Simultaneous use of traditional Chinese medicine (si-ni-tang) to treat septic shock patients: study protocol for a randomized controlled trial

Huang-Chi Chen, Wen-Chi Chen, Kai-Huang Lin, Yung-Hsiang Chen, Lun-Chien Lo, Tsung-Chieh Lee, Te-Chun Hsia, Chu-Hsien Wang, Shin-Hwar Wu, Hsin-Whae Hsu, Yu-Jun Chang, Yu-Chuen Huang, Tien-Hsiung Ku, Ming-Hwarng Horng, Huang-Chi Chen, Wen-Chi Chen, Kai-Huang Lin, Yung-Hsiang Chen, Lun-Chien Lo, Tsung-Chieh Lee, Te-Chun Hsia, Chu-Hsien Wang, Shin-Hwar Wu, Hsin-Whae Hsu, Yu-Jun Chang, Yu-Chuen Huang, Tien-Hsiung Ku, Ming-Hwarng Horng

Abstract

Background: Even though there are continually upgraded recommendations for managing sepsis, such as "Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock", mortality is still high. Si-ni-tang, a remedy documented in Shanghan Lun, a medical collection from ancient China, is used for treating patients with sepsis and septic shock. Using a well-designed clinical trial, we are eager to survey the effectiveness of the concurrent use of this remedy in restoring these patients' hemodynamic status, or "Yang Qi".

Methods/design: Patients admitted to our medical intensive care units with the diagnosis of septic shock, defined as persistent hypotension induced by sepsis despite adequate fluid resuscitation, are eligible for participation. The inclusion criteria include: age from 20 to 85 years, conditions meeting the definition of septic shock, use of vasopressors within 24 hours of entering the study, and use of a nasogastric tube for feeding. The enrolled patients are randomly allocated either to the si-ni-tang group or the placebo group. The prescription of the trial drugs (si-ni-tang/placebo) is 2.25 grams 4 times a day for 7 days or till shock reversal (if shock reversal occurs in less than 7 days). Data, including duration of vasopressor infusion, gender, age, co-morbidities, APACHE II score, predicted mortality, ICU mortality, ICU length of stay, hospital mortality, hospital length of stay, source of sepsis, and culture results, are collected for the following analysis.

Discussion: Si-ni-tang is composed of processed Zingiber officinale, Glycyrrhiza uralensis, and Aconitum carmichaeli. Zingiber officinale and Glycyrrhiza uralensis are found to have the ability to reduce pro-inflammatory cytokine production, to inhibit lipopolisaccharide-induced macrophage activation and function, and to lessen the bacterial load and suppress acute and chronic inflammation. Aconitum carmichaeli is known to have vasopressor activity, and positive chronotropic and inotropic effects. As this remedy has a potential benefit in treating septic shock patients, we designed a double-blind, prospective, randomized controlled trial and would like to publish the results and conclusions later.

Trial registration: ClinicalTrials.gov: NCT01223430.

Figures

Figure 1
Figure 1
Enrolment Flowchart. The figure illustrates how the participants are enrolled and allocated.

References

    1. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R. et al.Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008;36(1):296–327. doi: 10.1097/01.CCM.0000298158.12101.41.
    1. Wang H, Xu T, Lewin MR. Future possibilities for the treatment of septic shock with herbal components. Am J Emerg Med. 2009;27(1):107–112. doi: 10.1016/j.ajem.2008.08.003.
    1. Tripathi S, Maier KG, Bruch D, Kittur DS. Effect of 6-gingerol on pro-inflammatory cytokine production and costimulatory molecule expression in murine peritoneal macrophages. J Surg Res. 2007;138(2):209–213. doi: 10.1016/j.jss.2006.07.051.
    1. Tripathi S, Bruch D, Kittur DS. Ginger extract inhibits LPS induced macrophage activation and function. BMC Complement Altern Med. 2008;8:1. doi: 10.1186/1472-6882-8-1.
    1. Gaus K, Huang Y, Israel DA, Pendland SL, Adeniyi BA, Mahady GB. Standardized ginger (Zingiber officinale) extract reduces bacterial load and suppresses acute and chronic inflammation in Mongolian gerbils infected with cagAHelicobacter pylori. Pharm Biol. 2009;47(1):92–98. doi: 10.1080/13880200802448690.
    1. Bodet C, La VD, Gafner S, Bergeron C, Grenier D. A licorice extract reduces lipopolysaccharide-induced proinflammatory cytokine secretion by macrophages and whole blood. J Periodontol. 2008;79(9):1752–1761. doi: 10.1902/jop.2008.080052.
    1. Kim KR, Jeong CK, Park KK, Choi JH, Park JH, Lim SS, Chung WY. Anti-inflammatory effects of licorice and roasted licorice extracts on TPA-induced acute inflammation and collagen-induced arthritis in mice. J Biomed Biotechnol. 2010;2010:709378.
    1. Xie YC, Dong XW, Wu XM, Yan XF, Xie QM. Inhibitory effects of flavonoids extracted from licorice on lipopolysaccharide-induced acute pulmonary inflammation in mice. Int Immunopharmacol. 2009;9(2):194–200. doi: 10.1016/j.intimp.2008.11.004.
    1. Chan TY. Aconite poisoning. Clin Toxicol (Phila) 2009;47(4):279–285. doi: 10.1080/15563650902904407.
    1. Bisset NG. Arrow poisons in China. Part II. Aconitum--botany, chemistry, and pharmacology. J Ethnopharmacol. 1981;4(3):247–336. doi: 10.1016/0378-8741(81)90001-5.
    1. Kimura I, Makino M, Takamura Y, Islam MA, Kimura M. Positive chronotropic and inotropic effects of higenamine and its enhancing action on the aconitine-induced tachyarrhythmia in isolated murine atria. Jpn J Pharmacol. 1994;66(1):75–80. doi: 10.1254/jjp.66.75.

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