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Background & Aims: Metoclopramide nasal spray (MNS) was developed as an alternative to oral metoclopramide. Prior phase 2 studies demonstrated efficacy in reducing symptoms in women, but not men with diabetic gastroparesis. The aim of this phase 3 study was to further determine the safety and efficacy of MNS compared with placebo in reducing symptoms of diabetic gastroparesis in women., Methods: This US multicenter, randomized, double-blind, parallel group study enrolled women aged 18-75 years with diabetic gastroparesis and delayed gastric emptying. Subjects were randomized 1:1 to receive placebo or MNS 10 mg. The primary efficacy end point was change in mean daily Gastroparesis Symptom Assessment total score from baseline to Week 4. The Gastroparesis Symptom Assessment daily diary is a validated patient-reported outcome instrument that averages scores of nausea, early satiety, prolonged fullness, bloating, and upper abdominal pain on a 5-point ordinal scale., Results: Two hundred and five subjects were randomized to receive placebo (n = 103) or MNS (n = 102). Overall, the MNS group did not experience a significant reduction in symptoms compared with the placebo group from baseline to Week 4 (P = .881). However, subjects with moderate-to-severe symptoms at baseline had a significant treatment effect from Weeks 1 to 3 (P < .05) and experienced a significant reduction in nausea and upper abdominal pain for all 4 weeks versus placebo (P < .05). Treatment-emergent adverse events were primarily mild to moderate with headache and abdominal pain reported most frequently., Conclusions: Although the primary end point was not met using all enrolled patients, treatment with MNS provided significant relief for women with moderate-to-severe diabetic gastroparesis symptoms. MNS was well tolerated and demonstrated a similar safety profile to placebo. (ClinicalTrials.gov identifier: NCT02025725.)., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: We investigated whether two doses of dexamethasone are more effective than a single dose in reducing early postoperative nausea and vomiting (PONV) during total knee arthroplasty (TKA)., Methods: A total of 150 patients between June 2021 and June 2022 were randomized into 3 groups: two doses of normal saline (group A), a single dose of 10 mg dexamethasone before surgery and normal saline after surgery (group B), and two doses of 5 mg dexamethasone during the perioperative period (group C). Primary outcomes were incidences and severity of PONV within 24 hours after surgery, the number and consumption of patients requiring morphine and metoclopramine, and visual analog scale scores for nausea and vomiting at 2, 4, 6, and 24 hours after surgery. Blood glucose levels on days 1, 2, and 3 after operation and incidences of surgical site infection (SSI) as well as gastrointestinal bleeding (GIB) within 45 days after operation were compared., Results: Within 24 hours after operation, the number and consumption of patients requiring morphine and metoclopramide in groups B and C were significantly lower than those in group A. Incidences and severity of PONV in groups B and C were significantly lower than those in group A. And these differences between groups B and C were significant. At 2, 4, 6, and 24 hours after operation, there were significant differences in visual analog scale scores of PONV between groups A and B, A and C, as well as B and C. On postoperative days 1, 2, and 3, there were no significant differences in blood glucose levels among the groups, and there were no incidences of SSI or GIB in any group within 45 days after operation., Conclusion: Dexamethasone significantly reduces PONV within 24 hours after TKA, does not result in significant changes in postoperative blood glucose levels, and does not increase the risk of SSI or GIB, particularly on group C., Registration Number: ChiCTR2400088512., Registration Center: Chinese Clinical Trial Registry (ChiCTR). WEBSITE: www.chictr.org.cn., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Metoclopramide is an antiemetic agent prescribed for motion sickness, cancer chemotherapy, and pregnancy. The present work aimed to design a metoclopramide-loaded halloysite nanotubes (HNTs) drug-in-adhesive transdermal drug delivery system. Four formulations F1, F2, and F3 with different ratios of HNTs to metoclopramide and a F4 without HNTs were developed using acrylic adhesive DURO-TAK 387-2510 by the solvent casting method. These formulated patches were thoroughly evaluated and in-vitro release and permeation studies were performed. The optimized formulation was analyzed using skin irritation, SEM, DSC, and FTIR studies. The GASTROPLUS TCAT model was used to predict the in-vivo performance. HNT-based formulations exhibited controlled drug release, achieving approximately 60% in 4 h, compared to over 80% release in the same period from the formulation without HNT. The optimized formulation (F3) demonstrated a lag time of 1.802 h with a flux of 0.103 mg/cm 2 /hr. The shelf life was 19.279 months at 5 ± 3 °C. The C max , T max , AUC t, and AUC inf were predicted as 40.84 ng/mL, 6.32 h, 561.51 ng/mL×h and 599.61 ng/mL×h for a 30 mg patch. The study demonstrated that metoclopramide can be effectively loaded into HNTs and proved safe and effective in drug-in-adhesive type transdermal systems using HNTs as a drug carrier., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objective: To assess whether adding metoclopramide to a protocol of maropitant and pantoprazole would reduce incidence of ptyalism, vomiting and regurgitation in brachycephalic dogs undergoing thoracolumbar spinal surgery., Study Design: Randomized blinded controlled trial., Animals: A total of 43 brachycephalic dogs undergoing thoracolumbar spinal surgery., Methods: In addition to a standardized anaesthetic regimen, dogs were randomized to be administered either a 2 mg kg -1 day -1 metoclopramide constant rate infusion (CRI) or a saline solution at an equivalent infusion rate, started after anaesthetic induction and discontinued 5 hours after tracheal extubation. The presence of vomiting, regurgitation and pytalism, and short form of the Glasgow Composite Pain Scale pain scores were assessed by a blinded observer hourly for 4 hours, starting 1 hour postextubation., Results: Regurgitation occurred in six dogs postoperatively; three dogs were in the placebo group and three in the metoclopramide group. The odds ratio (OR) of regurgitation after surgery did not differ between groups [OR: 0.76, 95% confidence interval (CI): 0.13-4.3, p = 0.76]. The odds of observing ptyalism at 3 and 4 hours was approximately 15 times less than 1 hour postoperatively (both OR: 15.4, 95% CI: 1.8-130.7, p = 0.012) and did not differ based on the addition of metoclopramide (OR: 0.73, 95% CI: 0.07-8.0, p = 0.79). The odds of observing pain did not change over time and did not differ based on the addition of metoclopramide (OR: 0.71, 95% CI: 0.12-4.2, p = 0.71). Vomiting did not occur during the study (0.0%, 95% CI: 0.0-8.2%). No adverse effects were observed during the study period in either group., Conclusions and Clinical Relevance: The addition of a metoclopramide CRI to maropitant and pantoprazole did not result in a significant reduction in ptyalism or regurgitation in brachycephalic dogs undergoing thoracolumbar spinal surgery., (Copyright © 2024 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

The integration of Computerized Provider Order Entry (CPOE) systems in hospitals has been instrumental in reducing medication errors and enhancing patient safety. This study examines the implications of a software oversight in a CPOE system : Metoclopramide had a concentrated formulation (100 mg) delisted (and then not manufactured) in 2014 due to safety concerns. Despite this, the CPOE system continued to accept prescriptions for this formulation because it was not removed from the medication library by the pharmacist. The objective of our study was to describe this specific prescription error related to an outdated the medication library of the CPOE. We analyzed all metoclopramide prescriptions from 2014, to 2023. Our findings showed that errors involving 100 mg or more dosages were relatively rare, at 2.98 per 1000 prescriptions (34 errors in 11,372 prescriptions). Notably, 47.1% of these errors occurred during on-call shifts, and 68% of these errors led to actual administration. These errors correlated with periods of higher nurse workload. The findings advocate for the integration of dedicated pharmacists into ICU teams to minimize medication errors and enhance patient outcomes, and a proactive medication management in healthcare., (© 2024. The Author(s).)

Objective: To determine the pharmacokinetics (PK) of metoclopramide administered via intravenous continuous rate infusion (IV CRI) and subcutaneous (SC) bolus and evaluate for gastrointestinal motility and adverse side effects., Study Design: Experimental study; randomized, crossover design., Animals: Six healthy adult horses., Methods: Each horse received metoclopramide via IV CRI (0.04 mg/kg/h for 24 h) and SC bolus (0.08 mg/kg once), with ≥1 week washout period between. Plasma was analyzed by UPLC-MS/MS. Compartmental modeling was used to determine PK parameters for each treatment; nonparametric superposition was used to simulate multiple SC bolus regimens. Gastrointestinal motility and evidence of adverse effects were monitored., Results: T max (h) for SC bolus was 0.583 ± 0.204 versus 17.3 ± 6.41 for IV CRI, while C max (ng/mL) was 27.7 ± 6.38 versus 43.6 ± 9.97, respectively. AUC (h × ng/mL) was calculated as 902 ± 189 for 24 h IV CRI versus 244 ± 37.4 simulated for 0.08 mg/kg SC bolus every 8 h. Simulations revealed similar exposure between groups with administration of 0.96 mg/kg/day SC bolus, divided into three, four, or six doses. SC bolus bioavailability was estimated as 110 ± 11.5%. No clear trends in motility alteration were identified. No adverse effects were noted., Conclusion: Repeated SC boluses of metoclopramide at 0.08 mg/kg would result in lower total drug exposure and T max than IV CRI administration but would be highly bioavailable., Clinical Significance: Higher and/or more frequent SC bolus doses are needed to achieve a similar AUC to IV CRI. No adverse effects were noted; however, evaluation of alternative dosing strategies is warranted., (© 2024 The Author(s). Veterinary Surgery published by Wiley Periodicals LLC on behalf of American College of Veterinary Surgeons.)

Background: Intravenous ketorolac and metoclopramide are common emergency treatments for adult patients with migraine headaches. The comparison between ketorolac and metoclopramide for migraine treatment is an intriguing issue for research and clinical practice., Objectives: To provide an updated systematic review and meta-analysis of randomized clinical trials (RCTs) to help determine which treatment has better effects for migraine patients., Material and Methods: Intravenous ketorolac and metoclopramide were compared to evaluate whether intravenous ketorolac is associated with significant benefits for pain intensity, short-term headache relief and sustained headache relief among adult patients with migraines. Adverse effects were also analyzed. Five studies with a total of 674 adult patients were included in the analysis, which focused on the outcomes of pain intensity, short-term headache relief, sustained headache relief, and adverse effects., Results: The meta-analysis showed that the only modest but statistically significant difference was present in short-term headache relief when comparing intravenous ketorolac with intravenous metoclopramide. There were no significant differences between intravenous ketorolac and metoclopramide in terms of pain intensity, sustained headache relief or adverse effects., Conclusion: The results suggest that there are no significant differences in most treatment effects (aside from short-term headache relief) and adverse effects when comparing intravenous ketorolac with intravenous metoclopramide. However, the paucity of literature on this topic might have limited the interpretation of the current results. Thus, more relevant studies are warranted.

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]., (© 2024 John Wiley & Sons Ltd.)

Introduction: The 2021 American College of Gastroenterology Guidelines suggested using of intravenous erythromycin before endoscopy in patients with upper gastrointestinal bleeding (UGIB) to enhance endoscopic view and reduce the need for repeat endoscopy. Evidence on intravenous metoclopramide, which is more accessible, is scant, especially in patients with active UGIB. This study aimed to evaluate the efficacy of metoclopramide for gastric visualization in patients with active UGIB., Methods: Between April 10, 2021, and October 8, 2022, this double-blind, double-center randomized controlled trial enrolled patients with active UGIB (hematemesis or presence of fresh blood in the nasogastric tube). The eligible patients were randomly assigned in a concealed 1:1 allocation to metoclopramide or placebo. The primary outcome was adequate visualization by objective endoscopic visualized gastroduodenal scores (EVS). Secondary outcomes included mean difference in EVS, duration of esophagogastroduodenoscopy (EGD), immediate hemostasis, need for a second look EGD, units of blood transfusion, length of hospital stay, and 30-day rebleeding rate., Results: Of the 68 eligible patients, 3 of each group were excluded by protocol violation. Finally, 62 patients (31 metoclopramide and 31 placebo) were analyzed. The percentage of patients with adequate visualization in metoclopramide and placebo group was 77.4% and 61.6% (odds ratio [OR] 2.16 [0.71-6.58], P = 0.16). The need for a second look EGD in the 72 hours was lower in the metoclopramide group (3.2% vs 22.6%, OR 0.11 [0.01-0.99], P = 0.02), whereas the other secondary outcomes were not different. However, in gastric lesions subgroup analysis, metoclopramide improved the adequate visualization rate (92.9% vs 50%, OR 13 [1.32-128.10], P = 0.03) and mean EVS at fundus (1.79 ± 0.42 vs 1.29 ± 0.72; P = 0.03)., Discussion: Metoclopramide did not improve endoscopic visualization but decreased the need for second look EGD in patients with overall active UGIB. It improved gastric visualization in those with UGIB due to gastric lesions, primarily by improving visualization in the fundus ( ClinicalTrials.gov number NCT04771481)., (Copyright © 2023 by The American College of Gastroenterology.)

Background: The presence of gastrointestinal dysfunction is an outcome-relevant complication in critically ill ICU patients., Aims, Materials and Methods: The following review aims to show the importance of gastrointestinal dysfunction. Multimodal therapy for gastroparesis and paralytic ileus is discussed., Conclusion: Erythromycin and metoclopramide are options for gastroparesis, while neostigmine is commonly used for paralytic ileus., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Vomiting is one of the most common adverse events of chemotherapy. The purpose of this study was to systematically review the clinical efficacy of acupoint injection of metoclopramide in the treatment of post-chemotherapy vomiting., Methods: We searched 4 general English databases and 4 conventional Chinese databases, all with a time frame from database creation to December 2022. The retrieved clinical trials of acupoint injection of metoclopramide for post-chemotherapy vomiting were then subjected to meta-analysis and trial sequential analysis., Results: A total of 12 studies were included, with a total sample size of 965 cases. Meta-analysis showed that acupoint injection of metoclopramide was effective in improving anti-vomiting effective rate [odds ratio = 5.67, 95% confidence interval = (3.80,8.47), P < .00001] compared with intramuscular/intravenous injection, and trial sequential analysis showed that this benefit was conclusive. Subgroup analysis demonstrated that acupoint injection significantly improved the anti-vomiting effective rate at doses of 10 mg qd, 20 mg qd, and 30 mg qd, as well as at durations of 1 day and 5 days. Subgroup analysis also indicated that injection at the Zusanli acupoint significantly increased the anti-vomiting effective rate, while injection at the Neiguan acupoint had an anti-vomiting effective rate comparable to that of the control group. Harbord regression showed no significant publication bias (P = .730)., Conclusion: Acupoint injection of metoclopramide for post-chemotherapy vomiting is more effective than intramuscular and intravenous injections and is not limited by dose or duration of treatment, which may be the preferred way of administration., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Lactation induction in transgender women is a clinical and research priority in the field of breastfeeding medicine. To date, there are four case reports detailing successful induced lactation in transgender patients who wished to breastfeed. The Academy of Breast Feeding Medicine does not formally recommend a specific medication regimen for transgender patients due to lack of high-quality research. Case Presentation: A 50-year-old transgender woman with a hypercoagulable disorder who was able to lactate and breastfeed with novel hormone regimen management at a gender care clinic. Her baseline hormone treatment was an estradiol 0.3 mg transdermal patch every 72 hours and micronized progesterone 200 mg daily. Results: Within four weeks of initiating a modified hormone regimen (estradiol 0.4 mg patch every 72 hours, progesterone 300 mg daily, metoclopramide 10 mg three times daily), the patient was lactating spontaneously. On multiple occasions, she breastfed and expressed up to 30 mL of milk through pumping. Conclusion: This report offers a new effective hormone regimen for transgender patients who wish to lactate and cannot access domperidone-the galactagogue used in previous case reports. It also provides a review of previously published case reports on this subject. Future research in this field should prioritize cohort studies of transgender patients who desire lactation to further assess patient attitudes, experiences, and outcomes.

Objectives: To assess the comparative effectiveness and safety of parenteral agents for pain reduction in patients with acute migraine., Background: Parenteral agents have been shown to be effective in treating acute migraine pain; however, the comparative effectiveness of different approaches is unclear., Methods: Nine electronic databases and gray literature sources were searched to identify randomized clinical trials assessing parenteral agents to treat acute migraine pain in emergency settings. Two independent reviewers completed study screening, data extraction, and Cochrane risk-of-bias assessment, with differences being resolved by adjudication. The protocol of the review was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42018100096)., Results: A total of 97 unique studies were included, with most studies reporting a high or unclear risk of bias. Monotherapy, as well as combination therapy, successfully reduced pain scores prior to discharge. They also increased the proportion of patients reporting pain relief and being pain free. Across the pain outcomes assessed, combination therapy was one of the higher ranked approaches and provided robust improvements in pain outcomes, including lowering pain scores (mean difference -3.36, 95% confidence interval [CI] -4.64 to -2.08) and increasing the proportion of patients reporting pain relief (risk ratio [RR] 2.83, 95% CI 1.74-4.61). Neuroleptics and metoclopramide also ranked high in terms of the proportion of patients reporting pain relief (neuroleptics RR 2.76, 95% CI 2.12-3.60; metoclopramide RR 2.58, 95% CI 1.90-3.49) and being pain free before emergency department discharge (neuroleptics RR 4.8, 95% CI 3.61-6.49; metoclopramide RR 4.1, 95% CI 3.02-5.44). Most parenteral agents were associated with increased adverse events, particularly combination therapy and neuroleptics., Conclusions: Various parenteral agents were found to provide effective pain relief. Considering the consistent improvements across various outcomes, combination therapy, as well as monotherapy of either metoclopramide or neuroleptics are recommended as first-line options for managing acute migraine pain. There are risks of adverse events, especially akathisia, following treatment with these agents. We recommend that a shared decision-making model be considered to effectively identify the best treatment option based on the patient's needs., (© 2024 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Introduction: Headache is one of the most common neurological conditions among emergency department visits (ED), although the best therapy has not been identified yet. Therefore, in the current study, we aimed to compare the pain-relieving effect of metoclopramide and ketorolac in acute primary headaches patients., Methods: This double-blind, randomised clinical trial was conducted at Golestan Hospital, Ahvaz, Iran. This research involved all adult patients with acute primary (migraine or tension-type) headaches presented to the ED. Pain intensity was assessed with 0 to 10 verbal Numeric Rating Scales (NRS). The subjects were randomised into 10 mg intravenous (IV) metoclopramide or 30 mg IV ketorolac groups. Pain score and drug adverse reactions were compared between the two groups at baseline, 15, 30, and 60 min after baseline., Results: 108 patients completed this trial and were equally divided into two groups (mean age of 34 ± 8.54 years; 57.4% female). Before treatment, the mean pain score was 6.9 and 6.8 in metoclopramide and ketorolac groups, respectively (p > 0.05). Metoclopramide failed to provide more improvement in pain score at 30 min (p = 0.55) and 60 min (p = 0.15) from baseline. There were no serious adverse events in this study. Only five patients required rescue medication which four of them were in ketorolac group., Conclusion: We were unable to reject the null hypothesis that there would be no difference in pain outcomes between metoclopramide and ketorolac., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Typically, the killed form of microorganisms in combination with alum does not produce strong cellular immune responses. A recent investigation has indicated the role of dopamine D2 receptor antagonists like metoclopramide in reducing the polarization of immune responses toward Th2 immunity. This study was performed to evaluate the effects of a combination of alum and metoclopramide on the induction of cellular and humoral immunity in response to a heat-killed preparation ofSalmonella typhimurium(HKST). Wistar rats were immunized with the HKST vaccine alone or in combination with alum, metoclopramide, or the alum-metoclopramide mixture twice with a two-week interval. Fourteen days after the last vaccination, immune responses against S. typhimurium and the protective potential of the vaccines were assessed. The combination of alum and metoclopramide as an adjuvant augmented the potential of the HKST vaccine to enhance lymphocyte proliferation, delayed-type hypersensitivity reaction, and antibody titer. These results were concurrent with the polarization of immune response towards the Th1 response and improving protective immunity against S. typhimurium. Overall, the combination of alum and metoclopramide as an adjuvant synergistically enhanced cellular and humoral immunity after immunization with the HKST vaccine., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The current study was conducted to fabricate Metoclopramide HCL (MCH) and Sumatriptan succinate (SS) instant release buccal films (IRBF) without using any super disintegrant. The solvent casting method was used for the preparation of IRBFs and prepared IRBFs were physicochemically evaluated. Spectrophotometric analysis was done to determine the lambda max followed by the linearity determination of both drugs. Different concentrations such as 100, 125, and 150mg of hydrophilic polymer (HPMC E5) were employed but the concentration of glycerol was variable. Comparatively better results were observed for the formulation with 150mg of HPMC E5 and 30% glycerol. Formulated IRBFs showed good tensile strength with a mean disintegration time of 12.4-28.4 seconds and rapid dissolution with more than 50% drug release within 2 minutes. It was concluded that the chosen combination of polymers was appropriate for the fabrication of MCH and SS buccal strips.

Optimization of artificial reproduction is essential for minimizing genetic diversity, especially when fish are captured from their natural habitats and spawned in controlled conditions. In the present study, there was evaluation of the effects of gonadotropin-releasing hormone analogue (GnRHa) and human chorionic gonadotropin (hCG) with or without dopamine receptor antagonists such as domperidone (DOM) and metoclopramide (MET) on the spawning efficiency of African catfish (Clarias gariepinus) reared in captivity. The control group was intramuscularly (IM) injected with 1 mL of sterile saline solution. The fish specimens of the other six groups were injected IM with GnRHa or hCG, or in combination with either DOM or MET. None of the specimens had ovulations in the control group. There was the longest latency period in specimens treated with only GnRHa or hCG. There were the largest egg mass weight, fecundity, and hatchability (%) in specimens of the GnRHa + MET group. These findings indicate that GnRHa or hCG combined with dopamine receptor antagonists such as DOM and MET resulted in a marked enhancement of ovulation rate and increased the egg mass, fecundity, and hatchability of the treated C. gariepinus, and the values when there was inclusion of the MET treatment exceeded those when there was treatment with DOM., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Abstract: Acute dystonic reactions are a worrying reason for presentation to the pediatric emergency department and the pediatric neurology clinic in childhood. It must be diagnosed and treated quickly. The aim of this study was to examine the clinical presentations, etiological factors, and prognosis of patients presenting to our regional tertiary pediatric neurology clinic with a diagnosis of acute dystonic reactions in children.Nine pediatric patients who were treated for acute dystonic reactions between May, 2018 and May, 2020 and had adequate follow-up were included in the study. Medical record data were reviewed age, gender, etiology, features of family, treatment, and results.Three of the patients were female and 6 were male. Their average age was 11 years (4-17). All patients were evaluated as a drug-induced acute dystonic reaction. Of the 9 patients, 5 were due to metoclopramide, 3 were due to risperidone, and 1 was due to aripiprazole. It was learned that a similar situation against other drugs developed in the family history of 3 patients. As a treatment, all of them were intramuscularly applied biperiden suitable for their weight and 30 minutes dramatic improvement was observed. Additional dose had to be administered in only 1 case. All cases were discharged for 24 hours. No problem was observed in their follow-up.Drug-induced acute dystonic reaction can be diagnosed and has a clinical picture that completely resolves when effective treatment is applied. However, it should not be forgotten that it can reach life-threatening dimensions clinically., Competing Interests: The author has no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Prior epidemiological studies demonstrated that the p.D85N-Potassium voltage-gated channel subfamily E member 1 (KCNE1) common variant reduces repolarization reserve and predisposes to drug-induced QT prolongation/torsades de pointes. We sought to develop a cellular model for drug-induced long QT syndrome using a patient-specific induced pluripotent stem cell-derived cardiomyocyte (iPSC-CM)., Methods: p.D85N-KCNE1 iPSCs were generated from a 23-year-old female with an exaggerated heart rate-corrected QT interval response to metoclopramide (ΔQTc of 160 ms). Clustered regularly interspaced short palindromic repeats-associated 9 technology was used to generate gene-corrected isogenic iPSCs. Field potential duration and action potential duration (APD) were measured from iPSC-CMs., Results: At baseline, p.D85N-KCNE1 iPSC-CMs displayed significantly longer field potential duration (281±15 ms, n=13 versus 223±8.6 ms, n=14, P <0.01) and action potential duration at 90% repolarization (APD90; 579±22 ms, n=24 versus 465±33 ms, n=26, P <0.01) than isogenic-control iPSC-CMs. Dofetilide at a concentration of 2 nM increased significantly field potential duration (379±20 ms, n=13, P <0.01) and APD90 (666±11 ms, n=46, P <0.01) in p.D85N-KCNE1 iPSC-CMs but not in isogenic-control. The effect of dofetilide on APD90 (616±54 ms, n=7 versus 526±54 ms, n=10, P <0.05) was confirmed by Patch-clamp. Interestingly, treatment of p.D85N-KCNE1 iPSC-CMs with estrogen at a concentration of 1 nM exaggerated further dofetilide-induced APD90 prolongation (696±9 ms, n=81, P <0.01) and caused more early afterdepolarizations (11.7%) compared with isogenic control (APD90: 618±8 ms, n=115 and early afterdepolarizations: 2.6%, P <0.05)., Conclusions: This iPSC-CM study provides further evidence that the p.D85N-KCNE1 common variant in combination with environmental factors such as QT prolonging drugs and female sex is proarrhythmic.

Background Intravenous morphine administration can adversely affect platelet inhibition induced by P2Y 12 receptor inhibitors after acute myocardial infarction. In contrast, some evidence suggests that opioid agonists may have cardioprotective effects on the myocardium. The aim of this prospective, randomized MonAMI (Impact of Morphine Treatment With and Without Metoclopramide Coadministration on Platelet Inhibition in Acute Myocardial Infarction) trial was, therefore, to investigate the impact of morphine with or without metoclopramide coadministration on myocardial and microvascular injury. Methods and Results Patients with acute myocardial infarction (n=138) were assigned in a 1:1:1 ratio to ticagrelor 180 mg plus: (1) intravenous morphine 5 mg (morphine group); (2) intravenous morphine 5 mg and metoclopramide 10 mg (morphine+metoclopramide group); or (3) intravenous placebo (control group) administered before primary percutaneous coronary intervention. Cardiac magnetic resonance imaging was performed in 104 patients on day 1 to 4 after the index event. Infarct size was significantly smaller in the morphine only group as compared with controls (percentage of left ventricular mass, 15.5 versus 17.9; P =0.047). Furthermore, the number of patients with microvascular obstruction was significantly lower after morphine administration (28% versus 54%; P =0.022) and the extent of microvascular obstruction was smaller (percentage of left ventricular mass, 0 versus 0.74; P =0.037). In multivariable regression analysis, morphine administration was independently associated with a reduced risk for the occurrence of microvascular obstruction (odds ratio, 0.37; 95% CI, 0.14-0.93 [ P =0.035]). There was no significant difference in infarct size ( P =0.491) and extent ( P =0.753) or presence ( P =0.914) of microvascular obstruction when comparing the morphine+metoclopramide group with the control group. Conclusions In this randomized study, intravenous administration of morphine before primary percutaneous coronary intervention resulted in a significant reduction of myocardial and microvascular damage following acute myocardial infarction. This effect was not observed in the morphine plus metoclopramide group. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02627950.

Objective: To determine whether IV metoclopramide 20 mg + diphenhydramine 25 mg (M + D) was more efficacious than IV placebo for acute moderate or severe posttraumatic headache in the emergency room., Methods: We conducted this randomized, double-blind, placebo-controlled, parallel-group study in 2 urban emergency departments (EDs). Participants who experienced head trauma and presented to our EDs within 10 days with a headache fulfilling criteria for acute posttraumatic headache were included. We randomized participants in a 1:1 ratio to M + D or placebo. Participants, caregivers, and outcome assessors were blinded to assignment. The primary outcome was improvement in pain on a scale of 0 to 10 between baseline and 1 hour after treatment., Results: This study was completed between August 2017 and March 2020. We screened 414 patients for participation and randomized 160: 81 to M + D and 79 to placebo. Baseline characteristics were comparable between the groups. All enrolled participants provided primary outcome data. Patients receiving placebo reported mean improvement of 3.8 (SD 2.6), while those receiving M + D improved by 5.2 (SD 2.3), for a difference favoring metoclopramide of 1.4 (95% confidence interval [CI] 0.7-2.2, p < 0.01). Adverse events were reported by 35 of 81 (43%) patients who received metoclopramide and 22 of 79 (28%) of patients who received placebo (95% CI 1-30 for difference of 15%, p = 0.04)., Conclusion: M + D was more efficacious than placebo with regard to relief of posttraumatic headache in the ED., Trial Registration Information: ClinicalTrials.gov Identifier: NCT03220958., Classification of Evidence: This study provides Class I evidence that for patients with acute moderate or severe posttraumatic headache, IV M + D significantly improved pain compared to placebo., (© 2021 American Academy of Neurology.)

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancers. Chemotherapy is the most important therapeutic option for TNBC, and chemotherapy-induced nausea and vomiting (CINV) is inevitable. Metoclopramide is a good and cost-effective therapeutic option for chemotherapy-induced nausea and vomiting. However, it is not commonly used in breast cancer because it can increase serum prolactin levels by blocking dopamine D2 receptor. This study aimed at elucidating the effect of metoclopramide on triple-negative breast cancer, MDA-MB-231 cells were treated with various concentrations of metoclopramide, the cell proliferation was detected by MTT method, the apoptosis rate was detected by Annexin V/PI double staining method, the expression change of death-related protein was detected by Western Blot. We found that metoclopramide inhibits cell proliferation and induces cell apoptosis of MDA-MB-231 in a concentration-dependent manner, and the Bcl family was involved in this process.

The antiemetic and gastroprokinetic drug metoclopramide is a weak substrate of the blood-brain barrier (BBB) efflux transporter P-gp and displays central nervous system (CNS) side effects (i.e., extrapyramidal symptoms and tardive dyskinesia) caused by dopamine D 2 receptor blockade in the basal ganglia. These side effects occur with a higher incidence in elderly people. We used positron emission tomography to assess the brain distribution of [ 11 C]metoclopramide in young (n = 11, 26 ± 3 years) and elderly (n = 7, 68 ± 9 years) healthy men both after administration of a microdose (9 ± 7 µg) and a microdose co-injected with a therapeutic dose of unlabeled metoclopramide (10 mg). For both doses, elderly subjects had a significantly higher total volume of distribution (V T ) of [ 11 C]metoclopramide in the basal ganglia than young subjects (microdose: +26%, therapeutic dose: +41%). Increases in V T (= K 1 /k 2 ) were caused by significant decreases in the transfer rate constant of [ 11 C]metoclopramide from brain into plasma (k 2 , microdose: -18%, therapeutic dose: -30%), whereas the distributional clearance from plasma into brain (K 1 ) remained unaltered. This reduction in the clearance of [ 11 C]metoclopramide (k 2 ) from the brains of elderly subjects may be caused by an age-related decrease in the activity of P-gp at the BBB and may contribute to the higher incidence of CNS side effects of metoclopramide in the aged population. Our data suggest that an age-associated decrease in the clearance properties of the BBB may modulate the CNS effects or side effects of clinically used P-gp substrates., (© 2020 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Inadequate milk production by sows often limits the growth of piglets. A successful lactation requires prolactin (PRL)-induced differentiation of the alveolar epithelium within the mammary glands of sows between days 90-110 of gestation. We hypothesized that induction of late gestational hyperprolactinemia in primiparous sows by oral administration of the dopamine antagonist metoclopramide (MET) would enhance mammary epithelial differentiation, milk yield, and piglet growth rate and that these effects would carry over into a subsequent lactation. Twenty-six gilts were assigned to receive either MET (n = 13, 0.8 mg/kg) or vehicle (CON, n = 13) twice daily from days 90-110 of gestation. The same sows were followed into their second lactation without additional treatment. On day 90 of gestation, circulating PRL concentrations peaked 45 min after feeding MET (P < 0.001) and then returned to baseline 3 h later. This response occurred daily out to day 104 of gestation (P < 0.05). Compared with CON, MET-treated gilts had enlarged alveoli on gestation day 110 (P < 0.05). Treatment with MET did not affect feed intake, body weight, or body fatness during pregnancy or lactation. Piglets born to MET-treated sows had both increased body weights and average daily gain on lactation days 14 and 21 (P < 0.05). Milk intake by piglets was estimated from deuterium oxide dilution. Although milk intake by piglets nursing MET sows was not statistically different from those nursing CON sows on day 21 of lactation (P = 0.18), there was a greater increase in milk consumption by piglets born to MET-treated sows between days 9 and 21 of lactation than for those in CON litters (P < 0.001). In one group of second parity sows (n = 11) that were treated with MET during their first gestation, milk yield increased by 21% during their second lactation (P < 0.05) in association with a 14% decline in body fatness across lactation compared with a 7% decline in CON sows (P < 0.05). These findings demonstrate that MET-induced hyperprolactinemia in primiparous sows during late pregnancy can increase milk yield and piglet growth rate, setting the stage for further large-scale studies., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Due to the healthcare burden associated with migraines, prompt and effective treatment is vital to improve patient outcomes and ED workflow. This was a prospective, randomized, double-blind trial. Adults who presented to the ED with a diagnosis of migraine from August of 2019 to March of 2020 were included. Pregnant patients, or with renal impairment were excluded. Patients were randomized to receive intravenous magnesium, prochlorperazine, or metoclopramide. The primary outcome was change in pain from baseline on a numeric rating scale (NRS) evaluated at 30 min after initiation of infusion of study drug. Secondary outcomes included NRS at 60 and 120 min, ED length of stay, necessity for rescue analgesia, and adverse effects. A total of 157 patients were analyzed in this study. Sixty-one patients received magnesium, 52 received prochlorperazine, and 44 received metoclopramide. Most patients were white females, and the median age was 36 years. Hypertension and migraines were the most common comorbidities, with a third of the patients reporting an aura. There was a median decrease in NRS at 30 min of three points across all three treatment arms. The median decrease in NRS (IQR) at 60 min was -4 (2-6) in the magnesium group, -3 (2-5) in the metoclopramide group, and -4.5 (2-7) in the prochlorperazine group (p = 0.27). There were no statistically significant differences in ED length of stay, rescue analgesia, or adverse effects. Reported adverse effects were dizziness, anxiety, and akathisia. No significant difference was observed in NRS at 30 min between magnesium, metoclopramide and prochlorperazine., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the role of cation transporters (OCTs, MATEs) in the renal and hepatic disposition of the radiolabeled antiemetic drug [ 11 C]metoclopramide in mice with PET., Methods: PET was performed in wild-type mice after administration of an intravenous microdose (<1 μg) of [ 11 C]metoclopramide without and with co-administration of either unlabeled metoclopramide (5 or 10 mg/kg) or the prototypical cation transporter inhibitors cimetidine (150 mg/kg) or sulpiride (25 mg/kg). [ 11 C]Metoclopramide PET was also performed in wild-type and Slc22a1/2 (-/-) mice. Radiolabeled metabolites were measured at 15 min after radiotracer injection and PET data were corrected for radiolabeled metabolites., Results: [ 11 C]Metoclopramide was highly metabolized and [ 11 C]metoclopramide-derived radioactivity was excreted into the urine. The different investigated treatments decreased (~2.5-fold) the uptake of [ 11 C]metoclopramide from plasma into the kidney and liver, inhibited metabolism and decreased (up to 3.8-fold) urinary excretion, which resulted in increased plasma concentrations of [ 11 C]metoclopramide. Kidney and liver uptake were moderately (~1.3-fold) reduced in Slc22a1/2 (-/-) mice., Conclusions: Our results suggest a contribution of OCT1/2 to the kidney and liver uptake and of MATEs to the urinary excretion of [ 11 C]metoclopramide in mice. Cation transporters may contribute, next to variability in the activity of metabolizing enzymes, to variability in metoclopramide pharmacokinetics and side effects.

Study Objective: The objective of this study was to determine the analgesic efficacy and safety of intravenous, single-dose metoclopramide versus dexketoprofen trometamol versus metoclopramide+ dexketoprofen trometamol in patients presenting with acute migraine attack to the emergency department (ED)., Methods: This single-center, randomized, double-blind study was conducted in a tertiary care ED. Eligible patients met the migraine criteria of the International Headache Society were randomized to receive 10 mg intravenous metoclopramide, 50 mg intravenous dexketoprofen trometamol, or 50 mg dexketoprofen trometamol +10 mg metoclopramide. Visual analogue scale (VAS) was used for pain measurement at baseline, after 15 and 30 min. The primary outcome measure was the changes in the VAS scores at the 15th and 30th minutes of treatment. The secondary outcome measures were the presence of adverse effects and the requirement of rescue medicine., Results: Patients (n = 150) were randomized into 3 groups with similar VAS scores at baseline. While there was no significant difference between metoclopramide and dexketoprofen trometamol in reducing pain at the 15th and 30th minute (p = 0.618 and p = 0.862, respectively) and between metoclopramide and metoclopramide + dexketoprofen trometamol at the 15th minute (p = 0.074), metoclopramide + dexketoprofen trometamol was superior to both metoclopramide [mean difference: -13.2 mm (95% CI -23.1 to -3.3)] and dexketoprofen trometamol [mean difference: -11.02 mm (95% CI -20.9 to -1.1)] at the 30th min (p = 0.006 and p = 0.025 respectively). The rescue drug was required by 3 patients (6%) were in metoclopramide group, 4 patients (8%) in dexketoprofen trometamol group and one patient (2%) in the metoclopramide + dexketoprofen trometamol group. No side effects were observed in subjects in three treatment groups., Conclusion: No significant difference in VAS was found between three treatment groups at the 15th minute, but metoclopramide + dexketoprofen trometamol was superior to both metoclopramide and dexketoprofen trometamol at the 30th min., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Metoclopramide inhibits the central and peripheral D 2 receptors and is frequently prescribed in adults and children as an antiemetic or a prokinetic drug to control symptoms of upper gastrointestinal motor disorders. Metoclopramide is predominantly metabolized via N-dealkylation and it is primarily mediated by CYP2D6 which is highly polymorphic. Thus, the effects of CYP2D6 genetic polymorphism on the pharmacokinetics of metoclopramide were evaluated in this study. All volunteers were genotyped for CYP2D6 and divided into four different genotype groups (CYP2D6*wt/*wt [*wt = *1 or *2], CYP2D6*wt/*10, CYP2D6*10/*10, and CYP2D6*5/*10). Each subject received a single oral dose of metoclopramide 10 mg. Plasma concentrations of metoclopramide were measured by using HPLC-UV. Compared to CYP2D6*wt/*wt, AUC inf of CYP2D6*wt/*10, CYP2D6*10/*10, and CYP2D6*5/*10 significantly increased by 1.5-, 2.3-, and 2.5-fold, respectively. C max also increased significantly in comparison to CYP2D6*wt/*wt across all genotype groups, with 1.5-, 1.7-, and 1.7-fold increases seen in CYP2D6*wt/*10, CYP2D6*10/*10, and CYP2D6*5/*10 groups, respectively. The CL/F of metoclopramide decreased in CYP2D6 genotype groups with decreased function alleles, as decreases of 37%, 56% and 61% were observed in CYP2D6*wt/10, *10/10, and *5/*10 genotype groups in comparison to the CYP2D6*wt/*wt group. In conclusion, the genetic polymorphisms of CYP2D6 significantly affected metoclopramide pharmacokinetics.

Background: Greater occipital nerve blocks (GONB) are used increasingly to treat acute migraine., Objective: We conducted a randomized controlled trial to determine whether GONB was as effective as intravenous metoclopramide for migraine., Methods: This was a double-dummy, double-blind, parallel-arm, non-inferiority study conducted in 2 emergency departments (EDs). Patients with migraine of moderate or severe intensity were randomized to receive bilateral GONB with each side administered 3 mL of bupivacaine 0.5% or metoclopramide 10 mg IV, the putative standard of care. The primary outcome was improvement in pain on a 0-10 scale between time 0 and 1 hour later. To reject the null hypothesis that metoclopramide would be more efficacious in relieving pain, we required that the lower limit of the 95% CI for the difference in pain improvement between those randomized to GONB vs those randomized to metoclopramide be >-1.3, a validated minimum clinically important difference. Secondary outcomes included sustained headache relief, defined as achieving and maintaining for 48 hours a headache level of mild or none without the use of additional analgesic medication, and the use of rescue medication in the ED., Results: Over a 2.5-year study period, 1358 patients were screened for participation and 99 were randomized, 51 to GONB and 48 to metoclopramide. All of these patients were included in the primary analysis. Patients who received the GONB reported mean improvement of 5.0 (95% CI: 4.1, 5.8) while those who received metoclopramide reported a larger mean improvement of 6.1 (95% CI: 5.2, 6.9). The 95% CI for the between group difference of -1.1 was -2.3, 0.1. Sustained headache relief was reported by 11/51 (22%) GONB and 18/47 (38%) metoclopramide patients (95% CI for rounded difference of 17%: -1, 35%). Of the 51 GONB patients, 17 (33%) required rescue medication in the ED vs 8/48 (17%) metoclopramide patients (95% CI for rounded difference of 17%: 0, 33%). An adverse event was reported by 16/51 (31%) GONB patients and 18/48 (38%) metoclopramide patients (95% CI for (rounded) difference of 6%: -13, 25%)., Conclusion: GONB with bupivacaine was not as efficacious as IV metoclopramide for the first-line treatment of migraine in the ED., (© 2020 American Headache Society.)

Metoclopramide is commonly used for gastroesophageal reflux. The aims of the present study were to develop a pediatric population pharmacokinetic (PopPK) model, which was applied to simulate the metoclopramide exposure following dosing used in clinical practice. Opportunistic pharmacokinetic data were collected from pediatric patients receiving enteral or parenteral metoclopramide per standard of care and these data were simultaneously fitted using NONMEM. Allometric scaling with body weight was included a priori in the model. Using the final model, the steady-state maximum concentrations (C ss,max ) and the area under the metoclopramide plasma concentration-time curve at steady state from 0 to 6 hours (AUC ss,0-6h ) were simulated following 0.1 or 0.15 mg/kg orally every 6 hours in virtual patients, and compared with previously reported ranges associated with toxicity or the efficacy for gastroesophageal reflux in infants. A two-compartment model with first-order absorption best characterized 87 concentration measurements from 50 patients (median [range] postnatal age of 8.89 years [0.01-19.13]). There were 20 infants (≤ 2 years), 9 children (2 years to age ≤ 12 years), and 21 adolescents (> 12 years). Body weight was the only covariate included in the final model. For > 75% of virtual patients, simulated C ss,max and AUC ss,0-6h estimates were within the range associated with efficacy for gastroesophageal reflux in infants; however, slightly lower exposures were predicted in virtual patients < 2 years. Our study suggests that a metoclopramide enteral dose of 0.1 mg/kg every 6 hours, which was previously recommended for pediatric patients, results in simulated exposure generally within suggested ranges for the treatment of gastroesophageal reflux., (© 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society of Clinical Pharmacology and Therapeutics.)

Background and Objectives: Postoperative nausea and vomiting (PONV) is a common and undesirable complication observed after laparoscopic cholecystectomy (LC). We investigated the effects of auriculoacupuncture (AA) on the prevention of postoperative nausea and vomiting in the immediate postoperative period of uncomplicated laparoscopic cholecystectomy., Methods: Sixty-eight patients were randomly divided into two groups, auriculoacupuncture (n = 35) and control (n = 33) and then they were evaluated prospectively. The needle was placed before anaesthesia induction and remained for 20 minutes. Nausea intensity was evaluated using an analogic visual scale and PONV events were registered immediately after anaesthesia care unit admission and in the second, fourth and sixth hours after the surgery., Results: The auriculoacupuncture group had a significantly smaller incidence of nausea and vomiting than the control group throughout the whole postoperative period (16/35 vs. 27/33, p = 0.03 and 4/35 vs. 15/33, p = 0.005, respectively); the AA group had fewer nausea events 2hours (p = 0.03) and 6hours (p = 0.001) after surgery and fewer vomiting events 2hours (p = 0.01) and 6hours (p = 0.02) after surgery., Conclusions: Auriculoacupuncture can partially prevent postoperative nausea and vomiting when compared to metoclopramide alone after uncomplicated laparoscopic cholecystectomy. Auriculoacupuncture can be recommended as an adjuvant therapy for postoperative nausea and vomiting prevention in selected patients., (Copyright © 2019 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.)

Objective: The objective of this study was to assess the influence of enzyme suppression on the values of various pharmacokinetic factors of orally administered metoclopramide., Method: This study was conducted in two phases and a 4-week duration was adopted for drug washout. This randomized study involved 12 healthy human volunteers who received a single oral dose of metoclopramide 20 mg. After the washout period, volunteers received clarithromycin 500 mg two times per day for consecutive 5 days. On test day (fifth day), a single oral dose of metoclopramide 20 mg was also given to the volunteers, and collection of blood samples was conducted at pre-decided time points. Various pharmacokinetic parameters such as C max, T max , and AUC 0-∞ of metoclopramide were determined by analyzing the blood samples using a validated HPLC-UV method., Results: Clarithromycin increased the mean values of C max , AUC 0-∞ , and T 1/2 of metoclopramide by 46%, 78.6%, and 9.8%, respectively., Conclusion: Clarithromycin noticeably increased the concentration of plasma metoclopramide. This study's results provide in vivo confirmation of the CYP3A4 involvement in metoclopramide metabolism, in addition to CYP2D6. Therefore, metoclopramide pharmacokinetics may be clinically affected by clarithromycin and other potent enzyme inhibitors.

Purpose: To determine whether a single 10-mg intravenous dose of the promotility agent metoclopramide reduces the fluoroscopy time, radiation dose, and procedure time required for gastrojejunostomy (GJ) tube placement., Methods: This prospective, randomized, double-blind, placebo-controlled trial enrolled consecutive patients who underwent primary GJ tube placement at a single institution from April 10, 2018, to October 3, 2019. Exclusion criteria included age less than 18 years, inability to obtain consent, metoclopramide allergy or contraindication, and altered pyloric anatomy. Average fluoroscopy times, radiation doses, and procedure times were compared using t-tests. The full study protocol can be found at www.clinicaltrials.gov (NCT03331965)., Results: Of 110 participants randomized 1:1, 45 received metoclopramide and 51 received placebo and underwent GJ tube placement (38 females and 58 males; mean age, 55 ± 18 years). Demographics of the metoclopramide and placebo groups were similar. The fluoroscopy time required to advance a guide wire through the pylorus averaged 1.6 minutes (range, 0.3-10.1 minutes) in the metoclopramide group versus 4.1 minutes (range, 0.2-27.3 minutes) in the placebo group (P = .002). Total procedure fluoroscopy time averaged 5.8 minutes (range, 1.5-16.2 minutes) for the metoclopramide group versus 8.8 minutes (range, 2.8-29.7 minutes) for the placebo group (P = .002). Air kerma averaged 91 mGy (range, 13-354 mGy) for the metoclopramide group versus 130 mGy (range, 24-525 mGy) for the placebo group (P = .04). Total procedure time averaged 16.4 minutes (range, 8-51 minutes) for the metoclopramide group versus 19.9 minutes (range, 6-53 minutes) for the placebo group (P = .04). There were no drug-related adverse events and no significant differences in procedure-related complications., Conclusions: A single dose of metoclopramide reduced fluoroscopy time by 34%, radiation dose by 30%, and procedure time by 17% during GJ tube placement., (Copyright © 2020 SIR. Published by Elsevier Inc. All rights reserved.)

The study aimed to investigate the feasibility of incorporation of metoclopramide hydrochloride (MCP HCl) in mucoadhesive thermoreversible liquid suppository (MCP HCl -LS ) to bypass the first-pass metabolism and maximize its efficacy to be a promising substitute for parenteral therapy. MCP HCl -LS was formulated using Pluronic (PF127/PF68) and hydroxypropylmethylcellulose (HPMC) and in vitro evaluated through their gelation temperature, gel strength (GS), mucoadhesive force, and in vitro release studies. Also, the MCP HCl -LS was evaluated for its rheological behavior and examined for rectal mucosal integrity after administration. The results revealed that the MCP HCl -LS ; composed of PF127/PF68/HPMC (20/7/0.5% w/w) was in the liquid state at room temperature, experienced gelation at 30.23 °C, with suitable GS of 28.66 s and rectal retention force of 43.03 × 10 2  dyne/cm 2 . The pharmacokinetic data showed that the MCP HCl -LS exhibited a significant increase ( p  < 0.05) in AUC 0-480 (219.688 vs 172.333 ng.h.mL -1 of the marketed) and 1.3-fold increase in relative bioavailability compared to Primperan ® suppository, indicating that LS formula bypassed the first-pass metabolism. Moreover, MCP HCl -LS did not cause any morphological harm to the rectal tissues suggested that the developed formulation was safe and could be a potentially useful alternative drug carrier for rectal delivery of MCP HCl in patients experiencing chemotherapy-induced nausea and vomiting.

Gastrointestinal (GI) pathology is common in elasmobranchs; however, information regarding normal GI transit time and the effect of therapeutics on GI motility is lacking. The objective of this study was to determine baseline gastric emptying and GI transit times in cownose rays ( Rhinoptera bonasus ) and whitespotted bamboo sharks ( Chiloscyllium plagiosum ) via radiographic barium sulfate contrast studies. Additionally, a pilot study was undertaken to determine the effect of metoclopramide on GI transit time in whitespotted bamboo sharks. Eight cownose rays and eight whitespotted bamboo sharks were administered a 98% w/w barium sulfate suspension at 8 ml/kg via orogastric tube. Post-contrast radiographs were obtained at 2 min, 3, 6, 12, and 23 hr for rays; and 2 min, 3, 6, 9, 12, 16, 25, 30, 36, and every 12 hr until complete gastric emptying occurred for sharks. In cownose rays, the mean and standard error were established for time of initial spiral colon filling (3.4 ± 0.4 hr), complete spiral colon opacification (12 ± 0 hr), initial spiral colon emptying (21.6 ± 1.4 hr), and complete gastric emptying (23 ± 0 hr). In bamboo sharks, the mean and standard error were established for time of initial spiral colon filling (5.3 ± 0.5 hr), complete spiral colon opacification (12.4 ± 1.3 hr), initial spiral colon emptying (22.5 ± 2.7 hr), and complete gastric emptying (39.9 ± 3.3 hr). Cownose rays had a significantly shorter time to spiral colon filling and complete gastric emptying compared with bamboo sharks ( P < 0.05). Whitespotted bamboo sharks ( n = 8) were administered metoclopramide (0.4 mg/kg orally once daily for 10 days) and the barium series was repeated. Complete gastric emptying time was significantly shorter in treated sharks compared with control ( P < 0.05), suggesting that metoclopramide may be a useful therapeutic for GI motility disorders in elasmobranchs.

Background: Many women express concern about their ability to produce enough milk, and insufficient milk is frequently cited as the reason for supplementation and early termination of breastfeeding. When addressing this concern, it is important first to consider the influence of maternal and neonatal health, infant suck, proper latch, and feeding frequency on milk production, and that steps be taken to correct or compensate for any contributing issues. Oral galactagogues are substances that stimulate milk production. They may be pharmacological or non-pharmacological (natural). Natural galactagogues are usually botanical or other food agents. The choice between pharmacological or natural galactagogues is often influenced by familiarity and local customs. Evidence for the possible benefits and harms of galactagogues is important for making an informed decision on their use., Objectives: To assess the effect of oral galactagogues for increasing milk production in non-hospitalised breastfeeding mother-term infant pairs., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), Health Research and Development Network - Phillippines (HERDIN), Natural Products Alert (Napralert), the personal reference collection of author LM, and reference lists of retrieved studies (4 November 2019)., Selection Criteria: We included randomised controlled trials (RCTs) and quasi-RCTs (including published abstracts) comparing oral galactagogues with placebo, no treatment, or another oral galactagogue in mothers breastfeeding healthy term infants. We also included cluster-randomised trials but excluded cross-over trials., Data Collection and Analysis: We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. Two to four review authors independently selected the studies, assessed the risk of bias, extracted data for analysis and checked accuracy. Where necessary, we contacted the study authors for clarification., Main Results: Forty-one RCTs involving 3005 mothers and 3006 infants from at least 17 countries met the inclusion criteria. Studies were conducted either in hospitals immediately postpartum or in the community. There was considerable variation in mothers, particularly in parity and whether or not they had lactation insufficiency. Infants' ages at commencement of the studies ranged from newborn to 6 months. The overall certainty of evidence was low to very low because of high risk of biases (mainly due to lack of blinding), substantial clinical and statistical heterogeneity, and imprecision of measurements. Pharmacological galactagogues Nine studies compared a pharmacological galactagogue (domperidone, metoclopramide, sulpiride, thyrotropin-releasing hormone) with placebo or no treatment. The primary outcome of proportion of mothers who continued breastfeeding at 3, 4 and 6 months was not reported. Only one study (metoclopramide) reported on the outcome of infant weight, finding little or no difference (mean difference (MD) 23.0 grams, 95% confidence interval (CI) -47.71 to 93.71; 1 study, 20 participants; low-certainty evidence). Three studies (metoclopramide, domperidone, sulpiride) reported on milk volume, finding pharmacological galactagogues may increase milk volume (MD 63.82 mL, 95% CI 25.91 to 101.72; I² = 34%; 3 studies, 151 participants; low-certainty evidence). Subgroup analysis indicates there may be increased milk volume with each drug, but with varying CIs. There was limited reporting of adverse effects, none of which could be meta-analysed. Where reported, they were limited to minor complaints, such as tiredness, nausea, headache and dry mouth (very low-certainty evidence). No adverse effects were reported for infants. Natural galactagogues Twenty-seven studies compared natural oral galactagogues (banana flower, fennel, fenugreek, ginger, ixbut, levant cotton, moringa, palm dates, pork knuckle, shatavari, silymarin, torbangun leaves or other natural mixtures) with placebo or no treatment. One study (Mother's Milk Tea) reported breastfeeding rates at six months with a concluding statement of "no significant difference" (no data and no measure of significance provided, 60 participants, very low-certainty evidence). Three studies (fennel, fenugreek, moringa, mixed botanical tea) reported infant weight but could not be meta-analysed due to substantial clinical and statistical heterogeneity (I 2 = 60%, 275 participants, very low-certainty evidence). Subgroup analysis shows we are very uncertain whether fennel or fenugreek improves infant weight, whereas moringa and mixed botanical tea may increase infant weight compared to placebo. Thirteen studies (Bu Xue Sheng Ru, Chanbao, Cui Ru, banana flower, fenugreek, ginger, moringa, fenugreek, ginger and turmeric mix, ixbut, mixed botanical tea, Sheng Ru He Ji, silymarin, Xian Tong Ru, palm dates; 962 participants) reported on milk volume, but meta-analysis was not possible due to substantial heterogeneity (I 2 = 99%). The subgroup analysis for each intervention suggested either benefit or little or no difference (very low-certainty evidence). There was limited reporting of adverse effects, none of which could be meta-analysed. Where reported, they were limited to minor complaints such as mothers with urine that smelled like maple syrup and urticaria in infants (very low-certainty evidence). Galactagogue versus galactagogue Eight studies (Chanbao; Bue Xue Sheng Ru, domperidone, moringa, fenugreek, palm dates, torbangun, moloco, Mu Er Wu You, Kun Yuan Tong Ru) compared one oral galactagogue with another. We were unable to perform meta-analysis because there was only one small study for each match-up, so we do not know if one galactagogue is better than another for any outcome., Authors' Conclusions: Due to extremely limited, very low certainty evidence, we do not know whether galactagogues have any effect on proportion of mothers who continued breastfeeding at 3, 4 and 6 months. There is low-certainty evidence that pharmacological galactagogues may increase milk volume. There is some evidence from subgroup analyses that natural galactagogues may benefit infant weight and milk volume in mothers with healthy, term infants, but due to substantial heterogeneity of the studies, imprecision of measurements and incomplete reporting, we are very uncertain about the magnitude of the effect. We are also uncertain if one galactagogue performs better than another. With limited data on adverse effects, we are uncertain if there are any concerning adverse effects with any particular galactagogue; those reported were minor complaints. High-quality RCTs on the efficacy and safety of galactagogues are urgently needed. A set of core outcomes to standardise infant weight and milk volume measurement is also needed, as well as a strong basis for the dose and dosage form used., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Rationale: Acute pain states in the trigeminal region (headaches, dental pain) fall into the most prevalent painful conditions. Standard analgesics (paracetamol/NSAIDs) represent the cornerstone of their treatment, whereas triptans are primarily used in migraine attacks. Due to limited efficacy and/or side effects of current treatments, identifying favorable combinations of available drugs is justified., Objectives: Eslicarbazepine acetate (ESL) is a novel antiepileptic drug whose effectiveness against trigeminal pain was recently demonstrated. Here, we examined the interactions between ESL and several standard/alternative analgesics (paracetamol, propyphenazone, naproxen, zolmitriptan, and metoclopramide) in a model of trigeminal pain., Methods: The antinociceptive effects of orally administered ESL, standard/alternative analgesics, and two-drug ESL-analgesic combinations were examined in the orofacial formalin test in mice. The type of interaction between drugs was determined by isobolographic analysis., Results: ESL, analgesics, and two-drug ESL-analgesic combinations significantly and dose-dependently reduced nociceptive behaviour in the second, inflammatory phase of the test. Isobolographic analysis revealed that ESL interacted additively with paracetamol/propyphenazone/zolmitriptan and synergistically with naproxen/metoclopramide (with about a 4-fold and 3-fold reduction of doses in the ESL-naproxen and ESL-metoclopramide combination, respectively)., Conclusions: ESL interacted in a beneficial manner with several analgesics that are used for trigeminal pain treatment, producing synergistic interactions with naproxen/metoclopramide and additive interactions with paracetamol/propyphenazone/zolmitriptan. Our results suggest that combining ESL with analgesics could theoretically enable the use of lower doses of individual drugs for achieving pain relief.

Background: The incidences of dystonic reactions to metoclopramide and prochlorperazine have not been well characterized in children., Methods: Medical record data were reviewed for patients at a tertiary care pediatric hospital who received metoclopramide or prochlorperazine for treatment of headache., Results: A total of 4588 clinical encounters were identified, 2542 with prochlorperazine and 2046 with metoclopramide. One patient had a dystonic reaction with metoclopramide (0.049%). Eleven patients had a dystonic reaction with prochlorperazine (0.43%). The relative risk of a dystonic reaction with prochlorperazine over metoclopramide is 8.85 (95% confidence interval 1.15 to 68.5). There were differences between groups of patients who received metoclopramide versus prochlorperazine in terms of age, number of doses, and coadministration of diphenhydramine. In a logistic regression, administration of prochlorperazine over metoclopramide (P = 0.019) and greater number of doses (P < 0.001) remained associated with acute dystonic reactions., Conclusions: Dystonic reactions are rare events among pediatric patients treated for acute headache, but are more common with prochlorperazine than metoclopramide., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To assess whether metoclopramide is effective in shortening the duration of the first stage of labor in primiparous women., Methods: The present randomized, double-blind, placebo-controlled trial was conducted at King Faisal Hospital, Saudi Arabia (between July 30, 2013, and September 1, 2016), and sequentially recruited young nulliparous women admitted in spontaneous active labor with or without ruptured membranes. Eligible participants were randomly assigned to receive a slow intravenous injection of either metoclopramide or placebo and consistently managed according to the local institutional intrapartum protocol and received identical monitoring and supportive care. The primary outcome was the cervical dilatation rate., Results: Fifty-nine women were included in the metoclopramide group and 52 in the placebo group. The first stage of labor was significantly shorter in the metoclopramide group (203 minutes vs 230 minutes in the placebo group, P=0.019), with a faster cervical dilatation rate (2.4 ± 0.4 cm/h vs 1.9 ± 0.5 cm/h in the placebo group, P<0.001) and shorter interval from treatment administration until full cervical dilatation. There was a significantly higher probability of faster delivery among women who were treated with metoclopramide (log-rank test, χ 2 =5.997, P=0.014)., Conclusion: Metoclopramide safely reduced the duration of the first stage of labor and was not associated with major maternal or neonatal adverse outcomes. CLINICALTRIALS.GOV: NCT01937234., (© 2019 International Federation of Gynecology and Obstetrics.)

Polycystic ovary syndrome (PCOS) as well as hyperprolactinemia can cause infertility. In retrospective study the prolactin levels during the oral metoclopramide test among lean PCOS woman according to four phenotypes and free androgen index (FAI) were compared. The study population consisted of 314 lean PCOS women. The population was divided into four groups according to the FAI and menstrual cycle regularity. The group A consisted 126 women with FAI≥5 and irregular menstruation, the group B- 53 patients with FAI≥5 and regular menstruation. Group C- 70 patients with FAI<5 and irregular menstruation, group D - 65 patients with FAI<5 and regular menstruation. The ratio of prolactin value in 120th minute in the metoclopramide test to the basal prolactin value was higher in group D than in groups A and B. The prolactin basal concentration was higher in patients with FAI≥5 than in patients with FAI<5, (262.9 vs 228.9 µIU/ml; p<0.001). The ratio of prolactin in 60th minute (12.3 vs 16.7; p=0.006) and in the 120th minute (10.9 versus 13.3; p<0.001) of the metoclopramide test to the basal prolactin were lower in patients with FAI≥5. The prolactin secretion in lean PCOS women may be associated with their FAI.

New Findings: What is the Central question? Does dopamine, a pulmonary vascular vasodilator, contribute to the regulation of pulmonary diffusing capacity and capillary blood volume responses to exercise and exercise tolerance? What are the main findings and their importance? Dopamine appears not to be important for regulating pulmonary diffusing capacity or pulmonary capillary blood volume during exercise in healthy participants. Dopamine blockade trials demonstrated that endogenous dopamine is important for maintaining exercise tolerance; however, exogenous dopamine does not improve exercise tolerance., Abstract: Pulmonary capillary blood volume (V c ) and diffusing membrane capacity (D m ) expansion are important contributors to the increased pulmonary diffusing capacity (DL CO ) observed during upright exercise. Dopamine is a pulmonary vascular vasodilator, and recent studies suggest that it may play a role in V c regulation through changes in pulmonary vascular tone. The purpose of this study was to examine the effect of exogenous dopamine and dopamine receptor-2 (D 2 -receptor) blockade on DL CO , V c and D m at baseline and during cycle exercise, as well as time-to-exhaustion at 85% of V ̇ O 2 peak . We hypothesized that dopamine would increase DL CO , V c , D m and time-to-exhaustion, while D 2 -receptor blockade would have the opposite effect. We recruited 14 young, healthy, recreationally active subjects ( V ̇ O 2 peak 45.8 ± 6.6 ml kg -1  min -1 ). DL CO , V c and D m were determined at baseline and during exercise at 60% and 85% of V ̇ O 2 peak under the following randomly assigned and double blinded conditions: (1) intravenous saline and placebo pill, (2) intravenous dopamine (2 µg kg -1  min -1 ) and placebo pill, and (3) intravenous saline and D 2 -receptor antagonist (20 mg oral metoclopramide). Exogenous dopamine and dopamine blockade had no effect on DL CO , V c and D m responses at baseline or during exercise. Dopamine blockade reduced time-to-exhaustion by 47% (P = 0.04), but intravenous dopamine did not improve time-to-exhaustion. While dopamine modulation did not affect DL CO , V c or D m , the reduction in time-to-exhaustion with D 2 -receptor blockade suggests that endogenous dopamine is important for exercise tolerance., (© 2019 The Authors. Experimental Physiology © 2019 The Physiological Society.)

Background: Postoperative Nausea and Vomiting (PONV) is a dreadful and uncomfortable experience that significantly detracts patients' quality of life after surgery. This study aimed to examine the antiemetic effect of a single sub-hypnotic dose of propofol as prophylaxis for PONV., Method: In this prospective, double-blind, randomized control trial, 345 parturients presented for elective cesarean section at the Obstetric unit of Tamale Teaching Hospital were recruited. Each recruited parturient was randomly assigned to one of three groups; Propofol group (n = 115) represented those who received propofol 0.5 mg/kg, Metoclopramide group (n = 115) represented those who received metoclopramide 10 mg and, Control group (n = 115) represented those who received 0.9% saline. Spinal anesthesia with 0.5% hyperbaric bupivacaine 7.5-10 mg, and intrathecal morphine 0.2 mg was employed for the anesthesia., Results: The data indicate that 108 (93.9%) parturients from the control group, 10 (8.7%) from the propofol group and 8 (7.0%) from the metoclopramide group experienced some incidence of PONV. There was no significant difference in the incidence of PONV (nausea, vomiting, and none) between the propofol and the metoclopramide groups (P = 0.99; 0.31; and 0.35 respectively). Parturients who received antiemetic agents were 105 (97.2%), 1 (10.0%) and 3 (37.5%) from the control, propofol and metoclopramide groups respectively. The data indicated that 98 (85.2%) parturients from the control, 3 (2.6%) from propofol group, and 100 (87.0%) from the metoclopramide group experienced some levels of pruritus. There was a significant difference in the incidence of pruritus (mild, moderate, and no pruritus) between the metoclopramide and propofol groups (P <  0.01; P <  0.01; and P <  0.01 respectively)., Conclusion: A sub-hypnotic dose of propofol is effective as metoclopramide in the prevention of PONV in parturient undergoing cesarean section under spinal anesthesia with intrathecal morphine. Sub-hypnotic dose of propofol significantly reduces the incidence of postoperative pruritus following intrathecal morphine use., Trial Registration: Current control trial, registered at ISRCTN trial registry: ISRCTN15475205 . Date registered: 03/04/2019. Retrospectively registered.

Objective: To investigate the prophylactic effectiveness of preoperative administration of maropitant citrate and metoclopramide hydrochloride in preventing postoperative clinical gastroesophageal reflux (GER) in dogs and to identify risk factors for clinical postoperative GER in dogs., Animals: 93 client-owned dogs undergoing surgery at the Washington State University Veterinary Teaching Hospital between March 2016 and February 2017., Procedures: Dogs were randomly assigned to either the intervention group (preoperatively received maropitant and metoclopramide) or the control group (did not preoperatively receive maropitant and metoclopramide). After surgery, all dogs were recovered and monitored, and occurrences of GER were noted. The prophylactic effectiveness of maropitant and metoclopramide was evaluated, and univariate and multivariate logistic regression analyses were performed to identify variables associated with postoperative clinical GER in dogs., Results: No meaningful difference in the incidence of clinical GER during the postoperative period was detected between the control and intervention groups. Results indicated that variables associated with significantly increased odds of postoperative clinical GER included the male sex (OR, 9.2; 95% confidence interval [CI], 1.26 to 195.0), an overweight BCS (OR, 12.3; 95% CI, 2.1 to 135.1), gastrointestinal surgery (OR, 30.5; 95% CI, 3.0 to 786.9), and requirement for a dexmedetomidine constant rate infusion after surgery (OR, 9.6; 95% CI, 1.3 to 212.5)., Conclusions and Clinical Relevance: Findings indicated that incidence of clinical GER during the postoperative period was not lower for dogs that received preoperative prophylactic administration of metoclopramide and maropitant, compared with incidence dogs that did not receive the prophylactic treatment. Further research is required into alternative measures to prevent postoperative clinical GER in dogs.

Dexamethasone, metoclopramide, ketorolac, and chlorpromazine have been used for the treatment of migraine headache. However, the effectiveness of these drugs in pain relief and prevention of recurrence and their side effects have not been compared yet. This was a randomized, double-blind clinical trial. Subjects were randomized to four groups; each received one of the following drugs intravenously: dexamethasone 8 mg, ketorolac 30 mg, metoclopramide 10 mg, and chlorpromazine 25 mg. The severity of headache in the two groups was assessed at starting point, 1 h and 24 h after the administration of drug using the visual analogue scale (VAS) on a scale of 0 to 10. No significant difference was found in the severity of symptoms between the four study groups before treatment, 1 h, and 24 h after treatment. The effect of all mentioned drugs on acute migraine headache was statistically significant at 1 and 24 h post-treatment compared to baseline. No significant difference was detected in the number of unresponsive cases between the four groups. There was a trend toward higher effectiveness of dexamethasone in prevention of recurrence (P = 0.05). Side effects were more common in chlorpromazine and less common in the dexamethasone-treated patients (P < 0.001). The present clinical trial shows the effectiveness of dexamethasone in prevention of recurrence and low frequency of treatment side effects.

Objectives: The present study aimed to evaluate the efficacy and safety of intravenous metoclopramide for acute migraine treatment., Materials and Methods: A double-blind, randomized, parallel-group, placebo-controlled trial was carried out in an academic emergency department. After the patients were assessed for eligibility via the International Headache Society criteria for migraines, they were randomized into 10 mg intravenous metoclopramide and normal saline groups. The headache intensity was evaluated using an 11-point numeric rating scale (NRS) score. The primary outcome measure was determined as the median between-group change in the score at the 30th minute. The secondary outcome measures were rescue medication needs, adverse events, and emergency department (ED) revisits after discharge., Results: A total of 148 patients were randomized into two equal groups with similar baseline characteristics, including the baseline NRS scores (8 points). The median reduction in the NRS scores at the 30th minute was 4 [interquartile range (IQR): 2-6)] in the metoclopramide group and 3 (IQR: 1-4) in the normal saline group [median difference: -1.0, 95% confidence interval (CI): -2.1 to 0.1]. No serious adverse events were observed, and the rescue medication needs were similar in both groups., Conclusion: No difference was found between intravenous metoclopramide and placebo regarding efficacy and safety in patients with acute migraines., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Headache is a common chief complaint in the emergency department (ED) setting., Objectives: To compare analgesia with metoclopramide and diphenhydramine vs. intranasal ketamine among ED patients with primary headache., Methods: We enrolled a convenience sample of adults with a primary headache in a randomized, single-blind, placebo-controlled trial. We randomized patients to either a control arm (intravenous metoclopramide and diphenhydramine) or intranasal ketamine. The primary outcome was change in pain 0-100 mm visual analog scale (VAS) score measured at study start and 30 min post completion of initial medication administration. Secondary outcomes included side effects, hospital admission, and return to care within 48-72 h., Results: All 53 enrolled subjects completed the study, 26 of whom were allocated to the control arm and 27 to intranasal ketamine. The mean change in pain VAS score at 30 min post intervention was 22.2 mm in the control arm vs. 29.0 in the intranasal ketamine arm (effect size difference 6.8 mm, 95% confidence interval -5.8-19.4). The incidence of reported side effects was 65.4% in the control arm vs. 66.7% in the ketamine arm. Three patients (11.5%) allocated to the control arm required admission for headache pain control vs. 1 patient (3.7%) in the intranasal ketamine arm. Three (11.5%) additional patients in the control arm returned to the ED within 48-72 h for headache pain vs. none in the ketamine arm., Conclusions: In this small randomized study, intranasal ketamine was not superior to standard therapy among ED patients with primary headache syndromes., (Published by Elsevier Inc.)