Multi-Compartment Profiling of Bacterial and Host Metabolites Identifies Intestinal Dysbiosis and Its Functional Consequences in the Critically Ill Child.

OBJECTIVES: Adverse physiology and antibiotic exposure devastate the intestinal microbiome in critical illness. Time and cost implications limit the immediate clinical potential of microbial sequencing to identify or treat intestinal dysbiosis. Here, we examined whether metabolic profiling is a feasible method of monitoring intestinal dysbiosis in critically ill children. DESIGN: Prospective multicenter cohort study. SETTING: Three U.K.-based PICUs. PATIENTS: Mechanically ventilated critically ill (n = 60) and age-matched healthy children (n = 55). INTERVENTIONS: Collection of urine and fecal samples in children admitted to the PICU. A single fecal and urine sample was collected in healthy controls. MEASUREMENTS AND MAIN RESULTS: Untargeted and targeted metabolic profiling using 1H-nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry or urine and fecal samples. This was integrated with analysis of fecal bacterial 16S ribosomal RNA profiles and clinical disease severity indicators. We observed separation of global urinary and fecal metabolic profiles in critically ill compared with healthy children. Urinary excretion of mammalian-microbial co-metabolites hippurate, 4-cresol sulphate, and formate were reduced in critical illness compared with healthy children. Reduced fecal excretion of short-chain fatty acids (including butyrate, propionate, and acetate) were observed in the patient cohort, demonstrating that these metabolites also distinguished between critical illness and health. Dysregulation of intestinal bile metabolism was evidenced by increased primary and reduced secondary fecal bile acid excretion. Fecal butyrate correlated with days free of intensive care at 30 days (r = 0.38; p = 0.03), while urinary formate correlated inversely with vasopressor requirement (r = -0.2; p = 0.037). CONCLUSIONS: Disruption to the functional activity of the intestinal microbiome may result in worsening organ failure in the critically ill child. Profiling of bacterial metabolites in fecal and urine samples may support identification and treatment of intestinal dysbiosis in critical illness.

Whole genome sequencing reveals that genetic conditions are frequent in intensively ill children.

PURPOSE: With growing evidence that rare single gene disorders present in the neonatal period, there is a need for rapid, systematic, and comprehensive genomic diagnoses in ICUs to assist acute and long-term clinical decisions. This study aimed to identify genetic conditions in neonatal (NICU) and paediatric (PICU) intensive care populations. METHODS: We performed trio whole genome sequence (WGS) analysis on a prospective cohort of families recruited in NICU and PICU at a single site in the UK. We developed a research pipeline in collaboration with the National Health Service to deliver validated pertinent pathogenic findings within 2-3 weeks of recruitment. RESULTS: A total of 195 families had whole genome analysis performed (567 samples) and 21% received a molecular diagnosis for the underlying genetic condition in the child. The phenotypic description of the child was a poor predictor of the gene identified in 90% of cases, arguing for gene agnostic testing in NICU/PICU. The diagnosis affected clinical management in more than 65% of cases (83% in neonates) including modification of treatments and care pathways and/or informing palliative care decisions. A 2-3 week turnaround was sufficient to impact most clinical decision-making. CONCLUSIONS: The use of WGS in intensively ill children is acceptable and trio analysis facilitates diagnoses. A gene agnostic approach was effective in identifying an underlying genetic condition, with phenotypes and symptomatology being primarily used for data interpretation rather than gene selection. WGS analysis has the potential to be a first-line diagnostic tool for a subset of intensively ill children.

Management protocols for status epilepticus in the pediatric emergency room: systematic review article.

OBJECTIVE: This systematic review of national or regional guidelines published in English aimed to better understand variance in pre-hospital and emergency department treatment of status epilepticus. SOURCES: Systematic search of national or regional guidelines (January 2000 to February 2017) contained within PubMed and Google Scholar databases, and article reference lists. The search keywords were status epilepticus, prolonged seizure, treatment, and guideline. SUMMARY OF FINDINGS: 356 articles were retrieved and 13 were selected according to the inclusion criteria. In all six pre-hospital guidelines, the preferred route of medication administration was to use alternatives to the intravenous route: all recommended buccal and intranasal midazolam; three also recommended intramuscular midazolam, and five recommended using rectal diazepam. All 11 emergency department guidelines described three phases in therapy. Intravenous medication, by phase, was indicated as such: initial phase - ten/11 guidelines recommended lorazepam, and eight/11 recommended diazepam; second phase - most (ten/11) guidelines recommended phenytoin, but other options were phenobarbital (nine/11), valproic acid (six/11), and either fosphenytoin or levetiracetam (each four/11); third phase - four/11 guidelines included the choice of repeating second phase therapy, whereas the other guidelines recommended using a variety of intravenous anesthetic agents (thiopental, midazolam, propofol, and pentobarbital). CONCLUSIONS: All of the guidelines share a similar framework for management of status epilepticus. The choice in route of administration and drug type varied across guidelines. Hence, the adoption of a particular guideline should take account of local practice options in health service delivery.

Pilot Mechanistic Study of Insulin Modulation of Somatotrophic Hormones, Inflammation, and Lipid Metabolism During Critical Illness in Children.

OBJECTIVES: To evaluate the mechanism of insulin modulation on somatotrophic response, inflammation, and lipid metabolism in critically ill children. DESIGN: Open-label randomized mechanistic study. SETTING: Two-center, tertiary PICU study. PATIENTS: Thirty critically ill children between 1 month and 14 years old, requiring mechanical ventilation and with evidence of two or more organ system failures. INTERVENTIONS: Randomized physiologic design of hyperinsulinemic-euglycemic clamp using continuous insulin infusion at 0.1 U/kg/hr versus conventional management. MEASUREMENTS AND MAIN RESULTS: Thirteen children underwent hyperinsulinemic-euglycemic clamp. Blood samples for somatotrophic, inflammatory, and metabolic evaluation were obtained before randomization, and 24 and 72 hours later. A growth hormone oscillation profile was obtained during the first night. There was no difference between groups at baseline. Growth hormone resistance, increased proinflammatory cytokines, and increased lipolysis with low lipoprotein levels were present in all patients. Hyperinsulinemic-euglycemic clamp did not affect growth hormone, insulin-like growth factor-1 or insulin-like growth factor binding protein-3 levels. By day 2, insulin reduced insulin-like growth factor binding protein-1 levels. Tumor necrosis factor-α and interleukin-1ß were similar in both groups, whereas interleukin-6 levels reduced over time only in children receiving hyperinsulinemic-euglycemic clamp. Hyperinsulinemic-euglycemic clamp also decreased free fatty acid levels, which was accompanied by increased low-density lipoprotein cholesterol and relative increase in high-density lipoprotein levels. Total cholesterol and triglycerides were unchanged. CONCLUSIONS: Insulin does not reverse most of the somatotrophic changes induced by the stress of critical illness. Rather, it may improve lipid metabolism and down-regulate some markers of the inflammatory response.

Management protocols for status epilepticus in the pediatric emergency room: systematic review article / Protocolos de manejo de estado de mal epiléptico no pronto socorro pediátrico: análise sistemática

Abstract Objective: This systematic review of national or regional guidelines published in English aimed to better understand variance in pre-hospital and emergency department treatment of status epilepticus. Sources: Systematic search of national or regional guidelines (January 2000 to February 2017) contained within PubMed and Google Scholar databases, and article reference lists. The search keywords were status epilepticus, prolonged seizure, treatment, and guideline. Summary of findings: 356 articles were retrieved and 13 were selected according to the inclusion criteria. In all six pre-hospital guidelines, the preferred route of medication administration was to use alternatives to the intravenous route: all recommended buccal and intranasal midazolam; three also recommended intramuscular midazolam, and five recommended using rectal diazepam. All 11 emergency department guidelines described three phases in therapy. Intravenous medication, by phase, was indicated as such: initial phase - ten/11 guidelines recommended lorazepam, and eight/11 recommended diazepam; second phase - most (ten/11) guidelines recommended phenytoin, but other options were phenobarbital (nine/11), valproic acid (six/11), and either fosphenytoin or levetiracetam (each four/11); third phase - four/11 guidelines included the choice of repeating second phase therapy, whereas the other guidelines recommended using a variety of intravenous anesthetic agents (thiopental, midazolam, propofol, and pentobarbital). Conclusions: All of the guidelines share a similar framework for management of status epilepticus. The choice in route of administration and drug type varied across guidelines. Hence, the adoption of a particular guideline should take account of local practice options in health service delivery.

Resumo Objetivo: Esta análise sistemática de diretrizes nacionais ou regionais publicadas em inglês tem como objetivo entender melhor a diferença no tratamento do estado de mal epiléptico pré-hospitalar e no departamento de emergência. Fontes: Pesquisa sistemática de diretrizes nacionais ou regionais (janeiro de 2000 a fevereiro de 2017) contidas nas bases de dados do Pubmed e do Google Acadêmico e listas de referência de artigos. As palavras-chave da busca foram estado de mal epiléptico, convulsão prolongada, tratamento e diretriz. Resumo dos achados: Foram identificados 356 artigos e 13 foram selecionados de acordo com os critérios de inclusão. Em todas as seis diretrizes pré-hospitalares, o caminho preferencial de administração da medicação foi usar opções à via intravenosa: todas recomendaram midazolam bucal e intranasal; três também recomendaram midazolam intramuscular; e cinco recomendaram usar o diazepam via retal. Todas as 11 diretrizes de departamento de emergência descreveram três fases na terapia. No que diz respeito à medicação intravenosa, por fase, temos: fase inicial - 10/11 diretrizes recomendaram lorazepam e 8/11 recomendaram diazepam; segunda fase - a maioria (10/11) das diretrizes recomendou fenitoína, porém outras opções foram fenobarbital (9/11), ácido valproico (6/11) e fosfenitoína ou levetiracetam (individualmente, 4/11); terceira fase - 4/11 diretrizes incluíram a opção de repetir a terapia da segunda fase, ao passo que as outras diretrizes recomendaram usar diversos agentes anestésicos intravenosos (tiopental, midazolam, propofol e pentobarbital). Conclusões: Todas as diretrizes compartilham uma estrutura semelhante para manejo do estado de mal epiléptico. A escolha da via de administração e do tipo de medicamento variou em todas as diretrizes. Assim, a adoção de uma diretriz específica deve levar em consideração as opções da prática local na prestação de serviços de saúde.

Mesenteric near-infrared spectroscopy and risk of gastrointestinal complications in infants undergoing surgery for congenital heart disease.

We hypothesised that lower mesenteric near-infrared spectroscopy values would be associated with a greater incidence of gastrointestinal complications in children weighing <10 kg who were recovering from cardiac surgery. We evaluated mesenteric near-infrared spectroscopy, central venous oxygen saturation, and arterial blood gases for 48 hours post-operatively. Enteral feeding intake, gastrointestinal complications, and markers of organ dysfunction were monitored for 7 days. A total of 50 children, with median age of 16.7 (3.2-31.6) weeks, were studied. On admission, the average mesenteric near-infrared spectroscopy value was 71±18%, and the systemic oxygen saturation was 93±7.5%. Lower admission mesenteric near-infrared spectroscopy correlated with longer time to establish enteral feeds (r=-0.58, p<0.01) and shorter duration of feeds at 7 days (r=0.48, p<0.01). Children with gastrointestinal complications had significantly lower admission mesenteric near-infrared spectroscopy (58±18% versus 73±17%, p=0.01) and higher mesenteric arteriovenous difference of oxygen at admission [39 (23-47) % versus 19 (4-27) %, p=0.02]. Based on multiple logistic regression, admission mesenteric near-infrared spectroscopy was independently associated with gastrointestinal complications (Odds ratio, 0.95; 95% confidence interval, 0.93-0.97; p=0.03). Admission mesenteric near-infrared spectroscopy showed an area under the receiver operating characteristic curve of 0.76 to identify children who developed gastrointestinal complications, with a suggested cut-off value of 72% (78% sensitivity, 68% specificity). In this pilot study, we conclude that admission mesenteric near-infrared spectroscopy is associated with gastrointestinal complications and enteral feeding tolerance in children after cardiac surgery.

Early postoperative outcomes following surgical repair of complete atrioventricular septal defects: is down syndrome a risk factor?

OBJECTIVE: To evaluate the impact of Down syndrome on the early postoperative outcomes of children undergoing complete atrioventricular septal defect repair. DESIGN: Retrospective cohort study. SETTING: Single tertiary pediatric cardiac center. PATIENTS: All children admitted to PICU following biventricular surgical repair of complete atrioventricular septal defect from January 2004 to December 2009. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 107 children, 67 with Down syndrome, were included. Children with Down syndrome were operated earlier: 4 months (interquartile range, 3.5-6.6) versus 5.7 months (3-8.4) for Down syndrome and non-Down syndrome groups, respectively (p < 0.01). There was no early postoperative mortality. There was no significant difference in the prevalence of dysplastic atrioventricular valve between the two groups. Two children (2.9%) from Down syndrome and three children (7.5%) from non-Down syndrome group required early reoperation (p = 0.3). Junctional ectopic tachycardia was the most common arrhythmia, and the prevalence of junctional ectopic tachycardia was similar between the two groups (9% and 10% in Down syndrome and non-Down syndrome, respectively, p = 1). One patient from each group required insertion of permanent pacemaker for complete heart block. Children with Down syndrome had significantly higher prevalence of noncardiac complications, that is, pneumothorax, pleural effusions, and infections (p < 0.01), than children without Down syndrome. There was a trend for longer duration of mechanical ventilation in children with Down syndrome (41 hr [20-61 hr] vs 27.5 hr [15-62 hr], p = 0.2). However, there was no difference in duration of PICU stay between the two groups (2 d [1.3-3 d] vs 2 d [1-3 d], p = 0.9, respectively). CONCLUSIONS: In our study, we found no difference in the prevalence of atrioventricular valve dysplasia between children with and without Down syndrome undergoing complete atrioventricular septal defect repair. This finding contrasts with previously published data, and further confirmatory studies are required. Although clinical outcomes were similar, children with Down syndrome had a significantly higher prevalence of noncardiac complications in the early postoperative period than children without Down syndrome.

Meningococcal meningitis.

OPINION STATEMENT: Meningococcal meningitis (MM) is the most common presentation of meningococcal disease and an important cause of morbidity and mortality worldwide. When MM is associated with shock, early recognition and treatment of shock is essential. No investigation should delay starting antibiotics once the diagnosis is suspected. Corticosteroids can be started at the same time as the antibiotics or just before, but this is not a specific recommendation for MM. Low-dose steroids should be used in meningococcal disease with refractory shock. Altered blood flow, cerebral edema, and raised intracranial pressure are problems that should be considered in all patients with MM and decreased consciousness level. When mechanical ventilation is required, the target carbon dioxide level is 4.0 to 4.5 kPa, with avoidance of hypocapnia. Seizures, although not frequent, can occur in MM and require prompt treatment. Other treatments, such as mannitol and activated protein C, should be avoided. Potential new treatments requiring further investigation include neuroprotection with hypothermia or glycerol.

External validation of the paediatric logistic organ dysfunction score.

OBJECTIVE: External validation of the paediatric logistic organ dysfunction (PELOD) score in two paediatric intensive care units (PICU) in South America. METHODS: Prospective observational cohort study including all PICU admissions from July 2003 to December 2004 in Porto Alegre, Brazil, and from January 2004 to December 2004 in Buenos Aires, Argentina. The data collected included demographic variables, diagnosis, need for mechanical ventilation, length of PICU stay and mortality, and the 12 variables in the PELOD score. For each PELOD score variable, the worst daily value and the worst value of the whole PICU stay were used for the daily PELOD (dPELOD) and PELOD scores, respectively. RESULTS: A total of 1,476 admissions (51.3% from Argentina and 48.7% from Brazil) were analysed. Observed and predicted mortality were, respectively, 4.7% and 6.6%, with a standardized mortality ratio of 0.72. The score showed excellent discrimination capacity, with an area under the receiver operator characteristic (ROC) curve of 0.93 (0.88-0.98). The dPELOD score on days 1-5 also showed good discrimination capacities, with areas under the ROC curve >0.85. However, PELOD and dPELOD scores showed poor calibration with the Hosmer-Lemeshow test (chi-square 72.3, p < 0.001). This poor calibration was explained by a deficiency in the PELOD score where it fails to identify two risk intervals; 3.1-16.2% and 40-80%. CONCLUSIONS: The PELOD score is reproducible, has excellent discrimination, but over-predicts mortality and has poor calibration. Although the lack of calibration may not invalidate the score, the PELOD score is a discontinuous variable and we advise careful consideration when using it as a surrogate endpoint in clinical trials.

Pilot evaluation of continuous subcutaneous glucose monitoring in children with multiple organ dysfunction syndrome.

OBJECTIVE: To evaluate continuous subcutaneous glucose monitoring in pediatric critical illness. DESIGN: Prospective evaluation. SETTING: Mixed university pediatric intensive care unit. PATIENTS: Children aged 1 mo to 16 yrs requiring mechanical ventilation with at least two organ system failures. INTERVENTIONS: None. MEASUREMENTS: Blood samples obtained from an arterial line, measurements using point-of-care glucometer, and laboratory analysis were compared with continuous subcutaneous glucose monitoring. RESULTS: Fourteen patients yielded 11,880 continuous subcutaneous glucose monitoring measurements; 436 glucometer levels and 34 laboratory levels had mean time-paired glucose values of 108 +/- 29 mg/dL and 110 +/- 25 mg/dL, respectively. Mean continuous subcutaneous glucose monitoring glucose was 101 +/- 31 mg/dL for samples paired with glucometer and 95 +/- 40 mg/dL for samples paired with laboratory tests. Continuous subcutaneous glucose monitoring measurements correlated with glucometer (r = 0.44) and laboratory testing (r = 0.48). Mean absolute differences between continuous subcutaneous glucose monitoring measurement and glucometer and laboratory values were 18 +/- 16 mg/dL and 25 +/- 20 mg/dL, respectively. Clarke error grid analysis found 69% of the measurements to be in zone A (clinically accurate), 29% in zone B (benign errors), and 2% in zone D (failure to detect errors). The mean absolute relative difference between the continuous subcutaneous glucose monitoring measurement and glucometer and laboratory measurements were 17% and 23%, respectively. Bland-Altman analysis showed good agreement between continuous subcutaneous glucose monitoring and the other methods of glucose measurement. However, in the lower range (< or =74 mg/dL) 39% of the continuous subcutaneous glucose monitoring readings had a difference >15 mg/dL. On multiple regressions, only glucometer glucose values, continuous subcutaneous glucose monitoring levels, and base deficit were associated with the mean absolute relative difference. CONCLUSION: The performance of continuous subcutaneous glucose monitoring against point-of-care glucometer and laboratory measurements may be considered "good" using statistical definitions (Bland-Altman and Clarke error grid analysis). However, there are important limitations in children with large base deficit, being actively cooled, and with glucose in the lower range, which may limit its application.

Glycemic level in mechanically ventilated children with bronchiolitis.

OBJECTIVE: To evaluate in children with bronchiolitis requiring mechanical ventilation the association between blood glucose level and duration of mechanical ventilation and pediatric intensive care unit (PICU) stay. DESIGN: Retrospective cohort study. SETTING: University hospital PICU. PATIENTS: Children admitted to a university hospital PICU over a period of 3 yrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic data, infection with respiratory syncytial virus, history of prematurity, mechanical ventilator settings, and use of inotrope during illness were noted. In addition, C-reactive protein, alanine transaminase, and glucose levels were recorded. Data from 50 children with median (interquartile range) age of 2.2 (1.3-4.7) months were analyzed. There were 37 boys, 21 children had been premature babies, and 30 children were positive for respiratory syncytial virus. Hyperglycemia at any time was frequent (peak glucose > or =6.1 mmol/L [110 mg/dL] in 98% and >8.3 mmol/L [150 mg/dL] in 72%). Children with sustained hyperglycemia were more likely to be boys with higher alanine transaminase and C-reactive protein, requiring inotrope (p < .05). These children are more likely to have required high-frequency oscillation ventilation, required higher airway pressures, and had longer duration of mechanical ventilation and PICU stay (p < .05). Peak glucose and sustained peak glucose were not independently associated with duration of mechanical ventilation or PICU stay. Multiple regression showed that age, C-reactive protein, the need for inotrope, and respiratory syncytial virus infection were independent factors associated with duration of PICU stay. Glucose level was not a factor. CONCLUSIONS: Our findings show that hyperglycemia is frequent in children with bronchiolitis requiring mechanical ventilation, but we failed to show that this phenomenon was independently associated with prolonged duration of mechanical ventilation or PICU stay. Our observations raise the question whether tight glycemic control should be used in children with bronchiolitis.

Meningococcal disease and meningitis.

OBJECTIVE: To review the literature relevant to diagnosis and management of meningococcal disease (MD). SOURCES: Non-systematic review of medical literature through the MEDLINE database using the terms meningococcal, septic shock, diagnosis, and treatment. Articles were selected according to their relevance to the objective of the study and according to the authors' opinion. SUMMARY OF THE FINDINGS: MD is a leading cause of death due to infection in children. It progresses rapidly and a high level of suspicion is necessary for early diagnosis. Early intervention with aggressive fluid resuscitation and antibiotic therapy can significantly improve outcome. In the pediatric intensive care unit, a large amount of fluids may be required during the first few days and vasoactive drug infusions are often needed. Coagulopathy is frequent, but it has no specific treatment. The use of colloids and steroids may be beneficial, but other new therapies such as insulin and activated protein C still need further assessment. Rescue therapy with extracorporeal membrane oxygenation may be appropriate in cases complicated by severe acute respiratory distress syndrome, but not for refractory shock. Meningitis is often not diagnosed in MD because of the severity of illness and the inability to perform a lumbar puncture safely in a patient with coagulopathy, coma, or hemodynamic instability. When present, cerebral edema and altered cerebral blood flow are the main concerns. The use of osmolar solution may be necessary, but the main therapeutic intervention is to ensure adequate blood pressure for adequate cerebral perfusion. Seizures and hyponatremia should be aggressively treated. Steroids do not appear to affect outcome in meningococcal meningitis. CONCLUSIONS: MD is a life-threatening infection that requires early recognition and treatment. Time sensitive fluid resuscitation and antibiotic therapy are the most effective therapies for MD. Other therapies such as steroids may have a place in MD treatment but more definitive studies are necessary.

Doença meningocócica e meningite / Meningococcal disease and meningitis

OBJETIVO: Revisar a literatura pertinente ao diagnóstico e tratamento de doença meningocócica (DM). FONTES DOS DADOS: Revisão não-sistemática da literatura médica através de busca na base de dados MEDLINE usando os seguintes termos: meningocócico, choque séptico, diagnóstico, e tratamento. Os artigos foram selecionados de acordo com sua relevância para o objetivo do trabalho e de acordo com a opinião dos autores. SíNTESE DOS DADOS: A DM é uma das principais causas de morte em crianças, devido à infecção. Ela progride rapidamente e é preciso um alto grau de suspeita para se estabelecer o diagnóstico precocemente. Intervenção precoce com fluidoterapia agressiva e antibioticoterapia podem melhorar significativamente o desfecho. Na unidade de tratamento intensivo pediátrico, uma grande quantidade de volume pode ser necessário durante os primeiros dias e drogas vasoativas são geralmente usadas. Coagulopatia é freqüente, mas não tem tratamento específico. O uso de colóides e esteróides pode ser benéfico, mas outros tratamentos novos tais como insulina e proteína C ativada ainda precisam ser investigados em mais detalhe. O tratamento de resgate com circulação extracorpórea pode ser adequado em casos com complicações causadas pela síndrome do desconforto respiratório agudo grave, mas não no caso de choque refratário. A meningite geralmente não é diagnosticada na DM por causa da gravidade da doença e da incapacidade de realização de uma punção lombar com segurança em um paciente com coagulopatia, coma, ou instabilidade hemodinâmica. Quando presentes, edema cerebral e fluxo sangüíneo cerebral anormal são as principais preocupações. O uso de solução hiperosmolar pode ser necessário, mas a principal intervenção terapêutica é garantir pressão sangüínea adequada para que a perfusão cerebral seja adequada. Convulsões e hiponatremia devem ser tratadas agressivamente. Esteróides parecem não afetar o desfecho na meningite meningocócica. CONCLUSÕES: DM...

OBJECTIVE: To review the literature relevant to diagnosis and management of meningococcal disease (MD). SOURCES: Non-systematic review of medical literature through the MEDLINE database using the terms meningococcal, septic shock, diagnosis, and treatment. Articles were selected according to their relevance to the objective of the study and according to the authors’ opinion. SUMMARY OF THE FINDINGS: MD is a leading cause of death due to infection in children. It progresses rapidly and a high level of suspicion is necessary for early diagnosis. Early intervention with aggressive fluid resuscitation and antibiotic therapy can significantly improve outcome. In the pediatric intensive care unit, a large amount of fluids may be required during the first few days and vasoactive drug infusions are often needed. Coagulopathy is frequent, but it has no specific treatment. The use of colloids and steroids may be beneficial, but other new therapies such as insulin and activated protein C still need further assessment. Rescue therapy with extracorporeal membrane oxygenation may be appropriate in cases complicated by severe acute respiratory distress syndrome, but not for refractory shock. Meningitis is often not diagnosed in MD because of the severity of illness and the inability to perform a lumbar puncture safely in a patient with coagulopathy, coma, or hemodynamic instability. When present, cerebral edema and altered cerebral blood flow are the main concerns. The use of osmolar solution may be necessary, but the main therapeutic intervention is to ensure adequate blood pressure for adequate cerebral perfusion. Seizures and hyponatremia should be aggressively treated. Steroids do not appear to affect outcome in meningococcal meningitis. CONCLUSIONS: MD is a life-threatening infection that requires early recognition and treatment. Time sensitive fluid resuscitation and antibiotic therapy are the most effective therapies for MD. Other therapies...