Milrinone therapy for enterovirus 71-induced pulmonary edema and/or neurogenic shock in children: A randomized controlled trial

Chia Yu Chi, Truong Huu Khanh, Le Phan Kim Thoa, Fan Chen Tseng, Shih Min Wang, Le Quoc Thinh, Chia Chun Lin, Han Chieh Wu, Jen Ren Wang, Nguyen Thanh Hung, Tang Chi Thuong, Chung Ming Chang, Ih Jen Su, Ching Chuan Liu

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30 Citations (Scopus)


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. DESIGN:: Prospective, unicenter, open-label, randomized, controlled study. SETTING:: Inpatient ward of a large tertiary teaching hospital in Ho Chi Minh City, Vietnam. PATIENTS:: Children (≤18 yr old) admitted with proven enterovirus 71-induced pulmonary edema and/or neurogenic shock. INTERVENTIONS:: 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. 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.

Original languageEnglish
Pages (from-to)1754-1760
Number of pages7
JournalCritical care medicine
Issue number7
Publication statusPublished - 2013 Jul

All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine


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