The Effects of the Menstrual Cycle on the Hemodynamic Response to

Laryngoscopy and Tracheal Intubation

We designed this study to determine the effect of the menstrual cycle on the
hemodynamic response to tracheal intubation (TI). Sixty-two ASA I women who were either in
the follicular phase (group ! n " #$) or luteal phase (group %! n = #$) of their menstrual cycle
were included in the study. &atients recei'ed propofol and rocuronium for intubation.
(emodynamic 'ariables were recorded before administration of the I) anesthetic! as well as
after TI. *ate pressure products were calculated. +roups were similar in terms of demographic
data. *ate pressure products 'alues at the first minute after TI were significantly increased in
group % than were those in group (P , -.--$). We conclude that the phase of the menstrual
cycle is an important factor in the hemodynamic response to TI. (Anesth Analg .-$-/$$$0#1.23)
(ormonal! physical! and psychological fluctuations occur during the menstrual
cycle.
$!.
Anesthetic! analgesic! and antiemetic re4uirements! and perception of pain and serum
noradrenaline le'els! can change during the different stages of the menstrual cycle.
$21
Tracheal
intubation (TI) stimulates somatic and 'isceral nocicepti'e afferents in the airway and can
significantly increase arterial blood pressure and catecholamine le'els.
526
(owe'er! to the best of
our 7nowledge! there are no studies addressing the effects of the phases of the menstrual cycle on
the hemodynamic response to TI. The hypothesis of our study was that the luteal phase of the
menstrual cycle results in an increased rate pressure product (*&&) after TI in comparison with
that in the follicular phase. To test this hypothesis! we chose times during the menstrual cycle at
which hormonal profiles are different from each other! the follicular and luteal phases. This
prospecti'e and double-blind study was done to e'aluate the effects of the follicular and luteal
phases of the menstrual cycle on the *&& response to TI.
89T(:;S
After obtaining appro'al of the hospital ethics committee and written informed
consent! 1. women! $< to =6 years old! ASA physical status I! scheduled to ha'e general
anesthesia with TI for electi'e surgery were enrolled in this study. 9xclusion criteria were the
presence of neurological or psychiatric diseases! difficulty of communication! history of
combined oral contracepti'e use! irregular menstrual cycle! amenorrhea! total abdominal
hysterectomy and>or bilateral salphingoopherectomy! pregnancy! anticipated difficult TI! body
mass index ?#- 7g>m.! inta7e of analgesics @.= hours before the operation! recei'ing
medications 7nown to affect arterial blood pressure and heart rate ((*)! and hypersensiti'ity to
the study drugs.
$!5
All patients were premedicated with -.-5 mg>7g I8 midaAolam $ hour before the
induction of anesthesia. Bpon arri'al in the operating room! a .--gauge I) cannula was inserted
into a 'ein on the dorsum of the hand! and an I) infusion of lactated *ingerCs solution was
started at a rate of 3 m%>7g>hr. The patients were assigned into . groups according to the phase
of their menstrual cycle. The patients who were on the $st to $.th days after the first day of their
last menstruation were considered to be in the follicular phase of the cycle and assigned to group
. Those on the .-th to .=th days after the first day of the last menstruation were considered to
be in the luteal phase of the cycle and assigned to group %. Decause luteiniAing hormone pea7s
on the $#th day and progesterone starts to increase at the $<
th
day of the menstrual cycle! patients
in the $#th to $6th days of their last menstruation cycles were excluded to better discriminate
between the follicular and luteal phases.
$!#!$-
Dlood progesterone le'els start to decrease on the .=th day of the cycle! so we also
excluded patients on the .=th or more day of their cycle! using the same rationale.
$!#!$-
8enstrual
cycle duration and the patientsC day after the first day of the last menstruation were recorded.
&atients in both groups were monitored with continuous electrocardiography (;rager abius
+S,! ;rager 8edical A+ Eo! %uF bec7! +ermany)! cyclic nonin'asi'e arterial blood pressure
measurement with a standard adult cuff siAe! and pulse oximetry.
Administration of oxygen was performed for # minutes with 3 %>min fresh gas flow
of $--G oxygen. After oxygen administration! all patients were administered # mg>7g propofol
o'er #- seconds. After loss of eyelash reflex to touch! mas7 'entilation was initiated.
*ocuronium -.6 mg>7g was gi'en to facilitate TI. Sixty seconds later! TI was attempted. All TIs
were performed by the same anesthesiologist! who had not been informed of the patientsC group
assignments (Sedat (a7imogH lu)! to minimiAe bias. A 8acintosh # laryngoscope blade and a
5.3-mm endotracheal tube were used to perform tracheal intubation in the minimum possible
time! and the duration from start of tracheal intubation was recorded. Intubation time was defined
as the period from termination of manual 'entilation with a facemas7 to the restoration of
'entilation through the endotracheal tube!5 and was recorded by a researcher using a stopwatch.
We planned to exclude patients re4uiring ?$.- seconds to achie'e successful TI. &atientsC
systolic blood pressure! diastolic blood pressure! mean arterial blood pressure (8A&)! (*! and
Spo. were recorded before and after administration of the I) anesthetic and muscle relaxant!
immediately after TI and cuff inflation and $! .! #! =! 3! and $- minutes later.
*&&! which is calculated by the formula *&& " (* I systolic blood pressure! was
calculated for each time point and recorded. After intubation! anesthesia in all patients was
maintained with 11G nitrous oxide in oxygen and -.3G se'oflurane. )entilation was adJusted to
maintain end-tidal K:. (9T K:.) between #3 and =- mm (g. ;uring the data collection period!
no surgery was performed. The incision was delayed and no painful stimuli were gi'en until the
end of the study period. If TI could not be performed successfully in the first attempt! the patient
was excluded from the study. Atropine at a dose of -.3 mg was administered for bradycardia ((*
@ 3- beats per minute LbpmM). If 8A& decreased #-G below the control 'alue for a minimum of
1- seconds! 3 mg ephedrine was administered and recorded. If 8A& increased abo'e #-G
control 'alue for a minimum of 1- seconds! $ g>7g fentanyl was administered and recorded.
Komplications occurring during intubationNsuch as coughing! laryngospasm! or bronchospasm
Nwere also recorded. :ur primary hypothesis was that the luteal phase of the menstrual cycle
resulted in a larger increase in *&& at $ minute after endotracheal intubation. Sample siAe
estimation was based on the S; of a similar study performed by S7inner et al.$$ To use the *&&
($3!<<. , =-55) determined by S7inner et al.!$$ we administered propofol and rocuroniun for
intubation. To detect a .-G change in *&&! with an O error of -.-3 and a power of <-G! we
calculated that sample siAe should be at least .3 patients per group.
Table 1. Patient Characteristics
+rup (n " $) +rup % (n " $) &
Age (years) .5.1 P <.- .6.1 P 5.6 -.##
eight (!g) 1=.3 P $$.< 1#.< P $-.= -.<$
Height (cm) $1..6 P 3.6 $1..< P =.$ -.6.
Menstrual cycle duration (days) .5.$ P $.- .1.1 P $.# -.$1
Menstrual cycle day (after first day of
last menstruation)
1.$ P #.< ...5 P ..= @ -.-$
StudentCs t test. , follicular/ % , luteal
igure $. Systolic blood pressure (SD&)! diastolic blood pressure
(;D&)! and heart rate ((*) changes in beats per minute (bpm). " follicular/ % " luteal.
9stimating an approximately .-G dropout rate! we included #$ patients in each
group. The sample siAe estimation was performed using &ower Kalculator (;epartment of
Statistics! Bni'ersity of Kalifornia! %os Angeles/ http0>>www.stat.ubc.ca>,rollin>stats>ssiAe).
5!$$


Statistical &ac7age for the Social Sciences (S&SS) $$.3 was used for data analysis. Qumerical
data were gi'en as mean P sd and were analyAed using the StudentCs t test.
P @ -.-3 was considered statistically significant.
*9SB%TS
The groups were similar in terms of demographic data (P > -.-3). &atient
characteristics are shown in Table $. All TIs were successful on the first attempt with a mean
duration of 3# P $- and 3= P 6 seconds (ranging from #- to 5- seconds) in groups and %!
respecti'ely (P " -.5-3). Qone of the patients were excluded for long TI time. Defore
administration of the I) anesthetic! hemodynamic 'ariables were similar between the groups (P
? -.-3). *&& 'alues at the first minute after intubation were significantly higher in group % than
in group ($=!1<1 P ..5< mm (g R bpm and $$!$15 P .-16 mm (g R bpm! respecti'ely) (P @
-.--$). Khanges in the hemodynamic 'ariables are presented in igures $ and ..
Intergroup and intragroup analysis of the Spo. and 9T K:. 'alues re'ealed no
statistical difference (P ? -.-3). Qo patient in either group re4uired atropine! ephedrine! or
fentanyl. Qo patient had laryngospasm or bronchospasm.
igure .. *ate pressure product (*&&) changes. SP , -.--$
(between-groups follicular LM and group luteal L%M)! $ minute after intubation! StudentCs t test).
;ISKBSSI:Q
In this study we ha'e demonstrated that *&& at $ minute after TI significantly
increases in the luteal phase in comparison with that in the follicular phase of the menstrual
cycle. &re'ious studies and meta-analyses ha'e shown that thermal! pressure! ischemic!
'enipuncture! and propofol inJection pain increased in the luteal phase in comparison with the
follicular phase.
$!.!$.2$6
Studies ha'e demonstrated significant correlation between increased pain
sensiti'ity and increased progesterone! and decreasing estrogen le'els.
$.!$#
In addition! pre'ious
studies ha'e shown that in healthy women! plasma norepinephrine le'els and sympathetic
acti'ity were significantly higher in the luteal phase than in the follicular phase.
1!.-2.#
The
mechanism of the change of *&& response to endotracheal intubation in the different phases of
the menstrual cycle may be related to the increased response to nocicepti'e stimulus! plasma
norepinephrine le'els! and sympathetic acti'ity during the luteal phase.
The limitation of our study is that we did not measure estrogen and progesterone
le'els as was done in other similar studies.
$!=!3!.=2.5
(owe'er! we chose our sample group from
patients on the $st to $.th and .-th to .=th days of their cycle to ha'e . 'ery distincti'e
hormonal profiles in the groups. We chose a single time point to assess the impact of
endotracheal intubation on the phases of the menstrual cycle! because time itself may become a
co'ariate in the model! re4uiring more sophisticated modeling. We tested a simple hypothesis
that the time of the menstrual cycle may impact the hemodynamic response after a noxious
stimulus. In addition! the measurement of serum catecholamine would ha'e been useful.
In conclusion! we suggest that menstrual cycle phases can affect the se'erity of the
*&& response to TI. emale patients may ha'e significantly increased *&& response to TI in the
luteal phase of their menstrual cycle. Therefore! future studies in'estigating the hemodynamic
response to noxious stimulation should consider the phases of the menstrual cycle.
*99*9QK9S
$. (ancT )! Ayoglu (! UTlmaA 8! Uurtlu S! :7yay *;! 9rdogan +! Dasaran 8! Turan I:.
9ffects of menstrual cycle on the inJection pain due to propofol. 9ur V Anaesthesiol
.-$-/.50=.325
.. *iley III V%! *obinson 89! Wise 9A! &rice ;;. A meta-analytic re'iew of pain perception
across the menstrual cycle. &ain $666/<$0..32#3
#. 9rden )! UangTn W! 9r7alp E! ;elatiogH lu (! DahcXeci ! Seyhan A. Increased
progesterone production during the luteal phase of menstruation may decrease anesthetic
re4uirement. Anesth Analg .--3/$-$0$--52$$
=. Sener 9D! Eocamanoglu S! Ketin7aya 8D! Bstun 9! Dildi7 9! Tur A. 9ffects of menstrual
cycle on postoperati'e analgesic re4uirements! agitation! incidence of nausea and 'omiting
after gynecological laparoscopy. +ynecol :bstet In'est .--3/360 =623#
3. +ratA I! Allen 9! Afshar 8! Voslyn A! Duxbaum V! &rilliman D. The effects of the
menstrual cycle on the incidence of emesis and efficacy of ondansetron. Anesth Analg
$661/<#031326
1. Qa7agawa 8! :oTe T! Ta7ahashT Q! TanTguchT U! Anan ! UonemochT (! SaT7awa T.
Influence of menstrual cycle on YT inter'al dynamics. &acing Klin 9lectrophysiol
.--1/.601-52$#
5. *iad W! 8oussa A. %ornoxicam attenuates the haemodynamic responses to laryngoscopy
and tracheal intubation in the elderly. 9ur V Anaesthesiol .--</.305#.21
<. Smith V9! 8ac7enAie AA! Sanghera SS! et al. Kardio'ascular effect of fiberscope-guided
nasotracheal intubation. Anesthesia $6<6/==06-52$-
6. Shribman AV! Smith +! Achola EV. Kardio'ascular and catecholamine responses to
laryngoscopy with and without tracheal intubation. Dr V Anaesth $6<5/360.6326
$-. Speroff %! +lass *(! Ease Q+. *egulation of the menstrual cycle. In0 Speroff %! +lass
*(! Ease Q+! eds. Klinical +ynecologic 9ndocrinology and Infertility. 1th ed. Daltimore!
8;0%ippincott Williams Z Wil7ins! $6660.-$2=1
$$. S7inner (V! Diswas A! 8ahaJan *&. 9'aluation of intubating conditions with rocuronium
and either propofol or etomidate for rapid se4uence induction. Anaesthesia $66</3#05-.2
$-
$.. Stening E! 9ri7sson :! Wahren %! Derg +! (ammar 8! Dlom4'ist A. &ain sensations to
the cold pressor test in normally menstruating women0 comparison with men and relation
to menstrual phase and serum sex steroid le'els. Am V &hysiol *egul Integr Komp &hysiol
.--5/.6#0*$5$$21
$#. (ellstroFm D! Anderberg B8. &ain perception across the menstrual cycle phases in women
with chronic pain. &ercept 8ot S7ills .--#/610.-$2$$
$=. DaJaJ &! Arendt-Qielsen %! DaJaJ &! 8adsen (. Sensory changes during the o'ulatory phase
of the menstrual cycle in healthy women. 9ur V &ain .--$/30$#32==
$3. )iana 9S! Druno SS! de Sousa 8D. 8odulation by progesterone of pain sensiti'ity to
mechanical and ischemic stimuli in young and healthy women. *e' Dras +inecol :bstet
.--</#-0#-1 2$$
$1. )iana 9S! da Sil'a SD! de Sousa 8D. &erception of ischemic and pressing pain in young
women during menstrual cycle. Association with humor and cortisol le'els. Acta Kir Dras
.--3/.-0..-21
$5. SoFderberg E! SundstroFm &I! Qyberg S! DaFc7stroFm T! Qordh 9. &sychophysically
determined thresholds for thermal perception and pain perception in healthy women across
the menstrual cycle. Klin V &ain .--1/..01$-21
$<. Issele[e (! ;e %aat A! Dogaerts E! %ysens *. %ong-term fluctuations of pressure pain
thresholds in healthy men! normally menstruating women and oral contracepti'e users. 9ur
V &ain .--$/30.52#5
$6. *ing K! )eldhuiJAen 'an Wanten VV! Ea'ussanu 8. 9ffects of sex! phase of the menstrual
cycle and gonadal hormones on pain in healthy humans. Diol &sychol .--6/<$0$<626$
.-. Dlum I! %erman 8! 8israchi I! Qordenberg U! +ross7opf I! WeiAman A! %e'y-Schiff *!
Sul7es V! )ered U. %ac7 of plasma norepinephrine cyclicity! increased estradiol during the
follicular phase! and of progesterone and gonadotrophins at o'ulation in women with
premenstrual syndrome. Qeuropsychobiology .--=/3-0$- 23
.$. Koo7e W(! %udwig ;A! (ogg &S! 9c7berg ;%! Kon'ertino )A. ;oes the menstrual cycle
influence the sensiti'ity of 'agally mediated baroreflexes\ Klin Sci (%ond) .--./$-.01#62
==
... Sato Q! 8iya7e S! A7atsu V! Eumashiro 8. &ower spectral analysis of heart rate 'ariability
in healthy young women during the normal menstrual cycle. &sychosom 8ed
$663/350##$23
.#. Uildirir A! Eaba7ci +! A7gul 9! To7goAoglu %! :to A. 9ffects of menstrual cycle on
cardiac autonomic inner'ation as assessed by heart rate 'ariability. Ann Qonin'asi'e
9lectrocardiol .--./501-2#
.=. Kimino *! arella 8! 8ichelotti A! &ugliese *! 8artina *. ;oes the o'arian cycle
influence the pressure2pain threshold of the masticatory muscles in symptom-free women\
V :rofac &ain .---/$=0$-32$$
.3. Ka'lica D! Dere7et UuF cel S! ;arcXin Q! 8irAai IT! 9rbuFyuFn E. L&ain perception of
female professional 'olleyball players during different phases of menstruationM. Agri
.--6/.$0.6 2#3. LArticle in Tur7ishM
.1. )ignolo )! )edolin +8! de ArauJo Kdos *! *odrigues Konti &K. Influence of the
menstrual cycle on the pressure pain threshold of masticatory muscles in patients with
masticatory myofascial pain. :ral Surg :ral 8ed :ral &athol :ral *adiol 9ndod
.--</$-30#-<2$3
.5. To[ foli +*! *amacciato VK! )olpato 8K! 8eechan V+! *anali V! +roppo K. Anesthetic
efficacy and pain induced by dental anesthesia0 the influence of gender and menstrual
cycle. :ral Surg :ral 8ed :ral &athol :ral *adiol 9ndod .--5/$-#0e#=2< August