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ORIGINAL ARTICLE
Year : 2017  |  Volume : 31  |  Issue : 2  |  Page : 114-118

A comparative study of the antiemetic effect of intravenous palonosetron with granisetron for the prevention of postoperative nausea and vomiting following laparoscopic cholecystectomy under general anesthesia


Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal, Manipur, India

Date of Web Publication20-Apr-2017

Correspondence Address:
Longjam Eshori
Department of Anaesthesiology, Regional Institute of Medical Sciences, Imphal, Manipur
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-4958.204818

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  Abstract 

Background: Postoperative nausea and vomiting (PONV) is commonly experienced unpleasant complications of general anesthesia following laparoscopic cholecystectomy (LC). The present study was undertaken to compare the efficacy of palonosetron with granisetron in the prevention of PONV following LC under general anesthesia (GA). Materials and Methods: In a randomized, double-blinded study, after Ethical Committee approval, 100 adult patients aged 18–65 years, American Society of Anesthesiologists I/II undergoing elective LC under GA during a 2-year period in a Tertiary Care Hospital in Imphal were assigned into one of two groups. Group P (n = 50) received palonosetron 0.075 mg intravenous (IV) and Group G (n= 50) received granisetron 40 μg/kg body weight in 4 ml NS (0.9% normal saline added to get desired volume), 10 min before induction of anesthesia. Standardized anesthetic technique was used, and data were collected for PONV in postanesthesia care unit for 0–2 h and in the postoperative ward for 2–48 h. Results: The incidence of early PONV (0–2 h) was 28% in Group P (palonosetron) and 32% in Group G (granisetron), whereas the incidence of late PONV (2–48 h) was 18% in Group P and 32% in Group G. However, palonosetron had lesser delayed onset nausea (2–48 h) compared to granisetron (P = 0.037). Common side effects observed in the two groups were similar with no statistically significant difference between the groups. Conclusion: Prophylactic IV palonosetron was as effective as granisetron in preventing early (0–2 h) PONV. However, palonosetron was significantly better in the prevention of late onset nausea (2–48 h) in patients undergoing LC under GA without any major adverse effects.

Keywords: Granisetron, laparoscopic cholecystectomy, palonosetron, postoperative nausea and vomiting


How to cite this article:
Monohar PS, Eshori L, Singh LD, Singh NR, Rajkumar G, Haobam S. A comparative study of the antiemetic effect of intravenous palonosetron with granisetron for the prevention of postoperative nausea and vomiting following laparoscopic cholecystectomy under general anesthesia. J Med Soc 2017;31:114-8

How to cite this URL:
Monohar PS, Eshori L, Singh LD, Singh NR, Rajkumar G, Haobam S. A comparative study of the antiemetic effect of intravenous palonosetron with granisetron for the prevention of postoperative nausea and vomiting following laparoscopic cholecystectomy under general anesthesia. J Med Soc [serial online] 2017 [cited 2020 Oct 22];31:114-8. Available from: https://www.jmedsoc.org/text.asp?2017/31/2/114/204818


  Introduction Top


Laparoscopic cholecystectomy (LC) is the current gold standard treatment for cholelithiasis and nowadays done as a day care procedure.[1] Postoperative nausea and vomiting (PONV) is the most commonly observed adverse effect of anesthesia with the incidence between 60% and 72% following LC.[2],[3],[4] It is believed to be due to the creation of pneumoperitoneum leading to pressure on vagus nerve.[5] However, there are a number of factors influencing the occurrence of PONV such as patient factors, operative procedures, anesthetic drugs, and postoperative factors causing significant morbidity and delay in discharge.[6]

Granisetron is a highly selective and potent 5-HT3 receptor antagonist with long duration of action and more effective than the most commonly used antiemetic agents in preventing PONV.[7]

Palonosetron is a 5-HT3 receptor antagonist used for preventing chemotherapy-induced nausea and vomiting.[8] It has a greater binding affinity and longer half-life [9] and interacts with 5-HT3 receptors in an allosteric, positively cooperative manner at other sites,[10] leading to long-lasting effects on receptor ligand binding and functional responses.

Several studies using different drugs have been carried out for the prevention of PONV. However, there is limited literature available comparing granisetron and palonosetron in the prevention of PONV. Only a few studies have compared palonosetron with granisetron in laparoscopic cholecystectomy for PONV.[11],[12] This study was undertaken to assess the efficacy of palonosetron and granisetron in the prevention of PONV in patients who underwent LC under general anesthesia (GA).


  Materials and Methods Top


After Institutional Ethics Committee approval and written informed consent, 100 adult patients aged 18–65 years, American Society of Anesthesiologists (ASA) I and II [13] of both sexes scheduled for elective LC under GA were enrolled for this study at a Tertiary Care Hospital in Imphal, during the period of September 2013 to August 2015. Exclusion criteria included, patients having a history of any renal, liver, or gastrointestinal disease, motion sickness, PONV, and history of smoking or alcoholism. Pregnant, lactating, or menstruating women, patients with hypersensitivity to 5-HT3 antagonists, those who had taken antiemetic medication within the last 24 h, and patients who suffered from difficult intubation during induction of anesthesia were also excluded from the study.

For an α value of 5% and β value of 0.2 (power = 1 − β = 0.8, i.e., 80%) assuming complete response of 67% and 90% in granisetron and palonosetron, respectively, in 24–48 h, the sample size was fifty patients in each group based on an earlier study.[11]

Those patients willing to participate in the study were divided into two groups using simple randomization by a computer-generated random number chart. Group P received palonosetron (0.075 mg intravenous [IV]) and Group G received granisetron (40 mcg/kg body weight IV). The dose of the study drugs was taken up based on previous studies.[14],[15],[16] There was no placebo group in this study as PONV is a very distressing experience in LC and it would be unethical for the patients to go through it [17] [Figure 1].
Figure 1: Flowchart of the study

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All the patients were premedicated with 50 mg ranitidine IV and diclofenac 75 mg i.m. 30 min before surgery. The test drug, prepared by personnel blinded to the study, was administered 10 min before the induction of anesthesia. On the operation table, routine standard monitoring (electrocardiogram, pulse oximetry, and noninvasive blood pressure) was fixed and baseline vital parameters such as heart rate, blood pressure, and arterial oxygen saturation recorded. IV line was established with 18 G cannula in the nondominant hand and IV fluid (isotonic saline) to maintain the cannula patency. Patients in Group P received palonosetron 0.075 mg IV in 4 ml (0.9% normal saline was added to get desired volume) and Group G received IV granisetron 40 mcg/kg in 4 ml.

The anesthetic regimen and surgical procedure were standardized for both the groups. All patients were preoxygenated for 3 min. Anesthesia was induced with IV 2.5% thiopentone sodium (5 mg/kg body weight). With appropriate endotracheal tube, patients were intubated with rocuronium bromide (0.6 mg/kg body weight) without producing any local trauma during laryngoscopy, followed by intermittent positive pressure ventilation with 100% oxygen. The anesthesia was maintained with nitrous oxide, isoflurane in oxygen, intermittent bolus doses of rocuronium bromide (0.1–0.2 mg/kg body weight), and tramadol 2 mg/kg body weight IV.

Ventilation was controlled to maintain the end-tidal partial pressure of CO2 between 35 and 40 mmHg. During surgery, patients were placed in the reverse Trendelenburg position with the right side of the bed elevated and peritoneal cavity insufflated with carbon dioxide to keep intra-abdominal pressure <14 mmHg. At the cessation of surgery, residual neuromuscular block was reversed with IV glycopyrrolate 0.5 mg and neostigmine 2.5 mg and endotracheal tube then removed.

After surgery, data were collected up to 48 h postoperatively. The follow-up of the patients during the first 2 h was undertaken in the postanaesthesia care unit and thereafter (2–48 h) in the ward. All patients were also evaluated for PONV, rescue antiemetic and adverse effects of drugs for the first 48 h after anesthesia. Metoclopramide 10 mg IV was given as rescue antiemetic to the patient on request or when vomiting occurs.

Nausea was defined as unpleasant sensation associated with awareness of the urge to vomit. Retching was defined as the labored spastic, rhythmic contraction of the respiratory muscles without the expulsion of gastric contents. Vomiting was defined as the forceful expulsion of gastric contents from mouth. Complete response was defined as no PONV and no need for any rescue medication.

The data collected were statistically analyzed using Statistical package for social sciences for windows (SPSS) version 23.0 (Armonk, NY: IBM corp.) and presented in a tabulated manner. Comparisons between groups were performed using the Kruskal–Wallis one-way ANOVA by ranks or Fisher's exact test for small sample with a 5% risk or Mann–Whitney-Wilcoxon tests or Chi-square test, as appropriate. The results were expressed in mean ± standard deviation and number (%).


  Results Top


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 profiles and duration of anesthesia and surgery and presence of comorbidities

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The incidence of nausea, vomiting, retching, complete response, and the use of rescue antiemetic in the 0–2, 2–48, and 0–48 h intervals are shown in [Table 2]. The incidence of early PONV in the 0–2 h interval was 28% versus 32% in Group P and Group G, respectively, whereas late PONV (2–48 h) was 18% versus 32% in Group P and G, respectively. There was no statistical difference in the occurrence of early PONV. However, in late PONV, Group P (10%) had significantly less nausea compared to Group G (26%) (P = 0.037), whereas the incidence of vomiting was 10% each in both the groups. Retching was absent in all the patients. Complete response in Group P was 72% and 68% in Group G in the early 0–2 h period, whereas in the 2–48 h period, it was 82% versus 68%, respectively. In the overall study period of 0–48 h, incidence of PONV was 34% in Group P and 50% in Group G.
Table 2: Number (%) of patients having nausea, retching, vomiting, complete response, and rescue antiemetic in the 0-2, 2-48, and 0-48 h postoperative periods

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[Table 3] shows the incidence of adverse effects in both the groups in 0–48 h interval. There was no significant difference in both the groups in relation to the incidence of adverse effects.
Table 3: The incidence of adverse effects in the postoperative period

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  Discussion Top


PONV is one of the most common adverse effects following LC and has an incidence of around 60–72%.[2],[3],[4] It has the potential to delay the discharge after surgery and may lead to increased financial burden. The etiology of PONV after LC is not known but probably associated with operative factors including the effect of intraperitoneal CO2 insufflation with resultant residual stretching and irritation of the peritoneum, leading to pressure on the vagus nerve and thence, stimulation of the vomiting center in brain.[5] 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.[6],[18]

There was no statistical difference between the two groups, palonosetron and granisetron, with respect to their demographic profiles such as age, weight, height, sex, duration of anesthesia and surgery, presence of comorbidities, and ASA status. Hence, it can be presumed that the difference in effects between the two groups can be attributed to the study drugs administered.

In our study, the incidence of nausea in palonosetron group was 18% in 0–2 h interval and 10% in 2–48 h interval. Incidences reported by Bhattacharjee et al.[11] (6.6% in 0–3 h and 6.6% in 3–24 h), Gupta et al.[12] (5% in 0–4 h and 2.5% in 4–12 h), and Prabhakar and Borra [19] (3.3% in 0–4 h, 10% in 4–12 h, 13.3% in 12–24 h, and 10% in 24–48 h) were lower than that of our study. While Kovac et al.[15] (50% in 0–24 h) and Moon et al.[20] (20% in 0–2 h and 35% in 2–24 h) reported higher incidences. The findings of Shadangi et al.[21] (16.7% nausea in first 24 h) and Kim et al.[22] (22.2% nausea in first 48 h) are comparable with our findings. The difference in the incidence of nausea could be due to the different time intervals taken for the study. However, the incidence of nausea is higher in the granisetron group (22% in 0–2 h and 26% in 2–48 h) which is comparable with the findings of Syiemiong et al.[23] (17.5% in 0–2 h and 22.5% in 2–24 h). This could be due to a 30-fold higher affinity of palonosetron for the 5-HT3 receptors and slower elimination of the drug.[9],[10]

The incidence of vomiting is comparable in both palonosetron (10% each in 0–2 and 2–48 h intervals) and granisetron (16% in 0–2 h and 10% in 2–48 h). Palonosetron has a more profound antinauseatic effect than antiemetic effect.[14] This may explain why we got similar incidence of vomiting in both the drugs.

In the present study, we could not find a significant difference in complete response (palonosetron: 72% in 0–2 h and 82% in 2–48 h; granisetron: 68% each in both 0–2 and 2–48 h). This is in accordance with earlier studies.[22],[24] Similarly, there were no significant differences in the incidence of use of rescue antiemetic (palonosetron: 26% in 0–2 h and 16% in 2–48 h; granisetron: 32% in 0–2 h and 14% in 2–48 h). We have used metoclopramide as rescue antiemetic as it is recommended that rescue antiemetic in breakthrough PONV should be of a different class than the one used for prophylaxis.[25]

The incidence of adverse effects was found to be similar in both the groups with no serious adverse effect observed among the patients.

Both palonosetron and granisetron are 5-HT3 antagonists; however, palonosetron has a greater binding affinity and a longer biological half-life compared to older 5-HT3 antagonists such as granisetron [9] and interacts with 5-HT3 receptors in an allosteric, positively cooperative manner at other sites,[10] leading to long-lasting effects on receptor ligand binding and functional responses. This could be the reason for the better control of late onset PONV (nausea 2–48 h, P = 0.037) in the palonosetron group compared to the granisetron group even though the findings of the two drugs were almost comparable in early onset PONV.

However, there are certain limitations to our study. Only surgical patients undergoing LC under GA were included in the study. The results of this study, therefore, cannot be generalized and extrapolated neither to the surgeries done under regional anesthesia nor to patients of extreme age groups.


  Conclusion Top


Both granisetron and palonosetron were comparable in the prevention of early PONV, but palonosetron was more effective in the prevention of delayed PONV.

Palonosetron is equally effective as granisetron in the prevention of early onset PONV, whereas more effective in the prevention of delayed onset nausea with a similar adverse effect profile. However, further studies including patients undergoing other laparoscopic surgeries are recommended to apply the findings to the general population.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

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  [Table 1], [Table 2], [Table 3]


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[Pubmed] | [DOI]



 

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