Volume 18 Issue 2

Table of Content - Volume 18 Issue 2 - May 2021

Comparative study of efficacy of Ramosetron and Ondansetron for the prevention of postoperative nausea and vomiting (PONV) after laparoscopic cholecystectomy at a tertiary hospital

Maninder Singh¹, Rajdeep Kour^2*, Neha Sharma³

¹Consultant, Department of Anaesthesiology, Shri Mata Vaishno Devi Narayana Superspeciality Hospital, Katra, Jammu, INDIA.

^2,3Lecturer, Department of Anaesthesiology, Government Medical College, Jammu, INDIA.

Email: drrajdeepkour1@gmail.com

Abstract Background: The Use of antiemetic prophylaxis has become the standard approach to minimize the nausea and vomiting postoperatively after any surgery. In present study, we compared the efficacy of ramosetron and ondansetron for the prevention of postoperative nausea and vomiting (PONV) after laparoscopic cholecystectomy at a tertiary hospital. Material and Methods: This prospective, observational study was conducted in adult patients (20 - 60 yrs. of age), ASA grade 1 and 2, nonsmoker, scheduled for elective laparoscopic cholecystectomy.80 adult patients scheduled for elective laparoscopic cholecystectomy were randomised with computer generated random numbers by the process of randomization and were assigned to each group consisted of 40 patients. Group O: patients received Ondansetron 4mg i/v stat and Group R: patients received Ramosetron 0.3mg i/v stat. Results: Total 80 patients were considered in present study, divided into group-A (n=40, treated with Ondansetron) and group-B (n=40, treated with Ondansetron). There was no significant difference in mean age, height and weight of the patients of the two groups (p>0.05). Also ꭓ² test showed that there was no significant difference in ASA Grade of the patients of the two groups (p>0.05). Thus, the patients of the two groups were matched for all demographic parameters. There was no significant difference in mean of all of the haemodynamic parameters of the patients of the two groups (p>0.05). There was no significant difference in mean duration of anaesthesia, duration of surgery, mean time to vomit (from the time of extubation till first 48 hours), mean time to retching(from the time of extubation till first 48 hours) of the patients of the two groups. There was no significant association between status of vomiting, retching, status of nausea (from the time of extubation till first 48 hours) and requirement of rescue drug in different post-operative period between patients of the two groups. Conclusion: There was no significant difference in the incidence of postoperative nausea and vomiting for ondansetron and ramosetron group during first 48 hours after laparoscopic cholecystectomy.

Keywords: Ramosetron, ondansetron, postoperative nausea and vomiting (PONV), laparoscopic cholecystectomy.

INTRODUCTION

It has been one and a half century since the first anaesthesia was administered and despite the remarkable advances in this specialty and the development of newer anaesthetics the incidence of post-operative nausea and vomiting is still unacceptably high.¹ Generally, one third of patients undergoing surgery are known to suffer from post-operative nausea and vomiting or both and they often rate PONV worse than post-operative pain.² Laparoscopic surgery provides spectacular benefits to the patients and laparoscopic Cholecystectomy has become the gold standard for cholelithiasis. Despite the introduction of newer antiemetic drugs, short acting anaesthetic agents and minimal invasive surgical techniques, the incidence of postoperative nausea and vomiting has remained largely unchanged.³ Use of antiemetic prophylaxis has become the standard approach to minimize the nausea and vomiting postoperatively. Newer antiemetics have been studied for prevention and treatment of PONV in patients scheduled for Laparoscopic Cholecystectomy. Routinely employed drug classes are Prokinetics, Dopaminergic antagonists, 5HT3 antagonists, Butyrophenone, Anticholinergics, Phenothiazines, Antihistaminic, Benzamide and Steroids.⁴ 5HT3 receptor antagonists are considered better and safer. The commonly used drug of 5HT3 receptor antagonist group is Ondansetron. Ondansetron is being considered as a gold standard for the treatment of PONV. Various studies have shown that it is more effective in preventing early but not delayed PONV. This may be due to its shorter duration of action though it claims to have duration of action of 4-12hrs.⁵ Ramosetron is a recently developed 5HT3 receptor antagonists. It exhibit significantly greater binding affinity for 5HT3 receptors, with slower dissociation rate resulting in more potent and longer receptor antagonist effect.⁶ In the present study, we compared efficacy of ramosetron and ondansetron for the prevention of postoperative nausea and vomiting (PONV) after laparoscopic cholecystectomy at a tertiary hospital.

MATERIAL AND METHODS

This prospective, observational study was conducted in the Department of Anesthesiology and Intensive care Apollo Gleneagles hospital Kolkata. Study was approved by institutional ethics committee.

Inclusion criteria

Adult patient (20 - 60 yrs. of age), ASA grade 1 and 2, nonsmoker, scheduled for elective laparoscopic cholecystectomy

Exclusion criteria

Patient refusal, any known allergy or contraindication to any of the two drugs.
Pregnant and lactating females who vomited or received antiemetics within 24 h before surgery.
Hepatic, renal or cardiopulmonary co morbidities.
Alcoholism, diabetes, significant gastrointestinal disorders (for example peptic ulcer disease or gastro oesophageal reflux disease) .
Patient who have received cancer chemotherapy within 4 weeks
Patient not willing to participate in the study.
Patients with BMI > 30 kg/sq m.

80 adult patients were selected for elective laparoscopic cholecystectomy surgery. Patients were randomised with computer generated random numbers by the process of randomization and were assigned to each group consisted of 40 patients.

Group O: patients received Ondansetron 4mg i/v stat

Group R: patients received Ramosetron 0.3mg i/v stat

Pre-anesthetic check-up was done one day before surgery and it included detailed history, thorough physical examination (General and Systemic) and relevant investigations . Demographic profile including age, sex, height and weight were recorded and BMI was calculated. An informed written consent was taken from all the patients at the time of preanesthetic examination. In the operating room standard monitoring was done. Patients received Ondansetron 4mg or Ramosetron 0.3mg by slow i/v injections at the time of induction. All patients received 0.2mg of glycopyrrolate as a premedication. A standard anesthesia balanced anesthesia technique was used with fentanyl (2mcg/kg)as an opioid, propofol (2mg/kg)as an induction agent and atracurium (0.6mg/kg)for facilitating endotracheal intubation. Anesthesia was maintained with air and oxygen and sevoflurane and supplemented by intermittent atracurium and IPPV. A nasogastric tube was inserted to make the stomach empty of air and other contents. For laparoscopic surgical procedure peritoneal cavity was insufflated with CO2 to keep intra-abdominal pressure ≤ 12 mmHg. Perioperative analgesia was maintained with a balanced multimodal approach with fentanyl and paracetamol intravenously. Glycopyrrolate 10mcg/kg and Neostigmine 50 mcg/kg body weight were used as reversal agents. For postoperative pain control injection paracetamol 1 gram 8 hourly daily was given as a first line agent at 8 hourly intervals for first 24 hours. Close monitoring was done for 48 hrs. for either complete response of PONV or complaints of nausea, retching, vomiting and need for rescue antiemetic at intervals of 0-2, 2-6, 6-24, 24-48 hours post-surgery by direct questioning to the patient or to her attendant. Statistical Analysis was performed with help of Epi Info (TM) 3.5.3 which is a trademark of the Centres for Disease Control and Prevention (CDC). ꭓ²test was used to test the association between different study variables under study. Corrected ꭓ² test was used in case of any one of cell frequency was found less than 5 in the bivariate frequency distribution. Test of proportion (Z-test) was used to test the significant difference between two proportions. t-test was used to test the significant difference between means. p≤0.05 was considered statistically significant.

RESULTS

Total 80 patients were considered in present study, divided into group-A (n=40, treated with Ondansetron) and group-B (n=40, treated with Ramosetron). There was no significant difference in mean age, height and weight of the patients of the two groups (p>0.05). Also ꭓ² test showed that there was no significant difference in ASA Grade of the patients of the two groups (p>0.05). Thus, the patients of the two groups were matched for all demographic parameters.

Table 1: Comparison of demographic parameters

Demographic Parameters	Group-A (n=40)	Group-B (n=40)	t₅₈-value	p-value
Age (in years)	40.67±4.41	39.70±5.01	0.91	0.36
ASA (I : II)	28:12	32:8	ꭓ²=1.06	0.30
Height (in cm)	168.95±9.88	169.40±9.23	0.21	0.83
Weight (in kg)	58.55±4.33	58.42±4.55	0.13	0.89

t-test showed that there was no significant difference in mean of all of the haemodynamic parameters of the patients of the two groups (p>0.05).

Table 2: Comparison of baseline haemodynamic parameters

Haemodynamic Parameters	Group-A (n=40)	Group-B (n=40)	t₅₈-value	p-value
Heart Rate	74.85±4.85	75.30±5.21	0.40	0.68
SBP (mmHg)	126.67±5.82	126.62±6.67	0.03	0.97
DBP (mmHg)	72.85±4.61	72.07±3.92	0.81	0.41
SPO₂	99.77±0.42	99.67±0.47	1.01	0.31

t-test showed that there was no significant difference in mean duration of anaesthesia, duration of surgery, mean time to vomit (from the time of extubation till first 48 hours), mean time to retching(from the time of extubation till first 48 hours) of the patients of the two groups.

Table-3: Comparison of general characteristics

Time (in minutes)	Group-A (n=40)	Group-B (n=40)	t₅₈-value	p-value
Duration of anaesthesia (in minutes)	64.70±6.39	65.52±7.80	0.51	0.60
Duration of surgery (in minutes)	54.70±6.39	55.75±7.84	0.65	0.51
Time to vomiting	19.23±15.77	20.40±11.87	0.37	0.70
Time to retching	27.10±12.72	28.10±0.01	0.49	0.62
Time to nausea	22.21±17.66	19.01±11.80	0.95	0.82

No patients of the two groups had vomiting up to post-operative 2 hours. Only 1(2.5%) patient of Group-A and 1(2.5%) patient of Group-B had vomiting between 2 – 6 hours which was not statistically significant (Z=0.01;p=0.99). Proportion of patients with vomiting between 6-24 hours in Group-B (7.5%) was higher than that of Group-A (2.5%) but it was not significant (Z=1.62;p=0.11). Only 1(2.5%) patient of Group-A and 1(2.5%) patient of Group-B had vomiting between 24 – 48 hours which was not statistically significant (Z=0.01;p=0.99). Chi-square test showed that there was no significant association between status of vomiting(from the time of extubation till first 48 hours) and patients of the two groups (p=0.45). Thus, prevalence of vomiting was more or less equally distributed among the patients of Group-A (7.5%) and Group-B (12.5%).

Table 4: Comparison of status of vomiting of the patients of the two groups

Vomiting	Post-Operative Monitoring Time Period (in hours)
	0-2			2 -6			6-24			24-48
	Gr-A (n=40)	G-B (n=40)	Total	Gr-A (n=40)	G-B (n=40)	Total	Gr-A (n=40)	G-B (n=40)	Total	Gr-A (n=40)	G-B (n=40)	Total
Yes Row % Col %	0 0.0 0.0	0 0.0 0.0	0 0.0 0.0	1 50.0 2.5	1 50.0 2.5	2 100.0 2.5	1 25.0 2.5	3 75.0 7.5	4 100.0 5.0	1 50.0 2.5	1 50.0 2.5	2 100.0 2.5
No Row % Col %	40 50.0 100.0	40 50.0 100.0	80 100.0 100.0	39 50.0 97.5	39 50.0 97.5	78 100.0 97.5	39 51.3 97.5	37 48.7 92.5	76 100.0 95.0	39 50.0 97.5	39 50.0 97.5	78 100.0 97.5
TOTAL Row % Col %	40 50.0 100.0	40 50.0 100.0	80 100.0 100.0	40 50.0 100.0	40 50.0 100.0	80 100.0 100.0	40 50.0 100.0	40 50.0 100.0	80 100.0 100.0	40 50.0 100.0	40 50.0 100.0	80 100.0 100.0

No patients of the two groups had retching up to post-operative 6 hours. Only 1(2.5%) patient of Group-A had retching between 6 – 48 hours which was not statistically significant in comparison to Group-B (2.5%) (Z=0.01;p=0.99).

Chi-square (ꭓ²) test showed that there was no significant association between status of retching(from the time of extubation till first 48 hours) and patients of the two groups (p=0.55). Thus, prevalence of retching was more or less equally distributed among the patients of Group-A (5.0%) and Group-B (2.5%).

Table 5: Comparison of status of retching of the patients of the two groups.

Retching	Post-Operative Monitoring Time Period (in hours)
	0-2			2 -6			6-24			24-48
	Gr-A (n=40)	G-B (n=40)	Total	Gr-A (n=40)	G-B (n=40)	Total	Gr-A (n=40)	G-B (n=40)	Total	Gr-A (n=40)	G-B (n=40)	Total
Yes Row % Col %	0 0.0 0.0	0 0.0 0.0	0 0.0 0.0	0 0.0 0.0	0 0.0 0.0	0 0.0 0.0	1 100.0 2.5	0 0.0 0.0	1 100.0 1.3	1 100.0 2.5	1 100.0 2.5	2 100.0 2.5
No Row % Col %	40 50.0 100.0	40 50.0 100.0	80 100.0 100.0	40 50.0 100.0	40 50.0 100.0	80 100.0 100.0	39 49.4 97.5	40 50.6 100.0	79 100.0 98.8	39 49.4 97.5	39 49.4 97.5	78 100.0 97.5
TOTAL Row % Col %	40 50.0 100.0	40 50.0 100.0	80 100.0 100.0	40 50.0 100.0	40 50.0 100.0	80 100.0 100.0	40 50.0 100.0	40 50.0 100.0	80 100.0 100.0	40 50.0 100.0	40 50.0 100.0	80 100.0 100.0

Chi-square test showed that there was no significant association between status of nausea(from the time of extubation till first 48 hours) and patients of the two groups (p=0.76). Thus, prevalence of nausea was more or less equally distributed among the patients of Group-A (15.0%) and Group-B (17.5%) (Z=0.57;p=0.56).

Table 6: Comparison of overall status of nausea of the patients of the two groups.

Status of nausea	Group-A (n=40)	Group-B (n=40)	TOTAL
Occurred Row % Col %	6 46.2 15.0	7 53.8 17.5	13 100.0 16.3
Not Occurred Row % Col %	34 50.7 85.0	33 49.3 82.5	67 100.0 83.8
TOTAL Row % Col %	40 50.0 100.0	40 50.0 100.0	80 100.0 100.0

ꭓ²=0.09; p=0.76 NS- Not Significant

Chi-square test showed that there was no significant association between requirement of rescue drug in different post-operative period and patients of the two groups (p>0.05). Thus, no significant difference was found in requirement of rescue drug in the two groups. Chi-square test showed that there was no significant association between requirement of rescue drug (from the time of extubation till first 48 hours) and patients of the two groups (p=0.76). However, requirement of rescue drug was higher in Group-B (17.5%) than that of Group-A (15.0%) but there was no significant difference (Z=0.57;p=056).

Table 7: Comparison of requirement of rescue drug of the patients of the two groups.

Rescue Drug	Post-Operative Monitoring Time Period (in hours)
	0-2			2 -6			6-24			24-48
	Gr-A (n=40)	G-B (n=40)	Total	Gr-A (n=40)	G-B (n=40)	Total	Gr-A (n=40)	G-B (n=40)	Total	Gr-A (n=40)	G-B (n=40)	Total
Required Row % Col %	1 100.0 2.5	0 0.0 0.0	1 100.0 1.3	1 25.0 2.5	3 75.0 7.5	4 100.0 5.0	2 40.0 5.0	3 60.0 7.5	5 100.0 6.3	2 66.7 5.0	1 33.3 2.5	3 100.0 3.8
Not required Row % Col %	39 49.4 97.5	40 50.6 100.0	79 100.0 98.8	39 51.3 97.5	37 48.7 92.5	76 100.0 95.0	38 50.7 95.0	37 49.3 92.5	75 100.0 93.8	38 49.4 95.0	39 50.6 97.5	77 100.0 96.3
TOTAL Row % Col %	40 50.0 100.0	40 50.0 100.0	80 100.0 100.0	40 50.0 100.0	40 50.0 100.0	80 100.0 100.0	40 50.0 100.0	40 50.0 100.0	80 100.0 100.0	40 50.0 100.0	40 50.0 100.0	80 100.0 100.0
Chi-square test and p-values	Fisher Exact Test p=0.50			ꭓ²=1.05;p=0.30			ꭓ²=0.21;p=0.64			ꭓ²=0.34;p=0.55

DISCUSSION

Nausea, vomiting and retching occurring during first 24-48 hours after any surgery is usually defined as postoperative nausea and vomiting.¹ Post-Operative Nausea and Vomiting (PONV) is one of the most common distressing complications of anesthesia and surgery and may lead to severe post-operative complications. The incidence of nausea and vomiting after cholecystectomy performed by laparotomy or laparoscopy and concluded that laparoscopic cholecystectomy increases the incidence of PONV in early postoperative period probably by the effect of residual stretching and irritation of peritoneum and the risk is increased in females and in obese patients.⁷ Despite new anesthetic drugs and antiemetics particularly 5HT3 receptor antagonists, the incidence of PONV remained between 20% and 70%, supplementation of peri-operative oxygen administration reduces the incidence of PONV.⁸ Ramosetron is safe and effective to prevent postoperative nausea and vomiting. Recommended dose is 0.3 mg for prevention of postoperative nausea and vomiting.^9,10 Ramosetron is found more effective than dexamethasone and midazolam to prevent postoperative nausea vomiting.^11,12 The effect of ramosetron to prevent postoperative nausea and vomiting is comparable or better than that of granisetron.¹³ Aftab S et al. studied to determine the risk factors for PONV and found that incidence of PONV was significantly higher in female gender, patient with previous history of nausea and vomiting, motion sickness, patients undergoing laparoscopic cholecystectomy and eye surgery.¹⁴ Our results were in accordance with observation of Kim S I et al.,⁶ and Ryu J. et al.,¹⁵ who showed that ramosetron (0.3mg) was equally effective as ondansetron (8mg) to prevent postoperative nausea and vomiting. Ansari MM et al.⁴ showed that there were no significant difference between ramosetron (0.3mg) and ondansetron (4mg) in postoperative nausea and vomiting in first 24 hours after surgery but incidence of nausea and vomiting was significantly higher in ondansetron group in 24-48 hours interval. Requirement of rescue antiemetic were also higher in ondansetron group.but as per our study ondansetron was as effective as ramosetron in both 0-24 and 24-48hr interval but overall requirement of rescue antiemetic was higher in ondansetron group but difference was satistically insignificant. Banerjee D et al.,¹⁶ concluded that ramosetron is a very effective, safe antiemetic in the prevention of PONV than ondansetron with better efficacy and safety. Suh JH et al.,¹⁷ found that overall incidence of postoperative nausea and vomiting and severity of nausea was similar in both ondansetron (4m) and ramosetron (0.3) group but requirement of rescue antiemetic were higher in ondansetron group. Our results are in accordance with Yoon DG et al.,¹⁸ who found that there was no difference in ondansetron (4mg) and ramosetron (0.3mg) group in term of incidence of postoperative nausea and vomiting, severity of nausea and requirement of rescue antiemetic. In the absence of antiemetics, the incidence of emetic problems associated with anesthesia was around 33%. In this review they have discussed etiology of PONV played by age, sex, obesity, operative site and duration of anesthesia. Post-operative vomiting, however, is rarely a result of single factor and it is for this reason that management may not be successful.⁹ Effective prevention of PONV is very much beneficial for patients as well as treating physician/surgeons in terms of postoperative outcome.

CONCLUSION

Use of antiemetic prophylaxis has become the standard approach to minimize the nausea and vomiting postoperatively. There was no significant difference in the incidence of postoperative nausea and vomiting for ondansetron and ramosetron group during first 48 hours after laparoscopic cholecystectomy.

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