Meta-analysis of the efficacy of extradural clonidine to relieve postoperative pain: an impossible task

Abstract

Clonidine, an alpha2 adrenoceptor agonist, has anti-hypertensive and anti-nociceptive effects. It is commonly used in association with local anaesthetics and opioids to enhance the quality and duration of extradural analgesia in the postoperative period, and to decrease the incidence of side effects. As a sole analgesic, it has seldom been used to relieve postoperative pain. The dose of extradural clonidine to achieve good pain relief without deleterious side effects remains undetermined. In order to address this problem, we performed a computer search via two well-known databases, Medline and Excerpta Medica, covering the period from 1985 to September 1997. One hundred and fifty-nine articles were retrieved of which 38 dealt with extradural clonidine and postoperative pain. All but 16 studies suffered from serious design flaws, such as lack of controls and/or randomization, or inadequate statistical analysis. The data from these studies were difficult to interpret because of the tremendous variation in variables, especially dose of clonidine, level of extradural injection, time of administration, type of anaesthesia, type of surgery, and reference and rescue drugs. The simultaneous extradural use of local anaesthetics and opioids further hindered data interpretation, and precluded any meta-analysis. Proposals for a standard study design are made to help comparison between studies involving extradural clonidine and postoperative pain.

The addition of droperidol or clonidine to epidural tramadol shortens onset time and increases duration of postoperative analgesia

“…2,16,18 Furthermore, it has been stated that a combination of clonidine with fentanyl, sufentanil and morphine decreases the onset time of analgesia by 50%. 4,19,20 Consistent with previous reports, the present study shows that the onset time of analgesia was 16 min time with tramadol alone and that this time decreased to approximately eight minutes when either clonidine or droperidol was added.…”

“…[4][5][6][7][8] Epidural droperidol blocks mainly the fast, and to a lesser extent, the slow sodium channels and inhibits the formation of action potential. Clonidine, which is an alpha 2 adrenergic agonist, has an anti-nociceptive effect on a wide dynamic range of neurons and * receptors.…”

“…2,9,16 It has been suggested that the combination of clonidine with an opioid extends the duration of analgesia by two to three times. 1,4,10,15,21 Murthy et al 22 have found a lower volume of distribution for epidural tramadol and stated that the half-life was shorter than with iv usage. In the present study, we observed that the addition of clonidine or droperidol to tramadol extends the duration of analgesia by three times on average and, consequently, reduces daily tramadol requirements.…”

“…1,4,10,15,19 This leads us to believe that the significant increase in sedation observed in the tramadol-clonidine group was due to the addition of clonidine.…”

“…Although the studies using epidural clonidine have reported bradycardia and hypotension as the most frequent adverse effects, 1,4,10,15,19 no significant hemody-150 CANADIAN JOURNAL OF ANESTHESIA FIGURE 3 Sedation and nausea/vomiting scores ten minutes after epidural injection. FIGURE 4 Systolic blood pressure and heart rate in the postoperative period (mean ± SD).…”