Dobutamine for Management of Surgical Patients With Septic Shock

Director, Head of Anesthesiology and Critical Care, Principal Investigator, Professor

Septic shock is the last and most severe stage of sepsis and is defined by extremely low blood pressure, despite lots of intravenous fluids. The incidence of septic shock related cardiomyopathy was 10% to 70%. Besides, general anesthesia will inhibit the sympathetic nervous system, reduce myocardial contractility and aggravate cardiac dysfunction. No randomized controlled trials have yet explore the effects of dobutamine on clinical outcomes for patients with septic shock undergoing surgery under general anesthesia.

Study Overview

• Status: Completed
• Conditions: General Anesthesia; Surgical Patients; Patients With Septic Shock
• Intervention / Treatment: Drug: Dobutamine; Drug: Norepinephrine

Detailed Description

Sepsis, defined as life-threatening organ dysfunction, is caused by a dysregulated host response to infection, which 30-day mortality rate is about 24.4%. Septic shock is the last and most severe stage of sepsis and is defined by extremely low blood pressure, despite lots of intravenous fluids.

Surgical patients with septic shock are not rare. The incidence of septic shock related cardiomyopathy was 10% to 70%. Besides, general anesthesia will inhibit the sympathetic nervous system, reduce myocardial contractility and aggravate cardiac dysfunction, furthermore exacerbate hemodynamic instability, and then increase the incidence of AKI and patient mortality. Therefore, to improve cardiac function in patients with septic shock who received general anesthesia is the key to save patients life and improve prognosis.

The latest international guidelines for the treatment of septic shock recommend - in patients with septic shock combined with cardiac dysfunction, treatment with norepinephrine in combination with dobutamine is recommended if inadequate tissue perfusion persists after adequate fluid resuscitation and maintenance of blood pressure, but the level of evidence is weak.

Dobutamine acts on β-adrenergic receptors, which can improve tissue perfusion, and small doses of 2.5-5ug/kg/min can increase myocardial contractility and improve cardiac function in patients without increasing heart rate. Previous study has demonstrated that the combined use of norepinephrine and dobutamine can elevate left ventricular ejection fraction, cardiac index, improve tissue perfusion, and reduce mortality in patients with septic shock. No randomized controlled trials have yet explore the effects of dobutamine on clinical outcomes for patients with septic shock undergoing surgery under general anesthesia.

• Study Type: Interventional
• Enrollment (Actual): 584
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • the First Affiliated Hospital, School of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with 18 years or older
2. Sugery patients with septic shock and the duration of opration is more than 1 hour

Exclusion Criteria:

1. Pregnancy;
2. Long-term intakeβ-receptor blocker;
3. patietns with dobutamine used within 72h before enrollment;
4. Patients use Recombinant Human Brain Natriuretic Peptide(rhBNP), Levosimendan and Epinephrine within 72h before enrollment;
5. Patients with hyperthyroidism;
6. Allergy or known sensitivity to catecholamines（norepinephrine, dobutamine etc.）and genera anesthetics.
7. Patients and guardians refused to participate in this intervention clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dobutamine, norepinephrine; Patients will be initiated on Dobutamine at 5 mcg/kg/min while continuous infusion of norepinephrine titrated to maintain a mean arterial pressure at 65mmHg or more	Drug: Dobutamine; Patients with septic shock in Dobutamine group will be initiated on Dobutamine at 5 mcg/kg/min when electrocardiogram, invasive blood pressure, and oxygen saturation were monitored.; Drug: Norepinephrine; Norepinephrine was titrated to maintain a mean arterial pressure at 65mmHg or more in both groups.
Other: Norepinephrine; Norepinephrine was titrated to maintain a mean arterial pressure at 65mmHg or more	Drug: Norepinephrine; Norepinephrine was titrated to maintain a mean arterial pressure at 65mmHg or more in both groups.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sequential Organ Failure Assessment (SOFA) score	Sequential Organ Failure Assessment (SOFA) score, ranges from 0 to 24, with 24 being the worst	Day 1 Day 3 and Day 7 in ICU after surgery
Incidence of acute kidney injury after surgery	Incidence of acute kidney injury after surgery	within 1 week after surgery
Mortality	Mortality	in hospital and Day 28 and Day 90 after the surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lactate level measurement	Lactate level measurement	before surgery (0 hour), 1hour after begining of surgery and at the end of surgey
capillary filling time	capillary filling time	before surgery (0 hour), 1hour after begining of surgery and at the end of surgey
Central venous oxygen saturation (ScvO2)	Central venous oxygen saturation (ScvO2)	before surgery (0 hour), 1hour after begining of surgery and at the end of surgey
Urine volume	Urine volume	1hour after begining of surgery and at the end of surgey
Duration of norepinephrine intraoperatively	Duration of norepinephrine intraoperatively	intraoperatively
Cumulative dose of norepinephrine intraoperatively	Cumulative dose of norepinephrine intraoperatively	intraoperatively
Incidence of intraoperative arrythmia Incidence of intraoperative arrythmia	Incidence of intraoperative arrythmia	intraoperatively
Postoperative complication	Postoperative complication	through study completion, an average of 1 year
Length of hospital stay after sugery	Length of hospital stay after sugery	through study completion, an average of 1 year
ICU-free days with 28 days postoperatively	ICU-free days with 28 days postoperatively	28 days postoperatively
Duration of mechanical ventilation in ICU	Duration of mechanical ventilation in ICU	through study completion, an average of 1 year
Renal replacement therapy	Renal replacement therapy within the first 7 days after the surgery	through study completion, an average of 1 year
Duration of renal replacement therapy	Duration of renal replacement therapy	through study completion, an average of 1 year
ICU-Mortality	ICU-Mortality	through study completion, an average of 1 year
In-hosipital Mortality	In-hosipital Mortality	through study completion, an average of 1 year
Hospitalization costs	Hospitalization costs	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Zhejiang University
• Collaborators: Zhejiang Cancer Hospital; The First Affiliated Hospital of Anhui Medical University; The Second Hospital of Hebei Medical University; Southwest Hospital, China; Tongji Hospital; The First Affiliated Hospital of Soochow University; The First Affiliated Hospital of Zhengzhou University; Guizhou Provincial People's Hospital; Zhujiang Hospital; Henan Provincial People's Hospital; People's Hospital of Xinjiang Uygur Autonomous Region; Tianjin Medical University General Hospital; Renmin Hospital of Wuhan University; The First Affiliated Hospital of University of South China; Red Cross Hospital, Hangzhou, China; Zhejiang Provincial People's Hospital; The Central Hospital of Lishui City; First Affiliated Hospital of Xinjiang Medical University; Ningbo No. 1 Hospital; Fujian Provincial Hospital; Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University; Ningbo No.2 Hospital; Zunyi Medical College; Union hospital of Fujian Medical University; Weihai Municipal Hospital; Weifang People's Hospital; Lishui Country People's Hospital; Zhejiang Provincial Tongde Hospital; The First People's Hospital of Zunyi; Wuhan Third Hospital; First Affiliated Hospital of Shenzhen University; The Second Hospital University of South China; The First Affiliated Hospital of Shihezi University Medical College; Affiliated Hospital of Jiaxing University; Affiliated Hospital of Guangdong Medical University; Huaibei Peolple's Hospital; Anqing People's Hospital of Anhui Medical University; Wenzhou people's hospital，zhejiang province,China; The First Clinical College of Harbin University; Central Hospital of Heng Yang; Bijie Hospital of Zhejiang Provincial People's Hospital; Fuyang Hospital of Anhui Medical University; The Hospital of Suixi County

Publications and helpful links

General Publications

• Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.
• Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C, Simpson S, Wiersinga WJ, Alshamsi F, Angus DC, Arabi Y, Azevedo L, Beale R, Beilman G, Belley-Cote E, Burry L, Cecconi M, Centofanti J, Coz Yataco A, De Waele J, Dellinger RP, Doi K, Du B, Estenssoro E, Ferrer R, Gomersall C, Hodgson C, Moller MH, Iwashyna T, Jacob S, Kleinpell R, Klompas M, Koh Y, Kumar A, Kwizera A, Lobo S, Masur H, McGloughlin S, Mehta S, Mehta Y, Mer M, Nunnally M, Oczkowski S, Osborn T, Papathanassoglou E, Perner A, Puskarich M, Roberts J, Schweickert W, Seckel M, Sevransky J, Sprung CL, Welte T, Zimmerman J, Levy M. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021 Nov;47(11):1181-1247. doi: 10.1007/s00134-021-06506-y. Epub 2021 Oct 2. No abstract available.
• Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C; Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005 Aug 17;294(7):813-8. doi: 10.1001/jama.294.7.813.
• Singbartl K, Kellum JA. AKI in the ICU: definition, epidemiology, risk stratification, and outcomes. Kidney Int. 2012 May;81(9):819-25. doi: 10.1038/ki.2011.339. Epub 2011 Oct 5.
• Rudiger A, Singer M. Mechanisms of sepsis-induced cardiac dysfunction. Crit Care Med. 2007 Jun;35(6):1599-608. doi: 10.1097/01.CCM.0000266683.64081.02.
• Bauer M, Gerlach H, Vogelmann T, Preissing F, Stiefel J, Adam D. Mortality in sepsis and septic shock in Europe, North America and Australia between 2009 and 2019- results from a systematic review and meta-analysis. Crit Care. 2020 May 19;24(1):239. doi: 10.1186/s13054-020-02950-2.
• Liu J, Xie H, Ye Z, Li F, Wang L. Rates, predictors, and mortality of sepsis-associated acute kidney injury: a systematic review and meta-analysis. BMC Nephrol. 2020 Jul 31;21(1):318. doi: 10.1186/s12882-020-01974-8.
• Yang HS, Song BG, Kim JY, Kim SN, Kim TY. Impact of propofol anesthesia induction on cardiac function in low-risk patients as measured by intraoperative Doppler tissue imaging. J Am Soc Echocardiogr. 2013 Jul;26(7):727-35. doi: 10.1016/j.echo.2013.03.016. Epub 2013 Apr 24.
• Green DW. Cardiac output decrease and propofol: what is the mechanism? Br J Anaesth. 2015 Jan;114(1):163-4. doi: 10.1093/bja/aeu424. No abstract available.
• Zhu Y, Yin H, Zhang R, Ye X, Wei J. The effect of dobutamine in sepsis: a propensity score matched analysis. BMC Infect Dis. 2021 Nov 11;21(1):1151. doi: 10.1186/s12879-021-06852-8.

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2024
• Primary Completion (Actual): November 15, 2025
• Study Completion (Actual): November 15, 2025

Study Registration Dates

• First Submitted: May 23, 2024
• First Submitted That Met QC Criteria: June 11, 2024
• First Posted (Actual): June 17, 2024

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: November 27, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Shock, Septic; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Amines; Catechols; Phenols; Benzene Derivatives; Alcohols; Amino Alcohols; Ethanolamines; Phenethylamines; Ethylamines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Norepinephrine; Dobutamine
• Other Study ID Numbers: Dobutamine

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study protocol
• IPD Sharing Time Frame: after finishing the study
• IPD Sharing Access Criteria: The protocol is available from the investigator on reasonable request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No