Milton Harumi Miyoshi

Physiological, hormonal, and behavioral responses to a single fentanyl dose in intubated and ventilated preterm neonates

OBJECTIVE To study the responses of ventilated preterm neonates to a single dose of opioid. STUDY DESIGN In a randomized, double-blind, controlled trial, 22 mechanically ventilated preterm infants (< or = 32 weeks) were observed before medication and at 30 and 60 minutes after administration of fentanyl (3 micrograms/kg) or placebo. Heart rate, blood pressure, arterial blood gases, ventilator settings, and behavioral measures (Neonatal Facial Coding System and Modified Postoperative Comfort Score) were recorded during each period. Blood cortisol, growth hormone, glucose, and lactate were measured before and at 60 minutes after analgesia. Behavioral measures were assessed at the bedside and from video films recorded during each observation period. RESULTS Patients presented high basal levels of cortisol, growth hormone, and lactate. Behavioral scales indicated the presence of pain before any medication. In the fentanyl group, the maximum and minimum heart rate decreased and growth hormone level increased after analgesia. At the video analysis of behavioral measures, postoperative comfort score increased and neonatal facial coding system score decreased in the fentanyl group. CONCLUSION Single doses of fentanyl analgesia can reduce the physiologic/behavioral measures of pain and stress associated with mechanical ventilation in preterm infants.

Avanços em enterocolite necrosante

OBJETIVO: Avaliar relatos recentes sobre a enterocolite necrosante, com especial interesse na etiopatogenia, manejo e prevencao. FONTE DOS DADOS: Os artigos utilizados nessa revisao consistem em ensaios randomizados ou semi-randomizados, estudos de caso-controle, metanalises e artigos de revisao recentemente publicados. Alguns outros artigos foram selecionados devido a sua importância para o tema. RESULTADOS: A enterocolite necrosante e uma importante causa de morbimortalidade neonatal em prematuros. Entre esses, os nascidos com retardo de crescimento intra-uterino apresentam um risco mais elevado. O processo fisiopatologico inicia-se intra-utero e continua apos o nascimento. Entre outros fatores envolvidos na fisiopatologia, estao a acao da arginina na producao do oxido nitrico intestinal e a acao do fator de crescimento epidermico na regeneracao celular. A perfuracao intestinal ainda e um problema cirurgico, e evidencias melhores quanto a sua abordagem precisam ser avaliadas. Apos a cirurgia, a extensao da alca intestinal remanescente, a preservacao da valvula ileocecal, assim como a utilizacao precoce de leite materno ou solucao de aminoacidos, sao determinantes na duracao da nutricao parenteral e no sucesso da readaptacao intestinal. Estrategias preventivas estao centradas nas praticas alimentares e, recentemente, na suplementacao de aminoacidos. CONCLUSAO: Com um melhor entendimento do processo fisiopatologico, do manejo clinico e cirurgico, assim como das medidas de prevencao, importantes resultados serao alcancados em termos de reducao da morbimortalidade consequente a enterocolite necrosante.

Antenatal treatment with corticosteroids for preterm neonates: impact on the incidence of respiratory distress syndrome and intra-hospital mortality

CONTEXT Although the benefits of antenatal corticosteroids have been widely demonstrated in other countries, there are few studies among Brazilian newborn infants. OBJECTIVE To evaluate the effectiveness of antenatal corticosteroids on the incidence of respiratory distress syndrome and intra-hospital mortality among neonates with a gestational age of less than 34 weeks. TYPE OF STUDY Cross-sectional. SETTING A tertiary-care hospital. PARTICIPANTS Neonates exposed to any dose of antenatal corticosteroids for fetal maturation up to 7 days before delivery, and newborns paired by sex, birth weight, gestational age and time of birth that were not exposed to antenatal corticosteroids. The sample obtained consisted of 205 exposed newborns, 205 non-exposed and 39 newborns exposed to antenatal corticosteroids for whom it was not possible to find an unexposed pair. PROCEDURES Analysis of maternal and newborn records. MAIN MEASUREMENTS The primary clinical outcomes for the two groups were compared: the incidence of respiratory distress syndrome and intra-hospital mortality; as well as secondary outcomes related to neonatal morbidity. RESULTS Antenatal corticosteroids reduced the occurrence of respiratory distress syndrome (OR: 0.33; 95% CI: 0.21-0.51) and the protective effect persisted when adjusted for weight, gestational age and the presence of asphyxia (adjusted OR: 0.27; 95% CI: 0.17-0.43). The protective effect could also be detected through the reduction in the need for and number of doses of exogenous surfactant utilized and the number of days of mechanical ventilation needed for the newborns exposed to antenatal corticosteroids. Their use also reduced the occurrence of intra-hospital deaths (OR: 0.51: 95% CI: 0.38-0.82). However, when adjusted for weight, gestational age, presence of prenatal asphyxia, respiratory distress syndrome, necrotizing enterocolitis and use of mechanical ventilation, the antenatal corticosteroids did not maintain the protective effect in relation to death. With regard to other outcomes, antenatal corticosteroids reduced the incidence of intraventricular hemorrhage grades III and IV (OR: 0.28; 95% CI: 0.10-0.77). CONCLUSIONS Antenatal corticosteroids were effective in the reduction of morbidity and mortality among premature newborns in the population studied, and therefore their use should be stimulated within our environment.

Factors associated with clinical complications during intra-hospital transports in a neonatal unit in Brazil.

OBJECTIVE Analyze factors associated with clinical complications during intra-hospital transport of neonatal intensive care unit (NICU) patients. METHODS Prospective study of 641 infants submitted to 1197 intra-hospital transports at a public university NICU. Factors associated with clinical complications during intra-hospital transports were studied by multiple logistic regression analysis. RESULTS Included infants had a mean gestational age of 35.1 ± 3.8 weeks and a birth weight of 2328 ± 906 g. Underline diseases were: malformations (71.9%), infections (7.6%), respiratory distress (4.1%) and others (16.4%). Patients were transported for surgical procedures (22.6%), magnetic resonance (10.6%), tomography imaging (20.9%), contrasted exams (18.2%), ultrasound (10.4%) and others (17.3%). Clinical complications occurred in 327 (27.3%) transports and were associated (odds ratio; 95% CI) with: central nervous system malformations (1.6; 95% CI 1.0-2.0); use of supplemental oxygen (4.0; 95% CI 2.8-5.6); mechanical ventilation (5.0; 95% CI 3.5-7.5); transport for surgeries (4.0; 95% CI 1.1-14.0) and duration of the transport longer than 120 min (1.6; 95% CI 1.1-2.4). CONCLUSIONS Intra-hospital transports are associated with increased risk of clinical complications.

Predictive score for clinical complications during intra-hospital transports of infants treated in a neonatal unit

OBJECTIVE: To develop and validate a predictive score for clinical complications during intra-hospital transport of infants treated in neonatal units. METHODS: This was a cross-sectional study nested in a prospective cohort of infants transported within a public university hospital from January 2001 to December 2008. Transports during even (n = 301) and odd (n = 394) years were compared to develop and validate a predictive score. The points attributed to each score variable were derived from multiple logistic regression analysis. The predictive performance and the score calibration were analyzed by a receiver operating characteristic (ROC) curve and Hosmer-Lemeshow test, respectively. RESULTS: Infants with a mean gestational age of 35±4 weeks and a birth weight of 2457±841 g were studied. In the derivation cohort, clinical complications occurred in 74 (24.6%) transports. Logistic regression analysis identified five variables associated with these complications and assigned corresponding point values: gestation at birth [<28 weeks (6 pts); 28-34 weeks (3 pts); >34 weeks (2 pts)]; pre-transport temperature [<36.3°C or >37°C (3 pts); 36.3-37.0°C (2 pts)]; underlying pathological condition [CNS malformation (4 pts); other (2 pts)]; transport destination [surgery (5 pts); magnetic resonance or computed tomography imaging (3 pts); other (2 pts)]; and pre-transport respiratory support [mechanical ventilation (8 pts); supplemental oxygen (7 pts); no oxygen (2 pts)]. For the derivation and validation cohorts, the areas under the ROC curve were 0.770 and 0.712, respectively. Expected and observed frequencies of complications were similar between the two cohorts. CONCLUSION: The predictive score developed and validated in this study presented adequate discriminative power and calibration. This score can help identify infants at risk of clinical complications during intra-hospital transports.

Photogrammetry: an accurate and reliable tool to detect thoracic musculoskeletal abnormalities in preterm infants

OBJECTIVE To analyse the accuracy and reproducibility of photogrammetry in detecting thoracic abnormalities in infants born prematurely. DESIGN Cross-sectional study. SETTING The Premature Clinic at the Federal University of São Paolo. PARTICIPANTS Fifty-eight infants born prematurely in their first year of life. OUTCOME MEASURES Measurement of the manubrium/acromion/trapezius angle (degrees) and the deepest thoracic retraction (cm). Digitised photographs were analysed by two blinded physiotherapists using a computer program (SAPO; http://SAPO.incubadora.fapesp.br) to detect shoulder elevation and thoracic retraction. Physical examinations performed independently by two physiotherapists were used to assess the accuracy of the new tool. RESULTS Thoracic alterations were detected in 39 (67%) and in 40 (69%) infants by Physiotherapists 1 and 2, respectively (kappa coefficient=0.80). Using a receiver operating characteristic curve, measurement of the manubrium/acromion/trapezius angle and the deepest thoracic retraction indicated accuracy of 0.79 and 0.91, respectively. For measurement of the manubrium/acromion/trapezius angle, the Bland and Altman limits of agreement were -6.22 to 7.22° [mean difference (d)=0.5] for repeated measures by one physiotherapist, and -5.29 to 5.79° (d=0.75) between two physiotherapists. For thoracic retraction, the intra-rater limits of agreement were -0.14 to 0.18cm (d=0.02) and the inter-rater limits of agreement were -0.20 to -0.17cm (d=0.02). CONCLUSION SAPO provided an accurate and reliable tool for the detection of thoracic abnormalities in preterm infants.

Uso antenatal de corticosteróide e condições de nascimento de pré-termos nos hospitais da Rede Brasileira de Pesquisas Neonatais

PURPOSE: to assess the use of antenatal corticosteroid (AC) by mothers and its repercussion on the birth conditions of preterm babies at the eight university neonatal units belonging to the Brazilian Network of Neonatal Research. METHODS: an observational prospective cohort study. All 463 pregnant women with a gestational age (GA) of 23 to 34 weeks and their 514 newborn babies were evaluated during the period from August 1 to December 31, 2001. The data were obtained by maternal interview, by the analysis of the medical records and by the follow-up of the newborn infants, and analyzed statistically using c2, Mann-Whitney and ANOVA tests and multiple logistic regression, with the level of significance set at 0.05. RESULTS: 60.1% (282/463) of the pregnant women (a variation from 12.5 to 87.3% among units) received at least one AC dose. The AC use was directly associated with the number of prenatal visits, with maternal hypertension and with the antenatal use of tocolytic agents. Babies from treated pregnant women presented higher birth weight (1,379±421 vs 1,244±543 g), longer gestational age (30.9±2.0 vs 29.5±3.5 weeks), better Apgar scores at the 1st and 5th minute, and a reduced need for intervention in the delivery room. The use of AC, the GA and a baby small for GA independently improved the birth conditions. CONCLUSIONS: at most centers, AC was administered at frequencies below the desired ones, and in 50% of cases in an inadequate manner. Treatment was applied more to mothers who received appropriate prenatal care and was associated with better birth conditions.

Surfactant replacement therapy

OBJECTIVE: To analyze and update information about surfactant therapy replacement in newborns with lung diseases. SOURCES: Literature review, including textbooks, meta-analyses, prospective, randomized controlled trials, retrospective assessments and case studies. Literature was reviewed based on the authors clinical and scientific experience regarding surfactant replacement therapy in neonatal lung diseases. SUMMARY OF THE FINDINGS: Surfactant replacement therapy for the neonatal respiratory distress syndrome improves respiratory function, and reduces the need for oxygen supplementation and pressure support ventilation, in addition to minimizing the air leak syndrome. However, the use of surfactant did not prevent the occurrence of other intercurrent diseases such as patent ductus arteriosus, intraventricular hemorrhage, necrotizing enterocolitis, retinopathy of prematurity, and bronchopulmonary dysplasia. The surfactant treatment decreased neonatal mortality up to 40%. The effectiveness of exogenous surfactant on other respiratory diseases with surface film dysfunction, such as meconium aspiration syndrome, pneumonia, acute respiratory distress syndrome and congenital diaphragmatic hernia has not yet been widely accepted. CONCLUSIONS: Surfactant replacement is now considered the standard treatment for newborns with respiratory distress syndrome. We hope that, in the future, new synthetic surfactant preparations will be more effective in treating other infant respiratory diseases.

Medida da freqüência respiratória e do volume corrente para prever a falha na extubação de recém-nascidos de muito baixo peso em ventilação mecânica

OBJECTIVE: To verify if respiratory rate (RR), tidal volume (TV) and respiratory rate and tidal volume ratio (RR/TV) could predict extubation failure in very low birth weight infants submitted to mechanical ventilation. METHODS: This prospective observational study enrolled newborn infants with gestational age <37 weeks and birth weight <1,500g, mechanically ventilated from birth during 48 hours to 30 days and thought to be ready for extubation. As soon as the physicians decided for extubation, the neonates received endotracheal continuous positive airway pressure (CPAP) for 10 minutes while spontaneous RR, TV and RR/TV were measured using a fixed-orifice pneumotachograph positioned between the endotracheal tube and the ventilator circuit. Thereafter, the neonates were extubated to nasal CPAP. Extubation failure was defined as the need for reintubation within 48 hours. RESULTS: Of the 35 studied infants, 20 (57%) were successfully extubated and 15 (43%) required reintubation. RR and RR/TV before extubation had a trend to be higher in unsuccessfully extubated infants. TV was similar in both groups. Sensitivity and specificity of these parameters as predictors of extubation failure were 50 and 67% respectively for RR, 40 and 67% for TV and 40 and 73% for RR/TV. CONCLUSIONS: RR, TV and RR/TV showed low sensitivity and specificity to predict extubation failure in mechanically ventilated very low birth weight infants.

Costs of hospitalization in preterm infants: impact of antenatal steroid therapy

OBJECTIVE To estimate the costs of hospitalization in premature infants exposed or not to antenatal corticosteroids (ACS). METHOD Retrospective cohort analysis of premature infants with gestational age of 26-32 weeks without congenital malformations, born between January of 2006 and December of 2009 in a tertiary, public university hospital. Maternal and neonatal demographic data, neonatal morbidities, and hospital inpatient services during the hospitalization were collected. The costs were analyzed using the microcosting technique. RESULTS Of 220 patients that met the inclusion criteria, 211 (96%) charts were reviewed: 170 newborns received at least one dose of antenatal corticosteroid and 41 did not receive the antenatal medication. There was a 14-37% reduction of the different cost components in infants exposed to ACS when the entire population was analyzed, without statistical significance. Regarding premature infants who were discharged alive, there was a 24-47% reduction of the components of the hospital services costs for the ACS group, with a significant decrease in the length of stay in the neonatal intensive care unit (NICU). In very-low birth weight infants, considering only the survivors, ACS promoted a 30-50% reduction of all elements of the costs, with a 36% decrease in the total cost (p=0.008). The survivors with gestational age <30 weeks showed a decrease in the total cost of 38% (p=0.008) and a 49% reduction of NICU length of stay (p=0.011). CONCLUSION ACS reduces the costs of hospitalization of premature infants who are discharged alive, especially those with very low birth weight and <30 weeks of gestational age.