Page 176 Acute Pain Management

Epidural opioids
The behaviour of epidural opioids is also governed largely by their lipid solubility. The greater
sequestration of lipid soluble opioids into epidural fat and slow re‐release back into the
epidural space means that elimination from the epidural space is prolonged, resulting in
relatively smaller fractions of drug reaching the cerebrospinal fluid (Bernards et al, 2003).
Lipophilic opioids (eg fentanyl) have a faster onset but shorter duration of action compared
with hydrophilic drugs (eg morphine) (de Leon‐Casasola & Lema, 1996; Bernards, 2004).
Morphine is the least lipid soluble of the opioids administered epidurally; it has the slowest
onset and offset of action (Cousins & Mather, 1984) and the highest bioavailability in the spinal
cord after epidural administration (Bernards, 2004). As it has a prolonged analgesic effect it can
be given by intermittent bolus dose or infusion; the risk of respiratory depression may be
higher and analgesia less effective with bolus dose regimens (de Leon‐Casasola & Lema, 1996).
The evidence that epidural fentanyl acts via a spinal rather than systemic effect is conflicting
and it has been suggested that any benefit when comparing epidural with systemic fentanyl
alone is marginal (Wheatley et al, 2001; Bernards, 2004). However, the conflicting results may be
due to differing modes of administration. An infusion of epidural fentanyl appears to produce
analgesia by uptake into the systemic circulation, whereas a bolus dose of fentanyl produces
analgesia by a selective spinal mechanism (Ginosar et al, 2003 Level IV). There is no evidence of
benefit of epidural versus systemic administration of alfentanil or sufentanil (Bernards, 2004)
Pethidine is effective when administered epidurally by bolus dose, continuous infusion and by
CHAPTER 5 onset and offset of epidural analgesic action is more rapid than morphine (Ngan Kee, 1998
PCEA. It is more lipid soluble than morphine (but less than fentanyl and its analogues), thus its
Level IV). The analgesic effect of smaller doses appears to be spinally mediated but systemic
effects are likely after larger doses; in the smaller doses it is not known whether the local
anaesthetic properties of pethidine contribute significantly to pain relief (Ngan Kee, 1998
Level IV). Epidural pethidine has been used predominantly in the obstetric setting. After
Caesarean section epidural pethidine resulted in better pain relief and less sedation than IV
pethidine (Paech et al, 1994 Level II) but inferior analgesia compared with intrathecal morphine,
albeit with less pruritus, nausea and drowsiness (Paech et al, 2000 Level II).
Diamorphine (diacetylmorphine, heroin) is rapidly hydrolysed to (monoacetylmorphine) MAM
and morphine. Diamorphine and MAM are more lipid soluble than morphine and penetrate
the CNS more rapidly, although it is MAM and morphine that are thought to be responsible for
the analgesic effects of diamorphine (Miyoshi & Lackband, 2001). Epidural administration of
diamorphine is common in the United Kingdom and is effective whether administered by
intermittent bolus dose or infusion (McLeod et al, 2005).
The quality of epidural analgesia with hydromorphone is similar to morphine (Chaplan et al,
1992 Level II). In a comparison of epidural and IV hydromorphone, patients required twice as
much IV hydromorphone to obtain the same degree of analgesia (Liu et al, 1995 Level II).
The addition of butorphanol to epidural bupivacaine resulted in more rapid and prolonged
pain relief compared with butorphanol alone (Bharti & Chari, 2009 Level II).
An extended‐release suspension of morphine has been developed for epidural use
(Depodur™) consisting of morphine molecules suspended in liposome complexes (lipofoam).
Extended‐release epidural morphine (EREM) has been shown to be effective compared with
placebo after hip arthroplasty (Viscusi et al, 2005 Level II; Martin et al, 2006 Level II) and, using
doses of 10 mg or more, to lead to better pain relief compared with standard epidural
morphine (4 or 5 mg) and a reduction in the need for supplemental analgesics up to 48 hours
after hip arthroplasty (Viscusi et al, 2006 Level III‐1), lower abdominal surgery (Gambling et al, 2005
Level II) and Caesarean section (Carvalho et al, 2005 Level II; Carvalho et al, 2007 Level II).
128 Acute Pain Management: Scientific Evidence