Use of mirtazapine to reduce anxiety and nausea and vomiting

AORN Journal, May, 2008 by George Allen

Anesthesia & Analgesia

January 2008

Two of the most disagreeable experiences associated with surgery are preoperative anxiety and postoperative nausea and vomiting (PONV). Premedication with anxiolytic agents may attenuate the stress response to anesthesia; however, practitioners may be reluctant to provide sedative medication because of the concern that they may delay tracheal extubation or prolong discharge from the postanesthesia care unit. Additionally, there are still challenges to reducing the incidence of PONV despite the introduction of new antiemetic medications, short acting anesthetic agents, and the increasing use of minimally invasive surgical techniques.

Mirtazapine is an antidepressant that blocks 5-[HT.sub.2] and 5-[HT.sub.3] receptors (ie, serotonin [5-hydroxytryptamine, 5-HT]). It is a noradrenergic and specific serotonergic antidepressant with anxiolytic effects. In addition, mirtazapine may help to prevent nausea and vomiting. There have been several reports of successful use of mirtazapine in treating nausea and vomiting caused by pregnancy or chemotherapy and nonmechanical vomiting after gastric bypass. The purpose of this prospective, double-blind, randomized, placebo-controlled study was to test the hypothesis that premedication with mirtazapine can reduce preoperative anxiety and the risk of PONV.

Female patients ages 20 to 60 years undergoing gynecological procedures including abdominal total hysterectomy, myomectomy, laparoscopic myomectomy, and laparoscopic oophorectomy at a hospital in Taiwan were recruited for the study. A simplified score for predicting PONV was used to identify appropriate patients for the enrollment:

* female gender,

* nonsmoking status,

* history of PONV or motion sickness, and

* use of postoperative opioids.

Only patients who had at least two factors of these were enrolled. Excluded were patients with a history of peptic ulcer, diabetes mellitus, severe hypertension, Cushing's syndrome, and known hypersensitivity to mirtazapine or dexamethasone. Individuals taking any other antidepressant medications or steroids, taking any medications with antiemetic properties within 24 hours of surgery, or who were receiving monoamine oxidase inhibitors or were within two weeks of stopping monoamine oxidase inhibitors also were excluded. Dexamethasone 8 mg was used as an active control and was given to all the patients before induction of anesthesia.

Patients were randomly assigned to one of two groups: group M D (ie, mirtazapine 30 mg plus dexamethasone 8 mg) or group D (placebo plus dexamethasone 8 mg). Medications were given one hour before surgery in the holding area. Anxiety levels were assessed preoperatively using a 10-cm visual analogue scale (VAS) with one end labeled "not anxious at all" and the other labeled "extremely anxious." The assessments were performed before the study medications were administered and one hour after the medications were administered.

General anesthesia was induced following a standardized procedure. Postoperative pain and sedation levels were assessed using a VAS and the Ramsay Sedation Score. The incidence of PONV; the use of rescue antiemetic (ie, metoclopramide 10 mg given if two or more emetic episodes occurred or nausea persisted for more than 10 minutes); the postoperative Ramsay Sedation Score; and the VAS pain score were assessed one, two, and 24 hours after surgery. The severity of nausea was assessed using a verbal numerical rating scale ranging from zero to 10, with zero representing "no nausea" and 10 representing "the worst nausea possible." Any side effects that the patients reported and all episodes of vomiting were recorded. Either vomiting or retching was considered to be vomiting, and complete response was defined as no PONV and no administration of rescue antiemetic during the first 24 hour after anesthesia. Common statistical techniques including the Mann-Whitney test were used to analyze the data.

FINDINGS. Eighty patients were enrolled in and completed the study. There was no difference between the two groups in the Ramsay Sedation Scores and VAS pain scores at one, two, and 24 hours after surgery. Anxiety level was significantly lower in group M D after mirtazapine administration compared with group D (65 [ or -] 11 versus 44 [ or -] 10, P < .05). The incidence of vomiting over zero to 24 hours was significantly less in group M D (7.5% versus 30%, P < .01). Additionally, the complete response rate was higher (80% versus 50%, P < .01) and the requirement for rescue antiemetic administration was significantly less in group M D (5% versus 27.5%, P < .01).

CLINICAL IMPLICATIONS, The results of this study revealed that for women undergoing gynecologic surgery who are at moderate risk for PONV, premedication with mirtazapine 30 mg one hour before surgery reduced preoperative anxiety as well as the incidence of late PONV. The researchers noted, however, that additional studies are required to compare the safety and efficacy of mirtazapine as PONV prophylaxis with other serotonin 5-[HT.sub.3] receptor antagonists. Perioperative nurses should be prepared to participate in such studies.