preincisional and intraperitoneal ropivacaine plus normal saline infusion for postoperative pain...
TRANSCRIPT
Preincisional and intraperitoneal ropivacaine plus normal salineinfusion for postoperative pain relief after laparoscopiccholecystectomy: a randomized double-blind controlled trial
George Pappas-Gogos Æ Konstandinos E. Tsimogiannis Æ Nicolaos Zikos ÆKonstantinos Nikas Æ Adamantia Manataki Æ Evangelos C. Tsimoyiannis
Received: 6 April 2007 / Accepted: 18 October 2007 / Published online: 13 February 2008
� Springer Science+Business Media, LLC 2008
Abstract
Background A clinical trial was designed to assess the
use of preincisional and intraperitoneal ropivacaine, com-
bined or not with normal saline, to reduce pain after
laparoscopic cholecystectomy (LC).
Methods For this trial, 120 patients were randomly
assigned to six groups. For all the patients, preincisional
local infiltration of ropivacaine around the trocar wounds
was performed. Group A had infusion of ropivacaine at the
beginning of the LC. Group B had infusion of ropivacaine at
the beginning of the LC plus normal saline infusion at the
end. Group C had normal saline infusion and ropivacaine at
the end of the LC. Group D had infusion of ropivacaine at
the beginning of the LC plus normal saline infusion at the
end and a subhepatic closed drain. Group E had ropivacaine
at the end of the LC. Group F (control group) had neither
ropivacaine nor normal saline infusion. Shoulder tip and
abdominal pain were registered at 2, 4, 6, 12, 24, 48, and 72
h postoperatively using a visual analog score (VAS).
Results Significantly lower pain scores were observed in
group B than in group A at 2, 4, 6, 12, and 24 h or in groups
C, D, E, and F at 2, 4, 6, 12, 24, and 48 h. Group A also had
significantly lower pain scores than groups C, D, E, and F at
2, 4, 6, 12, 24, and 48 h. Requests for analgesics also were
significantly less in group B than in group A at 2, 4, 6, 12,
and 24 h or in groups C, D, and E at 2, 4, 6, 12, 24, and 48 h.
Demand for additional analgesia was less in group B than in
groups A, C, D, E, and F at 2, 4, 6, 12, and 24 h and in group
A than in groups C, D, E, and F at 2, 4, 6, and 12 h.
Conclusion Preincisional local infiltration plus intraperi-
toneal infusion of ropivacaine at the beginning of LC
combined with normal saline infusion at the end of the pro-
cedure is a safe and valid method for reducing pain after LC.
Keywords Abdominal pain � Laparoscopic
cholecystectomy � Local anesthetics � Normal saline �Ropivacaine hydrochloride � Shoulder pain �Trocar wounds
Laparoscopic cholecystectomy (LC), is the treatment of
choice for symptomatic cholelithiasis [1]. Findings have
shown that decreased pain and improved pulmonary
function tests are the benefits of LC compared with small-
incision cholecystectomy. However, LC it is not a pain-free
procedure [5].
Pain and time of convalescence are the two main
problems after LC [2]. Furthermore, postoperative pain has
been an important limiting factor for ambulatory LC [3, 4].
To date, the exact mechanism of pain has not been clari-
fied. Factors that may influence the degree of pain after LC
include the volume of residual gas, the type of gas used for
the pneumoperitoneum, the pressure thereby created, and the
temperature of insufflated gas [5]. The carbon dioxide (CO2)
gas remaining within the peritoneal cavity for a few days or
G. Pappas-Gogos � K. E. Tsimogiannis � N. Zikos � K. Nikas �E. C. Tsimoyiannis
Department of Surgery, G. Hatzikosta General Hospital,
Makriyanni Avenue, GR-45001 Ioannina, Greece
G. Pappas-Gogos
e-mail: [email protected]
A. Manataki
Department of Anesthesia, G. Hatzikosta General Hospital,
Makriyanni Avenue, GR-45001 Ioannina, Greece
E. C. Tsimoyiannis (&)
3, Hippocratus, Stavraki, GR-45332 Ioannina, Greece
e-mail: [email protected]
123
Surg Endosc (2008) 22:2036–2045
DOI 10.1007/s00464-008-9762-x
the hypothermia caused by the CO2 gas commonly causes
postoperative shoulder and abdominal pain, particularly
after the recommended early activity and ambulation [1].
Single trials have assessed the use of intraperitoneal local
anesthetics, but their results are controversial.
The use of a local anesthetic applied to the port wounds
provides some benefit in pain reduction, but it is short lived
[5]. Our previous study found the benefit of the intraperi-
toneal normal saline infusion at the end of the procedure to
be postoperative pain reduction after LC [1]. Another study
found that the combination of normal saline infusion and
bupivacaine at the end of the operation achieves better
results than normal saline alone. However, the combination
of normal saline infusion and bupivacaine without a closed
drain was as valuable as the normal saline infusion alone
followed by a subhepatic suction closed drain [6]. Ropiva-
caine is a long-acting, amid-type local anesthetic with
pharmacodynamic and pharmacokinetic properties similar
to those of bupivacaine [7]. In human volunteers ropivacaine
is less likely than bupivacaine to elicit adverse effects from
the central nervous system and the circulatory system [8].
This prospective, randomized, double-blind controlled
trial was designed to assess the efficacy of preincisional local
infiltration and intraperitoneal infusion of ropivacaine at
different stages of the procedure in combination with normal
saline infusion in reducing postoperative pain after LC.
Materials and methods
The study was approved by the scientific committee on
Human Rights in Research at G. Hatzikosta General Hos-
pital, Ioannina, Greece. Patients were administered elective
LC under general anesthesia. The criteria for exclusion
were an American Society of Anesthesiology (ASA)
physical status of 3 or more, conversion of the operation to
an open procedure, planned emergency LC or exploration
of the common bile duct, and chronic pain diseases other
than gallstone disease.
All the LCs in this study were performed by the same
surgeon. All the patients were placed in reverse Trendel-
enburg position (30�), with the table tilted downward to the
patient’s left. Using the Hasson technique, the pneumoper-
itoneum was created with a 10-mm umbilical trocar.
Another 10-mm trocar was placed in the midepigastrium just
to the right of the falciform ligament, and two 5-mm trocars
were placed in the right upper abdomen two fingerbreadths
below the right coastal margin in the midclavicular and the
midaxillary line. The gas used was CO2.
During laparoscopy, intraabdominal pressure was
maintained at 10 to 11 mmHg. The anesthesiologists fol-
lowed the same general anesthetic protocol. All patients
were premedicated with intravenous paracetamol, ondan-
setron hydrochloride, and ranitidine. Anesthesia was
induced using fentanyl (1.5 lg/kg), propofol (2-2.5 mg/
kg), and cis-atracurium (0.16 mg/kg). After endotracheal
intubation, all the patients were provided with mechanical
ventilation using sevoflurane (1–2%) and an air/oxygen
mixture (30% O2). In every patient, a nasogastric tube was
inserted at the beginning then removed after the interven-
tion. With the pain score as the primary criterion, a power
analysis (p = 0.90; a = 0.05 unilateral, Bonferroni cor-
rection) based on our previous studies [1, 6] showed that 18
to 20 patients were mandatory for each group.
From March 2005 to November 2006, 120 patients with
uncomplicated symptomatic cholelithiasis were random-
ized into six groups of 20 patients each (Table 1). Each
patient was invited to choose 1 envelope from 120 sealed
Table 1 Presentation of the different treatment protocols
Group of
patients
Time of intraperitoneal subdiaphragmatic
ropivacaine infusion
Time of intraperitoneal subdiaphragmatic
normal saline infusion
Subhepatic closed
drain placement
A (n = 20) Ropivacaine infusion at the beginning of the
operation after pneumoperitoneum creation
No normal saline infusion No drain
B (n = 20) Ropivacaine infusion at the beginning of the
operation after pneumoperitoneum creation
Normal saline infused at the end of the
operation and suctioned after
pneumoperitoneum deflation
No drain
C (n = 20) Ropivacaine infusion at the end of the operation
after pneumoperitoneum deflation and normal
saline suction
Normal saline infusion at the end of the
operation before ropivacaine infusion
No drain
D (n = 20) Ropivacaine infusion at the beginning of the
operation after pneumoperitoneum creation
Normal saline infused at the end of the
operation and suctioned after
pneumoperitoneum deflation
A closed drain was
placed
E (n = 20) Ropivacaine infusion at the end of the operation
after pneumoperitoneum deflation
No normal saline infusion No drain
F (n = 20) No ropivacaine infusion No normal saline infusion No drain
Surg Endosc (2008) 22:2036–2045 2037
123
envelopes that contained the assigned group and a serial
number from 1 to 20. Thus, all the patients were assigned
to one of the six groups randomly. The patients, the
anesthesiologists, and the staff responsible for the data
collection (pain-measuring scores and analgesic request)
were blinded to the study. Only the surgeon was informed
about the group of the patient.
For all the patients, 10 ml of a solution containing
ropivacaine hydrochloride (7.5 mg/ml) (Naropeine
ASTRA; Pharmaceutical Production AB, Sodertalje, Swe-
den) was infiltrated around the trocar wounds: 4 ml around
the umbilical port site and 2 ml around the others. All
incisions were made after ropivacaine infiltration.
For groups A, B, D, and E, 40 ml of ropivacaine solution
(2 mg/ml) was infused at the beginning of the procedure
under the right hemidiaphragm. The local anesthetic infu-
sion was performed using the suction device under visual
control.
For groups B, C, and D, normal saline 0.9% (30 ml/kg)
at 37�C was infused at the end of the procedure under the
right hemidiaphragm. The suction device was placed under
the right hemidiaphragm using visual control. Once the
pneumoperitoneum was deflated, normal saline was
suctioned.
For group C, ropivacaine was infused intraperitoneally
at the end of the procedure after normal saline had been
suctioned. A subhepatic closed drain was placed for 24 h in
group D only.
For group F (control group), neither intraperitoneal
infusion of ropivacaine nor normal saline was infused.
Abdominal and shoulder tip pain was registered at
postoperative hours 2, 4, 6, 12, 24, 48, and 72 h. To assess
postoperative pain 2, 4, 6, 12, 24, 48, and 72 h after the
operation, a visual analog scale (VAS) with a 10-cm ver-
tical score ranging from ‘‘no pain’’ to ‘‘worst possible
pain’’ was used.
After the patients had been adequately instructed about
the range measuring pain, they selected a value on the
scale. Thus, the pain intensity was monitored at the des-
ignated points in time. At each testing interval, one score
was obtained for abdominal pain and a second score for
shoulder pain. Nausea and vomiting were assessed at the
same intervals.
All patients were given suppositories of 4-(acetyl-
amino)-phenol 400 mg with codeine phosphate 20 mg plus
caffeine 50 mg (Lonarid N; Boehringer, Ingelheim, Ger-
many) on demand. In case of failure, additional analgesia
consisting of ketoprofen caps 200 mg (Oruvail; Rhone-
Poulenc Rorer, Germany) was administered as an intrave-
nous dose 1 mg/kg per single shot for nausea or vomiting.
Statistical analyses for the pain intensity scores were
performed using the Mann-Whitney U test. The differences
between the groups regarding the variables of nausea,
vomiting, and leaking were assessed with the use of the
chi-square testing, whereas the patients’ demographic data,
need for analgesics, and time of hospitalization were
compared using t-testing. All statistical analyses were
conducted with SPSS version 12.0 statistical software
(SPSS Inc., Chicago, IL, USA). The level of significance
was set at 0.05.
Results
The demographic characteristics of the patients in the six
groups are presented in Table 2. There were no significant
differences in the data, except that bile spillage was higher
for the group D patients, although this difference was not
significant. No intraoperative complications occurred for
the patients in any of the groups.
Seven patients were excluded from the study. Three of
these patients were bleeding from the umbilical wound, and
additional stitches had to be placed postoperatively. One
patient had a suppurative umbilical wound; one had an
umbilical pus collection; one had a subhepatic collection;
and at least one patient had pneumonitis on postoperative
Table 2 Demographic data and operative variables (mean ± standard deviation)a,b
Group
A B C D E F
(n = 20) (n = 20) (n = 20) (n = 20) (n = 20) (n = 20)
Age (years) 49.2 ± 16.9 57.9 ± 9.8 53.5 ± 15.9 60.5 ± 11.2 52.8 ± 13.1 53.05 ± 12.1
Weight (kg) 74.1 ± 13.3 68.05 ± 8.3 76.8 ± 14.6 78.4 ± 16.1 73 ± 8.2 78.5 ± 9.8
Height (cm) 166.5 ± 11.8 164.1 ± 5.9 163 ± 7.3 167.2 ± 7.8 166 ± 5.9 167.7 ± 6.1
Mean operative time (min) 37.8 ± 10,05 35.3 ± 9.4 40.8 ± 21.6 45.5 ± 18.3 40.3 ± 13.7 39.05 ± 12.9
Postoperative hospital stay (days) 1.05 ± 0.22 1.35 ± 0.58 1.15 ± 0.36 1.3 ± 0.8 1.3 ± 0.9 1.25 ± 0.66
Bile spillage (no. of patients) 2 3 2 5 2 3
Mean blood loss (ml) 6.4 9.9 5.9 7.7 5.8 6.1
a None of the differences in values between the groups were significantb Student’s t-test
2038 Surg Endosc (2008) 22:2036–2045
123
day 3. These conditions might potentially have influenced
postoperative pain perception, so all these patients were
randomly replaced by seven new patients to make the
sample homogeneous.
Pain scores (Table 3) analyses showed statistically sig-
nificant differences (regarding shoulder tip and abdominal
pain) between groups A and B at 2, 4, 6,12, and 24 h.
Significant lower pain scores were observed in group B
than in groups C, D, E, and F at 2, 4, 6, 12, 24, and 48 h.
The patients in group A reported significantly lower pain
score rates than the patients in groups C, D, E and F 2, 4, 6,
12, 24, and 48 h after LC (Figs. 1 and 2).
Table 3 Abdominal and shoulder pain scores rangea,b
Abdominal pain score range Group
Group
Time after operation (h) A (n = 20) B (n = 20) C (n = 20) D (n = 20) E (n = 20) F (n = 20)
2 2.3 ± 0.73 1.8 ± 0.82 2.85 ± 0.86 2.8 ± 0.75 3.1 ± 1.34 3.15 ± 1.31
4 2.7 ± 0.75 2.3 ± 0.72 3.3 ± 1.01 3.35 ± 1.16 3.65 ± 1.46 3.7 ± 1.50
6 4.5 ± 0.76 3.9 ± 0.96 5.35 ± 1.69 5.35 ± 1.46 5.0 ± 1.56 5.15 ± 1.50
12 4.65 ± 0.81 4.05 ± 0.93 5.55 ± 1.64 5.4 ± 1.47 5.15 ± 1.57 5.3 ± 1.50
24 3.8 ± 0.76 3.4 ± 0.67 4.35 ± 1.44 4.4 ± 1.21 4.45 ± 1.81 4.55 ± 1.78
48 2.2 ± 0.52 2.1 ± 0.54 2.9 ± 1.15 2.85 ± 0.91 3.05 ± 1.57 3.2 ± 1.37
72 1.15 ± 0.49 1.2 ± 0.61 1.6 ± 1.25 1.4 ± 0.49 1.25 ± 0.94 1.3 ± 0.9
Time after operation (h) Group p Value comparisonsc,d
(B vs A (A vs C) (A vs D) (A vs E) (A vs F) (B vs C) (B vs D) (B vs E) (B vs F)
2 0.026 0.017 0.026 0.039 0.017 \0.0001 \0.0001 \0.0001 \0.0001
4 0.029 0.027 0.043 0.007 0.006 \0.0001 \0.0001 \0.0001 \0.0001
6 0.019 0.031 0.028 0.033 0.004 \0.0001 \0.0001 \0.0001 \0.0001
12 0.036 0.036 0.031 0.020 0.002 \0.0001 \0.0001 \0.0001 \0.0001
24 0.033 0.034 0.027 0.038 0.008 \0.0001 \0.0001 \0.0001 \0.0001
48 0.507 0.006 0.004 0.004 \0.0001 \0.0001 \0.0001 0.004 \0.0001
72 0.681 0.276 0.059 0.804 0.815 0.292 0.096 0.920 0.868
Shoulder pain score range
Group
Time after operation (h) A (n = 20) B (n = 20) C (n = 20) D (n = 20) E (n = 20) F (n = 20)
2 1 ± 0.7 0.55 ± 0.50 1.45 ± 0.59 1.35 ± 0.47 1.35 ± 0.65 1.3 ± 0.46
4 1.45 ± 0.68 0.95 ± 0.74 1.85 ± 0.66 2.15 ± 1.20 1.85 ± 0.65 2.1 ± 1.26
6 2.2 ± 1.0 1.60 ± 0.87 3.05 ± 0.75 2.9 ± 0.83 2.9 ± 1.27 3.1 ± 0.77
12 2.45 ± 1.31 1.80 ± 0.93 3.05 ± 0.75 2.8 ± 0.40 2.9 ± 1.23 2.95 ± 0.38
24 2.1 ± 1.02 1.55 ± 0.93 2.7 ± 0.79 2.65 ± 0.48 2.75 ± 1.26 2.65 ± 0.66
48 1.65 ± 0.93 1.35 ± 0.73 2.2 ± 0.51 2.2 ± 0.75 2.25 ± 1.04 2.3 ± 1.23
72 0.85 ± 0.67 0.85 ± 0.66 0.9 ± 0.30 0.95 ± 0.59 1.1 ± 0.70 1 ± 0.55
Time after operation (h) Group p Value comparisonsc,d
(B vs A (A vs C) (A vs D) (A vs E) (A vs F) (B vs C) (B vs D) (B vs E) (B vs F)
2 0.016 0.006 0.010 0.019 0.015 \0.0001 \0.0001 \0.0001 \0.0001
4 0.022 0.029 0.035 0.012 0.008 \0.0001 \0.0001 \0.0001 \0.0001
6 0.012 0.001 0.010 0.010 \0.0001 \0.0001 \0.0001 \0.0001 \0.0001
12 0.030 0.012 0.028 0.045 0.001 \0.0001 \0.0001 \0.0001 \0.0001
24 0.032 0.035 0.021 0.039 0.020 \0.0001 \0.0001 \0.0001 \0.0001
48 0.167 0.010 0.024 0.029 0.004 \0.0001 \0.0001 \0.0001 \0.0001
72 1.000 0.535 0.495 0.163 0.269 0.461 0.382 0.070 0.149
a Pain scores were assessed by the visual analog scale (VAS)b Data are expressed as mean ± standard deviationc None of the differences in value for C vs D, C vs E, C vs F, D vs E, D vs F, and E vs F were statistically significantd Mann-Whitney U test
Surg Endosc (2008) 22:2036–2045 2039
123
The patients in group D (same procedure as for group B
but with a subhepatic drain applied) did not demonstrate
any apparent benefit. These patients may have been influ-
enced by the drain tube. As result, they registered pain
scores as in groups C, E, and F.
Nausea and vomiting (Table 4) occurred in all the
groups, but no significant differences were observed
between them. The mean number of Lonarid N supposi-
tories and eventually the additional analgesic (ketoprofen)
given to the patients of every group during the postopera-
tive period are shown in Table 5.
There were significant differences in the number of
Lonarid N suppositories requested (Table 5) between
groups A and B at 2, 4, 6, 12, and 24 h. Significant dif-
ferences also were registered for groups A and B compared
with groups C, D, and E at 2, 4, 6, 12, 24, and 48 h. Group
B also reported fewer requests for analgesia than group F at
72 h (Figs. 3 and 4).
With regard to additional analgesia demand (ketopro-
fen), group B reported significant lower analgesia request
rates than groups A, C, D, E, and F at 2, 4, 6, 12, and 24 h.
Significant differences between group A and groups C, D,
E, and F at 2, 4, 6, and 12 h also were registered.
Discussion
The establishment of LC as an outpatient procedure has
emphasized the clinical importance of reducing early
postoperative pain and nausea [1]. Early postoperative pain
that persists in many cases for 3 days or more is complex
and includes different pain components secondary to dif-
ferent pain mechanisms such as abdominal wall trauma,
intraabdominal trauma secondary to gallbladder removal,
abdominal distension by insufflated gas, and pneumoperi-
toneum using CO2 . The early mobilization increases
traction on peritoneal reflection by heavy viscera, which
lose suction support for their weight due to the creation of
peritoneal spaces by gas [1, 12]. It seems that the total
volume of CO2 may be a more important factor than the
duration of exposure. Jackson et al. [9] found that the
amount of residual gas correlated with the postoperative
pain.
Surprisingly, intraoperative bile spillage proved to be
associated with more rapid resolution of the pneumoperi-
toneum [10]. In our study, we did not observe any
improvement in postoperative pain for these patients.
Another pain mechanism may be the formation of
intraperitoneal carbonic acid from CO2. Intraperitoneal
acidosis has been documented in humans after CO2 pneu-
moperitoneum, but also has been found in patients with
argon pneumoperitoneum [11]. Pain after LC, described in
several studies as parietal, can be blocked by trocar wounds
before incisional infiltration and visceral or shoulder tip
pain, which theoretically can be blocked by intraperitoneal
infusion of local anesthetics. Several studies have reported
the use of local anesthetics for postoperative pain after LC
[18, 19].
Table 4 Analytical nausea and vomiting ratesa,b
Group
A (n = 20) B (n = 20) C (n = 20) D (n = 20) E (n = 20) F (n = 20)
No. of patients with nausea in early postoperative period (h)
2 0 0 1 0 1 1
4 1 0 0 1 1 1
6 1 2 2 2 1 1
12 1 1 1 1 0 0
24 1 1 1 1 1 0
48 0 1 0 0 1 1
72 0 0 0 0 0 1
No. of patients with vomiting in early postoperative period (h)
2 0 0 0 0 1 1
4 1 0 0 2 1 1
6 1 2 2 1 1 1
12 1 1 1 1 0 0
24 1 1 1 1 1 1
48 0 1 0 0 1 0
72 0 0 0 0 0 0
a None of the differences in value between the groups were significantb Chi-square test
2040 Surg Endosc (2008) 22:2036–2045
123
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\0
.00
01
\0
.00
01
48
0.1
02
0.0
04
\0
.00
01
0.0
02
\0
.00
01
\0
.00
01
\0
.00
01
\0
.00
01
\0
.00
01
72
1.0
00
0.1
23
0.2
28
0.2
19
0.9
90
.48
0.1
16
0.1
04
0.0
28
No
.o
fk
eto
pro
fen
Gro
up
Tim
eaf
ter
op
erat
ion
(h)
A(n
=2
0)
B(n
=2
0)
C(n
=2
0)
D(n
=2
0)
E(n
=2
0)
F(n
=2
0)
21
1(0
.55
±0
.60
)4
(0.2
0±
0.4
0)
17
(0.8
5±
0.3
6)
16
(0.8
0±
0.4
0)
19
(0.9
5±
0.2
1)
18
(0.9
0±
0.3
0)
41
1(0
.55
±0
.51
)4
(0.2
0±
0.4
0)
19
(0.9
5±
0.3
9)
16
(0.8
0±
0.4
0)
16
(0.8
0±
0.4
0)
17
(0.8
5±
0.3
6)
61
2(0
.60
±0
.50
)6
(0.3
0±
0.4
6)
19
(0.9
5±
0.3
9)
17
(0.8
5±
0.3
6)
18
(0.9
0±
0.4
4)
17
(0.8
5±
0.3
6)
12
13
(0.6
5±
0.4
9)
7(0
.35
±0
.48
)1
9(0
.95
±0
.39
)1
8(0
.90
±0
.30
)2
1(1
.05
±0
.59
)1
8(0
.90
±0
.30
)
24
14
(0.7
0±
0.5
7)
7(0
.35
±0
.48
)1
5(0
.75
±0
.43
)1
6(0
.80
±0
.40
)1
7(0
.85
±0
.36
)1
4(0
.70
±0
.46
)
48
8(0
.40
±0
.50
)7
(0.3
5±
0.4
8)
8(0
.40
±0
.49
)9
(0.4
5±
0.5
0)
9(0
.45
±0
.5)
9(0
.45
±0
.50
)
72
6(0
.30
±0
.47
)6
(0.3
0±
0.4
6)
7(0
.35
±0
.48
)9
(0.4
5±
0.5
0)
8(0
.40
±0
.50
)8
(0.4
0±
0.5
0)
Tim
eaf
ter
op
erat
ion
(h)
pV
alu
eb,c
(Bv
sA
)(A
vs
C)
(Av
sD
)(A
vs
E)
(Av
sF
)(B
vs
C)
(Bv
sD
)(B
vs
E)
(Bv
sF
)
20
.01
00
.00
90
.02
8\
0.0
00
1\
0.0
00
1\
0.0
00
1\
0.0
00
1\
0.0
00
1\
0.0
00
1
40
.00
5\
0.0
00
10
.02
10
.01
70
.00
1\
0.0
00
1\
0.0
00
1\
0.0
00
1\
0.0
00
1
Surg Endosc (2008) 22:2036–2045 2041
123
Local anesthetics produce block of Ad and C fibers.
Low pKa and high lipid solubility of a local anesthetic
favor A over C fiber block. The reverse is true for high pKa
and low lipid solubility. The lower lipid solubility of rop-
ivacaine is presumed to retard penetration of myelin
sheaths. This greater degree of differential block, with
ropivacaine at low concentration, and the property of fre-
quency-dependent block production were considered to
offer great clinical advantage in the provision of analgesia
with minimal motor block [16].
An editorial published by Albright [17] in 1979 asso-
ciated the long-acting local anesthetics bupivacaine and
etidocaine with cardiac arrest during local anesthesia and
sporadic cases of maternal death resulting from accidental
intravenous injection of 0.75% bupivacaine at the time of
extradural anesthesia for Caesarean section. This sequence
of events provided the necessity to develop a new local
anesthetic drug with a lower lipid solubility. Plain solutions
of ropivacaine produce a significantly longer duration of
dermal anesthesia than plain solutions of bupivacaine.
Preincisional wound infiltration with local anesthetics
seems to have provided some benefit in early postoperative
pain reduction, as concluded from several studies [5, 14,
22]. However, some studies found no such benefit [13, 15].
In our study, the trocar wounds of all patients were pre-
emptively infiltrated with 10 ml (7.5 mg/ml) of ropivacaine
hydrochloride.
Reports of study results with bupivacaine used as an
intraperitoneal local anesthetic have been conflicting. The
duration of pain suppression was limited, and no benefit
was shown in terms of earlier discharge or earlier return to
normal activity [5]. Ropivacaine (70 ml/0.25%) infiltrated
into cholecystectomy wounds significantly decreases
wound pain and increases the time until the first request for
postoperative analgesia compared with saline, as reported
by Gupta [18].
Two other authors also reported excellent results in
terms of decreased postoperative pain and diminished
request for postoperative analgesics after intraperitoneal
instillation of ropivacaine. Although Labaille et al. [20]
found that 100 mg of ropivacaine instilled intraperitoneally
at the beginning of the procedure is an optimal dose for
reducing pain after LC, they did not report any significant
benefit in terms of demand for postoperative analgesics.
Kucuk et al. [21] reported benefit in terms of both post-
operative pain and postoperative analgesics consumption
using 150 mg of ropivacaine. No authors observed any
toxic effect attributable to the local anesthetic.
In our study, we used 155 mg of ropivacaine (75 mg
infiltrated at the trocar wounds and 80 mg instilled
intraperitoneally under the right hemidiaphragm). We
also did not observe side effects attributable to the
ropivacaine.Ta
ble
5co
nti
nu
ed
No
.o
fL
on
arid
N
60
.02
50
.00
20
.01
20
.00
70
.00
8\
0.0
00
1\
0.0
00
1\
0.0
00
1\
0.0
00
1
12
0.0
28
0.0
06
0.0
05
0.0
05
0.0
02
\0
.00
01
\0
.00
01
\0
.00
01
\0
.00
01
24
0.0
16
0.6
83
0.3
86
0.1
29
1.0
00
\0
.00
01
\0
.00
01
\0
.00
01
\0
.00
01
48
0.7
11
1.0
00
0.6
91
0.6
84
0.6
79
0.6
18
0.2
99
0.2
82
0.2
71
72
1.0
00
0.6
87
0.2
28
0.4
05
0.3
99
0.6
07
0.1
16
0.2
72
0.2
61
aD
ata
are
exp
ress
edas
the
mea
nn
um
ber
of
anal
ges
ics
±st
and
ard
dev
iati
on
bN
on
eo
fth
ed
iffe
ren
ces
inv
alu
efo
rC
vs
D,
Cv
sE
,C
vs
F,
Dv
sE
,D
vs
F,
and
Ev
sF
wer
esi
gn
ifica
nt
cS
tud
ent’
st-
test
2042 Surg Endosc (2008) 22:2036–2045
123
A critical point regarding the effectiveness of local
anesthetics infused intraperitoneally seems to be the timing
of the procedure. Some authors maintain that the optimal
timing is at the beginning of the procedure before creation
of pneumoperitoneum [23–25]. Other authors have repor-
ted good outcomes immediately after pneumoperitoneum
creation [18, 19] or at the end of the procedure [20, 26].
Intraperitoneal normal saline infusion has been used in
several studies to achieve postoperative pain reduction
after LC. Two studies combined intraperitoneal normal
saline infusion with low-pressure pneumoperitoneum [27,
28]. In one of our previous studies, we found a significant
decrease in postoperative pain using normal saline infusion
alone at the end of the procedure [1], whereas in another
study combining intraperitoneal bupivacaine infusion at the
end of the procedure with normal saline infusion, we
reported better results in terms of postoperative pain
reduction after LC [6].
In the current study, we administered the ropivacaine
intraperitoneal infusion at the beginning or end of the
procedure with or without normal saline infusion. We
preferred to infuse ropivacaine immediately after creation
of the pneumoperitoneum under visual control. Normal
saline was infused under visual control, then suctioned
after complete pneumoperitoneum deflation. This was
achieved by positioning the suction device properly under
visual control before deflation of the pneumoperitoneum.
In group D, a subhepatic closed drain was placed for 24 h.
In one of our previous studies, we found that the postop-
erative pain was decreased for these patients. This was not
confirmed in the current study.
In our attempt to interpret the results of the first study,
we thought that a subhepatic closed drain placed for 24 h
might completely aspirate the CO2 remaining from the
pneumoperitoneum. In the current study, we observed that
the patients with a subhepatic closed drain were more
susceptible to the somatic pain than the patients belonging
to other groups.
Our group A patients (ropivacaine at the beginning of the
procedure without normal saline infusion) demonstrated a
significant postoperative pain decrease in comparison with
the other groups (except group B) for the first 48 h.
The group B patients (intraperitoneal ropivacaine infu-
sion at the beginning of LC plus normal saline infusion at
the end of the procedure and suction after pneumoperito-
neum deflation) had statistically significant better results
overall in terms of postoperative pain decrement. We found
a significant decrease in postoperative pain for the first 48 h
compared with groups C, D, E, and F. In addition, we
found a significant postoperative pain decrease for the first
24 h in comparison with group A. With regard to postop-
erative analgesia request rates, we found that they followed
the same rate as that for the pain scores.
The results of this study demonstrated that the intra-
peritoneal action of ropivacaine infused at the beginning of
the procedure (although possibly not excluding a systemic
analgesic action from intraperitoneal infusion) [20] com-
bined with optimal removal of CO2 and prevention of
hypothermia by normal saline infused at 37�C is the factor
primarily responsible for the superiority of group B. The
occurrence of nausea and vomiting was equally observed,
and there were no significant differences among the groups.
Group
FEDCBA
6
5
4
3
2
1
0
-1
Postoperative Shoulder Pain Scores
72h postop48h postop24h postop
12h postop6h postop4h postop2h postop
Mean
Fig. 1 Postoperative shoulder tip pain scores (mean ± standard
deviation) at different postoperative intervals for each group
Group
FEDCBA
Mean
10
7,5
5
2,5
0
Postoperative Abdominal Pain Scores
72h postop48h postop24h postop
12h postop6h postop4h postop2h postop
Fig. 2 Postoperative abdominal pain scores (mean ± standard devi-
ation) at different postoperative intervals for each group
Surg Endosc (2008) 22:2036–2045 2043
123
In conclusion, preincisional local infiltration of ropiva-
caine plus ropivacaine subdiaphragmatic infusion at the
beginning of the LC combined with normal saline infusion
between the liver and the diaphragm at the end of the
procedure represents a safe and valid method for reducing
pain after LC.
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Group
FEDCBA
Mean
4
3
2
1
0
-1
Lonarid N request after the operation
72h postop48h postop24h postop
12h postop6h postop4h postop2h postop
Fig. 3 Number of Lonarid N requests after the operation
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each group
Group
FEDCBA
Mean
3
2
1
0
-1
Ketoprofen request after the operation
72h postop48h postop24h postop
12h postop6h postop4h postop2h postop
Fig. 4 Number of ketoprofen requests after the operation
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each group
2044 Surg Endosc (2008) 22:2036–2045
123
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Surg Endosc (2008) 22:2036–2045 2045
123