title: Milrinone therapy for enterovirus 71-induced pulmonary edema and/or neurogenic shock in children: a randomized controlled trial.
abstract: OBJECTIVE
  Enterovirus 71-induced brainstem encephalitis with pulmonary edema and/or neurogenic shock (stage 3B) is associated with rapid mortality in children. In a small pilot study, we found that milrinone reduced early mortality compared with historical controls. This prospective, randomized control trial was designed to provide more definitive evidence of the ability of milrinone to reduce the 1-week mortality of stage 3B enterovirus 71 infections.
  
  
  METHODS
  Prospective, unicenter, open-label, randomized, controlled study.
  
  
  METHODS
  Inpatient ward of a large tertiary teaching hospital in Ho Chi Minh City, Vietnam.
  
  
  METHODS
  Children (≤ 18 yr old) admitted with proven enterovirus 71-induced pulmonary edema and/or neurogenic shock.
  
  
  METHODS
  Patients were randomly assigned to receive intravenous milrinone (0.5 μg/kg/min) (n = 22) or conventional management (n = 19). Both groups received dopamine or dobutamine and intravenous immunoglobulin.
  
  
  RESULTS
  The primary endpoint was 1-week mortality. The secondary endpoints included length of ventilator dependence and hospital stay and adverse events. The median age was 2 years with a predominance of boys in both groups. The 1-week mortality was significantly lower, 18.2% (4/22) in the milrinone compared with 57.9% (11/19) in the conventional management group (relative risk = 0.314 [95% CI, 0.12-0.83], p = 0.01). The median duration of ventilator-free days was longer in the milrinone treatment group (p = 0.01). There was no apparent neurologic sequela in the survivors in either group, and no drug-related adverse events were documented.
  
  
  CONCLUSIONS
  Milrinone significantly reduced the 1-week mortality of enterovirus 71-induced pulmonary edema and/or neurogenic shock without adverse effects. Further studies are needed to determine whether milrinone might be useful to prevent progression of earlier stages of brainstem encephalitis.
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli County, Taiwan.
authors.forename: Chia-Yu
authors.initials: CY
authors.lastname: Chi
authors.forename: Truong Huu
authors.initials: TH
authors.lastname: Khanh
authors.forename: Le Phan Kim
authors.initials: le PK
authors.lastname: Thoa
authors.forename: Fan-Chen
authors.initials: FC
authors.lastname: Tseng
authors.forename: Shih-Min
authors.initials: SM
authors.lastname: Wang
authors.forename: Le Quoc
authors.initials: le Q
authors.lastname: Thinh
authors.forename: Chia-Chun
authors.initials: CC
authors.lastname: Lin
authors.forename: Han-Chieh
authors.initials: HC
authors.lastname: Wu
authors.forename: Jen-Ren
authors.initials: JR
authors.lastname: Wang
authors.forename: Nguyen Thanh
authors.initials: NT
authors.lastname: Hung
authors.forename: Tang Chi
authors.initials: TC
authors.lastname: Thuong
authors.forename: Chung-Ming
authors.initials: CM
authors.lastname: Chang
authors.forename: Ih-Jen
authors.initials: IJ
authors.lastname: Su
authors.forename: Ching-Chuan
authors.initials: CC
authors.lastname: Liu
mesh_terms: D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002675:Child, Preschool; D004280:Dobutamine / Q000627:therapeutic use; D004298:Dopamine / Q000627:therapeutic use; D004769:Enterovirus Infections / Q000401:mortality / Q000821:virology*; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000627:therapeutic use; D007223:Infant; D007262:Infusions, Intravenous; D007902:Length of Stay; D008297:Male; D020105:Milrinone / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D011654:Pulmonary Edema / Q000188:drug therapy* / Q000401:mortality / Q000821:virology; D012121:Respiration, Artificial; D012769:Shock / Q000188:drug therapy* / Q000401:mortality / Q000821:virology; D014744:Vietnam
chemical_list: D002316:Cardiotonic Agents; D007136:Immunoglobulins; D004280:Dobutamine; D020105:Milrinone; D004298:Dopamine