High-volume hemofiltration in children with acute liver failure*.

OBJECTIVES: High-volume hemofiltration has shown beneficial effects in severe sepsis and multiple organ failure, improving hemodynamics and fluid balance. Recent studies suggest that acute liver failure shares many pathophysiologic similarities with sepsis. Therefore, we assessed the systemic effects of high-volume hemofiltration in children with acute liver failure. DESIGN: Retrospective observational cohort study. PATIENTS: Twenty-two children. SETTING: Forty-two-bed multidisciplinary pediatric and neonatal ICUs in a tertiary university hospital. INTERVENTION: We evaluated high-volume hemofiltration therapy as part of standard management of 22 children admitted in our unit for acute liver failure. Fifteen patients had fulminant hepatic failure, three had acute-on-chronic liver disease, and four had primary nonfunction. High-volume hemofiltration was initiated in patients requiring emergency liver transplantation and when hepatic encephalopathy grade higher than 2 and/or hemodynamic instability requiring vasopressors occurred. High-volume hemofiltration was defined by a flow of ultrafiltrate of more than 80 mL/kg/hr. Clinical and biological variables were assessed before and 24 and 48 hours after initiation of high-volume hemofiltration therapy. MEASUREMENTS AND MAIN RESULTS: High-volume hemofiltration was initiated with a median grade III of hepatic encephalopathy. The median flow of ultrafiltrate was 119 mL/kg/hr (range, 80-384). After 24 hours of high-volume hemofiltration treatment, we observed an increase in mean arterial pressure (p = 0.0002) and a decrease in serum creatinine (p = 0.0002). In half of the patients, the encephalopathy grade decreased. After 48 hours of treatment, mean arterial pressure (p = 0.0005), grade of hepatic encephalopathy (p = 0.04), and serum creatinine (p = 0.0002) improved. Overall mortality was 45.4% (n = 10). Emergency liver transplantation was performed in eight children. Five patients spontaneously recovered liver function. CONCLUSIONS: High-volume hemofiltration therapy significantly improves hemodynamic stability and neurological status in children with acute liver failure awaiting for emergency liver transplantation.

Isolated congenital asplenia: a French nationwide retrospective survey of 20 cases.

OBJECTIVE: To better describe the natural history, mode of inheritance, and the epidemiological and clinical features of isolated congenital asplenia, a rare and poorly understood primary immunodeficiency. STUDY DESIGN: A French national retrospective survey was conducted in hospital pediatric departments. A definitive diagnosis of ICA was based on the presence of Howell-Jolly bodies, a lack of detectable spleen, and no detectable cardiovascular malformation. RESULTS: The study included 20 patients (12 males and 8 females) from 10 kindreds neither related to each other nor consanguineous. The diagnosis of ICA was certain in 13 cases (65%) and probable in 7 cases (35%). Ten index cases led to diagnosis of 10 additional cases in relatives. Five cases were sporadic and 15 were familial, suggesting autosomal dominant inheritance. Median age was 12 months at first infection (range, 2-516 months), 11 months at diagnosis of asplenia (range, 0-510 months), and 9.9 years at last follow-up (range, 0.7-52 years). Fifteen patients sustained 18 episodes of invasive bacterial infection, caused mainly by Streptococcus pneumoniae (61%). Outcomes were poor, with 9 patients (45%) dying from fulminant infection. CONCLUSIONS: ICA is more common than was previously thought, with an autosomal dominant inheritance in at least some kindreds. Relatives of cases of ICA should be evaluated for ICA, as should children and young adults with invasive infection.

World Federation of Pediatric Intensive Care and Critical Care Societies: Global Sepsis Initiative.

BACKGROUND: According to World Health Organization estimates, sepsis accounts for 60%-80% of lost lives per year in childhood. Measures appropriate for resource-scarce and resource-abundant settings alike can reduce sepsis deaths. In this regard, the World Federation of Pediatric Intensive Care and Critical Care Societies Board of Directors announces the Global Pediatric Sepsis Initiative, a quality improvement program designed to improve quality of care for children with sepsis. OBJECTIVES: To announce the global sepsis initiative; to justify some of the bundles that are included; and to show some preliminary data and encourage participation. METHODS: The Global Pediatric Sepsis Initiative is developed as a Web-based education, demonstration, and pyramid bundles/checklist tool (http://www.pediatricsepsis.org or http://www.wfpiccs.org). Four health resource categories are included. Category A involves a nonindustrialized setting with mortality rate <5 yrs and >30 of 1,000 children. Category B involves a nonindustrialized setting with mortality rate <5 yrs and <30 of 1,000 children. Category C involves a developing industrialized nation. In category D, developed industrialized nation are determined and separate accompanying administrative and clinical parameters bundles or checklist quality improvement recommendations are provided, requiring greater resources and tasks as resource allocation increased from groups A to D, respectively. RESULTS: In the vanguard phase, data for 361 children (category A, n = 34; category B, n = 12; category C, n = 84; category D, n = 231) were successfully entered, and quality-assurance reports were sent to the 23 participating international centers. Analysis of bundles for categories C and D showed that reduction in mortality was associated with compliance with the resuscitation (odds ratio, 0.369; 95% confidence interval, 0.188-0.724; p < .0004) and intensive care unit management (odds ratio, 0.277; 95% confidence interval, 0.096-0.80) bundles. CONCLUSIONS: The World Federation of Pediatric Intensive Care and Critical Care Societies Global Pediatric Sepsis Initiative is online. Success in reducing pediatric mortality and morbidity, evaluated yearly as a measure of global child health care quality improvement, requires ongoing active recruitment of international participant centers. Please join us at http://www.pediatricsepsis.org or http://www.wfpiccs.org.

Clinical implications of hepatitis A virus ribonucleic acid detection and genotyping in acute liver failure in children in Argentina.

OBJECTIVES: To investigate the detection of hepatitis A virus ribonucleic acid in patients with acute liver failure and to assess if the results have any clinical implications for the evolution of acute liver failure in children. Hepatitis A infection, a vaccine-preventable disease, is an important cause of acute liver failure in children in Argentina. Universal vaccination in 1-yr-old children was implemented in June 2005. DESIGN: Observational study in which patients were divided into Group 1 consisting of positive hepatitis A virus ribonucleic acid and Group 2 consisting of negative hepatitis A virus ribonucleic acid. SETTING: Pediatric intensive care unit in National Pediatric Hospital "Dr. J. P. Garrahan," Buenos Aires, Argentina. PATIENTS: Thirty-three patients with the diagnosis of acute liver failure secondary to hepatitis A virus infection and admitted to the Garrahan Pediatric Hospital between September 2003 and September 2005 were enrolled in the study. Twenty of these children were admitted to the pediatric intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Samples for total ribonucleic acid detection and genotyping were obtained from serum and/or stools on admission. We found positive hepatitis A virus ribonucleic acid in 13 patients and negative hepatitis A virus ribonucleic acid in 20 patients. The following clinical variables were evaluated: time of evolution, hospital stay, admission to the pediatric intensive care unit, pediatric intensive care unit stay, time on mechanical ventilation, criteria for orthotopic liver transplantation, and mortality. Characterization of the isolates did not reveal differences related to genotype; all cases were IA. No statistical significance was found as to the variables. However, positive hepatitis A virus ribonucleic acid showed lower percentages of pediatric intensive care unit admissions, criteria for orthotopic liver transplantation, number of orthotopic liver transplantation, and mortality than the group of patients with negative hepatitis A virus ribonucleic acid. CONCLUSIONS: Hepatitis A virus genotyping studies did not show any particularities, all cases were IA and, thus, apparent associations between genotype and the clinical presentation of acute liver failure could not be found.

[Minor's medical information]. / Information du patient mineur.

Minor's medical information. In exercising parental authority, parents make medical treatment decisions on children's behalf. However, according to the French law, minors must receive clear medical informations and care-givers must seek their consent to treatment. In some situations, parental authority may be in conflict with child's will. This article examines legislative framework provided by the French law, to respect child's autonomy and situations in which parental authority is limited. In practice, the concept of child's 'best interests' remains the main key to resolve potential conflicts between parental authority and child's autonomy.

Information du patient mineur. Informer le patient mineur est non seulement une obligation juridique mais aussi un devoir médical et éthique. Cette attitude est l'une des faces de l'abandon du paternalisme médical. À chaque fois, c'est la notion « d'intérêt supérieur de l'enfant ¼ qui reste le fil conducteur qui guide le médecin. Nous aborderons ici différents aspects juridiques, médicaux et éthiques de cette question.

World Federation of Pediatric Intensive and Critical Care Societies-its global agenda.

The World Federation of Pediatric Intensive and Critical Care Societies (WFPICCS) is an international body that brings together international expertise, experience, and influence to improve the outcomes of children suffering from life-threatening illness and injury. Its mission is educational, scientific, and charitable in nature. WFPICCS is committed to a global environment, in which all children have access to intensive and critical care of the highest standard. It exists to find ways of improving the care of critically ill children throughout the world, and making that knowledge available to those who care for such children. As in an ideal world all children should have access to state of the art critical care services, this is unlikely to happen anytime soon. Faced with this reality, the member societies of the WFPICCS will strive to develop the best model and provide the best care for critically ill and injured children worldwide. The challenge is to find the appropriate role that we need to (and can effectively) play in decreasing both unnecessary death and suffering for children. Clearly, we cannot achieve these goals on our own, hence WFPICCS visualizes close cooperation and collaboration with other agencies offering care to critically ill or injured children such as the World Health Organization, World Federation of Societies of Intensive and Critical Care Medicine, International Pediatric Associations, and regional organizations and programs to achieve our objectives. We feel that this document while imperfect is a good starting point and hope that it will stimulate more discussion to guide the agenda of the federation for years to come.

Respiratory variations in aortic blood flow predict fluid responsiveness in ventilated children.

OBJECTIVE: To investigate whether respiratory variations in aortic blood flow velocity (DeltaVpeak ao), systolic arterial pressure (DeltaPS) and pulse pressure (DeltaPP) could accurately predict fluid responsiveness in ventilated children. DESIGN AND SETTING: Prospective study in a 18-bed pediatric intensive care unit. PATIENTS: Twenty-six children [median age 28.5 (16-44) months] with preserved left ventricular (LV) function. INTERVENTION: Standardized volume expansion (VE). MEASUREMENTS AND MAIN RESULTS: Analysis of aortic blood flow by transthoracic pulsed-Doppler allowed LV stroke volume measurement and on-line DeltaVpeak ao calculation. The VE-induced increase in LV stroke volume was >15% in 18 patients (responders) and <15% in 8 (non-responders). Before VE, the DeltaVpeak ao in responders was higher than that in non-responders [19% (12.1-26.3) vs. 9% (7.3-11.8), p=0.001], whereas DeltaPP and DeltaPS did not significantly differ between groups. The prediction of fluid responsiveness was higher with DeltaVpeak ao [ROC curve area 0.85 (95% IC 0.99-1.8), p=0.001] than with DeltaPS (0.64) or DeltaPP (0.59). The best cut-off for DeltaVpeak ao was 12%, with sensitivity, specificity, and positive and negative predictive values of 81.2%, 85.7%, 93% and 66.6%, respectively. A positive linear correlation was found between baseline DeltaVpeak ao and VE-induced gain in stroke volume (rho=0.68, p=0.001). CONCLUSIONS: While respiratory variations in aortic blood flow velocity measured by pulsed Doppler before VE accurately predict the effects of VE, DeltaPS and DeltaPP are of little value in ventilated children.

Physiological effects of noninvasive positive ventilation during acute moderate hypercapnic respiratory insufficiency in children.

INTRODUCTION: A prospective physiological study was performed in 12 paediatric patients with acute moderate hypercapnic respiratory insufficiency to assess the ability of noninvasive positive pressure ventilation (NPPV) to unload the respiratory muscles and improve gas exchange. MATERIALS AND METHODS: Breathing pattern, gas exchange, and inspiratory muscle effort were measured during spontaneous breathing and NPPV. RESULTS: NPPV was associated with a significant improvement in breathing pattern, gas exchange and respiratory muscle output. Tidal volume and minute ventilation increased by 33 and 17%, and oesophageal and diaphragmatic pressure time product decreased by 49 and 56%, respectively. This improvement in alveolar ventilation translated into a reduction in mean partial pressure in carbon dioxide from 48 to 40 mmHg (P = 0.01) and in respiratory rate from 48 to 41 breaths/min (P = 0.01). No difference between a clinical setting and a physiological setting of NPPV was observed. In conclusion, this study shows that NPPV is able to unload the respiratory muscles and improve clinical outcome in young patients admitted to the paediatric intensive care unit for acute moderate hypercapnic respiratory insufficiency.

Intercontinental differences in end-of-life attitudes in the pediatric intensive care unit: results of a worldwide survey.

OBJECTIVE: To examine intercontinental differences in end-of-life practices in pediatric intensive care units. DESIGN: An international survey. The on-line questionnaire consisted of two case scenarios with five questions each. The scenarios described the management of children in pediatric intensive care units and the questions dealt with the decision-making process and the modalities of forgoing life support. SETTING: The participants at the 5th World Congress on Pediatric Critical Care Medicine organized by the World Federation of Pediatric Intensive and Critical Care Societies (June 2007, Geneva, Switzerland) were invited to participate. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Six hundred sixty seven complete questionnaires were received from 71 countries, which were grouped into six continents: Europe (52.7%), North America (17.9%) and South America (9.5%), Asia (7.6%), Australia (6%), and Middle East (4.3%). In both scenarios, physicians played the major role in decision making in all of the continents. However, parents from North America, Australia, the Middle East, and Asia seem to be more involved in the decision-making process, compared with those from Europe and South America. In cases of septic shock, caregivers from Europe and South America are more prone to forego life support despite parents' wishes. In North America and Australia, parents' presence during cardiopulmonary resuscitation is usually accepted (89.7% and 92.3%, respectively), whereas their presence is less accepted in Asia (54%) and Europe (54.8%), or much less accepted in South America (25.8%) and the Middle East (7.1%). In both scenarios, the option to withhold rather than withdraw life supports was more commonly chosen among all continents, except South America, where the withdrawal of life support was more often proposed (51.6% vs. 45.2%). CONCLUSIONS: This study confirms that important intercontinental differences exist toward end-of-life issues in pediatric intensive care. Although the legal and ethical situation is rapidly evolving, a certain degree of paternalism seems to persist among European and South-American caregivers. This study suggests that ethical principles depend on the cultural roots of countries or continents, emphasizing the need to foster dialogue on end-of-life issues around the world to learn from each other and improve end-of-life care in pediatric intensive care units.

Forgoing life-sustaining or death-prolonging therapy in the pediatric ICU.

Most deaths in the pediatric intensive care unit occur after a decision to withhold or withdraw life-sustaining treatments. The management of children at the end of life can be divided into three steps. The first concerns the decision-making process. The second concerns the actions taken once a decision has been made to forego life-sustaining treatments. The third regards the evaluation of the decision and its implementation. The mission of pediatric intensive care has expanded to provide the best possible care to dying children and their families. Improving the quality of care received by dying children remains an ongoing challenge for every pediatric intensive care unit team member.

End-of-life care in children: the Brazilian and the international perspectives.

OBJECTIVE: To analyze the medical practices and the end-of-life care provided to children admitted to pediatric intensive care units in different parts of the globe. SOURCES: Articles on end-of-life care published during the last 20 years were selected from the PubMed, MEDLINE and LILACS databases, with emphasis on studies of death in pediatric intensive care units in Brazil, Latin America, Europe and North America, using the following keywords: death, bioethics, pediatric intensive care, cardiopulmonary resuscitation and life support limitation. SUMMARY OF THE FINDINGS: Publications on life support limitation (LSL) are concentrated in North America and Europe. In North American pediatric intensive care units there is a greater incidence of LSL (approximately 60%) than in Europe or Latin America (30-40%). These differences appear to be related to cultural, religious, legal and economic factors. Over the last decade, LSL in Brazilian pediatric intensive care units has increased from 6 to 40%, with do not resuscitate orders as the most common method. Also of note is the low level of family participation in the decision-making process. A recent resolution adopted by the Federal Medical Council (Conselho Federal de Medicina) regulated LSL in our country, demystifying a certain apprehension of a legal nature. The authors present a proposal for a protocol to be followed in these cases. CONCLUSIONS: The adoption of LSL with children in the final phases of irreversible diseases has ethical, moral and legal support. In Brazil, these measures are still being adopted in a timid manner, demanding a change in behavior, especially in the involvement of families in the decision-making process.

Nonketotic hyperglycemic coma in toddlers after unintentional methadone ingestion.

Methadone overdoses are increasing in parallel with the increased frequency of opiate substitution therapy in adults. Although unintentional methadone intoxication in children is rare, it is becoming more frequently recognized. We report 3 cases of unintentional methadone overdose in toddlers who initially displayed central nervous system depression associated with severe nonketotic hyperglycemia and discuss the possible pathophysiologic mechanisms of an underrecognized symptom of opiate intoxication in young children.

Noninvasive positive pressure ventilation: five years of experience in a pediatric intensive care unit.

OBJECTIVES: To evaluate the feasibility and outcome of noninvasive positive pressure ventilation (NPPV) in daily clinical practice. DESIGN: Observational retrospective cohort study. SETTING: Pediatric intensive care unit in a university hospital. PATIENTS: : Patients treated by NPPV, regardless of the indication, during five consecutive years (2000-2004). MEASUREMENTS AND RESULTS: A total of 114 patients were included, and 83 of the 114 patients (77%) were successfully treated by NPPV without intubation (NPPV success group). The success rate of NPPV was significantly lower (22%) in the patients with acute respiratory distress syndrome (p < .05) than in the other patients. The Pediatric Risk of Mortality II (p = .003) and Pediatric Logistic Organ Dysfunction scores (p = .002) at admission were significantly higher in patients who were unsuccessfully treated with NPPV (NPPV failure group). Baseline values of Pco2, pulse oximetry, and respiratory rate did not differ between the two groups. A significant decrease in Pco2 and respiratory rate within the first 2 hrs of NPPV was observed in the NPPV success group. Multivariate analysis showed that a diagnosis of acute respiratory distress syndrome (odds ratio, 76.8; 95% confidence interval, 4.4-1342; p = .003) and a high Pediatric Logistic Organ Dysfunction score (odds ratio, 1.09; 95% confidence interval, 1.01-1.17; p = .01) were independent predictive factors for NPPV failure. A total of 11 patients (9.6%), all belonging to the NPPV failure group, died during the study. CONCLUSIONS: This study demonstrates the feasibility and efficacy of NPPV in the daily practice of a pediatric intensive care unit. This ventilatory support could be proposed as a first-line treatment in children with acute respiratory distress, except in those with a diagnosis of acute respiratory distress syndrome.

Liver support for fulminant hepatic failure: is it time to use the molecular adsorbents recycling system in children?

OBJECTIVE: To describe the main liver support devices used for fulminant hepatic failure (FHF) and to review data on the Molecular Adsorbents Recycling System (MARS) and assess its efficiency in children. DATA SOURCE: Studies were identified through selected readings and a MEDLINE search from 1975 and 2004 using fulminant hepatic failure, acute liver failure, primary graft dysfunction, liver support, MARS, and extracorporeal liver assist device as key words. STUDY SELECTION: All original studies, including case reports, relating to the use of the MARS or albumin dialysis system were included. Additional attention was put on prognosis criteria of FHF severity in children. DATA EXTRACTION: Study design, numbers and diagnoses of patients, definite or bridging treatment, outcome measures, and complications were extracted and compiled. Results of individual trials were combined on the risk ratio scale. DATA SYNTHESIS: Nine randomized trials including 354 patients were identified. However, liver support failed to significantly affect mortality when compared with standard medical therapy. Albumin dialysis, and particularly MARS, emerges as an easily applicable technique for temporary liver support. Some well-designed studies have characterized its efficiency in a few indications, such as in intractable pruritus in chronic liver disease, in acute or chronic liver diseases, and in decompensated cirrhosis with hepatorenal syndrome. In adults and children with FHF, anecdotal reports suggest that MARS may stabilize the patient. However, no randomized controlled study has validated its use in this indication. A randomized controlled study is ongoing in adults with FHF. Such a trial seems to be unfeasible in children for several methodologic reasons. CONCLUSIONS: Although promising preliminary results suggest that MARS may have a significant position in the therapeutic arsenal for FHF, no sufficient data exist to justify its use in children. For as long as the results of the ongoing adult trial are not available, the indications of this expensive technique in children with FHF are limited.

Pneumococcal meningitis in a pediatric intensive care unit: prognostic factors in a series of 49 children.

BACKGROUND: Despite advances in antibiotic therapy strategies and in pediatric intensive care, prognosis of Streptococcus pneumoniae meningitis remains very poor. However, few prognostic studies have been published, especially in pediatric populations. METHODS: We conducted a prognostic study to determine the factors associated with hospital mortality of 49 children admitted in a single pediatric intensive care unit during a 12-yr period (1990-2002). RESULTS: Hospital mortality was 49% (24 of 49 patients), and neurologic sequels were observed in 47% of survivors. Among them, 90% had permanent sensory deafness. Based on univariable analyses, seven variables were associated with the outcome: Pediatric Risk of Mortality II score (p = .000005), Glasgow Coma Score of >8 (p = .001), use of mechanical ventilation (p = .001), platelet count (p = .007), white blood cells count (p = .002), cerebrospinal fluid glucose level (p = .02), and lack of corticosteroids use (p = .02). In multivariable analysis, only three factors were independently associated with in-hospital mortality: Pediatric Risk of Mortality II score (hazard ratio, 1.13; 95% confidence interval, 1.06-1.20; p = .0002), platelets count of >200 x 10/L (hazard ratio, 0.25; 95% confidence interval, 0.08-0.81; p = .021) and white blood cell count above 5 x 10/L (hazard ratio, 0.31; 95% confidence interval, 0.11-0.87; p = .026). CONCLUSIONS: S. pneumoniae meningitis remains a devastating childhood disease in developed countries. Three variables were independently associated with the in-hospital death in our series-high Pediatric Risk of Mortality II score, low white blood cells count, and low platelet count-reflecting the main importance of severe sepsis and neurologic presentation in establishing the prognosis of these patients.