Comparison of Dexamethasone-Diphenhydramine and Dexamethasone-Ondansetron in Preventing Post-Operative Nausea and Vomiting after Laparoscopic Cholecystectomy

Objective: To compare the efficacy of a combination of dexamethasone-dimenhydrinate with dexamethasone-ondansetron in preventing postoperative nausea and vomiting after laparoscopic cholecystectomy.
Methodology: A total of 160 patients were enrolled, 80 patients each to either group D for the Dexamethasone-Dimenhydrinate group or group O for Dexamethasone-Ondansetron. The study was carried out over a period of six months from 01-01-2022 to 30-06-2022. The study was held at the Department of Anaesthesia, Holy Family Hospital, Rawalpindi Medical University and Allied Hospital.
Results: The mean age of the patients was 42.3±13.2 and 42.4±14.0 in group D and group O, respectively. There were 40 (50%) males and females in Group D while 29 males (36.3%) and 51 females (63.7%) in Group o. Efficacy of combination dexamethasone+ dimenhydrinate with dexamethasone ondansetron in preventing PONV showed at 30 minutes (5.0% vs 12.5%; p=0.093), at 60 minutes (7.5% vs 20.0%; p=0.022), at 120 minutes (6.3% vs 17.5%; p=0.028) and 24 hours (5.0% vs 18.8%; p=0.007).
Conclusion: In conclusion, our study demonstrated that the dexamethasone–dimenhydrinate combination was more effective than the dexamethasone–ondansetron combination in preventing nausea and vomiting after laparoscopic cholecystectomy.
Keywords: Dexamethasone, dimenhydrinate, Ondansetron, Postoperative nausea and vomiting.

Anesthesiologists care for surgical patients in the perioperative and postoperative periods.¹ Postoperative nausea and vomiting (PONV) are one of the most common postoperative concerns with an incidence of up to 80% in high-risk patients, depending on the type of surgery and anaesthesia1. It is of great concern than even postoperative pain, to the surgical patients².PONV may lead to serious surgical complications such as wound dehiscence or surgical site bleeding, hematoma, aspiration and choking probability, and water and electrolyte disturbances resulting in increased healthcare costs due to lower patient satisfaction and delayed hospital discharge³. It is believed that PONV has a multifactorial origin⁴. These factors can be divided into patient-related characteristics (age, gender, obesity and smoking status as well as the history of motion sickness or previous PONY), anaesthetic-related (volatile anaesthetics, intraoperative use of opioid and blood. transfusion) and surgical-related factors (type and duration of surgery and use of postoperative analgesic opioids⁵.
Administration of antiemetic drugs to prevent and manage PONV is an important tool that should be used properly and regularly6. Considering the multifactorial aetiology of this complication, multimodal therapy is recommended for the prevention of PONV in high-risk patients⁷. Therefore, various drug combinations have been tried and found to be effective for this issue, albeit they had some side effects⁸.
The study done by Kizilcik et al., suggested that the dexamethasone-dimenhydrinate combination was more effective than dexamethasone-ondansetron in the prevention of nausea and vomiting after rhinoplasty operations¹. The additional antiemetic need in the dexamethasone-ondansetron group was significantly higher at 30 min after surgery (p=0.001). However, the difference in the reported incidence of vomiting after 60 minutes of surgery, which was 16.7% in the dexamethasone-ondansetron group versus 3.3% in the dexamethasone-dimenhydrinate group (p=0.195), was statistically insignificant¹.
Niazi et al reported that the efficacy of the Dimenhydrinate-dexamethasone combination was 88% while dexamethasone-ondansetron achieved efficacy in 65% of cases, which was statistically significant (<0.05)9. In perioperative medicine, Dimenhydrinate and ondansetron are the two most frequently used medications for PONV prophylaxis. There is still no medication that provides complete PONV prophylaxis. Numerous trials have compared ondansetron and dimenhydrinate in the prevention of PONV following laparoscopic surgery. Their findings are inconsistent, and there is no agreement on which drug is superior for PONV prophylaxis. Studies carried out in the Pakistani population are quite a few. We want to compare the efficacy of combination dexamethasone=dimenhydrinate with dexamethasone-ondansetron in preventing postoperative nausea and vomiting (PONV) after laparoscopic cholecystectomy. This will not only help in providing data for the Pakistani population in this regard as well as providing a cost-effective means in government setups to deal with this issue with evidence.

This was a randomized control trial conducted between 01-01-2022 and 30-06-2022. The study was conducted at the Department of Anaesthesia, Holy Family Hospital affiliated with Rawalpindi Medical University (RMU). The sample size was calculated using the OpenEpi sample size calculator, sample size was calculated from a reference study [1] taking the incidence of vomiting after 60 min of surgery to be 16.7% in the dexamethasone-Ondansetron group versus 3.3% in the Dexamethasone-Dimenhydrinate group. Keeping the power of study at 80%, and the level of significance at 5%, the minimally required sample size was calculated as 160 with at least 80 in each group. A consecutive non-probability sampling technique was used. Male and female patients aged between 18-65 years; ASA grade 1 & 2 who were planned for elective laparoscopic cholecystectomy were included. Exclusion criteria included allergies, pregnant ladies or patients taking any acute or chronic dexamethasone, ondansetron and dimenhydrinate.
Data Collection: After approval from the Institutional Research Forum of Rawalpindi Medical University, all patients fulfilling the selection criteria were registered through the anaesthesia department of Holy Family Hospital, RMU and Allied Hospital, Rawalpindi. Demographic history including age (in years) and sex (male or female) were taken. Informed written consent was taken by patients after explaining to them the purpose and procedure of the study and the randomization process. Randomization was done through a random number list already generated using SPSS software equally but randomly allocating 80 patients each to either group D for the Dexamethasone-Dimenhydrinate group or group O for Dexamethasone-Ondansetron. 80 patients in group D received 8 mg of dexamethasone and 50 mg of dimenhydrinate while group 0 received 8 mg of dexamethasone and 4 mg of ondansetron at 15 min post induction of general anaesthesia. General anaesthesia with intermittent positive pressure ventilation with endotracheal intubation was employed in all patients. Anaesthesia was maintained using isoflurane, oxygen/nitrous oxide mixture and nalbuphine. Postoperative pain was managed using ketorolac 0.5 mg/kg and tramadol 1.5 mg/kg. After completing the operation, the patients were evaluated for PONV at the 30th and 60th min in the postoperative period in the recovery room and at the 120th min and 24 hr in the ward by anaesthetic nurses. The patients were able to request antiemetic medications, and the drugs along with their doses will be recorded. The findings were recorded in structured pro forma attached as Annexure 1.
Data analysis: All the collected data were entered and analyzed using the statistical package of social sciences (SPSS version 22). Descriptive statistics were recorded for qualitative and quantitative variables. Qualitative variables like gender and PONV were measured as frequency and percentage. Quantitative data like age (in years) was presented as mean and standard deviation: Effect modifiers like age and gender were controlled by stratification. Post-stratified chi-square test was used. Efficacy between groups was compared by chi-square test. P-values less than 0.05 were considered statistically significant.

A total of 160 patients (80 in each group) were enrolled in the study. Group D received Dexamethasone-Dimenhydrinate while Group O administered a Dexamethasone-Ondansetron combination.
Patients ranged between 18-65 years of age with a mean age of 42.3±13.2 and 42.4±14.0 in group D and group-O, respectively. There were 40 (50%) males and females in Group D while 29 males (36.3%) and 51 females (63.7%) in Group o.
The efficacy of combination dexamethasone+dimtenhydrinate with dexa+methasone+ondansetron in preventing PONV showed at 30 minutes (5.0% vs 12.5%; p=0.093), at 60 minutes (7.5% vs 20.0%; p=0.022), at 120 minutes (6.3% vs 17.5%; p=0.028) and 24 hours (5.0% vs 18.8%; p=0.007) (Table III-VI).

Postoperative nausea and vomiting a well-described side effects related to the patient, anaesthetic and surgical factors. There are a lot of medications to prevent PONV, such as metoclopramide, dimenhydrinate, serotonin antagonists and dexamethasone. Although an antiemetic prophylaxis might not eliminate the risk of PONV, it can significantly reduce the incidence of nausea and vomiting¹⁰. However, no single excellent medication or method is there to describe. Various antiemetic drugs can be used for the treatment of PONV. Dexamethasone can decrease the incidence of PONV¹¹. However, some authors emphasize that the combination of antiemetic drugs can further reduce PONV compared to single-agent treatment¹², especially for high-risk patients¹³.
Dexamethasone is well-documented as an effective antiemetic. A single dose of dexamethasone administered perioperatively is rarely associated with significant side effects¹⁵. Preoperative dexamethasone 8 mg significantly reduces PONV and the use of rescue antiemetic¹⁶. Karanicolas et al published a systematic review and meta-analysis of 17 randomized controlled trials that evaluated the impact of prophylactic corticosteroid administration on PONV. The authors concluded that dexamethasone decreases the incidence of nausea and vomiting and that higher doses of dexamethasone (8–16 mg) are more effective than smaller doses (2–5 mg) in patients undergoing laparoscopic cholecystectomy¹⁷. Vomiting is the forceful expulsion of gastrointestinal contents through the mouth. Retching is the rhythmic action of the respiratory muscles preceding vomiting. Both retching and vomiting are objective patient experiences. Nausea is a subjective experience which may or may not be associated with vomiting¹⁸.
The mechanism of the vomiting reflex was first described by Borison and Wang (1953) to be a complex act involving the respiratory, gastrointestinal, and abdominal musculature controlled by the vomiting center. The vomiting center is situated in the lateral reticular formation close to the tractus solitarius in the brain stem. The vomiting center can be triggered by stimuli from the periphery: the oropharynx, the gastrointestinal tract, the mediastinum, renal pelvis, peritoneum and genitalia, and centrally from the CNS: cerebral cortex, labyrinthine, the visual center, the vestibular portion of the eighth cranial nerve, and the chemoreceptor trigger zone (CTZ) located in the area postrema at the base of the fourth ventricle¹⁹. As the area postrema has no effective blood-brain barrier, CTZ can be directly stimulated by chemicals in the cerebrospinal fluid (CSF) and blood¹⁹.
The CTZ has high concentrations of encephalin, dopamine, and opioid receptors. The area postrema is rich in opioid, dopamine (D) and serotonin (5-hydroxytryptamine (5-HT)) receptors. The nucleus of the solitary tract contains high concentrations of encephalin, histamine, muscarinic (M), and cholinergic receptors. Recently, substance P and neurokinin-1 (NK1) receptors were found to be involved in the regulation of emesis. At present it is generally accepted that the key to control PONV is the blocking of all the recognized receptors involved in emesis19. A combination of dexamethasone with other antiemetics is more effective than any single drug alone²⁰.
Ondansetron is a carbazalone derivative that is structurally related to serotonin and possesses specific 5-HT3 subtype receptor antagonist properties without altering dopamine, histamine, adrenergic, or cholinergic receptor activity. The most serious side effects of ondansetron are rare hypersensitivity reactions. Other more commonly reported side effects are headache, light-headedness, dizziness, flushing at the i.v. site, transient increases in the plasma concentrations of liver transaminase enzymes, a warm epigastric sensation, and constipation. Cardiac dysrhythmias have been reported after i.v. administration of ondansetron and metoclopramide [68]. It can be used effectively in PONV. However, it might not eliminate PONV, probably because it acts through the blockage of one receptor²¹.
In current study we compared the efficacy of combination dexamethasone+dimtenhydrinate with dexa+methasone-ondansetron in preventing PONV at 30 minutes (5.0% vs 12.5%; p=0.093), at 60 minutes (7.5% vs 20.0%; p=0.022), at 120 minutes (6.3% vs 17.5%; p=0.028) and 24 hours (5.0% vs 18.8%; p=0.007). Our findings are comparable with a study carried out by Kizilcik et al. ¹

In conclusion, our study demonstrated that the dexamethasone–dimenhydrinate combination was more effective than the dexamethasone–ondansetron combination in the prevention of nausea and vomiting after laparoscopic cholecystectomy.

1. Kizilcik N, Bilgen S, Menda F, Türe H, Aydın B, Kaspar EC, et al. Comparison of Dexamethasone-Dimenhydrinate and Dexamethasone-Ondansetron in the prevention of nausea and vomiting in postoperative patients. Aesthetic Plast Surg. 2017;41(1):204-10.
2. Phillips C, Brookes CD, Rich J, Arbon J, Turvey TA. Postoperative nausea and vomiting following orthognathic surgery. Int J Oral Maxillofac Surg. 2015;44(6):745-51. https://doi.org/10.1016%2Fj.ijom.2015.01.006
3. Brookes CD, Berry J, Rich J, Golden BA, Turvey TA, Blakey G 3rd, Kopp V, Phillips C, Anderson J. Multimodal protocol reduces postoperative nausea and vomiting in patients undergoing Le Fort I osteotomy. J Oral Maxillofac Surg. 2015;73(2): 324-32. https://doi.org/10.1016/j.joms.2014.08.007
4. Shilpa SN, Shailaja S, Hilda SS. Comparison of Efficacy of Clonidine versus Ondansetron for Prevention of Nausea and Vomiting Post Thyroidectomy: A Double-Blind Randomized Controlled Trial. J Clin Diagn Res. 2015;9(5): UC01-3. https://doi.org/10.7860%2FJCDR%2F2015%2F12721.5866
5. Ha SH, Kim H, Ju HM, Nam DJ, Min KT. Comparison of the antiemetic effect of ramosetron with ondansetron in patients undergoing microvascular decompression with retromastoid craniotomy: a preliminary report. Korean J Anesthesiol. 2015;68(4):386-91. https://doi.org/10.4097%2Fkjae.2015.68.4.386
6. Talebpour M, Ghiasnejad Omrani N, Imani F, Shariat Moharari R, Pourfakhr P, Khajavi MR. Comparison Effect of Promethazine/ Dexamethasone and Metoclopramide /Dexamethasone on Postoperative Nausea and Vomiting after Laparascopic Gastric Placation: A Randomized Clinical Trial. Anesth Pain Med. 2017;7(4): e57810. https://doi.org/10.5812%2Faapm.57810
7. Bilgen S, Kızılcık N, Haliloğlu M, Yıldırım G, Kaspar EÇ, Köner Ö. Effect of the dexamethasone-ondansetron combination versus dexamethasone-aprepitant combination to prevent postoperative nausea and vomiting. Turk J Anaesthesiol Reanim. 2018;46(5):373-380. https://doi.org/10.5152%2FTJAR.2018.53179
8. Urits I, Orhurhu V, Jones MR, Adamian L, Borchart M, Galasso A, Viswanath O. Postoperative Nausea and Vomiting in Paediatric Anaesthesia. Turk J Anaesthesiol Reanim. 2020;48(2):88-95. https://doi.org/10.5152/tjar.2019.67503
9. Niazi AK, Bukhari S, Ali SM, Arshad M, Taqi M. Role of Prophylactic Dimenhydrinate Versus Ondansetron as an Adjunct to Dexamethasone on Post-Operative Nausea and Vomiting in Laparoscopic Abdominal Procedures. InProceedings S.Z.M.C 2020;34(3):29-34.
10. Sánchez-Rodríguez PE, Fuentes-Orozco C, Gonzalez-Ojeda A. Effect of dexamethasone on postoperative symptoms in patients undergoing elective laparoscopic cholecystectomy: randomized clinical trial. A World J Surg. 2010; 34:895–900. https://doi.org/10.1007/s00268-010-0457-9
11. Singla NK, Singla SK, Chung F, Kutsogiannis DJ, Blackburn L, Lane SR, et al. Phase II study to evaluate the safety and efficacy of the oral neurokinin-1 receptor antagonist casopitant (GW679769) administered with ondansetron for the prevention of postoperative and postdischarge nausea and vomiting in high-risk patients. Anesthesiology. 2010; 113:74–82. https://doi.org/10.1097/aln.0b013e3181d7b13a
12. Fujii Y. The utility of antiemetics in the prevention and treatment of postoperative nausea and vomiting ,,in patients scheduled for laparoscopic cholecystectomy. Curr Pharm Des. 2005; 11:3173–83. https://doi.org/10.2174/1381612054864911
13. Golembiewski J, Tokumaru S. Pharmacological prophylaxis and management of adult postoperative/postdischarge nausea and vomiting. J Perianesth Nurs. 2006; 21:38597. https://doi.org/10.1016/j.jopan.2006.09.004
14. Jo YY, Lee JW, Shim JK, Lee WK, Choi YS. Ramosetron, dexamethasone, and their combination for the prevention of postoperative nausea and vomiting in women undergoing laparoscopic cholecystectomy. Surg Endosc. 2012; 26:2306–11. https://doi.org/10.1007/s00464-012-2180-0
15. Tolver MA, Strandfelt P, Bryld EB, Rosenberg J, Bisgaard T. Randomized clinical trial of dexamethasone versus placebo in laparoscopic inguinal hernia repair. Br J Surg. 2012; 99:1374–80. https://doi.org/10.1002/bjs.8876
16. Karanicolas PJ, Smith SE, Kanbur B, Davies E, Guyatt GH. The impact of prophylactic dexamethasone on nausea and vomiting after laparoscopic cholecystectomy: a systematic review and meta-analysis. Ann Surg. 2008; 248:751–62. https://doi.org/10.1097/sla.0b013e3181856024
17. Karanicolas PJ, Smith SE, Kanbur B, Davies E, Guyatt GH. The impact of prophylactic dexamethasone on nausea and vomiting after laparoscopic cholecystectomy: a systematic review and meta-analysis. Ann Surg. 2008; 248:751–62. https://doi.org/10.1097/sla.0b013e3181856024
18. Litomi T, Toriumi S, Kondo A, Akazawa T. Incidence of nausea and vomiting after cholecystectomy performed via laparotomy or laparoscopy. Masui 1995; 44:1627-31. PMID: 8583657.
19. Ganang WF. Review of medical physiology. 19th ed. California: Appleton and Lange 1999: 221-22.
20. Conway B. Prevention and management of postoperative nausea and vomiting in adults. AORN J 2009; 90:391-413. https://doi.org/10.1016/j.aorn.2009.06.026
21. Skledar SJ, Williams BA, Vallejo MC, Dalby PL, Waters JH, Glick R, et al. Eliminating postoperative nausea and vomiting in outpatient surgery with multimodal strategies including low doses of nonsedating, off-patent antiemetics: is "zero tolerance" achievable? ScientificWorldJournal 2007; 7:959-77. http://dx.doi.org/10.1100/tsw.2007.131,,,