Postoperative Hyperalgesia Clinical Trial
Official title:
A Study of Effect of Epidural Clonidine on Postoperative Pain Relief, Hyperalgesia and Chronic Pain in Patients Undergoing Colorectal Surgery
We propose performing a study in which we compare the effects of bupivacaine and fentanyl
with a different drug combination − bupivacaine and clonidine. The principal research
questions of the study are:
1. To compare the effect of clonidine (with bupivacaine), injected into the epidural space
on the extent of hyperalgesia (abnormal pain/sensitivity in the uninjured skin
surrounding the operation site) in patients undergoing operations for bowel disease,
with that of fentanyl (with bupivacaine).
2. To compare the effect of clonidine (with bupivacaine), injected into the epidural space
on the incidence of chronic pain 6 months after surgery for bowel disease, with that of
fentanyl (with bupivacaine).
In addition to pain at the surgical incision site, patients undergoing major bowel
operations commonly experience pain in the surrounding (uninjured)skin during the
postoperative period − this phenomenon is known as hyperalgesia. In most patients
hyperalgesia resolves with healing of the wound, but in some patients it persists. Recent
studies have shown that 25% of patients undergoing bowel surgery will have chronic pain at 1
year following surgery. This pain can be debilitating and has significant implications, both
for the individual and for society. For the individual there are significant physical,
mental, social and economic implications. The burden on society is significant because bowel
surgery operations are very common, and many of the 25% of the patients who develop chronic
pain will required ongoing treatment and unable to work.Chronic pain after surgery is
believed to be a result of changes in the central nervous system (i.e. brain and spinal
cord)occurring during and immediately after the surgery. Indeed the likelihood of a patient
developing chronic pain is related to the extent of hyperalgesia during the initial
post−operative period. Two other important predisposing factors are the emotional state of
the patient and the genetic predisposition of the patient to develop chronic pain states. In
our hospital, in common with most western hospitals, patients undergoing major bowel surgery
commonly have an epidural catheter (a soft plastic tube inserted in the space surrounding
the spinal cord fluid) inserted before the operation to facilitate the administration,
during the first few postoperative days, of a combination of a local anaesthetic agent
(bupivacaine in our hospital) and an opiate drug (a morphine−like medicine; fentanyl is used
in our hospital). Unfortunately, neither fentanyl nor bupivacaine appear to reduce the
incidence of hyperalgesia. In fact there is evidence that larger doses of opiates such as
fentanyl can increase the extent and severity of hyperalgesia. Moreover, although routinely
used in our hospital, fentanyl is associated with several adverse effects including nausea
and vomiting, generalised itching, sedation (sleepiness), and respiratory depression (slowed
respiration rate). Recent studies have shown that when clonidine is injected through an
epidural catheter, it can provide good pain relief in the immediate post−operative period,
and is also effective in reducing the extent of hyperalgesia in the area around the
incision. This, in turn may lead reduce the probability of patients developing persistent
pain. There is good evidence to show that when clonidine is used instead of fentanyl, the
adverse effects are reduced.
Although epidural clonidine has been used with success in different surgical settings, there
are no published studies comparing epidural combinations of bupivacaine and clonidine with
bupivacaine and fentanyl (or all 3 drugs together) in patients undergoing abdominal surgery.
There is now good evidence from animal and human studies to suggest that a combination of
fentanyl and clonidine has more pain−relieving effect than either of the two drugs
administered on its own.
We thus propose to compare the pain relieving effects of these three drug combinations in
patients undergoing abdominal operations for bowel resection.
There are various methods of detecting hyperalgesia. Measurement of sensitivity to touch and
pain in the skin around the incision site is a simple and reproducible method. This involves
use of simple devices − a brush (to test pain on touch) and a plastic pointed hair/filament
(to detect and measure abnormal sensitivity to a mildly painful stimulus in the area around
the incision). To determine the incidence of chronic pain we will follow up patients after
surgery by telephoning to ask them questions relating to the intensity of their pain as well
as its effect on their lifestyle. To assess the patients' emotional state before surgery we
will ask them to complete questionnaires known to be reliable and validated for detection of
anxiety and depression, for assessment of general well−being. For detection of genetic
predisposition to developing chronic pain, we will analyse patients' blood samples for genes
that are known to either reduce the effectiveness of pain−relieving medication,or to make
them more sensitive to painful stimuli.
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Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
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