The effects of methylene blue on hemodynamic parameters and cytokine levels in refractory septic shock.
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 microg/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.


CONCLUSIONS
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.
Park
Byung-Kyu
BK
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Shim
Tae-Sun
TS
Lim
Chae-Man
CM
Lee
Sang-Do
SD
Kim
Woo-Sung
WS
Kim
Dong-Soon
DS
Kim
Won-Dong
WD
Koh
Younsuck
Y
D000892:Anti-Infective Agents, Urinary / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D016207:Cytokines / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008751:Methylene Blue / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology; D012189:Retrospective Studies; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology
D000892:Anti-Infective Agents, Urinary; D016207:Cytokines; D008751:Methylene Blue