Luca Tortorolo

Interleukin-6 and Nerve Growth Factor Upregulation Correlates with Improved Outcome in Children with Severe Traumatic Brain Injury

Secondary brain damage after traumatic brain injury (TBI) involves neuro-inflammatory mechanisms that are mainly dependent on the intracerebral production of cytokines. Interleukin-6 (IL-6) may have a role both in the pathogenesis of neuronal damage and in the recovery mechanisms of injured neurons through the modulation of nerve growth factor (NGF) biosynthesis. However, the relationship between IL-6 and NGF expression and the severity and outcome of TBI remains controversial. We have conducted a prospective observational clinical study to determine whether the concentration of IL-6 and NGF in the cerebrospinal fluid (CSF) of children with TBI correlates with the severity of the injury and neurologic outcome of patients. CSF samples were collected from 29 children at 2 h (time T1) and 48 h (time T2) after severe TBI, and from 31 matched controls. TBI severity was evaluated by Glasgow Coma Scale (GCS) and neurologic outcome by Glasgow Outcome Score (GOS). CSF concentrations of IL-6 and NGF were measured by immunoenzymatic assays. Early NGF concentrations (T1) correlated significantly with head injury severity, whereas no correlation was found between GCS and IL-6. Furthermore, IL-6 and NGF upregulation after injury was associated with better neurologic outcomes. Based on these findings, we posit that NGF expression is a useful marker of brain damage following severe TBI. Moreover, the early upregulation of both IL-6 and NGF, which correlates with a favorable neurologic outcome, may reflect an endogenous attempt at neuroprotection in response to the damaging biochemical and molecular cascades triggered by traumatic insult.

NGF, DCX, and NSE upregulation correlates with severity and outcome of head trauma in children

Background: Secondary brain damage after traumatic brain injury (TBI) involves neuroinflammatory mechanisms, mainly dependent on the intracerebral production of specific biomarkers, such as cytokines, neurotrophic factors, and neuron-specific enolase (NSE). NSE is associated with neuronal damage, while neurotrophic factors play a neuroprotective role due to their ability to modulate neuronal precursor biosynthesis, such as doublecortin (DCX). However, the relationships between the expression of these factors and the severity and outcome of TBI are not understood. Methods: To determine whether the concentrations of neurotrophic factors (nerve growth factor [NGF], brain-derived neurotrophic factor [BDNF], glial-derived neurotrophic factor [GDNF]), DCX, and NSE in the CSF of children with TBI correlate with the severity of brain damage and neurologic outcome, we prospectively collected CSF samples from 32 children at 2 and 48 hours after admission for severe TBI and from 32 matched controls. Severity of TBI was evaluated by Glasgow Coma Scale and neurologic outcome by Glasgow Outcome Score. Results: Early NGF, DCX, and NSE concentrations correlated significantly with the severity of head injury, whereas no correlation was found for BDNF and GDNF. Furthermore, NGF and DCX upregulation and lower NSE expression were associated with better neurologic outcomes. No significant association was found between BDNF and GDNF expression and outcome. Conclusions: Nerve growth factor (NGF), doublecortin (DCX), and neuron-specific enolase concentrations in the CSF are useful markers of brain damage following severe traumatic brain injury (TBI). NGF and DCX upregulation correlates also with better neurologic outcome and could be useful to obtain clinical and prognostic information in children with severe TBI.

A scoring system to predict the evolution of respiratory distress syndrome into chronic lung disease in preterm infants

Objective: The purpose of this study was to develop and validate an empirical scoring system to predict the evolution of neonatal respiratory distress syndrome (RDS) into chronic lung disease (CLD) in preterm infants, by comparing it with a more complicated logistic regression model. Design: Clinical study. Setting: Neonatal intensive care unit. Patients: The retrospective analysis of a 3-year experience showed that a gestational age (GA) of less than 30 weeks, a birth weight (BW) of less than 1000 g, the diagnosis of hyaline membrane disease (HMD) and pulmonary interstitial emphysema (PIE) during the first 72 h of life, the peak inspiratory pressure (PIP) and the fraction of inspired oxygen (FIO2) were the highest relative risk factors correlated with the evolution of CLD. On this basis an empirical and a statistical scoring system were defined and prospectively applied at 3 and 5 days of life to 228 neonates with BW less than 1250 g. The results obtained with both scoring systems were then compared. Results: Of the 149 infants surviving at 28 days of life, 67 (GA: 29.9 ± 2.3 weeks; BW: 1058 ± 143 g) were normal and 82 (GA: 27.5 ± 3.9 weeks; BW: 838 ± 200 g) had CLD. Using a cut-off value of 4.0, the empirical scoring system showed a specificity of 97.0 % and a sensitivity of 92.7 % on the 3rd day of life; on the 5th day of life the specificity was still 95.5 %, while sensitivity remained 92.7 %. The areas under the ROC curves plotted with both scoring systems tested were similar. Conclusions: The proposed empirical scoring system is easy to use and is highly reliable. The application of this scoring system provides the opportunity to direct aggressive treatment for CLD toward only very high risk patients between the 3rd and 5th days of life.

Spontaneous minute ventilation is a predictor of extubation failure in extremely-low-birth-weight infants

Objective: To validate the percentage of time spent below a target value of spontaneous expiratory minute ventilation (<125 ml/min per kg) during a 2-h period of continuous positive airway pressure (CPAP) via an endotracheal tube (ETT) as a predictor of failed extubation in preterm infants.Methods: Forty-one infants intubated for at least 24 h, with birth weight between 500 and 1000 g, who were clinically stable and at ventilator setting compatible with an extubation attempt, were studied during a 2-h period of ETT CPAP. Dynamic lung compliance and total lung resistance were measured during a period of quiet breathing, while tidal volume (Vt), respiratory rate and the corresponding spontaneous expiratory minute ventilation values were calculated for the complete recording period of 2 h using a customized computer program. The time each patient spent below the target spontaneous expiratory minute ventilation value was reported as a percentage of the total recorded time (% spontaneous expiratory minute ventilation <125 ml/min per kg). Extubation failure was defined as the need for reintubation within 72 h.Results: Eleven out of 41 babies (26.8%) experienced failure of extubation (failure group) while 30 infants (73.2%) were successfully extubated (success group). There were no significant differences in dynamic lung compliance and lung resistance between the two groups, but the mean values of respiratory rate and spontaneous expiratory minute ventilation were significantly lower in the failure group than in the success group: 43 (37–56) breaths/min and 240 (160–353) ml/min per kg vs. 53 (28–67) breaths/min and 309 (223–434) ml/min per kg, respectively (p=0.0129 and p=0.0039). Moreover, the babies in whom extubation failed spent a longer time below the target value of spontaneous expiratory minute ventilation when compared with successfully extubated babies (p<0.0001). Percentage of time spent with spontaneous expiratory minute ventilation <125 ml/min per kg had a larger area than transcutaneous (Tc)PCO2, TcPO2and pulse oxymetry saturation (SpO2) under the receiver operator characteristic curves.Conclusion: The measurement of spontaneous expiratory minute ventilation prior to extubation could be useful in identifying those babies who are not ready for spontaneous ventilation.

Effect of Dexamethasone on Tracheobronchial Aspirate Fluid Cytology and Pulmonary Mechanics in Preterm Infants

The changes induced on respiratory mechanics and on tracheobronchial aspirate fluid (TAF) cytology by dexamethasone courses started at two different postnatal ages in preterm infants at risk of chronic lung disease (CLD) were reported in this clinical trial designed in two phases. The first phase of the study included 20 neonates with birth weight ≤1,250 g and gestational age ≤32 weeks, who were oxygen and ventilator dependent on the 10th day of life. They were randomly assigned to the moderately early dexamethasone (MED) group or to the control group. The second phase of the study included 20 neonates with the same characteristics, oxygen and ventilator dependent on the 4th day of life, randomly assigned to the early dexamethasone (ED) group or to the control group. Both treated groups received dexamethasone intravenously for 7 days (0.5 mg/kg/day for the first 3 days, 0.25 mg/kg/day for the next 3 days, and 0.125 mg/kg/day for the last day of treatment). The control groups received no steroid treatment. A significantly lower absolute cell count and percentage of neutrophils (PMN) in the TAF and significantly higher dynamic lung compliance (Cdyn) values were observed in both the MED treated compared to the untreated infants and the ED treated infants compared to the control group. Moreover these changes were more precocious in the ED Group compared to the MED Group. Our study suggests that dexamethasone could be more efficacious in reducing effects of ventilator-induced lung injury in preterm infants at high risk of CLD when started earlier.

Acute hydrocephalus as a consequence of mumps meningoencephalitis

Aqueductal stenosis can result from mumps meningoencephalitis. We report a case of acute hydrocephalus from an aqueductal stenosis developed immediately after a clinically evident mumps infection. The patient, aged two years, was treated with an antiedema therapy, and a ventriculoperitoneal shunt was placed. His clinical conditions rapidly improved. Only mumps virus was found in his cerebrospinal fluid culture. This case probably represents the earliest hydrocephalus from mumps, among those reported in the literature.

Intracranial hemorrhage at the onset of thrombotic thrombocytopenic purpura in an infant : Therapeutic approach and intensive care management

Thrombotic thrombocytopenic purpura (TTP) is quite rare in infancy and must be treated intensively as a life-threatening disease. Diffuse vascular thromboses may occur, and neurologic involvement is a cornerstone of the diagnosis of TTP. We describe a case of an infant who presented with a sudden cerebral hemorrhage and subsequently developed the typical clinical features of TTP. Emergency treatment in the Pediatric Intensive Care Unit (PICU) consisted of plasma therapy and exchange-transfusion (EXT) to arrest the intravascular process and the exsanguinating blood loss. Exchange-transfusion is a life-saving procedure that is rarely performed after the neonatal age.

Diluted porcine surfactant lung lavages in children with severe ARDS

Acute respiratory distress syndrome (ARDS) is characterized by damage to the arteriolar-capillary endothelium and alveolar epithelium that leads to surfactant deficiency and atelectasis. Alveolar collapse and pulmonary edema will further induce surfactant inactivation. Surfactant supplementation has been suggested but results are unpredictable. Poor response may be due to inhibition of administered surfactant by plasma components filling the alveolar space, severity of lung injury, time of surfactant application and inadequate dose. We report the course of gas exchange and pulmonary mechanics after instillation of surfactant in 14 children (3 months-7 years) with severe ARDS, defined as an oxygenation index (OI) > 30 and a partial pressure of oxygen/ fraction of Inspired oxygen (PaO2/FiO2) <150 . We used a diluted concentration of Curosurf (8 mg/ml) divided into 4 aliquots, for a total dose of 25 mg/kg. An additional aliquot was used for bronchoalveolar lavage before surfactant treatment. All children showed a dramatic response to surfactant with rapid and progressive increase in compliance and improvement of all respiratory mechanics. Mechanical ventilation settings were rapidly reduced and gas exchange improved with a PaO2/FiO2 >200 for more than 12 hours. Diluted surfactant lung lavages were able to increase blood gas exchange in all our patients despite previously severe gas exchange impairment. LUCA TORTOROLO ( ) • ANTONIO CHIARETTI • SILVIA PULITANÒ • ORAZIO GENOVESE • GIORGIO CONTI Pediatric Intensive Care Unit Emergency Department A. Gemelli Hospital of Rome Via A. Caroncini 27. 00197 Roma, Italy Phone: +39 360601422

Exogenous surfactant treatment in children with ARDS

Since the Food and Drug Administration (FDA) approved exogenous surfactant in the early 90s for the treatment of neonates with Hyaline Membrane Disease (HMD), many studies have focused on enlarging its indications for others types of lung injuries and for other age groups. Although in the past 20 years no studies have shown clear results about the efficacy of exogenous surfactant treatment in paediatric Acute Respiratory Distress Syndrome (ARDS), many of them were able to point out and better define very important aspects of this treatment like dosage, timing, ways of administration and usage of different types of surfactant (natural and synthetic). In this review we retrace the development of studies looking at the role of exogenous surfactant treatment in paediatric ARDS.

EXPIRATORY MINUTE SPONTANEOUS VENTILATION IS A PREDICTOR OF WEANING FROM MECHANICAL VENTILATION IN PRETERM INFANTS

EXPIRATORY MINUTE SPONTANEOUS VENTILATION IS A PREDICTOR OF WEANING FROM MECHANICAL VENTILATION IN PRETERM INFANTS