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Photoplethysmography-derived approximate entropy and sample entropy as measures of analgesia depth during propofol–remifentanil anesthesia

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The ability to monitor the physiological effect of the analgesic agent is of interest in clinical practice. Nonstationary changes would appear in photoplethysmography (PPG) during the analgesics-driven transition to analgesia. The present work studied the properties of nonlinear methods including approximate entropy (ApEn) and sample entropy (SampEn) derived from PPG responding to a nociceptive stimulus under various opioid concentrations. Forty patients with ASA I or II were randomized to receive one of the four possible remifentanil effect-compartment target concentrations (Ceremi) of 0, 1, 3, and 5 ng·ml−1 and a propofol effect-compartment target-controlled infusion to maintain the state entropy (SE) at 50 ± 10. Laryngeal mask airway (LMA) insertion was applied as a standard noxious stimulation. To optimize the performance of ApEn and SampEn, different coefficients were carefully evaluated. The monotonicity of ApEn and SampEn changing from low Ceremi to high Ceremi was assessed with prediction probabilities (PK). The result showed that low Ceremi (0 and 1 ng·ml−1) could be differentiated from high Ceremi (3 and 5 ng·ml−1) by ApEn and SampEn. Depending on the coefficient employed in algorithm: ApEn with k = 0.15 yielded the largest PK value (0.875) whereas SampEn gained its largest PK of 0.867 with k = 0.2. Thus, PPG-based ApEn and SampEn with appropriate k values have the potential to offer good quantification of analgesia depth under general anesthesia.

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This study was supported by the National Natural Science Foundation of China (Grant No: 81870868), Major Scientific Project of Zhejiang Lab (Grant No: 2018DG0ZX01) and China’s Natural Science Foundation #31627802.

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Authors and Affiliations



WC was responsible for study design, data analysis, manuscript preparation and revision. FJ contributed to the study design, data analysis and revised the manuscript for important intellectual content. XC and HC were involved in the study design, data collection, manuscript revision and project supervision. YF and CJ were responsible for data collection and interpretation of data. JM and SC contributed to data analysis and critical revision of the manuscript for important intellectual content. All authors read and approved the final manuscript.

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Correspondence to Hang Chen.

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The authors declare that they have no conflict of interest.

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All procedures performed on human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by the Research Ethics Committee (No. 20170131) and informed consent was obtained from all individual participants included in the study.

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Chen, W., Jiang, F., Chen, X. et al. Photoplethysmography-derived approximate entropy and sample entropy as measures of analgesia depth during propofol–remifentanil anesthesia. J Clin Monit Comput 35, 297–305 (2021).

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