The Relevance of Airway Resistance in Children Requiring Mechanical Ventilatory Support.

OBJECTIVES: To describe pulmonary resistance in children undergoing invasive mechanical ventilation (MV) for different causes. DESIGN: A cross-sectional study. SETTING: Two PICUs in the South region of Brazil. PATIENTS: Children 1 month to 15 years old undergoing MV for more than 24 hours were included. We recorded ventilator variables and measured pulmonary mechanics (inspiratory and expiratory resistance, auto positive end-expiratory pressure [PEEP], and dynamic and static compliance) in the first 48 hours of MV. INTERVENTIONS: Measurements of the respiratory mechanics variables during neuromuscular blockade. MEASUREMENTS AND MAIN RESULTS: A total of 113 children were included, 5 months (median [interquartile range (IQR) [2.0-21.5 mo]) old, and median (IQR) weight 6.5 kg (4.5-11.0 kg), with 60% male. Median (IQR) peak inspiratory pressure (PIP) was 30 cm H 2 O (26-35 cm H 2 O), and median (IQR) PEEP was 5 cm H 2 O (5-7 cm H 2 O). The median (IQR) duration of MV was 7 days (5-9 d), and mortality was nine of 113 (8%). The median (IQR) inspiratory and expiratory resistances were 94.0 cm H 2 O/L/s (52.5-155.5 cm H 2 O/L/s) and 117 cm H 2 O/L/s (71-162 cm H 2 O/L/s), with negative association with weight and age (Spearman -0.850). When we assess weight, in smaller children (< 10 kg) had increased pulmonary resistance, with mean values over 100 mH 2 O/L/s, which were higher than larger children ( p < 0.001). CONCLUSIONS: Increased pulmonary resistance is prevalent in the pediatric population undergoing invasive MV. Especially in children less than 1 year old, this variable should be considered when defining a ventilatory strategy.

Brazilian Translation, Cross-Cultural Adaptation, Validity, and Reliability of the EMpowerment of PArents in THe Intensive Care 30 (EMPATHIC-30) Questionnaire to Measure Parental Satisfaction in PICUs.

OBJECTIVES: To conduct the Brazilian translation, cross-cultural adaptation, validation, and reliability testing of the EMpowerment of PArents in THe Intensive Care (EMPATHIC-30). DESIGN: Prospective study. SETTING: PICU of a tertiary-care teaching hospital. PATIENTS: Parents (n = 141) completed the translated EMPATHIC-30 questionnaire 72 hours after their child's PICU discharge. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The translation and cultural adaptation were performed in accordance with the principles of good practice for the translation and cultural adaptation process for patient-reported outcomes measures. Sentences were adapted according to the Brazilian syntax. Total content validity coefficient was above the established average (> 0.8). Reliability was evaluated with the coefficients McDonald omega and Cronbach alpha. The lowest Cronbach alpha found was 0.47 (CI 95%, 0.35-0.59) in the organization domain, where the lowest response rate was also concentrated. The values of the other domains were as follows: 0.64 (95% CI, 0.55-0.73) for information, 0.77 (95% CI, 0.71-0.83) for care and treatment, 0.72 (95% CI, 0.66-0.78) for parent participation, and 0.72 (95% CI, 0.65-0.79) for professional attitudes. The total internal consistency independent of the domain was 0.90 (CI 95%, 0.88-0.92). With regard to McDonald Omega, values were identified: 0.68 (95% CI, 0.49-0.88) for information, 0.73 (95% CI, 0.61-0.85) for care and treatment, 0.85 (95% CI, 0.47-0.80) for parent participation, 0.85 (95% CI, 0.76-0.93), and 0.72 (95% CI, 0.58-0.86) for professional attitudes. CONCLUSIONS: EMPATHIC-30 has been translated and culturally adapted for the Brazilian population. Validation demonstrated an above-average total content validity coefficient, confirming the instrument content validity. A sufficient reliability was observed in both analyzed coefficients. The results support the use of the Brazilian version of EMPATHIC-30 for the evaluation of parents' satisfaction of children admitted to the PICU.

Prediction of Poor Outcomes for Septic Children According to Ferritin Levels in a Middle-Income Setting.

OBJECTIVES: To evaluate serum ferritin measured within 48 hours of admission as a prognostic marker and examine the association with unfavorable outcomes in a population of pediatric patients with sepsis and high prevalence of iron deficiency anemia in which this biomarker is routinely measured. DESIGN: Retrospective cohort study. SETTING: PICU of a tertiary care teaching hospital in a middle-income country in South America. PATIENTS: All patients 6 months to 18 years old (n = 350) admitted with a diagnosis of sepsis, suspected or proven, were eligible for inclusion. Exclusion criteria were length of PICU stay less than 8 hours and inherited or acquired disorder of iron metabolism that could interfere with serum ferritin levels. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Three-hundred twelve patients had their ferritin levels measured within 48 hours, and only 38 did not. The prevalence of iron deficiency anemia (hemoglobin < 11 g/dL and mean corpuscular volume < 80 fl was 40.3%. The median of the highest serum ferritin level within 48 hours was 150.5 ng/mL (interquartile range, 82.25-362 ng/mL), being associated with mortality (p < 0.001; Exp(B), 5.170; 95% CI, 2.619-10.205). A 10-fold increase in ferritin level was associated with a five-fold increase in mortality. There was a monotonic increase in mortality with increasing ferritin levels (p < 0.05). Regarding the discriminatory power of ferritin for mortality, the area under the receiver operating characteristic curve was 0.787 (95% CI, 0.737-0.83; p < 0.0001). CONCLUSIONS: Serum ferritin at lower thresholds predicts mortality in children with sepsis admitted to the ICU in a middle-income country with high prevalence of iron deficiency anemia.

Pilot Mechanistic Study of Insulin Modulation of Somatotrophic Hormones, Inflammation, and Lipid Metabolism During Critical Illness in Children.

OBJECTIVES: To evaluate the mechanism of insulin modulation on somatotrophic response, inflammation, and lipid metabolism in critically ill children. DESIGN: Open-label randomized mechanistic study. SETTING: Two-center, tertiary PICU study. PATIENTS: Thirty critically ill children between 1 month and 14 years old, requiring mechanical ventilation and with evidence of two or more organ system failures. INTERVENTIONS: Randomized physiologic design of hyperinsulinemic-euglycemic clamp using continuous insulin infusion at 0.1 U/kg/hr versus conventional management. MEASUREMENTS AND MAIN RESULTS: Thirteen children underwent hyperinsulinemic-euglycemic clamp. Blood samples for somatotrophic, inflammatory, and metabolic evaluation were obtained before randomization, and 24 and 72 hours later. A growth hormone oscillation profile was obtained during the first night. There was no difference between groups at baseline. Growth hormone resistance, increased proinflammatory cytokines, and increased lipolysis with low lipoprotein levels were present in all patients. Hyperinsulinemic-euglycemic clamp did not affect growth hormone, insulin-like growth factor-1 or insulin-like growth factor binding protein-3 levels. By day 2, insulin reduced insulin-like growth factor binding protein-1 levels. Tumor necrosis factor-α and interleukin-1ß were similar in both groups, whereas interleukin-6 levels reduced over time only in children receiving hyperinsulinemic-euglycemic clamp. Hyperinsulinemic-euglycemic clamp also decreased free fatty acid levels, which was accompanied by increased low-density lipoprotein cholesterol and relative increase in high-density lipoprotein levels. Total cholesterol and triglycerides were unchanged. CONCLUSIONS: Insulin does not reverse most of the somatotrophic changes induced by the stress of critical illness. Rather, it may improve lipid metabolism and down-regulate some markers of the inflammatory response.

Nurses' participation in the end-of-life process in two paediatric intensive care units in Brazil.

The aim of this study was to evaluate the medical and nursing care provided to children in the last 24 hours of life in two Brazilian paediatric intensive care units and analyse the nurses' participation in the decision-making process for life support limitation (LSL). The study was based on an analysis of the patients' medical charts, looking at the medical and nursing care provided in the last 24 hours of life during a 6-month period in the two units, and on semi-structured interviews with 20 nurses to evaluate their participation in LSL decisions. The children were classified into two groups: those who were to receive full cardiopulmonary resuscitation (CPR) and a non-CPR group. A total of 34 deaths occurred during the study period. Of these, 17 (50%) were children that had been in the non-CPR group; there were only 10 recorded LSL plans in their medical charts. In the interviews, only 30% of the nurses mentioned active participation in LSL decisions. In conclusion, the paediatric intensive care nurses in these two Brazilian units did not participate much in LSL decisions, and the care offered in the last hours of life to children with terminal and irreversible illness was not primarily directed toward comfort and alleviating suffering.

Risk factors for extubation failure in infants with severe acute bronchiolitis.

OBJECTIVE: To evaluate demographic characteristics, mechanical-ventilation parameters, blood gas values, and ventilatory indexes as predictors of extubation failure in infants with severe acute bronchiolitis. METHODS: We conducted a prospective observational study from March 2004 to September 2005 with consecutive infants (ages 1-12 months) with severe acute bronchiolitis and considered ready to be extubated. We calculated mean airway pressure and oxygenation index. Before extubation we measured respiratory rate, tidal volume, rapid shallow breathing index, maximal inspiratory pressure, and load/force balance. Arterial blood gases were measured 1 hour before extubation. Extubation was classified as a failure if the infant needed re-intubation within 48 hours. RESULTS: Extubation failure occurred in 6 (15%) of the 40 extubated infants. The respective median (and interquartile range) age, weight, and days of mechanical ventilation for the extubation-failure and extubation-success groups were: age 5 (3-8) months versus 4 (4-6) months (P = .87), weight 4 (3-5) kg versus 6 (5-7) kg (P < .001), and mechanical ventilation days 8 (6-23) d versus 6 (5-12) d (P = .52). There were no significant differences in arterial blood gas values or mechanical-ventilation parameters between the extubation-success and extubation-failure groups. There were statistically significant differences between the extubation-failure and extubation-success groups for 2 risk factors, weight or= 5 and rapid shallow breathing index >or= 6.7. CONCLUSIONS: In infants with severe acute bronchiolitis the extubation process is complex because of the combined features of this disease. Pediatric studies have not definitely determined predictive factors, weaning protocols, or ventilatory predictive indexes of extubation failure risk in infants with severe acute bronchiolitis. Lower minute volume and lower maximal inspiratory pressure had large areas under the curve of the receiver operating characteristic for extubation-failure risk in infants with severe acute bronchiolitis.

Prevalence, mortality and risk factors associated with very low birth weight preterm infants: an analysis of 33 years.

OBJECTIVE: To assess the prevalence, mortality and risk factors associated with the birth of very low birth weight preterm infants over a period of 33 years. METHODS: Four cross-sectional studies were analyzed, using data from perinatal interviews of birth cohorts in the city of Pelotas collected in 1982, 1993, 2004, and 2015. Based on perinatal questionnaires, anthropometric measurements of newborns and death certificates were analyzed to obtain the prevalence rate, neonatal mortality, and risk factors (maternal age, income and type of delivery) for very low birth weight. RESULTS: A total of 19,625 newborns were included in the study. In the years 1982, 1993, 2004, and 2015, there were, respectively, 5909, 5232, 4226, and 4258 births. The prevalence of very low birth weight was, respectively, 1.1% (n=64), 0.9% (n=46), 1.4% (n=61), and 1.3% (n=54). There was no statistical evidence of an increasing trend over time (p=0.11). Among the risk factors, family income in the three poorest quintiles was associated with prevalence rates that were approximately twice as high as in the richest quintile (p=0.003). Mortality per 1000 live births for neonates weighing <1500g decreased from 688 to 259 per thousand from 1982 to 2015 (p<0.001), but still represented 61% of neonatal deaths in the latter year. CONCLUSION: Although mortality in very low birth weight decreased by more than 60% in recent years, this group still contributes with more than half of neonatal deaths. Low family income remains an important risk factor in this scenario.

Profile and consequences of children requiring prolonged mechanical ventilation in three Brazilian pediatric intensive care units.

OBJECTIVE: To describe the characteristics of children submitted to prolonged mechanical ventilation (MV), and evaluate their mortality, and associated factors as well as the potential impact at admissions to the pediatric intensive care unit (PICU). METHODS: We conducted a retrospective study enrolling all children admitted to three Brazilian PICUs between January 2003 and December 2005 submitted to MV > or =21 days. The three selected PICUs were located in university-affiliated hospitals. From the medical charts were reported anthropometric data, diagnosis, ventilator parameters on the 21st day, length of MV, length of stay in the PICU, specific interventions (e.g., tracheostomy), and outcome. RESULTS: One hundred eighty-four children (190 admissions) were submitted to prolonged MV (2.5% of all admissions to these 3 Brazilian PICUs), with a median age of 6 months. The mortality rate was 48% and the median time on MV was 32 days. Tracheostomy was performed on only 19% of the patients and, on average after 32 days of intubation. Mortality was associated with peak inspiratory pressure >25 cm H2O (odds ratio = 2.3; 1.1-5.1), fraction of inspired oxygen >0.5 (odds ratio = 6.3; 2.2-18.1), and vasoactive drug infusion (odds ratio = 2.6; 1.1-5.9) on the 21st day of MV. Seventy-six children (1% of the all admissions) were dependent on MV without other organ failures were 830 PICU admissions and were potentially prevented. CONCLUSIONS: A small group of children admitted to the PICU requires prolonged MV. The elevated mortality rate is associated with higher ventilatory parameters and vasoactive drug support on the 21st day of MV. Stable children requiring prolonged MV in the PICU potentially prevent additional admissions of a large number of acute and unstable patients.

Fluid balance in pediatric patients in prone position: a pragmatic study.

OBJECTIVE: To verify the association between prone position, increased diuresis, and decreased cumulative fluid balance in critically ill pediatric patients who underwent mechanical ventilation (MV) for pulmonary causes and describe adverse events related to the use of the position. METHODS: This is a retrospective observational study. Patients aged between 1 month and 12 years who underwent MV for pulmonary causes, between January 2013 and December 2015, were selected and divided between those who were put on prone position (PG) and those who were not (CG) during the hospitalization at the Pediatric Intensive Care Unit (PICU). Data were analyzed longitudinally from D1 to D4. RESULTS: A total of 77 patients (PG = 37 and CG = 40) were analyzed. The general characteristics of both groups were similar. In the comparison between the groups, there was no increase in diuresis or decrease in cumulative fluid balance in the prone group. In the longitudinal analysis of D1 to D4, we saw that the PG presented higher diuresis (p = 0.034) and a lower cumulative fluid balance (p = 0.001) in D2. Regarding the use of diuretics, there was greater use of furosemide (P <0.001) and spironolactone (P = 0.04) in the PG. There was no increase in adverse events during the use of the prone position. CONCLUSION: The prone position was not associated with increased diuresis or decreased cumulative fluid balance in critically ill pediatric patients who underwent to MV for pulmonary causes.

Dexmedetomidine in anesthesia of children submitted to videolaparoscopic appendectomy: a double-blind, randomized and placebo-controlled study.

OBJECTIVES: To evaluate the hemodynamic responses to nociceptive stimuli in children submitted to videolaparoscopic appendectomy under balanced anesthesia with isoflurane and dexmedetomidine. METHODS: Randomized, double-blind and placebo-controlled study involving 26 children submitted to videolaparoscopic appendectomy carried out at Hospital São Lucas (PUCRS) between May 2004 and February 2005. Patients were assigned to two groups: (a) Dexmedetomidine group (n=13): infusion of 1 microg/kg over 10 minutes and maintenance dose of 0.5 microg/kg/h) as an adjuvant to inhaled isoflurane anesthesia; (b) Control group (n=13): normal saline infusion at a similar rate and volume of the dexmedetomidine infusion. During the different surgical and anesthetic periods, groups were compared regarding heart rate, systolic and diastolic arterial blood pressures as well as need of supplemental fentanyl infusion. Student's t test, ANOVA, and Finner's procedure were used for statistical analysis. RESULTS: During the strongest nociceptive stimuli (airway access and abdominal catheter placement), the heart rate and systolic blood pressure increased significantly (p<0.001) in the control group compared to the dexmedetomidine group. Compared to baseline levels, the hemodynamic responses to nociceptive stimuli were more stable when dexmedetomidine was used in combination with inhaled isoflurane anesthesia. The need for supplemental doses of fentanyl and the hemodynamic parameters were similar for both groups. CONCLUSION: Dexmedetomidine combined with inhaled isoflurane for anesthesia of children submitted to videolaparoscopic appendectomy, efficiently blocks the hemodynamic responses to nociceptive stimuli. When compared to placebo, the use of dexmedetomidine did not change the need for supplemental doses of fentanyl for maintenance of hemodynamic parameters during the intraoperative period.

Pharmacologic support of infants and children in septic shock.

OBJECTIVES: Septic shock (SS) is a frequent cause for admission to the pediatric intensive care unit, requiring prompt recognition and intervention to improve outcome. Our aim is to review the relevant literature related to the diagnosis and management of SS and present a sequential management for its treatment. SOURCES: Non-systematic review of medical literature using the MEDLINE database. Articles were selected according to their relevance to the objective and according to the authors' opinions. SUMMARY OF THE FINDINGS: The outcome of sepsis and SS is dependent on the early recognition and implementation of time-sensitive goal-directed therapies. These include rapid aggressive fluid resuscitation followed by a well-designed pharmacotherapy. The goals of the resuscitation are the restoration of microcirculation and improved organ tissue perfusion. Clinical and laboratory markers are needed to assess the adequacy of the treatments. Altered pharmacokinetic and pharmacodynamic responses dictate that vasoactive agents should be adjusted to achieve the predetermined goals. In initial resuscitation with isotonic solutions (> 60 mL/kg), either crystalloid (normal saline) or colloid infusion could be used. Despite adequate fluid resuscitation, if: (a) wide pulse pressure, low blood pressure, or bounding pulses (high cardiac output, low systemic vascular resistance--SVR) are present, norepinephrine should be considered; (b) prolonged capillary refill, weak pulses, narrow pulse pressure, normotensive (low cardiac output, high SVR), dopamine, epinephrine or dobutamine should be considered. Adjunctive therapy with stress dose of corticosteroid is indicated in selected populations. CONCLUSIONS: Septic shock hemodynamics is a changing process that requires frequent assessment and therapeutic adjustments.

Current perspectives for treating children with diabetic ketoacidosis.

OBJECTIVE: To review current concepts of physiopathology, diagnosis and treatment of diabetic ketoacidosis (DKA) in childhood, as well as preventive measures to avoid cerebral edema. SOURCES: The authors selected articles from MEDLINE with the keywords diabetes, ketoacidosis, hyperglycemia and cerebral edema, and priority was given to studies including children and that contained complete texts published in English, Portuguese or Spanish. Chapters of books published in Brazil describing the treatment of DKA in pediatric intensive care unit were also reviewed. Based on the reviewed literature and on the author's experience, the most efficient and recommended measures for DKA management are presented. SUMMARY OF THE FINDINGS: Normal saline solution (NaCl 0.9%) has been increasingly used for fast replacement and hydration, as a substitute to diluted (hypotonic) solutions, as well as contraindication of sodium bicarbonate to repair metabolic acidosis in DKA. Regular insulin should be used as continuous infusion (0.1 IU/kg/h) without the need of a loading dose. For fast corrections of glucose oscillations, a practical scheme using two bags of electrolytic solutions is presented. Cerebral edema, its physiopathological mechanism and current treatment are reviewed. CONCLUSIONS: Use of continuous infusion of regular insulin associated with adequate water and electrolyte replacement using isotonic solutions, besides being an effective treatment for DKA, preserves plasma osmolarity and prevents cerebral edema.

Pediatric emergency in Brazil: the consolidation of an area in the pediatric field.

OBJECTIVE: The aim of this study was to present a review on the evolution, development, and consolidation of the pediatric emergency abroad and in Brazil, as well as to discuss the residency program in this key area for pediatricians. DATA SOURCES: This was a narrative review, in which the authors used pre-selected documents utilized as the minimum requirements for the Residency Program in Pediatric Emergency Medicine and articles selected by interest for the theme development, at the SciELO and Medline databases, between 2000 and 2017. DATA SYNTHESIS: The historical antecedents and the initial evolution of pediatric emergency in Brazil, as well as several challenges were described, regarding the organization, the size, the training of professionals, and also the regulation of the professional practice in this new specialty. Additionally, a new pediatric emergency residency program to be implemented in Brazil is described. CONCLUSIONS: Pediatric emergency training will be a powerful stimulus to attract talented individuals, to establish them in this key area of medicine, where they can exercise their leadership by promoting care qualification, research, and teaching, as well as acting decisively in their management.

Cardiac dysfunction and ferritin as early markers of severity in pediatric sepsis.

OBJECTIVE: The aim of this study was to verify the association of echocardiogram, ferritin, C-reactive protein, and leukocyte count with unfavorable outcomes in pediatric sepsis. METHODS: A prospective cohort study was carried out from March to December 2014, with pediatric critical care patients aged between 28 days and 18 years. Inclusion criteria were diagnosis of sepsis, need for mechanical ventilation for more than 48h, and vasoactive drugs. Serum levels of C-reactive protein, ferritin, and leukocyte count were collected on the first day (D0), 24h (D1), and 72h (D3) after recruitment. Patients underwent transthoracic echocardiography to determine the ejection fraction of the left ventricle on D1 and D3. The outcomes measured were length of hospital stay and in the pediatric intensive care unit, mechanical ventilation duration, free hours of VM, duration of use of inotropic agents, maximum inotropic score, and mortality. RESULTS: Twenty patients completed the study. Patients with elevated ferritin levels on D0 had also fewer ventilator-free hours (p=0.046) and higher maximum inotropic score (p=0.009). Patients with cardiac dysfunction by echocardiogram on D1 had longer hospital stay (p=0.047), pediatric intensive care unit stay (p=0.020), duration of mechanical ventilation (p=0.011), maximum inotropic score (p=0.001), and fewer ventilator-free hours (p=0.020). CONCLUSION: Cardiac dysfunction by echocardiography and serum ferritin value was significantly associated with unfavorable outcomes in pediatric patients with sepsis.