|Year : 2013 | Volume
| Issue : 3 | Page : 194-198
A comparative study between ramosetron and granisetron for the prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy
Newstar Syiemiong, Lairenlakpam Deban Singh, Nongthombam Ratan Singh, Takhelmayum Hemjit Singh, Longjam Eshori Devi
Department of Anesthesiology, Regional Institute of Medical Sciences, Imphal, Manipur, India
|Date of Web Publication||19-Feb-2014|
Nongthombam Ratan Singh
Department of Anesthesiology, Regional Institute of Medical Sciences, Imphal - 795004, Manipur
Source of Support: None, Conflict of Interest: None
Background: The reported incidence of postoperative nausea and vomiting (PONV) following laparoscopic cholecystectomy (LC) is very high. Various treatment modalities have been tried by several workers with varying results. This study was undertaken to compare the efficacy of ramosetron and granisetron with the intention to prevent postoperative nausea and vomiting (PONV) after laparoscopic cholecystectomy in this part of the country. Materials and Methods: In a randomized, double-blind study in our tertiary care hospital, 80 inpatients of ASA I and II were enrolled and received either 3 mg granisetron or 0.3 mg ramosetron i.v. (n = 40 each) ten minutes before induction of anesthesia. Standardized anesthetic technique was used, and data was collected for early (0-2 hr) PONV in the post-anesthetic care unit (PACU) and late (2-24 hr) PONV in the ward. Results: The incidence of early PONV (0-2 hr) was 22.5% for granisetron and 15% for ramosetron (P > 0.05; 95% Confidence interval (CI) = 0.20 to 1.97; OR = 0.63), late PONV (2-24 hr) was 25% and 15%, respectively (P > 0.05; CI = 0.18 to 1.68; OR = 0.56). The most common side-effects observed in the two groups were headache and drowsiness, and these were mild and self-limiting. There was no significant difference in the side-effects of drugs between the two groups. Conclusion: PONV is a distressing symptom in laparoscopic cholecystectomy cases, and ramosetron is as effective as granisetron in preventing early (0-2 hr) and late (2-24 hr) PONV.
Keywords: Early and late PONV, Granisetron, Laparoscopic cholecystectomy, Ramosetron
|How to cite this article:|
Syiemiong N, Singh LD, Singh NR, Singh TH, Devi LE. A comparative study between ramosetron and granisetron for the prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy. J Med Soc 2013;27:194-8
|How to cite this URL:|
Syiemiong N, Singh LD, Singh NR, Singh TH, Devi LE. A comparative study between ramosetron and granisetron for the prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy. J Med Soc [serial online] 2013 [cited 2020 Oct 20];27:194-8. Available from: https://www.jmedsoc.org/text.asp?2013/27/3/194/127392
| Introduction|| |
Laparoscopic surgery has decreased the morbidity associated with cholecystectomy and has become an accepted procedure for symptomatic cholelithiasis, but postoperative nausea and vomiting (PONV) are the commonly observed adverse effects after general anesthesia in these patients, and its incidence ranges between 60% to 72%.  Although PONV is almost always self-limiting and non-fatal,  it can cause significant morbidity, including dehydration, electrolyte imbalance, suture dehiscence, venous hypertension, bleeding, aspiration, and delay in discharge (particularly for outpatient surgery). 
Over the years, there has been considerable reduction in the incidence of PONV with the introduction of anti-emetic prophylaxis like anti-cholinergics (scopolamine), anti-histaminics (diphenhydramine, cyclizine, promethazine, prochlorperazine), butyropheneones (droperidol), and benzamide (metoclopramide). However, these agents may cause undesirable adverse effects such as excessive sedation, hypotension, dry mouth, dysphoria, hallucinations, extrapyramidal symptoms, and dysrhythmogenic effects such as prolong QT interval with droperidol. 
Granisetron is a 5HT 3 receptor antagonist that is more effective than the most commonly used anti-emetic agents, droperidol and metoclopramide, in preventing PONV.  Ramosetron(R)-5-[(1-methyl-3-indolyl)cardonyl]-4, 5, 6, 7-tetrahydro-1H-benzimidazole hydrochloride, is a relatively newer 5HT 3 receptor antagonist with an affinity higher than that of the previously available drugs, ondansetron, granisetron and tropisetron.  Ramosetron has been introduced for the treatment of irritable bowel syndrome (IBS),  chemotherapy (cisplatin)-induced nausea and vomiting,  prevention of shivering following spinal anesthesia,  and of late in post-operative nausea and vomiting following gynecological,  strabismus,  and laparoscopic cholecystectomy surgeries,  with very few studies done for comparing the efficacy of this drug with other anti-emetics. , This study has been undertaken to compare the efficacy of ramosetron and granisetron with the intention to prevent postoperative nausea and vomiting following laparoscopic cholecystectomy in our set up.
| Materials and Methods|| |
After obtaining approval from Institutional Ethical committee and written informed consent, 80 adult inpatients (ASA Grade I and II) aged 18-65 years of both sexes scheduled for elective laparoscopic cholecystectomy were enrolled for this study at the Regional Institute of Medical Sciences, Imphal, a tertiary care hospital, during the period of July 2010 to June 2012. Patients with any gastrointestinal, liver or renal diseases, psychological illness, positive history of alcoholism and/or opioid addiction, those who had received steroid or any other anti-emetic medication within 24 hours before surgery or complained of preoperative nausea or vomiting including motion sickness or headache, hypersensitivity to 5HT 3 antagonist. Patients who were pregnant, lactating and menstruating women, or patients weighing more than 90 kg or anticipated difficult intubation during induction of anesthesia were also excluded from the study. Based on previous studies, , it was calculated that 40 patients per group would be required to demonstrate a 20% difference in values for a complete response at α = 0.05 with a power (1-β) of 80%. A randomization list was computer-generated, and patients were randomly allocated to two groups, (group G - granisetron and group R - ramosetron) with equal number of patients in each group according to this list [Figure 1].
Pre-anesthetic evaluations were done in all patients scheduled for elective laparoscopic cholecystectomy. Detailed history, physical examination, and basic investigations were performed in all patients. All patients received alprazolam 0.25-0.5 mg and ranitidine 300 mg orally the night before surgery. On arrival in the operation theater, routine monitoring devices were attached, including non-invasive arterial pressure, heart rate, ECG, and pulse-oximetry. A suitable peripheral vein was cannulated for administration of anesthetic agents and intravenous fluids. All patients were pre-medicated with 50 mg ranitidine intravenously (i.v) and glycopyrolate 0.2 mg i.m. one hour before surgery. Then, blinding was done by preparing the study medications in identical volume of 5 ml in syringes by a person not involved in the study, and the drugs were administered ten minutes before induction of anesthesia. Patients in group-G received granisetron 3 mg intravenously (i.v) and group-R received ramosetron 0.3 mg i.v. The anesthetic regime and surgical procedure were standardized for all patients. Anesthesia was induced with propofol 2 mg/kg i.v. and butorphanol 20 μg/kg i.v. Tracheal intubation was facilitated with succinylcholine 2 mg/kg i.v. and anesthesia maintained with N 2 O and isoflurane in oxygen. Atracurium 0.5 mg/kg i.v. was used as the muscle relaxant and repeated as required.
Ventilation was controlled and adjusted to maintain the end tidal partial pressure of CO 2 (PET CO 2 ) between 4.7 and 5.3 kPa (35-40 mm Hg). During surgery, patients were placed in the reverse trendelenburg position with the right side of the bed elevated and abdomen insufflated with carbon dioxide through a veress needle to a maximum of 14 mm Hg. At the cessation of surgery, glycopyrolate 0.5 mg and neostigmine 2.5 mg was administered to reverse the neuromuscular blockade, and tracheal tube was removed. All the patients received diclofenac sodium 75 mg i.m. and tramadol 2 mg/kg i.m about 20 minutes before the end of surgery. Intraoperative continuous ECG, non-invasive blood pressure, and pulse-oximetry were monitored.
After surgery, data was collected up to 24 hours postoperatively. The follow up of the patients during the first 2 hours was undertaken in the postoperative care unit (PACU) and thereafter (2-24 h) in the ward. During the first 2 hours after anesthesia in the PACU, vital signs such as non-invasive blood pressure, heart rate, respiratory rate, and hemoglobin oxygen saturation (SpO 2 ) were monitored in all patients. All patients of PONV (nausea, retching, vomiting), rescue anti-emetic, Numerical rating scale (NRS)  pain score, and adverse events were recorded within the first 24 h after anesthesia. Injection metoclopramide 10 mg i.v. was given as rescue anti-emetic to patient on request or when vomiting occurs.
Nausea was defined as the subjective unpleasant sensation associated with awareness of urge to vomit; retching was defined as the labored, spastic, rhythmic contraction of the respiratory muscles without the expulsion of gastric content; and vomiting was defined as the forceful expulsion of gastric contents from the mouth. Complete response (i.e., emesis free) was defined as no PONV and no need for another rescue anti-emetic medication. The data collected were analyzed by independent 't' test, Chi-square test, or Fischer's exact probability test as appropriate.
| Results|| |
The two groups were comparable with respect to their demographic profile as shown in [Table 1].
|Table 1: Distribution of patients with respect to their demographic profile and duration of anesthesia and surgery|
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In the 0-2 h interval, the incidence of PONV was 22.5% in group G as against 15% in group R. There was no statistical significance between the two groups in the 0-2 h interval for the incidence of PONV, complete response, and rescue anti-emetic use. (P > 0.05; CI 0.20 to 1.97; OR 0.63) [Table 2].
|Table 2: Number(%) of patients having nausea, retching, vomiting, rescue anti-emetic, and complete response during 0-2 hrs and 2-24 hrs after anesthesia|
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As shown in [Table 2], in the 2-24 h interval period, the incidence of PONV was 25% in group G as against 15% in group R. There was no statistical difference between the two groups with respect to the incidence of PONV, rescue anti-emetic use, and complete response (P > 0.05; CI 0.18 to 1.68; OR 0.56). In the overall 0-24 h interval, the incidence of PONV was 45% in group G versus 27.5% in group R. There was no significant statistical difference between the two groups with respect to their incidence of PONV, rescue anti-emetic use, and complete response (P > 0.05; CI 0.19 to 1.22; OR 0.48).
The side effects of the drugs noticed during the study were headache (12.5% in group G and 10% in group R), drowsiness (10% in group G and 12.5% in group R), and dizziness (5% in group G and 2.5% in group R). Rash was seen in one patient in group R. The differences of adverse effects in the two groups were found to be insignificant (P > 0.05) [Table 3].
| Discussion|| |
The etiology of PONV after laparoscopic cholecystectomy is not known but probably associated with operative factors including effect of intraperitoneal carbon dioxide insufflation on residual stretching and irritation of the peritoneum.  It is mostly believed to be multifactorial in origin.  There are certain risk factors that have been identified for the development of PONV. These are classified into factors that are patient-related, surgery-related, and anesthesia-related. Anesthesia-related risk factors are use of volatile anesthetics, N 2 O, postoperative opioids, postoperative pain, and intraoperative hypovolemia.  In our present study, we have standardized the factors that may play a role in the development or attenuation of PONV. We have also standardized the anesthetic technique for all the patients. There was no statistical difference between the two groups with respect to their demographic profile such as age, weight, height, sex, duration of anesthesia and surgery, NRS for pain, and ASA status. We can, therefore, presume that the difference in effects between the two groups can be attributed to the drugs administered. We did not choose a placebo group as control in our study because the patients we chose were having a 40% risk of developing PONV and denial of effective antiemetic treatment was unjustified and unethical. 
PONV may take place in single or multiple episodes, which may last minutes, hours, or even days. It is classified as early, occurring up to 2 to 6 hours after surgery, or late, occurring up to 24-48 hours after surgery.  The causative factors for early and late PONV may be different with use of volatile anesthetics being a main cause for early PONV.  We have, therefore, chosen 0-2 h interval for our study design for early PONV and 2-24 h interval for late PONV.
In a study by Ryu et al.,  it was observed that 20% of the cases in the ramosetron group experienced early PONV (0-2 hrs), while late PONV (2-24 hrs) was observed in 10% of the cases. These findings are comparable with findings of our study, where early PONV (0-2 hrs) was observed in 22.5% of the granisetron group and 15% of the ramosetron group; late PONV (12-24 hrs) in 25% of the granisetron group and 15% of the ramosetron group.
PONV in the 0-24 h interval, in the present study, was 45% in the granisetron group similar with 48% in the study by Naguib et al.  Other investigators reported lower incidences (15% by Fujii et al., 13% by Fujii et al.,  and 18% by Singh et al.  ). There was no statistical difference in the occurrence of early or late PONV and also in the overall PONV in our study similar to other studies.  The mechanism of action of 5HT 3 antagonist is by its selective and competitive binding to 5HT 3 receptors, thereby blocking serotonin binding at vagal afferents in the gut and in the regions of the central nervous system involved in emesis including the chemoreceptor trigger zone and nucleus tractus solitarius.  These are the mechanism by which granisetron and ramosetron probably act.
The most common side-effects of the drugs in the two groups observed in our study were headache (12.5% in group G and 10% in group R), drowsiness (10% in group G and 12.5% in group R), and dizziness (5% in group G and 2.5% in group R). Rash was observed in one patient in the ramosetron group. The side-effects were of mild nature and self-limiting. There was no significant statistical difference in the side-effects between the two groups. The side-effects observed in our study were similar with most of the other studies. ,
There were certain limitations in this study i.e. the bias of gender was not eliminated from the study. Further, it may also be extrapolated to a larger sample size to overcome the possibility of beta error- if any. The determination of the optimal regime and timing of administration of the anti-emetic therapy are also suggested for the best possible effects.
| Conclusion|| |
PONV is a distressing symptom in laparoscopic cholecystectomy cases. It may be concluded from this study that ramosetron is as effective as granisetron in preventing early (0-2 hr) and late (2-24 hr) PONV.
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[Table 1], [Table 2], [Table 3]