[More than three hours, less than three years. Safety of anesthetic procedures in children under three years, subject to surgeries of more than three hours]. / Más de tres horas y menos de tres años. Seguridad de procedimientos anestésicos en niños menores de tres años, sometidos a cirugías de más de tres horas.

The Food and Drug Administration (USA) warning (December 2016) on the safety of general anesthesia and sedation in patients younger that 3 years and pregnant women has raised many questions about the attitude that should be taken by professionals involved in the treatment of these patients. In view of this situation, the following Medical Scientific Societies: SEDAR, SECP, SECIP and SENeo have constituted a working group to analyze and clarify the safety of these techniques. In the present article, we conclude that at present both general anesthesia and deep sedation should continue to be considered safe techniques because there is no sufficient opposing evidence in clinical studies with humans. Despite this, we should not ignore the problem which must be followed carefully mainly in patients under three years of age undergoing anesthetic procedures longer than three hours or prolonged sedation in Neonatal or Pediatric Intensive Care Units.

La alerta de la FDA de diciembre 2016, sobre la seguridad de la anestesia general y las sedaciones en pacientes menores de 3 años y en mujeres embarazadas, ha suscitado numerosas dudas sobre la actitud que deben tomar los profesionales implicados en el tratamiento de estos pacientes. Ante esta situación, las siguientes Sociedades Científicas Médicas: SEDAR (Sociedad Española de Anestesia y Reanimación), SECP (Sociedad Española de Cirugía Pediátrica), SECIP (Sociedad Española de Cuidados Intensivos Pediátricos) y SENeo (Sociedad Española de Neonatología), han constituido un grupo de trabajo para analizar y clarificar la seguridad de estas técnicas. En este artículo concluimos que en el momento actual tanto la anestesia general como la sedación profunda deben seguir siendo consideradas como técnicas seguras, porque no existen evidencias de lo contrario en estudios con seres humanos. Esta seguridad no nos permite ignorar el problema, que debe ser seguido con atención, fundamentalmente en pacientes de menos de tres años, sometidos a procedimientos anestésicos de más de tres horas o a sedaciones prolongadas en las Unidades de Cuidados Intensivos Neonatales o Pediátricos.

Impact of a modification of the clinical practice guide of the American Academy of Pediatrics in the management of severe acute bronchiolitis in a pediatric intensive care unit.

OBJECTIVE: To describe the characteristics and evolution of patients with bronchiolitis admitted to a pediatric intensive care unit, and compare treatment pre- and post-publication of the American Academy of Pediatrics clinical practice guide. DESIGN: A descriptive and observational study was carried out between September 2010 and September 2017. SETTING: Pediatric intensive care unit. PATIENTS: Infants under one year of age with severe bronchiolitis. INTERVENTIONS: Two periods were compared (2010-14 and 2015-17), corresponding to before and after modification of the American Academy of Pediatrics guidelines for the management of bronchiolitis in hospital. MAIN VARIABLES: Patient sex, age, comorbidities, severity, etiology, administered treatment, bacterial infections, respiratory and inotropic support, length of stay and mortality. RESULTS: A total of 706 patients were enrolled, of which 414 (58.6%) males, with a median age of 47 days (IQR 25-100.25). Median bronchiolitis severity score (BROSJOD) upon admission: 9 points (IQR 7-11). Respiratory syncytial virus appeared in 460 (65.16%) patients. The first period (2010-14) included 340 patients and the second period (2015-17) 366 patients. More adrenalin and hypertonic saline nebulizations and more corticosteroid treatment were administered in the second period. More noninvasive ventilation and less conventional mechanical ventilation were used, and less inotropic support was needed, with no significant differences. The antibiotherapy rate decreased significantly (p=0.003). CONCLUSIONS: Despite the decrease in antibiotherapy, the use of nebulizations and glucocorticoids in these patients should be limited, as recommended by the guide.

Impact of a modification of the clinical practice guide of the American Academy of Pediatrics in the management of severe acute bronchiolitis in a pediatric intensive care unit. / Impacto de una modificación de la guía de práctica clínica de la Academia Americana de Pediatría en el manejo de la bronquiolitis aguda grave en una unidad de cuidados intensivos pediátricos.

OBJECTIVE: To describe the characteristics and evolution of patients with bronchiolitis admitted to a pediatric intensive care unit, and compare treatment pre- and post-publication of the American Academy of Pediatrics clinical practice guide. DESIGN: A descriptive and observational study was carried out between September 2010 and September 2017. SETTING: Pediatric intensive care unit. PATIENTS: Infants under one year of age with severe bronchiolitis. INTERVENTIONS: Two periods were compared (2010-14 and 2015-17), corresponding to before and after modification of the American Academy of Pediatrics guidelines for the management of bronchiolitis in hospital. MAIN VARIABLES: Patient sex, age, comorbidities, severity, etiology, administered treatment, bacterial infections, respiratory and inotropic support, length of stay and mortality. RESULTS: A total of 706 patients were enrolled, of which 414 (58.6%) males, with a median age of 47 days (IQR 25-100.25). Median bronchiolitis severity score (BROSJOD) upon admission: 9 points (IQR 7-11). Respiratory syncytial virus appeared in 460 (65.16%) patients. The first period (2010-14) included 340 patients and the second period (2015-17) 366 patients. More adrenalin and hypertonic saline nebulizations and more corticosteroid treatment were administered in the second period. More noninvasive ventilation and less conventional mechanical ventilation were used, and less inotropic support was needed, with no significant differences. The antibiotherapy rate decreased significantly (P=.003). CONCLUSIONS: Despite the decrease in antibiotherapy, the use of nebulizations and glucocorticoids in these patients should be limited, as recommended by the guide.

[ECMO: experience in paediatrics]. / ECMO: experiencia en edad pediátrica.

INTRODUCTION: ECMO (Extracorporeal Membrane Oxygenation) provides a vital support to patients with supposed reversible respiratory and/or cardiac failure, in whom conventional support techniques have been previously unsuccessful. OBJECTIVES: To determinate the criteria used in our hospital to put paediatric patients on ECMO, compare their clinical course depending on their pathology (respiratory failure, congenital heart disease or sepsis) and identify the sequelae attributable to this technique. MATERIAL AND METHOD: A retrospective review of clinical records of all patients on ECMO support in our centre, excluding those presenting typically in neonatal period. RESULTS: ECMO was used on 16 patients from June 2001 to January 2007, of which 50% were males. The median age was 7 months (from 21 days to 11 years). The reason for starting ECMO was respiratory failure in 11 cases (oxygenation index >40 and/or alveolar-arterial oxygen gradient >605), congenital heart disease in 2 and sepsis in 3 (due to shock unresponsive to adequate resuscitation). The median time to starting ECMO from PICU admission was 3.58 days (from 12h to 9 days). Venovenous cannulation was used initially in 8 patients, but 5 of them needed venoarterial ECMO later. The technique was used for a mean of 8 days (from 1 to 28 days). The main complication was the isolation of bacteria in different cultures (8 patients). The overall survival was 50% (6 patients with respiratory failure and both patients submitted to cardiac surgery). Extracorporeal support was withdrawn in 7 children because their clinical situation was irreversible. Another patient died seven days after successful decannulation. We have not found any serious sequel among survivors that could be attributable to this technique. CONCLUSIONS: Survival among children supported with ECMO in our hospital is similar to that recorded by the ELSO in 2004, although the prognosis depends on the initial pathology. There are different criteria for starting this technique depending on the underlying diseases: respiratory index of poor prognosis in patients with respiratory failure, haemodynamic instability in those with sepsis or cardiac failure after cardiovascular surgery. We have not found any serious sequel among the survivors which could be attributable to this technique.

[Preliminary clinical experience with PiCCO system in children with shock]. / Experiencia clínica de monitorización hemodinámica del shock mediante el sistema PiCCO.

PURPOSE: To evaluate the PiCCO hemodynamics monitor in terms of clinical usefulness in children with shock. METHODS: Prospective multicenter analytical study in children aged from one month to 18 years with shock admitted to five pediatric intensive care units. Measurements were made before and after three interventions: a) volume load; b) increases in vasoactive drugs; c) dosage changes of drugs that could lessen vascular resistance. Recorded parameters included thermodilution data, along with the usual hemodynamic parameters. RESULTS: A total of 120 measurements were performed on 35 patients: mean age 36 (2.6-156) months, mean weight 15 (5.8-72) kg. Shock etiology was septic in 37% of cases, cardiogenic in 26%, hypovolemic in 20% and neurogenic in 17%. No procedure related complication was noticed. Twenty-two volume challenges in 17 patients were registered. Volume load induced a significant intrathoracic blood volume index (ITBI) increase from 501(235-763) to 584 (418-810) ml/m(2), cardiac index (CI) 4.04 (2.58-6.25) to 4.48 (2.86-8.71) lmin-1m(2), and mean blood pressure from 74 (53-99) to 87 (59-112) mmHg. CI changes correlated with ITBI increase (r = 0.678, p = 0.001). 13 interventions to increase vasomotor tone were associated with an increase in contractility of 18% in systemic vascular resistance index (SVRI). CONCLUSIONS: Hemodynamic monitoring with the PiCCO system is feasible and seems safe in children with shock. PiCCO derived parameters could add clinically important information to assess preload state and its modifications with therapy.

Large de novo deletion in chromosome 12 affecting the PAH, IGF1, ASCL1, and TRA1 genes.

Phenylketonuria is one of the most common genetic diseases in humans, affecting 1 in 10,000 whites. Deletions are generally uncommon in genes in which no long highly homologous segments are present, and in phenylalanine hydroxylase (PAH) deficiency they represent only 5% of cases. We present the case of a girl affected by classical phenylketonuria who has been screened for mutations in the PAH gene. During the molecular study a large de novo deletion has detected in 12qter, including PAH, and the genes for insulin-like growth factor 1 (IGF1), human achaete-scute homolog 1 (ASCL1), and tumor rejection antigen (TRA1). The patient showed phenylketonuria, short stature, and pathological electro-oculography results in both eyes, with high affectation of the relative electrogenesis of the photoreceptor-pigment epithelium complex. She had previously been misdiagnosed as homozygous for the IVS8nt-7A-G mutation, instead of heterozygous for a mutation and a de novo deletion. As a result incorrect genetic counseling had been given. The deletion of the PAH, IGF1, and ASCL1 genes could explain the patient's phenotype corresponding to a contiguous gene syndrome. We stress the relevance of polymorphic marker haplotype analysis and the importance of family study in genetic recessive diseases, such as phenylketonuria, to avoid incorrect diagnosis and genetic counseling.

Decreased serum ubiquinone-10 concentrations in phenylketonuria.

BACKGROUND: Ubiquinone-10 is a lipid with important metabolic functions that may be decreased in phenylketonuria (PKU) because patients with PKU consume diets restricted in natural proteins. OBJECTIVE: We studied serum ubiquinone-10 concentrations in PKU patients. DESIGN: This was a retrospective, transversal study in which we compared serum ubiquinone-10, plasma cholesterol, plasma tyrosine, and plasma phenylalanine concentrations in 43 PKU patients with concentrations in a reference population (n = 102). Serum ubiquinone-10 concentrations were analyzed by HPLC with ultraviolet detection. Plasma tyrosine and phenylalanine were measured by ion-exchange chromatography. RESULTS: Serum ubiquinone-10 concentrations in PKU patients were significantly lower than in the reference population (P < 0.01 for patients aged 1 mo to <8 y and P < 0.00005 for patients aged 8-33 y). Moreover, 5 of 18 PKU patients (28%) in the younger age group and 10 of 23 (43%) in the older age group had serum ubiquinone-10 concentrations below the reference interval. CONCLUSIONS: Serum ubiquinone-10 deficiency appears to be related to the restricted diet of PKU patients. Because serum ubiquinone-10 plays a major antioxidant role in the protection of circulating lipoproteins, the correction of ubiquinone-10 concentrations should be considered in PKU patients. Further investigation seems advisable to elucidate whether the deficiency in serum ubiquinone-10 status is clinically significant.

Is there a relationship between plasma phenylalanine and cholesterol in phenylketonuric patients under dietary treatment?

OBJECTIVES: To study the lipid profile in a group of treated phenylketonuric patients (PKU; n = 61) compared with a group of inborn error of intermediary metabolism patients (IEM; n = 22), a group of hyperphenylalaninemic children (HPA; n = 37), and a control group without dietary restriction (n = 41). DESIGN AND METHODS: Phenylalanine was analyzed by ion exchange chromatography and triglycerides, cholesterol and HDL were determined by standard procedures with the Cobas Integra analyzer. RESULTS: Serum total cholesterol concentrations were significantly lower in PKU patients compared with IEM patients (whose cholesterol daily intake was similar to those of PKU patients), HPA children and the control group. A negative correlation was observed between cholesterol and phenylalanine concentrations in the PKU patients. CONCLUSIONS: Our findings support the hypothesis of a relationship between high plasma phenylalanine levels and an inhibition of cholesterogenesis, although the low cholesterol intake of the special diets may also decrease serum cholesterol values.

Antioxidant status in hyperphenylalaninemia.

Abnormal oxidative stress was observed in some inborn errors of metabolism owing to the accumulation of toxic metabolites leading to excessive free radical production and to the influence of restricted diets on the antioxidant status. Erythrocyte antioxidant enzymes activities and tocopherol concentrations were measured in a group of phenylketonuric (n = 42) and mild-hyperphenylalaninemic (n = 28) patients compared with 45 age-matched controls. We also determined plasma selenium levels in these groups. We also evaluated the possible relationship between antioxidant status and neuropsychological disorders. Erythrocyte glutathione peroxidase (GSH-Px) activity was significantly lower (P < 0.001) in both phenylketonuric and mild-hyperphenylalaninemic patients compared with the control group, but no differences were observed between the two groups of patients. Neuropsychological disturbances were more frequent in the group of PKU patients with low GSH-Px activity than in PKU patients with normal GSH-Px. Low GSH-Px activity might be explained in phenylketonuria as a result of a selenium deficiency caused by a poor selenium intake or absorption, but not in mild hyperphenylalaninemic patients with free diet. Selenium levels were normal in both groups of patients, so low glutathione peroxidase activity in both phenylketonuric and hyperphenylalaninemic groups might be influenced by other factors, such as the consequences of an unbalanced amino acid profile, common to both conditions.

[Acute disseminated encephalomyelitis in childhood. Report of 10 cases]. / Encefalomielitis aguda diseminada en la infancia: presentación de 10 casos.

INTRODUCTION: Acute disseminated encephalomyelitis (ADEM) is a postinfectious encephalitis that is usually preceded by an infectious disease or vaccination. The clinical presentation has a wide spectrum and complementary exams are none specific, except magnetic resonance imaging (MRI) findings showing multifocal white-matter lesions similar to those seen en multiple sclerosis. PATIENTS AND METHODS: We report 10 children with the diagnosis of ADEM. We describe the clinical course and response to treatment. RESULTS: The prodroms were fever in all cases except one. The most common neurological symptoms were consciousness impairment, headache and seizures. The cerebrospinal fluid examination was abnormal in 9 patients with positive serologic test to enterovirus in one of them. MRI showed hyperintense multifocal subcortical white-matter lesions on T2-mediated images. Treatment with steroids was given to 5 patients, steroids and immunoglobulins to one patient and symptomatic treatment to the rest. From the last group one patient relapsed and then received corticosteroid treatment. The follow up revealed a complete recovery in 6/7 patients that received steroids. Three patients have sequelae and of these, 2 received only symptomatic treatment. CONCLUSIONS: The diagnosis of ADEM is based on clinical and radiologic features, once other entities have been excluded. At the moment of suspicious of ADEM a brain-spinal chord MRI should be done, seeing that TAC brings not much information at the beginning. The treatment with steroids seems to be the most effective and the prognosis good, specially in cases that respond rapidly to it.

[Neuromuscular pathology in a critical pediatric patient]. / Patología neuromuscular del paciente crítico en pediatría.

OBJECTIVE: To describe and provide diagnosis guidelines for the neuromuscular pathology of the pediatric critical patients, manifested as extubation difficulty, based in our experience. CLINICAL CASES: A retrospective study has been performed on three patients in the Pediatric Intensive Care Unit that were diagnosed by using clinical, analytical and electromyographical findings. In the three patients the presence of the disorder was suspected due to the extubation difficulty and the hypotony. All them received vecuronium as neuromuscular blockage while dexamethasone was provided to one of them due to a nodal tachycardia. Myopathic causes were discarded in view of the normally of the muscular enzymes. The electromyography showed an axonal disorder in all three child. Neither lumbar puncture nor muscular biopsy were performed in any of them. CONCLUSIONS: The three patients were diagnosed for a drug neuropathy (neuromuscular blocked and/or corticotheraphy). There were described another causes of the critical patient polyneuropathy in the literature, but we didn't find any of them.

[Clinical, biomedical , neurological and molecular study of 11 patients with new mutations in PAH gene]. / Estudio clínico, bioquímico, neurológico y molecular de 11 pacientes que presentan mutaciones nuevas en el gen PAH.

INTRODUCTION: PKU is an autosomal recessive disorder. There is a broad spectrum phenotype which depends mainly on residual enzymatic activity and also on other factors such as modifying genes and non-genetic factors. This fact makes us consider that a multidisciplinary study of these patients is necessary to improve knowledge of the condition. OBJECTIVE: To establish phenotype-genotype correlation and classify nine new mutations according to severity. PATIENTS AND METHODS: We evaluated the clinical data obtained from a multidisciplinary trial of 11 patients with PKU/HPA who presented with nine new mutations (P275S, P279fsdelC, V388delTG, N61/I62/T63fsdel5bp, P281S, P362T, H1OOR, I164V and Y168H) identified during a molecular study of the PAH gene done in Catalonia (Spain). RESULTS AND CONCLUSION: In our patients the genotype is correlated with the biochemical phenotype whereas the cognitive phenotype depends on determining factors such as early diagnosis and diet. Therefore, although PKU may be considered to be a complex characteristic, the mutations in the PAH gene are the main determining factor of the metabolic phenotype of PKU. A multidisciplinary study is the best way to understand and control these patients.

[Use of decompressive craniectomy in the management of refractory intracranial hypertension in paediatric patients]. / Utilización de la craniectomía descompresiva en el manejo de la hipertensión intracraneal refractaria en la edad pediátrica.

INTRODUCTION AND OBJECTIVE: Intracranial hypertension (ICH) is the main cause of morbidity and mortality in patients with severe traumatic head injuries. Decompressive craniectomy (DC) is a surgical technique that allows to reduce intracranial pressure (ICP) and to improve cerebral blood flow. OBJECTIVE: To present our experience on DC for the treatment of ICH. PATIENTS AND METHODS: Retrospective review of patients admitted from January 2005 to December 2008 who had a traumatic brain injury (TBI) and uncontrollable intracranial hypertension despite optimal medical treatment and who needed DC. RESULTS: Fourteen patients with severe TBI were included in this series. Mean age was 14.2 years (4-20 years). The more frequent damages detected in cranial computerized tomography were diffuse brain lesions types II and III. Indication for DC was made if ICP levels were above 25 mmHg for more than 30 min despite optimal medical treatment. Clinical outcome was favourable in all patients apart from two. Neurological outcome was correct in 78.8% of patients (Glasgow Outcome Score 4 and 5) six months after PICU discharge. CONCLUSION: DC is an alternative for the management of refractory intracranial hypertension in children and adolescents with severe TBI. It could be used simultaneously with the barbiturate coma or as an alternative, particularly in haemodynamically unstable patients.

Do adult patients with phenylketonuria improve their quality of life after introduction/resumption of a phenylalanine-restricted diet?

AIM: To evaluate the possible influence of dietary treatment on the quality of life of adult patients with PKU (phenylketonuria) following late introduction or resumption of a Phe-restricted diet. METHODS: Fifteen adult patients with classical PKU (10F, 5M; mean age: 27.5 y, range: 16.4-37.5 y) were selected for the study. These patients had either resumed a restricted diet after a period of discontinuation, or were placed on a restricted diet after late diagnosis. All of them were interviewed about their quality of life using a 24-item questionnaire. RESULTS: The index of dietary control was poor (median Phe: 954 micromol/L) in 8/15 patients, regular (Phe: 514 micromol/L) in 4/15 and good (Phe: 354 micromol/L) in 3/15 patients. Fifty-three percent of patients reported that their state of health was very good, 47% described it as good, and 40% felt that their present health on-diet was better than it had been off-diet; 53% believed that they were calmer, quieter and less easily upset and 40% were more alert and were more able to maintain attention while on-diet. Thirty-three percent of the patients felt happier, and 27% felt more vital; 20% thought that they were less impulsive and aggressive, and that they were now less argumentative than before. Sixty percent of the patients felt that their quality of life had improved on-diet compared with the situation off-diet. CONCLUSION: More than half of our patients believed that their quality of life improved with a Phe-restricted diet; they reported feeling calmer, quieter, and less easily upset. Only 47% attained regular to good dietary control.

Use of the Pediatric Risk of Mortality Score as predictor of death and serious neurologic damage in children after submersion.

OBJECTIVE: To evaluate the Pediatric Risk of Mortality score (PRISM score) as a tool to evaluate the vital and neurologic prognosis of patients after submersion. METHODS: We conducted a retrospective analysis of the clinical histories of patients admitted to a tertiary pediatric hospital, Hospital Sant Joan de Déu, Barcelona, Spain from December 1977 to December 1999 as a consequence of near-drowning. PRISM score was calculated for each patient with data obtained upon arrival at the hospital. The probability of death was calculated using this score. RESULTS: There were 60 patients, divided into two groups as they were admitted to the Pediatric Intensive Care Unit (PICU group, n = 41) or to the Short Stay Unit (SSU group, n = 19). All patients in the SSU group survived without impairments, with PRISM scores or=24 or with probability of death >or=42% either died or had serious neurologic impairment. One third of patients with PRISM scores between 17 and 23 and/or probability of death between 16 and 42% either presented serious neurologic impairment or died. CONCLUSIONS: PRISM score enables the determination of either absence or presence of serious impairment or death in pediatric patients after submersion, if they present extreme values on this scale. However, in patients with intermediate PRISM scores, it is not possible to establish a reliable prognosis.