Short-term beneficial effects of methylene blue on kidney damage in septic shock patients.

Abstract

OBJECTIVE:

We previously demonstrated that upregulation of renal inducible nitric oxide synthase (iNOS) is associated with proximal tubule injury during systemic inflammation in humans. In this study we investigated the short-term effect of methylene blue (MB), an inhibitor of the NO pathway, on kidney damage and function in septic shock patients.

DESIGN AND SETTING:

A prospective clinical study conducted in an intensive care unit.

PATIENTS:

Nine patients (four men, five women, mean age 71 +/- 3 years) with confirmed or suspected bacterial infection and with refractory septic shock defined as a mean arterial pressure < or = 70 mmHg despite norepinephrine infusion > or = 0.2 microg/kg per minute.

INTERVENTIONS:

A 4 h continuous intravenous infusion of 1 mg/kg MB per hour.

MEASUREMENTS AND RESULTS:

The urinary excretion of NO metabolites decreased with median 90% (range 75-95%) from baseline to 6 h after MB administration. The first 24 h creatinine clearance improved by 51% (18-173%) after MB treatment but was still strongly impaired. During the first 6 h after the start of MB treatment both the urinary excretion of cytosolic glutathione S-transferase A1-1 and P1-1, markers for proximal and distal tubule damage, respectively, decreased by 45% (10-70%) and 70% (40-85) vs. baseline. After termination of the MB infusion the NO metabolites and markers of tubular injury returned to pretreatment levels.

CONCLUSIONS:

In septic patients with refractory shock short-term infusion of MB is associated with a decrease in NO production and an attenuation of the urinary excretion of renal tubular injury markers.

• Authors: Suzanne Heemskerk, Frank M P van Haren, Norbert A Foudraine, Wilbert H M Peters, Johannes G van der Hoeven, Frans G M Russel, Rosalinde Masereeuw, Peter Pickkers
• Journal: Intensive care medicine (Intensive Care Med) Vol. 34 Issue 2 Pg. 350-4 (Feb 2008) ISSN: 0342-4642 [Print] United States
• PMID: 17926021 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Nitric Oxide Synthase
• Glutathione Transferase
• Methylene Blue

Topics

• Acute Kidney Injury (drug therapy, enzymology, etiology)
• Aged
• Analysis of Variance
• Enzyme Inhibitors (therapeutic use)
• Female
• Glutathione Transferase (metabolism)
• Humans
• Male
• Methylene Blue (therapeutic use)
• Nitric Oxide Synthase (metabolism)
• Prospective Studies
• Shock, Septic (complications, enzymology)
• Treatment Outcome