Eur J Anaesthesiol 2022; 39:591–601

ORIGINAL ARTICLE

Single-injection regional analgesia techniques for

mastectomy surgery
A network meta-analysis
Alessandro De Cassai, Francesco Zarantonello, Federico Geraldini, Annalisa Boscolo,
Laura Pasin, Silvia De Pinto, Giovanni Leardini, Francesca Basile, Laura Disarò, Nicolò Sella,
Edward R. Mariano, Tommaso Pettenuzzo and Paolo Navalesi

BACKGROUND Patients undergoing mastectomy surgery
experience severe postoperative pain. Several regional tech-
niques have been developed to reduce pain intensity but it is
unclear, which of these techniques is most effective.
OBJECTIVES To synthesise direct and indirect comparisons
for the relative efficacy of different regional and local analge-
sia techniques in the setting of unilateral mastectomy. Post-
operative opioid consumption at 24 h, postoperative pain at
extubation, 1, 12 and 24 h, postoperative nausea and vomit-
ing were collected.
DESIGN Systematic review with network meta-analysis
(PROSPERO: CRD42021250651).
DATA SOURCE PubMed, Scopus, the Cochrane Central
Register of Controlled Trials (from inception until 7 July
2021).
ELIGIBILITY CRITERIA All randomised controlled trials
investigating single-injection regional and local analgesia
techniques in adult patients undergoing unilateral mastec-
tomy were included in our study without any language or
publication date restriction.
RESULTS Sixty-two included studies randomising 4074
patients and investigating nine techniques entered the
analysis. All techniques were associated with less opioid
consumption compared with controls The greatest mean
difference [95% confidence interval (CI)] was associated
with deep serratus anterior plane block: mean difference
–16.1 mg (95% CI, –20.7 to –11.6). The greatest reduction
in pain score was associated with the interpectoral-pecto-
serratus plane block (mean difference —1.3, 95% CI, —1.6
to — 1) at 12 h postoperatively, and with superficial serratus
anterior plane block (mean difference —1.4, 95% CI, —2.4
to —0.5) at 24 h. Interpectoral-pectoserratus plane block
resulted in the greatest statistically significant reduction in
postoperative nausea/vomiting when compared with pla-
cebo/no intervention with an OR of 0.23 (95% CI, 0.13 to
0.40).
CONCLUSION All techniques were associated with
superior analgesia and less opioid consumption compared
with controls. No single technique was identified as
superior to others. In comparison, local anaesthetic infil-
tration does not offer advantages over multimodal analge-
sia alone.
TRIAL REGISTRATION PROSPERO (CRD4202125065).
Published online 7 December 2021

From the UOC Anesthesia and Intensive Care Unit, University Hospital of Padua (ADC, FZ, FG, AB, LP, TP, PN), UOC Anesthesia and Intensive Care Unit, Department of
Medicine-DIMED, University of Padua, Padua, Italy (SDP, GL, FB, LD, NS, PN), Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School
of Medicine, Stanford (ERM) and Anesthesiology and Perioperative Care Service, Veterans Affairs Palo Alto Healthcare System, Palo Alto, California, USA (ERM)
Correspondence to Alessandro De Cassai, MD, UOC Anesthesia and Intensive Care Unit, Via Giustiniani 1, Padova 35127, Italy
Tel: +39 498213090; e-mail: alessandro.decassai@gmail.com

0265-0215 Copyright © 2021 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.
DOI:10.1097/EJA.0000000000001644

Copyright © 2022 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.
 592 De Cassai et al.
KEY POINTS

Patients undergoing mastectomy surgery experi-
ence severe postoperative pain.

Several regional techniques have been developed to
reduce pain intensity.

All techniques provided postoperative analgesia and
reduced opioid consumption.

The superiority of one technique over another was
not established.

Local anaesthetic infiltration has no advantages over
multimodal analgesia alone
Introduction
Mastectomy is a widely performed surgical procedure for
breast cancer patients. It has been reported that most
patients undergoing mastectomy surgery experienced
severe acute postoperative pain.1
Several regional analgesic techniques have been devel-
oped to improve postoperative pain, reduce perioperative
opioid consumption and opioid-related complications in
patients undergoing mastectomy.2 Clinical practice data
show that regional analgesia is rarely used for breast
surgery, including mastectomy: 13.8% in 2018.3
In recent years, increased interest in fascial plane blocks
has paved the way for the introduction of a wide variety of
regional anaesthesia techniques for patients undergoing
breast surgery.4,5 These techniques may be easier to
perform for the general anaesthesiologist without spe-
cialty training in regional anaesthesia and are included in
the PROSPECT guidelines for breast surgery.6 Our aim
was to synthesise direct and indirect comparisons for the
relative efficacy of different regional anaesthesia techni-
ques through network meta-analysis in the setting of
unilateral mastectomy. Network meta-analysis is a statis-
tical technique used to compare three or more interven-
tions at the same time using both direct and indirect
evidence. Indirect evidence is provided when two inter-
ventions have both been compared with another inter-
vention (e.g. with three interventions A, B and C; the
direct comparisons A vs. B and C vs. B also provide
indirect evidence of A vs. C). This allows an estimate
of the relative effects of the two interventions that have
not been directly compared.
Methods
This manuscript was prepared following the Preferred
Reporting Items for Systematic reviews and Meta-Anal-
ysis (PRISMA) Statement Guidelines.7 The PRISMA
checklist is available as supplementary digital content
Eur J Anaesthesiol 2022; 39:591–601
Copyright © 2022 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.
(Supplementary Digital Content 1, http://links.lww.com/
EJA/A663).
The protocol of this systematic review and meta-analysis
was written and registered in PROSPERO (reference:
CRD42021250651).
Eligibility criteria
All studies meeting the following PICOS criteria were
included: adult patients undergoing unilateral mastec-
tomy with or without lymph node dissection (P); any
single-injection regional or local analgesia technique (I);
any single-injection regional analgesia technique or any
placebo (C); postoperative opioid consumption (first
24 h), pain at 12 h, pain at 24 h, postoperative nausea
and vomiting (O); randomised controlled trial (S).
Exclusion criteria were: use of regional techniques in
combinations, continuous regional techniques and bilat-
eral surgery.
Deviations from protocol
Between the date of protocol registration and study
analysis, a standardised nomenclature for abdominal wall,
paraspinal and chest wall regional analgesic techniques
was published by an international working group from the
American Society of Regional Anesthesia and Pain Med-
icine (ASRA) and the European Society of Regional
Anaesthesia and Pain Therapy (ESRA).8 We elected to
adopt the novel nomenclature in our manuscript, for
example, we refer to the previously published ‘Pecs II
block’ as the combination of the ‘interpectoral plane
block and pectoserratus plane block’.
Considering that acute pain is one of the most important
challenges for mastectomy management, we decided to
include the following post hoc analysis: pain at extubation
and pain at 1 h postoperatively. We decided to add a
sensitivity analysis excluding studies at high risk of bias.
Search strategy
We performed a systematic search of the medical liter-
ature for the identification, screening and inclusion of
articles. The search was performed in the following
databases (last updated 6 July 2021): PubMed, Scopus,
the Cochrane Central Register of Controlled Trials
(CENTRAL). We also checked the reference lists of
included studies and of any related search results. For
specific information regarding our search strategy, see
supplementary material (Supplementary Digital Content
2, http://links.lww.com/EJA/A664). We did not apply any
restriction on language, status and year of publication.
Study selection
Two researchers (ADC and SDP) independently
screened titles and abstracts of the identified articles to

select relevant manuscripts. If a citation was considered
potentially relevant, it was reviewed in full text.
Data extraction and data retrieval
After identifying studies meeting inclusion criteria, three
authors (SDP, FB and LDS) manually reviewed and
assessed each of the included studies. Any disagreement
on study selection or data extraction was resolved through
consultation with another author (ADC).
The following information was collected: first author,
year of the study, total number of patients per group,
intervention (regional or local analgesic technique) and
control (alternate regional analgesic technique, placebo
or no intervention), 24 h postoperative dosage of opioids
in morphine milligram equivalents (MME), pain on
movement at extubation and at the first, 12th and 24th
postoperative hours, occurrence of postoperative nausea
and vomiting (PONV).
All classes of opioid were converted to intravenous MME
using the GlobalRPh morphine equivalent calculator,
considering 0% cross-tolerance modifier (http://www.
glo-balrph.com/narcotic).
The 11-point visual analogue scale (VAS) and the 11-
point numeric rating scale (NRS) were converted to a
common 11-point scale (0 to 10).
If data were missing, a request was sent by e-mail to the
corresponding author of the study. If no response was
received after our initial request, a second request was
sent 7 days later. A third and last request was sent 1 week
after the second one.
We contacted the authors of studies that included a
mixed population of breast surgery (e.g. mastectomy
and lumpectomy) in order to retrieve the data regarding
mastectomies only.
Quality assessment and certainty of evidence
assessment
Two researchers (FG and ADC) independently evalu-
ated the quality of included RCTs by using the Risk of
Bias (RoB) 2 Tool.9 Disagreements were resolved by
discussion with a third researcher (AB).
An overall risk of bias was expressed on a three-grade
scale (’low risk of bias’, ‘high risk of bias’ or ‘some
concerns’).
We used the Grades of Recommendation, Assessment,
Development and Evaluation (GRADE) approach to
assess the certainty of evidence related to each of the
outcomes.10
Statistical methods
Meta-analysis of data was performed using R version 4.1
(R Foundation for Statistical Computing, Vienna,
Austria) and the package ‘netmeta’.
Copyright © 2022 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.
Analgesia for mastectomy: meta-analysis 593
The treatment effect for continuous outcomes was
expressed as mean differences with 95% confidence
interval (CI). The treatment effect for dichotomous out-
comes was expressed as odds ratio (OR) with 95% CI. A
ranking among methods was performed based on the
frequentist analogue of the surface under the cumulative
ranking curve.11 Wherever necessary, we converted
reported median and interquartile ranges to estimated
mean and standard deviation (SD) using Hozo’s
method.12
Zero events were treated by applying a continuity cor-
rection adding one to each value.
When multiple local anaesthetic dosing regimens were
employed in the same study for the same block, means
and standard deviations were combined in a single group.
Inconsistency, heterogeneity and publication bias
analysis
For assessment of study heterogeneity, the chi-squared
test and I2 statistic were used (considering I2 values as
follows: low: <25%, moderate: 25 to 50% or high:
>50%).13 Within-design heterogeneity and between-
design inconsistency was evaluated using Cochrane Q.
A random effect model was preferred when I2 is greater
than 25%. Publication bias was evaluated both by a visual
inspection of funnel plots and by the Egger test (P
value < 0.05 indicating a possible publication bias).
Results
Study selection and data retrieval
The results of our search are shown in the PRISMA
diagram (Fig. 1). The initial screening identified 15
489 studies. Excluding 12 944 search by nonsuitable
titles or abstracts, we retrieved and assessed 1178 full-
text articles. After review, a further 1116 studies were
excluded as not meeting our predefined criteria. Finally,
62 studies evaluating nine different regional analgesia
techniques were used for the quantitative analysis.14–75
The regional and local analgesia techniques were: erector
spinae plane (ESP) block, local anaesthetic infiltration,
paravertebral block (PVB), pectoserratus plane (PS)
block, superficial serratus anterior plane (sSAP) block,
retrolaminar block, deep serratus anterior plane (dSAP)
block, rhomboid plane block, interpectoral-pectoserratus
(IP-PS) block. The network comparisons are graphically
depicted in Fig. 2.
Eight studies had data for each outcome. We requested
missing data from the remaining 54 corresponding
authors, and 13 (24.1%) were able to provide us with
the missing data.
Study characteristics
The 62 included studies randomised 4074 patients. Of
these, 1226 were allocated to placebo or no intervention
while 2848 had regional or local analgesia: 471 ESP block,
Eur J Anaesthesiol 2022; 39:591–601
 594 De Cassai et al.

Fig. 1 PRISMA flowchart

(n = 15 489) (n = 15)
• Pubmed (n = 14 026)
• Cochrane (n = 906) • References from retrieved articles (n = 15)
• Scopus (n = 557)

Records after removal of duplicates (n = 14 122)

Records screened (n = 14 122) Records excluded (n = 12 944)

Full text articles assessed for Excluded full texts (n = 1116)

eligibility (n = 1178) • Cohort studies (n = 25)
• Case reports (n = 17)
• Duplicates not detected at a previous stage (n = 22)
• Continuous regional anaesthesia (n = 21)
• Combination of regional anaesthesia (n = 16)
• Same regional anaesthesia with different anesthetics
without other comparison (n = 10)
• Other surgery (n = 8)
Included in the qualitative • Mixed surgery (ie. Mastectomy and lumpectomy) (n = 27)
analysis (n = 62) • Full text not retrieved (n = 1)
• Not pertinent (n = 969)

Flowchart of the study.

233 local anaesthetic infiltration, 778 IP-PS block, 719
PVB block, 133 PS block, 89 sSAP block, 83 retrolaminar
block, 284 dSAP block and 58 rhomboid plane block.
Study characteristics are available as supplementary
material (Supplementary Digital Content 3, http://
links.lww.com/EJA/A665).
According to the risk of bias evaluation, 34 studies were at
low risk of bias, 10 at high risk of bias, whereas some
concerns arose with the remainder (Fig. 3). The criteria
that guided us while assigning the risk of bias judgments
are available as supplementary material (Supplementary
Digital Content 4, http://links.lww.com/EJA/A666).
Postoperative opioid consumption at 24 h
Postoperative opioid consumption was evaluated in 48
studies. There is no result for this outcome in studies
involving retrolaminar block.
Compared with placebo, all regional analgesia techniques
were superior as regards reducing opioid consumption
but local anaesthetic infiltration was not (P ¼ 0.385). The
greatest reduction in opioids was obtained with dSAP
block: –16.1 MME (–20.7 to –11.6).
The quality ofevidence was rated as moderate because of
high heterogeneity (I2 99.4%).

Outcomes
Main outcomes
The network analysis is summarised in Tables 1 and 2
and graphically depicted in Fig. 4. Specific direct and
indirect evidence is detailed in supplementary material
(Supplementary Digital Content 5, http://links.lww.com/
EJA/A667).
Pain at 12 h
Postoperative pain at 12 h was evaluated in 48 studies.
Compared with placebo, the greatest reduction in pain
was associated with the IP-PS block, —1.3 (—1.6 to —1)
on an 11-point pain scale. Irrespective of block type, pain
scores in control groups were greater than those in
regional analgesia groups.

Eur J Anaesthesiol 2022; 39:591–601

Copyright © 2022 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.
 Analgesia for mastectomy: meta-analysis 595

Fig. 2 Network graph

Overview of the network comparisons. dSAP, deep serratus anterior plane block; ESP, erector spinae plane block; IP-PS, interpectoral-
pectoserratus block; LA, local anaesthetic infiltration; PS, pectoserratus plane block; PVB, paravertebral block; sSAP, superficial serratus anterior
plane block.

The quality of evidence is rated as moderate because of
high heterogeneity (I2 86.7%).
Pain at 24—h
Postoperative pain at 24 h was evaluated in 51 studies.
Compared with placebo, the greatest reduction in pain
was associated with the sSAP block [—1.4 (—2.4 to —0.5)
on an 11-point pain scale]. Irrespective of block type, pain
scores in control groups were greater than those in
regional analgesia groups.
The quality of evidence is rated as moderate because of
high heterogeneity (I2 89.6%).

Fig. 3 Risk of bias assessment

Bias arising from the randomisation process

Bias due to deviations from intended interventions
Bias due to missing outcome data
Bias in measurement of the outcome
Bias in selection of the reported result
Overall risk of bias

0% 25% 50% 75% 100%

Low risk Some concerns High risk

Overview of the Risk of Bias 2 assessment.

Eur J Anaesthesiol 2022; 39:591–601

Copyright © 2022 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.
 Table 1 Results of the network meta–analysis with the corresponding rank: all interventions compared with placebo/no treatment

Morphine 24 h (MME) Pain at extubation Pain at 1 h Pain at 12 h Pain at 24 h PONV

Rank Rank Rank Rank Rank Rank
n MD (95% CI) P value (P score) MD (95% CI) P value (P score) MD (95% CI) P value (P score) MD (95% CI) P value (P score) MD (95% CI) P value (P score) OR (95% CI) P value (P score)

dSAP 284 –16.1 (–20.7 to –11.6) <0.001 1 (0.972) –1.2 (–1.7 10 –0.7) < 0.001 8 (0.310) –1.2 (–1.810 –0.7) <0.001 5 (0.500) –0.7 (–1.2 to –0.3) 0.002 7 (0.436) –0.6 (–1 to –0.2) 0.004 8 (0.378) 0.49 (0.24 to 1.00) 0.051 7 (0.469)
sSAP 89 –10.5 (–17.2 1o –3.7) 0.002 2 (0.668) –3.0 (–4.7 to –1.2) < 0.001 1 (0.927) –2.7 (–4.510 –0.9) 0.003 2 (0.877) –0.8 (–2.1 to 0.5) 0.240 5 (0.523) –1.4 (–2.4 to –0.5) 0.003 1 (0.934) 0.43 (0.03 to 6.10) 0.533 5 (0.530)
596 De Cassai et al.

ESP 471 –8.2 (–11.2 to –5.1) <0.001 6 (0.477) –1.6 (–2.1 to –1.1) < 0.001 5 (0.538) –1.8 (–2.510 –1.2) <0.001 4 (0.673) –1 (–1.3 to –0.5) <0.001 4 (0.608) –0.8 (–1.1 to –0.4) <0.001 7 (0.409) 0.46 (0.25 to 0.83) 0.009 6 (0.509)
LA 233 –3.1 (–10.1 to 3.9) 0.385 8 (0.170) –1.4 (–2.2 to –0.5) 0.001 6 (0.411) –1.0 (–3.4 to 1.4) 0.413 6 (0.432) –0.1 (–0.9 to 0.7) 0.833 9 (0.138) –0.08 (–0.9 to 0.7) 0.843 9 (0.1 98) 1.00 (0.15 to 6.63) 1.000 8 (0.247)
PVB 719 –7.8 (–11.0 to –4.6) <0.001 7 (0.422) –1.4 (–1.8 to 0.9) < 0.001 7 (0.385) –2.1 (–2.8 to –1.4) <0.001 3 (0.757) –0.9 (–1.3 to –0.5) <0.001 3 (0.61 3) –1.0 (–1.3 to –0.6) <0.001 2 (0.811) 0.43 (0.22 to 0.82) 0.010 4 (0.548)
IP þ PS 778 –8.9 (–11.6 to –6.1) <0.001 5 (0.559) –2.0 (–2.4 to –1.5) < 0.001 3 (0.765) –2.3 (–3.0 to –1.7) <0.001 1 (0.879) –1.3 (–1.6 to –1) <0.001 1 (0.888) –0.9 (–1.2 to –0.6) <0.001 3 (0.624) 0.23 (0.13 to 0.40) <0.001 1 (0.870)
PS 133 –9.8 (–17.6 to –1.9) 0.014 3 (0.604) –2.1 (–3.0 to –1.3) < 0.001 2 (0.801) –0.3 (–1.7 to 1.1) 0.673 9 (0.220) –0.7 (–1.5 to 0.04) 0.064 8 (0.460) –0.8 (–1.5 to –0.04) 0.037 6 (0.501)
Rhomboid plane 58 –9.7 (–17.0 to –2.4) 0.008 4 (0.600) –1.0 (–2.3 to 0.3) 0.141 9 (0.279) –0.4 (–1.8 to 1.0) 0.574 8 (0.246) –0.8 (–1.6 to 0.1) 0.072 6 (0.496) –0.8 (–1.6 to –0.1 0.019 4 (0.599) 0.38 (0.09 to 1.42) 0.151 2 (0.604)
Retro- laminar 83 – – – –1.7 (–2.8 to –0.6) 0.002 4 (0.575) –0.6 –2.0 to 0.8) 0.400 7 (0.301) –1.2 (–2.5 to –0.1) 0.059 2 (0.737) –0.8 (–2.0 to 0.4) 0.208 5 (0.534) 0.38 (0.08 to 1.77 0.216 3 (0.596)
Placebo 1226 C c 9 (0.026) C c 1 0 (0.008) C C 10 (0.115) C C 10 (0.070) C C 1 0 (0.096) C C 9 (0.123)

C, comparison; dSAP, deep serratus anterior plane block; ESP, erector spinae block; IP þ PS, interpectoral –pectoserratus block; LA, local anaesthetic infiltration; MD, mean difference; MME, morphine milligram equivalents; OR,
odds ratio; PONV, postoperative nausea and vomiting; PS, pectoserratus block; PVB, paravertebral block; sSAP, superficial serratus anterior plane block.

Eur J Anaesthesiol 2022; 39:591–601

Discussion
Publication bias
Pain at extubation
Post hoc analysis

Sensitivity analysis
on a 11 points scale.

lww.com/EJA/A669).
links.lww.com/EJA/A668).
high heterogeneity (I2 97%).
high heterogeneity (I2 68.3%).

reported 1 h analgesic outcomes.

Pain at the first postoperative hour
Postoperative nausea and vomiting

the control and the pectoserratus plane block group.

showed a statistically significant reduction in postopera-

The sensitivity analysis is available as supplementary

significant difference in morphine consumption between
analgesic techniques reached statistical significance:
ative hour. Unlike the previous outcome, fewer regional
intervention. The highest reduction in PONV was
evaluated in any study. IP-PS block, ESP block and

that compared with any single-injection regional

cancer, the results of this network meta-analysis show
(P ¼ 0.02) (Supplementary Digital Content 7, http://links.
the postoperative opioid consumption at 24 h (P ¼ 0.417),
material (Supplementary Digital Content 6, http://
In addition, following sensitivity analysis, there were no
following exclusion of high risk of bias studies. No study
dSAP block, sSAP block, ESP block, paravertebral block
tive pain. The most effective treatment was sSAP block
studies. All interventions except rhomboid plane block
Postoperative pain at extubation was evaluated in 39
obtained with the IP-PS block - OR of 0.23 (0.13 to 0.40).
reduction in PONV when compared with placebo/no

publication bias for pain at extubation was calculated

for rhomboid plane block at 12 and 24 h no longer existed
Twenty-five studies evaluated pain at the first postoper-
with a reduction of —3.0 points (95% CI, —4.7 to —1.2)

For patients undergoing unilateral mastectomy for breast

(P ¼ 0.984) or PONV (P ¼ 0.894). However, a possible
pain at 1 h (P ¼ 0.505), pain at 12 h (P ¼ 0.482) or 24 h
The Egger‘s test revealed no potential publication bias in
Statistically significant differences in analgesic outcomes
and IP-PS block. Among them, the IP-PS block had the
The quality of evidence is rated as moderate because of
The quality of evidence is rated as moderate because of
paravertebral block resulted in a statistically significant
available for the pectoserratus block as this was not
PONV was evaluated in 46 studies. This outcome was not

greatest reduction in pain: —2.3 (95% CI, —3.0 to —1.7).

Copyright © 2022 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.
 Analgesia for mastectomy: meta-analysis 597

Table 2 Tabular representation of the network

Retrolaminar sSAP Rhomboid PVB Pectoserratus IP–PS ESP dSAP

Placebo block block block block block LA block block block
dSAP block 6MMM 1M 1 2MM 2MM –
224–230 30–30 30–30 76–75 55–55 –
ESP block 9MM 1 1M 4M 3 – 2MM
235–231 22–23 30–30 129–128 74–71 – 55–55
IP–PS block 12MM 1 10M 2M – 3 2MM
387–338 40–40 227–227 73–71 – 71–74 75–76
LA 2 1M – 2M
162–90 20–20 – 71–73
Pectoserratus block 2 1 –
103–74 30–30 –
PVB block 8M 1 – 1 1M 10M 4M 1
295–272 25–25 – 30–30 20–20 227–227 128–129 30–30
Rhomboid block 1 – 1M 1M
28–28 – 30–30 30–30
sSAP block 1 – 1 1
24–24 – 25–25 40–40
Retrolaminar block 1 – 1
60–62 – 23–23

Light yellow rows are the number of studies. White rows show the number of patient involved in the comparison. Each asterisk (M) represents a multiarm study. dSAP, deep
serratus anterior plane block; ESP, erector spinae block; IP þ PS, interpectoral–pectoserratus block; LA, local anaesthetic infiltration; MD, mean difference; OR, odds
ratio; PONV, postoperative nausea and vomiting; PS, pectoserratus block; PVB, paravertebral block; sSAP, superficial serratus anterior plane block.

analgesic technique local anaesthetic infiltration and The clinical significance of these findings deserves more
placebo/no intervention are less effective in reducing detailed discussion. Studies of postoperative pain have
opioid consumption and alleviating postoperative pain. recently been criticised for reporting outcomes that are
Our results do not indicate the superiority of one statistically significant but clinically meaningless.76 Pain
regional analgesia technique over the others. Ranks is, by definition, an individual experience.77 The chal-
among the outcomes are mixed, favouring dSAP block lenge posed to modern researchers in perioperative pain
for reduction of postoperative opioid consumption, sSAP management is to provide evidence that the intervention
for pain at extubation, IP-PS block for the reduction of led to an improvement in the patient’s perception of pain.
PONV and pain at 1 and 12 h, and sSAP for reduction of This analysis is only possible when the subjective
pain at 24 h. improvement of the symptom can be translated to an

Fig. 4 Forest plots comparing the interventions with placebo

(a) Regional Anaesthesia vs. Placebo (b) Regional Anaesthesia vs. Placebo (c) Regional Anaesthesia vs. Placebo

Treatment (Morphine consumption) MD 95% CI Treatment Postoperative Pain (Extubation) MD 95% CI Treatment Postoperative Pain (First Hour) MD 95% CI

–16.13 (–20.67 to –11.58) sSAP block –3.00 (–4.75 to –1.25) sSAP block –2.70 (–4.51 to –0.89)
dSAP
–10.52 (–17.25 to –3.78) Pectoserratus –2.15 (–2.99 to –1.30) IP+PS –2.32 (–2.97 to –1.68)
sSAP
–9.79 (–17.66 to –1.91) IP+PS –1.96 (–2.38 to –1.54) Paravertebral –2.06 (–2.76 to –1.36)
Pectoserratus
–9.71 (–16.99 to –2.43) Retrolaminar –1.70 (–2.80 to –0.60) ESP block –1.85 (–2.52 to –1.18)
Rhomboid
–8.87 (–11.61 to –6.12) ESP block –1.61 (–2.07 to –1.14) dSAP block –1.34 (–2.07 to –0.60)
IP+PS
LA –1.40 (–2.25 to –0.55) LA –1.00 (–3.40 to 1.40)
ESP –8.22 (–11.26 to –5.18)
Paravertebral –1.40 (–1.86 to –0.94) Retrolaminar –0.60 (–1.99 to 0.79)
PVB –7.80 (–10.99 to –4.61)
dSAP block –1.26 (–1.76 to –0.75) Rhomboid –0.40 (–1.79 to 0.99)
LA –3.12 (–10.16 to 3.92)
Rhomboid –1.00 (–2.33 to 0.33) Pectoserratus –0.30 (–1.69 to 1.09)
–20 –10 0 10 20 –4 –2 0 2 4 –4 –2 0 2 4

Favours Intervention Favours Placebo Favours Intervention Favours Placebo Favours Intervention Favours Placebo

(d) Regional Anaesthesia vs. Placebo (e) Regional Anaesthesia vs. Placebo (f) Regional Anaesthesia vs. Placebo

Treatment Postoperative pain (12 hours) MD 95% CI Treatment Postoperative Pain (24 hours) MD 9 5 % CI Treatment PONV OR 9 5 % CI
IP+PS –1.29 (–1.59 to –0.98)
sSAP –1.43 (–2.38 to –0.48) 0.23 (0.13 to 0.40)
Retrolaminar –1.22 (–2.41 to –0.03) IP+PS
PVB –0.98 (–1.33 to –0.63) 0.38 (0.08 to 1.77)
ESP –0.92 (–1.27 to –0.58) IP+PS –0.89 (–1.19 to –0.59) Retrolaminar
0.38 (0.10 to 1.43)
PVB –0.92 (–1.29 to –0.55) Rhomboid –0.85 (–1.56 to –0.14) Rhomboid
0.43 (0.03 to 6.11)
Rhomboid –0.83 (–1.53 to –0.13) ESP –0.77 (–1.09 to –0.45) sSAP block
0.43 (0.23 to 0.82)
sSAP –0.80 (–2.07 to 0.47) Retrolaminar –0.77 (–1.96 to 0.43) Paravertebral
0.46 (0.26 to 0.83)
dSAP –0.73 (–1.14 to –0.32) Pectoserratus –0.76 (–1.47 to –0.04) ESP block
0.49 (0.24 to 1.00)
Pectoserratus –0.71 (–1.42 to 0.00) dSAP –0.58 (–1.00 to –0.16) dSAP block 1.00 (0.15 to 6.63)
LA –0.09 (–0.88 to 0.70) LA –0.08 (–0.87 to 0.71 ) LA

–2 –1 0 1 2 –2 –1 0 1 2 –0.1 –0.5 1 2 10

Favours Intervention Favours Placebo Favours Intervention Favours Placebo Favours Intervention Favours Placebo

(a) Morphine consumption at 24 h; (b) postoperative pain at extubation; (c) postoperative pain at the first hour; (d) postoperative pain at 12 h; (e)
postoperative pain at 24 h; (f) postoperative nausea and vomiting. dSAP, deep serratus anterior plane block; ESP, erector spinae plane block; IP-PS,
interpectoral-pectoserratus block; LA, local anaesthetic infiltration; PS, pectoserratus plane block; PVB, paravertebral block; sSAP, superficial
serratus anterior plane block.

Eur J Anaesthesiol 2022; 39:591–601

Copyright © 2022 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.
 598 De Cassai et al.
objective numeric scale by the patient. In a recent review,
Hussain et al.76 used a cutoff of 1.1 points on the verbal
pain scale to detect clinically significant differences. This
minimal clinically significant difference was calculated as
the mean difference in pain scores when patients
received acute pain treatment in the emergency depart-
ment.78 Another clinical trial performed in the emer-
gency department79 considered 1.3 points as a minimal
clinically important difference in pain. In our results, only
IP-PS at 12 h (—1.3 points) and sSAP at 24 h (—1.4
points) demonstrate mean differences that approach
the clinically significant threshold, but the inclusion of
1.1 in the confidence intervals suggests that a clinically
significant benefit may not exist for some patients. We
speculate that the widespread use of multimodal pain
management strategies as recommended by guidelines6
may minimise the individual effect of any single element
of the regimen on overall pain experience even for
regional analgesia.
In contrast, the effect of regional analgesia on opioid
consumption in the first 24 h is both clinically and
statistically significant for all techniques. Although we
did not choose a predetermined threshold for clinical
significance, a 24 h difference of 10 MME has been
deemed clinically significant in other studies.76 Because
of the confidence interval overlap among the studied
interventions, there was no single best regional analgesia
technique identified. Given the evidence available, we
can recommend that a regional analgesia technique
should be included in a multimodal opioid-sparing anal-
gesic regimen for unilateral mastectomy patients but the
choice of technique may be left to the discretion of the
anaesthetist. Our findings support the use of any
regional analgesia technique over local anaesthetic infil-
tration as the latter has no advantages when compared
with placebo.
Interestingly, despite PVB being commonly considered
the gold standard for unilateral chest wall anaesthesia,80
our study does not show its superiority over the other
regional analgesia techniques for unilateral mastectomy
patients. This finding is in agreement with other meta-
analyses that compared PVB with IP-PS and reported no
advantage with PVB81 nor a greater pain reduction with
IP-PS.82 Our focus on single-injection blocks and the
exclusion of continuous nerve block techniques may have
limited the evidence base for PVB in our study. There is
evidence that continuous PVB for several days may have
important outcome advantages for mastectomy patients
in the short-term and long-term.83,84
In conjunction with general anaesthesia for breast sur-
gery, comparisons between different regional analgesia
techniques or versus placebo have been published in the
past. A meta-analysis comparing single injection PVB
with IP-PS85 found no difference in 24 h morphine con-
sumption but IP-PS showed a greater reduction in pain
Eur J Anaesthesiol 2022; 39:591–601
Copyright © 2022 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.
up to 6 h postoperatively, whereas at 12 and 24 h, there
was no significant difference between the two techni-
ques. In another study, when compared with local anaes-
thetic infiltration and SAP, IP-PS was not associated with
a reduction in pain, either at rest or during move-ment.81
A meta-analysis comparing ESP versus placebo found
that ESP provided a reduction in postoperative pain at 0,
6, 12 and 24 h, as well as a significant reduction in 24 h
morphine consumption.82 However, when comparing
ESP with IP-PS, the latter provided better pain control
up to 12 h postoperatively, while at 24 h, the difference
was not significant. Morphine consumption was lower in
IP-PS compared with ESP block, and there was no
difference regarding this outcome between ESP and
PVB.
With this plethora of information, network meta-analyses
provide the additional benefit of comparing different
techniques at the same time, with both direct and indirect
evidence helping to guarantee the best treatment for
the patients.
It is worth noting that this is not the first network meta-
analysis evaluating regional analgesia in breast surgery.86
However, Wong et al.86 included a wide variety of surgical
interventions (e.g. lumpectomies, partial mastectomies,
modified radical mastectomies) and analgesic modalities
(including single-injection, continuous infusion and the
combination of regional analgesic techniques), making
focused recommendations for a specific procedure like
mastectomy challenging. Furthermore, the classification
used by Wong et al. 86 is now outdated given the novel
nomenclature proposed by the ESRA/ASRA consensus.8
In our article, we examined a single surgical intervention
(mastectomy with or without lymph node dissection) and
single-injection regional analgesia techniques, attempt-
ing to answer a more focused clinical problem and
provide actionable information for the general anaesthe-
siologist.
In our network meta-analysis, local anaesthetic infiltra-
tion provided no advantages when compared with no
intervention in all the examined outcomes. This is likely
because of the rapid incorporation of opioid-sparing mul-
timodal analgesia for surgical patients as recommended
by the American Society of Breast Surgeons.87 We spec-
ulate that use of multimodal analgesia limits the potential
measured benefit of local anaesthetic infiltration.
Although our study suggests that a single-injection
regional block is preferred, we believe that local anaes-
thetic infiltration should not be considered for patients
without access to regional analgesia unless further studies
show a clinically significant effect. Instead, regional
anaesthesia experts should work to expand regional
anaesthesia training to more general anaesthesiologists
and thereby increase access to regional analgesia and
reduce inequalities in pain management for this patient
population.88

Our study has some limitations. First, for some compar-
isons, there are no RCTs or their number is limited and
for these comparisons, the evidence was mainly indirect.
For this reason, readers should exercise caution in some
results until new studies provide sufficient evidence for
such comparisons. Second, we were unable to find ran-
domised controlled trials for some regional techniques,
such as single injection epidural or intertransverse pro-
cess block. Moreover, some regional techniques (i.e.
pectoserratus block) were uncommon, with few trials
retrieved. Third, we examined only four outcomes, and
other important outcomes of interest, such as quality of
recovery may have been neglected. Fourth, we excluded
continuous nerve block studies, and there is evidence
that mastectomy patients may have a longer pain duration
that may benefit from extended regional analgesia.87
Fifth, the type of local anaesthetic and sensory block
duration have not been included in this analysis.
Conclusion
All the single-injection regional analgesia techniques
analysed were beneficial in providing postoperative anal-
gesia and reducing opioid consumption. Although we
were not able to establish the superiority of any one
technique over the others, one of these techniques should
be included in the pain management plan for mastectomy
patients. Local anaesthetic infiltration does not confer
any advantages over multimodal analgesia alone.
Acknowledgements relating to this article
Assistance with the study: none.
Financial support and sponsorship: none.
Conflicts of interest: none.
Presentation: none.
References
1 Zhao J, Han F, Yang Y, et al. Pectoral nerve block in anesthesia for modified
radical mastectomy: a meta-analysis based on randomized controlled trials.
Medicine (Baltimore) 2019; 98:e15423.
2 Dubowitz J, Hiller J, Riedel B. Anesthetic technique and cancer surgery
outcomes. Curr Opin Anaesthesiol 2021; 34:317–325.
3 Lam S, Qu H, Hannum M, et al. Trends in peripheral nerve block usage in
mastectomy and lumpectomy: analysis of a national database from 2010 to
2018. Anesth Analg 2021; 133:32–40.
4 Saadawi M, Layera S, Aliste J, et al. Erector spinae plane block: a narrative
review with systematic analysis of the evidence pertaining to clinical
indications and alternative truncal blocks. J Clin Anesth 2021; 68:110063.
5 Huang W, Wang W, Xie W, et al. Erector spinae plane block for
postoperative analgesia in breast and thoracic surgery: a systematic review
and meta-analysis. J Clin Anesth 2020; 66:109900.
6 Jacobs A, Lemoine A, Joshi GP, et al. PROSPECT Working Group
collaborators. PROSPECT guideline for oncological breast surgery: a
systematic review and procedure-specific postoperative pain management
recommendations. Anaesthesia 2020; 75:664–673.
7 Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting
systematic reviews and meta-analyses of studies that evaluate healthcare
interventions: explanation and elaboration. BMJ 2009; 339:b2700.
8 El-Boghdadly K, Wolmarans M, Stengel AD, et al. Standardizing
nomenclature in regional anesthesia: an ASRA-ESRA Delphi consensus
study of abdominal wall, paraspinal, and chest wall blocks. Reg Anesth
Pain Med 2021; 46:571–580.
9 Sterne JAC, Savovic J, Page MJ, et al. RoB 2: a revised tool for assessing
risk of bias in randomised trials. BMJ 2019; 366:l4898.
Copyright © 2022 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.
Analgesia for mastectomy: meta-analysis 599
10 Puhan MA, Schunemann HJ, Murad MH, et al., GRADE Working Group. A
GRADE Working Group approach forrating the qualityoftreatmenteffect
estimates from network meta-analysis. BMJ 2014; 349:g5630.
11 Rucker G, Schwarzer G. Ranking treatments in frequentist network
metaanalysis works without resampling methods. BMC Med Res Methodol
2015; 15:58.
12 2 Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from
the median, range, and thesizeofasample. BMC Med Res Methodol 2005;
5:13.
13 Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in
meta-analyses. BMJ 2003; 327:557–560.
14 Singh S, Kumar G, Akhileshwar. Ultrasound-guided erector spinae plane
block for postoperative analgesia in modified radical mastectomy: a
randomised control study. Indian JAnaesth 2019; 63:200–204.
15 Yao Y, Li H, He Q, et al. Efficacy of ultrasound-guided erector spinae plane
block on postoperative quality of recovery and analgesia after modified
radical mastectomy: randomized controlled trial. Reg Anesth Pain Med
2019; (Epub ahead of print].
16 He W, Wu Z, Zu L, et al. Application of erector spinae plane block guided
by ultrasound for postoperative analgesia in breast cancer surgery: a
randomized controlled trial. Cancer Commun (Lond) 2020; 40:122–125.
17 Seelam S, Nair AS, Christopher A, et al. Efficacy of single-shot ultrasound-
guided erector spinae plane block for postoperative analgesia after
mastectomy: a randomizedcontrolledstudy. Saudi J Anaesth 2020;
14:22–27.
18 Sharma S, Arora S, Jafra A, et al. Efficacy of erector spinae plane block for
postoperative analgesia in total mastectomy and axillary clearance: a
randomized controlled trial. Saudi J Anaesth 2020; 14:186–191.
19 Zielinski J, Jaworski R, Smietanska I, et al. A randomized, double-blind,
placebo-controlled trial of preemptive analgesia with bupivacaine in
patients undergoing mastectomy for carcinoma of the breast. Med Sci
Monit 2011; 17:CR589–CR597.
20 Mohamed SA, Abdel-Ghaffar HS. Effect of the addition of clonidine to
locally administered bupivacaine on acute and chronic postmastectomy
pain. J Clin Anesth 2013; 25:20–27.
21 Al Ja‘bari A, Robertson M, El-Boghdadly K, et al. A randomised controlled
trial of the pectoral nerves-2 (PECS-2) block for radical mastectomy.
Anaesthesia 2019; 74:1277–1281.
22 Neethu M, Pandey RK, Sharma A, et al. Pectoral nerve blocks to improve
analgesia after breast cancer surgery: a prospective, randomized and
controlled trial. J Clin Anesth 2018; 45:12–17.
23 Senapathi TGA, Widnyana IMG, Aribawa IGNM, et al.
Combinedultrasound-guided Pecs II block and general anesthesia are
effective for reducing pain from modified radical mastectomy. J Pain Res
2019; 12:1353–1358.
24 Deng W, Fu D, He L. Evaluation of pectoral nerve block in modified radical
mastectomy: comparison of three concentrations of ropivacaine. Clin Interv
Aging 2020; 15:937–944.
25 Syal K, Chandel A. Comparison of the postoperative analgesic effect of
paravertebral block, pectoral nerve block and local infiltration in patients
undergoing modified radical mastectomy: a randomised double-blind trial.
Indian J Anaesth 2017; 61:643–648.
26 Thomas M, Philip FA, Mathew AP, et al. Intraoperative pectoral nerve block
(Pec) for breast cancer surgery: a randomized controlled trial. J
Anaesthesiol Clin Pharmacol 2018; 34:318–323.
27 Wang K, Zhang X, Zhang T, et al. The efficacy of ultrasound-guided type II
pectoral nerve blocks in perioperative pain management for immediate
reconstruction after modified radical mastectomy: a prospective,
randomized study. Clin J Pain 2018; 34:231–236.
28 Altiparmak B, Korkmaz Toker M, Uysal AI, et al. Comparison of the effects of
modified pectoral nerve block and erector spinae plane block on
postoperative opioid consumption and pain scores of patients after radical
mastectomy surgery: a prospective, randomized, controlled trial. J Clin
Anesth 2019; 54:61–65.
29 Gad M, Abdelwahab K, Abdallah A, et al. Ultrasound-guided erector spinae
plane block compared to modified pectoral plane block for modified radical
mastectomy operations. Anesth Essays Res 2019; 13:334–339.
30 Kumar S, Goel D, Sharma SK, et al. A randomised controlled study of the
postoperative analgesic efficacy of ultrasound-guided pectoral nerve block
in the first 24 h after modified radical mastectomy. Indian J Anaesth 2018;
62:436–442.
31 Sinha C, Kumar A, Kumar A, et al. Pectoral nerve versus erector spinae
block for breast surgeries: a randomised controlled trial. Indian J Anaesth
2019; 63:617–622.
32 El Ghamry MR, Amer AF. Role of erector spinae plane block
versus paravertebral block in pain control after modified radical
mastectomy. a prospective randomised trial. Indian J Anaesth 2019;
63:1008–1014.
Eur J Anaesthesiol 2022; 39:591–601
 600 De Cassai et al.
33 Moustafa MA, Alabd AS, Ahmed AMM, et al. Erector spinae versus
paravertebral plane blocks in modified radical mastectomy: randomised
comparative study of the technique success rate among novice
anaesthesiologists. Indian J Anaesth 2020; 64:49–54.
34 Hamed IG, Fawaz AA, Rabie AH, et al. Ultrasound-guided thoracic
paravertebral block vs pectoral nerve block for postoperative analgesia
after modified radical mastectomy. Ain-Shams J Anesthesiol 2020; 12:30.
35 Kulhari S, Bharti N, Bala I, et al. Efficacy of pectoral nerve blockversus
thoracic paravertebral block for postoperative analgesia after radical
mastectomy: a randomized controlled trial. Br J Anaesth 2016; 117:382–
386.
36 Hetta DF, Rezk KM. Pectoralis-serratus interfascial plane block vs thoracic
paravertebral block for unilateral radical mastectomy with axillary
evacuation. J Clin Anesth 2016; 34:91–97.
37 Pillai VS, Ramesh B, Varughese SA, et al. Safety and efficacy of multiple
site thoracic paravertebral nerve block vs. modified pectoral nerve blockfor
postoperative analgesia after modified radical mastectomies-a randomised
controlled trial. Indian J Clin Anaesth 2021; 5:445.
38 Siddeshwara A, Singariya G, Kamal M, et al. Comparison of efficacy of
ultrasound-guided pectoral nerve block versus thoracic paravertebral block
using levobupivacaine and dexamethasone for postoperative analgesia
after modified radical mastectomy: a randomized controlled trial. Saudi J
Anaesth 2019; 13:325–331.
39 Joshi R, Singh MK, Bhattacharjee S, et al. Ultrasound guided paravertebral
block vs. modified PECS blockfor modified radical mastectomy. Anaesth
Pain Intensive care 2019; 23:172–177.
40 Tripathy S, Mandal I, Rao P, et al. Opioid-free anesthesia for breast cancer
surgery: a comparison of ultrasound guided paravertebral and pectoral
nerve blocks. A randomized controlled trial. J Anaesthesiol Clin Pharmacol
2019; 35:475–480.
41 Fujii T, Shibata Y, Akane A, et al. A randomised controlled trial of pectoral
nerve-2 (PECS 2) block vs. serratus plane block for chronic pain after
mastectomy. Anaesthesia 2019; 74:1558–1562.
42 Gupta K, Srikanth K, Girdhar KK, et al. Analgesic efficacy of ultrasound-
guided paravertebral block versus serratus plane blockfor modified radical
mastectomy: a randomised, controlled trial. Indian J Anaesth 2017;
61:381–386.
43 Bhuvaneswari V, Wig J, Mathew PJ, et al. Postoperative pain and analgesic
requirements after paravertebral block for mastectomy: a randomized
controlled trial of different concentrations of bupivacaine and fentanyl.
Indian J Anaesth 2012; 56:34–39.
44 Kundra P, Varadharajan R, Yuvaraj K, et al. Comparison of paravertebral
and interpleural block in patients undergoing modified radical mastectomy.
J Anaesthesiol Clin Pharmacol 2013; 29:459–464.
45 Yilmaz O, Saracoglu A, Bezen O, et al. Modifiye radikal mastektomi
uygulanan hastalarda torakal paravertebral blok uygulamasinin ameliyat
sonrasi analjezi uzerine etkileri [Effects of a thoracic paravertebral block on
postoperative analgesia in patients undergoing modified radical
mastectomy]. Agri 2014; 26:179–183.
46 Karmakar MK, Samy W, Li JW, et al. Thoracic paravertebral block
and its effects on chronic pain and health-related quality of life
after modified radical mastectomy. Reg Anesth Pain Med 2014; 39:289–
298.
47 Ali Hassn AM, Zanfaly HE, Biomy TA. Preemptive analgesia of ultrasound-
guided pectoral nerve block II with dexmedetomidine-bupivacaine for
controlling chronic pain after modified radical mastectomy. Res Opin
Anesth Intensive Care 2016; 3:6–13.
48 Kamiya Y, Hasegawa M, Yoshida T, et al. Impact of pectoral nerve block on
postoperative pain and quality of recovery in patients undergoing breast
cancer surgery: a randomised controlled trial. Eur J Anaesthesiol 2018;
35:215–223.
49 Onishi E, Murakami M, Nichino R, et al. Analgesic effect of double-level
retrolaminar paravertebral block for breast cancer surgery in the early
postoperative period: a placebo-controlled, randomized clinical trial.
Tohoku J Exp Med 2018; 245:179–185.
50 Rahimzadeh P, Imani F, Faiz SHR, et al. Impact of the ultrasound-guided
serratus anterior plane block on post-mastectomy pain: a randomised
clinical study. Turk J Anaesthesiol Reanim 2018; 46:388–392.
51 Kaur U, Shamshery C, Agarwal A, et al. Evaluation of postoperative pain in
patients undergoing modified radical mastectomy with pectoralis or
serratus-intercostal fascial plane blocks. Korean J Anesthesiol 2020;
73:425–433.
52 Abdelaziz Ahmed AA. Efficacy of pectoral nerve block using bupivacaine
with or without magnesium sulfate. Anesth Essays Res 2018; 12:440–
445.
53 Sotome S, Sawada A, Wada A, et al. Erector spinae plane block versus
retrolaminar block for postoperative analgesia after breast surgery: a
randomized controlled trial. J Anesth 2021; 35:27–34.
Eur J Anaesthesiol 2022; 39:591–601
Copyright © 2022 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.
54 Sharma S, Tiwari S, Sharma K, et al. Randomized controlled trial comparing
the efficacy of pectoral nerve block with general anesthesia alone in
patients undergoing unilateral mastectomy. Indian J Surg Oncol 2021;
12:158–163.
55 Elsabeeny WY, Shehab NN, Wadod MA, et al. Perioperative analgesic
modalities for breast cancer surgeries: a prospective randomised
controlled trial. J Pain Res 2020; 13:2885–2894.
56 Barrington MJ, Seah GJ, Gotmaker R, et al. Quality of recovery after breast
surgery: a multicenter randomized clinical trial comparing pectoral nerves
interfascial plane (pectoral nerves ii) block with surgical infiltration. Anesth
Analg 2020; 130:1559–1567.
57 Bakeer AH, Kamel KM, Abdelgalil AS, et al. Modified pectoral nerve block
versus serratus block for analgesia following modified radical mastectomy:
a randomized controlled trial. J Pain Res 2020; 13:1769–1775.
58 Lin ZM, Li MH, Zhang F, et al. Thoracic paravertebral blockade reduces
chronic postsurgical pain in breast cancer patients: a randomized
controlled trial. Pain Med 2020; 21:3539–3547.
59 Altiparmak B, Korkmaz Toker M, Uysal AI, et al. Evaluation of ultrasound-
guided rhomboid intercostal nerve block for postoperative analgesia in
breast cancer surgery: a prospective, randomized controlled trial. Reg
Anesth Pain Med 2020; 45:277–2782.
60 Jiang CW, Liu F, Zhou Q, et al. Comparison of rhomboid intercostal nerve
block, erector spinae plane block, and serratus plane block on analgesia for
modified radical mastectomy: a prospective randomized controlled trial. Int
J Clin Pract 2021; 16:e14539.
61 Yayik AM, Ahiskalioglu A, Sulak MM, et al. The effect of ultrasound-guided
superficial serratus plane block for acute postmastectomy pain after
modified radical mastectomy and axillary lymph node dissection: a
randomized controlled study. Anestezi Derg 2019; 27:121–127.
62 Amin SR, Abdelrahman EA, El Shahat Afify E, et al. Ultrasound-guided
serratus anterior plane block versus thoracic paravertebral block for
postmastectomy analgesia. Benha Med J 2018; 35:429–436.
63 Tang W, Luo G, Lu Y, et al. Application of a new serratus anterior plane
block in modified radical mastectomy under ultrasound guidance: a
prospective, randomized controlled trial. J Clin Anesth 2021; 74:110377.
64 Agarwal S, Bharati SJ, Bhatnagar S, et al. The comparison of the efficacy of
ultrasound-guided paravertebral block versus erector spinae plane block
for postoperative analgesia in modified radical mastectomy: a randomized
controlled trial. Saudi J Anaesth 2021; 15:137–143.
65 Annamalai G, Durairaj AK, Kailasam KR. Pectoral nerve block versus
thoracic paravertebral block-comparison of analgesic efficacy for
postoperative pain relief in modified radical mastectomy surgeries. J Evol
Med Dent Sci 2017; 6:4412–4416.
66 Wahba SS, Kamal SM. Thoracic paravertebral block versus pectoral nerve
block for analgesia after breast surgery. Egy J Anaesth 2014; 30:129–
135.
67 Arunakul P, Ruksa A. General anesthesia with thoracic paravertebral block
for modified radical mastectomy. J Med Assoc Thai 2010; 93 (Suppl 7):
S149–S153.
68 Xu J, Zhou Y, Wang Y, et al. Clinical evaluation of ultrasound-guided
thoracic paravertebral block (TPVB) effect on postoperative analgesia in
patients with breast cancer after radical mastectomy. Primary Healthcare
2016; 6:4.
69 Ibarra MM, S-Carralero GC, Vicente GU, et al. Comparaci
on entre
anestesia general con o sin bloqueo paravertebral preincisional con dosis
unicay dolor cr
onico postquirúrgico, en cirugı́a radical de c
oncer de mama
[Chronic postoperative pain after general anesthesia with or without a
single-dose preincisional paravertebral nerve block in radical breast cancer
surgery]. Rev Esp Anestesiol Reanim 2011; 58:290–294.
70 Aksu C, Kus A, Y€ orükoğlu HU, et al. Analgesic effect of the bilevel injection
erector spinae plane block after breast surgery: a randomized controlled
trial. Agri 2019; 31:132–137.
71 Gurkan Y, Aksu C, Kus A, et al. Ultrasound guided erector spinae plane
block reduces postoperative opioid consumption following breast surgery:
a randomized controlled study. J Clin Anesth 2018; 50:65–68.
72 Gurkan Y, Aksu C, Kus A, et al. Erector spinae plane block and thoracic
paravertebral block for breast surgery compared to IV-morphine: a
randomized controlled trial. J Clin Anesth 2020; 59:84–88.
73 Khemka R, Chakrborty A, Agrawal S, et al. Is COMBIPECS the answer to
perioperative analgesia for breast surgery? A double blinded randomized
controlled trial. Indian J Anaesth 2019; 63:530–536.
74 Martsiniv VV, Loskutov AO, Strokan MA, et al. Efficacy of pectoral nerve
block type II versus thoracic paravertebral block for analgesia in breast
cancer surgery. Klin Onkol 2020; 33:296–301.
75 Mazzinari G, Rovira L, Casasempere A, et al. Interfascial block at the
serratus muscle plane versus conventional analgesia in breast
surgery: a randomized controlled trial. Reg Anesth Pain Med 2019; 44:52–
58.

76 Hussain N, Brull R, Noble J, et al. Statistically significant but clinically
unimportant: a systematic review and meta-analysis of the analgesic
benefits of erector spinae plane blockfollowing breast cancer surgery. Reg
Anesth Pain Med 2021; 46:3–12.
77 Raja SN, Carr DB, Cohen M, et al. The revised International Association for
the Study of Pain definition of pain: concepts, challenges, and
compromises. Pain 2020; 161:1976–1982.
78 Kelly A. The minimum clinically significant difference in visual analogue
scale pain score does not differ with severity of pain. Emerg Med J 2001;
18:205–207.
79 Chang AK, Bijur PE, Esses D, et al. Effectofa single dose of oral opioid and
nonopioid analgesics on acute extremity pain in the emergency
department: a randomized clinical trial. JAMA 2017; 318:1661–1667.
80 Eason MJ, Wyatt R. Paravertebral thoracic block-a reappraisal.
Anaesthesia 1979; 34:638–642.
81 Meißner M, Austenfeld E, Kranke P, et al. Pectoral nerve blocks
for breast surgery: a meta–analysis. Eur J Anaesthesiol 2021; 38:383–
393.
82 Leong RW, Tan ESJ, Wong SN, et al. Efficacy of erector spinae plane block
for analgesia in breast surgery: a systematic review and meta-analysis.
Anaesthesia 2021; 76:404–413.
Copyright © 2022 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.
Analgesia for mastectomy: meta-analysis 601
83 Ilfeld BM, Madison SJ, Suresh PJ, et al. Persistent postmastectomy pain
and pain–related physical and emotional functioning with and without a
continuous paravertebral nerve block: a prospective 1-year follow-up
assessment of a randomized, triple–masked, placebo–controlledstudy.
Ann Surg Oncol 2015; 22:2017–2025.
84 Ilfeld BM, Madison SJ, Suresh PJ, et al. Treatment of postmastectomy pain
with ambulatory continuous paravertebral nerve blocks: a randomized,
triple–masked, placebo–controlled study. Reg Anesth Pain Med 2014;
39:89–96.
85 Jin Z, Durrands T, Li R, et al. Pectoral block versus paravertebral block: a
systematic review, meta-analysis and trial sequential analysis. Reg Anesth
Pain Med 2020; 45:727–732.
86 Wong HY, Pilling R, Young BWM, et al. Comparison of local and regional
anesthesia modalities in breast surgery: a systematic review and network
meta-analysis. J Clin Anesth 2021; 72:110274.
87 Brenin DR, Dietz JR, Baima J, et al. Pain management in breast surgery:
recommendations of a multidisciplinary expert panel-The American Society
of Breast Surgeons. Ann Surg Oncol 2020; 27:4588–4602.
88 Mariano ER, El–Boghdadly K, Ilfeld BM. Using postoperative pain
trajectories to define the role of regional analgesia in personalised pain
medicine. Anaesthesia 2021; 76:165–169.
Eur J Anaesthesiol 2022; 39:591–601