Page 117 Acute Pain Management
P. 117
difference between the groups; in the few patients not also taking illicit opioids, subjects
taking buprenorphine were less hyperalgesic than those taking methadone (Compton et al, 2001
Level III‐2).
Angst and Clark (Angst & Clark, 2006 Level I) summarised studies that investigated the effects of
a short‐duration remifentanil infusion in volunteer subjects with pre‐existing experimentally
induced mechanical hyperalgesia; the use of remifentanil was shown to aggravate
hyperalgesia, the magnitude of the effect was directly related to the dose given, and
coadministration of ketamine abolished the effect of remifentanil. Methadone‐maintained
subjects were shown to have a significant tolerance to remifentanil given by short‐duration
infusion, suggesting that opioid‐tolerant patients may require significantly higher doses for the
treatment of acute pain compared with opioid‐naive patients; dose‐dependent increases in
cold pressor tolerance were found (Hay et al, 2009 Level III‐2).
Clinical studies
It may be more difficult to distinguish between pharmacological tolerance and OIH in the
clinical setting when subjective pain scores are used to assess adequacy of analgesia (Chang et
al, 2007). Many of the studies to date provide only indirect evidence for the development of
OIH (Angst & Clark, 2006; Chu LF et al, 2008). A formal diagnosis of hyperalgesia requires
quantitative sensory testing (QST), that is, serial assessment of the responses to varying
intensities of a nociceptive stimulus in order to determine pain thresholds (Mitra, 2008). QST
before and after starting chronic opioid therapy, may assist in the differentiation between OIH
and pharmacological tolerance (Chu LF et al, 2008) but this is unlikely to become common CHAPTER 4
practice in the acute pain setting.
There have been a number of studies, summarised in reviews by Angst and Clark (Angst & Clark,
2006 Level IV) and Chu et al (Chu LF et al, 2008 Level IV), investigating the effects of intraoperative
use of a potent opioid (commonly a remifentanil infusion) on pain and postoperative opioid
requirements, but the results are conflicting. Some have shown that this leads to increased
pain and postoperative opioid requirements, and attributed this to OIH, other studies have not
been able to replicate these findings — leading to the suggestion that the outcome may be
dose‐dependent and more likely to occur when higher opioid doses are administered (Chu LF et
al, 2008). For example, morphine requirements and hyperalgesia and allodynia adjacent to the
surgical wound were greater following high‐dose intraoperative remifentanil infusions
compared with low‐dose infusions (Joly et al, 2005 Level II). A study in volunteers given
remifentanil infusions to obtain two different ‘but clinically relevant’ steady‐state target
concentrations of the drug, found that these were not associated with changes in response to
thermal, electrical and cold pressor stimuli (Angst et al, 2009 Level II).
Also, it is not yet clear from many of these papers whether this acute ‘apparent tolerance’ is
due to pharmacological tolerance or OIH (Angst & Clark, 2006; Mao, 2008). True differentiation
between pharmacological tolerance and OIH requires direct assessment of pain sensitivity, as
noted above (Mitra, 2008). However, if patients given a remifentanil infusion intraoperatively
report higher levels of postoperative pain than matched controls who have not received any
opioids, then OIH should be considered (Chang et al, 2007).
Severity of acute pain following a single subcutaneous (SC) injection of lignocaine was
compared in patients taking opioids for chronic pain and opioid‐naive controls; pain and
unpleasantness scores were higher in those patients taking opioids and correlated with opioid
dose and duration of treatment (Cohen et al, 2008 Level III‐2).
There are case reports of patients with cancer and chronic non‐cancer pain and taking high
doses of opioid, who developed OIH and whose pain relief improved following reduction of
Acute pain management: scientific evidence 69
