Milrinone Therapy for Enterovirus 71-Induced Pulmonary Edema and/or Neurogenic Shock in Children: A Randomized Controlled Trial* : Critical Care Medicine

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Pediatric Critical Care

Milrinone Therapy for Enterovirus 71-Induced Pulmonary Edema and/or Neurogenic Shock in Children

A Randomized Controlled Trial*

Chi, Chia-Yu MD1,2; Khanh, Truong Huu MD3; Thoa, Le Phan Kim MD3; Tseng, Fan-Chen PhD1; Wang, Shih-Min MD, PhD4,5; Thinh, Le Quoc MD3; Lin, Chia-Chun MSc1; Wu, Han-Chieh MSc1; Wang, Jen-Ren PhD5,6; Hung, Nguyen Thanh MD, PhD3; Thuong, Tang Chi MD3; Chang, Chung-Ming PhD1; Su, Ih-Jen MD, PhD1; Liu, Ching-Chuan MD, MPH2,5

Author Information
Critical Care Medicine 41(7):p 1754-1760, July 2013. | DOI: 10.1097/CCM.0b013e31828a2a85



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.


Prospective, unicenter, open-label, randomized, controlled study.


Inpatient ward of a large tertiary teaching hospital in Ho Chi Minh City, Vietnam.


Children (≤18 yr old) admitted with proven enterovirus 71-induced pulmonary edema and/or neurogenic shock.


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.

Measurements and Main 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.


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.

© 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins

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