Electro-acupuncture at Zusanli, Qihai, and Guanyuan Acupoints Regulate Immune Function in Patients With Sepsis (EAIm-sepsis)

Lectro-acupuncture at Zusanli, Qihai, and Guanyuan Acupoints Regulate Immune Function in Patients With Sepsis

The purpose of this study was to investigate the biochemical and clinical effects of electro-acupuncture in patients with sepsis.

Study Overview

• Status: Completed
• Conditions: Sepsis; Immune Dysfunction
• Intervention / Treatment: Device: electro-acupuncture

Detailed Description

Patients were randomly divided into an electro-acupuncture (EA) group and a Western medicine group(WM group) using restricted block randomization (1:1 ratio).

Patients in the Western medicine group received conventional treatment with Western medicine. According to the International Guidelines for Management of Sepsis and Septic Shock: 2016, conventional treatment includes antibiotics and other anti-infection measures, fluid management, mechanical ventilation, and nutritional support, but did not include the use of immunosuppressants or immune enhancers including hormones, gamma globulin, and thymosin. Patients in the electro-acupuncture group were treated with Western medicine and electro-acupuncture. Electro-acupuncture was given at the Zusanli (ST36), Guanyuan (CV4), and Qihai (CV6) acupoints, twice a day for 30 minutes, and for 5 days in total.

The indicators of immune dysfunction including the percentage of T lymphocyte subsets, percentage of natural killer (NK) cells, and serum soluble programed cell death protein (sPD-1) level, and clinical effect including APACHE-II and SOFA score, whole blood analysis, levels of tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP), were determined before treatment and after treatment for 5 days.

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • 2nd Affiliated Hospital of Guangzhou University of Chinese Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of sepsis;
• Signed the informed consent form.

Exclusion Criteria:

• Pregnancy or psychiatric disorder;
• Immune deficiency or using immunosuppressants or immune enhancers;
• History of malignancy;
• HIV positive;
• Unwilling to participate in the study or cooperate with the treatment. Patients who cannot tolerate electroacupuncture treatment or loss of follow-up for complicating with other diseases during the study would be dropped off.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Western medicine group(WM group); Patients in the Western medicine group received conventional treatment with Western medicine. According to International Guidelines for Management of Sepsis and Septic Shock: 2016, conventional treatment includes antibiotics and other anti-infection measures, fluid management, mechanical ventilation, and nutritional support, but does not include the use of immunosuppressants or immune enhancers including hormones, gamma globulin, and thymosin.
Experimental: electro-acupuncture (EA) group; Patients in the electro-acupuncture group were treated with Western medicine and electro-acupuncture. Electro-acupuncture was given at the Zusanli (ST36), Guanyuan (CV4), and Qihai (CV6) acupoints, twice a day for 30 minutes, and for 5 days in total.	Device: electro-acupuncture; Electro-acupuncture was given at the Zusanli (ST36), Guanyuan (CV4), and Qihai (CV6) acupoints, twice a day for 30 minutes, and for 5 days in total.; Acupoints were selected as follows. (1) Zusanli (ST36) belongs to zuyangming stomach meridian. It is located on the anterolateral part of the lower leg 3 inches (4 horizontal fingers) below the eye of the external knee between the fibula and the tibia, and a horizontal finger (middle finger) width from the front edge of the tibia. (2) Guan yuan (CV4) is located 3 inches below the umbilicus, on the midline of the abdomen. (3) Qihai (CV6) is located 1.5 inches below the umbilicus on the midline.; Acupuncture and electro-acupuncture methods were performed as follows. Participants were in the supine position, and needles was inserted in the skin . After the participant has acid, numbness, swelling, pain or other feelings, the electro-acupuncture device was connect to the acupuncture needle, the frequency was set to continuous wave.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of T lymphocyte subsets(%)	Detect proportion of CD3-T lymphocyte and CD4-T lymphocyte(%) in total T lymphocytes in blood by flow cytometry .	5 days after treatment was begun (at the 6th day)
Proportion of natural killer(NK) cells(%)	Detect proportion of NK cells in total lymphocytes in blood by flow cytometry.	5 days after treatment was begun (at the 6th day)
Level of sPD-1 level(pg/ml)	Serum soluble programed cell death protein (sPD-1) level in blood was measured with ELISA.	5 days after treatment was begun (at the 6th day)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neutrophils/Lymphocytes(N/L) ratio(%)	N/L ratio was defined as the ratio of neutrophils to lymphocytes. Whole blood analyzer was used to measure the count neutrophils and lymphocytes in the patient's blood, and calculate the ratio of neutrophil to lymphocyte count.	5 days after treatment was begun (at the 6th day)
Level of C-reactive protein (CRP) (mg/L)	Serum soluble CRP level in blood was measured with ELISA.	5 days after treatment was begun (at the 6th day)
Level of Tumor necrosis factor-α (TNF-α) (pg/ml)	Serum soluble TNF-α level in blood was measured with ELISA.	5 days after treatment was begun (at the 6th day)
Acute Physiology and Chronic Health Evaluation-Ⅱ(APACHE-Ⅱ) score	APACHE-Ⅱ score is used to evaluate the severity and prognosis of sepsis patients. Possible score range from 0 (the disease is mild and the prognosis is good) to 71(the disease is serious and the prognosis is poor).	5 days after treatment was begun (at the 6th day)
Sequential Organ Failure Assessment (SOFA) score	SOFA score is used to evaluate the severity of organ failure. Possible score range from 0 (organ failure is rare and mild) to 48(multiple organ failure, and it's serious).	5 days after treatment was begun (at the 6th day)

Collaborators and Investigators

• Sponsor: Guangdong Provincial Hospital of Traditional Chinese Medicine
• Investigators: Study Director: Guang Yang, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine

Publications and helpful links

General Publications

• Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-377. doi: 10.1007/s00134-017-4683-6. Epub 2017 Jan 18.
• Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, Colombara DV, Ikuta KS, Kissoon N, Finfer S, Fleischmann-Struzek C, Machado FR, Reinhart KK, Rowan K, Seymour CW, Watson RS, West TE, Marinho F, Hay SI, Lozano R, Lopez AD, Angus DC, Murray CJL, Naghavi M. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet. 2020 Jan 18;395(10219):200-211. doi: 10.1016/S0140-6736(19)32989-7.
• Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol. 2013 Dec;13(12):862-74. doi: 10.1038/nri3552. Epub 2013 Nov 15.
• Bosmann M, Ward PA. The inflammatory response in sepsis. Trends Immunol. 2013 Mar;34(3):129-36. doi: 10.1016/j.it.2012.09.004. Epub 2012 Oct 2.
• Yang G, Hu RY, Deng AJ, Huang Y, Li J. Effects of Electro-Acupuncture at Zusanli, Guanyuan for Sepsis Patients and Its Mechanism through Immune Regulation. Chin J Integr Med. 2016 Mar;22(3):219-24. doi: 10.1007/s11655-016-2462-9. Epub 2016 Jan 29.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Actual): February 28, 2021
• Study Completion (Actual): January 30, 2022

Study Registration Dates

• First Submitted: March 26, 2022
• First Submitted That Met QC Criteria: May 5, 2022
• First Posted (Actual): May 10, 2022

Study Record Updates

• Last Update Posted (Actual): May 10, 2022
• Last Update Submitted That Met QC Criteria: May 5, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Sepsis; Immune Dysfunction; Electro-acupuncture
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia; Immune System Diseases
• Other Study ID Numbers: EAIm-sepsis

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The data that support the findings of this study are available on request from the corrresponding author.The data are not publicly available due to privacy or ethical restrictions.The data that supprot the findings of this study are available from the corresponding author upon reasonable request.
• IPD Sharing Time Frame: June 1, 2023
• IPD Sharing Access Criteria: Doctor or medical researcher; Sign relevant confidentiality agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No