Comparison of dexamethasone, metoclopramide and

their combination in the prevention of postoperative

nausea and vomiting after laparoscopic

cholecystectomy

Nesek-Adam Višnja1, MD, MS, Grizelj-Stojčić Elvira1, MD, Rašić Žarko2, MD, PhD,

Čala Zoran2, MD, PhD, Mršić Viviana1, MD, Smiljanić Aleksandra1, MD

1Department of Anesthesiology, Resuscitation and Intensive Care, Sveti Duh General

Hospital, Zagreb, Croatia2University Department of Surgery, Sveti Duh General Hospital, Zagreb, Croatia

Grizelj-Stojčić Elvira – mladen.stojcic@zg.htnet.hrRašić Žarko - zarko.rasic@zg.htnet.hrZoran Čala - zoran.cala@bol-svduh.htnet.hr

Correspondence to:

Nesek-Adam Višnja, MD, MS

Žerjavićeva 12

HR-10000 Zagreb

Croatia

tihomir.adam@zg.htnet.hr

Phone: +385913712136

1

Abstract

Background: Postoperative nausea and vomiting (PONV) are one of the most common

complaints following anesthesia and surgery. This study was designed to evaluate the efficacy

of dexamethasone, metoclopramide and their combination to prevent PONV in patients

undergoing laparoscopic cholecystectomy.

Methods: One-hundred and sixty ASA physical status I and II patients were included in this

randomized, double blind, placebo-controlled study. Patients were randomly assigned to 4

groups (n=40 each): group 1 consisting of control patients administered 0.9% NaCl; group 2

patients received metoclopramide 10 mg just before the end of anesthesia; group 3 patients

received dexamethasone 8 mg after the induction of anesthesia; and group 4 patients received

dexamethasone 8 mg after the induction of anesthesia and metoclopramide 10 mg before the

end of anesthesia. The incidence of PONV, mean visual analogue pain scores at rest and on

movement, time to the first request for analgesia, side effects, and well-being score were

recorded during the first 24 h postoperatively.

Results: Data were analyzed using one-way analysis of variance (ANOVA) and χ2 test, with

p<0.05 considered statistically significant. The total incidence of PONV was 60% with

placebo, 45% with metoclopramide, 23% with dexamethasone, and 13% with the combination

of dexamethasone plus metoclopramide. None of the dexamethasone plus metoclopramide

group patients (p<0.05 vs groups 1 and 2) and one dexamethasone group patient (p<0.05 vs

group 1) required antiemetic rescue, as compared with four patients in the metoclopramide

group and six patients in the placebo group. Pain scores, the time to the first request for

analgesia, and side effects were similar across the study groups.

Conclusion: Dexamethasone and the combination of dexamethasone plus metoclopramide

were more effective in preventing PONV than metoclopramide and placebo.

Key words: laparoscopic cholecystectomy, postoperative nausea and vomiting,

dexamethasone, metoclopramide

2

Introduction

Postoperative nausea and vomiting (PONV) are one of the most common complaints

following anesthesia and surgery. The overall incidence of PONV has been estimated to 30%

depending on surgical, patient and postoperative factors [33]. The patients undergoing

laparoscopic cholecystectomy are especially prone to PONV, with the reported incidence of

53%-72% [20,22,23,25]. In an attempt to decrease such a high incidence, many antiemetics

have been studied [9,10,22,]. However, because of the multifactorial origin of PONV, none of

the currently available antiemetics is fully effective in all patients. At present, when

antiemetics of different pharmacological classes are available, it is possible to combine them

and provide better control of PONV without producing additional side effects [17].

Dexamethasone has been used as an antiemetic for more than 20 years in patients receiving

chemotherapy [15], with limited side effects [1], and has also been reported to decrease

PONV when added to the antiemetic regimen. [4,6]. Recently, a combination of ondansetron

and dexamethasone has been shown to be a highly effective prophylactic measure in patients

undergoing laparoscopic cholecystectomy [6]. However, the higher cost of ondansetron has

been a significant factor limiting its routine prophylactic use [28]. Therefore, we used

metoclopramide, the most common and low-cost antiemetic agent, instead of ondansetron.

We conducted a prospective randomized, double-blind, placebo-controlled study to evaluate

the efficacy of dexamethasone plus metoclopramide in comparison with either antiemetic

alone to prevent PONV in patients undergoing laparoscopic cholecystectomy.

3

Methods

One-hundred and sixty ASA physical status I and II patients scheduled for elective

laparoscopic cholecystectomy under general anesthesia were enrolled in this randomized

double-blind placebo-controlled study. The Hospital Ethics Committee approved the study

and a written informed consent was obtained from each patient. Patients under the age of 18

years or patients with previous allergic reaction to any of the protocol medications, and those

who had vomited or had received any antiemetic within 24 hours prior to surgery were

excluded. Exclusion criteria also included gastrointestinal, renal or liver disease, pregnancy,

smoking, history of motion sickness, and conversion to open cholecystectomy. Patients were

allocated randomly to one of the four medication groups (n=40 each). Study medications were

prepared by a technician anesthetist in identical 5-mL syringes and administered in a double-

blind fashion. Each patient received two syringes, one just after the induction of anesthesia

and the other at the end of surgery. After tracheal intubation, group 1 patients received

placebo (0.9% saline) in two syringes; group 2 received placebo after the induction of

anesthesia and metoclopramide 10 mg at the end of surgery; group 3 received dexamethasone

8 mg after the induction of anesthesia and placebo at the end of surgery; and group 4 received

dexamethasone 8 mg after the induction of anesthesia and metoclopramide 10 mg at the end

of surgery.

The same standardized anesthestic technique was used in all patients. General anesthesia was

induced with thiopental (5 mg/kg) and fentanyl (2 μg/kg) In all groups’ rocuronium bromide

(0.6 mg/kg) was given to facilitate tracheal intubation. Anesthesia was maintained with 1.0%-

2.5% (inspired concentration) isoflurane in oxygen. Additional fentanyl and rocuronium

bromide were used if necessary. Ventilation was controlled mechanically and was adjusted to

keep end-tidal CO2 between 35 and 40 mm Hg. Laparoscopic cholecystectomy was performed

by European technique using three ports. During surgery the patients were placed in reverse

Trendelenburg position and the abdominal cavity was insufflated with carbon dioxide until

the intra-abdominal pressure reached 12-14 mm Hg. A temporary nasogastric tube was placed

to promote emptying of gastric contents. Prior to endotracheal extubation, the nasogastric tube

was suctioned again and then removed. At the end of surgery, atropine 0.01 mg/kg and

neostigmine 0.05 mg/kg were administered i.v. for reversal of muscle relaxation, and the

trachea was extubated. All patients received i.v. lactated Ringer’s solution at a rate of 10

ml/kg during anesthesia and 2 ml/kg/h after anesthesia until patients tolerated oral fluids.

4

Patients were monitored during anesthesia by continued ECG, noninvasive blood pressure,

pulse oximetry and capnometry. All patients received supplementation of O2 – 4 L/min by a

facemask for 2 h postoperatively.

After surgery, patients were observed for 24 h. The incidence of nausea and vomiting was

recorded during three assessment periods, at 0-4, 4-12 and 12-24 h, by nursing staff without

knowledge of which antiemetic the patients had received. Vomiting was defined as forceful

expulsion of gastric contents through the mouth, whereas nausea was defined as a subjectively

unpleasant sensation associated with awareness of the urge to vomit1,6. We made no

distinction between vomiting and retching. Patients were asked to indicate nausea, vomiting

or retching experienced during the three study periods by “yes” or “no”. If patients

experienced nausea for 30 min, more than one emetic episode in 15 min, or if specifically

demanded antiemetic, a rescue antiemetic (10 mg thiethylperazine) was given intravenously.

Complete response was defined as the absence of nausea and vomiting throughout the study

period.

Postoperative analgesia was provided with a combination of metamizol 1.25 g and tramadol

hydrochloride 100 mg in 100 mL 0.9% NaCl over 20 min iv. Postoperative pain was also

recorded by nursing staff during three assessment periods: 0-4, 4-12 and 12-24 h. The severity

of postoperative pain with and without active movement was measured with the visual analog

scale (VAS), and analgesia was given upon request or when patients experienced pain of VAS

>3. If no relief was obtained or if the VAS exceeded score 5, an additional dose of tramadol

hydrochloride 25 mg was administered i.v. Time interval to the first administration of the

combination of tramadol hydrochloride and metamizol, and number of patients who needed

rescue analgesic were also recorded. The occurrence of side effects accompanying

dexamethasone and metoclopramide usage was recorded concomitantly with PONV

assessment. Patients were also asked to assess their postoperative state 24 h after surgery

using well-being score with regard to the incidence of nausea, vomiting, pain and side effects.

Well-being score was assessed on a 5-grade scale: 1 – very good; 2 – good; 3 – alternating; 4

– poor; 5 – very poor.

Results were calculated as mean standard deviation (SD). Statistical analysis was

performed using STATISTICA 6.0 software. Parametric data were analyzed with one-way

analysis of variance (ANOVA) and for non-parametric variables we used 2-test. The level of

significance was set at p<0.05.

Sample size was predetermined by power analysis based on the expectation that the total

incidence of PONV in the placebo group would be 60%, with a 40% reduction in the

5

incidence of PONV in the treatment group. The α error was set at 0.05 and β error at 0.2;

according to power analysis, any group size of 37 patients was considered adequate. We

decided to enroll 40 patients per group to allow dropout.

6

Results

All 160 patients enrolled in the study had their surgical procedures completed. There was no

statistically significant difference among the four groups according to patient age, body

weight and height, duration of anesthesia, surgery and CO2 insufflation, and total fentanyl

consumption (Table 1).

The incidence of nausea and vomiting in each treatment group during the three assessment

periods are shown in Table 2. As expected, the incidence of vomiting was less frequent than

nausea in all periods, because some patients experienced nausea without vomiting.

Total incidence of PONV during 24 h was 60% in placebo group, 45% in metoclopramide

group, 23% in dexamethasone group, and 13% in dexamethasone plus metoclopramide group.

Thus, patients receiving 8 mg dexamethasone had significantly less PONV than those

administered placebo (p=0.0007) or 10 mg metoclopramide (p=0.0333). Those receiving the

combination of 8 mg dexamethasone and 10 mg metoclopramide also had a significantly

lower incidence of PONV as compared to placebo (p<0.0001) and 10 mg metoclopramide

(p=0.0013).

During the 24-h study period there was no difference in the incidence in PONV between the

dexamethasone and dexamethasone plus metoclopramide groups (p=0.2392), or between the

placebo and metoclopramide groups (p =0.1792)

In addition, the rate of complete response (no PONV) was 40% in placebo group, 55% in

metoclopramide group (p=0.1792 vs group 1), 78% in dexamethasone group (p=0.0007 vs

group 1, p=0.0333 vs group 2), and 88% in dexamethasone plus metoclopramide group

(p<0.0001 vs group 1, p=0.0013 vs group 2).

At 24 h after surgery, only one patient from dexamethasone group required antiemetic rescue

compared to six patients from placebo group (p=0.0479) and four patients from

metoclopramide group (p=0.1659). None of the patients from dexamethasone plus

metoclopramide group required antiemetic rescue, which was significantly lower compared to

placebo (p=0.0109) and metoclopramide groups (p=0.0402).

Postoperative analgesia with the combination of tramadol hydrochloride and metamizol

showed no significant difference among the four groups in terms of pain intensity at rest and

on movement, number of patients receiving postoperative analgesia, and time to first

analgesic request (Table 3). The intensity of postoperative pain was relatively minor; at 24 h

7

after surgery all four patients groups reported a similar low VAS pain score (median at rest;

group 1, 2.0; group 2, 2.1, and 1.9 in groups 3 and 4 and median with moment; group 1, 2.3;

group 2, 2.4; and 2.2 in groups 3 and 4). Analgesic supplementation with tramadol

hydrochloride 25 mg intravenously was only requested by two group 1 patients and one group

2 patient, and none of group 3 and 4 patients.

The potential side effects include headache, dizziness, anxiety, sleep disturbances, sedation

and perineal itching. In our study, the most frequently reported side effects were sleep

disturbances, sedation and headache, with no significant between-group differences (Table 4).

Perineal itching was not observed in any of our patients.

The patient postoperative state is summarized in Table 5. Two patients from the placebo

group and none of the patients from other groups described their postoperative state as poor

and very poor. The patients administered dexamethasone and dexamethasone plus

metoclopramide reported a significantly higher rate (p<0.005) of very good postoperative

state than those receiving placebo. Also, the patients administered placebo reported a

significantly higher rate of alternating postoperative state than those receiving dexamethasone

(p=0.0231) and the combination of dexamethasone plus metoclopramide (p=0.0068).

8

Discussion

This study compared the efficacy of the combination of dexamethasone and metoclopramide

with either antiemetic alone in patients undergoing laparoscopic cholecystectomy. Although

laparoscopic cholecystectomy decreased surgical morbidity and has become an accepted

procedure for the treatment of cholelithiasis [24], the high incidence of PONV remains a

major clinical problem.

The etiology of PONV after laparoscopic surgery performed under general anesthesia is not

fully understood, but is probably multifactorial [33]. Several factors, including age, sex,

smoking, history of motion sickness, intraoperative use of fentanyl and isoflurane, residual

pneumoperitoneum after CO2 insufflation [7], peritoneum distension, diaphragm irritation and

visceral organ irritation and manipulation [16], have been considered to influence the

incidence of PONV. In this study, however, treatment groups were similar with respect to

demographic data and duration of anesthesia, surgery and CO2 insufflation, whereas those

with a history of motion sickness and smoking were excluded from the study. Therefore, the

difference in the incidence of PONV among the groups could be attributed to the variation in

the antiemetic drugs administered.

As mentioned before, dexamethasone is a corticostereoid with an anti-inflammatory effect

that provides postoperative analgesia [8], prevents nausea and vomiting in patients receiving

highly emetogenic cancer chemotherapy [1,15], and reduces postoperative nausea and

vomiting [8,27,30]. The recommended dose in the prevention of PONV is 8-10 mg.

Therefore, in our study a dose of 8 mg dexamethasone was chosen. The mechanism of the

antiemetic action of dexamethasone and the precise site of action remain unclear. A previous

study has suggested that dexamethasone may antagonize prostangladin [2] or release

endorphins [11], resulting in mood elevation, a sense of well-being, and stimulate appetite.

Dexamethasone was found to be effective when used alone in the prevention of PONV in

several studies [31,32]. Henzi et al. [13] analyzed 17 trials involving 1946 patients, which

compared prophylactic dexamethasone with placebo to prevent PONV, and found it to be

superior to placebo without evidence of any clinically relevant toxicity. In our study, we also

found the total incidence of PONV to be 60% when no antiemetic was given prophylactically,

to be significantly reduced to 23% upon the pretreatment with dexamethasone.

Metoclopramide is a central dopaminergic D2 receptor antagonist and a prokinetic drug,

increasing gastric emptying and shortening bowel transit time. The meta-analysis by Domino

9

et al. [5] has shown that metoclopramide is not as effective as ondansetron and droperidol in

preventing postoperative vomiting. Henzi et al. [12] also performed a meta-analysis of

metoclopramide and found the dose of 10 mg to have no significant anti-nausea effect. Our

results with metoclopramide are in agreement with the study results of Hanzi et al. [12]. In

our study metoclopramide proved to be a poor antiemetic agent in a dose of 10 mg, associated

with a high incidence of PONV (45%). We found no significant reduction of PONV on

comparing metoclopramide with placebo.

Several studies compared a single dose of dexamethasone with a single dose of

metoclopramide in the prophylaxis and treatment of PONV, and found dexamethasone to be

superior in the control of nausea and vomiting [14,29]. Our study confirmed this observation

in terms of better antiemetic effects of dexamethasone vs metoclopramide, with an incidence

of complete response of 78%.

However, current opinion questions the role of monotherapy, and combinations of

dexamethasone with some other antiemetics have been found to be more effective than any

drug alone [4,18,21]. Biswas et al. [4] demonstrated that granisetron plus dexamethasone

reduced the incidence of PONV after laparoscopic cholecystectomy more effectively than

granisetron alone. McKenzie et al. [21] studied ondansetron and ondansetron plus

dexamethasone in women undergoing general anesthesia for major gynecologic surgery, and

the results showed the combination to be more effective than ondansetron alone.

Because of the high cost of these agents, we decided to use the less expensive

metoclopramide in our study. Although some studies describe the combination of

metoclopramide and dexamethasone as an inefficient combination for the prevention of

PONV [8,19], our study found this combination to be effective when compared to placebo.

The total incidence of PONV after laparoscopy was only 13% in patients administered the

combination of dexamethasone plus metoclopramide. The more so, none of the patients from

the dexamethasone and metoclopramide group required rescue antiemetic, pointing to the

high efficacy of this antiemetic combination in the prevention of PONV. One of the potential

reasons why previous studies failed to show the beneficial effects of the combination of

dexamethasone and metoclopramide on the incidence of PONV as compared to placebo may

lie in the timing of metoclopramide administration. It has been recently confirmed that

metoclopramide, because of the short duration of its antiemetic effect, is more efficacious

when administered at the end of anesthesia than when given at its induction [26].

So, we believe that the favorable results recorded in our study could be attributed to the

administration of metoclopramide at the end of anesthesia.

10

Pain after laparoscopic cholecystectomy is relatively minor and most intense during the first 4

hours following surgery [3]. In our study, all the four patient groups experienced sufficient

pain relief upon administration of the combination of tramadol hydrochloride and metamizol,

and reported low VAS pain score (0-4) at rest and on movement.

The most common side effects observed in this study were headache, sedation and sleep

disturbances. These were relatively mild, and there were no differences in the incidence of

side effects among the treatment groups. To avoid perineal itching with dexamethasone, we

administered it after the induction of anesthesia.

In conclusion, the present study demonstrated the combination of dexamethasone plus

metoclopramide and dexamethasone alone to be superior to metoclopramide and placebo in

preventing PONV after laparoscopic cholecystectomy.

11

References

1. Aapro MS, Alberts DS (1981) Dexamethasone as an antiemetic in patients treated

with cisplatin. N Engl J Med 305:520

2. Aapro MS, Plezia PM, Alberts DS, Graham V, Jones SE, Surwit EA, Moon TE

(1984) Double-blind cross-over study of the antiemetic efficacy of high dose

dexamethasone versus high dose metoclopramide. J Clin Oncol 2:466-467

3. Bisgaard T, Klarskov B, Kristiansen VB, Callesen T, Schulze S, Kehlet H,

Rosenberg J (1999) Multi-regional local anesthetic infiltration during

laparoscopic cholecystectomy in patients receiving prophylactic multi modal

analgesia: a randomized, double blind, placebo-controlled study. Anesth Analg

89:1017-1024

4. Biswas BN, Rudra A (2003) Comparison of granisetron and granisetron plus

dexamethasone for the prevention of postoperative nausea and vomiting after

laparoscopic cholecystectomy. Acta Anaesthesiol Scand 47:79-83

5. Domino KB, Anderson EA, Polissar NL, Posner KL (1999) Comparative efficacy

and safety of ondansetron, droperidol, and metoclopramide for preventing

postoperative nausea and vomiting: a meta-analysis. Anesth Analg 88:1370-1279

6. Elhakim M, Nafie M, Mahmoud K, Atef A (2002) Dexamethasone 8 mg in

combination with ondansetron 4 mg appears to be optimal dose for the

prevention of nausea and vomiting after laparoscopic cholecystectomy. Can J

Anesth 49:922-926

7. Fredman B, Jedeikin R, Olsfanger D, Flor P, Gruzman A (1994) Residual

pneumoperitoneum: a cause of postoperative pain after laparoscopic

cholecystectomy. Anesth Analg 79:152-154

8. Fujii Y, Tanaka H, Toyooka H (1997) The effects of dexamethasone on

antiemetics in female patients undergoing gynaecologic surgery. Anesth Analg

85:913-917

9. Fujii Y, Uemara A, Tanaka H (2002) Prophylaxis of nausea and vomiting after

laparoscopic cholecystectomy with ramosetron: randomized controlled trial. Eur

J Surg 168:583-586

12

10. Glaser C, Sitzwohl C, Wallner T, Lerche A, Marhofer P, Schindler I (2004)

Dixyrazine for the prevention of postoperative nausea and vomiting after

laparoscopic cholecystectomy. Acta Anaesthesiol Scand 48:1287-1291

11. Harris AL (1982) Cytotoxic-therapy-induced vomiting is mediated via enkephalin

pathways. Lancet 1:714-716

12. Henzi I, Walder B, Tramer MR (1999) Metoclopramide in the prevention of

postoperative nausea and vomiting: a quantitative systematic review of

randomized, placebo controlled studies. Br J Anaesth 83:761-771

13. Henzi I, Walder B, Tramer MR (2000) Dexamethasone for postoperative nausea

and vomiting: a quantitative systematic review. Anesth Analg 90:186-194

14. Huang JC, Shieh JP, Tang CS, Tzeng JI, Chu KS, Wang JJ (2001) Low-dose

dexamethasone effectively prevents postoperative nausea and vomiting after

ambulatory laparoscopic surgery. Can J Anesth 48:973-977

15. Italian Group for Antiemetic Research (1995) Dexamethasone, granisetron, or

both for the prevention of nausea and vomiting during chemotherapy for cancer.

N Engl J Med 332:1-5

16. Kenny GN (1992) Risk factor for postoperative nausea and vomiting. Anaesthesia

49:6-10

17. Kovac AL (2000) Prevention and treatment of postoperative nausea and

vomiting. Drugs 59:213-243

18. Lopez-Olaondo L, Carrascosa F, Pueyo FJ, Mondero P, Busto N, Saez A (1996)

Combination of ondansetron and dexamethasone in the prophylaxis of

postoperative nausea and vomiting. Br J Anaesth 76:835-840

19. Maddali MM, Mathew J, Fahr J, Zarroung AW (2003) Postoperative nausea and

vomiting in diagnostic gynaecological procedure: comparison of the efficacy of

the combination of dexamethasone and metoclopramide with that of

dexamethasone and ondansetron. J Postgrad Med 49:302-306

20. Madsen MR, Jensen KEJ (1992) Postoperative pain and nausea after

laparoscopic cholecystectomy. Surg Laparosc Endosc 2:303-305

21. McKenzie R, Tantisira B, Karambelker DJ, Riley TJ, Abdelhady H (1994)

Comparison of ondansetron with ondansentron plus dexamethasone in the

prevention of postoperative nausea and vomiting. Anaest Analg 79:961-964

22. Naguib M, el Bakry A, Khoshim MH, Channa AB, el Gammal M, el Gammal K,

Eihattab YS, Attia M, Jaroudi R, Saddique A (1996) Prophylactic antiemetic

13

therapy with ondansetron, tropisetron, granisetron and metoclopramide in

patients undergoing laparoscopic cholecystectomy: a randomized, double-blind

comparison with placebo. Can J Anaesth 43:226-231

23. Nesek Adam V, Grizelj Stojčić E, Mršić V, Smiljanić A, Rašić Ž, Čala Z (2004)

Prophylactic antiemetics for laparoscopic cholecystectomy: droperidol,

metoclopramide, and droperidol plus metoclopramide. J Laparoendosc Adv Surg

14:212-221

24. NIH Consensus conference (1993) Gallstones and laparoscopic cholecystectomy

JAMA 269:1018-1024

25. Paxton LD, McKay AC, Mirakhur RK (1995) Prevention of nausea and vomiting

after day case gynaecological laparoscopy. A comparison of ondansetron,

droperidol, metoclopramide and placebo. Anaesthesia 50:403-406

26. Quaynor H, Raeder JC (2002) Incidence and severity of postoperative nausea

and vomiting are similar after metoclopramide 20 mg and ondansetron 8 mg

given by the end of laparoscopic cholecystectomies. Acta Anaesth Scand

46:109:113

27. Splinter WM, Roberts DJ (1997) Prophylaxis for vomiting by children after

tonsillectomy: dexamethasone versus perphenazine. Anesth Analg 85:534-537

28. Subramaiam B, Madan R, Sadhasivam S, Sennaraj B, Tamilselvan P. Rajeshwari

S, Jagan D, Shende D (2001) Dexamethasone is a cost-effective alternative to

ondansetron in preventing PONV after paediatric strabismus repair. Br J

Anaesth 86:84-89

29. Tzeng JI, Hsing CH, Chu CC, Chen YH, Wang JJ (2002) Low-dose

dexamethasone reduces postoperative nausea and vomiting after epidural

morphine: comparison of metoclopramide with saline. J Clin Anesth 14:19-23

30. Wang JJ, Ho ST, Lee SC, Liu YC, Liu YH, Liao YC (1999) The prophylactic

effect of dexamethasone on postoperative nausea and vomiting undergoing

thyroidectomy: a comparison of droperidol with saline. Anesth Analg 89:200-203

31. Wang JJ, Ho ST, Liu HS, Ho CM (2000) Prophylactic antiemetic effect of

dexamethasone in women undergoing ambulatory laparoscopic surgery. Br J

Anaesth 84:459-462

32. Wang JJ, Ho ST, Liu YH, Lee SC, Liu YC, Liao YC, Ho CM (1999)

Dexamethasone reduces nausea and vomiting after laparoscopic cholecystectomy.

Br J Anaesth 83:772-775

14

33. Watcha MF, White PF (1992) Postoperative nausea and vomiting. Its etiology,

treatment, and prevention. Anesthesiology 77:162-184

15

Table 1. Patient characteristics

Group 1 Placebo

Group 2 Metoclopramide

Group 3 Dexamethasone

Group 4Dexamethasone

plus metoclopramide

ASA I/II 24/16 26/14 25/15 22/18

Age (yrs) 54.9±15.5 49.4±13.9 49.6±11.7 50.9±14.5

Sex (M/F) 13/27 8/32 10/30 14/26

Weight (kg) 71.8±11.7 74.2±14.3 70.0 ±12.4 68.6±10.9

Height (cm) 172.0±12.4 173.7±12.7 170.0±11.2 171.3±12.2

Duration of anesthesia (min)

68±19 67±28 65±17 66±16

Duration of surgery (min)

51±20 49±25 47±18 47±17

Duration of PNP (min)

44±18 42±23 39±16 39±15

Fentanyl administered (μg)

199±52 188±61 199±58 187±52

Data presented as mean ± standard deviation (SD); no significant between-group differences(PNP – pneumoperitoneum

16

Table 2. Incidence of nausea and vomiting during 24 h postoperatively according to medication groups

Group 1

Placebo

Group 2

Metoclopramide

Group 3

Dexamethasone

Group 4

Dexametasone

plus

metoclopramide

0 – 4

nausea

vomiting

total PONV

rescue antiemetics

9 (23)

7 (18)

16 (40)

3 (8)

7(18)

5 (13)

12 (30)

3 (8)

4 (10)

2 (5)

6 (15) *

1 (3)

2 (5)*

2 (5)

4 (10) *†

0 (0)

4 – 12

nausea

vomiting

total PONV

rescue antiemetics

13 (33)

10 (25)

23 (58)

5 (13)

10 (25)

7 (18)

17 (43)

4 (10)

6 (15)

3 (8) *

9 (23) *

1 (3)

3 (8) *†

2 (5) *

5 (13) *†

0 (0) *†

12 –24

nausea

vomiting

total PONV

rescue antiemetics

14 (35)

10 (25)

24 (60)

6 (15)

11 (28)

7 (18)

18 (45)

4 (10)

6 (15) *

3 (8) *

9 (23) *†

1 (3) *

3 (8) *†

2 (5) *

5 (13) *†

0 (0) *†

Complete response 16 (40) 22 (55) 31 (78) *† 35 (88) *†

Number of patients (%) with nausea and vomiting during three-assessment period.

Significant differences (p<0.05) compared with: * group placebo; † group metoclopramide;

17

Table 3. Postoperative visual analog scale (VAS) pain score at rest and with activity,

first tramadol request, and analgesic rescue

VAS

(mean range)

At rest With

activity

Patients receiving

postoperative

analgesia

N (%)

Rescue

analgesic

N (%)

Time to first

tramadol

administration

(min)

Group 1

0 – 4 3.6 (1.9-4.9) 3.9 (2.3-5.3) 30 (75)

4 – 12 2.7 (1.8-5.4) 3.1 (2.0-6.0) 5 (13) 2 (5) 70.3±17.1

12 – 24 2.0 (1.5-2.7) 2.3 (1.8-3.0) 0 (0)

Total 0 - 24 35 (88)

Group 2

0 – 4 3.5 (1.8-4.9) 3.8 (2.0-5.3) 28 (70)

4 – 12 2.6 (1.6-5.6) 2.9 (1.9-6.1) 6 (15) 1 (3) 68.9±21.4

12 – 24 2.1 (1.6-2.9) 2.4 (1.9-3.1) 0 (0)

Total 0 - 24 34 (85)

Group 3

0 – 4 3.4 (1.7-4.9) 3.7 (1.9-5.3) 28 (70)

4 – 12 2.5 (1.6-4.2) 2.8 (1.9-4.5) 5 (13) 0 (0) 71.8±23.5

12 – 24 1.9 (1.5-2.7) 2.2 (1.8-2.9) 0 (0)

Total 0 - 24 33 (83)

Group 4

0 – 4 3.4 (1.8-4.8) 3.7 (2.1-5.2) 29 (73)

4 – 12 2.6 (1.8-4.1) 2.8 (2.0-4.3) 4 (10) 0 (0) 68.6±23.0

12 – 24 1.9 (1.6-2.7) 2.2 (1.9-3.1) 0 (0)

Total 0 – 24 33 (83)

There were no significant between – group differences.

18

Table 4. Incidence of side effects

Group 1Placebo

Group 2 Metoclopramide

Group 3 Dexamethasone

Group 4 Dexamethasone

plus metoclopramide

Headache 4 (10) 3 (8) 2 (5) 3 (8)

Dizziness 1 (3) 0 (0) 0 (0) 1 (3)

Anxiety 3 (8) 4 (10) 2 (5) 2 (5)

Perineal itching 0 (0) 0 (0) 0 (0) 0 (0)

Sedation 3 (8) 3 (8) 4 (10) 3 (8)

Sleep disturbance 6 (15) 5 (13) 3 (8) 4 (10)

Values are number (%) of patients.

19

Table 5. Postoperative well-being scores

Very good1

Good2

Alternating3

Poor4

Very poor5

Placebo

9 (23) 20 (50)

9 (23) 1 (3) 1 (3)

Metoclopramide 15 (38) 22 (55) 3 (8) 0 (0) 0 (0)

Dexamethasone

20 (50)* 19 (48)

1 (3) * 0 (0) 0 (0)

Dexamethasone plus

metoclopramide

23 (58) * 15 (38)

2 (5) * 0 (0) 0 (0)

Values are number (%) of patients.Significant differences from placebo: * p<0.05

20