Comparison of Ondansetron with Ondansetron and Dexamethasone in prevention of postoperative nausea vomiting in abdominal surgery

Nausea and vomiting is a common and distressing postoperative complication with an incidence of 25-43% after both inpatient and day care surgery1. Patients rate freedom from postoperative nausea and vomiting (PONV) as their most IJBAR (2013) 04 (01) www.ssjournals.com Abstract Purpose: To compare the efficacy of ondansetron-dexamethasone combination with ondansetron alone for prevention of postoperative nausea and vomiting (PONV).


Introduction
Nausea and vomiting is a common and distressing postoperative complication with an incidence of 25-43% after both inpatient and day care surgery 1 . Patients rate freedom from postoperative nausea and vomiting (PONV) as their most important postoperative requirement 2 . Surgical complications such as abdominal wound dehiscence, bleeding beneath skin flaps and loss of vitreous fluid following intraocular surgery may follow PONV 2 .
The search for rapid acting antiemetic with long duration without above side effects led to the introduction of ondansetron, a 5HT 3 receptor antagonist, shown to be effective in reducing PONV following various surgical procedures 3,4 . Dexamethasone has been found to be effective in the control of nausea and vomiting following chemotherapy and also effective in reducing incidence of PONV following surgery 5,6,7,8,9 .
The present study was carried out to determine effect of ondansetron alone and in combination with dexamethasone for patients undergoing exploratory laparotomy for various clinical conditions under general anaesthesia as the incidence of PONV is described as high in these patients 10 .

Material And Methods:
The present study has been carried out in the Department of Anaesthesiology J.N.M.C and Acharya Vinobha Bhave Rural Hospital, Sawangi during the period of July 2010 to August 2012. This is a randomized, prospective, double blind, Placebo controlled study in which 120 patients posted for exploratory laparotomy for various clinical conditions under general anaesthesia were studied, after the approval from the institutional Ethical Committee and written informed consent. All the patients belonging to ASA I -II of different age groups and weighing 30-80 kg were included in this study. At the pre-anaesthetic visit the patients were familiarized with post-operative questionnaires and postoperative nausea and vomiting score, as described later, Tablet diazepam 10 mg was given the night before surgery to all patients.
The patients were divided into three groups of 40 each.
Patients received one of the three regimes for prevention of PONV before induction.
Standard protocol of Balanced anaesthesia followed for each patient with endotracheal intubation.
Efforts were made to keep gastric distension to minimum using low airway pressure ventilation. After endotracheal intubation, nasogastric tube was placed to ensure baseline emptying of stomach, air and gastric contents.Intra operative hydration was corrected with crystalloids, blood loss was assessed and corrected.
Operative data included type of surgery ( ovarian mass, ovarian cycst, ectopic pregnancy, gall stones, appendicular lump, appendicular abscess, exploratory laparotomy ), induction dose of propofol, amount of opioids administered, duration of surgery, estimated blood loss and urine output.
At the end of procedure Patients were shifted to the recovery room for postoperative observation. Nausea and vomiting were looked from 0 min upto 24 hours. Retching and vomiting were grouped together under common term 'emetic episodes '.
Postoperatively rescue antiemetic was given if vomiting occurred, or nausea lasting more than 10 minutes. Injection metoclopramide was used as a rescue antiemetic in the dose 10 mg I.V.
Pain was observed with visual analog scores (VAS) 11 on a scale of 0 -10 at 2, 12 and 24 hours interval. We also observed the patients for side -effects if any. The primary end -point was a complete response, as defined by no nausea or emetic episode during 24 -hour period.
The data was collected and expressed as Mean + Standard Deviation. For statistical analysis one way analysis of variance (ANOVA) test by SPSS software 15.0 for windows 7 was used, and 'p' value < 0.05 was considered as statistically significant.  At 2 hours, 14 ( 35% ) patients had nausea in the Placebo group compared with 4 ( 10% ) in the Ondansetron group and 2 ( 5% ) in the ondansetron plus dexamethasone group. The difference between placebo and ondansetron plus dexamethasone group was statistically significant ( p < 0.05 ).

Observations and Results
At 12 hours, 30 ( 75% ) in the placebo group had nausea compared with 16 ( 40% ) in the Ondansetron group and 4 ( 10% ) in the ondansetron plus dexamethasone group. The difference was statistically significant when a) Placebo group was compared with ondansetron group ( p < 0.05). b) Placebo group was compared with ondansetron plus dexamethasone group ( p < 0.001 ). c) Ondansetron group was compared with ondansetron plus dexamethasone group ( p < 0.05 ).
At 24 hours, 32 ( 80% ) patients in placebo group had nausea compared with 20 ( 50% ) in Ondansetron group and 4 ( 10% ) in ondansetron plus dexamethasone group. The difference was statistically significant when: IJBAR (2013) 04 (01) www.ssjournals.com a) Placebo group was compared with ondansetron group ( p < 0.05 ). b) Placebo group was compared with ondansetron plus dexamethasone group ( p < 0.001 ). c) Ondansetron group was compared with ondansetron + dexamethasone group ( p < 0.01 ). At 2 hours, 10 ( 25% ) patients in the Placebo group had an emetic episode, whereas none of the patients in ondansetron group or ondansetron + dexamethasone group had an emetic episode. The difference was statistically significant when: a) Placebo group and ondansetron group were compared ( p < 0.05 ).
b) Placebo group and ondansetron plus dexamethasone group were compared ( p <0.05 ).
At 12 hours 20 ( 50% ) patients in the Placebo group had an emetic episode as against 6 ( 15% ) in ondansetron group and 2 ( 5% ) patients in ondansetron plus dexamethasone group.
The difference was statistically significant when : a) Placebo group and ondansetron group were compared ( p < 0.05 ) b) Placebo group and ondansetron plus dexamethasone group were compared ( p < 0.05 ).
At 24 hours, 18 ( 45% ) patients in the Placebo group had an emetic episode compared to 10 ( 25% ) in the ondansetron group and 2 ( 5% ) patients in the ondansetron plus dexamethasone group.
The difference was statistically significant between placebo group and ondansetron plus dexamethasone group ( p < 0.05 ).

Discussion
Postoperative nausea and vomiting is a common sequel of general anesthesia and a leading cause of delayed discharge and unanticipated hospital admissions after ambulatory surgery. Many factors have been thought to contribute to PONV a and we tried to control most of them. Patients with a low threshold for vomiting such as gastroparesis, motion sickness, previous PONV and obesity were excluded from the study.
We selected ondansetron (5HT 3 receptor antagonist) as our study drug and the dose was selected as 4mg as it was found to be the optimal dose for prevention of PONV as mentioned in different studies 12,13 . Suggestion on mechanism of action of dexamethasone include central or peripheral inhibition of production or secretion of serotonin, central inhibition of synthesis of prostaglandins or changes in the permeability of blood brain barrier to serum proteins 6,8,9 . We selected dexamethasone as our study drug and dose selected was 8mg as it was found to be optimal dose for prevention of PONV as We found that ondansetron 4 mg reduced postoperative nausea with the effect being more pronounced at 12 and 24 hour duration than at 2 hours. The combination of ondansetron plus dexamethasone significantly reduced nausea at 2, 12 and 24 hours compared to Placebo group as well as ondansetron group.Thus combination of ondansetron plus dexamethasone was more effective in prevention of nausea, though ondansetron used alone significantly reduces the incidence of nausea as well owing to potentiation.
Our results were comparable with various studies conducted by Claybon et al 1994 12 , Pearman et al 1994 13 , Sung et al 1993 16 and Helmer et al 1993 17 .
We also found that ondansetron 4 mg reduced postoperative emetic episodes more effectively at 2 and 12 hours as against at 24 hours. The combination of ondansetron with dexamethasone was more effective as compared to ondansetron alone in reducing the incidence of postoperative emetic episodes at 2 hrs, 12 hrs and 24 hrs. In our study, the requirement for rescue antiemetic was observed in 15 ( 75% ) patients in placebo group compared with 6 ( 30% ) in ondansetron group and only 2 patients ( 10% ) in ondansetron plus dexamethasone group ( Table no. 5 ). The difference was statistically significant at p <0.01 when ondansetron group was compared with placebo group.
The difference was statistically significant at p <0.001 when ondansetron plus dexamethasone group was compared with placebo group. However, the difference was not significant when ondansetron group was compared with ondansetron plus dexamethasone group p >0.05.
Results were comparable with studies conducted by Lopez et al 1996 11 and Bano et al 2008 21 . This effectively proves that ondansetron plus dexamethasone combination drastically reduces the need for rescue antiemetics. The findings in our study coincide with those of the above studies.
In our study we compared the incidence of postoperative pain in all the three groups at 2 hours, 12 hours and 24 hours according to the visual analog scale. It was observed that there was no significant difference in pain intensity between the groups at anytime (Graph 1).
These findings coincide with those of Lopez et al 1996 11 and Wang et al 2012 22 found no significant differences in pain intensity between all the three groups at any time interval. In our study we compared the incidence of sedation in all the three groups at 2 hours, 12 hours and 24 hours using the five point sedation scale (Graph 2).
There was no significant difference in sedation with no patients in category 0, 1 or 2 of sedation at anytime during the study.
These findings are similar to those of Lopez et al 1996 11 who found no significant difference in sedation with no patients in any of the groups being in category 0, 1 or 2 at anytime during the study. The only adverse effect we found in our study was headache reported in 3 patients in ondansetron and 4 in the ondansetron plus dexamethasone group (Table no. 6) In the study conducted by Lopez et al 1996 11 , headache was the most common adverse effect. Even Pearman et al 1994 13 in his study noted headache to be the most common adverse effect.This might be related to ondansetron.

Conclusion
1) Though ondansetron was effective in controlling postoperative nausea, the ondansetron plus dexamethasone combination was more effective overall.
2) Though ondansetron was effective in reducing postoperative emetic episodes, the combination of ondansetron plus dexamethasone was more effective.
3) The requirement for rescue antiemetic was less in ondansetron group and least in ondansetron plus dexamethasone group. 4) There was no significant difference between pain intensity and sedation between these groups at any time. 5) Only adverse effect reported was headache in ondansetron and ondansetron plus dexamethasone groups.
It can thus be concluded from the study that ondansetron plus dexamethasone combination is more effective in reducing incidence of PONV without causing any major side effects. Throughout the study, ondansetron plus dexamethasone combination was superior to ondansetron alone in all respects pointing towards the potentiating effect of dexamethasone.