Reply

Abstract

Reply We thank Koga and colleagues for referring to our article (1) and reporting the successful use of endotoxin adsorption therapy for pediatric endotoxin shock, in their letter to the editor. We would like to make a few comments regarding this case report. Sepsis remains a major cause of morbidity and mortality among children despite the availability of various treatments using antibiotics, fluids, or vasopressive/inotropic approaches. Children with severe sepsis have hospital mortality rates of 10.3% in the United States (2) and 17% in the United Kingdom (3). Several factors, including age and immune status, influence the defense mechanisms against infection in children. Susceptibility to infection in some children is linked to immaturity of the immune system or the immunocompromising effects of chemotherapy. In these children, bacteria and virulence such as endotoxin in the blood stimulate the systemic inflammatory response. Even under intensive care, these processes can rapidly progress to multiple organ dysfunction syndrome and death. Endotoxin, an outer membrane component of gram-negative bacteria, plays an important role in the pathogenesis of severe sepsis and septic shock. Endotoxemia is common in children admitted to pediatric intensive care units and may be associated with increased severity of illness (4). The international guidelines for the management of severe sepsis and septic shock recommend fluid resuscitation, antibiotics, source control, inotropes/vasopressors, and corticosteroids, if needed, for the treatment for pediatric septic shock (5). When these treatments are ineffective and the plasma endotoxin concentration or endotoxin activity assay is increased, endotoxin adsorption therapy by polymyxin B–immobilized fiber column direct hemoperfusion (PMX-DHP) can be used as an optional treatment in Japan. In their letter to the editor, Koga and colleagues reported the effective use of PMX-DHP therapy for endotoxin shock in an immunocompromised child. Polymyxin B–immobilized fiber column direct hemoperfusion therapy has been widely used in adult patients with septic shock in Japan. We have shown in the meta-analysis that PMX therapy for adult patients with septic shock had beneficial effects on the hemodynamics, pulmonary oxygenation, and mortality (1). These beneficial effects may be attributable to the direct adsorption of endotoxin, monocytes, activated neutrophils, and anandamide, as well as indirect decrease in inflammatory cytokines and other mediators. Children with septic shock have also received PMX-DHP therapy, but the pediatric use of the therapy has only been reported in English once, in a letter to the editor in Digestive Diseases and Sciences (6). The Japan Society for Premature and Newborn Medicine issued a guideline for PMX-DHP therapy for infants/neonates in Japanese in 2010. Polymyxin B–immobilized fiber column direct hemoperfusion therapy is indicated for pediatric patients with septic shock when the patients manifest endotoxemia associated with the criteria for pediatric sepsis (7). The criterion for excluding PMX-DHP therapy for pediatric patients with septic shock is intracranial bleeding or a tendency to bleed in general. The following are important points for PMX-DHP performance in children: (1) an appropriately sized catheter should be inserted for vascular access; (2) an appropriately sized PMX column should be used; (3) the blood flow rate should be gradually increased to 2 to 5mL/kg per minute to prevent circulatory collapse; (4) nafamostat mesilate should be infused at a rate of 0.5 to 1.0 mg/kg per hour for anticoagulant and thereafter maintained at the rate necessary to sustain activated clotting time for 150 to 200 s. When the priming volume is greater than 10% of the patient’s body weight, a mixture of a red blood cell suspension and physiological saline is needed to prevent anemia. The PMX-05R column or PMX-01R column is usually used for children with endotoxin shock, because circulating blood volumes are low. The former, the PMX-05R column, has a low priming volume (40 mL) and is used for children with body weights of 10 kg or over. The PMX-01R column, which has a lower priming volume (8 mL), has been used for smaller children (body weights <10 kg) since its introduction in Japan in April 2012. When administering PMX-DHP for children, physicians should be mindful of their lower circulating blood volumes. Electrocardiogram and blood pressure must be monitored during this therapy. Severe arrhythmia such as ventricular tachycardia or ventricular fibrillation may occur as a consequence of low circulating volumes several minutes after the initiation of extracorporeal circulation. Hence, the safety and efficacy of PMX-DHP therapy for high-risk children with septic shock have not yet to be confirmed. Nevertheless, we believe that PMX-DHP is a useful therapy for severe pediatric endotoxin shock. Chieko Mitaka Department of Critical Care Medicine Tokyo Medical and Dental University Graduate School Tokyo, Japan Makoto Tomita Clinical Research Center Tokyo Medical and Dental University Hospital of Medicine Tokyo, Japan