Lipid Peroxidation and Antioxidant Consumption as Early Markers of Neurosurgery-Related Brain Injury in Children.

BACKGROUND AND AIMS: Lipid peroxidation represents a marker of secondary brain injury both in traumatic and in non-traumatic conditions-as in major neurosurgical procedures-eventually leading to brain edema amplification and further brain damage. Malondialdehyde (MDA), a lipid peroxidation marker, and ascorbate, a marker of antioxidant status, can represent early indicators of this process within the cerebrospinal fluid (CSF). We hypothesized that changes in cerebral lipid peroxidation can be measured ex vivo following neurosurgery in children. METHODS: Thirty-six children (M:F = 19/17, median age 32.9 months; IQR 17.6-74.6) undergoing neurosurgery for brain tumor removal were admitted to the pediatric intensive care unit (PICU) in the postoperative period with an indwelling intraventricular catheter for intracranial pressure monitoring and CSF drainage. Plasma and CSF samples were obtained for serial measurement of MDA, ascorbate, and cytokines. RESULTS: An early brain-limited increase in lipid peroxidation was measured, with a significant increase from baseline of MDA in CSF (p = 0.007) but not in plasma. In parallel, ascorbate in CSF decreased (p = 0.05). Systemic inflammatory response following brain surgery was evidenced by plasma IL-6/IL-8 increase (p 0.0022 and 0.0106, respectively). No correlation was found between oxidative response and tumor site or histology (according to World Health Organization grading). Similarly, lipid peroxidation was unrelated to the length of surgery (mean 321 ± 73 min), or intraoperative blood loss (mean 20.9 ± 16.8% of preoperative volemia, 44% given hemotransfusions). Median PICU stay was 3.5 days (IQL range 2-5.5 d.), and postoperative ventilation need was 24 h (IQL range 20-61.5 h). The elevation in postoperative MDA in CSF compared with preoperative values correlated significantly with postoperative ventilation need (P = 0.05, r2 0168), while no difference in PICU stay was recorded. CONCLUSIONS: Our results indicate that lipid peroxidation increases consistently following brain surgery, and it is accompanied by a decrease in antioxidant defences; intraventricular catheterization offers a unique chance of oxidative process monitoring. Further studies are needed to evaluate whether monitoring post-neurosurgical oxidative stress in CSF is of prognostic utility.

Dexmedetomidine is effective and safe during NIV in infants and young children with acute respiratory failure.

BACKGROUND: Noninvasive ventilation (NIV) is increasingly utilized in infants and young children, though associated with high failure rates due to agitation and poor compliance, mostly if patient-ventilator synchronization is required. METHODS: A retrospective cohort study was carried out in an academic pediatric intensive care unit (PICU). Dexmedetomidine (DEX) was infused as unique sedative in 40 consecutive pediatric patients (median age 16 months) previously showing intolerance and agitation during NIV application. RESULTS: During NIV clinical application both COMFORT-B Score and Richmond Agitation-Sedation Scale (RASS) were serially evaluated. Four patients experiencing NIV failure, all due to pulmonary condition worsening, required intubation and invasive ventilation. 36 patients were successfully weaned from NIV under DEX sedation and discharged from PICU. All patients survived until home discharge. CONCLUSION: Our data suggest that DEX may represent an effective sedative agent in infants and children showing agitation during NIV. Early use of DEX in infants/children receiving NIV for acute respiratory failure (ARF) should be considered safe and capable of improving NIV, thus permitting both lung recruitment and patient-ventilator synchronization.

Acute myocarditis as a revealing clue of complete Kawasaki disease.

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Efficacy of high-dose methylprednisolone pulses in a child with noninfectious persistent pleuropericarditis revealing systemic juvenile idiopathic arthritis.

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Increased serum levels of proNGF, mature NGF and interleukins in burn-injured children.

OBJECTIVE: Burns are among the most common injuries in children. In burns of more than 20% of the total body surface area, a systemic inflammatory response involving several chemical mediators occurs. Among them, nerve growth factor (NGF) regulates the inflammatory response related to wound healing and promotes keratinocyte proliferation and angiogenesis. The aim of our study was to investigate the physiological response to injury in children with moderate-severe burns, assaying proNGF, mature NGF (mNGF), interleukins (IL)-1ß, and Il-10 serum levels. PATIENTS AND METHODS: This is a prospective observational study, including twelve children hospitalized for moderate-severe burns at the Gemelli Hospital (Rome). Their laboratory features were compared to those of patients with obstructive hydrocephalus who underwent surgery. RESULTS: Our results showed an increase in proNGF and mNGF serum levels. In burn patients, proNGF levels increased before mNGF, and serum concentrations of both were not correlated with burn extension and depth. The most significant levels of mNGF and proNGF were reported in scalds involving the face. Serum IL-1ß and IL-10 peak levels were reached with a time-course pattern similar to proNGF. CONCLUSIONS: Our preliminary results validate the hypothesis that serum levels of proNGF and mNGF may represent inflammatory biomarkers useful for monitoring burn patients and defining new strategies for their treatment.

Intrapulmonary drug administration in neonatal and paediatric critical care: a comprehensive review.

Administration of drugs directly into the respiratory tree first was proposed a long time ago. Surfactant is the paradigmatic example of such therapies. Many other drugs have been used in the same way and further compounds are under investigation for this aim. In the last two decades, despite the wide number of drugs available for direct lung administration in critical care patients, few controlled data exist regarding their use in neonates and infants. This review will focus on drugs clinically available in a critical care setting for neonates and infants, including bronchodilators, pulmonary vasodilators, anti-inflammatory agents, mucolytics, resuscitative anti-infective agents, surfactants and other drugs. We provide an evidence-based comprehensive review of drugs available for intratracheal administration in paediatric and neonatal critical care and we examine possible advantages and risks for each proposed indication.

Life-threatening complications of streptococcal sepsis: a PICU contemporary series.

BACKGROUND: Life-threatening streptococcal sepsis nowadays represents an uncommon event in previously healthy infants and children. Critically ill patients suffering from severe streptococcal sepsis complications may present with pre-antibiotic era clinical pictures and require a timely clinical approach to achieve restitutio ad integrum. RESULTS: We report a series of four patient groups affected by an uncommon life-threatening streptococcal sepsis, each of them exhibiting some distinct features. Streptococcus Agalactiae sepsis was associated with cerebral thrombotic/ischaemic lesions, whereas severe cardiogenic shock was prominent in the Streptococcus Viridans group; Streptococcus Faecalis and ß-hemolytic group A Streptococcus patients mostly reported lung complications. CONCLUSIONS: Previous antibiotic treatments should not delay aggressive treatment in the intensive care setting. Early diagnostic suspicion, as well as appropriate and aggressive treatment provided within an intensive care setting are crucial for the clinical outcome.

Measles-induced respiratory distress, air-leak and ARDS.

Young infants with measles requiring respiratory support have a significant risk for death and long-term complications. Even in developed countries, the occurrence of spontaneous air-leaks and acute respiratory distress syndrome (ARDS) still represent the most severe clinical presentation in early childhood, with a high fatality rate. A clinical series review from a tertiary university paediatric intensive care unit (PICU) was undertaken. During the 2006-2007 outbreak in Rome, Italy, a young infant presented with ARDS/spontaneous air-leak and needed aggressive ventilatory management and haemodynamic support. Both nebulised iloprost and intravenous pentoxifylline were administered during the acute hypoxaemic phase; the role of this pharmacologic approach in critically ill patients is still under debate. We observed four further cases of respiratory impairment requiring a non-invasive approach. Clinical-radiological findings ranged from interstitial pneumonia to bronchiolitis-like pictures. All patients were imported cases, representing an important epidemiological factor and future medical issue, though they were not malnourished nor affected by chronic diseases. We conclude that early respiratory assessment and timely PICU referral is of mainstem importance in the youngest infants with measles-induced respiratory failure. The protean nature of clinical presentation and the possibility of rapid respiratory deterioration should be highlighted, and infants from immigrant families may represent a susceptible high-risk group.

When to include ECoG electrode properties in volume conduction models.

OBJECTIVE: Implantable electrodes, such as electrocorticography (ECoG) grids, are used to record brain activity in applications like brain computer interfaces. To improve the spatial sensitivity of ECoG grid recordings, electrode properties need to be better understood. Therefore, the goal of this study is to analyze the importance of including electrodes explicitly in volume conduction calculations. APPROACH: We investigated the influence of ECoG electrode properties on potentials in three geometries with three different electrode models. We performed our simulations with FEMfuns, a volume conduction modeling software toolbox based on the finite element method. MAIN RESULTS: The presence of the electrode alters the potential distribution by an amount that depends on its surface impedance, its distance from the source and the strength of the source. Our modeling results show that when ECoG electrodes are near the sources the potentials in the underlying tissue are more uniform than without electrodes. We show that the recorded potential can change up to a factor of 3, if no extended electrode model is used. In conclusion, when the distance between an electrode and the source is equal to or smaller than the size of the electrode, electrode effects cannot be disregarded. Furthermore, the potential distribution of the tissue under the electrode is affected up to depths equal to the radius of the electrode. SIGNIFICANCE: This paper shows the importance of explicitly including electrode properties in volume conduction models for accurately interpreting ECoG measurements.

FEMfuns: A Volume Conduction Modeling Pipeline that Includes Resistive, Capacitive or Dispersive Tissue and Electrodes.

Applications such as brain computer interfaces require recordings of relevant neuronal population activity with high precision, for example, with electrocorticography (ECoG) grids. In order to achieve this, both the placement of the electrode grid on the cortex and the electrode properties, such as the electrode size and material, need to be optimized. For this purpose, it is essential to have a reliable tool that is able to simulate the extracellular potential, i.e., to solve the so-called ECoG forward problem, and to incorporate the properties of the electrodes explicitly in the model. In this study, this need is addressed by introducing the first open-source pipeline, FEMfuns (finite element method for useful neuroscience simulations), that allows neuroscientists to solve the forward problem in a variety of different geometrical domains, including different types of source models and electrode properties, such as resistive and capacitive materials. FEMfuns is based on the finite element method (FEM) implemented in FEniCS and includes the geometry tessellation, several electrode-electrolyte implementations and adaptive refinement options. The Python code of the pipeline is available under the GNU General Public License version 3 at https://github.com/meronvermaas/FEMfuns . We tested our pipeline with several geometries and source configurations such as a dipolar source in a multi-layer sphere model and a five-compartment realistically-shaped head model. Furthermore, we describe the main scripts in the pipeline, illustrating its flexible and versatile use. Provided with a sufficiently fine tessellation, the numerical solution of the forward problem approximates the analytical solution. Furthermore, we show dispersive material and interface effects in line with previous literature. Our results indicate substantial capacitive and dispersive effects due to the electrode-electrolyte interface when using stimulating electrodes. The results demonstrate that the pipeline presented in this paper is an accurate and flexible tool to simulate signals generated on electrode grids by the spatiotemporal electrical activity patterns produced by sources and thereby allows the user to optimize grids for brain computer interfaces including exploration of alternative electrode materials/properties.

Safety and efficacy of ultrasound assistance during internal jugular vein cannulation in neurosurgical infants.

OBJECTIVE: Ultrasound guidance (USG) for internal jugular cannulation is the best solution in difficult settings where paediatric patients are involved. This is an outcome study on efficacy and complications of the USG for the internal jugular vein (IJV) cannulation in neurosurgical infants as well as an ultrasound study of anatomical findings of the IJVs in infants. DESIGN AND SETTINGS: A prospective study conducted in two Academic Neurosurgical hospitals. PARTICIPANTS: In 191 babies (body weight <15 kg), anatomical findings were studied. We performed CVC echo guided placement in 135/191 infants (weighting <10 kg). RESULTS: After a brief training period, both institutions adopted a common protocol and USG device. We obtained successful cannulation in all patients. Carotid puncture (1.5%) was the only main complication registered and minor complications were poor. Time required for cannulation was 12.5 +/- 5.7 min. Anatomical findings (in 191 patients) were IJV laterality in 34.6% cases, IJV antero-lateral in 59.7% and anterior in 5.7%. A linear relation was found between weight and internal jugular vein diameter even if R(2) = 0.43 and the model cannot be used to predict the exact size of the vein. In 62/135 babies weighting <10 kg, anatomical measurements were done in supine and Trendelemburg position. Trendelemburg position increases significantly (P < 0.001) IJV diameter, but not IJV depth. CONCLUSIONS: We considered ultrasound guidance as the first choice in infants because it can enhance IJV cannulation success, safety, and allows one to measure relationships and diameter of the IJV and optimise the central line positioning.

Kidney injury owing to Streptococcus pneumoniae infection in critically ill infants and children: report of four cases.

Streptococcus pneumoniae sepsis has high morbidity, particularly if complicated by renal injury. Four patients with S. pneumonia invasive infections complicated by renal disorders are presented. The first case was an 18-month-old girl with pneumococcal empyema complicated by haemolytic uraemic (HUS) syndrome. She made a full recovery after mechanical ventilation, inotropic support and haemodiafiltration. The second was a 4-year-old boy who presented with acute post-infectious glomerulonephritis associated with bilateral pneumococcal pneumonia. He too made a complete recovery. The third was a newborn girl with pneumococcal meningitis complicated by acute respiratory distress syndrome and acute renal failure. The fourth patient was an 8-month-old boy with pneumococcal pneumonia and meningitis complicated by HUS and with fulminant thrombotic thrombocytopenic purpura. Despite full support including mechanical ventilation and haemodiafiltration, he died 4 days after admission. On follow-up, all three survivors recovered completely from their pulmonary symptoms and had normal renal function and cardio-circulatory status in the mid-term.

Intraventricular streptokinase infusion in acute post-haemorrhagic hydrocephalus.

Neonatal post-haemorrhagic hydrocephalus is a clinical condition with a high mortality and long-term morbidity. Its clinical management is difficult and not well standardized. We describe the case of a term baby suffering from acute intracranial hypertension caused by an intraventricular and thalamic haemorrhage. In this case, the external ventricular drain inserted to control intracranial pressure was ineffective because of repeated obstructions due to blood clots. Continuous intraventricular infusion of streptokinase of 20,000 U/day allowed quick lysis of the clots, drainage of the cerebrospinal fluid and relief from the coma. Although it did not prevent a permanent ventriculoperitoneal shunt, we obtained reabsorption of the intraventricular haemorrhage without rebleeding complications. We suggest the use of low-dose fibrinolytic infusion through an external drain for the treatment of acute intracranial hypertension following intraventricular haemorrhage in term infants.

[Acute psychosis and vigabatrin in childhood]. / Psicosi acuta e vigabatrin in età pediatrica.

Vigabatrin is an irreversible inhibitor of gamma-aminobutyrate (Gaba) aminotransferase, producing an increase in Gaba concentrations in the brain. It may prove to be an important drug in the treatment of refractory epilepsy, but would be payed attention to behavioural changes noted in association with vigabatrin treatment. Behaviour disturbances, as psychosis, associated to vigabatrin are ben described in adult patients, while are uncommon in childhood. We report a case of acute psychosis occurred in a child in treatment with vigabatrin.

[Clinical-instrumental dissociation in a case of Reye's syndrome]. / Dissociazione clinico-strumentale in un caso di sindrome di Reye.

We report the case of a boy 5 years old we admitted to our PICU with signs of impending hepatic failure (hypertransaminasemia, hyperammonemia, prolonged PT) following mild upper respiratory infection and irrepressible vomiting. We observed no neurological abnormalities excepting slight lethargy; on the contrary, EEG findings showed severe diffuse slowing and high-voltage Delta activity. Our diagnosis of Reye's syndrome was later confirmed by liver biopsy. Clinical and electrophysiological signs recovered after 48-72 hours and no explication was found for this anomalous Reye's syndrome presentation. Further studies are needed for understanding the basis of neurological involvement of stage I Reye's syndrome.

[Analgesic efficacy of ketorolac and fentanyl in pediatric intensive care]. / Efficacia analgesica del Ketorolac e del Fentanyl in Terapia Intensiva Pediatrica.

OBJECTIVE: To evaluate the efficacy of the two different drugs (Ketorolac and Fentanyl), used singularly or in association, in the management of postoperative pain in Picu. STUDY DESIGN: A randomized and prospective study. METHODS: 52 children were randomly assigned to receive intravenous Ketorolac and/or Fentanyl, according to four different analgesic treatments: A) Ketorolac 1.2 mg/kg every six hrs; B) Ketorolac 1.2 mg/kg (bolus) + 0.21 mg/ kg/hr; C) Fentanyl 1 gamma/kg/hr; D) Fentanyl 1 gamma/kg/hr + Ketorolac 0.21 mg/kg/hr. Each protocol was given to 13 children. The efficacy of treatments were evaluated by child's behaviour (Affective Facial Scale and CHEOPS score) and hemodynamical parameters (systolic and diastolic blood pressure, breathing rate, heart rate, oxygen saturation and oxygen arterial pressure) and analysed by statistical analysis. RESULTS: The children treated with protocol B (Ketorolac in continuous in infusion) showed better pain relief in respect to those treated with protocol A (Ketorolac in bolus), while the most efficient analgesia was obtained with the association of the two analgesic drugs (protocol D). Two cases of bradycardia, one case of hyperazotemia and one case of transaminase increase were noted. CONCLUSION: Ketorolac presents a good efficient analgesia, particularly evident when administered in continuous intravenous infusion. However, the association of this NSAID with an opioid drug can be favourably proposed in postoperative pain therapy of moderate to severe grade, since the confirmed analgesic efficacy is not aggravated by important side effects.

[The management of the child with head injury: our experience]. / Il management del bambino con trauma cranico: nostra esperienza.

OBJECTIVES: To analyze the group of children admitted to our Pediatric Intensive Care Unit (PICU) for neurotrauma and describe the management algorithms adopted by us for pediatric head injury. METHODS: All the children affected by head injury and admitted to PICU since november 1992 to november 2000 have been examined. Injury severity has been classified using the Glasgow Coma Score (GCS), while the long term neurological outcome with the Glasgow Outcome Score (GOS). We have described the clinical presentation, the kind and dynamics of injury and the clinical outcome one month after discharge. RESULTS: 210 children with head injury have been identified. Among them: 38 were affected by mild head injury, 50 by a moderate one and 122 by a severe one. The most frequent cause of injury has been represented by car accidents and motorbike or bicycle falls. The overall outcome has resulted good (GOS 4-5) in all children affected by mild or moderate head injury; on the other side, patients with severe injury have presented the following scores: GOS 1 (dead children) 14.7%, GOS 2 (persistent vegetative state) 1.6%, GOS 3 (severe disability) 22.2%, GOS 4 (mild disability) and GOS 5 (no disability) 61.5%. CONCLUSION: A correct management of children with head injury helps clinicians to improve outcome and to reduce mortality. Therapeutics algorithms suggested by us could be useful for the management of this kind of patients, not only when they are affected by a severe head injury but, also, when they suffer from a mild one, that is the most common event in the emergency room departments.