Effect of acupuncture on the prevention of nausea and vomiting after laparoscopic cholecystectomy: a randomized clinical trial / Efeitos da acupuntura para a prevenção de náuseas e vômitos após colecistectomia laparoscópica: estudo clínico randomizado

Abstract 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 2 h (p= 0.03) and 6 h (p= 0.001) after surgery and fewer vomiting events 2 h (p= 0.01) and 6 h (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.

Resumo Justificativa e objetivos: Náuseas e vômitos são complicações comuns e indesejáveis no pós-operatório de colecistectomia laparoscópica (CL). Nós investigamos os efeitos da auriculoacupuntura (AA) para a prevenção de náuseas e vômitos no período pós-operatório (NVPO) imediato da CL não complicada. Métodos: 68 pacientes foram aleatoriamente divididos em dois grupos, auriculoacupuntura (n = 35) e controle (n = 33), e foram avaliados prospectivamente. A agulha foi aplicada antes da indução anestésica e permaneceu no lugar por 20 minutos. A intensidade da náusea foi avaliada mediante escala visual analógica e episódios de NVPO foram registrados imediatamente após a admissão na unidade de recuperação anestésica e duas, quatro e seis horas após a cirurgia. Resultados: O grupo AA apresentou significativamente menos episódios de NVPO do que o grupo controle durante todo o período pós-operatório (16/35 vs. 27/33, p = 0,03 e 4/35 vs. 15/33, p = 0,005, respectivamente). O grupo auriculoacupuntura apresentou episódios de náuseas menos intensos às 2 horas (p = 0,03) e 6 horas (p = 0,001) após a cirurgia e menos episódios de vômitos 2 horas (p = 0,01) e 6 horas (p = 0,02) após a cirurgia. Conclusão: A auriculoacupuntura aliviou náuseas e vômitos no pós-operatório em número significante de pacientes, mas não foi capaz de prevenir náuseas e vômitos no pós-operatório em todos os pacientes. Ela pode ser recomendada como terapia adjuvante para prevenção de náuseas e vômitos no pós-operatório no pós-operatório de colecistectomia laparoscópica em pacientes selecionados.

[Effect of acupuncture on the prevention of nausea and vomiting after laparoscopic cholecystectomy: a randomized clinical trial]. / Efeitos da acupuntura para a prevenção de náuseas e vômitos após colecistectomia laparoscópica: estudo clínico randomizado.

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.

Wild Leporinus friderici induced spawning with different dose of mGnRHa and metoclopramide or carp pituitary extract

Breeding technology is of utmost importance for reproduction of wild fish in captivity for the reintroduction and selective breeding programs purposes. The main challenge is that when applied to wild undomesticated specimens, conventional protocols often cause breeders and/or embryo mortality and spawning failure. In this study, we evaluated the reproductive performance of wild Leporinus friderici, a great importance fish for subsistence fishing in South American rivers, applying conventional and lower-dose hormonal therapies by means of two consecutive experiments. In the first, a conventional (0.5 and 5.5 mg/kg) and a lower carp pituitary extract (CPE) dose (0.5 and 1.0 mg/kg) were applied. In the second, a conventional mammalian GnRH analogue associated with metoclopramide (mGnRHa + MET) (40 µg mGnRHa + 20 mg MET/kg) and a lower dose (4 μg mGnRHa + 2 mg MET/kg and 8 µg + 4 mg of mGnRHa + MET/kg) were applied. Ovulation was observed in all treatments, however, only lower CPE protocol provided viable embryos. High levels of 17α,20β-dihydroxy-4-pregnen-3-one (DHP) and 17β estradiol (E2) detected in conventional, but not in lower CPE dose, at ovulation, might be associated to the mortality of the embryos. The use of lower CPE dose applied here was the best way to obtain L. friderici viable embryos. These results directly contribute to the knowledge about poorly explored effects of reproductive management and hormonal therapies in wild-type breeders, showing that the use of reduced doses may be an alternative to reproductive success.

Wild Leporinus friderici induced spawning with different dose of mGnRHa and metoclopramide or carp pituitary extract

Breeding technology is of utmost importance for reproduction of wild fish in captivity for the reintroduction and selective breeding programs purposes. The main challenge is that when applied to wild undomesticated specimens, conventional protocols often cause breeders and/or embryo mortality and spawning failure. In this study, we evaluated the reproductive performance of wild Leporinus friderici, a great importance fish for subsistence fishing in South American rivers, applying conventional and lower-dose hormonal therapies by means of two consecutive experiments. In the first, a conventional (0.5 and 5.5 mg/kg) and a lower carp pituitary extract (CPE) dose (0.5 and 1.0 mg/kg) were applied. In the second, a conventional mammalian GnRH analogue associated with metoclopramide (mGnRHa + MET) (40 µg mGnRHa + 20 mg MET/kg) and a lower dose (4 μg mGnRHa + 2 mg MET/kg and 8 µg + 4 mg of mGnRHa + MET/kg) were applied. Ovulation was observed in all treatments, however, only lower CPE protocol provided viable embryos. High levels of 17α,20β-dihydroxy-4-pregnen-3-one (DHP) and 17β estradiol (E2) detected in conventional, but not in lower CPE dose, at ovulation, might be associated to the mortality of the embryos. The use of lower CPE dose applied here was the best way to obtain L. friderici viable embryos. These results directly contribute to the knowledge about poorly explored effects of reproductive management and hormonal therapies in wild-type breeders, showing that the use of reduced doses may be an alternative to reproductive success.(AU)

[Extrapyramidal adverse reactions to metoclopramide. A pharmacovigilance survey]. / Farmacovigilancia activa de metoclopramida 10 mg oral en pacientes del Programa de Alivio del Dolor y Cuidados Paliativos o diabetes mellitus tipo 2 en cinco hospitales del Servicio de Salud Viña del Mar-Quillota.

BACKGROUND: In 2013 the Chilean regulatory sanitary agency issued a warning concerning dose adjustment and use restriction to avoid severe adverse effects of metoclopramide such tardive dyskinesia. AIM: To study dyskinesia type adverse effects in a population using metoclopramide. MATERIAL AND METHODS: A cross sectional observational study was conducted among patients pertaining to palliative care and diabetes mellitus programs and consuming 10 mg/day or more of metoclopramide. Patients were interrogated looking for extrapiramidal signs and symptoms using a questionnaire validated by two neurologists. RESULTS: In 40% of diabetic patients with gastroparesia and 35% of palliative care patients, extrapyramidal adverse reactions to metoclopramide were suspected. Palliative Care patients suffered the largest number of adverse events. The period of use and individual doses of the drug were largely above Chilean regulatory agency recommendations in all cases. CONCLUSIONS: A significant number of patients using metoclopramide could experience extrapyramidal adverse reactions.

Farmacovigilancia activa de metoclopramida 10 mg oral en pacientes del Programa de Alivio del Dolor y Cuidados Paliativos o diabetes mellitus tipo 2 en cinco hospitales del Servicio de Salud Viña del Mar-Quillota / Extrapyramidal adverse reactions to metoclopramide: a pharmacovigilance survey

Background: In 2013 the Chilean regulatory sanitary agency issued a warning concerning dose adjustment and use restriction to avoid severe adverse effects of metoclopramide such tardive dyskinesia. Aim: To study dyskinesia type adverse effects in a population using metoclopramide. Material and Methods: A cross sectional observational study was conducted among patients pertaining to palliative care and diabetes mellitus programs and consuming 10 mg/day or more of metoclopramide. Patients were interrogated looking for extrapiramidal signs and symptoms using a questionnaire validated by two neurologists. Results: In 40% of diabetic patients with gastroparesia and 35% of palliative care patients, extrapyramidal adverse reactions to metoclopramide were suspected. Palliative Care patients suffered the largest number of adverse events. The period of use and individual doses of the drug were largely above Chilean regulatory agency recommendations in all cases. Conclusions: A significant number of patients using metoclopramide could experience extrapyramidal adverse reactions.

Bromopride, metoclopramide, or ondansetron for the treatment of vomiting in the pediatric emergency department: a randomized controlled trial / Bromoprida, metoclopramida ou ondansetrona no tratamento de vômito no departamento de emergência pediátrica: ensaio controlado randomizado

Abstract Objective: To compare the effectiveness of a single intramuscular dose of bromopride, metoclopramide, or ondansetron for treating vomiting. Methods: Randomized controlled trial including children 1-12 years of age presenting with acute vomiting at the pediatric emergency department. Outcomes: Number of children that stopped vomiting at one, six, and 24 h following treatment; episodes of diarrhea; acceptance of oral liquids; intravenous rehydration; return to hospital and side effects. Results: There were 175 children who completed the study. Within the first hour after treatment, all drugs were equally effective, with ondansetron preventing vomiting in 100%, bromopride in 96.6%, and metoclopramide in 94.8% of children (p = 0.288). Within six hours, ondansetron was successful in preventing vomiting in 98.3% of children, compared to bromopride and metoclopramide, which were successful in 91.5% and 84.4% of patients, respectively (p = 0.023). Within 24 h, ondansetron was superior to both other agents, as it remained efficacious in reducing vomiting in 96.6% of children, as opposed to 67.8% and 67.2% with bromopride and metoclopramide, respectively (p = 0.001). The ondansetron group showed better acceptance of oral liquids (p = 0.05) when compared to the bromopride and metoclopramide. The ondansetron group did not show any side effects in 75.9% of cases, compared to 54.2% and 53.5% in the bromopride and metoclopramide groups, respectively. Somnolence was the most common side effect. Conclusions: A single dose of ondansetron is superior to bromopride and metoclopramide in preventing vomiting six hours and 24 h following treatment. Oral fluid intake after receiving medication was statistically better with Ondansetronwhile also having less side effects compared to the other two agents.

Resumo Objetivo: Para comparar a eficacia de uma unica dose intramuscular de bromoprida, metoclopramida ou ondansetrona no tratamento de vomito. Métodos: Ensaio controlado randomizado incluindo crianc¸as de 1 a 12 anos de idade que apresentam vomito agudo no departamento de emergencia pediatrica. Desfechos: Numero de crianças que pararam de vomitar 1, 6 e 24 horas apos o tratamento; episodios de diarreia; aceitac¸ao de liquidos orais; reidratac¸ao intravenosa, retorno ao hospital e efeitos colaterais. Resultados: 175 crianças concluiram o estudo. Na primeira hora apos o tratamento, todos os medicamentos foram igualmente eficazes, sendo que a ondansetrona preveniu vomito em 100%, a bromoprida em 96,6% e metoclopramida em 94,8% das crianças (p = 0,288). Em 6 horas, a ondansetrona mostrou sucesso na prevençao do vomito em 98,3% das crianças, em comparac¸ao a bromoprida e a metoclopramida, que mostraram sucesso em 91,5% e 84,4% dos pacientes, respectivamente (p = 0,023). Em 24 horas, a ondansetrona foi superior aos dois outros agentes, pois ela continuou eficaz na reduçao do vomito em 96,6% das crianças, diferente de 67,8% e 67,2% com bromoprida e metoclopramida, respectivamente (p = 0,001). O grupo de ondansetrona mostrou melhor aceitaçao de liquidos orais (p = 0,05) em comparaçao a bromoprida e metoclopramida. O grupo de ondansetrona nao mostrou efeitos colaterais em 75,9% dos casos, em comparaçao a 54,2% e 53,5% dos grupos de bromoprida e metoclopramida. O efeito colateral mais comum foi sonolencia. Conclusões: Uma unica dose de ondansetrona e superior a bromoprida e metoclopramida no tratamento de vomito 6 horas e 24 horas apos o tratamento. A ingestao de fluidos orais apos receber medicaçao foi estatisticamente melhor com ondansetrona, ao mesmo tempo em que tambem apresentando menos efeitos colaterais em comparaçao aos outros dois agentes.

Bromopride, metoclopramide, or ondansetron for the treatment of vomiting in the pediatric emergency department: a randomized controlled trial.

OBJECTIVE: To compare the effectiveness of a single intramuscular dose of bromopride, metoclopramide, or ondansetron for treating vomiting. METHODS: Randomized controlled trial including children 1-12 years of age presenting with acute vomiting at the pediatric emergency department. OUTCOMES: Number of children that stopped vomiting at one, six, and 24h following treatment; episodes of diarrhea; acceptance of oral liquids; intravenous rehydration; return to hospital and side effects. RESULTS: There were 175 children who completed the study. Within the first hour after treatment, all drugs were equally effective, with ondansetron preventing vomiting in 100%, bromopride in 96.6%, and metoclopramide in 94.8% of children (p=0.288). Within six hours, ondansetron was successful in preventing vomiting in 98.3% of children, compared to bromopride and metoclopramide, which were successful in 91.5% and 84.4% of patients, respectively (p=0.023). Within 24h, ondansetron was superior to both other agents, as it remained efficacious in reducing vomiting in 96.6% of children, as opposed to 67.8% and 67.2% with bromopride and metoclopramide, respectively (p=0.001). The ondansetron group showed better acceptance of oral liquids (p=0.05) when compared to the bromopride and metoclopramide. The ondansetron group did not show any side effects in 75.9% of cases, compared to 54.2% and 53.5% in the bromopride and metoclopramide groups, respectively. Somnolence was the most common side effect. CONCLUSIONS: A single dose of ondansetron is superior to bromopride and metoclopramide in preventing vomiting six hours and 24h following treatment. Oral fluid intake after receiving medication was statistically better with Ondansetronwhile also having less side effects compared to the other two agents.

La metoclopramida en perfusión miocárdica con 99MTC-MIBI y la calidad de imágenes en estudios isotópicos. Hospital Militar Central, junio 2014 - julio 2015 / Metoclopramide in myocardial perfusion with 99mTc-MIBI and quality of images in isotopic studies. Central Military Hospital, June 2014 - July 2015

Objetivo: Determinar la influencia del uso de la metoclopramida durante la perfusión miocárdica con 99mTc-MIBI en la calidad de imágenes de estudios isotópicos realizados en el servicio de medicina nuclear del Hospital Militar Central durante junio del 2014 y julio del 2015. Material y métodos: estudio de tipo explicativo, retrospectivo y transversal. Para el estudio se trabajó con dos grupos: el primero 69 imágenes de perfusiones miocárdicas con uso de metoclopramida y el segundo 65 imágenes sin uso de metoclopramida con 99mTc-MIBI en el servicio de medicina nuclear del Hospital Militar Central durante los meses de junio del 2014 y julio del 2015. El programa estadístico utilizado fue SPSS v.21, utilizándose un análisis univariado de la calidad de imagen por medio de: valores mínimo, máximo, media y desviación estándar; para el análisis bivariado se comparó la calidad de imagen por medio de la prueba U de Mann-Whitney, usando previamente la prueba de Kolmogorov - Smirnov, trabajando con un nivel de significancia de 5 por ciento. Resultados: el 7.2 por ciento de los usuarios que usaron metoclopramida y el 18.5 por ciento que no usaron metoclopramida fueron de sexo femenino, el 92.8 por ciento de los usuarios que usaron metoclopramida y el 81.5 por ciento que no usaron metoclopramida fueron de sexo masculino. Al compararse la calidad de imagen entre los grupos de estudio en la condición de estrés para aquellos pacientes con uso de fármaco se encontró una diferencia muy significativa entre ambas (p=0,010) y al comparar la calidad de imagen entre los grupos de estudio en la condición de reposo para aquellos pacientes con esfuerzo físico, no se encontró diferencia significativa entre ambas (p=0,125). Cuando se comparó la calidad de imagen entre los grupos de estudio en la condición de estrés, se encontró una diferencia altamente significativa entre ambas (p<0,001), es decir, en los pacientes donde se empleó la metoclopramida se obtuvo una menor calidad de imagen...

Objective: to determine the influence of the use of metoclopramide during myocardial perfusion imaging with 99mTc-MIBI of images in the quality of isotopic studies in nuclear medicine service Central Military Hospital during June 2014 and July 2015. Methodology: explicative study, retrospective and transversal. For the study we worked with two groups: the first 69 images of myocardial perfusions with use of metoclopramide and the second 65 images without the use of metoclopramide with 99mTc-MIBI in the nuclear medicine service of the Central Military Hospital during the months of June 2014 and July 2015. The statistical program used was SPSS v.21, using a univariate analysis of image quality through: minimum, maximum, mean and standard deviation values; bivariate analysis for image quality was compared using the Mann- Whitney U test, previously using the Kolmogorov - Smirnov, working with a significance level of 5 per cent. Results: 7.2 per cent of users who used metoclopramide and 18.5 per cent who did not use metoclopramide were female, 92.8 per cent of users who used metoclopramide and 81.5 per cent who did not use metoclopramide were male. When comparing the picture quality between the study groups in the condition of stress for those patients using the drug was found a very significant difference between the two (p=0.010) and comparing the picture quality between the study groups in found rest condition for patients with physical effort, was found no significant difference between the two (p=0.125). When the image quality was compared between the study groups in the stress condition, a highly significant difference between the two was observed (p<0.001), ie in patients where metoclopramide is used a lower image quality was obtained was found than those who are not employed and comparing the picture quality between the study groups in the idle condition, a significant difference between the two (p=0.114) was not found. Conclusions: The metoclopramide...

Effects of metoclopramide-induced hyperprolactinemia on the prolactin and prolactin receptor expression of murine adrenal.

The aim of this study was to evaluate the effects of metoclopramide-induced hyperprolactinemia on the prolactin (PRL) and prolactin receptor's (PRLR) expression in the adrenal. For this purpose, a total of 12 animals with intact ovaries were allocated to two groups: G1 (saline solution) and G2 (metoclopramide). A total of 30 oophorectomized animals was randomized to five subgroups: G3 (saline solution), G4 (metoclopramide), G5 (metoclopramide + 17ß-estradiol), G6 (metoclopramide + progesterone), and G7 (metoclopramide + 17ß-estradiol + progesterone). Immunohistochemical analyses were evaluated semi-quantitatively. For PRLR, the area fraction of labeled cells (ALC) varied from 1 (0-10%) to 3 (> 50%). Based on the mean of the immunostaining intensity, G2 and G4 showed strong expression; G6 and G7 presented a mild reaction; and G1, G3, and G5 exhibited a weak reaction. Concerning PRL, the ALC varied from 1 (0-10%) to 3 (> 50%), and groups G6 and G7 showed a strong reaction; G2, G4, and G5 showed a mild reaction; and G1 and G3 exhibited a weak reaction. These findings suggest that metoclopramide-induced hyperprolactinemia increases PRL expression in the adrenal glands of mice. Furthermore, progesterone alone or in association with estrogen also increases PRL expression, but to a lesser extent.

Efectos extrapiramidales por metoclopramida en embarazo y recién nacido / Extrapyramidal effects for metoclopramide in pregnancy and newborn

Las náuseas y la emesis son complicaciones posoperatorias que pueden derivar en bronco aspiración, una situación clínica potencialmente fatal. Para su prevención, se usan medicamentos como la metoclopramida. Se presenta un reporte de caso de extrapiramidalismo por metoclopramida en el recién nacido y la madre. Es una reacción secundaria a un medicamento, clasificada como un evento serio y definitivo, de tipo A. Se requiere considerar el balance entre riesgo y beneficio de este medicamento en este tipo de condiciones, como también considerar otras medidas que eviten estos casos. El reporte de reacciones adversas a medicamentos es una actividad que contribuye al uso seguro de los medicamentos.

Postoperative nauseas and vomiting are complications that can lead to bronchoaspiration, a potentially fatal clinical event. Medications such as metoclopramide are used to prevent them. A case report of extrapyramidal signs in a newborn and mother metoclopramide is presented. It has been classified as a serious drug reaction, type A. The risk-benefit balance of this drug in such conditions should be considered as well as other measures to prevent such events. The reporting of adverse drug reactions is an activity that contributes to the safe use of medicines.

Effect of dimeticone and pepsin on the bioavailability of metoclopramide in healthy volunteers.

OBJECTIVE: To assess the effect of dimeticone and pepsin on the bioavailability of metoclopramide (CAS 7232-21-5) in healthy volunteers. METHODS: The study was conducted using a randomized, open, 2-period crossover design. The volunteers received single administration of 7-mg conventional metoclopramide capsule and a formulation containing metoclopramide (7 mg) plus dimeticone (40 mg) and pepsin (50 mg), with a 7-day interval between treatments. Serial blood samples were collected before dosing and during 24 h post-treatment. Plasma metoclopramide concentrations were analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The pharmacokinetics parameters AUC(last) and C(max) were obtained from the metoclopramide plasma concentration vs. time curves. RESULTS: Metoclopramide's association was bioequivalent to conventional capsule; 90% CIs for geometric mean treatment ratios of C(max) [108.0% (90% CI, 100.4-116.3%)], AUC(last) [103.3% (90% CI, 99.5-107.4%)] were within the predefined range. The metoclopramide formulations were well tolerated at the administered doses and no significant adverse reactions were observed. Thus, these results confirm the good bioavailability of metoclopramide in the new formulation and rule out any impaired absorption when the drugs are formulated in combination.

Tolerance to enteral nutrition therapy in traumatic brain injury patients.

OBJECTIVE: To evaluate the tolerance to enteral nutrition (EN) and the effects of pro-kinetic drugs in critical traumatic brain injury (TBI) patients. METHODS: Transversal observational study. A total of 32 out of 45 TBI patients of both genders receiving EN were evaluated in a trauma referral hospital intensive care unit (ICU). Data from each patient were collected for a period of 10 consecutive days after initiation of enteral feeding: gastric residue, presence of vomiting, abdominal distension, Glasgow coma scale and the use of pro-kinetic agents. RESULTS: In 20 of the 32 patients high levels of gastric residue were found. Of these 20 patients, half could not tolerate the diet within the first 72 hours following infusion. However, no association was found between disease severity and occurrence of gastrointestinal complications (p > 0.05). Feeding intolerance was observed in 75.0% (n = 24) of patients, even with the systematic use of metaclopramide from the outset of nutritional therapy. All patients with feeding intolerance who used erythromycin by nasogastric tube showed improvement. CONCLUSIONS: The high level of gastric residue was the most common feeding intolerance and the delivery of erythromycin by nasogastric tube seems to control gastrointestinal disorders in TBI patients.

Comparison of the pharmacokinetics of a new 30 mg modified-release tablet formulation of metoclopramide for once-a-day administration versus 10 mg immediate-release tablets: a single and multiple-dose, randomized, open-label, parallel study in healthy male subjects.

The study aimed to assess the pharmacokinetics of a new, modified-release metoclopramide tablet, and compare it to an immediate-release tablet. A single and multiple-dose, randomized, open-label, parallel, pharmacokinetic study was conducted. Investigational products were administered to 26 healthy Hispanic Mexican male volunteers for two consecutive days: either one 30 mg modified-release tablet every 24 h, or one 10 mg immediate-release tablet every 8 h. Blood samples were collected after the first and last doses of metoclopramide. Plasma metoclopramide concentrations were determined by high-performance liquid chromatography. Safety and tolerability were assessed through vital signs measurements, clinical evaluations, and spontaneous reports from study subjects. All 26 subjects were included in the analyses [mean (SD) age: 27 (8) years, range 18-50; BMI: 23.65 (2.22) kg/m², range 18.01-27.47)]. Peak plasmatic concentrations were not statistically different with both formulations, but occurred significantly later (p < 0.05) with the modified-release form [tmax: 3.15 (1.28) vs. 0.85 (0.32) h and tmax-ss: 2.92 (1.19) vs. 1.04 (0.43) h]. There was no difference noted in the average plasma concentrations [Cavgτ: 23.90 (7.90) vs. 20.64 (7.43) ng/mL after the first dose; and Cavg-ss: 31.14 (9.64) vs. 35.59 (12.29) ng/mL after the last dose, (p > 0.05)]. One adverse event was reported in the test group (diarrhea), and one in the reference group (headache). This study suggests that the 30 mg modified-release metoclopramide tablets show features compatible with slow-release formulations when compared to immediate-release tablets, and is suitable for once-a-day administration.

Strategic pain management: the identification and development of the IAHPC opioid essential prescription package.

The aim of this study was to determine by consensus the components of an opioid essential prescription package (OEPP) to be used when initiating a prescription for the control of moderate to severe chronic pain. Palliative care physicians (n=60) were sampled from the International Association for Hospice and Palliative Care (IAHPC) membership list to represent a range of countries of varying economic levels and diverse geographical regions. Using a Delphi study method, physicians were asked to rank preferences of drug and dosing schedule for first-line opioid, antiemetic, and laxative for the treatment of adults with chronic pain due to cancer and other life-threatening conditions. Overall response rates after two Delphi survey rounds were 95% (n=57) and 82% (n=49), respectively. A consensus (set at ≥75% agreement) was reached to include morphine as first-line opioid at a dose of 5 mg orally every 4 hours. Consensus was reached to include metoclopramide as a first-line antiemetic, but there was no consensus on "regular" or "as needed" administration. No consensus was reached regarding a first-line laxative, but a combination of senna and docusate secured 59% agreement. There was consensus (93% agreement) that laxatives should always be given regularly when opioid treatment is started. Further work is needed to establish a recommended dose of metoclopramide and a type and dose of laxative. The resulting OEPP is international in scope and is designed to ensure that opioids are better tolerated by reducing adverse effects of opioids, which could lead to more sustained improvements in pain management.

Case-crossover study of Burkholderia cepacia complex bloodstream infection associated with contaminated intravenous bromopride.

OBJECTIVE: To investigate an outbreak of healthcare-associated Burkholderia cepacia complex (BCC) primary bloodstream infections (BCC-BSI). DESIGN AND SETTING: Case-crossover study in a public hospital, a university hospital and a private hospital in Rio de Janeiro, Brazil, from March 2006 to May 2006. PATIENTS: Twenty-five patients with BCC-BSI. DESIGN: After determining the date BCC-BSI symptoms started for each patient, 3 time intervals of data collection were defined, each one with a duration of 3 days: the case period, starting just before BCC-BSI symptoms onset; the control period, starting 6 days before BCC-BSI symptoms onset; and the washout period, comprising the 3 days between the case period and the control period. Exposures evaluated were intravascular solutions and invasive devices and procedures. Potential risk factors were identified by using the McNemar chi(2) adjusted test. Cultures of samples of potentially contaminated solutions were performed. BCC strain typing was performed by pulsed-field gel electrophoresis using SpeI. RESULTS: The statistical analysis revealed that the use of bromopride and dipyrone was associated with BCC-BSI. A total of 21 clinical isolates from 17 (68%) of the 25 patients and an isolate obtained from the bromopride vial were available for strain typing. Six pulsotypes were detected. A predominant pulsotype (A) accounted for 11 isolates obtained from 11 patients (65%) in the 3 study hospitals. CONCLUSION: Our investigation, using a case-crossover design, of an outbreak of BCC-BSI infections concluded it was polyclonal but likely caused by infusion of contaminated bromopride. The epidemiological finding was validated by microbiological analysis. After recall of contaminated bromopride vials by the manufacturer, the outbreak was controlled.