Misoprostol administered sublingually at a dose of 12.5 µg versus vaginally at a dose of 25 µg for the induction of full-term labor: a randomized controlled trial.

BACKGROUND: Labor induction is defined as any procedure that stimulates uterine contractions before labor begins spontaneously. The vaginal and oral routes of administration of misoprostol are those most used for the induction of labor in routine practice, with the recommended dose being 25 µg. Nevertheless, the sublingual route may reduce the number of vaginal examinations required, increasing patient comfort and lowering the risk of maternal and fetal infection. Based on a previous systematic review, the objective of this study was to compare the frequency of tachysystole as the main outcome measure when misoprostol is administered sublingually at the dose of 12.5 µg versus vaginally at a dose of 25 µg to induce labor in a full-term pregnancy with a live fetus. METHODS: A randomized, placebo-controlled, triple-blind clinical trial was conducted at two maternity hospitals in northeastern Brazil. Two hundred patients with a full-term pregnancy, a live fetus, Bishop score ≤ 6 and an indication for induction of labor were included. Following randomization, one group received 12.5 µg misoprostol sublingually and a vaginal placebo, while the other group received a sublingual placebo and 25 µg misoprostol vaginally. The primary outcome was the frequency of tachysystole. Student's t-test, the chi-square test of association and Fisher's exact test were used, as appropriate. Risk ratios and their 95% confidence intervals were calculated. RESULTS: The frequency of tachysystole was lower in the group using 12.5 µg misoprostol sublingually compared to the group using 25 µg misoprostol vaginally (RR = 0.15; 95%CI: 0.02-0.97; p = 0.002). Failure to achieve vaginal delivery within 12 and 24 h was similar in both groups. Sublingual administration was preferred to vaginal administration by women in both groups; however, the difference was not statistically significant. CONCLUSION: The effectiveness of labor induction with low-dose sublingual misoprostol was similar to that achieved with vaginal administration of the recommended dose; however, the rate of tachysystole was lower in the sublingual group, and this route of administration may prove a safe alternative. TRIAL REGISTRATION: Registration number: NCT01406392, ClinicalTrials.gov. Date of registration: August 1, 2011.

Mucosal bacterial vaccines in clinical practice - a novel approach to an old problem?

SUMMARY OBJECTIVES To evaluate the efficacy of mucosal bacterial vaccines (MBV) in reducing the number of exacerbations in patients with chronic respiratory disease. METHODS A prospective cohort study of patients followed at the Pneumology Unit of the University and Hospital Centre of Coimbra, with frequent infectious exacerbations (3 or more) despite the best therapeutic strategies employed. MBV was used as additional therapy. The number of exacerbations 1 year before therapy and 1 year after it were analyzed. RESULTS A sample of 11 individuals, 45.5% male, mean age 62.5 years. Eight patients had non-cystic fibrosis bronchiectasis, 2 COPD (1 on long-term oxygen therapy), and 1 patient with Mounier Kuhn's syndrome. Three patients were on azithromycin, 1 on inhaled colistin, and 2 on inhaled tobramycin. Out of the 11 patients, one presented complication (fever), which led to a suspension of therapy (excluded from results). Of the 10 patients who completed treatment, 5 had bacterial colonization and were submitted to a custom vaccine. The remaining 6 completed the standard composition. The average of infectious exacerbations in the previous year was 4.3 (0.7 with hospitalization). In the year after therapy, the mean number was 1.5 (0.5 with hospitalization). CONCLUSION The results obtained in this study favor the use of bacterial immunostimulation to reduce the frequency of RRIs in patients with chronic respiratory disease.

RESUMO OBJETIVO Avaliar a eficácia de vacinas bacterianas de mucosa (MBV) na redução do número de exacerbações de pacientes com doença respiratória crônica. MÉTODOS Um estudo de coorte prospectivo incluindo pacientes da Unidade de Pneumologia da Universidade e Centro Hospitalar de Coimbra, com exacerbações infecciosas frequentes (3 ou mais), apesar do uso das melhores estratégias terapêuticas. MBVs foram usadas como terapia adicional. O número de exacerbações 1 ano antes da terapia e 1 ano após ela foram analisados. RESULTADOS Amostra incluiu 11 indivíduos, 45,5% do sexo masculino, com média de idade de 62,5 anos. Oito pacientes apresentaram bronquiectasia não relacionada à fibrose cística, 2 DPOC (1 em oxigenoterapia prolongada) e 1 paciente com síndrome de Mounier-Kuhn. Três pacientes estavam sendo medicados com azitromicina, 1 com colistina inalada e 2 com tobramicina inalada. Dos 11 pacientes, um apresentou complicação (febre), o que levou à suspensão da terapia (excluído dos resultados). Dos 10 pacientes que completaram o tratamento, 5 apresentaram colonização bacteriana e receberam uma vacina personalizada. Os 6 restantes foram tratados com a composição padrão. A média de exacerbações infecciosas no ano anterior foi de 4,3 (0,7 com hospitalização). No ano após a terapia, o número médio foi de 1,5 (0,5 com hospitalização). CONCLUSÃO Os resultados obtidos neste estudo favorecem o uso de imunoestimulação bacteriana para reduzir a frequência de infecções respiratórias recorrentes em pacientes com doença respiratória crônica.

Misoprostol administered sublingually at a dose of 12.5 µg versus vaginally at a dose of 25 µg for the induction of full-term labor: a randomized controlled trial protocol.

BACKGROUND: Various methods are currently used for the induction of labor. Nevertheless, the most effective method with the fewest side effects remains to be established. Misoprostol, administered vaginally, has been routinely used for this purpose; however, other forms of administration are being proposed, including the use of sublingual tablets. No studies have yet compared the effectiveness and safety of 12.5-µg misoprostol administered sublingually compared to a 25-µg vaginal dose of the drug for the induction of labor. METHODS: A triple-blind, multicenter, placebo-controlled, randomized clinical trial will be conducted in Brazil at the Instituto de Medicina Integral Prof. Fernando Figueira and at the Assis Chateaubriand Maternity Teaching Hospital of the Federal University of Ceará. A total of 140 patients with full-term pregnancies, a live fetus, a Bishop score ≤ 6 and a recommendation of induction of labor will be randomized to one of two groups. One group will receive 12.5-µg sublingual tablets of misoprostol and placebo vaginal tablets, while the other group will receive placebo sublingual tablets and vaginal tablets containing 25 µg of misoprostol. The principal endpoint is the rate of tachysystole. The secondary endpoints are vaginal delivery within 24 h of induction, uterine hyperstimulation, Cesarean section, severe neonatal morbidity or perinatal death, severe maternal morbidity or maternal death, and maternal preference regarding the route of administration of the drug. Student's t-test, and the chi-square test of association or Fisher's exact test, as appropriate, will be used in the data analysis. Risk ratios and their respective 95% confidence intervals will be calculated. DISCUSSION: Misoprostol has been identified as a safe, inexpensive, easily administered option for the induction of labor, with satisfactory results. An experimental study has shown that misoprostol administered sublingually at a dose of 25 µg appears to be effective and is associated with greater maternal satisfaction when labor is induced in women with an unfavorable cervix. Nevertheless, the rate of tachysystole remains high; therefore, further studies are required to determine the ideal dose and the ideal interval of time between doses. TRIAL REGISTRATION: ClinicalTrial.gov, NCT01406392 .

Baixa dose de misoprostol sublingual (12,5 µg) para indução do parto / Low dose of sublingual misoprostol (12.5 µg) for labor induction

OBJETIVO: Descrever os resultados maternos e perinatais utilizando 12,5 µg de misoprostol sublingual para indução do parto em gestantes com feto vivo a termo. MÉTODOS: Realizou-se um estudo multicêntrico, tipo ensaio clínico, aberto e não randomizado, no período de julho a dezembro de 2009. Foram incluídas 30 gestantes com indicação de indução do parto, a termo, feto vivo, escore de Bishop menor ou igual a seis, apresentação cefálica, peso fetal estimado menor que 4.000 g e índice de líquido amniótico maior que cinco. Foram excluídas mulheres com cicatriz uterina, alteração da vitalidade fetal, anomalias congênitas, gestação múltipla, restrição de crescimento intrauterino, hemorragia genital e contraindicações ao parto vaginal. O comprimido de misoprostol sublingual 12,5 µg foi administrado a cada seis horas, até o início do trabalho de parto, máximo de oito doses. RESULTADOS: O trabalho de parto foi induzido satisfatoriamente em 90% das gestantes. As médias dos intervalos entre a primeira dose e o início das contrações uterinas e o parto foram de 14,3±11,7 horas e 25,4±13 horas, respectivamente. A frequência de parto vaginal foi de 60%. A taquissistolia ocorreu em duas gestantes, sendo revertida em ambos os casos sem necessitar de cesariana. A eliminação de mecônio foi observada em quatro pacientes e o escore de Apgar foi menor que sete no quinto minuto em um recém-nascido. CONCLUSÃO: Os desfechos maternos e perinatais foram favoráveis depois da indução do parto com misoprostol sublingual na dose de 12,5 µg a cada seis horas. No entanto, são necessários ensaios clínicos controlados comparando esse esquema posológico com outras doses e vias de administração.

PURPOSE: To describe the maternal and perinatal outcomes after the use of 12.5 µg of sublingual misoprostol for labor induction in women with term pregnancy and a live fetus. METHODS: We conducted a multicenter, open and non-randomized clinical trial during the period from July to December 2009. We included 30 pregnant women with an indication for labor induction at term, carrying a live fetus, with a Bishop score of six or less, cephalic presentation, estimated fetal weight of less than 4,000 g and an amniotic fluid index greater than five. We excluded women with a previous uterine scar, non-reassuring fetal status, congenital anomalies, multiple pregnancy, intrauterine growth restriction, genital bleeding, and contraindications of vaginal delivery. A tablet of 12.5 µg sublingual misoprostol was administered every six hours, until the beginning of labor, with the maximum of eight doses. RESULTS: Labor was successfully induced in 90% of pregnant women. The mean interval between the first dose and the onset of uterine contractions and delivery was 14.3±11.7 hours and 25.4±13 hours, respectively. The frequency of vaginal delivery was 60%. Uterine tachysystole occurred in two pregnant women, being reversed in both cases without the need for cesarean section. Meconium-stained amniotic fluid was observed in four patients, and an Apgar score of less than 7 at five minutes in only one newborn. CONCLUSION: Maternal and perinatal outcomes were favorable after induction of labor with sublingual misoprostol at a dose of 12.5 µg every six hours. However, controlled trials are needed to compare this regimen with other doses and routes of administration.

Dinitrato de isosorbide sublingual en la urgencia hipertensiva

Se investigó el uso del dinitrato de isosorbide sublingual en la urgencia hipertensiva. Se estableció además una correlación con la nifedipina, de eficacia probada para este fin. Se estudiaron 80 pacientes con este diagnóstico, distribuidos aleatoriamente en 2 grupos, que recibieron 10 mg de nifedipina o dinitrato de isosorbide, si a los 45 min de la primera dosis no se había alcanzado el control se administró una segunda dosis. Se obtuvo la primera dosis de dinitrato de isosorbide, un mayor número de pacientes controlados (n = 29) a diferencia de la nifedipina (n = 19). Ambos fármacos lograron el control de 36 pacientes con la segunda dosis. La nifedipina causó cefalea ligera. En conclusión, el dinitrato de isosorbide resultó ser un medicamento eficaz, de fácil administración y con escasos efectos secundarios en el tratamiento de la urgencia hipertensiva y puede constituir una alternativa más en los servicios de urgencia.

The use of sublingual isosorbide dinitrate in the hypertensive urgency was investigated. It was also established a correlation with nifedipine, whose efficacy has been proved to this end. 80 patients with this diagnosis were studied and divided at random into 2 groups, who received 10 mg of nifedipine or isosorbide dinitrate and a second dosage if their pressure was not controlled 45 minutes after the first dosage. With the first dosage of isosorbide dinitrate a higher number of patients were controlled (n = 29) compared with nifedipine (n = 19). 36 patients were controlled with the second dosage of both drugs. Nifedipine caused mild cephalalgia. To conclude, isosorbide dinitrate proved to be an efficient drug, easy to administer and with a few side effects in the treatment of hypertensive urgency. It may be another alternative for urgency services.