SJA_227_12R5 ORIGINAL ARTICLE Page | 107 1 1 2 2 3 Granisetron versus tropisetron in the prevention 3 4 4 5 of postoperative nausea and vomiting after total 5 6 6 7 thyroidectomy 7 8 8 9 9 10 Artemisia Papadima, 10 11 ABSTRACT 11 Stavros Gourgiotis1, 12 Background: Postoperative nausea and vomiting (PONV) are frequently encountered 12 1 13 Emmanuel Lagoudianakis , after thyroidectomy. For PONV prevention, selective serotonin 5‑hydroxytryptamine 13 2 type 3 (5‑HT ) receptor antagonists are considered one of the first‑line therapy. We 14 Apostolos Pappas , 3 14 15 Charalampos Seretis1, report on the efficiency of granisetron and tropisetron, with that of placebo on the 15 prevention of PONV in patients undergoing total thyroidectomy. Methods: One hundred 2 16 Pantelis T. Antonakis , twenty‑seven patients were divided into three groups and randomized to receive 16 17 Haridimos Markogiannakis2, intravenously, prior to induction of anesthesia, tropisetron 5 mg, or granisetron 3 mg, 17 18 Ira Makri, or normal saline. All patients received additionally 0.625 mg droperidol. All episodes of 18 postoperative PONV during the first 24 h after surgery were evaluated. Results: Nausea 19 2 19 20 Andreas Manouras visual analogue scale (VAS) score was lower in tropisetron and granisetron groups than 20 21 Departments of Anesthesiology, the control group at all measurements (P<0.01) except for the 8‑h measurement for 21 Hippocrateion Hospital, 1Surgical, tropisetron (P=0.075). Moreover, granisetron performed better than tropisetron (P<0.011 22 401 General Army Hospital of at 4 h and P<0.01 at all other points of time) apart from the 2‑h measurement. Vomiting 22 23 Athens, 2Propedeutic Surgery, occurred in 22.2%, 27.5%, and 37.5% in granisetron, tropisetron, and control groups, 23 Hippocrateion Hospital, Athens 24 respectively (P=0.43). Conclusions: The combination of the 5‑HT3 antagonists with 24 Medical School, University of droperidol given before induction of anesthesia is well tolerated and superior to droperidol 25 Athens, Athens, Greece 25 26 alone in preventing nausea but not vomiting after total thyroidectomy. 26 27 Address for correspondence: 27 28 Dr. Stavros Gourgiotis, 28 29 41 Zakinthinou Street, 15669, 29 30 Papagou, Athens, Greece. Key words: Nausea, vomiting, thyroidectomy, granisetron, tropisetron 30 E‑mail: [email protected] 31 31 32 32 33 33 34 postoperative recovery.[5,6] Uncontrolled PONV remains 34 INTRODUCTION 35 the leading cause of delayed discharge or unexpected 35 36 readmission after ambulatory surgery.[7] Furthermore, it is 36 37 Postoperative nausea and vomiting (PONV) are two 37 of the most common and distressing complications a risk factor for postoperative bleeding, a complication of 38 particular concern due to the potential for neck hematoma 38 after anesthesia and surgery, and may lead to serious [5,8] 39 [1,2] formation and airway obstruction. Its incidence varies, 39 40 postoperative complications. The overall incidence of 40 PONV has been reported to be between 20% and 30%,[3] according to numerous anesthesia‑ and non–anesthesia‑ 41 related factors, yet remaining quite frequent.[9,10] PONV, 41 42 whereas reported incidence of PONV is between 63% and 42 84% in patients scheduled for thyroidectomy.[4] regardless of clinical severity, is an important issue from 43 the patients’ point of view[11]; improvement of the quality 43 44 44 PONV may represent the principal source of discomfort of care should therefore include reduction of the incidence 45 and severity of PONV.[12] 45 46 of the entire procedure and the most unpleasant aspect of 46 47 47 Access this article online Prevention strategies with drugs and nonpharmacologic 48 [13‑17] 48 Quick Response Code: interventions have been studied extensively. Serotonin 49 Website: receptor antagonists, particularly 5‑hydroxytryptamine 49 50 www.saudija.org 50 type 3 (5‑HT3) receptor antagonists, are an essential 51 constituent of prophylactic or rescue treatment of PONV 51 [18] 52 DOI: in patients at risk, according to respective guidelines. The 52 53 *** theoretic basis for these antagonists is sound, since they 53 54 54 exert their effects by binding to the 5‑HT3 receptor in the Saudi Journal of Anaesthesia Vol. 7, Issue 1, January-March 2013 Papadima, et al.: Prevention of postoperative nausea and vomiting Page | 108 1 chemoreceptor trigger zone and at vagal afferent neurons induction of anesthesia. All i.v. regimens were diluted with 1 2 in the gastrointestinal tract. Moreover, their side effects are N/S 0.9% to a volume of 5 mL. Upon entrance to the 2 3 minimal and especially their lack of sedation properties operative room schedule, a code number was assigned to 3 4 makes them particularly suitable for ambulatory surgery.[19] each patient. The anesthesiologist and staff nurses, as well 4 5 as the operative team, were blinded to the administered 5 6 Preclinical studies have indicated possible differences agent. 6 7 between tropisetron and granisetron.[20] Unlike granisetron 7 8 (an indazole), tropisetron is an indole compound. It has Protocol 8 9 high affinity and specificity for 5‑HT3 receptors but appears The anesthetic technique was identical in all patients. 9 10 to have a weak antagonistic effect on 5‑HT4 receptors, Patients fasted for at least 12 h preoperatively and received 10 11 whereas granisetron show no affinity for any other than oral premedication with 1.5 mg of bromazepam and 11 12 5‑HT3 receptors. Metabolism of tropisetron occurs 40 mg of omeprazol the night before surgery and 3 h 12 13 predominantly in the liver. before the operation. Ten minutes before induction to 13 14 anesthesia, all patients received 2.5 mg of midazolam and 14 15 The aim of this prospective, randomized, double‑blind, then parecoxib (40 mg/2 mL i.v.). In all cases, propofol 15 16 placebo‑controlled study was to evaluate and compare the 2 mg/kg and remifentanil 1 µg/kg were the induction 16 17 efficiency of tropisetron for preventing PONV compared drugs and cis‑atracurium 0.2 mg/kg was administered 17 18 with that of granisetron or placebo in patients undergoing for muscle relaxation. Meperidine (1 mg/kg) was 18 19 total thyroidectomy during the first 24 postoperative hours. intramuscularly (i.m.) administered after induction, and 19 20 maintenance of anesthesia was achieved with sevoflurane 20 21 METHODS minimum alveolar concentration (MAC) 1.0%‑1.5% in a 21 22 22 mixture of O2 to air and remifentanil in continuous infusion 23 Patients in this study were prospectively randomized (0.15‑0.2 µg/kg/min). 23 24 and data were prospectively recorded; then, data were 24 25 retrospectively collected and analyzed. After obtaining Nasogastric decompression was not employed, as patients 25 26 approval from the Ethical Committee of our hospital, were also included in a clinical audit, evaluating the 26 27 and after written informed consent, male or female necessity of nasogastric tube insertion in thyroid surgery. 27 28 patients scheduled for total thyroidectomy under general Intraoperative monitoring included electrocardiogram, 28 29 anesthesia from January 2009 until January 2010 were heart rate, arterial blood pressure (noninvasive method), 29 30 30 evaluated for study enrollment. Inclusion criteria were end expiratory CO2, O2 saturation, minute/volume, tidal 31 age between 18 and 75 years and American Society of volume, respiratory rate, airway pressures, and MAC 31 32 Anesthesiologists (ASA) physical status I or II. sevoflurane. Pulmonary ventilation was performed under 32 33 intermittent positive pressure ventilation (IPPV) with a 33 34 mixture of oxygen and air, maintaining fractional inspired 34 Exclusion criteria were known hypersensitivity to 5‑HT3 35 35 drugs, body mass index (BMI) ≥35, significant systemic oxygen (FiO2) at 0.5. Ventilation was adjusted to keep the 36 36 diseases, history of atypical or known gastrointestinal end‑tidal CO2 between 35 and 40 mmHg. Blood pressure 37 problems and/or previous gastrointestinal operations (not and heart rate variations were maintained within 20% of 37 38 including appendectomy), menstruation on admission, preoperative values by adjusting anesthetic depth, fluid 38 39 39 history of tinnitus, and reception of steroids, H2 antagonists, replacement, and vasoactive drug dosages. Adductor 40 anticholinergics, antihistamines, butyrophenones, pollicis stimulation over the ulnar nerve at the wrist was the 40 41 phenothiazines, or metoclopramide 24 h before admission. standard method of monitoring neuromuscular function. 41 42 Patients with an intrathoracic goiter or undergoing a Train‑of‑four (TOF) stimulations were used to assess the 42 43 difficult endotracheal intubation (more than two attempts presence of a residual neuromuscular block. No alternative 43 44 at tracheal intubation) were also excluded. No grants or forms of analgesic were administered to the patients. 44 45 funds from pharmaceutical companies were acquired. Atropine 1 mg and neostigmine 2.4 mg were used to 45 46 reverse residual neuromuscular blockade. All patients were 46 47 Study patients were enrolled and randomized with extubated on the operating table and were transported to 47 48 Bernoulli tables (which allow “complete” or “unrestricted” the postanesthesia care unit (PACU) with supplemental 48 49 randomization, minimizing both selection and accidental oxygen in consciousness with adequate self‑maintained 49 50 biases), to receive prophylactic either intravenous (i.v.) respiratory and cardiovascular function. 50 51 tropisetron 5 mg (1 mg/mL) (T group), i.v. granisetron 51 52 3 mg (G group), or i.v. 5 mL normal saline (N/S) Postoperative care 52 53 0.9% (control group, C group) in combination with Postoperatively, patients were observed for 24 h. A team 53 54 0.625 mg droperidol, approximately 5 min before of specially trained nurse anesthetists, blinded to the 54 Vol. 1, Issue 1, January-March 2013 Saudi Journal of Anaesthesia Papadima, et al.: Prevention of postoperative nausea and vomiting Page | 109 1 patient’s group, collected postoperative data.