1 Institut Arnault Tzanck, Saint Laurent du Var, Nice, France. 2 Hôpital Tenon, Assistance Publique Hôpitaux de Paris, Paris, France
Corresponding author: Department of Anaesthesia and Intensive Care, Hôpital Tenon, Rue de la Chine, F-75970 Paris Cedex 20, France. E-mail: francis.bonnet@tnn.ap-hop-paris.fr
Accepted for publication: November 7, 2002
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Abstract |
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Methods. In a double-blind randomized study, 45 patients having coronary artery bypass graft surgery were allocated randomly to receive i.v. patient-controlled analgesia (PCA) morphine (bolus, 1 mg; lock-out interval, 7 min) (control group), either alone or combined with intrathecal morphine 4 µg kg1 or with both intrathecal morphine 4 µg kg1 and clonidine 1 µg kg1. Intrathecal injections were performed before the induction of general anaesthesia. Pain was measured after surgery using a visual analogue scale (VAS). We recorded i.v. PCA morphine consumption during the 24 h after operation.
Results. Morphine dosage [median (25th75th percentiles)] was less in the first 24 h in the patients who were given intrathecal morphine + clonidine [7 (037) mg] than in other patients [40.5 (1561.5) mg in the intrathecal morphine group and 37 (30.551) mg in the i.v. morphine group]. VAS scores were lower after intrathecal morphine + clonidine compared with the control group. Time to extubation was less after intrathecal morphine + clonidine compared with the i.v. morphine group [225 (195330) vs 330 (300360) min, P<0.05].
Conclusion. Intrathecal morphine and clonidine provide effective analgesia after coronary artery bypass graft surgery and allow earlier extubation.
Br J Anaesth 2003; 90: 3003
Keywords: analgesia, postoperative; analgesics opioid, morphine; surgery, cardiovascular; sympathetic nervous system, clonidine
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Introduction |
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Intrathecal clonidine not only produces analgesia but can also augment the analgesic effect of morphine.8 9 The addition of intrathecal clonidine to morphine allows the dose of morphine to be reduced and reduces the risk of respiratory depression while maintaining good analgesia. Consequently, we assessed the analgesic effect of a combination of intrathecal morphine and clonidine in patients having CABG surgery.
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Patients and methods |
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Pain was measured at rest with a visual analogue scale (VAS) graded from 0 (no pain) to 100 (worst pain imaginable) every 30 min for the first 4 h in the ICU, each hour for the next 4 h, then every 2 h to 20 h and finally at 24 h.
We noted any evidence of respiratory depression (respiratory rate <10 bpm), hypertension (systolic arterial blood pressure 150 mm Hg), hypotension (systolic arterial blood pressure
75 mm Hg) and sedation. If necessary, hypertension was treated with a continuous infusion of nicardipine 15 mg h1 i.v. and hypotension with rapid fluid infusion followed by inotropic agents if necessary.
Our aim was to obtain a 50% decrease in i.v. PCA morphine consumption after intrathecal clonidine + morphine compared with the control group. On the basis of experience with i.v. PCA morphine requirements in CABG patients in our hospital, we calculated that a sample size of 15 patients in each group should detect such a difference with a type I error of 0.05 and a type II error of 0.10.
Statistical analysis was with the unpaired Students t-test for comparisons of duration of surgery, aortic cross-clamping and extracorporeal circulation. The Mann Whitney rank sum test was used to analyse morphine consumption, time to start PCA, time to extubation, VAS score, sufentanil consumption and duration of nicardipine treatment. P<0.05 was considered significant. Results are presented as mean (SD) or median (25th75th percentiles).
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Results |
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Discussion |
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Previous studies showed that the analgesic effect of intrathecal morphine depends on the time of administration. In CABG patients, giving intrathecal morphine after surgery is ineffective because of the slow onset of action.10 Dosing before surgery is effective provided the morphine dose is greater than 6 µg kg1.4 6 7 11 Such doses prolong the duration of controlled ventilation with possible respiratory complications.4 6 7 Some patients had a delayed respiratory depression after tracheal extubation, related to the combined use of intrathecal and i.v. morphine.6 12 On the other hand, smaller doses of morphine, as used in the present study in order to avoid prolonged respiratory depression, did not give adequate analgesia after CABG.
Intrathecal clonidine 12 µg kg1 can provide analgesia after orthopaedic surgery or caesarean section,1315 although the duration of action and the i.v. morphine sparing were limited. Intrathecal clonidine is thought to act on specific 2-adrenergic receptors located on the dorsal horn of the spinal cord.16 17 Isobolographic analysis indicates synergism of clonidine with intrathecal morphine.9 After total hip replacement, Grace and colleagues15 found no reduction in pain when clonidine was combined with morphine. However the level of pain was extremely low in the morphine group, making further improvement with clonidine difficult to demonstrate. Conversely, Goyagi and Nishikawa18 found that the duration of analgesia provided by intrathecal morphine 200 µg after abdominal hysterectomy was doubled by oral clonidine 5 µg kg1 before anaesthesia. In our study, the time to morphine administration was prolonged in the morphine + clonidine group. Although patients in the morphine + clonidine group were extubated earlier, their i.v. morphine requirement was markedly less than in the control group. This result was confirmed by the fact that VAS scores were lower in the morphine + clonidine group.
Clonidine reduces sympathetic activity and arterial blood pressure.19 In addition to its activity in the brainstem, intrathecal clonidine decreases the activity of presynaptic sympathetic neurones at the level of the thoracic spinal cord.20 Thus, clonidine administration may blunt the hypertensive response to pain in ICU patients. Consequently, less nicardipine was needed to control hypertension in patients given clonidine. In addition, in this limited series of patients with normal left ventricular function and an uncomplicated postoperative course, we found no hypotension requiring treatment after clonidine use. In this study, the effects of clonidine on the incidence of myocardial ischaemia were not noted, but others have suggested that clonidine may reduce cardiac ischaemic episodes in patients with known or possible coronary artery disease.21
Extubation was earlier in the morphine + clonidine group. Clonidine can cause sedation, but in our study sedation was never sufficient to prevent extubation. Reduced time to extubation could be explained by less sufentanil used during surgery in the morphine + clonidine group. Indeed, when the intraoperative opioid dose is reduced, the delay to extubation is not prolonged in patients receiving intrathecal morphine 10 µg kg1.22 A lower opioid requirement after intrathecal morphine and sufentanil given before surgery has been reported previously,23 but studies using fixed opioid doses failed to show this.4 6
In conclusion, the combination of intrathecal clonidine and morphine gives effective control of postoperative pain in CABG patients and reduces the duration of controlled ventilation. If patients have no contraindication to intrathecal administration, this technique will facilitate fast-track cardiac anaesthesia.
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References |
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