Methylene blue and refractory hypotension

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My name is Will Pendergraft, and I just completed the clinical portion of the joint nephrology fellowship between Brigham and Women’s Hospital and Massachusetts General Hospital. I was inspired for the first time by Nate Hellman during my residency at UCSF when I started to peruse this blog. If you have any free time, it’s worth looking back at his very first post from 2008. I am astonished by how he wrote these posts on a daily basis! As a contributor to the blog, my goal will be to provide short and useful, or at least interesting, nephrocentric snippets for first-year fellows.

With that said, I was walking through the cardiac surgery ICU at MGH a few months ago on my way to provide moral support for one of my co-fellows who was placing a difficult dialysis catheter in someone with almost no access, and upon entering the patient’s room, I noticed that the urine in the collection bag was of a Mediterranean shade (see image)! Given that we are differentialists by trade, has a pretty good list of what can cause different urine colors. The surgical team said they were intravenously infusing methylene blue “to improve the patient’s refractory hypotension,” an idea with which I was unfamiliar, so I sprinted to the nearest computer to look into this more deeply.
Methylene blue was created in 1876 and was first used in humans in 1881 by nobel laureate Paul Ehrlich to treat mild cases of malaria. It now has multiple indications, most notably including reduction of methemoglobin to hemoglobin in methemoglobinemia. Intravenous and oral formulations are easily excreted into the urine turning it blue to bluish-green. Interestingly, methylene blue also inhibits guanylate cyclase, a second messenger involved in nitric oxide-mediated vasodilation; thus, it prevents smooth muscle relaxation. In cases of shock where fluids, standard pressors du jour and steroids are ineffective, methylene blue may be another medication in the anti-hypotensive toolkit. Surprisingly, there are over ten clinical trials with positive results using methylene blue in refractory septic shock, and it is even used by anesthetists and surgeons to treat vasoplegia after cardiopulmonary bypass. The dosing regimen is 2 mg/kg IV once as a bolus followed by continuous infusion. Remember methylene blue the next time you see this shade of urine and be on the lookout for it in the cardiac surgery ICUs.
Posted by Will Pendergraft


  1. Hi, I take about 50mg Methylene blue for nootropic purposes. I am also curious if has adverse or helpful effects on Kidney function. See I have hypertension from sleep apnea, recently had a lot of foamy urine while doing a training cycle. Other health problems ensued when I got the flu earlier this year. I am about to check my protein ratio via urinalysis and do C-Kinase blood test. But I am wondering if the nootropic is helping me or if I should discontinue usage. Thanks in advance.

  2. Also can be used in pediatric overdose of Calcium Channel Blockers refractory to your pressors and other tricks.

  3. Hey Will, hope you are enjoying fellowship. It was a pleasure to work with you when u were a resident.

  4. I remember during my Fellowship years in the early 2000s, using MB being used for patients with CsA nephrotoxicity… as it inhibited oxygen free radical formation.
    BTW, chek out Nephrology Secrets 3rd Ed, Chapter 2… Mitch Rosne and I talked about purple urine bag syndrome, blue and red diaper syndromes, black urine disease, etc.

  5. There's a website about urine colors? And a discussion forum? Well, that's the highlight of MY day. LOL.

  6. Would not have known it, if you had not brought it up! Thanks…

  7. It's really curious. Methylenblue might cause systemic hypotension.

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