Therapeutic efficacy of milrinone in the management of enterovirus 71-induced pulmonary edema.
Hand, foot, and mouth disease and herpangina are the major clinical manifestations of enterovirus 71 (EV71) infections. Brain-stem encephalitis and pulmonary edema are severe complications that can lead to death. This study was designed to evaluate the potential therapeutic effect of milrinone, a phosphodiesterase (PDE) inhibitor, in the treatment of patients with EV71-induced pulmonary edema. We conducted a historically controlled trial of 24 children with severe EV71-induced pulmonary edema from April 1998-June 2003 in southern Taiwan. Patients were divided into groups treated before and after the introduction of milrinone therapy. Etiological diagnosis was established by viral cultures and confirmed by specific immunofluorescence and neutralization tests. All 24 patients were below 5 years of age. The mortality was lower in the milrinone-treated vs. nontreated group (36.4% vs. 92.3%, P=0.005). Sympathetic tachycardia was decreased in patients treated with milrinone compared to controls (144 +/- 17/min vs. 206 +/- 26/min, P=0.004). A marked decrease in IL-13 (77 +/- 9 pg/ml vs. 162 +/- 88 pg/ml, P=0.001) was observed in milrinone-treated patients compared to controls. There was a significant reduction in white blood cell (10,838 +/- 4,537/mm3 vs. 19,475 +/- 7,798/mm3, P=0.009) and platelet (257 +/- 45 x 10(3)/mm3 vs. 400 +/- 87 x 10(3)/mm3, P=0.001) counts in milrinone-treated patients compared to controls. These results were associated with improvement in sympathetic regulation and decrease in IL-13 production. Milrinone therapy may provide a useful therapeutic approach for this highly lethal disorder.
Wang
Shih-Min
SM
Department of Emergency Medicine, College of Medicine, National Cheng Kung University and Hospital, Tainan, Taiwan.
Lei
Huan-Yao
HY
Huang
Mei-Chih
MC
Wu
Jing-Min
JM
Chen
Chun-Ta
CT
Wang
Jieh-Neng
JN
Wang
Jen-Ren
JR
Liu
Ching-Chuan
CC
D015415:Biomarkers / Q000378:metabolism; D001772:Blood Cell Count; D001831:Body Temperature / Q000187:drug effects; D004769:Enterovirus Infections / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000821:virology*; D005260:Female; D006801:Humans; D007223:Infant; D007378:Interleukins / Q000378:metabolism; D008297:Male; D020105:Milrinone / Q000627:therapeutic use*; D010100:Oxygen / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D011654:Pulmonary Edema / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology / Q000821:virology*; D012121:Respiration, Artificial; D016019:Survival Analysis; D013616:Tachycardia, Sinus; D016896:Treatment Outcome
D015415:Biomarkers; D007378:Interleukins; D010726:Phosphodiesterase Inhibitors; D020105:Milrinone; D010100:Oxygen