Cir Cir 2013;81:359-368.

Analgesic efficacy of the incisional infiltration of

ropivacaine vs. ropivacaine with dexamethasone
during elective laparoscopic cholecystectomy
Gerardo Evaristo-Mndez,1 Javier Eduardo Garca de Alba-Garca,2 Jos Ernesto Sahagn-Flores,3
Flix Antonio Ventura-Sauceda,1 Jorge Uriel Mndez-Ibarra,1 Rogelio Ricardo Seplveda-Castro1

Abstract

Background: Incisional pain is the main obstacle for elective outpatient laparoscopic cholecystectomy. We evaluated the analgesic
efficacy of local infiltration of ropivacaine with dexamethasone (Rop/Dx) compared with ropivacaine (Rop) alone during the first 24 h
postoperativeof this surgery. Our hypothesis is that incisional pain intensity will be lower in patients from the Rop/Dx group.
Methods: In a randomized, controlled, double-blind trial clinical, 80patients were divided into two groups. Rop group (n =40) received
pre- and post-incisional infiltration with 150mg of ropivacaine in 8mL of 0.9% saline, whereas Rop/Dx group (n =40) received 150mg
of ropivacaine with 8mg of dexamethasone in 6mL of 0.9% saline. The intensity of pain at rest and movement was assessed at 2, 4, 8,
12, and 24h postoperatively by an 11-point numerical rating scale.
Results: Incisional pain scores in Rop/Dx group were significantly lower compared to the Rop group at 12h (p =0.05) and 24h (p =
0.01) at rest and at 12h (p =0.04) and 24h (p =0.01) during movement postoperatively.
Conclusions: We found initial evidence that ropivacaine with dexamethasone for local infiltration decreased incisional pain 12h post-
elective laparoscopic cholecystectomy with a good safety profile.

Key words: Laparoscopic cholecystectomy, incisional pain, dexamethasone.

Introduction first 24 h after this surgical intervention, with a predomi-

In elective laparoscopic cholecystectomy (LC), duration of
the postoperative convalescence of patients depends on se-
veral factors, the most important being pain. Without con-
sidering the scheme of administered analgesics, 40% of the
patients manifest pain of moderate to severe intensity in the
1
Departamento de Ciruga General, Hospital Regional Dr. Valentn
Gmez Faras, ISSSTE. Zapopan, Jalisco, Mxico
2
Unidad de Investigacin Social, Epidemiolgica y en Servicios de
Salud, IMSS, Guadalajara, Jalisco, Mxico
3
Departamento de Investigacin, Hospital Regional Dr. Valentn
Gmez Faras, ISSSTE. Zapopan, Jalisco, Mxico
Correspondence:
Gerardo Evaristo Mndez
Departamento de Ciruga General
Hospital Regional Dr. Valentn Gmez Faras
Sptimo piso. Av. Soledad Orozco 203
45150 Zapopan, Jalisco, Mxico
Tel: (33) 3836 0650, ext. 146
E-mail: gevaristo5@yahoo.com.mx
Received: 4-23-2013
Accepted: 6-28-2013
nance of incisional pain in incidence and intensity, com-
pared with visceral pain and referred pain to the shoulder.1
Multimodal analgesia is one of the techniques used to treat
postoperative pain which, when combining medications with
additive or synergistic effects and different mechanisms of
action, not only improves the efficiency of individual drugs
but also reduces their secondary effects.2 This method has
been recommended during the LC for its effectiveness,
although the medical literature does not allow for defini-
tive conclusions about the type and dose of drugs, the time
suitable for administration or its ideal combination.3 A cru-
cial component of multimodal analgesia in LC, in order to
decrease the intensity of acute pain in surgical wounds, is
incisional infiltration with local anesthetics. However, its
effect is limited to 3 or 4 h after a single dose, as in the case
of ropivacaine.4 Because the inflammation caused by tissue
injury plays an important role in the generation of incisional
pain, glucocorticoids are indicated for its relief in several
surgical procedures.5 The usual route of administration to
increase the duration of the analgesia and to reduce the in-
tensity of the pain is intravenous, especially for dexametha-
sone alone or as adjuvant treatment. However, other routes
of application, such as local, enable the achievement of
therapeutic actions with maximum concentration at the le-

Volume 81, No. 5, September-October 2013 359


sion site and with lower systemic toxicity.6 Because there is
still the need for multimodal analgesic protocols specific for
every laparoscopic procedure,7 the objective of this study is
to assess whether the incisional pain intensity is lower after
infiltration of surgical wounds with ropivacaine plus dexa-
methasone, compared with that obtained with ropivacaine
alone, during the first 24 h postoperative of elective LC.
Patients and Methods
Patients and Groups
We carried out a controlled, randomized, double-blind
clinical trial. The study was approved by the ethics com-
mittee of our hospital and was carried out in accordance
with the principles for human research, the Declaration of
Helsinki (2008 revised) and the Mexican General Health
Law in Research. All patients signed a consent form after
being informed of the different pain components that they
would experience at the conclusion of the surgery. Inclusion
criteria were patients who underwent elective LC for symp-
tomatic cholelithiasis using general anesthesia (class I-II of
the American Society of Anesthesiologists), either gender,
18 and <80years of age, and with postoperative incisional
type pain. Among the main exclusion criteria were patients
who received steroids, analgesics or who had undergone an
endoscopic papillotomy <1 week prior to surgery; heart,
kidney or liver failure and if the elective LC was planned
along with another intra-abdominal procedure. According
to institutional protocol, patients were admitted the night
before surgery. They were assigned, shortly after the in-
duction of anesthesia, to one of two groups using a list of
computer-generated random numbers with the closed and
opaque envelope delivered to the operating room. Between
November 8, 2011 and June 29, 2012, 40 patients received,
by local incisional infiltration, 150 mg of ropivacaine (7.5
mg/mL, i.e., 20 mL) plus 8 mL of saline solution 0.9% (Rop
group), whereas 40 patients received 150 mg of ropivacaine
with 8 mg of dexamethasone (2 mL) plus 6 mL of saline
solution 0.9% (Rop/Dx group). In both groups the total in-
filtration volume was 28 mL (14 mL before incisions and 14
mL at the conclusion of the surgery in the same locations).
Anesthesia
Oral premedication was not given prior to LC and the gene-
ral balanced anesthesia technique was similar in all cases.
Patients were premedicated with midazolam (0.05 mg/kg)
30 min before surgery and after the placement of a periphe-
ral venous access, which was maintained permeable with
360 Ciruga y Cirujanos
Evaristo-Mndez G et al.
crystalloid Ringer lactate solution (10-15 mL/kg). After
placing the instruments for standard monitoring (electrocar-
diography, non-invasive blood pressure, pulse oximetry and
capnography), IV anesthesia with propofol (2-2.5 mg/kg)
and fentanyl (2-4mg/kg) was induced. Tracheal intubation
was facilitated with rocuronium (600 g/kg). Anesthesia
was maintained with sevoflurane (2-3.5%) and 2-3 L/min
of 100% oxygen. To maintain analgesia and muscle relaxa-
tion, additional doses of fentanyl (2 g/kg/h) and rocuro-
nium (0.2mg/kg) were given. The minute ventilation was
adjusted to control and maintain a PcO2 at end expiration of
35 to 40mmHg. To reverse the neuromuscular paralysis at
the end of the surgical procedure, neostigmine (0.04mg/kg)
and atropine (100g/kg) were administered when required.
Patients received antibiotic prophylaxis with ceftriaxo-
ne (1g) 30min prior to initiation of surgery, ondansetron
(4mg) and pantoprazole (40mg) during the course of the
operation, and ketorolac (30mg) 30min before its comple-
tion, all administered IV. After anesthesia was discontinued
and tracheal extubation was done, patients were transferred
to a post-anesthesia care unit.
Surgery
LC was performed in the American position using a four
trocar technique. According to the research group assigned,
half of the solution (14 ml in the Rop group and 14 ml in the
Rop/Dx group) with the mixture of drugs and saline were in-
filtrated before incision and divided into equal volumes (3.5
ml) in the skin and subcutaneous tissue of each of the four
areas selected for the placement of the trocars. Pneumope-
ritoneum was created with CO2 using a Veress needle with
intraabdominal pressure maintained at 12mmHg during the
operation. With the patient in the inverted Trendelenburg
position at 30 and rotated towards the left side, dissection of
the gallbladder was carried out with laparoscopic Maryland
clamps, scissors or hook. Cholangiogram was done if indi-
cated. The remnants of the cystic duct and the cystic artery
were closed with titanium staples. The gallbladder was ex-
teriorized via the epigastric port. When necessary, a fascial
incision of 0.5-1cm was carried out through this port to
facilitate exteriorization of the gallbladder, which was not
systematically recorded. A Penrose drain was left on the in-
ferior surface of the liver through the 5-mm right lateral
port. The drain was removed, if indicated, at 12 to 24 h
postoperatively. At the conclusion of the surgery the CO2
was released (to decrease the probability of referred pain to
the shoulder) with manual compression of the abdomen and
the open ports. Before closure of infiltrated surgical wounds
equal volumes were used for each (3.5mL), the preperi-
toneal space, muscle, fascia, subcutaneous tissue and skin,
using half of the mixture that contained the saline solution
Incisional analgesia with dexamethasone in laparoscopic cholecystectomy
and the assigned drugs (14mL in Rop group and 14mL
Rop/Dx group). Only the fascia in the 10-mm ports was
closed with 0 absorbable suture. The skin of all ports was
closed with 3-0 absorbable sutures. The list and keys of the
randomization, as well as the scores of postoperative pain
intensity, were given only to the principal investigator who
carried out the statistical analysis at study completion.
Postoperative Course
For each patient the following data were collected: location
of abdominal pain before evaluating its incisional intensi-
ty, gender, age, body mass index (BMI), number of prior
abdominal surgeries, surgical time, anesthesia time, length
of hospital stay after surgery and quantity of opiates requi-
red. Complications detected were recorded during the 30
postoperative days. Pain intensity was evaluated with the
11-point Numerical Rating Scale (0 = no pain and 10 = the
worst pain) at rest and with movements (patients from the
supine to the seated position), in time frames established at
2, 4, 8, 12, and 24h postoperatively (except during sleep).
As part of the multimodal analgesic protocol, IV ketorolac
was administered (30mg) every 8h. The patients who had
severe pain (>7/10) received 10 mg of nalbufin (5 mg IV
and 5mg SC) as rescue analgesia. In case of nausea or vo-
miting, IV ondansetron was given (4mg) every 8h. Patient
discharge from the hospital, which was never <24h accor-
ding to institutional protocol, was decided by the treating
surgeon according to the criteria of a satisfactory control of
pain, complete mobility, and normal and stable vital signs.
The outpatient medication scheme was standardized in all
cases and consisted of paracetamol (500mg oral) each 6h
and celecoxib (200mg oral) every 12h, both for 4 days.
Statistical Analysis
To calculate the size of the sample, a 5% error was es-
tablished and the power (1-) at 80%. Initially a pilot stu-
dy was conducted with 20 patients not randomized (10/
group), which detected (60% of patients) a minimum di-
fference of 1.5 between the means of the two treatments
in study and a SD of 1.7. Subsequently, the Lehr formu-
la8 was applied with an estimated 15% loss. Thirty patients
per group were obtained, but 40 were analyzed by virtue of
their availability before the pre-set period to reach the sam-
ple size. Data were described with numbers, proportions
(%), median and mean SD. Categorical variables were
analyzed with the Pearson c2 test and, when appropriate,
with the Fisher exact test. For comparison of the means
and normally distributed data, Student t test was applied
for independent variables or the Welch test where applica-
Volume 81, No. 5, September-October 2013 361
ble. Mann-Whitney U test was used in the comparison of
median and non-normally distributed data. For analysis of
discontinuous data generated by the numerical rating scale,
we obtained graphs of pain-time for each patient from re-
peated measures of the established intervals (2, 4, 8, 12, and
24 h). Subsequently, the regression coefficient estimated by
the minimum squared as summary measures were applied.9
At the end, Mann-Whitney U test was used to compare the
statistical significance of these measures between groups.
In all cases, a two-tailed test was applied with a priori sta-
tistical significance set at p 0.05 and 95% CI. Statistical
analyses were done according to intention to treat basis of
the clinical trials utilizing a statistical package for the social
sciences (SPSS v.19.0; SPSS, Chicago, IL) for Windows,
Microsoft Excel 2007 (Microsoft, Redmond, WA) and EPI-
DAT v.3.1 (Pan American Health Organization).
Results
We allocated at random 80/139 patients recruited for the
study to receive treatment, and all completed the establis-
hed protocol (Figure1). In none of the cases was there an
indication for intraoperative cholangiogram and all inter-
ventions were carried out without complications. Demogra-
phic and perioperative data (Table1) such as age, gender,
BMI, number of previous abdominal surgeries, physical
condition of the ASA, surgical time and anesthesia time
were similar between groups. Only length of hospital stay
after LC was greater with statistical significance in the Rop
group compared with the Rop/Dx group (p =0.013; 95%
CI = 0.2442.006). Of the 59 patients excluded (Table2),
the most frequent causes were for refusal to sign informed
consent (27%), total or referred pain (15%), and pre-
dominantly visceral pain (12%). Sclerosed atrophic gall-
bladder (3%) and hepatic artery injury (2%) were reasons
for conversion to open cholecystectomy due to technical
difficulties in dissection and for adequate control of blee-
ding, respectively. In both situations, as well as in cases of
conversion due to prolonged surgical time (3%), the scores
of the numerical classification scale were obtained but were
not included in the final analysis of the study and their ran-
domization numbers were reassigned.
Figure2 shows the values in medians obtained by means
of measures of summary by regression coefficients for in-
tensity of incisional pain at rest. There were no significant
differences between Rop and Rop/Dx groups at 2h (nu-
merical rating scale, 4.7 vs. 4.5; p = 0.40), 4h (numerical
rating scale, 4.4 vs 4.2; p = 0.27) and 8h of the postopera-
tive period (numerical rating scale, 3.9 vs 3.5; p = 0.18).
Patients who received Rop/Dx did have less pain (with sta-
tistical significance) compared with the Rop group at 12 h

Eligibility values
Randomized (n = 80)
Assigned to Rop Group (n = 40)
Received assignment (n = 40)
Did not receive (n = 0)
Lost to follow-up (n = 0)
Assignment discontinued (n = 0)
Analyzed (n = 40)
Excluded from analysis (n = 0)
Figure1. CONSORT Diagram (Consolidated Standards of Reporting Trials) illustrating the flow of patients in parallel groups, exclusions,
randomization and follow-up. Rop, ropivacaine; Dx, dexamethasone.
(numerical rating scale, 2.8 vs 3.4; p =0.05) and 24h (nu-
merical rating scale, 0.8 vs 1.6; p = 0.01). During movement
(Figure3) there were no differences between the Rop and
Rop/Dx groups at 2h (numerical rating scale, 5.6 vs 5.6;
p = 0.37), 4h (numerical rating scale, 5.4 vs. 5.1; p = 0.22)
and 8h (numerical classification scale, 5.0 vs 4.2; p = 0.11).
At 12 (numerical rating scale, 3.5 vs 4.2; p = 0.04) and 24h
(numerical rating scale, 1.2 vs 2.5; p = 0.01) of the postop-
erative period the intensity of incisional pain was less in
the Rop/Dx group (with statistical significance). Nalbufine
intake during the first 24 h post-LC was greater in the Rop
group (3 5mg) than in the Rop/Dx group (2 4mg),
but without statistical significance (p =0.437; 95% CI =
-1.1612.661) (Table 3). There were two cases of superfi-
cial infection at the surgical site (one in each study group)
in the periumbilical wound for laparoscopic access. Finally,
there was no observation or report of any adverse effect at-
tributed to dexamethasone during the initial 30 postopera-
tive days.
362 Ciruga y Cirujanos
Evaristo-Mndez G et al.
Excluded (n = 59)
No inclusion criteria (n = 22)
Declined participation (n = 16)
Other reasons (n = 21)
Assigned to Rop/Dx group (n = 40)
Received assignment (n = 40 )
Did not receive (n = 0)
Lost to follow-up (n = 0)
Assignment discontinued (n = 0)
Analyzed (n = 40)
Excluidos del anlisis (n = 0)
Discussion
According to Bisgaard et al.,1 post-LC pain is a complex
of three clinically different components. These include the
intra-abdominal visceral pain, which is described as deep
and dull; referred pain to the shoulder; and incisional pain,
which is somatic in origin and easily located by the patients
on the surface of the anterior abdominal wall in the surgical
wounds. Total pain is comprised, simultaneously, by the
three mentioned components. The same authors highlight the
lack of studies of analgesic drug treatment of these compo-
nents separately, as well as the importance and prevalence of
incisional pain above the other two during the first day after
this surgical procedure. In Mexico and worldwide, there are
more elective and ambulatory LC done each day as opposed
other procedures, with a success rate of almost 70% with a
good patient selection, but still with pain as the main rea-
son for remaining in the hospital the same day of the inter-
vention.10 For these reasons, within the scope of multimodal
Incisional analgesia with dexamethasone in laparoscopic cholecystectomy

Table 1. Demographic data and perioperative variables of the patients

Rop group Rop/Dx group

Variable (n = 40 ) (n = 40 ) p value 95% CI

Age (years)a 46 10 45 10 0.872 -4.2254.975

Sex (M/F) (n)b 7 / 33 4 / 36 0.330
Weight (kg)a 74 14 71 11 0.269 -2.4288.578
Height (cm)a 165 7 164 9 0.412 -2.0474.947
BMI (kg/m2)a 27 4 26 4 0.365 -0.8902.390
Physical status ASA (I/II)b 23 / 17 23 / 17 1.000
Prior surgeries (n, %)b 12 (30%) 12 (30%) 1.000
Surgical time (min)a 59 15 61 13 0.648 -7.6084.758
Anesthesia time (min)a 78 19 81 14 0.376 -10.8454.145
POHS time (h)c 26 2 25 2 0.013 0.2442.006
Values expressed as mean SD and number or percentage patients.
a
Student t test.
b
Pearson c2 test.
c
Welch test.
Statistical significance p 0.05.
Rop, ropivacanae. Dx, dexamethasone; BMI, body mass index; ASA, American Society of Anesthesiologists;
POHS, postoperative hospital stay.

Table 2. Patients excluded from study and analysis

Inclusion criteria not found n (%)

<18 years of age 2 (3)

Patients with referred shoulder pain 4 (7)
Patients with visceral pain 7 (12)
Patients with total pain 9 (15)
Declined to participate
Did not sign informed consent 16 (27)
Other reasons
Pregnancy 1 (2)
BMI 35.0 kg/m 3 (5)
Uncontrolled arterial hypertension 3 (5)
Uncontrolled diabetes mellitus 4 (7)
Kidney disease 1 (2)
Liver disease 1 (2)
Alcohol abuse 2 (3)
LC with other abdominal procedure 1 (2)
Conversion to open surgery due to prolonged surgical time (>90 min) 2 (3)
Sclerosed atrophic gallbladder 2 (3)
Hepatic artery injury 1 (2)
Total 59 (100)

Volume 81, No. 5, September-October 2013 363

 Evaristo-Mndez G et al.

10.00 analgesia, we carried out this study to test the hypothesis that
9.00 local infiltration of ropivacaine with dexamethasone decrea-
ses the intensity of incisional pain, compared with ropivacai-
8.00
ne alone, in the first 24h post-elective LC.
Intensity of pain (NRS 0-10)

7.00 Incisional pain is caused by the interrelation of three fac-

6.00
tors: 1) impulses generated on the damaged nerve fibers;
2) inflammatory mediators; and 3) sensitization of the cir-
5.00 cuits that transmit pain to the spinal cord and at the central
4.00 level.11 Infiltration with ropivacaine at the laparoscopic ac-
cess sites for the LC basically acts to block the first of the
3.00
mechanisms described, but its effect is limited to the first 3
2.00 or 4 h postoperatively,4 which is clearly insufficient to treat
1.00 the patients in an outpatient manner after this operation. For
our study, because there was no clear evidence of obtaining
0.00
Rop Rop/Dx
greater analgesia using local anesthetics by means of their
preventive local infiltration, after the nociceptive stimulus
Treatment group
or when combining both techniques, we chose the last op-
2 hours 4 hours 24 hours tion because the three are equally effective and its selection
8 hours 12 hours
is at present due to the personal preference of the surgeon.12
There is also no agreement or specific information about
Figure2. Changes at rest of the incisional pain post-laparoscopic the dose of ropivacaine or the volume of saline solution for
cholecystectomy. Values are expressed as medians. Patients with dilution in incisional analgesia; therefore, we administered
dexamethasone had significantly less pain during 12- (p = 0.05) and the quantities used by other authors during elective LC.13
24-h periods (p = 0.01). NRS, numerical rating scale; Rop, ropivacai-
ne; Dx, dexamethasone. Statistical significance p 0. 05.
Regarding the glucocorticoids, Skjelbred and Lkken14 re-
ported for the first time their analgesic effects in patient who
had molar extraction. However, recent systematic reviews
on the efficacy of IV dexamethasone to relieve post-LC
pain are inconclusive.15 The use of this steroid as an analge-
10.00
sic has also been described in different surgical procedures
9.00 by means of its local infiltration to the soft tissues, alone or
8.00 as an adjuvant with local anesthetics.5,6,16 This recent his-
Intensity of pain (NRS 0-10)

7.00
tory, as well as the mechanisms of action of dexametha-
sone known up to now, provide sustenance and biological
6.00
credibility for its incisional use in our trial. In summary,
5.00 decrease in the synthesis of proinflammatory cytokines and
4.00
prostaglandins by activation of the protein annexin-1 and of
MAPK-1 (mitogen-activated protein phosphatase kinase),
3.00 the antagonist to NF-B (nuclear factor kappa-light-chain-
2.00 enhancer of activated B cells), inhibition of AP-1 (acti-
vating protein) and suppression in the transcription of the
1.00
COX-2 enzyme (cyclooxygenase-2) could contribute, via
0.00 independent routes within the cells, to the relief of pain by
Rop Rop / Dx this glucocorticoid.17
Treatment group
The inhibition of the transmission of signals in the C fi-
2 hours 4 hours 24 hours bers and the decrease in tissue concentration of neuropep-
tides can also participate in the analgesic effect that can be
8 hours 12 hours seen with its local application.18 The following mechanisms
have been described at the molecular level: 1) binding to
Figure3. Changes upon movement of the incisional pain post-la- response elements of the DNA with direct reduction in the
paroscopic cholecystectomy. Values are expressed as medians. Pa-
tients with dexamethasone had significantly less pain during 12- (p =
expression; 2) indirect interaction with transcriptional fac-
0.04) and 24-h periods (p = 0.01). NRS, numerical rating scale; Rop, tors; and 3) through receptors associated with membrane
ropivacaine; Dx, dexamethasone. Statistical significance p 0.05. and second messengers (nongenomic route).19 The latter

364 Ciruga y Cirujanos

Incisional analgesia with dexamethasone in laparoscopic cholecystectomy
Table 3. Consumption of opiod analgesics (nalbufin) for 24 h post-LC
Rop group
(n = 40)
Use of nalbufin, n (%) 11 (28)
Dose of nalbufin (mg) a
35
Values expressed as mean SD or numbers of patients and percentages.
a
Student t test.
Statistical significance p 0.05.
Rop,ropivacain; Dx,dexamethasone.
may explain the relatively rapid analgesic effect of dexa-
methasone before the increase in protein synthesis via ge-
nomic pathways.20 The medical literature is not uniform
about which steroid to use, its optimal dose and the timing
of its application to relieve pain. We selected 8 mg of dexa-
methasone sodium phosphate because of its rescue effect
of opioids and pain relief post-LC shown in some reports
as the minimum effective dose, long biological half-life
(36-54 h), faster onset of action than other preparations and
the possibility of being injected into soft tissue with low
systemic absorption.21
In this clinical trial with an active comparison (ropi-
vacaine), the intensity of incisional pain at rest decreased
more significantly in the Rop/Dx group after 12 h (p = 0.05)
and up to 24 h post-elective LC (p = 0.01). During move-
ment, the pain intensity was also statistically significantly
less in the Rop/Dx group at 12h (p = 0.04) and 24h (p =
0.01). Also, based on the Farrar et al. classification,22 the
percent decreases in the incisional pain relief at rest reach a
significantly important change (between 31 and 50%) from
12h of the postoperative period in the group with dexa-
methasone, as well as during movement in the same period
of time, but more moderate (21-30%). Therefore, with the
pre-established criteria in this investigation, we found ini-
tial evidence that patients in the Rop/Dx group reached the
maximum benefit and better incisional analgesia after 12
h, the time in which the majority of patients were found in
good clinical condition to be discharged from the hospital.
These findings have greater relevance if we take into con-
sideration that after 8h post-LC at rest during or movement,
there was a statistically significant tendency to have less
incisional pain in the Rop/Dx group. It was also evident that
patients obtained adequate relief of incisional pain during
the first hours with ropivacaine and ketorolac IV, whereas
the effect of dexamethasone was clinically evident. In our
hospital it is not the norm to administer dexamethasone in
the immediate preoperative period of elective LC for con-
trol of pain or to prevent postoperative nausea and vom-
iting. Taking advantage of this position it was possible to
Volume 81, No. 5, September-October 2013 365
Rop/Dx group
(n = 40) p value 95% CI
8 (20)
24 0.437 -1.1612.661
study, with the limitations inherent to all drug tests, its ad-
juvant analgesic incisional effect by local infiltration.
Although we did not find similar studies in the medi-
cal literature that support and directly compare our results
(for example, incisional infiltration of ropivacaine with
dexamethasone in laparoscopic surgery), there are reports
on decrease of pain in surgical wounds by combining lo-
cal anesthetics and glucocorticoids being injected into soft
tissue.16 These studies are relevant because they directly
evaluated the local effectiveness of the steroid in pain that
is not as complex as LC and also because multimodal an-
algesia was not used for its management. In particular,
dexamethasone demonstrated to be useful in the treatment
of acute pain in a mixture of bupivacaine, clonidine, and
epinephrine after administration via an interscalene brachi-
al plexus block in patients who had shoulder arthroscopy
performed,23 as well as to prolong the duration of analgesia
combined with bupivacaine after SC infiltration.24
In another study in which only one injection of ropiva-
caine 0.5% or bupivacaine 0.5% mixed with 8mg of dexa-
methasone was used for an interscalene block, analgesia
was prolonged more with ropivacaine than with bupiva-
caine (p = 0.0029).25 Montazeri et al.,6 in a double blind
clinical trial, randomly assigned 62 children scheduled for
tonsillectomy to receive peritonsillar infiltration with dexa-
methasone (0.5mg/kg, n = 31) or in a volume equivalent
with 0.9% saline solution (n = 31). All infiltrations were
done after induction of general anesthesia, but before be-
ing operated. Pain intensity was evaluated by means of the
visual analog scale (VAS) at 2, 4, and 8h postoperative
without statistical significance between groups. The authors
concluded that the pre-incisional injection of dexametha-
sone provided limited analgesia and that the insufficient
size of the sample could explain these findings. Ikeuchi et
al.,26 in a controlled clinical trial, evaluated the efficacy of
adding a steroid to a local anesthetic in incisional analgesia
during total knee arthroplasty. The researchers randomly
assigned 40 patients to an experimental group (n = 20) who
were injected in the periarticular region with a solution of

dexamethasone with ropivacaine and isepamicine, whereas
in the control group (n = 20) the glucocorticoid was omit-
ted from the analgesic mixture. The authors found that the
severity of pain with dexamethasone was less than in the
control group, with significant differences that were pro-
longed until the third postoperative day. Finally, Shantiaee
et al.27 evaluated the efficacy of the injection by periapical
infiltration of dexamethasone in decrease of postoperative
endodontic pain. Ninety patients were divided into three
groups and randomly assigned to receive morphine, normal
saline solution or the glucocorticoid. The decrease in pain
intensity at 4, 8, and 24h postoperatively was statistically
significant with dexamethasone and morphine, but not at 48
h. It was also observed that the steroid was more effective
(56.7% without pain) than morphine (43.3% without pain).
It is likely that the strict analgesic prophylaxis that we
use may have decreased the chance to reveal a significant
effect of the drugs under investigation, mainly on directly
interfering with the perception of pain by patients. How-
ever, it is not advisable for ethical reasons to administer
only incisional analgesia with LC, so that any clinical study
must take into consideration an adequate protocol of drugs
that covers all pain components in this surgery. Thus, we
used a scheme that has proven to be effective, economically
feasible and with a good safety profile.28 Similarly, it was
not an option include a placebo to reveal only the effect of
dexamethasone because ropivacaine has proven to be effec-
tive as incisional analgesia during the postoperative phase
of laparoscopic interventions.4 In addition, we consider that
in our study the opioids did not decrease the sensitivity to
reveal differences in the period from 0 to 24 h postopera-
tively because its use was infrequent and at low doses in
both study groups. Finally, pain intensity at 2 h after surgery
>4 at rest and >5 with movement in 90% of our patients
provided us the potential to show a statistically significant
additive effect of dexamethasone during the study period.
This is because adequate sensitivity of the trials that mea-
sured acute pain can only be achieved when patients experi-
ence it, at least, at moderate intensity (4-6/10 according to
the numerical rating scale).29
In most reports, administration of dexamethasone is usu-
ally done 1-2 h before surgery because, in theory, this is the
time of initiation of its biological action through modula-
tion of the protein synthesis and transcription.30 This may
explain its lack of clinically detectable adjuvant analgesia
in our study for the first hours post-LC. However, the opti-
mal time for its application remains to be made clear. There
are authors who administer it 90min before induction of
anesthesia and others who do so during or at the end of
the surgery. In both situations there is pain relief during the
early postoperative period.31 These latter pharmacological
actions can be explained by the non-genomic fast-acting
366 Ciruga y Cirujanos
Evaristo-Mndez G et al.
mechanisms of the glucocorticoids.20 In our study is likely
that the lack of significant additional analgesia with dexa-
methasone in the first hours of the postoperative period is
due to being the wrong time of application for administer-
ing relatively low doses of the drug. Although Bisgaard et
al.7 demonstrated that a single 8-mg dose decreased total
and incisional pain (even beyond the first 24 h post-LC),
Hval et al.32 only reached analgesic effects with 16mg of
dexamethasone in breast surgery, whereas other research-
ers have recommended doses of up to 0.2-0.4mg/kg of this
glucocorticoid to obtain an acceptable analgesia.33 Also, the
time necessary to perform the surgical intervention and for
recovery of the patients in the postanesthesia intensive care
unit, in our opinion, would have been sufficient to reach a
clinically evident effect in the early postoperative period if
administered 1-2 h before the procedure.
It should also be considered that the dose of ropivacaine
was perhaps insufficient in our study to provide greater pain
relief. Other authors have used quantities as high as 380
mg for preventive analgesia in LC.34 Finally, because it is
not clear if it is convenient to maintain circadian rhythm
(peak at 6 AM or 8 AM) in the injection of dexamethasone
to obtain best results or reduce their frequency of adverse
reactions, this tactic was not taken into account during the
final analysis on the effect of the medication.
One of the greatest criticisms of our study may be that
we used the numerical rating scale rather than the VAS as
a measuring tool. The latter tends to be used by most stud-
ies that assess the effectiveness of analgesic medications.
However, the 11-point numerical rating scale (0-10) is vali-
dated to measure the intensity and to assess the subjective
feeling of pain, is easy and quick to apply for patients, is re-
producible and works well for making treatment decisions
(or on the effect of pharmacological interventions) in the
first hours after a surgical procedure.35 In addition, the VAS
was developed to measure chronic pain, although it often
tends to be applied in the immediate postoperative period
without considering any of their individual scores in this
period have a 20mm inaccuracy.36 Because what is impor-
tant in trials that include pain as a principal result variable
is the rate at which it changes, the scores that we obtained
were considered to be within the ordinal scale and not as
a ratio scale, which many studies use to demonstrate their
results. More important, as Matthews et al.9 demonstrated,
there are serious problems associated with the common but
inadequate use of two tests separated each time when serial
measurements are analyzed to compare two groups (e.g.,
Student t test, Mann-Whitney U test or even the repeated
measures ANOVA). Utilizing these tests enormously in-
creases the p values of significance as in the case of the re-
sults reported by other authors from 0 postoperative hour.7
In agreement with Matthews et al., we used a highly recom-
Incisional analgesia with dexamethasone in laparoscopic cholecystectomy
mended approach that offers more information. When data
are analyzed for the first time, graphs of the response against
time for each patient are produced by means of regression
coefficients with minimum squares when the curves fol-
low a decreasing trend. Subsequently, summary measures
are obtained that will be verified by simple hypothesis tests
(Mann-Whitney U for our study). This method avoids all
problems mentioned with the analyses most commonly per-
formed, but incorrectly. Similarly, we do not use so-called
error bars that are often displayed in the graphs because
they do not offer important additional data. They relate ex-
clusively with the between-subject variations at each time.
Although it has been shown that a single dose admin-
istration of glucocorticoids is safe and effective to reduce
postoperative pain,5,37 the possible delay in healing and the
increase in the frequency of surgical wound infections is
one concern among surgeons. In our study we did not find
any alteration in wound healing during 30 days follow-up
post-LC. There was a superficial infection at the surgical
site in two cases during the same period of observation (one
in the Rop group at 8 days and another in the Rop/Dx group
at 12 postoperative days). These findings are similar to what
is reported in the medical literature.38 Genital, perineal or
anorectal itching that has a frequency of 50-70% after IV
dexamethasone administration were not documented in any
of our cases, nor were atrophy and depigmentation of the
skin (undesirable effects associated with subcutaneous ap-
plication), although the latter may take up to 2 months to
appear.39 In addition, in the case of skin atrophy, the use
in our investigation of a highly soluble compound such as
dexamethasone sodium phosphate could have contributed,
along with a low frequency of occurrence of this event
(0.6%), to reduce its risk when dexamethasone was admin-
istered within the incisions.40
In conclusion, pain is difficult to properly measure be-
cause it is a subjective symptom. Its perception depends on
personal experience and the ability of the person who ex-
periences it to describe its type and degree of intensity, as
well as depending on emotional, social, genetic and gender
factors. The complex nature of acute post-LC pain suggests
that its best treatment should be multimodal. Within this
framework of analgesia and under the conditions estab-
lished in our study, we obtained initial evidence that dexa-
methasone, for local infiltration, contributes to decrease the
intensity of incisional pain from the last 12 h on the first day
post-elective LC with a good safety profile. Clinical trials
with greater methodological rigor, larger sample size and
higher doses of dexamethasone may help validate our re-
sults and obtain statistical significance in the earliest hours
of the immediate postoperative period. From our findings
the need also arises, or so we believe, to evaluate ropiva-
caine with dexamethasone for incisional analgesia in other
Volume 81, No. 5, September-October 2013 367
laparoscopic surgeries in order to facilitate its management
on an outpatient basis.
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