Nitroprusside and methemoglobin

[pgg]

A few details are unclear to me.

Metabolism of SNP involves a few steps, including
. SNP + oxyHb --> 5 x CN- + 1 x metHb
. CN- + metHb --> cyanmetHb
(Skipping the other details concerning thiosulfate, amyl nitrate, etc etc.)


Question # 1 - Can you get a net production of methemoglobin from a SNP infusion? My understanding of this is that there is NO net production of methemoglobin because there's an excess of cyanide produced simultaneously, and any available metHb is sucked up and converted to cyanmetHb.

Does cyanmethemoglobin also produce a pulse ox reading of 85?

There's a question in Hall concerning a patient with a prolonged infusion of SNP presenting with a SpO2 of 85% and the correct answer per the key is methemoglobinemia.

There's also an old ITE question from 1994 in which the key states that methemoglobin is specifically NOT a consequence of SNP infusion (though the scenario implies a short-term infusion of SNP).

Where does the metHb come from after prolonged SNP infusions? The best answer I can come up with is that over time, the cyanmetHb dissociates to CN + metHb and that CN gets sucked up by thiosulfate that is produced in the interim. This isn't spelled out in any reference I can find though.


Question # 2 - Is it safe or appropriate to treat methemoglobinemia with methylene blue in the setting of a prolonged SNP infusion?

Morgan & Mikhail says yes. My understanding is that the answer here is a definite no, because methylene blue will also "fix" cyanmethemoglobin ... potentially dumping a lot of newly freed CN in the process.

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[SleepIsGood]

Morgan & Mikhail says yes. My understanding is that the answer here is a definite no, because methylene blue will also "fix" cyanmethemoglobin ... potentially dumping a lot of newly freed CN in the process.

See I agree with M n M in that I thought you could treat MetHb with Methylene Blue whether it's from SNP or prilocaine, or EMLA or benzocaine.

I've been told otherwise however.

If someone else coudl provide a reference that would be great.

 

[pgg]

If someone else coudl provide a reference that would be great.

3 weeks & 300+ views ... from the lack of discussion maybe this is less (or more) obvious than I think it is. Or maybe just uninteresting to others.

I've still got nothing definitive from a text, but this comments on the issues

http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=5761

Nitroprusside metabolism can lead to methemoglobin formation (a) through dissociation of cyanmethemoglobin formed in the original reaction of sodium nitroprusside with Hgb and (b) by direct oxidation of Hgb by the released nitroso group. Relatively large quantities of sodium nitroprusside, however, are required to produce significant methemoglobinemia.

In patients likely to have substantial amounts of cyanide bound to methemoglobin as cyanmethemoglobin, treatment of methemoglobinemia with methylene blue must be undertaken with extreme caution.

So I interpret this to mean that

1) The net production of metHb is due to dissociation of cyanmetHb and oxidation of Hb over time. Even though the metHb initially produced by SNP metabolism is immediately consumed by one of the 5 CN- molecules, eventually the cyanmetHb dissociates to metHb + CN- (which presumably is then sucked up by thiosulfate produced in the interim).

2) You can in fact hurt someone by treating their metHb with methylene blue if they have "substantial amounts" of cyanmetHb. In someone whose metHb is presumed due to SNP toxicity, I think you have to assume they have a lot of cyanmetHb too, and not just cowboy ahead with the methylene blue. Perhaps the best approach is to pretreat them with thiosulfate so the CN- liberated by methylene blue has somewhere to go.