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The combination of two opioids in the PCA syringe has also been investigated. There was
no difference in pain scores and side effects between fentanyl‐morphine and fentanyl PCA
(Friedman et al, 2008 Level II). Beneficial effects on pain relief and the incidence of pruritus in
a comparison of morphine, nalbuphine and varying combinations of the two drugs were
dependent on the ratio of drugs used (Yeh et al, 2008 Level II). The addition of alfentanil to
morphine resulted in no differences in pain relief or adverse effects compared with morphine
alone, although patients who received the alfentanil‐morphine mixture rated speed of onset
and effectiveness of analgesia as better (Ngan Kee et al, 1999 Level II). In contrast, compared
with tramadol alone, remifentanil added to tramadol improved pain relief, but increased total
opioid dose (Unlugenc, Tetiker et al, 2008 Level II).
On an individual patient basis, one opioid may be better tolerated than another and a change
to an alternative opioid may be beneficial if the patient is experiencing intolerable side effects
(Woodhouse et al, 1999 Level II).
Adverse effects of PCA opioids
As noted above and in Section 7.1.1, meta‐analyses and individual studies have shown that
the risk of side effects is similar for opioids administered by PCA or more traditional routes,
regardless of the opioid used.
A review of published cohort studies, case‐controlled studies and audit reports only (ie not
RCTs), reported the following incidences associated with the use of PCA: respiratory
depression 1.2% to 11.5% (depending whether respiratory rate or oxygen saturation were
used as indicators), nausea 32%, vomiting 20.7%, and pruritus 13.8% (Cashman & Dolin, 2004
Level IV; Dolin & Cashman, 2005 Level IV). Excessive sedation was not used as an indicator of
respiratory depression in any of the studies included in these reviews (see importance of
sedation score in Section 4.1).
In an audit of 700 patients who received PCA for postoperative pain relief, respiratory
depression was defined as a respiratory rate of <10 breaths/min and/or a sedation score of 2
(defined as ‘asleep but easily roused’); of the 13 patients (1.86%) reported with respiratory
depression, all had respiratory rates of <10 breaths/min and 11 also had sedation scores of 2 CHAPTER 7
(Shapiro et al, 2005 Level IV).
The incidence of PCA‐related sedation was reduced significantly in patients given concurrent
non‐steroidal anti‐inflammatory drugs (NSAIDs) (Marret et al, 2005 Level I).
Adjuvant drugs
Discussion of adjuvant drugs in this section will be confined to those added to the PCA opioid
solution. For additional information see Section 4.3.
Antiemetics
Droperidol added to the PCA morphine solution was an effective antiemetic with an NNT of
2.7 for nausea and 3.1 for vomiting (Tramèr & Walder, 1999 Level I). Tramèr’s group noted no
dose‐responsiveness with droperidol (Tramèr & Walder, 1999 Level I). However, in a comparison
of the effects of the addition of 0.5 mg, 1.5 mg and 5 mg droperidol to 100 mg PCA morphine,
the smallest dose had no significant antiemetic effect and the 1.5 mg dose was effective
against nausea but not vomiting (Culebras et al, 2003 Level II). The 5 mg dose significantly
reduced both nausea and vomiting, but at the cost of unacceptable sedation, which was not
seen at the other doses. In contrast to the NNTs reported by Tramèr et al (Tramèr & Walder,
1999 Level I), these results translate to NNTs of 3.7 for nausea and 8.3 for vomiting; as noted,
the higher dose increased the risk of sedation (Culebras et al, 2003 Level II).

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