Apoptosis in Polymorphonuclear Cells and Inflammatory Cytokines of Trauma Patients

Trauma Clinical Trial

Official title:

The Impact of Hypoxic Conditions on Apoptosis in Polymorphonuclear Cells and Inflammatory Cytokines of Trauma Patients at Emergency Department

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03319017
• Other study ID #: KUGH17229 (trauma)
• Status: Recruiting
• Phase: N/A
• First received: October 17, 2017
• Last updated: January 3, 2018
• Start date: December 1, 2017
• Est. completion date: November 30, 2018

Study information

• Verified date: December 2017
• Source: Korea University Guro Hospital
• Contact: Jung-Youn Kim, MD, Ph.D.
• Phone: 82-2-2626-3285
• Email: yellowwizard[@]hanmail.net
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study tries to find how hypoxia and hyperoxia, among types of the respiratory failure induced cell damage that can arise in the course of traumatic damage and treatment, influences apoptosis of PMN cells and IL-6 and tumor necrosis factor(TNF)-α as inflammatory cytokines.

Description:

Many patients visit an emergency room because of their trauma. Trauma patients account for around 25-35% in an emergency room. Trauma is the biggest cause of acquired disabilities, and is greatly related to death and disabilities of those aged less than 44. As such, since trauma leads to lowering personal life quality and greatly influences social and economic aspects, it is greatly dealt with in public medical service.

Primarily, patients with trauma experience a lot of bleeding and respiratory failure induced by multiple causes, and furthermore is likely to have hypovolaemic shock. Secondarily, the low blood flow induced by trauma and hypovolaemic shock triggers hypoxia and systemic inflammatory response syndrome(SIRS), and therefore lowering immunity leads to compensatory anti-inflammatory response syndrome(CARS). After that, failures to keep homeostasis, such as immune dysregulation induced acute respiratory distress syndrome (ARDS), multiple organ failure(MOF), immune function reduction, and inflammation overexpression, and other additional causes damage the patients who can end up being dead without recovery.

A trauma patient is able to be exposed to multiple complications of trauma and continue to have hypoxia and hyperoxia with multiple causes in the treatment step. Hypoxia triggers multiple organ failure by cell death and lack of oxygen, and especially is sensitive to nerve cells. Hyperoxia causes the problem of immunity system stimulation by oxygen radical and hydrogen peroxide(H2O2) secretion. As such, an oxygen condition can influence organ failure and inflammatory response in various ways. These hypoxia and hyperoxia are considered to be influential on post-trauma inflammation and on Polymorphonuclear Cells(PMN) and cytokine. A patient's oxygen condition control is the basic treatment of a trauma patient and is able to influence not only the maintenance of oxygen concentration in the body, but the immunity system for keeping body homeostasis to respond to trauma.

Therefore, it is important to know how a patient's oxygen condition influences cells in order to treat the patient. Nevertheless, there is no research on how hypoxia and hyperoxia influence PMN cell and inflammatory cytokine as inflammatory cells playing a critical role in post-trauma immunity function. Therefore, this study tries to find how hypoxia and hyperoxia, among types of the respiratory failure induced cell damage that can arise in the course of traumatic damage and treatment, influences apoptosis of PMN cells and IL-6 and tumor necrosis factor(TNF)-α as inflammatory cytokines. This study is expected to be used as a fundamental material for treating relevant patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: November 30, 2018
• Est. primary completion date: November 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

• Adults aged more than 19

• The patients who are diagnosed with multiple-trauma and have blood test in an emergency room. The patients with multiple-trauma are defined as the patients who have trauma in more than two regions.

Exclusion Criteria:

• The case where the check result of blood collection and oxygen saturation is able to influence treatment

Related Conditions & MeSH terms

• Trauma
• Wounds and Injuries

Intervention

Procedure:
• Multiple-trauma patients
The blood samples of the patients who agreed on this research are obtained in order to check their inflammatory response factor, and then their medical records are checked to find their initial ABGA result, lactate, C-reactive protein(CRP) known as initial inflammatory response, and procalcitonin. A patient's whole blood is collected in the tube with ethylene diaminetetracetic acid (EDTA) treatment. A modified method of Boyum's technique is applied so as to separate polymorphonuclear neutrophils. The separated polymorphonuclear neutrophils is collected so as to check apoptosis. And then, in the separated plasma, interleukin(IL)-6 and tumor necrosis factor(TNF)-a are measured, and its correlation with oxygen saturation will be analyzed.

Locations

Country	Name	City	State
Korea, Republic of	Korea University Guro Hospital	Seoul	Guro-gu

Sponsors (2)

Lead Sponsor	Collaborator
Korea University Guro Hospital	Korea University

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (14)

Brach MA, deVos S, Gruss HJ, Herrmann F. Prolongation of survival of human polymorphonuclear neutrophils by granulocyte-macrophage colony-stimulating factor is caused by inhibition of programmed cell death. Blood. 1992 Dec 1;80(11):2920-4. — View Citation

Ciesla DJ, Moore EE, Zallen G, Biffl WL, Silliman CC. Hypertonic saline attenuation of polymorphonuclear neutrophil cytotoxicity: timing is everything. J Trauma. 2000 Mar;48(3):388-95. — View Citation

Deitch EA. Multiple organ failure. Pathophysiology and potential future therapy. Ann Surg. 1992 Aug;216(2):117-34. Review. — View Citation

Elbim C, Estaquier J. Cytokines modulate neutrophil death. Eur Cytokine Netw. 2010 Mar;21(1):1-6. doi: 10.1684/ecn.2009.0183. Review. — View Citation

Giannoudis PV, Hildebrand F, Pape HC. Inflammatory serum markers in patients with multiple trauma. Can they predict outcome? J Bone Joint Surg Br. 2004 Apr;86(3):313-23. Review. — View Citation

Gillani S, Cao J, Suzuki T, Hak DJ. The effect of ischemia reperfusion injury on skeletal muscle. Injury. 2012 Jun;43(6):670-5. doi: 10.1016/j.injury.2011.03.008. Epub 2011 Apr 9. Review. — View Citation

Greenberg S, Grinstein S. Phagocytosis and innate immunity. Curr Opin Immunol. 2002 Feb;14(1):136-45. Review. — View Citation

Hsieh SC, Huang MH, Tsai CY, Tsai YY, Tsai ST, Sun KH, Yu HS, Han SH, Yu CL. The expression of genes modulating programmed cell death in normal human polymorphonuclear neutrophils. Biochem Biophys Res Commun. 1997 Apr 28;233(3):700-6. — View Citation

Kim JY, Hong YS, Choi SH, Yoon YH, Moon SW, Lee SW. Effect of hypertonic saline on apoptosis of polymorphonuclear cells. J Surg Res. 2012 Nov;178(1):401-8. doi: 10.1016/j.jss.2012.01.055. Epub 2012 Mar 23. — View Citation

Köller M, Clasbrummel B, Kollig E, Hahn MP, Muhr G. Major injury induces increased production of interleukin-10 in human granulocyte fractions. Langenbecks Arch Surg. 1998 Dec;383(6):460-5. — View Citation

Martin C, Boisson C, Haccoun M, Thomachot L, Mege JL. Patterns of cytokine evolution (tumor necrosis factor-alpha and interleukin-6) after septic shock, hemorrhagic shock, and severe trauma. Crit Care Med. 1997 Nov;25(11):1813-9. — View Citation

Menger MD, Vollmar B. Surgical trauma: hyperinflammation versus immunosuppression? Langenbecks Arch Surg. 2004 Nov;389(6):475-84. Epub 2004 May 28. Review. — View Citation

Moon S, Lee SH, Ryoo HW, Kim JK, Ahn JY, Kim SJ, Jeon JC, Lee KW, Sung AJ, Kim YJ, Lee DR, Do BS, Park SR, Lee JS. Preventable trauma death rate in Daegu, South Korea. Clin Exp Emerg Med. 2015 Dec 28;2(4):236-243. eCollection 2015 Dec. — View Citation

Roumen RM, Redl H, Schlag G, Zilow G, Sandtner W, Koller W, Hendriks T, Goris RJ. Inflammatory mediators in relation to the development of multiple organ failure in patients after severe blunt trauma. Crit Care Med. 1995 Mar;23(3):474-80. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measure interleukin(IL)-6	Measure in the separated plasma; Analyze correlation with oxygen saturation	At the occurrence of the event during visiting an emergency room, up to 3 hours
Secondary	Apoptosis of PMN check	A patient's whole blood is collected in the tube with ethylene	At the occurrence of the event during visiting an emergency room, up to 3 hours
Secondary	tumor necrosis factor(TNF)-a	Measure in the separated plasma	At the occurrence of the event during visiting an emergency room, up to 3 hours