Intraoperative clonidine to prevent postoperative emergence delirium following sevoflurane anesthesia in pediatric patients: a randomized clinical trial.

INTRODUCTION AND OBJECTIVE: Emergence Delirium (ED), particularly in children, is characterized by mental confusion, irritability, disorientation, and inconsolable crying. ED prolongs the time required in the Post-Anesthesia Care Unit (PACU) and increases concern and anxiety in parents. The present study aimed to determine the effectiveness and safety of low-dose clonidine in preventing ED in children receiving sevoflurane anesthesia for tonsillectomy/adenotonsillectomy. METHODS: A randomized, double-blind clinical trial was conducted between November 2013 and January 2014. Sixty-two children aged 2-12 years, scheduled to undergo tonsillectomy/adenotonsillectomy, and classified as American Society of Anesthesiologists (ASA) physical status I/II were included, with 29 being randomized to receive 1 µg.kg-1 clonidine intravenously, and 33 allocated to a control group that received no clonidine. Anesthesia was induced and maintained with sevoflurane. Children with altered state of consciousness, neurological deficit, history of allergy to dipyrone, or receiving other drugs such as preanesthetic agents were excluded from the study. The primary outcome was the presence of ED in the initial 20 minutes in the PACU according to the Pediatric Anesthesia Emergence Delirium (PAED) scale. The Chi-Square test and Fisher's two-tailed exact test were used for statistical analysis, as applicable. Significance level was set at 5%, and Risk Ratios (RR) and their 95% Confidence Intervals (95% CI) were calculated. RESULTS: The frequency of ED was significantly decreased in the group of children who received clonidine (17.2% vs. 57.6%; RR = 0.30; 95% CI 0.13-0.70; p =  0.001). There was no difference between groups with respect to the frequency of postoperative self-harm (falls and bruises), dislodged catheters, and for most of the other adverse events evaluated. CONCLUSIONS: The use of 1 µg.kg-1 intravenous clonidine during anesthesia induction can effectively reduce the incidence of ED in children undergoing elective tonsillectomy/adenotonsillectomy under general inhalation anesthesia with sevoflurane. CLINICALTRIALS. GOV IDENTIFIER: NCT02181543.

Pregnant women infected by the Zika virus: Ultrasound findings and growth patterns of fetuses with and without microcephaly.

OBJECTIVE: To compare ultrasound growth measurements of fetuses with and without microcephaly in suspected Zika virus infection. METHODS: A retrospective cohort study included pregnant women with suspected Zika virus infection to evaluate 110 fetuses with and without microcephaly. The women had been admitted to the fetal medicine unit between October 2015 and August 2016. Cases of fetal microcephaly resulting from other causes were excluded. Variables evaluated were the ultrasound measurements taken at fetal biometry. The relation between each fetal biometry measurement and gestational age was analyzed using fractional polynomials in random-effects regression models. To evaluate fetal growth, curves of the mean fetal biometric parameters were constructed as a function of gestational age. RESULTS: Mean biparietal diameter and mean head circumference increased in both groups as a function of gestational age. In the group with fetal microcephaly, mean head circumference was significantly larger in the 13th and 14th weeks of pregnancy, becoming smaller compared with the group without microcephaly from the 20th week onwards, with the difference increasing with gestational age. CONCLUSION: Fetal head circumference continues to increase until birth, even after a diagnosis of microcephaly, with a reduction only in the pace of growth. Growth decelerates as the pregnancy approaches term.

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.

Effectiveness of an oral versus sublingual loading dose of nifedipine for tocolysis.

OBJECTIVE: To determine the effectiveness of an oral versus sublingual loading dose of nifedipine for tocolysis. METHODS: An open, randomized clinical trial conducted between March 1, 2013, and April 31, 2014. Participants were pregnant women with a diagnosis of premature labor, single live fetus, topical pregnancy, gestational age 24-36 weeks, normal fetal vitality, cervical dilatation less than or equal to 4 cm, cervical effacement less than or equal to 80%, and intact amniotic membranes. They were randomized into two groups, oral and sublingual nifedipine, 20 mg loading dose, repeated every 30 minutes (maximum dose of 60 mg). The primary endpoint was the time until tocolysis and the secondary endpoints were the effectiveness of tocolysis within 90 minutes, 12 hours, and 48 hours; premature delivery within 48 hours; and maternal hemodynamic parameters and side effects. RESULTS: There were 80 patients randomized to oral (n=40) and sublingual (n=40) nifedipine. The time required for tocolysis was significantly less with sublingual nifedipine (160 minutes vs 340 minutes; P=0.0003). Sublingual nifedipine was also more successful than oral nifedipine at inhibiting premature labor within 90 minutes (n=8 [20.0%] vs n=1 [2.5%], P=0.014). There was no statistically significant difference between the groups for the other secondary endpoints. CONCLUSION: Compared with oral administration, a sublingual loading dose of nifedipine resulted in faster tocolysis in patients with premature labor. Brazilian Clinical Trials Registry (ReBEC): U1111-11566186.

Anal prevalence of HPV in women with pre-malignant lesion or cancer in the cervix and anal canal simultaneously: cross-sectional study.

OBJECTIVE: To determine the prevalence of anal HPV genotypes and associated factors in women with pre-malignant lesion or cancer in the cervix and anal canal. METHODS: A prospective, cross-sectional study analyzed DNA samples taken from women with cervical pre-malignant lesions or cancer to identify anal HPV by polymerase chain reaction (PCR). The prevalence of high-risk HPV (HR-HPV) in women with intraepithelial neoplasia and anal cancer was calculated; sociodemographic and clinical risk factors were identified using multivariate analysis. RESULTS: A total of 152 patients were included (mean age 37.8 ± 10.01 years), of whom 101 (66.4%) had anal HR-HPV. Fourteen different anal HPV types were identified. HPV 16 and 18 were found in 30 (52.6%) anal high-grade squamous intraepithelial lesions (HSIL), and HPV 31 and 33 in 21 (36.8%) lesions. In the logistic regression analysis, the factors that remained associated with HR-HPV types were: an anal histopathology report of HSIL or invasive carcinoma (odds ratio [OR] 8.96, 95% confidence interval [CI] 3.40-23.57; P<0.0001) and alcohol consumption (OR 2.20, 95% CI 1.01-4.80; P=0.04). CONCLUSION: Prevalence of HR-HPV is high in the anal canal of women with cervical and anal pre-malignant lesions simultaneously or cancer of the cervix and/or anal canal. HPV 16, 31, 33, and 18 were the four major genotypes identified.

Cross-sectional study of anal intraepithelial lesions in women with cervical neoplasia without HIV.

OBJECTIVE: To evaluate the prevalence of anal intraepithelial lesions and associated risk factors in women with cervical neoplasia. METHODS: The present cross-sectional study enrolled patients with intraepithelial or invasive cervical neoplasia who had been referred to the lower genital tract pathology outpatient department of the Instituto de Medicina Integral Prof. Fernando Figueira, Recife, Brazil, between December 1, 2008, and December 31, 2009; patients with HIV infections were excluded. All participants underwent anal cytology and high-resolution anoscopy; sociodemographic and clinical risk factors were identified using multivariate analysis. RESULTS: There were 324 patients included and 37 (11.4%) had anal intraepithelial neoplasia. Factors associated with anal intraepithelial neoplasia in the multivariate analysis were being older than 35 years of age (P=0.002), having completed no more than 4 years of education (P=0.012), anomalous anal cytology (P=0.003), and anomalous high-resolution anoscopy findings (P<0.001); subclinical HPV lesions on vulvoscopy (P=0.057) were not associated with anal intraepithelial neoplasia. CONCLUSION: The prevalence of anal intraepithelial neoplasia was high among patients with cervical neoplasia who did not have HIV, particularly patients older than 35 years.

Titrated oral misoprostol solution versus vaginal misoprostol for labor induction.

OBJECTIVE: To determine the efficacy and safety of a titrated oral misoprostol solution compared with vaginal misoprostol tablets for labor induction. METHODS: A randomized, triple-blind, multicenter clinical trial was conducted between March 2010 and June 2011. Women with a single gestation (n=200) were randomized to receive a titrated oral misoprostol solution (initial misoprostol dose 20 µg/hour; dose increased by 20 µg/hour every 6 hours up to 80 µg/hour for a maximum of 48 doses) or vaginal misoprostol tablets (25 µg of misoprostol every 6 hours for a maximum of 8 doses). Risk ratios (RR) and 95% confidence intervals (CIs) were calculated for maternal and perinatal outcomes. RESULTS: The frequencies of vaginal delivery not achieved within 12 hours (RR 0.87; 95% CI, 0.62-1.22) and within 24 hours (RR 1.11; 95% CI, 0.83-1.49) were similar in the 2 groups. No differences were found in terms of uterine hyperstimulation, unfavorable cervix at 12 and 24 hours, oxytocin augmentation, tachysystole, epidural analgesia, adverse effects, and perinatal outcome. Approximately 70% of the women preferred the oral solution. CONCLUSION: A titrated oral misoprostol solution was as effective and safe for labor induction as vaginal misoprostol tablets. ClinicalTrial.gov: NCT00 992524.

Misoprostol prior to inserting an intrauterine device in nulligravidas: a randomized clinical trial.

STUDY QUESTION: How effective is the vaginal administration of misoprostol in dilating the cervix prior to inserting an intrauterine device (IUD) in nulligravidas? SUMMARY ANSWER: The use of misoprostol at a dose of 400 µg administered vaginally 4 h prior to IUD insertion increased the ease of insertion and reduced the incidence of pain during the procedure, although the frequency of cramps increased following misoprostol use. WHAT IS KNOWN AND WHAT THIS PAPER ADDS: Misoprostol has been widely used in Obstetrics and Gynecology; however, its usefulness and efficacy in facilitating IUD insertion in nulligravidas have yet to be established. The present study shows that the benefits of misoprostol use prior to IUD insertion include facilitating insertion and reducing pain during the procedure; therefore, weighing up the benefits encountered against the only negative side effect (cramps prior to insertion), these results suggest that misoprostol use should become standard practice to facilitate IUD insertion in nulligravidas. STUDY DESIGN, SIZE DURATION: A randomized, double-blind clinical trial was conducted. PARTICIPANTS/MATERIALS, SETTING METHODS: Nulligravid women of reproductive age were submitted to IUD insertion between July 2009 and November 2011 at the Instituto de Medicina Integral Prof. Fernando Figueira in Recife, Pernambuco, Brazil. A total of 179 women were randomly allocated to two groups: 86 to receive 400 µg of misoprostol vaginally 4 h prior to IUD insertion and 93 to receive placebo. Risk ratios (RRs) were calculated as measures of relative risk, together with their 95% confidence intervals (95% CI). The number needed to treat (NNT) and the number needed to harm (NNH) were also calculated. MAIN RESULTS AND THE ROLE OF CHANCE: Significant differences were found between the groups for all the immediate end points studied, with less difficulty in inserting the IUD [RR = 0.49 (23/86 versus 51/93); 95% CI: 0.33-0.72; P = 0.00005], a lower risk of dilatation <4 mm [RR = 0.48 (24/86 versus 54/93); 95% CI: 0.33-0.70; P = 0.0001], a reduction in moderate-to-severe pain at IUD insertion [RR = 0.56 (32/86 versus 62/93]; 95% CI: 0.41-0.76; P = 0.00008), as well as a lesser likelihood of experiencing a disagreeable or very disagreeable sensation [RR = 0.49(29/86 versus 64/93); 95% CI: 0.35-0.68; P = 0.000004] in the group that was given misoprostol compared with the group that received placebo. There was no significant difference between the groups in relation to complications during IUD insertion. There were no cases of uterine perforation in either group. The frequency of cramps was 40% higher in the misoprostol group. LIMITATIONS, REASONS FOR CAUTION: The present study showed a positive balance between the benefits and risks of the use of misoprostol; however, it is not feasible to conclude that its use is imperative prior to IUD insertion in nulligravidas and IUD insertion should not be canceled when the medication is unavailable. WINDER IMPLICATIONS OF THE FINDINGS: In view of its effect in promoting cervical dilatation, misoprostol may be used prior to IUD insertion both in nulligravidas and in any women with cervical stenosis irrespective of parity. STUDY FUNDING: This study was funded by the Instituto de Medicina Integral Prof Fernando Figueira. COMPETING INTERESTS: None.