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Patient Sex and its Influence on General Anaesthesia

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Anaesth Intensive Care 2009; 37: 207-218

Patient sex and its influence on general anaesthesia

F. F. Buchanan*, P. S. Myles†, F. Cicuttini‡
Department of Anaesthesia and Perioperative Medicine, Alfred Hospital and Academic Board of Anaesthesia and Perioperative
Medicine, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia

Summary
Physiological and pharmacological differences exist between men and women. Women wake faster than men
following general anaesthesia. Women also differ from men in their postoperative recovery as reflected by differences
in postoperative pain, nausea and vomiting and overall quality of recovery. These gender differences seem to be
more pronounced in premenopausal women, suggesting hormonal mechanisms are a major contributing factor.
Key Words: gender, anaesthesia, analgesia, outcome

Men and women differ physiologically and in their PHYSIOLOGICAL DIFFERENCES

responses to some drugs1-3, but are these clinically Hormonal variability
relevant in anaesthesia? Women have historically
Many of the physiological differences between
been excluded from many drug development studies
women and men could be the result of the direct or
because of the variability induced by reproductive
indirect actions of female sex hormones. Endogenous
hormone flux and a concern for potential
female sex hormones are steroid-based substances
teratogenicity1,2. This selective exclusion of women
released in a cyclical manner from the age of
from clinical studies may have missed opportunities
menarche to menopause (Figure 1). In the early
to identify sex-specific differences in drug metabolism
follicular phase, plasma concentrations of oestrogen,
and efficacy3.
progesterone, follicle-stimulating hormone (FSH)
There is growing evidence to suggest that patient
and luteinising hormone are at their lowest, with
sex is an independent factor influencing post-
the oestradiol concentration at levels comparable to
operative outcomes and, in particular, speed of
males12. Progressively increased oestrogen secretion
recovery from general anaesthesia5-9. Whether this is
by the ovaries from the mid-to-late follicular
due to sex-related differences in pharmacokinetics
phase culminates in a sharp rise in oestrogen
or pharmacodynamics remains unclear10, with some
concentration; this in turn triggers surges in
investigators suggesting that the influence of patient
luteinising hormone and FSH just prior to ovulation.
sex on anaesthesia requirements and side-effects
In the early luteal phase, plasma concentrations
is clinically insignificant11. This review highlights
of oestrogen decrease while that of progesterone
the physiological and pharmacological differences
continues to increase and plateau. In the late luteal
between women and men relevant to general
phase, plasma concentrations of oestrogen and
anaesthesia and recovery after surgery.
progesterone fall rapidly while FSH concentrations
increase until the onset of menses, which then
heralds the start of another cycle.

Body composition differences

* M.B., B.S., F.A.N.Z.C.A., Research Fellow, Department of Anaesthesia
and Perioperative Medicine, Alfred Hospital.
† M.B., B.S., M.P.H., M.D., F.C.A.R.C.S.I., F.A.N.Z.C.A., Director,
Department of Anaesthesia and Perioperative Medicine, Alfred Hospital,
Professor and Chair, Academic Board of Anaesthesia and Perioperative
Medicine, Monash University and NHMRC Practitioner Fellow.
‡ M.B., B.S.(Hons.), Ph.D., M.Sc., D.L.S.H.T.M., F.R.A.C.P., F.A.F.P.H.M.,
Head, Rheumatology Unit, Alfred Hospital and Professor, Department of
Epidemiology and Preventive Medicine, Monash University.
Address for reprints: Dr F. F. Buchanan, Department of Anaesthesia and
Perioperative Medicine, Alfred Hospital, Commercial Road, Melbourne,
Vic 3004.
Accepted for publication on October 10, 2008.
Anaesthesia and Intensive Care, Vol. 37, No. 2, March 2009
Women and men have differences in body
mass index, waist circumference and body fat
composition13. Women typically have higher
percentages of body fat (~5 to 10%) and lower
muscle mass (~10%) compared with men2. A
consequence of increased body fat is that women
have a 15 to 20% decrease in total body water
compared with men14. Furthermore, the extracellular
fluid volume, to which total body water contributes,
varies in women during the menstrual cycle as a
result of changes in plasma volume15. This is due to
208 F. F. Buchanan, P. S. Myles, F. Cicuttini

Figure 1A: Plasma oestrogen and progesterone levels during a 28 day cycle in humans12.

Figure 1B: Plasma luteinising hormone (LH) and follicle stimulating hormone (FSH) levels during a 28-day cycle in humans12.

the cyclic effects oestrogen and progesterone have on Cardiovascular differences

plasma volume and capillary fluid dynamics via renal
sodium reabsorption and changing colloid osmotic
pressure15,16.
Electrolyte balance in women fluctuates during
the menstrual cycle. Plasma sodium levels increase
during the mid-follicular and ovulatory stages and
decrease throughout the luteal phase17. The decrease
in plasma sodium can be attributed to progesterone-
enhanced natriuresis during the luteal phase17,
as progesterone is a competitive antagonist to
aldosterone18.
Although males and females are born with the
same number of cardiac myocytes, cardiac
mass increases substantially more in men post-
adolescence19-21. Despite this, younger women have
better diastolic function and a larger left ventricular
ejection fraction compared with men22,23. The average
resting heart rate is three to five beats faster in
women, and this varies during the menstrual cycle,
being least during menses24. These cyclic fluctuations
in heart rate are not autonomic in nature and
persist despite complete autonomic blockade25.
Anaesthesia and Intensive Care, Vol. 37, No. 2, March 2009
 Gender and anaesthesia 209

When compared with men, women have a lower filtration fraction44, but may play a role in modulating
24-hour mean blood pressure, in the order of 6 to renal tubular function48. Plasma renin activity levels
10 mmHg26. This changes after menopause and, in are higher in men than in women, and in post-
fact, blood pressure exceeds that of men by the age menopausal women compared with younger
of 70 years27. women49.
Female sex hormones and androgens are likely
Metabolic differences
to play a role in the cardiovascular differences
Men have a higher basal metabolic rate than
between the sexes28. Oestrogens cause vasodilation
women, but this is due to their larger body size50,51.
due to enhanced production and secretion of the
Sedentary energy expenditure has been found to
endogenous vasodilator nitric oxide29. As with heart
be about 5 to 10% lower in women than men after
rate, blood pressure in women is affected by the
adjusting for differences in body composition, age
fluctuating levels of oestrogen that occur during
and activity50. Metabolism also fluctuates with the
the menstrual cycle, pregnancy and with exogenous
stage of the menstrual cycle, with progesterone
oestrogen supplementation30. Like oestrogen,
secretion mediating a 9% increase in 24-hour energy
progesterone also lowers blood pressure, but
expenditure during the luteal phase50,52.
synthetic progestins have been shown to increase
In women, core body temperature fluctuates by
blood pressure30.
0.3 to 0.5°C during the menstrual cycle. It increases
Respiratory differences during the luteal phase, reaching peak levels
Women have smaller lung volumes, maximal mid-phase due to the thermogenic effects of
expiratory flow rates and diffusion surfaces, progesterone53. Women and men differ in their
independent of body size31-33. Women also have thermal responses to exogenous and endogenous
reduced ventilatory response to exercise34. This is heat load and loss during rest and exercise because
due to smaller diameter airways relative to lung of their larger ratio of body surface to body mass,
size in women35,36. When women with normal lung greater subcutaneous fat content and lower exercise
function and varying fitness levels are subjected capacity53. Women, though, still maintain similar
to incremental exercise tests to maximal oxygen core body temperatures as a result of greater
consumption, they experience exercise-induced evaporative efficiency of sweating53.
hypoxaemia at levels of maximal oxygen consumption
that are substantially lower than those of men33,34,37. Table 1
The ventilatory response to CO2 and hypoxia, and Summary of known sex differences in physiology
the apnoeic threshold, are greater in men than
Physiological variable Female
women38-40.
Body fat 5-10% higher2,13
Progesterone is a known respiratory stimulant,
with women mildly hyperventilating during the luteal Muscle mass 10% lower2
phase of the menstrual cycle and during pregnancy41. Total body water 15-20% less14
The luteal phase is associated with an increase in Cardiac mass Lower20,21
minute ventilation, a reduction in PaCO2 and an
Diastolic function Better22
increased hypercapnoeic ventilatory response42.
Increased levels of progesterone also stimulate Left ventricular ejection fraction Higher23
ventilation at rest and during exercise41. Interestingly, Stroke volume Higher23
despite having a lower PaCO2 during the luteal phase Resting heart rate Higher24,25
of the menstrual cycle, no change in pH occurs
Cardiac cycle length Shorter24
throughout the menstrual cycle43. Instead, phase-
related changes in acid-base balance occur to ensure Blood pressure Lower (6-10 mmHg)
premenopause26
hydrogen ion concentrations remain relatively
Lung volumes Lower31-34
constant43.
Expiratory flow rates Lower31-35
Renal differences
Lung diffusion surface Lower36
Although women appear to have a lower
glomerular filtration rate and renal blood flow Exercise-induced hypoxaemia Higher31,34
compared with men44,45, this difference is accounted Ventilatory response to hypercapnia Less38-40
for by body size44,46,47. Varying concentrations of Ventilatory response to hypoxia Less38
plasma oestrogen have no measurable effect on
Apnoeic threshold Less38-40
renal blood flow, renal vascular resistance and
Anaesthesia and Intensive Care, Vol. 37, No. 2, March 2009
210 F. F. Buchanan, P. S. Myles, F. Cicuttini
Neurological differences
There are many sex differences in brain structure
and function54-57. Male brains are on average larger
and have a higher neuronal density, but with similar
cortical thickness, yet there is more neuronal
processing in females55. Some regions of the brain
have been found to be proportionally larger in
females than males and other regions larger
in males54. There are also regional sex differences
in cerebral glucose metabolism56, including the
amygdala, a key region involved in emotionally-
influenced memory57. This might explain the
apparent increased risk of awareness during surgery
in women.
PHARMACOLOGICAL DIFFERENCES
Pharmacokinetics
Bioavailability
Of the major factors influencing drug absorption,
only gastrointestinal motility has been shown to have
sex-based differences2,58-80. These are likely to be due
to female sex hormones59. Women have lower activity
of the enzyme alcohol dehydrogenase than men,
resulting in higher blood alcohol concentrations in
women following ingestion of an equivalent amount
of alcohol65. Although sex-based differences in
gastrointestinal motility and some gastric enzymes
do exist, these are not considered to be clinically
significant58.
Volume of distribution
Body fat increases in both sexes with age10. For
water-soluble drugs used in anaesthesia (such as
muscle relaxants), the volume of distribution can be
expected to be lower in women10. Indeed, numerous
studies have confirmed that women require less
vecuronium68-71, rocuronium72, pancuronium73 and
atracurium74 to produce an equivalent effect to that
of men. At equivalent doses plasma concentrations
of muscle relaxants are higher in women68-72.
For lipid-soluble drugs used in anaesthesia,
women can be expected to have a larger volume
of distribution. This has been shown with benzo-
diazepines such as diazepam75,76 and midazolam77,
and hypnotic drugs such as propofol78,79 and
eltanolone80.
Sex differences in volume of distribution may be
secondary to the physiological changes in water and
electrolyte balance that occur during normal and
abnormal fluctuations of the menstrual cycle2,3. To
date, few studies have examined the effect of this
variability on drug volume of distribution. If changes
in drug volume of distribution do occur with the
menstrual cycle, they are not likely to be large
enough to alter plasma drug concentration and thus
are unlikely to be of clinical significance3.
Protein binding
Any sex differences in plasma protein binding
will alter the free fraction of available drug and
this may contribute to pharmacokinetic differences
in drug action between men and women58. Studies
investigating the role sex hormones play on
plasma albumin levels are inconsistent. In one
study, comparing the protein binding of the
drugs chlorpromazine, propranolol, meperidine,
desipramine, salicylic acid and phenytoin in the
plasma of 64 healthy volunteers (35 males and 29
females), patient sex was not an independent factor
influencing plasma albumin levels81. However, a
study examining the effect of supra-physiological
levels of oestrogen on the protein binding of
bupivacaine in women undergoing in vitro
fertilisation procedures found that oestrogen
decreased the concentrations of serum albumin
and alpha1-acid glycoprotein, resulting in higher
concentrations of free bupivacaine82. A similar effect
was observed with exogenous oestradiol lowering
levels of alpha1-acid glycoprotein when propranolol
was studied83. During pregnancy the concentration
of several plasma proteins decrease, resulting in an
increased free fraction of drugs with high protein
binding, for example lignocaine, diazepam and
propranolol84. However, it is believed that protein
binding is not a major contributor to differences in
drug activity between men and women2,3,10.
Drug metabolism
Sex differences in drug metabolism are believed
to play the greatest role in pharmacokinetic
differences between the sexes58. Although cardiac
output and therefore hepatic blood flow is lower
in women, it is sex differences in hepatic enzyme
activity that is largely responsible for differences
in hepatic metabolism and therefore clearance of
drugs58. Both phase I and II reactions are likely to
be involved58.
Although sex differences in CYP 450 activity have
been proposed to exist6,7, current evidence supporting
this is limited, non-existent8 or conflicting44. Using
in vitro techniques, female livers have been shown
to have a significantly higher CYP3A4 content85
and activity86 compared with males, although a
later study could not confirm this finding87. Such in
vitro studies are limited, however, as they lack the
systemic hormonal environment of males and
females and this may lead to erroneous results58.
Anaesthesia and Intensive Care, Vol. 37, No. 2, March 2009
 Gender and anaesthesia
In vivo studies have also revealed similarly
conflicting results. For example, the metabolism
of the antibiotic erythromycin is widely used to
assess CYP3A4 activity in vivo88 and one study has
found that CYP3A4 activity is significantly greater
in women than in men89. Verapamil, a non-
dihydropyridine calcium channel blocker, is another
drug whose metabolism has been used as a marker
of CYP3A4 activity and for which hepatic
metabolism is greater in women than in men90.
Midazolam, being a substrate of CYP3A4, has also
been used to measure CYP3A4 activity91,92. Most
studies have failed to find any significant sex
differences in midazolam activity77,91-94, with the
exception of a greater clearance in women95,96.
One reason which may help to explain the
conflicting results obtained for CYP3A4 substrates
in terms of sex-based differences in hepatic
metabolism is the presence of the transporter
p-glycoprotein58. This is a membrane-bound transport
protein which lowers intracellular concentrations
of many types of drugs by promoting drug efflux97.
As a drug needs to be intracellular in order to
be metabolised by CYP3A4, higher numbers of
the transporter p-glycoprotein at the hepatocyte
membrane will decrease the rate of drug
metabolism97. Men have been found to have more
hepatic transporter p-glycoprotein98. This results in
higher intracellular drug concentrations in female
hepatocytes, with subsequent increased CYP3A4-
specific drug metabolism97 and clearance in women
for drugs that are both CYP3A4 and transporter
p-glycoprotein substrates97. Hence this can explain
sex-based differences in CYP3A4 activity between
midazolam and verapamil58. Verapamil is a
substrate for both CYP3A4 and the transporter
p-glycoprotein; midazolam is only a substrate for
CYP3A4.
A possible hormonal effect of oral contraceptive
use, menstrual cycle variations and pregnancy,
has been postulated as probable components of
sex-related differences in drug disposition3,10. Sex
hormones influence enzyme activity in hepatocytes
by determining the type and quantity of enzymes
produced2 and they do this both in an acute and
chronic basis99. The use of oral contraceptives may
modulate CYP 450 activity100. Pregnancy has been
shown to increase the activity of the hepatic enzyme
CYP2D6101. There is also some evidence that drug
clearance may vary with the day of the menstrual
cycle102. For example, the clearance of theophylline
and caffeine are highest during the early follicular
phase and most prolonged during the mid-luteal
phase103,104.
Anaesthesia and Intensive Care, Vol. 37, No. 2, March 2009
211
Menstrual variations in the clearance of intra-
venous anaesthetic drugs have not been studied10.
Previous studies examining the influence of the
menstrual cycle on midazolam80,105, alprazolam106 and
alfentanil105 metabolism have found no correlation
between the time of the cycle and drug clearance.
Alfentanil clearance, which is almost entirely
dependent on hepatic CYP3A4 activity107, is sex-
dependent108 with clearance higher in women than
in men. Hormonal influences may be involved as
clearance is approximately 70% higher in women
less than 50 years compared with older women109,
implying differences between pre- and post-
menopausal women.
Of the phase II reactions involved in drug
metabolism, only glucuronidation may be sex-
dependent10 with higher activities found in
men110,111. Drugs such as oxazepam, temazepam and
paracetamol are cleared faster in men112-114. Possible
hormonal influences may occur as the oestrogen
component of the oral contraceptive pill has been
associated with increased conjugation activity114,115.
From an anaesthetic point of view, propofol is a
drug whose clearance depends on both metabolism
and distribution116. Its rapid metabolism is linked
to glucuronidation of the parent drug to form the
propofol glucuronide (62%) and via cytochrome P450
to form other minor conjugates (38%)116. Numerous
studies have shown a higher clearance of propofol
in women78,79,116, but these differences are thought to
be of limited clinical importance.
Renal clearance of drugs
Renal clearance of drugs is dependent on
glomerular filtration and/or tubular secretion58. As
the glomerular filtration rate is proportional to body
weight46, any sex differences in the rate of renal
excretion of most drugs would reflect differences
Table 2
Summary of sex differences in pharmacokinetics
Pharmacological variable Females
Bioavailability Decreased gastric emptying time59,60
Volume of distribution Decreased for non-depolarising
muscle relaxants68-72
Increased for diazepam,
midazolam, propofol, eltanolone75-80
Protein binding Increased oestrogen decreases
albumin and alpha1-acid
glycoprotein82-84
Drug metabolism Possible increased89,90 or decreased
CYP3A4 activity91-95
Decreased glucuronidation108,109
Renal clearance No difference44
212 F. F. Buchanan, P. S. Myles, F. Cicuttini
in body size rather than true sex differences10.
Lower secretion rates for para-aminohippuric acid
and frusemide have been measured in female rats117
and for amantadine in women118. But more studies
are needed to better understand the extent of sex
differences on renal tubular secretion58.
SEX DIFFERENCES IN ANAESTHESIA
Pharmacodynamics
Sex hormones probably play a role in modulating
sex differences in anaesthesia. Oestrogen, progestin
and androgen receptors have been identified in
mammalian brains119, with effects beyond that
involved in reproductive behaviour and function120.
Oestrogen and progesterone bind to intracellular
receptors that influence genomically-directed
protein synthesis121, as well as by altering neuronal
excitability on neurotransmitter-gated ion channels
such as the GABAA receptor complex122. Of the
sex hormones, progesterone and its metabolites
are known to have hypnotic123, anxiolytic124, anti-
convulsant and analgesic effects123,125. They have also
been shown to increase the potency of inhalational
anaesthetics126, to demonstrate dose-dependent
hypnotic effects123, to induce sleep in humans127 and
induce general anaesthesia in animals at higher
doses128. Indeed, progesterone and its metabolites
have similar effects on sleep EEG patterns as the
benzodiazepines123.
Increased production of progesterone during the
luteal phase of the menstrual cycle may decrease
anaesthetic requirements129. Women in the luteal
phase of the menstrual cycle, when serum
progesterone levels are at their highest, were found
to have a significantly lower minimum alveolar
concentration (MAC) value for sevoflurane during
the maintenance phase of anaesthesia compared
to women in the follicular phase129. Progesterone
is thought to exert its sedating effect through the
direct action of its metabolites (particularly
5α-pregnanolone and 5β-pregnanolone) on the
GABAA receptor130, with comparable equimolar
potency to that of benzodiazepines131.
Unlike progesterone, oestrogen appears to have
the opposite effect on the GABA system in the
central nervous system. Oestrogen has been shown
to suppress GABAA-mediated inhibition in the
hippocampus, and have excitatory effects on the
cerebral cortex and cerebellum120,132. Oestrogens also
potentiate the binding of glutamate to N-methyl-
D-aspartate receptors133,134. Furthermore, changes
in plasma oestrogen levels are accompanied by
changes in a variety of other neurotransmitters
including acetylcholine, dopamine, serotonin and
endorphins135.
General anaesthetics affect a number of different
neurotransmitter receptors including the GABAA,
acetylcholine and glutamate receptors in the brain,
and glycine receptors in the spinal cord136-138.
Furthermore, as distinct neuroanatomic sites
correlate with distinct anaesthetic properties136, it
is possible that altered modulation of these same
receptor complexes at these sites of anaesthetic
action by sex steroid hormones may explain some of
the reported sex differences in general anaesthesia.
Few studies have specifically investigated possible
sex differences in the pharmacodynamic effects of
anaesthetic drugs.
Inhalational agents
The MAC of a volatile anaesthetic is a useful
measure of pharmacodynamic effect and this may
be sex dependent. In one small study, women
required larger concentrations of desflurane to
prevent movement in response to noxious electrical
stimulation compared to men139. Xenon, an inert
gas used to maintain general anaesthesia, has sex
differences in elderly patients with women requiring
26% less xenon than men to achieve MAC during
laparotomy140. Pregnancy is a time of hormonal flux
with increased circulating levels of oestrogen and
progesterone and characterised by a decrease in the
MAC of the volatile agents isoflurane141, halothane
and enflurane142.
The concept that MAC may be sex-dependent
was not supported by a pooled analysis of 258
patients previously anaesthetised with desflurane,
diethyl ether, halothane, methoxyflurane and
sevoflurane143. However, this retrospective analysis
may have been underpowered: extrapolating from
the standard errors of the MAC estimates in that
study143 identifies a possible sex difference that
would require a larger study to confirm or refute.
To date, most studies have been too small and thus
underpowered to clinically detect a difference and
further properly designed studies are needed.
Propofol
Several studies have found that women recover
more quickly from propofol-based anaesthesia
compared with men5-9. Although sex differences
in pharmacokinetics, with a more rapid decline in
plasma propofol concentration in women compared
with men, could explain the faster emergence after
propofol anaesthesia12, sex differences in central
sensitivity to propofol may also exist.
The available evidence supporting the influence
patient sex has on propofol sensitivity is conflicting.
Anaesthesia and Intensive Care, Vol. 37, No. 2, March 2009
 Gender and anaesthesia
While one study has found women to be more
sensitive to the effects of propofol based on lower
plasma concentrations required to produce similar
bispectral index (BIS) levels144, other studies have
found no difference145 or the reverse to be true146,149.
In the same studies, women required more propofol
to achieve the same depth of anaesthesia as
monitored by Narcotrend146,147. Reduced propofol
sensitivity in women is supported by a requirement
for more propofol to lose consciousness5,149,150 and
to maintain anaesthesia during surgery5,149,150, when
adjusted for body weight. Men are also more readily
sedated (as measured by auditory evoked potentials)
compared to women when given the same dose of
propofol150. Women also respond to verbal stimuli
more quickly than men following cessation of a
propofol infusion8. Here, no differences in plasma
propofol concentrations were observed either at
the end of surgery or at the time of emergence8.
However, this suggested sex difference in
pharmacodynamic effect to propofol may be age-
related. In elderly patients, the blood propofol
concentrations were approximately 10% lower in
female patients151. Interestingly, pharmacokinetic
analysis demonstrated a larger volume of
distribution and higher clearance in the female
patients to account for this difference in plasma
concentration151.
Patient sex has not consistently been shown to
influence the hypnotic requirements for loss of
consciousness. In one study, no sex differences were
observed for loss of consciousness with sevoflurane
or propofol145 when used with BIS145. This finding
contrasts with previous studies which examined sex
differences during general anaesthesia5, not just
those occurring at loss of consciousness. As the
mechanisms responsible for general anaesthesia are
dependent not just on hypnosis, but also on amnesia,
immobility and analgesia136, other effects of sex
on anaesthesia may be occurring to explain these
differences.
Most victims of awareness under anaesthesia
are women152; this suggests that sex may be an
independent factor contributing to sensitivity to
general anaesthesia. Recent evidence reinforces this
view. In a large subset analysis comparing recovery
characteristics from general anaesthesia of female
and male patients at risk of awareness, women had
higher BIS values during maintenance of general
anaesthesia despite similar amounts of anaesthetic
drug administration9. This suggests that women are
less sensitive to the hypnotic effect of anaesthetic
drugs than men and this may help explain the faster
recovery times in women5-9.
Anaesthesia and Intensive Care, Vol. 37, No. 2, March 2009
213
The reported differences in intraoperative recall
and emergence times between men and women
appear to be related to lighter levels of hypnosis,
as indicated by higher BIS values in women under-
going general anaesthesia5, but this apparent
difference may be related to reduced autonomic
responses (and generally lower blood pressure) in
female patients. This is an alternative explanation
as to why women appear ‘less sensitive’ to general
anaesthetics. A study titrating anaesthetic drug
administration to an objective validated endpoint
of hypnotic depth, such as BIS monitoring5, should
be able to resolve this issue.
Clinical differences in men and women following
general anaesthesia
Despite a faster speed of awakening – suggesting
a decreased sensitivity to the hypnotic effects of
anaesthetic drugs – women do not appear to be
discharged any faster after ambulatory surgery
compared with men153. Indeed, quality of recovery
may be slower in women. Perioperative sequelae
such as anaphylactic and anaphylactoid reactions154,
pain scores155, postoperative nausea and vomiting
(PONV)156, sore throat157, headache and backache157
have also been reported to be significantly higher
in women following general anaesthesia and would
therefore influence patient quality of recovery.
Female sex has been shown to be associated with
a worse outcome in terms of morbidity and
mortality158, increased length of hospital stay158 and
decreased functional outcome155, following some
types of surgery. Also, there is evidence that a sex
difference in quality of recovery may extend for
months beyond the initial surgery, with female
sex associated with more functional impairment
after cardiac surgery160 and cholecystectomy161. Sex
differences in quality of recovery also contribute
to lower rates of patient satisfaction in women
following general anaesthesia162.
PONV is a common problem and major
contributing factor impairing a patient’s quality of
recovery; it also prolongs recovery time and delays
patient discharge163. PONV is influenced by many
factors including site and duration of surgery,
anaesthetic agents and patient sex163. Indeed,
female sex is a known risk factor for PONV6,156,157,163:
women have a two-fold increased risk, but this
decreases after the age of 50 years11. This suggests
that hormonal influences may be contributing
to the PONV sensitivity. In one study of women
undergoing laparoscopic tubal ligation, there was a
correlation between the incidence of nausea and the
day of the menstrual cycle163. Here, the incidence of
214 F. F. Buchanan, P. S. Myles, F. Cicuttini

nausea was found to be greatest during the follicular   5. Gan TJ, Glass PS, Sigl J, Sebel P, Payne F, Rosow C et al.
phase compared to the luteal phase, with the peak Women emerge from general anesthesia with propofol/alfen-
tanil/nitrous oxide faster than men. Anesthesiology 1999;
incidence occurring during day five of the menstrual 90:1283-1287.
cycle163. This observation was confirmed in another   6. Myles PS, McLeod AD, Hunt JO, Fletcher H. Sex differences
study involving women undergoing gynaecological in speed of emergence and quality of recovery after anaesthe-
laparoscopy and laparotomy164. The greater sia: cohort study. BMJ 2001; 322:710-711.
incidence of PONV in women has been reported   7. Apfelbaum JL, Grasela TH, Hug CC Jr, McLeskey CH,
in a wide range of anaesthetic regimens and Nahrwold ML, Roizen MF et al. The initial clinical experience
surgical procedures6,11,156,157,163. of 1819 physicians in maintaining anesthesia with propofol:
characteristics associated with prolonged time to awakening.
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Table 3
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Anaesthesia and Intensive Care, Vol. 37, No. 2, March 2009
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