Wang, Jhi-Joung MD, DMSc*‡; Ho, Shung-Tai MD*; Lee, Shih-Chun MD†; Liu, Yao-Chi MD†; Ho, Chiu-Ming MD*
Postoperative nausea and vomiting (PONV) are common and unpleasant experiences associated with surgery (1,2). PONV after thyroidectomy is especially frequent, with previous studies reporting a rate of 60%–76% (3–6). Several studies have demonstrated that dexamethasone, a corticosteroid, has a potent antiemetic effect for the prophylaxis of PONV. The commonly used doses were 8–10 mg IV (6–10). In a previous study, we have shown that dexamethasone 10 mg significantly reduces the incidence of PONV in female patients undergoing thyroidectomy, but the minimum effective dose of dexamethasone for this purpose was not determined (6). Thus, the present study was undertaken to determine this dose of dexamethasone for the prevention of PONV, in a randomized, double-blinded comparison with placebo, in women undergoing thyroidectomy.
After obtaining IRB approval, written, informed consent was obtained from 225 adult female patients undergoing elective partial or total thyroidectomy. All patients were in a physiologically euthyroid state. Patients who had a history of PONV, motion sickness, gastrointestinal disorders, or receipt of antiemetic within 24 h before surgery were excluded from participation. Those patients who had an intrathoracic goiter or suffered from a difficult endotracheal intubation (more than two attempts at tracheal intubation) at the induction of anesthesia were also excluded. Patients provided detailed medical histories and demographic information, including age, weight, height, drug consumption, last menstrual cycle, as well as any history of PONV or motion sickness.
Before the study, a randomization table was used to assign patients to one of five groups (45 patients in each group). Immediately after the induction of anesthesia, patients received IV dexamethasone at doses of 10 mg (D10), 5 mg (D5), 2.5 mg (D2.5), 1.25 mg (D1.25), or saline (S), which was prepared as 2 mL of clear solution in identical syringes. 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 keep 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 head slightly hyperextended. At the completion of the operation, 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. A team of specially trained nurse anesthetists without knowledge of which drugs the patients had received collected the postoperative data. During the observation period, arterial blood pressure, heart rate, and respiratory rate were monitored every 4 h except when patients were asleep.
PONV was evaluated by the following variables: the incidences of nausea and vomiting, episodes of vomiting, rescue antiemetics, and complete responses. For the purpose of data collection, retching (same as vomiting but without expulsion of gastric contents) was considered vomiting. A vomiting episode was defined as the events of vomiting that occurred in a rapid sequence (<1 min between events). If events of vomiting were separate by >1 min, they were considered separate episodes (11). Vomiting that occurred more than four times within 24 h was considered severe. Rescue antiemetics (IV ondansetron 4 mg) were given if vomiting occurred or at the patient’s request. The treatment was repeated if necessary. The complete response was defined as no vomiting and no antiemetic medication during the 24-h postoperative period, and this was also the primary efficacy end point of the study. The PONV data were collected every 4 h, except when patients were asleep, by direct questioning by a team of specially trained nurse-anesthetists or by spontaneous complaint of the patients.
Postoperative pain was assessed with a 10-cm visual analog scale (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 side effects accompanying dexamethasone usage, such as wound infection or delayed wound healing, was evaluated and reported (by Y-CL). Duration of hospital stay was recorded also.
Sample size was predetermined by using a power analysis based on the assumptions that (a) the total incidence of nausea and vomiting in the saline group would be 60% (3–6), (b) a 30% reduction in the total incidence of nausea and vomiting (from 60% to 42%) in the treatment group would be of clinical relevance, and (c) α = 0.05, β = 0.1 (12). The analysis showed that 40 patients per group would be sufficient to detect the antiemetic effect of a small dose of dexamethasone (1.25 mg). A series of one-way analyses of variance were conducted to examine differences among the five 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 five groups with respect to nonparametric variables, followed by the Mann-Whitney ranked sum test for intergroup differences. Categorical variables were analyzed by using a series of 5×2 χ2 tests to determine differences among the five groups, followed by 2×2 χ2 tests or Fisher’s exact tests, as appropriate, for intergroup differences. All follow-up analyses were corrected for the number of simultaneous contrasts by using the Bonferroni adjustments. A P value <0.05 was considered significant.
Of the 225 patients enrolled in the study, 8 suffered from difficult intubations and were eliminated from the study. The data obtained from the remaining 217 patients were analyzed. Patient characteristics, such as age, weight, and height, as well as last menstrual cycle, duration of operation and anesthesia, the total doses of perioperative fentanyl, and duration of hospital stay were similar among the five groups (Table 1). During the 24-h observation period, arterial blood pressure, heart rate, and respiratory rate were stable and were not significantly different among groups.
Table 2 demonstrates the incidences of PONV. Groups D10 and D5 were significantly different from Group S in the following variables: the total incidences of nausea and vomiting, more than four vomiting episodes, the proportions of patients requiring rescue antiemetics, and the incidences of complete responses. The differences between Groups D10 and D5 were not significant. Dexamethasone 2.5 mg significantly reduced the total incidence of nausea and vomiting, but not the other variables in the saline control. The differences between Group D1.25 and Group S were not significant.
Within the 24-h observation period, there were no significant differences among groups regarding the percentage of patients requiring rescue analgesic for pain on the surgical site (26%–38%). The visual analog scale scores of wound pain (mean) among groups were similar (visual analog scale scores, 2.5–3.5). No patient reported wound infection or delayed wound healing during her stay in hospital.
PONV is one of the most common and annoying side effects after surgery performed under general anesthesia (1,2). The incidence of PONV after thyroidectomy in women under general anesthesia is relatively frequent (3–6). Risk factors, such as sex (female population), intense perioperative parasympathetic nerve stimulation, use of isoflurane, fentanyl or glycopyrrolate, and postoperative pain, may all contribute to these episodes (1–6). We controlled all of these factors within our study design. All patients were women who underwent thyroidectomy performed by the same team of anesthetists and surgeons. As predicted, the duration of anesthesia, operation, and the anesthetic drugs used (e.g., isoflurane, fentanyl, glycopyrrolate) were similar among groups. Postoperative wound pain was also similar among groups. Therefore, the differences in the occurrence of PONV among groups can be attributed to the differences in doses of dexamethasone administered.
Many articles have been published suggesting the use of dexamethasone as a prophylactic antiemetic for PONV (6–10). The commonly used doses are 8–10 mg IV. We recently demonstrated that dexamethasone 10 mg significantly reduces the incidence of PONV in female patients undergoing thyroidectomy, but the minimum effective dose of dexamethasone for this purpose was not determined (6). In the current study, the antiemetic effects of various doses of dexamethasone were evaluated. We found that dexamethasone 10 mg and 5 mg were more effective than saline control for the prevention of PONV associated with thyroidectomy. Dexamethasone 2.5 mg was partially effective and dexamethasone 1.25 mg was ineffective. Dexamethasone 5 mg IV may be the minimum effective dose for this purpose.
Although the minimum effective dose of dexamethasone in preventing PONV associated with major gynecologic surgery was suggested to be 2.5 mg in a recent report (13), we found that dexamethasone 2.5 mg was only partially effective for this purpose in patients undergoing thyroidectomy. This discrepancy may be explained by different applications and the relatively weak antiemetic effect of dexamethasone 2.5 mg.
The long-term administration of corticosteroids causes side effects such as increased risk of infection, glucose intolerance, delayed wound healing, superficial ulceration of gastric mucosa, and adrenal suppression (14). However, these side effects were not related to a single dose of dexamethasone (6–10). In the current study, no discernible side effect accompanying a single dose of dexamethasone 1.25 to 10 mg was found (e.g., wound infection or delayed wound healing), and there was no prolonged hospital stay.
Among the currently used antiemetics, 5-HT3 antagonists (e.g., ondansetron, granisetron) are effective, but their cost limits their widespread clinical application (1,4,9). Other antiemetics such as antihistamines (e.g., hydroxyzine), anticholinergics (e.g., scopolamine), and dopamine receptor antagonists (e.g., droperidol, metoclopramide) have undesirable side effects of excessive sedation, tachycardia, drug mouth, dysphoria, and extrapyramidal symptoms (1,4,9,10,15). Because a single dose of dexamethasone demonstrated a significant antiemetic effect without evident side effects (6–10), it is a valuable treatment for the prophylaxis of PONV.
In conclusion, dexamethasone 5 mg was as effective as dexamethasone 10 mg and was more effective than saline control for preventing PONV in women undergoing thyroidectomy. Dexamethasone 2.5 mg was partially effective and dexamethasone 1.25 mg was ineffective for this purpose. Dexamethasone 5 mg IV is suggested to be the minimum effective dose in this patient population.
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