The Impact of Normal Saline or Balanced Crystalloid on Plasma Chloride Concentration and Acute Kidney Injury in Patients With Predicted Severe Acute Pancreatitis: Protocol of a Phase II, Multicenter, Stepped-Wedge, Cluster-Randomized, Controlled Trial

Bo Ye; Mingfeng Huang; Tao Chen; Gordon Doig; Bin Wu; Mingzhi Chen; Shumin Tu; Xiaomei Chen; Mei Yang; Guoxiu Zhang; Qiang Li; Xinting Pan; Lijuan Zhao; Honghai Xia; Yan Chen; Lu Ke; Zhihui Tong; Rinaldo Bellomo; John Windsor; Weiqin Li

doi:10.3389/fmed.2021.731955

The Impact of Normal Saline or Balanced Crystalloid on Plasma Chloride Concentration and Acute Kidney Injury in Patients With Predicted Severe Acute Pancreatitis: Protocol of a Phase II, Multicenter, Stepped-Wedge, Cluster-Randomized, Controlled Trial

Front Med (Lausanne). 2021 Oct 4:8:731955. doi: 10.3389/fmed.2021.731955. eCollection 2021.

Authors

Bo Ye¹, Mingfeng Huang¹, Tao Chen², Gordon Doig³, Bin Wu⁴, Mingzhi Chen⁵, Shumin Tu⁶, Xiaomei Chen⁷, Mei Yang⁸, Guoxiu Zhang⁹, Qiang Li¹⁰, Xinting Pan¹¹, Lijuan Zhao¹², Honghai Xia¹³, Yan Chen¹⁴, Lu Ke^{1

14}, Zhihui Tong¹, Rinaldo Bellomo^{15

16

17

18}, John Windsor¹⁹, Weiqin Li^{1

14}

Affiliations

¹ Department of Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
² Global Health Trials Unit, Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
³ Northern Clinical School, Royal, North Shore Hospital, University of Sydney, Sydney, NSW, Australia.
⁴ Department of General Intensive Care Unit, The Third Hospital of Xiamen City, Xiamen, China.
⁵ Department of Critical Care Medicine, Jinjiang Hospital of Traditional Chinese Medicine, Jinjiang, China.
⁶ Department of Emergency, The First Hospital of Shangqiu City, Shangqiu, China.
⁷ Department of Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China.
⁸ Department of Intensive Care Unit, The Qujing NO.1 People's Hospital, Qujing, China.
⁹ Department of Emergency Intensive Care Unit, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.
¹⁰ Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
¹¹ Department of Emergency Intensive Care Unit, The Affiliated Hospital of Qingdao University, Qingdao, China.
¹² Department of Emergency Intensive Care Unit, First People's Hospital of Yunnan Province, Kunming, China.
¹³ Department of Emergency, The First Affiliated Hospital of the University of Science and Technology of China, Hefei, China.
¹⁴ National Institute of Healthcare Data Science at Nanjing University, Nanjing, China.
¹⁵ Department of Critical Care, The University of Melbourne, Melbourne, VIC, Australia.
¹⁶ Australian and New Zealand Research Center, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
¹⁷ Department of Intensive Care, Austin Hospital, Melbourne, VIC, Australia.
¹⁸ Department of Intensive Care, Royal Melbourne Hospital, Melbourne, VIC, Australia.
¹⁹ Surgical And Translational Research Center, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.

Abstract

Introduction/aim: The supraphysiologic chloride concentration of normal saline may contribute to acute kidney injury (AKI). Balanced crystalloids can decrease chloride concentration and AKI in critically ill patients. We aim to test the hypothesis that, in patients with predicted severe acute pancreatitis (pSAP), compared with saline, fluid therapy with balanced crystalloids will decrease plasma chloride concentration. Methods/Design: This is a multicenter, stepped-wedge, cluster-randomized, controlled trial. All eligible patients presenting to the 11 participating sites across China during the study period will be recruited. All sites will use saline for the first month and sequentially change to balanced crystalloids at the pre-determined and randomly allocated time point. The primary endpoint is the plasma chloride concentration on day 3 of enrollment. Secondary endpoints will include major adverse kidney events on hospital discharge or day 30 (MAKE 30) and free and alive days to day 30 for intensive care admission, invasive ventilation, vasopressors, and renal replacement therapy. Additional endpoints include daily serum chloride and sequential organ failure assessment (SOFA) score over the first seven days of enrollment. Discussion: This study will provide data to define the impact of normal saline vs. balanced crystalloids on plasma chloride concentration and clinical outcomes in pSAP patients. It will also provide the necessary data to power future large-scale randomized trials relating to fluid therapy. Ethics and Dissemination: This study was approved by the ethics committee of Jinling Hospital, Nanjing University (2020NZKY-015-01) and all the participating sites. The results of this trial will be disseminated in peer-reviewed journals and at scientific conferences. Trial registration: The trial has been registered at the Chinese Clinical Trials Registry (ChiCTR2100044432).

Keywords: acute kidney injury; acute pancreatitis; crystalloid; intravenous fluid; saline.