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advantage of the fact that cross‐tolerance is likely to be incomplete (Jage, 2005; Mitra, 2008) and
that the degree of OIH and tolerance appears to vary between opioids (see Section 4.1.3).
Other adjuvants
In an experimental pain setting using intradermal electrical pain stimuli, parecoxib given
before a remifentanil infusion, but not if given during, was shown to modulate the
hyperalgesia seen after withdrawal of the remifentanil (Troster et al, 2006 Level II).
Intrathecal gabapentin has also been shown to attenuate opioid tolerance in rats (Lin et al,
2005), but there are no data from human studies.
Prevention of withdrawal
Withdrawal from opioids is characterised by excitatory and autonomic symptoms including
abdominal cramping, muscle aches and pain, insomnia, dysphoria, anxiety, restlessness,
nausea and vomiting, diarrhoea, rhinorrhea and sneezing, trembling, yawning, runny eyes and
piloerection or ‘gooseflesh’ (Tetrault & O'Connor, 2008). The time of onset of withdrawal
symptoms after cessation of the drug will depend on the duration of action of the opioid
(Tetrault & O'Connor, 2008).
It should be prevented by maintenance of normal preadmission opioid regimens where
possible (including, for patients undergoing surgery, on the day of their procedure), or
appropriate substitutions with another opioid or the same opioid via another route (Carroll et
al, 2004; Mitra & Sinatra, 2004; Macintyre & Schug, 2007). It is important to verify preadmission
opioid doses, which may require contact with the patient’s doctor, pharmacist or, where
available, local regulatory authority. The use of additional unauthorised additional opioids (licit
or illicit) or of lower doses than prescribed, may affect both pain relief and the risk of adverse
effects.
While multimodal analgesic regimens (eg nsNSAIDs, paracetamol, ketamine, tramadol,
regional analgesia) are of analgesic benefit, opioid‐tolerant patients are at risk of opioid
withdrawal if a purely non‐opioid analgesic regimen or tramadol is used (Carroll et al, 2004;
Mitra & Sinatra, 2004; Macintyre & Schug, 2007). For this reason opioid antagonists (naloxone,
naltrexone) or mixed agonist‐antagonists (eg buprenorphine, pentazocine) should be also
avoided (unless the former are needed to treat respiratory depression) as their use may
precipitate acute withdrawal reactions (Alford et al, 2006).
Use of intrathecal or epidural opioids will not necessarily prevent symptoms of opioid
withdrawal and additional systemic opioids may be required (Carroll et al, 2004).
Clonidine, administered orally or parenterally, will aid in the symptomatic management of
CHAPTER 11 opioid withdrawal symptoms (Tetrault & O'Connor, 2008).
Management on discharge
Discharge planning must take into account any regulatory requirements (eg the authority to
prescribe an opioid may have be delegated to a particular physician only), the duration of use
of any additional opioids prescribed for the short‐term management of acute pain and the
weaning of those drugs and, in a small of minority patients, the potential for prescribed
opioids to be abused or misused. Appropriate use of non‐opioid analgesics where possible,
communication with the primary physician and health care professionals, and patient
education and support must all be considered.

426 Acute Pain Management: Scientific Evidence