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Cosmo et al, 2008 Level III‐2; Uchiyama et al, 2006 Level III‐2), and arthroscopic knee surgery
(Rosseland & Stubhaug, 2004 Level III‐2). However, in adolescent patients using PCA morphine in
the postoperative period, no difference was seen between male and female patients in
average daily pain ratings (Logan & Rose, 2004 Level III‐2). In a study of Chinese patients, females
consumed significantly less morphine than males (Chia et al, 2002 Level III‐2).
When pain is assessed at a longer time interval after surgery, there appears to be no
differences between male and female patients (Fillingim et al, 2009). For example, there was no
difference in pain after arthroscopic knee surgery at one year, although disability was greater
in females (Rosseland et al, 2008 Level III‐2), or in pain at 12 to 18 months after hip arthroplasty
(Nikolajsen, Brandsborg et al, 2006 Level III‐2).
Genetics
Genetic variability may also affect a patient’s response to opioids (see Section 1.6).
Psychological factors
Evidence of any effect of psychological factors such as anxiety on opioid requirements is
contradictory (see Section 1.2).
4.1.4 Adverse effects of opioids
CHAPTER 4 function and urinary retention. Meta‐analyses have shown that the risk of side effects from
Common adverse effects of opioids are sedation, pruritus, nausea, vomiting, slowing of GI

opioids administered by PCA is similar to the risks from traditional methods of systemic opioid
administration, with the exception of pruritus, which is increased in patients using PCA
(Hudcova et al, 2005 Level I).
Results from a review of all trials (including cohort studies, case‐controlled studies and audit
reports as well as randomised‐controlled trials) suggested that there may be differences in the
clinical setting (Cashman & Dolin, 2004; Dolin & Cashman, 2005). The following incidences (means)
were associated with the use of PCA opioids: respiratory depression 1.2% to 11.5% (using
decreased respiratory rate and oxygen desaturation, respectively, as indicators), nausea 32%,
vomiting 20.7%, pruritus 13.8% and excessive sedation 5.3%. The incidences reported for IM
opioid analgesia were: respiratory depression 0.8% to 37% (using the same indicators), nausea
17%, vomiting 21.9%, pruritus 3.4%, and excessive sedation 5.2% (Cashman & Dolin, 2004
Level IV; Dolin & Cashman, 2005 Level IV).
Clinically meaningful adverse effects of opioids are dose‐related. There was an increased risk
of 0.9% for nausea and 0.3% for vomiting for every 1 mg increase in PCA morphine
3
consumption after surgery (Marret et al, 2005 Level I ). In a later prospective evaluation of the
incidence of nausea and vomiting in elderly surgical inpatients requiring a length of stay
greater than 2 days and given no postoperative nausea and vomiting (PONV) prophylaxis,
there was also a direct correlation between increasing opioid dose and the incidence of both
nausea and vomiting (Roberts et al, 2005 Level IV). In patients after laparoscopic
cholecystectomy performed on an ambulatory basis, once a threshold dose was reached,
every 3 to 4 mg increase of morphine‐equivalent dose per day was associated with one
additional meaningful adverse event or patient‐day with such an event (Zhao et al, 2004 Level II).

3
This meta‐analysis includes a study or studies that have since been withdrawn from publication. Please refer to the
Introduction at the beginning of this document for comments regarding the management of retracted articles.
Expert advice suggested that withdrawal of the retracted articles would not influence the conclusions but that
reanalysis would be required for this to be confirmed. Marret et al (Marret et al, Anesthesiology 2009; 111:1279–89)
reanalysed the data included in this meta‐analysis after excluding that obtained from the retracted publications.
They concluded that removal of this information did not significantly alter the results.
62 Acute Pain Management: Scientific Evidence