Dexamethasone is a corticosteroid with strong antiinflammatory and prolonged antiemetic effects. It is a safe and effective antiemetic in patients receiving cancer chemotherapy (1–4). Though it reduces the incidence of postoperative vomiting (5–10) and surgery-related side effects, such as delayed wound healing and increased incidence of wound infection, the cautious use of dexamethasone in surgical patients is recommended. Studies in which dexamethasone was administered in doses of 8 mg orally, 0.15 mg/kg up to 8 mg, as well as dexamethasone 1 mg/kg up to 25 mg IV have reported favorable results for postoperative antiemesis (8–10). This randomized double-blind, dose-ranging study was undertaken to determine the minimum effective dose of dexamethasone for postoperative antiemesis in patients undergoing general anesthesia for major gynecological surgery.
After obtaining approval from the Human Investigation Committee and informed patient consent, one-hundred fifty ASA physical status I–II patients undergoing general anesthesia for elective major gynecological procedures were enrolled in this study. Patients with a history of motion sickness, gastrointestinal disturbances, postoperative nausea and vomiting (PONV) after general anesthesia, or who were menstruating or under hormonal therapy were excluded.
Immediately before the induction of anesthesia, patients were randomly assigned to 5 groups of 30 patients to receive dexamethasone, at doses of 10 mg (D10), 5 mg (D5), 2.5 mg (D2.5), 1.25 mg (D1.25), or saline (placebo) (P), which was prepared as 2 mL of clear solution in an identical syringe. Anesthesia was induced with fentanyl 2 μg/kg and diazepam 0.15 mg/kg IV. Tracheal intubation was facilitated with lidocaine 1.5 mg/kg, thiopental 4 mg/kg, and succinylcholine 1.5 mg/kg. General anesthesia was maintained with isoflurane or halothane, 50% nitrous oxide in oxygen, and IV infusion of atracurium at a rate of 0.25 mg · kg−1 · h−1. At the end of surgery, the trachea was extubated when peripheral nerve stimulation indicated a train-of-four ratio more than 75% without the use of an anticholinesterase drug. Types of surgery included abdominal total hysterectomy, myomectomy, and radical hysterectomy. For postoperative analgesia, a patient-controlled analgesia (Abbott Pain Management Provider) pump was programmed to deliver morphine 1.5 mg IV on demand with a lockout interval of 10 min. Pain intensity was rated by the patient using the visual analog pain score (VAPS) system (0–10; 0, no pain; 10, most severe pain imaginable). The level of sedation was assessed by staff on the acute pain team using a 0–3 scale (0, fully awake; 1, asleep with response to stimulus; 2, asleep without response to stimulus; 3, comatose). Episodes of vomiting, VAPS, sedation score, time to first morphine demand, and morphine consumption were recorded at 4, 8, 12, and 24 h after operation. Vomiting was defined as forceful expulsion of liquid gastric contents. Retching and nausea were not considered vomiting for the purpose of this investigation. Rescue antiemetic administration of prochlorperazine 10 mg im was given at the patient's request. Duration of hospital stay was recorded also.
Data were analyzed using one-way analysis of variance with a linear contrast, χ2 test with trend, and the Kruskal-Wallis test as appropriate. The sample size (30 patients in each group) was calculated to detect a decrease in incidence of vomiting from 60% to 40% after treatment, with a power of 70%. Data are presented as the means ± SD. A P value less than 0.05 was considered statistically significant.
There was no significant difference among groups with respect to age, weight, height, ASA status, surgery time, and duration of hospital stay (Table 1). Furthermore, VAPS, sedation score, time to first morphine demand, and morphine consumption at each time interval were all similar among groups (Table 2). The incidences of postoperative emesis in Groups D10, D5, and D2.5 were significantly less frequent than those of Groups D1.25 and P (Table 2). However, no difference was found among Groups D10, D5, and D2.5. Five patients in Group P requested a rescue antiemetic in contrast to none of the patients in the dexamethasone-treated groups. A consistent but statistically insignificant decrease of morphine consumption associated with the escalation of dexamethasone dosage was observed among groups for each of the time intervals (Table 2). No discernible side effects accompanying dexamethasone usage were observed.
PONV is one of the most common and annoying side effects after surgery performed under general anesthesia. Adult women are two to four times more likely to suffer PONV than men (11,12), and major gynecological surgery is known to carry a risk of 58% of PONV (13). In this study, demographic data, type and duration of surgeries, anesthesia administered, and analgesics used postoperatively were all similar among groups. Thus, it is reasonable to attribute differences of time to first morphine demand, morphine consumption, VAPS, sedation score, rescue antiemetic administration, the incidence of emesis, and the duration of hospital stay among groups to the different doses of dexamethasone administered.
Various doses of dexamethasone (from 8 mg orally to 1 mg/kg up to 25 mg IV) have been effective in providing postoperative antiemesis. Our previous study demonstrated dexamethasone 10 mg resulted in a significant decrease in the incidence of postoperative emesis (7). This study further demonstrated that dexamethasone 5 mg and 2.5 mg are equally effective as 10 mg, and that all of these doses resulted in significant reductions of the incidence of postoperative emesis when compared with Groups P or D 1.25 mg. Furthermore, there were no differences in the incidence of postoperative emesis among Groups D10, D5, and D2.5 and between Groups D1.25 and P. These results suggest that dexamethasone 2.5 mg represents the established minimum effective dose for the prevention of postoperative emesis after major gynecological surgery.
The fact that five patients of Group P requested rescue antiemetic as compared with none of the dexamethasone-treated groups suggests that dexamethasone can effectively reduce the extent of severity of postoperative emesis, even at a dose of 1.25 mg.
Baxendale et al. (8) reported decreased wound pain after tooth extraction after dexamethasone administration. In this study, VAPS and time to first morphine demand were similar among groups, although a consistent but insignificant decrease of morphine consumption, which was associated with the escalation of dexamethasone dosage, was observed among groups at various time intervals. The discrepancy between the results of Baxendale's study and ours may be attributed to different postoperative pain intensities between tooth extraction and major gynecological surgery. With its strong antiinflammatory effect, dexamethasone should theoretically be beneficial for acute surgical pain, whereas for those with mild pain, such as after tooth extraction, the pain can be reduced with dexamethasone administration to an extent that most patients can perceive a significant change in pain intensity. For those with the worst pain, such as after major surgery, the pain can only be slightly lessened with dexamethasone administration because its analgesic effect tends to be minimal and unsatisfactory.
The lack of difference in duration of hospital stay among groups implies that there was no additional wound infection or delayed healing accompanying dexamethasone usage. However, more detailed investigation with a longer follow-up would be necessary to prove this.
In conclusion, in this study, dexamethasone 2.5 mg was the minimum effective dose for preventing postoperative emesis in patients undergoing general anesthesia for major gynecological surgery. Yet, a dose of 1.25 mg can still effectively reduce the extent of severity of the emesis. The doses of 10 mg and 5 mg did not offer any therapeutic advantage over 2.5 mg. Moreover, we found no influence of preoperative administration of dexamethasone on postoperative pain in major gynecological surgery.
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