Effectiveness of SplashGuard Caregiver prototype in reducing the risk of aerosol transmission in intensive care unit rooms of SARS-CoV-2 patients: a prospective and simulation study.

BACKGROUND: The contagiousness of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is known to be linked to the emission of bioaerosols. Thus, aerosol-generating procedures (AGPs) could increase the risk of infection among healthcare workers (HCWs). AIM: To investigate the impact of an aerosol protection box, the SplashGuard Caregiver (SGGC) with suction system, by direct analysis of the presence of viral particles after an AGP, and by using the computational fluid dynamics (CFD) simulation method. METHODS: This prospective observational study investigated HCWs caring for patients with SARS-CoV-2 admitted to an intensive care unit (ICU). Rooms were categorized as: SGCG present and SGCG absent. Virus detection was performed through direct analysis, and using a CFD model to simulate the movement dynamics of airborne particles produced by a patient's respiratory activities. FINDINGS: Of the 67 analyses performed, three samples tested positive on quantitative polymerase chain reaction: one of 33 analyses in the SCCG group (3%) and two of 34 analyses in the non-SGCG group (5.9%). CFD simulations showed that: (1) reduction of the gaps of an SGCG could decrease the number of emitted particles remaining airborne within the room by up to 70%; and (2) positioning HCWs facing the opposite direction to the main air flow would reduce their exposure. CONCLUSIONS: This study documented the presence of SARS-CoV-2 among HCWs in a negative pressure ICU room of an infected patient with or without the use of an SGCG. The simulation will help to improve the design of the SGCG and the positioning of HCWs in the room.

Tracheostomy, respiratory support, and developmental outcomes in neonates with severe lung diseases: Retrospective study in one center.

OBJECTIVES: Pediatric tracheostomy has evolved significantly in the past few decades and the optimal timing to perform it in children with respiratory assistance is still debated. The objective of this study was to describe the indications, timing, complications, and outcomes of infants on respiratory support who had a tracheostomy in a tertiary pediatric intensive care unit (PICU). METHODS: All children younger than 18 months of corrected age requiring respiratory support for at least 1 week and who had a tracheostomy between January 2005 and December 2015 were included. Their demographic and clinical data and their outcomes at 24 months of corrected age were collected and analyzed after approval from the CHU Sainte-Justine ethics committee. RESULTS: During the study period, 18 children (14 preterm infants, 4 polymalformative syndromes, and 2 diaphragmatic hernias) were included. The median corrected age at tracheostomy was 97 days (0-289 days) and 94.4% were elective. The indications for tracheostomy were ventilation for more than 7 days with (61.1%) or without (38.9%) orolaryngotracheal anomaly. The median number of consultants involved per patient was 16 consultants (10-23 consultants). The median hospital length of stay was 122 days (8-365 days) before tracheostomy and 235 days (22-891 days) after tracheostomy. The median invasive ventilation time was 68 days (8-168 days) before tracheostomy and 64 days (5-982 days) after tracheostomy. In terms of complications, there were nine cases of tracheitis and five cases of tracheal granulomas. At 24 months of corrected age, 17 of 18 children survived, one of/17 was still hospitalized, three of 17 were decannulated, three of 17 received respiratory support via their tracheostomy, 11 of 17 were fed with a gastrostomy, and all had neurodevelopmental delay. CONCLUSION: Tracheostomy in infants requiring at least 1 week of ventilation is performed for complex cases and is favored for orolaryngotracheal anomalies. Clinicians should anticipate the need for developmental care in this population.

[Non-invasive ventilation in children: Do we need more evidence?] / Intérêt de la ventilation non invasive en réanimation pédiatrique : doit-on espérer un autre niveau de preuve ?

Respiratory failure is the leading cause of hospital admissions in the pediatric intensive care unit (PICU) and is associated with significant morbidity and mortality. Mechanical ventilation, preferentially delivered by a non-invasive route (NIV), is currently the first-line treatment for respiratory failure since it is associated with a reduction in the intubation rate. This ventilatory support is increasingly used in the PICU, but its wider use contrasts with the paucity of studies in this field. This review aims to describe the main indications of NIV in acute settings: (i) bronchiolitis; (ii) postextubation respiratory failure; (iii) acute respiratory distress syndrome; (iv) pneumonia; (v) status asthmaticus; (vi) acute chest syndrome; (vii) left heart failure; (viii) exacerbation of chronic respiratory failure; (ix) upper airway obstruction and (x) end-of-life care. Most of these data are based on descriptive studies and expert opinions, and few are from randomized trials. While the benefit of NIV is significant in some indications, such as bronchiolitis, it is more questionable in others. Monitoring these patients for the occurrence of NIV failure markers is crucial.

Acute kidney injury in children.

Acute kidney injury (AKI) affects 5% of critically ill hospitalized children and is a risk factor for increased morbidity and mortality. The current review focuses on new definitions of acute kidney injury, standardized to reflect the entire spectrum of the disease, as well as on ongoing research to identify early biomarkers of kidney injury. Its also provides an overview of current practice and available therapies, with emphasis on new strategies for the prevention and pharmacological treatment of diarrhea-associated hemolytic uremic syndrome. Furthermore, a decision-making algorithm is presented for the use of renal replacement therapies in critically ill children with AKI.

Hyperammonemia and neonatal cardiac failure.

Severe hyperammonemia (hyperNH3) in neonatal cardiac failure after cardiac surgery is rare. We report a case of a 2470-g female infant born at the week 37 of gestation with complex congenital heart disease (truncus arteriosus type III, interrupted aortic arch and tricuspid valve insufficiency) and hemodynamically non-significant intrahepatic arterio-venous malformation. She developed hyperNH3 (highest NH3 blood level: 467 µmol/L) without severe liver failure (INR of 1.9). The origin of the hyperNH3 was multifactorial including limited capacity of liver detoxification function due to congenital porto-caval shunt, liver ischemia, excessive protein intake and increased protein catabolic rate. HyperNH3 treatment partially succeeded in decreasing ammonia level and included discontinuation of protein intake, administration of phenylacetate and sodium benzoate. This case highlights the fact that NH3 detoxification by the liver has limitations for a neonate with multifactorial causes that decrease liver perfusion.

The care of critically ill children after hematopoietic SCT: a North American survey.

Although potentially curative, hematopoietic SCT (HSCT) is associated with significant morbidity. To improve outcomes, multicenter studies of critical illness in this patient population appear needed. To assist in the design of such studies, a survey was conducted to identify variations in care provided to critically ill pediatric HSCT patients. A survey was conducted of the highest volume pediatric HSCT centers in the United States (n=30) and Canada (n=4). One pediatric critical care medicine (PCCM) physician and one pediatric HSCT physician were surveyed at each institution. Analysis consisted of descriptive statistics. Thirty-three (29 United States/4 Canada) of 34 institutions responded. Although most HSCT units permit fluid boluses and nearly half permit some dose of dopamine, high-dose dopamine and other vasoactive infusions are rarely allowed there. Six institutions (21%) permit non-invasive ventilation on the HSCT unit. Criterion for PCCM consultation and therapies implemented before intubation vary significantly. High-frequency oscillatory ventilation and renal replacement therapy are commonly used for lung injury in patients failing conventional therapy. Variability exists in the location and type of therapy critically ill pediatric HSCT patients receive. Understanding this variability will help facilitate the design of clinical trials.

Pathophysiology of impaired ovarian function in galactosaemia.

Classical galactosaemia is an inherited inborn error of the major galactose assimilation pathway, caused by galactose-1-phosphate uridyltransferase (GALT) deficiency. Many GALT mutations have been described, with different clinical consequences. In severe forms, newborns present with a life-threatening, acute toxic syndrome that rapidly regresses under a galactose-restricted diet. However, long-term complications, particularly cognitive and motor abnormalities, as well as hypergonadotrophic hypogonadism in female patients are still unavoidable. The pathogenesis of galactose-induced ovarian toxicity remains unclear but probably involves galactose itself and its metabolites such as galactitol and UDP-galactose. Possible mechanisms of ovarian damage include direct toxicity of galactose and metabolites, deficient galactosylation of glycoproteins and glycolipids, oxidative stress and activation of apoptosis. As there is no aetiological treatment, clinical management of ovarian failure in galactosaemic patients principally relies on hormonal replacement therapy to induce pubertal development and to prevent bone loss and other consequences of estrogen deprivation. Further investigations will be necessary to better understand the metabolic flux of galactose through its biochemical pathways and the mechanisms of these secondary complications. The aim of this article is to present an extensive review on the pathogenesis and clinical management of galactose-induced premature ovarian failure.

Methylmalonic and propionic acidurias: management without or with a few supplements of specific amino acid mixture.

In a series of 137 patients with methylmalonic acidaemia (MMA) and propionic acidaemia (PA) diagnosed since the early 1970s, we report in more detail 81 patients (51 MMA and 30 PA) diagnosed between 1988 and 2005. In this series, 14% of patients died at initial access revealing the disease before or despite treatment, 18% died later, and the remainder (68%) are still alive. All patients were treated with the same protocol of enteral feeds with a low-protein diet adjusted to individual tolerance, carnitine, antibiotics, and only occasional use of an amino acid (AA) mixture. There was intensive follow-up and monitoring using measurements of urinary urea. Thirty-nine patients with severe forms, followed for more than 3 years, are analysed in particular detail. Of the 17 PA patients, 6 had moderate disability (all neonatal-onset forms), whereas 11 were normal or slightly delayed in their mental development. Four presented with cardiomyopathy, of whom 2 died. Of the 22 MMA patients, 13 presented in the neonatal period, of whom 3 died later, 2 are in renal failure and only 5 are still alive and have a normal or slightly delayed mental development. In the 9 patients with late-onset forms, there were no deaths and all patients but one have normal mental development. Among the 39 patients, only 40% were given an AA supplement at 3 years, and 50% between 6 and 11 years. The actual intake of natural protein was 0.92, 0.78 and 0.77 g/kg per day at 3, 6 and 11 years, respectively, in patients without AA supplementation, whereas it was 0.75, 0.74 and 0.54 g/kg per day in the group who received small quantities of AA (0.4-0.6 g/kg per day). In both groups, feeding disorders were frequent: 55% at 3 years, 35% at 6 years and 12% at 11 years. Many patients were given a food supplement by tube overnight or were even exclusively tube fed: 60% at 3 years, 48% at 6 years and still 27% at 11 years. Growth velocity was near the normal values. Plasma valine and isoleucine were low to very low, as were leucine and phenylalanine but to a lesser extent. Albumin, vitamins, trace elements and markers of bone metabolism were within the normal values. IGF1, 24-hour urine calcium and body mass density were low. Body composition showed a normal to low lean mass and a normal to high fat mass.

Feasibility of surgery for patent ductus arteriosus of premature babies in a neonatal intensive care unit.

Twenty-two premature neonates underwent surgical haemoclip closure of patent ductus arteriosus in a neonatal intensive care unit (NICU). Surgery was performed in the NICU in order to prevent hypothermia and interruption of care, and to avoid accidental vascular access removal and extubation. The results suggest that morbidity can be limited by performing the surgery in an NICU, and by switching from conventional to high-frequency mechanical ventilation in case of severe respiratory failure.

Fetal hypertension: an insight into the pathogenesis of the twin-twin transfusion syndrome.

OBJECTIVES: To investigate if systemic hypertension occurs in fetuses with twin-to-twin transfusion syndrome (TTTS). METHODS: We conducted an observational cohort study in a tertiary care centre in 23 pregnant women with TTTS. Polyhydramnios stuck twin sequence occurred at a median gestational age of 22 weeks (range 15-27). Biventricular myocardial hypertrophy was diagnosed in 22/23 recipient fetuses. In cases with atrioventricular valve regurgitation (AVR), it was possible to estimate the fetal systolic systemic blood pressure by ultrasound, on the basis of the simplified Bernouilli equation. The diagnosis of fetal hypertension (FHT) was made when the estimated systolic arterial pressure was equal to or above 1.6-fold the expected value. RESULTS: In 10 pregnancies (group A), fetal blood pressure could be assessed in recipients with AVR. The maximum velocities ranged from 2.9 to 5 m/s, leading to estimates of systemic fetal arterial pressure from 37 to 104 mmHg, that is, 1.6- to 2.8-fold the expected values. In 13 pregnancies (group B), fetal blood pressure could not be assessed in the absence of AVR. In group A, perinatal death (16/20) and hydrops (7/20) were significantly more frequent than in group B (8/26 and 1/26 respectively). CONCLUSION: Fetal systemic hypertension may occur in recipient twins and could play a role in the pathophysiology of TTTS.

[Fulminant coma: think hyperammonemia and urea cycle disorders]. / Coma d'évolution foudroyante: penser à l'hyperammoniémie quel que soit l'âge.

The authors report the case of 14-year-old boy admitted for acute coma without neurological focal symptom. The only relevant finding was the death of one uncle after a coma in the year 1992. This coma was associated with an ammonia blood level of 344 mumol l-1 and it rapidly lead to cerebral death despite a symptomatic treatment. The diagnosis of hereditary ornithine transcarbamylase deficiency was confirmed by liver biopsy in the immediate post-mortem period. The authors recommend the measurement of blood ammonia in every coma without diagnosis, whatever patient's age.

Spontaneous pneumomediastinum in children.

SUMMARY. Spontaneous pneumomediastinum (SPM) is rare in children, mainly affecting male adolescents. It is usually secondary to alveolar rupture in the pulmonary interstitium, followed by dissection of gas towards the hilum and mediastinum. Many pathological and physiological events can lead to alveolar rupture, but the most common cause in children is asthma. The clinical diagnosis is based on the symptom triad of chest pain, dyspnea, and subcutaneous emphysema, and is also based on Hamman's sign. The diagnosis is confirmed by chest radiography. The main differential diagnosis is esophageal perforation, which requires an esophagogram with contrast when there is the slightest doubt in the diagnosis. Spontaneous pneumomediastinum generally resolves spontaneously within a few days, meaning that ambulatory treatment is usually appropriate. Management consists of treating the underlying cause (if identified), rest, analgesics, and simple clinical monitoring. Predisposing factors should be identified and controlled to prevent recurrence. Cases of idiopathic SPM necessitate diagnostic pulmonary function tests after the acute episode, to establish whether the child has asthma.

Combined nutritional support and continuous extracorporeal removal therapy in the severe acute phase of maple syrup urine disease.

OBJECTIVE: The authors assessed the efficiency, tolerance and outcome of neonates and children with maple syrup urine disease (MSUD) in acute decompensation managed by endogenous and extracorporeal removal of accumulated MSUD metabolites. DESIGN: Single center cohort study. SETTING: Pediatric and neonatal intensive care unit in a tertiary care hospital. PATIENTS: Between January, 1991, and June, 1999, six neonates and six children in acute decompensation of MSUD were included in the study. Each of them had two of the three following criteria: comatose state, gastrointestinal intolerance, leucine plasma levels over 1700 micromol/l. INTERVENTIONS: Patients were treated by combined nutrition manipulation and continuous venovenous extracorporeal removal therapies (CECRT) including hemofiltration, hemodialysis or hemodiafiltration. A clinical and biological evaluation was performed before, during and following the treatment. RESULTS: Eleven out of the 12 patients survived. One child had two acute episodes at 6.5 and 9 years old. Eight patients recovered a normal cerebral performance category score. In all cases, plasma leucine level decreased according to a logarithmic mode within 11-24 h hemodiafiltration combined with nutritional support whereas, with nutrition alone after stopping CECRT, the decrease in leucine plasma levels was slower, following a linear mode. Eight patients were supplemented with valine and isoleucine for mean plasma values of 177+/-92 and 68+/-66, respectively. CONCLUSION: In severe acute decompensation of MSUD, CECRT combined with nutritional support limit central nervous system damage, by dramatically decreasing branched chain amino and keto acid levels.

Long term results of liver-kidney transplantation in children with primary hyperoxaluria.

From 1990 to 2000, we performed eight liver-kidney transplants in eight children, aged 1-16 years, with end-stage renal failure (ESRF) due to primary hyperoxaluria (PH1). The duration of dialysis before transplantation ranged from 2 to 42 months (mean 14 months) and was <1 year in four patients. Only the first patient underwent postoperative hemodialysis; in the other five, we chose to induce maximal diuresis from the first hours with intravenous and intragastric hyperhydration (> or =3 l/m2 per day). High water intake with nocturnal tube hydration was maintained for 6 months to 5 years, as long as oxaluria exceeded 0.5 mmol/day. A quadruple sequential immunosuppressive regimen was used. Two patients died during liver graft surgery. The other six patients are alive and well, with a mean follow-up of 7.4 years (range 5-11 years). Patient and graft survival is 75% at 5 years. At latest follow-up, liver tests were normal in all six patients; creatinine clearance ranged from 55 to 95 ml/min per 1.73 m2 (mean=74). Oxaluria was lower than 0.4 mmol/day in all patients (mean=0.22). The six patients underwent 15 renal biopsies, 1-11 years after transplantation. Chronic transplant nephropathy was present in four patients and mild cyclosporin nephrotoxicity in another. No oxalate crystals were seen and repeat ultrasonography has been consistently normal in all patients. The three patients with bone oxalosis showed progressive complete healing of bone lesions. All six children or adolescents now live a normal life. From this series, we conclude that early combined liver-kidney transplantation is the treatment of choice for children with ESRF due to primary hyperoxaluria.

[Severe malaria in children in intensive care. National survey 1990-1995]. / Paludisme grave de l'enfant en réanimation. Enquête nationale 1990-1995.

BACKGROUND: Severe malaria is a frequent complication of Plasmodium falciparum infections. More than one million children die of malaria each year. MATERIAL AND METHODS: A French survey was carried out on 15 cases admitted to pediatric intensive care units between 1990 and 1995. The aim of this work was to evaluate the occurrence, mortality, morbidity and treatment of severe malaria in French intensive care units. RESULTS: All cases were imported from Africa except one case of airport malaria. Diagnosis of many of these cases was delayed. All cases were treated with quinine, and five children received a loading dose. One child died and one has neurological sequelae. DISCUSSION: Despite improvement in management, the prognosis of severe malaria remains poor. With reference to the literature, we propose management of severe malaria, emphasizing the necessity of a rapid effect with a loading dose of quinine.

Branched chain amino acids induce apoptosis in neural cells without mitochondrial membrane depolarization or cytochrome c release: implications for neurological impairment associated with maple syrup urine disease.

Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by a deficiency in branched chain alpha-keto acid dehydrogenase that can result in neurodegenerative sequelae in human infants. In the present study, increased concentrations of MSUD metabolites, in particular alpha-keto isocaproic acid, specifically induced apoptosis in glial and neuronal cells in culture. Apoptosis was associated with a reduction in cell respiration but without impairment of respiratory chain function, without early changes in mitochondrial membrane potential and without cytochrome c release into the cytosol. Significantly, alpha-keto isocaproic acid also triggered neuronal apoptosis in vivo after intracerebral injection into the developing rat brain. These findings suggest that MSUD neurodegeneration may result, at least in part, from an accumulation of branched chain amino acids and their alpha-keto acid derivatives that trigger apoptosis through a cytochrome c-independent pathway.

[Intravascular rupture of a central venous catheter in a premature infant: retrieval by a nonsurgical technique]. / Rupture intravasculaire de cathéter épicutanéocave chez le prématuré: place du cathétérisme interventionnel.

UNLABELLED: Central venous access is a frequent procedure in pediatric intensive care and neonatology. Catheter fracture with migration of the distal portion into the vessels is rare but may have side effects such as thrombosis. CASE REPORT: We report the case of a premature infant who had at three weeks of age a retained central venous catheter fragment in the pulmonary artery. The fragment was successfully retrieved by a percutaneous endovascular technique. No complication was observed during the procedure and afterward. CONCLUSION: This technique has avoided either delicate surgery or thrombotic risk due to a persistent intravascular foreign body. The authors prompted this interventional procedure within 36 hours after catheter migration in a center experienced in neonatal interventional catheterization.

Primary human fibroblasts from a maple syrup urine disease patient undergo apoptosis following exposure to physiological concentrations of branched chain amino acids.

Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by a deficiency in branched chain alpha-ketoacid dehydrogenase. We have recently found that MSUD neurodegeneration may result, at least in part, from apoptosis triggered by branched chain amino acids and their alpha-ketoacid derivatives. In the present study, we investigated the sensitivity of MSUD fibroblasts to defined mixtures of MSUD metabolites. Defined combinations of MSUD metabolites, at levels comparable to those in MSUD patients, triggered cell death in skin fibroblasts from a MSUD patient, while control fibroblasts were resistant. The mechanism of cell death was confirmed as apoptosis by in situ end labeling.

Liver transplantation in urea cycle disorders.

We report here our experience in the long-term management of 28 patients with citrullinaemia, 13 patients with carbamoyl phosphate synthase deficiency and 15 patients with argininosuccinic aciduria. In addition, we report a national French survey of 119 patients with ornithine transcarbamylase (OTC) deficiency enzymatically characterized in our laboratory. We also include in this report four personal patients (two with OTC and two with citrullinaemia) who were liver transplanted, and one OTC patient from the National French survey. Although this retrospective series is not really representative of the modern treatment combining low protein diet and arginine, sodium benzoate and sodium phenylbutyrate, it is obvious that the long-term outcome of all urea cycle disorders remains very guarded. We highlight the severity of the neonatal forms of such disorders, and mostly for OTC-deficient males. According to this evidence, our policy is not to treat such severely affected patients in the neonatal period who die anyway spontaneously within 2 to 3 days. At the present time, we only have three patients with neonatal citrullinaemia, aged 1, 6 and 10 years respectively, who are still doing well. One of them has been successfully liver transplanted at 5 years. Another transplanted patient died in the post-surgical phase. We emphasize the unexpected severity of argininosuccinic aciduria in which there is no one patient doing well. This is a rather surprising finding as this disorder is easy to manage and rarely presents with recurrent attacks of hyperammonaemia when it is treated by arginine supplementation. This consideration would suggest to extend the indication of orthotopic liver transplantation in this disorder. Finally, the most difficult indication is in the late onset symptomatic female OTC group. In this last group, despite a significant residual activity due to heterozygote status, even with a variable lyonisation, only seven girls are still mentally and neurologically normal. Interestingly, three of these seven were liver-transplanted before the constitution of irreversible neurological damage. These three girls and their family declare their well-being, their feeling to be cured and enjoy their normal life.