title: Combination therapy with milrinone and esmolol for heart protection in patients with severe sepsis: a prospective, randomized trial.
abstract: OBJECTIVE
  As a β-adrenoceptor antagonist (β-blocker), esmolol can reduce cardiac output and the phosphodiesterase III inhibitor milrinone has been shown to improve heart contractility in patients with septic shock. This study was performed to assess the effects of esmolol combined with milrinone in patients with severe sepsis.
  
  
  METHODS
  This prospective randomized study was conducted in patients with severe sepsis in the intensive care unit of the Jiangxi Provincial People's Hospital (Nanchang, Jiangsu, China) between June 2013 and June 2014. Patients were randomly divided into control (C), milrinone (M), and milrinone-esmolol (ME) groups. The primary outcome was the rate of controlling the heart rate (HR) to achieve target levels. Secondary outcomes included the 28-day survival rate and changes in hemodynamic variables, organ function variables, myocardial injury markers, and the serum levels of proinflammatory factors.
  
  
  RESULTS
  A total of 90 patients with severe sepsis were included in this study (30 per group). The HR in the ME group was lower than in the M and C groups after 12 h. The rate of successful HR control during the first 96 h was significantly higher in the ME group (60.0 vs. 33.3 % in the M group, vs. 26.7 % in the C group). Also, patients in the ME group had higher 28-day overall survival compared with the M (Log rank statistic = 5.452; P = 0.020) and C groups (Log rank statistic = 10.206; P = 0.001). Additionally, several variables showed significant improvement in the ME group 96 h after treatment compared with the M and C groups (P < 0.05).
  
  
  CONCLUSIONS
  Combination therapy with milrinone and esmolol could improve cardiac function and the 28-day survival rate in patients with severe sepsis.
authors.affiliation: Medical College of Nanchang University, Nanchang, 330006, Jiangxi, China. zenggengwangw@163.com.|ICU, Jiangxi Provincial People's Hospital, No. 92 Patriotic Way, Nanchang, 330006, Jiangxi, China. zenggengwangw@163.com.
authors.forename: Zenggeng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital to Nanchang University, Nanchang, 30006, Jiangxi, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Wu
authors.affiliation: ICU, Jiangxi Provincial People's Hospital, No. 92 Patriotic Way, Nanchang, 330006, Jiangxi, China.
authors.forename: Xiangbi
authors.initials: X
authors.lastname: Nie
authors.affiliation: ICU, Jiangxi Provincial People's Hospital, No. 92 Patriotic Way, Nanchang, 330006, Jiangxi, China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Guo
authors.affiliation: ICU, Jiangxi Provincial People's Hospital, No. 92 Patriotic Way, Nanchang, 330006, Jiangxi, China.
authors.forename: Chunli
authors.initials: C
authors.lastname: Yang
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D020105:Milrinone / Q000008:administration & dosage / Q000627:therapeutic use*; D011412:Propanolamines / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D020011:Protective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018805:Sepsis / Q000150:complications*
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D002316:Cardiotonic Agents; D011412:Propanolamines; D020011:Protective Agents; D020105:Milrinone; C036604:esmolol