Extracorporeal hemocorrection in treatment of meningococcal septic shock in children

Purpose: to estimate the effectiveness of extracorporeal hemocorrection in treatment of refractory meningococcal septic shock in children.Methods: patients with generalized form of meningococcal infection, multi-organ system failure and refractory septic shock admitted to the resuscitation department of Children’s Clinical Research Center for Infectious Diseases of the Federal Medical and Biological Agency of Russia underwent extracorporeal hemocorrection (polymyxin adsorption, continuous veno-venous hemofiltration, continuous veno-venous hemodiafiltration). MultiFiltrate apparatus was used (Fresenius Medical Care, Germany).Results: application of extracorporeal hemocorrection technique in the therapy of refractory meningococcal septic shock reduced the mortality from 44.4% to 25%.Conclusion: effectiveness of extracorporeal hemocorrection when treating patients with refractory meningococcal septic shock is established. A small number of examined patients is a limitation of the study.

Central hemodynamic and splanchnic circulation in children with meningococcal septic shock

Meningococcal infection is caused by the bacterium Neisseria meningitidis (also termed meningococcus). Invasive meningococcal disease remains a rare infectious disease not only with high mortality but also with important morbidity and remains as a leading cause of sepsis and septic shock. The pathogenic mechanisms of microcirculatory disorders in meningococcal septic shock have been subject to controversy. This article presents the results of a study of 11 paediatric patients’ (4 boys and 7 girls) with meningococcal septic shock (Group I) who were hospitalized at the Regional Children's Infectious Hospital from 2009 to 2011. The average age of the patients was 37.4 ± 8.4 mo. Septic shock was diagnosed according to International Pediatric Sepsis Consensus Conference: definitions of criteria for sepsis and organ dysfunction in paediatrics. Heart rate, respiratory rate, systolic blood pressure, diastolic blood pressure, average blood pressure, SpO2 were monitored. The cardiac output, ejection fraction, fraction shortening, stroke volume were measured by ultrasound in M-mode by Teichholz method. Blood circulation in the a. mesenterica, a. hepatica, a. lienalis, a. renal sinister, v. porta, v. lienalis, v. renal sinister was determined by impulse Doppler’s wave. Acid-base and electrolytes level in serum, nitric oxide (NO), endothelin I, creatinine, C-reactivity protein and lactate blood level were measured. The control group consisted of 21 healthy children (9 boys and 12 girls), aged 37.5 ± 5.4 mo. in average (Group II). We used t-criteria (Student’s) and correlation with R-criteria (Spearmen) for statistical analysis. The data showed a statistically significant lower fraction of ejection, fraction of shortening, stroke volume in Group I. Moreover, our data showed a statistically high level of mesenterial and portal blood flow rate and high pulse index in v. renal sinister compared to healthy children. The blood level of NO was increased in Group I as well as in Group II. Direct correlations were determined between the level of NO and mesenteric, hepatic arterial and venous blood flow rate. Statistically significant inverse correlations between the level of NO and pulse resistive index in splanchnic vessels were discovered as well as inverse correlations between the NO level and the indicator of the severity of condition on PRISM scale (r = –0.952). At the same time, we have found no correlation between splanchnic circulation value and cardiac output. Based on the results of this study, we consider that NO has organ protective effects in children with meningococcal sepsis. Future research should aim to introduce new strategies of intensive care for patients with meningococcal septic shock with early use of inotrope and NO-donor therapy in fluid restriction combination.

Global Effect of Interleukin-10 on the Transcriptional Profile Induced by Neisseria meningitidis in Human Monocytes

ABSTRACTIn meningococcal septic shock, the dominant inducer of inflammation is lipopolysaccharide (LPS) in the outer membrane ofNeisseria meningitidis, while interleukin-10 (IL-10) is the principal anti-inflammatory cytokine. We have used microarrays and Ingenuity Pathway Analysis to study the global effects of IL-10 on gene expression induced byN. meningitidis, after exposure of human monocytes (n= 5) for 3 h toN. meningitidis(106cells/ml), recombinant human IL-10 (rhIL-10) (25 ng/ml), andN. meningitidiscombined with rhIL-10.N. meningitidisand IL-10 differentially expressed 3,579 and 648 genes, respectively. IL-10 downregulated 125 genes which were upregulated byN. meningitidis, including NLRP3, the key molecule of the NLRP3 inflammasome. IL-10 also upregulated 270 genes which were downregulated byN. meningitidis, including members of the leukocyte immunuglobulin-like receptor (LIR) family. Fifty-three genes revealed a synergistically increased expression whenN. meningitidisand IL-10 were combined. AIM2 (the principal molecule of the AIM2 inflammasome) was among these genes (fold change [FC], 18.3 versus 7.4 and 9.4 after stimulation byN. meningitidisand IL-10, respectively). We detected reduced concentrations (92% to 40%) of six cytokines (IL-1b, IL-6, IL-8, tumor necrosis factor alpha [TNF-α], macrophage inflammatory protein alpha [MIP-α], MIP-β) in the presence of IL-10, compared with concentrations with stimulation byN. meningitidisalone. Our data analysis of the effects of IL-10 on gene expression induced byN. meningitidissuggests that high plasma levels of IL-10 in meningococcal septic shock plasma may have a profound effect on a variety of functions and cellular processes in human monocytes, including cell-to-cell signaling, cellular movement, cellular development, antigen presentation, and cell death.