COMPARISION OF PRE-OPERATIVE ONDANSETRON VERSUS COMBINATION OF DEXAMETHASONE AND ONDANSETRON FOR POSTOPERATIVE NAUSEA AND VOMITING IN ELECTIVE LAPAROSCOPIC CHOLECYSTECTOMY.
Objective: To compare the efficacy of ondansetron with a combination of ondansetron and dexamethasone after elective laparoscopic cholecystectomy in terms of postoperative nausea and vomiting.
Study Design: Randomized controlled trial.
Place and Duration of Study: Department of Surgery, Combined Military Hospital Rawalpindi Pakistan, from Apr 2014 to Mar 2015.
Materials and Methods: Two hundred and twenty two patients fulfilling the inclusion criteria were selected for study and divided into two groups of 111 each. Group A was given ondansetron while group B was given combination of ondansetron and dexamethasone at induction of general anesthesia. Patients of both groups were observed at 24 hours postoperatively for nausea and vomiting.
Results: Sixty six patients in group A had nausea as compared to 50 patients in group B (p-value 0.03), 46 patients in group A had vomiting as compared to 19 patients in group B (p-value <0.001), showing statistically significant difference between the two groups.
Conclusion: Postoperative nausea and vomiting is significantly lower in ondansetron and dexamethasone combination group as compared to ondansetron alone group after elective laparoscopic cholecystectomy.
Keywords: Dexamethasone, Elective laparoscopic cholecystectomy, Ondansetron, Postoperative nausea and vomiting.
First reported laparoscopic cholecystectomy was performed by Phillipe Mouret, a French surgeon in 1987 and now it is considered the gold standard treatment for symptomatic cholelithiasis1. Laparoscopic cholecystectomy is the second most commonly performed general surgery procedure in United States2. It is becoming more popular day by day in our country owing to the advantage of rapid recovery and shorter hospital stay3. However, laparoscopic surgery is found to be associated with a high incidence of postoperative nausea and vomiting (PONV) which impairs achieving the above mentioned benefits4. Its incidence can be as high as 72% following laparoscopic cholecystectomy5. Many different factors like nature of surgery, uncorrected hypovolemia, pro-longed duration of general anesthesia and administration of opioid drugs can lead to PONV6. PONV is one of the major causes of patient dissatisfaction following surgery7.
A number of pharmacological agents have been tried for prevention and management of PONV but no agent is found to be 100% successful8. It has been proved that combination pharmacological modality is better than mono-therapy in this regard9. Selection of antiemetic drug is dependent upon its efficacy, safety and ease of dosing. Ondansetron is a selective 5-HT3 receptor antagonist and dexamethasone is a corticosteroid with potent antiemetic properties10. We conducted this study to compare the efficacy of combination therapy using ondansetron and dexamethasone with monotherapy using ondansetron alone for prophylaxis against nausea and vomiting after elective cholecystectomy.
PATIENTS AND METHODS
This study was randomized controlled trial conducted in department of Surgery Combined Military Hospital Rawalpindi from 1st April 2014 to 30th March 2015. Sample size was calculated by World Health Organization sample size calculator version 2.0. Even number of patients satisfying inclusion criteria were randomly selected on each operation list and divided into two groups by lottery. The same procedure was carried out on every operation list till the required sample size was achieved, 111 patients in each group. One group coded as "group A" received ondansetron alone (4mg) while the other group coded "group B" received combination of ondansetron (4mg) and dexamethasone (8mg). The study medications were prepared and presented to anesthetist as identical 2ml filled syringes, who administered drugs at the time of induction of anesthesia.
The response was assessed for 24 hrs post operatively by resident house officer using a pre tested close ended structured questionnaire. Both the anesthetist and the resident house officer were kept blinded. Both male and female patients between 25-60 years of age undergoing elective laparoscopic cholecystectomy fulfilling American society of anesthesiology (ASA) class I and II were included. Patients having previous midline laparotomy, taking medicine with known anti-emetic activity, having history of hypertension or vertigo and those requiring conversion from laparoscopic technique to open approach were not included in this study. After obtaining informed written consent, all relevant investigations were carried out in each patient. All patients underwent laparoscopic cholecystectomy after standard preparation under general anesthesia with endotracheal intubation.
Group A was given ondansetron while group B was given combination of ondansetron and dexamethasone at the time of induction of anesthesia. Patients of both groups were observed at 24 hours postoperatively for nausea and vomiting. antiemetic (meto-clopramide 10 mg I/V) was given if patient remained nauseous for more than 15 minutes or experienced vomiting. All the data was entered into the statistical package for social sciences (SPSS) version 18.0 and analyzed. Mean and standard deviation was calculated for quantitative variables like age. For qualitative variables like gender, nausea and vomiting, the frequency and percentage was calculated. Effect modifiers like age and gender were controlled by stratification. Chi-square test was applied and p-value of a$?0.05 was considered significant.
Table-I: Group wise incidence of nausea and vomiting
Table-II: Stratification of nausea with regard to age and gender.
###Group A###Group B
Table-III: Stratification of vomiting with regard to age and gender
###Group A###Group B
A total of 222 patients were included in the study during the study period. Out of total 222 patients, 18.9% (n=21) in group-A and 16.2% (n=18) in group-B were male and 81.1%(n=90) in group-A and 83.8% (n=93) in group-B were female. Age distribution of the patients showed that 23.4% (n=26) in group-A and 27% (n=30) in group-B were less than 40 years of age, whereas 76.6% (n=85) in group-A and 73% (n=81) in group-B were greater than 40 years of age, Mean +- SD was calculated as 43.51 +- 5.97 and 44.21 +- 6.11 respectively. Statistical analysis of the study revealed that 59.5% (n=66) in group A developed nausea as compared to 45.0% (n=50) in group B with p-value of 0.03. Similarly 41.4% (n=46) in group A and 17.1% (n=19) in group B developed vomiting, calculated p-value being <0.001 showing statistically significant difference between the two groups (table-I).
Stratification for nausea and vomiting with regard to age (p-value <0.013 and 0.018 respectively) and gender (p-value <0.001 and 0.033) was done showing significant difference between the two groups (table-II and III).
PONV is one of the most common symptoms occurring after laparoscopic surgery8. PONV is found to be even more distressing than post surgical pain with cost of recovery increasing significantly in patients that develop it in post-operative period11. Approximately one third of surgical patients experience nausea and vomiting in postoperative period triggered by four main receptorsin the body: histamine, serotonergic, dopaminergic and opiate12. High incidence of PONV after laparoscopic surgery can be caused by the stimulation of mechanoreceptors of gut by pneumoperitoneum which places pressure on vagus nerve and in turn stimulates the vomiting center in brain13. Persistent PONV is associated with a number of complications such as fluid and electrolyte imbalance, wound disruption, delay in mobilization and prolonged hospitalization causing significant adverse impact on patient well-being and health care resources14.
Hence strategies for prevention of PONV are a vital component of enhanced recovery after surgery protocols. Being multifocal in origin, multimodal combination pharmacological therapy is considered more appropriate for prophylaxis of PONV. Dexamethasone and ondansetron are the two most commonly used drugs for this purpose. Prophylactic dose of ondansetron and dexamethasone being 4mg and 8mg respectively is recommended in literature15 and we conducted this study by using the same doses of these drugs. Ondansetron and dexamethasone have also well-accepted roles in the prophylaxis of PONV after gynecological, obstetric, pediatric and ophthalmic surgery16. In this study we compared the efficacy of ondansetron with and without dexamethasone in the prevention of PONV after laparoscopic cholecystectomy. Our results showed statistically significant difference of PONV between group A and B (p-value <0.001), PONV being significantly less in group receiving both the drugs.
Our findings are in accordance with a study conducted by Banoand colleagues where they found that frequency of nausea and vomiting was significantlyless in ondansetron and dexamethasone combination group as compared to dexamethasone alone group (p-value 0.035)17. A higher incidence of PONV was observed in females in both study groups, similar to the finding mentioned in literature18. Ondansetron is proved to be specifically effective against vomiting. On the other hand, dexamethasone not only reduces the incidence of vomiting but is also effective in the prevention of nausea. This explains why the combined use of ondansetron and dexamethasone is very effective in reducing the overall incidence of both nausea and vomiting as both the drugs act as additive19. Similar results were found in studies conducted by Ahsan and colleagues (p-value 0.046)20 and Ahmed et al21.
Both studies involved patients undergoing laparoscopic cholecystectomy and combination versus only ondansetron was compared. In another study conducted by Mckenzie et al22 comparison of ondansetronand dexamethasone (group-I) with ondansetron (group-II) was done in female patients undergoing gynecological surgery. A complete response, defined as no emesis and no need for rescue antiemetic during the 24-hour post-operative period, occurred in 52% patients in the combination group as compared to 38% in ondansetron group (p=0.045). Vomiting was statistically less in combination groupthan ondansetron alone group (p=0.003). They concluded that the combination of ondansetron plus dexamethasone was more effective than ondansetron alone for prophylaxis against PONV. Similar findings were observed by Eidy and colleagues where they found that incidence of nausea and vomiting was significantly less in dexamethasone and ondansetron combination group as compared to ondansetron alone group (p-value 0.01)23.
A number of concerns exist regarding the safety of dexamethasone in postopera-tive period but use of single dose dexamethasone is found to be free from any significant side effects including delayed wound healing. Furthermore, it is not only effective in decreasing postoperative pain after laparoscopic cholecystectomybut also helps in improving respiratory functions in early postoperative period24.
LIMITATIONS OF STUDY
Study was carried out at single center and time frame was not considered when measuring incidence of PONV. Moreover, use of rescue antiemetic was not quantified thus ignoring important data.
Laparoscopic cholecystectomy has become the treatment of choice for cholelithiasis in today's modern era. The high incidence of PONV after laparoscopic surgery is well documented and is the main reason for prolonged hospital stay following surgery significantly increasing the cost of treatment. Identification of high risk cases and prophylactic antiemetic measures are the best modality in countering PONV. Combination of ondansetron and dexamethasone is an effective prophylactic measure and should be offered to all patients undergoing laparoscopic cholecystectomy.
CONFLICT OF INTEREST
This study has no conflict of interest to be declared by any author.
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|Publication:||Pakistan Armed Forces Medical Journal|
|Article Type:||Clinical report|
|Date:||Dec 31, 2018|
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