Efficacy of mirtazapine in preventing intrathecalmorphine‐induced nausea and vomiting after orthopaedic surgery*

Abstract

SummaryNausea and vomiting are frequent complications of intrathecal morphine. In this randomised, double-blind trial, we tested the efficacy of mirtazapine, an antidepressant that blocks receptors associated with vomiting, on the incidence of nausea and vomiting after intrathecal morphine. One hundred patients receiving spinal anaesthesia for lower limb surgery were assigned equally to take either an orally disintegrating form of 30 mg mirtazapine or matching placebo 1 h before surgery. Spinal anaesthesia was performed by injection of 15 mg isobaric bupivacaine 0.5% along with 0.2 mg preservative-free morphine. Nausea and vomiting were evaluated 3, 6, 12, 18 and 24 h after intrathecal morphine administration. The incidence of nausea and vomiting was significantly lower in patients receiving mirtazapine compared with placebo (26.5% vs 56.3%, respectively; p = 0.005). The mean (SD) onset time of postoperative nausea and vomiting was significantly delayed in mirtazapine patients: 9.4 (2.5) vs 5.2 (1.8) h, respectively; p < 0.0001. The severity of nausea and vomiting was also decreased after mirtazapine at the 3-6 h and 6-12 h periods. Our data indicate that pre-operative mirtazapine decreases the incidence, delays the onset and reduces the severity of nausea and vomiting induced by intrathecal morphine in patients undergoing spinal anaesthesia. A single dose of intrathecal morphine is often administered to patients undergoing major orthopaedic procedures to provide sustained postoperative analgesia. Postoperative nausea and vomiting (PONV) occurs frequently, with a reported incidence of up to 74% and lasting up to 24 h [1]. Serotonin (5-HT 3 ) receptor antagonists have been used as anti-emetics to prevent or to treat nausea and vomiting induced by intrathecal morphine [2][3][4][5][6]. Mirtazapine is a new antidepressant that selectively blocks postsynaptic 5-HT 2 and 5-HT 3 receptors [7]. As it blocks receptors associated with nausea and vomiting, mirtazapine had been shown to treat severe vomiting during pregnancy [8] and to treat cancer patients with pain, nausea and a variety of distressing symptoms [9,10]. Its anti-emetic effect has also been reported after laparoscopy surgery [11] and gastric bypass [12]. Its effect on the prevention of intrathecal morphine-induced PONV has not yet undergone evaluation. We therefore hypothesised that prophylactic mirtazapine would reduce the incidence and delay the onset of intrathecal morphine-induced PONV in patients undergoing orthopaedic surgery. MethodsThe protocol was approved by the Clinical Research Ethics

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The atypical antidepressant mirtazapine attenuates expression of morphine-induced place preference and motor sensitization

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Early Unpleasant Postoperative Symptoms for Patients Undergoing Primary Hip versus Primary Knee Replacement: Patient Perception

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