Effect of Thiamine on Serum Glucagon And Reactive Oxygen Species (ROS)

Sepsis Clinical Trial

Official title:

Effect of Thiamine on Serum Glucagon And Reactive Oxygen Species (ROS) in Perioperative Stress Response

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05663164
• Other study ID #: Interventional
• Status: Completed
• Phase: N/A
• Start date: October 1, 2022
• Est. completion date: December 1, 2022

Study information

• Verified date: December 2022
• Source: Universitas Sumatera Utara
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This research is a clinical trial with a Randomized Controlled Trial (RCT) design. The purpose is to identify the effect of intravenous thiamine administration compared to normal saline placebo on glucagon levels and ROS levels in patients undergoing general anesthesia surgery

Description:

Surgery may increase postoperative cortisol and blood glucose levels. Changes in normal metabolic patterns due to surgery stimulate gluconeogenesis, glycogenolysis, proteolysis, lipolysis, and cytogenesis. These result in hyperglycemia and ketosis conditions. Surgery and anesthesia lead to an immunosuppressive effect. Increased secretion of proinflammatory cytokines may also occur after the surgery.

Besides an increase in cortisol levels, surgery can also increase cytokine response and ROS production in patients who have undergone surgery under general anesthesia after 72 hours. ROS production can also be a useful indicator in assessing the severity of surgical trauma.

In surgical procedures, there is an acute increase in reactive oxidative stress (ROS). This occurs when ischemia is followed by reperfusion. ROS can trigger tissue injury seen in transplantation (liver and heart), the release of aortic clamps during abdominal and thoracic aortic surgery, the release of limb tourniquets during orthopedic surgery, and reperfusion during and after cardiopulmonary bypass. There is a thiamine deficiency in 20% of patients treated in the intensive care unit (ICU). Thiamine deficiency is a source of lactic acidosis that does not seem in severe sepsis and septic shock. An imbalance between the formation and removal of free radicals causes a pathological condition called oxidative stress. However, the human body uses antioxidants to suppress these free radicals. One of the antioxidants that can reduce oxidative stress is thiamine. Previous studies proved this finding. Thiamine has also been able to significantly prevent the expression of inflammatory cytokines and chemokines, depending on NF-B induced by thromboxane and PGI2 synthase.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 1, 2022
• Est. primary completion date: November 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Patients aged 18-65 years who undergo surgery under general anesthesia

• ASA physical statuses 1 and 2

• Sepsis

Exclusion Criteria:

• Refuse to participate

• Diabetes mellitus, experience shock sepsis or lactic acidosis

• Have a history of hypersensitivity (allergy) to thiamine

• Thiamine deficiency

• Take immunomodulatory drugs, antiplatelet or anticoagulants surgery duration > 6 hours, and thiamin regularly

• They experience massive bleeding and receive blood transfusions preoperatively, intraoperatively, or postoperatively

Related Conditions & MeSH terms

• Beriberi
• Sepsis
• Thiamine Deficiency

Intervention

Drug:
• Vitamin B
vitamin B1 (100mg) will be diluted in 50 ml 0.9% NACL(normal saline) and administered IV every 6 hours for 3 days
• Placebo
Normal saline (0.9% NaCl solution) volume to match all components

Locations

Country	Name	City	State
Indonesia	Faculty of Medicine Universitas Sumatera Utara	Medan	Sumatera Utara

Sponsors (1)

Lead Sponsor	Collaborator
Universitas Sumatera Utara

Country where clinical trial is conducted

Indonesia, 

References & Publications (9)

Costa NA, Gut AL, de Souza Dorna M, Pimentel JA, Cozzolino SM, Azevedo PS, Fernandes AA, Zornoff LA, de Paiva SA, Minicucci MF. Corrigendum to "serum thiamine concentration and oxidative stress as predictors of mortality in patients with septic shock" [J Crit care 2014;29(2):249-52]. J Crit Care. 2016 Dec;36:311. doi: 10.1016/j.jcrc.2016.07.001. Epub 2016 Jul 10. No abstract available. — View Citation

Cusack B, Buggy DJ. Anaesthesia, analgesia, and the surgical stress response. BJA Educ. 2020 Sep;20(9):321-328. doi: 10.1016/j.bjae.2020.04.006. Epub 2020 Jul 21. No abstract available. — View Citation

Davis G, Fayfman M, Reyes-Umpierrez D, Hafeez S, Pasquel FJ, Vellanki P, Haw JS, Peng L, Jacobs S, Umpierrez GE. Stress hyperglycemia in general surgery: Why should we care? J Diabetes Complications. 2018 Mar;32(3):305-309. doi: 10.1016/j.jdiacomp.2017.11.010. Epub 2017 Nov 29. — View Citation

Hazell AS, Faim S, Wertheimer G, Silva VR, Marques CS. The impact of oxidative stress in thiamine deficiency: a multifactorial targeting issue. Neurochem Int. 2013 Apr;62(5):796-802. doi: 10.1016/j.neuint.2013.01.009. Epub 2013 Jan 18. — View Citation

Karkabounas S, Papadopoulos N, Anastasiadou C, Gubili C, Peschos D, Daskalou T, Fikioris N, Simos YV, Kontargiris E, Gianakopoulos X, Ragos V, Chatzidimitriou M. Effects of alpha-Lipoic Acid, Carnosine, and Thiamine Supplementation in Obese Patients with Type 2 Diabetes Mellitus: A Randomized, Double-Blind Study. J Med Food. 2018 Dec;21(12):1197-1203. doi: 10.1089/jmf.2018.0007. Epub 2018 Oct 11. — View Citation

Lubis B, Lelo A, Amelia P, Prima A. The Effect of Thiamine, Ascorbic Acid, and the Combination of Them on the Levels of Matrix Metalloproteinase-9 (MMP-9) and Tissue Inhibitor of Matrix Metalloproteinase-1 (TIMP-1) in Sepsis Patients. Infect Drug Resist. 2022 Sep 30;15:5741-5751. doi: 10.2147/IDR.S378523. eCollection 2022. — View Citation

Luong KV, Nguyen LT. The impact of thiamine treatment in the diabetes mellitus. J Clin Med Res. 2012 Jun;4(3):153-60. doi: 10.4021/jocmr890w. Epub 2012 May 15. — View Citation

Prete A, Yan Q, Al-Tarrah K, Akturk HK, Prokop LJ, Alahdab F, Foster MA, Lord JM, Karavitaki N, Wass JA, Murad MH, Arlt W, Bancos I. The cortisol stress response induced by surgery: A systematic review and meta-analysis. Clin Endocrinol (Oxf). 2018 Nov;89(5):554-567. doi: 10.1111/cen.13820. Epub 2018 Aug 23. — View Citation

Sudhakaran S, Surani SR. Guidelines for Perioperative Management of the Diabetic Patient. Surg Res Pract. 2015;2015:284063. doi: 10.1155/2015/284063. Epub 2015 May 19. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glucagon Level	a hormone that your pancreas makes to help regulate your blood glucose (sugar) levels	On day 3 (at approximately 72 hours) after the first study drug dose
Primary	ROS Level	Reactive species is the common term for both free radicals and reactive oxygen species (ROS), which include radicals, such as superoxide radical anion and hydroxyl radical, and nonradicals, such as hydrogen peroxide	On day 3 (at approximately 72 hours) after the first study drug dose