Episode 110. The use of Methylene Blue for Refractory Hypotension with Rosa Malloy-Post, MD


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Guest For the podcast

Rosa Malloy-Post 

Hometown: Brooklyn, NY

College: Fort Lewis College Durango, CO

Medical school: University of Colorado

What you love about living in/moving to Charlotte: The food and the trees. Coming from Denver it’s nice to have some greenery.  The variety and concentration of good food is impressive, I haven’t had a bad meal yet. 

What you see yourself doing in 10 years: Who knows? I’m opened to exploring fellowship opportunities in toxicology or palliative care. I enjoy teaching so I see an academic career in my future.  I’ll most likely be somewhere in the mountain west. 

Methylene blue

History and Background

  • First synthesized in 1876 by Heinrich Caro at BASF as a blue textile dye, originally named “methyl blue”
  • In 1891, Paul Ehrlich discovered it could stain certain microorganisms and used it to differentiate bacterial species
  • Used as antiseptic/antibacterial in late 1800s, including treating tropical diseases like malaria
  • Approved by FDA in 1959 as a treatment for methemoglobinemia, a condition where hemoglobin is oxidized to the ferric (Fe3+) form, making it unable to carry oxygen. Doses of 1-2 mg/kg IV can reduce methoglobin levels by acting as an electron donor.
  • Studied as potential treatment for hypotension starting in 1980s. Case reports showed benefit in refractory septic shock. Proposed as nitric oxide scavenger and vasopressor.
  • Multiple human studies in 1990s looked at methylene blue for sepsis. Showed transient improvements in blood pressure but no mortality benefit.


  • heterocyclic aromatic molecule


  • two opposite actions on Hb

(1) low concentrations: methylene blue -> NADPH-dependent reduction to leucomethylene blue (due to action of methaemoglobin reductase) -> reduces methaemoglobin -> Hb

(2) high concentrations: methylene blue -> converts ferrous iron of reduced Hb to ferric ion -> forms methaemoglobin

  • inhibits guanylate cyclase (which is stimulated by NO and other mediators), thus decreasing C-GMP and vascular smooth muscle relaxation
  • MAO inhibition

  • Methaemoglobinaemia
    • 1-2mg/kg IV over 5 minutes followed by saline flush; repeat at 30-60 min if MetHb levels not falling
    • repeat dose every 6-8h when MetHb continues for days, e.g. dapsone toxicity
  • Vasoplegia
    • 1.5-2 mg/kg IV over 30-60min

      • methaemoglobinemia
        • — symptomatic
        • — asymptomatic with >20% MetHb, or >10% if risk factors such as anaemia or ischemic heart disease
      • vasoplegic shock post cardiopulmonary bypass
      • other possible roles in critical illness: hepatopulmonary syndrome, septic shock
      • other uses have included use as an antimalarial agent, anti-cancer treatment, treatment of ifosfamide neurotoxicity, as a dye/stain (e.g. test for aspiration), priapism
    • G6PD deficiency (lack of NADPH prevents methylene blue from working and may lead to haemolysis)
    • renal impairment
    • methaemoglobin reductase deficiency
    • nitrite-induced methaemoglobinaemia due to cyanide poisoning
    • hypersensitivity

    • inability to monitor oxygen saturation by SpO2 or continuous central venous saturation monitoring
    • non-specific symptoms: dizziness, headache, confusion, chest pain, shortness of breath, nausea and vomitng
    • local pain and irritation
    • blue staining of mucous membrane may mimic cyanosis
    • paradoxical methaemoglobinaemia due to direct oxidative effect on Hb (typically at very high doses > 7 mg/kg)
    • acute haemolytic anemia in G6PD deficiency (typically doses >15mg/kg)
    • anaphylaxis
    • MAO inhibiton may contribute to serotonin toxicity or hypertensive crisis

  • Key Clinical Studies
    • Levin et al. 2004 RCT in post-CABG vasoplegic shock
      • 28 patients, MB 2 mg/kg vs placebo
      • Marked improvement in hemodynamics
      • Mortality benefit – 0% vs 21% in placebo group (p=0.01)
    • Kirov et al. 2001 RCT in established septic shock
      • 20 patients, MB vs placebo
      • Increased MAP, decreased vasopressor needs
    • Porizka et al. 2020 retrospective study
      • Looked at MAP increase ≥10% to define “responders”
      • Improved survival in responders
    • Franz et al. 2021 case series
      • 11 patients with post-cardiotomy shock
      • 82% rate of MB response based on 20% MAP increase
      • Survival benefit in responders (92% vs 50%)


Jimmy L. Pruitt III, PharmD, BCPS, BCCCP

The Pharm So Hard Podcast is a show focused primarily on emergency medicine and hospital pharmacy related topics. To empower healthcare providers with the knowledge and skills they need to provide evidence-based, safe care for critically ill patients.

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