British Journal of Anaesthesia, 120 (2): 252e263 (2018)

doi: 10.1016/j.bja.2017.11.084
Advance Access Publication Date: 5 December 2017
Review Article

High-dose versus low-dose local anaesthetic for

transversus abdominis plane block post-Caesarean
delivery analgesia: a meta-analysis
S. C. Ng1,*, A. S. Habib2, S. Sodha1, B. Carvalho3 and P. Sultan1
1
Department of Anaesthesia, University College London Hospital, London, UK, 2Department of
Anesthesiology, Duke University School of Medicine, Durham, NC, USA and 3Department of
Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA,
USA

*Corresponding author. E-mail: sucheenng@gmail.com

Abstract
Background: The optimal local-anaesthetic (LA) dose for transversus-abdominis-plane (TAP) block is unclear. In this
meta-analysis, we aimed to determine whether TAP blocks for Caesarean delivery (CD) with low-dose (LD) LA demon-
strated non-inferiority in terms of analgesic efficacy, compared with high-dose (HD) LA.
Methods: A literature search was performed for randomised controlled trials examining the analgesic efficacy of TAP
blocks vs control after CD. The different dosing used in these studies was classified as HD or LD (bupivacaine equivalents
>50 or
50 mg per block side, respectively). The pooled results of each dose group vs control were indirectly compared
using the Q test. The primary outcome was 24 h opioid consumption. Secondary outcomes included 6 and 24 h post-
operative pain scores, time to first analgesia, 6 h opioid consumption, opioid-related side-effects, and maternal
satisfaction.
Results: Fourteen studies consisting of 770 women (389 TAP and 381 control) were included. Compared with controls, the
24 h opioid consumption (milligram morphine equivalents) was lower in HD [mean difference (MD) 95% confidence in-
terval (CI) e22.41 (e38.56, e6.26); P¼0.007; I2¼93%] and LD [MD 95% CI e16.29 (e29.74, e2.84); P¼0.02; I2¼98%] TAP groups.
However, no differences were demonstrated between the HD and LD groups (P¼0.57). There were also no differences
between the HD and LD groups for the 6 h opioid consumption, time to first analgesia, 6 and 24 h pain scores, post-
operative nausea and vomiting, pruritus, and maternal satisfaction.
Conclusions: Low-dose TAP blocks for Caesarean delivery provide analgesia and opioid-sparing effects comparable with
the high-dose blocks. This suggests that lower doses can be used to reduce local anaesthetic toxicity risk without
compromising the analgesic efficacy.

Keywords: anaesthetic; local; analgesia; Caesarean section; pain management

Editorial decision: August 29, 2017; Accepted: August 29, 2017

© 2017 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.
For Permissions, please email: permissions@elsevier.com

252

Editor’s key points
 The authors systematically reviewed the literature
regarding the analgesic efficacy of high-dose or low-
dose transversus abdominis plane (TAP) blocks after
Caesarean delivery.
 In the 14 studies considered (770 patients), both high-
and low-dose approaches appeared effective in
reducing 24 h morphine consumption, but there was no
apparent difference between the high- and low-dose
techniques in this, or other, outcome measures.
 The authors suggest that the data support the use of
low-dose TAP blocks, potentially reducing the risk of
systemic local anaesthetic toxicity.
The transversus abdominis plane (TAP) block was first
described by Rafi1 in 2001. After a Caesarean delivery (CD), TAP
blocks have been shown to play a valuable role in providing
adjunctive analgesia for patients who are undergoing CD with
spinal anaesthesia without intrathecal morphine (ITM),2e5 and
provide analgesic benefit to patients undergoing CD with
general anaesthesia.4,6,7
During pregnancy, enhanced sensitivity to local anaes-
thetics (LAs) as a result of altered physiology may increase
the risk of LA systemic toxicity (LAST).8,9 Even when the
recommended maximal allowable LA doses are adhered to,
the minimum toxic plasma concentrations can still be
exceeded.8 There have been several published cases of
toniceclonic convulsions in women receiving TAP block for
CD.9e11 However, utilising lower doses may compromise
the analgesic efficacy of the block. The optimum dosing
strategy balancing analgesic efficacy and LAST remains
unclear.
Whilst studies have explored TAP blocks in the non-
obstetric population and suggested similar efficacy between
lower doses and higher doses of LA,12e15 few studies have
directly compared post-CD analgesic outcomes after low-dose
(LD) and high-dose (HD) LA for TAP blocks.16,17 Singh and
colleagues16 concluded that in the presence of ITM, neither HD
nor LD LA TAP decreased pain scores at 24 h, whilst another
study demonstrated that LD LA TAP provided similar analgesia
effects compared with a higher-dose LA.17
This meta-analysis aimed to determine whether TAP
blocks for CD with LD LA demonstrated non-inferiority in
terms of analgesic efficacy, compared with HD LA. The pri-
mary outcome of the study was 24 h opioid (in milligram
morphine equivalents) usage postoperatively.
Methods
For this meta-analysis, the Preferred Reporting Items for Sys-
tematic Reviews and Meta-Analyses (PRISMA) recommenda-
tions were followed.18 As there is no universally accepted
definition for HD or LD LA doses for TAP blocks, we assigned
the various doses used in different studies to the HD and LD
groups as bupivacaine equivalents >50 and
50 mg per block
side, respectively. This cut-off value was chosen to reflect the
dosing strategy of bupivacaine 0.25%, 20 ml per side that is
commonly administered in the clinical setting and in pub-
lished research, to represent a lower-dose TAP block.
High- versus low-dose local anaesthetic TAP block - 253
A literature search was performed without language re-
striction on October 20, 2015 and repeated on April 7, 2016.
Searches were performed in PubMed (1966eApril 2016); US
National Library of Medicine, MEDLINE (1966eApril 2016);
Cochrane Central Register of Controlled Trials, CENTRAL
(1996eApril 2016); Cumulative Index to Nursing and Allied
Health Literature, CINAHL (1983eApril 2016); and Excerpta
Medica Database, EMBASE (1947eApril 2016). The literature
search was carried out with the following search terms:
transverse abdominis, transversus abdominis, transversus
abdominis plane block, transverse abdominis plane block,
TAP, TAP block; combined with Cesarean, Caesarean, C-sec-
tion, Cesarean delivery, Caesarean delivery (Supplementary
Appendix 1).
We identified randomised controlled trials comparing
either HD or LD (or both) single-shot TAP blocks compared
with control (no block, placebo block) for postoperative CD
analgesia. Studies were included if TAP blocks were performed
in the intraoperative period carried out by either landmark-
based or ultrasound-guided (USG) techniques, and patients
underwent either elective or emergency CD (or both) under
spinal or general anaesthesia. Studies were excluded if they
utilized catheter-based TAP blocks, did not use similar anal-
gesic adjuvants or long-acting intrathecal opioids within study
groups (e.g. intrathecal morphine in control group, but not TAP
group), and if TAP blocks were compared with other regional
block techniques (excluding spinal anaesthesia). Letters, ab-
stracts, case reports, reviews, comments, editorials, cadaveric
studies, animal studies, and studies in a language that the
authors were unable to translate were also excluded. A
consensus amongst all authors was sought to finalize the list
of studies to be included in the meta-analysis. Bibliographies
of included studies and relevant review papers were also
manually searched to capture any other relevant studies that
met the inclusion criteria that may not have been identified in
the original database search. We also searched for and
reviewed published abstracts, and where appropriate, the
authors were contacted.
The risk of bias for included studies was assessed using the
Cochrane Risk of Bias tool.19 The quality of included articles
was also evaluated using the Jadad score.20 Data extraction
was independently carried out by at least two individuals
(S.C.N. and S.S.). A standardized collection form was used for
data extraction. Any relevant outcome data common to more
than one paper were used for analysis. Discrepancies were
resolved by re-examining the original manuscript. When any
uncertainty arose, all authors were consulted and a consensus
achieved. Where data were reported in a clear graphical
format, the reviewers extracted the data from the graphs. If
the source data were unclear, attempts were made to contact
the authors.
The primary outcome was difference in cumulative 24 h
opioid consumption (in milligram morphine equivalents) be-
tween the HD and LD TAP block groups. Secondary outcomes
included 6 h opioid consumption; time to first analgesic
request; 24 h postoperative pain scores at rest and on move-
ment using pain rating scales; 6 h postoperative pain scores at
rest and on movement using pain rating scales; opioid-related
side-effects (nausea, vomiting, and pruritus); and patient
satisfaction. In order to standardize analysis, opioids were
converted to i.v. morphine equivalents (tramadol:morphine
10:121 and morphine oral:i.v. 2:122), and LA agents were
converted to bupivacaine equivalents based on previously
published ratios (ropivacaine:bupivacaine 1:0.623 and
 254 - Ng et al.

levobupivacaine:bupivacaine 1:124). Pain reported as visual,
verbal, or numerical rating scales was converted to a 0- to 100-
point scale (where 0¼no pain and 100¼worst pain imaginable).
Postoperative nausea and vomiting (PONV) were defined in our
analysis as any reported postoperative nausea or vomiting.
When these data were reported over different time intervals
rather than the entire duration of the study, the highest re-
ported incidence over the study period was used for the
analysis. When an individual study had more than two study
arms for comparison, we included only the group that received
a TAP block (vs control group) in observance with our inclusion
criteria.
calculated using random effects modelling. We combined
studies comparing HD TAP block vs placebo and those
comparing LD TAP block vs placebo, and calculated a pooled
effect size for each dose for the primary and secondary out-
comes. An indirect comparison of the HD and LD subgroups
was then performed using the Q test. Heterogeneity amongst
the studies was evaluated using the I2 statistic. To investigate
the impact of heterogeneity amongst the included studies, we
performed a number of sensitivity analyses for the primary
outcome of 24 h opioid consumption by excluding studies that
did not perform USG blocks, those that did not perform a sham
TAP block, and those who did not use a postoperative multi-
modal analgesic regimen.

Statistical analysis
Data were analysed using the Review Manager software
(RevMan, version 5.3.5; Nordic Cochrane Centre, The Cochrane
Collaboration, Copenhagen, Denmark). Mean differences
(MDs) and risk ratios with 95% confidence intervals (CIs) for
primary outcome and 99% CIs for secondary outcomes were
Results
Included studies
We retrieved all 20 shortlisted articles that were identified
from the literature search. A PRISMA flow diagram outlining
study selection is provided in Figure 1. The retrieved articles

Records idenƟfied through AddiƟonal records idenƟfied

IdenƟficaƟon

database searching through other sources

(n = 308) (n = 1)

Records aŌer duplicates removed

(n =151)
Screening

Records screened Records excluded

(n = 151) (n = 131)

Full-text arƟcles assessed Full-text arƟcles excluded,

for eligibility with reasons
Eligibility

(n =20) (n = 6)**

Studies included in
qualitaƟve synthesis
(n =14)
Included

Studies included in
quanƟtaƟve synthesis
(meta-analysis)
(n =14)*

*Included studies6 7 16 25-35

**Excluded studies summarized in Appendix 2

Fig 1. Literature search results.


were subsequently examined by two authors (S.C.N. and S.S.)
to assess the eligibility for inclusion in the meta-analysis. The
excluded trials are listed in Supplementary Appendix 2.
Fourteen randomized controlled trials met our inclusion
criteria.6,7,16,25e35 A total of 770 patients were included in the
final analysis: 389 patients in the TAP group and 381 patients in
the control group. Attempts were made to contact 10 authors,
and three authors responded.6,27,34
The methodology for each included study is summarized in
Table 1. All TAP blocks were performed at the end of CD with
the majority (10 studies) using USG to perform bilateral TAP
blockade.6,16,25,28e32,34,35 The comparator groups in 11 studies
had saline-based TAP blocks performed,16,25e32,34,35 and three
studies did not perform TAP blocks on comparator groups.6,7,33
Six included studies in this meta-analysis performed TAP
blocks at mid-axillary line,6,25,28,30,31,35 four at the triangle of
petit,7,26,27,33 one medial to mid-axillary line,34 one along the
mid- to anterior axillary line,16 and two did not state the site of
injection.29,32
Of the 14 studies, five utilized bupivacaine,7,27,30,33,34 two
utilized levobupivacaine,6,35 and seven utilized ropiva-
caine.16,25,26,28,29,31,32 Eleven studies utilized predetermined
doses of LA (ranging from 50 to 100 mg per block side of ropi-
vacaine,25,29,31,32 or from 37.5 to 100 mg per block side of
bupivacaine or levobupivacaine).6,7,28,30,33e35 The three
remaining trials utilized a weight-based dose of LA (range 0.75
to 1.5 mg kg1 per block side of ropivacaine16,26 or 1 mg kg1
per block side of bupivacaine27). The LD and HD group doses
ranged from bupivacaine equivalents 37.5 to 50 mg per side
and from 60 to 100 mg per side, respectively. The total doses of
LA utilized {mean [standard deviation (SD)]} in the LD and HD
groups were 87.9 (15.2) and 147.0 (29.6) mg, respectively
(P¼0.003). The LD and HD group volume ranges were 15 to 30
ml and 14.2 to 30 ml, respectively. The LA volumes adminis-
tered [mean (SD)] per block side did not vary between the LD
and HD groups [20.7 (4.5) and 20.4 (4.4) ml, respectively; P¼0.9].
The concentrations of LA varied amongst studies, including
ropivacaine (0.75% in one study,26 0.5% in four studies,16,25,28,31
0.375% in one study,29 and 0.25% in two studies16,32); bupiva-
caine (0.375% in two studies27,34 and 0.25% in three
studies7,30,33); and levobupivacaine (0.5% in one study35 and
0.25% in one study6). The LA concentrations [presented as
mean (SD) bupivacaine equivalents; mg ml1] were signifi-
cantly greater in the HD group compared with the LD group [LD
2.2 (0.5) mg ml1; HD 3.6 (0.8) mg ml1; P¼0.0009].
Six studies were excluded from the primary-outcome
analysis, as there were no data on the 24 h opioid consump-
tion.16,27,29,31,34,35 These studies were included in the
secondary-outcome analyses. In one study,34 two of the three
arms of the trial were analysed because the excluded arm
utilized clonidine as an adjuvant in the TAP block. Thirteen out
of the 14 studies included only elective CD patients, and one
study recruited elective and Category 3 CD (as defined by the
2010 Royal College of Obstetricians and Gynaecologists) pa-
tients.6 Of the studies excluded, one we were unable to
translate (Persian language),36 one study was excluded
because no inter-quartile range or SD data were available,37 one
was a non-randomized study,38 one was a retrospective
study,39 and two were studies where the TAP group did not
receive similar ITM as control group.40,41
Postoperative analgesia regimens varied amongst the
included studies (Table 2). The majority of studies (10 stud-
ies7,16,25e29,32e34) provided routine analgesia [paracetamol or
non-steroidal anti-inflammatory (NSAIDS) drugs, or both] and
High- versus low-dose local anaesthetic TAP block - 255
breakthrough analgesic options after CD. However, four
studies6,30,31,35 only provided analgesia on patient request or in
accordance to the study protocol pain rating scale. Of these
studies, three provided patient-controlled analgesia (PCA)
with i.v. morphine,6,30,35 whilst one study provided a variety of
analgesic options based on pain-rating-scale assessment (oral
paracetamol, NSAIDS, oxycodone with paracetamol, codeine
with paracetamol, or i.v. PCA morphine).31 The risk-of-bias
assessment of the included studies is summarized in
Figure 2. The majority of trials demonstrated a low risk of bias.
Primary outcome
For our primary outcome, eight studies6,7,25,26,28,30,32,33 con-
sisting of 73 patients in the HD group and 130 patients in the
LD group were analysed (n¼203). The 24 h postoperative opioid
consumption (milligram morphine equivalents) was signifi-
cantly less in the HD and LD TAP groups when compared with
control [HD: MD 95% CI e22.41 (e38.56, e6.26); P¼0.007, I2¼93%
and LD: MD 95% CI e16.29 (e29.74, e2.84); P¼0.02, I2¼98%], but
there was no difference between the two effect sizes (I2¼0%;
P¼0.57) (Fig. 3).
Sensitivity analyses for the primary outcome
Because of the high heterogeneity demonstrated in the com-
parisons between the HD, LD TAP, and control groups, three
additional sensitivity analyses were performed for the primary
outcome of the 24 h opioid consumption (Supplementary
Appendix 3): excluding studies that did not use USG (Sub-
group A; n¼123), excluding studies that did not perform a
sham TAP block (Subgroup B; n¼128), and excluding studies
that did not use a multimodal regimen for postoperative
analgesia (Subgroup C; n¼183). The analyses of Subgroups A, B,
and C demonstrated no differences in the 24 h opioid con-
sumption between the HD and LD TAP groups [Subgroup A: HD
MD 95% CI e14.14 (e17.15, e11.14), LD e18.14 (e41.69, 5.42), HD
vs LD group (P¼0.74; I2¼0%); Subgroup B: HD MD 95% CI e22.41
(e43.64,e1.19), LDe17.52 (e67.56, 32.53), HD vs LD group
(P¼0.82 I2¼0%); and Subgroup C: HD MD 95% CI e22.41 (e38.56,
e6.26), LD e11.22 (e18.13, e4.31), HD vs LD group (P¼0.21;
I2¼35.9%)].
Secondary outcomes
Additional analgesic outcomes (6 h opioid consumption, time
to first analgesic request, and 24 and 6 h pain scores at rest and
on movement), maternal side-effects (PONV and pruritus), and
maternal satisfaction are summarized in Table 3. There were
no differences between the HD and LD groups for any of these
outcomes.
There were no serious local complications associated with
the TAP block. However, there was one TAP study patient that
had an anaphylactoid reaction after receiving the study solu-
tion of ropivacaine 0.5%, 20 ml.25
Discussion
Based on indirect comparisons between the HD and LD TAP
blocks, this meta-analysis demonstrates no difference in
postoperative opioid consumption or pain scores after CD.
This suggests that there may be no additional analgesic benefit
in performing HD compared with LD TAP blocks for CD. TAP
blocks are used in current clinical practice to provide
Table 1 Summary of study methodology. HD, high dose; LD, low dose; PCA, patient-controlled analgesia; TAP, transversus abdominis plane; GA, General anaesthesia; ITF, intrathecal

256
fentanyl; ITM, intrathecal morphine; mg, milligram; mcg, microgram; h,hours; PO, Per Oral; PR, Per Rectum; PRN, pro re nata (as required); IV, intravenous; SC, subcutaneous. Control
groups used for analyses. If > 2 groups, following groups used for analyses : McMorrow-group 2 vs group 4; Bollag-group 2 vs group 3; Singh-group 1 vs group 3 and group 2 vs group 3;
Canovas-group 1 vs group 3.

-
Ng et al.
Author, publication Anaesthesia Study, group (n) Intrathecal opioids LD or HD TAP Drug, type, concentration, Analgesia administered to all patients
year, and country technique dose (mg), and additive
Intraoperative Postoperative, regular,
PRN

McDonnell and Spinal, hyperbaric 1. TAP (25) 1. ITF 25 mcg 1. HD 1. Ropivacaine, 0.75%, 1.5 Paracetamol 1 g Paracetamol 1 g per 6 h PO;
colleagues,26 2008, bupivacaine 2. Control (25) 2. ITF 25 mcg 2. Placebo TAP mg kg1 (maximum 150 PR, diclofenac 1 diclofenac 100 mg per 18
Ireland 0.5%, 12 mg mg per side), nil mg kg1 PR h PR; morphine PCA: 1
2. Saline (maximum 100 mg bolus, 6 min lockout,
mg) 4 h maximum dose
40 mg
Belavy and Spinal, hyperbaric 1. TAP (23) 1. ITF 15 mcg 1. HD 1. Ropivacaine, 0.5%, 100 Paracetamol 1 g Paracetamol 1 g per 6 h PO;
colleagues,25 2009, bupivacaine 2. Control (24) 2. ITF 15 mcg 2. Placebo TAP mg per side, nil PR, diclofenac ibuprofen 400 mg per 8 h
Australia 0.5%, 11 mg 2. Saline 20 ml per side 100 mg PR PO; morphine PCA: 1 mg
bolus, 5 min lockout for
24 h
Costello and Spinal, hyperbaric 1. TAP (47) 1. ITF 10 mcg, ITM 1. LD 1. Ropivacaine, 0.375%, 75 Paracetamol 1.3 g Paracetamol 1 g per 6h PO;
colleagues,29 2009, bupivacaine 2. Control (49) 100 mcg 2. Placebo TAP mg per side, nil PR, ketorolac 30 diclofenac 50 mg per 8h
Canada 0.75%, 12 mg 2. ITF 10 mcg, ITM 2. Saline 20 ml per side mg i.v. PO; PACU: morphine 2
100 mcg mg i.v. PRN, morphine 2
mg s.c. PRN for 24 h, and
then 5 mg PO PRN
Baaj and colleagues,30 Spinal, hyperbaric 1. TAP (20) 1. ITF 20 mcg 1. LD 1. Bupivacaine, 0.25%, 50 Nil Nil regular; morphine PCA:
2010, Saudi Arabia bupivacaine 2. Control (20) 2. ITF 20 mcg 2. Placebo TAP mg per side, nil 1 mg bolus, 10 min
0.5%, 10 mg 2. Saline 20 ml per side lockout for 24 h
McMorrow and Spinal, hyperbaric 1. TAPþITM (20) 1. ITF 10 mcg, ITM 1. HD 1. Bupivacaine, 0.375%, 1 Paracetamol 1 g Paracetamol 1 g per 6 h PO;
colleagues,27 2011, bupivacaine 11 2. TAPþIT 100 mcg 2. HD mg kg1 per side, nil PR, diclofenac diclofenac 100 mg per 18
Ireland e12.5 mg control (20) 2. ITF 10 mcg 3. Placebo TAP 2.Intrathecal : Saline 0.1 100 mg PR h PR; morphine PCA: 1
3. TAP controlþ 3. ITF 10 mcg, ITM 4. Placebo TAP ml, TAP : Bupivacaine, mg bolus, 5 min lockout
ITM (20) 100 mcg 0.375%,1 mg kg-1 per
4. TAP controlþ 4. ITF 10 mcg side,nil
IT control (20) 3. Saline
4. Intrathecal: Saline
0.1ml, TAP: Saline
Tan and colleagues,6 GA 1. TAP (20) 1. Nil 1. LD 1. Levobupivacaine, 0.25%, Morphine 0.15 mg Nil regular; morphine PCA:
2012, Singapore 2. Control (20) 2. Nil 2. No TAP 50 mg per side, nil kg1 i.v. 1 mg bolus, 5 min
2. Nil lockout, maximum 40
mg in 4 h
Sriramka and Spinal, hyperbaric 1. TAP (25) 1. ITF 25 mcg 1. HD 1. Ropivacaine, 0.5%, 100 Paracetamol 600 mg per 6 h
Panigrahi,28 2012, bupivacaine 2. Control (25) 2. ITF 25 mcg 2. Placebo TAP mg per side, nil PO, morphine 3 mg i.v.
India 0.5%, 7.5 mg 2. Saline 20 ml per side PRN
Eslamian and GA 1. TAP (24) 1. Nil 1. LD 1. Bupivacaine, 0.25%, 37.5 Morphine 0.1 mg Diclofenac 100 mg per 24 h
colleagues,7 2012, 2. Control (24) 2. Nil 2. No TAP mg per side, nil kg1 i.v., PR, tramadol 50 mg per 4
Iran 2. Nil sufentanil 15 h i.v. PRN
mcg i.v.

Continued
Table 1 Continued

Author, publication Anaesthesia Study, group (n) Intrathecal opioids LD or HD TAP Drug, type, concentration, Analgesia administered to all patients
year, and country technique dose (mg), and additive
Intraoperative Postoperative, regular,
PRN

Bollag and colleagues,34 Spinal, hyperbaric 1. TAP (clonidine) 1. ITF 25 mcg, ITM 1. HD 1. Bupivacaine, 0.375%, 75 Ketorolac 30 mg Paracetamol 1 g per 6 h PO,
2012, Brazil bupivacaine 12 (26) 100 mcg 2. HD mg per side, 75 mcg i.v. diclofenac 75 mg per 8 h
mg 2. TAP (25) 2. ITF 25 mcg, ITM 3. Placebo TAP clonidine per side PO, PACU morphine i.v.,
3. Control (30) 100 mcg 2. Bupivacaine, 0.375%, 75 tramadol 50 mg per 8 h
3. ITF 25 mcg, ITM mgþsaline 0.5 ml per PO, PRN
100 mcg side, nil
3. Saline 20.5 ml per side
Singh and colleagues,16 Spinal, bupivacaine 1. TAP (20) 1. ITF 10 mcg, ITM 1. HD 1. Ropivacaine, 0.5%, 3 mg Ketorolac 30 mg Ketorolac 30 mg i.v.,
2013, Canada 0.75%, 10e12 mg 2. TAP (19) 150 mcg 2. LD kg1 (maximum 300 mg) i.v. paracetamol 650 mg per
3. Control (20) 2. ITF 10 mcg, ITM 3. Placebo TAP total, nil 6 h PO for 24 h, codeine
150 mcg 2. Ropivacaine, 0.25%, 1.5 30 mg PO or oxycodone 5
3. ITF 10 mcg, ITM mg kg1 (maximum 150 e10 mg per 4 h PO PRN
150 mcg mg) total, nil
3. Saline 30 ml per side
Lee and colleagues,31 Spinal, hyperbaric 1. TAP (26) 1. ITF 15 mcg, ITM 1. HD 1. Ropivacaine, 0.5%, 100 PRN according to VRS: VRS
2009, USA bupivacaine 2. Control (25) 250 mcg 2. Placebo TAP mg per side, nil 1e3: paracetamol 1 g PO
0.75%, 9e12 mg 2. ITF 15 mcg, ITM 2. Saline 20 ml per side 6 h, VRS 4e5: ketorolac
250 mcg 30 mg i.v. or ibuprofen
800 mg per 6 h PO, VRS 6
e10: morphine 2 mg per
10 min i.v. (maximum 6

High- versus low-dose local anaesthetic TAP block

mg in PACU) or
paracetamol 600 mg with
codeine 60 mg 6 h PO,
oxycodone 10 mg with
paracetamol 650 mg 6 h
PO, þ/-PCA morphine
(regime not stated)
Canovas and Spinal, hyperbaric 1. Control (29) 1. ITF 10 mcg 1. Placebo TAP 1. Saline 20 ml per side Nil regular; PCA morphine:
colleagues,35 2013, levobupivacaine 2. ITM (30) 2. ITM 100 mcg 2. Placebo TAP 2. Saline 20 ml per side 1 mg bolus, 10 min
Spain 0.5%, 7.5e9 mg 3. TAP (29) 3. ITF 10 mcg 3. HD 3. Levobupivacaine, 0.5%, lockout, 6 bolus per h
100 mg per side, nil
McKeen and Spinal, hyperbaric 1. TAP (35) 1. ITF 15 mcg, ITM 1. LD 1. Ropivacaine, 0.25%, 50 Ketorolac 30 mg Naproxen 250 mg per 8 h
colleagues,32 2014, bupivacaine 12 2. Control (39) 100 mcg 2. Placebo TAP mg per side, nil i.v., paracetamol PO, paracetamol 1 g per 6
Canada mg 2. ITF 15 mcg, ITM 2. Saline 20 ml per side 1 g i.v. h PO, oxycodone 2.5e5
100 mcg mg per 6 h PO PRN
Srivastava and Spinal, heavy 1. TAP (31) 1. ITF 15 mcg 1. LD 1. Bupivacaine, 0.25%, 50 Diclofenac 75 mg Diclofenac 75 mg per 8 h
colleagues,33 2015, bupivacaine 2. Control (31) 2. ITF 15 mcg 2. No TAP mg per side, nil i.v. i.v.; PCA tramadol: 20 mg
India 0.5%, 10e11 mg 2. Nil dose, 10 min lockout,
and 1 h limit of 50 mg

-
257
 258
-
Ng et al.
Table 2 Study characteristics. NRS, numerical rating scale; PONV, postoperative nausea or vomiting; postop, postoperatively; TAP, transversus abdominis plane; USG, ultrasound guided;
VAS, visual analogue scale; VRS, verbal rating scale; þ, recorded; e, not recorded. *No values reported/not reported in published article. zUnclear whether NRS was a verbal or written
scale

Author and Timing Location Landmark/ Jadad Time Opioid Pain scores Adverse effects with opioids Satisfaction
publication year of TAP of TAP USG score to first use at
analgesia 24 h Measurement Rest Movement PONV Pruritus Sedation Anti-emetic
tool use
6 h 24 h 6 h 24 h

McDonnell and Postop Triangle Landmark 5 þ þ VAS 0e10 cm þ þ þ þ þ e þ e e

colleagues,26 2008 of petit
Belavy and Postop Mid-axillary USG 5 þ þ VAS 0e100 mm e e e e þ þ þ þ þ
colleagues,25 2009
Costello and Postop Not defined USG 5 e e VAS 0e10 cm þ þ þ e e e e e þ
colleagues,29 2009
Baaj and Postop Mid-axillary USG 3 e þ VAS 0e10 cm þ þ e þ þ e þ* þ þ
colleagues,30 2010
McMorrow and Postop Triangle Landmark 4 e e VAS 0e100 mm þ þ þ þ þ þ þ* þ þ
colleagues,27 2011 of petit
Tan and Postop Mid-axillary USG 5 e þ VAS 0e10 cm þ þ þ þ þ þ þ þ þ
colleagues,6 2012
Sriramka and Postop Mid-axillary USG 2 þ þ VAS 0e100 mm e e e e þ þ* þ* þ* e
colleagues,28 2012
Eslamian and Postop Triangle Landmark 5 þ þ VAS 0e10 cm þ þ þ þ e e e e e
colleagues,7 2012 of petit
Bollag and Postop Medial to USG 5 e e VRS-11 point þ þ þ þ þ þ þ e e
colleagues,34 2012 mid-axillary
Singh and Postop Mid- to anterior USG 5 þ e NRS-11 pointz þ þ þ þ þ* þ* þ* þ þ
colleagues,16 2013 axillary line
* *
Lee and Postop Mid-axillary USG 5 þ e VRS-11 point e þ e þ þ þ þ e þ*
colleagues,31 2013
Canovas and Postop Mid-axillary USG 5 þ e VAS 0e10 cm e þ e þ þ þ e e þ
colleagues,35 2013
z
McKeen and Postop Not defined USG 5 e þ NRS-11 point e þ e þ þ þ e e þ*
colleagues,32 2014
Srivastava and Postop Triangle Landmark 5 þ þ NRS-11 pointz e þ e þ þ e þ þ þ
colleagues,33 2015 of petit
 High- versus low-dose local anaesthetic TAP block
Fig 2. Risk of bias assessment of included studies.
additional analgesia after CD. Whilst the addition of TAP
blocks does not offer improved analgesia for CD under spinal
anaesthesia when using ITM,2,4,5,42 meta-analyses have shown
benefit when TAP block is used in conjunction with spinal
anaesthesia without long-acting opioids or when patients
undergo general anaesthesia for CD. To our knowledge, this is
the first meta-analysis examining the impact of HD vs LD TAP
blocks on postoperative analgesia requirements and pain
scores after CD.
The factors that may affect analgesia provided by TAP
blocks include location of injection, landmark vs USG, and LA
administered (including drug, total dose, concentration, and
volume). The variations in these factors may account for the
large heterogeneity demonstrated between the studies
included in this meta-analysis. The pattern of spread of LA
differs, depending on the site of injection into the TAP, which
may have important implications for the extent of analgesia
produced with each approach. Carney and colleagues43
demonstrated differences in LA spread in healthy volunteers
Fig 3. Forest plot for cumulative opioid consumption (in milligram morphine equivalents) over 24 h after Caesarean delivery. CI, confidence
interval; SD, standard deviation; TAP, transversus abdominis plane.
- 259
by utilising magnetic resonance imaging (MRI) and contrast,
and four different TAP techniques. The anterior subcostal and
mid-axillary approaches resulted in a predominantly anterior
spread within the TAP and relatively little posterior spread.
There was no spread to the paravertebral space with the
anterior subcostal approach. The mid-axillary TAP block
resulted in minimal contrast enhancement in the para-
vertebral space at T12 to L2. In contrast, the posterior ap-
proaches resulted in a predominantly posterior spread around
the quadratus lumborum to the paravertebral space from T5 to
L1 vertebral levels.43 Cadaveric TAP block studies utilising MRI
have also demonstrated that sensory block extension from T7
to L1 gradually recedes over 4e6 h with lidocaine 0.5%.44
Landmark techniques using the triangle of Petit, generally
regarded as the posterior approach for TAP blocks, result in
injectate spread posteriorly to the thoracolumbar para-
vertebral space.43 The potential blockade of the sympathetic
chain in the paravertebral space may explain the prolonged
analgesia seen with the posterior approach compared with
 260 - Ng et al.

lateral approaches commonly seen with USG techniques.45

Table 3 Summary of secondary analgesic outcomes and maternal side-effects. All variables presented as MDs with 99% CI, except PONV and pruritus, which are presented as RRs with

With the introduction of ultrasound technology, the different

Subgroup difference layers of the abdominal wall are easily identified in real time,

67
promoting various descriptions of TAP block injection
I2

0
0

0
0
0
0
0
0
points.46e48 Whilst these techniques provide analgesia to the
anterolateral abdominal wall, their efficacies may not be equal
(HD vs LD)

because of the location of injection into the TAP that facilitates

P-value

a different pattern of LA spread between the abdominal wall

0.90
0.62

0.69
0.95
0.88
0.58
0.86
0.82
0.08
muscles.43,44,49
99% CI. CI, confidence interval; HD, high dose; LD, low dose; MD, mean difference; N/A, not applicable; PONV, postoperative nausea and vomiting; RR, risk ratio

In a study of surgical patients undergoing inguinal hernia

repair, the patients were randomized to receive TAP block
the analysis
included in

either with bupivacaine 0.125% or 0.25%, 20 ml.12 The study

of studies
Number

demonstrated no difference between groups with pain scores

(visual analogue scale), time to first morphine requirement,
and 24 h morphine consumption. In obstetrics, Singh and
2
4

5
4
6
7
4
1
2
colleagues16 performed a dose-ranging study evaluating the
N/A
effect of TAP LA dose on analgesia in patients also receiving
95
98

96
96
82
95
44
I2

0
intrathecal morphine. The authors observed a significant
reduction in pain scores with movement at 6 and 12 h in the
P-value

0.0007

HD group (ropivacaine 3 mg kg1) compared with LD (ropiva-

0.002

0.07
0.11
0.14
0.15
0.39
0.93
0.78

caine 1.5 mg kg1), but no difference at 24 h. Few randomized

studies and no meta-analyses have explored the analgesic
e17.05 (e44.48, 10.37)

e13.14 (e36.85, 10.58)

effects of LA dose, volume, or concentration utilized for TAP

e6.14 (e11.27, e1.01)
253.15 (60.20, 446.28)
Low-dose vs control

e12.4 (e29.76, 4.96)

e4.86 (e13.39, 3.67)

e1.07 (e10.79, 8.65)

blocks in CD patients. Two meta-analyses examined TAP

MD or RR (99% CI)

blocks in all types of abdominal surgery, and included LA dose

0.69 (0.23, 2.09)
0.99 (0.64, 1.51)

and LA volume influence in their review.42,50 Abdallah and

colleagues50 demonstrated a trend towards superior analgesia
with 15 ml of LA per side of block, which may be attributable
to improved LA spread associated with larger volumes. How-
ever, when dividing groups into dilute (ropivacaine 0.2% and
bupivacaine 0.25%), intermediate (ropivacaine 0.375%, bupi-
the analysis
included in

vacaine 0.375%, and levobupivacaine 0.375%), concentrated

of studies
Number

(ropivacaine 0.5%, bupivacaine 0.5%, and levobupivacaine

0.5%), and highly concentrated (ropivacaine 0.75%) solutions,
they were unable to demonstrate an effect of LA concentration
4
3

4
4
6
6
4
4
3

on analgesia. In this meta-analysis, the LA dose varied be-

99

76
85
87
94
62
19
67
I2

tween the HD and LD groups because of differences in the LA

0

concentration rather than the LA volumes administered. The

P-value

LA volumes were not significantly different between the HD

0.0003
0.21

0.11
0.08
0.26
0.53
0.31
0.81
0.05

and LD groups, and so the effects of LA volume could not be

explored. A recent review by Baeriswyl and colleagues42 re-
ported no additional opioid-sparing effect above a volume of
228.22 (e243.32, 699.76)

12 ml of LA per block side (total bupivacaine equivalent dose of

High-dose vs control

e16.16 (e40.09, 7.77)

e4.93 (e8.46, e1.39)

e5.84 [e29.9, 18.22)

e8.92 (e23.11, 5.27)

e5.75 (e18.96, 7.47)

60 mg).
10.33 (e3.46, 24.12)
MD or RR (99% CI)

Local anaesthesia in the truncal regional anaesthesia

0.62 (0.18, 2.09)
1.03 (0.72, 1.48)

blocks may reach systemic threshold for LA toxicity. A recent

meta-analysis demonstrated this by evaluating the systemic
concentrations of LA after perioperative single-shot TAP or
rectus sheath block, and demonstrated that 8.6% of patients
had systemic concentrations that were above the commonly
acceptable threshold for LAST.51 The challenge facing anaes-
Movement

Movement

thesiologists caring for obstetric patients is to find a balance

between utilising a LA that provides effective analgesia whilst
Time to first analgesic request

Rest

Rest

minimising the risk of LAST. In pregnancy, enhanced sensi-

tivity as a result of altered physiology may lead to an increased
risk of LAST. Possible explanations include decreased protein
Six-hour pain score

binding;52 increased vascularity, cardiac output, and tissue

Twenty-four-hour

blood flow; and a hypothesized increased neuronal suscepti-

Six-hour opioid
consumption

bility to LA.53 TAP blocks for CD require the administration of

pain score

Satisfaction

large volumes of LA agent bilaterally in what is already a

Outcome

Pruritus

highly vascular area because of the effects of pregnancy.

PONV

Griffiths and colleagues8 utilized doses of ropivacaine 2.5 mg

kg1 diluted to 40 ml for TAP blocks in the elective CD popu-
lation under spinal anaesthesia, and assessed symptoms of

LAST and blood concentrations of ropivacaine. Even when
clinicians adhered to recommended maximum LA doses, the
LA concentrations often exceeded minimum toxic plasma
concentrations.8 Twelve of the 30 patients in their study had
recorded blood concentrations above the potential ropivacaine
toxic threshold of 2.2 mg ml1; three of these women man-
ifested symptoms of mild neurological toxicity. The women
that developed symptoms received ropivacaine 229 (19.1) mg
and asymptomatic women received mean doses of ropiva-
caine 196 (26.9) mg (mean values of bupivacaine equivalents
137 and 118 mg, respectively). There have been reported cases
of severe LAST after TAP blocks in the obstetric population.9e11
In these reports, the TAP LA dose ranged from 150 to 180 mg
bupivacaine equivalents. Including Griffiths and colleagues,8
these case reports would be classified as HD TAP blocks us-
ing our study definition. As LAST may even occur within the
recommended maximal allowable LA doses, our results sug-
gest that clinicians should utilize LD instead of HD TAP blocks
to provide comparable analgesic efficacy whilst reducing the
LAST risk.
This meta-analysis has several limitations. There is no
universally accepted definition for LD or HD for TAP blocks.
Therefore, for this meta-analysis, we agreed to assign HD and
LD of LA as bupivacaine equivalents >50 and
50 mg per block
side, respectively. The authors feel that this value reflects the
current clinical practice (e.g. our institutions utilize bupiva-
caine 0.25%, 20 ml per side), and utilising this cut-off value also
allowed for balanced reporting amongst the available studies
between the LD and HD subgroup analyses. Our result is based
on indirect comparisons between the HD and LD groups, as
studies rarely directly compared LD and HD groups. Therefore,
it was not possible to perform a meta-analysis solely utilising
studies performing direct comparisons between LD and HD.
Similar to meta-regressions, indirect comparisons based on
subgroup analyses are observational in nature, results there-
fore must be interpreted in the context of this limitation. We
acknowledge the relatively small number of patients utilized
for the primary-outcome analysis (8 studies; 203 patients). It is
also evident from the heterogeneity of the study designs that
there remains no consensus as to the most effective dose of LA
for TAP block for CD. The studies utilized different LA drugs,
LA doses, LA concentrations, LA volumes, and TAP techniques,
and intra- and postoperative analgesic regimens. For analysis,
equivalent dose conversions were carried out for the various
types of LA and opioids used in included studies. This meta-
analysis utilized the British National Formulary22 conversion
ratio for morphine. The authors acknowledge that the
different conversion ratios between i.v. and oral morphine
have been described (such as a 1:3 ratio), but this would not
have changed the findings and conclusion of this study.
We included studies with patients undergoing elective or
emergency CD, and using both USG or landmark approaches.
The accuracy of the landmark-based TAP blocks (utilized in 4
of the 14 studies in this meta-analysis) has been questioned
with previous studies reporting only 25% ideal TAP block
placement using this technique.54,55 Continuous and single-
shot wound-infiltration techniques were excluded in this
analysis. Published studies do indicate these techniques may
be as efficacious as TAP blocks11,56,57; however, there are few
studies directly comparing these techniques, with some con-
flicting results.58
The heterogeneity for the primary outcome of 24 h opioid
consumption was high. Performing subgroup analyses did not
affect heterogeneity and made no difference to the result for
High- versus low-dose local anaesthetic TAP block - 261
the primary outcome. We did not test for publication bias for
the primary outcome, as only eight studies reporting this
outcome were included and tests of publication bias are not
recommended for analyses, including less than 10 studies.59
Finally, it was not possible to acquire additional data from all
included trials despite efforts to contact authors.
In conclusion, this meta-analysis found no significant dif-
ferences in postoperative opioid use and pain after CD be-
tween HD and LD TAP blocks. Given the comparable analgesia,
we recommend the use of LD TAP blocks (i.e. bupivacaine
equivalents
50 mg per block side) in the CD setting in order to
mitigate the potential risks of LAST in this at-risk population.
Findings can reassure clinicians that LD TAP blocks can be
utilized without compromising the analgesic efficacy of TAP
blockade.
Authors’ contributions
Study design: all authors.
Data collection: S.C.N., A.S.H., S.S., P.S.
Data analysis: S.C.N., A.S.H., B.C., P.S.
Data interpretation: A.S.H., B.C., P.S.
Writing of the first draft of the paper: S.S., S.C.N
Writing of the paper: S.C.N., P.S., A.S.H., B.C.
Revisions and final approval of the version to be published: all
authors.
Acknowledgements
The authors would like to thank Maria Cristina Gutierrez, M.D.,
Assistant Clinical Professor, Department of Anesthesiology &
Pain Medicine, UC Davis Medical Center, Sacramento, CA,
USA, for translating a paper utilized in the analysis, and John
Hunting, M.P.H., Statistician, Duke University School of Med-
icine, Durham, NC, USA, for providing statistical assistance.
Supplementary data
Supplementary data related to this article can be found at
https://doi.org/10.1016/j.bja.2017.11.084.
Declaration of interest
None declared.
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