Postoperative nausea and vomiting after laparoscopic cholecystectomy remains a common problem despite routine antiemetic prophylaxis. Therefore, the authors investigated the effect of administering 4 mg intravenous dexamethasone as an adjunct to a 5-HT3 antagonist (12.5 mg intravenous dolasetron) with respect to patient outcome.


Outpatients (N = 140) were enrolled in this prospective, randomized, placebo-controlled, double-blind, institutional review board-approved protocol involving two antiemetic treatment groups. After induction of anesthesia, the control group received 1 ml intravenous saline, whereas the dexamethasone group received 4 mg intravenous dexamethasone. Both groups received 12.5 mg intravenous dolasetron at the time of gallbladder removal. A blinded observer recorded the recovery times, emetic episodes, rescue antiemetics, maximum nausea score, and time to achieve discharge criteria. Postdischarge side effects, as well as patient satisfaction and quality of recovery scores were assessed at 24 h after surgery.


Although there was no difference in the incidence of postoperative nausea and vomiting in the early recovery period, the dexamethasone group had a shorter stay in the day-surgery unit (136 +/- 57 vs. 179 +/- 62 min) and more rapidly achieved discharge criteria (161 +/- 32 vs. 209 +/- 39 min). In addition, fewer patients in the dexamethasone group experienced nausea at home within 24 h after discharge (13 vs. 28%, P < 0.05). Finally, the dexamethasone group reported higher quality of recovery and patient satisfaction scores (P < 0.05).


The authors conclude that the adjunctive use of 4 mg intravenous dexamethasone shortened the time to achieve discharge criteria and improved the quality of recovery and patient satisfaction scores after laparoscopic cholecystectomy procedures in outpatients receiving prophylaxis with 12.5 mg intravenous dolasetron.

DESPITE antiemetic prophylaxis, the incidence of postoperative nausea and vomiting (PONV) remains unacceptably high after laparoscopic cholecystectomy procedures. 1Recent studies suggest that the addition of dexamethasone, as part of a multimodal approach, can decrease PONV in high-risk patient populations. 2–4Studies involving ondansetron 4–7and granisetron 2,3have reported that the addition of dexamethasone can reduce PONV symptoms compared with the use of a 5-HT3antagonist alone. However, these studies have not demonstrated a significant benefit with respect to meaningful patient outcome measures. 8 

In a recent study, Zarate et al . 9reported that dolasetron, another 5-HT3antagonist, was more cost-effective than ondansetron for prophylaxis against PONV after otolaryngologic surgery. Dolasetron has been used for both the prophylaxis and treatment of PONV in high-risk outpatient surgical populations. 9–11However, it has not been studied in combination with dexamethasone, a potent corticosteroid with postoperative antiinflammatory and antiemetic effects. 12–14A recent study found that dexamethasone appeared to have beneficial effects in facilitating earlier discharge independent of its antiemetic activity. 15 

We therefore designed a prospective study to evaluate the effect of dexamethasone in combination with dolasetron on the incidence of PONV, requirement for rescue antiemetic drugs, and time to discharge after laparoscopic cholecystectomy. We hypothesized that the addition of dexamethasone would improve the recovery profile and patient satisfaction.

Materials and Methods

After obtaining approval from the local institutional review board (University of Texas Southwestern Medical Center, Dallas, TX) and written informed consent, 140 oupatients, American Society of Anesthesiologists physical status I and II, who were undergoing laparoscopic cholecystectomy procedures were studied according to a prospective, randomized, double-blind, placebo-controlled protocol. Patients were excluded if they had received a prophylactic antiemetic within 24 h of surgery, had preexisting abnormalities involving any major organ system, had a history of drug abuse, were pregnant, were more than 50% greater than their ideal body weight, or were allergic to the study drugs. Patients were randomly assigned to either the control or dexamethasone group, and the study medication (saline or 4 mg dexamethasone) was prepared and administered by an investigator not involved in the patient's care or data collection. The patient, anesthesiologist, and observer were all blinded with respect to the study group.

No premedication was administrated before entering the operating room. On arrival in the operating room, standard monitors were applied. After obtaining baseline vital signs, 2 mg intravenous midazolam was administered. Anesthesia was subsequently induced with 2 mg/kg intravenous propofol and 1 μg/kg intravenous fentanyl. Maintenance of anesthesia consisted of sevoflurane (1–2% end tidal) in combination with 65% nitrous oxide in oxygen. After tracheal intubation, the control group received 1 ml saline and the dexamethasone group received 4 mg (1 ml) intravenous dexamethasone from identical-appearing syringes according to a computer-generated randomization sequence. All patients were mechanically ventilated to maintain an end-tidal carbon dioxide concentration of 32–36 mm Hg. When the gallbladder was removed, 12.5 mg intravenous dolasetron was administered to all patients. At the end of surgery, 60 μg/kg intravenous neostigmine (5 mg maximum dose) and 12 μg/kg intravenous glycopyrrolate (1 mg maximum dose) were administered for reversal of residual neuromuscular blockade. Before skin closure, the surgeon injected a mixture of 1% lidocaine and 0.25% bupivacaine at the fascial level of each surgical portal. In addition, all patients also received 30 mg intravenous ketorolac for preventive analgesia. The maintenance anesthetic was discontinued when the laparoscope was withdrawn from the abdominal cavity, and the nitrous oxide was discontinued after the last skin suture was placed.

Demographic data were obtained, including gender, weight, age, and history of PONV, motion sickness or smoking. The duration of surgery (from incision to application of the bandage) and anesthesia (from induction to discontinuation of the inhaled anesthetic) was also recorded. Recovery times were determined at 1-min intervals after discontinuation of the maintenance anesthetic by a blinded observer, including the time to awakening (i.e ., opening eyes in response to a verbal command) and orientation to person and place, as well as the time to achieve a modified Aldrete score of 10 and a fast-track score of 12 or higher. 16,17In addition, the total intraoperative dosages of propofol and fentanyl, the volume of intravenous fluids administered during surgery, duration of stay in the step-down (phase II) recovery area and postanesthesia care unit, as well as time to achieve discharge criteria and actual hospital discharge were recorded.

The incidence of PONV was assessed at 15-min intervals in the postanesthesia care unit and subsequently at 30-min intervals until discharge by an investigator (M. C.) who was blinded to the study medication. An emetic episode was defined as vomiting or retching occurring in a 2-min period. 7The criteria for administering a rescue antiemetic was either a repeated or prolonged emetic episode (lasting > 5 min) or a request by the patient for treatment of their emetic symptoms. Promethazine (6.25 mg administered intravenously) was administered as the initial rescue antiemetic. If this first dose was ineffective, the same dose was repeated to a maximum of 25 mg administered intravenously. A second rescue antiemetic drug (0.625 mg intravenous droperidol) was administered only when the symptoms of PONV persisted after the maximum dose of promethazine administered. In the postanesthesia care unit, 25 μg intravenous fentanyl was administered at 3–5-min intervals as needed for acute pain relief. The time to receive the first rescue antiemetic and analgesic medication and the total doses were also recorded.

Fitness for discharge was assessed at 15-min intervals and required that the patient be awake and alert, with stable vital signs on standing, able to walk without assistance, and be free of postoperative side effects. Hydrocodone (5 mg) with 500 mg oral acetaminophen was prescribed at the time of discharge. A follow-up telephone call was made to all patients 24 h after surgery to determine the incidence of PONV after discharge and to assess their quality of recovery (QoR) and the patient's satisfaction with the management of their PONV symptoms (using 100-point verbal rating scales, where 0 = poor and 100 = excellent).

Statistical Analysis

An a priori  power analysis based on previous studies involving a similar ambulatory surgical population 2,7suggested that a group size of 67 would be adequate to determine a 40% difference in the incidence of PONV given an estimated baseline incidence of PONV in the control group of 50% (power = 0.80, α= 0.05). Data were analyzed using the Number Cruncher Statistical System (version 6.0; NCSS, Kaysville, UT) using the student t  test for continuous variables and chi-square test for categorical data. P < 0.05 was considered statistically significant, and data were expressed as mean values ± SD or number and percentages.


There were no significant differences between the two treatment groups with respect to demographic data, duration of surgery and anesthesia, and history of motion sickness, PONV, or smoking (table 1). The doses of anesthetic drugs, including propofol, fentanyl, and volume of perioperative intravenous fluid did not differ between the two groups. Similarly, there were no significant differences in recovery times to awakening, orientation, achievement of fast-track score of 12, Aldrete's score of 10, or initiating oral intake (table 2). Furthermore, the postoperative opioid analgesic requirement, the time to receive the first analgesic and antiemetic rescue, was also comparable for the two groups.

Despite the lack of difference in both the incidence of PONV or the complete response rate to the antiemetic prophylactic treatment between the two groups (table 3), patients in the dexamethasone group had a shorter average length of stay in the day-surgery unit and achieved discharge criteria earlier than those in the control group (table 2). In the postdischarge period, fewer patients in the dexamethasone group experienced nausea (table 3). More importantly, patients in the dexamethasone group reported higher QoR and patient satisfaction scores compared with those in the control group. None of the patients complained of confusion, depression, dysphoria, or other psychic disturbances after surgery.

In comparing the “fit for discharge” times, QoR scores, and satisfaction scores in patients who did (215 ± 89 min, 82 ± 20 mm, and 88 ± 12 mm, respectively) or did not (199 ± 70 min, 92 ± 15 mm, and 95 ± 8 mm, respectively) develop PONV, there were no statistically significant differences (P = 0.4, 0.2, and 0.16, respectively).


In contrast to previous studies by Fujii et al ., 2,3,18which suggested that the use of dexamethasone in combination with a 5-HT3antagonist decreased PONV compared with either drug alone, we failed to find that the combination was any more effective than the 5-HT3antagonist alone in reducing the incidence of PONV. However, the adjunctive use of dexamethasone did facilitate an earlier discharge, analogous to our recent findings in an outpatient population undergoing anorectal surgery. 15More importantly, these patients also reported higher QoR scores and degree of satisfaction with the management of their PONV symptoms.

The incidence of nausea and vomiting after laparoscopic cholecystectomy remains high (22–53%) when outpatients receive prophylaxis with a single antiemetic drug. 1In a study by Graczyk et al ., 19the incidence of PONV in the placebo group was 69%, whereas incidences of 41–48% were reported in the groups receiving doses of intravenous dolasetron ranging from 12.5 to 50 mg. In a study by Fujii et al . 2involving patients undergoing laparoscopic cholecystectomy, the addition of dexamethasone (8 mg) to granisetron (3 mg) reduced the incidence of PONV from 17% with the 5-HT3antagonist alone to 2% with the combination. However, concerns have been raised as to the reliability of these data. 20In our study, the incidence of PONV was nonsignificantly reduced from 49 to 35% by the addition of dexamethasone (4 mg). However, the differences in the incidences of PONV in the various studies may be related to differences in the type of surgery, anesthesia, and patient demographic characteristics.

The 12.5-mg dose of intravenous dolasetron that we chose to study was based on the results of a cost-effectiveness analysis that suggested that this dose of dolasetron was as effective as 25 mg intravenous dolasetron and 4 or 8 mg intravenous ondansetron in preventing PONV. 9In the current study, 12.5 mg intravenous dolasetron was administered after removal of the gallbladder, as recommended by the manufacturer. However, the incidences of nausea (49%) and vomiting (19%) remained high. Dexamethasone has been reported to be effective for antiemetic prophylaxis in both adult and pediatric patients, 13,21,22with an optimal dose of 5 mg at induction of anesthesia in adults. 23,24Although the incidences of nausea (35%) and vomiting (8%) were lower in the dexamethasone group, this difference did not achieve statistical significance (P = 0.1 and 0.3, respectively). Nevertheless, dexamethasone did facilitate the recovery process and improve patient satisfaction with their recovery after laparoscopic cholecystectomy. Analogous to our previous findings in outpatients undergoing anorectal surgery, a single 4-mg dose of dexamethasone improved the early recovery profile without significantly reducing the incidence of PONV. 15We would speculate that the mechanism responsible for the beneficial effects of dexamethasone on the recovery profile may relate to its mood altering effect and ability to produce an enhanced sense of patient well-being. 25 

This study could be criticized because we did not include a group that received no prophylactic antiemetic drugs. However, prophylactic antiemetics are routinely administered to all outpatients undergoing laparoscopic surgery procedures at our teaching institution because of the high incidence of PONV in this patient population. Our surgical and anesthesia colleagues did not feel it was ethical to withhold all prophylactic antiemetic drugs in this high-risk outpatient population. Given this concern and our recent findings in patients undergoing laparoscopic cholecystectomy procedures, 1,26we felt that it was not justified to withhold all prophylactic treatment.

In a recent editorial regarding the use of surrogate outcomes in PONV studies, Fisher 8suggested that studies reporting incidences of nausea and vomiting were useful only if clinically meaningful endpoints (i.e ., postanesthesia care unit stay, unplanned hospital admission, QoR, patient satisfaction) were influenced by the therapeutic intervention. In this study, the surrogate outcomes relating to the incidence of PONV did not achieve statistical significance. However, the clinically important outcomes relating to fitness for discharge, QoR, and patient satisfaction with their antiemetic management were significantly improved in the group receiving dexamethasone in combination with the 5-HT3antagonist. As true outcome measures, the improvement noted in the QoR and patient satisfaction suggests that a single 4-mg dose of dexamethasone may be a valuable adjunctive therapy during general anesthesia for adults undergoing ambulatory surgery.

In conclusion, compared with prophylaxis with dolasetron alone, patients receiving a combination of dexamethasone (4 mg) and dolasetron (12.5 mg) had an improved QoR and greater satisfaction with the management of their PONV symptoms, as well as a reduced incidence of nausea after discharge.


Song D, Whitten CW, White PF, Yu SY, Zarate E: Antiemetic activity of propofol after sevoflurane and desflurane anesthesia for outpatient laparoscopic cholecystectomy. A nesthesiology 1998; 89: 838–43
Fujii Y, Saitoh Y, Tanaka H, Toyooka H: Granisetron/dexamethasone combination for the prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy. Eur J Anaesthesiol 2000; 17: 64–8
Fujii Y, Saitoh Y, Tanaka H, Toyooka H: Granisetron/dexamethasone combination for reducing nausea and vomiting during and after spinal anesthesia for cesarean section. Anesth Analg 1999; 88: 1346–50
Splinter WM, Rhine EJ: Low-dose ondansetron with dexamethasone more effectively decreases vomiting after strabismus surgery in children than does high-dose ondansetron. A nesthesiology 1998; 88: 72–5
McKenzie R, Tantisira B, Karambelkar DJ, Riley TJ, Abdelhady H: Comparison of ondansetron with ondansetron plus dexamethasone in the prevention of postoperative nausea and vomiting. Anesth Analg 1994; 79: 961–4
Rajeeva V, Bhardwaj N, Batra YK, Dhaliwal LK: Comparison of ondansetron with ondansetron and dexamethasone in prevention of PONV in diagnostic laparoscopy. Can J Anaesth 1999; 46: 40–4
López-Olaondo L, Carrascosa F, Pueyo FJ, Monedero P, Busto N, Sáez A: Combination of ondansetron and dexamethasone in the prophylaxis of postoperative nausea and vomiting. Br J Anaesth 1996; 76: 835–40
Fisher DM: Surrogate outcomes: Meaningful not! (editorial). A nesthesiology 1999; 90: 355–6
Zarate E, Watcha MF, White PF, Klein KW, Sa Rego M, Stewart DG: A comparison of the costs and efficacy of ondansetron versus dolasetron for antiemetic prophylaxis. Anesth Analg 2000; 90: 1352–8
Philip BK, Pearman MH, Kovac AL, Chelly JE, Wetchler BV, McKenzie R, Monk TG, Dershwitz M, Mingus M, Sung YF, Hahne WF, Brown RA: Dolasetron for the prevention of postoperative nausea and vomiting following outpatient surgery with general anaesthesia: A randomized, placebo-controlled study. The Dolasetron PONV prevention Study Group. Eur J Anaesthesiol 2000; 17: 23–32
Philip BK, McLeskey CH, Chelly JE, McKenzie R, Kovac Al, Diemunsch P, DuBois DM: Pooled analysis of three large clinical trials to determine the optimal dose of dolasetron mesylate needed to prevent postoperative nausea and vomiting. The Dolasetron Prophylaxis Study Group. J Clin Anesth 2000; 12: 1–8
Baxendale BR, Vater M, Lavery KM: Dexamethasone reduces pain and swelling following extraction of third molar teeth. Anaesthesia 1993; 48: 961–4
Splinter WM, Roberts DJ: Dexamethasone decreases vomiting by children after tonsillectomy. Anesth Analg 1996; 83: 913–6
Liu K, Hsu CC, Chia YY: Effect of dexamethasone on postoperative emesis and pain. Br J Anaesth 1998; 80: 85–6
Coloma M, Duffy LL, White PF, Tongier WK, Huber PJ Jr: Dexamethasone facilitates discharge after outpatient anorectal surgery. Anesth Analg 2001; 92: 85–8
Aldrete JA: The post-anesthesia recovery score revisited (letter). J Clin Anesth 1995; 7: 89–91
White PF, Song D: New criteria for fast-tracking after outpatient anesthesia: A comparison with the modified Aldrete's scoring system. Anesth Analg 1999; 88: 1069–72
Fujii Y, Tanaka H, Toyooka H: Granisetron reduces the incidence and severity of nausea and vomiting after laparoscopic cholecystectomy. Can J Anaesth 1997; 44: 396–400
Graczyk SG, McKenzie R, Kallar S, Hickok CB, Melson T, Morrill B, Hahne WF, Brown RA: Intravenous dolasetron for the prevention of postoperative nausea and vomiting after outpatient laparoscopic gynecologic surgery. Anesth Analg 1997; 84: 325–30
Kranke P, Apfel CC, Roewer N: Reported data on granisetron and postoperative nausea and vomiting by Fujii et al. Are incredibly nice! (letter). Anesth Analg 2000; 90: 1004–7
Wang JJ, Ho ST, Liu YH, Lee SC, Liu YC, Liao YC, Ho CM: Dexamethasone reduces nausea and vomiting after laparoscopic cholecystectomy. Br J Anaesth 1999; 83: 772–5
Aouad MT, Siddik SS, Rizk LB, Zaytoun GM, Baraka AS: The effect of dexamethasone on postoperative vomiting after tonsillectomy. Anesth Analg 2001; 92: 636–40
Wang JJ, Ho ST, Lee SC, Liu YC, Ho CM: The use of dexamethasone for preventing postoperative nausea and vomiting in females undergoing thyroidectomy: A dose-ranging study. Anesth Analg 2000; 91: 1404–7
Wang JJ, Ho ST, Tzeng JI, Tang CS: The effect of timing of dexamethasone administration on its efficacy as a prophylactic antiemetic for postoperative nausea and vomiting. Anesth Analg 2000; 91: 136–9
Jacobs JWG, Geenen R, Evers AWM, van Jaarsveld CHM, Kraaimaat FW, Bijlsma JWJ: Short term effects of corticosteroid pulse treatment on disease activity and the wellbeing of patients with active rheumatoid arthritis. Ann Rheum Dis 2001; 60: 61–4
Zárate E, Mingus M, White PF, Chiu JW, Scuderi P, Loskota W, Daneshgari V: The use of transcutaneous acupoint electrical stimulation for preventing nausea and vomiting after laparoscopic surgery. Anesth Analg 2001; 92: 629–35