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Combination Therapy with Milrinone and Esmolol for Heart Protection in Patients with Severe Sepsis: A Prospective, Randomized Trial

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Abstract

Background and 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.

Result

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).

Conclusion

Combination therapy with milrinone and esmolol could improve cardiac function and the 28-day survival rate in patients with severe sepsis.

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Acknowledgments

QW participated in the design of this study. XN performed the statistical analysis. JG carried out the study, together with CY, and collected important background information. ZW drafted the manuscript. QW conceived of this study, participated in the design, and helped to draft the manuscript. All authors read and approved the final manuscript.

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    Authors and Affiliations

    1. Medical College of Nanchang University, Nanchang, 330006, Jiangxi, China

      Zenggeng Wang PhD

    2. ICU, Jiangxi Provincial People’s Hospital, No. 92 Patriotic Way, Nanchang, 330006, Jiangxi, China

      Zenggeng Wang PhD, Xiangbi Nie, Jinghua Guo & Chunli Yang

    3. Department of Cardiology, The Second Affiliated Hospital to Nanchang University, Nanchang, 30006, Jiangxi, China

      Qinghua Wu

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    1. Zenggeng Wang PhD
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    2. Qinghua Wu
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    Corresponding author

    Correspondence to Zenggeng Wang PhD.

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    Funding

    This work has no source of funding.

    Conflict of interest

    All authors declare that they have no conflict of interest to state.

    Ethical approval

    The Ethics Committee of the Jiangxi Provincial People’s Hospital (Nanchang, Jiangsu, China) approved this study.

    Informed consent

    Each patient or their caregivers signed a written informed consent after an adequate explanation of the study.

    Additional information

    Z. Wang and Q. Wu contributed equally to this work.

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    Wang, Z., Wu, Q., Nie, X. et al. Combination Therapy with Milrinone and Esmolol for Heart Protection in Patients with Severe Sepsis: A Prospective, Randomized Trial. Clin Drug Investig 35, 707–716 (2015). https://doi.org/10.1007/s40261-015-0325-3

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    • DOI: https://doi.org/10.1007/s40261-015-0325-3

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