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

• Published in: Intensive care medicine 2008-02, Vol.34 (2), p.350-354
• Main Authors: Heemskerk, Suzanne, van Haren, Frank M. P., Foudraine, Norbert A., Peters, Wilbert H. M., van der Hoeven, Johannes G., Russel, Frans G. M., Masereeuw, Rosalinde, Pickkers, Peter
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - drug therapy; Acute Kidney Injury - enzymology; Acute Kidney Injury - etiology; Aged; Analysis of Variance; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anesthesiology; Biological and medical sciences; Brief Report; Creatinine; Critical Care Medicine; Emergency and intensive care: infection, septic shock; Emergency Medicine; Enzyme Inhibitors - therapeutic use; Failure; Female; Glutathione Transferase - metabolism; Humans; Intensive; Intensive care; Intensive care medicine; Kidneys; Male; Medical sciences; Medicine; Medicine & Public Health; Metabolites; Methylene Blue - therapeutic use; Mortality; Multiple organ dysfunction syndrome; Nitric oxide; Nitric Oxide Synthase - metabolism; Pain Medicine; Pediatrics; Pneumology/Respiratory System; Prospective Studies; Sepsis; Shock, Septic - complications; Shock, Septic - enzymology; Treatment Outcome; Urine
• ISSN: 0342-4642; 1432-1238
• DOI: 10.1007/s00134-007-0867-9

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 ≤ 70 mmHg despite norepinephrine infusion ≥ 0.2 μg/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.