Page 330 Acute Pain Management

three RCTs of OTFC confirmed that the optimal OTFC dose correlated poorly with scheduled
or previous breakthrough opioid doses. The only clinical indicator of breakthrough dose was
age; the average final OTFC dose significantly decreased with increasing age (Hagen et al, 2007
Level II). In one trial, where patients were titrated to a successful dose of OTFC (69% patients),
OTFC was more successful than morphine in relieving breakthrough pain and patients
preferred OTFC (Coluzzi et al, 2001 Level II). A comparative study of OTFC and IV morphine for
breakthrough pain demonstrated analgesic superiority of IV morphine at 15 minutes but not
30 minutes and comparable adverse effects (Mercadante et al, 2007 Level III‐1).
A buccal tablet formulation of fentanyl was superior to OTFC with respect to bioavailability
and time to peak plasma concentration (Darwish et al, 2007 Level II), and provided relief from
breakthrough pain within 10 minutes (Slatkin et al, 2007 Level II).
9.7.4 Postoperative and procedural pain

Many of the issues relating to postoperative pain discussed in Sections 1.3 and 9.1 are
particularly pertinent in the patient with cancer. Cancer patients represent a high proportion
of patients undergoing thoracotomy, breast surgery, lymph node dissection from axillary,
inguinal or cervical regions, and limb amputation, all associated with persistent pain
syndromes that may respond to various interventions in the postoperative period. In addition,
cancer patients often will undergo radio‐ or chemotherapy after surgery; both are risk factors
for chronic postsurgical pain as outlined in Section 1.3. Chemotherapy has also been
considered a risk factor for phantom limb pain, contributing to the higher incidence of
phantom limb pain in children with cancer than with trauma (Smith & Thompson, 1995 Level IV),
but no prospective trials have confirmed this association.
Identification of prior use and tolerance to opioids is essential to ensure adequate analgesia in
the postoperative period, as discussed in Section 11.7.
The impact of analgesic techniques on immune response, and implications for cancer
progression, are new areas of research. A review of patients undergoing radical
prostatectomy, comparing outcomes after general anaesthesia plus epidural analgesia and
regional anaesthesia plus opioid therapy, suggested a 57% (95% CI 17% to 78%) lower risk of
cancer recurrence after the use of epidural analgesia (Biki et al, 2008 Level IV). Pre‐emptive
CHAPTER 9 epidural analgesia with lignocaine and morphine, established prior to radical hysterectomy for
cervical cancer, significantly reduced postoperative pain and modulated the immune response
to surgery to a greater extent than epidural established after peritoneal closure; interleukin‐6
rise was lowered and the duration of interleukin‐2 suppression was shortened (Hong & Lim,
2008 Level II). Similarly, different analgesics may have different effects on postoperative
immune suppression; in animals (Sacerdote et al, 1997) and in humans (Sacerdote et al, 2000
Level II) tramadol resulted in reduced immune suppression compared with morphine. The
clinical implications of this effect have not yet been evaluated.
Patients with cancer may undergo multiple painful procedures and attention to adequate
analgesia and anxiolysis is imperative, to reduce anticipatory stress prior to repeat
interventions. Simple techniques include use of topical local anaesthetic, premedication
or administration of breakthrough analgesia in advance, and administration of sedation
by trained personnel. Few trials have evaluated procedural pain in adult patients with cancer.
A review of interventions to decrease pain during mammography identified seven RCTs, but
conclusions were few and based on single studies due to inability to combine data from
different studies (Miller et al, 2008 Level I). The provision of prior information about the
procedure, increasing self‐control over the degree of breast compression, and the use of
breast cushions all decreased pain, whereas paracetamol did not.

282 Acute Pain Management: Scientific Evidence