The Incidence of Postoperative Nausea and Vomiting after Thyroidectomy using Three Anaesthetic Techniques

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1 The Journal of International Medical Research 2011; 39: The Incidence of Postoperative Nausea and Vomiting after Thyroidectomy using Three Anaesthetic Techniques YJ WON 1, JY YOO 2, YJ CHAE 1, DH KIM 1, SK PARK 1, HB CHO 1, JS KIM 1, JH LEE 1 AND SY LEE 1 1 Department of Anaesthesia and Pain Medicine, Ajou University, School of Medicine, Youngtong-Gu, Suwon, Republic of Korea; 2 Department of Anaesthesia and Pain Medicine, Ansan Korea University Medical Centre, Danwon-Gu, Ansan, Republic of Korea The choice of anaesthetics can affect the incidence of postoperative nausea and vomiting (PONV). This study compared the incidence of PONV in 177 female patients who underwent thyroidectomy, with anaesthesia induced and maintained using one of three regimens: (i) sevoflurane (thiopental sodium 4 5 mg/kg and sevoflurane vol% in 50% air); (ii) total intravenous anaesthesia (TIVA; propofol remifentanil [target blood concentrations µg/ml and ng/ml, respectively]); or (iii) combined inhalation and intravenous anaesthesia (sevoflurane 1.0 vol% in 50% air plus propofol remifentanil [target blood concentrations µg/ml and ng/ml, respectively]). The incidence and severity of PONV and the need for rescue antiemetics were assessed at 0 24 h postoperatively. Overall, the incidence of PONV was significantly lower in the TIVA and combined groups compared with the sevoflurane group (33.9%, 39.0% and 64.4%, respectively). In conclusion, the maintenance of anaesthesia with propofol remifentanil or sevoflurane propofol remifentanil decreased the incidence of PONV compared with sevoflurane alone. KEY WORDS: THYROIDECTOMY; POSTOPERATIVE NAUSEA AND VOMITING; SEVOFLURANE; PROPOFOL; REMIFENTANIL Introduction The incidence of postoperative nausea and vomiting (PONV) is estimated to be 20% 30% and is influenced by patient, anaesthetic and surgical factors. 1 7 Certain procedures such as thyroidectomy have been shown to have a high rate of PONV, with a reported incidence as high as 65% 75% As the practice of thyroid surgery shifts towards a shorter hospital stay, the importance of managing PONV increases because of its potential to delay discharge. 12 Additionally, vomiting may increase the risk of postoperative bleeding, which may potentially cause airway obstruction. 13 Compared with inhalational anaesthesia, total intravenous anaesthesia (TIVA) with propofol has been shown to decrease PONV, 10,11,14 17 especially in women. 10 Anaesthetic techniques without halogenated drugs show a relatively high incidence of awareness with recall during general 1834

2 anaesthesia. 18,19 Furthermore, commonly used TIVA combinations such as propofol remifentanil or propofol alfentanil show less haemodynamic stability compared with inhaled drugs. 20 For these reasons, we prefer to use combined anaesthesia with inhalational (sevoflurane) and intravenous (i.v.; propofol remifentanil) drugs. To our knowledge, however, there are no data on the incidence of PONV for combined anaesthesia. The present study compared the incidence of PONV in female patients who underwent thyroidectomy with anaesthesia maintained by sevoflurane, propofol remifenanil or sevoflurane propofol remifentanil. Patients and methods STUDY POPULATION Consecutive female patients in a euthyroid state and scheduled to undergo thyroidectomy under general anaesthesia at the Department of Anaesthesia and Pain Medicine, Ajou University, School of Medicine, Youngtong-Gu, Suwon, Republic of Korea, between March 2009 and December 2010, were prospectively enrolled in the study. Patients had to be aged years and have an American Society of Anesthesiologists (ASA) physical classification status of 1 or 2 to be eligible for the study. 21 Patients 50% over their ideal body weight, patients with gastrointestinal disease or patients who had taken antiemetics within 24 h prior to surgery were excluded from the study. A medical history (including previous motion sickness, PONV and smoking) were recorded along with demographic data. The study was approved by the Institutional Review Board of Ajou University, School of Medicine, and patients provided written informed consent to participate in the study. ANAESTHESIA Before the induction of anaesthesia, patients were randomly allocated by sealed-envelope to one of the following anaesthesia groups: (i) sevoflurane group (inhalational anaesthesia); (ii) TIVA group; and (iii) combined group (inhalation and i.v. anaesthesia). For the sevoflurane group, anaesthesia was induced with thiopental sodium (4 5 mg/kg) and maintained with sevoflurane vol% in 50% air. For the TIVA group, anaesthesia was induced and maintained with propofol i.v. (target blood concentration µg/ml) and remifentanil i.v. (target blood concentration ng/ml) without the use of inhalational anaesthetics. For the combined group, anaesthesia was induced and maintained with sevoflurane 1.0 vol% in 50% air, propofol i.v. (target blood concentration µg/ml) and remifentanil i.v. (target blood concentration ng/ml). All patients were given 0.6 mg/kg rocuronium i.v. to facilitate tracheal intubation. The concentrations of propofol and remifentanil in blood were controlled using an infusion device (Orchestra Module DPS and Base Primea ; Fresenius Vial, Brézins, France) and the depth of anaesthesia was monitored using a Bispectral Index Monitor (Aspect Medical Systems, Norwood, MA, USA). Ventilation was mechanically controlled with an O 2 /air mixture (fractional inspired oxygen, 0.5) and adjusted to keep an endtidal concentration of carbon dioxide between 35 and 40 mmhg throughout the operation. Muscle relaxation was antagonized by a combination of glycopyrrolate mg/kg i.v. and pyridostigmine 0.03 mg/kg i.v. at the end of surgery. Postoperative analgesia was provided using ketorolac tromethamine 30 mg i.v. (Tarasyn, Roche Korea, Seoul, Republic of Korea) as required. 1835

3 STUDY ASSESSMENTS Postoperative assessments were made in the postanaesthesia care unit at 1 h by interview, and at 6 h and 24 h by telephone interviews and medical record reviews by nursing staff or trainees. Patients, nursing staff and trainees who were responsible for follow-up in the postoperative period were blinded to the patient s anaesthesia group. Nausea was defined as a subjective, unpleasant sensation associated with awareness of the urge to vomit. Retching was defined as the laboured, spastic, rhythmic contraction of the respiratory muscles without expulsion of the gastric contents. Vomiting was defined as the forceful expulsion of gastric contents from the mouth. Each episode was recorded as either present or absent. If the patients had nausea, severity was recorded using the following scale: 1, mild nausea; 2, moderate nausea; 3, severe nausea. If the patients had retching or vomiting, severity of episodes were recorded using the following scale: 1, one episode; 2, two episodes; 3, three or more episodes. Rescue antiemetic (metoclopramide 10 mg i.v.) was administered at the patient s request. At the end of the study period, general satisfaction was evaluated using a numerical scale ranging from 0 (complete satisfaction) to 3 (complete dissatisfaction). Any other adverse events that occurred were also recorded. STATISTICAL ANALYSES The sample size for the study was predetermined using a power analysis based on the following assumptions: the incidence of PONV in the sevoflurane group would be 60% (based on previous studies); 8 10 a decrease in the incidence of PONV from 60% to 30% could be considered clinically significant; and the value of α would be 0.05 with a power (1 β) of 0.9. The analysis showed that 52 patients per group would be sufficient to detect the effect of anaesthesia method on the development of PONV (the number of patients was increased per group to 59). Statistical evaluation of the data was carried out using the SPSS statistical package, version 17.0 (SPSS Inc., Chicago, IL, USA) for Windows. Parametric data (age, weight, height, anaesthesia time, operation time) were analysed using one-way analysis of variance. Post hoc comparisons were made with Bonferroni s correction. Differences in the distribution of nausea and retching/vomiting severity scores and satisfaction score were assessed using the linear-by-linear association test. Discrete variables (history of motion sickness, previous PONV, smoking, presence of PONV such as nausea, retching or vomiting, and adverse events) were analysed using the χ 2 - test. A P-value < 0.05 was considered to be statistically significant. Results The study included 177 female patients (n = 59 per group). There were no significant differences in the patients demographic data among the three groups (Table 1). The incidence of nausea, vomiting with nausea and total PONV is given in Table 2. During the early postoperative period (0 6 h), the incidence of PONV in the TIVA group and combined group was significantly decreased compared with the sevoflurane group (P = and P = 0.016, respectively; Table 2). During the same period, the incidence of vomiting in the TIVA group was significantly decreased compared with the sevoflurane group (P = 0.024) (Table 2). There was no significant difference in the incidence of nausea among the three groups in the 0 6 h postoperative period. During the late post-operative period (6 1836

4 TABLE 1: Demographic characteristics and anaesthesia data for female patients (n = 177) undergoing thyroidectomy using different anaesthesia regimens Sevoflurane group TIVA group Combined group Parameter (n = 59) (n = 59) (n = 59) Age, years 46.5 ± ± ± 9.6 Weight, kg 61.6 ± ± ± 14.4 Height, cm ± ± ± 15.4 Anaesthesia duration, min ± ± ± 55.9 Surgery duration, min ± ± ± 46.8 History of motion sickness 30 (50.8) 30 (50.8) 26 (44.1) History of PONV 6 (10.2) 5 (8.5) 4 (6.8) History of smoking 2 (3.4) 7 (11.9) 2 (3.4) Data presented as mean ± SD or number (%) of patients. There were no statistically significant differences among the groups (P > 0.05); one-way analysis of variance with Bonferroni s correction. Sevoflurane group, anaesthesia induction with thiopental sodium and maintenance with sevoflurane; Total intravenous anaesthesia (TIVA) group, anaesthesia induction and maintenance with propofol remifentanil; Combined group, anaesthesia induction and maintenance with sevoflurane propofol remifentanil; PONV, postoperative nausea and vomiting. TABLE 2: Postoperative incidence of nausea, vomiting with nausea and total nausea and vomiting (PONV) for female patients (n = 177) undergoing thyroidectomy using different anaesthesia regimens Sevoflurane group TIVA group Combined group Parameter (n = 59) (n = 59) (n = 59) 0 6 h Nausea only 21 (35.6) 15 (25.4) 14 (23.7) Vomiting with nausea 12 (20.3) 3 (5.1) a 5 (8.5) PONV 33 (55.9) 18 (30.5) b 19 (32.2) c Rescue antiemetics 11 (18.6) 6 (10.2) 8 (13.6) 6 24 h Nausea only 9 (15.3) 6 (10.2) 12 (20.3) Vomiting with nausea 4 (6.8) 4 (6.8) 3 (5.1) PONV 13 (22.0) 10 (16.9) 15 (25.4) Rescue antiemetics 0 (0) 1 (1.7) 2 (3.4) Overall Nausea only 22 (37.3) 14 (23.7) 16 (27.1) Vomiting with nausea 16 (27.1) 6 (10.2) d 7 (11.9) d PONV 38 (64.4) 20 (33.9) e 23 (39.0) f Rescue antiemetics 12 (20.3) 7 (11.9) 9 (15.3) Data presented as number (%) of patients. Statistically significant difference versus sevoflurane group: a P = 0.024; b P = 0.009; c P = 0.016; d P = 0.032; e P = 0.002; f P = 0.016; there were no significant differences between the TIVA and combined groups (P > 0.05); χ 2 -test. Sevoflurane group, anaesthesia induction with thiopental sodium and maintenance with sevoflurane; Total intravenous anaesthesia (TIVA) group, anaesthesia induction and maintenance with propofol remifentanil; Combined group, anaesthesia induction and maintenance with sevoflurane propofol remifentanil. 1837

5 24 h), there were no significant differences in the incidence of nausea, vomiting or PONV between the three groups (Table 2). During the first 24-h postoperative period overall, there was no significant difference in the incidence of PONV between the TIVA and combined groups (Table 2). During this period, the incidence of PONV in the TIVA group and the combined group was significantly decreased compared with the sevoflurane group (P = and P = 0.016, respectively; Table 2). During the same period, the incidence of vomiting in the TIVA group and the combined group was significantly decreased compared with the sevoflurane group (both comparisons P = 0.032; Table 2). There was no significant difference in the incidence of nausea among the three groups in the 0 24 h postoperative period. With regard to nausea severity, retching/vomiting severity and satisfaction score, there were no significant differences among the groups during the 0 6 and 6 24-h postoperative periods (Table 3). There were no significant differences among the TABLE 3: Postoperative nausea severity, retching/vomiting severity and satisfaction scores for female patients (n = 177) undergoing thyroidectomy using different anaesthesia regimens Sevoflurane TIVA Combined Postoperative group group group Parameter period (h) Score (n = 59) (n = 59) (n = 59) Nausea severity Retching/vomiting severity Satisfaction score Data presented as number of patients. There were no statistically significant differences among the groups (P > 0.05); linear-by-linear association test. Sevoflurane group, anaesthesia induction with thiopental sodium and maintenance with sevoflurane; Total intravenous anaesthesia (TIVA) group, anaesthesia induction and maintenance with propofol remifentanil; Combined group, anaesthesia induction and maintenance with sevoflurane propofol remifentanil. Nausea severity scale: 1, mild; 2, moderate; 3, severe. Retching/vomiting severity scale: 1, one episode; 2, two episodes; and 3, three or more episodes. General satisfaction evaluated using a numerical scale: 0, complete satisfaction; 3 complete dissatisfaction. 1838

6 groups in the incidence of adverse events such as headache and dizziness during the 0 6 h and 6 24 h postoperative periods (Table 4). Discussion The present study showed that both the TIVA (propofol remifentanil) and combined anaesthesia (sevoflurane propofol remifentanil) methods decreased the incidence of PONV compared with inhalational anaesthesia (sevoflurane), with no significant differences between the TIVA and combined anaesthesia methods. Postoperative nausea and vomiting is a distressing and frequent adverse event that occurs as a result of surgery under anaesthesia, and has a reported incidence of 20% 30%. 1 Certain surgical procedures such as thyroidectomy are associated with a high incidence of PONV, which can reach 65% 75% Because patients typically have only mild to moderate pain after thyroid surgery, PONV may be perceived as the most unpleasant aspect of postperative recovery. Additionally, these symptoms predispose patients to aspiration of gastric contents, airway obstruction by haematoma, increased intraocular pressure, psychological distress and delayed discharge. 12,13 The cause of PONV after thyroidectomy is not clearly known, but it is probably related to several factors including sex, age and intense vagal stimulation (through surgical handling of the neck structure). 8,9 Other factors such as obesity, history of motion sickness, previous PONV, smoking and anaesthetic technique are also considered to affect the incidence of PONV. 1 7 The three groups in the present study were comparable with respect to patient demographics and type of operation. Thus, the differences in the incidence of PONV among these groups can safely be attributed to the anaesthetic drugs administered. It is unlikely that changes in the level of circulating thyroid hormones played a role in the production of nausea because, as part of the preoperative preparation, the patients were known to be in the euthyroid state at the time of surgery. The use of inhalational drugs is known to be a principal cause of PONV, especially during the early postoperative period. 6,22 Furthermore, nitrous oxide may increase the incidence of PONV. In a recent meta-analysis by Fernández-Guisasola et al. 23 PONV following anaesthesia increased from 27% without nitrous oxide to 33% with nitrous oxide. In previous studies, the incidence of PONV was reported to be as high as 71% when isoflurane and nitrous oxide were used for women who underwent TABLE 4: Postoperative (0 24 h) adverse events recorded for female patients (n = 177) undergoing thyroidectomy using different anaesthesia regimens Sevoflurane group TIVA group Combined group Adverse event (n = 59) (n = 59) (n = 59) Headache Dizziness Total Data presented as number of patients. There were no statistically significant differences among the groups (P > 0.05); χ 2 -test. Sevoflurane group, anaesthesia induction with thiopental sodium and maintenance with sevoflurane; Total intravenous anaesthesia (TIVA) group, anaesthesia induction and maintenance with propofol remifentanil; Combined group, anaesthesia induction and maintenance with sevoflurane propofol remifentanil. 1839

7 thyroidectomy. 9,10 The overall incidence of PONV in the present study was 64.4% when sevoflurane was administered without nitrous oxide for maintenance of anaesthesia. The use of propofol to maintain anaesthesia has been associated with a lower incidence of PONV. 8 11,14,17 Several antiemetic mechanisms for propofol have been postulated, including direct depression of the chemoreceptor trigger zone and centres implicated in nausea and vomiting. 24 Weak 5-hydroxytryptamine receptor type 3 antagonistic effects have been suggested. 25 The proposed concentration ranges for sedation and general anaesthesia using propofol are ng/ml and ng/ml, respectively, and the proposed concentrations required to treat PONV are lower than these values. 24,29 Gan et al. 24 and Gepts et al. 29 reported antiemetic plasma propofol concentrations of ng/ml and 424 ng/ml, respectively. Opioids induce PONV by various mechanisms including: a direct effect on the chemoreceptor trigger zone in the area postrema of the brain stem; sensitization of the vestibular organs to movement-induced emesis; increase of gastrointestinal secretion; gastric hypomotility; and delayed gastric emptying. 1,30 Remifentanil is a nonaccumulative ultra-short-acting opioid with a half-life of 8 10 min, 31 which could contribute to faster weaning from opioid side-effects such as PONV. The effect of remifentanil on the incidence of PONV is, however, unclear. Recently, Oh et al. 32 demonstrated that combining remifentanil with sevoflurane did not increase the incidence of PONV compared with sevoflurane alone. In other studies, TIVA with propofol remifentanil demonstrated a decrease in PONV The present study demonstrated that the incidence of PONV was significantly reduced in patients receiving TIVA with propofol remifentanil compared with those receiving sevoflurane alone, which was consistent with previous studies performed in other types of surgery Furthermore, combined anaesthesia with sevoflurane propofol remifentanil also significantly decreased the incidence of PONV compared with sevoflurane alone, but there was no significant difference in the incidence of PONV between this combined regimen and TIVA. There may be several reasons for this outcome. First, target blood concentrations of propofol of µg/ml in the TIVA group and µg/ml in the combined anaesthesia group were used, both of which are higher than the proposed antiemetic concentration. 24,29 Secondly, a lower concentration of sevoflurane was used for the combined group compared with that used for the sevoflurane group (1.0 vol% versus vol%). Gauger et al. 11 demonstrated that propofol decreased early, rather than late, PONV. The incidence of PONV in the present study was mainly decreased during the 0 6 h postoperative period, and was consistent with this previous result. 11 There were no significant differences among the three groups in terms of nausea severity scores, retching/vomiting severity scores and satisfaction scores. Additionally, the incidence of adverse events, such as headache and dizziness, was not significantly different among the three groups. A limitation of the present study was that no data were collected on the incidence of awareness with recall and haemodynamic stability. In the postanaesthesia care unit, however, no patients in the sevoflurane and combined anaesthesia groups complained of awareness with recall, and no significant 1840

8 incidences of hypotension or bradycardia were recorded. In summary, compared with sevoflurane alone, both TIVA (propofol remifentanil) or combined anaesthesia (sevoflurane propofol remifentanil) can produce the same decrease in PONV in female patients undergoing thyroidectomy. Conflicts of interest The authors had no conflicts of interest to declare in relation to this article. Received for publication 6 April 2011 Accepted subject to revision 11 April 2011 Revised accepted 11 August 2011 Copyright 2011 Field House Publishing LLP References 1 Watcha MF, White PF: Postoperative nausea and vomiting. Its etiology, treatment, and prevention. Anesthesiology 1992; 77: Palazzo MG, Strunin L: Anaesthesia and emesis. I: Etiology. Can Anaesth Soc J 1984; 31: Apfel CC, Läärä E, Koivuranta M, et al: A simplified risk score for predicting postoperative nausea and vomiting: conclusions from crossvalidations between two centers. Anesthesiology 1999; 91: Lerman J: Surgical and patient factors involved in postoperative nausea and vomiting. Br J Anaesth 1992; 69(7 suppl 1): 24S 32S. 5 Rabey PG, Smith G: Anaesthetic factors contributing to postoperative nausea and vomiting. Br J Anaesth 1992; 69(7 suppl 1): 40S 45S. 6 Apfel CC, Kranke P, Katz MH, et al: Volatile anaesthetics may be the main cause of early but not delayed postoperative vomiting: a randomized controlled trial of factorial design. Br J Anaesth 2002; 88: Sinclair DR, Chung F, Mezei G: Can postoperative nausea and vomiting be predicted? Anesthesiology 1999; 91: Ewalenko P, Janny S, Dejonckheere M, et al: Antiemetic effect of subhypnotic doses of propofol after thyroidectomy. Br J Anaesth 1996; 77: Sonner JM, Hynson JM, Clark O, et al: Nausea and vomiting following thyroid and parathyroid surgery. J Clin Anesth 1997; 9: Vari A, Gazzanelli S, Cavallaro G, et al: Postoperative nausea and vomiting (PONV) after thyroid surgery: a prospective, randomized study comparing totally intravenous versus inhalational anesthetics. Am Surg 2010; 76: Gauger PG, Shanks A, Morris M, et al: Propofol decreases early postoperative nausea and vomiting in patients undergoing thyroid and parathyroid operations. World J Surg 2008; 32: Mowschenson PM, Hodin RA: Outpatient thyroid and parathyroid surgery: a prospective study of feasibility, safety, and costs. Surgery 1995; 118: Kovac AL: Prevention and treatment of postoperative nausea and vomiting. Drugs 2000; 59: Visser K, Hassink EA, Bonsel GJ, et al: Randomized controlled trial of total intravenous anesthesia with propofol versus inhalation anesthesia with isoflurane nitrous oxide: postoperative nausea with vomiting and economic analysis. Anesthesiology 2001; 95: Brooker CD, Sutherland J, Cousins MJ: Propofol maintenance to reduce postoperative emesis in thyroidectomy patients: a group sequential comparison with isoflurane/nitrous oxide. Anaesth Intensive Care 1998; 26: Borgeat A, Wilder-Smith OH, Saiah M, et al: Subhypnotic doses of propofol possess direct antiemetic properties. Anesth Analg 1992; 74: Soppitt AJ, Glass PS, Howell S, et al: The use of propofol for its antiemetic effect: a survey of clinical practice in the United States. J Clin Anesth 2000; 12: Miller DR, Blew PG, Martineau RJ, et al: Midazolam and awareness with recall during total intravenous anaesthesia. Can J Anaesth 1996; 43: Errando CL, Sigl JC, Robles M, et al: Awareness with recall during general anaesthesia: a prospective observational evaluation of 4001 patients. Br J Anaesth 2008; 101: Vuyk J, Engbers FH, Burm AG, et al: Pharmacodynamic interaction between propofol and alfentanil when given for induction of anesthesia. Anesthesiology 1996; 84: Barash PG, Cullen BF, Stoelting RK (eds): Clinical Anesthesia, 5th edn. Philadelphia; Lippincott Williams and Wilkins, 2005: pp Apfel CC, Stoecklein K, Lipfert P: PONV: a problem of inhalational anaesthesia? Best Pract Res Clin Anaesthesiol 2005; 19: Fernández-Guisasola J, Gómez-Arnau JI, Cabrera Y, et al: Association between nitrous oxide and the incidence of postoperative nausea and vomiting in adults: a systematic 1841

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