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5.3 ADJUVANT DRUGS

5.3.1 Alpha-2 agonists
Neuraxial
Clonidine is an alpha‐2 adrenoceptor agonist that acts as an analgesic at the level of the spinal
cord. There is no human or animal evidence of neurotoxicity when preservative‐free clonidine
is administered intrathecally (Hodgson et al, 1999). Epidural clonidine is approved by the United
States Food and Drug Administration (FDA) for relief of chronic cancer pain.
Intrathecal clonidine given in doses from 15 to 150 mcg combined with intrathecal local
anaesthetic, significantly prolonged the time to two segment block regression but did not
affect the rate of onset of a complete block (Elia et al, 2008 Level I). Intrathecal clonidine also
prolonged the time to first analgesic request (median 101 min, range 35 to 310 min) and
duration of motor block but in a non‐dose‐dependent manner; intraoperative pain was
reduced but hypotension was more frequent (RR 1.8; 95% CI 1.4 to 2.3) (Elia et al, 2008 Level I).
Others have reported that the addition of either clonidine or dexmedetomidine to intrathecal
bupivacaine increased the speed of onset and duration of motor and sensory block without
additional side effects (Kanazi et al, 2006 Level II).
Intrathecal clonidine 100 mcg added to 500 mcg intrathecal morphine resulted in better pain
relief and faster time to extubation after cardiac surgery compared with intrathecal morphine
alone (Nader et al, 2009 Level II). In patients undergoing radical prostatectomy, the addition of
clonidine to intrathecal morphine prolonged analgesia compared with intrathecal morphine
alone and PCA morphine; intrathecal morphine alone was better than PCA (Andrieu et al,
2009 Level II). CHAPTER 5
A review by Roelants of multiple randomised controlled trials (RCTs) concluded that small
doses of intrathecal clonidine (30 mcg) combined with local anaesthetics and opioids
prolonged labour analgesia; hypotension may occur and was more common with higher doses
of clonidine (Roelants, 2006 Level II). Intrathecal clonidine combined with bupivacaine had a
postoperative antihyperalgesic effect at 48 hours after elective Caesarean delivery compared
with intrathecal bupivacaine‐sufentanil and intrathecal clonidine 75 mcg‐bupivacaine‐
sufentanil, however no reduction in pain scores or opioid requirements was observed
(Lavand'homme et al, 2008 Level II). In another study, the combination of subarachnoid
bupivacaine, fentanyl, morphine and clonidine significantly prolonged pain relief following
Caesarean section, but with increased sedation (Paech et al, 2004 Level II).
The addition of clonidine to PCEA with ropivacaine and morphine after total knee arthroplasty
decreased opioid requirements and improved analgesia without increasing side effects (Huang
et al, 2007 Level II). The addition of clonidine to epidural levobupivacaine, also after hip
arthroplasty, significantly reduced postoperative morphine requirements compared with
either drug alone (Milligan et al, 2000 Level II). Low‐dose infusion of clonidine alone via thoracic
epidural catheters after spinal surgery reduced systemic opioid requirements and nausea
without causing significant sedation or hypotension (Farmery & Wilson‐MacDonald, 2009 Level II).
In children, addition of clonidine to bupivacaine caudal injection increased the duration
(Ansermino et al, 2003 Level I) and quality of analgesia without an increase in side effects (Yildiz et
al, 2006 Level II) (see also Section 10.7.2).

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