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| ORIGINAL ARTICLE |
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| Year : 2022 | Volume
: 9
| Issue : 4 | Page : 268-274 |
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A comparative study between 1 and 3 mg of granisetron in the prevention of postoperative nausea and vomiting in strabismus ophthalmic surgeries during general anesthesia
Tamer M Khair, Mohamed Y.M Ahmed, Ahmed A Mohamed, Islam M Sayed, Tamer F.H Saafan
Department of Anesthesia, Faculty of Medicine, Cairo University, Cairo, Egypt
| Date of Submission | 01-Feb-2022 |
| Date of Acceptance | 10-Jul-2022 |
| Date of Web Publication | 29-Dec-2022 |
Correspondence Address:
MD Tamer M Khair
Department of Anesthesia, Faculty of Medicine, Cairo University, Cairo 11562
Egypt
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/roaic.roaic_8_22
Aims To compare the safety and efficacy of 1 and 3 mg of granisetron in the prevention of postoperative nausea and vomiting (PONV) in strabismus surgeries under general anesthesia.
Settings and design This single-blinded, randomized, controlled trial was conducted at the ophthalmology operating theater of Kasr Al-Ainy Hospitals.
Patients and methods We recruited 210 patients and allocated them randomly to receive either granisetron 1 mg (n=105) or 3 mg (n=105). The two groups were compared regarding demographic data, hemodynamic parameters, and percentage of patients with no complaints of PONV during the first 24 h.
Results There was no statistically significant difference upon comparison of the two groups regarding PONV (P>0.05). The two doses (1 and 3 mg) provided total control of nausea and vomiting in 46.7 and 43.8% of patients during the first 24 h postoperatively, respectively. Moreover, we found no significant difference between the two groups regarding mean values of the heart rate or mean arterial pressure both preoperatively and intraoperatively (P>0.05). However, during the postoperative 24 h, both groups had significant differences regarding mean values of heart rate and mean arterial pressure at 2–4 h, 8–12 h, and 12–24 h postoperatively.
Conclusions The comparison between two doses of granisetron (1 and 3 mg) showed no statistical difference regarding the total control of nausea and vomiting for 24 h postoperatively but showed a statistical difference regarding some postoperative vital sign readings.
Keywords: general anesthesia, granisetron, postoperative nausea and vomiting, strabismus
How to cite this article:
Khair TM, Ahmed MY, Mohamed AA, Sayed IM, Saafan TF. A comparative study between 1 and 3 mg of granisetron in the prevention of postoperative nausea and vomiting in strabismus ophthalmic surgeries during general anesthesia. Res Opin Anesth Intensive Care 2022;9:268-74 |
How to cite this URL:
Khair TM, Ahmed MY, Mohamed AA, Sayed IM, Saafan TF. A comparative study between 1 and 3 mg of granisetron in the prevention of postoperative nausea and vomiting in strabismus ophthalmic surgeries during general anesthesia. Res Opin Anesth Intensive Care [serial online] 2022 [cited 2023 Mar 26];9:268-74. Available from: http://www.roaic.eg.net/text.asp?2022/9/4/268/365802 |
| Introduction | |  |
Postoperative nausea and vomiting (PONV) are common and distressing symptoms after surgery under general anesthesia. Despite advances in balanced anesthesia in recent decades, PONV can result in delayed discharge from the postanesthesia care unit recovery room, unexpected hospitalization, and increase in medical costs [1].
The ocular surgery associated with the highest incidence of PONV is strabismus surgery, reaching up to 85%. Vomiting after surgery is more likely 2–8 h than being immediately postoperatively. Strabismus is a day-case procedure, and thus, patients must cope with emesis in the recovery room, when traveling, or at home [2].
In this study, we aimed to compare the safety and efficacy of two doses of granisetron in the prevention of PONV in strabismus ophthalmic surgeries under general anesthesia.
| Patients and methods | | |
Ethical considerations
We obtained approval from the Research Ethics Committee (MS-380-2020) and written informed consents from the study participants. This study was registered at the ClinicalTrials.gov (ID: NCT04918862).
Study design, settings, and date
This prospective, single-blinded, randomized, controlled study was conducted at the ophthalmology operating theater of Kasr Al-Ainy Hospitals, Cairo University, from January 2021 to May 2021.
Eligibility criteria
We recruited adult (≥18 year old) patients who were American Society of Anesthesiologists (ASA) physical status I or II and were scheduled for strabismus surgery under general anesthesia.
We excluded patients who were ASA III, ASA IV, pregnant, breastfeeding, or received an antiemetic drug in the preoperative day. We also excluded patients who had a history of motion sickness; known hypersensitivity or contraindication to any of the study medications’ chronic nausea and vomiting; experienced retching, vomiting, or moderate to severe nausea in the preoperative day; a BMI more than or equal to 36; gastrointestinal diseases (e.g. gastritis, hematemesis, or peptic ulcer); or diabetes mellitus.
Sample size calculation
In a previous study, the percent of patients with total control from nausea and vomiting in the first 24 h after receiving 1 mg of granisetron was 49.3% (it is the percentage of the total control after 1 mg not the incidence). We assumed that increasing the dose of granisetron to 3 mg could increase the percent of patients with total control from nausea and vomiting in the first 24 h by 40%. Using a power of 80%, and alpha error of 0.05, 204 patients were needed. The number was increased to 210 (105 per group) to compensate for possible dropouts.
Randomization and allocation concealment
The study participants (n=210) were randomly assigned into two groups (n=105 each) using a computer-generated sequence of numbers and closed envelopes.
Procedure
We enrolled 210 eligible patients and allocated them randomly to receive either granisetron 1 mg (group 1, n=105) or granisetron 3 mg (group 2, n=105).
The two groups were compared regarding demographic characteristics (age, sex, weight, and height), hemodynamic parameters [heart rate (HR) and mean arterial pressure (MAP)], and the duration of surgery.
They were also compared regarding the time from the end of the procedure to the first response in minutes and time to first oral intake postoperative in minutes. The comparison also included nausea control in the first 24 h, vomiting control in the first 24 h, and total control of nausea and vomiting in the first 24 h.
On arrival to the operation room, a data collection sheet was allotted for each patient, which included demographic data, medical history, hemodynamic parameters, occurrence, and onset of PONV.
For eligible patients, a standardized anesthesia regimen was followed.
Preoperative
In the preoperative preparation room, an intravenous access was obtained, monitors were applied, and sedation was given if needed. Patients were randomly allocated to a treatment group to receive one of the two doses of granisetron intravenous slowly over 5 min. Then patients were transferred to the operation room.
Anesthetic management
Monitoring
On arrival to the operating room, patients were reconnected to monitors (continuous ECG, noninvasive arterial blood pressure, and peripheral oxygen saturation). Patients were kept in the supine position with padding of pressure points.
Induction
Induction of general anesthesia was done by fentanyl (2 μg/kg intravenous) and propofol (2–2.5 mg/kg intravenous). After confirmation of unconsciousness, an intravenous injection of 0.5 mg/kg of atracurium was administered followed by endotracheal intubation using a cuffed endotracheal tube of suitable size after confirmation of adequate muscle relaxation.
Maintenance
Anesthesia was maintained with inhaled isoflurane 1% in (oxygen, air) with total fresh gas flow of 3 l/min controlled by mechanical ventilation using a closed circuit ventilation system and with maintenance of end-tidal carbon dioxide partial pressure within the range of 30–40 mmHg and maintenance of muscle relaxation by 0.1 mg/kg atracurium every 20–30 min. Adequate intraoperative fluids were given. Patients received 30 mg/kg paracetamol for intraoperative analgesia. At the end of surgery, patients were given full reversal of muscle relaxant by neostigmine (0.05 mg/kg) and atropine (0.02 mg/kg) followed by extubation to be ready for discharge.
Postoperative
Patients were transported to the recovery room, with routine monitoring by ECG, noninvasive blood pressure, pulse oximeter, and oxygen face mask (6 l/min). Patients received paracetamol for postoperative analgesia if needed.
For relief of pain, patients received ketorolac 30 mg intramuscularly (as effective as the major opioid analgesics, and unlike opioid analgesics, ketorolac does not depress ventilation and is not associated with nausea and vomiting, urinary retention, or sedation) [1].
The time from the end of surgery to first response to command, and to first oral intake, as well as any episodes of nausea and vomiting were recorded. We evaluated PONV using the nausea and vomiting score at 0–2 and 2–24 h ([Table 1]) [3].
The time of each vomiting episode was recorded immediately after tracheal extubation until 24 h after extubation. Vomiting episodes separated by less than 5 min were recorded as a single episode. Rescue medication (metoclopramide 0.15 mg/kg intravenous) was administered to any patient who experienced an episode of moderate or severe nausea, an episode of vomiting, or who requested rescue medication. Nausea and vomiting assessments were done 30 min after rescue medication administration, and response was defined as improvement or resolution of PONV symptoms. Adverse events were evaluated and recorded by the investigator during the entire observation period.
Measurement tools
They included the demographic characteristics, nausea and vomiting score, vital signs (HR in beats/min and MAP in mmHg), the duration of surgery, time to first oral intake, and time from end of surgery till the first response.
Outcomes
The primary outcome was the percent of patients with total control of nausea and vomiting over the first 24 h postoperatively. Secondary outcomes included detection of the optimal dose of granisetron, detection of attacks of either nausea or vomiting that occurred postoperatively or not, and hemodynamic variables (HR and MAP).
Statistical methods
Data were coded and entered using the Statistical Package for the Social Sciences (SPSS), version 26 (IBM Corp., Armonk, New York, USA). Data were summarized using the mean and SD for quantitative variables and frequencies (number of cases) and relative frequencies (percentages) for categorical variables. Comparisons between groups were done using unpaired t test [4]. For comparing categorical data, χ2 test was performed. Exact test was used instead when the expected frequency was less than 5 [5]. P values less than 0.05 were considered statistically significant.
| Results | | |
We recruited 210 patients who were allocated randomly to receive either granisetron 1 mg (group 1, n=105) or granisetron 3 mg (group 2, n=105). There was no significant difference between the two groups regarding the demographic data (P>0.05), as shown in [Table 2].
[Table 3] shows that the total control of nausea and vomiting in the first 24 h postoperatively in group 1 and group 2 was 46.7% (n=49) and 43.8% (n=46), respectively. Moreover, the two doses of granisetron (1 and 3 mg) provided effective prophylaxis against nausea alone during the first 24 h postoperatively in 48.6 and 43.8% of patients in group 1 and group 2, respectively, and the two doses provided effective prophylaxis against vomiting alone during the first 24 h postoperatively in 55.2 and 52.4% of patients in group 1 and group 2, respectively. The comparison also included the incidence of occurrence of PONV in the first 24 h postoperative, and the results were as follow: 53.3% (n=56) in group 1 and 56.2% (n=59) in group 2. There was no statistically significant difference when the two groups were compared regarding these four outcomes (P>0.05). | Table 3 Percentage of patients in the two groups with no nausea, no vomiting, or total control at first 24 h postoperatively
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The comparison between the two groups regarding preoperative and intraoperative HR was not statistically significant (P>0.05), as shown in [Table 4].
[Table 5] shows that the comparison between the two groups regarding the HR was statistically significant at the 2–4, 8–12, and 12–24 h postoperatively (P<0.001, 0.003, and <0.001, respectively).
In comparison of preoperative and intraoperative MAP between the two groups, there was no significant difference (P>0.05), as shown in [Table 6].
[Table 7] shows that the difference between the two groups regarding MAP was statistically significant in the 1–2, 2–4, 8–12, and 12–24 h postoperatively (P=0.001, P=0.024, P=0.007, and P<0.001, respectively).
| Discussion | | |
PONV are common after surgeries performed under general anesthesia. It is generally accepted that emetic sequelae such as PONV are of multifactorial origin and that the incidence of PONV after balanced anesthesia, despite the advances in the last decades, is still between 20 and 30%, which is considered relatively high [6].
When an intervention to prevent PONV is needed, selective serotonin type 3 (5-HT3) receptor antagonists are taken into consideration as a first-line therapy owing to their efficacy and protection as compared with other drugs [2]. Granisetron is a potent antiemetic with high selectivity for 5-HT3 receptor, resulting in fewer adverse effects than other antiemetics [7].
The primary outcome of this study was the total control of nausea and vomiting in the first 24 h; the comparison between the two groups was not statistically significant (P=0.677).
Inconsistent with our results, a study by Wilson et al. [8] compared placebo-controlled and three doses (0.1, 1.0, and 3.0 mg) of the 5-HT3 receptor antagonist, granisetron, as prophylactic therapy for the prevention of PONV in 527 adult patients undergoing elective open abdominal surgery or vaginal hysterectomy during general anesthesia. They found that the antiemetic prophylaxis with a single dose of granisetron 1.0 or 3.0 mg resulted in a significant reduction (P<0.001 compared with placebo) in the numbers of patients experiencing PONV. The two higher doses of granisetron (1.0 and 3.0 mg) provided effective prophylaxis against vomiting, with 78 and 77% of patients, respectively, being free from vomiting in the first 6 h after surgery, and 63 and 62% in the first 24 h, and the comparison between the 1 and 3 mg doses of granisetron was not statistically significant, although the two doses provided effective prophylaxis against nausea and vomiting.
Moreover, a study by Mikawa et al. [9] studied the optimal dose of granisetron for prophylaxis against postoperative emesis after gynecological surgery in 200 female patients who were randomly allocated to one of five groups: saline (as a control), granisetron 2 μg/kg, granisetron 5 μg/kg, granisetron 10 μg/kg, and granisetron 20 μg/kg. They found that the percentage of emesis-free patients was significantly greater in the 5–20-μg/kg granisetron groups than in the control and 2-μg/kg granisetron groups (18, 23, 68, 78, and 75% of patients receiving saline or granisetron 2, 5, 10, and 20 μg/kg, respectively). Granisetron doses of 5 μg/kg or larger were also superior to the saline and 2 μg/kg granisetron in treatment of PONV. In conclusion, the comparison between a low dose (granisetron 5 μg/kg) and a high dose (granisetron 20 μg/kg) was not statistically significant.
Another study by Hanaoka et al. [10] studied the efficacy, safety, and optimal dose of granisetron in the prophylactic control of PONV in patients undergoing gynecologic surgery or cholecystectomy and found that the no-vomiting rates in patients receiving granisetron 1 and 3 mg were significantly higher than that in the placebo group (83.7, 78.8, and 57.9%, respectively), and the comparison between the 1 and 3 mg doses of granisetron was not statistically significant.
Another study by Tsuji et al. [11] compared 1 and 3 mg intravenous doses of granisetron combined with dexamethasone, in patients with cancer receiving emetogenic chemotherapy. The study demonstrated that 1 mg of granisetron was not inferior in effect to 3 mg and there was no significant difference between the 1 and 3 mg of granisetron.
Another study by Wadaskar et al. [12] compared the efficacy and adverse effects of injection granisetron 40 μg/kg as a single dose and injection granisetron in two different doses (20 and 40 μg/kg) in combination with dexamethasone 160 μg/kg for prevention of PONV in patients undergoing general anesthesia for elective laparoscopic cholecystectomy and found that granisetron as a single agent in dose 40 μg/kg (3 mg) is effective as prophylactic antiemetic in preventing PONV in laparoscopic cholecystectomy. The combination of both drugs might be the reason for difference in the two results.
The secondary outcomes of this study included the optimal dose of granisetron, the incidence of occurrence of nausea and vomiting postoperative, and the hemodynamic variables.
The optimal dose of granisetron, which was concluded from this study, is 1 mg of granisetron, as the comparison between the two groups in total control of nausea and vomiting in the first 24 h was not statistically significant (P=0.677).
In consistent with our results, the study by Hanaoka et al. [10] suggested that the optimum dose of granisetron was 1 mg.
Moreover, another study by Tsuji et al. [11] recommended that 1 mg dose of intravenous granisetron should be the prophylactic regimen for the prevention of acute emesis.
In addition, another study by Kamanabrou [13] concluded that a single 40-μg/kg prophylactic dose provides optimal control of cytotoxicity-induced nausea and vomiting and a simple 3 mg single-dose intravenous regimen (equivalent to 40 μg/kg in a 75 kg person) is recommended for prevention of acute emesis associated with all cytotoxic regimens.
The comparison between the two groups regarding the incidence of occurrence of nausea and vomiting postoperative was not statistically significant.
Inconsistent with this result, the study by Wilson et al. [8] found the comparison between the 1 and 3 mg doses of granisetron was not statistically significant in the incidence of occurrence of nausea and vomiting postoperatively.
In contrast to this result, a study by Cieslak et al. [14] studied the dose–response relation and cost-effectiveness of granisetron for the prophylaxis of pediatric postoperative emesis. A total of 97 pediatric outpatients received a placebo or 10 or 40 μg/kg granisetron intravenous during standardized anesthesia. Episodes of postoperative retching, vomiting, and nausea were recorded, and the granisetron 40 μg/kg intravenous (3 mg) was more effective than a placebo or 10 μg/kg granisetron in decreasing the incidence and frequency of postoperative emesis.In this study, regarding the hemodynamic variables, the comparison between the two groups regarding the MAP was statistically significant in the 1–2, 2–4, 8–12, and 12–24 h postoperatively (P=0.001, P=0.024, P=0.007, and P<0.001, respectively).
The comparison between the two groups regarding the HR was statistically significant in the 2–4, 8–12, and 12–24 h postoperatively (P<0.001, P=0.003, and P<0.001, respectively).
In contrast to our results, a study by Wilson et al. [8] found no statistical difference between the two groups regarding vital signs.
Moreover, another study by Mikawa et al. [9] found no statistical difference between the two groups regarding the hemodynamics variability.
In this study, there was no significant difference on comparison between the two groups regarding demographic data, with a P value more than 0.05: age (P=0.107), weight (P=0.082), height (P=0.066), duration of surgery (P=0.538), time from end to first response (P=0.989), and time of first or an intake postoperative (P=0.111).
A limitation in our study was that it was a single-center study; however, we hypothesize that our results can be reproduced, as our study was in a major tertiary care hospital. Another limitation of our study was the use of a single antiemetic agent with a relative high incidence of PONV within 24 h. Only a rescue antiemetic was used when PONV occurred; however, it would have been used prophylactically.
| Conclusion | | |
PONV are common postoperative complications. Multiple efforts are being attempted to reduce the incidence of these complications to improve patients’ satisfaction. Among these efforts are pharmacological interventions, where the first line is considered the use of 5-HT3 antagonist (granisetron). The comparison between two doses of this drug 1 and 3 mg, respectively showed no statistical difference regarding the total control of PONV for 24 h postoperatively but showed a statistical difference regarding some postoperative vital sign readings.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Forrest JB, Heitlinger EL, Revell S. Ketorolac for postoperative pain management in children. Drug Saf 1997; 16:309–329.  |
| 2. | DCS. ASHP therapeutic guidelines on the pharmacologic management of nausea and vomiting in adult and pediatric patients receiving chemotherapy or radiation therapy or undergoing surgery. Am J Health Syst Pharm 1999; 56:729–764. |
| 3. | Honarmand A, Safavi M, Chegeni M, Hirmanpour A, Nazem M, Sarizdi SH. Prophylactic antiemetic effects of Midazolam, Ondansetron, and their combination after middle ear surgery. J Res Pharm Pract 2016; 5:16–21. [ PUBMED] [Full text] |
| 4. | Chan YH. Biostatistics 102: quantitative data − parametric & non-parametric tests. Singapore Med J 2003; 44:391–396. |
| 5. | Chan YH. Biostatistics 103: qualitative data − tests of independence. Singapore Med J 2003; 44:498–503. |
| 6. | Kovac AL. Prevention and treatment of postoperative nausea and vomiting. Drugs 2000; 59:213–243. |
| 7. | Andrews PL, Bhandari P, Davey PT, Bingham S, Marr HE, Blower PR. Are all 5-HT3 receptor antagonists the same?. Eur J Cancer 1992; 28A(Suppl 1):S2–S6. |
| 8. | Wilson AJ, Diemunsch P, Lindeque BG, Scheinin H, Helbo-Hansen HS, Kroeks MV et al. Single-dose i.v. granisetron in the prevention of postoperative nausea and vomiting. Br J Anaesth 1996; 76:515–518. |
| 9. | Mikawa K, Takao Y, Nishina K, Shiga M, Maekawa N, Obara H. Optimal dose of granisetron for prophylaxis against postoperative emesis after gynecological surgery. Anesth Analg 1997; 85:652–656. |
| 10. | Hanaoka K, Toyooka H, Kugimiya T, Ohashi Y. Efficacy of prophylactic intravenous granisetron in postoperative emesis in adults. J Anesth 2004; 18:158–165. |
| 11. | Tsuji D, Kim YI, Taku K, Nakagaki S, Ikematsu Y, Tsubota H et al. Comparative trial of two intravenous doses of granisetron (1 versus 3 mg) in the prevention of chemotherapy-induced acute emesis: a double-blind, randomized, non-inferiority trial. Support Care Cancer 2012; 20:1057–1064. |
| 12. | Wadaskar DR, Magar JS, Tendolkar BA. A study of comparing single dose granisetron with combination of granisetron with dexamethasone in preventing postoperative nausea vomiting in laparoscopic cholecystectomies. Int J Res Med Sci 2017; 4:3191–3197. |
| 13. | Kamanabrou D. Intravenous granisetron − establishing the optimal dose. The Granisetron Study Group. Eur J Cancer 1992; 28A(Suppl 1):S6–S11. |
| 14. | Cieslak GD, Watcha MF, Phillips MB, Pennant JH. The dose-response relation and cost-effectiveness of granisetron for the prophylaxis of pediatric postoperative emesis. Anesthesiology 1996; 85:1076–1085. |
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]
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