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Department of Anaesthesia and Perioperative Medicine, Alfred Hospital, Commercial Road, Melbourne, Victoria 3004, Australia
Academic Board of Anaesthesia and Perioperative Medicine and 3 Department of Epidemiology and Preventive Medicine, Monash
University, Melbourne, Australia
Methods. In a multicentre, prospective, matched cohort study, 500 ASA physical status I or
II patients of either sex undergoing general anaesthesia for elective surgery were recruited.
All subjects received a general anaesthetic through inhalation. Anaesthetic drugs and doses
used, bispectral index (BIS) scores, recovery times, pain scores, and 40-item quality of
recovery (QoR-40) scores for 3 days after general anaesthesia were recorded.
Results. Women had higher BIS scores at similar concentrations of anaesthesia (P,0.05).
Time to eye-opening (P,0.01) and time to obeying commands (P,0.01) were shorter in
women. Duration of recovery room stay was longer in women, who also had higher pain
scores and need for treatment of nausea and vomiting (all P,0.001). QoR-40 scores for
the first 3 days after general anaesthesia were lower in women (P,0.001). Plasma
progesterone concentrations in women negatively correlated with the time to eyeopening (r 20.53, P0.01).
Conclusions. Patient sex is an independent factor influencing the response to anaesthesia
and recovery after surgery. Women emerged faster from general anaesthesia but their
overall quality of recovery was poorer. Female sex hormones, particularly progesterone,
might be involved, with premenopausal women having faster recovery time but poor
overall recovery.
Keywords: anaesthesia, general; complications; gender; vomiting, nausea
Accepted for publication: 17 March 2011
to general anaesthesia are primarily because of pharmacokinetic (faster clearance) or pharmacodynamic (less response
at equal effect site concentrations) mechanisms.2
Some
& The Author [2011]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.
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Background. Numerous studies have shown that women emerge faster from general
anaesthesia than men, and differ in their postoperative recovery profile. The extent and
underlying mechanisms for these sex-related differences in general anaesthesia are
unclear.
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Methods
Study design
FE,volatile
FE,N2 O
+
MACage,volatile MACage,N2 O
where FE,volatile is the end-expired concentration of the volatile agent used and FE,N2 O is the end-expired concentration of
nitrous oxide.
Cessation of administration of general anaesthesia was
timed for the subject to emerge from anaesthesia after
final wound closure. Emergence from anaesthesia was
timed from the completion of wound dressing (time 0)
and included the time to spontaneous eye-opening, time to
obeying commands, and the time spent in the recovery
room (until eligible for discharge to the surgical ward).
Quality of recovery was assessed on each of the first 3
days after surgery using the 40-item quality of recovery
(QoR-40) score26 28 completed during recovery. The QoR-40
encompasses most aspects of a good quality of recovery
after surgery and anaesthesia, consisting of five dimensions
(physical comfort, emotional state, physical independence,
psychological support, and pain). The QoR-40 score ranges
from 40 (extremely poor quality of recovery) to 200 (excellent
quality of recovery).
Definition of outcomes
The main study outcomes were: (i) quality of recovery, using the
QoR-40 and verbal rating pain scores, and (ii) speed of recovery,
using time to eye-opening, time to obeying commands, and
time spent in the recovery room. The sample size was calculated to detect an 8% (SD 20%) improvement in the QoR-40,
with a type I error of 0.05 and a type II error of 0.2 for which
we needed to enrol at least 111 patients per group. Allowing
for dropouts and to account for sub-group analyses, we
planned to enrol 500 subjects (250 females, 250 males).
Statistical analysis
Descriptive statistics are expressed as number (%) or mean
(SD). Differences between women and men were examined
833
blocking agents, when used, were antagonized with neostigmine and atropine. End-tidal inhalation agent monitoring
was done using the Datex-Ohmeda Aisys Carestationw (GE
Healthcare, Helsinki, Finland), which has an accuracy of
+0.2%. Bispectral index (BIS) monitoring was used to
measure the hypnotic component of depth of anaesthesia,
though administration of anaesthesia was not titrated to
BIS. BIS measurements were made every 5 min for the first
hour and then every 10 min. A time-averaged mean BIS
score was then calculated for the duration of general anaesthesia. Intraoperative age-adjusted minimum alveolar concentration (MACage) was determined using the following
nomogram:24
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Buchanan et al.
Results
Female
(n5247)
P-value
Airway
Face mask
Laryngeal mask
1(0.39)
0(0)
0.001
176 (69)
131 (54)
79 (31)
113 (46)
254 (99)
243 (99)
2 (0.8)
1 (0.4)
Induction dose of
propofol (mg kg21)
2.8 (5.8)
2.5 (0.6)
0.23
Midazolam
co-induction dose
(mg kg21)
237 (93)
225 (93)
0.73
Tracheal tube
Induction agent
Male
(n5253)
Height (m)
1.78 (0.07)
1.64 (0.07)
Weight (kg)
Female
(n5247)
85.5 (13.3)
67.7 (12.7)
190 (78)
193 (75)
II
54 (22)
63 (25)
1.00 (0.05)
0.85 (0.05)
P-value
0.50
,0.0005
Isoflurane
,0.0005
89 (35)
99 (41)
120 (47)
86 (35)
Urological
11 (4.3)
6 (2.5)
ENT
17 (6.6)
15 (6.2)
Plastics
14 (5.5)
30 (12)
5 (2.0)
8 (3.3)
72 (28)
30 (12)
169 (66)
204 (84)
15 (5.9)
10 (4.1)
Previous PONV
10 (3.9)
74 (30)
,0.0005
Previous motion
sickness
13 (5.1)
41 (17)
,0.0005
Orthopaedic
Other
0.02
Intermediate
Major
119 (46)
156 (64)
Smoker
60 (23)
31 (13)
Ex-smoker
77 (31)
57 (23)
834
19 (7.4)
43 (18)
Social
218 (85)
197 (81)
Heavy
19 (7.4)
4 (1.6)
30 (22 34)
116 (48)
0.72
0.001
28 (11)
23 (9.4)
196 (77)
169 (69)
0.06
Desflurane
32 (13)
51 (21)
Nitrous oxide
154 (60)
114 (47)
0.003
Age-adjusted MAC
1.31 (0.3)
1.26 (0.3)
0.08
36 (7)
38 (8)
0.02
Fentanyl
140 (54)
124 (51)
0.39
0.63 (2.0)
0.72 (0.8)
0.24
0.01
None
,0.0005
78 (30)
65 (29)
Morphine
175 (68)
164 (67)
Pethidine
3 (1.2)
15 (6.2)
,0.0005
Morphine
0.12 (0.04)
0.13 (0.04)
,0.0005
Pethidine
1.2 (0.9)
1.3 (0.4)
0.41
Tramadol
99 (39)
96 (40)
0.79
Antiemetic
prophylaxis
71 (28)
209 (86)
,0.0005
237 (93)
232 (95)
0.25
80 (31)
67 (48)
,0.0005
65.0 (43.5)
70.8 (42.5)
0.13
LA infiltration
Alcohol use
Non-drinker
83 (32)
Additional opioid
Smoking status
Non-smoker
Sevoflurane
Average BIS
Extent of surgery
Minor
29 (19 33)
Neuromuscular
blocking agent
0.59
Volatile agent
Type of surgery
General
Thiopental
,0.0005
Waist-to-hip ratio
Propofol
,0.0005
Neuromuscular
block-reversal agent
used
Duration of
anaesthesia (min)
Male
(n5253)
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Female
(n5247)
51.2 (9.0)
53.2 (10.7)
0.03
7.7 (4.0)
5.3 (3.5)
,0.0005
78.4 (15.7)
75.6 (13.5)
0.18
8.3 (5.1)
6.80 (7.3)
0.01
33.7 (11.8)
38.8 (16.1)
,0.0005
17 (6.6)
39 (16)
,0.0005
Nausea
2 (0.8)
24 (9.9)
,0.0005
Vomiting
1 (0.4)
10 (4.1)
0.01
Treatment PONV
2 (0.8)
24 (9.9)
,0.0005
Time to eye-opening,
min
BIS score at eye-opening
Time to obeying
commands, min
Recovery room stay, min
Shivering
P-value
Pain scores*
4 (0 6)
Time period
Male (n5225)
Female (n5232)
P-value
Preoperative
199 (3.2)
197 (7.6)
,0.0005
Day 1
190 (12)
180 (19)
,0.0005
Day 2
194 (11)
186 (17)
,0.0005
Day 3
195 (10)
190 (17)
,0.0005
Male
(n5225)
Female
(n5232)
P-value
Before surgery
59.8 (1.5)
59.2 (2.6)
Day 1
55.8 (6.1)
51.2 (7.5)
0.001
Day 2
58.3 (4.7)
54.6 (6.3)
,0.0005
Day 3
58.9 (3.7)
56.3 (6.1)
,0.0005
0.014
0 (0 5)
0 (0 3)
Postoperative day 1
3 (2 5)
4 (3 6)
,0.0005
Before surgery
44.7 (1.5)
44.2 (4.3)
Postoperative day 2
2 (0 4)
3 (2 5)
,0.0005
Day 1
41.6 (6.0)
40.3 (5.9)
0.003
Postoperative day 3
1 (0 3)
2 (1 4)
,0.0005
Day 2
43.4 (5.2)
40.1 (6.2)
,0.0005
Day 3
43.9 (5.2)
43.4 (6.2)
,0.0005
0.99
2 (0 4)
,0.0005
,0.0005
Before surgery
25.0 (0.2)
25.0 (1.1)
Day 1
22.0 (2.1)
20.6 (3.6)
0.003
Day 2
23.1 (2.0)
21.8 (2.6)
,0.0005
Day 3
23.9 (1.8)
22.9 (2.8)
0.0012
Before surgery
35.0 (0.4)
34.7 (1.5)
0.033
Day 1
34.8 (0.8)
34.5 (1.7)
0.15
Day 2
34.9 (0.5)
34.6 (1.6)
0.069
Day 3
34.9 (0.5)
34.8 (1.2)
0.148
Before surgery
34.9 (0.7)
34.6 (1.4)
0.033
Day 1
32.4 (3.1)
30.1 (4.5)
0.0001
Day 2
33.6 (2.2)
31.3 (3.6)
,0.0005
Day 3
34.1 (2.2)
32.3 (3.4)
,0.0005
Pain (35)
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Characteristic
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Buchanan et al.
Table 6 Correlation of plasma sex steroid concentrations with perioperative indices adjusted for age and inhalation agent MAC in a random
sample of 28 women. BIS, bispectral index; QoR, quality of recovery
Oestrogen
Progesterone
Waist:hip ratio
P-value
20.22
0.29
0.86
0.38
0.02
0.94
Eye-opening time
20.04
0.83
20.53
0.01
0.26
,0.001
0.13
0.55
0.04
0.62
0.20
,0.001
20.22
0.29
20.01
0.96
0.33
,0.001
P-value
36.0 (6.8)
Premenopausal females
37.5 (8.5)
0.18
Post-menopausal females
38.9 (7.2)
0.04
1.00
P-value
Proportion
BIS score
Males ,52 yr
0.75
0.50
Male
Menopausal female
Premenopausal female
0.25
0.00
0
10
15
20
25
Proportion
1.00
Fig 2 Time to obeying commands after cessation of general
anaesthesia in males, premenopausal women, and postmenopausal women.
0.75
0.50
0.25
Male
Postmenopausal female
Premenopausal female
0.00
0
5
10
Analysis time (min)
15
Discussion
We found that patient sex is an independent factor influencing both responsiveness to general anaesthesia and recovery after anaesthesia. After matching subjects in our cohort
for age, ASA physical status, type and extent of surgery,
and other factors known to influence recovery, and adjusting
836
Patient group
P-value
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200
QoR-40 score
Table 8 Relationship between sex and time adjusted for age and
ASA status using Cox proportional hazards. *Derived from the
hazard ratio, where a value greater than 1.0 indicates an
increased likelihood of faster recovery time. Using male patients
as a reference
Recovery ratio (95%
CI)*
P-value
Premenopausal female
,0.005
Postmenopausal female
0.53
Age
0.28
170
ASA
0.43
Ex-smoker
0.95
Smoker
0.39
Eye-opening
Smoking status
Alcohol intake
0.98 (0.74 1.30)
0.90
Heavy
0.23
Intermediate
0.38
Major
0.98
0.45
Premenopausal female
,0.0005
Postmenopausal female
0.92
Age
0.10
0.28
Ex-smoker
0.29
Smoker
0.46
Social
0.14
Daily
0.03
Intermediate
0.45
Major
0.91
0.14
P<0.0005
0
2
Postoperative day
Extent of surgery
Neuromuscular blocking
agent use
Obeying commands
Smoking status
Alcohol intake
Extent of surgery
Neuromuscular blocking
agent use
837
Social
Male
Premenopausal female
Postmenopausal female
BJA
Conflict of interest
None.
Funding
The study was funded by an Australian and New Zealand
College of Anaesthetists project grant (02/014). Dr Frank
Buchanan was supported by an Australian and New
Zealand College of Anaesthetists Scholarship. Professor Paul
Myles is supported by an Australian National Health and
Medical Council Practitioner Fellowship.
838
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