title: High-Volume Hemofiltration in Critically Ill Patients With Secondary Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome: A Prospective Study in the PICU.
abstract: Hemophagocytic lymphohistiocytosis, which includes primary (familial) and secondary hemophagocytic lymphohistiocytosis, is a fatal disease in children. Macrophage activation syndrome was defined in patients who met secondary hemophagocytic lymphohistiocytosis criteria with an underlying autoimmune disease. High-volume hemofiltration has shown beneficial effects in severe sepsis and multiple organ dysfunction syndrome. Secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome shares many pathophysiologic similarities with sepsis. The present study assessed the effects of high-volume hemofiltration in children with secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome.
  
  
  
  A single-center nonrandomized concurrent control trial.
  
  
  
  The PICU of Shanghai Children's Hospital, Shanghai Jiao Tong University.
  
  
  
  Thirty-three critically ill secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome patients treated between January 2010 and December 2014.
  
  
  
  Thirty-three patients were divided into two groups: high-volume hemofiltration + hemophagocytic lymphohistiocytosis-2004 group (17 cases) or hemophagocytic lymphohistiocytosis-2004 group (16 cases). High-volume hemofiltration was defined as an ultrafiltrate flow rate of 50-70 mL/kg/hr. Clinical and biological variables were assessed before initiation and after 48 and 72 hours of high-volume hemofiltration therapy.
  
  
  
  The total mortality rate was 42.4% (14/33), but mortality at 28 days was not significantly different between the two groups (high-volume hemofiltration + hemophagocytic lymphohistiocytosis-2004 group: five deaths, 29.4%; hemophagocytic lymphohistiocytosis-2004 group: nine deaths, 56.3%; chi-square, 2.431; p = 0.119). Children received high-volume hemofiltration for 60.2 ± 42.0 hours. After 48 and 72 hours respectively, a significant decrease in serum ferritin (p < 0.001), aspartate aminotransferase (p = 0.037 and p < 0.001), total bilirubin (p = 0.041 and p = 0.037), and serum creatinine (p = 0.006 and p = 0.004) levels were observed. Furthermore, the natural killer-cell activity up-regulated (p = 0.047) after 72 hours. Furthermore, significantly decreased levels of serum tumor necrosis factor-α (from 91.5 ± 44.7 ng/L at 48 hr to 36.7 ± 24.9 ng/L at 72 hr; p = 0.007)) and interleukin-6 (from 46.9 ± 21.1 ng/L at 48 hr to 27.7 ± 14.5 ng/L at 72 hr; p < 0.0001) were observed. After 7 days, patients receiving high-volume hemofiltration had significantly lower bilirubin, creatinine, ferritin, procalcitonin, lactate dehydrogenase level, tumor necrosis factor-α, and interleukin-6 levels, and needed less mechanical ventilation compared with hemophagocytic lymphohistiocytosis-2004 group patients. No serious adverse events were observed.
  
  
  
  High-volume hemofiltration may improve organ function by decreasing cytokine levels (tumor necrosis factor-α and interleukin-6). High-volume hemofiltration may be an effective adjunctive treatment in secondary hemophagocytic lymphohistiocytosis/macrophage activation syndrome.
authors.affiliation: All authors: Department of Pediatric Intensive Care Unit, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Cui
authors.forename: Yu-Cai
authors.initials: YC
authors.lastname: Zhang
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Kang
authors.forename: Yu-Qian
authors.initials: YQ
authors.lastname: Ren
authors.forename: Hui-Jie
authors.initials: HJ
authors.lastname: Miao
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003422:Critical Care / Q000379:methods*; D005260:Female; D006440:Hemofiltration / Q000379:methods*; D006801:Humans; D007223:Infant; D015278:Intensive Care Units, Pediatric; D051359:Lymphohistiocytosis, Hemophagocytic / Q000150:complications / Q000401:mortality / Q000628:therapy*; D055501:Macrophage Activation Syndrome / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008297:Male; D011446:Prospective Studies; D016896:Treatment Outcome