A new method of ventilation inhomogeneity assessment based on a simulation study using clinical data on congenital diaphragmatic hernia cases.

Congenital Diaphragmatic Hernia (CDH) is a diaphragm defect associated with lung hypoplasia and ventilation inhomogeneity (VI). The affected neonates are usually born with respiratory failure and require mechanical ventilation after birth. However, significant interindividual VI differences make ventilation difficult. So far, there are no clinical methods of VI assessment that could be applied to optimize ventilation at the bedside. A new VI index is a ratio of time constants T1/T2 of gas flows in both lungs. Pressure-controlled ventilation simulations were conducted using an infant hybrid (numerical-physical) respiratory simulator connected to a ventilator. The parameters of the respiratory system model and ventilator settings were based on retrospective clinical data taken from three neonates (2, 2.6, 3.6 kg) treated in the Paediatric Teaching Clinical Hospital of the Medical University of Warsaw. We searched for relationships between respiratory system impedance (Z) and ventilation parameters: work of breathing (WOB), peak inspiratory pressure (PIP), and mean airway pressure (MAP). The study showed the increased VI described by the T1/T2 index value highly correlated with elevated Z, WOB, PIP and MAP (0.8-0.9, the Spearman correlation coefficients were significant at P < 0.001). It indicates that the T1/T2 index may help to improve the ventilation therapy of CDH neonates.

ESPNIC clinical practice guidelines: intravenous maintenance fluid therapy in acute and critically ill children- a systematic review and meta-analysis.

PURPOSE: Intravenous maintenance fluid therapy (IV-MFT) prescribing in acute and critically ill children is very variable among pediatric health care professionals. In order to provide up to date IV-MFT guidelines, the European Society of Pediatric and Neonatal Intensive Care (ESPNIC) undertook a systematic review to answer the following five main questions about IV-MFT: (i) the indications for use (ii) the role of isotonic fluid (iii) the role of balanced solutions (iv) IV fluid composition (calcium, magnesium, potassium, glucose and micronutrients) and v) and the optimal amount of fluid. METHODS: A multidisciplinary expert group within ESPNIC conducted this systematic review using the Scottish Intercollegiate Guidelines Network (SIGN) grading method. Five databases were searched for studies that answered these questions, in acute and critically children (from 37 weeks gestational age to 18 years), published until November 2020. The quality of evidence and risk of bias were assessed, and meta-analyses were undertaken when appropriate. A series of recommendations was derived and voted on by the expert group to achieve consensus through two voting rounds. RESULTS: 56 papers met the inclusion criteria, and 16 recommendations were produced. Outcome reporting was inconsistent among studies. Recommendations generated were based on a heterogeneous level of evidence, but consensus within the expert group was high. "Strong consensus" was reached for 11/16 (69%) and "consensus" for 5/16 (31%) of the recommendations. CONCLUSIONS: Key recommendations are to use isotonic balanced solutions providing glucose to restrict IV-MFT infusion volumes in most hospitalized children and to regularly monitor plasma electrolyte levels, serum glucose and fluid balance.

The case of fatal acute hemorrhagic necrotizing encephalitis in a two-month-old boy with Covid-19.

SARS-CoV-2 infection in healthy children is usually benign. However, severe, life-threatening cases have previously been reported, notably in infants. We must be aware that data on the natural history of COVID-19 are still full of gaps, especially as far as the pediatric population is concerned. Therefore, it is important to describe rare manifestations of SARS-CoV-2 acute infection in children. Here we present the case of acute hemorrhagic necrotizing encephalitis (AHNE) in a previously healthy, 2-month-old male infant with SARS-CoV-2 infection. After 2 days of fever with signs of respiratory tract infection, neurological manifestations appeared: irritability, nystagmus, agitation then apathy. As a consequence of apnea, he required emergent intubation and was transferred to our PICU. Brain MRI revealed diffuse areas of oedema associated with numerous symmetrical changes with punctate hemorrhages in basal ganglia, thalami, brainstem, and cerebral gray matter. CSF was clear with pleocytosis 484 cells/µl, elevated lactic acid and protein. Despite broad microbiological testing, only SARS-CoV2 was detected in PCR nasal swab. Therefore, acute hemorrhagic necrotizing encephalitis (AHNE) as a result of COVID-19 was the most probable diagnosis. The outcome was unfavorable - brain death was confirmed, life support was withdrawn.

Guidelines regarding ineffective maintenance of organ functions (futile therapy) in paediatric intensive care units.

In Poland, guidelines for the management of ineffective treatment of children in neonatal and paediatric departments developed by the Polish Neonatal Society and the Polish Paediatric Society, have been published. The specific problems of futile therapy in paediatric anaesthesiology and intensive care units should be defined and solved separately. For this purpose, the guidelines presented below were prepared. They present the principles for managing children for whom therapeutic options available in paedia-tric anaesthesiology and intensive care units have been exhausted and ineffectiveness of maintaining organ functions, i.e. futile therapy, has been suspected. The decision to withdraw futile therapy of a child is undoubtedly one of the most difficult for both doctors and parents, and for this reason, it should be made collectively, respecting the dignity of the child and his/her parents or legal representatives, and continuing the management aimed at relieving the child's pain and suffering, as well as minimising anxiety and fear. Due to the small amount of reliable evidence-based data, the guidelines constitute the consensus of the Group of Experts and are dedicated to minor patients treated in paediatric anaesthesiology and intensive care units.

Postnatal Evaluation of Congenital Chest Pathologies Using a Low-Dose Computed Tomography (CT) Protocol - a Pictorial Review.

Computed tomography with its excellent spatial and temporal resolution remains a valuable diagnostic modality in pediatrics. On the other hand an increasing attention has been placed on the radiation risks associated with CT imaging, especially in children. In recent years, many advances in CT hardware and software, for example, automatic exposure control tools and iterative reconstruction techniques, have allowed for a reduction of applied radiation doses while maintaining image quality. The purpose of this paper is to present our protocol for chest CT imaging in the youngest age group, together with a pictorial review of congenital pathologies of the chest, and to emphasize factors that optimize postnatal CT imaging in infants. In our opinion, modern CT imaging with the use of dose reduction techniques and iterative reconstructions allows for a proper visualization of chest pathologies in small children, which has no influence on observer performance. The presented review of low-dose diagnostic images of a wide spectrum of congenital pathologies may serve as an example of routine utilization of the current concepts in pediatric CT optimization.

Alexander disease - astrogliopathy considered as leukodystrophy - experience of an institution.

Alexander Disease (ALXDRD) is an autosomal dominant leukodystrophy caused by mutation in one allele of GFAP gene, encoding glial fibrillary acidic protein (GFAP). Most cases occur due to de novo. There are three clinical subtypes of ALXDRD: infantile, juvenile and adult form, but congenital form is also outlined. The disease's spectrum comprises of macrocephaly, progressive pyramidal signs, and seizures in congenital and infantile subtypes. Neuropathologically are enormous number of Rosenthal fibers (RF) mainly around vessels, in subependymal and subpial regions are found. The diagnosis is based on the typical findings on MRI: diffuse white mater lesions with frontal regions preponderance and possibly on the detection of the gene mutation. Here we present six Polish children affected of Alexander disease with congenital (1), infantile (4) and juvenile (1) form. Five of them were previously misdiagnosed as cerebral palsy or unspecific developmental delay; two patients had MRI because of another suspicion, before specific diagnosis was established. Molecular analysis performed in four cases confirmed mutations of GFAP gene; all mutation were de novo. The role of astroglia in brain is shortly reviewed.

Intraoperative fluid management in children - a comparison of three fluid regimens.

BACKGROUND: Fluid therapy is essential for safe perioperative management. Numerous reports of serious complications, including brain damage and death of children, as a result of inappropriate fluid management, have been published. The aim of this study was to assess the effects of intraoperative fluids on serum glucose and electrolytes concentrations as well as serum osmolality. METHODS: 91 children, ASA I and II, undergoing elective ENT surgery were enrolled to this prospective, randomized, open-label study. They were randomly assigned to receive: group G5W: 5% glucose in water solution, group GNaCl: 3.33% glucose in 0.3% NaCl, and group RA: Ringer's acetate. Serum glucose, sodium, potassium, phosphate concentrations and serum osmolality were analysed before induction of anaesthesia, immediately after completion of surgery and 60 min later. RESULTS: Postoperative hyperglycaemia was observed in 94% of children in group G5W and in 37% of group GNaCl. In all the groups glucose concentration increased significantly after surgery. Postoperative hyponatraemia occurred in 36% of patients in the group G5W, and in 3.7% in the group GNaCl. Neither hyperglycaemia nor hyponatremia occurred in the group RA. Postoperative osmolality decreased significantly in groups G5W and GNaCl and remained unchanged in the group RA. CONCLUSIONS: Ringer's acetate did not cause significant changes in glucose and electrolyte concentrations, so it seems to be the safest for intraoperative use in children undergoing elective surgery. Hypotonic fluids may cause hyperglycaemia and hyponatraemia so they should be avoided intraoperatively.

Neurogenic stunned myocardium - do we consider this diagnosis in patients with acute central nervous system injury and acute heart failure?

Neurogenic stunned myocardium (NSM) is defined as myocardial injury and dysfunction of a sudden onset, occurring after various types of acute brain injury as a result of an imbalance in the autonomic nervous system. The typical spectrum of clinically observed abnormalities includes acute left ventricular failure, not uncommonly progressing to cardiogenic shock with hypotension that requires inotropic agents, pulmonary oedema and various arrhythmias. Commonly-seen electrocardiographic changes include: prolonged QT interval, ST segment changes, T-wave inversion, a new Q-wave or U-wave. Echocardiography shows both an impaired both systolic and diastolic function of the left ventricle. Biochemical markers of NSM comprise metabolic acidosis and increased cardiac enzymes and markers: creatine kinase (CK), and CK-MB, troponin I and B-type natriuretic peptide. The main cause of NSM is myocardial injury induced by local catecholamine release from nerve endings within the myocardium. Recently, a theory has been proposed to classify NSM as one of the stress-related cardiomyopathies, together with Takotsubo cardiomyopathy, acute left ventricular failure in the critically ill, cardiomyopathy associated with pheochromacytoma and exogenous catecholamine administration. The occurrence of NSM increases the risk of life-threatening complications, death, and worsens neurologic outcome. As far as we know, treatment should generally focus on the underlying neurologic process in order to maximize neurologic recovery. Improvement in neurologic pathology leads to rapid improvement in cardiac function and its full recovery, as NSM is a fully reversible condition if the patient survives. Awareness of the existence of NSM and a deeper knowledge of its etiopathology may reduce diagnostic errors, optimise its treatment.

Tolerance of, and metabolic effects of, preoperative oral carbohydrate administration in children - a preliminary report.

BACKGROUND: The need for long preoperative fasting has been questioned. Recent data shows that intake of an oral carbohydrate-containing clear fluid prior to anaesthesia is safe and may have a positive impact on recovery and metabolic status and could improve glucose tolerance. Such solutions are routinely used in adults but not children. The aim of this study was to evaluate the safety, tolerance and influence of oral carbohydrate on selected metabolic parameters in children. METHODS: With ethics committee approval and parental informed consent, 20 children, aged 4-17 years, ASA status I or II, scheduled for abdominal or thoracic surgery were randomised either to Group 1 - receiving a 12.6% carbohydrate-containing drink (10 mL kg(-1) the evening before surgery and two hours before anaesthesia), or the control Group 2 - fasting. Serum glucose and insulin concentration were measured four times: before and after anaesthesia, in the evening after surgery, and the following morning. IGF-1 concentration was measured once, before surgery. Insulin resistance was assessed by the HOMA-IR equation. RESULTS: Oral carbohydrate solution was well tolerated and no adverse events were noted. Glucose concentrations were within the normal range in both groups. Insulin concentration did not show significant differences between groups, however before surgery it tended to be lower in Group 1. Insulin resistance after surgery was significantly higher in Group 2 (2.0 vs. 0.62, P = 0.03), also the increase in insulin resistance after operation was significant only in the control group (P = 0.03). CONCLUSION: Oral carbohydrates are safe, well tolerated and do not cause any perioperative adverse events. They seem to improve postoperative metabolism by decreasing insulin resistance.

Severe phenotypes of SMARD1 associated with novel mutations of the IGHMBP2 gene and nuclear degeneration of muscle and Schwann cells.

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a very rare autosomal recessive form of spinal muscular atrophy manifested in low birth weight, diaphragmatic palsy and distal muscular atrophy. Caused by a mutation in the IGHMBP2 gene, the disease is addressed here by reference to five Polish patients in which SMARD1 has been confirmed genetically. All presented a severe form of the disease and had evident symptoms during the second month of life; with four displaying weak cries, feeding difficulties and hypotonia from birth. Two were afflicted by severe dysfunction of the autonomic nervous system. Ultrastructural analysis of a muscle biopsy revealed progressive degeneration within the nuclei of the muscle cells and Schwann cells. Neuromuscular junctions were also defective. It proved possible to identify in our patients 6 novel IGHMBP2 mutations: three missense (c.595G>C, c.1682T>C and c.1794C>A), two nonsense (c.94C>T and c.1336C>T) and one in-frame deletion (c.1615_1623del). One nonsense mutation (c.429C>T) that had been described previously was also identified. Observation of our patients makes it clear that clinical picture is still the most important factor suggesting diagnosis of SMARD1, though further investigations concerning some of the symptoms are required. As the IGHMBP2 gene is characterized by significant heterogeneity, genetic counseling of affected families is rendered more complex. IGHMBP2 protein deficiency can lead to the degeneration of nuclei, in both muscle and Schwann cells.