Dose-Response Study of Phenylephrine for Preventing Spinal-Induced Hypotension During Cesarean Delivery with Combined Spinal-Epidural Anesthesia Under the Effect of Prophylactic Intravenous Ondansetron.

Background: Ondansetron reduces the median effective dose (ED50) of prophylactic phenylephrine to prevent spinal-induced hypotension (SIH) during cesarean delivery. However, the exact dose response of phenylephrine in combination with prophylactic ondansetron for preventing SIH is unknown. Therefore, this study aimed to determine the dose-response of phenylephrine to prevent SIH in cesarean delivery when 4 mg of ondansetron was used as a preventive method. Methods: A total of 80 parturients were enrolled and divided randomly into four groups (n = 20 in each group) who received either 0.2, 0.3, 0.4, or 0.5 µg/kg/min of prophylactic phenylephrine. Ten minutes before the initiation of spinal induction, 4 mg prophylactic ondansetron was administered. The effective dose of prophylactic phenylephrine was defined as the dose required to prevent hypotension after the period of intrathecal injection and up to neonatal delivery. The ED50 and ED90 of prophylactic phenylephrine and 95% confidence intervals (95% CI) were calculated using probit analysis. Results: The ED50 and ED90 for prophylactic phenylephrine to prevent SIH were 0.25 (95% CI, 0.15 to 0.30), and 0.45 (95% CI, 0.39 to 0.59) µg/kg/min, respectively. No significant differences were observed in the side effects and neonatal outcomes between the four groups. Conclusion: The administration of 4 mg of prophylactic ondansetron was associated with an ED50 of 0.25 (95% CI, 0.15~0.30) and ED90 of 0.45 (95% CI, 0.39~0.59) µg/kg/min for phenylephrine to prevent SIH.

The prophylactic antiemetic therapies in management of differentiated thyroid cancer patients with radioactive iodine therapy: a single-center, non-randomized clinical trial.

Objective: The present study was to investigate three different single-drug regimens to show which was more effective to reduce radioactive iodine therapy (RAI) associated nausea and vomiting, and to compare the occurrence of long-term gastrointestinal diseases after RAI therapy. Method: We performed a single-center, non-randomized clinical trial among patients who underwent RAI therapy from March 2016 to July 2022. Enrolled patients were divided into four cohorts based on the date of the treatment. cohort 1, with no preventive antiemetics; cohort 2, received 20 mg of pantoprazole per day for 3 days; cohort 3, received a 10 mg metoclopramide tablet two times daily for 3 days; cohort 4, oral ondansetron, 8 mg, twice daily for 3 days. The primary endpoints were proportion of patients who experience vomiting episodes and nausea during the 7-day hospital period. Secondary end points included Functional Living Index Emesis (FLIE) quality-of life questionnaires and the occurrence of gastrointestinal diseases. Results: A total of 1755 patients were analyzed, comprised of 1299 (74.0%) women and 456 (26.0%) men, with a median age of 44 years (range 18-78 years). The characteristics of patient were similar within the four groups. 465 (26.4%) patients developed RAI-associated nausea, and 186 (14.4%) patients developed RAI-associated vomiting. The rate of nausea was significantly decreased in the patients who were taking ondansetron when compared with the other cohorts (P<0.05), while the rate of vomiting (≥6 episodes) was slightly lower. As secondary endpoint, FLIE measures ondansetron scored highly compared to other cohorts, from baseline (mean score of 110.53 ± 17.54) to day 7 (mean score of 105.56 ± 12.48). In addition, 48 (2.7%) patients were found to be with gastrointestinal diseases at the end of one year follow up. Multiple RAI therapy and higher dose of I-131 per body weight revealed a significantly independent risk factors of developing gastrointestinal disorders. Conclusions: In conclusion, the present study demonstrated that short-term ondansetron could be an effective prophylactic agent in controlling RAI-associated nausea and vomiting. Furthermore, the risk of developing gastrointestinal disorders was significantly higher for patients with multiple RAI therapy and higher dose of I-131 per body weight.

Comparative efficacy of prophylactic protocols in reducing perioperative nausea and vomiting during video-assisted thoracoscopic radical resection of lung cancer.

Lung cancer, a global mortality leader, often necessitates Video-Assisted Thoracoscopic (VATS) surgery. However, post-operative nausea and vomiting (PONV) is common, highlighting a need for effective management and prevention strategies in this context. A retrospective case-control study at Fujian Medical University Union Hospital evaluated patients undergoing VATS radical resection of lung cancer between May and September 2022. Patients were categorized based on PONV prevention methods, and data encompassing demographics, surgical history, and postoperative adverse events s were analyzed to assess the association between prophylactic protocols and PONV incidence. The Netupitant and Palonosetron Hydrochloride (NEPA) group showed a significant reduction in PONV occurrences post-surgery compared to Ondansetron (ONDA) and Control groups, emphasizing NEPA's efficacy in alleviating PONV symptoms (P < 0.05). Furthermore, following VATS radical resection of lung cancer, NEPA markedly reduced the intensity of PONV symptoms in patients. Both univariate and multivariate logistic analyses corroborated that NEPA independently reduces PONV risk, with its protective effect also apparent in susceptible populations like females and non-smokers. NEPA utilization markedly reduced both the incidence and severity of PONV in patients undergoing VATS radical resection of lung cancer, serving as an independent protective factor in mitigating PONV risk post-surgery.

Effect of preoperative ondansetron on postoperative nausea in healthy dogs undergoing laparoscopic gastropexy and castration.

OBJECTIVE: To investigate if preoperative ondansetron reduces postoperative nausea associated with laparoscopic gastropexy and castration in dogs. STUDY DESIGN: Prospective clinical study. ANIMALS: Twenty client-owned, healthy male dogs. METHODS: Dogs were premedicated with dexmedetomidine (2-5 mcg kg-1) and methadone (0.2-0.5 mg kg-1) intramuscularly. General anesthesia was induced with propofol and maintained with an inhalant anesthetic agent. Dogs were randomized into group S (saline 0.1 mL kg-1, intravenously) or group O (ondansetron 0.2 mg kg-1, intravenously). Plasma and serum were collected before premedication and 3 hours postextubation to measure arginine vasopressin (AVP) and cortisol concentrations. Nausea scoring occurred before and 10 minutes after premedication, immediately after extubation, and at 1, 2 and 3 hours postextubation. Data were analyzed by mixed and split-plot anova with Bonferroni adjustment for the number of group comparisons. Significance was set at p < 0.05. RESULTS: Nausea scores increased over time at 1 (p = 0.01) and 2 (p < 0.001) hours postextubation in both groups compared with before premedication. Median nausea score (0-100 mm) for groups S and O before premedication were 2.5 and 0.5 mm, respectively. At 1 and 2 hours postextubation, group S scored 7.5 and 4.0 mm and group O scored 6.0 and 5.0 mm, respectively. No significant differences in nausea scores within or between groups were observed before premedication and 3 hours postextubation. Cortisol concentrations increased significantly 3 hours postextubation in both groups (p < 0.001) compared with before premedication, with no differences between groups. AVP concentrations showed no significant differences within or between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Preoperative intravenous administration of ondansetron (0.2 mg kg-1) did not impact postoperative nausea after laparoscopic gastropexy and castration. Investigation of higher doses of ondansetron on the incidence of postoperative nausea and vomiting in dogs after surgery is warranted.

The Management of Nausea and Vomiting in Pregnancy and Hyperemesis Gravidarum (Green-top Guideline No. 69).

An objective and validated index of nausea and vomiting such as the Pregnancy-Unique Quantification of Emesis (PUQE) and HyperEmesis Level Prediction (HELP) tools can be used to classify the severity of NVP and HG. [Grade C] Ketonuria is not an indicator of dehydration and should not be used to assess severity. [Grade A] There are safety and efficacy data for first line antiemetics such as anti (H1) histamines, phenothiazines and doxylamine/pyridoxine (Xonvea®) and they should be prescribed initially when required for NVP and HG (Appendix III). [Grade A] There is evidence that ondansetron is safe and effective. Its use as a second line antiemetic should not be discouraged if first line antiemetics are ineffective. Women can be reassured regarding a very small increase in the absolute risk of orofacial clefting with ondansetron use in the first trimester, which should be balanced with the risks of poorly managed HG. [Grade B] Metoclopramide is safe and effective and can be used alone or in combination with other antiemetics. [Grade B] Because of the risk of extrapyramidal effects metoclopramide should be used as second-line therapy. Intravenous doses should be administered by slow bolus injection over at least 3 minutes to help minimise these. [Grade C] Women should be asked about previous adverse reactions to antiemetic therapies. If adverse reactions occur, there should be prompt cessation of the medications. [GPP] Normal saline (0.9% NaCl) with additional potassium chloride in each bag, with administration guided by daily monitoring of electrolytes, is the most appropriate intravenous hydration. [Grade C] Combinations of different drugs should be used in women who do not respond to a single antiemetic. Suggested antiemetics for UK use are given in Appendix III. [GPP] Thiamine supplementation (either oral 100 mg tds or intravenous as part of vitamin B complex (Pabrinex®)) should be given to all women admitted with vomiting, or severely reduced dietary intake, especially before administration of dextrose or parenteral nutrition. [Grade D] All therapeutic measures should have been tried before considering termination of pregnancy. [Grade C].

Ondansetrón para el control de vómitos asociados a gastritis y gastroenteritis aguda en urgencias de Pediatría: uso, abuso y buen uso / Ondansetron for the control of vomiting associated with acute gastritis/gastroenteritis in Pediatric Emergencies: use, abuse and appropriate use

Introducción: el ondansetrón es un antiemético ampliamente utilizado en la práctica clínica para el control de vómitos asociados a gastritis y/o gastroenteritis aguda en niños. Sin embargo, la evidencia disponible es controvertida, sus indicaciones no están claramente definidas y no existe una unanimidad de uso en las guías de práctica clínica. Material y métodos: se realizó un estudio de cohortes retrospectivo en el que se incluyó un total de 825 niños entre 0 y 14 años con vómitos asociados a gastritis y/o gastroenteritis aguda que acudieron a Urgencias de Pediatría de un hospital terciario durante el año 2019. Se analizó la asociación entre el uso de ondansetrón y la necesidad de rehidratación intravenosa, las hospitalizaciones, el tiempo de permanencia en Urgencias y las nuevas consultas a Urgencias dentro de las 72 horas posteriores. Resultados: de la muestra estudiada, el 38,8% de los pacientes recibieron ondansetrón. La administración de ondansetrón redujo el riesgo de ingreso (OR 0,19; IC 95%: 0,04-0,84) y disminuyó el tiempo de permanencia en Urgencias (p = 0,000). No se encontraron diferencias significativas en la reducción de la necesidad de rehidratación intravenosa (OR 0,65; IC 95%: 0,40-1,05) ni en las nuevas visitas a Urgencias dentro de las 72 horas siguientes (OR 1,38; IC 95%: 0,82-2,31). Conclusiones: nuestros resultados sugieren que el uso de ondansetrón podría ser beneficioso en niños mayores de 6 meses con vómitos asociados a gastritis y/o gastroenteritis aguda y que presenten deshidratación de leve a moderada (AU)

Background: ondansetron is an antiemetic widely used in clinical practice for the control of vomiting associated with gastritis and/or acute gastroenteritis in children. However, the available evidence about its use is controversial, its directions for use are not clearly defined and there is no unanimity on its use in clinical practice guidelines.Methodology: we performed a retrospective cohort study which included a total of 825 children between 0 and 14 years, who presented symptoms of vomiting associated with gastritis and/or acute gastroenteritis and attended the Pediatric Emergency Department of a tertiary hospital in 2019. The association between the use of ondansetron and the need for intravenous rehydration, hospitalization, length of stay in the Pediatric Emergency Department and return visits to the emergency department within 72 hours was analysed.Results: of the sample studied, 38.7% of the patients received ondansetron. The administration of ondansetron reduced the risk of hospital admission (OR 0.19; 95% CI 0.04 to 0.84) and decreased the length of stay in the emergency department (p = 0.000). No significant differences were found in reducing the need for intravenous rehydration (OR 0.65; 95% CI 0.40 to 1.05) or in return visits to emergency department within 3 days (OR 1.38; 95% CI 0.82-2.31).Conclusions: our results suggest that the use of ondansetron could be beneficial in children older than 6 months with vomiting associated with gastritis and/or acute gastroenteritis and with mild-to-moderate dehydration. (AU)

A comparison of ondansetron and lidocaine in reducing injection pain of propofol: a randomized controlled study.

BACKGROUND: Direct stimulation of the afferent nerve endings in the venous endothelium is one explanation of propofol injection pain. Previous studies found that ondansetron can also block sodium channels. This effect is similar to that of lidocaine. OBJECTIVE: The primary outcome was the efficacy of ondansetron compared to lidocaine and placebo for the reduction of propofol injection pain. METHOD: This trial was conducted in 240 patients, American Society of Anesthesiologists classification I-III and aged between 18-65 years old, undergoing elective surgery, and having a 20-gauge intravenous catheter at the hand dorsum. Each group of 80 patients received 8 mg. of ondansetron in the O Group, 40 mg. of lidocaine in the L Group and normal saline in the C Group. The study medications were blindly administered to the patients through a 20-gauge intravenous catheter placed on the hand dorsum, and then 1 min later, the small dose of propofol (50 mg.) was infused via the syringe pump at a rate of 600 ml/hr. for 30 s. Following that, the syringe pump of propofol was temporarily stopped, and the patients were asked to rate their pain at the injection site. RESULT: The incidence of pain was lowest in the L group (66.2%) compared with the O (82.5%) and the C groups (85.0%) (P < 0.01). The median pain score in the L, O, and C groups were 2 (0-4), 4 (2-5), and 4.5 (2-6), respectively (P < 0.01). The incidences of no pain, mild, moderate, and severe pain were also significantly different in the L group (33.8%, 37.5%, 21.2%, and 7.5%, respectively) compared with those in the O group (17.5%, 31.2%, 31.2%, and 20.0%, respectively) and the C groups (15.0%, 22.5%, 40.0%, and 22.5%, respectively) (P < 0.01). CONCLUSION: Pretreatment with intravenous lidocaine, rather than ondansetron, can reduce the incidence and intensity of propofol-induced pain.

Oral Ondansetron Administration in Children Seeking Emergency Department Care for Acute Gastroenteritis: A Patient-Level Propensity-Matched Analysis.

STUDY OBJECTIVE: This study aimed to explore oral ondansetron usage and impact on outcomes in clinical practice. METHODS: This observational study was a planned secondary analysis of 2 trials conducted in 10 US and 6 Canadian institutions between 2014 and 2017. Children 3 to 48 months old with gastroenteritis and ≥3 episodes of vomiting in the 24 hours preceding emergency department (ED) presentation were included. Oral ondansetron was administered at the discretion of the provider. The principal outcomes were intravenous fluid administration and hospitalization at the index visit and during the subsequent 72 hours and diarrhea and vomiting frequency during the 24 hours following the ED visit. RESULTS: In total, 794 children were included. The median age was 16.0 months (interquartile range 10.0 to 26.0), and 50.1% (398/794) received oral ondansetron. In propensity-adjusted analysis (n=528), children administered oral ondansetron were less likely to receive intravenous fluids at the index visit (adjusted odds ratio [aOR] 0.50; 95% confidence interval [CI] 0.29 to 0.88). There were no differences in the frequencies of intravenous fluid administration within the first 72 hours (aOR 0.65; 95% CI 0.39 to 1.10) or hospitalization at the index visit (aOR 0.31; 95% CI 0.09 to 1.10) or the subsequent 72 hours (aOR 0.52; 95% CI 0.21 to 1.28). Episodes of vomiting (aRR 0.86; 95% CI 0.63 to 1.19) and diarrhea (aRR 1.11; 95% CI 0.93 to 1.32) during the 24 hours following ED discharge also did not differ. CONCLUSION: Among preschool-aged children with gastroenteritis seeking ED care, oral ondansetron administration was associated with a reduction in index ED visit intravenous fluid administration; it was not associated with intravenous fluids administered within 72 hours, hospitalization, or vomiting and diarrhea in the 24 hours following discharge.

Efficacy of ondansetron against emesis induced by a multiple-day cisplatin-based chemotherapy regimen for malignant lymphoma.

OBJECTIVES: This study aimed to evaluate the antiemetic efficacy of a 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA), ondansetron, in patients with malignant lymphoma receiving multi-day cisplatin-based combination chemotherapy. METHODS: We conducted a single-institution retrospective analysis of patients receiving the first course of an ESHAP (etoposide, cisplatin, methylprednisolone, cytarabine) regimen including 4-day continuous infusion of cisplatin (25 mg/m2/day). All patients received ondansetron 4 mg intravenously during 5-day administration of ESHAP. The primary endpoint was complete response (CR) for emesis, which was defined as absence of both emesis and rescue medications. Total control (TC) was defined as an absence of emetic episodes, including nausea and emesis, and complete protection (CP) was defined as an absence of emesis with addition of rescue antiemetics. Nausea and vomiting were assessed and graded daily by medical staff. RESULTS: Eighty-two patients were analyzed. Nausea and vomiting were generally well controlled, with the CR rates of emesis being 79% in the overall phase, 82% in the early phase (days 1-6), and 89% in the delayed phase (days 7-10). TC and CP were achieved in 51 patients (62%) and 77 patients (94%) in the overall phase. DISCUSSION: Most of the chemotherapy regimens for lymphoid malignancies include high-dose corticosteroid which may be also effective as antiemetics. Although NK1 receptor antagonist (NK1RA) is generally recommended for cisplatin-containing chemotherapy, it can interact with variety drugs. CONCLUSION: Although NK1RA is generally recommended for cisplatin-containing regimen, our results suggest that ondansetron effectively controlled emesis in patients receiving ESHAP therapy which includes high-dose corticosteroid.

The use of ondansetron for the treatment of nausea in dogs with vestibular syndrome.

BACKGROUND: Vestibular syndrome is often accompanied by nausea. Drugs currently approved for its treatment have been developed to stop vomiting but not nausea. The efficacy of 5-HT3 receptor antagonists to reduce nausea has been described for chemotherapy, but not for nausea secondary to vestibular disorders. METHODS: Sixteen dogs with vestibular syndrome-associated nausea were included in the open-label, multicentre study. The intensity of nausea-like behaviour was analysed before ondansetron administration (0.5 mg/kg i.v.) and 2 h afterwards, using a validated 5-point-scale. The occurrence and frequency of salivation, lip licking, restlessness, vocalisation, lethargy, and vomiting were assessed. RESULTS: All dogs initially showed signs of nausea, whereas only 31% showed vomitus. The intensity of nausea was significantly reduced in all dogs (p ≤ 0.0001) 2 h after ondansetron administration, including the clinical signs of nausea analysed in 11 dogs (salivation [p = 0.0078], lip licking [p = 0.0078], restlessness [p = 0.0039], and lethargy [p = 0.0078]) except for vocalisation (p > 0.9999). CONCLUSIONS: The results provide preliminary evidence of the potential benefit of ondansetron in the treatment of nausea, which was present in all examined dogs. Vomiting was only observed in 5 dogs indicating that nausea can occur separately and should not be perceived only as a preceding stimulation of the vomiting centre.

Uso de ondansetrón en el manejo de los vómitos asociados a gastroenteritis aguda en Pediatría de Atención Primaria. Posicionamiento del Grupo de Trabajo de Gastroenterología y Nutrición de la AEPap / Use of ondansetron in the management of vomiting associated with acute gastroenteritis in primary care pediatrics. Positioning of the Gastroenterology and Nutrition Working Group of the Spanish Association of Primary Care Pediatrics (AEPap)

Los vómitos incoercibles, asociados o no a gastroenteritis aguda (GEA), son la principal causa de deshidratación en niños, siendo un motivo de consulta frecuente en Atención Primaria (AP). Los posibles efectos secundarios de los antieméticos han dado lugar a una reducción drástica en su uso en las últimas décadas. Desde hace varios años existe experiencia en el uso de ondansetrón con buenos resultados para el tratamiento de los vómitos de repetición asociados a GEA, fundamentalmente en las unidades de urgencia hospitalaria. Su uso en Atención Primaria es mucho más limitado y no se dispone del fármaco en los botiquines de los centros de salud de la mayoría de las comunidades autónomas. El objetivo de esta revisión es analizar la efectividad para esta indicación y los efectos secundarios de ondansetrón y valorar la pertinencia de su uso en Atención Primaria (AU)

Incoercible vomiting associated with acute gastroenteritis (AGE) is the main cause of dehydration in children, being a frequent reason for consultation in primary care. The side effects of antemetics have led to a drastic reduction in their use in recent decades. For several years there has been experience in the use of ondansetron with good results for the treatment of repeated vomiting associated with AGE, mainly in hospital emergency units. Its use in primary care is much more limited and the drug is not available as emergency medication in the majority of the Spanish Primary Care Centers. The objective of this review is to analyze the effectiveness and side effects of ondansetron and assess the relevance of its use in primary care. (AU)

Effects of 5-HT3 receptor antagonists on cisplatin-induced kidney injury.

Nausea, vomiting, and renal injury are the common adverse effects associated with cisplatin. Cisplatin is excreted via the multidrug and toxin release (MATE) transporter, and the involvement of the MATE transporter in cisplatin-induced kidney injury has been reported. The MATE transporter is also involved in the excretion of ondansetron, but the effects of 5-HT3 receptor antagonists used clinically for cisplatin-induced renal injury have not been elucidated. Therefore, the aim of this study was to investigate the effects of 5-HT3 receptor antagonists in a mouse model of cisplatin-induced kidney injury and to validate the results using medical big data analysis of more than 1.4 million reports and a survey of 3000 hospital medical records. The concomitant use of a first-generation 5-HT3 receptor antagonist (ondansetron, granisetron, or ramosetron) significantly increased cisplatin accumulation in the kidneys and worsened renal damage. Conversely, the concomitant use of palonosetron had no effect on renal function compared with the use of cisplatin alone. Furthermore, an analysis of data from the US Food and Drug Administration Adverse Event Reporting System and retrospective medical records revealed that the combination treatment of cisplatin and a first-generation 5-HT3 receptor antagonist significantly increased the number of reported renal adverse events compared with the combination treatment of cisplatin and a second-generation 5-HT3 receptor antagonist. These results suggest that compared with the first-generation antagonists, second-generation 5-HT3 receptor antagonists do not worsen cisplatin-induced acute kidney injury. The findings should be validated in a prospective controlled trial before implementation in clinical practice.

Comparison of Pregnancy Outcomes of Patients Treated With Ondansetron vs Alternative Antiemetic Medications in a Multinational, Population-Based Cohort.

Importance: Ondansetron is frequently used to treat nausea and vomiting during pregnancy. Although some studies reported important safety signals, few studies have been sufficiently large to assess rare pregnancy outcomes. Objective: To study the association between ondansetron exposure during pregnancy and the risks of spontaneous abortion, stillbirth, and major congenital malformations. Design, Setting, and Participants: This is a cohort study conducted in 3 countries, with a meta-analysis. Participants included women and girls aged 12 to 55 years who experienced spontaneous abortion, induced abortion, stillbirth, or live birth between April 2002 and March 2016, as recorded in administrative data from 5 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba, and Ontario), the US IBM MarketScan Research Databases, and the UK Clinical Practice Research Datalink. The statistical analysis was completed in October 2020. Exposures: Exposure to ondansetron during pregnancy was compared with exposure to other commonly used antiemetics to minimize confounding by indication. Main Outcomes and Measures: The primary outcome was fetal death, defined as either spontaneous abortion or stillbirth. Secondary outcomes were the 2 components of the primary outcome and major congenital malformations identified during the year after a live birth. Adjusted hazard ratios were estimated using Cox proportional hazards models with time-dependent drug exposures and were adjusted using high-dimensional propensity scores. For major congenital malformations, adjusted odds ratios were estimated from logistic models. Site-level results were pooled using random-effects meta-analysis. Sensitivity analyses considered second-line antiemetic exposure and exposure specifically during 4 to 10 weeks of gestation. Results: Data from 456 963 pregnancies were included in this study of fetal death (249 787 [54.7%] in Canada, 197 913 [43.3%] in the US, and 9263 [2.0%] in the UK; maternal age, ≤24 years, 93 201 patients [20.4%]; 25-29 years, 149 117 patients [32.6%]; 30-34 years, 142 442 patients [31.2%]; and ≥35 years, 72 203 patients [15.8%]). Fetal death occurred in 12 907 (7.9%) of 163 810 pregnancies exposed to ondansetron, and 17 476 (5.7%) of 306 766 pregnancies exposed to other antiemetics. The adjusted hazard ratios were 0.91 (95% CI, 0.67-1.23) for fetal death with time-dependent ondansetron exposure during pregnancy, 0.82 (95% CI, 0.64-1.04) for spontaneous abortion, and 0.97 (95% CI, 0.79-1.20) for stillbirth. For major congenital malformations, the estimated odds ratio was 1.06 (95% CI, 0.91-1.22). Results of sensitivity analyses were generally consistent with those of the primary analyses. Conclusions and Relevance: In this large, multicenter cohort study, there was no association between ondansetron exposure during pregnancy and increased risk of fetal death, spontaneous abortion, stillbirth, or major congenital malformations compared with exposure to other antiemetic drugs.

Low-dose olanzapine, sedation and chemotherapy-induced nausea and vomiting: a prospective randomized controlled study.

Aims: Comparison of efficacy, safety and sedation between two doses of olanzapine in the control of chemotherapy-induced nausea and vomiting (CINV). Patients & methods: A prospective, randomized, double-blind, controlled study was conducted, enrolling 68 patients receiving a single-day cycle of high and moderately emetogenic chemotherapy. Patients received either of olanzapine 5 mg or 10 mg from day 1 through 3 in addition to ondansetron and dexamethasone. Control of CINV, nausea, sedation, quality of life (QoL) and adverse events were compared. Results: Nausea, emesis control and improvement of QoL were similar in both groups. Sedation severity was 133% higher with 10 mg olanzapine. Conclusions: Lower dose olanzapine is effective to control CINV with significantly reduced sedation.

Lay abstract Methods to prevent chemotherapy-induced nausea and vomiting (CINV) are often not sufficient for patients. Olanzapine, along with other similar drugs (antiemetics), improved control but is often sedating. In this study, a lower dose of olanzapine was compared with the conventional dose. Patients on cancer chemotherapy, which has high occurrence of nausea and vomiting, were given either the low dose or the conventional dose of olanzapine for 3 days, in addition to some other antiemetic agents. Control of nausea and vomiting was reasonably achieved with both doses of olanzapine. The lower dose was significantly less sedating. There were no serious side effects with either doses.

Single daily dosing versus divided dosing intravenous ondansetron to prevent chemotherapy-induced nausea and vomiting among children: A comparative randomized double-blind controlled trial.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is a common complication in cancer treatment. Ondansetron is an effective antiemetic drug widely used to prevent CINV; however, the effective administrative dosing strategies among pediatrics remain unclear. The study aimed to investigate clinical effectiveness of single daily dosing versus divided dosing ondansetron. METHODS: In all, 194 children undergoing chemotherapy were randomized to receive either single daily dosing (0.3 mg/kg/dose) or divided dosing (0.15 mg/kg/dose every 8 hours) intravenous ondansetron for 24 hours. Clinical parameters including number of emesis episodes, nausea scores, appetite levels, parent's satisfaction, and adverse effects within 24 hours were analyzed. RESULTS: No significant differences were found between the two dosing strategies concerning number of emesis episodes and parent's satisfaction. However, nonleukemic hematologic malignancies and concurrent administration of intrathecal methotrexate-hydrocortisone-cytarabine (IT-MHA) were associated with increased risk of acute-phase vomiting. Interestingly, none of the patients aged under 7 years, receiving divided dosing ondansetron, presented nausea symptoms compared with those receiving single daily dosing (p-value .034). No significant differences regarding headache were observed between the two dosing strategies and none of the patients experienced QTc prolongation. CONCLUSION: Ondansetron administered as divided dosing should be considered among children aged under 7 years to prevent chemotherapy-induced nausea and among patients receiving low emetogenic chemotherapy to maintain their appetite. Both administrative dosing strategies were well tolerated with no significant adverse effects.

Ondansetron versus ondansetron with dexamethasone to prevent intrathecal-morphine pruritus for caesarean patients: randomised double-blind trial.

The objective of this randomised, double blinded clinical trial was to evaluate the efficacy of prophylactic administration of 4 mg ondansetron as monotherapy versus combination therapy of 4 mg ondansetron plus 8 mg dexamethasone for the prevention of intrathecal morphine-associated pruritus in caesarean section within 24 h. A total of 194 patients were included, 96 patients in the monotherapy group and 98 in the combination group. One hour after the operation, 11.5% of patients in ondansetron group had failure of prophylaxis for pruritus compared to 13.5% of patients in the combination group (p = .66). This decreased throughout the follow-up to reach 0.0% and 1.0% at 24 h in the ondansetron vs. the combination groups respectively. There was no superiority of combining ondansetron with dexamethasone over the use of ondansetron as prophylactic antipruritic in parturients receiving intrathecal morphine for caesarean section.IMPACT STATEMENTWhat is already known on this subject? The incidence of pruritus has been reported to be between 36% and 60% in patients undergoing caesarean section with intrathecal morphine. Ondansetron has been identified as possible antipruritic agent while the antipruritic effect of dexamethasone is inconclusive.What do the results of this study add? The study demonstrated that there was no superiority of combining ondansetron with dexamethasone over the use of ondansetron as prophylactic antipruritic in parturients receiving intrathecal morphine for caesarean section. Moreover, it seems that there is no effect of combining ondansetron with dexamethasone over ondansetron alone on antiemetic consequences.What are the implications of these findings for clinical practice and/or further research? Ondansetron could be an effective antipruritic if used solely for patients undergoing caesarean section.

Preanesthetic nebulized ketamine vs preanesthetic oral ketamine for sedation and postoperative pain management in children for elective surgery: A retrospective analysis for effectiveness and safety.

ABSTRACT: Preoperative anxiety is a major problem in children leading to a poor outcome. Preanesthetic oral ketamine is generally used in children but has less bioavailability due to the first-pass effect. Even ketamine has an unpleasant taste. Preanesthetic inhaled ketamine is also reported effective and safe in children. The objectives of the study were to compare the effectiveness and safety of preanesthetic nebulized ketamine against preanesthetic oral ketamine for sedation and postoperative pain management in children.Children received 10 mg/kg oral ketamine (children received preanesthetic oral ketamine [OK cohort], n = 142), or nebulized with 3 mg/kg ketamine (children were preanesthetic nebulized with ketamine [NK cohort], n = 115), or received apple juice (children suspectable to preoperative ketamine and received apple juice only [OA cohort], n = 126) before anesthesia for elective surgery. Data regarding preoperative hemodynamic parameters, sedation score measurements, postoperative pain management, postoperative nausea and vomiting management, and postoperative complications were collected and analyzed.Preoperative hemodynamic parameters for oral and nebulized ketamine administration were stable. Nebulized ketamine was provided higher sedation than apple juice (P = .002, q = 4.859) and oral ketamine (P = .002, q = 3.526). Children of NK cohort had required fewer fentanyl consumption until discharge than those of OA (55.45 ±â€Š7.19 µG/ child vs 65.15 ±â€Š15.24 µG/ child, P < .0001, q = 9.859) and OK (55.45 ±â€Š7.19 µG/child vs 60.19 ±â€Š8.12 µG/child, P < .0001, q = 4.953) cohorts. Children of the NK cohort had consumed higher ondansetron syrup than those of the OA cohort but fewer than those of the OK cohort until discharge. Gastrointestinal side effects were reported in the OK cohort, and nose irritation and drowsiness were reported in the NK cohort.Like preanesthetic oral ketamine, preanesthetic inhaled ketamine also has safety for children. Preanesthetic inhaled ketamine can provide effective sedation in low doses during operation than preanesthetic oral ketamine.Level of evidence: III.

The impact of multimodal therapies on the comfort and safety of patients in the immediate post-anaesthetic period following gynaecological procedures - part I.

OBJECTIVES: Pain and postoperative nausea and vomiting are among the most unpleasant sensations experienced after surgery. Patients after gynaecological surgery are at higher risk for both complications. Former methods of pain management based mainly on opioid administration were much less safe, especially for elderly patients. In addition, they generated an even greater increase of postoperative nausea and vomiting. Multimodal therapies in anesthesiology are currently being used more and more often. These include both multimodal postoperative pain management and multimodal prophylaxis of postoperative nausea and vomiting. The aim of the study was to assess the benefits of the methods used for gynaecological patients in the immediate postanesthetic period. MATERIAL AND METHODS: The research material is an analysis of medical documentation of 150 patients from the gynaecology clinic who underwent surgical procedures of categories III and IV from October 2018 and until January 2019, carried out in one of the clinical hospitals in Szczecin at the Anesthesiology and Intensive Care Clinic. Patients were divided into 3 groups: 1. Patients who received multimodal analgesia using non-opioid and opioid analgesics. 2. Patients who received multimodal analgesia using non-opioid and opioid analgesics and adjuvants. 3. Patients who received multimodal analgesia using non-opioid and opioid analgesics and central blockade. RESULTS: The highest age was in the third group at 57.48 years of age, 50.86 in the second group, and 47.8 in the first group. Healthy patients classified as ASA 1 accounted for 14% of group I, 18% of group II and 10% of group III. Patients with severe systemic disease (ASA 3) constituted 30% of group III 18%, of group II and 8% of group I. Upon leaving the operating room, as many as 80% of the patients from groups II and III did not feel any pain. In group I was 52%. When entering the recovery room, 26% of the patients in group I, 10% in group III, and 8% in group II rated their pain as higher than 5. The most used antiemetic medication in the studied facility was ondansetron. In group II it was given to 36 (72%) patients, in group III to 23 (46%) patients, and 13 (26%) patients in group I. In the postanaesthetic care unit, 9 (18%) patients in group III, 6 (12%) patients in group I, and 3 (6%) patients in group II received ondansetron. Metoclopramide was given only to patients in group III - one intraoperatively, and the other in the recovery room. CONCLUSIONS: Multimodal analgesia is effective in pain treatment. The use of PONV prevention is used for gynaecological patients. The analysis of the surgical records facilitated the recognition of patient needs.

Effect of domperidone, ondansetron, olanzapine-containing antiemetic regimen on QTC interval in patients with malignancy: a prospective, observational, single-group, assessor-blinded study.

Domperidone, ondansetron and olanzapine can prolong the QT interval. The clinical use of combinations of these drugs is not uncommon. Our study aimed to determine the presence of any QTc prolonging effect of the combination when used as antiemetic in patients receiving cancer chemotherapy. We carried out a prospective, observational study of patients with malignancy who were to receive domperidone, ondansetron and olanzapine-containing antiemetic regimen. Electrocardiograms were recorded before and during the administration of antiemetics, for three consecutive days. A blinded assessor determined the QTc interval using Bazett and Fridericia formulae. Thirty-six patients completed the study; 23 (63.9%) were females. There was a statistically significant change in QTc with time (Fridericia, χ2(4) = 15.629, p = 0.004; Bazett, χ2(4) = 15.910, p = 0.003); QTc on Day 1 was more than that during baseline (p < 0.001); these differences were significant in females (Fridericia, χ2(4) = 13.753, p = 0.008; Bazett, χ2 (4) = 13.278, p = 0.010) but not in males (Fridericia, χ2 (4) = 4.419, p = 0.352; Bazett, χ2(4) = 4.280, p = 0.369). Two female patients had an absolute QTc prolongation (Bazett correction) of > 500 ms. However, no clinically significant adverse events occurred. The findings show that QTc prolongation is a concern with olanzapine alone and in combination with domperidone and ondansetron, and needs to be investigated further.

Absence of QT prolongation after administration of a 24-mg bimodal-release ondansetron pill (RHB-102).

OBJECTIVES: Prospective data evaluating the effect of ondansetron on the corrected QT (QTc) interval is lacking in emergency department clinical use. As part of a randomized trial of a 24-mg bimodal-release ondansetron (RHB-102) pill, we tested the effect of RHB-102 compared to placebo on QTc change. METHODS: This was a planned safety outcome analysis within a multicenter, double-blind, placebo-controlled trial. The trial compared the effects of RHB-102 among patients ≥12 years who presented to 21 centers with symptoms of acute gastroenteritis. Patients with an initial baseline electrocardiogram as well as a follow-up electrocardiogram 4 h later were included in the analysis. The safety endpoint for this analysis was the change from baseline in QTc interval at 4 h, the median time at which ondansetron serum level peaks. RESULTS: A total of 147 patients were included with a mean baseline QTc in the RHB-102 and placebo arms of 410 and 406 ms, respectively. There was no difference in the change in QTc at 4 h post-study drug administration between the RHB-102 (+4, 95% CI 1-8 ms) and placebo group (+5, 95% CI 1-9 ms). In the RHB-102 arm, 6.6% of patients had a QTc change >30 ms and in the placebo arm 3.6% (p = 0.48). No patient in either arm had a QTc change >60 ms after study drug administration. CONCLUSION: In patients with normal baseline QTc, 24-mg bimodal-release ondansetron did not prolong the QTc in comparison to placebo.