Guide to Pain Management in Low-Resource Settings

What if Shillah continues to have neuropathic 
pain later in pregnancy?
Good levels of evidence support both the effi
  cacy  and 
safety of typical doses of amitriptyline (initially 10–25 
mg orally at night). Ketamine, another potent analgesic, 
can be eff ective for both acute and neuropathic pain, 
although oral tablet or lozenge forms are still being de-
veloped. Ketamine has been used in large numbers of 
pregnant women without links to malformations, so 
it is considered safe, making it a valuable option when 
patients are admitted to hospital when either acute or 
neuropathic pain is diffi
  cult to manage(bolus up to 0.25 
mg/kg and initial infusion rate 5–10 mg/h). Because lo-
cal anesthetics are safe during pregnancy, lidocaine (lig-
nocaine) infusion (1 mg/kg over 20 minutes then 10–30 
mg/h, see the chapter on neuropathic pain) is another 
option that is eff ective in a minority of patients with 
neuropathic pain.
If gabapentin is available, it can be considered. 
It does not cause major malformations in animal stud-
ies and has not demonstrated evidence of harm in lim-
ited human experience to date. Mexiletine also appears 
to be of low risk to the fetus, but it is less eff ective and 
has more side eff ects. In contrast, carbamazepine, al-
though still used during pregnancy in some epileptic 
patients because its benefi t is considered to outweigh 
the risk of harm, should be avoided, even after the fi rst 
trimester, because it causes major and minor abnor-
malities, including spina bifi da, craniofacial defects, 
and coagulation disorders in humans. Th
  e selective se-
rotonin reuptake inhibitors and similar drugs (citalo-
pram, paroxetine, venlafaxine), lamotrigine (an anti-
convulsant) and pregabalin (a voltage-gated calcium 
channel blocker) have limited information available 
and are best avoided.

238
Author(s)
Case report 2 (analgesia             
when breastfeeding)
Agnes is a 28-year-old multigravid woman who has two 
children and is now 34 weeks pregnant. She comes from 
a good and sensible family that is well known to you. She 
has come to you for advice because the obstetrician has 
just booked her for an elective repeat cesarean delivery 
in 1 month. She has been told that the baby appears to 
be much bigger than last time, when she experienced 
failed progress of labor and had to have an urgent cesar-
ean section. Although she has been doing well and un-
derstands why it would be best to have another cesarean, 
she is very anxious and is not sure whether to have her 
operation at the district mission hospital or whether to 
ask if she can go to the referral hospital in the nearby city 
with better facilities.
Agnes is worried for two reasons. First, after her 
last cesarean she had a lot of pain, especially during the 
fi rst two days, and she is scared about suff ering the same 
experience. Second, local women elders had told her 
that if she had any strong painkillers after the operation, 
the baby would not be able to breastfeed—but she can-
not aff ord to use milk formula. You listen sympatheti-
cally because you are aware that many women are not 
getting very good pain management after their cesarean 
at the district hospital. You are planning to talk to the 
doctors there to suggest some simple changes that you 
think will improve the situation signifi cantly. You dis-
cuss with Agnes the options that are likely to be avail-
able for her postoperative analgesia at the two hospitals 
and their implications when she starts to breastfeed—
and then you make some recommendations and prom-
ise to contact the hospital to try and make sure she gets 
satisfactory treatment.
Does pain after cesarean delivery really need to 
be treated well?
Most women experience moderate to severe pain in 
the fi rst 48 hours after abdominal surgery, including ce-
sarean section, and both mother and baby will benefi t 
from good pain relief. If the mother is able to move in 
relative comfort, she can mobilize soon after recover-
ing from the anesthetic (within a few hours of surgery 
after a spinal anesthetic), which reduces the risk of pul-
monary infections and venous thromboembolism, an 
important cause of sudden death from pulmonary em-
bolism. She will be able to eat within hours of the op-
eration and continue to care for and interact with her 
baby, while establishing lactation and breastfeeding. 
Eff ective, regular, and early pain relief reduces the risk 
of moderate or severe pain after the fi rst one to three 
days such that most women need only paracetamol 
(acetaminophen) and/or an NSAID by the third to fi fth 
postoperative day (and may reduce the risk of chron-
ic wound pain later!). Most methods of postcesarean 
pain relief are based on opioids, the majority of which 
are considered safe for the breastfed baby if used only 
short-term during lactation.
What should the “district” hospital                      
be able to off er Agnes?
Th
  e best approach to acute pain management for Ag-
nes is a “multimodal” approach, which means combin-
ing diff erent painkillers or analgesic methods to reduce 
the dose and thus side eff ects of each component. An 
opioid such as morphine should be prescribed, pref-
erably using regular doses with extra supplementary 
doses if requested, for the fi rst 24–48 hours. If an in-
travenous method (patient-controlled analgesia or 
continuous infusion, see below for these referral hos-
pital methods) is unavailable, then the oral or subcuta-
neous route can be used. Intramuscular injections are 
more painful than subcutaneous (especially if the latter 
are given through a small cannula or ‘butterfl y”  nee-
dle); they have a higher risk of deep infection and are 
no more reliable in their effi
  cacy. Giving the opioid “as 
required” leads to undertreatment and poor pain relief 
because of inconsistent absorption pharmacokinet-
ics and individual response. If a range of doses is pre-
scribed, then the smallest can be used fi rst and substi-
tuted with a larger dose subsequently if required. Th
 e 
drug of choice is morphine, which may be available as 
a tablet or oral syrup (30–45 mg every 8 hours) or a 
parenteral formulation (subcutaneous 10–15 mg every 
6 hours). Oral codeine (60 mg every 6 hours) should 
only be used if another oral opioid is not available. 
During lactation, pethidine (meperidine) should be 
avoided unless there is no other alternative. It has an 
active metabolite, norpethidine (normeperidine), that 
has a very long elimination half-life in the newborn 
(approximately 72 hours), and as both accumulate in 
the neonate, the baby becomes sleepier and less active, 
and its ability to suck on the breast is impaired. Th
 ese 
eff ects are prominent when intravenous doses are giv-
en after cesarean delivery, but they also occur from 
lower intramuscular dosing during labor. If the baby 
is very premature and has worrisome apneic spells, all 

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239
opioid doses should be minimized and if possible sub-
stituted with tramadol, which is safe for the baby in the 
fi rst few days after delivery when breastfeeding is be-
ing established.
Every attempt should be made to make sure 
that Agnes also gets either an NSAID such as diclofe-
nac (a second choice is indomethacin, which has more 
side eff ects), paracetamol (acetaminophen), or even 
both. Th
  ese painkillers reduce the dose of morphine 
needed by 30–40% and 10–20% respectively, and an 
NSAID can reduce “cramping” pain from the uterus. 
Oral paracetamol (1 g every 6 hours) has almost no 
side eff ects and is contraindicated only in patients 
with severe liver dysfunction. An NSAID, preferably 
given at its maximum recommended dose (e.g., diclof-
enac 50 mg t.i.d. [three times daily] or indomethacin 
100 mg b.i.d. [twice daily]) and with food to avoid gas-
trointestinal upset, is contraindicated in women with 
hypertensive disease including preeclampsia, renal 
impairment, peptic ulcer, or symptomatic refl ux  dis-
ease, and in women with a bleeding disorder or cur-
rent bleeding risk.
An additional measure for the surgeon, that is 
not too expensive, is infi ltration of local anesthetic (for 
example, 0.25% bupivacaine up to a maximum dose of 
2 mg/kg) into the wound. Skin infi ltration alone is not 
eff ective, but injection beneath the rectus sheath fascia 
and subcutaneously may reduce the amount of opioid 
needed, with a low risk of complications.
What are the eff ects of these drugs                      
on the breastfed baby?
With a couple of exceptions, especially those apply-
ing to pethidine (meperidine), Agnes can be assured 
that all these drugs have been evaluated well and that 
they are considered safe and acceptable to use in the 
fi rst few days after delivery. At this time, production 
of breast milk is increasingly rapidly, but the content is 
still changing from protein-rich colostrum, which is a 
poor transfer medium for most drugs, to fat-rich milk. 
Th
  e transfer of morphine and codeine, paracetamol, and 
NSAIDs into breast milk is only 2–4% of the weight-
adjusted maternal dose, and none has adverse eff ects in 
the infant. 
Aspirin is not as good a choice as paracetamol/
acetaminophen, which has no detectable eff ects  de-
spite immature glucuronide conjugation. Aspirin is 
contraindicated in those at risk of bleeding due to its 
eff ect on platelet function, and although considered 
acceptable for use during lactation, it has been as-
sociated with the rare and serious condition of Reye’s 
syndrome in newborns, so prolonged administration 
should be avoided.
You should explain to Agnes that she should try 
to time her feeds to avoid the peak milk concentrations 
of the opioid she is taking, which will usually coincide 
with 1–2 hours after the last dose.
What other methods might the city referral 
hospital be able to off er Agnes?
Th
  ere may be a number of potentially superior meth-
ods of postoperative pain relief at the referral hospi-
tal that Agnes can consider and request. Intravenous 
morphine (and in some countries the metabolite-free 
but more expensive opioid fentanyl) provides better 
quality pain relief than subcutaneous or intramuscular 
morphine and is preferably administered using a pa-
tient-controlled analgesia (PCA) device (standard set-
ting, e.g., 1 mg bolus on demand, no continuous infu-
sion, 5-minute lockout interval) to safeguard patients 
from unintentional overdosing.
Neuraxial (spinal or epidural) opioid methods 
of analgesia provide better relief than intravenous, sub-
cutaneous, intramuscular, or oral opioid administration. 
If spinal anesthesia is used, then intrathecal morphine 
100–150 μg is a very safe and eff ective means of achiev-
ing excellent pain relief.
Morphine’s long elimination half-life in cere-
brospinal fl uid results in clinically good or excellent 
pain relief for 4–24 hours (on average 12 hours), es-
pecially if an oral NSAID is also given. Sedation, nau-
sea, and vomiting are common side eff ects after opi-
oids. In general, sedation will be greater after systemic 
administration (oral, intramuscular, and intravenous) 
and itch more severe after neuraxial (spinal or epi-
dural) administration. All patients receiving opioids, 
especially neuraxial, should be monitored for overse-
dation and low respiratory rate, although serious mor-
bidity is rare in the obstetric population. Many hos-
pitals and doctors appear especially concerned about 
spinal or epidural opioids, but when they are used 
correctly, case series suggest a signifi cantly higher risk 
of clinically important respiratory depression associ-
ated with intravenous opioid. Postoperative epidu-
ral analgesia is less likely to be available but is highly 
eff ective. It can be achieved with single or repeated 
(8–12 hourly) doses of morphine 3 mg or in technol-
ogy-rich hospitals, with epidural infusion or patient-

240
Author(s)
controlled epidural analgesia (PCEA) using fentanyl 
(2 μg bolus, 15 minute lockout time) or pethidine/me-
peridine (20 mg bolus, 15 minute lockout time). Th
 ese 
epidural methods are associated with lower rates of 
opioid consumption (by 20–50%) than intravenous 
opioid and although short-term epidural opioid ad-
ministration after cesarean delivery has not been well 
investigated, clinical experience suggests the breast-
fed neonate is not aff ected.
Immediate-release oxycodone (e.g., 5–10 mg 
regularly 4 hourly for 48 hours, with additional doses on 
request) is a more eff ective oral opioid than codeine and 
also tastes less unpleasant than oral morphine. Trama-
dol (50–100 mg intravenous or oral, repeated 2 hourly 
to a maximum of 600 mg per day) is also an excellent 
choice for postoperative pain relief. Agnes can also be 
reassured that short-term use for a couple of days im-
mediately postpartum is associated with low transfer of 
drug into breast milk (less than 3%) and that there are 
no apparent eff ects on the baby. In some countries the 
new generation of NSAIDs, the cyclooxygenase-2-spe-
cifi c inhibitors (COX-2 inhibitors) such as intravenous 
parecoxib (40 mg daily) and oral celecoxib (400 mg then 
200 mg 12 hourly) may be available, and because they 
have no eff ect on platelet function they are the best 
choice for women who are bleeding or at high risk of 
bleeding. However, they have not yet been adequately 
evaluated during human lactation, and although the risk 
of aff ecting the breastfeeding baby appears low, safety 
cannot be guaranteed. Some countries may also have in-
travenous paracetamol/acetaminophen, which provides 
higher and more rapid peak plasma concentrations than 
an equivalent oral dose.
Might any other local anesthetic blocks be 
useful in reducing Agnes’s risk of having poorly 
controlled pain?
Wound infusion of local anesthetic (or perhaps even di-
clofenac) is eff ective in reducing the dose of opioid need-
ed, but it requires expensive pumps and wound cath-
eters, so it is not likely to be available. If there is a doctor 
with suitable training, bilateral ilioinguinal and iliohypo-
gastric blocks into the abdominal wall near the anterior 
iliac crest, or a rectus sheath block, can achieve similar 
opioid dose-sparing in the fi rst 12–24 hours. Th
 e best 
peripheral nerve block, if someone has the knowledge 
and expertise, would be for Agnes to receive bilateral 
transverse abdominis plane (TAP) blocks. Th
 is regional 
analgesic block is performed using, for example, 20 mL 
of 0.25% bupivacaine or 0.5% ropivacaine on each side. 
Th
  e injection is made just above the pelvic brim in the 
posterior section of the triangle of Petit, in the gap be-
tween latissimus dorsi and the external oblique muscle. 
A “two-pop” (or in some countries ultrasound-guided) 
technique (as the blunt-tip needle passes through the 
external oblique fascial extension, then internal oblique 
fascia) allows local anesthetic to be deposited between 
the internal oblique and transverse abdominis muscles. 
Combined with oral analgesics, an eff ective TAP block 
covers the incision for cesarean delivery well (T10 to L1 
dermatomes) and lasts up to 36 hours.
Case report 3 (analgesics                   
in later pregnancy)
Th
 e nurse comes to tell you that Martine, a healthy 
woman in her fourth pregnancy at 33 weeks gestation 
who is attending the antenatal clinic, has been com-
plaining of severe stabbing pain both at the back of her 
pelvis and low down at the front. Th
  e pain has been get-
ting progressively worse for several weeks, and Martine 
can no longer care properly for her children. She fi nds it 
very painful to rise from a sitting position and is more 
comfortable crawling around the house on all four limbs 
than walking. When you see Martine, she explains that 
it took her 2 hours to walk from her house to the clinic, 
a journey that usually takes her 20 minutes. She is very 
tender to palpation over both the suprapubic region and 
upper buttocks. Th
  e pain is increased by “springing” the 
pelvis. “Please, is there anything that you can do to help 
me?”asks Martine. You explain that she appears to have 
symphysial diastasis with signifi cant separation and sec-
ondary disruption and infl ammation at the sacroiliac 
joints. You explain the problem and discuss an initial 
plan of management with her. You tell her that she can 
start on some strong medications if she has not improved 
within a week.
What sort of painful conditions occur        
during pregnancy?
Diastasis of the pubic symphysis is an example of a very 
painful and disabling condition that frequently occurs 
during and after pregnancy. However, the principles of 
drug treatment for pain present after the fi rst  trimes-
ter of pregnancy can be applied to most painful condi-
tions or diseases, including musculoskeletal pain (other 
examples are lumbar vertebral facet pain, disk protru-
sion or rupture); visceral pain (cholecystitis, renal 

Chapter Title
241
colic, degenerating uterine fi broids, or bowel pain); 
neuropathic pain (intercostal neuralgia, meralgia par-
esthetica of the lateral cutaneous nerve of the thigh, 
iliohypogastric and genitofemoral neuralgia, various 
cancer-induced neuralgias, post-traumatic complex 
regional pain syndrome, or post-amputation pain); 
migraine; and invasive cancer pain.
What initial treatment would you               
suggest for Martine?
Irrespective of the cause of the pain, nonpharmacologi-
cal pain management options should be considered and 
tried, where possible, before analgesic drugs are used 
for acute pain that appears likely to require prolonged 
treatment or a stepwise approach to continued manage-
ment. Your plan for Martine should start with physi-
cal therapies (for example referral to a therapist for a 
sacroiliac pelvic support belt; gentle manipulation and 
postural exercises; and local application of heat or ice, 
transcutaneous electrical nerve stimulation, acupunc-
ture or similar treatments), but it would also be reason-
able to introduce nonopioid analgesic drugs, bearing in 
mind their safety for the fetus and neonate. Paracetamol 
(acetaminophen) has been used in millions of pregnant 
women and is safe. Aspirin is acceptable, but its pro-
longed use is best avoided (see case 2 above). Tramadol 
has not been evaluated in large trials during pregnancy 
but is widely used after the fi rst trimester, so it would be 
acceptable for short-term use for Martine to reduce the 
severe pain until other measures have had a chance to 
become eff ective. It would not be ideal to continue tra-
madol for several weeks until the time of delivery, be-
cause a neonatal withdrawal syndrome at 24–36 hours 
has been reported.
NSAIDs have a limited role during pregnancy, 
and it is very important to understand the implications 
of prescribing them. Th
  ese drugs prevent prostaglan-
din-induced myometrial gap junction formation and 
transmembrane infl ux and sarcolemmal release of cal-
cium, making indomethacin an eff ective tocolytic drug 
that has been used to prevent preterm labor after the 
period of organogenesis. However, they are contrain-
dicated in later pregnancy, certainly after 32 weeks 
gestation (as applies to Martine), and some would ar-
gue from the start of fetal viability (23–24 weeks in re-
source-rich countries and hospitals). Th
  is leaves only a 
short period during the second trimester of pregnancy 
when these drugs may be useful. Fetal exposure in late 
pregnancy may result in oligohydramnios due to renal 
impairment, premature closure of the ductus arterio-
sus with subsequent neonatal pulmonary hyperten-
sion, and neonatal intracranial hemorrhage. Th
 ere is 
insuffi
  cient information about the eff ects of the COX-2 
inhibitors (e.g., celecoxib), so these agents should also 
be avoided.
Would local anesthetics or opioid drugs            
be suitable in this case?
It is the case with many painful conditions (including 
Martine’s) that the treatment you start with ultimate-
ly proves insuffi
  cient.  Th
  e possibility of a neuropathic 
component should be considered in Martine’s case, and 
the appropriate drug treatment is discussed in case 1 
above. However, the two main options to consider next 
for Martine are local anesthetic infi ltration and oral 
opioid analgesia. Infi ltration with local anesthetic pro-
vides temporary (and sometimes prolonged) relief of 
joint pain (another example is into the coccyx for coc-
cydynia, or into the facet joint for back pain) and myo-
fascial pain (for example into trigger points in the ab-
dominal wall, neck, or shoulders or the costochondral 
and intercostal area). A steroid such as triamcinolone 
could be included if infl ammation is suspected, but 
steroids are best omitted in the fi rst trimester and in 
repeated injections. Provided the operator has knowl-
edge of the relevant anatomy and adequate expertise, 
infi ltration is generally a low-risk procedure that can 
be useful both diagnostically and therapeutically. Th
 e 
local anesthetic drugs are of no or minimal risk to the 
fetus, although maximum dose limits for the individu-
al drug and the type of block should be applied. Extra 
care must be taken when injecting near major organs 
or the fetus (for example, when injecting near the blad-
der and lower uterine segment or cervix at the pubic 
symphysis). As a fi nal option, if epidural techniques are 
available in a referral hospital, a period of epidural an-
algesia with a combined local anesthetic and opioid can 
be very benefi cial.
If opioid analgesia is commenced during 
pregnancy, it would be best to arrange inpatient care 
for a few days. This strategy allows oral opioid titra-
tion and stabilization (see case 1 above) and supple-
mentation with intravenous opioid or intravenous 
ketamine to establish pain control. Oral or sublingual 
opioids (morphine, methadone, codeine, and in some 
countries oxycodone, buprenorphine, and fentanyl) 
can be used safely for short periods during pregnancy 
(and in some cases will already be prescribed or are 

242
Author(s)
being used by patients illicitly). If prolonged admin-
istration is expected, drugs without active metabo-
lites are preferable, for example methadone rather 
than morphine for maintenance therapy in opioid ad-
dicts. Although there is a slightly higher rate of low 
birth weight and stillbirth among women on chronic 
opioid therapy, the majority have good neonatal out-
comes. It has been suggested that chronic opioid use 
in pregnancy is associated with addictive behavior in 
later adult life, but observational evidence does not 
prove causality, and such findings should be viewed 
with some scepticism. Women who become opi-
oid tolerant and need escalating doses will provide a 
number of challenges in managing pain during labor, 
as well as during and after cesarean section. Options 
such as opioid rotation and multiple opioids may 
need to be considered (see chapter on chronic opioid 
therapy). These women need more interventions and 
increase the staff workload.
The neonatal effects of opioid analgesics be-
ing used at the time of childbirth are important, so 
a number of staff need to be aware of opioid con-
sumption, including the obstetrician, midwife, pe-
diatrician, and local doctor. Neonatal respiratory de-
pression may be present at birth, so staff skilled in 
neonatal resuscitation may be required; if possible, 
naloxone should be available. Also, the baby should 
be observed in a high-dependency care area if possi-
ble, and staff trained to watch for neonatal withdraw-
al/neonatal abstinence syndrome. This syndrome 
usually commences in the hours or days following 
birth (depending on the half-life of the specific opi-
oid, i.e., 6–36 hours for morphine and 24–72 hours 
for methadone and buprenorphine), but it is occa-
sionally delayed for several days. The risk is greatest 
if the mother has become opioid-tolerant and has 
needed an escalation dose or high maintenance doses 
(30–90% incidence with long-term methadone use 
and 50% incidence, but less severe, with buprenor-
phine maintenance therapy). Unfortunately, breast-
feeding does not prevent the syndrome. The signs 
and symptoms in the baby are due to autonomic 
overactivity (which can manifest as yawning, sneez-
ing, or fever) and cerebral irritability (for example 
tachypnea, tremor, increased tone, poor feeding be-
havior, and in severe cases, seizures). The severity of 
the syndrome also correlates partly with the maternal 
dose, so is most severe in opioid-tolerant or addicted 
women. The baby should be swaddled and nursed in 
a quiet environment, and some will need treatment with 
sedative drugs such as phenobarbitone (10 mg/day), di-
azepam, clonidine, or morphine (starting at 0.4–1.0 mg/
day in divided doses and increasing 10–20% every 2–3 
days as needed). Treatment may need to be continued 
for 4–20 days and sometimes much longer.