Page 439 Acute Pain Management

Paracetamol and non-steroidal anti-inflammatory drugs
The weight‐adjusted maternal dose of paracetamol transferred to the neonate was 1.85%
(Notarianni et al, 1987). Although neonatal glucuronide conjugation may be deficient, the drug is
considered safe as there have been no reports of adverse effects and levels in breast milk are
a fraction of the recommended neonatal doses.
If an anti‐inflammatory is required, nsNSAIDs are preferable to aspirin (Berlin & Briggs, 2005
Level IV). Despite similar proportional transfer as paracetamol, salicylates are eliminated slowly
by the neonate, cause platelet dysfunction and have been associated with Reye’s syndrome;
aspirin in analgesic doses cannot be recommended as safe (Bar‐Oz et al, 2003).
NsNSAIDs must be considered individually, but in general milk levels are low because they are
weak acids and extensively plasma protein bound. In particular, ibuprofen has very low
transfer (< 1% weight‐adjusted maternal dose), is short acting, free of active metabolites and
has the best documented safety (Ito, 2000). Diclofenac and ketorolac are minimally transported
into breast milk and short‐term or occasional use is compatible with breastfeeding. The safety
of naproxen is less clear but it is also considered compatible (Rathmell et al, 1997).
Indomethacin (indometacin) has been associated with central maternal side effects, such as
agitation and psychosis, in previously healthy postnatal women (Clunie et al, 2003 Level IV).
Following a single 200 mg dose of celecoxib, less than 0.5% of the weight‐adjusted maternal
dose was present in breast milk, suggesting that breastfeeding during routine dosing poses
minimal risk (Gardiner et al, 2006 Level III‐3; Hale et al, 2004 Level III‐3).
Opioids and tramadol
With some provisos, the short‐term use of opioids is generally considered safe during lactation
(Ravin, 1995) as most opioids are secreted into breast milk in low doses.
An association between opioid exposure in breast milk and episodes of apnoea and cyanosis in
infants has been described (Naumburg & Meny, 1988 Level IV), leading some to suggest that
opioids should be avoided if the neonate experiences such events during the first week of life.
Morphine has been recommended as the opioid of choice if potent analgesia is required in
breastfeeding mothers (Ito, 2000 Level IV). About 6% of the weight‐adjusted maternal dose of
morphine is transferred in breast milk (Feilberg et al, 1989), but the oral bioavailability in the
infant is low (about 25%), so only small amounts reach the infant. In mothers treated with
IV PCA morphine for 48 hours following Caesarean section, levels of morphine and M6G
were low in breast milk, suggesting minimal drug would be transferred to the neonate
(Baka et al, 2002).
Pharmacokinetic studies also suggest the more lipophilic opioids such as fentanyl and
alfentanil are unlikely to cause problems. Following a single dose of IV fentanyl, the weight‐
adjusted maternal dose received by the neonate was 3%, levels in colostrum became CHAPTER 11
undetectable within several hours and the nursing infant appeared unaffected (Steer et al,
1992 Level IV).
Breastfed infants whose mothers received pethidine (meperidine) were less alert and oriented
to auditory cues after Caesarean section than those of mothers receiving morphine (Wittels et
al, 1997 Level II). As norpethidine (normeperidine) accumulates in breast milk with repeated
use and has very slow neonatal elimination, pethidine use during breastfeeding is not
recommended (Ito, 2000).
Codeine has a milk‐to‐plasma ratio of slightly more than 1 suggesting it is generally safe (Meny
et al, 1993), but morphine toxicity and death has been reported in a breastfed neonate whose
mother was an ultra‐rapid metaboliser of codeine (Madadi et al, 2008 Level IV). A relationship
between infant central nervous system (CNS) symptoms (decreased alertness, lethargy, poor

Acute pain management: scientific evidence 391