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their use cannot be recommended. Specific safety alerts have been issued warning against use
in opioid‐naive patients, and highlighting the risk that increased body temperature, exposure
of patches to external heat sources, and concomitant use of CYP3A4 inhibitors may lead to
potentially dangerous rises in serum fentanyl levels (FDA, 2005).
However, transdermal fentanyl patches have been trialled in the management of
postoperative pain. For example, after hip arthroplasty (Minville et al, 2008 Level II) and
hysterectomy (Sandler et al, 1994 Level II), preoperative use significantly reduced postoperative
pain scores and PCA morphine requirements. However, the wide variability of clinical effect
(Peng & Sandler, 1999) and the high incidence of respiratory depression that can occur in the
postoperative setting (Sandler et al, 1994 Level II; Bulow et al, 1995 Level II), make transdermal
fentanyl preparations unsuitable for acute pain management.
Iontophoretic patient‐controlled transdermal delivery systems for fentanyl were introduced
for the management of acute pain, but marketing authority was later withdrawn after
discovery of a fault that could lead to triggering of the self‐activation of the system
(see Section 7.1.4).
Transdermal buprenorphine patches are available for the management of chronic and cancer
pain (Skaer, 2006). After application of the patch, steady state is achieved by day 3; after
removal of the patch, buprenorphine concentrations decrease by about 50% in 12 hours
(range 10 to 24 hours) (MIMS, 2008). Given the slow onset and offset of the drug, it is unlikely
to be of much use in the management of acute pain.

6.5.2 Other drugs
The results from studies looking at the use of transdermal nicotine patches for the
CHAPTER 6 management of postoperative pain have been inconclusive with both a reduction (Hong et al,
2008 Level II) and no reduction in pain scores (Habib et al, 2008 Level II; Turan et al, 2008 Level II),
and opioid‐sparing (Habib et al, 2008 Level II) and no opioid‐sparing (Hong et al, 2008 Level II;
Turan et al, 2008 Level II) reported.
Topical administration might result in effective systemic plasma concentrations, as a
transdermal ketamine patch delivering 25 mg over 24 hours reduced rescue analgesic
consumption after gynaecological surgery (Azevedo et al, 2000 Level II) and, in an
experimental pain study, use of a ketamine gel reduced capsaicin‐induced hyperalgesia
(Poyhia & Vainio, 2006).

6.6 TRANSMUCOSAL ROUTES

Drugs administered by transmucosal routes (IN, sublingual, buccal, and pulmonary) are rapidly
absorbed directly into the systemic circulation, thus bypassing hepatic first‐pass metabolism.
The drugs most commonly administered by transmucosal routes in acute pain management
are the more lipid‐soluble opioids.
6.6.1 Intranasal route

A variety of drugs can be administered by the IN route, including analgesic drugs. The human
nasal mucosa contains drug‐metabolising enzymes but the extent and clinical significance of
human nasal first‐pass metabolism is unknown (Dale et al, 2002). It is suggested that the volume
of a dose of any drug given intranasally should not exceed 150 microlitres (0.150 mL) in order
to avoid run‐off into the pharynx (Dale et al, 2002). Absorption through the nasal mucosa
depends on both the lipid solubility and degree of ionisation of the drug (Shelley & Paech, 2008).

160 Acute Pain Management: Scientific Evidence