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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”
Multiple human studies in 1990s looked at methylene blue for sepsis. Showed transient improvements in blood pressure but no mortality benefit.CLASS
- heterocyclic aromatic molecule
MECHANISM OF ACTION
- 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
DoseMethaemoglobinaemia- 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 toxicityVasoplegia- 1.5-2 mg/kg IV over 30-60min
— asymptomatic with >20% MetHb, or >10% if risk factors such as anaemia or ischemic heart diseasevasoplegic shock post cardiopulmonary bypassother possible roles in critical illness: hepatopulmonary syndrome, septic shockother 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
CONTRA-INDICATIONS- G6PD deficiency (lack of NADPH prevents methylene blue from working and may lead to haemolysis)
renal impairmentmethaemoglobin reductase deficiencynitrite-induced methaemoglobinaemia due to cyanide poisoninghypersensitivity- ADVERSE EVENTS
- 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 vomitnglocal pain and irritationblue staining of mucous membrane may mimic cyanosisparadoxical 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)anaphylaxisMAO 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 hemodynamicsMortality 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 needsPorizka et al. 2020 retrospective study- Looked at MAP increase ≥10% to define “responders”
Improved survival in respondersFranz et al. 2021 case series- 11 patients with post-cardiotomy shock
82% rate of MB response based on 20% MAP increaseSurvival benefit in responders (92% vs 50%)
The post Episode 110. The use of Methylene Blue for Refractory Hypotension with Rosa Malloy-Post, MD appeared first on The Pharm So Hard Podcast.
