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Background: Traumatic brain injury (TBI) is a major cause of death and disability worldwide. The decision-making process in the management of severe TBI must be based on the best available evidence to minimize the occurrence of secondary brain injuries. However, healthcare approaches to managing TBI patients exhibit considerable variation., Methods: Over an 18-month period, a multidisciplinary panel consisting of medical doctors, physiotherapists, nutritional therapists, and nurses performed a comprehensive review on various subtopics concerning TBI. The panel identified primary questions to be addressed using the Population, Intervention, Control, and Outcome (PICO) format and applied the Evidence to Decision (EtD) framework criteria for evaluating interventions. Subsequently, the panel formulated recommendations for the management of severe TBI in children., Results: Fourteen evidence-based recommendations have been devised for the management of severe TBI in children, covering nine topics, including imaging studies, neuromonitoring, prophylactic anticonvulsant use, hyperosmolar therapy, sedation and analgesia, mechanical ventilation strategies, nutritional therapy, blood transfusion, and decompressive craniectomy. For each topic, the panel provided clinical recommendations and identified research priorities., Conclusions: This review offers evidence-based strategies aimed to guide practitioners in the care of children who suffer from severe TBI., Competing Interests: Declarations: We confirm that the manuscript complies with all instructions to authors. We confirm that authorship requirements have been met and the final manuscript was approved by all authors. We confirm that this manuscript has not been published elsewhere and is not under consideration by another journal. We used the AGREE checklist for this manuscript. Ethical approval: Ethics approval for this study does not apply because it does not involve any data from human or animal participants. Conflict of interest: The authors have no conflicts of interest to disclose., (© 2024. Fondazione Società Italiana di Neurologia.)

Background and Purpose: Sepsis-surviving adult individuals commonly develop immunosuppression and increased susceptibility to secondary infections, an outcome mediated by the axis IL-33/ILC2s/M2 macrophages/Tregs. Nonetheless, the long-term immune consequences of paediatric sepsis are indeterminate. We sought to investigate the role of age in the genesis of immunosuppression following sepsis., Experimental Approach: Here, we compared the frequency of Tregs, the activation of the IL-33/ILC2s axis in M2 macrophages and the DNA methylation of epithelial lung cells from post-septic infant and adult mice. Likewise, sepsis-surviving mice were inoculated intranasally with Pseudomonas aeruginosa or by subcutaneous inoculation of the B16 melanoma cell line. Finally, blood samples from sepsis-surviving patients were collected and the concentration of IL-33 and Tregs frequency were assessed., Key Results: In contrast to 6-week-old mice, 2-week-old mice were resistant to secondary infection and did not show impairment in tumour controls upon melanoma challenge. Mechanistically, increased IL-33 levels, Tregs expansion, and activation of ILC2s and M2-macrophages were observed in 6-week-old but not 2-week-old post-septic mice. Moreover, impaired IL-33 production in 2-week-old post-septic mice was associated with increased DNA methylation in lung epithelial cells. Notably, IL-33 treatment boosted the expansion of Tregs and induced immunosuppression in 2-week-old mice. Clinically, adults but not paediatric post-septic patients exhibited higher counts of Tregs and seral IL-33 levels., Conclusion and Implications: These findings demonstrate a crucial and age-dependent role for IL-33 in post-sepsis immunosuppression. Thus, a better understanding of this process may lead to differential treatments for adult and paediatric sepsis., (© 2023 British Pharmacological Society.)

Background: We aimed to compare the effect of manual hyperinflation with versus without positive end-expiratory pressure (PEEP) on dynamic compliance of the respiratory system in pediatric patients undergoing congenital heart surgery; to assess the safety of the technique in this population., Methods: This was a randomized controlled trial conducted at the pediatric intensive care unit (PICU) of a tertiary-care hospital. Patients admitted to the PICU following cardiac surgery and receiving postoperative mechanical ventilation were randomized to the experimental or control group. Patients in the experimental group (n = 14) underwent manual hyperinflation with a PEEP valve set at 5 cm H2O, once daily, during the first 48 hours after surgery. Patients allocated to the control group (n = 16) underwent manual hyperinflation without PEEP, at the same time points. Lung mechanics was assessed before (T0) and 5 minutes (T5) after manual hyperinflation. The primary endpoint was dynamic compliance. Secondary outcomes included oxygen saturation index, duration of mechanical ventilation, length of stay, 28-day mortality and safety., Results: Demographic and clinical characteristics were comparable in both groups. There was no significant difference in dynamic compliance between times in each group (Day 1: (mean) 0.78 vs 0.81 and 0.70 vs 0.77; Day 2: 0.85 vs 0.78 and 0.67 vs 0.68 mL/kg/cm H2O, in experimental and control groups, respectively; P > .05). Mean deltas of dynamic compliance were not significantly different between groups. The proportion of patients extubated <72 hours after surgery was similar in experimental and control groups (43% vs 50%, respectively; P = .73). Oxygen saturation index, length of stay, and 28-day mortality were not significantly different between groups. None of the patients had hemodynamic instability., Conclusions: Manual hyperinflation was safe and well tolerated in pediatric patients following surgery for congenital heart disease. No significant change in dynamic compliance of the respiratory system or in oxygenation was observed with the use of manual hyperinflation with or without PEEP in this population., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Neutrophil extracellular traps (NETs) are innate defense mechanisms that are also implicated in the pathogenesis of organ dysfunction. However, the role of NETs in pediatric sepsis is unknown., Methods: Infant (2 weeks old) and adult (6 weeks old) mice were submitted to sepsis by intraperitoneal (i.p.) injection of bacteria suspension or lipopolysaccharide (LPS). Neutrophil infiltration, bacteremia, organ injury, and concentrations of cytokine, NETs, and DNase in the plasma were measured. Production of reactive oxygen and nitrogen species and release of NETs by neutrophils were also evaluated. To investigate the functional role of NETs, mice undergoing sepsis were treated with antibiotic plus rhDNase and the survival, organ injury, and levels of inflammatory markers and NETs were determined. Blood samples from pediatric and adult sepsis patients were collected and the concentrations of NETs measured., Results: Infant C57BL/6 mice subjected to sepsis or LPS-induced endotoxemia produced significantly higher levels of NETs than the adult mice. Moreover, compared to that of the adult mice, this outcome was accompanied by increased organ injury and production of inflammatory cytokines. The increased NETs were associated with elevated expression of Padi4 and histone H3 citrullination in the neutrophils. Furthermore, treatment of infant septic mice with rhDNase or a PAD-4 inhibitor markedly attenuated sepsis. Importantly, pediatric septic patients had high levels of NETs, and the severity of pediatric sepsis was positively correlated with the level of NETs., Conclusion: This study reveals a hitherto unrecognized mechanism of pediatric sepsis susceptibility and suggests that NETs represents a potential target to improve clinical outcomes of sepsis.

Objectives: To evaluate the discrepancies between clinical and autopsy diagnoses in patients who died in the pediatric intensive care units (PICUs) of a tertiary care university hospital., Methods: A prospective study of all consecutive autopsies discussed at monthly mortality conferences over 5 years. Discrepancies between premortem and autopsy diagnoses were classified according to modified Goldman et al criteria., Results: From January 1, 2011, to December 31, 2015, a total of 2,679 children were admitted to the two PICUs of our hospital; 257 (9.6%) died, 150 (58.4%) underwent autopsy, and 123 were included. Complete concordance between clinical and postmortem diagnoses was observed in 86 (69.9%) patients; 20 (16.3%) had a class I discrepancy, and eight (6.5%) had a class II discrepancy. Comparing 2011 and 2015, the rate of major discrepancies decreased from 31.6% to 15%., Conclusions: Our results emphasize the importance of autopsy to clarify the cause of death and its potential contribution to improvement of team performance and quality of care., (© American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Diabetic ketoacidosis (DKA), a common cause of severe metabolic acidosis, remains a life-threatening condition due to complications of both the disease and its treatment. This Acid-Base and Electrolyte Teaching Case discusses DKA management, emphasizing complications of treatment. Because cerebral edema is the most common cause of mortality and morbidity, especially in children with DKA, we emphasize its pathophysiology and implications for therapy. The risk for cerebral edema may be minimized by avoiding a bolus of insulin, excessive saline resuscitation, and a decrease in effective plasma osmolality early in treatment. A goal of fluid therapy is to lower muscle venous Pco 2 to ensure effective removal of hydrogen ions by bicarbonate buffer in muscle and diminish the binding of hydrogen ions to intracellular proteins in vital organs (such as the brain). In patients with DKA and a relatively low plasma potassium level, insulin administration may cause hypokalemia and cardiac arrhythmias. It is suggested in these cases to temporarily delay insulin administration and first administer potassium chloride intravenously to bring the plasma potassium level close to 4mmol/L. Sodium bicarbonate administration in adult patients should be individualized. We suggest it be considered in a subset of patients with moderately severe acidemia (pH<7.20 and plasma bicarbonate level < 12mmol/L) who are at risk for worsening acidemia, particularly if hemodynamically unstable. Sodium bicarbonate should not be administered to children with DKA, except if acidemia is very severe and hemodynamic instability is refractory to saline administration., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: We aimed to investigate the epidemiology, risk factors, and short- and medium-term outcome of acute kidney injury classified according to pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease, and Kidney Disease: Improving Global Outcomes criteria in critically ill children., Design: Prospective observational cohort study., Setting: Two eight-bed PICUs of a tertiary-care university hospital., Patients: A heterogeneous population of critically ill children., Interventions: None., Measurements and Main Results: Demographic, clinical, laboratory, and outcome data were collected on all patients admitted to the PICUs from August 2011 to January 2012, with at least 24 hours of PICU stay. Of the 214 consecutive admissions, 160 were analyzed. The prevalence of acute kidney injury according to pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease and Kidney Disease: Improving Global Outcomes criteria was 49.4% vs. 46.2%, respectively. A larger proportion of acute kidney injury episodes was categorized as Kidney Disease: Improving Global Outcomes stage 3 (50%) compared with pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease F (39.2%). Inotropic score greater than 10 was a risk factor for acute kidney injury severity. About 35% of patients with acute kidney injury who survived were discharged from the PICU with an estimated creatinine clearance less than 75 mL/min/1.73 m and one persisted with altered renal function 6 months after PICU discharge. Age 12 months old or younger was a risk factor for estimated creatinine clearance less than 75 mL/min/1.73 m at PICU discharge. Acute kidney injury and its severity were associated with increased PICU length of stay and longer duration of mechanical ventilation. Eleven patients died; nine had acute kidney injury (p < 0.05). The only risk factor associated with death after multivariate adjustment was Pediatric Risk of Mortality score greater than or equal to 10., Conclusions: Acute kidney injury defined by both pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease and Kidney Disease: Improving Global Outcomes criteria was associated with increased morbidity and mortality, and may lead to long-term renal dysfunction.

Objectives: We aimed to evaluate the value of serum cystatin C for detection of acute kidney injury and pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease categories in critically ill children and to investigate whether serum cystatin C was associated with outcome., Design: Prospective cohort study., Setting: PICU of a tertiary-care university hospital., Patients: A heterogeneous population of critically ill children., Interventions: None., Measurements and Main Results: Blood and 24-hour urine samples were collected daily over the first 2 days after PICU admission for measurement of serum cystatin C, serum creatinine, and creatinine clearance. Acute kidney injury was classified by pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease criteria. One hundred twenty-two children were prospectively enrolled; 40 (32.8%) developed acute kidney injury. Serum cystatin C was higher in patients with acute kidney injury compared with those who did not develop acute kidney injury at PICU admission (median, 0.90 mg/L vs 0.51 mg/L) and on the first (1.12 mg/L vs 0.57 mg/L) and second PICU days (1.15 mg/L vs 0.58 mg/L). Serum creatinine was higher in acute kidney injury group only on the first (0.50 mg/dL vs 0.40 mg/dL) and second PICU days (0.60 mg/dL vs 0.40 mg/dL). Serum cystatin C was increasingly higher according to acute kidney injury severity (Failure > Injury > Risk). Area under the receiver operating characteristic curve of cystatin C for acute kidney injury detection was 0.89. Serum cystatin C greater than 0.70 mg/L was associated with longer length of PICU stay (adjusted hazard ratio, 1.64) and prolonged duration of mechanical ventilation (adjusted hazard ratio, 1.82)., Conclusions: Cystatin C is an early and accurate biomarker for acute kidney injury and pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease categories, and it is associated with adverse clinical outcomes in a heterogeneous population of critically ill children.

Objective: There is no consensus on adequate adrenal response to critical illness. We aimed to evaluate adrenal function in critically ill children and its association with clinical outcome. We hypothesized that salivary cortisol would be a more appropriate tool to evaluate adrenal function in critically ill children., Methods: This was a prospective cohort study. The concentrations of serum total and salivary cortisol were measured in 34 critically ill children before and after stimulation with 250 μg adrenocorticotropic hormone (ACTH), and values were compared to a control group of healthy children (n = 15). Association between outcome and adrenal insufficiency defined by an increment in serum cortisol ≤250 nm (9 μg/dl) post-ACTH was assessed., Results: Serum total and salivary cortisol concentrations pre- and post-ACTH were significantly higher in patients, and they were correlated at baseline (r = 0·67; P < 0·0001) and after ACTH (r = 0·41; P = 0·02). The incidence of adrenal insufficiency was 32·3%. This group had higher Paediatric Risk of Mortality III score (P = 0·04) but Paediatric Logistic Organ Dysfunction and vasoactive inotropic scores, duration of mechanical ventilation and length of paediatric intensive care unit and hospital stay were not significantly different compared with those with an increment >250 nm (9 μg/dl) post-ACTH. An inverse correlation between salivary cortisol post-ACTH and vasoactive inotropic score (r = -0·56; P = 0·0008) was observed. A salivary cortisol concentration post-ACTH of ≤226 nm (8·2 μg/dl) had a sensitivity of 79% and a specificity of 62% to discriminate need for vasoactive or inotropic support (area under receiver operating characteristic (ROC) curve 0·74)., Conclusion: Adrenal insufficiency defined by the 'delta criterion' was not associated with outcome. A post-ACTH salivary cortisol of ≤226 nm (8·2 μg/dl) may be suggestive of an insufficient adrenal response to critical illness., (© 2014 John Wiley & Sons Ltd.)

Objectives: To test the tolerance and safety of an alveolar recruitment manoeuvre performed in the immediate postoperative period of corrective open heart surgery in children with congenital heart disease associated with excessive pulmonary blood flow and pulmonary arterial hypertension due to left-to-right shunt., Methods: Ten infants aged 1-24 months with congenital heart disease associated with excessive pulmonary blood flow and pulmonary artery hypertension (mean pulmonary artery pressure ≥ 25 mmHg) were evaluated. The alveolar recruitment manoeuvre was performed in the operating theatre right after skin closure, and consisted of three successive stages of 30 s each, intercalated by a 1-min interval of baseline ventilation. Positive end-expiratory pressure was set to 10 cmH2O in the first stage and to 15 cmH2O in the two last ones, while the peak inspiratory pressure was kept at to 30 cmH2O in the first stage and at 35 cmH2O in the latter ones. Haemodynamic and respiratory variables were recorded., Results: There was a slight but significant increase in mean pulmonary artery pressure from baseline to Stage 3 (P = 0.0009), as well as between Stages 1 and 2 (P = 0.0001), and 1 and 3 (P = 0.001), with no significant difference between Stages 2 and 3 (P = 0.06). Upon completion of the third stage, there were significant increases in arterial haemoglobin saturation as measured by pulse oximetry (P = 0.0009), arterial blood partial pressure of oxygen (P = 0.04), venous blood oxygen saturation of haemoglobin (P = 0.03) and arterial oxygen partial pressure over inspired oxygen fraction ratio (P = 0.04). A significant reduction in arterial blood partial pressure of carbon dioxide (P = 0.01) and in end tidal carbon dioxide also occurred (P = 0.009). The manoeuvre was well tolerated and besides a slight and transitory elevation in mean pulmonary artery, no other adverse haemodynamic or ventilatory effect was elicited., Conclusions: The alveolar recruitment manoeuvre seemed to be safe and well tolerated immediately after open heart surgery in infants liable to pulmonary hypertensive crises.

We aimed to investigate whether nuclear factor kappa-B activation, as evaluated by gene expression of its inhibitor (I-κBα) and cytokine serum levels, was associated with myocardial dysfunction and mortality in children with septic shock. Twenty children with septic shock were prospectively enrolled and grouped according to ejection fraction (EF) <45% (group 1) or EF ≥45% (group 2) on the first day after admission to the pediatric intensive care unit. No interventions were made. In the first day, patients from group 1 (n = 6) exhibited significantly greater tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-10 plasma levels. However, I-κBα gene expression was not different in both groups. Mortality and number of complications were significantly greater in group 1. Patients who died had greater plasma concentrations of TNF-α. In conclusion, TNF-α and IL-10 are involved in myocardial dysfunction accompanying septic shock in children, and TNF-α is associated with mortality.

Background: The diagnosis of ventilator-associated pneumonia (VAP) is a challenge, particularly after cardiac surgery. The use of biological markers of infection has been suggested to improve the accuracy of VAP diagnosis. We aimed to evaluate the usefulness of soluble triggering receptor expressed on myeloid cells (sTREM)-1 in the diagnosis of VAP following cardiac surgery., Methods: This was a prospective observational cohort study of children with congenital heart disease admitted to the pediatric intensive care unit (PICU) after surgery and who remained intubated and mechanically ventilated for at least 24 hours postoperatively. VAP was defined by the 2007 Centers for Disease Control and Prevention criteria. Blood, modified bronchoalveolar lavage (mBAL) fluid and exhaled ventilator condensate (EVC) were collected daily, starting immediately after surgery until the fifth postoperative day or until extubation for measurement of sTREM-1., Results: Thirty patients were included, 16 with VAP. Demographic variables, Pediatric Risk of Mortality (PRISM) and Risk Adjustment for Congenital Heart Surgery (RACHS)-1 scores, duration of surgery and length of cardiopulmonary bypass were not significantly diferent in patients with and without VAP. However, time on mechanical ventilation and length of stay in the PICU and in the hospital were significantly longer in the VAP group. Serum and mBAL fluid sTREM-1 concentrations were similar in both groups. In the VAP group, 12 of 16 patients had sTREM-1 detected in EVC, whereas it was undetectable in all but two patients in the non-VAP group over the study period (p = 0.0013) (sensitivity 0.75, specificity 0.86, positive predictive value 0.86, negative predictive value 0.75, positive likelihood ratio (LR) 5.25, negative LR 0.29)., Conclusion: Measurement of sTREM-1 in EVC may be useful for the diagnosis of VAP after cardiac surgery.

Objectives: To investigate whether the development of hypokalemia in patients with diabetic ketoacidosis (DKA) treated in the pediatric critical care unit (PCCU) could be caused by increased potassium (K(+)) excretion and its association with insulin treatment., Study Design: In this prospective observational study of patients with DKA admitted to the PCCU, blood and timed urine samples were collected for measurement of sodium (Na(+)), K(+), and creatinine concentrations and for calculations of Na(+) and K(+) balances. K(+) excretion rate was expressed as urine K(+)-to-creatinine ratio and fractional excretion of K(+)., Results: Of 31 patients, 25 (81%) developed hypokalemia (plasma K(+) concentration <3.5 mmol/L) in the PCCU at a median time of 24 hours after therapy began. At nadir plasma K(+) concentration, urine K(+)-to-creatinine ratio and fractional excretion of K(+) were greater in patients who developed hypokalemia compared with those without hypokalemia (19.8 vs 6.7, P = .04; and 31.3% vs 9.4%, P = .004, respectively). Patients in the hypokalemia group received a continuous infusion of intravenous insulin for a longer time (36.5 vs 20 hours, P = .015) and greater amount of Na(+) (19.4 vs 12.8 mmol/kg, P = .02). At peak kaliuresis, insulin dose was higher in the hypokalemia group (median 0.07, range 0-0.24 vs median 0.025, range 0-0.05 IU/kg; P = .01), and there was a significant correlation between K(+) and Na(+) excretion (r = 0.67, P < .0001)., Conclusions: Hypokalemia was a delayed complication of DKA treatment in the PCCU, associated with high K(+) and Na(+) excretion rates and a prolonged infusion of high doses of insulin., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Objectives: To investigate whether perioperative serum levels of oxidative stress markers, thiobarbituric acid reactive substances (TBARS), and carbonyl moieties are associated with outcomes in children after heart surgery., Background: Oxidative stress markers are increased following heart surgery with cardiopulmonary bypass (CPB) and can play a role in ischemia-reperfusion injury, but its associations with myocardial dysfunction, low cardiac output syndrome (LCOS), and outcomes are not proven., Methods: In a retrospective secondary analysis of a cohort study comprising 55 children (median age, 109 [2-611] days), we compared pre-, intra- and postoperative serum levels of TBARS and carbonyl moieties among patients with and without postoperative LCOS, cyanotic and acyanotic congenital heart disease (CHD), and survivors and nonsurvivors. We also assessed the independent effect of TBARS and carbonyl moieties peak levels on the mortality-adjusted hospital length of stay (aLOS)., Results: Patients who developed postoperative LCOS (n = 36) were significantly younger, more frequently cyanotic, more severely ill, and underwent more complex procedures with longer CPB. However, TBARS and carbonyl moieties serum levels did not change significantly over time. Moreover, they were not significantly different in patients with or without LCOS, cyanotic and acyanotic CHD, or survivors and nonsurvivors. There was a significant correlation between TBARS and tumor necrosis factor alpha (TNF-α) peak serum levels. Neither TBARS nor carbonyl moieties peak serum levels were independently associated with aLOS., Conclusions: In conclusion, oxidative stress markers TBARS and carbonyl moieties were not associated with the development of LCOS, the aLOS, or mortality in children after heart surgery with CPB., (© 2012 Blackwell Publishing Ltd.)

Purpose: We aimed to test the convergent validity of the COMFORT scale and the Cardiac Analgesic Assessment Scale (CAAS) and to evaluate changes in physiological parameters over time in response to a painful procedure in neonates and infants following cardiac surgery., Methods: From October 2006 to May 2008, 16 children were prospectively evaluated over 1-3 days after cardiac surgery while they remained on mechanical ventilation and received infusions of sedatives and analgesics. Pain was assessed by the COMFORT scale and CAAS before and during endotracheal tube suctioning. Heart rate, systemic systolic blood pressure, pulmonary artery pressure, oxygen saturation and pupil size were recorded at the same times., Results: During endotracheal suctioning on the first day, there was a significant increase in COMFORT and CAAS scores, systemic systolic blood pressure tended to decrease, pulmonary artery pressure significantly increased and there was a significant reduction in oxygen saturation. Heart rate and pupil size did not change significantly during the painful procedure throughout the study. COMFORT scores significantly correlated with CAAS scores on all days. Nevertheless, agreement for the detection of pain between both scales was weak (κ<0.5). The COMFORT scale detected more patients with pain., Conclusions: There was poor agreement between the COMFORT scale and CAAS for detection of pain in neonates and infants who had undergone cardiac surgery. A reduction in systemic systolic blood pressure and a rise in pulmonary artery pressure were observed during painful stimulation on the first post-operative day. For this population, a pain scale scoring physiological parameters according to their variation to higher and lower values should be developed.

The goal of this study was to examine the prevalence, assessment and management of pediatric pain in a public teaching hospital. The study sample consisted of 121 inpatients (70 infants, 36 children, and 15 adolescents), their families, 40 physicians, and 43 nurses. All participants were interviewed except infants and children who could not communicate due to their clinical status. The interview included open-ended questions concerning the inpatients' pain symptoms during the 24 h preceding data collection, as well as pain assessment and pharmacological/non-pharmacological management of pain. The data were obtained from 100% of the eligible inpatients. Thirty-four children/adolescents (28%) answered the questionnaire and for the other 72% (unable to communicate), the family/health professional caregivers reported pain. Among these 34 persons, 20 children/adolescents reported pain, 68% of whom reported that they received pharmacological intervention for pain relief. Eighty-two family caregivers were available on the day of data collection. Of these, 40 family caregivers (49%) had observed their child's pain response. In addition, 74% reported that the inpatients received pharmacological management. Physicians reported that only 38% of the inpatients exhibited pain signs, which were predominantly acute pain detected during clinical procedures. They reported that 66% of patients received pharmacological intervention. The nurses reported pain signs in 50% of the inpatients, which were detected during clinical procedures. The nurses reported that pain was managed in 78% of inpatients by using pharmacological and/or non-pharmacological interventions. The findings provide evidence of the high prevalence of pain in pediatric inpatients and the under-recognition of pain by health professionals.

Purpose: To evaluate the growth of children after repair of Tetralogy of Fallot, as well as the influence of residual lesions and socio-economic status., Methods: A total of 17 children, including 10 boys with a median age of 16 months at surgery, were enrolled in a retrospective cohort, in a tertiary care university hospital. Anthropometric (as z-scores), clinical, nutritional, and social data were collected., Results: Weight-for-age and weight-for-height z-scores decreased pre-operatively and recovered post-operatively in almost all patients, most markedly weight for age. Weight-for-height z-scores improved, but were still lower than birth values in the long term. Long-term height-for-age z-scores were higher than those at birth, surgery, and 3 months post-operatively. Most patients showed catch-up growth for height for age (70%), weight for age (82%), and weight for height (70%). Post-operative residual lesions (76%) influenced weight-for-age z-scores. Despite the fact that most patients (70%) were from low-income families, energy intake was above the estimated requirement for age and gender in all but one patient. There was no influence of socio-economic status on pre- and post-operative growth. Bone age was delayed and long-term-predicted height was within mid-parental height limits in 16 children (93%)., Conclusion: Children submitted to Tetralogy of Fallot repair had pre-operative acute growth restriction and showed post-operative catch-up growth for weight and height. Acute growth restriction could still be present in the long term.

Objective: Cardiopulmonary bypass is associated with ischemia-reperfusion injury to multiple organs. We aimed to evaluate whether remote ischemic preconditioning performed the day before surgery for congenital heart disease with cardiopulmonary bypass attenuates the postoperative inflammatory response and myocardial dysfunction., Methods: This was a prospective, randomized, single-blind, controlled trial. Children allocated to remote ischemic preconditioning underwent 4 periods of 5 minutes of lower limb ischemia by a blood pressure cuff intercalated with 5 minutes of reperfusion. Blood samples were collected 4, 12, 24, and 48 hours after cardiopulmonary bypass to evaluate nuclear factor kappa B activation in leukocytes by quantification of mRNA of I kappa B alpha by real-time quantitative polymerase chain reaction and for interleukin-8 and 10 plasma concentration measurements by enzyme-linked immunosorbent assay. Myocardial dysfunction was assessed by N-terminal pro-B-type natriuretic peptide and cardiac troponin I plasma concentrations, measured by chemiluminescence, and clinical parameters of low cardiac output syndrome., Results: Twelve children were allocated to remote ischemic preconditioning, and 10 children were allocated to the control group. Demographic data and Risk Adjustment for Congenital Heart Surgery 1 classification were comparable in both groups. Remote ischemic preconditioning group had lower postoperative values of N-terminal pro-B-type natriuretic peptide, but cardiac troponin I levels were not significantly different between groups. Interleukin-8 and 10 concentrations and I kappa B alpha gene expression were similar in both groups. Postoperative morbidity was similar in both groups; there were no postoperative deaths in either group., Conclusions: Late remote ischemic preconditioning did not provide clinically relevant cardioprotection to children undergoing cardiopulmonary bypass., (Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Submitted July 20, 2011; Accepted October 6, 2011. Neoaortic root dilatation and neoaortic valve regurgitation following the arterial switch operation for transposition of the great arteries may ultimately require neoaortic root and/or neoaortic valve surgery. The ideal surgical approach to these lesions remains debatable. Hazekamp et al, in 1997, introduced the replacement of the neoaortic root by the neopulmonary autograft and named this procedure the switch back Ross operation. We report two patients who were successfully treated at our institution with the switch back Ross operation, with good results at, respectively, four- and five-year follow-up.

The objective of this study is to retrospectively report the results of interventions for controlling a vancomycin-resistant enterococcus (VRE) outbreak in a tertiary-care pediatric intensive care unit (PICU) of a University Hospital. After identification of the outbreak, interventions were made at the following levels: patient care, microbiological surveillance, and medical and nursing staff training. Data were collected from computer-based databases and from the electronic prescription system. Vancomycin use progressively increased after March 2008, peaking in August 2009. Five cases of VRE infection were identified, with 3 deaths. After the interventions, we noted a significant reduction in vancomycin prescription and use (75% reduction), and the last case of VRE infection was identified 4 months later. The survivors remained colonized until hospital discharge. After interventions there was a transient increase in PICU length-of-stay and mortality. Since then, the use of vancomycin has remained relatively constant and strict, no other cases of VRE infection or colonization have been identified and length-of-stay and mortality returned to baseline. In conclusion, we showed that a bundle intervention aiming at a strict control of vancomycin use and full compliance with the Hospital Infection Control Practices Advisory Committee guidelines, along with contact precautions and hand-hygiene promotion, can be effective in reducing vancomycin use and the emergence and spread of vancomycin-resistant bacteria in a tertiary-care PICU.

The 2009 pandemic influenza A (H1N1) caused significant morbidity and mortality. Acute lung injury is the hallmark of the disease, but multiple organ system dysfunction can develop and lead to death. Therefore, we sought to investigate whether there was postmortem evidence of H1N1 presence and virus-induced organ injury in autopsy specimens. Five cases in which patients died of influenza A (H1N1) virus infection were studied. The lungs of all patients showed macroscopic and microscopic findings already described for H1N1 (consolidation, edema, hemorrhage, alveolar damage, hyaline membrane, and inflammation), and H1N1 viruses were present in alveolar cells in immunochemical studies. Acute tubular necrosis was present in all cases, but there was no evidence of direct virus-induced kidney injury. Nevertheless, H1N1 viruses were found in the cytoplasm of glomerular macrophages in the kidneys of 4 patients. Therefore, our data provide strong evidence that H1N1 presence is not restricted to the lungs.

Aims: To evaluate cell catabolism by balance of nitrogen and phosphate, and creatinine excretion in children post-cardiac surgery; to establish protein and energy requirements to minimize catabolism; and to assess nutritional therapy by following these parameters and serial anthropometric measurements., Methods: A prospective observational study of children with congenital heart disease undergoing cardiac surgery. Blood samples and 24-h urine collections were obtained postoperatively for creatinine measurement and nitrogen and phosphate balance. Anthropometric measurements (weight, mid-arm muscle circumference and triceps skinfold thickness) were obtained preoperatively and at paediatric intensive care unit and hospital discharge., Results: Eleven children were studied for 3-10 postoperative days. Anabolism was associated with higher protein and energy intakes compared to catabolism (1.1 vs. 0.1 g/kg/day and 54 vs. 17 kcal/kg/day, respectively). On days with anabolism, phosphate balance was greater compared with that on days with catabolism. Daily creatinine excretion did not correlate with protein balance. Anthropometric measurements did not change significantly over time., Conclusions: Children with congenital heart disease undergoing cardiac surgery achieved anabolism with >55 kcal/kg/day and >1 g/kg/day of protein. Balance of phosphate was useful to monitor cell breakdown. Anthropometric measurements were not valuable to evaluate nutritional therapy in this population., (© 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.)

Objective: To evaluate the effect of oral hygiene with 0.12% chlorhexidine gluconate on the incidence of nosocomial pneumonia and ventilator-associated pneumonia (VAP) in children undergoing cardiac surgery., Design: Prospective, randomized, double-blind, placebo-controlled trial., Setting: Pediatric intensive care unit (PICU) at a tertiary care hospital., Patients: One hundred sixty children undergoing surgery for congenital heart disease, randomized into 2 groups: chlorhexidine (n = 87) and control (n = 73)., Interventions: Oral hygiene with 0.12% chlorhexidine gluconate or placebo preoperatively and twice a day postoperatively until PICU discharge or death., Results: Patients in experimental and control groups had similar ages (median, 12.2 vs 10.8 months; P = .72) and risk adjustment for congenital heart surgery 1 score distribution (66% in category 1 or 2 in both groups; P = .17). The incidence of nosocomial pneumonia was 29.8% versus 24.6% (P = .46) and the incidence of VAP was 18.3% versus 15% (P = .57) in the chlorhexidine and the control group, respectively. There was no difference in intubation time (P = .34), need for reintubation (P = .37), time interval between hospitalization and nosocomial pneumonia diagnosis (P = .63), time interval between surgery and nosocomial pneumonia diagnosis (P = .10), and time on antibiotics (P = .77) and vasoactive drugs (P = .16) between groups. Median length of PICU stay (3 vs 4 days; P = .53), median length of hospital stay (12 vs 11 days; P = .67), and 28-day mortality (5.7% vs 6.8%; P = .77) were also similar in the chlorhexidine and the control group., Conclusions: Oral hygiene with 0.12% chlorhexidine gluconate did not reduce the incidence of nosocomial pneumonia and VAP in children undergoing cardiac surgery., Trial Registration: ClinicalTrials.gov identifier: NCT00829842 .

The authors report a case of abdominal compartment syndrome caused by massive pyonephrosis in an infant with primary obstructive megaureter successfully treated with emergency surgical decompression.

Aim: To evaluate whether the ventricular septal defect (VSD) size, along with the degree of preoperative growth impairment and age at repair, may influence postoperative growth, and if VSD size can be useful to identify children at risk for preoperative failure to thrive., Methods: Sixty-eight children submitted to VSD repair in a Brazilian tertiary-care institution were evaluated. Weight and height measurements were converted to Z-scores. Ventricular septal defect size was normalized by dividing it by the aortic root diameter (VSD/Ao ratio)., Results: Twenty-six patients (38%) had significantly low weight-for-height, 10 patients (15%) had significantly low height-for-age and 13 patients (19%) had both conditions at repair. Catch-up growth occurred in 82% of patients for weight-for-age, in 75% of patients for height-for-age and in 89% of patients for weight-for-height. Weight-for-height Z-scores at surgery were significantly lower in patients who underwent repair before 9 months of age. The VSD/Ao ratio did not associate with any other data. On multivariate analysis, weight-for-age Z-scores and age at surgery were independent predictors of long-term weight and height respectively., Conclusion: The VSD/Ao ratio was not a good predictor of preoperative failure to thrive. Most patients had preoperative growth impairment and presented catch-up growth after repair. Preoperative growth status and age at surgery influenced long-term growth., (© 2010 The Author(s)/Journal Compilation © 2010 Foundation Acta Paediatrica.)

Objective: To evaluate if the hemostatic high-dose aprotinin seems to reduce the inflammatory process after extracorporeal circulation (ECC) in children., Methods: A prospective randomized study was conducted on children aged 30 days to 4 years submitted to correction of acyanogenic congenital heart disease with ECC and divided into two groups: Control (n=9) and Aprotinin (n=10). In the Aprotinin Group the drug was administered before and during ECC and the systemic inflammatory response and hemostatic and multiorgan dysfunctions were analyzed on the basis of clinical and biochemical markers. Differences were considered to be significant when P<0.05., Results: The groups were similar regarding demographic and intraoperative variables, except for a greater hemodilution in the Aprotinin Group. The drug had no benefit regarding time of mechanical pulmonary ventilation, permanence in the postoperative ICU and length of, Conclusion: In this series, hemostatic high-dose aprotinin did not minimize the clinical manifestations or serum markers of the inflammatory systemic response.

The incidence of cerebral edema during therapy of diabetic ketoacidosis (DKA) in children remains unacceptably high-this suggests that current treatment may not be ideal and that important risk factors for the development of cerebral edema have not been recognized. We suggest that there are two major sources for an occult generation of osmole-free water in these patients: first, fluid with a low concentration of electrolytes that was retained in the lumen of the stomach when the patient arrived in hospital; second, infusion of glucose in water at a time when this solution can be converted into water with little glucose. In a retrospective chart review of 30 patients who were admitted with a diagnosis of DKA and a blood sugar > 900 mg/dL (50 mmol/L), there were clues to suggest that some of the retained fluid in the stomach was absorbed. To minimize the likelihood of creating a dangerous degree of cerebral edema in patients with DKA, it is important to define the likely composition of fluid retained in the stomach on admission, to look for signs of absorption of some of this fluid during therapy, and to be especially vigilant once fat-derived brain fuels have disappeared, because this is the time when glucose oxidation in the brain should increase markedly, generating osmole-free water.

Objective: To evaluate if the use of hemostatic high-dose aprotinin seems influence to myocardial, renal and metabolic functions in children submitted to surgical correction with extracorporeal circulation (ECC). Material and Methods A prospective randomized study was conducted on children aged 30 days to 4 years submitted to correction of acyanogenic congenital heart disease with ECC and divided into two groups: Control (n=9) and Aprotinin (n=10). In the Aprotinin Group the drug was administered before and during ECC and the myocardial and multiorgan dysfunctions were analyzed on the basis of clinical and biochemical markers. Differences were considered to be significant when P<0.05., Results: The groups were similar regarding demographic and intraoperative variables, except for a greater hemodilution in the Aprotinin Group. The drug had no benefit regarding time of mechanical pulmonary ventilation, permanence in the pediatric postoperative intensive care unit (ICU) and length of hospitalization, or regarding the use of inotropic drugs and renal function. The partial arterial oxygen pressure/inspired oxygen fraction ratio (PaO2/FiO2) was significantly reduced 24h after surgery in the Control Group. Blood loss was similar for both groups. Cardiac troponin I (cTnI), creatine kinase MB fraction (CKMB), serum glutamic-oxaloacetic transaminase (SGOT) and the aminoterminal fraction of natriuretic peptide type B (NT-proBNP) did not differ significantly between groups. Post-ECC blood lactate concentration and metabolic acidosis was more intense in the Aprotinin Group. There were no complications with the use of aprotinin., Conclusion: High-dose aprotinin did not significant influence in serum markers troponin I, NT-proBNP and renal function, but did associated with hemodilution, blood lactate concentration and metabolic acidosis more intense.

Objective: Evaluation of the hemostatic and platelets effects in children with acyanogenic congenital heart disease undergone on-pump surgery who received aprotinin., Methods: A prospective randomized study was performed on children aged 30 days to 4 years who had undergone correction of acyanogenic congenital heart disease using cardiopulmonary bypass (CPB) and were divided into two groups: Control (n=9) and Aprotinin (n=10). In the Aprotinin Group the drug was administered before and during CPB and the hemostatic dysfunction was analyzed by clinical and biochemical markers. Differences were considered to be significant when P<0.05., Results: The groups were similar regarding demographic and intraoperative variables, except for a greater hemodilution in the Aprotinin Group. The drug presented no benefit regarding time of mechanical pulmonary ventilation, stay in the postoperative intensive care unit and hospital, or regarding the use of inotropic drugs and renal function. Platelet concentration was preserved with the use of Aprotinin, whereas thrombocytopenia occurred in the Control Group since the initiation of CPB. Blood loss was similar for both groups. There were no complications with the use of Aprotinin., Conclusion: Aprotinin quantitatively preserved the blood platelets in children with acyanogenic congenital heart disease.

Objectives: The aims of this review were to summarize a) the consensus definitions of normal and pathologic intra-abdominal pressure (IAP); b) the techniques to measure IAP; c) the risk factors for intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS); d) the pathophysiology of ACS; and e) the current recommendations for management and prevention of ACS., Data Sources: PubMed was searched using the following terms: ACS, IAH, IAP, and abdominal decompression., Data Synthesis: ACS represents the natural progression of end-organ dysfunction caused by increased IAP and develops if IAH is not recognized and treated appropriately. Although the reported incidence of ACS is relatively low in critically ill children (0.6%-4.7%) it may be under-recognized and under-reported. The diagnosis of IAH/ACS depends on a high index of suspicion and the accurate and frequent measurement of IAP in patients at risk. Mortality from ACS remains high (50%-60%) even when decompression of the abdomen is performed early, which highlights the importance of detection and treatment of elevated IAP before end-organ damage occurs., Conclusions: A widespread awareness of the recognition and current approach to management and prevention of IAH and ACS is needed among pediatric intensivists, so outcome of these life-threatening disease processes might be improved.

Low cardiac output syndrome (LCOS) is a common problem following cardiac surgery with cardiopulmonary bypass (CPB) in neonates and infants, and its early recognition remains a challenging task. We aimed to test whether a multimarker approach combining inflammatory and cardiac markers provides complementary information for prediction of LCOS and death in children submitted to cardiac surgery with CPB. Forty-six children younger than 18 months with congenital heart defects were prospectively enrolled. No intervention was made. Blood samples were collected pre-operatively, during CPB and post-operatively (PO) for measurement of interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha, cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Clinical data and outcome variables were recorded. Logistic regression was used to identify predictors of LCOS and death. Multivariate logistic regression identified pre-operative NT-proBNP and IL-8 4h PO as independent predictors of LCOS, while cTnI 4h PO and CPB length were independent predictors of death. The use of inflammatory and cardiac markers in combination improved sensitivity, negative predictive value and accuracy of the models. In conclusion, the combined assessment of inflammatory and cardiac biochemical markers can be useful for identifying young children at increased risk for LCOS and death after heart surgery with CPB.

Background: The major stress response to critical illness leads to a catabolic state and loss of lean body mass., Aims: To test whether an increased rate of creatinine excretion might provide unique and timely information to monitor cell catabolism; to relate this information to balances of cell constituents (nitrogen, potassium, phosphate and magnesium); to evaluate the effectiveness of nutritional therapy to reverse this catabolic process., Design: Prospective observational study., Methods: Children with severe traumatic brain injury admitted to the paediatric critical care units of The Hospital for Sick Children, Toronto, Canada and Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil were studied. Complete 24 h urine collections were obtained for measurement of creatinine excretion rate and daily balances of nitrogen, potassium, phosphate and magnesium., Results: Seventeen patients were studied for 3-10 days. On Day 1, all had negative balances for protein and phosphate. Balances for these intracellular constituents became positive when protein intake was >/=1 g/kg/day and energy intake was >/=50% of estimated energy expenditure (P < 0.0001). Creatinine excretion rate was positively correlated with the urea appearance rate (r = 0.60; P < 0.0001), and negatively with protein balance (r = -0.45; P < 0.0001). Sepsis developed in four patients; before its clinical detection, there were negative balances for all intracellular markers and an abrupt rise in the excretion of creatinine., Conclusion: Negative balances of intracellular components and an increase in rate of creatinine excretion heralded the onset of catabolism.

In this teaching exercise, the goal is to demonstrate how an application of principles of physiology can reveal the basis for a severe degree of acidaemia (pH 6.81, bicarbonate <3 mmol/l (P(HCO(3))), PCO(2) 8 mmHg), why it was tolerated for a long period of time, and the issues for its therapy in an 8-year-old female with diabetic ketoacidosis. The relatively low value for the anion gap in plasma (19 mEq/l) suggested that its cause was both a direct and an indirect loss of NaHCO(3). Professor McCance suggested that ileus due to hypokalaemia might cause this direct loss of NaHCO(3), and that an excessive excretion of ketoacid anions without NH(4)(+) in the urine accounted for the indirect loss of NaHCO(3). In addition, he suspected that another factor also contributing to the severity of the acidaemia was a low input of alkali. He was also able to explain why there was a 16-h delay before there was a rise in the P(HCO(3)) once therapy began. The missing links in this interesting story, including a possible basis for the hypokalaemia, emerge during the discussion between the medical team and Professor McCance.

Context and Objective: Neonatal resuscitation should be part of medical school curriculums. We aimed to evaluate medical school graduates' knowledge of neonatal resuscitation., Design and Setting: Cross-sectional study on the performance of candidates sitting a medical residency exam at Hospital das Clínicas, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, in 2004., Methods: There were two questions on neonatal resuscitation. One question in the theory test aimed at evaluating basic knowledge on the initial approach towards newly born infants. The question in the practical exam was designed to evaluate the candidate's ability to perform the initial steps of resuscitation and to establish bag-mask ventilation., Results: Out of 642 candidates from 74 medical schools, 151 (23.5%) answered the theory question correctly. Significantly more physicians from public medical schools in the State of São Paulo answered correctly than did those from other schools in Brazil (52.5% versus 9.2%; p < 0.05). A total of 436 candidates did the practical exam. The grades among graduates from medical schools belonging to the State of São Paulo were significantly higher than among those from other schools (5.9 +/- 2.6 versus 4.1 +/- 2.1; p < 0.001). The grades for the practical question among candidates who had answered the theory question correctly were significantly higher than those obtained by candidates who had given wrong answers (p < 0.05)., Conclusion: Medical school graduates' knowledge of neonate resuscitation in the delivery room is quite precarious. Emphasis on neonatal resuscitation training is urgently needed in medical schools.

Objectives: To test whether a drop in effective plasma osmolality (P(Eff osm); 2 x plasma sodium [P(Na)] + plasma glucose concentrations) during therapy for diabetic ketoacidosis (DKA) is associated with an increased risk of cerebral edema (CE), and whether the development of hypernatremia to prevent a drop in the P(Eff osm) is dangerous., Study Design: This study is a retrospective comparison of a CE group (n = 12) and non-CE groups with hypernatremia (n = 44) and without hypernatremia (n = 13)., Results: The development of CE (at 6.8 +/- 1.5 hours) was associated with a drop in P(Eff osm) from 304 +/- 5 to 290 +/- 5 mOsm/kg (P < .001). Control patients did not show this drop in P(Eff osm) at 4 hours (1 +/- 2 and 2 +/- 2 vs -9 +/- 2 mOsm/kg; P < .01), because of a larger rise in P(Na) and/or a smaller drop in plasma glucose. During this period, the CE group received more near-isotonic fluids (69 +/- 9 vs 35 +/- 2 and 27 +/- 3 mL/kg; P < .001). The CE group had a higher mortality (3/12 vs 0/57; P = .003), and more neurologic sequelae (5/12 vs 1/57; P < .001)., Conclusions: CE during therapy for DKA was associated with a drop in P(Eff osm). An adequate rise in P(Na) may be needed to prevent this drop in P(Eff osm).

This teaching exercise demonstrates how the application of principles of physiology can identify the cause of a severe degree of hyperglycaemia (plasma glucose concentration 80 mmol/l) in a very young patient with newly diagnosed diabetes mellitus, determine whether the patient has diabetic ketoacidosis, and highlight the potential risks for this patient on admission and during initial therapy. A consultation with Professor McCance was sought to determine whether this patient had an unusual degree of 'insulin resistance'. There were also uncertainties regarding the acid-base diagnosis. The patient did not appear to have an important degree of metabolic acidosis as judged from his pH of 7.39 and plasma bicarbonate concentration of 20 mmol/l in arterial blood; hence the diagnostic impression was that he had a hyperglycaemic hyperosmolar state. However, his plasma anion gap was significantly elevated, and remained so for 60 h, despite the administration of insulin. Issues in management concerning the basis for this severe degree of hyperglycaemia and how to minimize the risk of developing cerebral oedema are addressed. The missing links in this interesting story emerge during a discussion between the medical team and their mentor, Professor McCance.

Background: Glucocorticoids (GC) represent the mainstay of treatment of idiopathic nephrotic syndrome (INS) and might be involved in the pathogenesis of the disease. We evaluated basal secretion of cortisol, number and affinity of glucocorticoid receptors, dexamethasone (Dex)-mediated inhibition of concanavalin-A (Con-A)-stimulated peripheral blood mononuclear cell (PBMC) proliferation, and cytokine secretion in patients with INS., Methods: Blood and saliva were obtained from 20 INS patients in relapse and 11 control patients. Cortisol concentrations were measured by radioimmunoassay. PBMC were isolated for binding and in vitro GC sensitivity assays. Cytokines were measured in supernatants of PBMC culture by enzyme-linked immunosorbent assay (ELISA)., Results: Salivary cortisol concentrations were similar in INS patients and control patients. Density and affinity of GC receptors were similar in steroid-sensitive (SS) patients and control, whereas in steroid-resistant (SR) patients they were variable. Lymphocyte proliferation after Con-A stimulation was inhibited by Dex in a dose-dependent manner in control and SS patients. Control and all clinically SS patients were steroid-sensitive by in vitro test, but control patients significantly presented more suppression of PBMC proliferation compared with SS patients. Basal- and Con-A-stimulated interleukin (IL)-6, IL-10, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha levels were similar in control and INS patients, and all cytokines but IL-10 were significantly inhibited by Dex 10-6 mol/L. In SR patients, cytokine secretion remained elevated after treatment with high doses of Dex., Conclusion: Abnormalities of number and affinity of the GC receptor and altered secretion of cytokines may be involved in tissue sensitivity to GC in INS patients.

Cerebral oedema is the most common cause of mortality and morbidity during the first day of conventional treatment for diabetic ketoacidosis in paediatric patients. It is possible that therapy contributes to its development. Risk factors that predispose to cerebral oedema should lead to an expansion of the intracellular and/or the extracellular fluid compartment(s) of the brain because water normally accounts for close to 80% of brain weight. With respect to the intracellular fluid compartment, the driving force to cause cell swelling is a gain of effective osmoles in brain cells and/or a significant decline in the effective osmolality of the extracellular fluid compartment. Factors leading to an expansion of the intracerebral extracellular fluid volume can be predicted from Starling forces acting at the blood-brain barrier. Some of these risk factors have an early impact, while others have their major effects later during therapy for diabetic ketoacidosis. Based on a theoretical analysis, suggestions to modify current therapy for diabetic ketoacidosis in children are provided.

Background: The reported prevalence of cerebral salt wasting has increased in the past three decades. A cerebral lesion and a large natriuresis without a known stimulus to excrete so much sodium (Na ) constitute its essential two elements., Objectives: To review the topic of cerebral salt wasting. There is a diagnostic problem because it is difficult to confirm that a stimulus for the renal excretion of Na is absent., Design: Review article., Intervention: None., Main Results: Three fallacies concerning cerebral salt wasting are stressed: first, cerebral salt wasting is a common disorder; second, hyponatremia should be one of its diagnostic features; and third, most patients have a negative balance for Na when the diagnosis of cerebral salt wasting is made. Three causes for the large natriuresis were considered: first, a severe degree of extracellular fluid volume expansion could down-regulate transporters involved in renal Na resorption; second, an adrenergic surge could cause a pressure natriuresis; and third, natriuretic agents might become more potent when the effective extracellular fluid volume is high., Conclusions: Cerebral salt wasting is probably much less common than the literature suggests. With optimal treatment in the intensive care unit, hyponatremia should not develop.

Object: Two major criteria are necessary to diagnose cerebral salt wasting (CSW): a cerebral lesion and a large urinary excretion of Na+ and Cl- at a time when the extracellular fluid (ECF) volume is contracted. Nevertheless, it is difficult for the physician to confirm from bedside observation that a patient has a contracted ECF volume. Hyponatremia, although frequently present, should not be a criterion for a diagnosis of salt wasting. A contracted ECF volume is unlikely if there are positive balances of Na+ and Cl-. The goal of this study was to assess the accuracy of calculating balances for Na+ plus K+ and of Cl- over 1 to 10 days in an intensive care unit (ICU) setting., Methods: A prospective comparison of measured and estimated quantities of Na+ plus K+ and of Cl- excreted over 1 to 10 days in 10 children and 12 adults who had recently received a traumatic brain injury or undergone recent neurosurgery. Plasma concentrations of electrolytes were recorded at the beginning and end of the study period. The total volumes infused and excreted and the concentrations of Na+, K+, and Cl- in the infusate were obtained from each patient's ICU chart. The electrolytes in the patients' urine were measured and calculated. Correlations between measured and calculated values for excretions of Cl- and of Na+ plus K+ were excellent., Conclusions: Mass balances for Na+ plus K+ and for Cl- can be accurately estimated. These data provide information to support or refute a clinical diagnosis of CSW. The danger of relying on balances for these electrolytes measured within a single day to diagnose CSW is illustrated.

The usual way to decide why hyponatremia or hypernatremia has developed and to plan goals for its therapy is to analyze events in electrolyte-free water (EFW) terms. We shall demonstrate that an EFW balance does not supply this information. Rather, one must calculate mass balances for water and sodium plus potassium separately (a tonicity balance) to understand the basis for the change in natremia and the proper goals for its therapy. These points are illustrated with a clinical example.

OBJECTIVE: To estimate, semiquantitatively, the proteinuria of nephrotic patients by the use of the value of protein/creatinine ratio in single urine samples and determine its correlation with 24-hour proteinuria.METHODS: Analysis of 30 single urine samples and thirty 24-hour urine samples from 20 children with nephrosis followed up at the Division of Pediatric Nephrology of the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo. Proteinuria in single urine samples and 24-hour urine samples was measured by the turbidimetric method with 3% sulfosalicylic acid. Urinary creatinine concentration was measured by the method of Hare, modified by Haugen and Blegen, adapted to the microtechnique.RESULTS: An excellent correlation was observed between 24-hour proteinuria and the protein/creatinine ratio in single urine samples, by linear regression analysis before (r = 0.82; p < 0.001) and after logarithmic transformation (r = 0.93; p < 0.001). All patients with 24-hour proteinuria at physiological levels (less than 0.1 g/m(2)/day) had a protein/creatinine ratio of less than 0.1 (mg/mg) in single urine samples. All patients with nephrotic 24-hour proteinuria (more than 1.0 g/m(2)/day) had a protein/creatinine ratio of more than 1.0 (mg/mg). The patients with intermediate proteinuria (between 0.1 and 1.0 g/m(2)/day) had a protein/creatinine ratio distributed on the three levels.CONCLUSIONS: The protein/creatinine ratio in a single urine sample is a simple and reliable method for the evaluation of proteinuria and eliminates the errors due to inadequate 24-hour urine collection.