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Anesth Analg 1999;89:200
© 1999 International Anesthesia Research Society

GENERAL ARTICLES

The Prophylactic Effect of Dexamethasone on Postoperative Nausea and Vomiting in Women Undergoing Thyroidectomy: A Comparison of Droperidol with Saline

Jhi-Joung Wang, MD, DMSc*,{ddagger}, Shung-Tai Ho, MD*, Shih-Chun Lee, MD{dagger}, Yao-Chi Liu, MD{dagger}, Yun-Hou Liu, MD{ddagger}, and Yuan-Chung Liao, MD{ddagger}

Departments of *Anesthesiology and {dagger}Surgery, Tri-Service General Hospital, National Defense Medical Center; and {ddagger}Department of Anesthesiology, Cathay General Hospital, Taipei, Taiwan

Address correspondence and reprint requests to Jhi-Joung Wang, MD, DMSc, Department of Anesthesiology, Tri-Service General Hospital/National Defense Medical Center, No. 8, Sec. 3, Ting-Chow Rd., Taipei, Taiwan. Address e-mail to painlab{at}tpts5.seed.net.tw


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
The aim of this study was to evaluate the prophylactic effect of dexamethasone on postoperative nausea and vomiting (PONV) in women undergoing thyroidectomy. Droperidol and saline served as controls. One hundred twenty women (n = 40 in each of three groups) undergoing thyroidectomy under general anesthesia were enrolled in this randomized, double-blinded, placebo-controlled study. Immediately before the induction of anesthesia, Group 1 received IV dexamethasone 10 mg, whereas Groups 2 and 3 received IV droperidol 1.25 mg and saline, respectively. We found that both dexamethasone and droperidol significantly decreased the total incidence of PONV compared with saline, with an incidence of 32%, 35%, and 76%, respectively (P < 0.01; Group 1 versus Group 3, Group 2 versus Group 3). Patients who received droperidol, however, reported a higher intensity of sore throat and a more frequent incidence of restlessness than those who received dexamethasone. We conclude that, although both dexamethasone and droperidol are effective as prophylactic antiemetics in women undergoing thyroidectomy, droperidol produces more side effects.

Implications: We compared the prophylactic administration of dexamethasone to prevent nausea and vomiting with droperidol and saline in women undergoing thyroidectomy. Both dexamethasone and droperidol significantly reduced postoperative nausea and vomiting, but droperidol produced more side effects, which suggests that dexamethasone is a useful treatment in these patients.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Postoperative nausea and vomiting (PONV) are common after surgery (1,2). PONV after thyroidectomy is especially frequent, with previous studies reporting a rate of 63%–84% (3–6). Most of the currently used antiemetic drugs (e.g., anticholinergics, dopamine receptor antagonists, antihistamines) have clinically significant side effects (e.g., dysphasia, restlessness, dry mouth, changes in blood pressure, and extrapyramidal symptoms) (2,7,8).

Dexamethasone is effective in preventing the nausea and vomiting associated with cancer chemotherapy (9–12). Dexamethasone has also been found to be effective in preventing PONV in patients undergoing tonsillectomy and abdominal hysterectomy (13–18). Although dexamethasone may also prevent PONV in patients undergoing thyroidectomy, this has never been tested. The aim of this study was to evaluate the prophylactic effect of dexamethasone on PONV in women undergoing thyroidectomy. Droperidol, a commonly used antiemetic (19,20), and saline were used as controls.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
After obtaining institutional review board approval, written informed consent was obtained from 120 adult female patients undergoing elective partial or total thyroidectomy. All patients were in a physiologically euthyroid state. Patients who had an intrathoracic goiter, gastrointestinal disorders, a history of motion sickness, or who had received an antiemetic within 48 h before surgery were excluded from participation. In addition, patients who had suffered from a difficult endotracheal intubation (more than two attempts at tracheal intubation) at the induction of anesthesia were also excluded.

Before the study, a randomization table was used to assign patients into one of three groups. One minute before the induction of anesthesia, Group 1 received IV dexamethasone 10 mg (2 mL), Group 2 received IV droperidol 1.25 mg (2 mL), and Group 3 received IV saline (2 mL). The randomized process and the identity of the study drugs were blinded from the patients, the anesthetists during surgery, and the investigators who collected the postoperative data.

The anesthetic technique was identical in all patients. Anesthesia was induced with IV propofol (2–2.5 mg/kg), glycopyrrolate (0.2 mg) and fentanyl (2 µg/kg). Tracheal intubation was facilitated by the administration of IV vecuronium (0.15 mg/kg). Anesthesia was maintained with 1.0%–2.5% (inspired concentration) isoflurane in oxygen. Supplementary analgesia was provided with boluses of IV fentanyl 50–100 µg. Ventilation was controlled mechanically and adjusted to maintain an end-tidal concentration of CO2 between 30 and 40 mm Hg. Muscle relaxation was maintained with IV vecuronium. The thyroidectomy was performed with patients in the supine position, with the head slightly hyperextended. At the completion of the surgery, IV glycopyrrolate (0.6 mg) and neostigmine (3 mg) were administered for reversal of the residual paralysis, and the trachea was extubated.

Postoperatively, patients were observed for 24 h. During the observation period, arterial blood pressure, heart rate, and respiratory rate were monitored every 4 h except during sleep. Arterial oxygen saturation (SaO2) was monitored continuously.

PONV was evaluated on a 3-point ordinal scale: 0 = no symptoms, 1 = nausea (subjective unpleasant sensation with awareness of urge to vomit), 2 = vomiting (spasmodic contractions of abdominal wall and diaphragmatic muscles with forceful expulsion of gastric content). For the purpose of data collection, retching (same as vomiting but without expulsion of gastric content) was considered vomiting. All episodes of PONV were recorded every 4 h (except during sleep) by direct questioning by specifically trained nurses or by spontaneous complaint of the patients. Rescue antiemetics (IV ondansetron 4 mg) were given if vomiting occurred or at the patient's request. The treatment was repeated if necessary.

Postoperative pain at the surgical site was assessed by using a 10-cm visual analog scale (VAS; 0 = no pain to 10 = most severe pain) score. When patients complained of pain and requested analgesia, IM diclofenac 75 mg (every 12 h) was given.

The occurrence of a sore throat was recorded, and its intensity was assessed by using a 10-cm VAS score. A sore throat was treated with 7% povidone-iodine gargle solution. Restlessness, a common droperidol-related side effect (7), was also evaluated. Restlessness was defined as a sensation of nervousness with an inability to keep still or with unpleasant subjective promptings to move (7,8). Restlessness was treated with IM diphenhydramine 30 mg.

Sample size was predetermined. We expected a 30% difference among groups (13–18) in the proportion of patients requiring rescue IV ondansetron for PONV, given a standard deviation of 40%. The {alpha} error was set at 0.05 (two-sided) and the ß error at 0.10. The projected sample size was 37 patients. A series of one-way analyses of variance were conducted to examine differences among the three study groups with respect to parametric variables. If a significant difference was found, the Bonferroni t-test was used to detect the intergroup differences. The Kruskal-Wallis test was used to determine differences among the three groups with respect to nonparametric variables, followed by the Mann-Whitney rank-sum test for intergroup differences. Categorical variables were analyzed by using a series of 3 x 2 {chi}2 tests to determine differences among the three groups, followed by 2 x 2 {chi}2 test for intergroup differences. All follow-up analyses were corrected for the number of simultaneous contrasts using the Bonferroni adjustments. A P value <0.05 was considered significant.


   Results
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 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Of the 120 patients enrolled in the study, 4 patients had suffered from difficult intubations and were eliminated. The data obtained from the remaining 116 patients were analyzed. The patients' characteristics (e.g., age, weight, and height), duration of anesthesia and surgery, and the total doses of perioperative fentanyl were similar among the three groups (Table 1).


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  		Table 1. Patient Characteristics
 
During the 24-h observation period, arterial blood pressure, heart rate, and respiratory rate were stable and were not significantly different among the three groups. No patients demonstrated a SaO2 <90%.

The incidence of nausea was not different among the three groups (Table 2). However, patients in Group 1 or Group 2 had a less frequent incidence of nausea when combined with vomiting than those in Group 3 (P < 0.01; Group 1 versus Group 3, Group 2 versus Group 3) (Table 2). The differences between Group 1 and 2 were not significant.


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  		Table 2. Incidence of Nausea and/or Vomiting After Thyroidectomy
 
There were no significant differences among the three groups regarding the percentage of patients requiring rescue analgesic (29% in Group 1, 38% in Group 2, and 42% in Group 3) and the pain scores (medians) at the surgical site (2.5 in Group 1, 2.8 in Group 2, and 2.9 in Group 3) during the study period. Sore throat was reported by all patients, but its intensity varied among the groups. Patients in Group 1 reported a lower pain score of sore throat than those in the other two groups throughout the study period ( P < 0.01; Group 1 versus Group 2, Group 1 versus Group 3) (Table 3). Nine patients (23%) in Group 2 reported restlessness. In contrast, no patient in the other two groups reported the same symptom (P < 0.01; Group 1 versus Group 2, Group 3 versus Group 2).


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  		Table 3. Intensity of Sore Throat Using Visual Analog Scale Scores
 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
PONV is a common and distressing side effect in patients undergoing thyroidectomy (3–6). We found that the total incidence of PONV was 76% in patients undergoing thyroidectomy when no antiemetic was given prophylactically. After pretreatment with either dexamethasone or droperidol, the incidence of PONV was significantly reduced. Both dexamethasone and droperidol are effective in preventing PONV after thyroidectomy.

Several studies have demonstrated dexamethasone's efficacy with minimal adverse events in the prevention of nausea and vomiting associated with chemotherapy (9–12). Dexamethasone has also been found to be effective in the prevention of PONV in patients undergoing tonsillectomy and hysterectomy (13–18). In the present study, dexamethasone was also found to be effective in the prevention of PONV in patients undergoing thyroidectomy.

The etiology of PONV in patients undergoing thyroidectomy is not fully understood. Risk factors, such as gender (female population); intense perioperative parasympathetic nerve stimulation; use of isoflurane, fentanyl, or glycopyrrolate; and postoperative pain, may all contribute to these episodes (1–6). Because any of these factors could have interfered with the interpretation of the study results, we controlled for all of these factors within the study design. All patients were women who underwent thyroidectomy performed by the same team of anesthetists and surgeons. As predicted, the duration of anesthesia, surgery, and the anesthetics used (isoflurane, fentanyl, glycopyrrolate, etc.) were similar among the groups. In addition, postoperative pain at the surgical site was also similar among the groups. Therefore, the differences in the occurrence of PONV among the groups can be attributed to the study drugs.

The exact mechanism by which dexamethasone exerts an antiemetic action is not known, but it may involve central inhibition of prostaglandin synthesis and/or a decrease in serotonin turnover in the central nervous system (21,22). Despite these possible mechanisms, we also suggest that the strong antiinflammatory effect of dexamethasone on neck structures (e.g., pharynx, larynx, trachea, and surrounding tissues) may also play a role in its antiemetic effect in patients undergoing thyroidectomy. Dexamethasone has strong antiinflammatory actions and is extensively used in otolaryngology (13–15,23,24). In patients undergoing thyroidectomy, significant edema and inflammation around the neck tissues may sustain evoked parasympathetic impulses through vagus, recurrent laryngeal, and glossopharyngeal nerves to the vomiting center, thus initiating vomiting responses (1–6,25,26). Dexamethasone may significantly reduce tissue inflammation around the neck and thus reduce the ascending parasympathetic impulses to the vomiting center and reduce PONV.

Droperidol also has a potent antiemetic effect (19,20). Previous studies have demonstrated that its effect is equal to ondansetron and superior to metoclopramide in preventing PONV (19,20). The recommended dose for this purpose is 1.25 mg in female patients undergoing a laparoscopy (20). We also found droperidol 1.25 mg to be effective in preventing PONV in female patients undergoing thyroidectomy. However, restlessness was a frequent side effect. Although this side effect was relieved by the IM administration of diphenhydramine, it nevertheless produced marked mental distress in our patients.

Cost is an ever-increasing concern in today's healthcare system. Both of the prophylactic antiemetics we used are relatively inexpensive. Dexamethasone 10 mg cost $36 new Taiwan dollar (NT), whereas droperidol 1.25 mg cost $9 NT. This is remarkably less expensive than a similar effective dose of an alternate antiemetic, ondansetron, which cost $450 NT for a 4-mg dose. This is the reason ondansetron was not chosen as our first-line prophylactic antiemetic.

In conclusion, the prophylactic administration of either IV dexamethasone 10 mg or IV droperidol 1.25 mg significantly reduced the incidence of PONV in patients undergoing thyroidectomy. However, patients who received droperidol reported a higher intensity of sore throat and a more frequent incidence of restlessness than those receiving dexamethasone. We suggest that IV dexamethasone 10 mg is a useful treatment for preventing PONV in women undergoing thyroidectomy.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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Accepted for publication April 8, 1999.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins and Stanford University Libraries' HighWire Press®. Copyright 1999 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press