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Safety studies and widespread clinical experience with morphine, fentanyl and sufentanil have
shown no neurotoxicity or behavioural changes at normal clinical intrathecal doses (Hodgson et
al, 1999 Level IV). Other opioid agonists or partial agonists do not have animal or human
safety data.
Early clinical studies used very high intrathecal morphine doses (ie 500 mcg or more), however
adequate postoperative analgesia with fewer adverse effects may be obtained with
significantly less morphine — although at lower doses there is not a clear dose‐response
relationship for some side effects or pain relief (Meylan et al, 2009 Level I). A meta‐analysis
comparing intrathecal morphine doses of less than 300 mcg, equal to or greater than 300 mcg,
and placebo reported a greater risk of respiratory depression and of nausea and vomiting with
the higher, but not lower, doses of morphine, while the incidence of pruritus was increased for
all doses (Gehling & Tryba, 2009 Level I).
Following hip and knee arthroplasty, intrathecal morphine (100 to 300 mcg) provided excellent
analgesia for 24 hours after surgery with no difference in side effects; after hip arthroplasty
only there was a significant reduction in postoperative patient‐controlled (PCA) morphine
requirements (Rathmell et al, 2003 Level II). Following knee arthroplasty, intrathecal morphine
500 mcg compared with 200 mcg reduced supplemental rescue analgesia (tramadol) over
24 hours with no difference in adverse event rates (Bowrey et al, 2005 Level II), and 200 mcg was
as effective as 300 mcg with no difference in side effects; both were superior to 100 mcg
(Hassett et al, 2008 Level II). After hip arthroplasty, 100 mcg and 200 mcg doses of intrathecal
morphine produced good and comparable pain relief and reductions in postoperative
morphine requirements; 50 mcg was ineffective (Murphy et al, 2003 Level II).
When combined with low‐dose bupivacaine for Caesarean section, 100 mcg intrathecal
morphine produced analgesia comparable with doses as high as 400 mcg, with significantly CHAPTER 5
less pruritus (Girgin et al, 2008 Level II). A single dose of morphine (100 mcg) added to a spinal
anaesthetic for Caesarean section prolonged the time to first postoperative analgesic
administration resulting in at least 11 hours of effective analgesia. Adverse effects included
pruritus (43%), nausea (10%) and vomiting (12%). The rate of respiratory depression was low
(see below). In these patients, sufentanil and fentanyl showed no analgesic benefits (Dahl et al,
1999 Level I).
The addition of 10 mcg sufentanil to 0.4 mg intrathecal morphine did not potentiate
postoperative analgesia or reduce intraoperative opioid requirements in patients undergoing
major colorectal surgery (Culebras et al, 2007 Level II). The addition of intrathecal fentanyl to
low‐dose spinal bupivacaine for anorectal surgery resulted in more pruritus but lower mean
recovery and discharge times, with fewer analgesic requests in the fentanyl group (Gurbet et al,
2008 Level II).
In a more recent study, intrathecal sufentanil provided shorter postoperative analgesia (mean
6.3 hours) than intrathecal morphine (mean 19.5 hours) with no difference in side effects
(Karaman et al, 2006 Level II). In another comparison of intrathecal morphine (100 mcg) and
intrathecal pethidine (10 mg) for analgesia following Caesarean section in a non‐blinded study,
patients receiving morphine had longer analgesia and fewer intraoperative side effects than
the pethidine group, but experienced more pruritus (Kumar et al, 2007 Level II).
For more information on effectiveness and side effects related to the use of intrathecal
opioids see Section 7.3.

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