ORIGINAL ARTICLE

Local Anesthesia Combined With Sedation

Compared With General Anesthesia for
Ambulatory Operative Hysteroscopy:
A Randomized Study
Lone Dragnes Brix, MHSc, RN, Theis Muncholm Thillemann, MD, PhD,
Lone Nikolajsen, MD, DMSc

Purpose: The purpose of this study was to compare two anesthetic tech-
niques for postoperative pain after ambulatory operative hysteroscopy.
Design: A randomized trial.
Methods: Women (N 5 153) scheduled for ambulatory operative
hysteroscopy were assigned to receive either paracervical local anesthesia
combined with sedation (group LA 1 S; n 5 76) or general anesthesia
(group GA; n 5 77). Primary outcome was the worst pain intensity score
in the postanesthesia care unit (PACU) rated by the patients on a
numerical rating scale.
Finding: Data from 144 patients were available for analysis (LA 1 S:
n 5 69; GA: n 5 75). There were no significant differences in worst
pain intensity between groups in the PACU (P 5 .13) or after discharge
from PACU (P 5 .40). In group LA 1 S, fewer patients received treatment
with intravenous fentanyl intraoperatively (P , .01) and time until
discharge from PACU was shorter (P , .01). More patients in group
LA 1 S experienced vomiting after discharge (P , .05).
Conclusions: Local anesthesia with sedation can be recommended as a
first choice anesthetic technique for operative ambulatory hysteroscopy.
Keywords: postoperative pain, anesthesia, ambulatory surgery, opera-
tive hysteroscopy.
2016 by American Society of PeriAnesthesia Nurses

HYSTEROSCOPY PROCEDURES SUCH as poly- care providers, such as a decrease in complication

pectomy, endometrial ablation, and myomectomy rates, a short recovery time with rapid return
are frequently performed in ambulatory surgery to work, and shorter hospital stays and thus
settings,1 with many benefits for the patients and reduced costs.2-4

Lone Dragnes Brix, MHSc, RN, PhD student at the
Department of Anesthesiology, Horsens Regional Hospital,
Horsens, Denmark; Theis Muncholm Thillemann, MD, PhD,
Speciality registrar at the Department of Orthopedic Surgery,
Aarhus University Hospital, Aarhus, Denmark; and Lone
Nikolajsen, MD, DMSc, Research consultant at the Danish
Pain Research Centre and Department of Anesthesiology,
Aarhus University Hospital, Aarhus, Denmark.
L.D.B. has received funding from the Family Hede Nielsen
Foundation, the Gurli and Hans Engell Friis Foundation,
the Aase and Ejnar Danielsens Foundation (10-001290),
and the Health Research Fund of Central Denmark. The foun-
dations had no influence on the study design, collection, anal-
ysis or interpretation of data, or in writing the article or in the
decision to submit it for publication.
Conflicts of interest: None to report.
Address correspondence to Lone Dragnes Brix, Department
of Anesthesiology, Horsens Regional Hospital, Sundvej 30,
Horsens 8700, Denmark; e-mail address: lonebrix@rm.dk.
2016 by American Society of PeriAnesthesia Nurses
1089-9472/$36.00
http://dx.doi.org/10.1016/j.jopan.2015.09.009

Journal of PeriAnesthesia Nursing, Vol -, No - (-), 2016: pp 1-8 1

2 BRIX, THILLEMANN, AND NIKOLAJSEN
Hysteroscopy is painful, and various methods for
anesthesia have been described, including paracer-
vical local anesthetic injections combined with
sedation and general anesthesia.5-7 Effective
postoperative pain management is essential for
early discharge after ambulatory surgery.
However, there is no consensus on the choice of
anesthesia. We therefore decided to compare
two commonly used anesthetic methods:
paracervical local anesthesia combined with
sedation (LA 1 S) and general anesthesia (GA).
Materials and Methods
Patients
The study was approved by the Central Denmark Re-
gion Committees on Health Research Ethics
(M-20110023), the Danish Health and Medicines
Authority (EudraCT number: 2010-023843-13),
and the Danish Data Protection Agency. It was
registered at Clinicaltrial.gov (NCT01412632),
conducted in accordance with guidelines for Good
Clinical Practice (GCP), and monitored by the
GCP-unit at Aarhus University Hospital, Denmark.
After obtaining written informed consent, 153
patients were enrolled at the Day Surgery Unit at
Horsens Regional Hospital, Denmark. Inclusion
criteria were planned operative hysteroscopy
procedure and age $18 years. Exclusion criteria
were pregnancy, fibroids .3 3 3 cm, body mass
index $40, psychiatric illness, inability to commu-
nicate in Danish, or known allergy to remifentanil,
propofol, or prilocaine.
Randomization and Intervention
On the day of surgery, patients were randomized to
receive LA 1 S or GA by using sequentially
numbered opaque-sealed envelopes. Randomiza-
tion was performed in block sizes of 20 patients,
each with a ratio of 1:1 according to a computer-
generated sequence. Both groups received dexa-
methasone 8 mg, paracetamol 1 g, and ibuprofen
600 mg orally as premedication before anesthesia.
If ibuprofen was contraindicated, it was replaced
by tramadol 50 mg orally. According to the
standard protocol of postoperative nausea and
vomiting (PONV) prophylaxis, intraoperative
4-mg intravenous (IV) ondansetron was used for
patients with a high risk of PONV.
For patients in group LA 1 S, anesthesia was
induced with propofol 2.5 mg/kg/hour and remi-
fentanil 12.5 mcg/kg/hour. When the patient
was able to sense the effect of remifentanil, infu-
sion rates were reduced and maintained by a
continuous infusion of propofol 1.33 mg/kg/
hour and remifentanil 3 to 5 mcg/kg/hour. The
infusion rates were adjusted equal to a patient
sedation level at 3 to 4 on the Ramsay Sedation
Scale (1 to 6). Using a .4 3 35 long needle, the
gynecologist applied 3.60- to 7.2-mL Citanest
Dental Octapressin (30 mg/mL 1 .54 mcg/mL
prilocaine hydrochloride 1 felypressin; Pierrel
S.p.A., Capua, Italy) for paracervical local anes-
thesia. Bolus doses of 50- to 100-mcg fentanyl
IV were used for treatment of intraoperative
pain $3 on a Numerical Rating Scale (NRS;
0 5 no pain and 10 5 worst pain possible).
For patients in group GA, anesthesia was induced
with propofol 10 mg/kg/hour and remifentanil
50 mcg/kg/hour; and when the patient was able
to sense the effect of remifentanil, a bolus dose
of propofol 2 to 2.5 mg/kg was given. Hereafter,
the infusions were maintained by continuous infu-
sion of propofol 5 mg/kg/hour and remifentanil
2.5 mcg/kg/hour. The infusion rates were adjusted
equal to a patient sedation level at 6 on Ramsay
Sedation Scale, 1 to 6. The airway was managed
with a laryngeal mask, and the lungs were venti-
lated with 40% to 45% oxygen in air. Bolus doses
of 50- to 100-mcg fentanyl IV were used for
intraoperative pain, guided by increases in pulse
and blood pressure and/or motor unrest during
anesthesia. In both groups, remifentanil and pro-
pofol infusions were discontinued 4 to 5 minutes
before the end of surgery. Surgery was performed
by experienced gynecologists specialized in hys-
teroscopic procedures and trained in paracervical
local anesthesia.
The same team of anesthesia providers and nurses
in the PACU took care of and treated the two
groups according to standard protocols regarding
pain and PONV/postdischarge nausea and vomit-
ing (PDNV).
Care and Treatment
In the PACU, intensity of pain (NRS, 0-10) and
nausea and vomiting (yes/no) were assessed at
arrival, and every 15 minutes, or with shorter
LOCAL ANESTHESIA COMBINED WITH SEDATION
intervals if any changes in the intensity of pain,
nausea, and/or vomiting occurred. Pain in the
PACU (NRS $ 3) was treated with bolus doses of
25- to 50-mcg fentanyl IV with a maximum of
300 mcg in the PACU. PONV in the PACU was
treated with 4-mg ondansetron IV, .625-mg dehy-
drobenzperidol (droperidol) IV, and 10-mg meto-
clopramide IV. Shivering in the PACU was treated
with 20-mg pethidine IV.
Oral postoperative analgesic treatment was started
before discharge from the PACU and consisted of
paracetamol (acetaminophen) 1 g orally every
6 hours up to 4 g daily and ibuprofen 600 mg orally,
up to 1,800 mg daily as rescue medication. If
ibuprofen was contraindicated, it was replaced
by oral tramadol 50 mg, up to 200 mg daily.
Patients were discharged directly from the PACU
and were provided these oral analgesics to use at
home.
Data Collection and Outcome Measures
Baseline patient characteristics were collected
from medical records. The primary outcome mea-
sure was the worst pain intensity score in the
PACU rated by the patients on the NRS (0-10)
from arrival to the PACU until discharge. Second-
ary outcome measures were use of intraoperative
fentanyl (no/yes), use of analgesic and antiemetic
medication in the PACU (no/yes), PONV (no/yes),
time until discharge from PACU (minutes), recalled
worst pain after discharge (NRS, 0-10), and
recalled PDNV (no/yes).
Before discharge, all patients were supplied with a
questionnaire including questions regarding pain
and side effects during the 2 weeks after surgery.
The questionnaire was a log for the investigator
to document the patients verbal response when
they were contacted by phone 2 weeks after sur-
gery and asked to recall the worst pain after
discharge from PACU and PDNV.
Statistical Analysis
The sample size calculation was based on an
expected difference of 1 on the NRS with 80% po-
wer (a 5 .05, b 5 .2). A sample size of 47 per
group was required, ie, a total of 94 patients. Based
on an expected response rate of 65% after 2 weeks,
it was decided to include at least 150 patients.
3
Normality of data was tested without pointing to-
ward normal distribution. Therefore, nonpara-
metric testing was performed. Fisher exact test
was used for dichotomous covariates and the
Wilcoxon rank sum test for continuous covariates.
Results are presented as frequencies or medians
with range as appropriate. All P values are two
sided, and those below .05 were considered signif-
icant. Intention-to-treat analysis was performed.
EpiData, version 3.1 (Epidata Association, Odense,
Denmark), was used for double entry, and statisti-
cal analysis was performed with Stata software,
version 12.0 (StataCorp, TX).
Results
A total of 364 women were assessed for eligibility
from November 2011 through June 2013; 22 were
excluded based on the exclusion criteria, 157
declined to participate (72 preferred LA 1 S, 50
preferred GA, 35 declined to participate for other
reasons), and 32 were excluded because of logistic
reasons. One hundred fifty-three patients were
randomized: 76 to the LA 1 S group and 77 to
the GA group (Figure 1). Baseline characteristics
including age, height, weight, body mass index,
smoking status, surgical procedure, and duration
of surgery were comparable between groups
(Table 1).
There was no significant difference in worst pain
intensity between group LA 1 S and group GA in
the PACU (1.5 [0 to 8] vs 2.2 [0 to 9], P 5 .13, me-
dian [Range]; Figure 2A). Intraoperatively, fewer
patients in the LA 1 S group received treatment
with fentanyl IV (14 vs 62; P , .01; Table 2). In
the PACU, there was no statistical difference be-
tween group LA 1 S and group GA in the number
of patients treated with fentanyl IV (6 vs 13;
P 5 .13; Table 2). There was no significant differ-
ence in the number of patients who experienced
nausea in the PACU between group LA 1 S and
group GA (4 vs 4; P 5 .90) or the number of
patients who received ondansetron IV (4 vs 4;
P 5 .90). In group LA 1 S, fewer patients received
PONV prophylaxis (5 vs 31; P , .01). None of the
patients vomited during hospitalization (Table 3).
Time in the PACU (63 [15 to 210] vs 81 [15 to
200] minutes, P , .01, median [range]) and time
from start of surgery until discharge (99 [40 to
305] vs 121 [60 to 265] minutes, P , .01) were
significantly shorter in group LA 1 S group.
4 BRIX, THILLEMANN, AND NIKOLAJSEN

Analyzed Analyzed

Figure 1. CONSORT study flow diagram. BMI, body mass index; CONSORT, CONsolidated Standards of Reporting
Trials; GA, general anesthesia; LA 1 S, local anesthesia combined with sedation.

Two weeks after discharge from PACU, there was Discussion

no significant difference in recalled worst pain
intensity between group LA 1 S and group GA
(1.5 [0 to 8] vs 1.5 [0 to 8], P 5 .40, median
[Range]; Figure 2B). A total of 12 patients, five
in the LA 1 S and seven in group GA, recalled
having suffered from nausea (P 5 .46) and four
patients, all belonging to group LA 1 S, recalled
having vomited after discharge (P 5 .05;
Table 3).
In this study of ambulatory operative hysteroscopy
procedures, LA 1 S did not significantly decrease
patients worst pain intensity in the PACU. Howev-
er, the number of patients treated with IV fentanyl
intraoperatively and time from start of surgery un-
til discharge from PACU were significantly reduced
in group LA 1 S. More patients in group LA 1 S
vomited after discharge.
LOCAL ANESTHESIA COMBINED WITH SEDATION 5

Table 1. Baseline Demographic and Clinical Characteristics of Study Participants

Baseline Characteristics LA 1 S (n 5 69) GA (n 5 75) P value
Age (y) 47 45 .05
[29 to 78] [27 to 67]
Height (m) 1.67 1.68 .28
[153 to 185] [150 to 187]
Weight (kg) 71 kg 73 kg .97
[48 to 100] [50 to 111]
BMI (kg/m2) 25.2 24.6 .93
[18.6 to 37.2] [19.2 to 38.1]
Smoking status (no/yes/missing) 53/16/0 63/10/2 .14
Surgical procedure
Endometrial ablation 33 46 .06
Myomectomy 2 2
Polymectomy 22 19
Combined operations 12 8
Duration of surgery (min) 35 37.5 .07
[15 to 95] [20 to 80]
BMI, body mass index; GA, general anesthesia; LA 1 S, local anesthesia combined with sedation; PACU, postanes-
thetic care unit.
Patient characteristics in the interventions group (LA 1 S) and in the control group (GA).
Median [range].

Some methodological issues must be considered. be judged as having received either LA 1 S or GA

First is the lack of blinding. Attempts to blind the just by observation on arrival in the PACU. Finally,
study would have failed for several reasons. In most patients knew how they were anesthetized.
the operating room, blinding was obviously not
possible and in the PACU, the organization of the Second, the lack of difference can be attributed to
unit, with the nursing staff working in both the low pain intensity score in both groups. In the pre-
operating room and in the PACU made blinding sent study, both groups received propofol, which
impossible. In addition, almost every patient could is associated with significantly less postoperative
40

40
30

30
Number of patients

Number of patients
20

20
10

10
0

0 1 2 3 4 5 6 7 8 9 10 0 1 2 3 4 5 6 7 8 9 10
NRS, 0-10 NRS, 0-10

LA+S GA LA+S GA

Figure 2. A1B: Maximum pain intensity in the PACU (A) and after discharge (B) The maximum pain intensity
scores in the PACU (A) and after discharge (B) after ambulatory operative hysteroscopy. GA, general anesthesia;
LA 1 S, local anesthesia combined with sedation; NRS 0-10, Numerical Rating Scale from 0 5 no pain to
10 5 worst pain possible; PACU 5 postanesthesia care unit.
6 BRIX, THILLEMANN, AND NIKOLAJSEN

Table 2. Number of Patients Who Received Fentanyl Intraoperatively and in the PACU
Analgesic medication LA 1 S (n 5 69) GA (n 5 75) P Value
Fentanyl IV intraoperatively (no/yes) 55/14 13/62 , .01
Fentanyl IV in PACU (no/yes) 63/6 62/13 .13
GA, general anesthesia; IV, intravenous; LA 1 S, local anesthesia with sedation; PACU, postanesthetic care unit.
Bold indicates significant level was set at P , 0.05.

pain. Combined with a short duration of surgery,
this may have contributed to the low pain inten-
sity.8-12 A presumably large proportion of
patients declined to participate because they had
strong preferences regarding either general
anesthesia or local anesthesia combined with
sedation. Being given a choice of anesthetic
induction method can reduce anxiety,13 and the
enrolled patients may therefore have a higher level
of anxiety and pain intensity than all patients
eligible for the study. The most anxious patients
may have chosen not to participate in the study.
However, the low pain score is in accordance
with other studies which found that gynecological
patients have fewer postoperative symptoms,
including postoperative pain, than orthopaedic
and general surgery patients.14-16
Third, patients were interviewed by telephone
2 weeks after surgery regarding the worst pain in-
tensity after discharge. The pain intensity score
after discharge may be influenced by recall bias,
due to the fact that patients were asked to recall
the worst pain after discharge from PACU on the
NRS.
Compared with previous studies, we found that
patients in both groups had a lower incidence of
nausea in the PACU12,17 and after discharge.18
The lower incidence of nausea in the PACU
is, however, similar to recent findings showing
that patients who were anesthetized with
remifentanil-propofol had less postoperative nausea
than patients anesthetized with remifentanil only.19
A previous study found as many as 36% of patients
who experienced PDNV did not experience
nausea and vomiting before discharge from hospi-
tal.17 In the present study, only patients in group
LA 1 S vomited after discharge. This could be
attributed to the lower number of patients in the
LA 1 S group who received PONV prophylaxis
because of a lower risk of PONV. PDNV is consid-
ered to be a growing concern, and suitable strate-
gies should be planned for patients after discharge
because patients often do not have access to
antiemetic treatment after discharge.11,17
Preventing PDNV is important because it may
delay the resumption of normal activities,
readiness for work, and have a negative impact
on the patients experience and recovery.9,12

Table 3. Number of Patients Who Experienced PONV, PDNV, and Received Antiemetic Treatment
PONV LA 1 S (n 5 69) GA (n 5 75) P Value
Ondansetron (no/yes) intraop 64/5 44/31 , .01
Nausea (no/yes) 66/4 71/4 .90
Vomiting (no/yes) 69/0 75/0
Ondansetron (no/yes) PACU 65/4 71/4 .90
DHB (no/yes) 70/0 74/1 .52
PDNV LA 1 S (n 5 62) GA (n 5 69)
Nausea (no/yes) 57/5 62/7 .46
Vomiting (no/yes) 58/4 69/0 , .05
GA, general anesthesia; DHB, dehydrobenzperidol; LA 1 S, local anesthesia combined with sedation; PACU, postanes-
thesia care unit; PDNV, postdischarge nausea and vomiting; PONV, postoperative nausea and vomiting.
The number of patients who experienced PONV, PDNV, and received antiemetic treatment.
LOCAL ANESTHESIA COMBINED WITH SEDATION
As in the present study, another Danish study
found a significantly reduced time from surgery
until discharge in patients who were anesthetized
with paracervical local anesthesia with sedation
compared to patients who were anesthetized
with general anesthesia for ambulatory operative
hysteroscopy.19
Although some methodological issues exist, as
described, the present study is distinguished by
successful randomization and adherence to the
principles of GCP. No serious side effects were
observed. We find external validity to be strength-
ened by the fact that the study was carried out in a
daily clinical setting with the anesthesia protocols
and discharge criteria reflecting daily practice.
Overall, the findings of the study can be general-
ized to women having operative hysteroscopy pro-
cedures in an ambulatory surgery setting.
Recommendations for future studies include hav-
ing a smaller team of specially trained providers
who are responsible for data collection and a
data collection instrument using a series of
possible responses instead of dichotomous
answers. Further studies should also monitor
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