבה-הבדלי סטורציה בין ירושלים לרחובות

Page 4: GENDER-LINKED DIFFERENCE IN BLOOD OXYGEN SATURATION · •The difference remained significant even after considering age, BMI and BSA and was not related to respiratory rate, body

SaO2 is slightly higher in women than in

men (98.6 (SD 1.1)% versus 97.9 (SD

0.9)%; p = 0.001).

Page 5: GENDER-LINKED DIFFERENCE IN BLOOD OXYGEN SATURATION · •The difference remained significant even after considering age, BMI and BSA and was not related to respiratory rate, body
Page 6: GENDER-LINKED DIFFERENCE IN BLOOD OXYGEN SATURATION · •The difference remained significant even after considering age, BMI and BSA and was not related to respiratory rate, body

Analysis of Hypoxic and Hypercapnic

Ventilatory Response in Healthy

Volunteers

• 210 males, 332 females!

• No association was seen between HLA-DQB1*06:02 and

HVR or HCVR

Page 7: GENDER-LINKED DIFFERENCE IN BLOOD OXYGEN SATURATION · •The difference remained significant even after considering age, BMI and BSA and was not related to respiratory rate, body

Table 1. Baseline epidemiologic and physiologic data.

Goldberg S, Ollila HM, Lin L, Sharifi H, Rico T, et al. (2017) Analysis of Hypoxic and Hypercapnic Ventilatory Response in Healthy

Volunteers. PLOS ONE 12(1): e0168930. https://doi.org/10.1371/journal.pone.0168930

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0168930

Page 8: GENDER-LINKED DIFFERENCE IN BLOOD OXYGEN SATURATION · •The difference remained significant even after considering age, BMI and BSA and was not related to respiratory rate, body

Baseline epidemiologic and physiologic dataVariable Men

(n = 210)

Women

(n = 332)

p value *

Baseline respiratory rate (RR)

(breaths/min)

12.4 ± 4.6 13.4 ± 4.1 0.007

Baseline minute ventilation (MV)

(liters/min)

10.00 ± 3.43 8.08 ± 2.36 <0.001

RR/BSA (breaths/min/m2) 6.4 ± 2.8 7.9 ± 2.8 <0.001

MV/BSA (liters/min/m2) 5.14 ± 1.77 4.78 ± 1.46 0.016

Baseline SpO2 (%) unadjusted 96.6 ± 1.7 98.0 ± 1.3 <0.001

Baseline SpO2 (%) adjusted ¶ <0.001

Baseline EtCO2 (%) unadjusted 4.82 ± 1.02 4.65 ± 0.68 0.025

Baseline EtCO2 (%) adjusted ¶ 0.012

* p value is assessed as men versus women.

† Mean age from 542 participants, as data for age were missing from 9 participants.

‡ Data for gender were missing from 9 participants.

§ A total of 538 participants were tested for HLA-DQB1*0602, of whom 209 were men and 329 were women.

¶ Adjusted for age, ethnicity and BMI.

Page 9: GENDER-LINKED DIFFERENCE IN BLOOD OXYGEN SATURATION · •The difference remained significant even after considering age, BMI and BSA and was not related to respiratory rate, body

Table 3. Hypoxic (HVR) and hypercapnic (HCVR) ventilatory responses in males vs females.

Goldberg S, Ollila HM, Lin L, Sharifi H, Rico T, et al. (2017) Analysis of Hypoxic and Hypercapnic Ventilatory Response in Healthy

Volunteers. PLOS ONE 12(1): e0168930. https://doi.org/10.1371/journal.pone.0168930

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0168930

Page 10: GENDER-LINKED DIFFERENCE IN BLOOD OXYGEN SATURATION · •The difference remained significant even after considering age, BMI and BSA and was not related to respiratory rate, body

Hypoxic (HVR) and hypercapnic (HCVR)

ventilatory responses in males vs females.

Males Females P-value

HVR (liter/minute/%SpO2)

להפוקסמיהתגובה0.43±0.27

(n=170)

0.28±0.17

(n=251)

<0.001

HVR/BSA

(liter/minute/%SpO2/m2)

0.22±0.131

(n=169)

0.16±0.10

(n=249)

<0.001

HVR/BLMV (liter/minute/%

SpO2)/(liter/minute)

0.046± 0.035

(n=169)

0.040±0.04

2

(n= 251)

0.055

HCVR (liter/minute/%co2) 3.30±1.76

(n=125)

2.89±1.41

(n=236)

0.045

HCVR/BSA

(liter/minute/%CO2/m2)

1.74±1.06

(n=125)

1.71±0.87

(n=233)

0.713

HCVR/BLMV (liter/minute/%

SpO2)/(liter/minute)

להפרקרביהתגובה

0.368±0.335

(n=125)

0.497±1.61(n=236)

0.178

Page 11: GENDER-LINKED DIFFERENCE IN BLOOD OXYGEN SATURATION · •The difference remained significant even after considering age, BMI and BSA and was not related to respiratory rate, body

GENDER-LINKED

DIFFERENCE IN BLOOD

OXYGEN SATURATION

Page 12: GENDER-LINKED DIFFERENCE IN BLOOD OXYGEN SATURATION · •The difference remained significant even after considering age, BMI and BSA and was not related to respiratory rate, body

מבוא

חמצן בין נשים לגבריםבריוויוןלא ידוע אם יש הבדל •

עד היום נעשה רק מחקר אחד שמטרתו הראשונית הייתה להשוות •סטורציה בין המינים

• Ricart A, et.al. Sex-linked differences in pulse oxymetry. Br J Sports Med 2008

• women have a higher baseline SpO2 at rest (98.6% versus 97.9%).

של נשימהסטימולטורפרוגסטרון הוא •

עלית חום הגוף בחציו השני של המחזור החודשי יכולה להקטין את •ריוויון החמצן

גברים לנשים בגיל ( 1להשוות ריוויון חמצן בין -מטרות המחקר•בין ילודים ממין זכר ( 2הפוריות תוך התחשבות במחזור החודשי ו

.למין נקבה

Page 13: GENDER-LINKED DIFFERENCE IN BLOOD OXYGEN SATURATION · •The difference remained significant even after considering age, BMI and BSA and was not related to respiratory rate, body

שיטות

• We studied 2 cohorts of patients

• Young (18-40 years ) healthy adult volunteers.

• Newborns

• Adult female participants were given a menstrual cycle

questionnaire and classified as being in follicular, luteal, or

undetermined phase.

• Anthropometric variables, respiratory rate, pulse rate and

body temperature, were measured.

Page 14: GENDER-LINKED DIFFERENCE IN BLOOD OXYGEN SATURATION · •The difference remained significant even after considering age, BMI and BSA and was not related to respiratory rate, body

Pulse Oximetry Measurements

• Masimo Radical-7 motion resistant pulse oximeter

• on the index finger of the left hand, subjects' palm resting on a

table, and the radial artery free from compression

• rest in a sitting position for 5 minutes

• Using an averaging mode of 12 seconds, the measurements were

conducted for a period of at least 90 seconds after a stable and

sharp pulsatile pulse waveform appeared

• Perfusion index (signal quality index) was steadily > 1

• SpO2 value for each subject was determined by averaging the last

90 seconds.

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Newborn measurements

• Newborn measurements were obtained from a reanalysis

of data obtained in a previous study

• Newborns aged 25-67 hours who were born either at the

Shaare Zedek Medical Center or at the Lis Maternity

Hospital

• Only healthy, term, appropriate for gestational age

newborns of nonsmoking mothers were enrolled

• The measurements were performed consecutively on the

palm of the right hand (pre-ductal) and immediately

thereafter on the sole of the left foot (post-ductal).

Page 16: GENDER-LINKED DIFFERENCE IN BLOOD OXYGEN SATURATION · •The difference remained significant even after considering age, BMI and BSA and was not related to respiratory rate, body

Adults: Results: univariate analysisMales

(n=105)Females(n=102)

P-Value

Demographic Data

Age, years (±SD) 27.94 (5.61) 24.69 (5.02) <0.001

City of residency

Jerusalem 83 (79%) 84 (82.4%) 0.547

Other 22 (21%) 18 (17.6%)

BMI (±SD) 25.79 (3.81) 23.73 (4.24) <0.001

Measurements

Pulse Rate/min (± SD) 75.17 (11.37) 77.62 (10.9) 0.115

Respiratory Rate/min (±SD) 18.45 (3.61) 17.90 (3.60) 0.277

Body Temp. )C˚) )±SD) 36.71 (0.23) 36.74 (0.22) 0.372

SpO2 (%±SD) 97.154 (1.22) 98.619 (1.02) <0.001

Page 17: GENDER-LINKED DIFFERENCE IN BLOOD OXYGEN SATURATION · •The difference remained significant even after considering age, BMI and BSA and was not related to respiratory rate, body

(=102n(לעומת נשים ( =105n(מדידת סטורציה גברים

94

95

96

97

98

99

100

FemalesMales

Page 18: GENDER-LINKED DIFFERENCE IN BLOOD OXYGEN SATURATION · •The difference remained significant even after considering age, BMI and BSA and was not related to respiratory rate, body

90

91

92

93

94

95

96

97

98

99

100

0 20 40 60 80 100 120

Males Females

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Adults: Results : multivariate analysis

• The dependent variable: SpO2

• The independent variables were gender, BMI,

BSA and age

• Only gender remained significant in the final

analysis (p=0.002)

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menstrual phase and SpO2

• No correlation was found

• follicular phase:

• N= 32 (31.4%)

• mean SpO2: 98.83±0.91 %;

• luteal phase

• N=25 (24.5%)

• mean SpO2: 98.50±1.06%

• unidentified phase

• N=45(44.1%)

• mean SpO2: 98.54±1.07 %

• (p=0.380).

Page 21: GENDER-LINKED DIFFERENCE IN BLOOD OXYGEN SATURATION · •The difference remained significant even after considering age, BMI and BSA and was not related to respiratory rate, body

Newborn

infants

Males Females P-Value

Sea level:

n=80; 56 males (47%)

right hand (Pre

ductal)

98.26

(±1.38)

98.34

(±1.43)

0.81

left leg (Post ductal) 98.69

(±1.22)

99.11

(±1.02)

0.09

760 meters:

n=119; 43 males (53.75%)

right hand (Pre

ductal)

97.67(±1.7

1)

97.91(±1.50) 0.40

left leg (Post ductal) 98.23(±1.64) 98.55(±1.21) 0.22

Page 22: GENDER-LINKED DIFFERENCE IN BLOOD OXYGEN SATURATION · •The difference remained significant even after considering age, BMI and BSA and was not related to respiratory rate, body

Previous studies

• Study on patients in an emergency room that did not

exclude smokers, also found higher SpO2 in females

(0.7% higher in African American females and 0.6%

higher in white females). Witting et al. Am J Emerg2008

• Study of arterial blood gasses in healthy volunteers (10

men and 10 women) reported a higher mean arterial

oxygen tension in women than in men (99 mmHg versus

92 mmHg ) Andrews et.al. Am J Clin Pathol 1981

Page 23: GENDER-LINKED DIFFERENCE IN BLOOD OXYGEN SATURATION · •The difference remained significant even after considering age, BMI and BSA and was not related to respiratory rate, body

• A study that compared transcutaneous partial pressure of

oxygen (TcPO2) between the genders also found higher

values in females Orenstein A et.al Ann Plast Surg

Page 24: GENDER-LINKED DIFFERENCE IN BLOOD OXYGEN SATURATION · •The difference remained significant even after considering age, BMI and BSA and was not related to respiratory rate, body

summary

• In the young adult group, the average SpO2 in females was

1.47% higher than the average SpO2 in males.

• The difference remained significant even after considering age,

BMI and BSA and was not related to respiratory rate, body

temperature or the phase of the menstrual cycle in women.

• In newborns there was no difference in oxygen saturation

between genders.

ממחקרים קודמים אנחנו יודעים גם•

שלהם קטן יותרMVשלהם קטן יותר וגם TVאבל , נשים נושמות מעט יותר מהר •

•2COנמוך יותר בנשים

נמוכה יותר בנשיםלהיפוקסיהתגובה •

2COמתאמצות פחות ומצליחות יותר הן לחמצן והן להוריד -כלומר

Page 25: GENDER-LINKED DIFFERENCE IN BLOOD OXYGEN SATURATION · •The difference remained significant even after considering age, BMI and BSA and was not related to respiratory rate, body

Possible mechanisms

• Since we found that the difference does not exist in

infants, it is possible that age-related hormonal

differences are involved

• These hormones may have a direct effect on the central or

peripheral centers responsible for control of breathing or indirectly

inducing changes in the morphology and function of the respiratory

system

• Progesterone :

• No relative tachypnea in the female volunteers

• No any difference in SpO2 between women in different phases of

the menstrual cycle.

Page 26: GENDER-LINKED DIFFERENCE IN BLOOD OXYGEN SATURATION · •The difference remained significant even after considering age, BMI and BSA and was not related to respiratory rate, body

Possible mechanisms

• Dead space• Lower dead space would lead to more efficient breathing and

higher SpO2.

• Women have smaller conducting airways than men, even when matched for lung size

• A-a gradient: ?

• Hemoglobin affinity?

• Lower hemoglobin?• Low hemoglobin is associated with an increased level of 2,3 DPG

because of the lower oxygen carrying capacity of the blood, in a similar way to the condition at high altitude

• This shifts the oxyhemoglobin curve to the right, decreasing the affinity of oxygen to the hemoglobin and reducing the SpO2.

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Study limitations

• Lack of additional physiologic data

• Minute ventilation

• Dead space analysis

• A-a gradient calculation

• pO2

• Hemoglobin concentration

• Progesterone and testosterone concentrations.

• In addition, it is not clear whether differences measured in our

study performed in mild altitude are applicable to sea level.

Page 28: GENDER-LINKED DIFFERENCE IN BLOOD OXYGEN SATURATION · •The difference remained significant even after considering age, BMI and BSA and was not related to respiratory rate, body

Implementation and future direction

• If we define normal lower levels of SpO2 as 2 standard deviations below the mean, the lowest normal level of SpO2 in young adult healthy males at mild altitude is 94.7% and in females 96.8%.

• Thus, from a clinical standpoint, levels that are still normal in males may be consistent with disease in females.

מתבצע כרגע מחקר בילדי בית הספר •

מתוכנן מחקר במתנדבים בריאים לאחר גיל הפריון•

מתוכנן מחקר שמטרתו לבדוק אם יש הבדל בין המינים בתגובה •.להיפוקסיה