We thank Dr. Mallat for their interest in our study of stepwise lactate kinetics-oriented hemodynamic therapy and for putting forward a statistical problem [1]. Central venous oxygen saturation (ScvO2)-targeted therapy was recommended by the Surviving Sepsis Campaign (SCC) guidelines in 2012 [2] and we initially envisaged that the stepwise lactate kinetics strategy was, at least, not inferior to the ScvO2 target strategy. Therefore, the design of non-inferiority analysis was adopted at the beginning of the trial.
We rechecked and recalculated the data by non-inferiority and superiority test. The lactate kinetics group mortality rate (P1) was 18.3% and the Scvo2 group mortality rate (P2) was 27.9%. The standard error for the mortality difference between the two groups was 0.0441, and thus the mortality difference was –0.0944 (95% confidence interval –0.1809 to –0.0080). The upper limit of the interval is less than 0, and thus the superiority conclusion is established. At this point, regardless of the non-inferior value (0.15 or 0.10), non-inferior conclusions must be established.
Additionally, the non-inferiority threshold of 10% is indeed more reasonable according to a previous study [3].Therefore, regardless of whether the non-inferiority threshold is set at 10% or 15%, no effect on the final conclusion was seen in this study.
Last, but not the least, the latest sepsis guidelines released by the SCC in 2016 have weakened early goal-directed therapy (EGDT) and highlighted the importance of normalization of lactate [4], which also supports the conclusion we draw that stepwise lactate kinetics-oriented hemodynamic therapy can reduce mortality in patients with sepsis-associated hyperlactatemia compared with ScvO2-oriented therapy.
Acknowledgements
We thank Prof. Guangliang Shan and Dr. Biao Zhang from the Department of Epidemiology and Biostatistics, Institute of Basic Medicine Sciences, Chinese Academy of Medical Sciences (CAMS) & School of Basic Medicine, Peking Union Medical College for helping us to check and perform the statistical analysis.
Funding
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Availability of data and materials
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Abbreviations
- EGDT
Early goal-directed therapy
- SCC
Surviving Sepsis Campaign
- ScvO2
Central venous oxygen saturation
Authors’ contributions
XZ, LS, and DL drafted the manuscript. All authors read and approved the final manuscript.
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Competing interests
The authors declare that they have no competing interests.
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Footnotes
See related Letter by Mallat, https://ccforum.biomedcentral.com/articles/10.1186/s13054-017-1685-2
This comment refers to the article available at: https://doi.org/10.1186/s13054-017-1685-2.
Contributor Information
Xiang Zhou, Email: zx_pumc@163.com.
Dawei Liu, Phone: +86-10-69152305, Email: dwliu98@163.com.
Longxiang Su, Email: slx77@163.com.
References
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Data Availability Statement
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