The role of renal biomarkers to predict the need of surgery in congenital urinary tract obstruction in infants.

INTRODUCTION: The diagnosis of renal function impairment and deterioration in congenital urinary tract obstruction (UTO) continues to be extremely challenging. The use of new renal biomarkers in this setting may favor early renal injury detection, allowing for a reliable choice of optimal therapeutic options and the prevention or minimization of definitive renal damage. OBJECTIVE: The aim of the study was to investigate a selection of promising biomarkers of renal injury with the intention of evaluating and comparing their profile with clinically based decisions for surgical intervention of infants with congenital obstructive uropathies. STUDY DESIGN: The first-year profile of renal biomarkers, serum creatinine (sCr), serum and urine cystatin C (CyC), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), transforming growth factor beta-1 (TGF-ß1), retinol-binding protein (RBP), and microalbuminuria (µALB), was analyzed in a cohort of 37 infants with congenital UTO, divided into three subgroups, 14 cases with grade III unilateral hydro(uretero)nephrosis, 13 cases with grade III bilateral hydro(uretero)nephrosis, and 10 cases with low urinary tract obstruction (LUTO), compared with 24 healthy infants matched by gestational age and birth weight. Serum and urine samples were stored at -70 °C and thereafter analyzed by quantitative enzymatic immunoassay. RESULTS: Compared with the control group (Figure), all renal biomarker values were significantly increased in patients (P ≤ 0.02). In the unilateral hydronephrosis and LUTO group, RBP (P ≤ 0.043), NGAL (P ≤ 0.043), KIM-1 (P ≤ 0.03), and TGF-ß1 (P ≤ 0.034) values dropped significantly after surgery. Neutrophil gelatinase-associated lipocalin alone and in combination with urine and serum CyC demonstrated the best performance in determining the need for surgery (area under the curve, 0.801 and 0.881, respectively). Biomarker profile analysis was suggestive of surgical intervention in 55.4% (7/13) of non-operated cases, and most of the biomarker values were above the cutoff levels within at least 3 months before the clinically based surgical decision in 58% (14/24) of all operated patients. DISCUSSION: To the best of the authors' knowledge, this is the first study to present the clinical use of selected group of serum and urinary biomarkers in the setting of UTO to distinguish between patients who would benefit from surgery intervention. The most promising results were obtained using NGAL, RBP, TGF-ß1, and KIM-1, especially in the unilateral hydro(uretero)nephrosis and LUTO subgroups when compared with the control group. CONCLUSIONS: Urine biomarkers, alone and in combination, demonstrated high potential as a non-invasive diagnostic tool for identifying infants who may benefit from earlier surgical intervention.

Unplanned extubation in a paediatric intensive care unit: impact of a quality improvement programme.

Unplanned tracheal extubation is an important quality issue in current medical practice as it is a common occurrence in paediatric intensive care units. We have assessed the effectiveness of a continuous quality improvement programme in reducing the incidence of unplanned extubation over a 5-year period. After a 2-year baseline period, we developed action plans to address the issues identified. Following implementation of the programme, the overall incidence of unplanned extubation decreased from 2.9 unplanned extubations per 100 intubated patient days in the first year to 0.6 in the last year (p = 0.0001). This reduction was the result of a decrease in unplanned extubation in children younger than 2 years of age. Although mortality was similar to that of children who did not experience an unplanned extubation, those with an unplanned extubation had a significantly longer duration of mechanical ventilation, longer stay in the intensive care unit, and longer hospital stay. We found that the implementation of a continuous quality improvement programme is effective in reducing the overall incidence of unplanned extubations.

Assessment of splanchnic perfusion with gastric tonometry in the immediate postoperative period of cardiac surgery in children.

OBJECTIVE - A prospective, nonrandomized clinical study to assess splanchnic perfusion based on intramucosal pH in the postoperative period of cardiac surgery and to check the evolution of patients during hospitalization. METHODS - We studied 10 children, during the immediate postoperative period after elective cardiac surgery. Sequential intramucosal pH measurements were taken, without dobutamine (T0) and with 5mcg/kg/min (T1) and 10 (T2) mcg/kg/min. In the pediatric intensive care unit, intramucosal pH measurements were made on admission and 4, 8, 12, and 24 hours thereafter. RESULTS - The patients had an increase in intramucosal pH values with dobutamine 10mcg/kg/min [7.19+/- 0.09 (T0), 7.16+/-0.13(T1), and 7.32+/-0.16(T2)], (p=0.103). During the hospitalization period, the intramucosal pH values were the following: 7.20+/-0.13 (upon admission), 7.27+/-0.16 (after 4 hours), 7.26+/-0.07 (after 8 hours), 7.32+/-0.12 (after 12 hours), and 7.38+/-0.08 (after 24 hours), (p=0.045). No deaths occurred, and none of the patients developed multiple organ and systems dysfunction. CONCLUSION - An increase in and normalization of intramucosal pH was observed after dobutamine use. Measurement of intramucosal pH is a type of monitoring that is easy to perform and free of complications in children during the postoperative period of cardiac surgery.

[Airway pressure release in postoperative cardiac surgery in pediatric patients]. / Liberação de pressão de vias aéreas em pacientes pediátricos submetidos à cirurgia cardíaca.

OBJECTIVE: Comparison of three modes of MV: intermittent mandatory ventilation with positive end expiratory pressure (IMV + PEEP), APRV and continuous positive airway pressure (CPAP) in children during cardiac surgery post operative with pulmonary hypertension and mild or moderate pulmonary lesion. METHODS: Ten patients were studied with respiratory monitoring (Bear Neonatal Volume Monitor-1) in MV with a continuous flow, time cycled and pressure limited ventilator. The cardiocirculatory variables analyzed were central venous pressure (CVP), oxygen extraction ratio, cardiac rate, systolic arterial pressure, and arterial-mixed venous CO2 difference. Friedman's test (nonparametric) was used to compare the variables in three modalities of ventilation and the Wilcoxon test was used for the variables obtained in two of the modalities. RESULTS: The mean airway pressure (MAP) showed a significant increasing during APRV compared to IMV + PEEP (p = 0.012). The positive inspiratory pressure (PIP), the minute volume and the ratio of oxygen arterial pressure to oxygen inspired fraction (PaO2/FiO2) didn't show statistical difference. During APRV there was a significant decrease in respiratory rate (p = 0.004) and an increase in tidal volume (p = 0.045) when compared to CPAP and IMV + PEEP. In the cardiocirculatory system only CVP showed a significant increased (p = 0.019) during APRV. CONCLUSION: Due to the methodology utilized MAP was higher with APRV resulting in an increased tidal volume without respiratory or cardiocirculatory adverse effects when the three modes were compared. Our results suggest that APRV is a simple and safe method of ventilation.

[Withdrawal syndrome associated with cessation of fentanyl and midazolam in pediatrics]. / Síndrome de abstinência associada à interrupção da infusão de fentanil e midazolam em pediatria.

PURPOSE: To determine the incidence of abstinence syndrome in children interned in the Pediatric Intensive Care Unit (PICU) in fentanyl use and midazolam. METHODS: Evaluation of 36 children interned in PICU of the Hospital São Paulo--Federal University of São Paulo, in the period from March to September 1997, with age varying from 5 days to 22 months (22 masc: 14 fem) who used fentanyl use and midazolam for more than 24 hours. Used the Escore Neonatal of Abstinence adapted by Finnegan determines the occurrence of abstinence syndrome in was used to children 2 years old or less. Sustain larger or equal for 8 is considered as abstinence syndrome. Correlated the abstinence syndrome with the accumulated total dose, infusion velocity, daily dose and time of use of the fentanyl and midazolam. RESULTS: Certain abstinence syndrome in 18 (50%) of the 36 children. Applied Mann Whitney's statistical test to compare the groups with and without abstinence syndrome. Dose accumulated of fentanyl total (5732.7 +/- 5114.91 vs 624.2 +/- 591.2 mcg, p < 0.005), dose daily of fentanyl (98.54 +/- 6.12 vs 36.23 +/- 23.42 mcg/Kg/dia, p < 0.005), velocity of infusion of the fentayl (4.09 +/- 2.75 vs 1.5 +/- 0.95 mcg/Kg/hora, p < 0.005), time of use of the fentanyl (10.2 +/- 5.1 vs 3.16 +/- 1.09 days, p < 0.005), dose accumulated of midazolam total (118.8 +/- 86.97 vs 20.03 +/- 14.79 mg, p < 0.005), dose daily of midazolam (2.32 +/- 0.86 vs 1.21 +/- 0.68 mg/Kg/dia, p < 0.005), velocity of midazolam infusion (0.13 +/- 0.16 vs 0.05 +/- 0.02 mg/Kg/hora, p < 0.005) and time of use of the midazolam (9.20 +/- 4.67 vs 2.55 +/- 1.54 days, p < 0.005) they were considered significant. CONCLUSION: The abstinence syndrome presents an elevated incidence in children interned in PICU owing to the interruption of the fentanyl infusion and midazolam and in these patients it was related with the dose and the time of use.

Inhaled nitric oxide and high concentrations of oxygen in pediatrics patients with congenital cardiopathy and pulmonary hypertension: report of five cases.

Five patients with ages ranging from 6 months to 3 years were analyzed. All received inhaled nitric oxide (NO--20 parts per million (ppm)) and oxygen (O2--at a concentration of 90-95%) by means of an oxygen hood. Mean Pulmonary Artery Pressure (MPAP), Mean Aortic Pressure (MAoP), Pulmonary Vascular Resistance (PVR) and Systemic Vascular Resistance (SVR) were measured and the calculation of their relationship to pulmonary/systemic flow (Qp/Qs) was performed by the catheterization of the femoral artery vein. Three patients presented reduction in PVR and increase in Qp/Qs. There were no systemic alterations or any side effect from using NO.

Evolution of the nutritional support pattern in pediatric intensive care.

OBJECTIVES: To evaluate patterns of usage and monitoring of nutritional support in a Pediatric ICU of a teaching hospital and the role of an education program in nutritional support given throughout the resident physician training. DESIGN: In a historical cohort study, records from children who received nutritional support during the year 1992 were analyzed. Thereafter a continuing education program in Nutritional Support was conveyed to the residents. In a second phase of the study, the same parameters were reevaluated in children who received nutritional support throughout the year 1995. SETTING: Pediatric Intensive Care Unit of Department of Pediatrics, Escola Paulista de Medicina. PATIENTS: All the children who were given nutritional support during a period of five days or more. Based on this criteria 37 children were selected for the first phase of this study, and 35 for the second one. INTERVENTION: The education program included theoretical lectures about basic themes of nutritional support and journal article reading sessions. It was given to successive groups of residents on a weekly schedule. MEASUREMENTS: Daily records of fluid, protein, caloric and micronutrient supply, nutritional assessment and metabolic monitoring. RESULTS: In the first phase of the study, an exclusively parenteral route was utilized for 80.5%, and a digestive route 19.5% of the time period. Nutritional assessment was performed on 3 children; no patient had the nutritional goals set. The nitrogen to nonprotein calories ratio and the vitamin supply were inadequate, whilst the supply of trace elements was adequate except for zinc. Nutritional monitoring was performed on almost all patients but without uniformity. In the second phase, the exclusive parenteral route was used for 69.7% and the digestive route for 30.3% of the time period; no significant increase in the use of the digestive route was detected. The nonprotein calories to nitrogen ratio and micronutrient supply were adequate. The frequency of nutritional assessment increased, but deficiency in nutritional monitoring and infrequent enteral feeding were still detected. CONCLUSION: There were deficiencies in the implementation of nutritional support, which were partially corrected in the second phase of the study by the training of the residents. Reinforcement of the education program, which should be applied to the whole medical staff, and the organization of a multidisciplinary team in charge of coordinating the provision of nutritional support are suggested.

[Effects on the pulmonary function after single dose of exogenous pulmonary surfactant in children with acute respiratory distress syndrome]. / Efeitos na função pulmonar após utilização de surfactante pulmonar exógeno na síndrome do desconforto respiratório agudo na criança.

The Acute Respiratory Distress Syndrome (ARDS) is a pulmonary lesion of multifactorial cause in which the surfactant system is altered owing to inactivation and impairment of composition and metabolism. The use of exogenous pulmonary surfactant is a therapeutic option with the objective to maintain alveolar stability thus improving the pulmonary compliance (increasing the residual functional capacity), oxygenation and ventilatory mechanics. A study carried out on two pediatric patients with ARDS submitted to mechanic pulmonary ventilation, applying a single dose of exogenous pulmonary surfactant is described. The patients were evaluated using arterial and venous gasometry before and after the use of surfactant, observing increment in oxygenation, reduction of shunt fraction, improvement in ventilation immediately after exogenous pulmonary surfactant instillation and return to the previous situation after 240 minutes in case 1 and 120 minutes in case 2. More prospective clinical and randomized studies are needed to effectively evaluate this therapeutic modality.

[Nutritional and metabolic support in the pediatric ICU]. / Suporte nutricional-metabólico em UTI pediátrica.

UNLABELLED: Nutritional support has been considered an important part of the treatment of critically ill patients. The information about the current clinical pattern of nutrition support in hospitals may provide a basis for future modification and improvement of its prescription and use. OBJECTIVES: 1) To evaluate patterns of usage and monitoring of nutritional support in critically ill children; 2) To recommend policies aiming at the improvement of the nutritional support quality. PATIENTS AND METHOD: Records of 37 patients receiving nutritional support throughout one year were reviewed. RESULTS: From a total of 425 days of therapy, the single parenteral route was utilized in 80.50% the digestive route (tube feeding or oral route) in 19.5% of this time. A previous nutritional assessment was performed in 3 children; no patient had the nutrition goals set. The nitrogen to nonprotein calories ratio ranged between 1:80 and 1:250. Only 29.7% of the patients had their estimated caloric needs supplied and this goal was achieved only in those patients who were on enteral tube feeding. Patients did not achieved their goals for vitamins. The supply of oligoelements was adequate except zinc. Nutritional monitoring parameters including weight, serum albumin and serum triglycerides were performed in almost all the patients but without uniformity. CONCLUSION: There was a lack in the implementation of nutritional support. Inadequacy of protein and micronutrients supply, irregular nutritional monitoring and infrequent enteral feeding were detected. A minimal standard for nutritional and metabolic monitoring and the organization of a multidisciplinary team in charge of coordinating the providing of nutritional support are suggested.

Nutritional and metabolic assessment of critically ill children.

In a prospective study, with the objective of determining the metabolic profile, response to nutrient supply, and role of nutritional and metabolic assessment parameters in children admitted to a pediatric ICU, 11 patients in the age group 2-12 were studied. The assessment was carried out during the first 72 hours of admission, and again seven days later, and included the following parameters; caloric supply; nitrogen supply; prealbumin serum level; urinary urea nitrogen; nitrogen balance and creatinine-height index. The evolution of the parameters in the two stages of the study showed the following results: The urinary urea nitrogen median value at admission was 7.5 g/m2 of corporeal surface, and did not present significant changes seven days later. There was a significant increase in caloric supply from 42.9 to 70.3 kcal/kg, and in nitrogen supply, from 4.7 to 10.2 g/m2 of corporeal surface p 0.01. The level of nitrogen balance rose from -5.6 to 2.5 g/24 h (p < 0.03), and that of prealbumin, from 16.7 to 26.3 mg/dl (p < 0.03). There was a significant reduction in the creatinine-height index, from 86.2 percent to 55.0 percent p 0.01. The magnitude of urinary urea nitrogen excretion at admission varied 2.5-13.8 g/m2 of corporeal surface. Based on this parameter, it was not possible to establish a characteristic metabolic profile for the conditions studied. Notwithstanding an increase in the protein and caloric supply, prealbumin level and nitrogen balance observed in the second stage of the study, the patients lost muscle mass and entered into a malnutrition process, probably due to intense protein catabolism and the poor response to nutrition supply that occurs in metabolic stress.

Adult respiratory distress syndrome in newborns: 5 cases.

Aiming to set out the occurrence of the Adult Respiratory Distress Syndrome (ARDS) in the neonatal period, and according to recent descriptions in literature, we prospectively analyzed 5 cases. The criterion adopted to characterize ARDS was the expanded definition of the syndrome suggested by Murray & Matthay, (10), conjointly with non-invasive cardiac monitoring, to exclude pulmonary edema resulting from myocardial dysfunction. For each case, evolution was briefly described, as well as the predisposing conditions associated to the clinical score punctuation for diagnosis, stressing the importance of adequate identification and fastest possible management of such source of systemic effects. Upon admission at the intensive care unit (Ped. ICU), the five cases were either related to sepsis or to the syndrome of multiple organ failure, or to both. Both syndromes were essentially triggered by severe anoxia neonatorum, respiratory distress of the newborn and/or previous hospitalization with hypoxemia and use of a higher inspired fraction of oxygen. The primary causes of death were related to uncontrolled infection or shock, and not directly related to pulmonary failure.

Respiratory monitoring: pulse oximetry and capnography in children during anesthesia and intensive care.

Monitoring the critical care patient by pulse oximetry and capnography permits the early diagnosis and follow-up of various clinical events in a precise manner, with considerable safety and with no need for invasive procedures. These techniques have been extensively evaluated in adults, but only recently have they been studied in pediatric patients, including newborn infants. In the present review we discuss the working principles, indications, advantages and limitations of each technique, as well as the interpretation of the results.

Nasoduodenal feeding of the critically ill child.

Malnutrition frequently occurs among hospitalized children (19, 23, 24) and is associated with increased rates of morbidity and mortality (3, 5). Because of this hypercatabolic condition, a critically ill patient may undergo a process of acute malnutrition within a few days (7, 27, 34). The nutritional or metabolic support provided in these situations is usually by the parenteral or enteral route, depending on the presence of a functioning digestive tract. When exclusively parenteral feeding is used, prolonged fasting may deprive the intestine of specific nutrients and reduce its function of nutrient processing and absorption for lack of a substrate, with the consequent occurrence of atrophy. Clinical and experimental studies have demonstrated the advantages of the enteral route, which is more physiological, has a lower rate of complications and involves easier administration when compared to the parenteral route. Experimental studies (15, 21) have shown a hypoplastic response of the intestinal mucosa of rats after 3 days of parenteral nutrition when compared to controls submitted to enteral feeding. This response was measured in terms of mucosal weight, villus hypoplasia, DNA protein content, enzyme activity, and pancreatic function. Similar changes detected in clinical studies were rapidly reversed to normal after feeding by the digestive route (13). It is suggested that the mechanism of these alterations may involve the absence of intraluminal amino acids needed for enzyme synthesis rather than the lack of specific substrates inducing enzyme production.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation between free bilirubin and indirect bilirubin in normal newborn infants with non-hemolytic jaundice and effect of hemolysis on free bilirubin measurement by the peroxidase method.

The present study was undertaken to determine the correlation between free bilirubin and indirect bilirubin in normal newborn infants with non-hemolytic jaundice, and the possible effect of hemolysis on free bilirubin measurement by the peroxidase method. A prospective study protocol was applied at the Neonatal Unit of the Department of Pediatrics, Escola Paulista de Medicina. Forty-three newborn infants were submitted to measurement of free bilirubin and bilirubin fractions and the extent of hemolysis of the sample was determined. Data were analyzed statistically by the Student t-test. A positive and moderate correlation (r = 0.668; p < 0.01) was detected between free bilirubin and indirect bilirubin. The linear regression equation calculated by the least squares method was as follows: f(x) = 4.562 + 0.382x. The concentration of free bilirubin was inversely proportional to sample hemolysis, the difference being greater at 50 mg/dl hemolysis. Despite these results, however, the use of this correlation is delicate due to the impossibility of establishing it in individual cases. Also, since the samples may show some degree of hemolysis, this factor should be minimized by appropriate sample collection before free bilirubin measurement.