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4.3.6 Alpha-2 agonists

Systemic administration (oral, IM, IV) of single doses of the alpha‐2 agonists clonidine (Bernard
et al, 1991 Level II; De Kock et al, 1992 Level II; Park et al, 1996 Level II); and dexmedetomidine (Aho
et al, 1991 Level II; Jalonen et al, 1997 Level II; Arain et al, 2004 Level II) decreased perioperative
opioid requirements in surgical patients.
The addition of clonidine to morphine for PCA significantly improved postoperative analgesia
(for the first 12 hours only) with less nausea and vomiting compared with morphine alone;
however there was no reduction in morphine requirements (Jeffs et al, 2002 Level II). Higher
doses of clonidine resulted in a significant reduction in opioid requirements but a greater
degree of sedation and hypotension (Marinangeli et al, 2002 Level II).
Intraoperative dexmedetomidine infusion significantly reduced opioid requirements, nausea,
vomiting and itch, but not pain or sedation scores compared with placebo, for up to 48 hours
after abdominal hysterectomy (Gurbet et al, 2006 Level II). A combination of dexmedetomidine
and morphine for PCA resulted in significantly better pain relief, a lower incidence of nausea
but not vomiting and significant opioid‐sparing compared with morphine alone (Lin et al, 2009
Level II).
In the intensive care setting, IV dexmedetomidine infusions used for sedation of ventilated
patients resulted in a 50% reduction in morphine requirements (Venn et al, 1999 Level II).
CHAPTER 4 Key message

1. The use of systemic alpha‐2‐agonists consistently improves perioperative opioid analgesia
but the frequency and severity of side effects may limit their clinical usefulness (U)
(Level II).

4.3.7 Salmon calcitonin and bisphosphonates
Calcitonin
Calcitonin is a 32 amino acid peptide hormone that regulates calcium homeostasis in
vertebrates. It also has analgesic properties, primarily through receptor‐mediated modulation
of serotonergic activity in pain pathways of the central nervous system. Salmon calcitonin has
a greater potency than mammalian forms of the hormone and is therefore reproduced as a
synthetic drug for pharmaceutical use. The adverse effects of calcitonin therapy such as
sedation, nausea, skin flushing and diarrhoea may reflect increased serotonergic activity. In
rodents, the 5HT3 antagonist tropisetron reduced its analgesic efficacy, which may be relevant
in humans during the treatment of nausea and vomiting (Visser, 2005).
Salmon calcitonin, (IV, SC, IM, IN or rectal) reduces acute pain at rest and on movement and
improves mobilisation (in 7 to 28 days) in patients with osteoporotic vertebral fractures and
side effects are usually minor and mainly gastrointestinal (Blau & Hoehns, 2003 Level I; Knopp et
al, 2005 Level I).
IV (and likely SC) salmon calcitonin is effective in the treatment of acute phantom limb pain
(Jaeger & Maier, 1992 Level II). However, it was not effective for chronic phantom limb pain
(Eichenberger et al, 2008 Level II).
A meta‐analysis concluded that salmon calcitonin was beneficial in the treatment of chronic
regional pain syndrome (CRPS) (Perez et al, 2001 Level I). However, the two placebo‐controlled
trials of the five in the meta‐analysis produced conflicting results. A more recent study found
that calcitonin was no more effective than paracetamol in improving pain and function in CRPS
over a 2‐month period in patients receiving physical therapy following upper limb trauma
(Sahin et al, 2006 Level II).
92 Acute Pain Management: Scientific Evidence