Korean J Intern Med.  2005 Jun;20(2):123-128. 10.3904/kjim.2005.20.2.123.

The Effects of Methylene Blue on Hemodynamic Parameters and Cytokine Levels in Refractory Septic Shock

• Park BK
• Shim TS
• Lim CM
• Lee SD
• Kim WS
• Kim DS
• Kim WD
• Koh Y

• KMID: 1718033
• DOI: http://doi.org/10.3904/kjim.2005.20.2.123

Abstract

BACKGROUND
Endogenous nitric oxide (NO) induces the peripheral vasodilation via the activation of guanylate cyclase in patients with septic shock. The purpose of this study was to assess the acute effects of methylene blue (MB), which is an inhibitor of guanylate cyclase, on the hemodynamics and on the production of pro-inflammatory cytokines and nitric oxide (NO) in patients with refractory septic shock. METHODS: Twenty consecutive patients with refractory septic shock, which was defined as shock refractory to a dopamine infusion of more than 20 microgram/kg/min with the appropriate use of antibiotics and adequate volume replacement, received MB infusion of 1 mg/kg intravenously. The hemodynamic and respiratory variables were measured at baseline, 30, 60 and 120 min after an infusion of MB (1 mg/kg). The blood levels of NO, IL-1, IL-10 and TNF-alpha were measured at baseline, 30 and 120 min after MB infusion. RESULTS: The administration of MB induced an increase in the systemic vascular resistance (SVR) that resulted in an increase of the mean arterial pressure (MAP) in patients with refractory septic shock, and this was without a decrease in cardiac output. The administered MB induced an increase in pulmonary vascular resistance (PVR) that resulted in an increase of pulmonary arterial pressure (PAP), without any deterioration of gas exchange. However, the increases in SVR and PVR were not associated with the alteration of endogenous production of NO, IL-1, IL-10 and TNF-alpha. CONCLUSION: MB transiently elevated the MAP by increasing the SVR without altering the endogenous productions of NO, IL-1, IL-10 and TNF-alpha during the study period in patients with refractory septic shock.

Keyword

Septic shock; Methylene blue; Guanylate cyclase; Hemodynamics; NO; Cytokines

MeSH Terms

Anti-Infective Agents, Urinary/administration & dosage/*therapeutic use
Blood Pressure/*drug effects/physiology
Comparative Study
Cytokines/*blood
Enzyme-Linked Immunosorbent Assay
Female
Humans
Infusions, Intravenous
Male
Methylene Blue/administration & dosage/*therapeutic use
Middle Aged
Pulmonary Circulation/drug effects/physiology
Research Support, Non-U.S. Gov't
Retrospective Studies
Shock, Septic/blood/*drug therapy/physiopathology
Treatment Outcome
Vascular Resistance/*drug effects/physiology