Association between Acute Respiratory Acidosis and Hyperkalemia During Esophageal Cancer Surgery in the Prone Position: A Multicenter Retrospective Observational Study Protocol

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Abstract

Introduction Esophagectomy in the prone position can induce acute respiratory acidosis. While it is known that metabolic acidosis can significantly elevate serum potassium, the effect of respiratory acidosis is conventionally considered to cause minimal or no elevation. However, clinical practice in this surgical setting sometimes reveals a greater-than-expected degree of hyperkalemia. The objective of this study is to investigate the association between this acute respiratory acidosis and hyperkalemia, and to explore its clinical implications. Methods and analysis This is a retrospective, two-center observational study of adult patients who underwent thoracoscopic esophagectomy in the prone position at two major Japanese institutions between January 2022 and December 2024. The primary outcome is the mean difference in serum potassium levels between the supine (baseline) and prone-position phases, analyzed as a paired-design within each patient. Key secondary outcomes include: 1) a multivariable analysis to identify factors associated with the magnitude of potassium increase; 2) a sensitivity analysis of the primary outcome after excluding cases with significant metabolic acidosis (e.g., base excess < −5 mEq/L); and 3) correlation analyses between the change in potassium and various physiological parameters, including PaCO 2 and markers of metabolic stress. Analyses will include the paired t-test, correlation analyses, and multivariable regression models. Ethics and dissemination This study protocol has been approved by the institutional review boards of Aichi Medical University (serving as the central review board) and the Aichi Cancer Center. The requirement for individual informed consent was waived, and an opt-out policy is in place for patient notification. The findings will be disseminated through presentations at academic conferences and publication in a peer-reviewed journal. Trial registration number The study protocol has been registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR: [UMIN000058829]).
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Abstract

Introduction Esophagectomy in the prone position can induce acute respiratory acidosis. While it is known that metabolic acidosis can significantly elevate serum potassium, the effect of respiratory acidosis is conventionally considered to cause minimal or no elevation. However, clinical practice in this surgical setting sometimes reveals a greater-than-expected degree of hyperkalemia. The objective of this study is to investigate the association between this acute respiratory acidosis and hyperkalemia, and to explore its clinical implications.

Methods

and analysis This is a retrospective, two-center observational study of adult patients who underwent thoracoscopic esophagectomy in the prone position at two major Japanese institutions between January 2022 and December 2024. The primary outcome is the mean difference in serum potassium levels between the supine (baseline) and prone-position phases, analyzed as a paired-design within each patient. Key secondary outcomes include: 1) a multivariable analysis to identify factors associated with the magnitude of potassium increase; 2) a sensitivity analysis of the primary outcome after excluding cases with significant metabolic acidosis (e.g., base excess < −5 mEq/L); and 3) correlation analyses between the change in potassium and various physiological parameters, including PaCO2 and markers of metabolic stress. Analyses will include the paired t-test, correlation analyses, and multivariable regression models. Ethics and dissemination This study protocol has been approved by the institutional review boards of Aichi Medical University (serving as the central review board) and the Aichi Cancer Center. The requirement for individual informed consent was waived, and an opt-out policy is in place for patient notification. The findings will be disseminated through presentations at academic conferences and publication in a peer-reviewed journal. Trial registration number The study protocol has been registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR: [UMIN000058829]). Competing Interest Statement The authors have declared no competing interest. Funding Statement The author(s) received no specific funding for this work. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study protocol has been approved by the institutional review board of Aichi Medical University (Approval number: [2025-088]) and the Aichi Cancer Center. As this is a retrospective study using anonymized data, the requirement for individual written informed consent was waived. An opt-out policy is in place for patient notification via institutional websites. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability Data cannot be shared publicly due to ethical and privacy restrictions on patient data. This protocol is for a study where data extraction has not yet begun. Upon completion of the study, anonymized data may be available from the Aichi Medical University Institutional Review Board (contact via amu_ethics{at}aichi-med-u.ac.jp ) for qualified researchers who meet the criteria for access to confidential data. The preliminary data used for the sample size calculation is subject to these same restrictions.

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