Available via license: CC BY-NC-ND 4.0
Content may be subject to copyright.
Original Article
34 ASIAN JOURNAL OF SURGERY VOL 30 • NO1 • JANUARY 2007
© 2007 Elsevier. All rights reserved.
Preemptive Ropivacaine Local Anaesthetic
Infiltration Versus Postoperative Ropivacaine
Wound Infiltration in Mastectomy: Postoperative
Pain and Drain Outputs
M.A.I. Rica, A. Norlia, M. Rohaizak and I. Naqiyah, Department of Surgery, Faculty of Medicine,
Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
OBJECTIVE: The aim of this study was to investigate if preemptive local infiltration (PLA) with ropivacaine
could improve postoperative pain and determine its effect on drain output postmastectomy with axillary
dissection.
METHODS: This was a prospective, randomized trial comprising 30 women allocated to two groups:
one to receive postoperative wound infiltration (POW) of 20 mL of 0.2% (40mg) ropivacaine (Naropin®)
versus PLA with 20 mL of 0.2% ropivacaine (Naropin®) diluted with 80mL of 0.9% saline, total volume
100 mL. A visual analogue scale (0–100mm) and angle of shoulder abduction were used for evaluation of
pain. Postoperatively, all patients received oral ibuprofen 400mg tds.
RESULTS: There was no significant difference in postoperative pain for the first 3 days between the two
groups. There were wider shoulder abduction angles in the 1st and 3rd postoperative days in the PLA group,
but this was not significant. Operative time was significantly shorter in the PLA group than in the POW
group (69.34 ±59.37 minutes vs. 109.67 ±26.96 minutes; p=0.02). The axillary drain was removed earlier
in the preemptive group, 5.4 ±1.55 days versus 6.8 ±2.04 days in the postoperative group (p=0.04).
CONCLUSION: We found no difference in postoperative pain between preemptive tumescent ropiva-
caine infiltration and postoperative ropivacaine wound infiltration. [Asian J Surg 2007;30(1):34–9]
Key Words: drain output, mastectomy, postoperative pain, ropivacaine
Introduction
Breast cancer is the commonest cancer in Malaysian
women, making up to one-third of newly diagnosed
cancer cases in Malaysian women.1The age standardized
rate of female breast cancer in Malaysia is the highest
for Chinese (70.1/100,000 population), followed by
Indians (61.7/100,000), and lowest in Malays (41.9/
100,000).1
Mastectomy is an operation that alters self-image,
requiring the patient to adapt and accept the new body
image after operation. Patient comfort from adequate post-
operative pain control contributes to improved morale
after operation and motivation for early limb physiother-
apy. In addition, it has been suggested that early postoper-
ative pain may actually play a role in the development of
postmastectomy chronic pain syndrome.3Women who
experience greater postoperative pain are more likely to
Address correspondence and reprint requests to Dr M.A.I. Rica, Department of Surgery, Faculty of Medicine, Universiti
Kebangsaan Malaysia, Jalan Yaacob Latiff, Cheras 56000, Kuala Lumpur, Malaysia.
E-mail: rica@mail.hukm.ukm.my ●Date of acceptance: 22 February 2006
have chronic pain later, with persistently higher anxiety
and depression up to 1 year after operation.3
The aim of this pilot study was to see if the delivery of
local anaesthesia in a tumescent manner in mastectomy
would have any effects on drain outputs postoperatively.
In addition, by using a protocol approach to postopera-
tive analgesia, we also looked for possible differences in
postoperative pain control between the two groups.
Patients and methods
This was a prospective, randomized study that enrolled
patients undergoing mastectomy and axillary clearance. The
study was approved by the Medical Research Committee of
Hospital University Kebangsaan Malaysia (HUKM). From
December 2003 to May 2004, women who were scheduled
for operation were invited to participate in this study.
The operation was to be performed by any one of three
surgeons in the Division of Breast and Endocrine Surgery
at HUKM.
All patients who underwent mastectomy and axillary
clearance (level II) for breast carcinoma regardless of stage
of tumour were included in the study. Patients with mental
retardation and psychiatric illnesses that would interfere
with perception of pain were excluded from the study. After
obtaining written informed consent, patients were random-
ized to receive either preemptive subdermal infiltration with
100 mL of local infiltration, made up of 80 mL of 0.9%
normal saline and 20 mL of 0.2% ropivacaine (40mg ropi-
vacaine) or postoperative wound infiltration (POW) with
20 mL of 0.2% ropivacaine just prior to wound closure.
The preemptive local anaesthesia was infiltrated when
the patient was under general anaesthesia, cleaned and
draped, after the planned surgical incision was marked with
a permanent marker but before the skin incision was
made. A 20 mL syringe attached to a 20G spinal needle was
used to infiltrate the fluid. Of 100 mL infiltrate, 50 mL
was infiltrated into the breast bed area, 20 mL each into
the superior and inferior mastectomy flaps which were to
be raised, and a final 10 mL into the axillary area.
For patients who were randomized to receive wound
infiltration, 20 mL of 0.2% ropivacaine (Naropin®) was infil-
trated into the superior and inferior parts of the wound
with a 23G needle in equally divided doses just prior to clo-
sure. Postoperative analgesia was standardized to ibuprofen
400 mg 8 hours for all patients. This was prescribed with
oral magnesium trisilicate (Gelusil®). Patients were allowed
to have 1G paracetamol for breakthrough pain on a PRN/
QID basis, and this was charted.
All patients had preoperative assessment and received
general anaesthesia and endotracheal intubation. Patients
did not receive intrathecal or epidural medications. Dura-
tion of operation was measured in minutes from the time
incision was made till the time the wound was closed.
Pain was assessed by patients with a visual analogue
scale (VAS) score system. The scores were obtained during
daily morning rounds. When obtaining the VAS score,
the previous scores, i.e. the previous mark on the 10 cm
line, were not revealed to the patient. Shoulder abduction
angles were also charted daily at the same time. Angles
were measured making sure that the abducted arm
was in line with the shoulder. Drain charting was done
daily and drains were removed if 24-hour output was
≤20 mL. Drains were removed on day 7 irrespective of the
drain output volumes. For easier analysis of data, only
data from the first 3 days were analysed. The data were
analysed using SPSS version 12.0 (SPSS Inc., Chicago, IL,
USA). A pvalue of less than 0.05 was considered significant.
Results
All parameters were normal in distribution. The data were
summarized using mean ±standard deviations. Analy-
sis was done using independent sample ttests and also
analysis of variance with corresponding 95% confidence
intervals.
There were 30 women enrolled into this study, but one
had to be excluded as her drains were removed prematurely.
There were 16 Malays, 12 Chinese and two Indian patients.
This reflected the national population make up.
There were no demographic differences between the
two study populations. The mean age of the two study
groups were 58 and 53 years, respectively, which would be
expected for patients diagnosed with breast carcinoma in
our population. Surgery with preemptive tumescent local
infiltration (TLA) took a significantly shorter time than
without (69.34 ±59.37 minutes vs. 109.67±26.96 minutes;
p=0.02) (Table 1).
Although the preemptive TLA infiltration group had
wider angles of shoulder abduction postoperatively on
days 1 and 3, this was not statistically significant (Table 2).
Mean axillary drain outputs were lower for the preemp-
tive TLA infiltration group; however, this was not statisti-
cally significant (Table 3). There was also no statistical
■ PREEMPTIVE ROPIVACAINE INFILTRATION ■
ASIAN JOURNAL OF SURGERY VOL 30 • NO1 • JANUARY 2007 35
■ RICA et al ■
36 ASIAN JOURNAL OF SURGERY VOL 30 • NO1 • JANUARY 2007
significance between the two groups in terms of breast
drain outputs (Table 4).
The breast drains were taken off after the same mean
number of days postoperatively for the two groups. The
axillary drains, however, were taken off earlier, 5.4 days
(mean) in the preemptive TLA infiltration group as com-
pared to 6.8 days (mean) in the wound infiltration group
(Table 5).
Although it was not an objective of this study, we
found that Malays had significantly higher VAS scores
on the 1st (38.33 ±18.48) and 2nd postoperative days
(38.37 ±13.12) compared to Indians (0.75±10.61) and
Chinese (20.79 ±21.96), respectively.
There were no major postoperative complications
experienced in this study, namely skin flap ischaemia, major
blood loss or wound infections.
Table 1. Demographic characteristics and duration of operation of the two study populations
Preemptive subdermal TLA infiltration Wound edge infiltration p
Weight (kg) 60.00 ±9.27 54.71 ±7.96 0.105
Height (m) 1.46 ±0.19 1.56 ±0.07 0.074
BMI (kg/m2) 25.64 ±15.44 22.51 ±3.64 0.174
Age (yr) 58.47 ±10.47 53.07 ±11.51 0.451
Duration of operation (min) 69.34 ±59.37 109.67 ±26.96 0.024
BMI =body mass index; TLA =tumescent local infiltration.
Table 2. Mean shoulder abduction angle from 1st to 3rd postoperative days between the two groups
Angle of shoulder abduction (degrees)
p
Preemptive TLA infiltration POW
Day 1 93.93 ±18.09 86.33 ±34.04 0.452
Day 2 100.33 ±18.91 101.6 ±28.58 0.887
Day 3 115.47 ±21.29 98.24 ±48.655 0.219
TLA =tumescent local infiltration; POW =postoperative wound infiltration.
Table 3. Mean axillary drain outputs for the two groups
Axillary drain output (mL)
tp
Preemptive TLA infiltration POW
Day 1 55.2 ±25.72 77.2 ±46.31 1.608 0.119
Day 2 57.8 ±33.04 73.87 ±67.37 0.829 0.414
Day 3 44.67 ±31.64 51.27 ±39.76 0.503 0.618
TLA =tumescent local infiltration; POW =postoperative wound infiltration.
Table 4. Mean breast drain outputs for the two groups
Breast drain output (mL)
tp
Preemptive TLA infiltration POW
Day 1 34.93 ±26.90 44.8 ±40.76 0.782 0.441
Day 2 50.47 ±23.43 63.27 ±89.62 0.535 0.597
Day 3 34.53 ±24.16 51.73 ±65.92 0.949 0.351
TLA =tumescent local infiltration; POW =postoperative wound infiltration.
■ PREEMPTIVE ROPIVACAINE INFILTRATION ■
ASIAN JOURNAL OF SURGERY VOL 30 • NO1 • JANUARY 2007 37
Discussion
In order for a preemptive analgesia to be effective, the
anaesthetic agent must be able to prevent central sensiti-
zation caused by incisional and inflammatory injury as a
result of surgery.3,4 The agent must therefore have a fast
enough onset to induce anaesthesia before the incision is
made and a long enough duration of action to cover the
operative (incisional injury) and the immediate postoper-
ative (inflammatory injury) period. The onset of action of
ropivacaine is about 1–5 minutes and its duration of
action is between 692 and 793 minutes when injected
undiluted intradermally.5One study, which looked into
the appropriateness of ropivacaine in tumescent anaes-
thesia, found that the mean duration of absence of pain
was 15.6 hours with a maximum of 30 hours.6This long
duration of anaesthesia should be adequate to cover the
pain during mastectomy and also the pain during the
postoperative period. Ropivacaine is therefore an ideal
anaesthetic agent that could act in a preemptive manner.
Although there are no studies looking into postmas-
tectomy pain after 24 hours, there are two studies that
have investigated ropivacaine infiltration and its effect on
postmastectomy pain in the immediate postoperative
period (first 24 hours). These studies had conflicting
results, one study favoured ropivacaine while the other
failed to show any beneficial analgesic effect of ropivacaine
compared to saline infiltration in breast surgery in the
first 24 hours postoperatively.7,8
The group from Germany found that 20 mL of
7.5mg/mL ropivacaine (150 mg) administered subcuta-
neously was effective in reducing pain in patients who
underwent mastectomy with axillary node dissection.7
The ropivacaine group had lower VAS scores and also
reduced postoperative requirement of intravenous opi-
ods. The Swedish group however found that there were no
significant differences between VAS scores after giving
0.3 mL/kg of 3.75mg/mL (average patient weighing 60 kg
would receive 65 mg ropivacaine with this protocol)
before surgery.8The results of these two studies should be
interpreted with caution, as both were small studies with
about 30 patients in the whole study population. However,
the conflicting results of these studies do raise the issue of
dosing. There is a possibility that the relatively low dose
of ropivacaine (65 mg vs. 150 mg) is not sufficient to affect
postoperative pain.
The main aim of this study was to assess the tumescent
delivery of local anaesthesia in mastectomy as compared
to POW. There would be a variation in the distribution
of anaesthetic agent between the two groups, i.e. the infil-
trate in the tumescent group will have been widely distri-
buted though diluted, and the infiltrate in the other
group will have been concentrated within the area of the
suture line. Although we did look at postoperative pain,
we anticipated that this would not be significant between
the two groups, as the dose of ropivacaine used was much
lower than that used in previous studies, which had yielded
significant results. Indeed, our results showed lower VAS
scores in the preemptive group on the 1st and 3rd post-
operative days, but this was not statistically significant
(Table 6).
Although the recommended dose of ropivacaine used
in a field block or infiltration is 2–225 mg, one study has
demonstrated that 300 mg of ropivacaine (∼5 mg/kg for
the average patient in this particular study) was well
tolerated by 37 patients during inguinal hernia repair and
significantly reduced postoperative pain.9In addition,
postoperative pain was lower up to the 7th postoperative
day with significantly reduced verbal pain scores and higher
patient satisfaction.10 It was postulated by the authors
that their study was able to produce longer postoperative
analgesia due to the higher dose they used.
Other studies using lower doses of ropivacaine infil-
tration such as 200 mg (herniorraphy) and 175mg (chole-
cystectomy) only demonstrated a dose-dependent reduction
in pain limited to 6 hours postoperatively.11,12 Therefore,
lower doses may not only be capable of acting in a preemp-
tive manner, but may not last long enough postoperatively.
Table 5. Mean number of days when axillary drain and breast drain were removed in the two study populations
Preemptive TLA infiltration POW tp
Postoperative day axillary drain removed 5.4 ±1.55 6.8 ±2.04 2.11 0.04
Postoperative day breast drain removed 5.6 ±2.09 5.6 ±2.13 0.09 0.93
TLA =tumescent local infiltration; POW =postoperative wound infiltration.
However, increasing doses of ropivacaine exceeding 300mg
may not clinically yield a difference in terms of postoper-
ative pain. Pettersson et al demonstrated in their study
that there was no difference in postoperative pain after
herniorrhaphy between wound infiltration with 300 mg
or 375 mg.13
VAS scores were higher on the 2nd postoperative day
for both groups. This was noticed during data collection
that patients complained of more pain on the 2nd postop-
erative day. This increase in pain is attributed to patients
starting to do early postoperative limb physiotherapy.
The higher VAS on the 2nd postoperative day however was
not reflected in the mean angle of shoulder abduction,
which showed a trend of steadily improving from days 1 to
3 postoperatively. Therefore, although the patients seemed
to experience more pain on the 2nd postoperative day, this
did not affect their shoulder abduction.
Although there were no patients who perceived the
postoperative pain to be moderate or severe (mean VAS
more than half of 100 mm), the mean VAS in our study pop-
ulation had significantly higher VAS compared to one study
of preemptive ropivacaine infiltration in partial mastec-
tomy.14 In that study, during the immediate postopera-
tive period, the mean VAS was about 30 mm but steadily
decreased until at 24 hours postoperatively, their patients
had no pain at all (VAS, 0 mm). In addition to this, unlike
the patients in our study who received standardized post-
operative analgesia, the patients in that study did not receive
any analgesia unless their VAS was more than 30mm. It is
possible that the extent of surgery was less for this group of
patients, although we cannot be specific since the term
“partial mastectomy” is ambiguous. However, there was
one patient in our study who did not complain of any post-
operative pain and two others who also had no pain but
only after the 2nd postoperative day.
The perception of pain is a personal experience influ-
enced by many factors including genetic, environmental
and cultural factors. However, a small Singaporean
study15 used a computerized thermal sensory testing device
to compare the pain thresholds of Malays, Chinese and
Indians when stripping of the stratum corneum of the
hand and forehead was done with adhesive tape. They
found no difference in pain threshold perception between
the races and concluded that between these races, there
appeared to be no difference in pain perception. In our
study, although this was not an intended study objective,
there was a significant inter-racial difference in postopera-
tive pain. The Malay patients experienced the most post-
operative pain on the 1st and 2nd postoperative days as
compared to the Indian and Chinese patients, respectively.
Our results however are not representative of the pain tol-
erance of these ethnic groups, as they are a special subset
of the population and cancer in itself may influence the
perception of pain. In addition to this, it would not be
possible to compare the pain of stratum corneum stripping
to postmastectomy pain.
In vitro studies have shown that ropivacaine reduces
platelet function by reducing platelet aggregation, which
would affect clotting function.16 This could theoretically
increase drain output and increase haematoma formation.
However, we found that the mean drain outputs for axil-
lary and breast drains in the first 3 postoperative days were
all less in the preemptive TLA infiltration group than in the
postoperative wound edge infiltration group, although
these differences were not statistically significant. No
patients developed haematoma postoperatively. In addi-
tion, the axillary drain was removed significantly earlier in
the TLA infiltration group than in the wound infiltration
group. All of the above observations can be attributed to
the vasoconstrictive properties of ropivacaine. An in vitro
study in pigs showed that ropivacaine is able to decrease
cutaneous blood flow by 52–54% as opposed to bupiva-
caine and saline, which increases vascularity.17 In vitro
studies in dog and human show that ropivacaine induces
■ RICA et al ■
38 ASIAN JOURNAL OF SURGERY VOL 30 • NO1 • JANUARY 2007
Table 6. Visual analogue scale (VAS) score on the 1st to 3rd postoperative days for the two groups
VAS score (mm)
tp
Preemptive TLA infiltration POW
Day 1 34.25 ±21.91 26.03 ±20.23 1.04 0.303
Day 2 35.75 ±20.10 27.17 ±17.53 1.227 0.23
Day 3 16.67 ±15.85 21.7 ±14.69 0.886 0.383
TLA =tumescent local infiltration; POW =postoperative wound infiltration.
■ PREEMPTIVE ROPIVACAINE INFILTRATION ■
ASIAN JOURNAL OF SURGERY VOL 30 • NO1 • JANUARY 2007 39
vessel contractility, thereby inducing vasoconstriction.18,19
These findings would suggest that the vasoconstrictive
property of ropivacaine makes it an ideal agent when used
in tumescent anaesthesia. The tumescent liquid vasocon-
stricts microvasculature, potentially decreasing bleeding
and serous discharge after operation. The tumescent liquid
also creates an artificial plane (hydrodissection), thereby
potentially making surgery easier.20 This could also
explain the significantly shorter duration of operation
time in the TLA as compared to the wound edge infiltra-
tion group.
In this pilot study, preoperative ropivacaine tumescent
infiltration was beneficial in terms of shorter duration
of operation and earlier removal of the axillary drain.
The shorter duration of operation is most probably due
to easier creation of skin flaps as a result of hydrodissec-
tion by the tumescent fluid. The earlier removal of axil-
lary drain is attributed to the vasoconstrictive effects of
ropivacaine.
References
1. Malaysian National Cancer Registry Report 2002, released July
2003.
2. Tasmuth T, Estlanderb AM, Kalso E. Effect of present pain and
mood on the memory of past postoperative pain in women treated
surgically for breast cancer. Pain 1996;69:343–7.
3. Ballantyne J. Preemptive analgesia: an unsolved problem. Curr
Opin Anesthesiol 2001;14:499–504.
4. Kissin I. Preemptive analgesia. Anesthesiology 2000;93:1139–42.
5. Moffit DL, De Berker DA, Kennedy CTK, et al. Assessment of
ropivacaine as a local anaesthetic for skin infiltration in skin
surgery. Dermatol Surg 2001;27:437–40.
6. Breuninger H, Hobbach PS, Schimek F. Ropivacaine: an impor-
tant anesthetic agent for slow infusion and other forms of
tumescent anesthesia. Dermatol Surg 1999;25:799–802.
7. Horn E-P, Gottschalk A, Schroeder F, et al. Ropivacaine
wound infiltration in patients following modified mastectomy
with axillary node dissection. J Am Soc Anesthesiol 2000e.
[Abstract 883]
8. Johansson A, Axelson J, Ingvar C, et al. Preoperative ropivacaine
infiltration in breast surgery. Acta Anaesthesiol Scand 2000;44:
1093–8.
9. Naropin Core Data Sheet, September 2003.
10. Narchi P, Carry PY, Catoire P, et al. Postoperative pain relief and
recovery with ropivacaine infiltration after inguinal hernia repair.
Ambul Surg 1998;6:221–6.
11. Johansson B, Hallerback B, Subberod A, et al. Preoperative local
infiltration with ropivacaine for postoperative pain relief after
inguinal hernia repair. A randomized controlled trial. Eur J Surg
1997;163:1–8.
12. Johansson B, Glise H, Hallerback B, et al. Preoperative local infil-
tration with ropivacaine for postoperative pain relief after chole-
cystectomy. Anesth Analg 1994;78:210–4.
13. Pettersson N, Emanuelsson BM, Reventlid H. High-dose ropiva-
caine wound infiltration for pain relief after inguinal hernia repair.
A clinical and pharmacokinetic evaluation. Reg Anesth Pain Med
1998;23:189–96.
14. Johansson A, Axelson J, Ingvar C, et al. Preoperative ropivacaine
infiltration in breast surgery. Acta Anaesthesiol Scand 2000;44:
1093–8.
15. Yosipovitch G, Meredith G, Chan YH. Do ethnicity and gender
have an impact on pain thresholds in minor dermatologic
procedures? A study on thermal pain perception thresholds in
Asian ethnic groups. Skin Res Technol 2004;10:38–42.
16. De Iuliis A, Zanatta L, Vincenti E, et al. Differences of ropiva-
caine and bupivacaine relevant to antiinflammatory activity,
platelet aggregation and antioxidant activity in vitro. Farmaco
2001;56:153–7.
17. Kopacz DJ, Carpenter RL, Mackey DC. Effect of ropivacaine on
cutaneous capillary blood flow in pigs. Anesthesiology 1989;71:
69–74.
18. Nakamura K, Toda H, Kakuyama M, et al. Direct vascular effect
of ropivacaine in femoral artery and vein of the dog. Acta
Anaesthesiol Scand 1993;37:269–73.
19. Gehrardini G, Samuelson U, Jernbeck J, et al. Comparison of
vascular effects of ropivacaine and lidocaine on isolated rings
of human arteries. Acta Anaesthesiol Scand 1995;39:765–8.
20. Samper A, Blanch A. Improved subcutaneous mastectomy with
hydrodissection of the subcutaneous space. Plast Reconstr Surg
2003;112:694–5.
