This is no small topic. And I don’t plan to give a definitive take on this but here’s some thoughts.
I’m also planning one on why methaemoglobinaemia is a good thing. Seriously.1 What is methaemoglobinaemia?
Iron is normally found in Hb in the ferrous (Fe2+) state. In metHb the iron is in the ferric (Fe3+) state.
MetHb is unable to bind oxygen and any nomral Hb left will have greater affinity for the O2 and not want to give it up. Together this shifts the good old oxy-Hb dissociation curve to the left (as does carboxyhaemoglobin)
Note this is importantly different from cyanide toxicity, where the interruption is in the electron transport chain and oxygen transport is unaffected.
- congenital – we’ll not worry too much about these
- iatrogenic – the big one we should be aware of LA toxicity (notably prilocaine, and though rarely used I have seen this). The other notable one is metoclopramide which was new to me… Dapsone is another but when did you last see someone on dapsone? [UPDATE 2015 – just recently saw a dapsone OD, multiple doses of blue over a few days…]
- poisoning – the nitrites (amyl nitrite or sodium nitrite). Doses as small as 3 or 4g are known to be fatal for an adult. Of note sodium nitrite is widely used in food preservation and appears and tastes like normal salt. So imagine the potential for problems there. See this report for an example. In industrial settings it is often highly coloured to make it conspicuous.
3 Clinical Features?
Hopefully you know the general effects of tissue hypoxia – it makes you sick, potentially very sick.
The more useful clinical features are probably:
- blueish skin colour – naturally bog-standard hypoxemia will cause this but there is more of a blueish tinge to it. Note the blue men of Lurgan who were a famous case series of congenital metHb. Lurgan is a whole 5 minutes away from where I grew up and where I practice. Just saying…
- chocolate brown discoloration of the blood. In one of the cases I’ve seen it was a lot more dramatic than the colour shown below
- plays silly buggers with your SaO2 readings – as i’m sure you all know (ahem…) that standard sats probes emit only two wavelengths (650nm and 940nm) that correspond to the absorption of oxy- and deoxy- haemoglobin. MetHb absorbs at yet a different wavelength and so is not picked up usually on basic monitoring. The same is true of COHb. You can get sats probes that measure different wavelengths but that’s a whole different discussion…
- also worth considering if your sats don’t get better despite O2
4 How do you make the diagnosis?
- a history of exposure to something that might cause it
- a raised MetHb level – most blood gas machines will measure this (if they have a thing called a co-oximeter). If your machine lists COHb levels then it’ll probably give you MetHb levels too. A level above 20% is often quoted to stimulate treatment
- methylene blue – you remember that funny dye from high school chemistry? and remember that cupboard in your ED that has all the antidotes that you can’t pronounce in it? – it’ll be in there.
- 1-2 mg/kg IV over 5 minutes, response should be “rapid”
- doses can be repeated but there’s reports of badness beyond 7 mg/kg
- note that UpToDate suggests that methylene blue is measured as MetHb in standard co-oximeter readings so I doubt that you can use MetHb to judge clinical response. Anyone know any better on this? I couldn’t find much.
- I’m presuming you’re all find with good supportive care like airway and fluids and all that
6 How Does Methylene Blue Work?
- to be honest, I really care that you know when to give it but if you insist…
- methylene blue provides an artificial electron transporter to allow reduction of the ferric MetHb back to the good ferrous Hb.
7 Some observations
This is rare stuff, lets face it. I’ve seen a grand total of one severe poisoning from this. But to be perfectly honest if we don’t know this stuff, then no one else in the hospital will. And remember – people won’t always tell you about drug exposures so you have to be able to put the diagnosis together in the absence of information. After all that’s what we do right?
Matthew Mac Partlin added a few comments with some good bits that were useful to me at least!
- deoxygenated blood reds up nicely when exposed to air, but Met-Hb blood keeps its chocolatey colour.
- Watch that SpO2 when you give the methylene blue! It usually takes a spectacular dive as the ferrous-Hb is released.
- Occupational methaemoglobinaemia. Mechanisms of production, features, diagnosis and management including the use of methylene blue. Bradberry SM Toxicol Rev. 2003;22(1):13-27. PMID 14579544
- Toxicology Handbook 2nd Ed Murray et al Churchill Livingstone 2011
- Wikipedia – though beware what you find there…