Organ donation by Maastricht-III pediatric patients: Recommendations of the Groupe Francophone de Réanimation et Urgences Pédiatriques (GFRUP) and Association des Anesthésistes Réanimateurs Pédiatriques d'Expression Française (ADARPEF). Part II: Specific organizational and technical considerations.

A panel of pediatric experts met to develop recommendations on the technical requirements specific to pediatric controlled donation after planned withdrawal of life-sustaining therapies (Maastricht category III). The panel recommends following the withdrawal of life-sustaining therapies protocol usually applied in each unit, which may or may not include immediate extubation. The organ retrieval process should be halted if death does not occur within 3 h of life-support discontinuation. Circulatory arrest is defined as loss of pulsatile arterial pressure and should be followed by a 5-min no-touch observation period. Death is declared based on a list of clinical criteria assessed by two senior physicians. The no-flow time should be no longer than 30, 45, and 90 min for the liver, kidneys, and lungs, respectively. At present, the panel does not recommend pediatric heart donation after death by circulatory arrest. The mean arterial pressure cutoff that defines the start of the functional warm ischemia (FWI) phase is 45 mmHg in patients older than 5 years and/or weighing more than 20 kg. The panel recommends normothermic regional perfusion in these patients. The FWI phase should not exceed 30 and 45 min for retrieving the pancreas and liver, respectively. There is no time limit to the FWI phase for the lungs and kidneys. The panel recommends routine sharing of experience with Maastricht-III donation among all healthcare institutions involved in order to ensure optimal outcome assessment and continuous discussion on the potential difficulties, notably those related to the management of normothermic regional perfusion in small children.

Malignant arterial hypertension in a 2-month-old girl: Etiological diagnosis and treatment.

A 2-month-old girl presented with malignant arterial hypertension revealing bilateral renal artery stenosis secondary to neurofibromatosis type 1 (NF1). Life-supporting care was initiated immediately. High-dose peripheral vasodilator therapy induced life-threatening toxicity; vascular surgery was therefore performed. Technical difficulties due to the young age and low body weight of the patient resulted in fatal bleeding. Renovascular disease is an important cause of pediatric hypertension. NF1-associated renovascular hypertension in young pediatric patients is rare, and its highly specialized management is best delivered via a multidisciplinary approach. The long-term prognosis remains poor.

Organ donation by Maastricht-III pediatric patients: Recommendations of the Groupe Francophone de Réanimation et Urgences Pédiatriques (GFRUP) and Association des Anesthésistes Réanimateurs Pédiatriques d'Expression Française (ADARPEF) Part I: Ethical considerations and family care.

The French Transplant Health Authority (Agence de la Biomédecine) has broadened its organ- and tissue-donation criteria to include pediatric patients whose death is defined by circulatory criteria and after the planned withdrawal of life-sustaining therapies (WLST) (Maastricht category III). A panel of pediatric experts convened to translate data in the international literature into recommendations for organ and tissue donation in this patient subgroup. The panel estimated that, among children aged 5 years or over with severe irreversible neurological injury (due to primary neurological injury or post-anoxic brain injury) and no progression to brain death, the number of potential donors, although small, deserves attention. The experts emphasized the importance of adhering strictly to the collegial procedure for deciding to withdraw life support. Once this decision is made, the available data should be used to evaluate whether the patient might be a potential donor, before suggesting organ donation to the parents. This suggestion should be reserved for parents who have unequivocally manifested their acceptance of WLST. The discussion with the parents should include both the pediatric intensive care unit (PICU) team under the responsibility of a senior physician and the hospital organ- and tissue-procurement team. All recommendations about family care during the end of life of a child in the PICU must be followed. The course and potential challenges of organ donation in Maastricht-III pediatric patients must be anticipated. The panel of experts recommended strict compliance with French recommendations (by the Groupe Francophone de Réanimation et Urgences Pédiatriques) about WLST and providing deep and continuous sedation until circulatory arrest. The experts identified the PICU as the best place to implement life-support discontinuation and emphasized the importance of returning the body to the PICU after organ donation. French law prohibits the transfer of these patients from one hospital to another. A description of the expert-panel recommendations regarding the organization and techniques appropriate for children who die after controlled circulatory arrest (Maastricht III) is published simultaneously in the current issue of this journal..

Use of continuous infusion of clonidine for sedation in critically ill infants and children.

BACKGROUND: Adequate sedation and analgesia are required for critically ill children in order to minimize discomfort, reduce anxiety, and facilitate care. This is commonly achieved through a combination of opioids and benzodiazepines. Prolonged use of these agents is associated with tolerance and withdrawal. Clonidine as an adjunctive sedative agent may reduce sedation-related adverse events. OBJECTIVE: Our first aim was to describe the indication for clonidine administration and its secondary effects in a mixed cohort of critically ill children. Our secondary aim was to measure the consumption of sedatives during two study periods: before and after the use of clonidine in our pediatric intensive care unit (PICU). METHODS: This was a single-center study conducted in a tertiary PICU and encompassed retrospective chart review of patients who received clonidine between November 2013 and April 2015. We collected data on clonidine dosage, duration of administration, indication for the prescription, and potential side effects. We analyzed the total consumption of sedatives over 18 months, before and after the introduction of clonidine in our sedation protocol. RESULTS: A total of patients received clonidine, with a mean age of 2.2 ± 2.8 years. The primary reason for intensive care admission was respiratory failure (48%). The main indication for clonidine administration was increasing requirement for morphine and midazolam (60%). The mean duration of clonidine infusion was 9 ± 7.3 days. Bradycardia and hypotension occurred in five patients (11.6%) and nine patients (21%), respectively. These side effects did not result in any major intervention. Younger age was a risk factor for clonidine-associated bradycardia. We observed a significant decrease in morphine and midazolam consumption with clonidine as a comedication. Compared with the pre-study period, consumption decreased by 19.7% for morphine and by 59% for midazolam (calculated as milligram/admission). CONCLUSION: Continuous infusion of clonidine in critically ill children is safe and effective. Clonidine is a sedative-sparing agent and this can help reduce complications associated with prolonged use of opioids and benzodiazepines.

Congenital central hypoventilation syndrome and Hirschsprung disease: A retrospective review of the French National Registry Center on 33 cases.

AIM OF THE STUDY: Congenital Central Hypoventilation Syndrome (CCHS) is a rare affection associated to Hirschsprung disease (HD) in 20% of the cases. Using the French CCHS registry, we described the population of patients suffering from both CCHS and HD reporting the outcome on these patients. METHODS: Medical records were reviewed. Epidemiological, clinical, histological and genetic data were analyzed and extracted from the national French registry data. RESULTS: 33 patients had CCHS and HD. Thirty percent had a severe form of CCHS (Death owing to CCHS or 24/24 ventilation beyond 1 year old). Fifty four percent required tracheotomy. HD's pathologic segment was classic (Rectosigmoid and left colic form) in 20% and long (Above the splenic flexure) in 80%. Twenty four percent were treated with daily irrigation, 21% had colostomy without undergoing pullthrough, and 55% underwent optimal treatment (pull through). We failed to demonstrate a correlation between severity of CCHS and HD's length. The rate of mortality was 57% and was higher in the long HD group (p = 0.0005). Fourteen patients were still alive, aged 1 to 31 years old. Ninety two percent were weaned off the 24/24 ventilation. Regarding the intestinal function, 38% presented with soiling and 30% with chronic diarrhea. Hundred percent had CCHS follow-up while only 35% had no surgical follow-up in regard to the HD. CONCLUSIONS: This is the largest study regarding the CCHS / HD association and its long-term followup. Mortality is high demonstrating that a multidisciplinary follow-up on respiratory and intestinal function is necessary to improve outcome. Level III study.

[Acute respiratory distress syndrome in childhood: Changing definition and news from the Pediatric Consensus Conference]. / Syndrome de détresse respiratoire aiguë de l'enfant : évolution de la définition et nouveautés de la conférence de consensus pédiatrique.

Acute respiratory distress syndrome (ARDS) is a rapidly progressive hypoxemic respiratory insufficiency induced by alveolar filling mainly caused by alveolocapillary wall disruption, following direct or indirect pulmonary injury. Much less frequent in children than in adults, pediatric intensivists had long applied adult guidelines to their daily practice. In 2015, experts from the Pediatric Acute Lung Injury Consensus Conference (PALICC) published the first international guidelines specifically dedicated to pediatric ARDS. After a short summary of the history of the ARDS definition since its first report in 1967, we describe the main diagnostic and therapeutic guidelines for PALICC.

Guidelines for proton pump inhibitor prescriptions in paediatric intensive care unit.

Background Stress ulcer prophylaxis (SUP) is recommended in some situations to prevent upper gastrointestinal bleeding and is a component of standard care for patients admitted to the intensive care unit (ICU). Proton pump inhibitors (PPIs), already among the most widely prescribed drug classes, are being increasingly used. Objective To describe PPI prescribing patterns and their changes after the dissemination of guidelines. Setting Paediatric ICU (PICU), Robert-Debré Teaching Hospital, Paris, France, which admits about 800 patients annually, from full-term neonates to 18-year-olds. Method Prospective observational study with two 6-week observation periods (July-August and September-October, 2013), before and after dissemination in the PICU of PPI prescribing guidelines. Main outcome measure Changes in PPI prescribing patterns (prevalence, dosage, and indication) after the guidelines. Results The number of patients admitted to the PICU was 77 (mean age 4.6 years [range 1 day-18 years]) before and 70 (mean age 3.8 years [range 1 day-17 years]) after the guidelines. During both periods, SUP was the most common reason for PPI prescribing. The proportion of patients prescribed PPIs dropped significantly, from 51% before the guidelines to 30% after the guidelines (p < 0.001). Mean daily dosage also decreased significantly, from 1.5 mg/kg/(range 0.5-4.4) to 1.1 mg/kg (range 0.7-1.8) (p < 0.002). None of the patients experienced upper gastrointestinal bleeding during either period. Conclusion Off-label PPI prescribing for SUP was common in our PICU. The introduction of guidelines was associated with a significant decrease in PPI use and dosage. This study confirms that guidelines can change PPI prescribings patterns in paediatric practice.

Sudden deaths in adult-worn baby carriers: 19 cases.

Soft infant carriers such as slings have become extremely popular in the west and are usually considered safe. We report 19 cases of sudden unexpected death in infancy (SUDI) linked to infant carrier. Most patients were healthy full-term babies less than 3 months of age, and suffocation was the most frequent cause of death. CONCLUSION: Infant carriers represent an underestimated cause of death by suffocation in neonates. WHAT IS KNOWN: • Sudden unexpected deaths in infancy linked to infant carrier have been only sparsely reported. WHAT IS NEW: • We report a series of 19 cases strongly suggesting age of less than 3 months as a risk factor and suffocation as the mechanism of death.

Outcome of invasive mechanical ventilation after pediatric allogeneic hematopoietic SCT: results from a prospective, multicenter registry.

Exact data on prognosis of children receiving invasive mechanical ventilation (IMV) after allogeneic hematopoietic SCT (HSCT) is lacking. We therefore started a prospective registry in four European university HSCT centers (Leiden, Paris, Prague and Utrecht) and their pediatric intensive care units (PICUs). The registry started in January 2009. In January 2013, the four centers together had treated a total of 83 admissions with IMV. The case fatality rate in these patients was 52%. Mortality 6 months after PICU discharge was 45%. There were significant differences between centers in the proportion of children who received IMV after HSCT (6-23%, P<0.01), in severity of disease on admission to PICU (predicted mortality 14-37%, P<0.01), in applying noninvasive ventilation before IMV (3-75% of admissions, P<0.01) and in the use of renal replacement therapy (RRT) (8-58% of admissions, P<0.01). Severe impairment in oxygenation, use of RRT and CMV viremia were independent predictors of mortality. Our study shows that mortality in children receiving IMV after HSCT remains high, but has clearly improved compared with older studies. Patient selection and treatment in PICU differed significantly between centers, which underscores the need to standardize and optimize the PICU admission criteria, ventilatory strategies and therapies applied in PICU.

[Superficial skin infections and bacterial dermohypodermitis]. / Infections superficielles de la peau et dermo-hypodermites bactériennes.

Staphylococcus aureus and Streptococcus pyogenes are the two main bacteria involved in skin infections in children. Mild infections like limited impetigo and furonculosis should preferentially be treated by topical antibiotics (mupirocine or fucidic acid). Empiric antimicrobial therapy of dermohypodermitis consists in amoxicillin-clavulanate through oral route (80 mg/kg/d) or parenteral route (150 mg/kg amoxicillin per d. in 3-4 doses) for complicated features: risk factors of extension of the infection, sepsis or fast evolution. Clindamycin (40 mg/kg/d per d. in 3 doses) should be added to the beta-lactam treatment in case of toxinic shock, surgical necrotizing soft tissues or fasciitis infections.

[Pediatric intermediate care unit in general hospital: recent survey in French Polynesia]. / Unité de surveillance continue pédiatrique en centre hospitalier général : l'expérience récente de l'hôpital de Polynésie française.

In 2006, decrees relating to pediatric critical care defined the main rules of pediatric intermediate care units (PIMU). These units ensure continuous monitoring of children at risk of critical deterioration without requiring invasive support. In French Polynesia, a PIMU has been integrated into the general pediatric ward since the new hospital opened in November 2010. We conducted a prospective observational study of patients admitted to the PIMU depending on whether they were surgical patients or were secondarily transferred to the ICU or were transferred via long-distance medical air transport for specialized care. For the very first operational year, 199 children (median age, 3 years old) were admitted to the PIMU: for the most part respiratory (31.7%) and neurologic (23.6%) failures were involved. Surgical patients more often required a prosthesis or treatments associated with serious adverse effects than nonsurgical patients (respectively, 46% vs. 16%, P<0.01; 29% vs. 7%, P<0.01) and the length of the hospital stay was longer (5 days vs. 2, P<0.01). Patients who were secondarily transferred to the ICU had a higher admission Pediatric RISk of Mortality (PRISM) score (6 vs. 4, P<0.01) and required more treatments associated with serious adverse effects (50% vs. 20%, P<0.01) than nontransferred patients. The length of the hospital stay was longer (6days) for patients who underwent long-distance medical transport. In addition to PIMU defining criteria, the use of treatments associated with serious adverse effects should be considered risk factors of impaired prognosis in local practical procedures. Assessment of PIMU activity should take into account that intensive surgical care and geographical isolation are closely related to increased length of hospital stay.

[Neonatal renal venous thrombosis: the recent experience of Robert-Debré hospital]. / Thrombose néonatale des veines rénales : l'expérience récente de l'hôpital Robert-Debré

Neonatal renal venous thrombosis (NRVT) is a rare disease, with variable consequences on kidney function. We report a retrospective study of 9 newborns with NRVT admitted to our hospital from 1996 to 2005. The median age at diagnosis was 2 days (range, 1-10 days). In 7 patients, diagnosis was suspected based on one classical clinical or biological sign and was confirmed by ultrasound. Seven newborns had at least one known obstetrical or neonatal risk factor. NRVT was unilateral in three cases, was bilateral in 6 cases, and was associated with inferior vena cava thrombosis in 5 patients, with surrenal hemorrhage in 3 patients. Three patients did not receive specific treatment. The median delay between diagnosis and specific treatment was 20 h (range, 3-36 h). Three patients were treated by fibrinolysis, including 2 with bilateral NRVT, 2 newborns received heparins, and 1 patient was treated with a vitamin K antagonist. With a median evaluation time of 5 years and 2 months for 6 patients, 5 patients recovered their kidney function completely and the 6th child has moderate renal failure. It seems illusory to wait for randomized control studies to appreciate the potential long-term benefit of treatments on kidney function after a NRVT, whose bilateral forms appear to be more severe. A case-by-case approach appears better adapted. These results reinforce recommendations that suggest an early pediatric nephrologic follow-up for all newborns with a NRVT.

Encephalomyocarditis virus mortality in semi-wild bonobos (Pan panicus).

BACKGROUND: Fatal myocarditis from encephalomyocarditis virus (EMCV) infection has previously been identified in sporadic and epidemic forms in many species of captive non-human primates probably including one bonobo (Pan paniscus). METHODS: We investigated the deaths of two bonobos that were suspicious of EMCV using a combination of histopathology, immunohistochemistry and, for one of the two bonobos, reverse transcription PCR. RESULTS: Histopathological examination of heart tissue from the two bonobos showed changes characteristic of EMCV. Immunohistochemical studies confirmed the presence of EMCV antigen in heart tissue of both and in kidney and intestine of one of the bonobos. EMCV RNA was also isolated from the serum of the bonobo tested. CONCLUSION: Together, these findings confirm that EMCV was responsible for deaths of the two bonobos. Strict separation of bonobos in particular and captive primates in general from potential sources of EMCV contamination should be maintained to prevent mortality caused by EMCV.

Mortality in out-of-hospital premature births.

AIM: To determine whether the mortality for out-of-hospital (OOH) premature births was higher than for in-hospital premature births and identify additional risk factors. PATIENTS AND METHODS: A historical cohort study of a consecutive series of live-born, OOH, births of 24-35 weeks gestation cared for by two Transport Teams working in and around Paris, France 1994-2005. Matching with in-hospital births was according to gestational age, antenatal steroid use, the mode of delivery and nearest year of birth. RESULTS: Eighty-five OOH premature births were identified, of whom 83 met inclusion criteria, and 132 matching in-hospital premature births were selected. There was 18% mortality in the OOH group compared with 8% for the in-hospital group [p = 0.04, OR 2.9, (CI 95% 1.0-8.4)]. Variables significantly associated (p < 0.05) with the OOH birth were HIV infection, lower maternal age and endo-tracheal intubation, lack of medical follow-up during pregnancy, low temperature and low birth weight. CONCLUSIONS: Mortality was more than twice as high in out-of-hospital deliveries than for in-hospital matched controls. Hypothermia was an important associated risk factor. Measures such as oxygen administration to maintain an appropriate saturation for gestational age, the provision of polyethylene plastic wraps and skin-to-skin contact are recommended.

Invasive group A streptococcal infection in children: clinical manifestations and molecular characterization in a French pediatric tertiary care center.

Invasive group A streptococcal (GAS) infections have a broad and evolving clinical spectrum, associated with various GAS genotypes and/or virulence factors that are only poorly described in children. We aimed to assess the clinical and molecular characteristics of invasive GAS infections in 28 children admitted from 2000 to 2007 at a large French pediatric tertiary care center. The GAS isolates were characterized molecularly by emm-typing and by the determination of the main virulence factors: speA, speB, speC, smeZ-1, ssa, sic, and silC. The median age of the children was 2.9 years. Osteoarticular infection (OAI) was the main clinical manifestation (n=15/28, 53%). emm-1 predominated (n=10/28), followed by emm-12, 3, and 4. No significant correlation was found between emm type and clinical manifestations, but emm-1 predominated in cases of OAI (n=7/15) and was associated with speA, speB, smeZ-1, and sic virulence factor genes. In this pediatric study, we describe a predominance of OAI associated with emm-1 GAS. Further larger international pediatric studies, including host immunity evaluation, are needed in order to better assess the pathogenesis of GAS infection in children.

[Neonatal renal venous thrombosis in 2008]. / Thrombose néonatale des veines rénales en 2008.

Venous thromboses are rare in childhood. In the neonatal period, these are mainly neonatal renal venous thromboses (NRVT). We propose a synthesis of the main recent reviews on NRVT published over the last 15 years. These studies reported the higher male prevalence, the predominance of left kidney vein involvement, the increasing incidence in premature newborns, and a high level of thrombophilia in screened newborns. The usual presentation of NRVT, which associates abdominal mass, macroscopic hematuria, and thrombocytopenia, has been progressively modified by these new epidemiological features. The abdominal Doppler ultrasound scan is widely used for diagnosis and must be systematically associated with a transfontanellar ultrasound to look for cerebral hemorrhage, which should be a contraindication for anticoagulation. Recent consensus recommends at least prophylactic heparin therapy in the majority of cases to prevent thrombus extension. Fibrinolysis should be reserved for bilateral thrombosis with systemic effects. Despite improvements in screening and care, mean-term and long-term sequellae such as kidney atrophia, moderate renal insufficiency, systemic hypertension, and relapses in case of thrombophilia are still frequent and severe. A systematic follow-up by pediatric nephrologists is recommended.