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Departments of *Anesthesiology and Surgery, Chi-Mei Medical Center, Tainan, Taiwan; and Department of Anesthesiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
Address correspondence and reprint requests to Jhi-Joung Wang, MD, DMS, Department of Anesthesiology, Chi-Mei Medical Center, Tainan, Taiwan. Address e-mail to 400002{at}mail.chimei.org.tw
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Abstract |
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IMPLICATIONS: We evaluated the prophylactic effect of small-dose dexamethasone (5 mg) on postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic cholecystectomy. Tropisetron (2 mg) and saline served as controls. We found that dexamethasone 5 mg (IV) significantly reduced the incidence of PONV in these patients, and, at this dose, dexamethasone was as effective as tropisetron and was more effective than placebo.
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Introduction |
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Dexamethasone, a corticosteroid, is an inexpensive and effective antiemetic drug, with minimal side effects after a single-dose administration (3,6,11–15). It was first reported in 1981 as an effective antiemetic in patients receiving cancer chemotherapy (12). Since then, dexamethasone has been widely applied in the prevention of nausea and vomiting after chemotherapy (13–15). Dexamethasone also reduces the incidence of PONV (3). The commonly used dose is 8 to 10 mg (3,6), but the minimal effective dose is suggested to be 5 mg for PONV in patients undergoing thyroidectomy (11). Dexamethasone 8 mg is also effective for PONV after LC (6). However, a smaller dose has not yet been evaluated. The aim of the study was to evaluate the efficacy of small-dose dexamethasone (5 mg) on the prophylaxis of nausea and vomiting after LC. Tropisetron (2 mg), a currently used antiemetic for PONV (1,2,8–10), and saline were used as controls.
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Methods |
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In the preoperative holding area, patients were allocated randomly to one of the three groups (n = 40 each) by use of a computer-generated random number table. Study medications were prepared by a nurse anesthetist in identical 2-mL syringes to ensure blinding of the anesthesiologists. Immediately after the induction of anesthesia, patients in the Dexamethasone group received dexamethasone 5 mg IV, and those in the Tropisetron group received tropisetron 2 mg IV. Patients in the Placebo group received IV saline. Patients and the investigators who collected the postoperative data were blinded to the randomization.
Anesthesia was induced with propofol 2–2.5 mg/kg IV, glycopyrrolate 0.2 mg IV, and fentanyl 2 µg/kg IV. Tracheal intubation was facilitated with vecuronium 0.15 mg/kg IV. Anesthesia was maintained with 1.0%–2.5% (inspired concentration) isoflurane in oxygen. Ventilation was controlled mechanically and adjusted to keep an end-tidal CO2 partial pressure of 30–40 mm Hg, with an anesthetic/respiratory gas analyzer (Capnomac Ultima; Datex, Helsinki, Finland). Neuromuscular block was maintained with vecuronium IV. After tracheal intubation, a nasogastric tube was placed to promote baseline emptying of the stomach of air and gastric contents. During surgery, patients were positioned in the reverse Trendelenburg position, with the right side of the bed elevated. The abdomen was insufflated with CO2, with an intraabdominal pressure of 10–16 mm Hg. LC was performed under video guidance with four punctures of the abdomen. The IV fluid used during surgery was 0.9% saline. At the end of surgery, glycopyrrolate 0.6 mg IV and neostigmine 3 mg IV were administered for reversal of neuromuscular block, and the trachea was extubated.
After surgery, patients were observed for 24 h. Immediately after surgery, patients were transported to the postanesthetic care unit. During their 1-h stay in the postanesthetic care unit, vital signs were monitored every 15 min, and oxygen saturation was monitored continuously by pulse oximetry. IV saline (0.9%) was given as maintenance fluid for each patient. Tenoxicam 20 mg IV was given routinely for the prevention of postoperative pain. During the following observatory period in the ward, arterial blood pressure, heart rate, and respiratory rate were monitored every 4 h (from 8:00 AM to 10:00 PM).
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, 20 mg of tenoxicam (every 12 h IV) was given.
Nausea and vomiting were evaluated by the following variables: the incidence 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 content) 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 separated by >1 min, they were considered separate episodes. Vomiting that occurred more than four times within 24 h was considered severe vomiting. Rescue antiemetics (metoclopramide 10 mg IV) were given if vomiting occurred or at the patient’s request. The treatment was repeated if necessary. The complete response was defined as no nausea, no vomiting, and no antiemetic medication during a 24-h postoperative period, and this was also the primary efficacy end point of the study. The data of PONV were collected every 4 h (from 8:00 AM to 10:00 PM) by direct questioning by a team of nurse anesthetists or by spontaneous complaint of the patients. The patients and the investigators who collected the data were blinded to the patient’s group. Side effects (e.g., headache), if present, were recorded.
Sample size was predetermined by using a power analysis based on the following assumptions: 1) the total incidence of nausea and vomiting in the Saline group would be 60% (6), 2) a 30% reduction in the total incidence of nausea and vomiting (from 60% to 42%) in the treatment groups would be of clinical relevance, and 3) 
= 0.05 and ß = 0.2 (16). The analysis showed that 40 patients per group would be sufficient (16). A series of one-way analyses of variance was conducted to examine differences among the three groups with respect to parametric variables. If a significant difference was found, the Bonferroni Student’s t-test with correction 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 U-test for intergroup differences. Categorical variables were analyzed by using a series of 3 x 2 
2 tests to determine differences among the three groups, followed by 2 x 2 2 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.
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Discussion |
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Several studies have demonstrated dexamethasone’s efficacy in the prevention of nausea and vomiting associated with chemotherapy (12–15). Dexamethasone also prevents PONV in patients undergoing hysterectomy, tonsillectomy, and thyroidectomy (3,6,11). The dose often used is 8 to 10 mg (3), but the minimal effective dose is 5 mg in patients undergoing thyroidectomy (11). Dexamethasone 8 mg is also effective in reducing the incidence of PONV after LC (6). We further found that dexamethasone 5 mg was also effective for this purpose.
The exact mechanism by which dexamethasone, a corticosteroid, exerts an antiemetic action is not fully understood. However, its antiemetic action, at least in part, may be via the blockage of the corticoreceptors in the nucleus tractus solitarius of the central nervous system (19). Dexamethasone may also exert its antiemetic action through some peripheral mechanism (3,6,11). Dexamethasone, a corticosteroid, has strong antiinflammatory actions and may significantly reduce tissue inflammation around the surgical sites and thus reduce the ascending parasympathetic impulses (e.g., vagus) to the vomiting center and reduce PONV.
The etiology of PONV after LC is not fully understood. Risk factors such as a long period of CO2 insufflation; gall bladder surgery; intraoperative use of isoflurane, fentanyl, and glycopyrrolate; female sex; and postoperative pain may contribute to these episodes (1,2). Because these risk factors may interfere with the interpretation of the study data, we controlled these within the study design. All patients were given LC for cholelithiasis by the same team of anesthesiologists and surgeons. The duration of anesthesia, surgery, and CO2 insufflation and the anesthetic drugs were similar among groups. In addition, after random allocation, sex distributions among groups were similar, as were postoperative pain scores. Therefore, the differences in the occurrence of PONV among groups can be attributed to the study drugs.
Tropisetron, a serotonin subtype 3 receptor antagonist, is primarily used in the prevention of chemo-therapy-related nausea and vomiting (20,21). It has also been applied to the prophylaxis of PONV (8–10). Although 2 and 5 mg of tropisetron are frequently used in the prevention of PONV, 2 mg is recommended for this purpose (8–10,22). Our study is in agreement with this finding.
Cost is an ever-increasing concern in today’s health care system. Prophylactic antiemetic with dexamethasone is relatively inexpensive. Dexamethasone at a dosage of 5 mg costs 18 new Taiwan dollars (equal to US $0.50), which is remarkably less expensive than a similar effective dose of tropisetron 2 mg, which costs US $12. Therefore, dexamethasone 5 mg is a more reasonable choice than tropisetron 2 mg for the prevention of PONV.
In conclusion, prophylactic IV dexamethasone 5 mg significantly reduces the incidence of PONV in patients undergoing LC. At this dose, dexamethasone is as effective as tropisetron 2 mg and is more effective than placebo.
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This article has been cited by other articles:
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  A. L Kovac Meta-Analysis of the Use of Rescue Antiemetics Following PONV Prophylactic Failure with 5-HT3 Antagonist/Dexamethasone Versus Single-Agent Therapies Ann. Pharmacother., May 1, 2006; 40(5): 873 - 887. [Abstract] [Full Text] [PDF]
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 A. Goldfaden and J. D. Birkmeyer Evidence-Based Practice in Laparoscopic Surgery: Perioperative Care Surgical Innovation, March 1, 2005; 12(1): 51 - 61. [Abstract] [PDF]
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