Virtual clinical QT exposure-response studies - A translational computational approach.

BACKGROUND AND PURPOSE: A recent paradigm shift in proarrhythmic risk assessment suggests that the integration of clinical, non-clinical, and computational evidence can be used to reach a comprehensive understanding of the proarrhythmic potential of drug candidates. While current computational methodologies focus on predicting the incidence of proarrhythmic events after drug administration, the objective of this study is to predict concentration-response relationships of QTc as a clinical endpoint. EXPERIMENTAL APPROACH: Full heart computational models reproducing human cardiac populations were created to predict the concentration-response relationship of changes in the QT interval as recommended for clinical trials. The concentration-response relationship of the QT-interval prolongation obtained from the computational cardiac population was compared against the relationship from clinical trial data for a set of well-characterized compounds: moxifloxacin, dofetilide, verapamil, and ondansetron. KEY RESULTS: Computationally derived concentration-response relationships of QT interval changes for three of the four drugs had slopes within the confidence interval of clinical trials (dofetilide, moxifloxacin and verapamil) when compared to placebo-corrected concentration-ΔQT and concentration-ΔQT regressions. Moxifloxacin showed a higher intercept, outside the confidence interval of the clinical data, demonstrating that in this example, the standard linear regression does not appropriately capture the concentration-response results at very low concentrations. The concentrations corresponding to a mean QTc prolongation of 10 ms were consistently lower in the computational model than in clinical data. The critical concentration varied within an approximate ratio of 0.5 (moxifloxacin and ondansetron) and 1 times (dofetilide, verapamil) the critical concentration observed in human clinical trials. Notably, no other in silico methodology can approximate the human critical concentration values for a QT interval prolongation of 10 ms. CONCLUSION AND IMPLICATIONS: Computational concentration-response modelling of a virtual population of high-resolution, 3-dimensional cardiac models can provide comparable information to clinical data and could be used to complement pre-clinical and clinical safety packages. It provides access to an unlimited exposure range to support trial design and can improve the understanding of pre-clinical-clinical translation.

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.

Prevention of postoperative nausea and vomiting after orthognathic surgery: a scoping review.

INTRODUCTION: Postoperative nausea and vomiting (PONV) is one of the most common adverse events following orthognathic surgery. It's a distressing feeling for patients and continues to be the cause of postoperative complications such as bleeding, delayed healing, and wound infection. This scoping review aims to identify effective PONV prophylaxis strategies during orthognathic surgery that have emerged in the past 15 years. METHODS: We searched Pubmed, Cochrane Controlled Register of Trials, and Embase from 2008 to May 2023. Studies meeting the following criteria were eligible for inclusion: (1) recruited patients undergo any orthognathic surgery; (2) evaluated any pharmacologic or non-pharmacologic method to prevent PONV. Studies meeting the following criteria were excluded: (1) case series, review papers, or retrospective studies; (2) did not report our prespecified outcomes. RESULTS: Twenty-one studies were included in this review. Pharmacological methods for PONV prevention include ondansetron and dexamethasone (3 studies), peripheral nerve block technique (4 studies), dexmedetomidine (1 study), pregabalin (2 studies), nefopam (2 studies), remifentanil (1 study), propofol (2 studies), and penehyclidine (1 study). Non-pharmacologic methods include capsicum plaster (1 study), throat packs (2 studies) and gastric aspiration (2 studies). CONCLUSIONS: Based on current evidence, we conclude that prophylactic antiemetics like dexamethasone, ondansetron, and penehyclidine are the first defense against PONV. Multimodal analgesia with nerve block techniques and non-opioid analgesics should be considered due to their notable opioid-sparing and PONV preventive effect. For the non-pharmacological methods, throat packs are not recommended for routine use because of their poor effect and serious complications. More prospective RCTs are required to confirm whether gastric aspiration can prevent PONV effectively for patients undergoing orthognathic surgery.

Comparison of Nausea and Vomiting Incidence After Laparoscopic Cholecystectomy With Pretreatment With Haloperidol and Ondansetron: A Randomization Clinical Trial Study.

OBJECTIVE: Nausea and vomiting after surgery are the most common complications. Therefore, we performed this study to compare the effect of ondansetron and haloperidol on nausea and vomiting after laparoscopic cholecystectomy. PATIENTS AND METHODS: In this randomized clinical trial, 60 patients candidates for elective laparoscopic cholecystectomy were allocated to haloperidol (0.05 mg/kg, n = 30) and ondansetron (0.15 mg/kg, n = 30) groups. An Ocular Analog Scale was used to assess postoperative nausea and vomiting. Every 15 minutes in the recovery room, heart rate and blood pressure were measured up to 6 hours after surgery. In addition, patient satisfaction was assessed postoperatively. RESULTS: Haloperidol and ondansetron have the same effect on postoperative nausea and vomiting in the recovery room and ward. It was found that the trend of Visual Analog Scale variable changes in the recovery room was similar in the haloperidol and ondansetron group ( P = 0.58); it was also true for the ward ( P = 0.79). Comparing the length of stay in a recovery room in the 2 groups was not statistically significant ( P = 0.19). In addition, the 2 groups did not differ in satisfaction postoperatively ( P = 0.82). CONCLUSION: Haloperidol and ondansetron had an equal effect on reducing nausea and vomiting in the recovery room and ward after laparoscopic cholecystectomy. Patient satisfaction and length of stay in the recovery room did not differ between groups.

Mechanisms underlying the laxative effect of lactulose: A randomized placebo-controlled trial showing increased small bowel water and motility unaltered by the 5-HT3 receptor antagonist, ondansetron.

BACKGROUND: Lactulose is a laxative which accelerates transit and softens stool. Our aim was to investigate its mechanism of action and use this model of diarrhea to investigate the anti-diarrheal actions of ondansetron. METHODS: A double-blind, randomized, placebo-controlled crossover study of the effect of ondansetron 8 mg in 16 healthy volunteers. Serial MRI scans were performed fasted and 6 h after a meal. Participants then received lactulose 13.6 g twice daily and study drug for a further 36 h. On Day 3, they had further serial MRI scans for 4 h. Measurements included small bowel water content (SBWC), colonic volume, colonic gas, small bowel motility, whole gut transit, and ascending colon relaxation time (T1AC), a measure of colonic water content. KEY RESULTS: Lactulose increased area under the curve (AUC) of SBWC from 0 to 240 min, mean difference 14.2 L · min (95% CI 4.1, 24.3), p = 0.009, and substantially increased small bowel motility after 4 h (mean (95% CI) 523 (457-646) a.u. to 852 (771-1178) a.u., p = 0.007). There were no changes in T1AC after 36 h treatment. Ondansetron did not significantly alter SBWC, small bowel motility, transit, colonic volumes, colonic gas nor T1AC, with or without lactulose. CONCLUSION & INFERENCES: Lactulose increases SBWC and stimulates small bowel motility; however, unexpectedly it did not significantly alter colonic water content, suggesting its laxative effect is not osmotic but due to stimulation of motility. Ondansetron's lack of effect on intestinal water suggests its anti-diarrheal effect is not due to inhibition of secretion but more likely altered colonic motility.

Review article: Efficacy of prophylactic ondansetron versus placebo or control in reducing vomiting in children undergoing ketamine procedural sedation in the emergency department: A systematic review and meta-analysis.

Ketamine is commonly used for procedural sedation anaesthesia in paediatric patients undergoing painful procedures in the ED. Ketamine's safety profile is excellent, but ketamine-associated vomiting (KAV) is common. Routine ondansetron prophylaxis could reduce KAV incidence. This literature review evaluated the efficacy of prophylactic ondansetron in reducing KAV incidence. A systematic literature review was performed on databases and trial registries on 14 January 2023 to identify randomised controlled trials. The primary outcome was reduction in KAV incidence, for any route of prophylactic ondansetron, in ED and up to 24 h post-discharge. ED length of stay, parental satisfaction and time to resumption of normal diet were secondary outcomes. Data analysis was performed using Revman 5.3. Meta-analysis was performed using random effects modelling. Risk of bias was assessed using the Cochrane Risk-of-Bias 2 tool. Evidence quality was assessed using Grading of Recommendation, Assessment Development and Evaluation methodology. Five trials with 920 participants met the eligibility criteria. Prophylactic ondansetron resulted in a reduction in KAV incidence overall odds ratio of 0.51 (95% confidence interval: 0.36-0.73). Intravenous and intramuscular prophylactic ondansetron showed benefit whereas the effect of oral administration was unclear. There was no difference between groups for secondary outcomes overall. The quality of evidence was deemed to be low overall because of high risk of bias and imprecision in outcome measures. This review found low to moderate certainty evidence that prophylactic ondansetron reduces KAV incidence. Methodologically rigorous research, with appropriately timed prophylactic ondansetron based on the route of administration, would further elucidate prophylactic oral ondansetron's efficacy.

Comparison of three different prophylactic treatments for postoperative nausea and vomiting after total joint arthroplasty under general anesthesia: a randomized clinical trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) after total joint arthroplasty is common and associated with delayed recovery. This study was performed to evaluate the efficacy of three different prophylactic regimens for PONV after total joint arthroplasty under general anesthesia. METHODS: Patients undergoing primary total hip or knee arthroplasty were randomized to Group A (ondansetron), Group B (10 mg dexamethasone plus ondansetron and mosapride), or Group C (three doses of 10 mg dexamethasone plus ondansetron and mosapride). The primary outcome was the total incidence of PONV during postoperative 48 h. The secondary outcomes were complete response, rescue antiemetic treatment, opioid consumption, time until first defecation, postoperative appetite score, satisfaction score, length of hospital stay, blood glucose level, and complications. RESULTS: Patients in Group C experienced a lower incidence of total PONV (29.3%, p = 0.001) and a higher incidence of complete response (70.7%, p = 0.001) than did patients in Group A (51.9%, 48.2%, respectively). Patients in Group C also experienced a lower incidence of severe PONV (4.3%) than patients in Group A (25.9%, p<0.001) and B (20.4%, p<0.001). Moreover, less rescue antiemetic treatment (1.4 ± 0.5 mg Metoclopramide) and postoperative opioid consumption (1.8 ± 0.3 mg Oxycodone, 6.0 ± 1.0 mg Pethidine) was needed in Group C. Additionally, a shorter time until first defecation, shorter length of stay, and better postoperative appetite scores and satisfaction scores were detected in patients in Group C. A slight increase in the fasting blood glucose level was observed in Group C, and the complications were comparable among the groups. CONCLUSION: Combined use of ondansetron, mosapride and three doses of dexamethasone can provide better antiemetic effectiveness, postoperative appetite, bowel function recovery, and pain relief than a single dose or ondansetron only. TRIAL REGISTRATION INFORMATION: The protocol was registered at the Chinese Clinical Trial Registry (ChiCTR1800015896, April 27, 2018).

Comparative dose-response study on the infusion of norepinephrine combined with intravenous ondansetron versus placebo for preventing hypotension during spinal anesthesia for cesarean section: a randomised controlled trial.

BACKGROUND: Ondansetron has been reported to attenuate the incidence of spinal anaesthesia-induced hypotension (SAIH) and norepinephrine requirement during caesarean section. However, no quantitative study has evaluated the extent of this effect. This study aimed to determine the dose-response of prophylactic infusion of norepinephrine to prevent SAIH in parturients who received intravenous ondansetron or placebo before spinal anaesthesia for caesarean section. The median effective dose (ED 50 ) and 90% effective dose (ED 90 ) were compared to evaluate the effect of ondansetron versus placebo on the norepinephrine requirement. MATERIALS AND METHODS: One hundred fifty parturients undergoing caesarean section were randomized to receive either 0.1 mg/kg ondansetron (group O) or saline control (group C) 10 min before spinal anaesthesia. The parturients were randomly assigned to one of five different norepinephrine infusion groups: 0.02, 0.04, 0.06, 0.08 or 0.10 µg/kg/min. An effective infusion dose of norepinephrine was defined as non-occurrence of hypotension during the study period. The values for ED 50 and ED 90 of norepinephrine infusion were determined using probit regression. Differences between the two groups were evaluated by comparing the relative median potency with 95% CIs. RESULTS: The ED 50 values were 0.033 (95% CIs, 0.024-0.043) µg/kg/min in group C and 0.021 (95% CIs, 0.013-0.029) µg/kg/min in group O. The ED 90 values were 0.091 (95% CIs 0.068-0.147) µg/kg/min in group C and 0.059 (95% CIs 0.044-0.089) µg/kg/min in group O, respectively. The estimate of the relative median potency for norepinephrine in group C versus group O was 0.643 (95% CIs, 0.363-0.956). The incidence of side effects was comparable between groups. No significant difference in neonatal outcomes. CONCLUSION: Intravenous ondansetron 0.1 mg/kg before spinal anaesthesia significantly reduced the dose requirement of prophylactic norepinephrine infusion in parturients undergoing elective caesarean section. This finding is potentially useful for clinical practice and further research.

Ondansetron for Low Anterior Resection Syndrome (LARS): A Double-Blind, Placebo-Controlled, Cross-Over, Randomized Study.

OBJECTIVE: The aim of the study was to examine the efficacity and safety of ondansetron, a serotonin receptor antagonist, to treat patients with low anterior resection syndrome (LARS). BACKGROUND: LARS after rectal resection is common and debilitating. Current management strategies include behavioral and dietary modifications, physiotherapy, antidiarrheal drugs, enemas, and neuromodulation, but the results are not always satisfactory. METHODS: This is a randomized, multicentric, double-blinded, placebo-controlled, and cross-over study. Patients with LARS (LARS score >20) no longer than 2 years after rectal resection were randomized to receive either 4 weeks of ondansetron followed by 4 weeks of placebo (O-P group) or 4 weeks of placebo followed by 4 weeks of ondansetron (P-O group). The primary endpoint was LARS severity measured using the LARS score; secondary endpoints were incontinence (Vaizey score) and irritable bowel syndrome quality of life (IBS-QoL questionnaire). Patients' scores and questionnaires were completed at baseline and after each 4-week treatment period. RESULTS: Of 46 randomized patients, 38 were included in the analysis. From baseline to the end of the first period, in the O-P group, the mean (SD) LARS score decreased by 25% [from 36.6 (5.6) to 27.3 (11.5)] and the proportion of patients with major LARS (score >30) went from 15/17 (88%) to 7/17 (41%), ( P =0.001). In the P-O group, the mean (SD) LARS score decreased by 12% [from 37 (4.8) to 32.6 (9.1)], and the proportion of major LARS went from 19/21 (90%) to 16/21 (76%). After crossover, LARS scores deteriorated again in the O-P group receiving placebo, but further improved in the P-O group receiving ondansetron. Mean Vaizey scores and IBS QoL scores followed a similar pattern. CONCLUSIONS: Ondansetron is a safe and simple treatment that appears to improve both symptoms and QoL in LARS patients.

Impact of body weight-based dosing of palonosetron and ondansetron on postoperative nausea and vomiting following laparoscopic sleeve gastrectomy: a randomized, double-blind study.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a frequent adverse effect following laparoscopic sleeve gastrectomy. Palonosetron with a standard dosing (75 µg) schedule has been questioned due to its low efficiency in obese patients. This study aimed to investigate the effectiveness and safety of the body weight-based dosing of palonosetron in managing PONV following laparoscopic sleeve gastrectomy. METHODS: A single-center, prospective, double-blinded randomized study was conducted between August 2021 and December 2021. Patients who underwent laparoscopic sleeve gastrectomy were prospectively recruited in the study. One hundred patients were randomly divided into palonosetron (Group P) and ondansetron (Group O). The demographic and clinical variables were recorded. The primary outcome of the study was the incidence of PONV between the two groups during the hospitalization. The secondary outcomes were the number of rescue anti-emetic and analgesic medications and the Functional Living Index-Emesis scores. RESULTS: There were 50 patients in each group (Group P and Group O). There were significant differences in the scores of POVN, nausea, and vomiting favoring Group P. In Group P, the rate of patients using rescue anti-emetics was significantly lower. The incidence of complete response and proportion of patients with higher Functional Living Index-Emesis scores were significantly higher in patients using palonosetron. CONCLUSIONS: The use of palonosetron significantly reduced the incidence of PONV following laparoscopic sleeve gastrectomy. There was a significant improvement in the scores of Functional Living Index-Emesis in patients using palonosetron.

Perioperative use of low dose haloperidol safely reduces episodes of postoperative nausea/vomiting and length of stay following elective minimally invasive bariatric surgery.

INTRODUCTION: While total intravenous anesthesia (TIVA) protocols include Dexamethasone and Ondansetron prophylaxis, bariatric patients continue to be considered at particularly high risk for postoperative nausea/vomiting (PONV). A multimodal approach for prophylaxis is recommended by the Bariatric Enhanced Recovery After Surgery (ERAS) Society however, there remains a lack of consensus on the optimal strategy to manage PONV in these patients. Haloperidol has been shown at low doses to have a therapeutic effect in treatment of refractory nausea and in PONV prophylaxis in other high risk surgical populations. We sought to investigate its efficacy as a prophylactic medication for PONV in the bariatric population and to identify which perioperative strategies were most effective at reducing episodes of PONV. METHODS: An institutional bariatric database was created by retrospectively reviewing patients undergoing elective minimally invasive bariatric procedures from 2018 to 2022. Demographic data reviewed included age, gender, preoperative body mass index (BMI), ethnicity, and primary language. Primary endpoints included patient reported episodes of PONV, total doses of Ondansetron administered, need for a second antiemetic (rescue medication), complication rate (most commonly readmission within 30 days), and length of stay. Fisher's exact test, Mann-Whitney test, and ANOVA were used to evaluate the effect of perioperative management on various endpoints. RESULTS: A total of 475 patients were analyzed with Haloperidol being utilized in 15.8% of all patients. Patients receiving Haloperidol were less likely to require Ondansetron outside of the immediate perioperative period (34.7% vs. 49.8%, p = 0.02), experienced less PONV (41.3% vs. 64.3%, p = 0.01) and also had a decreased median length of stay (27.3 vs. 35.8 h, p < 0.0001). CONCLUSIONS: Addition of low dose Haloperidol to Bariatric ERAS protocols decreases incidence of PONV and the need for additional antiemetic coverage resulting in a significantly shorter length of stay, increasing the likelihood of safe discharge on postoperative day 1.

Comparison of adding magnesium sulfate, dexmedetomidine and ondansetron to lidocaine for gargling before laryngoscopy and endotracheal intubation to prevent sore throat: a randomized clinical trial.

Postoperative sore throat is one well-recognized complication, occurring most frequently following tracheal intubation. Effective prevention of postoperative sore throat has been recognized as a top priority, bringing pleasant feelings and satisfaction to patients. This study aimed to assess the efficacy of magnesium sulfate, dexmedetomidine and ondansetron gargle with lidocaine administrated prior to laryngoscopy and tracheal intubation for postoperative sore throat prevention alongside hemodynamic management. This double-blind randomized clinical trial enrolled 105 general anesthesia-administered patients who had undergone laryngoscopy and endotracheal intubation, and they were equally randomized into three groups: magnesium sulfate, dexmedetomidine, and ondansetron groups. No significant intergroup difference was seen in oxygen saturation, non-invasive blood pressure, heart rate, duration of surgery, postoperative complications, analgesic consumption, and incidence of cough and hoarseness. The results showed statistically significant intergroup differences in pain scores and average pain intensity in the dexmedetomidine group was significantly lower than the other groups. Results suggest that dexmedetomidine gargle with lidocaine before general anesthesia induction could be recommended as an option depending on the patient's general condition and the anesthesiologist's discretion.

Vomiting after intrathecal chemotherapy under anesthesia in pediatric patients with hematologic cancers: A cohort study.

INTRODUCTION: Despite preventive strategies, vomiting is an adverse event affecting patients with cancer. However, literature on the incidence and risk factors for vomiting in pediatric patients with cancer are scarce. AIM: To assess the incidence and risk factors for vomiting within 24 h and goodness of fit for the Eberhart score in pediatric patients with hematologic cancers after receiving intrathecal chemotherapy under deep sedation. METHODS: This prospective cohort study included patients under 20 years of age with hematologic cancers who were scheduled to undergo intrathecal chemotherapy under anesthesia. The primary outcome was the occurrence of vomiting within 24 h after the end of anesthesia. Sociodemographic and procedure data and underlying diseases were collected. Patients were monitored during the procedure, in the postanesthesia care unit, and the day after (by phone call). RESULTS: A total of 139 patients were included, and the incidence of vomiting was 30.9% within 24 h after intrathecal chemotherapy under anesthesia, with 90.7% of vomiting prior to 6 h. Prophylactic ondansetron was administered prior to the procedure to 45.3% of patients. Risk factors for vomiting were female gender (hazard ratio: 2.47, 95% confidence interval: 1.35-4.53, p: .003), consolidation phase of treatment (hazard ratio: 2.16, 95% confidence interval: 1.10-4.24, p: .025), and history of kinetosis (hazard ratio: 2.49, 95% confidence interval: 1.31-4.70, p: .005). Incidence of vomit was higher than estimated by the Eberhart score distribution (observed incidence in patients with a score of zero: 33.3%; with a score of one: 28.8%; with a score of two: 60%). CONCLUSION: A high incidence of vomiting was observed within 24 h after intrathecal chemotherapy under propofol deep sedation. Risk factors for this outcome were established (being female, consolidation phase of treatment, and previous kinetosis), and evidence suggested that the Eberhart score was not suitable for the studied population.

PROMETHAZINE-INDUCED THROMBOPHLEBITIS IN A NIGERIAN MAN: A CASE REPORT.

Introduction: Promethazine is a phenothiazine derivative that possesses antihistamine, anti-dopaminergic and anticholinergic properties. It is commonly used to treat motion sickness, allergic conditions, nausea and vomiting, in addition to its use as a sedative. Promethazine has vesicant properties and is highly caustic to the intima of blood vessels and surrounding tissues. Intravenous administration may result in thrombophlebitis, unintentional intra-arterial administration, perivascular extravasation and tissue necrosis. To the best of our knowledge there is no previous published report of promethazine-induced thrombophlebitis from sub- Saharan Africa. Case Report: A 29-year-old Nigerian male was admitted at our hospital on account of malaria with acute gastroenteritis. Due to persistent vomiting, he was administered 25 mg of promethazine injection via a size 22G intravenous cannula which was inserted the previous day on the anteromedial aspect of his right forearm and maintained with continuous intravenous crystalloid infusion. Upon administration of promethazine, he experienced intense burning and erythema. The cannula was removed immediately, another cannula was inserted on the contralateral arm, and promethazine was replaced with ondansetron. Subsequently, he developed a tender, subcutaneous cord-like swelling extending from the middle-third of the anteromedial aspect of his right forearm, corresponding with the site of previous venous cannulation. Ultrasonography revealed a hypoechoic, non-compressible basilic vein, with no flow on colour Doppler interrogation, in keeping with superficial thrombophlebitis. He was treated with a topical anti-inflammatory agent, and the pain and redness subsided after four weeks. Conclusion: The preferred parenteral route of administration of promethazine is deep intramuscular injection. Recommendations to prevent promethazine-induced thrombophlebitis include: use of large and patent veins, use of lower doses, drug dilution and slow administration, use of alternative therapies, and patient education. Promethazine-induced tissue injury is under-reported in this part of the world. Creating awareness through this case report would help reduce the morbidity following promethazine administration.

Assessing the impact of aprepitant and ondansetron on postoperative nausea and vomiting in orthognathic surgeries: a randomized controlled trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a common side effect associated with general anesthesia. Both ondansetron and aprepitant been effectively used to prevent PONV. However, there is a disagreement of opinions regarding the superiority of these two drugs. This study aims to compare the efficacy of aprepitant with ondansetron in preventing PONV following orthognathic surgeries. METHODS: In this double-blinded clinical trial, 80 patients scheduled for orthognathic surgery at Imam Hossein Hospital, Tehran, Iran, were randomly assigned to two groups. A standardized anesthesia protocol was used for all patients. The first group received a placebo capsule administered one hour before the surgical procedure along with 4 mg (2 ml) of ondansetron intravenously after anesthesia induction. The second group was given 80 mg aprepitant capsules one hour before the surgery, followed by an injection of 2 ml intravenous distilled water after anesthesia induction. The occurrence and severity of PONV, the amount of rescue medication required, and the complete response of patients assessed within 24 h after the surgery. RESULTS: There were no significant differences in demographic data between the two groups. Patients in the aprepitant group had a significantly lower incidence and severity of nausea (2.5% versus 27.5%), vomiting (5% versus 25%), and required fewer rescue medications (7.5% versus 62.5%) compared to the ondansetron group. Additionally, the aprepitant group showed a higher complete response rate (90% versus 67.5%) in the 0-2 and 12-24 postoperative hours. CONCLUSION: According to the findings of this study, aprepitant has demonstrated a greater efficacy in preventing PONV following orthognathic surgery, when compared to ondansetron. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT code: IRCT20211205053279N3), date of registration: 16/12/2022.

Effect of ondansetron compared to lidocaine and placebo for reducing propofol injection pain: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Propofol is the most commonly used intravenous anesthetic medication and is most commonly associated with post-operative pain. Several drugs are investigated to reduce post-operative pain caused by propofol injection. Ondansetron is a potent anti-emetic drug showing promising results as an analgesic. This meta-analysis aims to compare the efficacy of ondansetron to placebo and lidocaine in reducing post-operative pain caused by propofol injection. METHODS: PubMed, Embase, Cochrane Library, Web of Science, and Scopus were searched for relevant randomized controlled trials (RCTs) till May 2022. We conducted a meta-analysis using RevMan software version 5.4, and we assessed the quality of included RCTs using the Cochrane risk of bias tool. RESULTS: In our study, we included 23 RCTs with 2957 participants. Compared to placebo, ondansetron significantly increased the rate of no pain [risk ratio (RR) = 2.36, 95% confidence interval (CI) (1.39-4.01)], and reduced moderate [RR = 0.39, 95% CI (0.30-0.52)] and severe pain [RR = 0.34, 95% CI (0.24-0.50)]. Furthermore, ondansetron significantly reduced PONV [RR = 0.73, 95% CI (0.58, 0.91)]. On the other hand, ondansetron showed an inferior efficacy to lidocaine regarding the incidence of no, moderate, and severe pain. CONCLUSION: Ondansetron is effective in reducing post-operative propofol-induced pain. However, lidocaine is more effective than it.

Prevalence, Risk Factors, and Management of Postoperative Nausea and Vomiting After Laparoscopic Sleeve Gastrectomy (a Retrospective Multicentric Study).

PURPOSE: Postoperative nausea and vomiting (PONV) is a frequent unappealing laparoscopic sleeve gastrectomy (LSG) sequel. The study's purpose was to determine the prevalence, risk factors of PONV, and management of PONV after LSG. PATIENTS AND METHODS: This multicenter retrospective study included patients with morbid obesity who had LSG between January 2022 and April 2023. The age range for LSG was 16 to 65 years, and the eligibility requirements included morbid obesity according to international guidelines. RESULTS: PONV was experienced by 74.6% of patients who underwent LSG at 6 h postoperative. Multivariate analysis revealed that female gender, smokers, preoperative GERD, gastropexy, and severity of pain were found to be independent risk variables of the development of PONV, while antral preservation, opioid-free analgesia, and intraoperative combined analgesia were found to be independent protective variables against the development of PONV. Combined intravenous ondansetron and metoclopramide improved 92.6% of patients who developed PONV. Dexamethasone and antihistamines drugs are given for 42 cases with persistent PONV after using intravenous ondansetron and metoclopramide. Pain management postoperatively by opioid-free analgesia managed PONV. Helicobacter pylori status has no role in the development of PONV after LSG. CONCLUSION: Female gender, smoking, presence of preoperative GERD, gastropexy, and severity of pain were found to be independent risk variables of the development of PONV, while antral preservation, opioid-free analgesia, and intraoperative combined analgesia were observed to be independent protective factors against the occurrence of PONV. Combined intravenous ondansetron and metoclopramide improved PONV. Dexamethasone and antihistamines drugs are given for persistent PONV.

The efficacy of aprepitant for the prevention of postoperative nausea and vomiting: A meta-analysis.

BACKGROUND: Postoperative nausea and vomiting (PONV) is one of the common adverse reactions after surgery. Recent randomized controlled trials (RCTs) investigating antiemetic drugs suggest that aprepitant has the strongest antiemetic effect of any single drug. This meta-analysis aimed to explore the efficacy of aprepitant for preventing PONV based on the existing literature. METHODS: To identify RCTs investigating the use of aprepitant for PONV prevention, we searched PubMed, Embase, and Cochrane Library databases for articles published prior to March 20, 2022. Seventeen RCTs were identified, with 3299 patients, meeting the inclusion criteria. PONV incidence, complete response, 80 mg aprepitant combined with dexamethasone and ondansetron, vomiting, nausea, and analgesic dose-response were the main outcomes measured. RESULTS: Compared with the control group, PONV incidence was significantly reduced among those receiving aprepitant (odds ratio [OR]: 0.34; 95% confidence interval [CI]: 0.26, 0.44; P < .0001), with a more complete response (OR: 1.35; 95% CI: 1.14, 1.59; P = .0004). Supplementation of 80 mg aprepitant in combination with dexamethasone and ondansetron substantially improved the effects of PONV (OR: 0.36; 95% CI: 0.16, 0.82; P = .01). Further, administration of 80 mg aprepitant was better at preventing vomiting than nausea (OR: 8.6; 95% CI: 3.84, 19. 29; P < .00001). No statistically significant difference between the dose-response of analgesics was identified (mean difference: -1.09; 95% CI: -6.48, 4.30; P = .69). The risk of bias was assessed independently by paired evaluators. CONCLUSION: Aprepitant effectively reduces the incidence of PONV; however, the effects of postoperative analgesia require further exploration.

Preoperative versus intraoperative antiemetic strategies in patients undergoing laparoscopic cholecystectomy: A randomised double-blind study.

BACKGROUND: Previous studies have determined ondansetron's efficacy in preventing and treating postoperative nausea and vomiting (PONV). However, evidence regarding the timing of drug administration in relation to the surgical procedure remains vague. OBJECTIVE: To compare the preoperative and intraoperative administration of ondansetron on the incidence of PONV. DESIGN: Single-centred, randomised, double-blind trial. Patients were recruited between November 2018 and April 2021. Follow-up for PONV and retching was up to 24 h. SETTING: Aretaieio University Hospital, Greece. PATIENTS: A total of 121 patients undergoing elective laparoscopic cholecystectomy gave written consent. INTERVENTIONS: Patients were randomly allocated to the preoperative or the intraoperative group. The preoperative group received 4 mg of ondansetron dissolved in 100 ml of 0.9% saline 1 hour before induction of anaesthesia and 100 ml of 0.9% saline 30 min before end of surgery. The intraoperative group received 100 ml of 0.9% saline 1 h before induction of anaesthesia and 4 mg of ondansetron dissolved in 100 ml of 0.9% saline 30 min before end of surgery. MAIN OUTCOME MEASURES: The primary outcome was the incidence of nausea and/or vomiting combined at 24 h. RESULTS: No difference was found between the two groups regarding either the incidence of nausea and vomiting at 24 h (1.7% for the preoperative group versus 5.3% for the intraoperative group, P  = 0.31) or the incidence of nausea, vomiting and retching combined (5.3% for the preoperative group versus 10.5% for the intraoperative group, P  = 0.30). There was no difference between the groups in the pain intensity at rest or with coughing in the post anaesthesia care unit, at 4, 8 and 24 h postoperatively ( P  = 0.961, 0.929, 0.748 and 0.883 at rest, and 0.974, 0.220, 0.235 and 0.317 with coughing, respectively). CONCLUSION: Under the current study design, we found no difference in the incidence of PONV between the administration of ondansetron 1 h before induction of anaesthesia and the intraoperative administration of ondansetron 30 min before the end of surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT03023306.