GRANISETRON AND ONDANSETRON ON POST OPERATIVE NAUSEA AND VOMITING IN LAPAROSCOPIC CHOLECYSTECTOMY UNDER GENERAL ANESTHESIA AT BIR HOSPITAL KATHMANDU , NEPAL

Methodology It was a randomized, single blind study, conducted in 75 pa ents undergoing laparoscopic cholecystectomy. Pa ents were divided into two groups: Group O and Group G. Pa ents in group O were given 0.1 mg/kg Ondansetron intravenously (IV) and pa ents in Group G were given 0.04 mg/kg Granisetron. The standard general anesthe c technique was administered to all the pa ents. Episodes of nausea, retching and vomi ng were assessed during the first 24 hours a er anesthesia. Collected data was applied with appropriate test in SPSS 16 and overall significance level was considered at 95% confidence interval (p ≤ 0.05).


INTRODUCTION
PONV is defined as any vomi ng, retching or nausea occurring within the first 24-48 h a er surgery.PONV remains one of the most common complica ons related to surgery and anesthesia.PONV has been characterized as big 'li le problem.In all adult pa ents undergoing surgery incidence of PONV is around 20-30 % of all adult pa ents.A er laparoscopic surgeries the incidence of PONV ranges from 36-82 % and in certain gynecological laparoscopic 4 procedure can be as high as 73 %.There are mul ple contribu ng factors related for PONV.The factors related to anesthesia are opioids given periopera vely any me or benzodiazepines, inhala onal agents, postopera ve pain, pa ent immobiliza on,wide varia on in haemodynamic periopera vely and delayed ini a on of oral intake.⁵If any an -eme c treatment is not given following laparoscopic Cholecystectomy the incidence of PONV is considerably high.⁶PONV is one of the commonest complain following anesthesia, and can result in morbidity like bleeding, pulmonary aspira on of gastric contents, delayed hospital discharge, unexpected hospital admission, fluid and electrolyte disturbances, wound dehiscence, and decreased 7 pa ent sa sfac on.All these factors reduce the quality of life and interfere with regular pa ents' treatment.So an effec ve an eme c therapy is always required.Serotonin (5-HT3) receptor antagonist acts on chemoreceptor trigger zone and at vagal afferents in the gastrointes nal tract by producing pure antagonism of the 5-HT3 receptor.Many drugs have been tried to prevent PONV.In 1990s when 5HT3 receptor antagonist were introduced than a major advance in the treatment of PONV was made because there were very few side effects that were seen with commonly 8 used tradi onal ant eme cs.The commonly used effec ve drug for preven on of PONV is Ondansetron; 4 mg intravenously.But another 5HT3 receptor antagonist Granisetron which is recently introduced has more potent and longer ac ng ac vity against.⁹

METHODOLOGY
This study was compara ve, prospec ve, randomized and single blinded study.A er approval from the IRB, NAMS, from the every pa ents who were enrolled in the study Informed wri en consent was taken and were randomly allocated into two groups by lo ery method.Pa ents with ASA grade I and II undergoing laparoscopic cholecystectomy of age 15 to 65 years were included.Pa ents with history of mo on sickness, migraine, or any other neurological problems, history of postopera ve nausea and vomi ng during a previous surgery, who received anyt eme cs 48 hours prior to surgery, pregnant/ lacta ng females and surgery more than two hours were excluded from the study.
Group G was given 0.04 mg/kg of Granisetron.Group O was given 0.1mg/kg of Ondansetron.
There were 40 pa ents in each group.Pre-anaesthe c check up was done one day prior to the surgery, and informed consent was taken.Pa ent was kept nil per oral at least for 6 hr prior to anesthesia.Monitors were a ached and all baseline hemodynamic parameters were recorded: NIBP, Pulse, ECG, and SPO .Intravenous access was done.Pa ents 2 were preloaded with 10ml/kg of ringer lactate over 10 min.Injec on Midazolam 0.04 mg/kg IV and Fentanyl 1.5mcg /kg IV was given before induc on.Pre-oxygena on was done for 3 minutes.Pa ents were induced with inj.Propofol 2mg/kg.A er check ven la on pa ent was paralyzed with muscle relaxant Vecuronium 0.1 mg /kg.Mechanical ven la on was done with bag and mask for 3 minutes iIntuba on was done with appropriate size endotracheal tube.Maintained general anesthesia with oxygen, halothane, IPPV and Vecuronium.The study drug was given, 30 minutes before the end of surgery.Reversal of residual muscle relaxa on was done with Neos gmine (0.05mg/kg) and Glycopyrollate (0.01mg/kg).Once extuba on criterion was met, the pa ent was extubated.
The pa ent was then taken to postopera ve care unit.Nausea, vomi ng, pulse, blood pressure, both systolic and diastolic was recorded.Any stomach contents expelled from the mouth was referred as vomi ng.Involuntary a empt to vomit but no expulsion of stomach contents was referred as 15 retching.Emesis-free was defined as no any eme c episodes during the specified me period.Nausea and vomi ng will be evaluated on a three point scale.0 = none 1 = nausea 2 = vomi ng.(Retching event was considered as vomi ng event) Nausea assessment was made periopera vely, postopera vely (immediately a er tracheal extuba on), 0 to 4hr,4 to 12hrs and12 to 24 hr therea er.The percentage of pa ents who have no vomi ng and no nausea during the 24 hr postopera ve period in terms of three point scale gave the efficacy of study drugs.Rescue an eme c for vomi ng or persistent nausea at the discre on of a physician or at the pa ent's request inj.metoclopramide 10mg IV was given.As a postopera ve analgesic supplement, each group received inj.Pethidine 0.8 mg/kg + Phenargan 0.5mg/kg IM 8 hourly.Any complica on was managed according to the standard protocols of the hospitals.
Total 80 pa ents were randomly taken randomly 40 in each group.Three in group O and two in group G were excluded.Data collec on was done by filling the pro forma prepared by previous study acontaining the demographic details of the pa ent (age, weight and sex), hemodynamic changes and the severity of PONV at 4 hrs, 4 to 12 hrs and 12 to 24 hrs.Data were collected and recorded as per pro forma.Numeric outcome scores were generated from the dummy tables.Collected data was analyzed by means of sta s cal so ware SPSS 16 and appropriate tests-chi-square test for propor ons like incidence, and severity of PONV and independent t-test for con nuous parametric data like age and weight.Overall significance level was considered at 95 % confidence interval (p < 0.05).

DISCUSSION
PONV is very unpleasant side effects of surgery and anesthesia, which causes dissa sfac on and distress to pa ents.PONV is of mul -factorial origin.The incidence of PONV a er general anesthesia, despite the advances in an eme c therapy is s ll found to be high.Gold  which is higher in incidence to this study.This might be due to drug given at the me of induc on instead of at the end of surgery that was done in this study.In this study, 26% pa ents in Granisetron group as compared to 54% in Ondansetron group have PONV; the difference incidence was sta s cally highly significant.In the study done by Ommiad

CONCLUSION
This study concluded that Granisetron is more effec ve g i ve n p ro p hy l a c ca l l y t h a n O n d a n s e t ro n g i ve n prophylac cally for preven on of PONV following laparoscopic cholecystectomy in the first 24 hours.

RECOMMENDATIONS
We recommend the prophylac c an eme c Inj. Granisetron 0.04mg/kg intravenous at the end of laparoscopic cholecystectomy to prevent Post opera ve nausea and vomi ng.

LIMITATION OF THE STUDY
Only laparoscopic cholecystectomy pa ents were involved.

Table 1 : Comparison of age and weight between two groups (n =75)Table 2 : Incidence of PONV in two groups (n = 75) Table 3 Incidence of PONV in two groups in different me intervals (n=75)
Similarly 18 pa ents were in one to 2 hour group in group O and 15 in group G.This data is sta s cally non significant between two groups as p value is 0.424 (P value >0.05).Incidence nausea in pa ents for surgical me < 1 hour is 11.9 %, in comparison to 24.2% in pa ents with surgical me 1 to 2 hours.Similarly, vomi ng is also 2.3% in pa ent with surgical me < 1 hours and 33.3 % in pa ents with surgical me 1 to 2 hours.
There were total 6 males and 31 females in group O and 5 males and 33 females in group G.The distribu on of sample among both the group was found to be sta s cally nonsignificant.Among 39 total females, 14 experienced nausea and 11 experienced vomi ng.Among 11 male pa ents, no pa ent experienced nausea and vomi ng.Dura on of surgery divided into two groups as less than 1 hour and one to two hours.In group O, 19 pa ents were within one hour group and 23 pa ents were within one hour group in G group.
16 al noted that the most common reasons requiring admission a er day care surgery are bleeding, In study done by Bha acharya et al found the incidence of PONV in Odansetron group was 10% this difference in incidence in PONV might be due to varia on of type of surgery and short dura on of surgery in rela on 14 to this study.Study done by Gupta et al incidence of PONV is 70% which is higher in incidence to this study this might be due to drug given at the me of induc on instead of at the 15 end of surgery that was done in this study.Incidence of PONV in Granisetron group is 26% in this study.In the study done by Ommid et al there was 29% incidence of 13 PONV.The result was similar to this study.Study done by Bha acharya et al found the incidence of PONV in Granisetron group was 7% this difference in incidence in PONV might be due to varia on in type of surgery and short 14 dura on of surgery in rela on to this study.In study done by Gupta et al incidence of PONV was 45% in Granisetron group16 13because a er laparoscopic surgeries PONV is distressing.It was decided not to include a control group in this study.Total 80 cases were randomized, 40 pa ents in each group.Total excluded cases were five.Three cases were excluded due to Laparoscopic cholecystectomy converted to open cholecystectomy and two were excluded due to increase in dura on of surgery more than two hours.Incidence of PONV in Ondansetron group is 54% in this study.Similar incidence was found in study done by Mohamad13Ommid et al is 52%.
Granisetron group as compared to 20% in Ondansetron group.The incidence of PONV in our study is less compared to incidence of PONV in that study.This difference may be explained by varia on in type and the dura on of surgical procedure in the study done.They studied pa ents undergoing laparoscopic tubal liga on under general anaesthesia and post opera ve opioid analgesia was avoided and only diclofenac was introduced.In this study there is sta s cally significant reduc on of nausea in two groups in 12 to 24 hours.Incidence of nausea was 19% in Ondansetron group and 8% in Granisetron group which was sta s cally significant (p value <0.05).Incidence of vomi ng was 13% in Ondansetron group and 3% in Granisetron group.But the overall incidence of nausea and vomi ng was decreased in 12 to 24 hours than in first 12 hours.Ommid et al found sta s cally significant difference in nausea in 12 to 24 hours but incidence of vomi ng was not 13 significant between the two groups.Similarly Gupta at el also found sta s cally not significant data in 12 to 24 hours 13 et al the result were similar to this study.Granisetron group has 20% incidence of PONV as compared to 52% in Ondansetron group and the study was also conducted in laparoscopic cholecystectomy.But Bha acharya et al in 2003 in Kolkata found incidence of PONV 10% pa ents in 15 in incidence of vomi ng.