[Show abstract][Hide abstract] ABSTRACT: Objetivo
Comparar la eficacia de midazolam intramuscular (MDZ-IM) con la de diazepam intravenoso (DZP-IV) para convulsiones en niños.
Ensayo clínico aleatorizado.
Servicio de Urgencias Pediátricas.
Niños de entre 2 meses y 14 años internados con convulsiones.
Los pacientes fueron aleatorizados para recibir DZP-IV o MDZ-IM.
Tiempo hasta el inicio del tratamiento (minutos), tiempo entre la administración del medicamento y el cese de la convulsión (minutos), tiempo hasta el cese de la convulsión (minutos), y tasa de fallo del tratamiento. El tratamiento fue considerado exitoso cuando las convulsiones cesaron en los 5 min tras la administración del medicamento.
Completaron el estudio 32 niños (16 por grupo). No fue posible obtener acceso intravenoso en 4 pacientes (25%) del grupo DZP-IV. El tiempo entre la internación y el tratamiento fue menor en el grupo MDZ-IM (2,8 vs. 7,4 min; p < 0,001), así como el tiempo hasta el cese de la convulsión (7,3 vs. 10,6 min; p = 0,006). En 2 niños de cada grupo (12,5%), las convulsiones continuaron después de 10 min de tratamiento. No hubo diferencias entre los grupos en los parámetros fisiológicos o eventos adversos (p = 0,171); un niño (6,3%) del grupo MDZ-IM presentó hipotensión, y 5 del grupo DZP-IV (31%) presentaron hiperactividad o vómitos.
Dada su eficacia, facilidad y velocidad de administración, MDZ-IM es una excelente opción para el tratamiento de convulsiones infantiles, posibilitando un tratamiento precoz y reduciendo la duración de la convulsión. No hubo diferencias en las complicaciones al aplicar MDZ-IM o DZP-IV.
[Show abstract][Hide abstract] ABSTRACT: Carbohydrate metabolism is essential for survival and a constant supply of carbohydrate provides the substrate for the metabolic pathways that fuel cell activity. Under normal circumstances a complex neuroendocrine mechanism maintains glucose level within an optimal range. Shortage of carbohydrate (i.e., hypoglycaemia) is a severe threat to homeostasis and triggers the stress response. Indeed, hypoglycaemia is recognised as a 'gold standard' stressor for the activation of the neuroendocrine system (e.g., the insulin tolerance test)(1,2). When blood glucose concentrations drop to potentially harmful levels, neuroendocrine counter-regulatory changes promote resistance to glucose uptake in peripheral tissues and stimulates glycogenolysis in the liver, tailoring cell and tissue metabolic supply according to the body's need. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the feasibility and safe operationalization of a pediatric glycemic control protocol in the setting of a general pediatric intensive care unit in a developing country.
Prospective, observational cohort study carried out over 12 months.
Fourteen-bed pediatric intensive care unit in Brazil.
Children requiring mechanical ventilation with at least one organ system dysfunction were included.
Glucose was monitored and insulin used for persistent hyperglycemia (glucose >140 mg/dL [7.8 mmol/L] for at least two observations separated by at least a 1-hr interval), with a target glucose during insulin use of 60-140 mg/dL (3.3-7.8 mmol/L).
Out of 410 admissions, 144 children met the criteria for applying the protocol. One hundred fourteen of 144 (79%) children had at least one peak glucose level that was hyperglycemic, but only 44 (31%) children required insulin. Insulin infusion was most frequently started on day 1 (61%), with a glucose level at the time of 229 ± 79 mg/dL (12.7 ± 4.4 mmol/L). The mean glucose level after 6 hrs of insulin was 172 ± 87 mg/dL (9.6 ± 4.8 mmol/L), and the time to achieve the target glucose range was 9.5 (2-20) hrs (median [interquartile range]). The overall duration of insulin was 24.5 (10-48) hrs, and the average dose required was 0.06 ± 0.03 U/kg/hr. In the whole series, the peak glucose level was 202 ± 93 mg/dL (11.2 ± 5.2 mmol/L), with no difference between survivors and nonsurvivors. There was no difference in mortality when different glucose bands were considered and no association between glucose level and mortality. The overall rate of hypoglycemia (glucose <40 mg/dL [2.2 mmol/L]) was 8.3%, and it was more common in those receiving insulin (20% vs. 3%, p < .05).
Hyperglycemia is frequent in critically ill children managed in a pediatric intensive care unit in a developing country. Using a glycemic control protocol, one-third of these children required insulin, but attendants should be aware of a significant risk of hypoglycemia in this setting. Based on these data, a trial to detect a 20% relative reduction in mortality (power 90%, p = .05) associated with insulin in a similar population would need to screen >10,000 patients.
Pediatric Critical Care Medicine 10/2010; 12(3):265-70. · 2.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OPINION STATEMENT: Meningococcal meningitis (MM) is the most common presentation of meningococcal disease and an important cause of morbidity and mortality worldwide. When MM is associated with shock, early recognition and treatment of shock is essential. No investigation should delay starting antibiotics once the diagnosis is suspected. Corticosteroids can be started at the same time as the antibiotics or just before, but this is not a specific recommendation for MM. Low-dose steroids should be used in meningococcal disease with refractory shock. Altered blood flow, cerebral edema, and raised intracranial pressure are problems that should be considered in all patients with MM and decreased consciousness level. When mechanical ventilation is required, the target carbon dioxide level is 4.0 to 4.5 kPa, with avoidance of hypocapnia. Seizures, although not frequent, can occur in MM and require prompt treatment. Other treatments, such as mannitol and activated protein C, should be avoided. Potential new treatments requiring further investigation include neuroprotection with hypothermia or glycerol.
Current Treatment Options in Neurology 09/2010; 12(5):464-74. · 1.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate continuous subcutaneous glucose monitoring in pediatric critical illness.
Mixed university pediatric intensive care unit.
Children aged 1 mo to 16 yrs requiring mechanical ventilation with at least two organ system failures.
Blood samples obtained from an arterial line, measurements using point-of-care glucometer, and laboratory analysis were compared with continuous subcutaneous glucose monitoring.
Fourteen patients yielded 11,880 continuous subcutaneous glucose monitoring measurements; 436 glucometer levels and 34 laboratory levels had mean time-paired glucose values of 108 +/- 29 mg/dL and 110 +/- 25 mg/dL, respectively. Mean continuous subcutaneous glucose monitoring glucose was 101 +/- 31 mg/dL for samples paired with glucometer and 95 +/- 40 mg/dL for samples paired with laboratory tests. Continuous subcutaneous glucose monitoring measurements correlated with glucometer (r = 0.44) and laboratory testing (r = 0.48). Mean absolute differences between continuous subcutaneous glucose monitoring measurement and glucometer and laboratory values were 18 +/- 16 mg/dL and 25 +/- 20 mg/dL, respectively. Clarke error grid analysis found 69% of the measurements to be in zone A (clinically accurate), 29% in zone B (benign errors), and 2% in zone D (failure to detect errors). The mean absolute relative difference between the continuous subcutaneous glucose monitoring measurement and glucometer and laboratory measurements were 17% and 23%, respectively. Bland-Altman analysis showed good agreement between continuous subcutaneous glucose monitoring and the other methods of glucose measurement. However, in the lower range (< or =74 mg/dL) 39% of the continuous subcutaneous glucose monitoring readings had a difference >15 mg/dL. On multiple regressions, only glucometer glucose values, continuous subcutaneous glucose monitoring levels, and base deficit were associated with the mean absolute relative difference.
The performance of continuous subcutaneous glucose monitoring against point-of-care glucometer and laboratory measurements may be considered "good" using statistical definitions (Bland-Altman and Clarke error grid analysis). However, there are important limitations in children with large base deficit, being actively cooled, and with glucose in the lower range, which may limit its application.
Pediatric Critical Care Medicine 11/2009; 11(3):415-9. · 2.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: External validation of the paediatric logistic organ dysfunction (PELOD) score in two paediatric intensive care units (PICU) in South America.
Prospective observational cohort study including all PICU admissions from July 2003 to December 2004 in Porto Alegre, Brazil, and from January 2004 to December 2004 in Buenos Aires, Argentina. The data collected included demographic variables, diagnosis, need for mechanical ventilation, length of PICU stay and mortality, and the 12 variables in the PELOD score. For each PELOD score variable, the worst daily value and the worst value of the whole PICU stay were used for the daily PELOD (dPELOD) and PELOD scores, respectively.
A total of 1,476 admissions (51.3% from Argentina and 48.7% from Brazil) were analysed. Observed and predicted mortality were, respectively, 4.7% and 6.6%, with a standardized mortality ratio of 0.72. The score showed excellent discrimination capacity, with an area under the receiver operator characteristic (ROC) curve of 0.93 (0.88-0.98). The dPELOD score on days 1-5 also showed good discrimination capacities, with areas under the ROC curve >0.85. However, PELOD and dPELOD scores showed poor calibration with the Hosmer-Lemeshow test (chi-square 72.3, p < 0.001). This poor calibration was explained by a deficiency in the PELOD score where it fails to identify two risk intervals; 3.1-16.2% and 40-80%.
The PELOD score is reproducible, has excellent discrimination, but over-predicts mortality and has poor calibration. Although the lack of calibration may not invalidate the score, the PELOD score is a discontinuous variable and we advise careful consideration when using it as a surrogate endpoint in clinical trials.
European Journal of Intensive Care Medicine 05/2009; 36(1):116-22. · 5.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the safety of low-dose vasopressin infusion in critically ill children requiring prolonged mechanical ventilation (MV) at risk of developing sedation/analgesia-related hypotension.
Randomized pilot safety study in children expected to require MV for at least 3 days. Children received either vasopressin (0.0005 U/kg/min) or sodium chloride (0.9%) infusion for a period of 48 h. Haemodynamic variables, urine output and serum electrolytes were closely monitored and analyzed.
Twelve children in each group had similar baseline characteristics. Vasopressin infusion was associated with an 8 mmol/L fall in serum sodium concentration (p < 0.01) and with higher incidence of hyponatraemia (8 vs. 66%, p < 0.01). In normotensive children, low-dose vasopressin also induced a reversible decrease in urine output, and acutely increased blood pressure (p < 0.01). After stopping the vasopressin there was rebound hypotension (p < 0.01).
Low-dose vasopressin infusion in haemodynamically stable, but critically ill, children is associated with reduction in urine output and decreased serum sodium level, yielding a high incidence of hyponatraemia. We conclude that these effects limit further study of prophylactic vasopressin for sedation-related hypotension in a randomized controlled trial.
European Journal of Intensive Care Medicine 02/2009; 35(2):355-9. · 5.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To review the literature about the pathophysiology of hyperglycemia and glycemic control in children and adults with sepsis and critical illness.
Non-systematic survey of the medical literature using MEDLINE and terms hyperglycemia, glycemic control, intensive insulin therapy, sepsis and intensive care. Articles were selected according to their relevance based on the authors' opinion.
Hyperglycemia is frequent in critically ill children and it is associated with worsened outcome. In adults, there is no consensus on the efficacy and safety of glycemic control. We describe the possible mechanisms involved in glucose toxicity and the beneficial effects of glycemic control. Initial studies showed that use of insulin to achieve glycemic control reduced morbidity and mortality in adult intensive care; however, recent studies have failed to confirm these findings. Importantly, it is evident that glycemic control is associated with increased incidence of hypoglycemia. The efficacy of glycemic control has not yet been studied in critically ill children.
Glycemic control is a novel therapeutic option in critical care. Conflicting evidence in adults means that before we apply this approach to pediatrics it will need to be assessed in clinical trial.
Jornal de Pediatria 12/2007; 83(5 Suppl):S128-36. · 0.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate in children with bronchiolitis requiring mechanical ventilation the association between blood glucose level and duration of mechanical ventilation and pediatric intensive care unit (PICU) stay.
Retrospective cohort study.
University hospital PICU.
Children admitted to a university hospital PICU over a period of 3 yrs.
Demographic data, infection with respiratory syncytial virus, history of prematurity, mechanical ventilator settings, and use of inotrope during illness were noted. In addition, C-reactive protein, alanine transaminase, and glucose levels were recorded. Data from 50 children with median (interquartile range) age of 2.2 (1.3-4.7) months were analyzed. There were 37 boys, 21 children had been premature babies, and 30 children were positive for respiratory syncytial virus. Hyperglycemia at any time was frequent (peak glucose > or =6.1 mmol/L [110 mg/dL] in 98% and >8.3 mmol/L [150 mg/dL] in 72%). Children with sustained hyperglycemia were more likely to be boys with higher alanine transaminase and C-reactive protein, requiring inotrope (p < .05). These children are more likely to have required high-frequency oscillation ventilation, required higher airway pressures, and had longer duration of mechanical ventilation and PICU stay (p < .05). Peak glucose and sustained peak glucose were not independently associated with duration of mechanical ventilation or PICU stay. Multiple regression showed that age, C-reactive protein, the need for inotrope, and respiratory syncytial virus infection were independent factors associated with duration of PICU stay. Glucose level was not a factor.
Our findings show that hyperglycemia is frequent in children with bronchiolitis requiring mechanical ventilation, but we failed to show that this phenomenon was independently associated with prolonged duration of mechanical ventilation or PICU stay. Our observations raise the question whether tight glycemic control should be used in children with bronchiolitis.
Pediatric Critical Care Medicine 12/2007; 8(6):546-50. · 2.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate serum ferritin level in children with severe sepsis and septic shock and its association with mortality.
A cohort study of 36 children aged 1 month-16 years with severe sepsis or septic shock requiring intensive care was conducted. Serum ferritin levels were measured at the time of diagnosis of sepsis and a ferritin index (FI=observed serum ferritin divided by the upper limit of normal ferritin for age and gender) was calculated.
The median age (range) of the children was 6 (2-100) months. Ferritin was <200 ng/mL in 13 children, 200-500 ng/mL in 11 children and >500 ng/mL in 12 children. The mortality associated with these groups was 23%, 9% and 58%, respectively. A ferritin>500 ng/mL was associated with a 3.2 (1.3-7.9) relative risk of death (p=0.01). FI of 1.7 was the best cutoff value for identifying those who died. In a logistic regression analysis, ferritin level and PRISM were independently associated with mortality.
Ferritin is raised in children with septic shock and high ferritin level is associated with poorer outcome.
[Show abstract][Hide abstract] ABSTRACT: To describe the serum cortisol profile and evaluate the adrenal response in children with septic shock, and determine the influence of these factors on the outcome and mortality in this group.
Between May and November 2003, 22 children with septic shock admitted to two pediatric intensive care units in southern Brazil were followed. Adrenal function was evaluated based on the levels of cortisol measured on the occasion of the diagnosis of septic shock and on the response of serum cortisol 30 min after the administration of intravenous corticotrophin (0.5 microg/1.73m(2)). Adrenal insufficiency was defined as a baseline serum cortisol below 690 nmol/l and/or a cortisol response to corticotrophin less than 250 nmol/l.
Adrenal insufficiency was detected in 17 patients (77.3%). All patients who died had baseline cortisol higher than 690 nmol/l. A cortisol response to corticotrophin less than 250 nmol/l was associated with a 60% mortality (RR = 7.2, 1.03-50.28). Regression analysis showed that the combination of baseline cortisol higher than 690 nmol/l and a cortisol response to corticotrophin less than 250 nmol/l were associated with mortality after correction for gender and PRISM.
Adrenal insufficiency is a frequent finding in children with septic shock. The low-dose corticotrophin stimulation test seems to be an important tool to distinguish between a normal cortisol response to stress and evidence of adrenal failure. Mortality was significantly higher in children that failed to respond to a corticotrophin stimulation test.
Intensive Care Medicine 10/2007; 33(9):1609-13. · 5.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To review the literature relevant to diagnosis and management of meningococcal disease (MD).
Non-systematic review of medical literature through the MEDLINE database using the terms meningococcal, septic shock, diagnosis, and treatment. Articles were selected according to their relevance to the objective of the study and according to the authors' opinion.
MD is a leading cause of death due to infection in children. It progresses rapidly and a high level of suspicion is necessary for early diagnosis. Early intervention with aggressive fluid resuscitation and antibiotic therapy can significantly improve outcome. In the pediatric intensive care unit, a large amount of fluids may be required during the first few days and vasoactive drug infusions are often needed. Coagulopathy is frequent, but it has no specific treatment. The use of colloids and steroids may be beneficial, but other new therapies such as insulin and activated protein C still need further assessment. Rescue therapy with extracorporeal membrane oxygenation may be appropriate in cases complicated by severe acute respiratory distress syndrome, but not for refractory shock. Meningitis is often not diagnosed in MD because of the severity of illness and the inability to perform a lumbar puncture safely in a patient with coagulopathy, coma, or hemodynamic instability. When present, cerebral edema and altered cerebral blood flow are the main concerns. The use of osmolar solution may be necessary, but the main therapeutic intervention is to ensure adequate blood pressure for adequate cerebral perfusion. Seizures and hyponatremia should be aggressively treated. Steroids do not appear to affect outcome in meningococcal meningitis.
MD is a life-threatening infection that requires early recognition and treatment. Time sensitive fluid resuscitation and antibiotic therapy are the most effective therapies for MD. Other therapies such as steroids may have a place in MD treatment but more definitive studies are necessary.
Jornal de Pediatria 06/2007; 83(2 Suppl):S46-53. · 0.94 Impact Factor