Administration Of Granisetron Research Articles

Comparison of granisetron 10 µg/kg vs 40 µg/kg intravenous for prophylaxis of shivering after spinal anesthesia for lower abdominal surgery

Background & Objective: Postanesthetic shivering is one of the many complications during recovery that is marked by vasoconstriction and involuntary movements in several muscle groups and psychologically is an incredibly uncomfortable experience for the patient. The 5-HT3 receptor antagonist granisetron can potentially be used to manage postanesthetic shivering through the thermoregulation neurotransmission system. This study aims to compare the effects of administering 10 µg/kg or 40 µg/kg of granisetron intravenously on the grade of shivering post spinal anesthesia in lower abdominal surgeries. Methodology: This study was a single-blind experimental study conducted on 30 patients who underwent spinal anesthesia for lower abdominal surgeries in Dr. Hasan Sadikin Hospital Bandung. There were no statistical differences of age, weight, height, BMI, core temperature before anesthesia, block height, room temperature, total bleeding, input volume, duration of surgery, and use of ephedrine between the two intervention groups. Results: Administration of 40 µg/kg intravenous granisetron could maintain the body temperature above 36.56 °C , better than the 10 µg/kg intravenous granisetron with the lowest temperature at 35.31 °C. Regarding the grade of shivering, administration of 40 µg/kg granisetron IV was able to improve postanesthetic shivering up to grade 2 in 3 (20%) patients, while 10 µg/kg intravenous granisetron improved grade of shivering to grade 3 in 5 (33%) patients, these results were statistically significant (P < 0.05). Conclusion: In conclusion, administration of granisetron 40 µg/kg IV reduces the incidence and severity of shivering post spinal anesthesia, and maintains a better core temperature compared to granisetron 10 µg/kg IV.Keywords: 5-Ht3 Receptor Antagonist; Granisetron; Postanesthetic Shivering; Prophylaxis
 Citation: Wahid WR, Pradian E, Prihartono MA. Comparison of granisetron 10 µg/kg vs 40 µg/kg intravenous for prophylaxis of shivering after spinal anesthesia for lower abdominal surgery. Anaesth. pain intensive care 2023;27(4):553−557; DOI: 10.35975/apic.v27i4.2265
 Received: October 20, 2021; Reviewed: March 19, 2023; Accepted: June 22, 2023

Comparative Efficacy of Granisetron and Droperidol After Orthognathic Surgery for Prophylaxis of Postoperative Nausea and Vomiting: A Retrospective Study

In the fall of 2021, granisetron was approved for postoperative nausea and vomiting (PONV) management in Japan. However, the comparative efficacy of droperidol and granisetron in the field of orthognathic surgery has not been determined. We compare the efficacy of droperidol and granisetron for PONV prophylaxis following orthognathic surgery. We performed a retrospective cohort study of patients who underwent orthognathic surgery at a single institution from September 2020 to December 2022. Patients who had undergone Le Fort I osteotomy with sagittal split ramus osteotomy or isolated sagittal split ramus osteotomy were included. Patients were divided into three groups; the isolated droperidol (D), isolated granisetron (G), and droperidol with granisetron (DG) groups. General anesthesia was performed using total intravenous anesthesia for all patients; however, droperidol and granisetron were administered at the anesthesiologist's discretion. PONV prophylactic therapy included isolated droperidol, isolated granisetron, and droperidol with granisetron administration. Postoperative nausea (PON) and postoperative vomiting (POV) were determined through medical examination within 48hours following surgery. Secondary outcomes included complications due to droperidol and/or granisetron administration. Age, sex, body mass index, Apfel's score, duration of surgery, duration of anesthesia, intraoperative blood loss, and type of surgery. Statistical analysis was conducted using Fisher exact test, Mann-Whitney U test with Bonferroni correction for univariate comparison, and modified Poisson regression for comparison of PON and POV efficacy for multivariate analyses. P values <.05 were considered statistically significant. Our study included 218 participants. There were no significant differences in covariates between groups D (n=111), G (n=52), and DG (n=55). No significant difference in PON incidence was observed between groups. However, POV incidence was significantly lower in group DG than group D (relative risk, 0.21; 95% confidence interval, 0.05 to 0.86; P=.03). No significant difference in complication incidence was observed between groups. Granisetron was as effective as droperidol for PONV management, while droperidol combined with granisetron was more effective than isolated droperidol for POV management. As compared to the use of each drug separately, their combination was considered safe, with no increase in complication rates.

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.

COMPARISON OF TWO DIFFERENT DOSAGES OF COMBINATION OF INTRAVENOUS GRANISETRON WITH INTRAVENOUS DEXAMETHASONE AS A PROPHYLAXIS FOR NAUSEA AND VOMITING IN CAESAREAN SECTION WITH SUBARACHNOID BLOCK

Granisetron can be used to treat and prevent nausea and vomiting in patients receiving chemotherapy or radiotherapy, as well as during or after surgery. To compare the effects of two doses of intravenous granisetron on nausea and vomiting in Caesarean section with subarachnoid block. This study was a randomized double-blind clinical trial. Subjects were randomized into two groups: Granisetron 10 mcg/kg (GD10) and granisetron 25 mcg/kg (GD25). Dexamethasone 0.1 mg/kg was also administered to all subjects. A total of 21 subjects were included for each group. Data was analyzed using Mann Whitney U test. The results When comparing the incidence of nausea and vomiting in the GD10 and GD25 groups, there was a significant difference in the incidence of nausea (p = 0.001). In the GD10 group, there were nine participants who experienced nausea, whereas the GD25 group had none. Neither of the groups experienced vomiting, hence no additional therapy given to both groups. Granisetron is a selective 5-HT3 receptor antagonist and an effective antiemetic during and after neuraxial anesthesia for Caesarean section. The combination of granisetron and dexamethasone has been reported to be more potent than granisetron alone. Administration of granisetron 25 mcg/kg had a positive impact on patients, with no incidence of nausea and vomiting compared to administration of granisetron 10 mcg/kg.

Granisetron attenuates liver injury and inflammation in a rat model of cecal ligation and puncture-induced sepsis

Background and aimsSepsis induced liver injury is recognized as a serious complication in intensive care units, it is deeply associated with oxidative stress, inflammation and subsequent pyroptosis. Hepatic pyroptosis known to aggravate sepsis-induced liver injury. Previous studies proved that granisetron has anti-inflammatory and antioxidant properties. Accordingly, this study aimed to evaluate the efficacy of granisetron on sepsis-induced liver damage using a cecal ligation and puncture (CLP) model in rats. Main methodsMale albino rats were randomly divided into four groups: a sham control group, a granisetron control group, a CLP-induced sepsis group and a granisetron-treated CLP group. Markers of oxidative stress, inflammation, pyroptosis-related proteins and liver function were measured in addition to the histopathological study. Key findingsGranisetron pretreatment significantly decreased mortality and improved liver function, as indicated by decreased ALT, AST, and total bilirubin and increased albumin content. Moreover, granisetron increased GPx activity and downregulated hepatic MDA. Furthermore, granisetron administration significantly reduced TNF-α, IL-6, HMGB1 and NF-κB. It also decreased the expression of receptor for advanced glycation end and TLR4 in the liver tissue. Interestingly, granisetron inhibited pyroptosis as it reduced NLRP3, IL-1β and caspase-1. Granisetron was shown to increase Nrf2 and HO-1. In addition, granisetron treatment repaired, to some extent, the abnormal architecture of hepatic tissue. SignificanceOur results suggested that granisetron is a potential therapeutic agent for sepsis-associated liver injury, possibly acting by inhibiting oxidative stress, inflammation and subsequent pyroptosis. KeywordsCLP, Granisetron, Liver injury, NLRP3, Sepsis.

A clinical survey on the electrocardiogram after intravenous granisetron hydrochloride administration in clinically normal dogs

Cardiac side effect of 5-hydroxytryptamine-3 receptor antagonists has been a concern for clinicians. There is a substantial need for greater clarity about the safety of granisetron hydrochloride, an antiemetic agent of this class used in oncological and parvoviral gastroenteritis with acute vomiting in dogs. This study aimed to assess the electrocardiographic effects of a single dose of intravenous granisetron. We randomly assigned 16 adult crossbreed female healthy dogs into two groups of intervention and control and injected them intravenously with granisetron and normal saline, respectively, at a dose of 0.5 ml/kg over one minute. Standard electrocardiography (ECG) was recorded at the baseline, as well as 5, 15, 30, 60, 120, 360, and 720 minutes after the intervention. Heart rate and ECG parameters (PR intervals, QRS duration, ST-segment, T-wave amplitudes, QT, JT, QTc and JTc intervals) were evaluated in lead II.No significant difference was observed between the intervention and the control groups in any of the measured variables at any of the time-points. Mean values of measured parameters showed no significant difference compared with baseline values in the control group, while the granisetron group saw statistically significant but clinically asymptomatic changes in heart rate, PR, QRS, QT, JT, and QTc at different time-points, compared to the baseline values (P&lt;0.05). In conclusion, Granisetron administration was not associated with clinically significant adverse effects on ECG variables or heart rate. Thus, it can be regarded as a relatively safe drug.

Comparison of IV granisetron and IV palonosetron on hemodynamics and sensory and motor block after spinal anesthesia with hyperbaric bupivacaine in patients undergoing abdominal hysterectomy.

Background and Aims:The present study evaluated the effects of two 5-HT3 serotonin receptor antagonists; granisetron and palonosetron on hemodynamics, sensory, and motor blockade induced by intrathecal bupivacaine in patients undergoing abdominal hysterectomy.Material and Methods:In total, 126 female patients (ASA I and II physical status) undergoing abdominal hysterectomy under spinal anesthesia with intrathecal bupivacaine were randomly divided into three groups out of which 40 patients in each group were evaluated for final outcome. Group G received intravenous 1 mg granisetron, group P received intravenous palonosetron 0.075 mg, and group C received intravenous normal saline. Study drug was given 5 min before the spinal anesthesia. Systolic, diastolic and mean arterial blood pressure, heart rate, sensory and motor blockade were assessed.Results:The systolic blood pressure, diastolic blood pressure, mean arterial pressure, and heart rate showed no significant differences among the three groups. Time to reach peak sensory block and modified Bromage 3 motor block, time to two segmental regression of sensory block, and motor regression to modified Bromage score of 0 were not statistically different among the three groups. Although statistically significant early regression of sensory block to segment S1 was seen in group G as compared to group P and group C, it was of no clinical significance. The incidence of nausea and vomiting was significantly lower in group G and P.Conclusion:Intravenous administration of granisetron and palonosetron before intrathecal bupivacaine does not attenuate the hemodynamic changes in patients undergoing abdominal hysterectomy. Further, both 5-HT3 receptors antagonists do not have clinically significant effects on the spinal blockade produced by hyperbaric bupivacaine.

Granisetron protects polymicrobial sepsis-induced acute lung injury in mice

Sepsis is a serious condition with a high mortality rate worldwide. Granisetron is an anti-nausea drug for patients undergoing chemotherapy. Here we aimed to identify the novel effect of granisetron on sepsis-induced acute lung injury (ALI). Our results showed that mice treated with granisetron displayed less severe lung damage than controls. Granisetron administration reduced pulmonary neutrophil recruitment after CLP. Moreover, the expressions of Cxcl1 and Cxcl2 were diminished in the presence of granisetron in THP-1 macrophages after lipopolysaccharide exposure. Additionally, granisetron could inhibit the activation of p38 MAPK and NLRP3 inflammasome both in vivo and in vitro. Collectively, granisetron protects against sepsis-induced ALI by suppressing macrophage Cxcl1/Cxcl2 expression and neutrophil recruitment in the lung.

Blockade of 5-HT3 receptors with granisetron does not affect trigeminothalamic nociceptive transmission in rats: Implication for migraine.

One way to expand the existing range of anti-migraine drugs seems to be the search for pharmacological agents with anti-cephalalgic properties among medicines approved for clinical indications other than migraine. Numerous experimental and clinical data imply that selective serotonin 5-HT3 receptor antagonists can be considered as potential anti-migraine agents. Therefore, the objective of our work was to examine the impact of selective 5-HT3 receptor blockade with granisetron on migraine-related nociceptive transmission within the spinal trigeminal nucleus (STN) and the ventroposteromedial nucleus of the thalamus (VPM). Using an electrophysiological model of trigemino-durovascular nociception in anaesthetised male Wistar rats, we evaluated the effects of intravenous administration of granisetron on ongoing firing and dural electrical stimulation-evoked responses of the spinal trigeminal and thalamic cells. Granisetron did not substantially affect responses of the STN and VPM neurons to electrical stimulation of the dura mater as well as did not cause steady changes in ongoing firing of the spinal trigeminal cells. The results obtained argue against the use of 5-HT3 receptor antagonists for treating migraine. These data also lead to the conclusion that in the absence of sustained sensitisation of neurons along the trigemino-thalamo-cortical pathway the role of 5-HT3 receptor-dependent mechanisms in serotonergic modulation of trigeminovascular nociceptive transmission can hardly be considered crucial.

COMPARISON OF THE ANTIEMETIC EFFECTIVENESS BETWEEN GRANISETRON AND DEXAMETHASONE WITH ONDANSETRON AND DEXAMETHASONE IN ACUTE-PHASE CHEMOTHERAPY PATIENTS

Nausea and vomiting may occur in patients receiving chemotherapy, a condition referred to as chemotherapy-induced nausea and vomiting. The provision of combined dexamethasone and ondansetron or granisetron is the therapeutic management of acute phase nausea and vomiting in cytostatics with a high risk of nausea and vomiting. Granisetron has been known to have better pharmacokinetics and pharmacodynamics compared to ondansetron, so it is possible to have nausea and vomiting suppressing effect higher than that of ondansetron. This study aimed to compare antiemetic effectiveness of granisetron and dexamethasone with ondansetron and dexamethasone in acute-phase chemotherapy patients. This study was conducted in patients who received the combination of cisplatin-paclitaxel and cisplatin-fluorouracil, double-blind, with samples comprised new head and neck surgical oncology patients. Measurement of nausea and vomiting during the acute phase of chemotherapy was conducted using Index of Nausea, Vomiting, and Retching (INVR). Observation of nausea and vomiting in the patients was done during the first 12 hours after administration of cisplatin and interviews were conducted on h 12. Results showed that there was no difference in the effectiveness of nausea and vomiting suppression in the administration of granisetron and dexamethasone compared to ondanstron and dexamethasone in acute phase chemotherapy patients (p = 0.076).

Granisetron and carvedilol can protect experimental rats againstadjuvant-induced arthritis

Context: Rheumatoid arthritis (RA), a disabling autoimmune disorder of the joints as well as other organs, affects about 1% of population. Unfortunately, all current treatments of RA cause severe gastrointestinal, renal and other complications.Objective: We aimed to evaluate the possible antiarthritic effects of a serotonin 5-HT3 receptor blocker, granisetron, and a nonselective adrenergic receptor blocker, carvedilol, on complete Freund's adjuvant-induced RA in adult female albino rats.Materials and methods: Rats were allocated into a normal control group, an arthritis control group, two reference treatment groups receiving dexamethasone (1.5 mg/kg/day) and methotrexate (1 mg/kg/day), and two treatment groups receiving granisetron (2.5 mg/kg/day) and carvedilol (10 mg/kg/day). Serum-specific rheumatoid, immunological, inflammatory and oxidative stress biomarkers were assessed. A confirmatory histopathological study on joints and spleens was performed.Results: Granisetron administration significantly improved all the measured biomarkers, with the values of rheumatoid factor, matrix metalloproteinase-3, cartilage oligomeric matrix protein, immunoglobulin G, antinuclear antibody and myeloperoxidase being restored back to normal levels. Carvedilol administration significantly improved all biomarkers, with serum MPO value restored back to normal levels.Discussion and conclusions: Serotonin 5-HT3 receptor blockers and adrenergic receptor blockers, represented by granisetron and carvedilol, may represent new promising protective strategies against RA, at least owing to immune-modulator, anti-inflammatory and antioxidant potentials.

Amelioration of Pain on Injection of Propofol: A Comparison of Pretreatment with Granisetron Vs Lignocaine.

Pain during propofol injection is a very commonly and frequently encountered event during induction of anaesthesia. A 5HT3 antagonists like granisetron are commonly used just prior to intravenous propofol as pre anaesthetic medication to prevent emesis in patients. Comparison of pre treatment with granisetron versus lignocaine with respect to amelioration of pain induced by injection of propofol, in patient admitted for elective surgery with general anaesthesia. A randomized double blinded controlled study was conducted with patients divided into three groups with (n=30) in each group. Group I (the placebo group) received 2 ml of 0.9% normal saline, Group II received 2 ml of 1% lignocaine and Group III received 2 ml of granisetron (1 mg/ml) as pre treatment medication respectively. The patient's complain regarding pain on intravenous propofol administration was recorded using the Verbal Rating Score. Pulse, BP, SpO2 were noted meticulously on three occasions-immediately after pre-treatment, injecting full dose of propofol (not for pain assessment) and after 10 minutes. The results were analysed using the null hypothesis and two sample t-tests. It was observed and obvious that the relief of pain was significant (p<0.05) when granisetron or lignocaine was compared with the placebo group. But there was insignificant difference (p>0.05) when granisetron was compared with lignocaine in terms of relieve of pain induced by propofol. It was concluded that parenteral administration of granisetron can be considered to be superior to lignocaine as pre treatment medication for pain relief after propofol injection along with the advantage of its anti-emetic effect.

Different drugs for prevention of post subarachnoid block shivering. Randomized, controlled, double blind study

BackgroundShivering is one of the most stressful complications for both the surgeon and the anesthesiologist during neuraxial anesthesia. The aim of this prospective randomized double blinded study was to evaluate the effectiveness of preoperative administration of granisetron, dexmedetomidine, and tramadol in prevention of shivering in patients undergoing elective operations with subarachnoid anesthesia.Methods320 patients ASA I or II aged between 18 and 65 years scheduled for elective operations under subarachnoid block were included in the study. They were divided randomly into four equal groups, and 10 min before performance of subarachnoid block, patients in group G (n = 80) received 40 μg/kg intravenous infusion of granisetron in 100 ml of normal saline, patients in group D (n = 80) received 0.5 μg/kg intravenous infusion of dexmedetomidine in 100 ml of normal saline, patients in group T (n = 80) received 1 mg/kg intravenous infusion of tramadol in 100 ml of normal saline, and patients in group C (n = 80) received 100 ml of normal saline as control.The following parameters were assessed: heart rate, mean arterial blood pressure, SPo2 and core temperature at the following times: 0 time, 5 min,10 min, 15 min, then every 15 min till end of the surgery. The incidence and intensity of shivering during the operation were recorded.ResultsStudy found statistically significant decrease in the incidence of shivering in group G, group D, and group T in comparison with group C without statistical significant difference between group G, group D, and group T. There was no statistical significant difference in the core temperature between the four groups.ConclusionPreoperative administration of granisetron, dexmedetomidine, and tramadol was effective in decreasing the incidence and intensity of post subarachnoid shivering without increasing the incidence of the side effects.

Pharmacodynamics of transdermal granisetron in women with nausea and vomiting of pregnancy

Limited options exist for women with nausea and vomiting of pregnancy (NVP) who cannot tolerate oral intake. Transdermal delivery of granisetron, a 5-hydroxytryptamine-3 receptor antagonist, provides an effective alternative for such patients. The objective of this study was to evaluate the pharmacodynamics of granisetron administered intravenously (IV) and as a sustained release transdermal patch in women with NVP. We recruited 16 women with singleton gestation between 12 0/7-18 6/7 weeks who were receiving treatment for NVP and had a Pregnancy Unique Quantification of Emesis and Nausea (PUQE) score of ≥6. All consenting subjects received 1 mg of granisetron as an IV infusion over 5 minutes and blood was obtained prior to the infusion and at 10, 20, 30, and 60 minutes and at 2, 4, 6, 8, 12, and 24 hours after the start of the infusion. After a minimum washout of 48 hours after initiation of IV granisetron, a 52-cm(2) granisetron patch (34.3 mg) was placed on the upper arm of all subjects for 7 days. Blood was drawn prior to patch placement and daily thereafter for 9 days. The subjects were evaluated daily. The PUQE score was obtained from these subjects prior to the IV infusion and daily for 2 days after and again prior to and daily for 9 days after patch placement. Complete data were available in 15 women after IV administration and 13 women after patch placement. One woman stopped participation during the IV infusion while data were not available in 2 additional women after patch placement due to noncompliance. Peak plasma granisetron concentrations after IV and transdermal administration were similar (∼10 ng/mL). Prior to IV administration of granisetron, the PUQE score was 8.6 ± 1.8 (mean ± SD). The PUQE scores were significantly reduced for the ensuing 2 days (P < .01). The PUQE score prior to patch placement was 7.6 ± 2.4. Scores were significantly (P < .001) reduced within 1 day of patch placement and stayed significantly reduced during the ensuing 6 days of patch placement. The patch was removed on the seventh day and PUQE scores increased significantly on the third day after patch removal. No serious side effects were reported either during IV administration or patch placement. Granisetron significantly improved symptoms of nausea and vomiting as gauged by the PUQE score. After IV infusion the reduction in PUQE score was observed within 1 day. When granisetron wasadministered as a patch, benefit likewise was seen within 1 day suggesting rapid absorption of the medication transdermally. The beneficial effect of transdermal granisetron on the PUQE score persisted for the entire 7 days during which the patch was in place. In this small cohort, the granisetron patch appeared to be efficacious in reducing the symptoms of nausea and vomiting. The patch provides another option for treating this disorder and may be particularly useful in women who cannot tolerate oral medications.

To Push or Not to Push: The Benefit of Administering Anti-Emetics By Intravenous Push

BackgroundPrevention of chemotherapy-induced nausea and vomiting is crucial for maintaining the quality of life of cancer patients. Granisetron and dexamethasone are commonly used medications prior to chemotherapy to minimize these adverse effects. There are no well-defined guidelines on the route of administration of medications that are administered prior to chemotherapy. With the ever increasing cost of cancer care, innovative methods need to be employed to maximize utilization of resources.MethodsA retrospective chart review was performed to identify patients who received granisetron and dexamethasone prior to emetogenic chemotherapy. The primary study site was the cancer center of a tertiary care community hospital. Over a two month period there were 1552 instances when patients received dexamethasone or granisetron prior to emetogenic chemotherapy. Patients either received medications by intravenous piggyback (IVPB) or intravenous push (IVP). The time spent on delivering medication by the two routes and the rate of occurrence of nausea and vomiting requiring the administration of rescue medications were compared.ResultsPatients who received granisetron and dexamethasone by IVPB had a 2.8% rate of adverse effect rate requiring rescue medications (n=806) and patients who received the medication by IVP had a 2.9% rate of adverse effects requiring rescue medications (n=746). There was no statistical significance in the occurrence of nausea and vomiting requiring rescue medications between the two groups (p>0.80). The total average duration for administration of granisetron and dexamethasone by IVPB was 30 minutes and two minutes by IVP. The average cost of an IVP is $57 as compared to $161 for IVPB based on national average costs.ConclusionsAn average of 28 minutes of chemotherapy chair time is saved on each patient for each session of chemotherapy by administering granisetron and dexamethasone by IVP. Approximately $167,000 would have been saved if the above IVPB group received medications by IVP. This sum excludes nursing costs, chemotherapy chair costs and other disposable charges. The route of administration of the medications did not affect the rate of occurrence of adverse effects requiring rescue medications. The utilization of the intravenous push route will save the patient time and reduce nursing hours without compromising on the effectiveness of the drugs while adding to sizeable cost savings. DisclosuresNo relevant conflicts of interest to declare.

Effects of Selective Blockade of 5-HT3 Receptors on Physiological Markers of Abdominal Pain in Conscious Dogs

Experiments on conscious dogs addressed the effects of blockade of type 3 serotonin receptors on visceromotor reactions and changes in heart rate (HR) initiated by nociceptive distension of the rectum. Distension of the rectal walls with pressures of 20–60 mmHg were found not to produce significant changes in the electromyographic activity of the abdominal muscles or HR. Distension of the intestine with a pressure of 80 mmHg and greater produced marked visceromotor reactions (contractions of the abdominal muscles) and increases in HR (tachycardia), which are regarded as markers for the occurrence of pain sensations. Use of these indicators allowed the first demonstration in conscious dogs of the dose-dependent antinociceptive effect of blockade of 5-HT3 receptors with granisetron. Administration of granisetron at doses of 0.25, 0.5, and 1.0 mg/kg was accompanied by prolonged (at least 90 min) decreases in visceromotor reactions to nociceptive rectal distension by 33.6 ± 9.2%, 58.0 ± 8.6%, and 76.7 ± 5.5% of baseline, respectively. In turn, the inhibitory effect of granisetron on tachycardia induced by painful rectal stimulation was seen only immediately after administration. Thus, studies on conscious dogs demonstrated the antinociceptive effect of granisetron in relation to abdominal pain, which may be relevant in the development of pharmacological agents to treat pain in patients with irritable bowel syndrome.

PWSC2-4 - Randomized Controlled Study Comparing Two Doses of Intravenous Granisetron Chemotherapy-Induced Nausea and Vomiting

Objective: The aim of this study was to assess the non-inferiority of 1 mg to 3 mg granisetron injection for the treatment of acute chemotherapy-induced nausea and vomiting and to evaluate the tolerability of granisetron given at 1 mg in Japanese cancer patients.Methods: Patients with cancer receiving highly emetogenic chemotherapy were enrolled in this single-blind randomized controlled study. Patients were randomly assigned to receive granisetron at a single dose of 1 mg or 3 mg. The primary endpoint was the rate of complete protection from emetic events(no vomiting, no retching, and no need for rescue medication)during the first 24 hours following the initiation of chemotherapy.Results: There were 89 patients in the 1-mg group and 90 patients in the 3-mg group. Complete protection was achieved in 70 patients(78.7%) in the 1-mg group and 73(81.1%) patients in the 3-mg group. The one-sided test did not reveal non-inferiority of either dose of granisetron to the other at a 5.0% significance level.Conclusion: Our data failed to show the non-inferiority of 1 mg to 3 mg of granisetron administered as a single dose. However, the rate of complete protection from nausea and vomiting was similar in the two groups. Given the recommended dosage in the guidelines and the economic need for reduction of medical care expenses in Japan, prophylactic administration of granisetron at 1 mg may be an appropriate treatment alternative for acute chemotherapy-induced nausea and vomiting in cancer patients.

Evaluating the various phases of cisplatin-induced emesis in rats

Use of cisplatin as a chemotherapeutic agent causes acute and delayed emesis. Kaolin, saccharin solution and normal feed consumption have been evaluated as an index of cisplatin-induced emesis in rats; however, the most preferable of these methods for evaluating the various phases of emesis remains unclear. In the current study, kaolin, saccharin solution and normal feed consumption following cisplatin administration (6 mg/kg intraperitoneally) were simultaneously investigated in rats. Kaolin consumption increased significantly following cisplatin administration and was attenuated by granisetron administration 0–24 h following the injection. Saccharin solution consumption, however, decreased significantly 0–48 h following cisplatin administration, however, was attenuated by administration of granisetron within 0–24 h only. A reduced intake of normal feed was observed in the control group and was reversed by granisetron within the 0–72 h period. The present study indicates that kaolin consumption may be evaluated as an index of cisplatin-induced acute emesis and saccharin solution consumption may be evaluated as an index of delayed emesis, while normal feed consumption as an indicator of anorexia nervosa may be suitable to evaluate all phases of emesis and serve as an indicator of quality of life.

Theoretical evaluation of antiemetic effects of 5-HT3 receptor antagonists for prevention of vomiting induced by cisplatin

5-HT(3) receptor antagonists are widely used as antiemetic agents in clinical setting, of which palonosetron, with a long elimination half life (t(1/2)), has recently become available. It is important to evaluate the concentration of serotonin when investigating the antiemetic effects of 5-HT(3) receptor antagonists, as those effects are not based solely on the t(1/2) value. We theoretically evaluated the antiemetic effects of three 5-HT(3) receptor antagonists (granisetron, azasetron, palonosetron) on cisplatin-induced nausea and vomiting by estimating the time course of the 5-HT(3) receptor occupancy of serotonin. We estimated the 5-HT(3) receptor occupancy of serotonin in the small intestine, based on the time course of plasma concentration of each 5-HT(3) receptor antagonist and the time course of concentration of serotonin near the 5-HT(3) receptor in the small intestine after administration of cisplatin. The antiemetic effect of each 5-HT(3) receptor antagonist was evaluated based on the normal level of 5-HT(3) receptor occupancy of serotonin. Our results suggest that an adequate antiemetic effect will be provided when a dose of 75 mg/m(2) of cisplatin is given to patients along with any single administration of granisetron, azasetron, or palonosetron at a usual dose. On the other hand, the 5-HT(3) receptor occupancy of serotonin was found to be significantly lower than normal for several days after administration of palonosetron, as compared to granisetron and azasetron, indicating that constipation may be induced. Our results show that granisetron, azasetron, and palonosetron each have an adequate antiemetic effect after administration of 75 mg/m(2) of cisplatin.

Granisetron versus ondansetron for post-operative nausea and vomiting prophylaxis in elective craniotomies for brain tumors: A randomized controlled double-blind study

Context:Post-operative nausea and vomiting (PONV) pose unique challenges in neurosurgical patients that warrant its study separate from other surgical groups.Setting and Design:This prospective, randomized, double-blind study was carried out to compare and to evaluate the efficacy and safety of three antiemetic combinations for PONV prophylaxis following craniotomy.Materials and Methods:A total of 75 anesthesiologist status I/II patients undergoing elective craniotomy for brain tumors were randomized into three groups, G, O and D, to receive single doses of dexamethasone 8 mg at induction with either granisetron 1 mg, ondansetron 4 mg or normal saline 2 ml at the time of dural closure respectively. Episodes of nausea, retching, vomiting and number of rescue antiemetic (RAE) were noted for 48 h post-operatively.Statistical Analysis:Analysis of variance with post-hoc significance and Chi-square test with fisher exact correction were used for statistical analysis. P <0.05 was considered to be significant and P < 0.001 as highly significant.Results:We found that the incidence and number of vomiting episodes and RAE required were significantly low in Group G and O compared with Group D; P < 0.05. However, incidence of nausea and retching were comparable among all groups. The anti-nausea and anti-retching efficacy of all the three groups was comparable.Conclusions:Single dose administration of granisetron 1 mg or ondansetron 4 mg at the time of dural closure with dexamethasone 8 mg provide an effective and superior prophylaxis against vomiting compared with dexamethasone alone without interfering with post-operative recovery and neurocognitive monitoring and hence important in post-operative neurosurgical care.