Comparative evaluation of ondansetron, granisetron and ramosetron to prevent post-operative nausea and vomiting.
The present study was undertaken to compare the antiemetic efficacies of ondansetron, granisetron and ramosetron in preventing post-operative nausea and vomiting after general anaesthesia.
PHYSIOLOGY OF VOMITING: Nausea is defined as a subjective unpleasant sensation associated with awareness of the urge to vomit.
General Mechanism of Emesis: Three major components comprising of the vomiting reflex can be identified as:
1. Emetic detectors.
2. Integrative mechanisms.
3. Motor components.
Abdominal visceral afferents:
Two types of vagal afferent fibres are involved:
1. Mechanoreceptors: Located in the muscular wall of the gut and are activated by contraction or distension (e.g. by over eating or obstruction) of the gut.
2. Chemoreceptors: Located in the mucosa of the upper gut and responds to mucosal stroking, acid, alkali, hypertonic solutions, temperature and irritants. (2)
a) Area Postrema.
b) Vestibular system.
c) Higher Influence.
Input from higher centres (e.g. Limbic system) can induce nausea and vomiting. (3)
Vomiting Centre: Vomiting is a stereotyped motor programme involving co- ordination between the autonomic and somatic components of the nervous system.
MOTOR COMPONENTS OF THE VOMITING REFLEX:
The act of emesis involves a sequence of events that can be divided into:
a. Pre-ejection phase.
b. Ejection phase.
c. Post-ejection phase.
The Vomiting Act: Once the vomiting centre is stimulated, the effects are a deep breath, raising of the hyoid bone and larynx to pull the crico-oesophageal sphincter open, closing of the glottis and tilting of the soft palate to close the posterior nares. A strong downward contraction of the diaphragm along with simultaneous contraction of all abdominal muscles follows. Finally the gastrooesophageal sphincter relaxes, allowing expulsion of gastric contents upwards through the oesophagus. (4)
Post Ejection Phase: It consists of autonomic and visceral responses that return the body to a quiescent phase with or without residual nausea. (4)
Courses of Postoperative Nausea and Vomiting: The mechanisms of postoperative nausea and vomiting are multifactorial and are discussed under the following headings:
1. Preoperative factors.
2. Intraoperative factors.
3. Postoperative factors.
Food: Food induces abdominal vagal afferent activation by its volume and chemical composition.
Anxiety and Stress: The increased incidence of emesis in anxious patients is due to catecholamine release or excessive air swallowing. (4)
1. Atropine delays gastric emptying leading to post-surgical stasis.
2. Opioids decrease gastric emptying with an increase in central and duodenal tone.
1. Results from indirect effects of prolonged inhibition of the antiemetic centre by anaesthetic drugs.
2. Physiological effects of anesthetics.
General effects of surgery:
1. Reduced gastrointestinal motility and increased concentrations of vasopressin predispose to postoperative nausea and vomiting.
2. Ocular surgery especially squint surgery. Due to oculoemetic and oculogastric reflex.
3. In middle ear surgery is caused by activation of vestibular afferent pathways and stimulation of Arnold's nerve.
4. Mechanical stimulation of the pharynx results in the activation of glossopharyngeal afferents.
5. Intra-abdominal operations.
6. Gynaecological surgery. (5)
1. Residual effects of drugs and anesthetics.
MECHANISM OF ACTION OF ANTIEMETIC AGENTS: Four neurotransmitter systems play important roles in mediating the emetic response.
1. Dopaminergic (D2).
2. Histaminergic (H1).
3. Cholinergic muscarinic.
4. Serotonin (5HT3).
The area postrema is rich in dopamine, opioid and serotonic (5HR3) receptors. The nucleus tractus solitarius is rich in enkepalin, histaminic and cholinergic muscarinic receptors. The vomiting centre receives separate input from different types of receptors. Antagonism of any one signal by an antiemetic drug alleviates emesis associated with stimulation of that receptor.
MATERIALS AND METHODS: The present study was carried out to compare the efficacy of ondansetron, granisetron and ramosetron for prevention of post-operative nausea and vomiting after general anaesthesia. Total 120 patients were enrolled belonging to ASA grade I and II, 12-58 yrs. age group undergoing surgical procedures under general anaesthesia.
At pre-anaesthetic interview, day before surgery, patients were familiarized with the postoperative questionnaire.
Group 1 (n=30): Received Inj. Ondansetron 0.15mg/kg I.V.
Group 2 (n=30): Received Inj. Granisetron 10mcg/kg I.V.
Group 3 (n=30): Received Inj. Ramosetron 0.3mg I.V.
Group 4 (n=30): Received Inj. Normal Saline (0.9%) 2ml I.V.
ANAESTHETIC PROCEDURE: Patients were preoxygenated with 100% O2 for 3 minutes. Then patients were premedicated with inj. Glycopyrrolate 0.005mg/kg, inj. Midazolam 0.02mg/kg and inj. Fentanyl 2mcg/kg. Inj. Ondansetron or inj. Granisetron or Inj, Ramosetron or Inj. Normal saline was administered intravenously 3minutes before induction according to the respective study group. Then patient was induced with inj. Thiopentone sodium 3-5mg/kg body weight and endotracheal intubation was facilitated with Injection Succinylcholine 1.5mg/kg.
Maintenance of anaesthesia was given with nitrous oxide (60%) and oxygen (40%) and isoflurane and Injection Vecuronium Patient was monitored during anaesthesia using continuous ECG, heart rate, blood pressure and pulse oximetry. On completion of surgery, neuromuscular block was reversed with Injection Neostigmine 0.05mg/kg and Injection Glycopyrrolate 0.008mg/kg. Injection Diclofenac 1mg/kg i.m. was given for postoperative analgesia.
Score Table (Wadaskar et al, 2009) Score table:
"0": No nausea.
"1": Mild nausea.
"2": Severe nausea.
"3": Mild vomiting.
"4" Severe vomiting.
Base line comparison of groups:
AGE: The study included the patients of age group between 12 to 58 years of age. In present study the age (Mean [+ or -] SD) in group 1 was 33.06 [+ or -] 7.96, in group 2 was 35.36 [+ or -] 8.37, in group 3 was 35.53[+ or -] 7.32 and in group 4 was 34.5 [+ or - ] 6.41 The age is comparable in all the four groups. This is shown in Table 1. (2,6,7)
DURATION OF ANAESTHESIA: In our study, the duration of anaesthesia in minutes (Mean [+ or -] SD) in group 1 was 108.00 [+ or -] 27.96, in group 2 was 111.00 [+ or -] 26.30, in group 3 was 112.00 [+ or -] 28.33 and in group 4 was 109.00 [+ or -] 29.98. The duration of anaesthesia in minutes (Mean [+ or -] SD) in patients of all the four groups was comparable. This is shown in Table 1. (8,9,10)
COMPARISON OF PONV SCORE AMONG ALL GROUPS IN 24 HOURS:
PONV 1 (Mild nausea not requiring rescue antiemetic): In our study, the number (Percentage) of patients with mild nausea (PONV 1) not requiring rescue antiemetic in group 1 was 10(33.3%), group 2 was 2(6.6%), group 3 was 6(20%) and group 4 was 5(16.6%) (Table- 2). Thus, the incidence of mild nausea not requiring rescue antiemetic was least in granisetron group. (7,11)
PONV 2, 3 & 4 (Severe nausea or vomiting requiring rescue antiemetic): In our study, the number (Percentage) of patients with severe nausea or vomiting (PONV 2, 3, 4) requiring rescue antiemetic in group 1 was 12(40%), group 2 was 5(16.6%), group 3 was 8(26.6%) and group 4 was 19(63.3%) (Table- 3). Thus, the incidence of severe nausea or vomiting requiring rescue antiemetic was least in granisetron group. (2,4,12)
PONV 0 (No nausea or vomiting): In our study, the number (Percentage) of patients with no nausea or vomiting (PONV 0) in group 1 was 8(26.6%), group 2 was 23(76.6%), group 3 was 16(53.3%) and group 4 was 6(20%) (Table- 4). Thus, the number (Percentage) of nausea and vomiting free patients was least in granisetron group. (2,6,12)
Table 1: Comparison of Age and Duration of Anaesthesia Variables Group-1 Group-2 Group-3 Group-4 Age 33.06 [+ 35.36 [+ 35.53 [+ 34.5 [+ or (in or -] 7.96 or -] 8.37 or -] 7.32 -] 6.41 yrs.) Duration 108.00 [+ 111.00 [+ 112.00 [+ 109.00 [+ of or -] or -] or -] or -] Anaesthesia 27.96 26.30 28.33 29.98 (in minutes) Variables p value(independent 't' test) 1Vs2 1Vs3 1Vs4 2Vs3 2Vs4 3 Vs 4 Age .2804 .2171 .4357 .9349 .6670 .5761 (in yrs.) Duration .6703 .5842 .8942 .8878 .7846 .6919 of Anaesthesia (in minutes)
The above table represents the mean and standard deviation of age and duration of anaesthesia in all the four groups and the comparison of p values among all the four groups. No significant difference in the four groups with respect to age and duration of anaesthesia was found. (p>0.05).
The above table 2 AND FIGURE 2 represents number (Percentage) of patients with mild nausea not requiring rescue antiemetic (In 24 hours). The least incidence of nausea not requiring rescue antiemetic was found in group 2(p < 0.035).
The above table represents number (percentage) of patients with severe nausea or vomiting requiring rescue antiemetic (In 24 hours).The incidence of severe nausea or vomiting requiring rescue antiemetic was least in group 2 followed by group 3, then group 1(p <0.05) and then group 4.
The above table & FIGURE 4 represents number (Percentage) of patients with no nausea or vomiting for 24 hours postoperatively The incidence of no nausea or vomiting for 24 hours postoperatively was maximum in group 2 followed by group 3, then group 1 and the group 4.
The above table and figure 5 represents the mean and standard deviation of all types of PONV scores in all four groups. It is clear that PONV score for all types was least in group 2 followed by group 3, group 1 and group 4 respectively.
CONCLUSION: So, it can be concluded that granisetron is more effective drug than ramosetron and ondansetron for controlling postoperative nausea and vomiting with less incidence of side effects. We observed minimal emetic and nausea episodes in the postoperative period in patients who had received intravenous granisetron in comparison to intravenous Ramosetron and ondansetron.
(1.) Watcha MF, White PF: Post-operative nausea and vomiting: Its etiology, treatment and prevention. Anaesthesiology 77: 162-184, 1992.
(2.) Bhattcharya D, Banerjee A. Comparison of Ondansetron and Granisetron for prevention of nausea and vomiting following day care gynecological laproscopy. Indian journal Anaesthesia 2003, 47(4); 279-282.
(3.) Sinha Prabhat K, Sushil P. Ondansetron in prophylaxis of postoperative nausea and vomiting in patients undergoing breast surgery: A placebo-controlled double blind study. Journal Indian MED. ASSOC. vol 102, No. 2, FEB 2004.
(4.) Sarbari Swaika, Anirban Pal. Surojit Chatterjee, Debashish Saha, Nidhi Dawar: Ondansetron, ramosetron, or palonosetron: Which is a better choice of antiemetic to prevent postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy?; Anaesthesia: Essays and Researches; 5(2); Jul-Dec 2011.
(5.) Gold BS, Kitz DS, Lecky JA, Neuhans JH. Unanticipated admission to the hospital following ambulatory surgery. JAMA 1989; 262: 3008-10.
(6.) Wadaskar, N. Swarnkar, A. Yadav: Granisetron has superior control over postoperative nausea and vomiting than ondansetron in gynaecological surgeries: a placebo controlled double-blind clinical study. The Internet Journal of Anaesthesiology. 2009: 20; 1. DOI: 10.5580/2069.
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(10.) Yoshitaka Fuji, Hiroyoshi, Tanaka, Hidenori Toyooka. Prevention of postoperative nausea and vomiting with granisetron: A randomized, double blind comparison with droperidol. Can J. Anaesth 1995/42: 10/pp 852-6.
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Kailash Chandra Sharma , Geeta Singh , H. S. Nanda , Abhishek Kumar Barnwal 
[1.] Kailash Chandra Sharma
[2.] Geeta Singh
[3.] H. S. Nanda
[4.] Abhishek Kumar Barnwal
PARTICULARS OF CONTRIBUTORS:
[1.] Associate Professor, Department of Anaesthesia, Shri Ram Murti Smarak Institute of Medical Sciences, Bareilly.
[2.] Assistant Professor, Department of Anaesthesia, Shri Ram Murti Smarak Institute of Medical Sciences, Bareilly.
[3.] Professor and HOD, Department of Anaesthesia, Shri Ram Murti Smarak Institute of Medical Sciences, Bareilly.
[4.] Senior Resident, Department of Anaesthesia, Shri Ram Murti Smarak Institute of Medical Sciences, Bareilly.
FINANCIAL OR OTHER COMPETING INTERESTS: None
NAME ADDRESS EMAIL ID OF THE CORRESPONDING AUTHOR:
Dr. Kailash Chandra Sharma, 76, Residency Garden, Stadium Road, Bareilly-243005.
Date of Submission: 12/10/2015. Date of Peer Review: 13/10/2015. Date of Acceptance: 15/10/2015. Date of Publishing: 21/10/2015.
Table 2: Number (Percentage) Of Patients with Mild Nausea (Ponv 1) Not Requiring Rescue Antiemetic (In 24 Hours) GROUP 1 GROUP 2 GROUP 3 GROUP 4 p value (n=30) (n=30) (n=30) (n=30) (ANOVA) NO. OF PATIENTS 10 2 6 5 0.035 PERCENTAGE OF 33.3% 6.6% 20% 16.6% PATIENTS Table 3: Number (Percentage) of Patients with Severe Ausea or Vomiting (Ponv 2, 3 & 4) Requiring Rescue Antiemetic (In 24 Hours) GROUP 1 GROUP 2 GROUP 3 GROUP 4 p value (n=30) (n=30) (n=30) (n=30) (ANOVA) NO. OF PATIENTS 12 5 8 19 0.028 PERCENTAGE OF 40% 16.6% 26.6% 63.3% PATIENTS Table 4: Number (Percentage) of Patients With No Nausea or Vomiting (Ponv 0) For 24 Hours GROUP 1 GROUP 2 GROUP 3 GROUP 4 p value (n=30) (n=30) (n=30) (n=30) (ANOVA) NO. OF PATIENTS 8 23 16 6 0.018 PERCENTAGE OF 26.6% 76.6% 53.3% 20% PATIENTS Table 5: Comparison of Mean Ponv Score in the Four Groups Group 1 Group 2 Group 3 Group 4 PONV .4 [+ or -] .15 [+ or -] .325 [+ or -] .6917 [+ or -] (Mean .7928 .5747 .6412 1.0516 [+ or -] S.D.) p value (ANOVA) 1 Vs2 1 Vs3 1 Vs4 2 Vs3 2 Vs4 3 Vs4 PONV .0056 .0614 .0160 .0341 .0000 .0000 (Mean [+ or -] S.D.) Fig. 1 AGE (IN YEARS) GROUP 1 33.06666667 GROUP 2 35.36666667 GROUP 3 35.53333333 GROUP 4 34.53333333 Note: Table made from bar graph. Fig. 2 NO. OF PATIENTS WITH MILD NAUSEA (PONV 1) GROUP-1(n=30) 10 GROUP-2(n=30) 2 GROUP-3(n=30) 6 GROUP-4(4=30) 5 Note: Table made from bar graph. Fig. 3 NO. OF PATIENTS WITH SEVERE NAUSEA OR VOMITING(PONV 2,3 & 4) GROUP-1(n=30) 12 GROUP-2(n=30) 5 GROUP-3(n=30) 8 GROUP-4(n=30) 19 Note: Table made from bar graph. Fig. 4 NO. OF PATIENTS WITH NO NAUSEA OR VOMITING(PONV 0) GROUP-1(n=30) 8 GROUP-2(n=30) 23 GROUP-3(n=30) 16 GROUP-4(n=30) 6 Note: Table made from bar graph. Fig. 5 COMPARISON OF MEAN PONV SCORE IN ALL FOUR GROUPS GROUP 1 0.4 GROUP 2 0.15 GROUP 3 0.325 GROUP 4 0.6917 Note: Table made from bar graph.
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|Title Annotation:||ORIGINAL ARTICLE|
|Author:||Sharma, Kailash Chandra; Singh, Geeta; Nanda, H.S.; Barnwal, Abhishek Kumar|
|Publication:||Journal of Evolution of Medical and Dental Sciences|
|Date:||Oct 22, 2015|
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