Trends in Anaesthesia and Critical Care 4 (2014) 189e194

Contents lists available at ScienceDirect

Trends in Anaesthesia and Critical Care

journal homepage: www.elsevier.com/locate/tacc

REVIEW

Post-caesarean analgesia
Sarah Kwok a, Hao Wang b, Ban Leong Sng a, b, *
a
b

Department of Women's Anaesthesia, KK Women's and Children's Hospital, Singapore

Duke-NUS Graduate Medical School, Singapore

s u m m a r y
Keywords:
Caesarean section
Pain
Regional anaesthesia
Opioid

Post-caesarean section analgesia is centred on the concept of multimodal analgesia. The analgesic
regimen should provide optimal pain relief with minimal maternal side effects and minimal infant
exposure via breastfeeding. Neuraxial opioids (morphine, diamorphine, fentanyl, pethidine) are utilized
since regional techniques are commonly administered during caesarean section. Systemic analgesia
using opioid based patient controlled analgesia (morphine, fentanyl) is commonly used when general
anaesthesia is administered during caesarean section. To reduce opioid adverse effects, paracetamol and
non-steroidal anti-inammatory agents are commonly prescribed concomitantly. Increasingly, local
anaesthetic blocks are used such as the transversus abdominis plane block to improve analgesia especially when general anaesthesia is administered or neuraxial morphine is not used.
2014 Elsevier Ltd. All rights reserved.

1. Introduction

of a variety of analgesics with differing mechanisms of action which

in combination can have additive or even synergistic effects but
with a reduction in side effects experienced as lower doses of each
class of drug are needed.2 For example, non-steroidal anti-inammatory drugs (NSAIDs) are routinely prescribed alongside neuraxial morphine as the combination has been shown to provide
improved post-operative analgesia.3e6 Huang et al. demonstrated
that NSAIDs are particularly effective at reducing the visceral pain
of uterine cramps that may follow delivery.6

Management of post-operative pain is critical in mothers undergoing caesarean delivery, as adequate pain relief is required for
mothers to quickly regain mobility and begin to care for the
newborn. Failure to do so may increase the maternal risk for
thromboembolic events, and may adversely affect the success of
breast feeding. In addition, severe acute pain after caesarean delivery may progress to chronic pain and therefore requires effective
management.1 An ideal analgesia regimen would provide optimal
pain relief with minimal maternal side effects and minimal infant
exposure via breast milk, and is easy to administer. While the
approach to post-caesarean pain has evolved signicantly over the
years encompassing a wide variety of analgesics, techniques, and
regimens, the current trend is towards the use of a balanced,
multimodal analgesia. This review will examine the evidence for
commonly used drugs and techniques, as well as new
developments in post-caesarean analgesia.

2. Multimodal analgesia
Multimodal analgesia utilizes analgesics acting on different
aspects of the pain pathway. Hence patients can receive the benets

* Corresponding author. KK Women's and Children's Hospital, 100 Bukit Timah

Road, 229899 Singapore, Singapore. Tel.: 65 6563941081; fax: 65 62912661.
E-mail addresses: Sng.Ban.Leong@kkh.com.sg, blsngdr@yahoo.com.sg (B.L. Sng).
http://dx.doi.org/10.1016/j.tacc.2014.10.001
2210-8440/ 2014 Elsevier Ltd. All rights reserved.

3. Neuraxial analgesia
Regional anaesthesia accounts for 91.8% of caesarean delivery in
2011 in the United Kingdom.7 It provides a safe and effective
method of administering neuraxial opioid analgesia with a welldened side effect prole. Several large reviews and studies have
concluded that neuraxial opioids provide higher quality analgesia
compared with the intravenous route.8e11 A number of opioids are
currently in use and they differ in their potency, duration of action
and side effects. Intrathecal fentanyl and sufentanil whilst
providing excellent intra-operative conditions have short-lived
analgesic effects due to their high lipid solubility and rapid uptake into the dorsal horn; therefore they provide little postoperative analgesia. In contrast, morphine has low lipid solubility
and penetrates neural tissue slowly resulting in a longer duration of
action. However, its rostral spread within the subarachnoid space
by bulk ow could lead to complications such as delayed
respiratory depression.

190

S. Kwok et al. / Trends in Anaesthesia and Critical Care 4 (2014) 189e194

3.1. Intrathecal opioids

Opioids administered into the subarachnoid space act on the mu
receptors in the substantia gelatinosa of the dorsal horn by suppressing excitatory neuropeptide release from C bres.12 Intrathecal morphine has been given in doses ranging from 0.075 mg13
to 0.5 mg14 providing highly effective post-operative analgesia.
However, there appears to be a ceiling analgesic effect demonstrated by several studies. A meta-analysis of intrathecal opioids
revealed high quality analgesia provided by 0.1e0.2 mg of intrathecal morphine but no additional benet above 0.2 mg.9 Median
time to rst request for supplemental analgesia was 27 h (range
11e29 h). Additionally, intrathecal morphine at doses of 0.05, 0.1
and 0.2 mg reduced pain scores and decreased consumption of
supplemental analgesia from 0 to 24 h postoperatively in all comparisons. Palmer et al. randomized 108 women undergoing elective
caesarean section to receive 1 of 9 different doses of intrathecal
morphine ranging from 0.025 to 0.5 mg with intravenous (IV) patient controlled analgesia (PCA) consumption as primary
outcome.13 The authors demonstrated the 0.075 mg group used
45.7 mg less morphine compared with the control group but there
was no signicant difference in PCA use with doses above 0.075 mg.
Cardoso et al. concluded that a 0.1 mg dose of intrathecal morphine
was optimal but also found doses of 0.025e0.05 mg combined with
a non-steroidal anti-inammatory drug to be effective.3 However,
there are studies which have reported that in a small percentage of
women, doses of 0.1 mg may be inadequate. Swart et al. found that
in women who were given 0.1 mg intrathecal morphine during
their elective caesarean section, the majority used less than 10 mg
of PCA morphine in the post-operative period but 10% of them used
more than 40 mg.15 Although intrathecal morphine is an effective
form of analgesia, monitoring of pain scores, a dedicated acute pain
service and provision of multimodal analgesia is still required.
Despite superior analgesia, the signicant adverse effects of
pruritus, nausea and vomiting, reactivation of herpes simplex,
urinary retention, sedation and delayed respiratory depression,
which have a higher incidence with intrathecal morphine
compared with parenteral opioids, may contribute to lower patient
satisfaction scores.9e11 Dahl et al. estimated that if a 0.1 mg dose is
used, 43% of the patients will have pruritus, 12% will suffer from
vomiting and 10% from nausea; all of whom would not have
experienced these side effects without treatment. Pruritus is often
cited as the most frequent and unpleasant adverse event. One
randomized prospective study16 showed signicantly higher incidences of pruritus and nausea in doses of 0.25 mg of morphine
compared to 0.1 mg.
Respiratory depression is a rare but serious complication of
which the incidence in the post-caesarean population is likely to be
low.9 Morphine is highly ionized and does not penetrate into lipidrich tissues and has an extended duration in the cerebrospinal uid.
Morphine spreads cephalad in the spinal space from bulk ow
reaching the trigeminal nerve distribution in about 6e9 h after
intrathecal injection in volunteers.17 Abouleish et al. performed a
prospective study investigating the analgesic and side effect prole
of 0.2 mg in 856 parturients and found respiratory depression
(dened by a SpO2 <85% or a respiratory rate of <10 breaths per
minute) in eight patients (0.93%) all of whom were morbidly
obese.18 Hence, women who are at higher risk of respiratory complications, for example those with obstructive sleep apnoea or who
are obese should be closely monitored.

common drug used via this route as a bolus. There are limited
studies comparing the efcacy of the epidural versus intrathecal
route. Sarvela et al. compared intrathecal morphine 0.1 mg or
0.2 mg with 3 mg epidural morphine. They found no difference in
the quality of analgesia but rescue analgesia was requested more
often in the 0.1 mg group.19 Palmer et al. performed a dose response
study and administered saline or one of four doses of morphine
(1.25, 2.5, 3.75 or 5 mg) and found no difference in PCA morphine
for doses above 3.75 mg i.e. no difference in analgesic effect.20 The
duration of analgesic effect was about 18e26 h.
Extended release epidural morphine or Depodur in which
morphine is encapsulated in lipid foam particles results in prolonged drug delivery and extended dose-dependent half-life.
Extended release epidural morphine at 10 mg and 15 mg has been
shown to have less pain in the rst 48 h after caesarean delivery
when compared to standard epidural morphine 5 mg.21 Another
study compared extended release epidural morphine 10 mg with
conventional epidural morphine 4 mg and found that the extended
release formulation had lower pain scores with a similar side effect
prole.22
3.3. Epidural diamorphine
Diamorphine is popular via the epidural route for postcaesarean analgesia in the United Kingdom and is predominantly
administered as a bolus. Bloor et al. used diamorphine doses
ranging from 2 mg23,24 to 5 mg.25 Hallworth et al. compared
intrathecal (0.25 mg) with epidural (5 mg) diamorphine in 50
parturients undergoing elective caesarean section in addition to
intrathecal bupivacaine 10 mg using a combined spinal-epidural
technique. Both groups produced similar durations of postoperative analgesia, quality of analgesia and degree of pruritus
but the intrathecal group had a signicantly lower incidence of
post-operative nausea and vomiting. However, one could argue
that Bloor et al.'s study24 is more relevant as they used more
standard doses. They compared 3 mg of epidural diamorphine with
0.3 mg of intrathecal diamorphine and found a similar quality of
analgesia but a higher incidence and severity of pruritus in the
intrathecal group. The epidural group also had a shorter duration of
action (as dened by the time to rst request of supplementary
analgesia) but a lower incidence of nausea and vomiting.
3.4. Epidural fentanyl
Fentanyl is highly lipid soluble compared to morphine and
therefore has a faster onset and shorter duration of action. Therefore, it is commonly given as an epidural infusion rather than as a
bolus for post-operative analgesia. However, arguments against
epidural infusion include increased risks of infection and haematoma formation associated with prolonged in situ epidural catheters, as well as reduced mobility. There are relatively sparse
published data looking into the role of epidural fentanyl in postoperative analgesia. Cohen et al. investigated IV versus epidural
fentanyl infusion after elective caesarean section.26 The groups
given IV rather than epidural fentanyl required higher rates of
infusion and larger total doses of the drug, reported more pain and
experienced more adverse events such as sedation, nausea and
vomiting. Cooper et al. reported improved analgesia with patient
controlled epidural fentanyl compared to IV morphine with less
nausea and drowsiness.27

3.2. Epidural morphine

3.5. Epidural pethidine

Epidural analgesia may provide post-operative analgesia as

either a bolus or continuous infusion. Morphine is the most

Epidural pethidine is commonly administered as patient

controlled epidural analgesia with 20 mg bolus with a lockout of

S. Kwok et al. / Trends in Anaesthesia and Critical Care 4 (2014) 189e194

15 min. Although epidural pethidine resulted in higher pain scores

when compared to intrathecal morphine 100 mcg, there is a
reduction in pruritus and nausea requiring treatment.28 Epidural
pethidine is a more favourable mode of delivery compared to IV
pethidine with lower pain scores and less sedation.29
4. Systemic analgesia
4.1. Intravenous and intramuscular analgesia
Intravenous patient controlled analgesia (PCA) is a popular
method of providing post-caesarean pain relief, as it provides
individualized pain relief, greater patient autonomy, and reduces
the anaesthetist and nursing workload. In general, opioid analgesics administered via patient-controlled IV route confer less
optimal pain relief compared to neuraxial analgesia.29e33 Morphine
is the standard drug of choice. However, compared to epidural
morphine, IV PCA morphine is associated with higher patient
satisfaction and less opioid side effects such as pruritus and delayed
respiratory depression.30,31,33 Thus IV PCA morphine may be an
excellent alternative in post-caesarean delivery patients who
cannot receive neuraxial analgesia.
Fentanyl is another commonly used opioid in postsurgical PCA.
A comparison of equivalent doses of morphine, fentanyl and
pethidine in postsurgical PCA found no difference in patient satisfaction and the incidence of side effects except more pruritus was
experienced in the morphine group.34 Limitations of fentanyl PCA
appear to be its relatively higher cost, more programming interventions and lack of clinical benet over morphine.35 Pethidine
has been used in the setting of post-caesarean analgesia, and
although studies show that they may provide equivalent pain relief
and a comparable if not better maternal side-effect prole
compared to morphine or fentanyl,32,34,36 concerns about neonatal
exposure in breast-feeding mothers may limit its use. Pethidine and
its active metabolite are known to accumulate in breast milk and
breast-fed infants. This is likely due to impaired neonatal metabolism,36,37 and PCA pethidine in nursing mothers was associated
with signicantly poorer neonatal alertness and orientation than
morphine.36,38 Morphine-alfentanil combination PCA has been
shown to result in faster onset of analgesia,39 but the optimal
regimen needs to be further dened and there are no data on breast
milk transfer. A recent retrospective caseecontrol study found that
a single dose of IV methadone given intra-operatively and postdelivery may reduce post-operative opioid consumption whilst
achieving effective analgesia.40
Recently low dose IV ketamine given during spinal anaesthesia
(pre-emptively) has been proposed to prolong post-caesarean
analgesia and reduce opioid consumption. Ketamine, an N-methylD-aspartate (NMDA) antagonist, exerts its analgesic effect mainly
through central desensitization and reducing opioid tolerance.41,42
A 2006 Cochrane review found that ketamine in sub-anaesthetic
dose is effective in reducing morphine requirements in the rst
24 h after surgery. Evidence amongst caesarean delivery patients is
mixed, primarily due to a difference in the method of anaesthesia
and concomitant modalities used. Evidence supporting the use of
low dose ketamine appears to come from studies where spinal
anaesthesia was administered without the addition of long acting
intrathecal opioids42,43; in comparison, when intrathecal morphine
was co-administered during spinal anaesthesia,44 or when PCA
fentanyl was used post-operatively,45 low dose ketamine does not
appear to have any opioid-sparing effect, nor is it associated with
lower pain scores.
Intramuscular (IM) opioids are easy to administer but are found
to result in less optimal pain relief and lower patient satisfaction
than either the epidural or intravenous PCA route.30,31 A single IM

191

dose of tramadol and diclofenac combination has been demonstrated to produce better analgesia than monotherapy or placebo
and requires less morphine analgesic rescue.46
4.2. Oral analgesia
Oral opioids are used for post-operative analgesia as step-down
therapy from intravenous opioids or when newer and more
expensive analgesic delivery regimens such as PCA are not readily
available.47,48 Earlier studies show that oral morphine provides
satisfactory pain relief, is easy to administer and is substantially less
expensive.47 More recent randomized trials showed oral
oxycodone-paracetamol provides better pain relief and is associated with less opioid side effects such as nausea, sedation and
pruritus compared to IV PCA morphine.49 Compared to intrathecal
morphine, multimodal analgesia regimen based on oral oxycodone
produces comparable post-operative pain relief with a lower incidence of pruritus, but was associated with lower satisfaction and
more requirements for additional analgesics.50
Tramadol is another effective analgesic in post-operative pain51
with a well-known side effect prole. It can be administered
through oral, IV, or IM routes, and produces less constipation and
emesis than equianalgesic doses of opioids.52 Compared to oral
naproxen, oral tramadol on either a xed interval or on request
regimen affords comparable pain relief after caesarean delivery and
similar breastfeeding scores, but is associated with a higher incidence of maternal adverse effects (nausea, vomiting, sedation) and
request for additional analgesics.53 IV tramadol administered in
combination with a diclofenac suppository has been shown to
produce better analgesia than an IV diclofenaceparacetamol combination, with few and comparable side effects except a higher
incidence of nausea amongst the tramadol group.54 Both oxycodone and tramadol can be an acceptable alternative in the setting of
multimodal analgesia particularly in patients who do not tolerate
the adverse effects of opioid analgesia.
Paracetamol is thought to produce analgesia both as a selective
COX-2 inhibitor as well as through central mechanisms, although
the exact mechanism of action is still unclear. Unlike opioids and
NSAIDs, it produces very few side effects at therapeutic doses,
making it a popular analgesic choice for post-operative mild to
moderate pain, frequently as part of a multimodal analgesia
regimen. A Cochrane review of 51 randomized placebo-controlled
studies shows that a single dose of paracetamol provides effective
analgesia for about half of the patients with acute post-operative
pain, for a period of about 4 h, and is associated with few, mainly
mild, adverse events.55 Recently, availability of the parenteral
formulation of paracetamol provides an attractive option to treat
immediate post-surgical pain due to its faster onset and higher
bioavailability. A review of 36 randomized studies compared
either IV paracetamol or IV prodrug propacetamol with placebo
and active controls. A single dose of both IV propacetamol and IV
paracetamol was found to provide around 4 h of effective analgesia for about 37% of patients with acute post-operative pain,
with few adverse events.56 When administered with PCA
morphine after major surgery, paracetamol given IV or orally is
found to have a signicant morphine-sparing effect though
without signicant reduction in morphine related side-effects.57
However, the evidence is less straightforward in the setting of
post-caesarean analgesia, where a paracetamol/diclofenac combination is favoured over monotherapy with either drug, and the
opioid-sparing effect of paracetamol over placebo is controversial.58,59 More recently, IV paracetamol has been found to reduce
post-operative nausea and vomiting in patients receiving general
anaesthesia, independent from the effect of reduced opioid
consumption.60

192

S. Kwok et al. / Trends in Anaesthesia and Critical Care 4 (2014) 189e194

Non-steroidal anti-inammatory drugs (NSAIDs) are effective in

reducing visceral pain after caesarean section and have a wellknown opioid-sparing effect associated with reduced opioidrelated side effects when used in multimodal analgesia.48 Due to
non-selective inhibition of COX-1 and COX-2, NSAIDs may be
associated with undesirable side effects such as platelet, gastrointestinal, and renal dysfunction. Of the NSAIDs family, ibuprofen and
ketorolac are perhaps ideal agents, with low relative infant doses
(<0.6%).61 Ketorolac has been shown to have a signicant opioidsparing effect in both intravenous PCA and patient-controlled
epidural analgesia (PCEA) after caesarean delivery4,62; the combination of ketorolac with PCEA resulted in a 30% opioid-sparing
effect, though there was no signicant reduction in pain relief or
opioid-related side-effects. Ketorolac has received a black-box
warning from the Food and Drug Administration (FDA) where it is
contraindicated in paediatric patients, as well as in labour and
delivery due to concerns about uterine haemorrhage. However, no
signicant adverse effects were observed in nursing infants, and
the same FDA warning recommends caution when administering
ketorolac to nursing women. Another NSAID, diclofenac has been
shown to produce a signicant opioid-sparing effect after caesarean
delivery.58,59 A recent systematic review of 21 randomized control
trials found that NSAIDs/paracetamol combination produces superior post-operative analgesia compared to monotherapy; the
pain intensity and analgesic supplementation was 35.0% and 38.8%
lesser, respectively, in the positive studies for the combination
versus paracetamol group, and 37.7% and 31.3% lesser, respectively,
in the positive studies for the combination versus the NSAID
group.63 In terms of dosing regimens, xed-interval oral ibuprofen
produces lower pain scores and higher maternal satisfaction
compared with a regimen based on patient demand for postcaesarean pain.64
5. Wound inltration and peripheral nerve blocks
A number of nerve blocks have been used for post-operative
analgesia including ilio-inguinal, ilio-hypogastric and transversus
abdominis plane (TAP) blocks. The benets of these blocks are that
they can be performed on patients under general anaesthesia, in
situ catheters allow for continuous analgesia and they are less
invasive than neuraxial blocks. These blocks aim to reduce the pain
arising from the surgical site through the anterolateral abdominal
wall. Innervation of the abdominal wall arises from spinal nerves
T7eL1. These include the intercostal nerves (T7e11), subcostal
nerves (T12) and ilioinguinal and iliohypogastric nerves (L1).
5.1. TAP block
TAP blocks can be performed using a blind landmark technique
or under ultrasound guidance. Two recent systematic reviews
investigated the efcacy of the TAP block compared with placebo
and in the presence and absence of intrathecal morphine with
24 h morphine consumption as their primary outcomes. Abdallah
et al.65 found from ve randomised controlled trials that TAP block
reduced the mean 24 h i.v. morphine consumption by 24 mg when
intrathecal morphine was not used. It also reduced visual analogue
scale pain scores and opioid related side effects. However, in the
presence of intrathecal morphine, there was no signicant difference between the two groups. Similarly, Mishriky et al.66 included
nine studies in their meta-analysis and found that the TAP block
signicantly reduced opioid consumption (mg morphine equivalents) after caesarean delivery at 6 h (mean difference [MD] 10.18;
95% condence interval [CI] 13.03 to 7.34), at 12 h (MD 13.83;
95% CI 22.77 to 4.89), and at 24 h (MD 20.23; 95% CI 33.69 to
6.77) when patients did not receive intrathecal morphine. The

authors concluded that TAP blocks signicantly enhanced postoperative analgesia when intrathecal morphine was not used but
showed no improvement when it was used. Furthermore, Tan
et al.67 compared TAP block with no block in 40 women undergoing
caesarean section under general anaesthesia and found the patients
who received the TAP block used signicantly less morphine in 24 h
than those in the control group (12.3 (2.6) vs. 31.4 mg (3.1),
P < 0.001) and had higher satisfaction scores (16 (80%) vs. 5 (25%),
P 0.012).
5.2. Wound inltration
Continuous wound inltration can be given with infusion
catheters but they have yielded mixed results. This may be due to
differences in technique and placement of catheter such as subcutaneous, subfascial or sub-rectus, as well as differences in the
dosing regimen with choices such as single bolus, continuous
infusion and patient controlled boluses. O'Neill et al. randomised 58
women to receive either ropivacaine via a multiorice wound
catheter placed below the fascia or an epidural bolus of 2 mg
morphine every 12 h.68 The pain scores at rest were lower in the
continuous wound infusion group at 2, 6, 24, 48 h as was the
incidence of nausea, vomiting, pruritus and urinary retention.
Lavand'homme et al. investigated administering a diclofenac infusion via an intrawound catheter and compared it to infusions of
0.2% ropivacaine and saline; the latter two groups also received the
same dose of diclofenac intravenously.69 They found that the
intrawound diclofenac group required signicantly less morphine
in 48 h (18 mg [95% CI, 12.7e22.2]) compared with the saline and
intravenous diclofenac group (38 mg [95% CI, 28.8e43.7]) and the
ropivacaine and intravenous diclofenac group (28 mg [95% CI,
18.2e32]) without unique adverse effects. This suggests the presence of peripheral analgesic properties of diclofenac independent
from its systemic effect. The same authors in another study investigating wound instillation of diclofenac, ropivacaine or saline with
the latter groups also receiving intravenous diclofenac, found that
not only was the diclofenac infusion group equivalent to ropivacaine and more effective than systemic diclofenac alone to reduce
morphine consumption, but it signicantly reduced the incidence
of residual pain one and six months postoperatively.70
6. Analgesia and breast feeding
Analgesia administered to nursing mothers after caesarean delivery must take into consideration the need for optimal maternal
pain relief while minimizing potential adverse effects to the infants.
The transfer of drug substances to the neonate is dependent on
multiple factors including drug characteristics, feeding pattern and
volume, and infant metabolism. Useful parameters for assessing the
risk of maternal analgesia to the infant include relative infant dose
(RID) and infant exposure. Amongst the common post-caesarean
analgesics, paracetamol and NSAIDs are considered safe at
maternal therapeutic doses with few reported side effects to the
infant.61,71,72 Despite an FDA black box warning for ketorolac use in
labour and delivery, it too has a low RID and no adverse effects have
been observed in nursing infants. Amongst opioids, tramadol (and
its active metabolite) has been shown to have a combined RID of
2.88% and is not associated with increased adverse effects on the
nursing infant compared to alternative analgesics.52 Intravenous
morphine, fentanyl and epidural pethidine are found in low levels
in breast milk; however, systemic pethidine has been shown to
result in poorer neonatal alertness and orientation.38 Low-dose
methadone therapy (20 mg per day) does not pose an appreciable
risk to breast-fed infants; whilst exposure to oxycodone may reach
a level of 10% of the therapeutic dose.73

S. Kwok et al. / Trends in Anaesthesia and Critical Care 4 (2014) 189e194

7. Conclusion
Patients undergoing caesarean delivery require effective postoperative analgesia to allow early mobilisation to enhance the
mother's care of her newborn and facilitate breastfeeding. It needs
to be safe, easy to administer and have limited transfer into breast
milk. There should be a multimodal approach with a combination
of techniques which limit adverse effects but provide high quality
analgesia. This can be accomplished with neuraxial analgesia which
has been shown to provide superior analgesia to parenteral opioids
but with a high incidence of side effects. In the absence of a neuraxial technique, peripheral blocks such as the TAP block will also
provide effective analgesia when co-administered with systemic
analgesics.
Conict of interest
There is no conict of interest of note.
References
1. Lavand'homme P. Postcesarean analgesia: effective strategies and association
with chronic pain. Curr Opin Anaesthesiol 2006;19(3):244e8.
2. Maves TJ, Gebhart GF. Antinociceptive synergy between intrathecal morphine
and lidocaine during visceral and somatic nociception in the rat. Anesthesiology
1992;76(1):91e9.
3. Cardoso MM, Carvalho JC, Amaro AR, Prado AA, Cappelli EL. Small doses of
intrathecal morphine combined with systemic diclofenac for postoperative
pain control after cesarean delivery. Anesth Analg 1998;86(3):538e41.
4. Pavy TJ, Paech MJ, Evans SF. The effect of intravenous ketorolac on opioid
requirement and pain after cesarean delivery. Anesth Analg 2001;92(4):
1010e4.
5. Pavy TJ, Gambling DR, Merrick PM, Douglas MJ. Rectal indomethacin potentiates spinal morphine analgesia after caesarean delivery. Anaesth Intensive Care
1995;23(5):555e9.
6. Huang YC, Tsai SK, Huang CH, Wang MH, Lin PL, Chen LK, et al. Intravenous
tenoxicam reduces uterine cramps after Cesarean delivery. Can J Anaesth
2002;49(4):384e7.
7. OAA. http://www.oaa-anaes.ac.uk/assets/_managed/editor/File/NOAD/NOAD%
202011%20nal.pdf (accessed 5 May 2014).
8. Rosaeg OP, Lui AC, Cicutti NJ, Bragg PR, Crossan ML, Krepski B. Peri-operative
multimodal pain therapy for caesarean section: analgesia and tness for
discharge. Can J Anaesth 1997;44(8):803e9.
9. Dahl JB, Jeppesen IS, Jrgensen H, Wetterslev J, Miniche S. Intraoperative and
postoperative analgesic efcacy and adverse effects of intrathecal opioids in
patients undergoing cesarean section with spinal anesthesia: a qualitative and
quantitative systematic review of randomized controlled trials. Anesthesiology
1999;91(6):1919e27.
10. Gwirtz KH, Young JV, Byers RS, Alley C, Levin K, Walker SG, et al. The safety and
efcacy of intrathecal opioid analgesia for acute postoperative pain: seven
years' experience with 5969 surgical patients at Indiana University Hospital.
Anesth Analg 1999;88(3):599e604.
11. Block BM, Liu SS, Rowlingson AJ, Cowan AR, Cowan Jr JA, Wu CL. Efcacy of
postoperative epidural analgesia: a meta-analysis. JAMA 2003;290(18):
2455e63.
12. Cousins MJ, Mather LE. Intrathecal and epidural administration of opioids.
Anesthesiology 1984;61(3):276e310.
13. Palmer CM, Emerson S, Volgoropolous D, Alves D. Dose-response relationship
of intrathecal morphine for postcesarean analgesia. Anesthesiology 1999;90(2):
437e44. Erratum in: Anesthesiology 1999;90(4):1241.
14. Chadwick HS, Ready LB. Intrathecal and epidural morphine sulfate for postcesarean analgesia: a clinical comparison. Anesthesiology 1988;68(6):925e9.
15. Swart M, Sewell J, Thomas D. Intrathecal morphine for caesarean section: an
assessment of pain relief, satisfaction and side-effects. Anaesthesia 1997;52(4):
373e7.
16. Yang T, Breen TW, Archer D, Fick G. Comparison of 0.25 mg and 0.1 mg
intrathecal morphine for analgesia after Cesarean section. Can J Anesth
1999;46(9):856e60.
17. Bromage PR, Camporesi EM, Durant PA, Nielsen CH. Rostral spread of epidural
morphine. Anesthesiology 1982;56(6):431e6.
18. Abouleish E, Rawal N, Rashad MN. The addition of 0.2 mg subarachnoid
morphine to hyperbaric bupivacaine for cesarean delivery: a prospective study
of 856 cases. Reg Anesth 1991;16(3):137e40.
19. Sarvela J, Halonen P, Soikkeli A, Korttila K. A double-blinded, randomized
comparison of intrathecal and epidural morphine for elective cesarean delivery. Anesth Analg 2002;95(2):436e40.
20. Palmer CM, Nogami WM, Van Maren G, Alves DM. Postcesarean epidural
morphine: a dose-response study. Anesth Analg 2000;90(4):887e91.

193

21. Carvalho B, Riley E, Cohen SE, Gambling D, Palmer C, Huffnagle HJ, et al.,
DepoSur Study Group. Single-dose, sustained-release epidural morphine in the
management of postoperative pain after elective cesarean delivery: results of a
multicenter randomized controlled study. Anesth Analg 2005;100(4):1150e8.
22. Carvalho B, Roland LM, Chu LF, Campitelli 3rd VA, Riley ET. Single-dose,
extended-release epidural morphine (DepoDur) compared to conventional
epidural morphine for post-cesarean pain. Anesth Analg 2007;105(1):176e83.
23. Bloor GK, Sinden M, McGregor R. An audit of single dose epidural diamorphine
during elective caesarean section at a district general hospital. Int J Obstet
Anesth 1999;8(1):11e6.
24. Bloor GK, Thompson M, Chung N. A randomised, double-blind comparison of
subarachnoid and epidural diamorphine for elective caesarean section using a
combined spinal-epidural technique. Int J Obstet Anesth 2000;9(4):233e7.
25. Hallworth SP, Fernando R, Bell R, Parry MG, Lim GH. Comparison of intrathecal
and epidural diamorphine for elective caesarean section using a combined
spinal-epidural technique. Br J Anaesth 1999;82(2):228e32.
26. Cohen S, Pantuck CB, Amar D, Burley E, Pantuck EJ. The primary action of
epidural fentanyl after cesarean delivery is via a spinal mechanism. Anesth
Analg 2002;94(3):674e9.
27. Cooper DW, Saleh U, Taylor M, Whyte S, Ryall D, Kokri MS, et al. Patientcontrolled analgesia: epdiural fentanyl and i.v. morphine compared after
caesarean section. Br J Anaesth 1999;82(3):366e70.
28. Paech MJ, Pavy TJ, Orlikowski CE, Kuh J, Yeo ST, Lim K, et al. Postoperative
intraspinal opioid analgesia after caesarean section; a randomised comparison
of subarachnoid morphine and epidural pethidine. Int J Obstet Anesth
2000;9(4):238e45.
29. Paech MJ, Moore JS, Evans SF. Meperidine for patient-controlled analgesia after
cesarean section. Intravenous versus epidural administration. Anesthesiology
1994;80(6):1268e76.
30. Eisenach JC, Grice SC, Dewan DM. Patient-controlled analgesia following cesarean section: a comparison with epidural and intramuscular narcotics.
Anesthesiology 1988;68(3):444e8.
31. Harrison DM, Sinatra R, Morgese L, Chung JH. Epidural narcotic and patientcontrolled analgesia for post-cesarean section pain relief. Anesthesiology
1988;68(3):454e7.
32. Ngan Kee WD, Lam KK, Chen PP, Gin T. Comparison of patient-controlled
epidural analgesia with patient-controlled intravenous analgesia using pethidine or fentanyl. Anaesth Intensive Care 1997;25(2):126e32.
33. Rapp-Zingraff N, Bayoumeu F, Baka N, Hamon I, Virion JM, Laxenaire MC.
Analgesia after caesarean section: patient-controlled intravenous morphine vs
epidural morphine. Int J Obstet Anesth 1997;6(2):87e92.
34. Woodhouse A, Hobbes AF, Mather LE, Gibson M. A comparison of morphine,
pethidine and fentanyl in the postsurgical patient-controlled analgesia environment. Pain 1996;64(1):115e21.
35. Howell PR, Gambling DR, Pavy T, McMorland G, Douglas MJ. Patient-controlled
analgesia following caesarean section under general anaesthesia: a comparison
of fentanyl with morphine. Can J Anaesth 1995;42(1):41e5.
36. Wittels B, Scott DT, Sinatra RS. Exogenous opioids in human breast milk and
acute neonatal neurobehavior: a preliminary study. Anesthesiology 1990;73(5):
864e9.
37. Al-Tamimi Y, Ilett KF, Paech MJ, O'Halloran SJ, Hartmann PE. Estimation of
infant dose and exposure to pethidine and norpethidine via breast milk
following patient-controlled epidural pethidine for analgesia post caesarean
delivery. Int J Obstet Anesth 2011;20(2):128e34.
38. Wittels B, Glosten B, Faure EA, Moawad AH, Ismail M, Hibbard J, et al. Postcesarean analgesia with both epidural morphine and intravenous patientcontrolled analgesia: neurobehavioral outcomes among nursing neonates.
Anesth Analg 1997;85(3):600e6.
39. Ngan Kee WD, Khaw KS, Wong EL. Randomised double-blind comparison of
morphine vs. a morphine-alfentanil combination for patient-controlled analgesia. Anaesthesia 1999 Jul;54(7):629e33.
40. Russell T, Mitchell C, Paech MJ, Pavy T. Efcacy and safety of intraoperative
intravenous methadone during general anaesthesia for caesarean delivery: a
retrospective case-control study. Int J Obstet Anesth 2013;22(1):47e51.
41. Bell RF, Dahl JB, Moore RA, Kalso E. Perioperative ketamine for acute postoperative pain. Cochrane Database Syst Rev 2006;1:CD004603.
42. Menkiti ID, Desalu I, Kushimo OT. Low-dose intravenous ketamine improves
postoperative analgesia after caesarean delivery with spinal bupivacaine in
African parturients. Int J Obstet Anesth 2012;21(3):217e21.
43. Behdad S, Hajiesmaeili MR, Abbasi HR, Ayatollahi V, Khadiv Z, Sedaghat A.
Analgesic effects of intravenous ketamine during spinal anesthesia in pregnant
women undergone caesarean section; a randomized clinical trial. Anesth Pain
Med 2013;3(2):230e3.
44. Bauchat JR, Higgins N, Wojciechowski KG, McCarthy RJ, Toledo P, Wong CA.
Low-dose ketamine with multimodal postcesarean delivery analgesia: a randomized controlled trial. Int J Obstet Anesth 2011;20(1):3e9.
45. Han SY, Jin HC, Yang WD, Lee JH, Cho SH, Chae WS, et al. The effect of low-dose
ketamine on post-caesarean delivery analgesia after spinal anesthesia. Korean J
Pain 2013;26(3):270e6.
46. Wilder-Smith CH, Hill L, Dyer RA, Torr G, Coetzee E. Postoperative sensitization
and pain after cesarean delivery and the effects of single im doses of tramadol
and diclofenac alone and in combination. Anesth Analg 2003;97(2):526e33.
47. Jakobi P, Weiner Z, Solt I, Alpert I, Itskovitz-Eldor J, Zimmer EZ. Oral analgesia
in the treatment of post-cesarean pain. Eur J Obstet Gynecol Reprod Biol
2000;93(1):61e4.

194

S. Kwok et al. / Trends in Anaesthesia and Critical Care 4 (2014) 189e194

48. McDonnell NJ, Keating ML, Muchatuta NA, Pavy TJ, Paech MJ. Analgesia after
caesarean delivery. Anaesth Intensive Care 2009;37(4):539e51.
49. Davis KM, Esposito MA, Meyer BA. Oral analgesia compared with intravenous
patient-controlled analgesia for pain after cesarean delivery: a randomized
controlled trial. Am J Obstet Gynecol 2006;194(4):967e71.
50. McDonnell NJ, Paech MJ, Browning RM, Nathan EA. A randomised comparison
of regular oral oxycodone and intrathecal morphine for post-caesarean analgesia. Int J Obstet Anesth 2010;19(1):16e23.
51. Moore RA, McQuay HJ. Single-patient data meta-analysis of 3453 postoperative
patients: oral tramadol versus placebo, codeine and combination analgesics.
Pain 1997;69(3):287e94.
52. Bloor M, Paech MJ, Kaye R. Tramadol in pregnancy and lactation. Int J Obstet
Anesth 2012;21(2):163e7.
53. Sammour RN, Ohel G, Cohen M, Gonen R. Oral naproxen versus oral tramadol
for analgesia after cesarean delivery. Int J Gynaecol Obstet 2011;113(2):144e7.
54. Mitra S, Khandelwal P, Sehgal A. Diclofenac-tramadol vs. diclofenacacetaminophen combinations for pain relief after caesarean section. Acta
Anaesthesiol Scand 2012;56(6):706e11.
55. Toms L, McQuay HJ, Derry S, Moore RA. Single dose oral paracetamol (acetaminophen) for postoperative pain in adults. Cochrane Database Syst Rev
2008;4:CD004602.
56. Tzortzopoulou A, McNicol ED, Cepeda MS, Francia MB, Farhat T, Schumann R.
Single dose intravenous propacetamol or intravenous paracetamol for postoperative pain. Cochrane Database Syst Rev 2011;10:CD007126.
57. Remy C, Marret E, Bonnet F. Effects of acetaminophen on morphine side-effects
and consumption after major surgery: meta-analysis of randomized controlled
trials. Br J Anaesth 2005;94(4):505e13.
58. Siddik SM, Aouad MT, Jalbout MI, Rizk LB, Kamar GH, Baraka AS. Diclofenac
and/or propacetamol for postoperative pain management after cesarean delivery in patients receiving patient controlled analgesia morphine. Reg Anesth
Pain Med 2001;26(4):310e5.
59. Munishankar B, Fettes P, Moore C, McLeod GA. A double-blind randomised
controlled trial of paracetamol, diclofenac or the combination for pain relief
after caesarean section. Int J Obstet Anesth 2008;17(1):9e14.
60. Apfel CC, Turan A, Souza K, Pergolizzi J, Hornuss C. Intravenous acetaminophen
reduces postoperative nausea and vomiting: a systematic review and metaanalysis. Pain 2013;154(5):677e89.

n Arturo, Martnez-Larran
~ aga Maria Rosa, Ramos Eva, Castellano V.
61. Anado
Chapter 6 e Transfer of drugs and xenobiotics through milk. Reproductive and
developmental toxicology. 2011. p. 57e71.

62. Lowder JL, Shackelford DP, Holbert D, Beste TM. A randomized, controlled trial
to compare ketorolac tromethamine versus placebo after cesarean section to
reduce pain and narcotic usage. Am J Obstet Gynecol 2003;189(6):1559e62.
discussion 62.
63. Ong CK, Seymour RA, Lirk P, Merry AF. Combining paracetamol (acetaminophen) with nonsteroidal antiinammatory drugs: a qualitative systematic review of analgesic efcacy for acute postoperative pain. Anesth Analg
2010;110(4):1170e9.
64. Jakobi P, Solt I, Tamir A, Zimmer EZ. Over-the-counter oral analgesia for
postcesarean pain. Am J Obstet Gynecol 2002;187(4):1066e9.
65. Abdallah FW, Halpern SH, Margarido CB. Transversus abdominis plane block
for postoperative analgesia after Caesarean delivery performed under spinal
anaesthesia. A systematic review and meta-analysis. Br J Anaesth 2012;109(5):
679e87.
66. Mishriky BM, George RB, Habib AS. Transversus abdominis plane block for
analgesia after Cesarean delivery: a systematic review and meta-analysis. Can J
Anesth 2012;59(8):766e78.
67. Tan TT, Teoh WH, Woo DC, Ocampo CE, Shah MK, Sia AT. A randomised trial of
the analgesic efcacy of ultrasound-guided transversus abdominis plane block
after caesarean delivery under general anaesthesia. Eur J Anaesthesiol
2012;29(2):88e94.
68. O'Neill P, Duarte F, Ribeiro I, Centeno MJ, Moreira J. Ropivacaine continuous
wound infusion versus epidural morphine for postoperative analgesia after
cesarean delivery: a randomized controlled trial. Anesth Analg 2012;114(1):
179e85.
69. Lavand'homme PM, Roelants F, Waterloos H, De Kock MF. Postoperative
analgesic effects of continuous wound inltration with diclofenac after elective
cesarean delivery. Anesthesiology 2007;106(6):1220e5.
70. Lavand'homme PM, Roelants F, Mercier V, Waterloos H. Continuous wound
instillation after cesarean section: local analgesic effect of diclofenac. Anesthesiology 2004;100(Supp. 1):A22.
71. American Academy of Pediatrics Committee on Drugs. Transfer of drugs and
other chemicals into human milk. Pediatrics 2001;108(3):776e89.
72. Berlin CM, Briggs GG. Drugs and chemicals in human milk. Semin Fetal Neonatal
Med 2005;10(2):149e59.
73. Ito S. Drug therapy for breast-feeding women. N Engl J Med 2000;343(2):
118e26. Erratum in: N Engl J Med 2000;343(18):1348.