Efficacy and safety of heart rate control with esmolol on the incidence and duration of organ failure in predicted severe acute pancreatitis: protocol of a multicenter, open-label, randomized controlled trial

IntroductionOveractivation of the sympathetic nerve system can lead to a sustained increase in heart rate, which may impair blood perfusion and organ function. Previous studies have demonstrated that the use of β-blockers like esmolol can reduce heart rate, thereby improving clinical outcomes in pat...

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Main Authors: Mingfeng Huang, Rong Wei, Lu Ke, Weijian Li, Jian Song, Haibin Ni, Xiaofei Huang, Yun Sun, Lu Fu, Yanhua Li, Dong Zhang, Bin Han, Jing Zhang, Yingying Hu, Chong Zhang, Zhongyan Sheng, Wenwen Feng, Lin Gao, Wenjian Mao, Yuxiu Liu, Bo Ye, Zhihui Tong, Weiqin Li
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Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2025.1642721/full
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author Mingfeng Huang
Rong Wei
Lu Ke
Weijian Li
Jian Song
Haibin Ni
Xiaofei Huang
Yun Sun
Lu Fu
Yanhua Li
Dong Zhang
Bin Han
Jing Zhang
Yingying Hu
Chong Zhang
Zhongyan Sheng
Wenwen Feng
Lin Gao
Wenjian Mao
Yuxiu Liu
Yuxiu Liu
Bo Ye
Zhihui Tong
Weiqin Li
author_facet Mingfeng Huang
Rong Wei
Lu Ke
Weijian Li
Jian Song
Haibin Ni
Xiaofei Huang
Yun Sun
Lu Fu
Yanhua Li
Dong Zhang
Bin Han
Jing Zhang
Yingying Hu
Chong Zhang
Zhongyan Sheng
Wenwen Feng
Lin Gao
Wenjian Mao
Yuxiu Liu
Yuxiu Liu
Bo Ye
Zhihui Tong
Weiqin Li
author_sort Mingfeng Huang
collection DOAJ
description IntroductionOveractivation of the sympathetic nerve system can lead to a sustained increase in heart rate, which may impair blood perfusion and organ function. Previous studies have demonstrated that the use of β-blockers like esmolol can reduce heart rate, thereby improving clinical outcomes in patients with septic shock. For acute pancreatitis (AP), which shares a similar inflammatory pathophysiology with sepsis, previous experimental and observational studies showed significant sympathetic excitation during the acute phase, and the use of β-blockers might be clinically beneficial. This study aims to test the hypothesis that early intravenous esmolol administration to control heart rate will improve the incidence and duration of organ failure in patients with predicted severe acute pancreatitis (pSAP).MethodsThis is an investigator-initiated, multicenter, open-label, randomized controlled trial. All patients with pSAP who still exhibit elevated heart rate (≥110 bpm) after 6 h of adequate intravenous fluid resuscitation within the first 72 h of symptom onset will be screened for eligibility. A total of 146 participants will be randomized to receive either esmolol or standard care. Patients in the esmolol group will receive a continuous esmolol infusion to maintain a heart rate between 80 and 94 beats per minute (bpm) within the first 96 h of randomization. The primary endpoint is organ failure free and alive days (OFFDs) to day 14 after trial entry. Secondary endpoints are comprised of both process and clinical measures, including heart rate variability, the proportion of patients’ heart rate recovered to <95 bpm, changes in plasma interleukin-6 and C-reactive protein between day 1 and day 5, in hospital and 90-day mortality, new-onset organ failure, free and alive days to day 30 for intensive care admission, and requirement of mechanical ventilation, vasopressor use, and renal replacement therapy.DiscussionThis study will provide top-class evidence concerning the effects of heart rate control with a classic β-blocker on the incidence and duration of organ failure in patients with pSAP and increased heart rate.Ethics and disseminationThis study has been approved by the ethics committee of Jinling Hospital, Nanjing University (2022DZKY-076-02) and all participating sites. Results will be disseminated through peer-reviewed journals and scientific conferences.Trial registrationIdentifier, ChiCTR2400080160.
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spelling doaj-art-a2a602a7a7d84d8dbed2725ff2deca4a2025-08-20T03:34:36ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-07-011210.3389/fmed.2025.16427211642721Efficacy and safety of heart rate control with esmolol on the incidence and duration of organ failure in predicted severe acute pancreatitis: protocol of a multicenter, open-label, randomized controlled trialMingfeng Huang0Rong Wei1Lu Ke2Weijian Li3Jian Song4Haibin Ni5Xiaofei Huang6Yun Sun7Lu Fu8Yanhua Li9Dong Zhang10Bin Han11Jing Zhang12Yingying Hu13Chong Zhang14Zhongyan Sheng15Wenwen Feng16Lin Gao17Wenjian Mao18Yuxiu Liu19Yuxiu Liu20Bo Ye21Zhihui Tong22Weiqin Li23Department of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaJinling Clinical Medical College, Nanjing Medical University, Nanjing, ChinaDepartment of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaThe Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, ChinaThe Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, ChinaAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaAffiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaThe First Department of Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaThe First Department of Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, ChinaDepartment of Critical Care Medicine, The First Hospital of Jilin University, Changchun, ChinaDepartment of Critical Care Medicine, The First Hospital of Jilin University, Changchun, ChinaDepartment of Emergency, The First People's Hospital Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, ChinaDepartment of Emergency, The First People's Hospital Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, ChinaThe First Affiliated Hospital of Henan University of Science & Technology, Luoyang, Henan, ChinaThe First Affiliated Hospital of Henan University of Science & Technology, Luoyang, Henan, ChinaDepartment of Critical Care Medicine, Qianxinan People's Hospital, Qianxinan, Guizhou, ChinaDepartment of Critical Care Medicine, Qianxinan People's Hospital, Qianxinan, Guizhou, ChinaDepartment of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaDepartment of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaDepartment of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China0Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, ChinaDepartment of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaJinling Clinical Medical College, Nanjing Medical University, Nanjing, ChinaDepartment of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaIntroductionOveractivation of the sympathetic nerve system can lead to a sustained increase in heart rate, which may impair blood perfusion and organ function. Previous studies have demonstrated that the use of β-blockers like esmolol can reduce heart rate, thereby improving clinical outcomes in patients with septic shock. For acute pancreatitis (AP), which shares a similar inflammatory pathophysiology with sepsis, previous experimental and observational studies showed significant sympathetic excitation during the acute phase, and the use of β-blockers might be clinically beneficial. This study aims to test the hypothesis that early intravenous esmolol administration to control heart rate will improve the incidence and duration of organ failure in patients with predicted severe acute pancreatitis (pSAP).MethodsThis is an investigator-initiated, multicenter, open-label, randomized controlled trial. All patients with pSAP who still exhibit elevated heart rate (≥110 bpm) after 6 h of adequate intravenous fluid resuscitation within the first 72 h of symptom onset will be screened for eligibility. A total of 146 participants will be randomized to receive either esmolol or standard care. Patients in the esmolol group will receive a continuous esmolol infusion to maintain a heart rate between 80 and 94 beats per minute (bpm) within the first 96 h of randomization. The primary endpoint is organ failure free and alive days (OFFDs) to day 14 after trial entry. Secondary endpoints are comprised of both process and clinical measures, including heart rate variability, the proportion of patients’ heart rate recovered to <95 bpm, changes in plasma interleukin-6 and C-reactive protein between day 1 and day 5, in hospital and 90-day mortality, new-onset organ failure, free and alive days to day 30 for intensive care admission, and requirement of mechanical ventilation, vasopressor use, and renal replacement therapy.DiscussionThis study will provide top-class evidence concerning the effects of heart rate control with a classic β-blocker on the incidence and duration of organ failure in patients with pSAP and increased heart rate.Ethics and disseminationThis study has been approved by the ethics committee of Jinling Hospital, Nanjing University (2022DZKY-076-02) and all participating sites. Results will be disseminated through peer-reviewed journals and scientific conferences.Trial registrationIdentifier, ChiCTR2400080160.https://www.frontiersin.org/articles/10.3389/fmed.2025.1642721/fullacute pancreatitisβ-blockersesmololheart rateorgan function
spellingShingle Mingfeng Huang
Rong Wei
Lu Ke
Weijian Li
Jian Song
Haibin Ni
Xiaofei Huang
Yun Sun
Lu Fu
Yanhua Li
Dong Zhang
Bin Han
Jing Zhang
Yingying Hu
Chong Zhang
Zhongyan Sheng
Wenwen Feng
Lin Gao
Wenjian Mao
Yuxiu Liu
Yuxiu Liu
Bo Ye
Zhihui Tong
Weiqin Li
Efficacy and safety of heart rate control with esmolol on the incidence and duration of organ failure in predicted severe acute pancreatitis: protocol of a multicenter, open-label, randomized controlled trial
Frontiers in Medicine
acute pancreatitis
β-blockers
esmolol
heart rate
organ function
title Efficacy and safety of heart rate control with esmolol on the incidence and duration of organ failure in predicted severe acute pancreatitis: protocol of a multicenter, open-label, randomized controlled trial
title_full Efficacy and safety of heart rate control with esmolol on the incidence and duration of organ failure in predicted severe acute pancreatitis: protocol of a multicenter, open-label, randomized controlled trial
title_fullStr Efficacy and safety of heart rate control with esmolol on the incidence and duration of organ failure in predicted severe acute pancreatitis: protocol of a multicenter, open-label, randomized controlled trial
title_full_unstemmed Efficacy and safety of heart rate control with esmolol on the incidence and duration of organ failure in predicted severe acute pancreatitis: protocol of a multicenter, open-label, randomized controlled trial
title_short Efficacy and safety of heart rate control with esmolol on the incidence and duration of organ failure in predicted severe acute pancreatitis: protocol of a multicenter, open-label, randomized controlled trial
title_sort efficacy and safety of heart rate control with esmolol on the incidence and duration of organ failure in predicted severe acute pancreatitis protocol of a multicenter open label randomized controlled trial
topic acute pancreatitis
β-blockers
esmolol
heart rate
organ function
url https://www.frontiersin.org/articles/10.3389/fmed.2025.1642721/full
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