The Effect of Granisetron, Ondansetron, and Meperidine in Preventing Postoperative Shivering: Controlled Clinical Trial.

BACKGROUND: Recently, use of HT35 receptor antagonists to prevent postoperative shivering has attracted a great deal of attention. This study was conducted with the aim of investigating the effectiveness of granisetron as an HT35 antagonist when compared with ondansetron and meperidine in preventing postoperative shivering. MATERIAL AND METHODS: In this triple blind random clinical trial study, 90 patients 18-50 years of age with ASA Class I and II undergoing general anesthesia were randomly assigned into one of the three drug groups: O (4-mg ondansetron), G (40 µg/kg of granisetron), and P (25 mg meperidine), immediately before induction of anesthesia. After anesthesia induction, at the end of the surgery, after the entrance and after leaving the recovery state, central temperature, peripheral temperature, heart rate, systolic blood pressure, diastolic blood pressure, and shivering were measured and documented. Two-tailed P < 0.05 was considered significant. RESULTS: In the meperidine, ondansetron, and granisetron groups, 4 (13.3%), 3 (10%), and 10 (33.3%) of patients experienced shivering during recovery, where the difference between the ondansetron and granisetron groups was significant (p-value=0.02). The variations in the mean arterial pressure during the investigation stages only in the ondansetron group were not significant (p>0.05). At the beginning of recovery, the reduction of peripheral temperature significantly was lower in the ondansetron group (p<0.05), while reduction of the central temperature was significantly (p<0.05) higher in the granisetron group. By the end of the recovery, the variations in the peripheral temperature across the three groups were consistent with the changes at the beginning of recovery, but variations of the central temperature across the three groups was not significantly diverse. CONCLUSION: Granisetron was not found to be much effective in preventing postoperative shivering. Ondansetron and meperidine were equally effective in preventing postoperative shivering. Ondansetron also causes less hemodynamic changes compared to other drugs, while granisetron is more effective in terms of preventing nausea and vomiting.

A case-control study on the clinical characteristics of granisetron-related arrhythmias and the development of a predictive nomogram.

BACKGROUND: Automatic monitoring and assessment are increasingly employed in drug safety evaluations using hospital information system data. The increasing concern about granisetron-related arrhythmias requires real-world studies to improve our understanding of its safety. AIM: This study aimed to analyze the incidence, clinical characteristics, and risk factors of granisetron-related arrhythmias in hospitalized patients using real-world data obtained from the Adverse Drug Event Active Surveillance and Assessment System-II (ADE-ASAS-II) and concurrently aimed to develop and validate a nomogram to predict the occurrence of arrhythmias. METHOD: Retrospective automatic monitoring of inpatients using granisetron was conducted in a Chinese hospital from January 1, 2017, to December 31, 2021, to determine the incidence of arrhythmias using ADE-ASAS- II. Propensity score matching was used to balance confounders and analyze clinical characteristics. Based on risk factors identified through logistic regression analysis, a prediction nomogram was established and internally validated using the Bootstrap method. RESULTS: Arrhythmias occurred in 178 of 72,508 cases taking granisetron with an incidence of 0.3%. Independent risk factors for granisetron-related arrhythmias included medication duration, comorbid cardiovascular disease, concomitant use of other 5-hydroxytryptamine 3 receptor antagonists, alanine aminotransferase > 40 U/L, and blood urea nitrogen > 7.5 mmol/L. The nomogram demonstrated good differentiation and calibration, with enhanced clinical benefit observed when the risk threshold ranged from 0.10 to 0.82. CONCLUSION: The nomogram, based on the five identified independent risk factors, may be valuable in predicting the risk of granisetron-related arrhythmias in the administered population, offering significant clinical applications.

Incidence of Radiation-induced Nausea and Vomiting: A Prospective Single-institution Pilot Study.

Radiation-induced nausea and vomiting (RINV) is a frequent adverse event that occurs in patients undergoing radiotherapy. However, research on RINV is underrepresented. This prospective single-institution exploratory pilot study investigated the incidence of RINV according to the irradiation site and observed the efficacy of symptomatic antiemetic treatment in controlling symptoms of RINV. The primary outcomes were the proportions of emesis-free days and nausea-free days. The secondary endpoints included the time to the first episode of RINV, frequency of vomiting, and severity of nausea, including its impact on eating habits and weight loss. Fifteen patients were enrolled in each group (minimal, low, and moderate emetogenic risk). All patients received greater than 20 Gy in five fractions. Evaluation was based on weekly questionnaires completed by patients during routine clinic visits. Nausea and vomiting occurred in 11 and 0 patients, respectively. Six of 15 patients in the minimal-risk group, 1 in the low-risk group, and 4 in the moderate-risk group experienced nausea. Although all 11 symptomatic patients were offered antiemetics, only 3 used them, who reported satisfactory control of nausea. The percentage of emesis-free days for all patients was 100% and the percentage of nausea-free days for the 11 patients who developed RINV was 38%. An unexpectedly high percentage of patients in the minimal-risk group experienced nausea; all had breast cancer. Future studies should investigate factors beyond the irradiation site, including the characteristics of the patient and the treatment, to better predict an individual's risk of RINV.

The use of granisetron on bupivacaine induced sciatic nerve block in rats.

PURPOSE: The effects of the 5-hydroxytryptamine (5-HT3) receptor antagonists on regional anaesthesia are complex and unclear. The present study was designed to test the hypothesis that granisetron, a selective 5-HT3 receptor antagonist, would decrease the duration of motor block, sensory block, and proprioception in a dose-dependent fashion in a rat model of bupivacaine-induced sciatic nerve blockade. MATERIALS AND METHODS: Thirty-eight male Wistar Albino rats that received unilateral sciatic nerve blocks were randomly divided into five experimental groups. Group B received a perineural of 0.3 ml of bupivacaine alone; Group BG800 received perineural 0.3 ml of bupivacaine and 800 µg of granisetron 10 min later; Group BG1200 received perineural 0.3 ml of bupivacaine and 1200 µg of granisetron 10 min later; Group BG1200IP received a perineural 0.3 ml of bupivacaine and an intraperitoneal injection of 1200 µg of granisetron 10 min later; and Group S was sham operated. A blinded investigator assessed motor, sensory and proprioception function every 10 min until the return of normal function. RESULTS: The medians for recovery times in Group B, Group BG800, Group BG1200, and Group BG1200IP were 105, 64, 85, and 120 min for motor function, respectively; 80, 64, 84, and 104 min for sensory function; 80, 63, 85, and 108 min were calculated for the proprioception function. The time to the return of normal motor, sensory, and proprioception function was not statistically significantly different between the groups (p > 0.05). Motor block did not develop in any of the rats in Group S. CONCLUSIONS: Local and systemic application of granisetron was not significantly decrease the duration of bupivacaine induced motor, sensory, and proprioception block of sciatic nerve in rat.

Effects of ketamine, granisetron and dexmedetomidine on postoperative shivering and hemodynamic changes after general anesthesia: a double-blind randomized clinical trial.

Postoperative shivering is one of the most common complications of surgeries. The current research compared the effects of ketamine, granisetron, and dexmedetomidine on reducing postoperative shivering after general anesthesia. This double-blind clinical trial enrolled 148 patients (39.08 ± 5.99 years old) who had been admitted to Vali-Asr Hospital of Arak, Iran in 2019-2021. The study drugs, including dexmedetomidine, ketamine, granisetron and normal saline, were administered in corresponding groups 30 minutes before the end of surgery. The results showed that dexmedetomidine reduced mean arterial pressure and heart rate in patients. The lowest incidence of shivering was observed in the dexmedetomidine group and it increased the duration of recovery. Overall, dexmedetomidine is recommended to reduce postoperative shivering after general anesthesia, but the increase in duration of recovery should be considered.

Efficacy of Granisetron versus Sufentanil on Reducing Myoclonic Movements Following Etomidate: Double-blind, randomised clinical trial.

Objectives: This study aimed to reduce the intensity of myoclonus movements by comparing the effectiveness of granisetron and sufentanil in reducing the intensity of etomidate-induced myoclonic movements. Etomidate-induced myoclonus occurs in up to 85% of patients under general anaesthesia. This type of myoclonus can induce significant clinical and economic problems in patients with special conditions. Methods: This double-blind randomised clinical trial study consisted of 96 adult patients recruited between January and July 2021 from Mashhad University of Medical Sciences, Mashhad, Iran. Using block randomisation, subjects were divided into three groups of 32 patients: the group receiving granisetron 40 µg/kg (group G), the group receiving sufentanil 0.2 µg/kg (group S) and the control group who did not receive the pretreatment (group C). Patients received these medications as pretreatments 120 seconds before induction with etomidate. After the injection of etomidate with a dose of 0.3 mg/kg, the incidence of myoclonus was evaluated. After evaluating the myoclonus, the full dose of narcotics (fentanyl 1 µg/kg) and muscle relaxants (atracurium 0.5 mg/kg) were administered to patients and a suitable airway was established for them. Results: The findings indicated that granisetron reduced the intensity and incidence of myoclonic movements more than sufentanil. In addition, myoclonic movements were observed at a significantly higher intensity in the control group (P = 0.001). Conclusion: The results obtained from the current study indicate that granisetron and sufentanil as pretreatments are effective for reducing myoclonus in patients.

Evaluating Aprepitant single-dose plus granisetron and dexamethasone in children receiving highly emetogenic chemotherapy for the prevention of chemotherapy-induced nausea and vomiting: A triple-blinded randomized clinical trial

ABSTRACT Introduction: This study was performed to evaluate the degree of 3-day chemotherapy-induced nausea and vomiting (CINV) in children with cancer who received highly emetogenic chemotherapy (HEC) to ascertain the efficacy of aprepitant single-dose on dayL 1 plus granisetron and dexamethasone (DEX). Methods: This clinical trial study was conducted on 120 patients in the age range of 5 to 18 years old who received chemotherapy. Patients were divided into two groups; Group A received aprepitant at 125 mg/kg on day 1 orally, followed by 80 mg/kg daily on days 2 and 3 and Group B received a single dose of aprepitant 125 mg/kg on day 1 orally and placebo on days 2 and 3. All groups received granisetron 3 mg/m2 on day 1 and DEX on days 1 to 3. The primary and secondary endpoints were to evaluate the proportion of patients with acute, delayed and overall CINV within each group. Results: There were no significant differences between the two groups for vomiting, nausea or the use of rescue therapy. The number of patients without vomiting on day 1 was similar in both groups (96.5% vs. 98.3%, respectively; p = 0.848). Conclusion: According to the results of this study, a single dose of aprepitant 125 mg/kg was as effective as administering three doses of aprepitant on 3 days. Therefore, the use of a single dose of aprepitant in combination with other standard treatment regimens to prevent CINV in children who received HEC was safe and efficacious and can be beneficial.

Population pharmacokinetic analysis of transdermal granisetron in healthy Chinese and Caucasian volunteers.

Granisetron patches are a prolonged delivery transdermal system that is used to prevent Chemotherapy-induced nausea and vomiting (CINV). To date, no pharmacokinetics comparison between Chinese and Caucasian populations has been conducted for granisetron patches. This study focused on the ethnic differences in pharmacokinetics (PK) of granisetron transdermal delivery system (GTDS) between Chinese and Caucasians and the influence of demographic covariates on pharmacokinetics (age, weight, height, body mass index, sex). To achieve this, blood concentration data were collected from 112 Caucasian healthy subjects participating in four clinical trials and 24 Chinese healthy subjects from one clinical trial, after a single application of the granisetron transdermal delivery system. A nonlinear mixed-effects model method of Phoenix NLME software was used to establish a population pharmacokinetic (Pop PK) model for Caucasian subjects. Bootstrap and visual predictive check (VPC) were used to validate the model. Based on the analysis a one-compartment model with first-order absorption and a first-order elimination well described the PK characteristics of GTDS. The apparent systemic clearance was determined to be 31316.3 mL/h and the central compartment volume of distribution was 6299.03 L. None of the five covariates (age, weight, height, body mass index, and sex) included in the Pop PK were significant covariates affecting PK. The final Pop PK model was used to simulate the Caucasian blood concentration by applying the dosing regimen used for the Chinese population. Comparison of the simulated Caucasian PK data with observed clinical PK data from Chinese healthy subjects revealed no significant differences in the main parameters, AUClast and Cavg, between the two groups. These findings suggested that no dose adjustment was required when applied to the Chinese population. In conclusion, this Pop PK study comparing the transdermal patch in Chinese and Caucasian healthy subjects provided valuable insights for optimizing dosage across ethnicities.

Comparison of Intravenous Granisetron and Ondansetron on Hemodynamics and Sensory Motor Block After Spinal Anaesthesia With Hyperbaric Bupivacaine in Patients Undergoing Elective Surgery: A Randomized Double-Blind Study.

BACKGROUND: Bezold Jarisch reflex (BJR) is mediated by peripheral serotonin receptor 5-HT3 type. BJR and sympathetic blockade are important causes of hypotension and bradycardia after spinal anaesthesia. Premedication with serotonin receptor antagonists has a role in the attenuation of hemodynamic disturbances. AIM: To compare the effect of intravenous granisetron and ondansetron on the hemodynamic and sensory-motor block after spinal anaesthesia with hyperbaric bupivacaine in patients undergoing elective surgery. METHODOLOGY: Ninety patients posted for elective surgery under spinal anaesthesia were randomly divided into three groups of 30 each. Group A patients received ondansetron 4mg, group B received granisetron 1mg, and group C received normal saline intravenously. Hemodynamic variables such as heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, and peripheral oxygen saturation, were recorded at baseline and then 2 minutes intervals for 20 minutes and thereafter every 5 minutes till the end of the surgery. The onset and duration of sensory and motor block were recorded at baseline and then every 2 minutes till the complete block was achieved. RESULT: No patient was excluded from our study. During the intergroup comparison, heart rate and mean arterial pressure remained stable in group A compared to groups B and C. Time to reach peak sensory block level T4 was faster in group A compared to group B and group C. The rate of sensory block regression to two segments (T4 to T6) and thereafter up to T10, T12, and S1 was faster in group B compared to groups A and C. The attainment of complete motor block, Modified Bromage Score (MBS)=4 was faster in group A compared to group B and group C. The rate of motor block regression to MBS=3 and MBS=0 was faster in group B compared to group A and group C. CONCLUSION: Premedication with ondansetron 4mg and granisetron 1mg intravenously significantly reduces ephedrine use. Ondansetron provides better hemodynamic stability, earlier onset of the sensory and motor blocks as well as prolonged duration of sensory and motor blocks, and duration of analgesia compared to granisetron.

Efficacy appraisal of four regimens (granisetron, ketamine, dexmedetomidine, and lidocaine combined with fentanyl) for cystoscopy-associated sedation and analgesia and catheter-related bladder tolerance: a randomized clinical trial.

The authors sought to quantify the clinical impacts of granisetron, ketamine, dexmedetomidine, and lidocaine combined with fentanyl, for procedural sedation and analgesia in cystoscopy and for bladder catheter tolerance. This double-blind trial recruited four stratified blocked randomized eligible groups of patients (n = 120) formerly identified as needing cystoscopy, each receiving one of the above four anesthetic agents. Dexmedetomidine-sedated subjects experienced less pain from 5 to 120 minutes after the beginning of procedure, and next the ketamine manifested a better pain relief experienced. Sedation score was found to be rather more satisfactory in the early-mentioned from 15 to 55 minutes and at 90 and 105 minutes after procedure. The mean opioid use was observed lower in the dexmedetomidine treated patients and next in the ketamine administered patients. Considering the findings emanating from the study and the lack of complications that need to be treated, dexmedetomidine and ketamine afforded superior pain relief, greater sedation, and less postoperative opioid use in patients undergoing cystoscopy, and thus, they could be suggested to be combined with fentanyl during outpatient cystoscopy.

5-Hydroxytryptamine: a potential therapeutic target in amyotrophic lateral sclerosis.

Previous studies have indicated that the pathogenesis of amyotrophic lateral sclerosis (ALS) is closely linked to 5-hydroxytryptamine (5-HT). To investigate this further, we administered 5-HT receptor antagonists to SOD1*G93A transgenic (ALS mouse model) and wide-type mice. This involved intraperitoneal injections of either granisetron, piboserod, or ritanserin, which inhibit the 5-HT3, 5-HT4, and 5-HT2 receptors, respectively. The transgenic mice were found to have fewer 5-HT-positive cells in the spinal cord compared with wide-type mice. We found that the administration of granisetron reduced the body weight of the transgenic mice, while piboserod and ritanserin worsened the motor functioning, as assessed using a hanging wire test. However, none of the 5-HT receptor antagonists affected the disease progression. We analyzed the distribution and/or expression of TAR DNA binding protein 43 (TDP-43) and superoxide dismutase 1 G93A (SOD1-G93A), which form abnormal aggregates in ALS. We found that the expression of these proteins increased following the administration of all three 5-HT receptor antagonists. In addition, the disease-related mislocalization of TDP-43 to the cytoplasm increased markedly for all three drugs. In certain anatomical regions, the 5-HT receptor antagonists also led to a marked increase in the number of astrocytes and microglia and a decrease in the number of neurons. These results indicate that 5-HT deficiency may play a role in the pathogenesis of amyotrophic lateral sclerosis by inducing the abnormal expression and/or distribution of TDP-43 and SOD1-G93A and by activating glial cells. 5-HT could therefore be a potential therapeutic target for amyotrophic lateral sclerosis.

Effects of ondansetron, metoclopramide and granisetron on perioperative nausea and vomiting in patients undergone bariatric surgery: a randomized clinical trial.

INTRODUCTION: Post-operative nausea and vomiting (PONV) is a common problem after sleeve gastrectomy. In recent years, following the increase in the number of such operations, special attention has been paid to preventing PONV. Additionally, several prophylaxis methods have been developed, including enhanced recovery after surgery (ERAS) and preventive antiemetics. Nevertheless, PONV has not been completely eliminated, and the clinicians are trying to reduce the incidence of PONV yet. METHODS: After successful ERAS implementation, patients were divided into five groups, including control and experimental groups. Metoclopramide (MA), ondansetron (OA), granisetron (GA), and a combination of metoclopramide and ondansetron (MO) were used as antiemetics for each group. The frequency of PONV during the first and second days of admission was recorded using a subjective PONV scale. RESULTS: A total of 130 patients were enrolled in this study. The MO group showed a lower incidence of PONV (46.1%) compared to the control group (53.8%) and other groups. Furthermore, the MO group did not require rescue antiemetics, however, one-third of control cases used rescue antiemetics (0 vs. 34%). CONCLUSION: Using the combination of metoclopramide and ondansetron is recommended as the antiemetic regimen for the reduction of PONV after sleeve gastrectomy. This combination is more helpful when implemented alongside ERAS protocols.

Evaluating Aprepitant single-dose plus granisetron and dexamethasone in children receiving highly emetogenic chemotherapy for the prevention of chemotherapy-induced nausea and vomiting: A triple-blinded randomized clinical trial.

INTRODUCTION: This study was performed to evaluate the degree of 3-day chemotherapy-induced nausea and vomiting (CINV) in children with cancer who received highly emetogenic chemotherapy (HEC) to ascertain the efficacy of aprepitant single-dose on dayL 1 plus granisetron and dexamethasone (DEX). METHODS: This clinical trial study was conducted on 120 patients in the age range of 5 to 18 years old who received chemotherapy. Patients were divided into two groups; Group A received aprepitant at 125 mg/kg on day 1 orally, followed by 80 mg/kg daily on days 2 and 3 and Group B received a single dose of aprepitant 125 mg/kg on day 1 orally and placebo on days 2 and 3. All groups received granisetron 3 mg/m2 on day 1 and DEX on days 1 to 3. The primary and secondary endpoints were to evaluate the proportion of patients with acute, delayed and overall CINV within each group. RESULTS: There were no significant differences between the two groups for vomiting, nausea or the use of rescue therapy. The number of patients without vomiting on day 1 was similar in both groups (96.5% vs. 98.3%, respectively; p = 0.848). CONCLUSION: According to the results of this study, a single dose of aprepitant 125 mg/kg was as effective as administering three doses of aprepitant on 3 days. Therefore, the use of a single dose of aprepitant in combination with other standard treatment regimens to prevent CINV in children who received HEC was safe and efficacious and can be beneficial.

Efficacy of the granisetron transdermal system for the control of nausea and vomiting induced by highly emetogenic chemotherapy: a multicenter, randomized, controlled trial.

BACKGROUND/AIMS: We compared the efficacy of the granisetron transdermal system (GTS) with that of ondansetron for controlling chemotherapy-induced nausea and vomiting (CINV) in patients treated with highly emetogenic chemotherapy (HEC). METHODS: We randomized a total of 389 patients to groups treated by GTS and ondansetron before HEC. The primary endpoint was the percentage of patients achieving complete response (CR; no retching/vomiting/rescue medication) of CINV from the time of chemotherapy initiation to 24 hours after the last administration of chemotherapy (prespecified non-inferiority margin of 15%). Quality of life (QoL) was also assessed using the Functional Living Index-Emesis (FLIE). RESULTS: The per protocol analysis included 152 (47.80%) and 166 patients (52.20%) in the GTS and ondansetron groups, respectively. In the full analysis set, the most common diagnosis, regimen, and period of chemotherapy were lung cancer (149 patients, 40.27%), cisplatin-based regimen (297 patients, 80.27%), and 1 day chemotherapy (221 patients, 59.73%). The CR rates were 86.84% and 90.36% in the GTS and ondansetron groups, respectively; the treatment difference was -3.52% (95% confidence interval, -10.52 to 3.48) and met the primary endpoint, indicating that GTS was not inferior to ondansetron. Patient satisfaction, assessed on the FLIE, showed significantly higher scores in the GTS group compared to the ondansetron group (mean ± standard deviation, 1,547.38 ± 306.00 and 1,494.07 ± 312.05 mm, respectively; p = 0.0449). CONCLUSION: GTS provided effective, safe, and well-tolerated control of CINV and improved the QoL in HEC.

Role Of Granisetron In Minimising Use Of Meperidine As A Rescue Drug For Post Spinal Shivering.

BACKGROUND: Shivering is one of the most common adverse outcomes associated with the administration of spinal anaesthesia, which, when clinically relevant, leads to numerous detrimental effects on the human body. Hence, its management becomes imperative. Meperidine, an opioid analgesic, is the drug of choice for this condition. However, the use of meperidine is controversial, as it carries the devastating adverse effect of respiratory depression. We explored the role of granisetron, a 5HT3 antagonist and a commonly used antiemetic premedication, in minimising the incidence of post-spinal shivering and decreasing the use of meperidine as a rescue drug. METHODS: Overall, 160 parturient patients, between the ages 18-50, undergoing uncomplicated, elective caesarean section, were enrolled in the study, and randomized into two groups with 80 participants each: Group A received 3ml of normal saline, and Group B was administered 3 mg granisetron,15 minutes before spinal anaesthesia institution. Incidence of clinically relevant shivering (score of 3 or more) was noted, and it was recorded whether meperidine was used or not. RESULTS: 67.5% of participants in Group A, and 32.5% of patients in Group B, experienced clinically relevant shivering, with 62.5% of patients in Group A and 28.75% in Group B warranting the use of meperidine. There was a statistically significant difference between the two groups in terms of incidence of clinically relevant shivering, and meperidine consumption (p-value <0.001). CONCLUSIONS: Premedication with 3 mg granisetron effectively attenuates the occurrence of post-spinal shivering and, hence, lowers the requirement of meperidine as rescue medication.

Adjunctive granisetron therapy in patients with sepsis or septic shock (GRANTISS): A single-center, single-blinded, randomized, controlled clinical trial.

Background: In preclinical experiments, we demonstrated that the 5-HT3 receptor antagonist granisetron results in reduced inflammation and improved survival in septic mice. This randomized controlled trial was designed to assess the efficacy and safety of granisetron in patients with sepsis. Methods: Adult patients with sepsis and procalcitonin ≥ 2 ng/ml were randomized in a 1:1 ratio to receive intravenous granisetron (3 mg every 8 h) or normal saline at the same volume and frequency for 4 days or until intensive care unit discharge. The primary outcome was 28-day all-cause mortality. Secondary outcomes included the duration of supportive therapies for organ function, changes in sequential organ failure assessment scores over 96 h, procalcitonin reduction rate over 96 h, the incidence of new organ dysfunction, and changes in laboratory variable over 96 h. Adverse events were monitored as the safety outcome. Results: The modified intention-to-treat analysis included 150 septic patients. The 28-day all-cause mortalities in the granisetron and placebo groups were 34.7% and 35.6%, respectively (odds ratio, 0.96; 95% CI, 0.49-1.89). No differences were observed in secondary outcomes. In the subgroup analysis of patients without abdominal or digestive tract infections, the 28-day mortality in the granisetron group was 10.9% lower than mortality in the placebo group. Adverse events were not statistically different between the groups. Conclusion: Granisetron did not improve 28-day mortality in patients with sepsis. However, a further clinical trial targeted to septic patients without abdominal/digestive tract infections perhaps is worthy of consideration.

Granisetron versus Ondansetron: Comparison of 5HT3 antagonists in preventing spinal anaesthesia induced hemodynamic instability in obstetric patients.

Objectives: To evaluate and compare the Ondansetron and Granisetron in preventing spinal anaesthesia induced hemodynamic instability in obstetric patients. Methods: The comparative analytical study was conducted at Combined Military Hospital, Rawalpindi, from September to October, 2021. One hundred and twenty pregnant women undergoing cesarean section, were enrolled in the study via non probability convenience sampling, and divided into three groups containing 40 participants each based on the type of antiemetic premedication they received, if any: Group N were those not requiring antiemetic premedication, Group O consisted of those given ondansetron 4mg, and Group G had those receiving 3mg granisetron, 15 minutes prior to administration of spinal anaesthesia. Systolic blood pressures and heart rates were recorded before and at multiple intervals after spinal anaesthesia was administered. Episodes of hypotension and bradycardia were recorded. Requirement of phenylephrine and atropine as rescue drugs was recorded for each participant. Results: There was a statistically significant difference in incidence of hypotension among the three groups (p value <0.001), with both drugs being superior to the control group (p value <0.001 for both), and 3mg granisetron being superior to 4mg ondansetron (p value <0.001). As for incidence of bradycardia, ondansetron and granisetron were superior to control group (p value 0.03 and <0.001 respectively), but there was no significant difference between the two drug groups (p value 0.094). Conclusion: High dose granisetron (3mg) is superior to low dose ondansetron (4mg) in preventing hemodynamic fluctuations induced by spinal anaesthesia.

Granisetron-mediated augmentation of sertraline therapeutic effect in obsessive-compulsive disorder: a double-blind placebo-controlled, randomized clinical trial.

BACKGROUND: Medications currently recommended for the treatment of Obsessive-Compulsive Disorder (OCD) usually relieve the severity of symptoms by as much as 20-30%, and satisfactory treatment is obtained in 40-60% of patients with OCD. Nevertheless, the remaining symptoms continue to impair the patients' function. Therefore, it is necessary to investigate possible strategies to improve the mitigation of symptoms. In this study, the main objective was to examine and investigate the effectiveness of granisetron, which is a serotonin 5-hydroxytryptamine receptor type 3 (5-HT3) antagonist, as an adjunct therapy to selective serotonin reuptake inhibitors, for the purpose of ameliorating OCD symptoms. METHODS: fifty-eight patients diagnosed with OCD, based on Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, who had a Yale-Brown obsessive-compulsive scale (Y-BOCS) score of more than 21 were recruited in a double-blinded, parallel-group, placebo-controlled, clinical trial of 10 weeks to receive either granisetron (1 mg twice daily) and sertraline (100 mg daily initially followed by 200 mg daily after week 4) or placebo and sertraline. The primary outcome was OCD symptoms measured by the Y-BOCS. RESULTS: Y-BOCS total score significantly dropped in both groups (28.9 to 17.7 for granisetron plus sertraline and 27.5 to 19.3 for placebo plus sertraline group with a slightly greater drop for granisetron plus sertraline group), while the granisetron plus sertraline group experienced a significantly greater reduction in obsession scores (Greenhouse-Geisser F(2.32,97.57) = 4.52,p-value = 0.01). Moreover, in comparison with the placebo plus sertraline group, the proportion of the patients showing complete response was considerably higher among the granisetron plus sertraline group (P-value < 0.01). No major adverse effects were observed in any of the groups. CONCLUSION: The results suggest that granisetron augmentation of sertraline may increase the rate of response in patients with moderate to severe non-refractory OCD. Further studies are suggested in this regard.

Intranasal Delivery of Granisetron to the Brain via Nanostructured Cubosomes-Based In Situ Gel for Improved Management of Chemotherapy-Induced Emesis.

This research aimed to boost granisetron (GS) delivery to the brain via the intranasal route to better manage chemotherapy-induced emesis. Glycerol monooleate (GMO), Poloxamer 407 (P 407) and Tween 80 (T 80) were used to formulate GS-loaded cubosomes (GS-CBS) utilizing a melt dispersion-emulsification technique. GS-CBS were characterized by testing particle diameter, surface charge and entrapment efficiency. The formulations were optimized using a Box-Behnken statistical design, and the optimum formula (including GMO with a concentration of 4.9%, P 407 with a concentration of 10%, and T 80 with a concentration of 1%) was investigated for morphology, release behavior, ex vivo permeation through the nasal mucosa, and physical stability. Moreover, the optimal formula was incorporated into a thermosensitive gel and subjected to histopathological and in vivo biodistribution experiments. It demonstrated sustained release characteristics, increased ex vivo permeability and improved physical stability. Moreover, the cubosomal in situ gel was safe and biocompatible when applied to the nasal mucosa. Furthermore, compared to a drug solution, the nose-to-brain pathway enhanced bioavailability and brain distribution. Finally, the cubosomal in situ gel may be a potential nanocarrier for GS delivery to the brain through nose-to-brain pathway.

Propofol + Granisetron vs. Propofol + Metoclopramide in Symptom Management of Acute Migraine Headache; a Double-Blind Randomized Clinical Trial.

Introduction: Acute headache is one of the most common reasons for emergency department (ED) visits. This study aimed to compare the combination of propofol and granisetron with propofol and metoclopramide in symptom management of acute migraine headache. Methods: In this double-blind randomized clinical trial, 60 adult patients with acute migraine headache who referred to ED were randomly divided into two groups of propofol + metoclopramide and propofol + granisetron. Pain and nausea/vomiting severity as well as blood pressure were compared between groups 30, 45, and 60 minutes after treatment. Results: The two groups had similar situation regarding mean age (p = 0.606), sex distribution (p = 0.793), baseline severity of pain (p = 0.642), frequency of nausea/vomiting (p = 0.488), and vital signs (p > 0.05). The severity of pain was similar in the two groups 30 (p = 0.731), 45 (p = 0.460), and 60 (p = 0.712) minutes after treatment. The number of patients with resistant nausea and vomiting 60 minutes after treatment was significantly higher in metoclopramide group (30.0% versus 10.0%; p = 0.033). Diastolic pressure 60 minutes after treatment (81.43 ±8.94 vs. 74.97 ± 4.8; p = 0.001) and heart rate 30 minutes after treatment (68.87 ±6.52 vs. 73.57± 7.62; p = 0.013) had statistically significant differences between the groups. Conclusion: The combination of propofol and granisetron was superior to propofol and metoclopramide in case of controlling nausea and vomiting of cases with acute migraine headache; meanwhile, no differences were observed in case of pain relief and hemodynamic status between the two groups.